bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Profiling of Patients with Colorectal Cancer and Matched Targeted Therapy in Phase I Clinical Trials
Authors: Dienstmann Rodrigo , Serpico Danila , Rodon Jordi , Saura Cristina , Macarulla Teresa , Elez Elena , Alsina Maria , Capdevila Jaume , Perez-Garcia Jose , Sánchez-Ollé Gessamí , Aura Claudia , Prudkin Ludmila , Landolfi Stefania , Hernández-Losa Javier , Vivancos Ana , Tabernero Josep 
Published: June 2012

Abstract
Clinical experience increasingly suggests that molecular prescreening and biomarker enrichment strategies in phase I trials with targeted therapies will improve the outcomes of patients with cancer. In keeping with the exigencies of a personalized oncology program, tumors from patients with advanced chemorefractory colorectal cancer were analyzed for specific aberrations (KRAS/BRAF/PIK3CA mutations, PTEN and pMET expression). Patients were subsequently offered phase I trials with matched targeted agents (MTA) directed at the identified anomalies. During 2010 and 2011, tumor molecular analysis was conducted in 254 patients: KRAS mutations (80 of 254, 31.5%), BRAF mutations (24 of 196, 12.2%), PIK3CA mutations (15 of 114, 13.2%), KRAS and PIK3CA mutations (9 of 114, 7.9%), low PTEN expression (97 of 183, 53.0%), and high pMET expression (38 of 64, 59.4%). In total, 68 patients received 82 different MTAs: phosphoinositide 3-kinase (PI3K) pathway inhibitor (if PIK3CA mutation, n = 10; or low PTEN, n = 32), PI3K pathway inhibitor plus MEK inhibitor (if KRAS mutation, n = 10; or BRAF mutation, n = 1), second-generation anti-EGF receptor monoclonal antibodies (if wild-type KRAS, n = 11), anti-hepatocyte growth factor monoclonal antibody (if high pMET, n = 10), mTOR inhibitor plus anti-insulin-like growth factor-1 receptor monoclonal antibody (if low PTEN, n = 5), and BRAF inhibitor (if BRAF mutation, n = 3). Median time-to-treatment failure on MTA was 7.9 versus 16.3 weeks for their prior systemic antitumor therapy (P &lt; 0.001). Partial response was seen in 1 patient [1.2%, PI3K inhibitor with PIK3CA mutation] and stable disease &gt;16 weeks in 10 cases (12.2%). These results suggest that matching chemorefractory patients with colorectal cancer with targeted agents in phase I trials based on the current molecular profile does not confer a significant clinical benefit. Mol Cancer Ther; 11(9); 2062–71. ©2012 AACR.
Learning to Sample: Eye Tracking and fMRI Indices of Changes in Object Perception
Authors: Emberson Lauren L. , Amso Dima 
Published: June 2012

Abstract
We used an fMRI/eye-tracking approach to examine the mechanisms involved in learning to segment a novel, occluded object in a scene. Previous research has suggested a role for effective visual sampling and prior experience in the development of mature object perception. However, it remains unclear how the naive system integrates across variable sampled experiences to induce perceptual change. We generated a Target Scene in which a novel occluded Target Object could be perceived as either “disconnected” or “complete.” We presented one group of participants with this scene in alternating sequence with variable visual experience: three Paired Scenes consisting of the same Target Object in variable rotations and states of occlusion. A second control group was presented with similar Paired Scenes that did not incorporate the Target Object. We found that, relative to the Control condition, participants in the Training condition were significantly more likely to change their percept from “disconnected” to “connected,” as indexed by pretraining and posttraining test performance. In addition, gaze patterns during Target Scene inspection differed as a function of variable object exposure. We found increased looking to the Target Object in the Training compared with the Control condition. This pattern was not restricted to participants who changed their initial “disconnected” object percept. Neuroimaging data suggest an involvement of the hippocampus and BG, as well as visual cortical and fronto-parietal regions, in using ongoing regular experience to enable changes in amodal completion.
BOLD Responses to Tactile Stimuli in Visual and Auditory Cortex Depend on the Frequency Content of Stimulation
Authors: Nordmark Per F. , Pruszynski J. Andrew , Johansson Roland S. 
Published: June 2012

Abstract
Although some brain areas preferentially process information from a particular sensory modality, these areas can also respond to other modalities. Here we used fMRI to show that such responsiveness to tactile stimuli depends on the temporal frequency of stimulation. Participants performed a tactile threshold-tracking task where the tip of either their left or right middle finger was stimulated at 3, 20, or 100 Hz. Whole-brain analysis revealed an effect of stimulus frequency in two regions: the auditory cortex and the visual cortex. The BOLD response in the auditory cortex was stronger during stimulation at hearable frequencies (20 and 100 Hz) whereas the response in the visual cortex was suppressed at infrasonic frequencies (3 Hz). Regardless of which hand was stimulated, the frequency-dependent effects were lateralized to the left auditory cortex and the right visual cortex. Furthermore, the frequency-dependent effects in both areas were abolished when the participants performed a visual task while receiving identical tactile stimulation as in the tactile threshold-tracking task. We interpret these findings in the context of the metamodal theory of brain function, which posits that brain areas contribute to sensory processing by performing specific computations regardless of input modality.
Context-dependent Changes in Functional Connectivity of Auditory Cortices during the Perception of Object Words
Authors: van Dam Wessel O. , van Dongen Eelco V. , Bekkering Harold , Rueschemeyer Shirley-Ann 
Published: June 2012

Abstract
Embodied theories hold that cognitive concepts are grounded in our sensorimotor systems. Specifically, a number of behavioral and neuroimaging studies have buttressed the idea that language concepts are represented in areas involved in perception and action [Pulvermueller, F. Brain mechanisms linking language and action. Nature Reviews Neuroscience, 6, 576–582, 2005; Barsalou, L. W. Perceptual symbol systems. Behavioral and Brain Sciences, 22, 577–660, 1999]. Proponents of a strong embodied account argue that activity in perception/action areas is triggered automatically upon encountering a word and reflect static semantic representations. In contrast to what would be expected if lexical semantic representations are automatically triggered upon encountering a word, a number of studies failed to find motor-related activity for words with a putative action-semantic component [Raposo, A., Moss, H. E., Stamatakis, E. A., & Tyler, L. K. Modulation of motor and premotor cortices by actions, action words and action sentences. Neuropsychologia, 47, 388–396, 2009; Rueschemeyer, S.-A., Brass, M., & Friederici, A. D. Comprehending prehending: Neural correlates of processing verbs with motor stems. Journal of Cognitive Neuroscience, 19, 855–865, 2007]. In a recent fMRI study, Van Dam and colleagues [Van Dam, W. O., Van Dijk, M., Bekkering, H., & Rueschemeyer, S.-A. Flexibility in embodied lexical-semantic representations. Human Brain Mapping, in press] showed that the degree to which a modality-specific region contributes to a representation considerably changes as a function of context. In the current study, we presented words for which both motor and visual properties (e.g., tennis ball, boxing glove) were important in constituting the concept. Our aim was to corroborate on earlier findings of flexible and context-dependent language representations by testing whether functional integration between auditory brain regions and perception/action areas is modulated by context. Functional connectivity was investigated by means of a psychophysiological interaction analysis, in which we found that bilateral superior temporal gyrus was more strongly connected with brain regions relevant for coding action information: (1) for Action Color words vs. Abstract words, and (2) for Action Color words presented in a context that emphasized action vs. a context that emphasized color properties.
Impaired Conflict Adaptation in an Emotional Task Context following Rostral Anterior Cingulate Cortex Lesions in Humans
Authors: Maier Martin E. , di Pellegrino Giuseppe 
Published: June 2012

Abstract
Recent brain imaging studies have implicated the rostral ACC (rACC) in the resolution of conflict between competing response tendencies in emotional task contexts, but not in neutral task contexts. This study tested the hypothesis that the rACC is necessary for such context-specific conflict adaptation. To this end, a group of patients with lesions of the rACC, a group of brain-damaged controls, and a group of normal controls classified the emotional expression (emotional task context) or the gender (neutral task context) of faces while ignoring congruent and incongruent words written across the faces. In all three groups, performance was worse with incongruent as compared with congruent stimuli in both task contexts. In the two control groups, this congruency effect was reduced following incongruent trials in both task contexts. By contrast, the rACC group displayed such conflict adaptation only in the neutral, but not in the emotional, task context. These results show that the rACC is necessary for conflict adaptation in emotional but not in neutral task contexts and suggest that the regulation of behavior is context specific.
Evaluating Data Assimilation Algorithms
Authors: Law K. J. H. , Stuart A. M. 
Published: June 2012

Abstract
Data assimilation leads naturally to a Bayesian formulation in which the posterior probability distribution of the system state, given all the observations on a time window of interest, plays a central conceptual role. The aim of this paper is to use this Bayesian posterior probability distribution as a gold standard against which to evaluate various commonly used data assimilation algorithms.
A key aspect of geophysical data assimilation is the high dimensionality and limited predictability of the computational model. This paper examines the two-dimensional Navier–Stokes equations in a periodic geometry, which has these features and yet is tractable for explicit and accurate computation of the posterior distribution by state-of-the-art statistical sampling techniques. The commonly used algorithms that are evaluated, as quantified by the relative error in reproducing moments of the posterior, are four-dimensional variational data assimilation (4DVAR) and a variety of sequential filtering approximations based on three-dimensional variational data assimilation (3DVAR) and on extended and ensemble Kalman filters.
The primary conclusions are that, under the assumption of a well-defined posterior probability distribution, (i) with appropriate parameter choices, approximate filters can perform well in reproducing the mean of the desired probability distribution, (ii) they do not perform as well in reproducing the covariance, and (iii) the error is compounded by the need to modify the covariance, in order to induce stability. Thus, filters can be a useful tool in predicting mean behavior but should be viewed with caution as predictors of uncertainty. These conclusions are intrinsic to the algorithms when assumptions underlying them are not valid and will not change if the model complexity is increased.
‘Earning and learning’ in those with psychotic disorders: The second Australian national survey of psychosis
Authors: Waghorn Geoffrey , Saha Sukanta , Harvey Carol , Morgan Vera A , Waterreus Anna , Bush Robert , Castle David , Galletly Cherrie , Stain Helen J , Neil Amanda L , McGorry Patrick , McGrath John J 
Published: June 2012

Objective: Participation in mainstream education and employment facilitates both the recovery and the social inclusion of people with psychotic disorders. As part of the second Australian survey of psychosis, we assessed labour force activity and participation in formal education among working age adults with psychotic disorders. Method: Data were drawn from a large national community prevalence survey of adults with psychotic disorders. Known as the Survey of High Impact Psychosis (SHIP), it was conducted in seven Australian catchment areas during March to December 2010. Current and past year labour force activity, current employment, past year participation in formal education and vocational training, and key clinical and demographic characteristics were examined in a sample of 1825 participants. Results: Only 22.4% of people with psychotic disorders were found to be employed (either full-time or part-time) in the month prior to the survey. In the previous 12 months, 32.7% were employed at some time. Of those in competitive employment, the majority worked part-time (63.9%), while a quarter worked 38 or more hours per week (23.4%). In terms of educational attainment, 18.4% reported difficulties with reading or writing, while 31.9% completed high school, which represents 12 years of formal education. Conclusions: The proportion currently employed has remained stable at 22% since the last national survey in 1997. Policy makers and service providers could do more to ensure people with psychotic disorders obtain access to more effective forms of assistance with respect to both their continuing education and employment. More effective vocational and educational interventions for people with psychotic disorders appear to be urgently needed.
Evaluation of the Maquet Neonatal and Pediatric Quadrox I with an integrated arterial line filter during cardiopulmonary bypass
Authors: Melchior RW , Schiavo K , Frey T , Rogers D , Patel J , Chelnik K , Rosenthal T 
Published: June 2012

Background: Perfusion equipment has evolved since its introduction into clinical practice more than fifty years ago to include smaller cardiopulmonary bypass (CPB) circuits and components. Perfusionists are now exploring the function of new oxygenators with an integrated arterial line filter (IALF). The purpose of this trial was to examine the Maquet Quadrox-I Neonatal and Pediatric oxygenators with IALF in a clinical setting, with respect to gas transfer, heat exchange co-efficiency (HEC), trans-membrane pressure (TMP) gradient and clinical experience. Methods: The Maquet Quadrox-I Neonatal oxygenator was used on 30 patients ranging from 2.2-13.1 kg. The Maquet Quadrox-I Pediatric oxygenator was used on 15 patients ranging from 12.7-24.5 kg. Arterial and venous blood gases were taken once the patient was stable on CPB and, subsequently, every 30 minutes afterwards, as per institution protocol. The values for gas transfer rates, HEC and TMP gradient were stratified into three main categories with each oxygenator: normothermia, cooling and re-warming. Results: During all conditions, the gas transfer rate with both oxygenators was efficient. The HEC values showed efficient heat exchanger performance during all conditions with both oxygenators. While maintaining CPB flow within the manufacturer’s recommended flow rate for each oxygenator, the TMP gradient range for the Neonatal Quadrox-I was 10-40 mmHg and the Pediatric Quadrox-I was 10-60 mmHg. During the clinical trial, foam was shown to break through the cardiotomy on several occasions when high sucker return was required. Conclusion: This new line of oxygenators performed well with regards to gas transfer, HEC and TMP gradient, but there were clinical experiences that did not meet expectations. There were repeated incidences with the venous reservoir which ultimately cast a negative light on the design of this new product from Maquet. In the future, the authors would like to evaluate updated versions of this product from Maquet and any other pediatric perfusion devices that could help the patient in the clinical arena.
Influence of foam structure and service environment on sound absorption characteristics of polyimide foams
Authors: Liu Xiao-Yan , Zhan Mao-Sheng , Wang Kai 
Published: June 2012

The sound absorption properties of open-celled polyimide foams at room temperature and high temperatures were tested by an AWA6122A standing wave tube and a temperature controllable impedance tube, respectively. The sound absorption characteristics of polyimide foams at room temperature were analyzed by applying the rigid end model and Helmholtz resonator model. The effects of material structures (thickness, density and cell size) and material service environments (frequency of sound wave, ambient temperature and mechanical crushing) on the sound absorption coefficients ( α) were investigated. The results showed that the models can predict the numerical relationship between the structure parameters and α. At frequencies below 1600 Hz the value of α increased with the increase of foam thickness and foam density and decreased with the increase of cell size. In contrast to untreated polyimide foams, the first resonant frequencies of mechanically crushed polyimide foams moved to higher frequencies and αincreased at higher frequencies. With an increase in temperature, at the same frequencies below 2000 Hz, the αof polyimide foams decreased and the first resonant frequencies trended to move towards higher frequencies. The experimental data indicated that the sound absorption properties of polyimide foams were significantly influenced by foam structures and service environments.
All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4)
Authors: Iland Harry J. , Bradstock Ken , Supple Shane G. , Catalano Alberto , Collins Marnie , Hertzberg Mark , Browett Peter , Grigg Andrew , Firkin Frank , Hugman Amanda , Reynolds John , Di Iulio Juliana , Tiley Campbell , Taylor Kerry , Filshie Robin , Seldon Michael , Taper John , Szer Jeff , Moore John , Bashford John , Seymour John F. 
Published: June 2012

Abstract
The treatment of acute promyelocytic leukemia has improved considerably after recognition of the effectiveness of all-trans-retinoic acid (ATRA), anthracycline-based chemotherapy, and arsenic trioxide (ATO). Here we report the use of all 3 agents in combination in an APML4 phase 2 protocol. For induction, ATO was superimposed on an ATRA and idarubicin backbone, with scheduling designed to exploit antileukemic synergy while minimizing cardiotoxicity and the severity of differentiation syndrome. Consolidation comprised 2 cycles of ATRA and ATO without chemotherapy, followed by 2 years of maintenance with ATRA, oral methotrexate, and 6-mercaptopurine. Of 124 evaluable patients, there were 4 (3.2%) early deaths, 118 (95%) hematologic complete remissions, and all 112 patients who commenced consolidation attained molecular complete remission. The 2-year rate for freedom from relapse is 97.5%, failure-free survival 88.1%, and overall survival 93.2%. These outcomes were not influenced by FLT3 mutation status, whereas failure-free survival was correlated with Sanz risk stratification (P[trend] = .03). Compared with our previously reported ATRA/idarubicin-based protocol (APML3), APML4 patients had statistically significantly improved freedom from relapse (P = .006) and failure-free survival (P = .01). In conclusion, the use of ATO in both induction and consolidation achieved excellent outcomes despite a substantial reduction in anthracycline exposure. This trial was registered at the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as ACTRN12605000070639.
Prolonged early G1 arrest by selective CDK4/CDK6 inhibition sensitizes myeloma cells to cytotoxic killing through cell cycle–coupled loss of IRF4
Authors: Huang Xiangao , Di Liberto Maurizio , Jayabalan David , Liang Jun , Ely Scott , Bretz Jamieson , Shaffer Arthur L. , Louie Tracey , Chen Isan , Randolph Sophia , Hahn William C. , Staudt Louis M. , Niesvizky Ruben , Moore Malcolm A. S. , Chen-Kiang Selina 
Published: June 2012

AbstractDysregulation of cyclin-dependent kinase 4 (CDK4) and CDK6 by gain of function or loss of inhibition is common in human cancer, including multiple myeloma, but success in targeting CDK with broad-spectrum inhibitors has been modest. By selective and reversible inhibition of CDK4/CDK6, we have developed a strategy to both inhibit proliferation and enhance cytotoxic killing of cancer cells. We show that induction of prolonged early-G1 arrest (pG1) by CDK4/CDK6 inhibition halts gene expression in early-G1 and prevents expression of genes programmed for other cell-cycle phases. Removal of the early-G1 block leads to S-phase synchronization (pG1-S) but fails to completely restore scheduled gene expression. Consequently, the IRF4 protein required to protect myeloma cells from apoptosis is markedly reduced in pG1 and further in pG1-S in response to cytotoxic agents, such as the proteasome inhibitor bortezomib. The coordinated loss of IRF4 and gain of Bim sensitize myeloma tumor cells to bortezomib-induced apoptosis in pG1 in the absence of Noxa and more profoundly in pG1-S in cooperation with Noxa in vitro. Induction of pG1 and pG1-S by reversible CDK4/CDK6 inhibition further augments tumor-specific bortezomib killing in myeloma xenografts. Reversible inhibition of CDK4/CDK6 in sequential combination therapy thus represents a novel mechanism-based cancer therapy.
Manipulation of the carbon storage regulator system for metabolite remodeling and biofuel production in Escherichia coli
Authors: McKee Adrienne E , Rutherford Becky J , Chivian Dylan C , Baidoo Edward K , Juminaga Darmawi , Kuo Dwight , Benke Peter I , Dietrich Jeffrey A , Ma Suzanne M , Arkin Adam P , Petzold Christopher J , Adams Paul D , Keasling Jay D , Chhabra Swapnil R 
Published: June 2012

Abstract

Background
Microbial engineering strategies that elicit global metabolic perturbations have the capacity to increase organism robustness for targeted metabolite production. In particular, perturbations to regulators of cellular systems that impact glycolysis and amino acid production while simultaneously decreasing fermentation by-products such as acetate and CO2 make ideal targets. Intriguingly, perturbation of the Carbon Storage Regulator (Csr) system has been previously implicated in large changes in central carbon metabolism in E. coli. Therefore, we hypothesized that perturbation of the Csr system through the CsrA-CsrB ribonucleoprotein complex might increase production of biofuels and their intermediates from heterologous pathways.

Results
We engaged the CsrA-CsrB ribonucleoprotein complex of E. coli via overexpression of CsrB. CsrB is a 350-nucleotide non-coding RNA that antagonizes CsrA, an RNA-binding protein that regulates translation of specific mRNA targets. By using shotgun proteomics and targeted metabolomics we established that elevation of CsrB levels leads to alterations in metabolite and protein levels in glycolysis, the TCA cycle and amino acid levels. Consequently, we show that such changes can be suitably applied to improve the production of desired compounds through the native fatty acid and heterologous n-butanol and isoprenoid pathways by up to two-fold. We also observed concomitant decreases in undesirable fermentation by-products such as acetate and CO2.

Conclusions
We have demonstrated that simple engineering of the RNA-based Csr global regulatory system constitutes a novel approach to obtaining pathway-independent improvements within engineered hosts. Additionally, since Csr is conserved across most prokaryotic species, this approach may also be amenable to a wide variety of production hosts.