bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Woodward factor: Arthur Smith Woodward's legacy to geology in Australia and Antarctica
Authors: Turner Susan , Long John 
Published: October 2015

Abstract

In the pioneering century of Australian geology the ‘BM’ (British Museum (Natural History): now NHMUK) London played a major role in assessing the palaeontology and stratigraphical relations of samples sent across long distances by local men, both professional and amateur. Eighteen-year-old Arthur Woodward (1864–1944) joined the museum in 1882, was ordered to change his name and was catapulted into vertebrate palaeontology, beginning work on Australian fossils in 1888. His subsequent career spanned six decades across the nineteenth to mid-twentieth centuries and, although Smith (renamed to distinguish him from NHMUK colleagues) Woodward never visited Australia, he made significant contributions to the study of Australian fossil fishes and other vertebrates. ‘ASW’ described Australian and Antarctic Palaeozoic to Quaternary fossils in some 30 papers, often deciding or confirming the age of Australasian rock units for the first time, many of which have contributed to our understanding of fish evolution. Smith Woodward's legacy to vertebrate palaeontology was blighted by one late middle-age misjudgement, which led him away from his first-chosen path. ASW's work, especially on palaeoichthyology with his four-part
Catalogue of Fossil Fishes
, was one of the foundations for vertebrate palaeontology in Australia; it continues to resonate, and influenced subsequent generations via his unofficial student Edwin Sherbon Hills. Some taxa, however, have never been revisited.
A Preclinical Model of Malignant Peripheral Nerve Sheath Tumor-like Melanoma Is Characterized by Infiltrating Mast Cells
Authors: Hölzel Michael , Landsberg Jennifer , Glodde Nicole , Bald Tobias , Rogava Meri , Riesenberg Stefanie , Becker Albert , Jönsson Göran , Tüting Thomas 
Published: October 2015

Abstract
Human melanomas exhibit considerable genetic, pathologic, and microenvironmental heterogeneity. Genetically engineered mice have successfully been used to model the genomic aberrations contributing to melanoma pathogenesis, but their ability to recapitulate the phenotypic variability of human disease and the complex interactions with the immune system have not been addressed. Here, we report the unexpected finding that immune cell–poor pigmented and immune cell–rich amelanotic melanomas developed simultaneously in Cdk4R24C-mutant mice upon melanocyte-specific conditional activation of oncogenic BrafV600E and a single application of the carcinogen 7,12-dimethylbenz(a)anthracene. Interestingly, amelanotic melanomas showed morphologic and molecular features of malignant peripheral nerve sheath tumors (MPNST). A bioinformatic cross-species comparison using a gene expression signature of MPNST-like mouse melanomas identified a subset of human melanomas with a similar histomorphology. Furthermore, this subset of human melanomas was found to be highly associated with a mast cell gene signature, and accordingly, mouse MPNST-like melanomas were also extensively infiltrated by mast cells and expressed mast cell chemoattractants similar to human counterparts. A transplantable mouse MPNST-like melanoma cell line recapitulated mast cell recruitment in syngeneic mice, demonstrating that this cell state can directly reconstitute the histomorphologic and microenvironmental features of primary MPNST-like melanomas. Our study emphasizes the importance of reciprocal, phenotype-dependent melanoma–immune cell interactions and highlights a critical role for mast cells in a subset of melanomas. Moreover, our BrafV600E-Cdk4R24C model represents an attractive system for the development of therapeutic approaches that can target the heterogeneous tumor microenvironment characteristic of human melanomas. Cancer Res; 76(2); 251–63. ©2015 AACR.
Cancer-Specific Production of N-Acetylaspartate via NAT8L Overexpression in Non–Small Cell Lung Cancer and Its Potential as a Circulating Biomarker
Authors: Lou Tzu-Fang , Sethuraman Deepa , Dospoy Patrick , Srivastva Pallevi , Kim Hyun Seok , Kim Joongsoo , Ma Xiaotu , Chen Pei-Hsuan , Huffman Kenneth E. , Frink Robin E. , Larsen Jill E. , Lewis Cheryl , Um Sang-Won , Kim Duk-Hwan , Ahn Jung-Mo , DeBerardinis Ralph J. , White Michael A. , Minna John D. , Yoo Hyuntae 
Published: October 2015

Abstract
In order to identify new cancer-associated metabolites that may be useful for early detection of lung cancer, we performed a global metabolite profiling of a non–small cell lung cancer (NSCLC) line and immortalized normal lung epithelial cells from the same patient. Among several metabolites with significant cancer/normal differences, we identified a unique metabolic compound, N-acetylaspartate (NAA), in cancer cells—undetectable in normal lung epithelium. NAA's cancer-specific detection was validated in additional cancer and control lung cells as well as selected NSCLC patient tumors and control tissues. NAA's cancer specificity was further supported in our analysis of NAA synthetase (gene symbol: NAT8L) gene expression levels in The Cancer Genome Atlas: elevated NAT8L expression in approximately 40% of adenocarcinoma and squamous cell carcinoma cases (N = 577), with minimal expression in all nonmalignant lung tissues (N = 74). We then showed that NAT8L is functionally involved in NAA production of NSCLC cells through siRNA-mediated suppression of NAT8L, which caused selective reduction of intracellular and secreted NAA. Our cell culture experiments also indicated that NAA biosynthesis in NSCLC cells depends on glutamine availability. For preliminary evaluation of NAA's clinical potential as a circulating biomarker, we developed a sensitive NAA blood assay and found that NAA blood levels were elevated in 46% of NSCLC patients (N = 13) in comparison with age-matched healthy controls (N = 21) among individuals aged 55 years or younger. Taken together, these results indicate that NAA is produced specifically in NSCLC tumors through NAT8L overexpression, and its extracellular secretion can be detected in blood. Cancer Prev Res; 9(1); 43–52. ©2015 AACR.
Methylseleninic Acid Superactivates p53-Senescence Cancer Progression Barrier in Prostate Lesions of Pten-Knockout Mouse
Authors: Wang Lei , Guo Xiaolan , Wang Ji , Jiang Cheng , Bosland Maarten C. , Lü Junxuan , Deng Yibin 
Published: October 2015

Abstract
Monomethylated selenium (MM-Se) forms that are precursors of methylselenol, such as methylseleninic acid (MSeA), differ in metabolism and anticancer activities in preclinical cell and animal models from seleno-methionine that had failed to exert preventive efficacy against prostate cancer in North American men. Given that human prostate cancer arises from precancerous lesions such as high-grade prostatic intraepithelial neoplasia (HG-PIN), which frequently have lost phosphatase and tensin homolog (PTEN) tumor suppressor permitting phosphatidylinositol-3-OH kinase (PI3K)–protein kinase B (AKT) oncogenic signaling, we tested the efficacy of MSeA to inhibit HG-PIN progression in Pten prostate-specific knockout (KO) mice and assessed the mechanistic involvement of p53-mediated cellular senescence and of the androgen receptor (AR). We observed that short-term (4 weeks) oral MSeA treatment significantly increased expression of P53 and P21Cip1 proteins and senescence-associated-β-galactosidase staining, and reduced Ki67 cell proliferation index in Pten KO prostate epithelium. Long-term (25 weeks) MSeA administration significantly suppressed HG-PIN phenotype, tumor weight, and prevented emergence of invasive carcinoma in Pten KO mice. Mechanistically, the long-term MSeA treatment not only sustained P53-mediated senescence, but also markedly reduced AKT phosphorylation and AR abundance in the Pten KO prostate. Importantly, these cellular and molecular changes were not observed in the prostate of wild-type littermates which were similarly treated with MSeA. Because p53 signaling is likely to be intact in HG-PIN compared with advanced prostate cancer, the selective superactivation of p53-mediated senescence by MSeA suggests a new paradigm of cancer chemoprevention by strengthening a cancer progression barrier through induction of irreversible senescence with additional suppression of AR and AKT oncogenic signaling. Cancer Prev Res; 9(1); 35–42. ©2015 AACR.
Matrix metalloproteinase-2 enhances platelet deposition on collagen under flow conditions
Authors: Momi Stefania , Groot Philip G. de , Battiston Monica , Marco Luigi de , Falcinelli Emanuela , Guglielmini Giuseppe , Appolloni Viviana , Gresele Paolo 
Published: October 2015

SummaryPlatelets contain and release matrix metalloproteinase-2 (MMP-2) that in turn potentiates platelet aggregation. Platelet deposition on a damaged vascular wall is the first, crucial, step leading to thrombosis. Little is known about the effects of MMP-2 on platelet activation and adhesion under flow conditions. We studied the effect of MMP-2 on shear-dependent platelet activation using the O’Brien filtration system, and on platelet deposition using a parallel-plate perfusion chamber. Preincubation of human whole blood with active MMP-2 (50 ng/ml, i. e. 0.78 nM) shortened filter closure time (from 51.8 ± 3.6 sec to 40 ± 2.7 sec, p< 0.05) and increased retained platelets (from 72.3 ± 2.3 % to 81.1 ± 1.8 %, p< 0.05) in the O’Brien system, an effect prevented by a specific MMP-2 inhibitor. High shear stress induced the release of MMP-2 from platelets, while TIMP-2 levels were not significantly reduced, therefore, the MMP-2/TIMP-2 ratio increased significantly showing enhanced MMP-2 activity. Preincubation of whole blood with active MMP-2 (0.5 to 50 ng/ml, i.e 0.0078 to 0.78 nM) increased dose-dependently human platelet deposition on collagen under high shear-rate flow conditions (3000 sec-1) (maximum +47.0 ± 11.9 %, p< 0.05, with 50 ng/ml), while pre-incubation with a MMP-2 inhibitor reduced platelet deposition. In real-time microscopy studies, increased deposition of platelets on collagen induced by MMP-2 started 85 sec from the beginning of perfusion, and was abolished by a GPIIb/IIIa antagonist, while MMP-2 had no effect on platelet deposition on fibrinogen or VWF. Confocal microscopy showed that MMP-2 enhances thrombus volume (+20.0 ± 3.0 % vs control) rather than adhesion. In conclusion, we show that MMP-2 potentiates shear-induced platelet activation by enhancing thrombus formation.Supplementary Material to this article is available online at www.thrombosis-online.com.
Patient-Centered Decision Support in Acute Ischemic Stroke
Authors: Decker Carole , Chhatriwalla Emily , Gialde Elizabeth , Garavalia Brian , Summers Debbie , Quinlan Miriam E. , Cheng Eric , Rymer Marilyn , Saver Jeffrey L. , Chen Er , Kent David M. , Spertus John A. 
Published: October 2015

Background—
National guidelines endorse recombinant tissue-type plasminogen activator (r-tPA) in eligible patients with acute ischemic stroke to improve patients’ functional recovery. However, 23% to 40% of ideal candidates with acute ischemic stroke for reperfusion are not treated, perhaps because of the difficulty in explaining the benefits and risks of r-tPA within the frenetic pace of emergency department care. To support better knowledge transfer and creation of a shared decision-making tool, we conducted qualitative interviews to define the information needs and preferred presentation format for stroke survivors, caregivers, and clinicians considering r-tPA treatment.

Methods and Results—
A multidisciplinary team used qualitative research methods to identify informational needs and strategies for describing the benefits and risks of r-tPA in a clinical setting. Through focus groups (n=10) of stroke survivors (n=39) and caregivers (n=24) and individual interviews with emergency physicians (n=23) and advanced practice nurses (n=20), several themes emerged. Survivors and caregivers preferred a broader definition of a good outcome (independence, rather than no significant disability), simpler graphs as compared with detailed pictographs, and presentation of both population and individualized benefits (framed positively) and risk of receiving r-tPA. Some physicians expressed skepticism with the data and the ability to present risk/benefit information emergently, whereas other physicians and most advanced practice nurses thought such information would improve care. Physicians stressed the importance of presenting the risk of thrombolytic-related intracranial hemorrhage.

Conclusions—
This study suggests that a positively framed risk–benefit tool with graphical presentations of general and patient-specific risk estimates could support patients and providers in considering r-tPA for acute ischemic stroke.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01864928.
Care Trajectories of Veterans in the 12 Months After Hospitalization for Acute Ischemic Stroke
Authors: Arling Greg , Ofner Susan , Reeves Mathew J. , Myers Laura J. , Williams Linda S. , Daggy Joanne K. , Phipps Michael S. , Chumbler Neale , Bravata Dawn M. 
Published: October 2015

Background—
Recovery after a stroke varies greatly between individuals and is reflected by wide variation in the use of institutional and home care services. This study sought to classify veterans according to their care trajectories in the 12 months after hospitalization for ischemic stroke.

Methods and Results—
The sample consisted of 3811 veterans hospitalized for ischemic stroke in Veterans Health Administration facilities in 2007. Three outcomes—nursing home care, home care, and mortality—were modeled jointly >12 months using latent class growth analysis. Data on Veterans’ care use and cost came from the Veterans Administration and Medicare. Covariates included stroke severity (National Institutes of Health Stroke Scale), functional status (functional independence measure score), age, marital status, chronic conditions, and prestroke ambulation. Five care trajectories were identified: 49% of Veterans had Rapid Recovery with little or no use of care; 15% had a Steady Recovery with initially high nursing home or home care that tapered off; 9% had Long-Term Home Care; 13% had Long-Term Nursing Home Care; and 14% had an Unstable trajectory with multiple transitions between long-term and acute care settings. Care use was greatest for individuals with more severe strokes, lower functioning at hospital discharge, and older age. Average annual costs were highest for individuals with the Long-Term Nursing Home trajectory ($63 082), closely followed by individuals with the Unstable trajectory ($58 720). Individual with the Rapid Recovery trajectory had the lowest costs ($9271).

Conclusions—
Care trajectories after stroke were associated with stroke severity and functional dependency and they had a dramatic impact on subsequent costs.
Future Changes in Convective Storm Days over the Northeastern United States Using Linear Discriminant Analysis Applied to CMIP5 Predictions
Authors: Li Harrison , Colle Brian A. 
Published: October 2015

Abstract
Future changes in the frequency of environmental conditions conducive for convective storm days (“CE days”) are determined for the northeastern United States (NEUS) during the warm seasons (April–September) of the twenty-first century. Statistical relationships between historical runs of seven models in phase 5 of the Coupled Model Intercomparison Project (CMIP5) and radar-classified convective storm days are developed using linear discriminant analysis (LDA), and these relationships are then applied to analyze changes in the convective environment under the high-emissions representative concentration pathway 8.5 (RCP8.5) scenario over the period 2006–99. The 1996–2007 warm seasons are used to train the LDA thresholds using convective precipitation from two reanalysis datasets and radar data, and the 1979–95 and 2008–10 warm seasons are used to verify these thresholds. For the CMIP5 historical period (1979–2005), the frequency of warm season CE days averaged across the CMIP5 models is slightly greater than that derived using reanalysis data, although both methods indicate a slight increasing trend through the historical period. Between 2006 and 2099, warm season CE day frequency is predicted to increase substantially at an average rate of 4–5 days decade−1 (50%–80% increase over the entire period). These changes are mostly attributed to a predicted 30%–40% increase in midlevel precipitable water between the historical period and the last few decades of the twenty-first century. Consistent with previous studies, there is decreasing deep-layer vertical wind shear as a result of a weakening horizontal temperature gradient, but this is outweighed by increases in instability led by the moisture increases.
Latitudinal Dependence of Wind-Induced Near-Inertial Energy
Authors: Zhai Xiaoming 
Published: October 2015

AbstractMidlatitude storms, accounting for the majority of wind energy input to near-inertial motions in the ocean, are known to shift their track significantly from one year to another. The consequence of such storm track shifts on wind-induced near-inertial energy (NIE) is yet unknown. Here, the latitudinal dependence of wind-induced NIE is first analyzed in the framework of the slab model and then tested using two numerical ocean models. It is found that the NIE input by pure inertial wind stress forcing, which dominates the wind energy input to near-inertial motions, is independent of latitude. As a consequence, the NIE generated by white-noise wind stress forcing is also latitudinally independent. In contrast, the NIE generated by red-noise wind stress forcing shows strong dependence on latitude owing to longer inertial periods at lower latitudes capable of sampling greater inertial wind stress forcing. Given that the observed surface wind stress spectra are red, results from this study suggest that an equatorward shift of the storm track is likely to result in an increase in wind-induced NIE in the ocean, while the opposite is true for a poleward shift.
Modifications to the Near-Storm Environment Induced by Simulated Supercell Thunderstorms
Authors: Nowotarski Christopher J. , Markowski Paul M. 
Published: October 2015

Abstract
This study investigates the changes that simulated supercell thunderstorms impart on their surroundings. Supercells are simulated in a strongly sheared convective boundary layer comprising horizontal roll vortices. In sensitivity tests, the effects of cloud shading on the near-storm environment are explored through the removal of cloud ice, water, and hydrometeor effects on parameterized radiation. All of the simulated supercells increase the low-level shear in their proximal environment; however, this effect is more pronounced when cloud shading is included. Shading stabilizes the boundary layer beneath the cirrus anvil, diminishes boundary layer rolls and their attendant thermodynamic perturbations, and reduces the intensity of resolved turbulent mixing in the convective boundary layer. Anvil shading also acts to reduce the buoyancy of inflow air and the horizontal buoyancy gradient along the forward-flank outflow boundary.
Lung Disease, Oxidative Stress, and Oxygen Requirements in Preterm Infants
Authors: Moore Tiffany A. , Schmid Kendra K. , Anderson-Berry Ann , Berger Ann M. 
Published: October 2015

Background: The role of oxidative stress remains unclear in the multifactorial pathophysiologic mechanism of lung disease in preterm infants. Aims: The aim of this study was to examine the associations among chronic lung disease (CLD), oxidative stress, and oxygen requirements in preterm infants. Design: Prospective, longitudinal, and correlational design. Subjects: Preterm infants born at <32 weeks’ gestation ( N = 31), median gestation of 29.0 weeks (range 24.9–31.7). Measurements: The diagnosis of CLD was obtained from the medical record. Oxidative stress was measured using 8-hydroxydeoxyguanosine (8-OHdG) in the cord blood at birth and urine on Days 1 and 7. Oxygen requirements were measured using fraction of inspired oxygen (FIO2) recorded in the first hour after birth/admission and the average FIO2 during the first 12 hr and 7 days after birth. Descriptive statistics are presented. Comparison analyses were performed using Kruskal–Wallis and Fisher’s exact tests. Results: Infants with CLD ( n = 12) had lower gestational age ( p = .04) and weight ( p = .04) at birth, more days on the ventilator ( p = .004), and longer neonatal intensive care unit stay ( p = .04) compared to infants without CLD ( n = 19). CLD was associated with lower oxidative stress levels ( p = .03) and higher oxygen requirements during the first 12 hr ( p = .025) and on Day 7 ( p = .001). Lower oxidative stress levels on Day 7 were associated with higher oxygen requirements in the first 12 hr ( p = .01) and on Day 7 ( p = .03). Conclusion: Our results linking CLD and higher oxygen requirements with low oxidative stress contradict previous reports. Findings identify a gap in knowledge for postresuscitation oxygen therapy in preterm infants and expose the role of oxidative stress from inflammation and intermittent hypoxia in the etiology of CLD.
The potential role for ocrelizumab in the treatment of multiple sclerosis: current evidence and future prospects
Authors: Sorensen Per Soelberg , Blinkenberg Morten 
Published: October 2015

B cells play a central role in the pathogenesis in multiple sclerosis (MS), being involved in the activation of proinflammatory T cells, secretion of proinflammatory cytokines, and production of autoantibodies directed against myelin. Hence, the usage of B-cell-depleting monoclonal antibodies as therapy for autoimmune diseases including MS lay near at hand. Rituximab was the first therapeutic B-cell-depleting chimeric monoclonal antibody to be used successfully in MS. Ocrelizumab, a second-generation humanized anti-CD20 antibody, was explored in a large phase II, randomized, placebo-controlled multicentre trial in patients with relapsing–remitting disease. Compared with placebo, two doses of ocrelizumab (600 and 2000 mg on days 1 and 15) showed a pronounced effect on disease activity seen in magnetic resonance imaging (MRI) as gadolinium-enhanced lesions (89% and 96% relative reduction, both p < 0.001) and also had a significant effect on relapses. In exploratory analyses, both doses of ocrelizumab had better effect on gadolinium-enhanced lesions than interferon beta-1a intramuscularly that was used as a reference arm. Adverse effects were mainly infusion-related reactions, in particular during the first infusion. Serious infections occurred at similar rates in ocrelizumab and placebo-treated patients, and no opportunistic infections were reported. However, progressive multifocal leukoencephalopathy (PML) has been reported in patients treated with anti-CD20 monoclonal antibodies for other indications. Other anti-CD20 monoclonal antibodies have been tested as treatments for MS, including ofatumumab that has shown beneficial results in placebo-controlled phase II trials in patients with relapsing–remitting MS. Ocrelizumab is now in phase III development for the treatment of relapsing–remitting MS, as well as primary progressive MS, and the results of ongoing clinical trials are eagerly awaited and will determine the place of ocrelizumab in the armamentarium of MS therapies.
A novel role for von Willebrand factor in the pathogenesis of experimental cerebral malaria
Authors: O’Regan Niamh , Gegenbauer Kristina , O’Sullivan Jamie M. , Maleki Sanaz , Brophy Teresa M. , Dalton Niall , Chion Alain , Fallon Padraic G. , Grau Georges E. , Budde Ulrich , Smith Owen P. , Craig Alister G. , Preston Roger J. S. , O’Donnell James S. 
Published: October 2015

Key Points
ECM is associated with an early marked increase in plasma VWF levels and accumulation of UL-VWF multimers. Following P berghei infection, VWF−/− mice survive significantly longer compared with WT controls.