bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA17: Pathway dependence and drug synergism in NF1-associated malignant peripheral nerve sheath tumors using the zebrafish model
Authors: Ki Dong Hyuk , He Shuning , Look A. Thomas 
Published: August 2018

Abstract
Malignant peripheral nerve sheath tumors (MPNSTs) are very aggressive and often metastatic soft tissue sarcomas, which are frequently found in patients who have neurofibromatosis type 1 (NF1). Currently, surgical excision is the only curative therapy for MPNST; however, many patients have unresectable or metastatic tumors at diagnosis and the recurrence rate after surgery is high. Chemotherapy regimens are only partially effective and associated with significant toxicity that can severely reduce quality of life. To establish a preclinical model of this highly malignant tumor, we developed a faithful in vivo MPNST transplantation assay to assess pathway dependence. mCherry-labeled MPNSTs cells were harvested from nf1 and p53 mutant zebrafish and implanted into the pericardial space of embryos at 2 dpf. 24 hours later, we added multiple pathway inhibitors or DMSO vehicle to the fish water and the embryos were incubated for 4 days. Drugs in clinical use for MPNST were tested such as inhibitors of MEK (trametinib), RTK (sunitinib), mTOR (rapamycin), HSP90 (ganetespib), microtubules (vincristine), alkylating agents (cytoxan), XPO I (selinexor), topo II (etoposide), and topo I (topotecan). Of these, only topotecan and selinexor showed significant cytotoxic responses at their MTDs. These two inhibitors were also active in human MPNST cell lines, and we are testing to see if their tumor cell cytotoxic effects are synergistic. Clinical trials of Topo I and XPO I inhibitors have not been reported for MPNST, and our results indicate that these two drugs should be evaluated clinically in patients with this tumor. We are now assessing FDA-approved drugs to identify those that synergize with topotecan and selinexor to induce sustained MPNST cell death and improved survival at tolerable dosages. Our long-range goal is to define active combinations of three or more non-cross resistant drugs that exhibit synergistic and sustained tumor cell cytotoxicity at dosages tolerable to the host.
Citation Format: Dong Hyuk Ki, Shuning He, A. Thomas Look. Pathway dependence and drug synergism in NF1-associated malignant peripheral nerve sheath tumors using the zebrafish model [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr IA17.
Abstract PR12: Histone H3K36 mutations promote sarcomagenesis through altered histone methylation landscape
Authors: Lu Chao , Jain Siddhant , Hoelper Dominik , Bechet Denise , Ran Leili , Andrulis Irene , Dickson Brendan , Majewski Jacek , Thompson Craig , Chi Ping , Garcia Benjamin , Jabado Nada , Lewis Peter , Allis C. David 
Published: August 2018

Abstract
Several types of bone/cartilage tumors reportedly contain high-frequency missense mutations in histone H3, yet the underlying oncogenic mechanism remains poorly characterized. We find that the H3 lysine 36 to methionine (H3K36M) mutation, identified in &gt;90% of chondroblastomas, impairs the differentiation of mesenchymal progenitor cells and generates undifferentiated sarcoma in vivo. H3K36M mutant nucleosomes inhibit the enzymatic activities of several H3K36 methyltransferases, resulting in globally diminished H3K36 methylation. Depletion of H3K36 methyltransferases, or expressing an H3K36I mutant that similarly inhibits H3K36 methylation, is sufficient to phenocopy H3K36M mutation. Following the loss of H3K36 methylation, a genome-wide gain in H3K27 methylation leads to a redistribution of polycomb repressive complex 1 and de-repression of polycomb target genes known to block mesenchymal differentiation. Our findings are mirrored in human undifferentiated sarcomas where novel K36M/I mutations in H3.1 are identified in rare pediatric cases.
This abstract is also being presented as Poster A12.
Citation Format: Chao Lu, Siddhant Jain, Dominik Hoelper, Denise Bechet, Leili Ran, Irene Andrulis, Brendan Dickson, Jacek Majewski, Craig Thompson, Ping Chi, Benjamin Garcia, Nada Jabado, Peter Lewis, C. David Allis. Histone H3K36 mutations promote sarcomagenesis through altered histone methylation landscape [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr PR12.
Will I lose my license for that? A closer look at Canadian disciplinary hearings and what it means for pharmacists’ practice to full scope
Authors: Foong E. Ai-Leng , Grindrod Kelly A. , Houle Sherilyn K. D. 
Published: August 2018

Objective: Concerns about liability from clinical errors have been cited as a barrier preventing greater adoption of practice change. Our objective was to determine the most common actions or omissions that result in disciplinary action for pharmacists and the restrictive actions imposed. Methods: Canadian disciplinary reports were reviewed. Cases were coded as charges of professional misconduct, unskilled practice or dishonest business practices. Results: There were 558 disciplinary cases from 10 provinces that occurred between January 2010 and July 2017. Professional misconduct charges commonly involved stealing/diverting or inappropriately dispensing narcotic drugs, pharmacy supervision/premises charges and refusing to cooperate with the college. Charges of unskilled practice included dispensing the wrong drug, failing to assess the appropriateness of a drug order, providing the wrong dose and failing to counsel. Fraudulent billing practices and accepting rebates from generic drug companies were the most common dishonest business practices. Professional misconduct, unskilled practice and dishonest business practice charges were involved in 342 (61%), 169 (30%) and 191 (34%) cases, respectively. Most cases occurred in community pharmacies and were not caused by an isolated clinical error. Fines were the most common penalty, followed by temporary license suspensions, professional development and reprimands. License revocations were the least common (4%), often involving professional misconduct. Conclusion: This review suggests that disciplinary action against a pharmacist for an isolated, unintentional clinical error is uncommon and that losing a license is rare. Fear of disciplinary action should not be a barrier to practice change or the provision of full-scope patient care services.
Clinical impact of mineralocorticoid receptor antagonists treatment after acute coronary syndrome in the real world: A propensity score matching analysis
Authors: Agra-Bermejo Rosa , Cordero Alberto , Rodríguez-Mañero Moisés , García Acuña Jose M , Álvarez Álvarez Belén , Martínez Álvaro , Álvarez Rodríguez Leyre , Abou-Jokh Charigan , Cid Álvarez Belén , González-Juanatey Jose Ramón 
Published: August 2018

Background: Recent studies suggest that the benefit of mineralocorticoid receptor antagonists in the acute coronary syndrome setting is controversial. The aim of this study was to examine the current long-term prognostic benefit of mineralocorticoid receptor antagonists in patients with acute coronary syndrome. Material and methods: We conducted a retrospective cohort study of 8318 consecutive acute coronary syndrome patients. Baseline patient characteristics were examined and a follow-up period was established for registry of death, major cardiovascular adverse events and heart failure re-hospitalization. We performed a propensity-matching analysis to draw up two groups of patients paired according to whether or not they had been treated with mineralocorticoid receptor antagonists. The prognostic value of mineralocorticoid receptor antagonists to predict events during follow-up was analysed using Cox regression. Results: Among the study participants, only 524 patients (6.3%) were discharged on mineralocorticoid receptor antagonists. Patients on mineralocorticoid receptor antagonists had a different clinical and pharmacological profile. These differences disappeared after the propensity score analysis. The median follow-up was 40.7 months. After the propensity score analysis, the cardiovascular mortality and heart failure readmission rates were similar between patients who were discharged on mineralocorticoid receptor antagonists and those whose not. The use of mineralocorticoid receptor antagonists was only associated with a reduction in major cardiovascular adverse events (hazard ratio=0.83, 95% confidence interval 0.69–0.97, p=0.001). Conclusions: Our results do not corroborate the long-term benefit of mineralocorticoid receptor antagonists to improve survival after acute coronary syndrome in a large cohort of patients with heart failure or reduced left ventricular ejection fraction and diabetes. Their prescription was associated with a significantly lower incidence of major cardiovascular adverse events during the long-term follow-up without effect on heart failure development.
Transformation of the company system and birth of the “white-collar” miner: the case of progressive company Taiheiyo Coalmine during the period of economic growth in Japan
Authors: Shimazaki Naoko 
Published: August 2018

AbstractFollowing the postwar reconstruction period, Japan enjoyed rapid economic growth from the mid-1950s to the mid-1970s. During those years, Japanese companies, mainly manufacturers, established the Japanese-style production system. However, the coal industry was left behind by the economic growth. One reason for this was the “energy revolution” that occurred in the mid-1950s, namely the replacement of coal with oil as the main energy source. This shift turned coalmining into a declining industry. Coal companies were forced into corporate restructuring, triggering an era of rationalization. Facing this situation, Taiheiyo Coalmine Co. Ltd. took the modernization of its management system further than other mines. As a result, it took up a shift to the Japanese-style production system. This transformation was developed by the joint efforts of labor and management and the company survived through to the twentieth century and still continues to operate today run by the successor to Taiheiyo Coalmine. This paper sets out to elucidate the transformation of the work environment and the change in workers’ attitudes in the 1960s and 1970s.
Near-surface scattered waves enhancement with source-receiver interferometry
Authors: Xu Jixiang , Dong Shitai , Cui Huajuan , Zhang Yan , Hu Ying , Sun Xiping 
Published: August 2018

Near-surface scattered waves (NSWs) are the main noise in seismic data in areas with a complex near surface and can be divided into surface-to-surface scattered waves and body-to-surface scattered waves. We have developed a method for NSW enhancement that uses modified source-receiver interferometry. The method consists of two parts. First, deconvolutional intersource interferometry is used to cancel the common raypath of seismic waves from a near-surface scatterer to the common receiver and the receiver function. Second, convolutional interreceiver interferometry is used to compensate the common raypath of seismic waves from the common source to the near-surface scatterer and the source function. For an isotropic point scatterer near the earth’s surface in modified source-receiver interferometry, a body-to-surface scattered wave can be reconstructed by constructive interference not only among three body-to-surface scattered waves but also among a body-to-surface scattered wave and two surface-to-surface scattered waves; a surface-to-surface scattered wave can be reconstructed by constructive interference not only among three surface-to-surface scattered waves but also among a surface-to-surface scattered wave and two body-to-surface scattered waves. According to stationary phase analysis based on the superposition principle, we have developed a so-called dual-wheel driving configuration of modified source-receiver interferometry for enhancing NSWs in the data of conventional seismic exploration. The main advantages of the scheme are that (1) it can be used to enhance NSWs without the need for any a priori knowledge of topography and near-surface velocity, (2) it can be used to reconstruct NSWs from real sources to real receivers, including 3D near-surface side-scattered waves, and (3) it can be applied to conventional seismic data with finite-frequency bandwidth, spatially limited and sparse arrays, different source and receiver functions, and static correction. Numerically simulated data and field seismic data are used to demonstrate the feasibility and effectiveness of the scheme.
Clinical Validation of the Prognostic Stage Groups of the Eighth-Edition TNM Staging for Medullary Thyroid Carcinoma
Authors: Park So Young , Cho Yoon Young , Kim Hye In , Choe Jun-Ho , Kim Jung-Han , Kim Jee Soo , Oh Young Lyun , Hahn Soo Yeon , Shin Jung Hee , Kim Kyunga , Kim Sun Wook , Chung Jae Hoon , Kim Tae Hyuk 
Published: August 2018

Abstract

Context
Despite advances in thyroid cancer staging systems, considerable controversy about the current staging system for medullary thyroid carcinoma (MTC) continues.

Objective
We aimed to evaluate the prognostic performance of the current eighth edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control TNM staging system (TNM-8) and the alternative proposed prognostic stage groups based on recursive partitioning analysis (TNM-RPA).

Design, Setting, and Patients
We retrospectively analyzed 182 patients with MTC treated at a single tertiary Korean hospital between 1995 and 2015.

Interventions and Main Outcome Measures
Survival analysis was conducted according to TNM-8 and TNM-RPA. The area under the receiver-operating characteristic curve (AUC), the proportion of variation explained (PVE), and the Harrell concordance index (C-index) were used to evaluate predictive performance.

Results
Under TNM-8, only two (1.1%) patients were downstaged compared with the seventh edition of the AJCC TNM staging system (TNM-7). The AUC at 10 years, PVE, and C-index were 0.679, 8.7%, and 0.744 for TNM-7 and 0.681, 8.9%, and 0.747 for TNM-8, respectively. Under TNM-RPA, 104 (57.14%) patients were downstaged compared with TNM-8. TNM-RPA had better prognostic performance with respect to cancer-specific survival (AUC at 10 years, 0.750; PVE, 20.9%; C-index, 0.881).

Conclusions
The predictive performance of the revised TNM-8 in patients with MTC has not changed despite its modification from TNM-7. The proposed changes in TNM-RPA were statistically valid and may present a more reproducible system that better estimates cancer-specific survival of individual patients.
Advances in Electromagnetic Therapy for Wound Healing
Authors: Madduri Bala , Anand Avnika Singh , Kohli Himani , Oza Manan , Chauhan Satish , Amitabh Mr , Kohli Ekta , Sharma Sanjeev Kumar 
Published: August 2018

<p>Understanding the molecular basis of wound healing and tissue regeneration continues to remain as one of the major challenges in modern medicine. There is absolute necessity to unveil the rather elusive mechanism with a special emphasis on the approaches to accelerate wound healing. Low frequency low intensity Pulsed electromagnetic therapy is evidenced to have a significant impact on wound repair and regeneration. It provides a non-invasive reparative technique to treat an injury. <em>In vitro </em>studies reported a significant effect of electromagnetic field on neovascularisation and angiogenesis. There are also many pieces of evidence which support its efficiency in reducing the duration of wound healing and improving the tensile strength of scars. Here, we compared the traditional stigma associated with pulsed electromagnetic fields and weighed them with its potential therapeutic effect on wound healing. Furthermore, we emphasized the need for more focused research to determine the therapeutic strategies and optimised parameters of pulsed electromagnetic field that can assure efficient wound healing and regeneration. </p>
Poly (γ-) Glutamic Acid : A Promising Biopolymer
Authors: Kumarr Mrithula Mahalakshmi , Raj Janifer Xavier , Gopalan Natarajan , Ramana Karna Venkata , Sharma Rakesh Kumar 
Published: August 2018

<p>Poly (γ-) glutamic acid is a polymer of L or D - Glutamic acid units produced by microorganisms as a defense mechanism as an act of stress tolerance. Production of γ-PGA by microbial source has been gaining attention due to its low cost of production and varied application with high compatibility and high biodegradability. Its application ranges from food industry to waste water treatment. γ-PGA is a major constituent of Japanese food - natto. PGA has vast applications in food, pharmaceuticals, healthcare, water treatment and other fields. The high research interest that currently is developing for γ-PGA is due to its potential as a biomedical material with a high biocompatibility and a fair biodegradability. In fact, γ-PGA is extensively used as a food additive and it is known to be hydrolytically degradable by water with or without intervening of proteases. An incessant number of publications dealing with the use of γ-PGA as drug delivery system are appearing in these last few years and several processes have been developed at large scale which are able to afford great amounts of this compound for industrial uses.</p>
A Survey of Adversarial Machine Learning in Cyber Warfare
Authors: Duddu Vasisht 
Published: August 2018

<div class="page" title="Page 1"><div class="layoutArea"><div class="column"><p>The changing nature of warfare has seen a paradigm shift from the conventional to asymmetric, contactless warfare such as information and cyber warfare. Excessive dependence on information and communication technologies, cloud infrastructures, big data analytics, data-mining and automation in decision making poses grave threats to business and economy in adversarial environments. Adversarial machine learning is a fast growing area of research which studies the design of Machine Learning algorithms that are robust in adversarial environments. This paper presents a comprehensive survey of this emerging area and the various techniques of adversary modelling. We explore the threat models for Machine Learning systems and describe the various techniques to attack and defend them. We present privacy issues in these models and describe a cyber-warfare test-bed to test the effectiveness of the various attack-defence strategies and conclude with some open problems in this area of research.</p><p> </p></div></div></div>
The effect mechanism of Ginnalin A as a homeopathic agent on various cancer cell lines
Authors: Vural Hasibe 
Published: August 2018

Abstract
Epidemiological and experimental studies have shown that natural products are beneficial for the protection against cancer. Maple syrup is a natural sweetener often consumed throughout the world. Maple syrup contains various phenolic compounds such as lignans, coumarin and Ginnalin A (GA). The aim of this study was to investigate the effects of GA shown to have cytotoxic and apoptotic effects in several human carcinoma cell lines. The effect of GA on cell viability was determined by a XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) assay as described in the manufacturer’s instruction. Total RNA was isolated from cancer cells using TRIzol Reagent and reverse transcription was performed using Script™ cDNA Synthesis Kit (Bio-Rad) according to the manufacturer’s instructions. Expressions of important genes in apoptosis including MMP-2, MMP-9, TIMP-1, TIMP-2, CDH1 and CDH2, were investigated in dose and control groups by qPCR (quantitative real time- polymerase chain reaction).
When compared with the control group, qPCR results illustrated that a significant increase in gene expression was observed in the expressions of CDH1, TIMP-1 and TIMP-2 by 3.52, 5.13 and 2.67 times respectively. Research has shown that Ginnalin A can demonstrate an anti-metastatic effect by regulating the expression of important genes in metastasis on cancer cell lines. Furthermore, in this study the activation of caspase-8 in apoptotic signaling pathways and the pro-apoptotic caspases required for extrinsic apoptotic signal transduction was defined.
Magnetic resonance T1-mapping evaluates the degree of thyroid destruction in patients with autoimmune thyroiditis
Authors: Liu Jia , Liu Min , Chen Zhe , Jia Yumei , Wang Guang 
Published: August 2018

Objective
Autoimmune thyroiditis (AIT) is the most common autoimmune thyroid disease. Longitudinal relaxation time mapping (T1-mapping) measured by MRI is a new technique for assessing interstitial fibrosis of some organs, such as heart and liver. This study aimed to evaluate the relationship between T1-mapping value and thyroid function and determine the usefulness of T1-mapping in identifying thyroid destruction in AIT patients.

Methods
This case–control study recruited 57 drug-naïve AIT patients and 17 healthy controls. All participants were given thyroid MRI, and T1-mapping values were measured using a modified look-locker inversion-recovery sequence.

Results
AIT patients had significantly higher thyroid T1-mapping values than the healthy controls (1.077 ± 177 vs 778 ± 82.9 ms; P < 0.01). A significant increase in thyroid T1-mapping values was presented along with the increased severity of thyroid dysfunction (P < 0.01). Correlation analyses showed that increased thyroid T1-mapping values were associated with higher TSH and lower FT3 and FT4 levels (TSH: r = 0.75; FT3: r = −0.47; FT4: r = −0.72; all P < 0.01). Receiver-operating characteristic curve analysis revealed a high diagnostic value of T1-mapping values for the degree of thyroid destruction (area under the curve was 0.95, 95% CI: 0.90–0.99, P < 0.01).

Conclusions
AIT patients have higher thyroid T1-mapping values than the healthy controls, and the T1-mapping values increased with the progression of thyroid dysfunction. Thyroid T1-mapping value might be a new index to quantitatively evaluate the degree of thyroid destruction in AIT patients.
Educação a distância e formação docente
Authors: Oliveira Simone Aparecida Possarli 
Published: August 2018

A educação a distância surge no cenário nacional como uma forma de democratização do ensino, preparando profissionais para atuação nas mais diversas áreas da educação. Com a formação de professores não poderia ser diferente. Contudo, cabe questionar: essa modalidade de ensino possibilita uma formação integral deste docente em meio ao processo de formação? Tendo em mente que esta trajetória formativa é toda permeada pelas tecnologias digitais de informação e comunicação em seus processos de ensino-aprendizagem. Esta pesquisa objetiva, portanto, investigar esse aspecto. Este artigo, de caráter qualitativo, busca, a partir de uma pesquisa bibliográfica, refletir sobre as contribuições dessa modalidade de ensino para a formação de professores, bem como averiguar a sua contribuição para a democratização do ensino no cenário nacional. Como fundamentação teórica utiliza-se dos estudos de Kensky (2010), Moran (2000), Lobo Neto (2006), Azevedo (2012, 2013, 2014), Bahia (2015), Belloni (2015), Demo (2009), Freire (1987), Masetto (2009) e Nóvoa (2009).