bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enantiospecific Suzuki–Miyaura Coupling of Nonbenzylic α‐(Acylamino)alkylboronic Acid Derivatives
Authors: Ohmura Toshimichi , Miwa Kyoko , Awano Tomotsugu , Suginome Michinori 
Published: May 2018

AbstractSuzuki–Miyaura coupling of nonbenzylic α‐(acylamino)alkylboron compounds with aryl halides is established. A Pd/PCy2Ph catalyst promotes the reaction efficiently at 145 °C. The reaction of enantioenriched α‐(acylamino)alkylboron compounds affords chiral 1‐arylalkylamides in high enantiospecificity and inversion of configuration.
Necessary and Sufficient Stability Criterion and Stabilization for Positive 2‐D Continuous‐Time Systems with Multiple Delays
Authors: Duan Zhaoxia , Ghous Imran , Wang Bing , Shen Jian 
Published: May 2018

AbstractThis paper addresses the stability and control problem of the linear positive two‐dimensional (2‐D) continuous‐time systems in Roesser model with multiple time delays. The contribution lies in two aspects. First, a simple novel proof is provided to establish necessary and sufficient conditions of asymptotic stability for 2‐D continuous delayed systems. It turns out that the magnitude of delays has no any impact on the stability of these systems, which is completely determined by the system matrices. Second, a necessary and sufficient condition for the existence of state‐feedback controllers is proposed for general delayed 2‐D systems, which ensures the non‐negativity and the stability of the resulting closed‐loop systems. Two examples are given to validate the proposed methods.
Screening in toddlers and preschoolers at risk for autism spectrum disorder: Evaluating a novel mobile‐health screening tool
Authors: Kanne Stephen M. , Carpenter Laura Arnstein , Warren Zachary 
Published: May 2018

There are many available tools with varying levels of accuracy designed to screen for Autism Spectrum Disorder (ASD) in young children, both in the general population and specifically among those referred for developmental concerns. With burgeoning waitlists for comprehensive diagnostic ASD assessments, finding accurate methods and tools for advancing diagnostic triage becomes increasingly important. The current study compares the efficacy of four oft used paper and pencil measures, the Modified Checklist for Autism in Toddlers Revised with Follow‐up, the Social Responsiveness Scale, Second Edition, and the Social Communication Questionnaire, and the Child Behavior Checklist to a novel mobile‐health screening tool developed by Cognoa, Inc. (Cognoa) in a group of children 18–72 months of age. The Cognoa tool may have potential benefits as it integrates a series of parent‐report questions with remote clinical ratings of brief video segments uploaded via parent's smartphones to calculate level of ASD risk. Participants were referred to one of three tertiary care diagnostic centers for ASD‐related concerns (n = 230) and received a best estimate ASD diagnosis. Analysis and comparison of psychometric properties indicated potential advantages for Cognoa within this clinical sample across age ranges not often covered by another single measure/tool. Autism Res 2018, 11: 1038–1049. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.Lay SummaryWith the wait times getting longer for comprehensive Autism Spectrum Disorder (ASD) diagnostic assessments, it is becoming increasingly important to find accurate tools to screen for ASD. The current study compares four screening measures that have been in use for some time to a novel mobile‐health screening tool, called Cognoa. The Cognoa tool is novel because it integrates parent‐report questions with clinical ratings of brief video segments uploaded via parent's smartphones to calculate ASD risk. Two hundred thirty children who were referred to one of three ASD specialty diagnostic centers to see if they had ASD participated in the study. A direct comparison indicated potential advantages for Cognoa not often covered by another single measure/tool.
Predictors of quality of life for autistic adults
Authors: Mason David , McConachie Helen , Garland Deborah , Petrou Alex , Rodgers Jacqui , Parr Jeremy R. 
Published: May 2018

AbstractResearch with adults on the autism spectrum is as yet limited in scope and quality. The present study describes quality of life (QoL) of a large sample of autistic adults in the UK and investigates characteristics that may be predictive of QoL. A total of 370 autistic adults from the Adult Autism Spectrum Cohort‐UK (ASC‐UK) completed the WHOQoL‐BREF, and the Social Responsiveness Scale (SRS, autism symptom severity), along with the ASC‐UK registration questionnaire giving information on mental health and their life situation. QoL for autistic adults was lower than for the general population for each WHOQoL domain. Younger participants reported higher QoL than older participants in psychological and environment domains. Males reported higher physical QoL than females, and females reported higher social QoL than males. Significant positive predictors of QoL were: being employed (physical QoL), receiving support (social and environment QoL), and being in a relationship (social QoL). Having a mental health condition and higher SRS total score were negative predictors of QoL across all four domains. Autistic adults require access to effective mental health interventions, and informal and formal support for their social difficulties, to improve their quality of life. Autism Res 2018, 11: 1138–1147. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc.Lay summaryThere has been limited research into the lived experience of autistic adults. Using the World Health Organization quality of life measure, we found that autistic people (370) in the UK reported their quality of life to be lower than that of the general population. Better quality of life was associated with being in a relationship; those with a mental health condition had poorer quality of life. This research suggests some ways in which autistic people can be helped to improve their quality of life.
Building a minimal and generalizable model of transcription factor–based biosensors: Showcasing flavonoids
Authors: Trabelsi Heykel , Koch Mathilde , Faulon Jean‐Loup 
Published: May 2018

AbstractProgress in synthetic biology tools has transformed the way we engineer living cells. Applications of circuit design have reached a new level, offering solutions for metabolic engineering challenges that include developing screening approaches for libraries of pathway variants. The use of transcription‐factor‐based biosensors for screening has shown promising results, but the quantitative relationship between the sensors and the sensed molecules still needs more rational understanding. Herein, we have successfully developed a novel biosensor to detect pinocembrin based on a transcriptional regulator. The FdeR transcription factor (TF), known to respond to naringenin, was combined with a fluorescent reporter protein. By varying the copy number of its plasmid and the concentration of the biosensor TF through a combinatorial library, different responses have been recorded and modeled. The fitted model provides a tool to understand the impact of these parameters on the biosensor behavior in terms of dose–response and time curves and offers guidelines to build constructs oriented to increased sensitivity and or ability of linear detection at higher titers. Our model, the first to explicitly take into account the impact of plasmid copy number on biosensor sensitivity using Hill‐based formalism, is able to explain uncharacterized systems without extensive knowledge of the properties of the TF. Moreover, it can be used to model the response of the biosensor to different compounds (here naringenin and pinocembrin) with minimal parameter refitting.
Creation and implementation of a flipped jigsaw activity to stimulate interest in biochemistry among medical students
Authors: Williams Charlene , Perlis Susan , Gaughan John , Phadtare Sangita 
Published: May 2018

AbstractLearner‐centered pedagogical methods that are based on clinical application of basic science concepts through active learning and problem solving are shown to be effective for improving knowledge retention. As the clinical relevance of biochemistry is not always apparent to health‐profession students, effective teaching of medical biochemistry should highlight the implications of biochemical concepts in pathology, minimize memorization, and make the concepts memorable for long‐term retention. Here, we report the creation and successful implementation of a flipped jigsaw activity that was developed to stimulate interest in learning biochemistry among medical students. The activity combined the elements of a flipped classroom for learning concepts followed by a jigsaw activity to retrieve these concepts by solving clinical cases, answering case‐based questions, and creating concept maps. The students' reception of the activity was very positive. They commented that the activity provided them an opportunity to review and synthesize information, helped to gage their learning by applying this information and work with peers. Students' improved performance especially for answering the comprehension‐based questions correctly in the postquiz as well as the depth of information included in the postquiz concept maps suggested that the activity helped them to understand how different clinical scenarios develop owing to deviations in basic biochemical pathways. Although this activity was created for medical students, the format of this activity can also be useful for other health‐professional students as well as undergraduate and graduate students. © 2018 by The International Union of Biochemistry and Molecular Biology, 46:343–353, 2018.
Ceruloplasmin in Parkinson's disease and the nonmotor symptoms
Authors: Zhao Xuemei , Shao Ziqiang , Zhang Yu , Liu Fang , Liu Zhibo , Liu Zunjing 
Published: May 2018

AbstractObjectivesTo investigate the relationship between ceruloplasmin (CP) and Parkinson's disease (PD), and the correlation between CP level and the time difference between nonmotor symptoms and motor symptoms and the diagnosis were also mentioned.Materials and MethodsSixty‐six patients diagnosed with PD for the first time were included in the study. They were divided into CP reduction group (31 cases) and CP normal group (35 cases) according to their CP level. The estimated time difference between nonmotor symptoms and motor symptoms and the diagnosis were recorded respectively. The magnetic sensitive nigra phase value was measured by susceptibility weighted imaging (SWI).ResultsCeruloplasmin level was middling correlated with age (r = .561, p < .001). There was strong negative correlation between CP level and UPDRS scores (r = −.727, p < .001). The CP level was significantly correlated with the magnetic sensitive nigra phase value (r = .891, p < .001). CP level showed moderate correlation with the time difference from nonmotor symptoms to motor symptoms (r = .559, p < .001), besides, the time difference between nonmotor symptoms and the diagnosis (r = .525, p < .001) and CP level was also moderately related.ConclusionsCeruloplasmin interference in iron metabolism was closely related with PD development. And there were slight corrections between CP level and the time difference from nonmotor symptoms to motor symptoms or the diagnosis.
Starvation tactics using natural compounds for advanced cancers: pharmacodynamics, clinical efficacy, and predictive biomarkers
Authors: El Bairi Khalid , Amrani Mariam , Afqir Said 
Published: May 2018

AbstractThe high mortality associated with oncological diseases is mostly due to tumors in advanced stages, and their management is a major challenge in modern oncology. Angiogenesis is a defined hallmark of cancer and predisposes to metastatic invasion and dissemination and is therefore an important druggable target for cancer drug discovery. Recently, because of drug resistance and poor prognosis, new anticancer drugs from natural sources targeting tumor vessels have attracted more attention and have been used in several randomized and controlled clinical trials as therapeutic options. Here, we outline and discuss potential natural compounds as salvage treatment for advanced cancers from recent and ongoing clinical trials and real‐world studies. We also discuss predictive biomarkers for patients' selection to optimize the use of these potential anticancer drugs.
FABP4 suppresses proliferation and invasion of hepatocellular carcinoma cells and predicts a poor prognosis for hepatocellular carcinoma
Authors: Zhong Cheng‐Qian , Zhang Xiu‐Ping , Ma Ning , Zhang Er‐Bin , Li Jing‐Jing , Jiang Ya‐Bo , Gao Yu‐Zhen , Yuan Yan‐Mei , Lan Shi‐Qian , Xie Dong , Cheng Shu‐Qun 
Published: May 2018

AbstractAdipocyte fatty acid‐binding protein (FABP4) is abundant in macrophage and adipocyte. It is known to be involved in lipid metabolism. The role of FABP4 has been reported in various cancers, such as non‐small cell lung cancer, breast cancer, ovarian cancer, and prostatic cancer. However, its role remains unclear in hepatocellular carcinoma (HCC). In our study, we investigated the expression of FABP4 at both mRNA and protein levels, and by examining 175 cases of patients with cancer of the liver tissue microarray, the significance between the expression of FABP4 and clinical characteristics had been discussed. We found that FABP4 was lowly expressed in HCC tissues compared to the corresponding tissue adjacent, and the expression of FABP4 was significantly associated with the tumor size, PVTT, recurrence‐free survival and overall survival. Moreover, multivariate Cox regression analysis indicated that the expression of FABP4, Alb, AFP, HBsAg, and PVTT were independent risk factors for overall survival, and the expression of FABP4, AFP, GGT, tumor size, and encapsulation were independent risk factors for HCC recurrence. In addition, we revealed that FABP4 suppressed HCC cell proliferation and invasion in vitro. Moreover, overexpression of FABP4 led to inhibit tumor growth and decreased tumor volume in vivo. These phenotypes were associated with altered expression of Snail and p‐STAT3. Our studies thus suggest that FABP4 could be a potential target for HCC chemotherapy.
A multicenter phase II trial of neoadjuvant letrozole plus low‐dose cyclophosphamide in postmenopausal patients with estrogen receptor‐positive breast cancer (JBCRG‐07): therapeutic efficacy and clinical implications of circulating endothelial cells
Authors: Ueno Takayuki , Masuda Norikazu , Kamigaki Shunji , Morimoto Takashi , Akiyama Futoshi , Kurosumi Masafumi , Tsuda Hitoshi , Mikami Yoshiki , Tanaka Sunao , Morita Satoshi , Toi Masakazu 
Published: May 2018

AbstractNeoadjuvant endocrine therapy has been reported to decrease tumor size, which leads to increased breast conservation rates. To improve the clinical response, metronomic chemotherapy with endocrine therapy is a promising strategy. A multicenter phase II single‐arm neoadjuvant trial with letrozole and cyclophosphamide was conducted. Eligibility criteria included postmenopausal status, T2–4 N0–1, and estrogen receptor‐positive breast carcinoma. Letrozole (2.5 mg) plus cyclophosphamide (50 mg) was given orally once a day for 24 weeks. The primary endpoint was the clinical response rate (CRR). To investigate anti‐angiogenic effects, circulating endothelial cells (CECs) were quantified using the CellSearch system. From October 2007 to March 2010, 41 patients were enrolled. The CRR was 67.5% (52.0–80.0%), which was above the prespecified threshold (65%). The conversion rate from total mastectomy to breast‐conserving surgery was 64% (18/28). Grade 3 or greater nonhematological toxicity was not reported. Clinical response was associated with improved disease‐free survival (DFS) (P = 0.020). The increase in CEC counts at 8 weeks was observed in nonresponders (P = 0.004) but not in responders. Patients with higher CEC counts at baseline or post‐treatment showed worse DFS than those with lower counts (P < 0.001 at baseline and = 0.014 post‐treatment). Multivariate analysis showed that post‐treatment CEC counts but not pretreatment counts were independently correlated with DFS (P = 0.046). In conclusion, neoadjuvant letrozole plus cyclophosphamide showed a good clinical response for postmenopausal patients with estrogen receptor‐positive breast cancer. CEC quantification is a promising tool for treatment monitoring and prognostic stratification for metronomic therapy following validation of our results in larger studies. Clinical trial registration number: UMIN000001331 Phase II study of neoadjuvant letrozole combined with low‐dose metronomic cyclophosphamide for postmenopausal women with endocrine‐responsive breast cancer (JBCRG‐07)
Lenvatinib inhibits angiogenesis and tumor fibroblast growth factor signaling pathways in human hepatocellular carcinoma models
Authors: Matsuki Masahiro , Hoshi Taisuke , Yamamoto Yuji , Ikemori‐Kawada Megumi , Minoshima Yukinori , Funahashi Yasuhiro , Matsui Junji 
Published: May 2018

AbstractUnresectable hepatocellular carcinoma (uHCC) is one of the most lethal and prevalent cancers worldwide, and current systemic therapeutic options for uHCC are limited. Lenvatinib, a multiple receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptors (FGFRs), recently demonstrated a treatment effect on overall survival by statistical confirmation of noninferiority to sorafenib in a phase 3 study of uHCC. Here, we investigated mechanisms underlying the antitumor activity of lenvatinib in preclinical HCC models. In vitro proliferation assay of nine human HCC cell lines showed that lenvatinib selectively inhibited proliferation of FGF signal‐activated HCC cells including FGF19‐expressing Hep3B2.1‐7. Lenvatinib suppressed phosphorylation of FRS2, a substrate of FGFR1–4, in these cells in a concentration‐dependent manner. Lenvatinib inhibited in vivo tumor growth in Hep3B2.1‐7 and SNU‐398 xenografts and decreased phosphorylation of FRS2 and Erk1/2 within the tumor tissues. Lenvatinib also exerted antitumor activity and potently reduced tumor microvessel density in PLC/PRF/5 xenograft model and two HCC patient‐derived xenograft models. These results suggest that lenvatinib has antitumor activity consistently across diverse HCC models, and that targeting of tumor FGF signaling pathways and anti‐angiogenic activity underlies its antitumor activity against HCC tumors.
A novel dual‐marker expression panel for easy and accurate risk stratification of patients with gastric cancer
Authors: Kanda Mitsuro , Murotani Kenta , Tanaka Haruyoshi , Miwa Takashi , Umeda Shinichi , Tanaka Chie , Kobayashi Daisuke , Hayashi Masamichi , Hattori Norifumi , Suenaga Masaya , Yamada Suguru , Nakayama Goro , Fujiwara Michitaka , Kodera Yasuhiro 
Published: May 2018

AbstractDevelopment of specific biomarkers is necessary for individualized management of patients with gastric cancer. The aim of this study was to design a simple expression panel comprising novel molecular markers for precise risk stratification. Patients (n = 200) who underwent gastrectomy for gastric cancer were randomly assigned into learning and validation sets. Tissue mRNA expression levels of 15 candidate molecular markers were determined using quantitative PCR analysis. A dual‐marker expression panel was created according to concordance index (C‐index) values of overall survival for all 105 combinations of two markers in the learning set. The reproducibility and clinical significance of the dual‐marker expression panel were evaluated in the validation set. The patient characteristics of the learning and validation sets were well balanced. The C‐index values of combinations were significantly higher compared with those of single markers. The panel with the highest C‐index (0.718) of the learning set comprised SYT8 and MAGED2, which clearly stratified patients into low‐, intermediate‐, and high‐risk groups. The reproducibility of the panel was demonstrated in the validation set. High expression scores were significantly associated with larger tumor size, vascular invasion, lymph node metastasis, peritoneal metastasis, and advanced disease. The dual‐marker expression panel provides a simple tool that clearly stratifies patients with gastric cancer into low‐, intermediate‐, and high risk after gastrectomy.
Downregulation of NDR1 contributes to metastasis of prostate cancer cells via activating epithelial‐mesenchymal transition
Authors: Yue Juntao , Sun Huimin , Liu Shijie , Yu Fei , Wang Shanshan , Wang Fuli , Shen Ruixiong , Zhu Feng , Zhang Lei , Shao Chen 
Published: May 2018

AbstractThe 5‐year survival rate decreases rapidly once the prostate cancer has invaded distant organs, although patients with localized prostate cancer have a good prognosis. In recent years, increasing numbers of reports showed that circulating tumor cells (CTCs) may play an important role in tumor metastasis and they have stronger potential of invasion and migration compared with their parental cells. In our previous investigation, we isolated CTCs from prostate cancer cell lines PC3. In this study, we found a novel antimetastasis gene NDR1 by analyzing different gene expression between CTCs and PC3. Lower NDR1 gene and protein expression were found in both prostate cancer cell lines and clinical specimens. Besides, NDR1 function acting as metastasis inhibitor was discovered both in vitro and in vivo. Further, we also discovered that several epithelial‐mesenchymal transition (EMT)‐related genes were upregulated when decreased NDR1 in PC3 cell lines. Therefore, our results revealed a role of NDR1 in the suppression of prostate cancer cell metastasis and provided a potential mechanism of action, thus offering new therapeutic strategies against prostate cancer metastasis.
Assessment of different mathematical models for diffusion‐weighted imaging as quantitative biomarkers for differentiating benign from malignant solid hepatic lesions
Authors: Hu Yao , Tang Hao , Li Haojie , Li Anqin , Li Jiali , Hu Daoyu , Li Zhen , Kamel Ihab R. 
Published: May 2018

AbstractTo quantitatively compare the monoexponential, biexponential, and stretched‐exponential diffusion‐weighted imaging (DWI) models in differentiating benign from malignant solid hepatic lesions. The institutional review board approved this retrospective study and waived the informed consent requirement. A total of 188 patients with 288 hepatic lesions included 202 malignant lesions and 86 benign lesions were assessed (confirmed by pathology or clinical follow‐up for 6 months). All patients underwent hepatic 3.0‐T MRI, including multi‐b DWI that used 12 b values. The ADC, Dp, Dt, perfusion fraction (fp), α, and DDC values for normal liver, benign liver lesions, and malignant liver lesions were calculated. Independent sample t tests were used for comparisons. The diagnostic performance of the parameters was evaluated using ROC analysis. The AUC value for each model was also calculated. The value of Dp was significantly lower in benign lesions than in normal hepatic parenchyma while others were significantly higher (P < .001). Whereas Values of Dt and α in malignant hepatic lesions were significantly higher than in normal hepatic parenchyma (P < .001), and the Dp value was significantly lower (P < .001). Values of ADC, fp, DDC, and α for malignant hepatic lesions were significantly lower than those for benign hepatic lesions (P < .001). ROC analysis showed that the diagnostic value of the biexponential model of normal hepatic parenchyma vs benign hepatic lesions and normal hepatic parenchyma vs malignant hepatic lesions was high (0.946 and 0.876, respectively). In the differential diagnosis of benign and malignant hepatic lesions, DDC had the highest AUC value (0.819). The biexponential and stretched‐exponential DWI may provide additional information and improve the differential diagnosis of benign and malignant hepatic lesions compared with the monoexponential DWI.