bluuebunny/crossref_metadata_2025_split huggingface dataset:
Corpora amylacea in gastrointestinal leiomyomas: a clinical, light microscopic, ultrastructural and immunohistochemical study with comparison to hyaline globules
Authors: Hechtman Jaclyn Frances , Gordon Ronald E , McBride Russell B , Harpaz Noam 
Published: July 2013

ContextCorpora amylacea (CA) are inclusions with starch-like composition that occur in various conditions. We have observed CA in gastrointestinal leiomyomas (GILM) and hypothesised that they differ from intracytoplasmic hyaline globules (HG) of GILM. We aimed to investigate the anatomical distribution, prevalence, staining characteristics and ultrastructural features of CA and compare them with HG of GILM.DesignSlides from a consecutive series of resected GILM and bland spindle cell tumours were examined for CA and HG. Special stains, electron microscopy and elemental analysis were performed on select leiomyomas.ResultsCA occurred in 13/35 GILM (37%) from the following sites: oesophagus (4/8), stomach (5/7) including one frozen section, small intestine (1/2) and large intestine (3/18), but were not identified in 19 gastrointestinal stromal tumours (12 gastric, 7 small intestinal; p=0.0019), five schwannomas (three gastric, two small intestinal; p=0.154) and 35 non-GILM (p=0.0001). The densities of CA ranged from one per 4–200 mm2. CA stained intensely with periodic acid Schiff after diastase predigestion (PASD), Alcian blue and ubiquitin, and faintly in peripheral zones for desmin and smooth muscle actin. Ultrastructurally, CA consisted of an electron-dense outer layer and a fibrillar core with scattered particle matter. HG were present in all leiomyomas, but showed variable staining for PASD, negative staining for Alcian blue and ubiquitin, and positive staining for smooth muscle markers.ConclusionsCA are a distinctive histological feature of approximately one third of GILM with different composition to HG. These differences may represent divergent degenerative processes or different stages of a single degenerative process over time.
Age-adjusted infarct volume threshold for good outcome after endovascular treatment
Authors: Ribo Marc , Flores Alan , Mansilla Eloy , Rubiera Marta , Tomasello Alejandro , Coscojuela Pilar , Pagola Jorge , Rodriguez-Luna David , Muchada Marian , Alvarez-Sabín José , Molina Carlos A 
Published: July 2013

Background and purposeInfarct volume and age are strong predictors of outcome in patients with stroke. We aimed to determine the impact of infarct volume on outcome according to age.MethodsConsecutive patients with acute stroke with documented internal carotid artery/middle cerebral artery occlusion who underwent endovascular procedures were studied. Patients were categorized in three age groups: <70 years (G1), 70–79 years (G2), ≥80 years (G3). The Alberta Stroke Program Early CT score (ASPECTS) was graded on initial CT. Time of successful recanalization (Thrombolysis In Cerebral Infarct (TICI) ≥2b )and good outcome at 3 months (modified Rankin Scale score ≤2) were recorded. Infarct volume was measured on the 24 h control CT.ResultsA total of 214 patients were studied (G1: 68; G2: 74; G3: 72). For all patients the mean infarct volume was 94.7±127 mL; 35.6% had a good outcome. We observed larger infarct volumes in patients with a bad outcome in each age group (G1: 22 vs 182 mL, p<0.01/G2: 22 vs 164 mL, p<0.01/G3: 7.6 vs 132 mL, p<0.01). However, the target cut-off infarct volume that better predicted a good outcome decreased as age increased: G1: 49 mL (sensitivity 80%, specificity 92.6%); G2: 32.5 mL (sensitivity 80%, specificity 81%); G3: 15.2 mL (sensitivity 81.3%, specificity 86.7%). Overall, after adjusting for age, occlusion location, baseline NIH Stroke Scale score and infarct volume, the only predictor of a good outcome was achieving a final infarct volume less than the age-adjusted target (OR 5.5, 95% CI 1.6 to 18.8; p<0.01). The probability of achieving an infarct volume less than the age-adjusted target decreased according to baseline ASPECTS, time and degree of recanalization.ConclusionsAge-adjusted infarct size might represent a powerful surrogate marker of stroke outcome and further refine the predictive accuracy of infarct volume on prognosis in patients with stroke undergoing endovascular treatment. This information may be used in the design of new trials to individualize selection criteria for different age groups.
Novel application of a balloon-anchoring technique for the realignment of a prolapsed Pipeline Embolization Device: a technical report
Authors: Crowley R Webster , Abla Adib A , Ducruet Andrew F , McDougall Cameron G , Albuquerque Felipe C 
Published: July 2013

BackgroundFlow-diverting stents represent a substantial advancement in the treatment of cerebral aneurysms. They can, however, be associated with unique complications that may require management through adjunctive techniques.ObjectiveTo present a technical report of a salvage technique used to realign a prolapsed Pipeline Embolization Device (PED) during the treatment of a giant internal carotid artery (ICA) aneurysm.MethodsA patient in his late 70s with an incidental giant supraclinoid ICA aneurysm presented for endovascular consideration. Treatment was planned using the PED. Following placement of the device there were two focal areas of incomplete expansion and balloon angioplasty was performed. This manipulation resulted in foreshortening of the distal aspect of the PED which caused the device to prolapse into the aneurysm. After multiple unsuccessful attempts to regain distal access, a salvage technique was attempted in which a balloon was inflated in the middle cerebral artery and, by applying traction, the PED was realigned with the parent artery.ResultsAfter the PED was realigned, direct distal catheter access was achieved and a second Pipeline device was deployed, successfully covering the aneurysm neck with resultant flow stasis. The patient had no postoperative issues and was discharged 2 days later without deficit.ConclusionsThe balloon-anchoring technique was successfully used to realign a PED that had prolapsed into a giant ICA aneurysm. This maneuver prevented potentially disastrous complications and allowed the satisfactory completion of the aneurysm embolization. This represents a useful salvage technique that should be considered when encountering a prolapsed stent.
Trends in junior doctors' certainty about their career choice of eventual clinical specialty: UK surveys
Authors: Surman Geraldine , Lambert Trevor W , Goldacre Michael J 
Published: July 2013

Abstract

Introduction
The paper explores whether UK qualified junior doctors' certainty about their choice of eventual clinical specialty has changed in recent years following structural changes to postgraduate training.

Materials and methods
We analysed data from questionnaire surveys of all doctors who qualified in the UK in 11 ‘year of qualification’ cohorts between 1974 and 2009. We report on responses to questions at years 1, 3 and 5 after qualifying.

Results
Overall, 1 year after qualification, 28.6% (6576/23018) of doctors specified that they were certain about their choice of future specialty, 47.7% specified that their choice was probable and 23.7% were uncertain about it. By year 3 after qualification, 88% of doctors specified that their current specialty choice was definitely or probably their final choice, as did 95% in year 5. Levels of certainty in year 1 showed little change across the cohorts who qualified between 1974 and 2002 (average 28% ‘definite’), dropped in the 2005 cohort and then increased to 38% in the qualifiers of 2008 and 2009. Similar changes occurred in years 3 and 5 among doctors surveyed after 2005. There was large variation in certainty of choice by specialty chosen but no important difference between men and women.

Conclusions
Levels of confidence about early choice of specialty are now higher than they were prior to the 2005 changes to postgraduate training.
Evaluation of aqueous tear production in dogs after general anaesthesia with medetomidine‐propofol‐carprofen‐halothane
Authors: Komnenou A. T. H. , Kazakos G. M. , Savvas I. , Thomas A. L. N. 
Published: July 2013

The influence of an anaesthetic protocol, which included medetomidine, propofol, carprofen and halothane on tear production in the dog. There are no previous studies on the effects of this combination on tear production in dogs or in any other species. The present study included 39 dogs, which underwent non‐ophthalmic surgery in our clinic. Preanaesthetically, all dogs had normal tear production (18.62±3.65 mm/minute) as this was recorded with Schirmer tear test I (STT I) and the ophthalmologic examination did not reveal anything abnormal. Tear production readings were recorded before the administration of premedication, at the end of anaesthesia, one hour and two hours postanaesthesia. No reverse agent was administrated. At the end of anaesthesia (right eye (oculus dexter, OD) P<0.0005, left eye (oculus sinister, OS) P<0.0005), as well as one hour postanaesthesia (OD P=0.020, OS P=0.001) there was a statistically significant reduction in tear production, which returned to normal values two hours postanaesthesia, regardless of the duration of the operation. This anaesthetic combination resulted in a decrease in tear production and, therefore, the use of tear substitute treatment in dogs undergoing anaesthesia with this protocol (combination) from the time the sedative is given until at least two hours after the end of anaesthesia is highly recommended.
Palaeoenvironmental records from the West Antarctic Peninsula drift sediments over the last 75 ka
Authors: Vautravers Maryline J. , Hodell David A. , Channell James E. T. , Hillenbrand Claus-Dieter , Hall Mike , Smith James , Larter Robert D. 
Published: July 2013

Abstract

We present results of a multi-proxy study on marine sediment core JR179-PC466 recovered from the crest of a sediment drift off the West Antarctic Peninsula at approximately 2300 m water depth. The 10.45 m-long core consists dominantly of glaciomarine terrigenous sediments, with only traces of calcium carbonate (<1 wt%). Despite the very low abundance of calcareous foraminifera, planktonic shell numbers are sufficient for stable isotope analyses in two-thirds of the samples studied. The core chronology is based on oxygen isotope stratigraphy and correlation of its relative palaeomagnetic intensity (RPI) with a stacked reference curve. According to the age model, core PC466 spans the last 75 ka, with average sedimentation rates of between about 4 and 25 cm ka
−1
. Planktonic foraminifera abundances fluctuate between 0 and 30 individuals per gram throughout the core, with minima observed during Marine Isotope Stage (MIS) 2 (14–29 ka before present, BP) and MIS4 (57–71 ka BP). Planktonic foraminifera are present in the Holocene but more abundant in sediments deposited during MIS3 (29–57 ka BP), owing to less dilution by terrigenous detritus and/or better carbonate preservation. During MIS3, foraminifera maxima correlate with Antarctic warming events as recorded in the δ
18
O signal of the EPICA Dronning Maud Land (EDML) ice core. They indicate higher planktonic foraminifera production and better carbonate preservation west of the Antarctic Peninsula during that time. The abundance of ice-rafted detritus (IRD) in core PC466 increased during the last deglaciation between about 19 and 11 ka BP, when numerous icebergs drifted across the core site, thereby releasing IRD. During this time, sea-level rise destabilized the Antarctic Peninsula (APIS) and West Antarctic (WAIS) ice sheets that had advanced onto the shelf during the sea-level low-stand of the Last Glacial Maximum (LGM;
c
. 19–23 ka BP). Overall, our results demonstrate that it is possible to establish an age model and reconstruct palaeoceanographical and climatic changes at high temporal resolution from sedimentary sequences recovered at 2300 m water depth from a West Antarctic drift.
ANTXR1, a Stem Cell-Enriched Functional Biomarker, Connects Collagen Signaling to Cancer Stem-like Cells and Metastasis in Breast Cancer
Authors: Chen Daohong , Bhat-Nakshatri Poornima , Goswami Chirayu , Badve Sunil , Nakshatri Harikrishna 
Published: July 2013

Abstract
Cancer stem-like cells are thought to contribute to tumor recurrence. The anthrax toxin receptor 1 (ANTXR1) has been identified as a functional biomarker of normal stem cells and breast cancer stem-like cells. Primary stem cell-enriched basal cells (CD49f+/EpCAM−/Lin−) expressed higher levels of ANTXR1 compared with mature luminal cells. CD49f+/EpCAM−, CD44+/EpCAM−, CD44+/CD24−, or ALDEFLUOR-positive subpopulations of breast cancer cells were enriched for ANTXR1 expression. CD44+/CD24−/ANTXR1+ cells displayed enhanced self-renewal as measured by mammosphere assay compared with CD44+/CD24−/ANTXR1− cells. Activation of ANTXR1 by its natural ligand C5A, a fragment of collagen VI α3, increased stem cell self-renewal in mammosphere assays and Wnt signaling including the expression of the Wnt receptor–lipoprotein receptor-related protein 6 (LRP6), phosphorylation of GSK3α/β, and elevated expression of Wnt target genes. RNAi-mediated silencing of ANTXR1 enhanced the expression of luminal-enriched genes but diminished Wnt signaling including reduced LRP6 and ZEB1 expression, self-renewal, invasion, tumorigenicity, and metastasis. ANTXR1 silencing also reduced the expression of HSPA1A, which is overexpressed in metastatic breast cancer stem cells. Analysis of public databases revealed ANTXR1 amplification in medullary breast carcinoma and overexpression in estrogen receptor-negative breast cancers with the worst outcome. Furthermore, ANTXR1 is among the 10% most overexpressed genes in breast cancer and is coexpressed with collagen VI. Thus, ANTXR1:C5A interactions bridge a network of collagen cleavage and remodeling in the tumor microenvironment, linking it to a stemness signaling network that drives metastatic progression. Cancer Res; 73(18); 5821–33. ©2013 AACR.
HOXB13 Mediates Tamoxifen Resistance and Invasiveness in Human Breast Cancer by Suppressing ERα and Inducing IL-6 Expression
Authors: Shah Nilay , Jin Kideok , Cruz Leigh-Ann , Park Sunju , Sadik Helen , Cho Soonweng , Goswami Chirayu Pankaj , Nakshatri Harikrishna , Gupta Rajnish , Chang Howard Y. , Zhang Zhe , Cimino-Mathews Ashley , Cope Leslie , Umbricht Christopher , Sukumar Saraswati 
Published: July 2013

Abstract
Most breast cancers expressing the estrogen receptor α (ERα) are treated successfully with the receptor antagonist tamoxifen (TAM), but many of these tumors recur. Elevated expression of the homeodomain transcription factor HOXB13 correlates with TAM-resistance in ERα-positive (ER+) breast cancer, but little is known regarding the underlying mechanism. Our comprehensive evaluation of HOX gene expression using tiling microarrays, with validation, showed that distant metastases from TAM-resistant patients also displayed high HOXB13 expression, suggesting a role for HOXB13 in tumor dissemination and survival. Here we show that HOXB13 confers TAM resistance by directly downregulating ERα transcription and protein expression. HOXB13 elevation promoted cell proliferation in vitro and growth of tumor xenografts in vivo. Mechanistic investigations showed that HOXB13 transcriptionally upregulated interleukin (IL)-6, activating the mTOR pathway via STAT3 phosphorylation to promote cell proliferation and fibroblast recruitment. Accordingly, mTOR inhibition suppressed fibroblast recruitment and proliferation of HOXB13-expressing ER+ breast cancer cells and tumor xenografts, alone or in combination with TAM. Taken together, our results establish a function for HOXB13 in TAM resistance through direct suppression of ERα and they identify the IL-6 pathways as mediator of disease progression and recurrence. Cancer Res; 73(17); 5449–58. ©2013 AACR.
Pesticide Exposure and Inherited Variants in Vitamin D Pathway Genes in Relation to Prostate Cancer
Authors: Karami Sara , Andreotti Gabriella , Koutros Stella , Barry Kathryn Hughes , Moore Lee E. , Han Summer , Hoppin Jane A. , Sandler Dale P. , Lubin Jay H. , Burdette Laurie A. , Yuenger Jeffrey , Yeager Meredith , Freeman Laura E. Beane , Blair Aaron , Alavanja Michael C.R. 
Published: July 2013

AbstractBackground: Vitamin D and its metabolites are believed to impede carcinogenesis by stimulating cell differentiation, inhibiting cell proliferation, and inducing apoptosis. Certain pesticides have been shown to deregulate vitamin D's anticarcinogenic properties. We hypothesize that certain pesticides may be linked to prostate cancer via an interaction with vitamin D genetic variants.Methods: We evaluated interactions between 41 pesticides and 152 single-nucleotide polymorphisms (SNP) in nine vitamin D pathway genes among 776 prostate cancer cases and 1,444 male controls in a nested case–control study of Caucasian pesticide applicators within the Agricultural Health Study. We assessed Pinteraction values using likelihood ratio tests from unconditional logistic regression and a false discovery rate (FDR) to account for multiple comparisons.Results: Five significant interactions (P &lt; 0.01) displayed a monotonic increase in prostate cancer risk with individual pesticide use in one genotype and no association in the other. These interactions involved parathion and terbufos use and three vitamin D genes (VDR, RXRB, and GC). The exposure–response pattern among participants with increasing parathion use with the homozygous CC genotype for GC rs7041 compared with unexposed participants was noteworthy [low vs. no exposure: OR, 2.58, 95% confidence interval (CI), 1.07–6.25; high vs. no exposure: OR, 3.09, 95% CI, 1.10–8.68; Pinteraction = 3.8 × 10−3].Conclusions: In this study, genetic variations in vitamin D pathway genes, particularly GC rs7041, an SNP previously linked to lower circulating vitamin D levels, modified pesticide associations with prostate cancer risk.Impact: Because our study is the first to examine this relationship, additional studies are needed to rule out chance findings. Cancer Epidemiol Biomarkers Prev; 22(9); 1557–66. ©2013 AACR.
Mutual Regulation between Raf/MEK/ERK Signaling and Y-Box–Binding Protein-1 Promotes Prostate Cancer Progression
Authors: Imada Kenjiro , Shiota Masaki , Kohashi Kenichi , Kuroiwa Kentaro , Song YooHyun , Sugimoto Masaaki , Naito Seiji , Oda Yoshinao 
Published: July 2013

Abstract
Purpose: Y-box–binding protein-1 (YB-1) is known to conduct various functions related to cell proliferation, anti-apoptosis, epithelial–mesenchymal transition, and castration resistance in prostate cancer. However, it is still unknown how YB-1 affects cancer biology, especially its correlations with the mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, we aimed to examine the interaction between YB-1 and the MAPK pathway in prostate cancer.
Experimental Design: Quantitative real-time PCR, Western blotting, and co-immunoprecipitation assay were conducted in prostate cancer cells. YB-1, phosphorylated YB-1 (p-YB-1), and ERK2 protein expressions in 165 clinical specimens of prostate cancer were investigated by immunohistochemistry. YB-1, p-YB-1, and ERK2 nuclear expressions were compared with clinicopathologic characteristics and patient prognoses.
Results: EGF upregulated p-YB-1, whereas MEK inhibitor (U0126, PD98059) decreased p-YB-1. Inversely, silencing of YB-1 using siRNA decreased the expression of ERK2 and phosphorylated MEK, ERK1/2, and RSK. Furthermore, YB-1 interacted with ERK2 and Raf-1 and regulated their expressions, through the proteasomal pathway. Immunohistochemical staining showed a significant correlation among the nuclear expressions of YB-1, p-YB-1, and ERK2. The Cox proportional hazards model revealed that high ERK2 expression was an independent prognostic factor [HR, 7.947; 95% confidence interval (CI), 3.527–20.508; P &lt; 0.0001].
Conclusion: We revealed the functional relationship between YB-1 and MAPK signaling and its biochemical relevance to the progression of prostate cancer. In addition, ERK2 expression was an independent prognostic factor. These findings suggest that both the ERK pathway and YB-1 may be promising molecular targets for prostate cancer diagnosis and therapeutics. Clin Cancer Res; 19(17); 4638–50. ©2013 AACR.
Accelerated Tumor Growth Mediated by Sublytic Levels of Antibody-Induced Complement Activation Is Associated with Activation of the PI3K/AKT Survival Pathway
Authors: Wu Xiaohong , Ragupathi Govind , Panageas Katherine , Hong Feng , Livingston Philip O. 
Published: July 2013

Abstract
Purpose: We addressed the possibility that low levels of tumor cell-bound antibodies targeting gangliosides might accelerate tumor growth.
Experimental Design: To test this hypothesis, we treated mice with a range of monoclonal antibody (mAb) doses against GM2, GD2, GD3, and CD20 after challenge with tumors expressing these antigens and tested the activity of the same mAbs in vitro. We also explored the mechanisms behind the complement-mediated tumor growth acceleration that we observed and an approach to overcome it.
Results: Serologically detectable levels of IgM-mAb against GM2 are able to delay or prevent tumor growth of high GM2 expressing cell lines both in vitro and in a SCID mouse model, whereas very low levels of this mAb resulted in slight but consistent acceleration of tumor growth in both settings. Surprisingly, this is not restricted to IgM mAb targeting GM2 but consistent against an IgG mAb targeting GD3 as well. These findings were mirrored by in vitro studies with antibodies against these antigens as well as GD2 and CD20 (with Rituxan), and shown to be complement-dependent in all cases. Complement-mediated accelerated growth of cultured tumor cell lines initiated by low mAb levels was associated with activation of the phosphoinositide 3-kinase (PI3K)/AKT survival pathway and significantly elevated levels of both p-AKT and p-PRAS40. This complement-mediated PI3K activation and accelerated tumor growth in vitro and in vivo are eliminated by PI3K inhibitors NVP-BEZ235 and Wortmannin. These PI3K inhibitors also significantly increased efficacy of high doses of these four mAbs.
Conclusion: Our findings suggest that manipulation of the PI3K/AKT pathway and its signaling network can significantly increase the potency of passively administered mAbs and vaccine-induced antibodies targeting a variety of tumor cell surface antigens. Clin Cancer Res; 19(17); 4728–39. ©2013 AACR.