bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the Value of Radiomics Features Based on B-Mode and Contrast-Enhanced Ultrasound in Discriminating the Nature of Thyroid Nodules
Authors: Guo Shi Yan , Zhou Ping , Zhang Yan , Jiang Li Qing , Zhao Yong Feng 
Published: October 2021

BackgroundWith the improvement of ultrasound imaging resolution and the application of various new technologies, the detection rate of thyroid nodules has increased greatly in recent years. However, there are still challenges in accurately diagnosing the nature of thyroid nodules. This study aimed to evaluate the clinical application value of the radiomics features extracted from B-mode ultrasound (B-US) images combined with contrast-enhanced ultrasound (CEUS) images in the differentiation of benign and malignant thyroid nodules by comparing the diagnostic performance of four logistic models.MethodsWe retrospectively collected and ultimately included B-US images and CEUS images of 123 nodules from 123 patients, and then extracted the corresponding radiomics features from these images respectively. Meanwhile, a senior radiologist combined the thyroid imaging reporting and data system (TI-RADS) and the enhancement pattern of the ultrasonography to make a graded diagnosis of the malignancy of these nodules. Next, based on these radiomics features and grades, logistic regression was used to help build the models (B-US radiomics model, CEUS radiomics model, B-US+CEUS radiomics model, and TI-RADS+CEUS model). Finally, the study assessed the diagnostic performance of these radiomics features with a comparison of the area under the curve (AUC) of the receiver operating characteristic curve of four logistic models for predicting the benignity or malignancy of thyroid nodules.ResultsThe AUC in the differential diagnosis of the nature of thyroid nodules was 0.791 for the B-US radiomics model, 0.766 for the CEUS radiomics model, 0.861 for the B-US+CEUS radiomics model, and 0.785 for the TI-RADS+CEUS model. Compared to the TI-RADS+CEUS model, there was no statistical significance observed in AUC between the B-US radiomics model, CEUS radiomics model, B-US+CEUS radiomics model, and TI-RADS+CEUS model (P&gt;0.05). However, a significant difference was observed between the single B-US radiomics model or CEUS radiomics model and B-US+CEUS radiomics model (P&lt;0.05).ConclusionIn our study, the B-US radiomics model, CEUS radiomics model, and B-US+CEUS radiomics model demonstrated similar performance with the TI-RADS+CEUS model of senior radiologists in diagnosing the benignity or malignancy of thyroid nodules, while the B-US+CEUS radiomics model showed better diagnostic performance than single B-US radiomics model or CEUS radiomics model. It was proved that B-US radiomics features and CEUS radiomics features are of high clinical value as the combination of the two had better diagnostic performance.
Anti-Tumor Effects of Chinese Medicine Compounds by Regulating Immune Cells in Microenvironment
Authors: Chen Fengqian , Li Jingquan , Wang Hui , Ba Qian 
Published: October 2021

As the main cause of death in the world, cancer is one of the major health threats for humans. In recent years, traditional Chinese medicine has gained great attention in oncology due to the features of multi-targets, multi-pathways, and slight side effects. Moreover, lots of traditional Chinese medicine can exert immunomodulatory effects in vivo. In the tumor microenvironment, tumor cells, immune cells as well as other stromal cells often coexist. With the development of cancer, tumor cells proliferate uncontrollably, metastasize aggressively, and modulate the proportion and status of immune cells to debilitate the antitumor immunity. Reversal of immunosuppressive tumor microenvironment plays an essential role in cancer prevention and therapy. Immunotherapy has become the most promising strategy for cancer therapy. Chinese medicine compounds can stimulate the activation and function of immune cells, such as promoting the maturation of dendritic cells and inducing the differentiation of myeloid-derived suppressor cells to dendritic cells and macrophages. In the present review, we summarize and discuss the effects of Chinese medicine compounds on immune cells in the tumor microenvironment, including innate immune cells (dendritic cells, natural killer cells, macrophages, and myeloid-derived suppressor cells) and adaptive immune cells (CD4+/CD8+ T lymphocytes and regulatory T cells), and the various immunomodulatory roles of Chinese medicine compounds in cancer therapy such as improving tumor-derived inflammation, enhancing the immunity after surgery or chemotherapy, blocking the immune checkpoints, et al., aiming to provide more thoughts for the anti-tumor mechanisms and applications of Chinese medicine compounds in terms of tumor immunity.
Second Malignant Neoplasms in Patients With Rhabdomyosarcoma
Authors: Zhen Hongnan , Liu Zhikai , Guan Hui , Ma Jiabin , Wang Wenhui , Shen Jing , Miao Zheng , Zhang Fuquan 
Published: October 2021

ObjectiveRhabdomyosarcoma (RMS) is a rare malignant tumor. The main treatment modality is comprehensive with chemotherapy, radiotherapy, and surgery. With the advancement in recent decades, patient survival has been prolonged, and long-term complications are attracting increasing attention among both physicians and patients. This study aimed to present the survival of patients with RMS and analyze the risk factors for the development of a second malignant neoplasm (SMN).MethodsThe Surveillance, Epidemiology, and End Results (SEER) Program 18 registry database from 1973 to 2015 of the National Cancer Institute of the United States was used for the survival analyses, and the SEER 9 for the SMN analysis.ResultsThe 5-, 10-, and 20-year overall survival rates of the patients with RMS were 45%, 43%, and 33%, respectively. The risk of SMN was significantly higher in patients with RMS compared to the general population (SIR=1.95, 95% CI: 1.44 – 2.57, p &lt; 0.001). The risk of developing SMN was increased in multiple locations, including the bones and joints (SIR = 35.25) soft tissues including the heart (SIR = 22.5), breasts (SIR = 2.10), male genital organs (SIR = 118.14), urinary system (SIR = 2.36), brain (SIR = 9.21), and all nervous system organs (SIR = 8.59). The multivariate analysis indicated that RMS in the limbs and earlier diagnosis time were independent risk factors for the development of SMN. Patients with head and neck (OR = 0.546, 95% CI: 0.313 – 0.952, p = 0.033) and trunk RMS (OR = 0.322, 95% CI: 0.184 – 0.564. p &lt; 0.001) and a later diagnosis time were less likely to develop SMN (OR = 0.496, 95% CI: 0.421 – 0.585, p &lt; 0.001).ConclusionThis study describes the risk factors associated with the development of SMN in patients with RMS, which is helpful for the personalized screening of high-risk patients with RMS.
Artificial Intelligence Combined With Big Data to Predict Lymph Node Involvement in Prostate Cancer: A Population-Based Study
Authors: Wei Liwei , Huang Yongdi , Chen Zheng , Lei Hongyu , Qin Xiaoping , Cui Lihong , Zhuo Yumin 
Published: October 2021

BackgroundA more accurate preoperative prediction of lymph node involvement (LNI) in prostate cancer (PCa) would improve clinical treatment and follow-up strategies of this disease. We developed a predictive model based on machine learning (ML) combined with big data to achieve this.MethodsClinicopathological characteristics of 2,884 PCa patients who underwent extended pelvic lymph node dissection (ePLND) were collected from the U.S. National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Eight variables were included to establish an ML model. Model performance was evaluated by the receiver operating characteristic (ROC) curves and calibration plots for predictive accuracy. Decision curve analysis (DCA) and cutoff values were obtained to estimate its clinical utility.ResultsThree hundred and forty-four (11.9%) patients were identified with LNI. The five most important factors were the Gleason score, T stage of disease, percentage of positive cores, tumor size, and prostate-specific antigen levels with 158, 137, 128, 113, and 88 points, respectively. The XGBoost (XGB) model showed the best predictive performance and had the highest net benefit when compared with the other algorithms, achieving an area under the curve of 0.883. With a 5%~20% cutoff value, the XGB model performed best in reducing omissions and avoiding overtreatment of patients when dealing with LNI. This model also had a lower false-negative rate and a higher percentage of ePLND was avoided. In addition, DCA showed it has the highest net benefit across the whole range of threshold probabilities.ConclusionsWe established an ML model based on big data for predicting LNI in PCa, and it could lead to a reduction of approximately 50% of ePLND cases. In addition, only ≤3% of patients were misdiagnosed with a cutoff value ranging from 5% to 20%. This promising study warrants further validation by using a larger prospective dataset.
Efficacy and Toxicity of Three Induction Chemotherapy Regimens in Locoregionally Advanced Nasopharyngeal Carcinoma: Outcomes of 10-Year Follow-Up
Authors: Peng Hao , Chen Binbin , He Shuiqing , Tian Li , Huang Ying 
Published: October 2021

Background/ObjectiveWe aimed to compare the 10-year survival outcomes of induction docetaxel plus cisplatin and 5-fluorouracil (TPF), docetaxel plus cisplatin (TP), and cisplatin plus 5-fluorouracil (PF) regimens additional to concurrent chemoradiotherapy (CRT) in locoregionally advanced nasopharyngeal carcinoma (NPC).MethodsEligible patients with newly diagnosed stage III-IVA NPC were included. Propensity score matching (PSM) was used to balance prognostic covariates. Survival outcomes and toxicities between different groups were compared.ResultsA total of 855 patients between 2009 and 2012 were included, with 395 (46.2%), 258 (30.2%), and 202 (23.6%) receiving TPF plus CRT, TP plus CRT, and PF plus CRT regimens, respectively. After a median follow-up of 111.8 months, multivariate analysis both in the whole cohort and PSM selected 202 pairs showed that TPF plus CRT and TP plus CRT achieved significantly better 10-year overall survival (OS) than PF plus CRT. Sensitivity analysis after excluding patients with T3-4N0 disease demonstrated that TPF plus CRT still achieved significantly better OS than PF plus CRT (HR, 0.580; 95% CI, 0.395-0.852; P = 0.005), while the difference between TP plus CRT and PF plus CRT was marginally significant (HR, 0.712; 95% CI, 0.503-1.008; P = 0.056). With regard to toxicity profile, PF regimen achieved the lowest grade 3–5 toxicities (27.3%).ConclusionTPF plus CRT and TP plus CRT were better than PF plus CRT in improving the 10-year OS of patients with stage III-IVA NPC.
Dynamics of Adaptive Immune Cell and NK Cell Subsets in Patients With Ankylosing Spondylitis After IL-17A Inhibition by Secukinumab
Authors: Jiang Yutong , Yang Mingcan , Zhang Yanli , Huang Yefei , Wu Jialing , Xie Ya , Wei Qiujing , Liao Zetao , Gu Jieruo 
Published: October 2021

Background: Anti-IL-17A therapy is generally effectively applied in patients with Ankylosing Spondylitis (AS) to achieve and maintain remission. However, the influence of anti-IL-17A on the composition of the immune system is not apparent. Our prospective study was to explore the changes in immune imbalance regarding T cell, B cell and natural killer (NK) cell subsets after secukinumab treatment in AS patients.Methods: Immune cell distribution of 43 AS patients treated with secukinumab for 12 weeks and 47 healthy controls (HC) were evaluated. Flow cytometry using monoclonal antibodies against 25 surface markers was accomplished to explore the frequencies of lineage subsets. The differences between HC, AS pre-treatment, and post-treatment were compared using the paired Wilcoxon test, Mann-Whitney U test, and ANOVA.Results: AS patients had altered immune cell distribution regarding T cell and B cell subsets. Apart from activated differentiation of CD4+ T cell, CD8+ T cell and B cell, higher levels of cytotoxic T (Tc) two cells and Tc17 cells were noted in AS patients. We confirmed that helper T (Th) one cell became decreased; however, Th17 cells and T follicular helper (Tfh) 17 cells went increased in AS. After 12 weeks of secukinumab therapy, CRP and ASDAS became significantly decreased, and meanwhile, the proportions of Th1 cells, Tfh17 cells and classic switched B cells were changed towards those of HC. A decreased CRP was positively correlated with a decrease in the frequency of naïve CD8+ T cells (p = 0.039) and B cells (p = 0.007) after secukinumab treatment. An elevated level of T cells at baseline was detected in patients who had a good response to secukinumab (p = 0.005).Conclusion: Our study confirmed that AS patients had significant multiple immune cell dysregulation. Anti-IL-17A therapy (Secukinumab) could reverse partial immune cell imbalance.
Effects of Volume-Price Contracts on Pharmaceutical Prices: A Retrospective Comparative Study of Public Hospitals in Hubei of China
Authors: Li Zhuoxian , Liu Chaojie , Zuo Keyuan , Liu Junjie , Tang Yuqing 
Published: October 2021

Background: Pharmaceutical expenditure has been increasing worldwide. Many countries have attempted to contain the increase through collective bargaining, including in China. In 2015, the Chinese government introduced a new policy to empower regional governments to reduce pharmaceutical prices through its existing tendering system which enables a lower price for products with higher procurement volumes. Xiangyang municipality in Hubei province took a lead in piloting this initiative.Objectives: This study aimed to evaluate the effects of the volume-price contract initiative on pharmaceutical price procured by the public hospitals in Xiangyang.Methods: A retrospective comparative design was adopted. The price of cardiovascular medicines (349 products under 164 International Nonproprietary Names) procured by the public hospitals in Xiangyang was compared with those procured in Yichang municipality in Hubei. A total of 15,921 procurement records over the period from January 2017 to December 2018 were examined (Xiangyang started the volume-price contract initiative in January 2018). Generalized linear regression models with a difference-in-differences approach which could reflect the differences between the two cities between January 2018 and December 2018 were established to test the effects of the volume-price contract initiative on pharmaceutical prices.Results: On average, the procurement price for cardiovascular medicines adjusted by defined daily dosage in Xiangyang dropped by 41.51%, compared with a 0.22% decrease in Yichang. The difference-in-differences results showed that the volume-price contract initiative resulted in a 36.24% drop (p = 0.006) in the price (30.23% for the original brands, p = 0.008), in addition to the therapeutic competition effect (31.61% reduction in the price, p = 0.002). The top 100 domestic suppliers were highly responsive to the initiative (82.80% drop in the price, p = 0.001).Conclusion: The volume-price contract initiative has the potential to bring down the price of pharmaceutical supplies. Higher responses from the domestic suppliers are evident.
Attenuation of Circulating Trimethylamine N-Oxide Prevents the Progression of Cardiac and Renal Dysfunction in a Rat Model of Chronic Cardiorenal Syndrome
Authors: Zou Deling , Li Yanyu , Sun Guangping 
Published: October 2021

Chronic heart failure (HF) frequently causes progressive decline in kidney function, known as cardiorenal syndrome-2 (CRS2). Current treatment options for CRS2 remain unacceptably limited. Trimethylamine-N-oxide (TMAO), a metabolite of gut microbiota, has recently been implicated in the pathogenesis of both HF and chronic kidney disease. Here we examined whether circulating TMAO is elevated in CRS2 and if so, whether attenuation of circulating TMAO would ameliorate the progression of CRS2. Sprague-Dawley rats underwent surgery for myocardial infarction (MI) or sham (week 0) followed by subtotal (5/6) nephrectomy (STNx) or sham at week 4 to induce CRS2 or control. At week 6, MI + STNx rats and control rats received vehicle or 1.0% 3,3-Dimethyl-1-butanol (DMB, a TMAO inhibitor) treatment for 8 weeks. Compared with control rats, MI + STNx rats exhibited elevated serum TMAO at week 6, which was increased further at week 14 but was attenuated by DMB treatment. MI + STNx rats showed cardiac dysfunction as assessed by echocardiography and renal dysfunction as evidenced by increased serum creatinine and urinary kidney injury molecule-1 and decreased creatinine clearance at week 6. The cardiac and renal dysfunction in MI + STNx rats was exacerbated at week 14 but was prevented by DMB treatment. Molecular and histological studies revealed myocyte hypertrophy and increases in interstitial myocardial fibrosis and gene expression of pro-hypertrophic and pro-fibrotic markers in both heart and kidney at week 14, which were accompanied by elevated gene expression of proinflammatory cytokines. The changes in molecular and histological parameters observed in MI + STNx rats were significantly reduced by DMB treatment. These findings suggest that rats with CRS2 have elevated circulating TMAO, which is associated with the exacerbation of cardiac and renal dysfunction. Attenuation of circulating TMAO can ameliorate cardiac and renal injury and prevents the progression of CRS2.
Contributions of UDP-Glucuronosyltransferases to Human Hepatic and Intestinal Metabolism of Ticagrelor and Inhibition of UGTs and Cytochrome P450 Enzymes by Ticagrelor and its Glucuronidated Metabolite
Authors: Liu Shuaibing , Hou Lei , Li Cai , Zhao Yibo , Yao Xia , Zhang Xiaojian , Tian Xin 
Published: October 2021

Ticagrelor is the first reversibly binding, direct-acting, oral P2Y12 receptor inhibitor. The contribution of UDP-glucuronosyltransferases (UGTs) enzymes to the metabolism of ticagrelor to its glucuronide conjugation, ticagrelor-O-glucuronide, in human liver microsomes (HLM) and human intestinal microsomes (HIM), was well characterized in the current study. The inhibition potential of human major UGTs by ticagrelor and ticagrelor-O-glucuronide was explored. The inhibitory effects of ticagrelor-O-glucuronide on cytochrome P450s (CYPs) enzymes were investigated as well. Ticagrelor glucuronidation exhibits substrate inhibition kinetics in both HLM and HIM with apparent Km values of 5.65 and 2.52 μM, Vmax values of 8.03 and 0.90 pmol min−1·mg protein−1, Ksi values of 1,343.0 and 292.9 respectively. The in vitro intrinsic clearances (Vmax/Km) for ticagrelor glucuronidation by HLM and HIM were 1.42 and 0.36 μl min−1·mg protein−1, respectively. Study with recombinant human UGTs suggested that multiple UGT isoforms including UGT1A9, UGT1A7, UGT1A3, UGT1A4, UGT1A1, UGT2B7 and UGT1A8 are involved in the conversion of ticagrelor to ticagrelor-O-glucuronide with UGT1A9 showing highest catalytic activity. The results were further supported by the inhibition studies on ticagrelor glucuronidation with typical UGT inhibitors in pooled HLM and HIM. Little or no inhibition of UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9 and UGT2B7 by ticagrelor and ticagrelor-O-glucuronide was noted. Ticagrelor-O-glucuronide also exhibited limited inhibitory effects toward CYP2C8, CYP2D6 and CYP3A4. In contrast, ticagrelor-O-glucuronide weakly inhibited CYP2B6, CYP2C9 and CYP2C19 activity with apparent IC50 values of 45.0, 20.0 and 18.8 μM, respectively. The potential of ticagrelor-O-glucuronide to cause drug-drug interactions warrant further study.
Categorical Perception of Mandarin Pitch Directions by Cantonese-Speaking Musicians and Non-musicians
Authors: Chen Si , Yang Yike , Wayland Ratree 
Published: October 2021

Purpose:This study is to investigate whether Cantonese-speaking musicians may show stronger CP than Cantonese-speaking non-musicians in perceiving pitch directions generated based on Mandarin tones. It also aims to examine whether musicians may be more effective in processing stimuli and more sensitive to subtle differences caused by vowel quality.Methods:Cantonese-speaking musicians and non-musicians performed a categorical identification and a discrimination task on rising and falling continua of fundamental frequency generated based on Mandarin level, rising and falling tones on two vowels with nine duration values.Results:Cantonese-speaking musicians exhibited a stronger categorical perception (CP) of pitch contours than non-musicians based on the identification and discrimination tasks. Compared to non-musicians, musicians were also more sensitive to the change of stimulus duration and to the intrinsicF0in pitch perception in pitch processing.Conclusion:The CP was strengthened due to musical experience and musicians benefited more from increased stimulus duration and were more efficient in pitch processing. Musicians might be able to better use the extra time to form an auditory representation with more acoustic details. Even with more efficiency in pitch processing, musicians' ability to detect subtle pitch changes caused by intrinsicF0was not undermined, which is likely due to their superior ability to process temporal information. These results thus suggest musicians may have a great advantage in learning tones of a second language.
The Mirroring Dance: Synchrony and Interaction Quality of Five Adolescents and Adults on the Autism Spectrum in Dance/Movement Therapy
Authors: Manders Elizabeth , Goodill Sharon , Koch Sabine C. , Giarelli Ellen , Polansky Marcia , Fisher Kathleen , Fuchs Thomas 
Published: October 2021

Background: Individuals on the autism spectrum are often described as having atypical social interactions. Ideally, interactional synchrony helps any interaction flow smoothly with each individual responding verbally, non-verbally, and/or emotionally within a short timeframe. Differences in interactional synchrony may impact how individuals on the autism spectrum experience social encounters.Method: This mixed methods pilot study examined interactional synchrony in five cases of adolescents and adults on the autism spectrum through secondary analysis of video of the participants in movement-based mirroring tasks during dance/movement therapy. Raters described the movement and interactions of the participants while they were leading and following mirroring and engaged in open-ended free dances with a partner. Videos were also scored on measures of affective engagement, flow of the interaction, and synchrony.Results: One of the most striking findings of this study was the difference between engagement in the instructions of the task and engagement with the partner: participants often followed the instructions for the mirroring tasks with little further social engagement with their partner. When participants did engage in moments of social initiation, attunement to the partner, and interactive behaviors, these did not develop into longer interactions. A paired t-test of the correlation coefficients for each participant showed that scores on synchrony and affective engagement were more strongly positively correlated in the less structured open-ended dance and in video clips of interactive behaviors, than in the videos of simply leading or following mirroring. Synchrony was also significantly more strongly positively correlated with the observed flow of the interaction than with observed affective engagement. With the small sample size, however, most of the correlation coefficients were not significant and should be tested on a larger sample.Discussion: Interpersonal synchrony may not be sufficient to effectively support social engagement when individuals on the autism spectrum simply follow instructions to synchronize their movements. Synchrony-based interventions may therefore need to include more complex open-ended social scenarios as interactional synchrony may then be more correlated with perceived interaction quality. Therapists may also need to partner with participants to model using non-verbal social behaviors to develop interactions within mirroring tasks.