pinecone/core-2020-05-10-deduplication huggingface dataset:
Evaluating the Accessibility of Three Open-Source Learning Content Management Systems: A Comparative Study

Learning content management systems (LCMSs) have become increasingly popular in the educational
field over the past few years. However, problems in system design can create difficulties in the interactions
between LCMSs and an important sector of the user population. The assessment and monitoring of
LCMS accessibility are vital for the guarantee of universal accessibility in education. This article presents a
comparative study of the accessibility of three web-based, open-source LCMSs: Moodle, ATutor, and Sakai.
Results of the study indicate that barriers to accessibility are present in each of the three systems evaluated. A
primary aim of the study is to help detect and correct these barriers such that the goal of universal access in
educational environments may one day be achieved.This study was partially funded by the Research Network MA2VICMR (S2009/TIC-1542) and by GEMMA (TSI-020302-2010-141) and SAGAS (TSI-020100-2010-184) research projects
Interactive Learning Management System to Develop Spatial Visualization Abilities

An Interactive Learning Management System (ILMS) is presented, which functions as a web-based Spatial Visualization Ability (SVA) learning support tool for students of engineering graphics and as a management tool for teachers to track student learning. This software is designed to fill the gaps in student knowledge, giving them more uniform spatial visualization abilities when enrolling on University Engineering degrees. The ILMS_SVA consists of: (1) a Content Management System (CMS); (2) a preliminary level assessment test; (3) a web-based tool for exercise management and self-assessment incorporating a 3D viewer that functions as an interactive tutorial (IT), allowing the manipulation of 3D objects in every exercise; (4) a database. It is designed for three types of users (student, teacher, and administrator), and has been validated with engineering graphics students at the University of Burgos (Spain) by means of experimental trials in the classroom and a user satisfaction survey, over two academic years. The results indicate that use of this tool improved SVA among students generally and was even of greater effectiveness for those students that accessed engineering courses with no prior knowledge of Technical Drawing
JavaVis: An Integrated Computer Vision Library for Teaching Computer Vision

In this article, we present a new framework oriented to teach Computer Vision related subjects called JavaVis. It is a computer vision library divided in three main areas: 2D package is featured for classical computer vision processing; 3D package, which includes a complete 3D geometric toolset, is used for 3D vision computing; Desktop package comprises a tool for graphic designing and testing of new algorithms. JavaVis is designed to be easy to use, both for launching and testing existing algorithms and for developing new ones.This work was supported by project GRE10‐35 from Universidad de Alicante (Spain) and grant GITE‐09017‐UA of University of Alicante
Design of an experimental twin-rotor multi-input multi-output system

Twin-rotor multi-input multi-output system (TRMS) is a popular experimental setup utilized mostly for development and evaluation of aerovehicle control algorithms. Motivated by its popularity, construction steps of a TRMS setup in an academic setting are presented in this paper. Specifically, design of mechanical and electronic hardware components and development of related computer software are described in detail. Preliminary experiment results are also presented to demonstrate the performance of the system. © 2015 Wiley Periodicals, Inc.Scientific Research Projects Commission of Izmir Institute of Technology (2010-IYTE-15
Verifying the frequency ratios in the musical scale of just intonation with "hear-and-see" learning tools

In engineering colleges, Acoustics often includes the musical scale topic, which is not very popular with most engineering students. In order to face this situation, this paper presents two alternative or complementary “hear-and-see” learning tools for the musical scale of just intonation. The first one combines the hearing of musical notes from an electric organ with the display on an oscilloscope from which the frequency ratios are\ud
inferred. Alternatively, the frequencies are computed in advance on the basis of the theoretical frequency ratios, and an audio editor allows to hear the resulting notes, while the PC screen can display similar graphs to those on the oscilloscope.Postprint (author's final draft
Characterizing the outcomes of metastatic papillary renal cell carcinoma

Outcomes of metastatic papillary renal cell carcinoma (pRCC) patients are poorly characterized in the era of targeted therapy. A total of 5474 patients with metastatic renal cell carcinoma (mRCC) in the International mRCC Database Consortium (IMDC) were retrospectively analyzed. Outcomes were compared between clear cell (ccRCC; n = 5008) and papillary patients (n = 466), and recorded type I and type II papillary patients (n = 30 and n = 165, respectively). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) favored ccRCC over pRCC. OS was 8 months longer in ccRCC patients and the hazard ratio of death was 0.71 for ccRCC patients. No differences in PFS or ORR were detected between type I and II PRCC in this limited dataset. The median OS for type I pRCC was 20.0 months while the median OS for type II was 12.6 months (P = 0.096). The IMDC prognostic model was able to stratify pRCC patients into favorable risk (OS = 34.1 months), intermediate risk (OS = 17.0 months), and poor-risk groups (OS = 6.0 months). pRCC patient outcomes were inferior to ccRCC, even after controlling for IMDC prognostic factors. The IMDC prognostic model was able to effectively stratify pRCC patients.status: publishe
Vessel co-option in primary human tumors and metastases:  an obstacle to effective anti-angiogenic treatment?

Angiogenesis has been regarded as essential for tumor growth and progression.
Studies of many human tumors, however, suggest that their microcirculation
may be provided by nonsprouting vessels and that a variety of tumors can grow
and metastasize without angiogenesis. Vessel co-option, where tumor cells
migrate along the preexisting vessels of the host organ, is regarded as an alternative
tumor blood supply. Vessel co-option may occur in many malignancies,
but so far mostly reported in highly vascularized tissues such as brain, lung,
and liver. In primary and metastatic lung cancer and liver metastasis from different
primary origins, as much as 10–30% of the tumors are reported to use
this alternative blood supply. In addition, vessel co-option is introduced as a
potential explanation of antiangiogenic drug resistance, although the impact of
vessel co-option in this clinical setting is still to be further explored. In this
review we discuss tumor vessel co-option with specific examples of vessel cooption
in primary and secondary tumors and a consideration of the clinical
implications of this alternative tumor blood supply
CEACAM1 long isoform has opposite effects on the growth of human mastocytosis and medullary thyroid carcinoma cells

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed in a number of tumor cell types. The immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing isoforms of this molecule which possess a long cytoplasmic tail (CEACAM1-L) generally play inhibitory roles in cell function by interacting with Src homology 2 domain-containing tyrosine phosphatase (SHP)-1 and/or SHP-2. Src family kinases (SFKs) are also known to bind to and phosphorylate CEACAM1-L isoforms. Here, we report that CEACAM1 was uniquely expressed at high levels in both human neoplastic mast cells (mastocytosis) and medullary thyroid carcinoma cell (MTC) lines, when compared with their expression in nonneoplastic mast cells or nonneoplastic C cells. This expression was mainly derived from CEACAM1-L isoforms based upon assessment of CEACAM1 mRNA expression. CEACAM1 knockdown upregulated cell growth of HMC1.2 cells harboring KIT mutations detected in clinical mastocytosis, whereas downregulated the growth of TT cells harboring RET mutations detected in clinical MTCs. Immunoblotting, ELISA and immunoprecipitaion analysis showed that activated SHP-1 is preferentially associated with CEACAM1 in HMC1.2 cells harboring KIT mutations, whereas Src family kinases (SFKs) are preferentially associated with CEACAM1 in TT cells harboring RET mutations. These studies suggest that the dominantly interacting proteins SHP1 or SFK determine whether CEACAM1-L displays a positive or negative role in tumor cells
PD-1 as a potential target in cancer therapy

Recently, an improved understanding of the molecular mechanisms governing the host response to tumors has led to the identification of checkpoint signaling pathways involved in limiting the anticancer immune response. One of the most critical checkpoint pathways responsible for mediating tumor-induced immune suppression is the programmed death-1 (PD-1) pathway, normally involved in promoting tolerance and preventing tissue damage in settings of chronic inflammation. Many human solid tumors express PD ligand 1 (PD-L1), and this is often associated with a worse prognosis. Tumor-infiltrating lymphocytes from patients with cancer typically express PD-1 and have impaired antitumor functionality. Proof-of-concept has come from several preclinical studies in which blockade of PD-1 or PD-L1 enhanced T-cell function and tumor cell lysis. Three monoclonal antibodies against PD-1, and one against PD-L1, have reported phase 1 data. All four agents have shown encouraging preliminary activity, and those that have been evaluated in larger patient populations appear to have encouraging safety profiles. Additional data are eagerly awaited. This review summarizes emerging clinical data and potential of PD-1 pathway–targeted antibodies in development. If subsequent investigations confirm the initial results, it is conceivable that agents blocking the PD-1/PD-L1 pathway will prove valuable additions to the growing armamentarium of targeted immunotherapeutic agents. Next-generation immunotherapy agents that target the PD-1 checkpoint pathway are demonstrating antitumor activity and encouraging safety profiles in early clinical trials. Current and future clinical trials will provide new insights, and the evaluation of biomarkers and rational combination therapies is ongoing
Treatment with the vascular disruptive agent OXi4503 induces an immediate and widespread epithelial to mesenchymal transition in the surviving tumor

Epithelial to mesenchymal transition (EMT) is considered an important mechanism in tumor resistance to drug treatments; however, in vivo observation of this process has been limited. In this study we demonstrated an immediate and\ud
widespread EMT involving all surviving tumor cells following treatment of a mouse model of colorectal liver metastases with the vascular disruptive agent OXi4503. EMT was characterized by significant downregulation of E-cadherin, relocation and nuclear accumulation of b-catenin as well as significant upregulation of ZEB1 and vimentin. Concomitantly, significant temporal upregulation in hypoxia and the pro-angiogenic growth factors hypoxia-inducible factor 1-alpha, hepatocyte growth factor, vascular endothelial growth factor and transforming growth factor-beta were seen within the surviving tumor. The process\ud
of EMT was transient and by 5 days after treatment tumor cell reversion to epithelial morphology was evident. This reversal, termed mesenchymal to epithelial transition (MET) is a process implicated in the development of new metastases\ud
but has not been observed in vivo histologically. Similar EMT changes were observed in response to other antitumor treatments including chemotherapy, thermal ablation, and antiangiogenic treatments in our mouse colorectal metastasis\ud
model and in a murine orthotopic breast cancer model after OXi4503 treatment. These results suggest that EMT may be an early mechanism adopted by tumors in response to injury and hypoxic stress, such that inhibition of EMT in combination with other therapies could play a significant role in future\ud
cancer therapy
Anticancer efficacy of the hypoxia-activated prodrug evofosfamide is enhanced in combination with proapoptotic receptor agonists against osteosarcoma

Tumor hypoxia is a major cause of treatment failure for a variety of malignancies. However, hypoxia also leads to treatment opportunities as demonstrated by the development of compounds that target regions of hypoxia within tumors. Evofosfamide is a hypoxia-activated prodrug that is created by linking the hypoxia-seeking 2-nitroimidazole moiety to the cytotoxic bromo-isophosphoramide mustard (Br-IPM). When evofosfamide is delivered to hypoxic regions of tumors, the DNA cross-linking toxin, Br-IPM, is released leading to cell death. This study assessed the anticancer efficacy of evofosfamide in combination with the Proapoptotic Receptor Agonists (PARAs) dulanermin and drozitumab against human osteosarcoma in vitro and in an intratibial murine model of osteosarcoma. Under hypoxic conditions in vitro, evofosfamide cooperated with dulanermin and drozitumab, resulting in the potentiation of cytotoxicity to osteosarcoma cells. In contrast, under the same conditions, primary human osteoblasts were resistant to treatment. Animals transplanted with osteosarcoma cells directly into their tibiae developed mixed osteosclerotic/osteolytic bone lesions and consequently developed lung metastases 3 weeks post cancer cell transplantation. Tumor burden in the bone was reduced by evofosfamide treatment alone and in combination with drozitumab and prevented osteosarcoma-induced bone destruction while also reducing the growth of pulmonary metastases. These results suggest that evofosfamide may be an attractive therapeutic agent, with strong anticancer activity alone or in combination with either drozitumab or dulanermin against osteosarcoma.Vasilios Liapis, Aneta Zysk, Mark DeNichilo, Irene Zinonos, Shelley Hay, Vasilios Panagopoulos, Alexandra Shoubridge, Christopher Difelice, Vladimir Ponomarev, Wendy Ingman, Gerald J. Atkins, David M. Findlay, Andrew C. W. Zannettino and Andreas Evdokio
Hormone factors play a favorable role in female head and neck cancer risk.

Due to lower female incidence, estimates of exogenous and endogenous hormonal factors in head and neck cancers (HNCs, comprising cancers of the oral cavity, oropharynx, hypopharynx, and larynx) among women have been inconsistent and unable to account for key HNC risk factors. We pooled data from 11 studies from Europe, North America, and Japan. Analysis included 1572 HNC female cases and 4343 controls. Pooled odds ratios (ORs) estimates and their 95% confidence intervals (CIs) were calculated using multivariate logistic regression models adjusting for tobacco smoking and alcohol drinking. Lower risk was observed in women who used hormone replacement therapy (HRT) (OR = 0.58; 95% CI: 0.34-0.77). Pregnancy (OR = 0.61; 95% CI: 0.42-0.90) and giving birth (OR = 0.59; 95% CI: 0.38-0.90) at &lt;35 years of age were inversely associated with HNCs. An inverse association with HNC was observed with age at start of HRT use (OR = 0.59; 95% CI: 0.39-0.90) for each additional 10 years and with duration of use (OR = 0.87; 95% CI: 0.76-0.99 for every 3 years). Exogenous female hormone use is associated with a nearly twofold risk reduction in female HNCs. The lower female HNC incidence may, in part, be explained by endogenous and exogenous estrogen exposures
Cytoreductive nephrectomy for metastatic renal cell carcinoma: inequities in access exist despite improved survival

The use of cytoreductive nephrectomy (CRN) in the targeted therapy era is still debated. We aimed to determine factors associated with reduced use of CRN and determine the effect of CRN on overall survival in patients with metastatic renal cell carcinoma (RCC). All advanced RCC diagnosed between 2001 and 2009 in New South Wales, Australia, were identified from the Central Cancer Registry. Records of treatment and death were electronically linked. Follow-up was to the end of 2011. Multivariable logistic regression analysis was used to determine factors associated with the receipt of CRN. Cox proportional hazards model was used to determine factors associated with survival. A total of 1062 patients were identified with metastatic RCC of whom 289 (27%) received CRN. There was no difference in the use of CRN over the time period of the study. Females (OR 0.68 (95% CI: 0.48–0.96)), unmarried individuals (OR 0.68 (95% CI: 0.48–0.96)), treatment in a nonteaching hospital (OR 0.26 (95% CI: 0.18–0.36)) and individuals without private insurance (OR 0.29 (95% CI: 0.20–0.41)) all had reduced likelihood of receiving CRN. On multivariable analysis, not receiving CRN resulted in a 90% increase in death (HR 1.90 (95% CI: 1.61–2.25)). In addition, increasing age (P < 0.001), increasing Charlson comorbidity status (P = 0.002) and female gender also had a significant independent association with death. Despite a strong association with improved survival, individuals who are elderly, female, have treatment in a nonteaching facility or have no private insurance have a reduced likelihood of receiving CRN.Full Tex
Central nervous system relapse in patients over 80 years with diffuse large B-cell lymphoma : an analysis of two LYSA studies

CNS relapse is reported in 2-5% of diffuse large B-cell lymphoma (DLBCL) patients, dramatically decreasing overall survival (OS). Very few studies address incidence and risk factors of CNS relapse in very elderly patients, a challenging population to treat given their commonly associated comorbidities. A retrospective analysis was performed of 270 DLBCL patients >80 years treated between 2004 and 2013 in two multicentre phase II LYSA trials (LNH03-7B, LNH09-7B) evaluating the addition of rituximab or ofatumumab to mini-CHOP as front-line therapy. No patients received CNS prophylaxis. CNS relapse was evaluated according to cumulative incidence, patient characteristics, risk factors, and survival. Median age was 83 years (range: 79-95). After a median follow-up of 28.7 months, eight patients had CNS relapse (3.0%). Median time between inclusion and CNS relapse was 19.2 months (range: 3.2-32.6). Patients survived a median of 1.5 months after CNS relapse (range: 0.4-4.1). Median OS from relapse was significantly lower in CNS relapse patients (1.5 months, 95% CI: 0.4-3.5) compared to patients with non-CNS relapse (6.6 months; 95% CI: 4.6- 11.9). No baseline characteristics were associated with CNS relapse. The proportion of patients with CNS disease did not differ significantly between patients with low-intermediate risk according to CNS-IPI and patients with high risk (3% vs. 2.8%, P = 1.00). CNS relapse cumulative incidence in very elderly treatment-naive patients is 1.8% at 2 years and is associated with poor survival. This population had a long median time to CNS relapse. Absence of prophylaxis did not strongly impact CNS relapse incidence
A first-in-human phase I, multicenter, open-label, dose-escalation study of the oral RAF/VEGFR-2 inhibitor (RAF265) in locally advanced or metastatic melanoma independent from BRAF mutation status

To establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety profile, and anti-tumor efficacy of RAF265. We conducted a multicenter, open-label, phase-I, dose-escalation trial of RAF265, an orally available RAF kinase/VEGFR-2 inhibitor, in patients with advanced or metastatic melanoma. Pharmacokinetic (PK) analysis, pharmacodynamics (PD) and tumor response assessment were conducted. We evaluated metabolic tumor response by 18[F]-fluorodeoxyglucose-positron-emission tomography (FDG-PET), tissue biomarkers using immunohistochemistry (IHC), and modulators of angiogenesis. RAF265 has a serum half-life of approximately 200 h. The MTD was 48 mg once daily given continuously. Among 77 patients, most common treatment-related adverse effects were fatigue (52%), diarrhea (34%), weight loss (31%) and vitreous floaters (27%). Eight of 66 evaluable patients (12.1%) had an objective response, including seven partial and one complete response. Responses occurred in BRAF-mutant and BRAF wild-type (WT) patients. Twelve of 58 (20.7%) evaluable patients had a partial metabolic response. On-treatment versus pretreatment IHC staining in 23 patients showed dose-dependent p-ERK inhibition. We observed a significant temporal increase in placental growth factor levels and decrease in soluble vascular endothelial growth factor receptor 2 (sVEGFR-2) levels in all dose levels. RAF265 is an oral RAF/VEGFR-2 inhibitor that produced antitumor responses, metabolic responses, and modulated angiogenic growth factor levels. Antitumor activity occurred in patients with BRAF-mutant and BRAF-WT disease. Despite low activity at tolerable doses, this study provides a framework for the development of pan-RAF inhibitors and modulators of angiogenesis for the treatment of melanoma
Identification of hereditary cancer in the general population: development and validation of a screening questionnaire for obtaining the family history of cancer

One of the challenges for Latin American countries is to include in their healthcare
systems technologies that can be applied to hereditary cancer detection
and management. The aim of the study is to create and validate a questionnaire
to identify individuals with possible risk for hereditary cancer predisposition
syndromes (HCPS), using different strategies in a Cancer Prevention Service in
Brazil. The primary screening questionnaire (PSQ) was developed to identify
families at-risk for HCPS. The PSQ was validated using discrimination measures,
and the reproducibility was estimated through kappa coefficient. Patients with
at least one affirmative answer had the pedigree drawn using three alternative
interview approaches: in-person, by telephone, or letter. Validation of these
approaches was done. Kappa and intraclass correlation coefficients were used
to analyze data’s reproducibility considering the presence of clinical criteria for
HCPS. The PSQ was applied to a convenience sample of 20,000 women of
which 3121 (15.6%) answered at least one affirmative question and 1938 had
their pedigrees drawn. The PSQ showed sensitivity and specificity scores of
94.4% and 75%, respectively, and a kappa of 0.64. The strategies for pedigree
drawing had reproducibility coefficients of 0.976 and 0.850 for the telephone
and letter approaches, respectively. Pedigree analysis allowed us to identify 465
individuals (24.0%) fulfilling at least one clinical criterion for HCPS. The PSQ
fulfills its function, allowing the identification of HCPS at-risk families. The
use of alternative screening methods may reduce the number of excluded at-risk
individuals/families who live in locations where oncogenetic services are not
established.Research supported by Barretos Cancer
Hospital. EIP has a grant from FAPESP
(FAPESP, SP, Brazil, #2013/24633-2). N
Campacci is supported by a PhD fellowship
from FAPESP (FAPESP, SP, Brazil,
#2015/02444-9).info:eu-repo/semantics/publishedVersio