bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulinoma‐associated protein 1 immunostaining for various types of neuroendocrine tumors on FNA smears
Authors: Hou Tieying , Gan Qiong , Joseph Cicily T. , Sun Xiaoping , Gong Yun 
Published: June 2020

BackgroundInsulinoma‐associated protein 1 (INSM1) has recently emerged as a reliable nuclear immunostaining marker for detecting neuroendocrine tumors (NETs) in paraffin‐embedded surgical samples and cytologic cell blocks, but the reliability of INSM1 staining on cytologic smears is understudied. This study investigated the performance of INSM1 staining on cytologic smears for the detection of various NETs in comparison with chromogranin (CG) and synaptophysin (SYN).MethodsINSM1, CG, and SYN were stained on cytologic smears of 70 NETs, including 20 pancreatic NETs, 10 lung carcinoid tumors, 11 small cell lung carcinomas (SCLCs), 10 medullary thyroid carcinomas, 10 Merkel cell carcinomas, 4 thymic atypical carcinoid tumors, and 5 olfactory neuroblastomas. The detection rate, the percentage of positive cells, and the staining intensity were recorded.ResultsThe overall detection rate of INSM1 (94%) was higher than the rates of CG (79%) and SYN (89%). The detection rate of INSM1 was higher than the rates of CG and SYN in SCLC, Merkel cell carcinoma, and olfactory neuroblastoma; higher than the rate of CG and equal to the rate of SYN in pancreatic NETs and medullary thyroid carcinoma; equal to the rate of CG and higher than the rate of SYN in thymic atypical carcinoid tumors; and equal to the rate of CG and lower than the rate of SYN in lung carcinoid tumors. INSM1 staining was easier to interpret than CG and SYN staining, especially in high‐grade NETs.ConclusionsINSM1 can be reliably stained on cytologic smears and outperforms CG and SYN in the verification of clinically or radiologically suspected NETs.
Two Dimensional Oblique Molecular Packing within a Model Peptide Ribbon Aggregate
Authors: Kuczera Stefan , Rüter Axel , Roger Kevin , Olsson Ulf 
Published: June 2020

AbstractA10K (A=alanine, K=lysine) model peptides self‐assemble into ribbon‐like β‐sheet aggregates. Here, we report an X‐ray diffraction investigation on a flow‐aligned dispersion of these self‐assembly structures. The two‐dimensional wide‐angle X‐ray scattering pattern suggests that peptide pack in a two‐dimensional oblique lattice, essentially identical to the crystalline packing of polyalanine, An (for n>4). One side of the oblique unit cell, corresponding to the anti‐parallel β‐sheet, is oriented along the ribbon's axis. Together with recently published small angle X‐ray scattering data of the same system, this work thus yields a detailed description of the self‐assembled ribbon aggregates, down to the molecular length scale. Notably, our results highlight the importance of the crystalline peptide packing within its self‐assembly aggregates, which is often neglected.
An Electronic Health Record Text Mining Tool to Collect Real‐World Drug Treatment Outcomes: A Validation Study in Patients With Metastatic Renal Cell Carcinoma
Authors: van Laar Sylvia A. , Gombert‐Handoko Kim B. , Guchelaar Henk‐Jan , Zwaveling Juliëtte 
Published: June 2020

Real‐world evidence can close the inferential gap between marketing authorization studies and clinical practice. However, the current standard for real‐world data extraction from electronic health records (EHRs) for treatment evaluation is manual review (MR), which is time‐consuming and laborious. Clinical Data Collector (CDC) is a novel natural language processing and text mining software tool for both structured and unstructured EHR data and only shows relevant EHR sections improving efficiency. We investigated CDC as a real‐world data (RWD) collection method, through application of CDC queries for patient inclusion and information extraction on a cohort of patients with metastatic renal cell carcinoma (RCC) receiving systemic drug treatment. Baseline patient characteristics, disease characteristics, and treatment outcomes were extracted and these were compared with MR for validation. One hundred patients receiving 175 treatments were included using CDC, which corresponded to 99% with MR. Calculated median overall survival was 21.7 months (95% confidence interval (CI) 18.7–24.8) vs. 21.7 months (95% CI 18.6–24.8) and progression‐free survival 8.9 months (95% CI 5.4–12.4) vs. 7.6 months (95% CI 5.7–9.4) for CDC vs. MR, respectively. Highest F1‐score was found for cancer‐related variables (88.1–100), followed by comorbidities (71.5–90.4) and adverse drug events (53.3–74.5), with most diverse scores on international metastatic RCC database criteria (51.4–100). Mean data collection time was 12 minutes (CDC) vs. 86 minutes (MR). In conclusion, CDC is a promising tool for retrieving RWD from EHRs because the correct patient population can be identified as well as relevant outcome data, such as overall survival and progression‐free survival.
Monitoring CAR‐T cell kinetics in clinical trials by multiparametric flow cytometry: Benefits and challenges
Authors: Sarikonda Ghanashyam , Pahuja Anil , Kalfoglou Creton , Burns Kerri , Nguyen Kevin , Ch'en Irene L. , Pollner Reinhold , Tangri Shabnam , Dakappagari Naveen 
Published: June 2020

AbstractExceptional clinical responses produced by the first chimeric antigen receptor T [CAR‐T] cell therapies, and their entry into commercial markets prompted a logarithmic increase in the number of next generation CAR‐T clinical trials. As a result, there is a growing interest in understanding the analytical approaches utilized for reliable monitoring of these “living” drugs, and the challenges encountered during their clinical development. Multiparametric flow cytometry (MFC) assays have played a crucial role in understanding the phenotype and function of first approved CAR‐T therapies. Herein, three main areas for monitoring CAR‐T therapies in clinical trials are discussed: (1) analytical considerations critical for development of MFC assays for the reliable enumeration of CAR‐T levels, (2) operational challenges associated with clinical trial sampling and transportation, and (3) differential cellular kinetics observed by MFC and qPCR analyses and their relationship with efficacy (measurable residual disease levels). Initial experiences described here may enable design of fit‐for‐purpose tools and help to more rapidly advance the development of next generation CAR‐T therapies.
An improved distance‐based ant colony optimization routing for vehicular ad hoc networks
Authors: Ramamoorthy Raghu , Thangavelu Menakadevi 
Published: June 2020

SummaryVehicular ad hoc network (VANET) has earned tremendous attraction in the recent period due to its usage in a wireless intelligent transportation system. VANET is a unique form of mobile ad hoc network (MANET). Routing issues such as high mobility of nodes, frequent path breaks, the blind broadcasting of messages, and bandwidth constraints in VANET increase communication cost, frequent path failure, and overhead and decrease efficiency in routing, and shortest path in routing provides solutions to overcome all these problems. Finding the shortest path between source and destination in the VANET road scenario is a challenging task. Long path increases network overhead, communication cost, and frequent path failure and decreases routing efficiency. To increase efficiency in routing a novel, improved distance‐based ant colony optimization routing (IDBACOR) is proposed. The proposed IDBACOR determines intervehicular distance, and it is triggered by modified ant colony optimization (modified ACO). The modified ACO method is a metaheuristic approach, motivated by the natural behavior of ants. The simulation result indicates that the overall performance of our proposed scheme is better than ant colony optimization (ACO), opposition‐based ant colony optimization (OACO), and greedy routing with ant colony optimization (GRACO) in terms of throughput, average communication cost, average propagation delay, average routing overhead, and average packet delivery ratio.
Predicting child effortful control: An integrative analysis of child physiological, familial, and community factors
Authors: Sun Xiaoning , Measelle Jeffrey , Ablow Jennifer C. 
Published: June 2020

AbstractEffortful control (EC) is a regulatory capacity that refers to children's ability to inhibit a dominant response to perform a subdominant response. Although attempts have been made to identify early predictors of children's EC, the confluence and interaction of child‐, familial‐, and community factors has not been pursued adequately. This study investigated how predictors from different aspects of children's rearing environment interacted to predict later EC. In a sample of 88 primiparous women with elevated depressive symptomotology and low household income, we examined how children's own psychobiology (baseline cortisol), familial relationship (mother–child attachment), and community resources (social support) at 17 months independently and jointly predicted EC at age 5. Our results showed that, controlling for maternal depressive symptomotology and household income, predictors from child‐, familial‐, and community‐aspect function integratively, rather than independently, in predicting later EC. Specifically, within the context of a secure attachment relationship, baseline cortisol positively predicts later EC only for children of mothers who reported low social support. Whereas within the context of an insecure attachment relationship, baseline cortisol negatively predicts later EC, regardless of the perceived social support levels. Our results highlighted the importance of taking into consideration predictors from multiple aspects for intervention designs.
Maternal approach behaviors toward neonatal calls are impaired by mother's experiences of raising pups with a risk gene variant for autism
Authors: Kato Risa , Machida Akihiro , Nomoto Kensaku , Kang Gina , Hiramoto Takeshi , Tanigaki Kenji , Mogi Kazutaka , Hiroi Noboru , Kikusui Takefumi 
Published: June 2020

AbstractHow the intrinsic sequence structure of neonatal mouse pup ultrasonic vocalization (USV) and maternal experiences determine maternal behaviors in mice is poorly understood. Our previous work showed that pups with a Tbx1 heterozygous (HT) mutation, a genetic risk for autism spectrum disorder (ASD), emit altered call sequences that do not induce maternal approach behaviors in C57BL6/J mothers. Here, we tested how maternal approach behaviors induced by wild‐type and HT USVs are influenced by the mother's experience in raising pups of these two genotypes. The results showed that wild‐type USVs were effective in inducing maternal approach behaviors when mothers raised wild‐type but not HT pups. The USVs of HT pups were ineffective regardless of whether mothers raised HT or wild‐type pups. However, the sequence structure of pup USVs had no effect on the general, non‐directional incentive motivation of maternal behaviors. Our data show how the mother's experience with a pup with a genetic risk for ASD alters the intrinsic incentive values of USV sequences in maternal approach behaviors.
Determination of Chlorpromazine Hydrochloride with a Layered Double Hydroxide Modified Glassy Carbon Electrode as a Nanocatalyst
Authors: Jaberi Seyedeh Yasaman Shajaripour , Ghaffarinejad Ali , Kamalifar Mohsen , Heidari Mozhgan 
Published: June 2020

AbstractWe report a simple and sensitive voltammetric sensor for the determination of chlorpromazine (CPZ) based on Ni−Al layered double hydroxide (NiAlLDH) modified glassy carbon electrode (GCE). NiAlLDH was simply electrodeposited on GCE surface in a very short time. The response linear range was 1×10−3–1×10−9 mol L−1, with a detection limit of 1×10−9 mol L−1. The NiAlLDH film showed well defined and well separate peaks for dopamine, ascorbic acid, uric acid and CPZ in the same solution. The proposed electrode was used to measure the active pharmaceutical ingredient of CPZ tablet as a real sample.
Explaining the causal effect of adherence to medication on cholesterol through the marginal patient
Authors: Depalo Domenico 
Published: June 2020

AbstractThis paper investigates the relation between adherence to prescribed medication and reduction of cholesterol in Italy, taking into account the possible sorting of patients into treatment and the heterogeneity of the effect. As predicted by a theoretical model, I find that patients who benefit most from medication are more likely to adhere to prescribed regime than those who benefit least. These results are used to study the effects of three hypothetical policies that aim at increasing the share of patients adherent to prescribed medication: one policy is directed toward patients, one toward physicians, and one toward both patients and physicians. For each policy, I describe the observable characteristics of patients induced into treatment. Although the policy with the highest return is directed toward patients, the policies differ substantially with respect to the population affected. Therefore, a policy with lower return that targets better the desired population may be preferred to the policy with the highest return.
Jurisdiction concerning annex actions in the context of the insolvency and Brussels Ibis regulations
Authors: Fabok Zoltan 
Published: June 2020

AbstractThe legislation of the European Union has addressed the private international law aspects of civil and commercial matters and those of insolvency cases separately. While the Brussels Ibis Regulation (and its predecessors) focuses on “classic” civil of commercial cases, insolvency proceedings are subject to the (recast) Insolvency Regulation. However, the close interference between the two related areas of law—commercial and insolvency—results in a category of cases that are commercial and contentious in nature, and so they would tend to gravitate towards the Brussels regime, but yet they are so closely connected to the insolvency proceedings that justifies a special approach. This article focuses on the question of international jurisdiction regarding these “annex actions” in the context of the EU law. It will attempt to explore the historical roots of the current provisions and the evolution of both the European legislation and the relevant case law. The examination of this progression provides a better understanding of the current legislation and answers some questions apparently left open in the recast Insolvency Regulation.
Six autoantibodies as potential serum biomarkers of hepatocellular carcinoma: A prospective multicenter study
Authors: Okada Rei , Otsuka Yuichiro , Wakabayashi Taiga , Shinoda Masahiro , Aoki Takeshi , Murakami Masahiko , Arizumi Shunichi , Yamamoto Masakazu , Aramaki Osamu , Takayama Tadatoshi , Wakiyama Shigeki , Yanaga Katsuhiko , Amikura Katsumi , Kaneko Hironori , Shimada Hideaki 
Published: June 2020

AbstractSerum autoantibodies have been reported to react with tumor‐associated antigen (TAA) in various cancers. This multicenter study evaluated the diagnostic and prognostic value of six autoantibodies against a panel of six hepatocellular carcinoma (HCC)‐associated antigens, including Sui1, p62, RalA, p53, NY‐ESO‐1 and c‐myc. A total of 160 patients with HCC and 74 healthy controls were prospectively enrolled from six institutions. Serum antibody titers were determined by enzyme‐linked immunosorbent assays. The sensitivities were 19% for Sui1, 18% for p62, 17% for RalA, 11% for p53, 10% for NY‐ESO‐1 and 9% for c‐myc. Overall sensitivity of the TAA panel (56%) was higher than that of α‐fetoprotein (41%, P < .05). The combined sensitivity of the TAA panel and α‐fetoprotein was significantly higher than that of α‐fetoprotein alone (P < .001). The difference in overall survival of TAA panel‐positive and panel‐negative patients was significant when the Stage I/II patients were combined (P = .023). Overall survival was worse in NY‐ESO‐1 antibody‐positive than in NY‐ESO‐1 antibody‐negative patients (P = .002). Multivariate analysis found that positivity for the TAA panel was independently associated with poor prognosis (P = .030). This TAA panel may have diagnostic and prognostic value in the patients with HCC.
Segmentation of tumor using PCA based modified fuzzy C means algorithms on MR brain images
Authors: Yepuganti Karuna , Saladi Saritha , Narasimhulu C. V. 
Published: June 2020

AbstractIn the field of medical sciences, automatic detection of tumor using magnetic resonance (MR) brain images is a major research area. The goal of the proposed work is to identify the tumors in MR images using segmentation methods and to locate the affected regions of the brain more accurately. Medical images have vast information but they are difficult to examine with lesser computational time. An innovative process is proposed to extract tumor cells using the discrete wavelet transform (DWT). After extracting features with DWT feature reduction is carried out with the principal component analysis (PCA). Modified fuzzy C means (MFCM) technique is used for segmenting the tumor cells. The efficiency of the proposed method to identify different abnormalities in real MR images for intracranial neoplasm detection, tuberculoma, and bilateral thalamic fungal granulomas identification is tested. The results obtained are shown in‐terms of Accuracy, Dice Similarity Index (DSI), and Jaccard Index (JI) measures. The performance of the proposed method is tested in terms of performance measures like Accuracy, DSI, and JI. These results are compared with the conventional fuzzy C means (FCM) method.
Mothers’ self‐reported emotion dysregulation: A potentially valid method in the field of infant mental health
Authors: Leerkes Esther M. , Su Jinni , Sommers Savannah A. 
Published: June 2020

ABSTRACTIn the current study, we evaluated the extent to which mothers reported emotion dysregulation on the Difficulties with Emotion Regulation Questionnaire (DERS) (a) converged with physiological indices of emotion dysregulation while parenting, (b) correlated with maternal sensitivity, and (c) predicted infant attachment disorganization and behavior problems in a sample of 259 mothers and their infants. When infants were 6 months old, mothers’ physiological arousal and regulation were measured during parenting tasks and mothers completed the DERS. Maternal sensitivity was observed during distress‐eliciting tasks when infants were 6 and 14 months old. Infant attachment disorganization was assessed during the Strange Situation when infants were 14 months old and mothers reported on infants’ behavior problems when infants were 27 months old. Mothers who reported greater emotion regulation difficulties were more physiologically dysregulated during stressful parenting tasks and also showed lower levels of maternal sensitivity at 6 months. Mother‐reported dysregulation predicted higher likelihood of infant attachment disorganization and more behavior problems. Results suggest that the DERS is a valid measure of maternal emotional dysregulation and may be a useful tool for future research and intervention efforts aimed toward promoting positive parenting and early child adjustment.
What makes leader cells arise: Intrinsic properties and support from neighboring cells
Authors: Chen Bing‐Jun , Wu Jia‐Shun , Tang Ya‐Jie , Tang Ya‐Ling , Liang Xin‐Hua 
Published: June 2020

AbstractCancer cells collectively invading as a cohesive and polarized group is termed collective invasion, which is a fundamental property of many types of cancers. In this multicellular unit, cancer cells are heterogeneous, consisting of two morphologically and functionally distinct subpopulations, leader cells and follower cells. Leader cells at the invasive front are responsible for exploring the microenvironment, paving the way, and transmitting information to follower cells. Here, in this review, we will describe the important role of leader cells in collective invasion and the emerging underlying mechanisms of leader cell formation including intrinsic properties and the support from neighboring cells. It will help us to elucidate the essence of collective invasion and provide new anticancer therapeutic clues.
Systematic identification, development, and validation of prognostic biomarkers involving the tumor‐immune microenvironment for glioblastoma
Authors: Zhao Binghao , Wang Yuekun , Wang Yaning , Chen Wenlin , Liu Peng Hao , Kong Ziren , Dai Congxin , Wang Yu , Ma Wenbin 
Published: June 2020

AbstractGliomas are infiltrative neoplasms with a highly invasive nature. Due to its distinct genomic, genetic and epigenetic features, the immune prognostic signature (IPS) and immune microenvironment of glioblastoma (GBM) merit further research. We aimed to explore prognosis‐related immune genes and develop an IPS model for predicting prognosis in GBM. RNA‐sequencing data, as well as clinical information, from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) public cohorts were analyzed. To develop the IPS, least absolute shrinkage and selection operator (LASSO) Cox analysis was performed for immune‐related genes that were differentially expressed between GBM and normal tissues. Then, interaction effects of the IPS on the immune microenvironment were systematically analyzed; the precise prognostic model was developed based on the IPS and clinical data and was then further validated. A total of 21 immune prognostic genes were identified based on GBM microenvironment status. An 8‐gene IPS was established, and the GBM patients were effectively stratified into low‐ and high‐risk groups in the TCGA cohort as a training set. Univariate and multivariate Cox analyses revealed that IPS was an independent prognostic factor, and the prognostic performance of individual IPS genes was systematically illustrated. In addition, a comprehensive and novel nomogram model was initially established to estimate overall survival in TCGA‐GBM patients, and high‐risk patients had higher levels of dendritic cell and neutrophil infiltration. Furthermore, the nomogram model was developed and validated in the CGGA validation set. The low‐risk IPS was linked to a stronger response to anti‐PD‐L1 immunotherapy and clinical advantages in the IMvigor210 cohort. This novel IPS with promising biomarkers classifies GBM patients into subgroups with distinct clinical outcomes and immunophenotypes. Our findings and this resource may help to characterize the immune microenvironment, inform cancer immunotherapy and facilitate the development of precision immuno‐oncology.