bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutant p53 dictates the oncogenic activity of c-Abl in triple-negative breast cancers
Authors: Morrison Chevaun D , Chang Jenny C , Keri Ruth A , Schiemann William P 
Published: June 2017

AbstractWe recently established c-Abl as a potent suppressor of triple-negative breast cancer (TNBC) progression through its reactivation of a p53:p21 signaling axis coupled to senescence. Moreover, we observed co-expression of p53 and c-Abl to be essential for normal mammary epithelial cell physiology, as this relationship is lost upon breast cancer progression. Cytoplasmic c-Abl activity is markedly increased in some TNBCs and contributes to disease progression; however, the mechanisms underlying these events remain largely unknown. In addressing this question, we show here that c-Abl is predominantly restricted to the cytoplasm of human MDA-MB-231 TNBC cells, and to the nucleus of human MCF-7 luminal A cells. TTK is a mitotic protein kinase that phosphorylates c-Abl on Thr735, thereby creating a recognition binding motif for 14-3-3 adaptor proteins in response to oxidative stress. By interrogating the METABRIC database, we observed a significant correlation between p53 expression and that of c-Abl and TTK in basal-like breast cancers. Moreover, heterologous expression of TTK in MCF-7 cells significantly stimulated their growth in part via a c-Abl-dependent mechanism. Conversely, depleting TTK expression in MDA-MB-231 cells not only inhibited their organoid growth in 3D-cultures, but also sensitized them to the tumor suppressing activities of c-Abl independent of its subcellular localization. Moreover, we show that mutant p53 forms cytoplasmic complexes with c-Abl, thereby dictating the subcellular localization of c-Abl and the sensitivity of MDA-MB-231 cells to Imatinib. In response to nutrient deprivation, c-Abl:p53 complexes readily accumulate in the nucleus, resulting in the hyperactivation of c-Abl and initiation of its anti-tumor activities. Collectively, we identified a novel mutant p53:c-Abl cytoplasmic signaling complex that promotes MDA-MB-231 cell growth and highlights the contextual cues that confer oncogenic activity to c-Abl in breast cancer.
Understanding dynamic friction through spontaneously evolving laboratory earthquakes
Authors: Rubino V. , Rosakis A. J. , Lapusta N. 
Published: June 2017

AbstractFriction plays a key role in how ruptures unzip faults in the Earth’s crust and release waves that cause destructive shaking. Yet dynamic friction evolution is one of the biggest uncertainties in earthquake science. Here we report on novel measurements of evolving local friction during spontaneously developing mini-earthquakes in the laboratory, enabled by our ultrahigh speed full-field imaging technique. The technique captures the evolution of displacements, velocities and stresses of dynamic ruptures, whose rupture speed range from sub-Rayleigh to supershear. The observed friction has complex evolution, featuring initial velocity strengthening followed by substantial velocity weakening. Our measurements are consistent with rate-and-state friction formulations supplemented with flash heating but not with widely used slip-weakening friction laws. This study develops a new approach for measuring local evolution of dynamic friction and has important implications for understanding earthquake hazard since laws governing frictional resistance of faults are vital ingredients in physically-based predictive models of the earthquake source.
Miniature probe for mapping mechanical properties of vascular lesions using acoustic radiation force optical coherence elastography
Authors: Qu Yueqiao , Ma Teng , He Youmin , Yu Mingyue , Zhu Jiang , Miao Yusi , Dai Cuixia , Patel Pranav , Shung K. Kirk , Zhou Qifa , Chen Zhongping 
Published: June 2017

AbstractCardiovascular diseases are the leading cause of fatalities in the United States. Atherosclerotic plaques are one of the primary complications that can lead to strokes and heart attacks if left untreated. It is essential to diagnose the disease early and distinguish vulnerable plaques from harmless ones. Many methods focus on the structural or molecular properties of plaques. Mechanical properties have been shown to change drastically when abnormalities develop in arterial tissue. We report the development of an acoustic radiation force optical coherence elastography (ARF-OCE) system that uses an integrated miniature ultrasound and optical coherence tomography (OCT) probe to map the relative elasticity of vascular tissues. We demonstrate the capability of the miniature probe to map the biomechanical properties in phantom and human cadaver carotid arteries.
Evaluating Surgeon Estimation of Cup Position in Total Hip Arthroplasty: A Cadaver Study
Authors: Vigdorchik Jonathan , Cross MIchael , Miller Theodore , Bogner Eric , Muir Jeffrey , Schwarzkopf Ran 
Published: June 2017

AbstractInaccurate placement of components during total hip arthroplasty (THA) can lead to significant postoperative complications including revision surgery. Traditionally, surgeons grossly estimate component positioning intraoperatively using anatomical landmarks; however, evidence indicates that this surgeon assessment may not be reliable. The purpose of this study was to determine the accuracy of surgeon estimates of component position as compared with imaging (radiographs and computed tomography [CT] scan) and a new surgical navigation system. Three board-certified orthopaedic surgeons each performed four THA procedures on six cadavers (12 hips). Radiographs and CT scans were obtained postoperatively. The “gold standard” measurements of implanted cup anteversion and inclination were derived from three-dimensional renderings created from postoperative CTs. A reference value for cup position was created by aligning the anterior pelvic plane in each rendering coplanar with the CT table. Following each procedure, surgeons provided their estimate of acetabular cup component orientation. Surgeon estimates were compared with data gathered from postoperative radiographs, CT scans, and the navigation device. Surgeon estimates of anteversion and inclination were within 10 degrees of reference values in 64% (7/11) and 82% (9/11) of cases, respectively. Surgeon estimates of anteversion differed from reference values by a mean of 7.6 ± 5 degrees, whereas inclination differed from reference values by a mean of 6.1 ± 5.1 degrees (all means absolute). Radiographic measurements differed from reference values by 7.8 ± 4.3 degrees (p > 0.05) and 2.7 ± 2.3 degrees (p = 0.06) for anteversion and inclination, respectively, whereas CT values differed by 2.5 ± 1.6 degrees (p = 0.004) and 2.3 ± 2.1 degrees (p = 0.04). The navigation system differed from reference values by 4 ± 4 degrees (p = 0.08) and 4.2 ± 3.2 degrees (p = 0.31). Surgeons underestimated anteversion and inclination by 7.7 ± 4.8 degrees and 6.9 ± 4.8 degrees, respectively. Surgeon underestimation was observed in 8/11 (73%) cases, with anteversion underestimated by > 5 degrees in 5/8 (62%) cases and inclination underestimated by > 5 degrees in 4/8 (50%) cases. Our findings suggest that surgeons tend to underestimate both anteversion and inclination and that the accuracy of their estimates is similar to that of radiographs. CT scans and the navigation system were able to provide more accurate measurements of cup position.
Quality in consecutive interpreting
Authors: Al-Kharabsheh Aladdin 
Published: June 2017

AbstractGiven the lack of sensitization to the multi-dimensional concept ofquality, and given the versatility of the concept ofrelevance, the present investigation attempts to examine the premise that Relevance Theory (RT) can function as a standard or a benchmark for maximizing and/or optimizing quality in CI. Whilst the theoretical part relies heavily on Ernst-August Gutt’s seminal workTranslation and Relevance: Cognition and Context(2000), the practical part draws on some empirical data obtained from trainee-interpreters’ recorded sessions at the Hashemite University (Jordan) in order to provide a relevance-driven account for some semantic, syntactic, and cultural difficulties and problems in CI. The study arrives at the main conclusion that the degree of quality in CI largely depends on the degree of relevance achieved by the interpreter’s TL version, i.e., quality in CI would rise exponentially with the degree of relevance achieved by the interpreter’s TL version. The study also concludes that the pragmatic RT can be considered a reliable instrument, a reliable frame of reference, or a reliable screening system that can ensure both relevance-building and a correspondingly concomitant quality-building in CI, i.e., RT can possibly fine-tune the interpreters’ performance in the booth.
Avoiding initiation of repair in L2 conversations-for-learning
Authors: Hauser Eric 
Published: June 2017

AbstractUsing audio-recorded data from second language (L2) English conversations-for-learning between an L2 user of English and a first language (L1) user of English (the researcher), this study analyzes cases in which the L1 user avoids initiation of repair. In each case, the L2 user appears to have misunderstood something said by the L1 user. Instead of initiating repair in next turn on the L2 user’s talk, or in third position on his own talk, the L1 user goes along, at least briefly, with the direction set by the L2 user. Often, the L1 user, sooner or later, returns to the misunderstood talk. Avoidance of repair initiation is one way in which the L1 user contributes to the construction of the L2 user as interactionally competent to participate in conversations-for-learning.
A Multicenter Pivotal Study to Evaluate Tissue Stabilized—Guided Subcision Using the Cellfina Device for the Treatment of Cellulite With 3-Year Follow-Up
Authors: Kaminer Michael S. , Coleman William P. , Weiss Robert A. , Robinson Deanne M. , Grossman Jody 
Published: June 2017

BACKGROUND
Cellulite is a common female cosmetic concern for which no single treatment option had been proven effective over the long term. A novel tissue stabilized-guided subsicion system (TS-GS system) has demonstrated significant reduction in the appearance of cellulite after treatment.

OBJECTIVE
The objective of this extended follow-up period was to assess the effectiveness of TS-GS out to 3 years after initial treatment.

PATIENTS AND METHODS
After completing an open-label, multicenter, pivotal study, 45 subjects were followed for an extended period of up to 3 years after receiving a single treatment using the TS-GS system. Treatment areas were photographed prior to the procedure and at multiple time points post-treatment throughout the 3 years. In this open-label study, subjects served as their own controls. Effectiveness was assessed based on blinded independent physician panel assessments of improvement from baseline using a cellulite severity scale. Subject aesthetic improvement and patient-reported satisfaction were also collected.

RESULTS
The results of this trial supported Food and Drug Administration clearance of the device for the long-term reduction in the appearance of cellulite following TS-GS.

CONCLUSION
These data further demonstrate the safety and efficacy of this treatment with no reduction in treatment benefits out to 3 years.
Treatment Patterns, Outcomes, and Patient Satisfaction of Primary Epidermally Limited Nonmelanoma Skin Cancer
Authors: Drew Benjamin A. , Karia Pritesh S. , Mora Ariana N. , Liang Christine A. , Schmults Chrysalyne D. 
Published: June 2017

BACKGROUND
Epidermally limited nonmelanoma skin cancer (ELNMSC) (superficial basal cell carcinoma [SBCC] and squamous cell carcinoma in situ [SCCIS]) is common. Data on outcomes and patient satisfaction are lacking.

OBJECTIVE
To examine treatment efficacy and satisfaction in ELNMSC patients.

PATIENTS AND METHODS
Retrospective cohort study of adults with primary SBCC or SCCIS. A 25% random subset completed a satisfaction questionnaire.

RESULTS
Five hundred and fifty patients with 227 SBCC and 451 SCCIS were included; 329 tumors (49%) were treated with Mohs micrographic surgery (MMS) and 349 (51%) with non-MMS (imiquimod [n = 26], 5% 5-fluorouracil [n = 234], ingenol mebutate [n = 32], or cryotherapy [n = 57]). Five-year recurrence-free survival was high in both groups, with MMS having a small but statistically significant advantage (99% vs 95%, p = .004). More MMS patients were willing to undergo treatment again (97% vs 86%, p = .024). Dissatisfaction was mostly due to prolonged treatment course and pain associated with non-MMS treatments.

CONCLUSION
Surgical and nonsurgical treatments for primary ELNMSC have low recurrence rates, though cure rate and patient satisfaction are higher with MMS. Treatment choice for epidermal NMSC may be guided through patient preferences regarding ability to comply with topical treatment, out-of-pocket costs, desire to treat surrounding field disease, and desire to avoid a surgical scar.
Prevalence of Anal Dysplasia in Human Immunodeficiency Virus–Infected Transgender Women
Authors: Kobayashi Takaaki , Sigel Keith , Gaisa Michael 
Published: June 2017

Abstract
Although human immunodeficiency virus–infected men who have sex with men are at high risk for anal cancer, little is known about the prevalence of anal dysplasia in human immunodeficiency virus (HIV)-infected transgender women. Our study found that prevalence rates of abnormal anal cytology and histology in HIV-infected transgender women were similar to those in HIV-infected men who have sex with men.
Current directions in research and treatment of fear of cancer recurrence
Authors: Sharpe Louise , Thewes Belinda , Butow Phyllis 
Published: June 2017

Purpose of review
An expert meeting in Ottawa in 2015 galvanized efforts to answer key questions relevant to the understanding and management of fear of cancer recurrence (FCR). The aim of this review is to summarize key developments.

Recent findings
A consensus on the definition of FCR has helped to further research in this area. There have been a number of theories put forward to account for the development of FCR, all of which share key components. Importantly, a number of important trials have been published that confirm both brief and more intensive interventions can successfully treat FCR.

Summary
The consensus definition of FCR is an important development, as is the development of treatments for FCR. There are now evidence-based options for the management of patients with clinical levels of FCR. Future research priorities include determining the optimal cut-off points for identifying clinically significant FCR, testing the major tenets of the recent theoretical formulations of FCR; and determining the relative efficacy and cost-effectiveness of different treatment approaches for managing FCR.
Linkage mapping of yeast cross protection connects gene expression variation to a higher-order organismal trait
Authors: Stuecker Tara N. , Scholes Amanda N. , Lewis Jeffrey A. 
Published: June 2017

AbstractGene expression variation is extensive in nature, and is hypothesized to play a major role in shaping phenotypic diversity. However, connecting differences in gene expression across individuals to higher-order organismal traits is not trivial. In many cases, gene expression variation may be evolutionarily neutral, and in other cases expression variation may only affect phenotype under specific conditions. To understand connections between gene expression variation and stress defense phenotypes, we have been leveraging extensive natural variation in the gene expression response to acute ethanol in laboratory and wildSaccharomyces cerevisiaestrains. Previous work found that the genetic architecture underlying these expression differences included dozens of “hotspot” loci that affected many transcripts intrans. In the present study, we provide new evidence that one of these expression QTL hotspot loci is responsible for natural variation in one particular stress defense phenotype—ethanol-induced cross protection against severe doses of H2O2. The causative polymorphism is in the heme-activated transcription factor Hap1p, which we show directly impacts cross protection, but not the basal H2O2resistance of unstressed cells. This provides further support that distinct cellular mechanisms underlie basal and acquired stress resistance. We also show that the Hap1p-dependent cross protection relies on novel regulation of cytosolic catalase T (Ctt1p) during ethanol stress in wild strains. Because ethanol accumulation precedes aerobic respiration and accompanying reactive oxygen species formation, wild strains with the ability to anticipate impending oxidative stress would likely be at an advantage. This study highlights how strategically chosen traits that better correlate with gene expression changes can improve our power to identify novel connections between gene expression variation and higher-order organismal phenotypes.
Myocardial injury in critically ill patients with community-acquired pneumonia
Authors: Frencken Jos. F. , van Baal Lottie , Kappen Teus H. , Donker Dirk W. , Horn Janneke , van der Poll Tom , van Klei Wilton A. , Bonten Marc J.M. , Cremer Olaf L. ,   on behalf of the MARS consortium
Published: June 2017

AbstractBackgroundMyocardial injury, as reflected by elevated cardiac troponin levels in plasma, is common in patients with community-acquired pneumonia (CAP), but its temporal dynamics and etiology remain unknown. Our aim was to determine the incidence of troponin release in patients with CAP and identify risk factors which may point to underlying etiologic mechanisms.MethodsWe included consecutive patients admitted with severe CAP to two intensive care units in the Netherlands between 2011 and 2015. High-sensitivity cardiac troponin I was measured daily during the first week. We used multivariable linear regression to identify variables associated with troponin release on admission, and mixed-effects regression to model the daily rise and fall of troponin levels over time.ResultsAmong 200 eligible patients, 179 were included, yielding 792 observation days. A total of 152 (85%) patients developed raised troponin levels >26 ng/L. Baseline factors independently associated with troponin release included coronary artery disease (160% increase, 95% CI 7–529), smoking (304% increase, 95% CI 59-924), and higher APACHE IV score (2% increase, 95% CI 0.7-3.3), whereasStaphylococcus aureusas a causative pathogen was protective (67% reduction, 95% CI 9-88). Time-dependent risk factors independently associated with daily increase in troponin concentrations included reduced platelet count (1.7% increase, 95% CI 0.1-3.4), tachycardia (1.6% increase, 95% CI 0.3-3), hypotension (5.1% increase, 95% CI 1-9.4) and dobutamine use (38.4% increase 95% CI 8.8-76).ConclusionsCardiac injury develops in a majority of patients with severe CAP. Myocardial oxygen supply-demand mismatch and activated coagulation are potential causes of this injury.
Balancing the Local and the Universal in Maintaining Ethical Access to a Genomics Biobank
Authors: Heeney Catherine , Kerr Shona M. 
Published: June 2017

AbstractBackgroundIssues of balancing data accessibility with ethical considerations and governance of a genomics research biobank, Generation Scotland, are explored within the evolving policy landscape of the past ten years. During this time data sharing and open data access have become increasingly important topics in biomedical research. Decisions around data access are influenced by local arrangements for governance and practices such as linkage to health records, and the global through policies for biobanking and the sharing of data with large-scale biomedical research data resources and consortia.MethodsWe use a literature review of policy relevant documents which apply to the conduct of biobanks in two areas: support for open access and the protection of data subjects and researchers managing a bioresource. We present examples of decision making within a biobank based upon observations of the Generation Scotland Access Committee. We reflect upon how the drive towards open access raises ethical dilemmas for established biorepositories containing data and samples from human subjects.ResultsDespite much discussion in science policy literature about standardisation, the contextual aspects of biobanking are often overlooked. Using our engagement with GS we demonstrate the importance of local arrangements in the creation of a responsive ethical approach to biorepository governance. We argue that governance decisions regarding access to the biobank are intertwined with considerations about maintenance and viability at the local level. We show that in addition to the focus upon ever more universal and standardised practices, the local expertise gained in the management of such repositories must be supported.ConclusionsA commitment to open access in genomics research has found almost universal backing in science and health policy circles, but repositories of data and samples from human subjects may have to operate under managed access, to protect privacy, align with participant consent and ensure that the resource can be managed in a sustainable way. Data access committees need to be reflexive and flexible, to cope with changing technology and opportunities and threats from the wider data sharing environment. To understand these interactions also involves nurturing what is particular about the biobank in its local context.
A model for sheath formation coupled to motility inLeptothrix ochracea
Authors: Vesenka James , Havu James , Emerson David 
Published: June 2017

AbstractOptical and atomic force microscopy (AFM) of naturally occurringLeptothrix ochraceawas used to study the fine structure of sheaths and cells. Morphology of young sheaths suggests the scaffold chains have strong self-adhesion. Evidence from un-encapsulated cells indicates fresh scaffold production through cell walls. Simple diffusion arguments are used to explain the morphology of the sheath structure. We propose a novel cell motility model based on previously published video data, our AFM images of naked cells, and simple flow calculations. The model indicates that motility results from differential shear forces resulting from extrusion of sheath material that passively pushes a filament of connected cells forward as the surrounding sheath material hardens behind the cell train.
Variation in neuronal activity state, axonal projection target, and position principally define the transcriptional identity of individual neocortical projection neurons
Authors: Chevée Maxime , Robertson Johanna D. , Cannon Gabrielle H. , Brown Solange P. , Goff Loyal A. 
Published: June 2017

ABSTRACTSingle-cell RNA sequencing technologies have generated the first catalogs of transcriptionally defined neuronal subtypes of the brain. However, the biologically informative cellular processes that contribute to neuronal subtype specification and transcriptional heterogeneity remain unclear. By comparing the gene expression profiles of single layer 6 corticothalamic neurons in somatosensory cortex, we show that transcriptional subtypes primarily reflect axonal projection pattern, laminar position within the cortex, and neuronal activity state. Pseudotemporal ordering of 1023 cellular responses to manipulation of sensory input demonstrates that changes in expression of activity-induced genes both reinforced cell-type identity and contributed to increased transcriptional heterogeneity within each cell type. This is due to cell-type specific biases in the choice of transcriptional states following manipulation of neuronal activity. These results reveal that axonal projection pattern, laminar position, and activity state define significant axes of variation that contribute both to the transcriptional identity of individual neurons and to the transcriptional heterogeneity within each neuronal subtype.