bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of the Proprioceptive Neuromuscular Facilitation Contraction Sequence on Motor Skill Learning-Related Increases in the Maximal Rate of Wrist Flexion Torque Development
Authors: Green Lara A. , McGuire Jessica , Gabriel David A.
Published: November 2021

Background: The proprioceptive neuromuscular facilitation (PNF) reciprocal contraction pattern has the potential to increase the maximum rate of torque development. However, it is a more complex resistive exercise task and may interfere with improvements in the maximum rate of torque development due to motor skill learning, as observed for unidirectional contractions. The purpose of this study was to examine the cost-benefit of using the PNF exercise technique to increase the maximum rate of torque development.

Methods: Twenty-six participants completed isometric maximal extension-to-flexion (experimental PNF group) or flexion-only (control group) contractions at the wrist. Ten of the assigned contractions were performed on each of three sessions separated by 48-h for skill acquisition. Retention was assessed with 5 contractions performed 2-weeks after acquisition. Torque and surface electromyographic (sEMG) activity were analyzed for evidence of facilitated contractions between groups, as well as alterations in muscle coordination assessed across test sessions. The criterion measures were: mean maximal isometric wrist flexion toque; the maximal rate of torque development (dτ/dtmax); root-mean-square error (RMSE) variability of the rate of torque versus torque phase-plane; the rate of wrist flexion muscle activation (Q30); a coactivation ratio for wrist flexor and extensor sEMG activity; and wrist flexor electromechanical delay (EMD).

Results: There were no significant differences between groups with respect to maximal wrist flexion torque, dτ/dtmax or RMSE variability of torque trajectories. Both groups exhibited a progressive increase in maximal strength (+23.35% p < 0.01, η2 = 0.655) and in dτ/dtmax (+19.84% p = 0.08, η2 = 0.150) from the start of acquisition to retention. RMSE was lowest after a 2-week rest interval (−18.2% p = 0.04, η2 = 0.198). There were no significant differences between groups in the rate of muscle activation or the coactivation ratio. There was a reduction in coactivation that was retained after a 2-week rest interval (−32.60%, p = 0.02, η2 = 0.266). Alternatively, EMD was significantly greater in the experimental group (Δ 77.43%, p < 0.01, η2 = 0.809) across all sessions. However, both groups had a similar pattern of improvement to the third consecutive day of testing (−16.82%, p = 0.049, η2 = 0.189), but returned close to baseline value after the 2-week rest interval.

Discussion: The wrist extension-to-flexion contraction pattern did not result in a greater maximal rate of torque development than simple contractions of the wrist flexors. There was no difference between groups with respect to motor skill learning. The main adaptation in neuromotor control was a decrease in coactivation, not the maximal rate of muscle activation.
Developmental Factors That Predict Head Movement During Resting-State Functional Magnetic Resonance Imaging in 3–7-Year-Old Stuttering and Non-stuttering Children
Authors: Johnson Chelsea A. , Garnett Emily O. , Chow Ho Ming , Spray Gregory J. , Zhu David C. , Chang Soo-Eun
Published: November 2021

Early childhood marks a period of dynamic neurocognitive development. Preschool-age coincides with the onset of many childhood disorders and is a developmental period that is frequently studied to determine markers of neurodevelopmental disorders. Magnetic resonance imaging (MRI) is often used to explore typical brain development and the neural bases of neurodevelopmental disorders. However, acquiring high-quality MRI data in young children is challenging. The enclosed space and loud sounds can trigger unease and cause excessive head movement. A better understanding of potential factors that predict successful MRI acquisition would increase chances of collecting useable data in children with and without neurodevelopmental disorders. We investigated whether age, sex, stuttering status, and childhood temperament as measured using the Child Behavioral Questionnaire, could predict movement extent during resting-state functional MRI (rs-fMRI) in 76 children aged 3–7 years, including 42 children who stutter (CWS). We found that age, sex, and temperament factors could predict motion during rs-fMRI scans. The CWS were not found to differ significantly from controls in temperament or head movement during scanning. Sex and age were significant predictors of movement. However, age was no longer a significant predictor when temperament, specifically effortful control, was considered. Controlling for age, boys with higher effortful control scores moved less during rs-fMRI procedures. Additionally, boys who showed higher negative affectivity showed a trend for greater movement. Considering temperament factors in addition to age and sex may help predict the success of acquiring useable rs-fMRI (and likely general brain MRI) data in young children in MR neuroimaging.
DIBR-Synthesized Image Quality Assessment With Texture and Depth Information
Authors: Wang Guangcheng , Shi Quan , Shao Yeqin , Tang Lijuan
Published: November 2021

Accurately predicting the quality of depth-image-based-rendering (DIBR) synthesized images is of great significance in promoting DIBR techniques. Recently, many DIBR-synthesized image quality assessment (IQA) algorithms have been proposed to quantify the distortion that existed in texture images. However, these methods ignore the damage of DIBR algorithms on the depth structure of DIBR-synthesized images and thus fail to accurately evaluate the visual quality of DIBR-synthesized images. To this end, this paper presents a DIBR-synthesized image quality assessment metric with Texture and Depth Information, dubbed as TDI. TDI predicts the quality of DIBR-synthesized images by jointly measuring the synthesized image's colorfulness, texture structure, and depth structure. The design principle of our TDI includes two points: (1) DIBR technologies bring color deviation to DIBR-synthesized images, and so measuring colorfulness can effectively predict the quality of DIBR-synthesized images. (2) In the hole-filling process, DIBR technologies introduce the local geometric distortion, which destroys the texture structure of DIBR-synthesized images and affects the relationship between the foreground and background of DIBR-synthesized images. Thus, we can accurately evaluate DIBR-synthesized image quality through a joint representation of texture and depth structures. Experiments show that our TDI outperforms the competing state-of-the-art algorithms in predicting the visual quality of DIBR-synthesized images.
Topological Data Analysis as a New Tool for EEG Processing
Authors: Xu Xiaoqi , Drougard Nicolas , Roy Raphaëlle N.
Published: November 2021

Electroencephalography (EEG) is a widely used cerebral activity measuring device for both clinical and everyday life applications. In addition to denoising and potential classification, a crucial step in EEG processing is to extract relevant features. Topological data analysis (TDA) as an emerging tool enables to analyse and understand data from a different angle than traditionally used methods. As a higher dimensional analogy of graph analysis, TDA can model rich interactions beyond pairwise relations. It also distinguishes different dynamics of EEG time series. TDA remains largely unknown to the EEG processing community while it fits well the heterogeneous nature of EEG signals. This short review aims to give a quick introduction to TDA and how it can be applied to EEG analysis in various applications including brain-computer interfaces (BCIs). After introducing the objective of the article, the main concepts and ideas of TDA are explained. Next, how to implement it for EEG processing is detailed, and lastly the article discusses the benefits and limitations of the method.
Non-Coding RNAs in Glioma Microenvironment and Angiogenesis
Authors: Li Dongxue , Zhang Zhe , Xia Chengyu , Niu Chaoshi , Zhou Wenchao
Published: November 2021

Glioma, especially glioblastoma, is the most common and lethal brain tumor. In line with the complicated vascularization processes and the strong intratumoral heterogeneity, tumor-associated blood vessels in glioma are regulated by multiple types of cells through a variety of molecular mechanisms. Components of the tumor microenvironment, including tumor cells and tumor-associated stromata, produce various types of molecular mediators to regulate glioma angiogenesis. As critical regulatory molecules, non-coding RNAs (ncRNAs) inside cells or secreted to the tumor microenvironment play essential roles in glioma angiogenesis. In this review, we briefly summarize recent studies about the production, delivery, and functions of ncRNAs in the tumor microenvironment, as well as the molecular mechanisms underlying the regulation of angiogenesis by ncRNAs. We also discuss the ncRNA-based therapeutic strategies in the anti-angiogenic therapy for glioma treatment.
Plasma Vitamin E and the Risk of First Stroke in Hypertensive Patients: A Nested Case-Control Study
Authors: Song Yun , Li Jingyi , Liu Lishun , Xu Richard , Zhou Ziyi , Xu Benjamin , Lin Tengfei , Chen Ping , Li Huan , Li Youbao , Liu Chengzhang , Huang Xiao , Wang Binyan , Zhang Yan , Li Jianping , Huo Yong , Ren Fazheng , Xu Xiping , Zhang Hao , Qin Xianhui
Published: November 2021

Background: The association between plasma vitamin E levels and first stroke risk in men and women remains unclear.

Objective: We aimed to examine the prospective association between plasma vitamin E and first stroke, and evaluate the effect modifiers for the association, among hypertensive patients.

Design: The study sample was drawn from the China Stroke Primary Prevention Trial (CSPPT), which randomized a total of 20,702 hypertensive patients to a double-blind, daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. This nested case-control study, including 618 first stroke cases and 618 controls matched for age, sex, treatment group, and study site, was conducted after the completion of the CSPPT.

Results: The median follow-up duration was 4.5 years. Among men, a significantly higher risk of first stroke (adjusted OR, 1.67; 95%CI: 1.01, 2.77) was found for those with plasma vitamin E ≥7.1 μg/mL (≥quartile 1) compared with those with plasma vitamin E < 7.1 μg/mL. Subgroup analyses further showed that the association between vitamin E (≥7.1 vs. <7.1 μg/mL) and first stroke in men was significantly stronger in non-drinkers (adjusted OR, 2.64; 95%CI: 1.41, 4.96), compared to current drinkers (adjusted OR, 0.84; 95% CI: 0.43, 1.66, P-interaction = 0.008). However, there was no significant association between plasma vitamin E and first stroke in women (P-interaction between sex and plasma vitamin E = 0.048).

Conclusions: Among Chinese hypertensive patients, there was a statistically significant positive association between baseline plasma vitamin E and the risk of first stroke in men, but not in women.

Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT00794885, Identifier: NCT00794885.
Dietary Intake and Biomarkers of α-Linolenic Acid and Mortality: A Meta-Analysis of Prospective Cohort Studies
Authors: Chen Li-Hua , Hu Qingjing , Li Guijie , Zhang Li , Qin Li-Qiang , Zuo Hui , Xu Guangfei
Published: November 2021

Background: The association between α-linolenic acid (ALA) and mortality is inconsistent and has not been summarized systematically.

Objective: The purpose was to conduct a meta-analysis that synthesized the results of prospective cohort studies to investigate associations between ALA intake and mortality.

Methods: We conducted a comprehensive search on PubMed, Embase, and Web of Science databases on May 1, 2021, for relevant prospective cohort studies which reported associations of ALA (assessed by dietary surveys and/or ALA concentrations in body tissues) with mortality from all-cause, cardiovascular disease (CVD), and other diseases. Multivariable-adjusted relative risks (RRs) were pooled by a random or fixed-effects model.

Results: A total of 34 prospective cohort studies, of which 17 reported dietary ALA intake, 14 for ALA biomarkers, and the remaining 3 reported both of intake and biomarkers. The studies included 6,58,634 participants, and deaths were classified into all-cause mortality (56,898), CVD mortality (19,123), and other diseases mortality (19,061). Pooled RRs of ALA intake were 0.93 (95% CI: 0.86, 1.01, I2 = 71.2%) for all-cause mortality, 0.90 (95% CI: 0.83, 0.98, I2 = 22.1%) for CVD mortality, and 0.94 (95% CI: 0.83, 1.06, I2 = 73.3%) for other diseases mortality. The two-stage random-effects dose-response analysis showed a linear relationship between dietary ALA intake and CVD-mortality and each 0.5% energy increment of ALA intake was associated with a 5% lower risk of CVD-mortality (RR: 0.95; 95% CI: 0.90, 1.00). Pooled RRs per SD increment of ALA biomarkers were 0.99 (95% CI: 0.96, 1.01, I2 = 27%) for all-cause mortality, 1.00 (95% CI: 0.98, 1.03, I2 = 0%) for CVD mortality and 0.98 (95% CI: 0.95, 1.01, I2 = 0%) for other diseases mortality.

Conclusions: This meta-analysis summarizing the available prospective cohort studies indicated that ALA intake was associated with reduced risk of mortality, especially CVD mortality. Our findings suggest that ALA consumption may be beneficial for death prevention. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO; identifier: CRD42021264532.
Impact of Prebiotic β-glucan Treatment at Juvenile Age on the Gut Microbiota Composition and the Eventual Type 1 Diabetes Onset in Non-obese Diabetic Mice
Authors: Taylor Harrison B. , Vasu Chenthamarakshan
Published: November 2021

Complex dietary polysaccharides such as β-glucans are widely used for their anti-inflammatory properties. We reported before that oral administration of Yeast β-glucan (YBG) in adult mice can help delay type 1 diabetes (T1D) onset and suppress gut inflammation through modulation of the structure and function of gut microbiota. Since juvenile age is characterized by profoundly changing immature gut microbiota, we examined the impact of oral treatment with YBG in non-obese diabetic (NOD) mice at this age. Juvenile mice that received daily oral administration of YBG starting at 15 days of age for 7 or 30 days were examined for changes in gut microbiota, immune characteristics, and T1D incidence. Mice that received YBG for 30 days but not 7 days, showed considerable changes in the composition and diversity of fecal microbiota as compared to controls. Predictive functional analysis, based on 16S rDNA sequences, revealed overrepresentation of glycan biosynthesis and metabolism, energy metabolism, and fatty acid biosynthesis pathways in mice that received YBG for 30 days. Immune phenotype of the colon showed skewing toward immune regulatory and Th17 cytokines with increases in IL-10, IL-17, and IL-21 and a decrease in TNF-α, although increases in some pro-inflammatory cytokines (IL-1b, IFN-γ) were observed. Most importantly, mice that received YBG treatment for 30 days showed significantly suppressed insulitis and delayed onset of hyperglycemia compared to controls. Overall, this study suggests that oral consumption of YBG beginning at pre-diabetic juvenile ages could have positive maturational changes to gut microbiota and immune functions and could result in a delay in the disease onset in those who are pre-disposed to T1D.
Assessment and Prognostic Value of Immediate Changes in Post-Ablation Intratumor Density Heterogeneity of Pulmonary Tumors via Radiomics-Based Computed Tomography Features
Authors: Liu Bo , Li Chunhai , Sun Xiaorong , Zhou Wei , Sun Jing , Liu Hong , Li Shuying , Jia Haipeng , Xing Ligang , Dong Xinzhe
Published: November 2021

Objectives

To retrospectively observe the instantaneous changes in intratumor density heterogeneity after microwave ablation (MWA) of lung tumors and to determine their prognostic value in predicting treatment response and local tumor progression (LTP).

Methods

Pre- and post-MWA computed tomography (CT) images of 50 patients (37-males; 13-females; mean-age 65.9 ± 9.7y, 39 primary and 11 metastasis) were analyzed to evaluate changes in intratumor density. Global, regional, and local scale radiomics features were extracted to assess intratumor density heterogeneity. In four to six weeks, chest enhanced CT was used as the baseline evaluation of treatment response. The correlations between the parametric variation immediately after ablation and the visual score of ablation response (Rvisu) were analyzed by nonparametric Spearman correlation analysis. The 1-year LTP discrimination power was assessed using the area under the receiver operating characteristic (ROC) curves. A Cox proportional hazards regression model was used to identify the independent prognostic features.

Results

Although no significant volume changes were observed after ablation, the radiomics parameters changed in different directions and degrees. The mean intensity value from baseline CT image was 30.3 ± 23.2, and the post-MWA CT image was -60.9 ± 89.8. The ratio of values change was then calculated by a unified formulation. The largest increase (522.3%) was observed for cluster prominence, while the mean CT value showed the largest decline (321.4%). The pulmonary tumors had a mean diameter of 3.4 ± 0.8 cm. Complete ablation was documented in 36 patients. Significant correlations were observed between Rvisu and quantitative features. The highest correlations were observed for changes in local features after MWA, with r ranging from 0.594 to 0.782. LTP developed in 22 patients. The Cox regression model revealed Δcontrast% and response score as independent predictors (Δcontrast%: odds ratio [OR]=5.61, p=0.001; Rvisu: OR=1.73, p=0019). ROC curve analysis showed that Δcontrast% was a better predictor of 1-year LTP. with higher sensitivity (83.5% vs. 71.2%) and specificity (87.1% vs. 76.8%) than those for Rvisu.

Conclusions

The changes in intratumor density heterogeneity after MWA could be characterized by analysis of radiomics features. Real-time density changes could predict treatment response and LTP in patients with pulmonary tumors earlier, especially for tumors with larger diameters.
Intertumoral Heterogeneity of Primary Breast Tumors and Synchronous Axillary Lymph Node Metastases Reflected in IHC-Assessed Expression of Routine and Nonstandard Biomarkers
Authors: Kuncman Wojciech , Orzechowska Magdalena , Kuncman Łukasz , Kordek Radzisław , Taran Katarzyna
Published: November 2021

Breast cancer (BC) remains a significant healthcare challenge. Routinely, the treatment strategy is determined by immunohistochemistry (IHC)-based assessment of the key proteins such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67. However, it is estimated that over 75% of deaths result from metastatic tumors, indicating a need to develop more accurate protocols for intertumoral heterogeneity assessment and their consequences on prognosis. Therefore, the aim of this preliminary study was the identification of the expression profiles of routinely used biomarkers (ER, PR, HER2, Ki-67) and additional relevant proteins [Bcl-2, cyclin D1, E-cadherin, Snail+Slug, gross cystic disease fluid protein 15 (GCDFP-15), programmed death receptor 1 (PD-L1), and phosphatase of regenerating liver 3 (PRL-3)] in breast primary tumors (PTs) and paired synchronous axillary lymph node (ALN) metastases. A total of 67 tissue samples met the inclusion criteria for the study. The expression status of biomarkers was assessed in PTs and ALN metastases using tissue microarrays followed by IHC. In 11 cases, the shift of intrinsic molecular BC subtype was noticed between PTs and paired ALN metastases. Moreover, a significant disproportion in E-cadherin presence (p = 0.0002) was noted in both foci, and the expression status of all proteins except for HER2 demonstrated considerable variance (k = 1, p < 0.0001). Importantly, in around 30% of cases, the ALN metastases demonstrated discordance, i.e., loss/gain of expression, compared to the PTs. Intertumoral synchronous heterogeneity in both foci (primary tumor and node metastasis) is an essential phenomenon affecting the clinical subtype and characteristics of BC. Furthermore, a greater understanding of this event could potentially improve therapeutic efficacy.
Intertumoural Heterogeneity and Branch Evolution of Synchronous Multiple Primary Lung Adenocarcinomas by Next-Generation Sequencing Analysis
Authors: Zhang Qinleng , Jia Hui , Wang Zhendan , Hao Shaoyu , Huang Haiyan , Yang Airong , Han Lu , Song Pingping
Published: November 2021

Objectives

Multiple primary lung cancers (MPLCs) are an increasingly well-known clinical phenomenon, but there is a lack of high-level evidence for their optimal clinical diagnosis and therapeutic approaches. Thus, we analysed genetic variation to determine the intertumoural heterogeneity and branch evolution of synchronous multiple primary lung adenocarcinomas.

Methods

We performed multiplex mutational sequencing on 93 synchronous multiple primary lung adenocarcinoma lesions from 42 patients who underwent surgical resection.

Results

The high discordance rate of mutation was 92.9% (n=39) between tumours in individual patients. EGFR, TP53 and KRAS mutations were detected in 57 (61.3%), 19 (20.4%) and 11 (11.8%) of the 93 tumours, respectively. 16 cases of multiple primary lung adenocarcinomas simultaneously harboured EGFR mutations and TP53 mutations. Matching mutations between paired tumours were observed in 1 (2.4%) patient for P20. The genotypes were all EGFR L858R mutations, but the pathological type of P20T1 was lepidic predominant, and P20T2 was adenocarcinoma in situ. In the phylogenetic tree, genetic variations were divided into trunk, shared and branch subtypes. Branch mutations accounted for 91.09% of variations in sMPLA, while the ratio of trunk (4.95%) and shared (3.96%) variations was significantly lower.

Conclusions

Remarkable intertumoural heterogeneity and frequent branch mutations were found in synchronous multiple primary lung adenocarcinomas.
Distinctive Signaling Profiles With Distinct Biological and Clinical Implications in Aggressive CLL Subsets With Stereotyped B-Cell Receptor Immunoglobulin
Authors: Gerousi Marina , Laidou Stamatia , Gemenetzi Katerina , Stamatopoulos Kostas , Chatzidimitriou Anastasia
Published: November 2021

The ontogeny and evolution of chronic lymphocytic leukemia (CLL) are critically dependent on interactions between leukemic cells and their microenvironment, including antigens, the latter recognized through the clonotypic B-cell receptor immunoglobulin (BcR IG). Antigen selection is key to the pathogenesis of CLL, as evidenced by the remarkable skewing of the BcR IG gene repertoire, culminating in BcR IG stereotypy, referring to the existence of subsets of patients with (quasi)identical BcR IG. Notably, certain of these subsets have been found to display distinct, subset-biased biological background, clinical presentation, and outcome, including the response to treatment. This points to BcR IG centrality while also emphasizing the need to dissect the signaling pathways triggered by the distinctive BcR IG expressed by different subsets, particularly those with aggressive clinical behavior. In this mini-review, we discuss the current knowledge on the implicated signaling pathways as well as the recurrent gene mutations in these pathways that characterize major aggressive stereotyped subsets. Special emphasis is given on the intertwining of BcR IG and Toll-like receptor (TLR) signaling and the molecular characterization of signaling activation, which has revealed novel players implicated in shaping clinical aggressiveness in CLL, e.g., the histone methyltransferase EZH2 and the transcription factor p63.
Adherence to Direct Oral Anticoagulants in Patients With Non-Valvular Atrial Fibrillation: A Cross-National Comparison in Six European Countries (2008–2015)
Authors: Sabaté M. , Vidal X. , Ballarin E. , Rottenkolber M. , Schmiedl S. , Grave B. , Huerta C. , Martin-Merino E. , Montero D. , Leon-Muñoz L. M. , Gasse C. , Moore N. , Droz C. , Lassalle R. , Aakjær M. , Andersen M. , De Bruin M. L. , Souverein P. , Klungel O. H. , Gardarsdottir H. , Ibáñez L.
Published: November 2021

Aims: To describe and compare the adherence to different direct oral anticoagulants (DOACs) in eight European databases representing six countries.

Methods: Longitudinal drug utilization study of new users (≥18 years) of DOACs (dabigatran, rivaroxaban, apixaban) with a diagnosis of non-valvular atrial fibrillation (2008–2015). Adherence was examined by estimating persistence, switching, and discontinuation rates at 12 months. Primary non-adherence was estimated in BIFAP and SIDIAP databases.

Results: The highest persistence rate was seen for apixaban in the CPRD database (81%) and the lowest for dabigatran in the Mondriaan database (22%). The switching rate for all DOACs ranged from 2.4 to 13.1% (Mondriaan and EGB databases, respectively). Dabigatran had the highest switching rate from 5.0 to 20.0% (Mondriaan and EGB databases, respectively). The discontinuation rate for all DOACs ranged from 16.0 to 63.9% (CPRD and Bavarian CD databases, respectively). Dabigatran had the highest rate of discontinuers, except in the Bavarian CD and AOK NORDWEST databases, ranging from 23.2 to 64.6% (CPRD and Mondriaan databases, respectively). Combined primary non-adherence for examined DOACs was 11.1% in BIFAP and 14.0% in SIDIAP. There were differences in population coverage and in the type of drug data source among the databases.

Conclusion: Despite the differences in the characteristics of the databases and in demographic and baseline characteristics of the included population that could explain some of the observed discrepancies, we can observe a similar pattern throughout the databases. Apixaban was the DOAC with the highest persistence. Dabigatran had the highest proportion of discontinuers and switchers at 12 months in most databases (EMA/2015/27/PH).
Evaluation of Efficacy and Safety for Kanglaite Injection in the Control of the Malignant Pleural Effusions via Thoracic Perfusion: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Zhu Guanghui , Wang Xinmiao , Li Jie , Zhang Ying , Gao Ruike , Zhang Xiaoxiao , Xu Bowen , Hu Jiaqi , Dai Minghao , Chen Jiayang
Published: November 2021

Background: Kanglaite injection (KLTI) is a traditional Chinese medicine (TCM) preparation with anti-tumor activity, which has been used to treat malignant tumors in China. The purpose of this study was to evaluate the efficacy and safety of intrapleural infusion with KLTI in the treatment of malignant pleural effusion (MPE).

Methods: Randomized controlled trials (RCTs) on the efficacy and safety of intrathoracic infusion with KLTI in the treatment of MPE were searched from the PubMed, EMBASE, the Cochrane Library, CNKI, VIP, Wanfang and CBM databases. The primary outcome was objective remission rate (ORR). Secondary outcomes included quality of life (QOL) and incidence of adverse events (AEs). The Stata15.1 software and RevMan5.3 software were used to calculate risk ratios (RR) at 95% confidence intervals (CI) and conduct the meta-analysis.

Results: This meta-analysis included 20 RCTs, involving 1,291 patients. The ORR of intrapleural infusion with KLTI + chemotherapy drugs in the treatment of MPE was higher than that of chemotherapy alone (RR) 1.23; 95%CI; 1.11–1.36, I2 = 0%, z = 3.876, p = 0.000]. When KLTI is combined with cisplatin or KLTI 200 ml is used in every time, it is more advantageous to improve ORR. Moreover, compared with intrapleural infusion of chemotherapy drugs alone, KLTI combined with chemotherapy drugs significantly improved the QOL of patients with MPE (RR 1.28; 95%CI; 1.70–1.53, I2 = 0%, z = 2.70, p = 0.007). In addition, the participation of KLTI reduced the gastrointestinal reaction (RR 0.79; 95% CI; 0.66–0.96; I2 = 0%, z = 2.37, p = 0.018) and renal damage (RR 0.468; 95% CI; 0.23–0.945, I2 = 0%, z = 2.11, p = 0.035) caused by chemotherapy drugs, but did not increase other adverse reactions (p > 0.05).

Conclusion: The efficacy and safety of traditional chemotherapy drugs plus KLTI was superior to traditional chemotherapy drugs alone via intrapleural injection in controlling MPE, which suggested that KLTI can be used to treat MPE. However, a more rigorous RCT should be designed and completed before it is widely recommended.
XPC Protein Improves Lung Adenocarcinoma Prognosis by Inhibiting Lung Cancer Cell Stemness
Authors: Wang Weiyu , Ma Shengyao , Ding Zhenyu , Yang Yang , Wang Huaijie , Yang Kunning , Cai Xiaoshan , Li Hanyue , Gao Zhiqin , Qu Meihua
Published: November 2021

Objective: Xeroderma Pigmentosum Complementation Group C (XPC) is a protein involving in nucleotide excision repair (NER). XPC also plays an important role in the lung cancer occurrence with the mechanism remian unclear up to date. Studies showed that the increased stemness of lung cancer cells is related to the recurrence and metastasis of lung cancer. This study aimed to study and analyze the correlation of XPC with lung cancer stem cell biomarkers expression and the overall survival (OS) of lung adenocarcinoma patients.

Methods: 140 cases of clinical lung adenocarcinoma tissue samples and 48 cases of paired paracancerous tissue samples were made into tissue microarray. Immunohistochemistry (IHC) was used to detect the expression of XPC and CD133 in cancer and paracancerous tissues. Semi-quantitative analysis and statistics were performed by Pannoramic Digital Slide Scanner. The expression of XPC and CD133 in fresh tissues was verified by Western blotting assay. siXPC was used to knock down XPC in lung cancer cell lines to study the effect of XPC on the expression of lung cancer stem cell biomarkers and the ability of cell invasion. And shXPC was used to knockdown XPC in A549 and H1650 to study the effect of XPC on the expression of lung cancer stem cell biomarkers.

Results: IHC and Western blotting results showed that XPC expression significantly decreased, while CD133 expression significantly increased in cancer tissues comparing to paracancerous tissues (PXPC < 0.0001, PCD133 = 0.0395). The high level of XPC in cancer was associated with a better prognosis (Log-rank p = 0.0577) in lung adenocarcinoma patients. Downregulation of XPC in lung cancer cells showed increased expression of cancer stem cell biomarkers and the increased cell invasion abilities.

Conclusion: It is suggested that XPC can exert the ability of anti-tumor formation, tumor invasion and metastasis inhibition, and prognostic survival improvement in lung adenocarcinoma patients by regulating the stemness of lung cancer cells.
A Review of the Ethnopharmacology, Phytochemistry, Pharmacology, Application, Quality Control, Processing, Toxicology, and Pharmacokinetics of the Dried Rhizome of Atractylodes macrocephala
Authors: Yang Liu , Yu Huan , Hou Ajiao , Man Wenjing , Wang Song , Zhang Jiaxu , Wang Xuejiao , Zheng Senwang , Jiang Hai , Kuang Haixue
Published: November 2021

The product investigated herein is the dried rhizome ofAtractylodes macrocephalaKoidz. [Asteraceae] (Baizhu), which is also known as Dongbaizhu, Wuzhu, Yuzhu, Zhezhu, and Zhongzhu, among others. It invigorates thespleen, replenishesqi, and removesdampness, diuresis, and hidroschesis, and impacts fetal safety. It is often used for the treatment of diseases such asspleenfunction deficiency, abdominal distension, diarrhea, sputum, vertigo, edema, fever, and sweating and also aids cessation of minimal vaginal bleeding during pregnancy. In this study, research pertaining to the ethnopharmacology, application, phytochemistry, analytical methods, quality control, processing, pharmacology, toxicology, and pharmacokinetics of Baizhu has been reviewed. Relevant information and data reported for Baizhu were collected from CNKI, VIP, PubMed, Web of Science, scientific databases, Chinese Medicinal Material Encyclopedia, Chinese herbal medicine classics, Chinese medicine dictionary, doctoral and master’s theses, and so on. Baizhu demonstrates diuretic, antidiuretic, anti-inflammatory effects and antitumor function and aids regulation of gastrointestinal function, hypoglycemic effect, analgesic action, protection on the liver ischemia-reperfusion injury (IRI) in rats, inhibition of aromatase, treatment of bone disease, strengthening myocardial contraction ability, detoxification and cholagogic effect, fall hematic fat action, such as the treatment of acute renal injury, and so on. It also can be an anticoagulant, improve the nervous system disease, affect the immune system, and regulate uterine smooth muscle, antioxidation, antiaging, and antibacterial effect. Sesquiterpenoids, triterpenoids, polyacetylenes, phenylpropanoids, coumarins, flavonoids, flavonoid glycosides, steroids, benzoquinones, polysaccharides, and other compounds were isolated from Baizhu. Among them, sesquiterpenoids, polysaccharides, and polyacetylenes are the main components of Baizhu. Baizhu exhibits a wide range of pharmacological effects and constitutes a considerable proportion of the composition of many proprietary crude drugs. It mainly affects the endocrine, nervous, and urinary systems. The presented information suggests that we should focus on the development of new drugs related to Baizhu, including specific components, to achieve a greater therapeutic potential that can be considered to further explore the information related to Baizhu.
Prevalence of Antibiotic Purchase Online and Associated Factors Among Chinese Residents: A Nationwide Community Survey of 2019
Authors: Sun Na , Gong Yanhong , Liu Jiaming , Wu Jianxiong , An Rongrong , Dong Yue , Zhu Yi , Mu Ketao , Zhang Guopeng , Yin Xiaoxv
Published: November 2021

Introduction: Online sales of antibiotics have increased public access to these medicines. This study aimed to analyze the online antibiotic purchase behavior of the Chinese residents and identify its associated factors.

Methods: We conducted a nationwide cross-sectional online survey among Chinese community residents from January 20 to February 28, 2019. A structured questionnaire was used to collect data on their sociodemographic characteristics, health-related variables, and the online antibiotic purchase behavior in the past 3 months. Descriptive statistics and logistic regression analyses were used. The statistical analyses were performed using SAS version 9.4 (SAS Institute Inc.).

Results: A total of 101,120 respondents were included in the analysis. The weighted prevalence of antibiotic purchase online was 3.71% (95% CI, 3.53–3.88%). Residents who purchased antibiotics online were more likely to be older (age≥65 years), be a male, live in rural areas, have a higher education level, report an excellent economic status, suffer from chronic diseases, and search for health information on the internet.

Conclusion: Numerous residents had purchased antibiotics online in the past 3 months throughout China. We should pay more attention to this behavior. There is a need to strengthen regulation of antibiotic sales online and improve public education on antibiotic purchase online. More comprehensive information on antibiotic purchase online as well as the advantages and disadvantages of online sales of antibiotics should be investigated in the future studies.
A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives
Authors: Brishty Shejuti Rahman , Hossain Md. Jamal , Khandaker Mayeen Uddin , Faruque Mohammad Rashed Iqbal , Osman Hamid , Rahman S. M. Abdur
Published: November 2021

Nowadays, nitrogenous heterocyclic molecules have attracted a great deal of interest among medicinal chemists. Among these potential heterocyclic drugs, benzimidazole scaffolds are considerably prevalent. Due to their isostructural pharmacophore of naturally occurring active biomolecules, benzimidazole derivatives have significant importance as chemotherapeutic agents in diverse clinical conditions. Researchers have synthesized plenty of benzimidazole derivatives in the last decades, amidst a large share of these compounds exerted excellent bioactivity against many ailments with outstanding bioavailability, safety, and stability profiles. In this comprehensive review, we have summarized the bioactivity of the benzimidazole derivatives reported in recent literature (2012–2021) with their available structure-activity relationship. Compounds bearing benzimidazole nucleus possess broad-spectrum pharmacological properties ranging from common antibacterial effects to the world’s most virulent diseases. Several promising therapeutic candidates are undergoing human trials, and some of these are going to be approved for clinical use. However, notable challenges, such as drug resistance, costly and tedious synthetic methods, little structural information of receptors, lack of advanced software, and so on, are still viable to be overcome for further research.
Pharmacokinetics and Disposition of Heparin-Binding Growth Factor Midkine Antisense Oligonucleotide Nanoliposomes in Experimental Animal Species and Prediction of Human Pharmacokinetics Using a Physiologically Based Pharmacokinetic Model
Authors: Bai Haihong , Cheng Yuanguo , Che Jinjing
Published: November 2021

Encapsulating the antisense oligonucleotide drug MK-ASODN with nanoliposomes greatly improved its potency and targeting to the heparin-binding growth factor midkine. The disposition and pharmacokinetic (PK) parameters of MK-ASODN nanoliposomes were studied in monkeys and rats, and the human PK parameters were predicted based on preclinical data using a physiologically based pharmacokinetic (PBPK) model. Following intravenous injection, the drug plasma concentration rapidly declined in a multiexponential manner, and the drug was rapidly transferred to tissues from the circulation. The terminal t1/2 in plasma was clearly longer than that of the unmodified antisense nucleic acid drug. According to the AUC,MK-ASODN nanoliposomes were mainly distributed in the kidney, spleen, and liver. . MK-ASODN nanoliposomes were highly plasma protein bound, limiting their urinary excretion. Very little MK-ASODN nanoliposomes were detected in urine or feces. The plasma disposition of MK-ASODN nanoliposomes appeared nonlinear over the studied dose range of 11.5–46 mg kg−1. The monkey PBPK model of MK-ASODN nanoliposomes was well established and successfully extrapolated to predict MK-ASODN nanoliposome PK in humans. These disposition and PK data support further development in phase I clinical studies.
Development and Benchmarking of a Monte Carlo Dose Engine for Proton Radiation Therapy
Authors: Lysakovski Peter , Ferrari Alfredo , Tessonnier Thomas , Besuglow Judith , Kopp Benedikt , Mein Stewart , Haberer Thomas , Debus Jürgen , Mairani Andrea
Published: November 2021

Dose calculation algorithms based on Monte Carlo (MC) simulations play a crucial role in radiotherapy. Here, the development and benchmarking of a novel MC dose engine, MonteRay, is presented for proton therapy aiming to support clinical activity at the Heidelberg Ion Beam Therapy center (HIT) and the development of MRI (magnetic resonance imaging)-guided particle therapy. Comparisons against dosimetric data and gold standard MC FLUKA calculations at different levels of complexity, ranging from single pencil beams in water to patient plans, showed high levels of agreement, validating the physical approach implemented in the dose engine. Additionally, MonteRay has been found to match satisfactorily to FLUKA dose predictions in magnetic fields both in homogeneous and heterogeneous scenarios advocating its use for future MRI-guided proton therapy applications. Benchmarked on 150 MeV protons transported on a 2 × 2 × 2 mm3 grid, MonteRay achieved a high computational throughput and was able to simulate the histories of more than 30,000 primary protons per second on a single CPU core.
Exploring Optimality of Piecewise Polynomial Interpolation Functions for Lung Field Modeling in 2D Chest X-Ray Images
Authors: Kumar Rohit , Bhattacharya Subrata , Murmu Govind
Published: November 2021

In this paper, a landmark based approach, using five different interpolating polynomials (linear, cubic convolution, cubic spline, PCHIP, and Makima) for modeling of lung field region in 2D chest X-ray images have been presented. Japanese Society of Radiological Technology (JSRT) database which is publicly available has been used for evaluation of the proposed method. Selected radiographs are anatomically landmarked using 17 and 16 anatomical landmark points to represent left and right lung field regions, respectively. Local, piecewise polynomial interpolation is then employed to create additional semilandmark points to form the lung contour. Jaccard similarity coefficients and Dice coefficients have been used to find accuracy of the modeled shape through comparison with the prepared ground truth. With the optimality condition of three intermediate semilandmark points, PCHIP interpolation method with an execution time of 5.04873 s is found to be the most promising candidate for lung field modeling with an average Dice coefficient (DC) of 98.20 and 98.54% (for the left and right lung field, respectively) and with the average Jaccard similarity coefficient (JSC) of 96.47 and 97.13% for these two lung field regions. While performance of Makima and cubic convolution is close to the PCHIP with the same optimality condition, i.e., three intermediate semilandmark points, the optimality condition for the cubic spline method is of at least seven intermediate semilandmark points which, however, does not result in better performance in terms of accuracy or execution time.
Intrauterine Programming of Cardiovascular Diseases in Maternal Diabetes
Authors: Higa Romina , Leonardi María Laura , Jawerbaum Alicia
Published: November 2021

Maternal diabetes is a prevalent pathology that increases the risk of cardiovascular diseases in the offspring, the heart being one of the main target organs affected from the fetal stage until the adult life. Metabolic, pro-oxidant, and proinflammatory alterations in the fetal heart constitute the first steps in the adverse fetal programming of cardiovascular disease in the context of maternal diabetes. This review discusses both human and experimental studies addressing putative mechanisms involved in this fetal programming of heart damage in maternal diabetes. These include cardiac epigenetic changes, alterations in cardiac carbohydrate and lipid metabolism, damaging effects caused by a pro-oxidant and proinflammatory environment, alterations in the cardiac extracellular matrix remodeling, and specific signaling pathways. Putative actions to prevent cardiovascular impairments in the offspring of mothers with diabetes are also discussed.
The Effect of Law Students in Entrepreneurial Psychology Under the Artificial Intelligence Technology
Authors: Xu Chengjin , Zhang Zhe
Published: November 2021

With the increasingly serious employment situation in China, the government and schools encourage college students to start businesses to alleviate employment pressure. College student's successful entrepreneurship depends on national preferential policies, social support, and, most importantly, their healthy and solid psychological quality and entrepreneurial psychological quality. The purpose is to understand the entrepreneurial psychology of college students and study the entrepreneurial psychological effect. Firstly, the four aspects of entrepreneurial psychology are summarized, including entrepreneurial awareness, entrepreneurial volition, entrepreneurial ability, and entrepreneurial personality. Secondly, the research status of college students' entrepreneurial psychology is reviewed, and the existing problems are pointed out. Thirdly, the combined model of wavelet transform and Neural Network (NN) is proposed, and the feasibility of the proposed model is evaluated through the analysis of college students' entrepreneurial psychology. The wavelet NN is used in experimental design to predict college students' entrepreneurial psychology, and the predicted results are compared with the actual value. From the perspective of the prediction results of entrepreneurial psychology, the combination of wavelet algorithm and neural network is more accurate for entrepreneurial psychology prediction and evaluation results of law students. Overall, the difference between the predicted value and the actual value is within 0.3 points, which is relatively stable. According to the analysis of single-factor results, the scores of students of different majors in the four dimensions of entrepreneurial psychology are all higher than 3.5, but there is no significant difference among the four dimensions (P > 0.05), indicating that the major has no significant impact on entrepreneurial psychology; law students with different educational backgrounds have significant differences in entrepreneurial psychology (P < 0.05), among which students with a master's degree have the strongest entrepreneurial will, while doctoral students have the lowest entrepreneurial will; in terms of entrepreneurial psychological capital, men's self-efficacy is higher than women's, and the difference is significant (P < 0.05). The difference between males and females in the scores of entrepreneurial psychological factors' four aspects is not very obvious. In terms of entrepreneurial psychological capital, males' self-efficacy is significantly higher than females' (P < 0.05). Artificial Intelligence (AI) technology has great application prospects in the prediction and evaluation of college students' entrepreneurial psychology, and college students' entrepreneurial psychology is highly correlated with gender and education.
Children’s Learning of Non-adjacent Dependencies Using a Web-Based Computer Game Setting
Authors: Marimon Mireia , Hofmann Andrea , Veríssimo João , Männel Claudia , Friederici Angela D. , Höhle Barbara , Wartenburger Isabell
Published: November 2021

Infants show impressive speech decoding abilities and detect acoustic regularities that highlight the syntactic relations of a language, often codedvianon-adjacent dependencies (NADs, e.g.,issinging). It has been claimed that infants learn NADs implicitly and associatively through passive listening and that there is a shift from effortless associative learning to a more controlled learning of NADs after the age of 2 years, potentially driven by the maturation of the prefrontal cortex. To investigate if older children are able to learn NADs,Lammertink et al. (2019)recently developed a word-monitoring serial reaction time (SRT) task and could show that 6–11-year-old children learned the NADs, as their reaction times (RTs) increased then they were presented with violated NADs. In the current study we adapted their experimental paradigm and tested NAD learning in a younger group of 52 children between the age of 4–8 years in a remote, web-based, game-like setting (whack-a-mole). Children were exposed to Italian phrases containing NADs and had to monitor the occurrence of a target syllable, which was the second element of the NAD. After exposure, children did a “Stem Completion” task in which they were presented with the first element of the NAD and had to choose the second element of the NAD to complete the stimuli. Our findings show that, despite large variability in the data, children aged 4–8 years are sensitive to NADs; they show the expected differences in r RTs in the SRT task and could transfer the NAD-rule in the Stem Completion task. We discuss these results with respect to the development of NAD dependency learning in childhood and the practical impact and limitations of collecting these data in a web-based setting.