bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic Ability of Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Prostate Cancer and Clinically Significant Prostate Cancer in Equivocal Lesions: A Systematic Review and Meta-Analysis
Authors: Zeng Jing , Cheng Qingqing , Zhang Dong , Fan Meng , Shi Changzheng , Luo Liangping 
Published: February 2021

BackgroundDynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) now has been used to diagnose prostate cancer (PCa). Equivocal lesions are defined as PIRADS category 3 or a Likert scale of 1 to 5 category 3 lesions. Currently, there are no clear recommendations for the management of these lesions. This study aimed to estimate the diagnostic capacity of DCE-MRI for PCa and clinically significant prostate cancer (csPCa) in equivocal lesions.Materials and methodsTwo researchers searched PubMed, Embase and Web of Science to identify studies that met our subject. We searched for articles that mention the accuracy of the diagnosis of DCE-MRI for PCa or csPCa in equivocal lesions and used histopathological results as the reference standard. We used a tool (the Quality Assessment of Diagnostic Accuracy Studies-2 tool) to evaluate the quality of the studies that we screened out. Meta-regression was used to explore the reasons for heterogeneity in results.ResultsTen articles were eventually included in our study. The sensitivity, specificity and 95% confidence intervals (CI) for DCE-MRI in diagnosing csPCa were 0.67 (95% CI, 0.56–0.76), 0.58 (95% CI, 0.46–0.68). The sensitivity and specificity and 95% CI for DCE-MRI in diagnosing PCa were 0.57 (95% CI, 0.46–0.68), 0.58 (95% CI, 0.45–0.70). The areas under the curve (AUC) of DCE-MRI were 0.67 (95% CI, 0.63–0.71) and 0.60 (95% CI, 0.55–0.64) while diagnosing csPCa and PCa. Through meta-regression, we found that study design, magnetic field strength, the definition of csPCa, and the scoring system were the sources of heterogeneity.ConclusionThe results of our study indicate that the role of DCE-MRI in equivocal lesions may be limited.
Prostate-Specific Membrane Antigen Uptake and Survival in Metastatic Castration-Resistant Prostate Cancer
Authors: Vlachostergios Panagiotis J. , Niaz Muhammad Junaid , Sun Michael , Mosallaie Seyed Ali , Thomas Charlene , Christos Paul J. , Osborne Joseph R. , Molina Ana M. , Nanus David M. , Bander Neil H. , Tagawa Scott T. 
Published: February 2021

BackgroundProstate-specific membrane antigen (PSMA) imaging has been suggested as highly sensitive modality for detection of metastases in patients with biochemically recurrent or advanced prostate cancer (PCa). PSMA expression is associated with grade and stage and has a relationship with androgen receptor signaling. The aim of this study was to evaluate the prognostic utility of radiographic PSMA expression in men with metastatic castration-resistant prostate cancer (mCRPC).MethodsPatients with mCRPC and available baseline PSMA imaging were studied. Images by planar/single-photon emission computed tomography (SPECT) or positron emission tomography (PET)/CT were reviewed. Planar/SPECT images were scored semi-quantitatively and PET/CT scored quantitatively with comparison of tumor uptake to liver uptake on a scale of 0–4 in order to determine an imaging score (IS). The IS (high: 2–4 versus low: 0–1), subsequent receipt of life-prolonging systemic therapies (taxane chemotherapy, potent androgen receptor pathway inhibitors, sipuleucel-T, and radium-223), and the CALGB prognostic risk stratification of patients were analyzed according to overall survival (OS) in univariate and multivariate Cox’s proportional hazards models.ResultsHigh PSMA expression (IS 2–4) was found in 179 (75.21%) patients, and 59 (24.79%) patients had low PSMA uptake. The median OS of the entire cohort was 16.8 (95%CI: 14.9–19.3) months. Patients with a high IS had a significantly shorter OS of 15.8 (95%CI 13.0–18.1) months compared to those with low expression [22.7 (95%CI: 17.7–30.7) months, p = 0.002]. After accounting for use of life-prolonging therapies (p&lt;0.001) and CALGB prognostic groups (p = 0.001), high PSMA IS emerged as an independent prognostic factor for OS [HR(95%CI): 1.7 (1.2–2.2); p = 0.003].ConclusionPresence of high radiographic PSMA expression on SPECT or PET/CT may portend a poor prognosis in patients with mCRPC treated with standard systemic therapies. This provides implications for therapeutic targeting of PSMA-avid disease as a means to improve outcomes.
Sex Differences in Time to Treat and Outcomes for Gliomas
Authors: Stabellini Nickolas , Krebs Halle , Patil Nirav , Waite Kristin , Barnholtz-Sloan Jill S. 
Published: February 2021

BackgroundGliomas are the most common type of primary malignant brain tumor in adults, representing one third of all primary and central nervous system (CNS) tumors and 80% of malignant tumors diagnosed in the Western world. Epidemiological data indicate that the overall incidence and mortality of cancer is higher in males, while females have a better prognosis. The goal of this study is to determine whether there are sex differences in the time to treat and clinical outcomes in patients with gliomaMethodsGlioblastoma (GB) and Lower Grade Glioma (LGG) patients were defined per the Central Brain Tumor Registry of the United States (CBTRUS) from the National Cancer Database (NCDB) for diagnosis years 2004 to 2016. Associations between sex and time to treatment variables as well as associations between sex and multiple clinical outcomes were assessed using univariable and multivariable models.ResultsA total of 176,100 patients were used for analysis (124,502 GBM and 51,598 LGG). Males had a statistically significant association with &gt;7 days to surgery (OR = 1.09, CI 1.05–1.13, p &lt; 0.001) but this association was not observed in the multivariable model (OR = 1.05, CI 0.96–1.16, p = 0.25). After adjustment for key variables including time to treat variables, males with GB and LGG had a higher risk of death (HR = 1.11, CI 1.09–1.13, p &lt; 0.001, HR = 1.09, CI 1.03–1.15, p &lt; 0.001; respectfully). Sex differences in 90-day mortality for GBM were not found after adjustment (OR for males = 0.99, CI 0.91–1.08, p = 0.93). For LGG, both the univariable and multivariable logistic regression models showed no sex differences in 90-day mortality (OR for males = 1.03, CI 0.94–1.12, p = 0.45; multivariable OR for males = 0.81, CI 0.62–1.06, p = 0.13).ConclusionsBased on NCDB data, there were no statistically significant differences in time to treatment between males and females, however males had a higher proportion of GB and LGG as well as a higher risk of death compared to females.
Case Report: De novo Variants of KMT2E Cause O'Donnell-Luria-Rodan Syndrome: Additional Cases and Literature Review
Authors: Li Yang , Fan Lijuan , Luo Rong , Yang Zuozhen , Yuan Meng , Zhang Jinxiu , Gan Jing 
Published: February 2021

Introduction: O'Donnell-Luria-Rodan syndrome was recently identified as an autosomal dominant systemic disorder caused by variants in KMT2E. It is characterized by global developmental delay, some patients also exhibit autism, seizures, hypotonia, and/or feeding difficulties.Methods: Whole-exome sequencing of family trios were performed for two independent children with unexplained recurrent seizures and developmental delay. Both cases were identified as having de novo variants in KMT2E. We also collected and summarized the clinical data and diagnosed them with O'Donnell-Luria-Rodan syndrome. Structural-prediction programs were used to draw the variants' locations.Results: A 186 G&gt;A synonymous variant [NM_182931.3:exon4: c.186G&gt;A (p.Ala62=)] was found in one family, resulting in alternative splicing acid. A 5417 C&gt;T transition variant [NM_182931.3:exon27: c.5417C&gt;T (p.Pro1806Leu)] was found in another family, resulting in 1806 Pro-to-Leu substitution. Both variants were classified as likely pathogenic according to the ACMG (American College of Medical Genetics and Genomics) guidelines and verified by Sanger sequencing.Conclusion: To date, three studies of O'Donnell-Luria-Rodan syndrome have been reported with heterogeneous clinical manifestations. As a newly recognized inherited systemic disorder, O'Donnell-Luria-Rodan syndrome needs to be paid more attention, especially in gene testing.
Potential Natural Products Against Respiratory Viruses: A Perspective to Develop Anti-COVID-19 Medicines
Authors: Omrani Marzieh , Keshavarz Mohsen , Nejad Ebrahimi Samad , Mehrabi Meysam , McGaw Lyndy J. , Ali Abdalla Muna , Mehrbod Parvaneh 
Published: February 2021

The emergence of viral pneumonia caused by a novel coronavirus (CoV), known as the 2019 novel coronavirus (2019-nCoV), resulted in a contagious acute respiratory infectious disease in December 2019 in Wuhan, Hubei Province, China. Its alarmingly quick transmission to many countries across the world and a considerable percentage of morbidity and mortality made the World Health Organization recognize it as a pandemic on March 11, 2020. The perceived risk of infection has led many research groups to study COVID-19 from different aspects. In this literature review, the phylogenetics and taxonomy of COVID-19 coronavirus, epidemiology, and respiratory viruses similar to COVID-19 and their mode of action are documented in an approach to understand the behavior of the current virus. Moreover, we suggest targeting the receptors of SARS-CoV and SARS-CoV-2 such as ACE2 and other proteins including 3CLpro and PLpro for improving antiviral activity and immune response against COVID-19 disease. Additionally, since phytochemicals play an essential role in complementary therapies for viral infections, we summarized different bioactive natural products against the mentioned respiratory viruses with a focus on influenza A, SARS-CoV, MERS, and COVID-19.Based on current literature, 130 compounds have antiviral potential, and of these, 94 metabolites demonstrated bioactivity against coronaviruses. Interestingly, these are classified in different groups of natural products, including alkaloids, flavonoids, terpenoids, and others. Most of these compounds comprise flavonoid skeletons. Based on our survey, xanthoangelol E (88), isolated fromAngelica keiskei(Miq.) Koidz showed inhibitory activity against SARS-CoV PLpro with the best IC50value of 1.2 μM. Additionally, hispidulin (3), quercetin (6), rutin (8), saikosaponin D (36), glycyrrhizin (47), and hesperetin (55) had remarkable antiviral potential against different viral infections. Among these compounds, quercetin (6) exhibited antiviral activities against influenza A, SARS-CoV, and COVID-19 and this seems to be a highly promising compound. In addition, our report discusses the obstacles and future perspectives to highlight the importance of developing screening programs to investigate potential natural medicines against COVID-19.
Fuyuan Xingnao Decoction Promotes Angiogenesis Through the Rab1/AT1R Pathway in Diabetes Mellitus Complicated With Cerebral Infarction
Authors: Deng Dong , Qu Yao , Sun Lihua , Jia Liyang , Bu Jianhong , Ye Miaoqing , Chen Zhenyi , Geng Yun , Zhou Shuang , Fang Bangjiang 
Published: February 2021

Fuyuan Xingnao decoction (FYXN), a traditional Chinese formula comprised of seven herbs, has been utilized to treat diabetes mellitus complicated with cerebral infarction (DMCI) for years. Yet, its protective and regulatory mechanism is poorly understood. The aim of the study is to investigate the effects of FYXN on DMCI in vitro and in vivo, as well as its mechanism in angiogenesis. For in vivo experiments, FYXN was administered to DMCI rats with streptozotocin (STZ) injection-induced diabetes. Then middle cerebral artery occlusion (MCAO) was conducted and the cerebral cortex sections of the rats were obtained. The ultrastructure of cerebral microvessels and new vessel density of ischemic penumbra were evaluated by the transmission electron microscopy (TEM) assay and immunohistochemistry, respectively. Protein and mRNA expression levels of Rab1/AT1R in cortex were assayed by Western blotting and real-time fluorescence quantitative real-time polymerase chain reaction (RT-qPCR). In vitro, FYXN serum was produced in rats on the fourth day 2 h after the last FYXN administration. Green fluorescence was observed after transfection with lentivirus packaged Rab1-WT or siRNA for 24 h. The activity of brain microvascular endothelial cells (BMECs) treated with sera from these rats was tested by MTT assay and Transwell assays, respectively. The expression of AT1R on the cell membrane and endoplasmic reticulum of BMECs was evaluated by immunofluorescence staining. Protein expression levels of signaling molecules in the Rab1/AT1R pathways were also detected. Results showed that in vivo, FYXN treatment significantly intensified CD31 staining in the cortical areas and enhanced the mRNA and protein levels of AT1R, Ang II, Rab1a, Rab1b and VEGF expression in ischemic cerebral cortex tissues. In vitro, the expression levels of AT1R, Ang II, Rab1a, Rab1b and VEGF in the cerebral infarction model group were significantly higher than those in the control group, with further increases after administration of FYXN drug serum. FYXN promoted the proliferation and migration of BMECs by activating the Rab1/AT1R signaling pathway. In conclusion, FYXN exerts a protective effect against DMCI by promoting angiogenesis via the Rab1/AT1R pathway, which provides strong evidence for the therapeutic effect of FYXN on DMCI.
Associations Between Using Chinese Herbal Medicine and Long-Term Outcome Among Pre-dialysis Diabetic Nephropathy Patients: A Retrospective Population-Based Cohort Study
Authors: Guo Jenny Chun-Ling , Pan Heng-Chih , Yeh Bo-Yan , Lu Yen Chu , Chen Jiun-Liang , Yang Ching-Wei , Chen Yu-Chun , Lin Yi-Hsuan , Chen Hsing-Yu 
Published: February 2021

Background: Chronic kidney disease (CKD) has become a worldwide burden due to the high co-morbidity and mortality. Diabetic nephropathy (DN) is one of the leading causes of CKD, and pre-dialysis is one of the most critical stages before the end-stage renal disease (ESRD). Although Chinese herbal medicine (CHM) use is not uncommon, the feasibility of using CHM among pre-dialysis DN patients remains unclear.Materials and methods: We analyzed a population-based cohort, retrieved from Taiwan’s National Health Insurance Research Database, to study the long-term outcome of using CHM among incident pre-dialysis DN patients from January 1, 2004, to December 31, 2007. All patients were followed up to 5 years or the occurrence of mortality. The risks of all-cause mortality and ESRD were carried out using Kaplan-Meier and competing risk estimation, respectively. Further, we demonstrated the CHM prescriptions and core CHMs using the Chinese herbal medicine network (CMN) analysis.Results: A total of 6,648 incident pre-dialysis DN patients were analyzed, including 877 CHM users and 5,771 CHM nonusers. With overlap weighing for balancing all accessible covariates between CHM users and nonusers, we found the use of CHM was associated with lower all-cause mortality (0.22 versus 0.56; log-rank test: p-value &lt;0.001), and the risk of mortality was 0.42 (95% CI: 0.36–0.49; p-value &lt;0.001) by adjusting all accessible covariates. Further, the use of CHM was associated with a lower risk of ESRD (cause-specific hazard ratio: 0.59, 95%CI: 0.55–0.63; p-value &lt;0.001). Also, from the 5,901 CHM prescriptions, we found Ji-Sheng-Shen-Qi-Wan, Astragalus mongholicus Bunge or (Astragalus membranaceus (Fisch.) Bge.), Plantago asiatica L. (or Plantago depressa Willd.), Salvia miltiorrhiza Bunge, and Rheum palmatum L. (or Rheum tanguticum (Maxim. ex Regel) Balf., Rheum officinale Baill.) were used as core CHMs for different CHM indications. Use of core CHMs was associated with a lower risk of mortality than CHM users without using core CHMs.Conclusions: The use of CHM seemed feasible among pre-dialysis DN patients; however, the beneficial effects still need to be validated by well-designed clinical trials.
Modeling and Simulation to Support Phase Ib/IIa Dose Selection for WBP216, A Long Half-Life Fully Human Monoclonal Antibody Against Interleukin-6
Authors: Tang Xiange , Zeng Xiaofeng , Guan Xiaoduo , Chen Rui , Hu Pei 
Published: February 2021

WBP216 is an innovative IL-6 antibody, presenting high affinity to IL-6 and a long half-life (40–60 days). To optimize the dosage regimen for future clinical trials, pharmacokinetics (PK) and pharmacodynamics (PD) of WBP216 would be firstly characterized in Chinese rheumatoid arthritis (RA) patients. PK, CRP and DAS28 data of WBP216 were collected from 26 RA patients in a single ascending dose study. Non-linear mixed effects modeling was used for a population PK/PD analysis. A two-compartment model with a sequential zero-first order absorption and a first order elimination best described PK behavior of WBP216. Apparent systemic clearance was 0.015 L/h, central volume was 8.04 L. CRP as the fast-decreasing endpoint and DAS28 as the slow-reacting endpoint were both fitted well through an indirect response model. The baseline of ALT and free IL-6 were found associated with PK/PD parameters during covariates exploration. Simulation results confirmed that a loading dose regimen either of administration at weeks 0, 2, and 6 or doubling the maintenance dose level, followed by maintenance dosing of 75–150 mg every 8 weeks, was expected to provide a best risk/benefit ratio in future clinical studies. We hope this first PK/PD study of WBP216 in Chinese RA patients will help in the clinical development of WBP216 in future and provide a reference to the dosage optimization of similar antibodies with long half-life.Clinical Trial Registration:CTR20170306
Identification of Plasma hsa_circ_0005397 and Combined With Serum AFP, AFP-L3 as Potential Biomarkers for Hepatocellular Carcinoma
Authors: Liu Ruoyu , Li Yi , Wu Anqi , Kong Mingzhu , Ding Weijia , Hu Zeyang , Chen Lin , Cai Weihua , Wang Feng 
Published: February 2021

Background: Mounting evidence has demonstrated that circular RNA (circRNA) plays crucial roles in the occurrence and development of hepatocellular carcinoma (HCC). However, the expression pattern and clinical application value of plasma circRNA in HCC are still largely unknown. Herein, we explored the role of plasma hsa_circ_0005397 in diagnosis and prognosis of HCC.Methods: The expression level of plasma hsa_circ_0005397 was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The identification and origin of plasma hsa_circ_0005397 were confirmed by RNase R assay, Sanger sequencing and HCC cell culture. In addition, its diagnostic value was assessed by receiver operating characteristic (ROC) curve and prognostic value was evaluated by dynamics monitoring and Kaplan–Meier curve analyses in HCC patients.Results: The expression of plasma hsa_circ_0005397 was higher in patients with HCC than that in patients with benign liver diseases and healthy controls (both p &lt; 0.05). Moreover, it was closely correlated with tumor size (p = 0.020) and TNM stage (p = 0.006) of HCC patients. The area under the ROC curve of plasma hsa_circ_0005397 was 0.737 and 95% confidence interval was 0.671–0.795. Furthermore, the combination of plasma hsa_cic_0005397, serum AFP and AFP-L3 could improve the diagnostic sensitivity of HCC. Additionally, dynamic monitoring plasma hsa_cic_0005397 might help us predict recurrence or metastasis in HCC patients after surgical resection. Besides, the increased plasma hsa_cic_0005397 was closely correlated with shorter overall survival of HCC patients (p = 0.007).Conclusion: Plasma has_circ_0005397 represents a novel noninvasive biomarker for HCC. Moreover, the combination of plasma hsa_cic_0005397, serum AFP and AFP-L3 might improve the diagnostic value for HCC.
Magnetic Resonance-Compatible Arm-Crank Ergometry: A New Platform Linking Whole-Body Calorimetry to Upper-Extremity Biomechanics and Arm Muscle Metabolism
Authors: Vegter Riemer J. K. , van den Brink Sebastiaan , Mouton Leonora J. , Sibeijn-Kuiper Anita , van der Woude Lucas H. V. , Jeneson Jeroen A. L. 
Published: February 2021

IntroductionEvaluation of the effect of human upper-body training regimens may benefit from knowledge of local energy expenditure in arm muscles. To that end, we developed a novel arm-crank ergometry platform for use in a clinical magnetic resonance (MR) scanner with31P spectroscopy capability to study arm muscle energetics. Complementary datasets on heart-rate, whole-body oxygen consumption, proximal arm-muscle electrical activity and power output, were obtained in a mock-up scanner. The utility of the platform was tested by a preliminary study over 4 weeks of skill practice on the efficiency of execution of a dynamic arm-cranking task in healthy subjects.ResultsThe new platform successfully recorded the first everin vivo31P MR spectra from the human biceps brachii (BB) muscle during dynamic exercise in five healthy subjects. Changes in BB energy- and pH balance varied considerably between individuals. Surface electromyography and mechanical force recordings revealed that individuals employed different arm muscle recruitment strategies, using either predominantly elbow flexor muscles (pull strategy; two subjects), elbow extensor muscles (push strategy; one subject) or a combination of both (two subjects). The magnitude of observed changes in BB energy- and pH balance during ACT execution correlated closely with each strategy. Skill practice improved muscle coordination but did not alter individual strategies. Mechanical efficiency on group level seemed to increase as a result of practice, but the outcomes generated by the new platform showed the additional caution necessary for the interpretation that total energy cost was actually reduced at the same workload.ConclusionThe presented platform integrates dynamicin vivo31P MRS recordings from proximal arm muscles with whole-body calorimetry, surface electromyography and biomechanical measurements. This new methodology enables evaluation of cyclic motor performance and outcomes of upper-body training regimens in healthy novices. It may be equally useful for investigations of exercise physiology in lower-limb impaired athletes and wheelchair users as well as frail patients including patients with debilitating muscle disease and the elderly.