bluuebunny/crossref_metadata_2025_split huggingface dataset:
Draft Genome Sequence of Fervidicella metallireducens Strain AeB
T
, an Iron-Reducing Thermoanaerobe from the Great Artesian Basin
Authors: Patel Bharat K. C. 
Published: May 2014

ABSTRACT

The genome sequence of
Fervidicella metallireducens
strain AeB
T
, a curved, heterotrophic, thermoanaerobic, and iron-reducing bacterium isolated from a gray microbial mat colonizing the free-flowing waters of a Great Artesian Basin (GAB) bore well located in outback Queensland, Australia, is reported here. The analysis of the 2.9-Mb sequence indicates that the attributes of the genome are consistent with its physiological and phenotypic traits.
The Experience of Acupuncture Care from the Perspective of People with Chronic Low Back Pain: A Grounded Theory Study
Authors: Stomski N J , Mackintosh S F , Stanley M 
Published: May 2014

Objectives To explore the experience of acupuncture care from the perspective of people with chronic low back pain. Methods A grounded theory, qualitative study using indepth interviews was undertaken with 11 people who had received acupuncture care for chronic low back pain. Interviews were audio-recorded and transcribed verbatim. Initial, focused and theoretical coding were used to identify a core category and several other categories. Results The core category, Reclaiming Control, was related to the sense of well-being experienced by most of the participants as a result of undergoing acupuncture care. The other categories were Gaining Sanctuary, Gaining Trust and Working Together. These categories reflected the processes of participants entering an aesthetically appealing, calm and relaxing space; developing confidence in the acupuncturists’ ability to care for them; and negotiating strategies and sharing decision-making with acupuncturists about their care. Conclusions Clinicians using acupuncture as a management strategy for low back pain may elicit an immediate sense of calmness in patients with subsequent well-being benefits. A sense of calmness may also be enhanced through providing a relaxing physical environment. The transactional and interpersonal processes of establishing trust and rapport, and shared decision-making are important for clients. Shared decision-making can be improved by clinicians carefully considering the explanation of issues and plans to a particular patient, especially by developing an understanding of each patient's worldview and using language that the suits each individual's healthcare orientation. Our findings should be interpreted cautiously as the results may be generalisable only to private practice in affluent countries, and whether the findings are representative beyond this setting remains unclear.
Carotid I's, L's and T's: collaterals shape the outcome of intracranial carotid occlusion in acute ischemic stroke
Authors: Liebeskind David S , Flint Alexander C , Budzik Ronald F , Xiang Bin , Smith Wade S , Duckwiler Gary R , Nogueira Raul G 
Published: May 2014

BackgroundCollaterals may affect revascularization, ischemic severity, and clinical outcomes in acute stroke owing to internal carotid artery (ICA) occlusion.ObjectiveTo examine the hypothesis that morphology of occlusive thrombus and collateral flow patterns may influence the outcome of ICA occlusions after mechanical thrombectomy.MethodsPooled analyses of ICA occlusions in the MERCI and Multi-MERCI trials employed central angiography review readings to categorize lesions as I, L, or T clots and functional lesions based on collateral flow patterns. Demographic variables, procedural details, and clinical outcomes were compared across ICA lesion types.ResultsA total of 72 subjects (mean age 67 years (SD 16), 51% female, median National Institutes of Health Stroke Scale 20 (range 8–35)) were included, with 90-day modified Rankin score ≤2 in 28% and 51% mortality. Clots were categorized as an I lesion in 9/72 (12.5%), L lesion in 12/72 (16.7%), and T lesion in 51/72 (70.8%). Based on collateral flow patterns, cases were categorized as having a functional I lesion in 7/72 (9.7%), functional L in 38/72 (52.8%), and functional T in only 27/72 (37.5%). Multivariate analyses showed that a functional T lesion, with insufficient collateral flow to ipsilateral anterior cerebral arteries via the contralateral ICA, was a strong predictor of both revascularization success and subsequent clinical outcomes.ConclusionsCollateral flow patterns distinguish the nature and impact of ICA occlusions on expected revascularization and subsequent clinical outcomes in acute ischemic stroke. The nomenclature of terminal ICA occlusions introduced here (carotid I's, L's, and T's) may enhance future endovascular trials targeting such proximal occlusions.Trial registration numberNCT00318071 (http://clinicaltrials.gov). MERCI was not registered because enrollment began before July 1, 2005.
Health professionals’ knowledge of driving restrictions following stroke and TIA: experience from a hyperacute stroke centre
Authors: Batool Saiqa , Roberts Adele Pryce , Kalra Lalit , Manawadu Dulka 
Published: May 2014

Abstract

Background and purpose
Assessment of fitness to drive (FTD) is important after stroke or transient ischaemic attack (TIA) to ensure that neither patients nor public are at risk. This is particularly important in patients with TIAs or minor stroke as many are discharged directly from emergency departments by a range of health professionals. We assessed stroke-related FTD knowledge among physicians’ and allied health professionals’ (AHPs) treating patients with stroke at a hyperacute stroke centre.

Methods
Knowledge of FTD restrictions following a stroke or TIA for domestic and commercial use was assessed in 195 physicians and 45 AHPs using a multiple-choice questionnaire between January and December 2009. The effect of discipline, seniority, previous instruction in FTD restrictions and experience in stroke medicine on FTD was assessed.

Results
The correct driving restriction following stroke with domestic and commercial license was known to 29% and 73% of physicians, respectively. For AHPs, these figures were 36% and 20%. For TIA with domestic and commercial license, this was 37% and 43% for physicians, and 44% and 11% for AHPs. 25% of physicians and 11% of AHPs believed that no driving restrictions applied after a TIA. The correct office for reporting FTD was known to 180 (92%) doctors and 31 (69%) AHPs (p=0.0001); 160 (82%) physicians and 27 (60%) AHPs correctly identified that reporting was the patients’ responsibility (p=0.001). FTD knowledge correlated with post in stroke (OR 3.2 (95% CI 1.6 to 6.2, p=0.001)) but not with seniority or previous FTD education.

Conclusions
Health professionals providing stroke care showed limited knowledge of FTD regulations after minor stroke or TIA. Imparting accurate information on driving restrictions is an important but neglected part of stroke management.
Enhanced Sealing Project (ESP): evolution of a full-sized bentonite and concrete shaft seal
Authors: Dixon D. A. , Priyanto D. G. , Martino J. B. , De Combarieu M. , Johansson R. , Korkeakoski P. , Villagran J. 
Published: May 2014

Abstract

A full-scale shaft seal was designed and installed in the 5 m-diameter access shaft at Atomic Energy of Canada Limited's (AECL's) Underground Research Laboratory at the point where the shaft intersects an ancient water-bearing, low-angle thrust fault at a depth of
c.
275 m in granitic rock. The seal consists of a 6 m-thick bentonite-based component sandwiched between 3 m-thick, keyed upper and lower concrete components. This design was adopted in order to limit the mixing of saline groundwater from the deeper regime with the fresher, near-surface groundwater regime. Construction of the shaft seal was done as part of Canada's Nuclear Legacy Liabilities Program. A jointly funded monitoring project, called the Enhanced Sealing Project (ESP), was developed by AECL (Canada) and jointly funded by NWMO (Canada), SKB (Sweden), Posiva Oy (Finland), and ANDRA (France), and since mid 2009 the thermal, hydraulic and mechanical evolution of the seal has been constantly monitored. The evolution of the type of seal being monitored in the ESP is of relevance to repository closure planning by demonstrating the functionality of shaft seals. Although constructed in a crystalline rock medium, the results of the ESP are relevant to the performance of seals in a variety of host rock types.
Oncogenic Protein MTBP Interacts with MYC to Promote Tumorigenesis
Authors: Grieb Brian C. , Gramling Mark W. , Arrate Maria Pia , Chen Xi , Beauparlant Stephen L. , Haines Dale S. , Xiao Hua , Eischen Christine M. 
Published: May 2014

Abstract
Despite its involvement in most human cancers, MYC continues to pose a challenge as a readily tractable therapeutic target. Here we identify the MYC transcriptional cofactors TIP48 and TIP49 and MYC as novel binding partners of Mdm2-binding protein (MTBP), a functionally undefined protein that we show is oncogenic and overexpressed in many human cancers. MTBP associated with MYC at promoters and increased MYC-mediated transcription, proliferation, neoplastic transformation, and tumor development. In breast cancer specimens, we determined overexpression of both MYC and MTBP was associated with a reduction in 10-year patient survival compared with MYC overexpression alone. MTBP was also frequently co-amplified with MYC in many human cancers. Mechanistic investigations implicated associations with TIP48/TIP49 as well as MYC in MTBP function in cellular transformation and the growth of human breast cancer cells. Taken together, our findings show MTBP functions with MYC to promote malignancy, identifying this protein as a novel general therapeutic target in human cancer. Cancer Res; 74(13); 3591–602. ©2014 AACR.
Prolyl Isomerase Pin1 Acts Downstream of miR200c to Promote Cancer Stem–like Cell Traits in Breast Cancer
Authors: Luo Man-Li , Gong Chang , Chen Chun-Hau , Lee Daniel Y. , Hu Hai , Huang Pengyu , Yao Yandan , Guo Wenjun , Reinhardt Ferenc , Wulf Gerburg , Lieberman Judy , Zhou Xiao Zhen , Song Erwei , Lu Kun Ping 
Published: May 2014

Abstract
Breast cancer stem–like cells (BCSC) have been implicated in tumor growth, metastasis, drug resistance, and relapse but druggable targets in appropriate subsets of this cell population have yet to be identified. Here we identify a fundamental role for the prolyl isomerase Pin1 in driving BCSC expansion, invasiveness, and tumorigenicity, defining it as a key target of miR200c, which is known to be a critical regulator in BCSC. Pin1 overexpression expanded the growth and tumorigenicity of BCSC and triggered epithelial–mesenchymal transition. Conversely, genetic or pharmacological inhibition of Pin1 reduced the abundance and self-renewal activity of BCSC. Moreover, moderate overexpression of miR200c-resistant Pin1 rescued the BCSC defect in miR200c-expressing cells. Genetic deletion of Pin1 also decreased the abundance and repopulating capability of normal mouse mammary stem cells. In human cells, freshly isolated from reduction mammoplasty tissues, Pin1 overexpression endowed BCSC traits to normal breast epithelial cells, expanding both luminal and basal/myoepithelial lineages in these cells. In contrast, Pin1 silencing in primary breast cancer cells freshly isolated from clinical samples inhibited the expansion, self-renewal activity, and tumorigenesis of BCSC in vitro and in vivo. Overall, our work demonstrated that Pin1 is a pivotal regulator acting downstream of miR200c to drive BCSC and breast tumorigenicity, highlighting a new therapeutic target to eradicate BCSC. Cancer Res; 74(13); 3603–16. ©2014 AACR.
Use of CA125 and HE4 Serum Markers to Predict Ovarian Cancer in Elevated-Risk Women
Authors: Karlan Beth Y. , Thorpe Jason , Watabayashi Kate , Drescher Charles W. , Palomares Melanie , Daly Mary B. , Paley Pam , Hillard Paula , Andersen M. Robyn , Anderson Garnet , Drapkin Ronny , Urban Nicole 
Published: May 2014

Abstract
Background: Serum markers are used before pelvic imaging to improve specificity and positive predictive value (PPV) of ovarian cancer multimodal screening strategies.
Methods: We conducted a randomized controlled pilot trial to estimate surgical PPV of a “2 of 3 tests positive” screening rule, and to compare use of HE4 as a first-line (Arm 1) versus a second-line (Arm 2) screen, in women at high and elevated risk for epithelial ovarian cancer (EOC) at five study sites. Semiannual screening was offered to 208 women ages 25 to 80 years with deleterious BRCA germline mutations and to 834 women ages 35 to 80 years with pedigrees suggesting inherited susceptibility. Annual screening was offered to 130 women ages 45 to 80 years (Risk Group 3) with epidemiologic and serum marker risk factors. Rising marker levels were identified using the parametric empirical Bayes algorithm.
Results: Both strategies yielded surgical PPV above 25%. Protocol-indicated surgery was performed in 6 women, identifying two ovarian malignancies and yielding a surgical PPV in both arms combined of 33% (95% confidence interval: 4%–78%), 25% in Arm 1 and 50% in Arm 2. Surgical consultation was recommended for 37 women (26 in Arm 1 and 11 in Arm 2). On the basis of 12 women with at least 2 of 3 tests positive (CA125, HE4, or imaging), an intent-to-treat analysis yielded PPV of 14% in Arm 1 and 20% in Arm 2.
Conclusions: Positive screens were more frequent when HE4 was included in the primary screen.
Impact: HE4 may be useful as a confirmatory screen when rising CA125 is used alone as a primary screen. Cancer Epidemiol Biomarkers Prev; 23(7); 1383–93. ©2014 AACR.
A Randomized, Multicenter, Placebo-Controlled Clinical Trial of Racotumomab-Alum Vaccine as Switch Maintenance Therapy in Advanced Non–Small Cell Lung Cancer Patients
Authors: Alfonso Sailyn , Valdés-Zayas Anet , Santiesteban Eduardo R. , Flores Yoanna I. , Areces Fernando , Hernández Maurenis , Viada Carmen E. , Mendoza Ivis C. , Guerra Pedro P. , García Elena , Ortiz Ramón A. , de la Torre Ana V. , Cepeda Meylán , Pérez Kirenia , Chong Eric , Hernández Ana María , Toledo Darien , González Zuyén , Mazorra Zaima , Crombet Tania , Pérez Rolando , Vázquez Ana María , Macías Amparo E. 
Published: May 2014

Abstract
Purpose: Racotumomab-alum is an anti-idiotype vaccine targeting the NeuGcGM3 tumor-associated ganglioside. This clinical trial was conducted to provide a preliminary estimate of efficacy and safety of racotumomab as switch maintenance for patients with advanced non–small cell lung cancer (NSCLC).
Experimental design: Patients with stage IIIb/IV NSCLC who have at least stable disease after first-line chemotherapy were randomized 1:1 to racotumomab-alum (5 immunizations every 2 weeks and re-immunizations every 4 weeks) or placebo. Treatment was administered beyond progressive disease, until severe performance status worsening or toxicity. At progression, only five patients per group received further anticancer therapy. The primary endpoint was overall survival (OS).
Results: One-hundred and seventy-six patients were randomized to racotumomab-alum (n = 87) and placebo (n = 89). Median OS was 8.23 and 6.80 months, respectively [HR, 0.63; 95% confidence interval (CI), 0.46–0.87; P = 0.004]. Median progression-free survival (PFS) in vaccinated patients was 5.33 versus 3.90 months for placebo (HR, 0.73; 95% CI 0.53–0.99; P = 0.039). The most common adverse events in the racotumomab-alum arm were burning and pain at the injection site, bone pain, and asthenia. A high antibody response of IgM and IgG isotype against the NeuGcGM3 ganglioside was obtained. Hyperimmune sera were able to specifically recognize and kill the NeuGcGM3-expressing L1210 cell line. Patients who developed anti-NeuGcGM3 antibodies capable to bind and kill ≥30% L1210 cells showed longer median survival times.
Conclusions: Switch maintenance with racotumomab-alum is an effective and a well-tolerated treatment option for patients with advanced NSCLC. Clin Cancer Res; 20(14); 3660–71. ©2014 AACR.
Molecular Pathways: Harnessing E2F1 Regulation for Prosenescence Therapy in p53-Defective Cancer Cells
Authors: Laine Anni , Westermarck Jukka 
Published: May 2014

Abstract
Induction of terminal proliferation arrest, senescence, is important for in vivo tumor-suppressive function of p53. Moreover, p53-mutant cells are highly resistant to senescence induction by either oncogenic signaling during cellular transformation or in response to different therapies. Senescence resistance in p53-mutant cells has been attributed mostly to inhibition of the checkpoint function of p53 in response to senescence-inducing stress signals. Here, we review very recent evidence that offers an alternative explanation for senescence resistance in p53-defective cancer cells: p21-mediated E2F1 expression. We discuss the potential relevance of these findings for senescence-inducing therapies and highlight cyclin-dependent kinases (CDK) and mechanisms downstream of retinoblastoma protein (RB) as prospective prosenescence therapeutic targets. In particular, we discuss recent findings indicating an important role for the E2F1–CIP2A feedback loop in causing senescence resistance in p53-compromised cancer cells. We further propose that targeting of the E2F1–CIP2A feedback loop could provide a prosenescence therapeutic approach that is effective in both p53-deficient and RB-deficient cancer cells, which together constitute the great majority of all cancer cells. Diagnostic evaluation of the described senescence resistance mechanisms in human tumors might also be informative for patient stratification for already existing therapies. Clin Cancer Res; 20(14); 3644–50. ©2014 AACR.
Computational Repositioning and Preclinical Validation of Pentamidine for Renal Cell Cancer
Authors: Zerbini Luiz Fernando , Bhasin Manoj K. , de Vasconcellos Jaira F. , Paccez Juliano D. , Gu Xuesong , Kung Andrew L. , Libermann Towia A. 
Published: May 2014

AbstractAlthough early stages of clear cell renal cell carcinoma (ccRCC) are curable, survival outcome for metastatic ccRCC remains poor. We previously established a highly accurate signature of differentially expressed genes that distinguish ccRCC from normal kidney. The purpose of this study was to apply a new individualized bioinformatics analysis (IBA) strategy to these transcriptome data in conjunction with Gene Set Enrichment Analysis of the Connectivity Map (C-MAP) database to identify and reposition FDA-approved drugs for anticancer therapy. Here, we demonstrate that one of the drugs predicted to revert the RCC gene signature toward normal kidney, pentamidine, is effective against RCC cells in culture and in a RCC xenograft model. ccRCC-specific gene expression signatures of individual patients were used to query the C-MAP software. Eight drugs with negative correlation and P-value &lt;0.05 were analyzed for efficacy against RCC in vitro and in vivo. Our data demonstrate consistency across most patients with ccRCC for the set of high-scoring drugs. Most of the selected high-scoring drugs potently induce apoptosis in RCC cells. Several drugs also demonstrate selectivity for Von Hippel-Lindau negative RCC cells. Most importantly, at least one of these drugs, pentamidine, slows tumor growth in the 786-O human ccRCC xenograft mouse model. Our findings suggest that pentamidine might be a new therapeutic agent to be combined with current standard-of-care regimens for patients with metastatic ccRCC and support our notion that IBA combined with C-MAP analysis enables repurposing of FDA-approved drugs for potential anti-RCC therapy. Mol Cancer Ther; 13(7); 1929–41. ©2014 AACR.
Tim-3: An Emerging Target in the Cancer Immunotherapy Landscape
Authors: Anderson Ana C. 
Published: May 2014

Abstract
The cancer immunotherapy field has grown exponentially in the past few years, largely driven by the success of immune checkpoint blockade. Therapies targeting the immune checkpoint molecules CTLA-4 and PD-1 have achieved objective responses in melanoma, renal cancer, and lung cancer; however, a large number of patients are still suffering with these cancers that are not benefiting from these therapies. Moreover, several cancers have proved to be largely refractory to therapies that target CTLA-4 and PD-1. This has catalyzed interest in targeting novel immune checkpoint receptors with the goal of realizing the full potential of checkpoint blockade for treating cancer. In this regard, the immune checkpoint receptor Tim-3 exhibits several unique features that make it an intriguing candidate for the next wave of therapies that target immune checkpoints in cancer. Cancer Immunol Res; 2(5); 393–8. ©2014 AACR.
Mixed-Lineage Kinase 3 Deficiency Promotes Neointima Formation Through Increased Activation of the RhoA Pathway in Vascular Smooth Muscle Cells
Authors: Gadang Vidya , Konaniah Eddy , Hui David Y. , Jaeschke Anja 
Published: May 2014

Objective—
Mitogen-activated protein kinase pathways play an important role in neointima formation secondary to vascular injury, in part by promoting proliferation of vascular smooth muscle cells (VSMC). Mixed-lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase that activates multiple mitogen-activated protein kinase pathways and has been implicated in regulating proliferation in several cell types. However, the role of MLK3 in VSMC proliferation and neointima formation is unknown. The aim of this study was to determine the function of MLK3 in the development of neointimal hyperplasia and to elucidate the underlying mechanisms.

Approach and Results—

Neointima formation was analyzed after endothelial denudation of carotid arteries from wild-type and MLK3-deficient mice. MLK3 deficiency promoted injury-induced neointima formation and increased proliferation of primary VSMC derived from aortas isolated from MLK3-deficient mice compared with wild-type mice. Furthermore, MLK3 deficiency increased the activation of p63Rho guanine nucleotide exchange factor, RhoA, and Rho kinase in VSMC, a pathway known to promote neointimal hyperplasia, and reconstitution of MLK3 expression attenuated Rho kinase activation. Furthermore, cJun NH
2
-terminal kinase activation was decreased in MLK3-deficient VSMC, and proliferation of wild-type but not MLK3 knockout cells treated with a cJun NH
2
-terminal kinase inhibitor was attenuated.

Conclusions—

We demonstrate that MLK3 limits RhoA activation and injury-induced neointima formation by binding to and inhibiting the activation of p63Rho guanine nucleotide exchange factor, a RhoA activator. In MLK3-deficient cells, activation of p63Rho guanine nucleotide exchange factor proceeds in an unchecked manner, leading to a net increase in RhoA pathway activation. Reconstitution of MLK3 expression restores MLK3/p63Rho guanine nucleotide exchange factor interaction, which is attenuated by feedback from activated cJun NH
2
-terminal kinase.