bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Assessment of the Intracranial Vasculature of Infants and Adults Using iCafe (Intracranial Artery Feature Extraction)
Authors: Chen Li , Shaw Dennis W. W. , Dager Stephen R. , Corrigan Neva M. , Chu Baocheng , Kleinhans Natalia M. , Kuhl Patricia K. , Hwang Jenq-Neng , Yuan Chun
Published: May 2021

Comprehensive quantification of intracranial artery features may help to assess and understand regional variations of blood supply during early brain development and aging. We analyzed vasculature features of 27 healthy infants during natural sleep, 13 infants at 7-months (7.3 ± 1.0 month), and 14 infants at 12-months (11.7 ± 0.4 month), and 13 older healthy, awake adults (62.8 ± 8.7 years) to investigate age-related vascular differences as a preliminary study of vascular changes associated with brain development. 3D time-of-flight (TOF) magnetic resonance angiography (MRA) acquisitions were processed in iCafe, a technique to quantify arterial features (http://icafe.clatfd.cn), to characterize intracranial vasculature. Overall, adult subjects were found to have increased ACA length, tortuosity, and vasculature density compared to both 7-month-old and 12-month-old infants, as well as MCA length compared to 7-month-old infants. No brain laterality differences were observed for any vascular measures in either infant or adult age groups. Reduced skull and brain sharpness, indicative of increased head motion and brain/vascular pulsation, respectively, were observed in infants but not correlated with length, tortuosity, or vasculature density measures. Quantitative analysis of TOF MRA using iCafe may provide an objective approach for systematic study of infant brain vascular development and for clinical assessment of adult and pediatric brain vascular diseases.
Increased Postoperative Fasting Glucose Is Associated With Unfavorable Outcomes in Patients Treated With Mechanical Thrombectomy Treatment
Authors: Shi Zongjie , Guo Shunyuan , Pan Jie , Xu Chao , Geng Yu , Zheng Sujie
Published: May 2021

Background and objective: Hyperglycemia on admission was associated with worse clinical outcomes after mechanical thrombectomy (MT) of acute ischemic stroke (AIS). We evaluated whether increased postoperative fasting glucose (PFG) was also related to poor clinical outcomes in patients who underwent MT treatment.

Methods: Consecutive patients with large vessel occlusion underwent MT in our center were included. Admission glucose and fasting glucose levels after MT treatment were evaluated. Primary outcome was 90-day unfavorable outcomes (modified Rankin Scale score of 3–6). Secondary outcome was the rate of symptomatic intracranial hemorrhage (sICH) after MT treatment. The association of PFG and 90-day clinical outcome after MT treatment was determined using logistic regression analyses.

Results: One hundred twenty seven patients were collected. The median postoperative fasting glucose level was 6.27 mmol/L (IQR 5.59–7.62). Fourteen patients (11.02%) had sICH, and fifty-eight patients (45.67%) had unfavorable outcomes at 90-day after MT. After adjustment for potential confounding factors, PFG level was an independent predictor of 90-day unfavorable outcome (OR 1.265; 95% CI 1.017–1.575; p = 0.035) and sICH (OR 1.523; 95% CI 1.056–2.195; p = 0.024) after MT. In addition, older age, higher baseline NIHSS score, and higher postoperative NLR were also associated with unfavorable outcomes at 90-day after MT treatment.

Conclusions: Increased PFG is associated with unfavorable outcomes at 90-day and an increased risk of sICH in patients underwent MT treatment.
Different Functional Network Connectivity Patterns in Epilepsy: A Rest-State fMRI Study on Mesial Temporal Lobe Epilepsy and Benign Epilepsy With Centrotemporal Spike
Authors: Fu Cong , Aisikaer Aikedan , Chen Zhijuan , Yu Qing , Yin Jianzhong , Yang Weidong
Published: May 2021

The stark discrepancy in the prognosis of epilepsy is closely related to brain damage features and underlying mechanisms, which have not yet been unraveled. In this study, differences in the epileptic brain functional connectivity states were explored through a network-based connectivity analysis between intractable mesial temporal lobe epilepsy (MTLE) patients and benign epilepsy with centrotemporal spikes (BECT). Resting state fMRI imaging data were collected for 14 MTLE patients, 12 BECT patients and 16 healthy controls (HCs). Independent component analysis (ICA) was performed to identify the cortical functional networks. Subcortical nuclei of interest were extracted from the Harvard-Oxford probability atlas. Network-based statistics were used to detect functional connectivity (FC) alterations across intranetworks and internetworks, including the connectivity between cortical networks and subcortical nuclei. Compared with HCs, MTLE patients showed significant lower activity between the connectivity of cortical networks and subcortical nuclei (especially hippocampus) and lower internetwork FC involving the lateral temporal lobe; BECT patients showed normal cortical-subcortical FC with hyperconnectivity between cortical networks. Together, cortical-subcortical hypoconnectivity in MTLE suggested a low efficiency and collaborative network pattern, and this might be relevant to the final decompensatory state and the intractable prognosis. Conversely, cortical-subcortical region with normal connectivity remained well in global cooperativity, and compensatory internetwork hyperconnectivity caused by widespread cortical abnormal discharge, which might account for the self-limited clinical outcome in BECT. Based on the fMRI functional network study, different brain network patterns might provide a better explanation of mechanisms in different types of epilepsy.
The Epidemiology of COVID-19 and MS-Related Characteristics in a National Sample of People With MS in China
Authors: Zhang Yao , Yin Hexiang , Xu Yan , Xu Tao , Peng Bin , Cui Liying , Zhang Shuyang
Published: May 2021

Few studies have focused on immune status and disease activity in MS patients during the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to investigate immune status, COVID-19 infection, and attacks in MS patients during the pandemic. An online questionnaire about COVID-19 infection, MS attack, and MS treatment during the pandemic was administered to all 525 MS patients registered in our hospital database from January 1, 2011, to June 1, 2020. Only 384 responded, of which 361 patients could be included in the final analysis. During the pandemic, 42.1% of the 361 patients and 65.0% of the 234 patients on immunotherapies were exposed to teriflunomide. Compared to patients who didn't receive treatment, patients exposed to DMTs had significantly lower levels of neutrophils (P < 0.01) and immunoglobulin G (P < 0.01), and patients exposed to immunosuppressants had significantly lower levels of immunoglobulin G (P < 0.05). Over 80% of our patients followed effective protective measures and none of the 361 MS patients in our cohort contracted COVID-19. Patients whose treatment was disrupted had a significantly higher annualized relapse rate (ARR) during than before the pandemic (P < 0.01), while the ARR of patients with continuous treatment or without treatment remained unchanged. During the pandemic, the risk of MS attack due to treatment disruption possibly outweighs the risk of COVID-19 infection under preventive measures, and MS treatment maintenance might be necessary.
Examining the Relationship Between Speech Perception, Production Distinctness, and Production Variability
Authors: Cheng Hung-Shao , Niziolek Caroline A. , Buchwald Adam , McAllister Tara
Published: May 2021

Several studies have demonstrated that individuals’ ability to perceive a speech sound contrast is related to the production of that contrast in their native language. The theoretical account for this relationship is that speech perception and production have a shared multimodal representation in relevant sensory spaces (e.g., auditory and somatosensory domains). This gives rise to a prediction that individuals with more narrowly defined targets will produce greater separation between contrasting sounds, as well as lower variability in the production of each sound. However, empirical studies that tested this hypothesis, particularly with regard to variability, have reported mixed outcomes. The current study investigates the relationship between perceptual ability and production ability, focusing on the auditory domain. We examined whether individuals’ categorical labeling consistency for the American English /ε/–/æ/ contrast, measured using a perceptual identification task, is related to distance between the centroids of vowel categories in acoustic space (i.e., vowel contrast distance) and to two measures of production variability: the overall distribution of repeated tokens for the vowels (i.e., area of the ellipse) and the proportional within-trial decrease in variability as defined as the magnitude of self-correction to the initial acoustic variation of each token (i.e., centering ratio). No significant associations were found between categorical labeling consistency and vowel contrast distance, between categorical labeling consistency and area of the ellipse, or between categorical labeling consistency and centering ratio. These null results suggest that the perception-production relation may not be as robust as suggested by a widely adopted theoretical framing in terms of the size of auditory target regions. However, the present results may also be attributable to choices in implementation (e.g., the use of model talkers instead of continua derived from the participants’ own productions) that should be subject to further investigation.
A Review of Neurofeedback Training for Improving Sport Performance From the Perspective of User Experience
Authors: Gong Anmin , Gu Feng , Nan Wenya , Qu Yi , Jiang Changhao , Fu Yunfa
Published: May 2021

Neurofeedback training (NFT) is a non-invasive, safe, and effective method of regulating the nerve state of the brain. Presently, NFT is widely used to prevent and rehabilitate brain diseases and improve an individual’s external performance. Among the various NFT methods, NFT to improve sport performance (SP-NFT) has become an important research and application focus worldwide. Several studies have shown that the method is effective in improving brain function and motor control performance. However, appropriate reviews and prospective directions for this technology are lacking. This paper proposes an SP-NFT classification method based on user experience, classifies and discusses various SP-NFT research schemes reported in the existing literature, and reviews the technical principles, application scenarios, and usage characteristics of different SP-NFT schemes. Several key issues in SP-NFT development, including the factors involved in neural mechanisms, scheme selection, learning basis, and experimental implementation, are discussed. Finally, directions for the future development of SP-NFT, including SP-NFT based on other electroencephalograph characteristics, SP-NFT integrated with other technologies, and SP-NFT commercialization, are suggested. These discussions are expected to provide some valuable ideas to researchers in related fields.
Metabolomic Characterization of Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)
Authors: Murgia Federica , Gagliano Antonella , Tanca Marcello G. , Or-Geva Noga , Hendren Aran , Carucci Sara , Pintor Manuela , Cera Francesca , Cossu Fausto , Sotgiu Stefano , Atzori Luigi , Zuddas Alessandro
Published: May 2021

Introduction

PANS is a controversial clinical entity, consisting of a complex constellation of psychiatric symptoms, adventitious changes, and expression of various serological alterations, likely sustained by an autoimmune/inflammatory disease. Detection of novel biomarkers of PANS is highly desirable for both diagnostic and therapeutic management of affected patients. Analysis of metabolites has proven useful in detecting biomarkers for other neuroimmune-psychiatric diseases. Here, we utilize the metabolomics approach to determine whether it is possible to define a specific metabolic pattern in patients affected by PANS compared to healthy subjects.

Design

This observational case-control study tested consecutive patients referred for PANS between June 2019 to May 2020. A PANS diagnosis was confirmed according to the PANS working criteria (National Institute of Mental Health [NIMH], 2010). Healthy age and sex-matched subjects were recruited as controls.

Methods

Thirty-four outpatients referred for PANS (mean age 9.5 years; SD 2.9, 71% male) and 25 neurotypical subjects matched for age and gender, were subjected to metabolite analysis. Serum samples were obtained from each participant and were analyzed using Nuclear Magnetic Resonance (NMR) spectroscopy. Subsequently, multivariate and univariate statistical analyses and Receiver Operator Curves (ROC) were performed.

Results

Separation of the samples, in line with the presence of PANS diagnosis, was observed by applying a supervised model (R2X = 0.44, R2Y = 0.54, Q2 = 0.44, p-value < 0.0001). The significantly altered variables were 2-Hydroxybutyrate, glycine, glutamine, histidine, tryptophan. Pathway analysis indicated that phenylalanine, tyrosine, and tryptophan metabolism, as well as glutamine and glutamate metabolism, exhibited the largest deviations from neurotypical controls.

Conclusion

We found a unique plasma metabolic profile in PANS patients, significantly differing from that of healthy children, that suggests the involvement of specific patterns of neurotransmission (tryptophan, glycine, histamine/histidine) as well as a more general state of neuroinflammation and oxidative stress (glutamine, 2-Hydroxybutyrate, and tryptophan-kynurenine pathway) in the disorder. This metabolomics study offers new insights into biological mechanisms underpinning the disorder and supports research of other potential biomarkers implicated in PANS.
Imaging Time Series of Eye Tracking Data to Classify Attentional States
Authors: Vortmann Lisa-Marie , Knychalla Jannes , Annerer-Walcher Sonja , Benedek Mathias , Putze Felix
Published: May 2021

It has been shown that conclusions about the human mental state can be drawn from eye gaze behavior by several previous studies. For this reason, eye tracking recordings are suitable as input data for attentional state classifiers. In current state-of-the-art studies, the extracted eye tracking feature set usually consists of descriptive statistics about specific eye movement characteristics (i.e., fixations, saccades, blinks, vergence, and pupil dilation). We suggest an Imaging Time Series approach for eye tracking data followed by classification using a convolutional neural net to improve the classification accuracy. We compared multiple algorithms that used the one-dimensional statistical summary feature set as input with two different implementations of the newly suggested method for three different data sets that target different aspects of attention. The results show that our two-dimensional image features with the convolutional neural net outperform the classical classifiers for most analyses, especially regarding generalization over participants and tasks. We conclude that current attentional state classifiers that are based on eye tracking can be optimized by adjusting the feature set while requiring less feature engineering and our future work will focus on a more detailed and suited investigation of this approach for other scenarios and data sets.
A Transfer Model Based on Supervised Multi-Layer Dictionary Learning for Brain Tumor MRI Image Recognition
Authors: Gu Yi , Li Kang
Published: May 2021

Artificial intelligence (AI) is an effective technology for automatic brain tumor MRI image recognition. The training of an AI model requires a large number of labeled data, but medical data needs to be labeled by professional clinicians, which makes data collection complex and expensive. Moreover, a traditional AI model requires that the training data and test data must follow the independent and identically distributed. To solve this problem, we propose a transfer model based on supervised multi-layer dictionary learning (TSMDL) for brain tumor MRI image recognition in this paper. With the help of the knowledge learned from related domains, the goal of this model is to solve the task of transfer learning where the target domain has only a small number of labeled samples. Based on the framework of multi-layer dictionary learning, the proposed model learns the common shared dictionary of source and target domains in each layer to explore the intrinsic connections and shared information between different domains. At the same time, by making full use of the label information of samples, the Laplacian regularization term is introduced to make the dictionary coding of similar samples as close as possible and the dictionary coding of different class samples as different as possible. The recognition experiments on brain MRI image datasets REMBRANDT and Figshare show that the model performs better than competitive state of-the-art methods.
Astroglial Connexins in Neurodegenerative Diseases
Authors: Huang Xiaomin , Su Yixun , Wang Nan , Li Hui , Li Zhigang , Yin Guowei , Chen Hui , Niu Jianqin , Yi Chenju
Published: May 2021

Astrocytes play a crucial role in the maintenance of the normal functions of the Central Nervous System (CNS). During the pathogenesis of neurodegenerative diseases, astrocytes undergo morphological and functional remodeling, a process called reactive astrogliosis, in response to the insults to the CNS. One of the key aspects of the reactive astrocytes is the change in the expression and function of connexins. Connexins are channel proteins that highly expressed in astrocytes, forming gap junction channels and hemichannels, allowing diffusional trafficking of small molecules. Alterations of astrocytic connexin expression and function found in neurodegenerative diseases have been shown to affect the disease progression by changing neuronal function and survival. In this review, we will summarize the role of astroglial connexins in neurodegenerative diseases including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Also, we will discuss why targeting connexins can be a plausible therapeutic strategy to manage these neurodegenerative diseases.
Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13
Authors: Falvella Ana Caroline Brambilla , Smith Bradley Joseph , Silva-Costa Licia C. , Valença Aline G. F. , Crunfli Fernanda , Zuardi Antonio W. , Hallak Jaime E. , Crippa José A. , Almeida Valéria de , Martins-de-Souza Daniel
Published: May 2021

Cannabidiol, a compound of Cannabis sativa, has been proposed as an alternative treatment of schizophrenia. Preclinical and clinical data have suggested that cannabidiol shares more similarity with atypical antipsychotics than typical, both of which are customarily used to manage schizophrenia symptoms. While oligodendrocytes are known to be relevant targets of antipsychotics, the biochemical knowledge in this regard is still limited. Here we evaluated the molecular pathways modulated by cannabidiol compared to the antipsychotics clozapine (atypical) and haloperidol (typical), additionally evaluating the effects of benztropine, a muscarinic receptor antagonist that displays a protective effect in oligodendrocytes and myelination. For this purpose, we employed nano-chromatography coupled with mass spectrometry to investigate the proteomic response to these drugs both in healthy oligodendrocytic cells and in a cuprizone-based toxicity model, using the human oligodendrocyte precursor cell line MO3.13. Cannabidiol shares similarities of biochemical pathways with clozapine and benztropine, in agreement with other studies that indicated an atypical antipsychotic profile. All drugs tested affected metabolic and gene expression pathways and cannabidiol, benztropine, and clozapine modulated cell proliferation and apoptosis when administered after cuprizone-induced toxicity. These general pathways are associated with cuprizone-induced cytotoxicity in MO3.13 cells, indicating a possible proteomic approach when acting against the toxic effects of cuprizone. In conclusion, although modeling oligodendrocytic cytotoxicity with cuprizone does not represent the entirety of the pathophysiology of oligodendrocyte impairments, these results provide insight into the mechanisms associated with the effects of cannabidiol and antipsychotics against cuprizone toxicity, offering new directions of study for myelin-related processes and deficits.
Current Methodological Pitfalls and Caveats in the Assessment of Exercise-Induced Changes in Peripheral Brain-Derived Neurotrophic Factor: How Result Reproducibility Can Be Improved
Authors: Nicolini Chiara , Nelson Aimee J.
Published: May 2021

Neural mechanisms, such as enhanced neuroplasticity within the motor system, underpin exercise-induced motor improvements. Being a key mediator of motor plasticity, brain-derived neurotrophic factor (BDNF) is likely to play an important role in mediating exercise positive effects on motor function. Difficulties in assessing brain BDNF levels in humans have drawn attention to quantification of blood BDNF and raise the question of whether peripheral BDNF contributes to exercise-related motor improvements. Methodological and non-methodological factors influence measurements of blood BDNF introducing a substantial variability that complicates result interpretation and leads to inconsistencies among studies. Here, we discuss methodology-related issues and approaches emerging from current findings to reduce variability and increase result reproducibility.
Hengshun Aromatic Vinegar Ameliorates Vascular Endothelial Injury via Regulating PKCζ-Mediated Oxidative Stress and Apoptosis
Authors: Li Xin , Gao Meng , Zhu Shenghu , Yin Lianhong , Zhang Bao , Qi Yan , Zhao Yanyan , Yu Yongjian , Xu Lina
Published: May 2021

Vascular endothelial injury (VEI) is an early event of atherosclerosis, and reversing endothelial dysfunction has become a new trend in the prevention and treatment of cardiovascular diseases. Hengshun aromatic vinegar (HSAV), a traditional vinegar, has been reported to have many pharmacological activities, but its effect against VEI and the molecular mechanism are still unknown. In this study, effects of HSAV on VEI were evaluated in H2O2-induced human umbilical vein endothelial cells (HUVECs) and methionine-induced VEI in rats. Results showed that HSAV significantly increased cell viability, inhibited apoptosis, and reduced the generation of reactive oxygen species (ROS) in H2O2-induced HUVECs. Meanwhile, HSAV decreased serum homocysteine (Hcy), endothelin 1 (ET-1), and oxidized low-density lipoprotein (ox-LDL) levels, increased nitric oxide (NO) and endothelin nitric oxide synthase (eNOS) levels, ameliorated pathological changes in rats with VEI induced by methionine. In parallel, HSAV relieved oxidative stress by decreasing malondialdehyde (MDA) level and increasing superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) levels in rats with VEI. Mechanism studies indicated that HSAV markedly downregulated the expression of protein kinase C zeta (PKCζ), and consequently regulated sirtuin 1 (Sirt1)-mediated oxidative stress signal pathway, and protein inhibitor of activated STATy (PIASy)-mediated apoptosis pathway, leading to the alleviation of oxidative stress and inhibition of apoptosis. These regulative effects of HSAV were further validated by knockdown and overexpression of PKCζ in vitro. In conclusion, HSAV showed protective effect against VEI by inhibiting PKCζ and, thereby, ameliorating oxidative stress and inhibiting apoptosis. This study not only provides guidance for the consumption of vinegar in daily life but also promotes the development of diet supplement for disease prevention.
Dietary Selenium Intake and Type-2 Diabetes: A Cross-Sectional Population-Based Study on CUME Project
Authors: Dias João Pedro Viana , Costa Sobrinho Paulo de Souza , Pimenta Adriano Marçal , Hermsdorff Helen Hermana Miranda , Bressan Josefina , Nobre Luciana Neri
Published: May 2021

Background and Aim: Previous studies have suggested that the specific association between selenium (Se) and diabetes remains unclear. This study aimed to investigate the association between dietary Se and type-2 diabetes (T2D) in the Brazilian cohort [Cohort of Universities of Minas Gerais (CUME)].

Methods and Results: This cross-sectional study was conducted with a large sample comprising 4,106 participants of the CUME project, a concurrent open cohort restricted to a highly educated population group, composed of graduates of federal institutions of higher education located in the State of Minas Gerais, Brazil. Data on socioeconomic and dietary characteristics, as well as anthropometric measures, were collected from each subject for analysis. The sample was classified into energy-adjusted tertiles of dietary Se intake (μg/day). Differences in the continuous data were evaluated by the Kruskal–Wallis H-test (abnormal data), and the χ2-test assessed differences in qualitative data. As there was no relationship between T2D and Se intake in the bivariate analysis, multivariate analysis was not performed. The prevalence of T2D in the studied population was 2.8%. The mean age was 36 years. Regarding gender, 1,209 are males and 2,807 are females. Among females, the mean Se intake was 165.12 μg/day and the mean intake was 157.4 μg/day. Among males, it was 168.4 μg/day. Significant differences were observed across all Se intake tertiles in terms of age, gender, activity level, alcohol intake, energy intake, sugar, carbohydrates, lipids, fiber, and energy-adjusted meat intake. However, no significant differences were observed across all Se intake tertiles in terms of BMI, smoking status, and T2D. The results indicated that there was no significant association between dietary Se intake and the prevalence of T2D.

Conclusion: Dietary Se intake was not associated with the prevalence of T2D, despite the high intake of this micronutrient in the sample. These results contradict studies that identified the association between Se intake and T2D, with values of Se intake much lower than those observed in this study. Thus, this relationship seems to remain controversial.
A Drug Repositioning Approach Identifies a Combination of Compounds as a Potential Regimen for Chronic Lymphocytic Leukemia Treatment
Authors: Nehdi Atef , Samman Nosaibah , Mashhour Abdullah , Alhallaj Alshaimaa , Trivilegio Thadeo , Gul Sheraz , Reinshagen Jeanette , Alaskar Ahmed , Gmati Gamal , Abuelgasim Khadega A. , Mansour Fatmah , Boudjelal Mohamed
Published: May 2021

Drug repositioning is a promising and powerful innovative strategy in the field of drug discovery. In this study, we screened a compound-library containing 800 Food and Drug Administration approved drugs for their anti-leukemic effect. All screening activities made use of human peripheral blood mononuclear cells (PBMCs), isolated from healthy or leukemic donors. Compounds with confirmed cytotoxicity were selected and classified in three groups: i) anti-neoplastic compounds which are drugs used in leukemia treatment, ii) compounds known to have an anti-cancer effect and iii) compounds demonstrating an anti-leukemic potential for the first time. The latter group was the most interesting from a drug repositioning perspective and yielded a single compound, namely Isoprenaline which is a non-selective β-adrenergic agonist. Analysis of the cytotoxic effect of this drug indicated that it induces sustainable intracellular ATP depletion leading, over time, to necrotic cell death. We exploited the Isoprenaline-induced intracellular ATP depletion to sensitize primary leukemic cells to fludarabine (purine analogue) and Ibrutinib (Bruton’s tyrosine kinase inhibitor) treatment. In-vitro treatment of primary leukemic cells with a combination of Isoprenaline/fludarabine or Isoprenaline/Ibrutinib showed a very high synergistic effect. These combinations could constitute a new efficient regimen for CLL treatment following successful evaluation in animal models and clinical trials.
TPX2 Enhanced the Activation of the HGF/ETS-1 Pathway and Increased the Invasion of Endocrine-Independent Prostate Carcinoma Cells
Authors: Zhou Hongqing , Liu Mingsheng , Shao Tao , Xie Pingbo , Zhu Shaojie , Wang Wei , Miao Qiong , Peng Jiaxi , Zhang Peng
Published: May 2021

The prognosis for endocrine-independent prostate carcinoma is still poor due to its highly metastatic feature. In the present work, TPX2 (the targeting protein for Xklp2), which is known as a micro-tubulin interacted protein, was identified as a novel coactivator of ETS-1, a transcription factor that plays a central role in mediating the metastasis of human malignancies. TPX2 enhanced the transcription factor activation of ETS-1 and increased the expression of ETS-1’s downstream metastasis-related genes, such as mmp3 or mmp9, induced by HGF (hepatocyte growth factor), a typical agonist of the HGF/c-MET/ETS-1 pathway. The protein-interaction between TPX2 and ETS-1 was examined using immunoprecipitation (IP). TPX2 enhanced the accumulation of ETS-1 in the nuclear and the recruitment of its binding element (EST binding site, EBS) located in the promoter region of its downstream gene, mmp9. Moreover, TPX2 enhanced the in vitro or in vivo invasion of a typical endocrine-independent prostate carcinoma cell line, PC-3. Therefore, TPX2 enhanced the activation of the HGF/ETS-1 pathway to enhance the invasion of endocrine-independent prostate carcinoma cells and thus it would be a promising target for prostate carcinoma treatment.
Image-Guided Robotic Radiosurgery for the Treatment of Same Site Spinal Metastasis Recurrences
Authors: Ehret Felix , Mose Lucas , Kufeld Markus , Fürweger Christoph , Windisch Paul , Haidenberger Alfred , Schichor Christian , Tonn Jörg-Christian , Muacevic Alexander
Published: May 2021

Background

Due to recent medical advancements, patients suffering from metastatic spinal disease have a prolonged life expectancy than several decades ago, and some will eventually experience relapses. Data for the retreatment of spinal metastasis recurrences occurring at the very same macroscopic spot as the initially treated lesion are limited. Previous studies mainly included recurrences in the boundary areas as well as other macroscopic parts of the initially affected vertebrae. This study exclusively analyzes the efficacy and safety of spinal reirradiation for recurrences on the same site utilizing single-session robotic radiosurgery.

Materials and Methods

Patients between 2005 and 2020 who received radiotherapy for a spinal metastasis suffering from a local recurrence were eligible for analysis. Only patients undergoing a single-session reirradiation were included. All recurrences must have been occurred in the same location as the initial lesion. This was defined as a macroscopic recurrence on computed tomography occurring at the same site as the initial spinal metastasis. All other lesions, including those in the boundary areas or other parts of the initially affected vertebrae, were excluded.

Results

Fifty-three patients with fifty-three lesions were retreated for spinal metastases. The median dose and number of fractions for the initial radiotherapy were 36 Gy and 15, respectively. Eleven patients were initially treated with stereotactic body radiotherapy. Retreatment was performed with a median dose of 18 Gy prescribed to a median isodose of 70%. The local control was 77% after a median follow-up of 22.2 months. Patients experiencing a second recurrence received a lower dose (p = 0.04), mostly below 18 Gy, and had a worse coverage (p = 0.01) than those showing local tumor control. 51% of patients experienced an improvement in pain control after treatment delivery. Besides, four vertebral compression fractures (7% of patients) but no other adverse events higher than grade 2 were observed.

Conclusion

Single-session robotic radiosurgery appears to be a safe, time-saving, and effective treatment modality for spinal metastasis recurrences occurring in the same initial location if a considerable dose and coverage can be applied. Treatment results are comparable to reirradiated metastases in the boundary areas.
LINC00467 Promotes Tumor Progression via Regulation of the NF-kb Signal Axis in Bladder Cancer
Authors: Xiao Jiawei , Gong Lian , Xiao Mengqing , He Dong , Xiang Liang , Wang Zhanwang , Cheng Yaxin , Deng Liping , Cao Ke
Published: May 2021

Purpose

Long non-coding RNAs (lncRNAs) play an important role in the occurrence and development of bladder cancer, but the underlying molecular mechanisms remain largely unknown. In this study, we found that LINC00467 was significantly highly expressed in bladder cancer through bioinformatic analysis. The present study aimed to explore the role of LINC00467 in bladder cancer and its possible underlying molecular mechanisms.

Methods

The expression of LINC00467 was obtained from GEO (GSE31189), the TCGA database, and qRT-PCR. The role of LINC00467 in bladder cancer was assessed both in vitro and in vivo. RIP, RNA pulldown, and CO-IP were used to demonstrate the potential mechanism by which LINC00467 regulates the progression of bladder cancer.

Results

Through the analysis of GEO (GSE133624) and the TCGA database, it was found that LINC00467 was highly expressed in bladder cancer tissues and that the expression of LINC00467 was significantly negatively correlated with patient prognosis. Cell and animal experiments suggest that LINC00467 promotes the proliferation and invasion of bladder cancer cells. On the one hand, LINC00467 can directly bind to NF-kb-p65 mRNA to stabilize its expression. On the other hand, LINC00467 can directly bind to NF-kb-p65 to promote its translocation into the nucleus to activate the NF-κB signaling pathway, which promotes the progression of bladder cancer.

Conclusions

LINC00467 is highly expressed in bladder cancer and can promote the progression of bladder cancer by regulating the NF-κB signaling pathway. Therefore, targeting LINC00467 is very likely to provide a new strategy for the treatment of bladder cancer and for improving patient prognosis.
Derivation and Validation of a Prognostic Scoring Model Based on Clinical and Pathological Features for Risk Stratification in Oral Squamous Cell Carcinoma Patients: A Retrospective Multicenter Study
Authors: Zhou Jiaying , Li Huan , Cheng Bin , Cao Ruoyan , Zou Fengyuan , Yang Dong , Liu Xiang , Song Ming , Wu Tong
Published: May 2021

Objective

To develop and validate a simple-to-use prognostic scoring model based on clinical and pathological features which can predict overall survival (OS) of patients with oral squamous cell carcinoma (OSCC) and facilitate personalized treatment planning.

Materials and Methods

OSCC patients (n = 404) from a public hospital were divided into a training cohort (n = 282) and an internal validation cohort (n = 122). A total of 12 clinical and pathological features were included in Kaplan–Meier analysis to identify the factors associated with OS. Multivariable Cox proportional hazards regression analysis was performed to further identify important variables and establish prognostic models. Nomogram was generated to predict the individual’s 1-, 3- and 5-year OS rates. The performance of the prognostic scoring model was compared with that of the pathological one and the AJCC TNM staging system by the receiver operating characteristic curve (ROC), concordance index (C-index), calibration curve, and decision curve analysis (DCA). Patients were classified into high- and low-risk groups according to the risk scores of the nomogram. The nomogram-illustrated model was independently tested in an external validation cohort of 95 patients.

Results

Four significant variables (physical examination-tumor size, imaging examination-tumor size, pathological nodal involvement stage, and histologic grade) were included into the nomogram-illustrated model (clinical–pathological model). The area under the ROC curve (AUC) of the clinical–pathological model was 0.687, 0.719, and 0.722 for 1-, 3- and 5-year survival, respectively, which was superior to that of the pathological model (AUC = 0.649, 0.707, 0.717, respectively) and AJCC TNM staging system (AUC = 0.628, 0.668, 0.677, respectively). The clinical–pathological model exhibited improved discriminative power compared with pathological model and AJCC TNM staging system (C-index = 0.755, 0.702, 0.642, respectively) in the external validation cohort. The calibration curves and DCA also displayed excellent predictive performances.

Conclusion

This clinical and pathological feature based prognostic scoring model showed better predictive ability compared with the pathological one, which would be a useful tool of personalized accurate risk stratification and precision therapy planning for OSCC patients.
Angiogenesis Inhibitors in Small Cell Lung Cancer
Authors: Montanino Agnese , Manzo Anna , Carillio Guido , Palumbo Giuliano , Esposito Giovanna , Sforza Vincenzo , Costanzo Raffaele , Sandomenico Claudia , Botti Gerardo , Piccirillo Maria C. , Cascetta Priscilla , Pascarella Giacomo , La Manna Carmine , Normanno Nicola , Morabito Alessandro
Published: May 2021

Inhibition of angiogenesis has been demonstrated to be an efficacious strategy in treating several tumors. Vascular endothelial growth factor (VEGF) is the most important protein with proangiogenic functions and it is overexpressed in small cell lung cancer (SCLC). Bevacizumab, a monoclonal antibody directed against VEGF, showed a promising activity in combination with etoposide and cisplatin as first-line treatment of patients with extended stage (ES)-SCLC and two randomized studies confirmed that bevacizumab improved PFS, but failed to prolong OS. Instead, disappointing results have been observed with endostar, sunitinib, sorafenib, vandetanib, and thalidomide in combination with chemotherapy in the first-line setting, with sunitinib in the maintenance setting, with sunitinib, cediranib and nintedanib as single agents or ziv-aflibercept in combination with topotecan in second-line setting. Only anlotinib improved OS and PFS as third-line therapy in Chinese patients with SCLC, and it was approved with this indication in China. Future challenges are the evaluation of the role of angiogenesis inhibitors in combination with immune- checkpoint inhibitors and chemotherapy in SCLC patients and the identification of predictive biomarkers of response to both agents.
The Impact of VEGF Inhibition on Clinical Outcomes in Patients With Advanced Non-Small Cell Lung Cancer Treated With Immunotherapy: A Retrospective Cohort Study
Authors: Tanimura Keiko , Yamada Tadaaki , Omura Ayaka , Shiotsu Shinsuke , Kataoka Nobutaka , Takeda Takayuki , Taniguchi Ryusuke , Yamada Takahiro , Takeuchi Mayumi , Chihara Yusuke , Morimoto Yoshie , Iwasaku Masahiro , Kaneko Yoshiko , Uchino Junji , Takayama Koichi
Published: May 2021

Background

In recent years, immune checkpoint inhibitors (ICIs) in combination with chemotherapy have increased survival in patients with advanced non-small cell lung cancer (NSCLC). Vascular endothelial growth factor (VEGF), which plays a key role in tumor angiogenesis, is an immunological modulator; therefore, it is expected that anti-VEGF therapy in combination with ICIs enhances the antitumor effect of ICIs. In the present study, we investigated the impact of VEGF inhibition on clinical outcomes of NSCLC patients, including the efficacy of ICI treatment.

Methods

A total of 105 patients with advanced NSCLC who had been treated with ICIs were retrospectively analyzed to examine the relationship between the history of treatment with anti-VEGF agents and the clinical outcomes with ICI monotherapy.

Results

Patients who had received anti-VEGF therapy prior to ICIs showed shortened progression-free survival of ICI treatment and a decreased overall response rate to ICI treatment. By contrast, anti-VEGF therapy after ICI treatment was associated with increased survival, especially in patients who had also received anti-VEGF therapy prior to ICI therapy.

Conclusions

These retrospective observations suggest that anti-VEGF therapy prior to ICIs might be a negative predictor of response to ICIs. The sequence of anti-VEGF therapy might play a role in its ability to predict survival in NSCLC patients. Further investigation is warranted to identify the role of VEGF inhibition in altering clinical outcomes after immunotherapy.
Current and Future Role of Medical Imaging in Guiding the Management of Patients With Relapsed and Refractory Non-Hodgkin Lymphoma Treated With CAR T-Cell Therapy
Authors: Vercellino Laetitia , de Jong Dorine , di Blasi Roberta , Kanoun Salim , Reshef Ran , Schwartz Lawrence H. , Dercle Laurent
Published: May 2021

Chimeric antigen receptor (CAR) T-cells are a novel immunotherapy available for patients with refractory/relapsed non-Hodgkin lymphoma. In this indication, clinical trials have demonstrated that CAR T-cells achieve high rates of response, complete response, and long-term response (up to 80%, 60%, and 40%, respectively). Nonetheless, the majority of patients ultimately relapsed. This review provides an overview about the current and future role of medical imaging in guiding the management of non-Hodgkin lymphoma patients treated with CAR T-cells. It discusses the value of predictive and prognostic biomarkers to better stratify the risk of relapse, and provide a patient-tailored therapeutic strategy. At baseline, high tumor volume (assessed on CT-scan or on [18F]-FDG PET/CT) is a prognostic factor associated with treatment failure. Response assessment has not been studied extensively yet. Available data suggests that current response assessment developed on CT-scan or on [18F]-FDG PET/CT for cytotoxic systemic therapies remains relevant to estimate lymphoma response to CAR T-cell therapy. Nonetheless, atypical patterns of response and progression have been observed and should be further analyzed. The potential advantages as well as limitations of artificial intelligence and radiomics as tools providing high throughput quantitative imaging features is described.
Pomalidomide and Dexamethasone Are Effective in Relapsed or Refractory Multiple Myeloma in a Real-Life Setting: A Multicenter Retrospective Study in Taiwan
Authors: Hung Yu-Chin , Gau Jyh-Pyng , Huang Shang-Yi , Ko Bor-Sheng , Teng Chieh-Lin Jerry
Published: May 2021

Background

The therapeutic options of relapsed or refractory multiple myeloma (RRMM) remain a challenge. The MM-003 trial demonstrated that RRMM patients treated with pomalidomide and dexamethasone (Pom/Dex) have better progression-free survival (PFS) than those treated with high-dose dexamethasone alone. However, the real-world effectiveness of Pom/Dex in these patients in Taiwan remains unclear.

Methods

This multicenter, registry-based study retrospectively reviewed the medical records of 49 consecutive patients undergoing Pom/Dex treatment for RRMM. We investigated the overall response rate (ORR) and PFS in these patients. The patients were stratified into two groups: those who received two (n=33) and those who received more than two (n=16) prior lines of treatment according to the numbers of regimens before Pom/Dex therapy. The differences in ORR and PFS between these two groups were further analyzed. We also analyzed factors attributed to disease progression.

Results

The ORR was 47.7%, and the median PFS was 4.0 months (range, 0.1−21.1). Patients who received two prior lines of treatment had a higher ORR than those who received more than two prior lines of treatment (55.2% vs. 33.3%; p=0.045). The median PFS of these groups was 4.8 and 3.9 months, respectively (p=0.805). Primary lenalidomide refractoriness reduced the risk of myeloma progression following Pom/Dex treatment (hazard ratio, 0.14; p=0.001).

Conclusions

The median PFS following Pom/Dex treatment in Taiwanese RRMM patients in a real-world setting was similar to that reported by the MM-003 trial. Primary lenalidomide refractoriness should not be an obstacle for Pom/Dex treatment in RRMM.
Ultrasonic Features of Uncommon Congenital Heterotopic Colon and Pancreas in the Neck: An Extremely Rare Case Report
Authors: Wei Yingli , Pan Zhihao , Kang Xiaoling , Huang Cuiqing , Chen Dan
Published: May 2021

Congenital heterotopic colon and pancreas localized to the neck has not been reported. Herein, we describe an extremely uncommon case of congenital heterotopic colon and pancreas aberrantly presented within a cyst on the neck, and the thickened wall of the cyst on ultrasound may represent an important ultrasonic feature.
Comparison of Peak Oxygen Consumption During Exercise Testing Between Sexes Among Children and Adolescents in Taiwan
Authors: Tuan Sheng-Hui , Chen Guan-Bo , Chen Chia-Hsin , Chen Yi-Jen , Liou I-Hsiu , Su Yen-Tung , Lin Ko-Long
Published: May 2021

Objective: Studies among Western children have observed that the peak oxygen consumption (peak V˙O2) of boys is higher than that of girls, and this difference increases as children progress through adolescence. However, the maturation process and social expectation toward Eastern boys and girls are much different from their Western counterparts. This study aimed to provide baseline information on cardiopulmonary fitness (CRF) of Taiwanese children and adolescents in relation to age and sex. We also evaluated the correlation between body mass and CRF and compared the CRF between non-obese and overweight/obese children.

Methods: We conducted a retrospective study of children and adolescents aged 4–18 years in Taiwan. Participants were classified into four groups based on age (group 1, aged 4–6; group 2, aged 7–9; group 3, aged 10–13; and group 4, aged 14–18 years). All participants completed symptom-limited exercise test by treadmill and anthropometric measurements through bioelectrical impedance method.

Results: In total, 897 (448 men, 449 women) participants were analyzed. Boys had higher peak V˙O2 (all p < 0.01) and peak metabolic equivalent (MET, all p < 0.05) than girls in all the four groups. Age significantly (P < 0.001) correlated with peak V˙O2 in all participants, boys, and girls, with coefficients of determination (R2) of 0.9349, 0.9433, and 0.9085, respectively. The peak V˙O2 (all p < 0.001) of all the groups and peak MET (all p < 0.05) of group 2–4 associated with BMI and FMI modestly to moderately. Non-obese children had higher peak MET in group 1 (p = 0.049) and group 2–4 (all p < 0.001) than overweight/obese children significantly.

Conclusions: The difference in peak V˙O2 and anthropometry–body composition between sexes was observed earlier in children in Taiwan than those in Western countries. Non-obese children had better CRF than overweight/obese children and the difference presented since preschool age.