bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRAF Fusions Define a Distinct Molecular Subset of Melanomas with Potential Sensitivity to MEK Inhibition
Authors: Hutchinson Katherine E. , Lipson Doron , Stephens Philip J. , Otto Geoff , Lehmann Brian D. , Lyle Pamela L. , Vnencak-Jones Cindy L. , Ross Jeffrey S. , Pietenpol Jennifer A. , Sosman Jeffrey A. , Puzanov Igor , Miller Vincent A. , Pao William 
Published: December 2013

Abstract
Purpose: Recurrent “driver” mutations at specific loci in BRAF, NRAS, KIT, GNAQ, and GNA11 define clinically relevant molecular subsets of melanoma, but more than 30% are “pan-negative” for these recurrent mutations. We sought to identify additional potential drivers in “pan-negative” melanoma.
Experimental Design: Using a targeted next-generation sequencing (NGS) assay (FoundationOne™) and targeted RNA sequencing, we identified a novel PAPSS1-BRAF fusion in a “pan-negative” melanoma. We then analyzed NGS data from 51 additional melanomas genotyped by FoundationOne™, as well as melanoma RNA, whole-genome and whole-exome sequencing data in The Cancer Genome Atlas (TCGA), to determine the potential frequency of BRAF fusions in melanoma. We characterized the signaling properties of confirmed molecular alterations by ectopic expression of engineered cDNAs in 293H cells.
Results: Activation of the mitogen-activated protein kinase (MAPK) pathway in cells by ectopic expression of PAPSS1-BRAF was abrogated by mitogen-activated protein kinase kinase (MEK) inhibition but not by BRAF inhibition. NGS data analysis of 51 additional melanomas revealed a second BRAF fusion (TRIM24-BRAF) in a “pan-negative” sample; MAPK signaling induced by TRIM24-BRAF was also MEK inhibitor sensitive. Through mining TCGA skin cutaneous melanoma dataset, we further identified two potential BRAF fusions in another 49 “pan-negative” cases.
Conclusions: BRAF fusions define a new molecular subset of melanoma, potentially comprising 4% to 8% of “pan-negative” cases. Their presence may explain an unexpected clinical response to MEK inhibitor therapy or assist in selecting patients for MEK-directed therapy. Clin Cancer Res; 19(24); 6696–702. ©2013 AACR.
Interpersonal Competence in Young Adulthood and Right Laterality in White Matter
Authors: De Pisapia Nicola , Serra Mauro , Rigo Paola , Jager Justin , Papinutto Nico , Esposito Gianluca , Venuti Paola , Bornstein Marc H. 
Published: December 2013

Abstract
The right hemisphere of the human brain is known to be involved in processes underlying emotion and social cognition. Clinical neuropsychology investigations and brain lesion studies have linked a number of personality and social disorders to abnormal white matter (WM) integrity in the right hemisphere. Here, we tested the hypothesis that interpersonal competencies are associated with integrity of WM tracts in the right hemisphere of healthy young adults. Thirty-one participants underwent diffusion tensor imaging scanning. Fractional anisotropy was used to quantify water diffusion. After the scanning session, participants completed the Adolescent Interpersonal Competence Questionnaire. Fractional anisotropy was subsequently correlated with Adolescent Interpersonal Competence Questionnaire scores using tract-based spatial statistics. Higher interpersonal competencies are related to higher WM integrity in several major tracts of the right hemisphere, in specific the uncinate fasciculus, the cingulum, the forceps minor, the infero-fronto occipital fasciculus, the inferior longitudinal fasciculus, and the superior longitudinal fasciculus. These results provide the first direct analysis of the neuroanatomical basis of interpersonal competencies and young adult self-reported skills in social contexts.
Dissociating Motivation from Reward in Human Striatal Activity
Authors: Miller Eric M. , Shankar Maya U. , Knutson Brian , McClure Samuel M. 
Published: December 2013

Abstract
Neural activity in the striatum has consistently been shown to scale with the value of anticipated rewards. As a result, it is common across a number of neuroscientific subdiscliplines to associate activation in the striatum with anticipation of a rewarding outcome or a positive emotional state. However, most studies have failed to dissociate expected value from the motivation associated with seeking a reward. Although motivation generally scales positively with increases in potential reward, there are circumstances in which this linkage does not apply. The current study dissociates value-related activation from that induced by motivation alone by employing a task in which motivation increased as anticipated reward decreased. This design reverses the typical relationship between motivation and reward, allowing us to differentially investigate fMRI BOLD responses that scale with each. We report that activity scaled differently with value and motivation across the striatum. Specifically, responses in the caudate and putamen increased with motivation, whereas nucleus accumbens activity increased with expected reward. Consistent with this, self-report ratings indicated a positive association between caudate and putamen activity and arousal, whereas activity in the nucleus accumbens was more associated with liking. We conclude that there exist regional limits on inferring reward expectation from striatal activation.
White Noise Improves Learning by Modulating Activity in Dopaminergic Midbrain Regions and Right Superior Temporal Sulcus
Authors: Rausch Vanessa H. , Bauch Eva M. , Bunzeck Nico 
Published: December 2013

Abstract
In neural systems, information processing can be facilitated by adding an optimal level of white noise. Although this phenomenon, the so-called stochastic resonance, has traditionally been linked with perception, recent evidence indicates that white noise may also exert positive effects on cognitive functions, such as learning and memory. The underlying neural mechanisms, however, remain unclear. Here, on the basis of recent theories, we tested the hypothesis that auditory white noise, when presented during the encoding of scene images, enhances subsequent recognition memory performance and modulates activity within the dopaminergic midbrain (i.e., substantia nigra/ventral tegmental area, SN/VTA). Indeed, in a behavioral experiment, we can show in healthy humans that auditory white noise—but not control sounds, such as a sinus tone—slightly improves recognition memory. In an fMRI experiment, white noise selectively enhances stimulus-driven phasic activity in the SN/VTA and auditory cortex. Moreover, it induces stronger connectivity between SN/VTA and right STS, which, in addition, exhibited a positive correlation with subsequent memory improvement by white noise. Our results suggest that the beneficial effects of auditory white noise on learning depend on dopaminergic neuromodulation and enhanced connectivity between midbrain regions and the STS—a key player in attention modulation. Moreover, they indicate that white noise could be particularly useful to facilitate learning in conditions where changes of the mesolimbic system are causally related to memory deficits including healthy and pathological aging.
Reorganization of Retinotopic Maps after Occipital Lobe Infarction
Authors: Vaina Lucia M. , Soloviev Sergei , Calabro Finnegan J. , Buonanno Ferdinando , Passingham Richard , Cowey Alan 
Published: December 2013

Abstract
We studied patient JS, who had a right occipital infarct that encroached on visual areas V1, V2v, and VP. When tested psychophysically, he was very impaired at detecting the direction of motion in random dot displays where a variable proportion of dots moving in one direction (signal) were embedded in masking motion noise (noise dots). The impairment on this motion coherence task was especially marked when the display was presented to the upper left (affected) visual quadrant, contralateral to his lesion. However, with extensive training, by 11 months his threshold fell to the level of healthy participants. Training on the motion coherence task generalized to another motion task, the motion discontinuity task, on which he had to detect the presence of an edge that was defined by the difference in the direction of the coherently moving dots (signal) within the display. He was much better at this task at 8 than 3 months, and this improvement was associated with an increase in the activation of the human MT complex (hMT+) and in the kinetic occipital region as shown by repeated fMRI scans. We also used fMRI to perform retinotopic mapping at 3, 8, and 11 months after the infarct. We quantified the retinotopy and areal shifts by measuring the distances between the center of mass of functionally defined areas, computed in spherical surface-based coordinates. The functionally defined retinotopic areas V1, V2v, V2d, and VP were initially smaller in the lesioned right hemisphere, but they increased in size between 3 and 11 months. This change was not found in the normal, left hemisphere of the patient or in either hemispheres of the healthy control participants. We were interested in whether practice on the motion coherence task promoted the changes in the retinotopic maps. We compared the results for patient JS with those from another patient (PF) who had a comparable lesion but had not been given such practice. We found similar changes in the maps in the lesioned hemisphere of PF. However, PF was only scanned at 3 and 7 months, and the biggest shifts in patient JS were found between 8 and 11 months. Thus, it is important to carry out a prospective study with a trained and untrained group so as to determine whether the patterns of reorganization that we have observed can be further promoted by training.
Seasonal Climate Variability and Change in the Pacific Northwest of the United States
Authors: Abatzoglou John T. , Rupp David E. , Mote Philip W. 
Published: December 2013

Abstract
Observed changes in climate of the U.S. Pacific Northwest since the early twentieth century were examined using four different datasets. Annual mean temperature increased by approximately 0.6°–0.8°C from 1901 to 2012, with corroborating indicators including a lengthened freeze-free season, increased temperature of the coldest night of the year, and increased growing-season potential evapotranspiration. Seasonal temperature trends over shorter time scales (&lt;50 yr) were variable. Despite increased warming rates in most seasons over the last half century, nonsignificant cooling was observed during spring from 1980 to 2012. Observations show a long-term increase in spring precipitation; however, decreased summer and autumn precipitation and increased potential evapotranspiration have resulted in larger climatic water deficits over the past four decades. A bootstrapped multiple linear regression model was used to better resolve the temporal heterogeneity of seasonal temperature and precipitation trends and to apportion trends to internal climate variability, solar variability, volcanic aerosols, and anthropogenic forcing. The El Niño–Southern Oscillation and the Pacific–North American pattern were the primary modulators of seasonal temperature trends on multidecadal time scales: solar and volcanic forcing were nonsignificant predictors and contributed weakly to observed trends. Anthropogenic forcing was a significant predictor of, and the leading contributor to, long-term warming; natural factors alone fail to explain the observed warming. Conversely, poor model skill for seasonal precipitation suggests that other factors need to be considered to understand the sources of seasonal precipitation trends.
New approaches towards chronic pain: patient experiences of a solution-focused pain management programme
Authors: Dargan Peter J , Simm Rebecca , Murray Craig 
Published: December 2013

Research has suggested that Solution-Focused Brief Therapy (SFBT) may be effective in facilitating meaningful change for those living with chronic pain. This study aimed to further this understanding through exploring the experiences of people living with chronic pain, who had attended an 8-week solution-focused pain management programme. The design of this study was conducted in consultation with a service-user advisory group, and employed a qualitative and interpretative design rooted in critical community psychology, participatory research frameworks and emancipatory disability research. Five participants opted-in to the study following an opportunity sampling method of persons who had attended a programme in the last 18 months. Interviews were transcribed verbatim and analysed using inductive thematic analysis. Five main themes were identified: ‘Accessing the pain management programme’, ‘A solution-focused group’, ‘The solution-focused clinician’, ‘Solutions and changes’ and ‘Challenges and improvements’. Clinical and research implications of the findings are discussed. Summary points There has been an international proliferation of pain management programmes (PMPs) aimed at helping those with chronic pain to live well, despite an unremitting condition. Arguably, the most popular psychological approaches used within PMPs are informed by cognitive behavioural therapy (CBT). Despite a supportive evidence base for psychological approaches in pain management, there is a recognised need for further research into alternative approaches and their effectiveness. Emerging research and policy recommendations are beginning to value the expertise of those living with chronic conditions, particularly how these perspectives can be used to develop effective treatments and services. SFBT is an approach aimed at achieving a patient’s goals or ‘preferred future’ through identifying and utilising their expertise. SFBT may have significant efficacy in helping those with chronic conditions to live improved, meaningful lives.
A ventilation intervention study in classrooms to improve indoor air quality: the FRESH study
Authors: Rosbach Jeannette TM , Vonk Machiel , Duijm Frans , van Ginkel Jan T , Gehring Ulrike , Brunekreef Bert 
Published: December 2013

Abstract

Background
Classroom ventilation rates often do not meet building standards, although it is considered to be important to improve indoor air quality. Poor indoor air quality is thought to influence both children’s health and performance. Poor ventilation in The Netherlands most often occurs in the heating season. To improve classroom ventilation a tailor made mechanical ventilation device was developed to improve outdoor air supply. This paper studies the effect of this intervention.

Methods
The FRESH study (Forced-ventilation Related Environmental School Health) was designed to investigate the effect of a CO2 controlled mechanical ventilation intervention on classroom CO2 levels using a longitudinal cross-over design. Target CO2 concentrations were 800 and 1200 parts per million (ppm), respectively. The study included 18 classrooms from 17 schools from the north-eastern part of The Netherlands, 12 experimental classrooms and 6 control classrooms. Data on indoor levels of CO2, temperature and relative humidity were collected during three consecutive weeks per school during the heating seasons of 2010–2012. Associations between the intervention and weekly average indoor CO2 levels, classroom temperature and relative humidity were assessed by means of mixed models with random school-effects.

Results
At baseline, mean CO2 concentration for all schools was 1335 ppm (range: 763–2000 ppm). The intervention was able to significantly decrease CO2 levels in the intervention classrooms (F (2,10) = 17.59, p < 0.001), with a mean decrease of 491 ppm. With the target set at 800 ppm, mean CO2 was 841 ppm (range: 743–925 ppm); with the target set at 1200 ppm, mean CO2 was 975 ppm (range: 887–1077 ppm).

Conclusions
Although the device was not capable of precisely achieving the two predefined levels of CO2, our study showed that classroom CO2 levels can be reduced by intervening on classroom ventilation using a CO2 controlled mechanical ventilation system.
A mandatory modification in extracorporeal biventricular assist device (BIVAD) implantation: intercostal tunnel application: a case report
Authors: Oto Oztekin , Albayrak Gokhan , Ugurlu Baran , Kuserli Yusuf , Ozpelit Ebru , Guneri Sema 
Published: December 2013

Abstract
In this case, our patient was a heart transplant candidate connected to a respiratory system. An extracorporeal biventricular assist device (BIVAD) was the only option in order to bridge to transplantation. In routine procedures, it is recommended that Berlin Heart Excor cannulas be removed through the subfascial subcostal tunnel. As the severely dilated right ventricle compressed the apex of the left ventricle, which was also dilated to the mid-back zone of the left hemithorax, the whole length of the Extracorporeal BIVAD apical cannula had to remain within the thorax; however, the cannula was removed from the body by creating a tunnel at the 7th intercostal space. In the long-term follow-up, this compulsory modification has proven to be safe and effective.
Evaluation of culture media for the production of secondary metabolites in a natural products screening program
Authors: VanderMolen Karen M , Raja Huzefa A , El-Elimat Tamam , Oberlies Nicholas H 
Published: December 2013

Abstract
Variation in the growing environment can have significant impacts on the quantity and diversity of fungal secondary metabolites. In the industrial setting, optimization of growing conditions can lead to significantly increased production of a compound of interest. Such optimization becomes challenging in a drug-discovery screening situation, as the ideal conditions for one organism may induce poor metabolic diversity for a different organism. Here, the impact of different media types, including six liquid media and five solid media, on the secondary metabolite production of three fungal strains was examined in the context of the drug-discovery screening process. The relative production of marker compounds was used to evaluate the usefulness and reliability of each medium for the purpose of producing secondary metabolites.
Investigation of heavy metals in frequently utilized medicinal plants collected from environmentally diverse locations of north western India
Authors: Kulhari Alpana , Sheorayan Arun , Bajar Somvir , Sarkar Susheel , Chaudhury Ashok , Kalia Rajwant K. 
Published: December 2013

Abstract
The increasing prevalence of environmental pollution, especially soil contamination with heavy metals has led to their uptake in the human food chains through plant parts. Accumulation and magnification of heavy metals in human tissues through consumption of herbal remedies can cause hazardous impacts on health. Therefore, chemical profiling of nine heavy metals (Mn, Cr, Pb, Fe, Cd, Co, Zn, Ni and Hg) was undertaken in stem and leaf samples of ten medicinal plants (Acacia nilotica, Bacopa monnieri, Commiphora wightii, Ficus religiosa, Glycyrrhiza glabra, Hemidesmus indicus, Salvadora oleoides, Terminalia bellirica, Terminalia chebula and Withania somnifera) collected from environmentally diverse regions of Haryana and Rajasthan states in North-Western India. Concentration of all heavy metals, except Cr, was within permissible limits in the tested stem and leaf samples. Leaf samples had consistently more Cr compared to respective stem samples with highest concentration in leaf samples of Bacopa monnieri (13.19 ± 0.0480 ppm) and stem samples of Withania somnifera (4.93 ± 0.0185 ppm) both collected from Bahadurgarh (heavy industrial area), Haryana. This amount was beyond the permissible limit of 2.0 ppm defined by WHO for raw herbal material. Other two most perilous metals Pb (2.64 ± 0.0260) and Cd (0.04 ± 0.0274) were also recorded in Bahadurgarh region, although below permissible limits. Concentration of Hg remained below detectable levels in all the leaf and stem samples tested. These results suggested that cultivation of medicinal plants and other dietary herbs should be curtailed near environmentally polluted especially industrial areas for avoidance of health hazards.
Next generation sequencing-based expression profiling identifies signatures from benign stromal proliferations that define stromal components of breast cancer
Authors: Guo Xiangqian , Zhu Shirley X , Brunner Alayne L , van de Rijn Matt , West Robert B 
Published: December 2013

Abstract
Introduction
Multiple studies have shown that the tumor microenvironment (TME) of carcinomas can play an important role in the initiation, progression, and metastasis of cancer. Here we test the hypothesis that specific benign fibrous soft tissue tumor gene expression profiles may represent distinct stromal fibroblastic reaction types that occur in different breast cancers. The discovered stromal profiles could classify breast cancer based on the type of stromal reaction patterns in the TME.

Methods
Next generation sequencing-based gene expression profiling (3SEQ) was performed on formalin fixed, paraffin embedded (FFPE) samples of 10 types of fibrous soft tissue tumors. We determined the extent to which these signatures could identify distinct subsets of breast cancers in four publicly available breast cancer datasets.

Results
A total of 53 fibrous tumors were sequenced by 3SEQ with an average of 29 million reads per sample. Both the gene signatures derived from elastofibroma (EF) and fibroma of tendon sheath (FOTS) demonstrated robust outcome results for survival in the four breast cancer datasets. The breast cancers positive for the EF signature (20-33% of the cohort) demonstrated significantly better outcome for survival. In contrast, the FOTS signature-positive breast cancers (11-35% of the cohort) had a worse outcome.

Conclusions
We defined and validated two new stromal signatures in breast cancer (EF and FOTS), which are significantly associated with prognosis. Our group has previously identified novel cancer stromal gene expression signatures associated with outcome differences in breast cancer by gene expression profiling of three soft tissue tumors, desmoid-type fibromatosis (DTF), solitary fibrous tumor (SFT), and tenosynovial giant cell tumor (TGCT/CSF1), as surrogates for stromal expression patterns. By combining the stromal signatures of EF and FOTS, with our previously identified DTF and TGCT/CSF1 signatures we can now characterize clinically relevant stromal expression profiles in the TME for between 74% to 90% of all breast cancers.