bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effectiveness of Coxiella burnetii Vaccines in Occupationally Exposed Populations: A Systematic Review and Meta‐Analysis
Authors: O'Neill T. J. , Sargeant J. M. , Poljak Z. 
Published: May 2013

SummaryTo estimate the effect of vaccination in preventing acute Q fever in individuals occupationally exposed to Coxiella burnetii, a systematic review and meta‐analysis were undertaken in controlled trials and observational studies. Publications were obtained through a scoping study of English and non‐English articles, and those reporting a commercially licensed or licensable vaccine compared with an unvaccinated or placebo control group were included in the review. Two authors performed independent assessment of risk of systematic error and data extraction. One controlled trial and five cohort publications met the inclusion criteria. All trials used a Henzerling phase I vaccine. A random‐effects meta‐analysis estimated significant protection in abattoir workers (RR = 0.07; 95% confidence interval [CI] 0.02–0.22) compared with the control individuals. In individuals with rare or sporadic contact with the abattoir, a significant benefit of vaccination was also found (RR = 0.06; 95% CI 0–0.93). Overall, the vaccine effectively prevented acute Q fever in individuals responsible for handling animals or their products and those working in the abattoir but not directly exposed to animals (RR = 0.06; 95% CI 0.02–0.18). Caution must be taken when interpreting the effect of C. burnetii vaccination as significant heterogeneity amongst publications was observed. A meta‐regression found no significant univariate associations. This may reflect the uncertainty provided by reported data in the cohort publications. Potential systematic biases were present in the publications, and evidence included may not be sufficiently robust to extrapolate the effect of vaccination on occupationally exposed groups beyond the population of abattoir employees in Australia where all included studies occurred.
Draft Genome Sequence of Dematiaceous Coelomycete
Pyrenochaeta
sp. Strain UM 256, Isolated from Skin Scraping
Authors: Yew Su Mei , Chan Chai Ling , Soo-Hoo Tuck Soon , Na Shiang Ling , Ong Seong Siang , Hassan Hamimah , Ngeow Yun Fong , Hoh Chee Choong , Lee Kok Wei , Yee Wai Yan , Ng Kee Peng 
Published: May 2013

ABSTRACT

Pyrenochaeta
, classified under the order
Pleosporales
, is known to cause diseases in plants and humans. Here, we report a draft genome sequence of a
Pyrenochaeta
sp. isolated from a skin scraping, with an estimated genome size of 39.4 Mb. Genes associated with the synthesis of proteases, toxins, plant cell wall degradation, and multidrug resistance were found.
Complete Genome Sequence of
Pseudomonas denitrificans
ATCC 13867
Authors: Ainala Satish Kumar , Somasundar Ashok , Park Sunghoon 
Published: May 2013

ABSTRACT

Pseudomonas denitrificans
ATCC 13867, a Gram-negative facultative anaerobic bacterium, is known to produce vitamin B
12
under aerobic conditions. This paper reports the annotated whole-genome sequence of the circular chromosome of this organism.
Draft Genome Sequence of an Escherichia coli O157:H43 Strain Isolated from Cattle
Authors: Sváb Domonkos , Horváth Balázs , Szűcs Attila , Maróti Gergely , Tóth István 
Published: May 2013

ABSTRACT

Here we report the draft genome sequence of an
Escherichia coli
O157:H43 strain, designated T22, with an atypical virulence gene profile and isolated from healthy cattle. T22 produces cytolethal distending toxin V (CDT-V) and belongs to phylogenetic group B1 and sequence type 155 (ST155).
Draft Genome Sequence of a Thermophilic Member of the
Bacillaceae
, Anoxybacillus flavithermus Strain Kn10, Isolated from the Kan-nawa Hot Spring in Japan
Authors: Matsutani Minenosuke , Shirakihara Yasuo , Imada Katsumi , Yakushi Toshiharu , Matsushita Kazunobu 
Published: May 2013

ABSTRACT

Here, we report the draft genome sequence of the
Anoxybacillus flavithermus
Kn10 strain (NBRC 109594), isolated from a water drain of the Kan-nawa Hot Spring in Japan. The draft genome sequence is composed of 90 contigs for 2,772,624 bp with 41.6% G+C content and contains 2,883 protein-coding genes and 80 tRNA genes.
Characteristics of central lesions in patients with dizziness determined by diffusion MRI in the emergency department
Authors: Lee Dong Hwan , Kim Won Young , Shim Byoung Soo , Kim Tae Su , Ahn Joong Ho , Chung Jong Woo , Yoon Tae Hyun , Park Hong Ju 
Published: May 2013

BackgroundTo describe the rate and risk factors of central lesions among patients with dizziness in the emergency department based on diffusion-weighted MRI, which otologists consulted for evaluation of patients with dizziness need to know.Methods902 Consecutive patients who presented with dizziness symptoms as a chief complaint in the emergency department (ED) of our tertiary referral centre between January 2011 and June 2011 were studied. Central lesions were confirmed by diffusion-weighted MRI. Univariate and multivariate analyses were used for factors predictive of central lesions.ResultsOf 645 patients who underwent MRI, 23 (3.6%) had acute central lesions (22 infarcts/1 haemorrhage). Univariate analyses revealed that older age, hypertension, atrial fibrillation, non-whirling type of dizziness symptoms and combined neurological symptoms were significantly associated with the development of central lesions (p<0.05). The incidence of central lesions in patients aged in their 40s, 50s, 60s, 70s and ≥80s was 0, 3.9%, 3.4%, 7.4% and 16.7%. Multivariate analyses showed that hypertension (p=0.01, OR=3.42), symptoms of non-whirling type (p=0.03, OR=3.12) and combined neurological symptoms (p<0.01, OR=16.72) were independent predictors of central lesions.ConclusionsAlthough dizziness in the ED is generally benign, the prevalence of acute central lesions was 3.6% among 645 patients with dizziness who underwent MRI. Old age (>50 years), hypertension, non-whirling type of dizziness symptoms and associated neurological symptoms were significant risk factors for central lesions.
Correlation between the expression of Id-1 and hyperthermia-associated molecules in oral squamous cell carcinoma
Authors: Zhao Jun , Wang Shengzhi , Liu Na , Tang Xiufa 
Published: May 2013

ObjectiveTo investigate the expression of inhibitor of differentiation/DNA binding (Id-1), phosphatidylinositol-3-kinase/protein kinase B pathway proteins and hyperthermia-associated protein and their association with various clinicopathological factors in oral squamous cell cancer (OSCC), and explore the relationship among them in OSCC.MethodsId-1, phosphorylated protein kinase B (p-Akt), phosphorylated glycogen synthase kinase 3β (p-GSK3β) and phosphorylated heat shock factor 1 (p-HSF1) expression were assessed immunohistochemically in 76 OSCC.ResultsId-1 (73.8%), p-Akt (65.8%), p-GSK3β (60.5%) and p-HSF1 (75%) were found to be overexpressed in most of the oral cancer samples tested, and the expressions of them are correlated with advanced clinical stage, metastasis and recurrence (p<0.01), but there is no apparent relationship with gender, age, differentiation and habits (p>0.05). Survival curves show that the survival of patients with high Id-1, p-Akt, p-GSK3β and p-HSF1 expression was significantly worse than those with low Id-1, p-Akt, p-GSK3β and p-HSF1 expression (p=0.000). Id-1 expression was significantly higher in cases with high expression of p-Akt, p-GSK3β and p-HSF1 than in those with low expression (p=0.002, p=0.003, p=0.001).ConclusionsThis study revealed that there was a positive correlation between Id-1 expression and the expression of p-Akt, p-GSK3β and p-HSF1. The inhibition of Id-1 expression can improve the efficacy of hyperthermia in OSCC.
Influence of source materials and fractionating assemblage on magmatism along the Aegean Arc, and implications for crustal growth
Authors: Elburg Marlina A. , Smet Ingrid , De Pelsmaeker Elien 
Published: May 2013

Abstract
Volcanic products from Methana, Santorini and Nisyros show mineralogical and geochemical characteristics that can be linked to their differentiation at different crustal levels, and varying sources of subducted sediments. The products from Methana, in the western part of the arc, where the overriding plate is thicker, are affected by amphibole fractionation and crustal contamination. Santorini volcano, in the central part of the arc, is located on an extensively thinned section of the overriding plate; it shows high Y-contents, a-typical for average continental crust. Crustal contamination is minor, similar to Nisyros volcano. Products of the latter, easternmost volcanic centre have been variably affected by amphibole fractionation. Its sub-arc magma source is different from the central and western part of the arc, reflecting sedimentary input from the Nile.
Amphibole fractionation, caused by crystallization at greater depths, seems necessary to lower Y-contents and yield volcanic products that resemble average continental crust in this respect. In detail, however, none of the magmatic products of the Aegean Arc displays MREE–HREE patterns or levels of compatible elements that are an exact match for average continental crust. Garnet stability and mixing processes appear crucial to obtain the REE and compatible element characteristics of continental crust.
Novel Recombinant Human B7-H4 Antibodies Overcome Tumoral Immune Escape to Potentiate T-Cell Antitumor Responses
Authors: Dangaj Denarda , Lanitis Evripidis , Zhao Aizhi , Joshi Shree , Cheng Yi , Sandaltzopoulos Raphael , Ra Hyun-Jeong , Danet-Desnoyers Gwenn , Powell Daniel J. , Scholler Nathalie 
Published: May 2013

AbstractB7-H4 (VTCN1, B7x, B7s) is a ligand for inhibitory coreceptors on T cells implicated in antigenic tolerization. B7-H4 is expressed by tumor cells and tumor-associated macrophages (TAM), but its potential contributions to tumoral immune escape and therapeutic targeting have been less studied. To interrogate B7-H4 expression on tumor cells, we analyzed fresh primary ovarian cancer cells collected from patient ascites and solid tumors, and established cell lines before and after in vivo passaging. B7-H4 expression was detected on the surface of all fresh primary human tumors and tumor xenotransplants, but not on most established cell lines, and B7-H4 was lost rapidly by tumor xenograft cells after short-term in vitro culture. These results indicated an in vivo requirement for B7-H4 induction and defined conditions for targeting studies. To generate anti-B7-H4–targeting reagents, we isolated antibodies by differential cell screening of a yeast-display single-chain fragments variable (scFv) library derived from patients with ovarian cancer. We identified anti-B7-H4 scFv that reversed in vitro inhibition of CD3-stimulated T cells by B7-H4 protein. Notably, these reagents rescued tumor antigen-specific T-cell activation, which was otherwise inhibited by coculture with antigen-loaded B7-H4+ APCs, B7-H4+ tumor cells, or B7-H4- tumor cells mixed with B7-H4+ TAMs; peritoneal administration of anti-B7-H4 scFv delayed the growth of established tumors. Together, our findings showed that cell surface expression of B7-H4 occurs only in tumors in vivo and that antibody binding of B7-H4 could restore antitumor T-cell responses. We suggest that blocking of B7-H4/B7-H4 ligand interactions may represent a feasible therapeutic strategy for ovarian cancer. Cancer Res; 73(15); 4820–9. ©2013 AACR.
PML-RARα and Its Phosphorylation Regulate PML Oligomerization and HIPK2 Stability
Authors: Shima Yutaka , Honma Yuki , Kitabayashi Issay 
Published: May 2013

Abstract
The PML gene is frequently fused to the retinoic acid receptor α (RARα) gene in acute promyelocytic leukemia (APL), generating a characteristic PML-RARα oncogenic chimera. PML-RARα disrupts the discrete nuclear speckles termed nuclear bodies, which are formed in PML, suggesting that nuclear body disruption is involved in leukemogenesis. Nuclear body formation that relies upon PML oligomerization and its stabilization of the hypoxia-inducible protein kinase (HIPK)-2 is disrupted by expression of the PML-RARα chimera. Here, we report that disruption of nuclear bodies is also mediated by PML-RARα inhibition of PML oligomerization. PKA-mediated phosphorylation of PML-RARα blocked its ability to inhibit PML oligomerization and destabilize HIPK2. Our results establish that both PML oligomerization and HIPK2 stabilization at nuclear bodies are important for APL cell differentiation, offering insights into the basis for the most common prodifferentiation therapies of APL used clinically. Cancer Res; 73(14); 4278–88. ©2013 AACR.
HMGA2 Is a Driver of Tumor Metastasis
Authors: Morishita Asahiro , Zaidi M. Raza , Mitoro Akira , Sankarasharma Devipriya , Szabolcs Matthias , Okada Yasunori , D'Armiento Jeanine , Chada Kiran 
Published: May 2013

Abstract
The non-histone chromatin-binding protein HMGA2 is expressed predominantly in the mesenchyme before its differentiation, but it is also expressed in tumors of epithelial origin. Ectopic expression of HMGA2 in epithelial cells induces epithelial–mesenchymal transition (EMT), which has been implicated in the acquisition of metastatic characters in tumor cells. However, little is known about in vivo modulation of HMGA2 and its effector functions in tumor metastasis. Here, we report that HMGA2 loss of function in a mouse model of cancer reduces tumor multiplicity. HMGA2-positive cells were identified at the invasive front of human and mouse tumors. In addition, in a mouse allograft model, HMGA2 overexpression converted nonmetastatic 4TO7 breast cancer cells to metastatic cells that homed specifically to liver. Interestingly, expression of HMGA2 enhanced TGFβ signaling by activating expression of the TGFβ type II receptor, which also localized to the invasive front of tumors. Together our results argued that HMGA2 plays a critical role in EMT by activating the TGFβ signaling pathway, thereby inducing invasion and metastasis of human epithelial cancers. Cancer Res; 73(14); 4289–99. ©2013 AACR.
Antitumor Activity of a Humanized, Bivalent Immunotoxin Targeting Fn14-Positive Solid Tumors
Authors: Zhou Hong , Hittelman Walter N. , Yagita Hideo , Cheung Lawrence H. , Martin Stuart S. , Winkles Jeffrey A. , Rosenblum Michael G. 
Published: May 2013

Abstract
The TNF-like weak inducer of apoptosis (TWEAK; TNFSF12) receptor Fn14 (TNFRSF12A) is expressed at low levels in normal tissues but frequently highly expressed in a wide range of tumor types such as lung, melanoma, and breast, and therefore it is a potentially unique therapeutic target for these diverse tumor types. We have generated a recombinant protein containing a humanized, dimeric single-chain anti–fibroblast growth factor-inducible 14-kDa protein (Fn14) antibody fused to recombinant gelonin toxin as a potential therapeutic agent (designated hSGZ). The hSGZ immunotoxin is a highly potent and selective agent that kills Fn14-positive (Fn14+) tumor cells in vitro. Treatment of cells expressing the MDR protein MDR1 (ABCB1B) showed no cross-resistance to hSGZ. Induced overexpression of Fn14 levels in MCF7 cells through HER2 (ERBB2) signaling translated to an improved therapeutic index of hSGZ treatment. In combination with trastuzumab, hSGZ showed an additive or synergistic cytotoxic effect on HER2+/Fn14+ breast cancer cell lines. Also, hSGZ treatment inhibited Erb3/Akt signaling in HER2-overexpressing breast cancer cells. Pharmacokinetic studies in mice revealed that hSGZ exhibited a biexponential clearance from plasma with a rapid initial clearance (t1/2α = 1.26 hours) followed by a seven-fold longer plasma half-life (t1/2β = 7.29 hours). At 24, 48, and 72 hours after injection, uptake of the hSGZ into tumors was 5.1, 4.8, and 4.7%ID/g, with a tumor-to-muscle ratio of 5.6, 6.2, and 9.0, respectively. Therapeutic efficacy studies showed significant tumor inhibition effects using an MDA-MB-231/Luc breast cancer xenograft model. Our findings show that hSGZ is an effective anticancer agent and a potential candidate for clinical studies. Cancer Res; 73(14); 4439–50. ©2013 AACR.
TRAF6 Upregulates Expression of HIF-1α and Promotes Tumor Angiogenesis
Authors: Sun Heng , Li Xue-Bing , Meng Ya , Fan Li , Li Min , Fang Jing 
Published: May 2013

Abstract
TNF receptor (TNFR)–associated factor TRAF6 is a key activator of NF-κB, playing a critical role in the regulation of innate immune responses and their connection to adaptive immune responses. TRAF6 interactions determine receptor-induced cell death versus survival. TRAF6 has been implicated in cancer but its contributions have not been investigated deeply. In this study, we show that TRAF6 upregulates expression of hypoxia-inducible factor (HIF)–1α. TRAF6 affects HIF-1α protein levels but has little effect on mRNA level. TRAF6 increases HIF-1α protein independent of oxygen. We found that TRAF6 binds HIF-1α and mediates its K63-linked polyubiquitination. The E3 ligase activity of TRAF6 was required to increase HIF-1α protein levels. Finally, we showed that TRAF6 promoted tumor angiogenesis and growth. Our results reveal how TRAF6 functions to upregulate HIF-1α expression and promote tumor angiogenesis. Cancer Res; 73(15); 4950–9. ©2013 AACR.
Genotype-Specific Abnormalities in Mitochondrial Function Associate with Distinct Profiles of Energy Metabolism and Catecholamine Content in Pheochromocytoma and Paraganglioma
Authors: Rao Jyotsna U. , Engelke Udo F.H. , Rodenburg Richard J.T. , Wevers Ron A. , Pacak Karel , Eisenhofer Graeme , Qin Nan , Kusters Benno , Goudswaard Angelina G. , Lenders Jacques W.M. , Hermus Ad R.M.M. , Mensenkamp Arjen R. , Kunst Henricus P.M. , Sweep Fred C.G.J. , Timmers Henri J.L.M. 
Published: May 2013

Abstract
Purpose: Pheochromocytomas and paragangliomas (PGL) are neuroendocrine tumors of sympathetic and parasympathetic paraganglia. This study investigated the relationships between genotype-specific differences in mitochondrial function and catecholamine content in PGL tumors.
Experimental Design: Respiratory chain enzyme assays and 1H-nuclear magnetic resonance (NMR) spectroscopy at 500 MHz were conducted on homogenates of 35 sporadic PGLs and 59 PGLs from patients with hereditary mutations in succinate dehydrogenase subunits B and D (SDHB, SDHD), succinate dehydrogenase assembly factor 2, von Hippel-Lindau (VHL), rearranged during transfection (RET), neurofibromatosis type 1 (NF1), and myc-associated factor X.
Results: In SDHx-related PGLs, a significant decrease in complex II activity (P &lt; 0.0001) and a significant increase in complex I, III, and IV enzyme activities were observed when compared to sporadic, RET, and NF1 tumors. Also, a significant increase in citrate synthase (P &lt; 0.0001) enzyme activity was observed in SDHx-related PGLs when compared to sporadic-, VHL-, RET-, and NF1-related tumors. An increase in succinate accumulation (P &lt; 0.001) and decrease in ATP/ADP/AMP accumulation (P &lt; 0.001) was observed when compared to sporadic PGLs and PGLs of other genotypes. Positive correlations (P &lt; 0.01) were observed between respiratory chain complex II activity and total catecholamine content and ATP/ADP/AMP and total catecholamine contents in tumor tissues.
Conclusions: This study for the first time establishes a relationship between determinants of energy metabolism, like activity of respiratory chain enzyme complex II, ATP/ADP/AMP content, and catecholamine content in PGL tumors. Also, this study for the first time successfully uses NMR spectroscopy to detect catecholamines in PGL tumors and provides ex vivo evidence for the accumulation of succinate in PGL tumors with an SDHx mutation. Clin Cancer Res; 19(14); 3787–95. ©2013 AACR.
HMGB1 in Cancer: Good, Bad, or Both?
Authors: Kang Rui , Zhang Qiuhong , Zeh Herbert J. , Lotze Michael T. , Tang Daolin 
Published: May 2013

Abstract
Forty years ago, high mobility group box 1 (HMGB1) was discovered in calf thymus and named according to its electrophoretic mobility in polyacrylamide gels. Now, we know that HMGB1 performs dual functions. Inside the cell, HMGB1 is a highly conserved chromosomal protein acting as a DNA chaperone. Outside of the cell, HMGB1 is a prototypical damage-associated molecular pattern, acting with cytokines, chemokines, and growth factors. During tumor development and in cancer therapy, HMGB1 has been reported to play paradoxical roles in promoting both cell survival and death by regulating multiple signaling pathways, including inflammation, immunity, genome stability, proliferation, metastasis, metabolism, apoptosis, and autophagy. Here, we review the current knowledge of both HMGB1′s oncogenic and tumor-suppressive roles and the potential strategies that target HMGB1 for the prevention and treatment of cancer. Clin Cancer Res; 19(15); 4046–57. ©2013 AACR.
Aging Impairs Electrical Conduction Along Endothelium of Resistance Arteries Through Enhanced Ca2+-Activated K
+
Channel Activation
Authors: Behringer Erik J. , Shaw Rebecca L. , Westcott Erika B. , Socha Matthew J. , Segal Steven S. 
Published: May 2013

Objective—

Intercellular conduction of electrical signals underlies spreading vasodilation of resistance arteries. Small- and intermediate-conductance Ca
2+
-activated K
+
channels of endothelial cells serve a dual function by initiating hyperpolarization and modulating electrical conduction. We tested the hypothesis that regulation of electrical signaling by small- and intermediate-conductance Ca
2+
-activated K
+
channels is altered with advancing age.

Approach and Results—

Intact endothelial tubes (60 µm wide; 1–3 mm long) were freshly isolated from male C57BL/6 mouse (Young: 4–6 months; Intermediate: 12–14 months; Old: 24–26 months) superior epigastric arteries. Using dual intracellular microelectrodes, current was injected (±0.1–3 nA) at site 1 while recording membrane potential (
V
m
) at site 2 (separation distance: 50–2000 µm). Across age groups, greatest differences were observed between Young and Old. Resting
V
m
in Old (−38±1 mV) was more negative (
P
<0.05) than Young (−30±1 mV). Maximal hyperpolarization to both direct (NS309) and indirect (acetylcholine) activation of small- and intermediate-conductance Ca
2+
-activated K
+
channels was sustained (Δ
V
m
≈−40 mV) with age. The length constant (λ) for electrical conduction was reduced (
P
<0.05) from 1630±80 µm (Young) to 1320±80 µm (Old). Inhibiting small- and intermediate-conductance Ca
2+
-activated K
+
channels with apamin+charybdotoxin or scavenging hydrogen peroxide (H
2
O
2
) with catalase improved electrical conduction (
P
<0.05) in Old. Exogenous H
2
O
2
(200 µmol/L) in Young evoked hyperpolarization and impaired electrical conduction; these effects were blocked by apamin+charybdotoxin.

Conclusions—
Enhanced current loss through Ca2+-activated K+ channel activation impairs electrical conduction along the endothelium of resistance arteries with aging. Attenuating the spatial domain of electrical signaling will restrict the spread of vasodilation and thereby contribute to blood flow limitations associated with advanced age.