bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intratumoral genetic heterogeneity in metastatic melanoma is accompanied by variation in malignant behaviors
Authors: Anaka Matthew , Hudson Christopher , Lo Pu-Han , Do Hongdo , Caballero Otavia L , Davis Ian D , Dobrovic Alexander , Cebon Jonathan , Behren Andreas 
Published: October 2013

Abstract

Background
Intratumoral heterogeneity is a major obstacle for the treatment of cancer, as the presence of even minor populations that are insensitive to therapy can lead to disease relapse. Increased clonal diversity has been correlated with a poor prognosis for cancer patients, and we therefore examined genetic, transcriptional, and functional diversity in metastatic melanoma.

Methods
Amplicon sequencing and SNP microarrays were used to profile somatic mutations and DNA copy number changes in multiple regions from metastatic lesions. Clonal genetic and transcriptional heterogeneity was also assessed in single cell clones from early passage cell lines, which were then subjected to clonogenicity and drug sensitivity assays.

Results
MAPK pathway and tumor suppressor mutations were identified in all regions of the melanoma metastases analyzed. In contrast, we identified copy number abnormalities present in only some regions in addition to homogeneously present changes, suggesting ongoing genetic evolution following metastatic spread. Copy number heterogeneity from a tumor was represented in matched cell line clones, which also varied in their clonogenicity and drug sensitivity. Minor clones were identified based on dissimilarity to the parental cell line, and these clones were the most clonogenic and least sensitive to drugs. Finally, treatment of a polyclonal cell line with paclitaxel to enrich for drug-resistant cells resulted in the adoption of a gene expression profile with features of one of the minor clones, supporting the idea that these populations can mediate disease relapse.

Conclusion
Our results support the hypothesis that minor clones might have major consequences for patient outcomes in melanoma.
Pharmacokinetic study and evaluation of the safety of taurolidine for dogs with osteosarcoma
Authors: Marley Kevin , Helfand Stuart C , Simpson Jennifer , Mata John E , Tracewell William G , Brownlee Lisa , Bracha Shay , Séguin Bernard 
Published: October 2013

Abstract

Background
Osteosarcoma in dogs and humans share many similarities and the dog has been described as an excellent model to study this disease. The median survival in dogs has not improved in the last 25 years. Taurolidine has been shown to be cytotoxic to canine and human osteosarcoma in vitro. The goals of this study were to determine the pharmacokinetics and safety of taurolidine in healthy dogs and the safety of taurolidine in combination with doxorubicin or carboplatin in dogs with osteosarcoma.

Methods
Two percent taurolidine was infused into six healthy dogs (150 mg/kg) over a period of two hours and blood samples were taken periodically. One dog received taurolidine with polyvinylpyrrolidone (PVP) as its carrier and later received PVP-free taurolidine as did all other dogs in this study. Serum taurolidine concentrations were determined using high-performance liquid chromatography (HPLC) online coupled to ESI-MS/MS in the multiple reaction monitoring mode. Subsequently, the same dose of taurolidine was infused to seven dogs with osteosarcoma also treated with doxorubicin or carboplatin.

Results
Taurolidine infusion was safe in 6 healthy dogs and there were no significant side effects. Maximum taurolidine serum concentrations ranged between 229 to 646 μM. The dog that received taurolidine with PVP had an immediate allergic reaction but recovered fully after the infusion was stopped. Three additional dogs with osteosarcoma received doxorubicin and taurolidine without PVP. Toxicities included dilated cardiomyopathy, protein-losing nephropathy, renal insufficiency and vasculopathy at the injection site. One dog was switched to carboplatin instead of doxorubicin and an additional 4 dogs with osteosarcoma received taurolidine-carboplatin combination. One incidence of ototoxicity occurred with the taurolidine- carboplatin combination. Bone marrow and gastro-intestinal toxicity did not appear increased with taurolidine over doxorubicin or carboplatin alone.

Conclusions
Taurolidine did not substantially exacerbate bone marrow or gastro-intestinal toxicity however, it is possible that taurolidine increased other toxicities of doxorubicin and carboplatin. Administering taurolidine in combination with 30 mg/m2 doxorubicin in dogs is not recommended but taurolidine in combination with carboplatin (300 mg/m2) appears safe.
Clinical predictive value of manual muscle strength testing during critical illness: an observational cohort study
Authors: Connolly Bronwen A , Jones Gareth D , Curtis Alexandra A , Murphy Patrick B , Douiri Abdel , Hopkinson Nicholas S , Polkey Michael I , Moxham John , Hart Nicholas 
Published: October 2013

Abstract
Introduction
Impaired skeletal muscle function has important clinical outcome implications for survivors of critical illness. Previous studies employing volitional manual muscle testing for diagnosing intensive care unit-acquired weakness (ICU-AW) during the early stages of critical illness have only provided limited data on outcome. This study aimed to determine inter-observer agreement and clinical predictive value of the Medical Research Council sum score (MRC-SS) test in critically ill patients.

Methods
Study 1: Inter-observer agreement for ICU-AW between two clinicians in critically ill patients within ICU (n = 20) was compared with simulated presentations (n = 20). Study 2: MRC-SS at awakening in an unselected sequential ICU cohort was used to determine the clinical predictive value (n = 94) for outcomes of ICU and hospital mortality and length of stay.

Results
Although the intra-class correlation coefficient (ICC) for MRC-SS in the ICU was 0.94 (95% CI 0.85–0.98), κ statistic for diagnosis of ICU-AW (MRC-SS <48/60) was only 0.60 (95% CI 0.25–0.95). Agreement for simulated weakness presentations was almost complete (ICC 1.0 (95% CI 0.99–1.0), with a κ statistic of 1.0 (95% CI 1.0–1.0)). There was no association observed between ability to perform the MRC-SS and clinical outcome and no association between ICU-AW and mortality. Although ICU-AW demonstrated limited positive predictive value for ICU (54.2%; 95% CI 39.2–68.6) and hospital (66.7%; 95% CI 51.6–79.6) length of stay, the negative predictive value for ICU length of stay was clinically acceptable (88.2%; 95% CI 63.6–98.5).

Conclusions
These data highlight the limited clinical applicability of volitional muscle strength testing in critically ill patients. Alternative non-volitional strategies are required for assessment and monitoring of muscle function in the early stages of critical illness.
Interactive effects of competition and predator cues on immune responses of leopard frogs at metamorphosis
Authors: Groner Maya L. , Rollins-Smith Louise A. , Reinert Laura K. , Hempel John , Bier Mark E. , Relyea Rick A. 
Published: October 2013

Summary
Recent hypotheses suggest that immunosuppression, resulting from altered environmental conditions, may contribute to increased incidence of amphibian disease around the world. Antimicrobial peptides (AMPs) in amphibian skin are an important innate immune defense against fungal, viral and bacterial pathogens. Their release is tightly coupled with release of the stress hormone, norepinephrine. During metamorphosis, AMPs may constitute the primary immune response in the skin of some species because acquired immune functions are temporarily suppressed in order to prevent autoimmunity against new adult antigens. Suppression of AMPs during this transitional stage may impact disease rates. We exposed leopard frog tadpoles (Lithobates pipiens) to a factorial combination of competitor and caged-predator environments and measured their development, growth, and production of hydrophobic skin peptides after metamorphosis. In the absence of predator cues, or if the exposure to predator cues was late in ontogeny, competition caused more than a 250% increase in mass-standardized hydrophobic skin peptides. Predator cues caused a decrease in mass-standardized hydrophobic skin peptides when the exposure was late in ontogeny under low competition, but otherwise had no effect. Liquid chromatography mass spectrometry/mass spectrometry of the skin peptides showed that they may include three previously uncharacterized AMPs in the brevinin and temporin families. Both of these peptide families have previously been shown to inhibit harmful microbes including Batrachochytrium dendrobatidis, the fungal pathogen associated with global amphibian declines. Our study shows that amphibians may be able to adjust their skin peptide defenses in response to stressors that are experienced early in ontogeny and that these effects extend through an important life history transition.
Non-stressful temperature effect on oxidative balance and life history traits in adults fish (Oryzias latipes)
Authors: Hemmer-Brepson Claire , Replumaz Leslie , Romestaing Caroline , Voituron Yann , Daufresne Martin 
Published: October 2013

Summary
Temperature is well known to affect many biological and ecological traits, and especially of ectotherm species. From a physiological point of view, temperature is also positively correlated to metabolism and is often associated with an increase in reactive oxygen species (ROS) production. It has recently been suggested that ROS play a role in lifespan and resources allocation. However, only a few authors have attempted to explore the relationships between temperature, resources allocation and oxidative balance on ectotherms. Here, we propose to measure the effect of temperature on growth, reproductive effort, offspring quantity and quality, hatching and survival rates and the associated proximal costs with the quantification of oxidative balance elements. We reared adult fish (Oryzias latipes) at two non-stressful temperatures (20°C and 30°C) during a relatively long period (4 months, about the entire adult life). The results show a trade-off between reproduction and maintenance because (i) growth did not significantly differ between the 2 thermal groups. As expected (ii) metabolism is higher for warm-acclimated individuals, but (iii) ROS-dependent damages seem to not differ between the two groups, probably due to the higher rate of activation of (iv) the antioxidant enzyme (SOD) for warm-acclimated fish. These higher metabolisms and allocation toward antioxidant defences, are associated with an earlier reproduction and a lower quality of offspring. These interesting results bring new perspectives in terms of prediction of the impact of global warming on biota through the use of ecological theories based on oxidative balance and metabolism.
Pathology Consultation on Anticoagulation Monitoring
Authors: Wool Geoffrey D. , Lu Chuanyi M. 
Published: October 2013

AbstractObjectives:To review various anticoagulation therapies and related laboratory monitoring issues, with a focus on factor X–related chromogenic assays.Methods:A case-based approach is used to review pertinent published literatures and product inserts of anticoagulation drugs and to look back on clinical use of factor X–related chromogenic assays.Results:The number of anticoagulants available to clinicians has increased greatly in the past decade. Whether and how these anticoagulants should be monitored are areas of uncertainty for clinicians, which can lead to misuse of laboratory assays and suboptimal patient management. Factor X–related assays are of particular concern because of the similar and often confusing test names. Based on a common clinical case scenario and literature review regarding anticoagulant monitoring, an up-to-date discussion and review of the various factor X–related assays are provided, focusing on the differences in test designs and clinical utilities between the chromogenic anti-Xa and chromogenic factor X activity assays.Conclusions:Anticoagulation therapy and related laboratory monitoring are rapidly evolving areas of clinical practices. A good knowledge of relevant laboratory assays and their clinical applications is necessary to help optimize patient care.
Shots to the mind: Violence, the brain and biomedicine in popular novels and film in post-1960s America
Authors: Quinlan Sean M. 
Published: October 2013

Abstract
This article traces an unlikely and gruesome subject: how and why images of people getting shot in the head have become so pervasive in contemporary US fiction and film. Adopting a historical-genealogical approach, the analysis explores how the so-called headshot image emerged from two socio-cultural trends. First, the headshot referenced key historical traumas from the 1960s that involved the deaths of Ernest Hemingway, J. F. Kennedy and Nguyễn Văn Lém. Second, it drew upon strong anxieties over the new brain death diagnosis that was established by medical authorities in the late 1960s. The analysis then traces how this image was subsequently elaborated in books such as Mario Puzo’s The Godfather (1969) and Lawrence Sanders’ The First Deadly Sin (1973), as well as films such as Ted Post’s Magnum Force (1973) and Michael Cimino’s The Deer Hunter (1978). Finally, the article demonstrates key uses of the headshot in the recent novels of Don DeLillo and Cormac McCarthy. In all this, the headshot points to a much deeper undercurrent of narcissism and fragmentation that characterizes post-1960s culture in the United States.
Neighbourhoods or nothing? Social relations in David Lynch's Blue Velvet
Authors: Martin Richard 
Published: October 2013

Abstract
David Lynch’s Blue Velvet (1986) raises significant questions concerning small-town social relations in the United States, the corrupting powers of industrial urbanism and the notion of propinquity. It is a vivid rejoinder to the idealization of the small town and to comfortable notions of community in general. Through a close reading of the spatial strategies employed in Blue Velvet, this article maps Lynch’s conception of the neighbour and the neighbourhood. The analysis encompasses the political rhetoric of Ronald Reagan and Sarah Palin, the planning ideas of New Urbanism and critiques of the neighbour articulated by Freud and Žižek, as well as placing Blue Velvet in the context of Lynch’s other work.
‘It’s not your country any more’. Contested national narratives and the Columbus Day parade protests in Denver
Authors: Hitchmough Sam 
Published: October 2013

Abstract
This article explores long-standing American Indian opposition to Columbus Day in Denver. In 2007, Glenn Morris, a leading activist from the American Indian Movement of Colorado, stated that the rejection of the racist philosophy behind Columbus Day ‘may be the most important issue facing Indian country today’. Activism aimed at Columbus Day and the parades is a struggle over identity and historical memory, and Denver forms a distinctive, complex and emotive stage. The ideological nature of American Indian opposition to the holiday is examined and discussed as a blend of patriotic counter-narrative and nationalistic counter-memory. The opposition aims to highlight the historical actions of Columbus, but this is ultimately less important than confronting the way in which a conservative, individualistic myth of Columbus infuses itself into American society and psyche; the crux of activism revolves around the legacy of Columbus and the wider issues of decolonization that this raises.
Continental conjecture: Ephemera, imitation and America’s (late) modernist canons in the Three Mountains Press and Robert McAlmon’s Contact Editions
Authors: White Eric B. 
Published: October 2013

Abstract
Despite exciting occasional interest from critics of modernist fiction, autobiography and expatriate publishing, the writer-editor Robert McAlmon has remained on the margins of American modernist studies. Paradoxically, however, his fine press publishing house Contact Editions, in partnership with William Bird’s Three Mountains Press, played a central role in negotiating and problematizing mechanisms of canon formation at the onset of the late modernist cultural turn. The hallmarks of late modernism are revealed in prototypical form in selected titles they published – books which deliberately distorted the features of ‘major’ contemporaneous works to critique the failures and exclusions of high modernism. This essay examines the ‘American background’ of such responses through the lens of McAlmon’s editorial and literary career. Taking his contributions to American little magazines of the early 1920s as its point of departure, the essay explores how his publishing partnerships and intellectual transactions shaped his poetics of imitation, ephemera, and hybridity (emphases which modernists often connected to America as a literary subject). To this end, it also explores deluxe editions by William Carlos Williams, Ernest Hemingway, Gertrude Stein and Djuna Barnes, and concludes with readings of McAlmon’s Portrait of a Generation (1926a) and North America: Continent of Conjecture (1929a). Together, these works gave a physical shape to and archly satirical accounts of the themes and materials that accumulated in the wake of high modernism.
Androgen deprivation decreases prostate specific antigen in the absence of tumor: implications for interpretation of PSA results
Authors: Wenisch Judith M. , Mayr Florian B. , Spiel Alexander O. , Radicioni Milko , Jilma Bernd , Jilma-Stohlawetz Petra 
Published: October 2013

Abstract

Background: Prostate-specific antigen (PSA) is used as an outcome measure for relapsed disease in prostate cancer. Nonetheless, there are considerable concerns about its indiscriminate use as a surrogate endpoint for cell growth or survival. We hypothesized that treatment with a luteinizing hormone releasing hormone (LHRH) analog would decrease PSA levels even in the absence of malignant disease.

Methods: We determined testosterone and PSA levels in 30 healthy volunteers after a single intramuscular injection of a LHRH depot formulation. Testosterone and PSA levels were quantified by radioimmunoassay and electrochemi-luminescence immunoassay, respectively.

Results: After an initial flare-up during the first 3 days testosterone decreased reaching castration levels in 18 of the 30 young men (60%). After the nadir on day 28, testosterone levels increased to normal again. Changes in PSA paralleled those of testosterone. Castration reduced PSA levels by 29% (95% CI 19%–39%) compared to baseline (p<0.0001).

Conclusions: LHRH superagonists decrease PSA levels by testosterone deprivation. Conferring these findings to tumor patients, decreases in PSA after treatment with LHRH analogs might not only reflect disease regression but also a direct testosterone mediated effect on PSA. Thus, PSA levels should be cautiously interpreted when patients receive hormonal therapy.
Surface Morphology and Electric Property of the AlGaN/AlN/GaN Multilayers with Varying the AlN Thickness
Authors: Huang Shih-Chun , Chen Wen-Ray , Lin Jia-Ching , Chang Kuo-Jen , Lin Wen-Jen , Wang Li-Chun 
Published: October 2013

ABSTRACTThe surface morphologies of AlGaN/AlN/GaN HEMT structures were examined by using the atomic force microscopy (AFM).These HEMT structures have been grown by metalorganic chemical vapor deposition (MOCVD) onto the sapphire (0001) substrates where the thicknesses of AlN interlayers were varied from 0 to 5 nm. After the growth of GaN buffer layer, the AlN intermediate and AlGaN top layers were subsequently deposited at 1130°C in an trimethylaluminum (TMAl) and ammonia (NH3) atmosphere. The surface of AlGaN layers shows the thick- and fine-thread patterns.It was found that the root-mean-square (RMS) roughness of the samples with 0, 0.5, 2.5 and 5nm AlN interlayer thickness are 0.503, 0.534, 0.534 and 0.601nm, respectively. Although the cracks and rougher surfaces show that the qualities of AlGaN barrier layers have slightly degraded in the samples with thicker AlN layer. These phenomena could be attributed to the lattice mismatch and the growth temperature. In addition, the room-temperature two-dimensional electron gas (2DEG) mobility and density analysis were performed on the AlGaN surfaces and the measured results were discussed in detail.
Spinal Cord Injury Functional Ambulation Profile: A Preliminary Look at Responsiveness
Authors: Musselman Kristin E. , Yang Jaynie F. 
Published: October 2013

Background
The Spinal Cord Injury Functional Ambulation Profile (SCI-FAP) is a valid, reliable measure of walking skill (eg, walking while negotiating obstacles, doors, and stairs).

Objective
The responsiveness of the SCI-FAP was assessed at least 7 months after spinal cord injury (SCI) and compared with that of the 10-Meter Walk Test (10MWT) and the Six-Minute Walk Test (6MWT).

Design
A secondary analysis of data collected during a randomized, single-blind, crossover trial was performed.

Methods
Participants had incomplete SCI and could walk at least 5 m without manual assistance. After 3 or 4 baseline assessments, participants completed 2 months of precision training (stepping over obstacles and onto targets on the ground) and 2 months of endurance training (treadmill training with body weight support, if needed). Walking function was assessed with the SCI-FAP, 10MWT, and 6MWT. Internal responsiveness was evaluated through change scores and standardized response means (SRMs). External responsiveness was gauged by correlating change scores on the SCI-FAP, 10MWT, and 6MWT. The minimal detectable change was calculated from the standard error of measurement from the baseline assessments.

Results
The SCI-FAP scores improved with both interventions. The magnitude of change was greater for participants whose pretraining self-selected speed was less than 0.5 m/s. The SCI-FAP had moderate SRMs. The 10MWT (fastest speed) and 6MWT had the largest SRMs after precision training and endurance training, respectively. The minimal detectable change in the SCI-FAP was 96 points.

Limitations
The convenience sample was small and all participants could ambulate independently (with devices); therefore, the generalizability of the findings is limited.

Conclusions
The SCI-FAP was responsive to changes in walking ability in participants who had incomplete SCI and walked at slow speeds, but overall the 10MWT and 6MWT were more responsive.