LLukas22/scidocs huggingface dataset:
CBP Activity Mediates Effects of the Histone Deacetylase Inhibitor Butyrate on WNT Activity and Apoptosis in Colon Cancer Cells

Mutations in the WNT/beta-catenin pathway are responsible for initiating the majority of colorectal cancers (CRCs). We have previously shown that hyperactivation of this signaling by histone deacetylase inhibitors (HDACis) such as butyrate, a fermentation product of dietary fiber, promotes CRC cell apoptosis. The extent of association between beta-catenin and the transcriptional coactivator CREB-binding protein (CBP) influences WNT/catenin signaling and, therefore, colonic cell physiology. CBP functions as a histone acetylase (HAT); therefore, we hypothesized that the modulation of WNT/catenin activity by CBP modifies the ability of the HDACi butyrate to hyperinduce WNT signaling and apoptosis in CRC cells. Our findings indicate that CBP affects the hyperinduction of WNT activity by butyrate. ICG-001, which specifically blocks association between CBP and beta-catenin, abrogates the butyrate-triggered increase in the number of CRC cells with high levels of WNT/catenin signaling. Combination treatment of CRC cells with ICG-001 and butyrate results in cell type-specific effects on apoptosis. Further, both butyrate and ICG-001 repress CRC cell proliferation, with additive effects in suppressing cell growth. Our study strongly suggests that ICG-001-like agents would be effective against butyrate/HDACi-resistant CRC cells. Therefore, ICG-001-like agents may represent an important therapeutic option for CRCs that exhibit low-fold hyperactivation of WNT activity and apoptosis in the presence of HDACis. The findings generated from this study may lead to approaches that utilize modulation of CBP activity to facilitate CRC therapeutic or chemopreventive strategies.
Asthma control measurement using five different questionnaires: a prospective study.

UNLABELLED
Questionnaires play a key place in the assessment of asthma control. Different questionnaires have been developed. However, it remains largely unknown whether they can be used interchangeably. We wondered whether the panel of frequently used scores would give similar measurement of asthma control. The present study aimed to assess the agreement between five specific questionnaires.


METHODS
In this prospective study, ninety-nine patients completed five commonly used asthma control scores: the GINA, the Asthma Control Test™, the Royal College of Physician score, the Asthma Therapy Assessment Questionnaire (ATAQ), and the Asthma Control Questionnaire(©) (ACQ). The kappa coefficient was used to assess the agreement between questionnaires.


RESULTS
The agreement between the GINA and other scores was only moderate (kappa coefficients amounted from 0.41 to 0.60). With respect to the "controlled" level, all the other scores gave higher results than GINA. All other scores also tended to underestimate GINA "uncontrolled level". For the "partly controlled level" defined by 3 of the 5 questionnaires, ACQ identified the same percentage of patients than GINA while ATAQ overestimated this percentage.


CONCLUSION
This study shows only moderate agreement between five commonly used asthma control scores. The GINA score showed the lowest percentage of controlled and the highest percentage of uncontrolled asthma. As a consequence, all these scores do not seem to evaluate the same symptoms.


TRIAL REGISTRATION NUMBER
NCT01350661.
Convolutional Neural Networks over Tree Structures for Programming Language Processing

Session: Feb. 15, 2016, 2‐3:30 pm Chair: Xiaobai Liu, San Diego State University (SDSU) Oral Presentations 920: On the Depth of Deep Neural Networks: A Theoretical View. Shizhao Sun, Wei Chen, Liwei Wang, Xiaoguang Liu, Tie‐Yan Liu 1229: How Important Is Weight Symmetry in Backpropagation? Qianli Liao, Joel Z. Leibo, Tomaso Poggio 1769: Deep Learning with S‐shaped Rectified Linear Activation Units. Xiaojie Jin, Chunyan Xu, Jiashi Feng, Yunchao Wei, Junjun Xiong, Shuicheng Yan 1142: Learning Step Size Controllers for Robust Neural Network Training. Christian Daniel, Jonathan Taylor, Sebastian Nowozin
A phase I study of histone deacetylase inhibitor, pracinostat (SB939), in pediatric patients with refractory solid tumors: IND203 a trial of the NCIC IND program/C17 pediatric phase I consortium.

BACKGROUND
Pracinostat (SB939) is a potent oral inhibitor of class 1, 2, and 4 histone deacetylases (HDAC). The adult recommended phase II dose (RP2D) is 60 mg po three times per week (t.i.w.) for 3 weeks every 4 weeks. This study assessed the toxicities and pharmacokinetics of pracinostat and determined the RP2D in children with refractory solid tumors.


METHODS
Pediatric patients with refractory solid tumors were treated with oral pracinostat t.i.w. for 3 consecutive weeks, followed by 1 week off dosing. Three dose levels-25, 35, and 45 mg/m(2) were evaluated using a standard 3 + 3 cohort design. Pharmacokinetic (PK) studies were optional.


RESULTS
Twelve patients were enrolled. The most common diagnosis was Ewing sarcoma. Most adverse events (AEs) were hematological with five (40%) patients experiencing grade 3 neutropenia. Non-hematological AEs were generally grade 1. No dose limiting toxicities occurred. More hematological and non-hematological AEs occurred at 45 mg/m(2) : Two of five patients experienced Grade 3 neutropenia and one each Grade 3 thrombocytopenia and leucopenia, Grade 1 fatigue and anorexia occurred in three. The RP2D was declared to be 45 mg/m(2) (comparable to an adult dose of 80 mg). One patient had a best response of stable disease (duration of 2.9 months). Three patients on 25 mg/m(2) and one each on 35 and 45 mg/m(2) participated in the PK study. No dose related changes in Cmax or AUC occurred.


CONCLUSIONS
Pracinostat is reasonably well tolerated in children with refractory solid tumors. The RP2D is 45 mg/m(2) .
BRAF mutation and CDKN2A deletion define a clinically distinct subgroup of childhood secondary high-grade glioma.

PURPOSE
To uncover the genetic events leading to transformation of pediatric low-grade glioma (PLGG) to secondary high-grade glioma (sHGG).


PATIENTS AND METHODS
We retrospectively identified patients with sHGG from a population-based cohort of 886 patients with PLGG with long clinical follow-up. Exome sequencing and array CGH were performed on available samples followed by detailed genetic analysis of the entire sHGG cohort. Clinical and outcome data of genetically distinct subgroups were obtained.


RESULTS
sHGG was observed in 2.9% of PLGGs (26 of 886 patients). Patients with sHGG had a high frequency of nonsilent somatic mutations compared with patients with primary pediatric high-grade glioma (HGG; median, 25 mutations per exome; P = .0042). Alterations in chromatin-modifying genes and telomere-maintenance pathways were commonly observed, whereas no sHGG harbored the BRAF-KIAA1549 fusion. The most recurrent alterations were BRAF V600E and CDKN2A deletion in 39% and 57% of sHGGs, respectively. Importantly, all BRAF V600E and 80% of CDKN2A alterations could be traced back to their PLGG counterparts. BRAF V600E distinguished sHGG from primary HGG (P = .0023), whereas BRAF and CDKN2A alterations were less commonly observed in PLGG that did not transform (P < .001 and P < .001 respectively). PLGGs with BRAF mutations had longer latency to transformation than wild-type PLGG (median, 6.65 years [range, 3.5 to 20.3 years] v 1.59 years [range, 0.32 to 15.9 years], respectively; P = .0389). Furthermore, 5-year overall survival was 75% ± 15% and 29% ± 12% for children with BRAF mutant and wild-type tumors, respectively (P = .024).


CONCLUSION
BRAF V600E mutations and CDKN2A deletions constitute a clinically distinct subtype of sHGG. The prolonged course to transformation for BRAF V600E PLGGs provides an opportunity for surgical interventions, surveillance, and targeted therapies to mitigate the outcome of sHGG.
Obtaining visual continuations with Visualcode

This paper briefly describes Visualcode and its use in the design of the RainbowScheme program visualization system. RainbowScheme represents Scheme continuations using a combination of text, colors, icons and tree-structured environments. "Visual continuations" greatly facilitate the understanding of the run-time behaviors of Scheme programs.
Biomechanical Evaluation of the Medial Stabilizers of the Patella.

BACKGROUND
Quantification of the biomechanical properties of each individual medial patellar ligament will facilitate an understanding of injury patterns and enhance anatomic reconstruction techniques by improving the selection of grafts possessing appropriate biomechanical properties for each ligament.


PURPOSE
To determine the ultimate failure load, stiffness, and mechanism of failure of the medial patellofemoral ligament (MPFL), medial patellotibial ligament (MPTL), and medial patellomeniscal ligament (MPML) to assist with selection of graft tissue for anatomic reconstructions.


STUDY DESIGN
Descriptive laboratory study.


METHODS
Twenty-two nonpaired, fresh-frozen cadaveric knees were dissected free of all soft tissue structures except for the MPFL, MPTL, and MPML. Two specimens were ultimately excluded because their medial structure fibers were lacerated during dissection. The patella was obliquely cut to test the MPFL and the MPTL-MPML complex separately. To ensure that the common patellar insertion of the MPTL and MPML was not compromised during testing, only one each of the MPML and MPTL were tested per specimen (n = 10 each). Specimens were secured in a dynamic tensile testing machine, and the ultimate load, stiffness, and mechanism of failure of each ligament (MPFL = 20, MPML = 10, and MPTL = 10) were recorded.


RESULTS
The mean ± SD ultimate load of the MPFL (178 ± 46 N) was not significantly greater than that of the MPTL (147 ± 80 N; P = .706) but was significantly greater than that of the MPML (105 ± 62 N; P = .001). The mean ultimate load of the MPTL was not significantly different from that of the MPML ( P = .210). Of the 20 MPFLs tested, 16 failed by midsubstance rupture and 4 by bony avulsion on the femur. Of the 10 MPTLs tested, 9 failed by midsubstance rupture and 1 by bony avulsion on the patella. Finally, of the 10 MPMLs tested, all 10 failed by midsubstance rupture. No significant difference was found in mean stiffness between the MPFL (23 ± 6 N/mm2) and the MPTL (31 ± 21 N/mm2; P = .169), but a significant difference was found between the MPFL and the MPML (14 ± 8 N/mm2; P = .003) and between the MPTL and MPML ( P = .028).


CONCLUSION
The MPFL and MPTL had comparable ultimate loads and stiffness, while the MPML had lower failure loads and stiffness. Midsubstance failure was the most common type of failure; therefore, reconstruction grafts should meet or exceed the values reported herein.


CLINICAL RELEVANCE
For an anatomic medial-sided knee reconstruction, the individual biomechanical contributions of the medial patellar ligamentous structures (MPFL, MPTL, and MPML) need to be characterized to facilitate an optimal reconstruction design.
Socioeconomic factors and processes associated with domestic violence in rural Bangladesh.

CONTEXT
Although the pervasiveness of domestic violence against women in Bangladesh is well documented, specific risk factors, particularly those that can be affected by policies and programs, are not well understood.


METHODS
In 2001-2002, surveys, in-depth interviews and small group discussions were conducted with married women from six Bangladeshi villages to examine the types and severity of domestic violence, and to explore the pathways through which women's social and economic circumstances may influence their vulnerability to violence in marriage. Women's odds of experiencing domestic violence in the past year were assessed by logistic regression analysis.


RESULTS
Of about 1,200 women surveyed, 67% had ever experienced domestic violence, and 35% had done so in the past year. According to the qualitative findings, participants expected women with more education and income to be less vulnerable to domestic violence; they also believed (or hoped) that having a dowry or a registered marriage could strengthen a women's position in her marriage. Yet, of these potential factors, only education was associated with significantly reduced odds of violence; meanwhile, the odds were increased for women who had a dowry agreement or had personal earnings that contributed more than nominally to the marital household. Women strongly supported educating their daughters, but pressures remain to marry them early, in part to avoid high dowry costs.


CONCLUSIONS
In rural Bangladesh, women's social and economic circumstances may influence their risk of domestic violence in complex and contradictory ways. Findings also suggest a disconnect between women's emerging expectations and their current realities.
Fluid Dynamics and Biofilm Removal Generated by Syringe-delivered and 2 Ultrasonic-assisted Irrigation Methods: A Novel Experimental Approach.

INTRODUCTION
Thorough understanding of fluid dynamics in root canal irrigation and corresponding antibiofilm capacity will support improved disinfection strategies. This study aimed to develop a standardized, simulated root canal model that allows real-time analysis of fluid/irrigation dynamics and its correlation with biofilm elimination.


METHODS
A maxillary incisor with an instrumented root canal was imaged with micro-computed tomography. The canal volume was reconstructed in 3 dimensions and replicated in soft lithography-based models microfabricated from polyethylene glycol-modified polydimethylsiloxane. Canals were irrigated by using a syringe (SI) and 2 ultrasonic-assisted methods, intermittent (IUAI) and continuous (CUAI). Real-time fluid movement within the apical 3 mm of canals was imaged by using microparticle image velocimetry. In similar models, canals were inoculated with Enterococcus faecalis to grow 3-week-old biofilms. Biofilm reduction by irrigation with SI, CUAI, and IUAI was assessed by using a crystal violet assay and compared with an untreated control.


RESULTS
SI generated higher velocity and shear stress in the apical 1-2 mm than 0-1 and 2-3 mm. IUAI generated consistently low shear stress in the apical 3 mm. CUAI generated consistently high levels of velocity and shear stress; it was the highest of the groups in the apical 0-1 and 2-3 mm. Biofilm was significantly reduced compared with the control only by CUAI (two-sample permutation test, P = .005).


CONCLUSIONS
CUAI exhibited the highest mechanical effects of fluid flow in the apical 3 mm, which correlated with significant biofilm reduction. The soft lithography-based models provided a novel model/method for study of correlations between fluid dynamics and the antibiofilm capacity of root canal irrigation methods.
Denial of Service Attacks on Inter-Vehicle Communication Networks

Future safety systems will rely on the transmission of vehicle positions and kinematics through direct vehicle-to-vehicle wireless communication. The wireless access in vehicular environments (WAVE) standards, however, are vulnerable to denial of service (DoS) attacks which could significantly reduce the message delivery rate for these heartbeat messages. The WAVE standards were implemented in a simulation system in order to evaluate three different types of DoS attacks on these messages in a highway environment. These simulations show that the characteristics of the vehicular environments and heart-beat messages amplify the effect of these attacks, reducing the performance in the network in areas far from the attacking node. The amplification was due to the aggregate strength of the attacker's and legitimate node's signals. These combined signals reduced both the ability of nodes to receive messages clearly and the ability of nodes to detect that media is idle.
Coping effectiveness training for men living with HIV: results from a randomized clinical trial testing a group-based intervention.

OBJECTIVE
This randomized clinical trial was designed to compare the effects of a theory-based coping effectiveness training (CET) intervention with an active informational control (HIV-Info) condition and a waiting-list control (WLC) condition on psychological distress and positive mood in HIV-seropositive gay men.


MATERIALS AND METHODS
The authors recruited 149 self-identified gay or bisexual men who were 21 to 60 years of age, reported depressed mood, and had CD4 levels of 200 to 700 cells/mm(3). CET and HIV-Info participants attended 10 90-minute group sessions during the 3-month intervention phase and six maintenance sessions over the remainder of the year. Participants were assessed at baseline and at 3, 6, and 12 months. Data were collected 1992 to 1994, before the introduction of HAART. Analyses were based on the 128 participants who completed the 3-month assessment.


RESULTS
After the 3-month intervention phase, when compared with HIV-Info, CET participants showed significantly greater decreases in perceived stress and burnout, and regression analyses indicated that significant increases in coping self-efficacy mediated the improvements in perceived stress and burnout. Compared with WLC, CET participants also showed significantly greater decreases in anxiety, and regression analyses indicated that significant increases in positive states of mind mediated the improvements in anxiety. Significant treatment group differences for positive morale were maintained at 6 and 12 months. In addition, optimism continued to increase in the CET and HIV-Info treatment groups during the maintenance phase.


CONCLUSIONS
CET can be an effective strategy for managing psychological distress and improving positive psychological states in patients confronting chronic illness.
Fast human detection with cascaded ensembles on the GPU

We investigate a fast pedestrian localization framework that integrates the cascade-of-rejectors approach with the Histograms of Oriented Gradients (HoG) features on a data parallel architecture. The salient features of humans are captured by HoG blocks of variable sizes and locations which are chosen by the AdaBoost algorithm from a large set of possible blocks. We use the integral image representation for histogram computation and a rejection cascade in a sliding-windows manner, both of which can be implemented in a data parallel fashion. Utilizing the NVIDIA CUDA framework to realize this method on a Graphics Processing Unit (GPU), we report a speed up by a factor of 13 over our CPU implementation. For a 1280×960 image our parallel technique attains a processing speed of 2.5 to 8 frames per second depending on the image scanning density, which is similar to the recent GPU implementation of the original HoG algorithm in [3].
Phase I trial of Uracil-Tegafur (UFT) plus oral leucovorin: 14-day schedule

We previously reported results of a Phase II trial of UFT [Taiho Pharmaceutical Ltd., Tokyo, Japan; (BMS-200604) Bristol-Myers Squibb, Princeton, NJ], an oral 4:1 molar concentration of uracil and tegafur, plus oral leucovorin for metastatic colorectal carcinoma (Pazdur et al, J. Clin. Oncol. 12:2296-2300, 1994]. Our results demonstrated that a 28-day schedule of this combination produced a response rate similar to that obtained with conventional intravenous fluorouracil (5-FU)-plus-leucovorin regimens but without the severe or life-threatening neutropenia or oral mucositis that complicates intravenous 5-FU regimens. The current Phase I trial examines the dose-limiting toxic effects and maximum tolerated dose of a 14-consecutive-day schedule of UFT plus oral leucovorin in 14 patients who had histologically proven cancer and had received prior chemotherapy. The daily UFT plus leucovorin dose was divided into three doses administered orally every 8 hours. In this study, the UFT dose was escalated while the leucovorin dose remained at 150 mg/day. Of the 14 patients, 4 were initially treated at the 350-mg/m2/day UFT level for 14 days without any dose-limiting toxic reactions. Subsequently, another 7 patients were treated at the 400-mg/m2/day level; grade 3 diarrhea developed in 3 of these 7 (with severe abdominal cramping in 2 cases and severe nausea and vomiting unresponsive to antiemetics in the third). To better define the starting dose for phase II studies, an additional 3 patients were treated at the 350-mg/m2/day dose level. Of the total 7 patients treated at 350 mg/m2/day, grade 3 toxic events (diarrhea) developed in 2 patients. Grade 1-2 toxic effects noted at this level included fatigue, stomatitis, skin rash, abdominal pain, nausea, and vomiting. Neither partial nor complete responses were observed in this trial. The maximum tolerated dose of this schedule is 350 mg/m2/day UFT plus 150 mg/day oral leucovorin. However, because of this schedule's inferior dose intensity compared with that of the 28-day schedule of UFT plus leucovorin, subsequent development of UFT in the United States has focused on the 28-day regimen.
MEGA-CC: computing core of molecular evolutionary genetics analysis program for automated and iterative data analysis

UNLABELLED
There is a growing need in the research community to apply the molecular evolutionary genetics analysis (MEGA) software tool for batch processing a large number of datasets and to integrate it into analysis workflows. Therefore, we now make available the computing core of the MEGA software as a stand-alone executable (MEGA-CC), along with an analysis prototyper (MEGA-Proto). MEGA-CC provides users with access to all the computational analyses available through MEGA's graphical user interface version. This includes methods for multiple sequence alignment, substitution model selection, evolutionary distance estimation, phylogeny inference, substitution rate and pattern estimation, tests of natural selection and ancestral sequence inference. Additionally, we have upgraded the source code for phylogenetic analysis using the maximum likelihood methods for parallel execution on multiple processors and cores. Here, we describe MEGA-CC and outline the steps for using MEGA-CC in tandem with MEGA-Proto for iterative and automated data analysis.


AVAILABILITY
http://www.megasoftware.net/.