bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicentre cohort study assessing day of week effect and outcome from emergency appendicectomy
Authors: Ferguson Henry JM , Hall Nigel J , Bhangu Aneel 
Published: February 2014

BackgroundThere is evidence to suggest that patients undergoing treatment at weekends may be subject to different care processes and outcomes compared with weekdays. This study aimed to determine whether clinical outcomes from weekend appendicectomy are different from those performed on weekdays.MethodMulticentre cohort study during May–June 2012 from 95 centres (89 within the UK). The primary outcome was the 30-day adverse event rate. Multilevel modelling was used to account for clustering within hospitals while adjusting for case mix to produce adjusted ORs and 95% CIs.ResultsWhen compared with Monday, there were no significant differences for other days of the week considering 30-day adverse events in adjusted models. On Sunday, rates of simple appendicitis were highest, and rates of normal (OR 0.62, 95% CI 0.42 to 0.90) and complex appendicitis (OR 0.65, 95% CI 0.46 to 0.93) lowest. This was accompanied by a 43% lower likelihood in use of laparoscopy on Sunday (OR 0.47, 95% CI 0.32 to 0.69), accompanied by the lowest level of consultant presence for the week. When pooling weekends and weekdays, laparoscopy use remained less likely at the weekend (OR 0.68, 95% CI 0.55 to 0.83), with no significant difference for 30-day adverse event rate (OR 1.01, 95% CI 0.80 to 1.29).ConclusionsThis study found that weekend appendicectomy was not associated with increased 30-day adverse events. It cannot rule out smaller increases that may be shown by larger studies. It further illustrated that patients operated on at weekends were subject to different care processes, which may expose them to risk.
Improving room layouts for venepuncture, cannulation and ABG equipment on surgical wards
Authors: Pedley Ryan , Whitehouse Anna , Hammond Sarah 
Published: February 2014

AbstractThe Productive Ward series has effectively helped to standardise the storage of equipment in hospital ward treatment rooms; however, in our organisation equipment for venepunture and cannulation had been excluded. This resulted in clinicians having to navigate several unfamiliar environments while on-call and hence waste valuable time searching for basic equipment.We aimed to make it easier to locate and identify the basic equipment used for cannulation, venepuncture, and arterial blood gas sampling and more efficient to collect. We examined the initial layout of equipment on four surgical wards in a large teaching hospital. The time taken for junior doctors, nurses, health care assistants, and physician assistants to gather equipment on these wards was recorded along with a process map of steps involved. Our intervention was to relocate the equipment into adjacent storage and make it easily identifiable by the use of a 'red dot'. Following these changes we repeated the measurements.There was an overall reduction in the mean time taken to gather the equipment required to insert a venous cannula on an unfamiliar ward from 2 min 41 s pre-intervention (range 52 s to 6 mins 58 s, n = 23) to 26 s post-intervention (range 8 s to 1 min 20 s, n = 51). Additionally, the number of steps involved in the process was reduced from 16 to five. All of the 32 junior doctors surveyed felt that faster identification improved patient safety.A significant reduction in the time wasted by clinicians searching for venepuncture equipment on surgical wards has been achieved by simplifying the storage, layout, and identification of this kit. The accumulated benefit includes increased productivity, familiarity, and safety, which is paramount when attending unwell patients on unfamiliar wards.
Thrombus density predicts successful recanalization with Solitaire stent retriever thrombectomy in acute ischemic stroke
Authors: Mokin Maxim , Morr Simon , Natarajan Sabareesh K , Lin Ning , Snyder Kenneth V , Hopkins L Nelson , Siddiqui Adnan H , Levy Elad I 
Published: February 2014

BackgroundThrombus characteristics, including Hounsfield unit (HU) value to measure density and thrombus volume and length, can predict successful recanalization following IV thrombolysis with recombinant tissue plasminogen activator. Conflicting and limited data exist regarding the value of assessing thrombus properties in acute stroke cases treated with endovascular IA approaches.MethodsWe retrospectively reviewed cases of anterior circulation acute ischemic stroke in which a Solitaire stent retriever (ev3-Covidien) was the primary treatment device. We measured the following thrombus characteristics: absolute and corrected HU values; thrombus length and volume; clot burden score; and vessel bifurcation involvement. Fisher's exact test and the t test were used to study the association between these clot characteristics and successful recanalization (Thrombolysis in Cerebral Infarction (TICI) score 2b–3).ResultsWe identified 41 patients with anterior circulation stroke treated with the Solitaire stent retriever as the primary treatment device. Successful recanalization (TICI score 2b–3) was achieved in 59% of cases. Higher absolute and corrected HU values were strongly predictive of successful recanalization (49.9±7.6 vs 43.8±6.6, p=0.01 for absolute HU values and 1.2±0.2 vs 1.0±0.1, p=0.03 for HU ratio in TICI 2b–3 and TICI 0–2a groups, respectively). There was no significant difference between recanalization and non-recanalization groups in the other thrombus characteristics studied.ConclusionsIn acute stroke treated with Solitaire stent retriever thrombectomy, higher thrombus HU values are predictive of successful recanalization. Such information can be used in decision making when estimating recanalization success rate with different endovascular treatment approaches.
Endovascular superselective treatment of brain tumors: a new endovascular era? A quick review
Authors: Peschillo Simone , Miscusi Massimo , Missori Paolo 
Published: February 2014

BackgroundIntra-arterial therapy for malignant brain tumors, especially high-grade gliomas, has been administered since the 1950s and 1960s when the structure of the blood–brain barrier was first described. However, only with the advent of modern techniques used by endovascular neurosurgeons has it been possible to proceed with the release of chemotherapeutic agents in an ultraselective mode by superselective intra-arterial cerebral infusion (SIACI).MethodsA brief review was performed of all the published works from January 2000 to December 2013 in which the main issue was the superselective endovascular treatment of brain tumors with chemotherapy drugs.ResultsIntra-arterial non-selective therapy has been reported to be effective in chemosensitive tumors whereas the results in glioblastoma, at least in the pre-bevacizumab era, have been disappointing.ConclusionsIf the SIACI method for delivering bevacizumab after disruption of the blood–brain barrier is proved to be safe and effective in larger phase II and III trials, this paradigm may significantly alter the way chemotherapies are delivered to patients with both diffusely infiltrating low-grade and those with high-grade malignant brainstem gliomas and open a new endovascular era.
Ultrasound Guided Core Biopsy versus Fine Needle Aspiration for Evaluation of Axillary Lymphadenopathy in Patients with Breast Cancer
Authors: Ganott Marie A. , Zuley Margarita L. , Abrams Gordon S. , Lu Amy H. , Kelly Amy E. , Sumkin Jules H. , Chivukula Mamatha , Carter Gloria , Austin R. Marshall , Bandos Andriy I. 
Published: February 2014

Rationale and Objectives. To compare the sensitivities of ultrasound guided core biopsy and fine needle aspiration (FNA) for detection of axillary lymph node metastases in patients with a current diagnosis of ipsilateral breast cancer. Materials and Methods. From December 2008 to December 2010, 105 patients with breast cancer and abnormal appearing lymph nodes in the ipsilateral axilla consented to undergo FNA of an axillary node immediately followed by core biopsy of the same node, both with ultrasound guidance. Experienced pathologists evaluated the aspirate cytology without knowledge of the core histology. Cytology and core biopsy results were compared to sentinel node excision or axillary dissection pathology. Sensitivities were compared using McNemar’s test. Results. Of 70 patients with axillary node metastases, FNA was positive in 55/70 (78.6%) and core was positive in 61/70 (87.1%) (P = 0.18). The FNA and core results were discordant in 14/70 (20%) patients. Ten cases were FNA negative/core positive. Four cases were FNA positive/core negative. Conclusion. Core biopsy detected six (8.6%) more cases of metastatic lymphadenopathy than FNA but the difference in sensitivities was not statistically significant. Core biopsy should be considered if the node is clearly imaged and readily accessible. FNA is a good alternative when a smaller needle is desired due to node location or other patient factors. This trial is registered with NCT01920139.
PP2A-B55β Antagonizes Cyclin E1 Proteolysis and Promotes Its Dysregulation in Cancer
Authors: Tan YingMeei , Sun Dahui , Jiang Weijian , Klotz-Noack Kathleen , Vashisht Ajay A. , Wohlschlegel James , Widschwendter Martin , Spruck Charles 
Published: February 2014

Abstract
Cyclin E1 regulates the initiation of S-phase in cellular division. However, in many cancers, cyclin E1 is aberrantly overexpressed and this molecular phenotype correlates with increased tumor aggressiveness and poor patient survival. The molecular cause(s) of cyclin E1 abnormalities in cancers is poorly understood. Here, we show that cyclin E1 overexpression in cancer is promoted by dysregulation of the protein phosphatase PP2A-B55β. PP2A-B55β targets the N- and C-terminal phosphodegrons of cyclin E1 for dephosphorylation, thus protecting it from degradation mediated by the SCFFbxw7 ubiquitin ligase. Augmented B55β expression stabilizes cyclin E1 and promotes its overexpression in cancer-derived cell lines and breast tumors. Conversely, B55β ablation enforces the degradation of cyclin E1 and inhibits cancer cell proliferation in vitro and tumor formation in vivo. Therefore, PP2A-B55β promotes cyclin E1 overexpression by antagonizing its degradation and its inhibition could represent a therapeutic mechanism for abrogating cyclin E1 function in cancers. Cancer Res; 74(7); 2006–14. ©2014 AACR.
Apoptosis Imaging for Monitoring DR5 Antibody Accumulation and Pharmacodynamics in Brain Tumors Noninvasively
Authors: Weber Thomas G. , Osl Franz , Renner Anja , Pöschinger Thomas , Galbán Stefanie , Rehemtulla Alnawaz , Scheuer Werner 
Published: February 2014

AbstractHigh-grade gliomas often possess an impaired blood–brain barrier (BBB), which allows delivery of large molecules to brain tumors. However, achieving optimal drug concentrations in brain tumors remains a significant hurdle for treating patients successfully. Thus, detailed investigations of drug activities in gliomas are needed. To investigate BBB penetration, pharmacodynamics, and tumor retention kinetics of an agonistic DR5 antibody in a brain tumor xenograft model, we utilized a noninvasive imaging method for longitudinal monitoring of apoptosis induction. Brain tumors were induced by intracranial (i.c.) implantation of a luciferase-expressing tumor cell line as a reporter. To quantify accumulation of anti-DR5 in brain tumors, we generated a dosage–response curve for apoptosis induction after i.c. delivery of fluorescence-labeled anti-DR5 at different dosages. Assuming 100% drug delivery after i.c. application, the amount of accumulated antibody after i.v. application was calculated relative to its apoptosis induction. We found that up to 0.20% to 0.97% of antibody delivered i.v. reached the brain tumor, but that apoptosis induction declined quickly within 24 hours. These results were confirmed by three-dimensional fluorescence microscopy of antibody accumulation in explanted brains. Nonetheless, significant antitumor efficacy was documented after anti-DR5 delivery. We further demonstrated that antibody penetration was facilitated by an impaired BBB in brain tumors. These imaging methods enable the quantification of antibody accumulation and pharmacodynamics in brain tumors, offering a holistic approach for assessment of central nervous system–targeting drugs. Cancer Res; 74(7); 1913–23. ©2014 AACR.
Cofilin Drives Cell-Invasive and Metastatic Responses to TGF-β in Prostate Cancer
Authors: Collazo Joanne , Zhu Beibei , Larkin Spencer , Martin Sarah K. , Pu Hong , Horbinski Craig , Koochekpour Shahriar , Kyprianou Natasha 
Published: February 2014

Abstract
Cofilin (CFL) is an F-actin–severing protein required for the cytoskeleton reorganization and filopodia formation, which drives cell migration. CFL binding and severing of F-actin is controlled by Ser3 phosphorylation, but the contributions of this step to cell migration during invasion and metastasis of cancer cells are unclear. In this study, we addressed the question in prostate cancer cells, including the response to TGF-β, a critical regulator of migration. In cells expressing wild-type CFL, TGF-β treatment increased LIMK-2 activity and cofilin phosphorylation, decreasing filopodia formation. Conversely, constitutively active CFL (SerAla) promoted filipodia formation and cell migration mediated by TGF-β. Notably, in cocultures of prostate cancer epithelial cells and cancer-associated fibroblasts, active CFL promoted invasive migration in response to TGF-β in the microenvironment. Further, constitutively active CFL elevated the metastatic ability of prostate cancer cells in vivo. We found that levels of active CFL correlated with metastasis in a mouse model of prostate tumor and that in human prostate cancer, CFL expression was increased significantly in metastatic tumors. Our findings show that the actin-severing protein CFL coordinates responses to TGF-β that are needed for invasive cancer migration and metastasis. Cancer Res; 74(8); 2362–73. ©2014 AACR.
Urinary Levels of Melatonin and Risk of Postmenopausal Breast Cancer: Women's Health Initiative Observational Cohort
Authors: Sturgeon Susan R. , Doherty Ashley , Reeves Katherine W. , Bigelow Carol , Stanczyk Frank Z. , Ockene Judith K. , Liu Simin , Manson JoAnn E. , Neuhouser Marian L. 
Published: February 2014

AbstractBackground: Results from prospective studies on the association between urinary levels of melatonin and risk of postmenopausal breast cancer have been mixed. Several although not all studies have found lower urinary levels of melatonin in women who developed breast cancer compared with cancer-free women.Methods: We examined the association between urinary levels of melatonin and breast cancer risk in postmenopausal women in a case–control study nested in the Women's Health Initiative Observational Cohort. Levels of 6-sulfatoxymelatonin were measured in first morning voids from 258 women who later developed breast cancer and from 515 matched controls. Multivariable conditional logistic regression was used to calculate ORs and 95% confidence intervals (CI).Results: Fully adjusted risk estimates of breast cancer, relative to the lowest quartile level of creatinine-adjusted melatonin, were 1.07 (95% CI, 0.67–1.71), 1.26 (95% CI, 0.79–2.01), and 1.25 (95% CI, 0.78–2.02) for women in the second, third, and highest quartile (Ptrend = 0.27). Comparable results for cases diagnosed less than four years after urinary collection and matched controls were 1.0, 1.25 (95% CI, 0.51–3.06), 1.85 (95% CI, 0.75–4.57), and 1.94 (95% CI, 0.75–5.03; Ptrend = 0.11). Melatonin levels and breast cancer were not associated in cases diagnosed four or more years after urinary collection and matched controls (Ptrend = 0.89).Conclusions: We found no evidence that higher urinary levels of melatonin are inversely associated with breast cancer risk in postmenopausal women.Impact: Accumulating discrepancies in results across studies warrant further exploration. Cancer Epidemiol Biomarkers Prev; 23(4); 629–37. ©2014 AACR.
Novel Target for Peptide-Based Imaging and Treatment of Brain Tumors
Authors: Hyvönen Maija , Enbäck Juulia , Huhtala Tuulia , Lammi Johanna , Sihto Harri , Weisell Janne , Joensuu Heikki , Rosenthal-Aizman Katri , El-Andaloussi Samir , Langel Ulo , Närvänen Ale , Bergers Gabriele , Laakkonen Pirjo 
Published: February 2014

Abstract
Malignant gliomas are associated with high mortality due to infiltrative growth, recurrence, and malignant progression. Even with the most efficient therapy combinations, median survival of the glioblastoma multiforme (grade 4) patients is less than 15 months. Therefore, new treatment approaches are urgently needed. We describe here identification of a novel homing peptide that recognizes tumor vessels and invasive tumor satellites in glioblastomas. We demonstrate successful brain tumor imaging using radiolabeled peptide in whole-body SPECT/CT imaging. Peptide-targeted delivery of chemotherapeutics prolonged the lifespan of mice bearing invasive brain tumors and significantly reduced the number of tumor satellites compared with the free drug. Moreover, we identified mammary-derived growth inhibitor (MDGI/H-FABP/FABP3) as the interacting partner for our peptide on brain tumor tissue. MDGI was expressed in human brain tumor specimens in a grade-dependent manner and its expression positively correlated with the histologic grade of the tumor, suggesting MDGI as a novel marker for malignant gliomas. Mol Cancer Ther; 13(4); 996–1007. ©2014 AACR.
CD4 T-cell Subsets and Tumor Immunity: The Helpful and the Not-so-Helpful
Authors: Kim Hye-Jung , Cantor Harvey 
Published: February 2014

AbstractResearch over the past decade has revealed the increasingly complex biologic features of the CD4+ T-cell lineage. This T-cell subset, which was originally defined on the basis of helper activity in antibody responses, expresses receptors that recognize peptides that have been processed and presented by specialized antigen-presenting cells. At the core of the adaptive immune response, CD4 T cells display a large degree of plasticity and the ability to differentiate into multiple sublineages in response to developmental and environmental cues. These differentiated sublineages can orchestrate a broad range of effector activities during the initiation, expansion, and memory phase of an immune response. The contribution of CD4 cells to host defense against pathogenic invasion and regulation of autoimmunity is now well established. Emerging evidence suggests that CD4 cells also actively participate in shaping antitumor immunity. Here, we outline the biologic properties of CD4 T-cell subsets with an emphasis on their contribution to the antitumor response. Cancer Immunol Res; 2(2); 91–98. ©2014 AACR.
Killer Immunoglobulin-like Receptors and Tumor Immunity
Authors: Benson Don M. , Caligiuri Michael A. 
Published: February 2014

Abstract
Natural killer (NK) cells, large granular lymphocytes comprising a key cellular subset of innate immunity, were originally named for their capacity to elicit potent cytotoxicity against tumor cells independent of prior sensitization or gene rearrangement. This process is facilitated through the expression of activating and inhibitory receptors that provide for NK cell “education” and a subsequent ability to survey, recognize, and lyse infected or transformed cells, especially those lacking or possessing mutated MHC class I expression. Since these original observations were made, how NK cells recognize candidate target cells continues to be the topic of ongoing investigation. It is now appreciated that NK cells express a diverse repertoire of activating and inhibitory receptors of which killer immunoglobulin-like receptors (KIR) appear to play a critical role in mediating self-tolerance as well as facilitating cytotoxicity against infected or transformed cells. In addition, in the presence of an activating signal, the absence or mismatch of MHC class I molecules on such targets (which serve as inhibitory KIR ligands) promotes NK cell–mediated lysis. An increasing understanding of the complexities of KIR biology has provided recent opportunities to leverage the NK cell versus tumor effect as a novel avenue of immunotherapy for cancer. The present review summarizes the current understanding of KIR expression and function and highlights ongoing efforts to translate these discoveries into novel NK cell–mediated immunotherapies for cancer. Cancer Immunol Res; 2(2); 99–104. ©2014 AACR.
Noninvasive Assessment of Hypoxia in Rabbit Advanced Atherosclerosis Using
18
F-fluoromisonidazole Positron Emission Tomographic Imaging
Authors: Mateo Jesus , Izquierdo-Garcia David , Badimon Juan J. , Fayad Zahi A. , Fuster Valentin 
Published: February 2014

Background—
Hypoxia is an important microenvironmental factor influencing atherosclerosis progression by inducing foam-cell formation, metabolic adaptation of infiltrated macrophages, and plaque neovascularization. Therefore, imaging plaque hypoxia could serve as a marker of lesions at risk.

Methods and Results—

Advanced aortic atherosclerosis was induced in 18 rabbits by atherogenic diet and double balloon endothelial denudation. Animals underwent
18
F-fluoromisonidazole positron emission tomographic and
18
F-fluorodeoxyglucose positron emission tomographic imaging after 6 to 8 months (atherosclerosis induction) and 12 to 16 months (progression) of diet initiation. Four rabbits fed standard chow served as controls. Radiotracer uptake of the abdominal aorta was measured using standardized uptake values. After imaging, plaque hypoxia (pimonidazole), macrophages (RAM-11), neovessels (CD31), and hypoxia-inducible factor-1α were assessed by immunohistochemistry.
18
F-fluoromisonidazole uptake increased with time on diet (standardized uptake value mean, 0.10±0.01 in nonatherosclerotic animals versus 0.20±0.03 [
P
=0.002] at induction and 0.25±0.03 [
P
<0.001] at progression). Ex vivo positron emission tomographic imaging corroborated the
18
F-fluoromisonidazole uptake by the aorta of atherosclerotic rabbits.
18
F-fluorodeoxyglucose uptake also augmented in atherosclerotic animals, with an standardized uptake value mean of 0.43±0.02 at induction versus 0.35±0.02 in nonatherosclerotic animals (
P
=0.031) and no further increase at progression. By immunohistochemistry, hypoxia was mainly located in the macrophage-rich areas within the atheromatous core, whereas the macrophages close to the lumen were hypoxia-negative. Intraplaque neovessels were found predominantly in macrophage-rich hypoxic regions (pimonidazole
+
/hypoxia-inducible factor-1α
+
/RAM-11
+
).

Conclusions—

Plaque hypoxia increases with disease progression and is present in macrophage-rich areas associated with neovascularization.
18
F-fluoromisonidazole positron emission tomographic imaging emerges as a new tool for the detection of atherosclerotic lesions.