bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Anti-Macrophage Migration Inhibitory Factor Antibodies Inhibit Growth of Human Prostate Cancer Cells In Vitro and In Vivo
Authors: Hussain Filza , Freissmuth Michael , Völkel Dirk , Thiele Michael , Douillard Patrice , Antoine Gerhard , Thurner Patrick , Ehrlich Hartmut , Schwarz Hans-Peter , Scheiflinger Friedrich , Kerschbaumer Randolf J. 
Published: April 2013

Abstract
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine, originally discovered for its eponymous effect and now known for pleiotropic biologic properties in immunology and oncology. Circulating MIF levels are elevated in several types of human cancer including prostate cancer. MIF is released presumably by both stromal and tumor cells and enhances malignant growth and metastasis by diverse mechanisms, such as stimulating tumor cell proliferation, suppressing apoptotic death, facilitating invasion of the extracellular matrix, and promoting angiogenesis. Recently described fully human anti-MIF antibodies were tested in vitro and in vivo for their ability to influence growth rate and invasion of the human PC3 prostate cancer cell line. In vitro, the selected candidate antibodies BaxG03, BaxB01, and BaxM159 reduced cell growth and viability by inhibiting MIF-induced phosphorylation of the central kinases p44/42 mitogen-activated protein kinase [extracellular signal–regulated kinase-1 and -2 (ERK1/2)] and protein kinase B (AKT). Incubation of cells in the presence of the antibodies also promoted activation of caspase-3/7. The antibodies furthermore inhibited MIF-promoted invasion and chemotaxis as transmigration through Matrigel along a MIF gradient was impaired. In vivo, pharmacokinetic parameters (half-life, volume of distribution, and bioavailability) of the antibodies were determined and a proof-of-concept was obtained in a PC3-xenograft mouse model. Treatment with human anti-MIF antibodies blunted xenograft tumor growth in a dose-dependent manner. We therefore conclude that the anti-MIF antibodies described neutralize some of the key tumor-promoting activities of MIF and thus limit tumor growth in vivo. Mol Cancer Ther; 12(7); 1223–34. ©2013 AACR.
Integrative Genomic Characterization of Oral Squamous Cell Carcinoma Identifies Frequent Somatic Drivers
Authors: Pickering Curtis R. , Zhang Jiexin , Yoo Suk Young , Bengtsson Linnea , Moorthy Shhyam , Neskey David M. , Zhao Mei , Ortega Alves Marcus V. , Chang Kyle , Drummond Jennifer , Cortez Elsa , Xie Tong-xin , Zhang Di , Chung Woonbok , Issa Jean-Pierre J. , Zweidler-McKay Patrick A. , Wu Xifeng , El-Naggar Adel K. , Weinstein John N. , Wang Jing , Muzny Donna M. , Gibbs Richard A. , Wheeler David A. , Myers Jeffrey N. , Frederick Mitchell J. 
Published: April 2013

Abstract
The survival of patients with oral squamous cell carcinoma (OSCC) has not changed significantly in several decades, leading clinicians and investigators to search for promising molecular targets. To this end, we conducted comprehensive genomic analysis of gene expression, copy number, methylation, and point mutations in OSCC. Integrated analysis revealed more somatic events than previously reported, identifying four major driver pathways (mitogenic signaling, Notch, cell cycle, and TP53) and two additional key genes (FAT1, CASP8). The Notch pathway was defective in 66% of patients, and in follow-up studies of mechanism, functional NOTCH1 signaling inhibited proliferation of OSCC cell lines. Frequent mutation of caspase-8 (CASP8) defines a new molecular subtype of OSCC with few copy number changes. Although genomic alterations are dominated by loss of tumor suppressor genes, 80% of patients harbored at least one genomic alteration in a targetable gene, suggesting that novel approaches to treatment may be possible for this debilitating subset of head and neck cancers.
Significance: This is the first integrated genomic analysis of OSCC. Only through integrated multiplatform analysis was it possible to identify four key pathways. We also discovered a new disease subtype associated with CASP8 and HRAS mutation. Finally, many candidate targetable events were found and provide hope for future genomically driven therapeutic strategies. Cancer Discov; 3(7); 770–81. ©2013 AACR.
See related commentary by Iglesias-Bartolome et al., p. 722
This article is highlighted in the In This Issue feature, p. 705
Bile Acid Receptor TGR5 Agonism Induces NO Production and Reduces Monocyte Adhesion in Vascular Endothelial Cells
Authors: Kida Taiki , Tsubosaka Yoshiki , Hori Masatoshi , Ozaki Hiroshi , Murata Takahisa 
Published: April 2013

Objective—
TGR5 is a G-protein–coupled receptor for bile acids. So far, little is known about the function of TGR5 in vascular endothelial cells.

Approach and Results—

In bovine aortic endothelial cells, treatment with a bile acid having a high affinity to TGR5, taurolithocholic acid (TLCA), significantly increased NO production. This effect was abolished by small interfering RNA–mediated depletion of TGR5. TLCA-induced NO production was also observed in human umbilical vein endothelial cells measured via intracellular cGMP accumulation. TLCA increased endothelial NO synthase
ser1177
phosphorylation in human umbilical vein endothelial cells. This response was accompanied by increased Akt
ser473
phosphorylation and intracellular Ca
2+
. Inhibition of these signals significantly decreased TLCA-induced NO production. We next examined whether TGR5-mediated NO production affects inflammatory responses of endothelial cells. In human umbilical vein endothelial cells, TLCA significantly reduced tumor necrosis factor-α–induced adhesion of monocytes, vascular cell adhesion molecule-1 expression, and activation of nuclear factor-κB. TLCA also inhibited lipopolysaccharide-induced monocyte adhesion to mesenteric venules in vivo. These inhibitory effects of TLCA were abrogated by NO synthase inhibition.

Conclusions—

TGR5 agonism induces NO production via Akt activation and intracellular Ca
2+
increase in vascular endothelial cells, and this function inhibits monocyte adhesion in response to inflammatory stimuli.
Diabetes Mellitus
Authors: Khoury Jane C. , Kleindorfer Dawn , Alwell Kathleen , Moomaw Charles J. , Woo Daniel , Adeoye Opeolu , Flaherty Matthew L. , Khatri Pooja , Ferioli Simona , Broderick Joseph P. , Kissela Brett M. 
Published: April 2013

Background and Purpose—
We previously reported increased incidence of ischemic stroke among both blacks and whites with diabetes mellitus, especially in those aged <55 years. With rising prevalence of diabetes mellitus in the past decade, we revisit the impact of diabetes mellitus on stroke incidence in the same population (≈1.3 million) 5 and 10 years later.

Methods—
This is a population-based study. First ischemic strokes among black and white residents of the 5-county Greater Cincinnati/Northern Kentucky region, aged ≥20 years, for periods 7/1993 to 6/1994, 1999, and 2005, were included in this analysis. Incidence rates were adjusted for sex, race, and age, as appropriate, to the 2000 US population.

Results—
History of diabetes mellitus among first ischemic strokes was reported for 493/1709 (28%) in 1993/1994, 522/1778 (29%) in 1999, and 544/1680 (33%) in 2005. Risk ratios (95% confidence interval) for rates of stroke in those with versus without diabetes mellitus for blacks reduced significantly from 5.6 in 1993/1994 to 3.2 in 2005; for whites the risk ratio remained stable at 3.8 in 1993/1994 and 2005. However, risk ratios varied with age, with an overall 5- to 14-fold increased risk observed in those aged 20 to 65 years.

Conclusions—
Those with diabetes mellitus remain at greatly increased risk for stroke at all ages, especially <65 years, regardless of race. The rates and risk ratios for 1999 and 2005, although similar to those previously reported for the mid-1990s, take on increased significance, given the epidemic of diabetes mellitus and metabolic syndrome throughout the US and the world.
Impact of image quality, radiologists, lung segments, and Gunnar eyewear on detectability of lung nodules in chest CT
Authors: Christe Andreas , Ebner Lukas , Steiger Philipp , Parikh Sachin R , Shah Akash D , Roychoudhury Kingshuk , Vock Peter , Roos Justus E 
Published: April 2013

Background Despite the increasingly higher spatial and contrast resolution of CT, nodular lesions are prone to be missed on chest CT. Tinted lenses increase visual acuity and contrast sensitivity by filtering short wavelength light of solar and artificial origin. Purpose To test the impact of Gunnar eyewear, image quality (standard versus low dose CT) and nodule location on detectability of lung nodules in CT and to compare their individual influence. Material and Methods A pre-existing database of CT images of patients with lung nodules >5 mm, scanned with standard does image quality (150 ref mAs/120 kVp) and lower dose/quality (40 ref mAs/120 kVp), was used. Five radiologists read 60 chest CTs twice: once with Gunnar glasses and once without glasses with a 1 month break between. At both read-outs the cases were shown at lower dose or standard dose level to quantify the influence of both variables (eyewear vs. image quality) on nodule sensitivity. Results The sensitivity of CT for lung nodules increased significantly using Gunnar eyewear for two readers and insignificantly for two other readers. Over all, the mean sensitivity of all radiologist raised significantly from 50% to 53%, using the glasses ( P value = 0.034). In contrast, sensitivity for lung nodules was not significantly affected by lowering the image quality from 150 to 40 ref mAs. The average sensitivity was 52% at low dose level, that was even 0.7% higher than at standard dose level ( P value = 0.40). The strongest impact on sensitivity had the factors readers and nodule location (lung segments). Conclusion Sensitivity for lung nodules was significantly enhanced by Gunnar eyewear (+3%), while lower image quality (40 ref mAs) had no impact on nodule sensitivity. Not using the glasses had a bigger impact on sensitivity than lowering the image quality.
MicroPET-CT evaluation of interstitial brachytherapy in pancreatic carcinoma xenografts
Authors: Jian Lu , Zhongmin Wang , Kemin Chen , Yunfeng Zheng , Gang Huang 
Published: April 2013

Background Interstitial brachytherapy (IBT) has been introduced as treatment for unresectable pancreatic cancers to maximize local dose and minimize irradiation of surrounding normal tissue. MicroPET-CT systems provide excellent anatomic and molecular information. Purpose To use 18F-FDG micro-positron emission tomography (PET)/computed tomography (CT) to evaluate the therapeutic effect of 125I interstitial brachytherapy on transplantation tumor of human pancreatic carcinoma in Balb/c-nu mice. Material and Methods Xenograft models were created by subcutaneous injection of Swl990 human pancreatic cancer cell suspensions into the immunodeficient Balb/c-nu mice. The study was randomly divided into three groups: control group ( n = 6), empty seed implant group ( n = 6), and 125I seed implant group ( n = 6), respectively. Before and 1 week after treatment, 18F-FDG microPET-CT scan was performed. In-vivo cell proliferation and apoptosis were monitored by thymidine kinase 1 (TK1) immunostaining and Dutp-biotin nick end labeling (TUNEL) assay. Results Our results showed that before treatment the SUVmax and SUVmean values among three groups had no significant statistical difference. One week after treatment the SUVmax and SUVmean in 125I seed implant group were significantly lower than before, while for the empty seed group and control group there were no significant difference compared with before treatment. Immunohistochemical analysis of tumor tissue revealed significantly less TK1 positive cells in 125I seed implant group than in empty seed group and control group. The index of apoptosis was slightly higher in 125I seed implant group than in empty seed group and control group as evaluated by TUNEL assay. Conclusion These results suggest that 18F-FDG microPET-CT may be useful as a non-invasive imaging modality to assess early response to 125I seed brachytherapy in a pancreatic carcinoma Xenograft.
Glue embolization for gastroduodenal ulcer bleeding: contribution to hemodynamics and healing process
Authors: Mine Takahiko , Murata S , Nakazawa K , Onozawa S , Ueda T , Miyauchi M , Morita S , Kumita S 
Published: April 2013

Background Although the morbidity of bowel ischemic events after glue embolization has been suggested, a causal relationship between glue and ischemia has not been clearly established. Purpose To evaluate the efficiency and safety of transcatheter arterial embolization with n-butyl cyanoacrylate (NBCA–TAE) for upper gastrointestinal hemorrhage (GIH). Material and Methods Between October 2006 and October 2012, 21 patients with upper GIH underwent NBCA–TAE, and endoscopic data were obtained within 30 days of follow-up. Shock index prior to and immediately after NBCA–TAE were compared to determine changes in hemodynamics. Days to Forrest type III, as assessed by follow-up endoscopy, was used as an indicator of the healing process. Other clinical outcomes included days for starting ingestion and for hospital discharge. Results Sixteen gastric and five duodenal ulcers, classified into Forrest type I, were treated. Immediate hemostasis was achieved in all the patients, and no re-bleeding occurred within the follow-up period. Shock index significantly ( P < 0.001) improved from before (0.99 ± 0.076) to immediately after NBCA–TAE (0.67 ± 0.038). Sequential mucosal healing processes were observed in all the patients, and the number of days to Forrest type III was 9.6 ± 7.1. The number of days for starting ingestion and hospital discharge was 9.0 ± 4.5 and 15 ± 7.7 days, respectively. Conclusion NBCA–TAE is an effective and safe method for the control of nonvariceal upper GIH, in terms of contribution to hemodynamics and healing process of the gastroduodenal mucosa.
Accuracy of iodine removal using dual-energy CT with or without a tin filter: an experimental phantom study
Authors: Kawai Tatsuya , Takeuchi Mitsuru , Hara Masaki , Ohashi Kazuya , Suzuki Hirochika , Yamada Kiyotaka , Sugimura Yuya , Shibamoto Yuta 
Published: April 2013

Background The effects of a tin filter on virtual non-enhanced (VNE) images created by dual-energy CT have not been well evaluated. Purpose To compare the accuracy of VNE images between those with and without a tin filter. Material and Methods Two different types of columnar phantoms made of agarose gel were evaluated. Phantom A contained various concentrations of iodine (4.5–1590 HU at 120 kVp). Phantom B consisted of a central component (0, 10, 25, and 40 mgI/cm3) and a surrounding component (0, 50, 100, and 200 mgI/cm3) with variable iodine concentration. They were scanned by dual-source CT in conventional single-energy mode and dual-energy mode with and without a tin filter. CT values on each gel at the corresponding points were measured and the accuracy of iodine removal was evaluated. Results On VNE images, the CT number of the gel of Phantom A fell within the range between –15 and +15 HU under 626 and 881 HU at single-energy 120 kVp with and without a tin filter, respectively. With attenuation over these thresholds, iodine concentration of gels was underestimated with the tin filter but overestimated without it. For Phantom B, the mean CT numbers on VNE images in the central gel component surrounded by the gel with iodine concentrations of 0, 50, 100, and 200 mgI/cm3 were in the range of –19–+6 HU and 21–100 HU with and without the tin filter, respectively. Conclusion Both with and without a tin filter, iodine removal was accurate under a threshold of iodine concentration. Although a surrounding structure with higher attenuation decreased the accuracy, a tin filter improved the margin of error.
Variability in ACL Tunnel Placement
Authors: Wolf Brian R. , Ramme Austin J. , Wright Rick W. , Brophy Robert H. , McCarty Eric C. , Vidal Armando R. , Parker Richard D. , Andrish Jack T. , Amendola Annunziato ,   MOON Knee Group, Grosland Nicole M. , Britton Carla L. , Dunn Warren R. , Spindler Kurt P. , Cox Charles L. , Carey James L. , Kaeding Christopher C. , Flanigan David C. , Matava Matthew J. , Smith Matthew V. , Marx Robert G. , Jones Morgan H. 
Published: April 2013

Background: Multicenter and multisurgeon cohort studies on anterior cruciate ligament (ACL) reconstruction are becoming more common. Minimal information exists on intersurgeon and intrasurgeon variability in ACL tunnel placement. Purpose/Hypothesis: The purpose of this study was to analyze intersurgeon and intrasurgeon variability in ACL tunnel placement in a series of The Multicenter Orthopaedic Outcomes Network (MOON) ACL reconstruction patients and in a clinical cohort of ACL reconstruction patients. The hypothesis was that there would be minimal variability between surgeons in ACL tunnel placement. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Seventy-eight patients who underwent ACL reconstruction by 8 surgeons had postoperative imaging with computed tomography, and ACL tunnel location and angulation were analyzed using 3-dimensional surface processing and measurement. Intersurgeon and intrasurgeon variability in ACL tunnel placement was analyzed. Results: For intersurgeon variability, the range in mean ACL femoral tunnel depth between surgeons was 22%. For femoral tunnel height, there was a 19% range. Tibial tunnel location from anterior to posterior on the plateau had a 16% range in mean results. There was only a small range of 4% for mean tibial tunnel location from the medial to lateral dimension. For intrasurgeon variability, femoral tunnel depth demonstrated the largest ranges, and tibial tunnel location from medial to lateral on the plateau demonstrated the least variability. Overall, surgeons were relatively consistent within their own cases. Using applied measurement criteria, 85% of femoral tunnels and 90% of tibial tunnels fell within applied literature-based guidelines. Ninety-one percent of the axes of the femoral tunnels fell within the boundaries of the femoral footprint. Conclusion: The data demonstrate that surgeons performing ACL reconstructions are relatively consistent between each other. There is, however, variability of average tunnel placement up to 22% of mean condylar depth, likely reflecting the difference in individual surgeons’ preferred tunnel locations. Individual surgeons are relatively consistent in their cases of ACL tunnels.
Developing parent expertise: A framework to guide parental care following diagnosis of Type 1 diabetes in a young child
Authors: Niedel Selaine , Traynor Michael , Tamborlane William , Acerini Carlo , McKee Martin 
Published: April 2013

Objectives This article examines how health professionals guide parental acquisition of knowledge and development of expertise following diagnosis of Type 1 diabetes in a young child. Methods Fifty-five consultations from two outpatient paediatric diabetes clinics, one in the UK and one in the US, were audio recorded, transcribed and analysed; eight exemplar extracts are presented here. Participants were parents, whose child younger than 6 years of age had been diagnosed with diabetes within the previous 14 months, and health professionals, who were experienced doctors, nurses, dieticians and social workers. Results Over the first year following diagnosis, experienced health professionals use four strategies to enable parental self-management of their child's diabetes. Clinicians begin by setting expectations to define the shared responsibilities for the management of the child's disease. Next, they introduce two concepts, trial and error, to help parents respond to variations in blood glucose values and pattern recognition, to help parents refine therapy. As parents gain confidence, clinicians encourage independent pro-active management. Together, these four strategies form a framework to enable development of parental expertise. Conclusions This framework addresses the needs of parents and guides their socialization as they assume the role of an expert health care provider for their child. If incorporated into clinical guidelines and health professional training programmes, the framework could facilitate improved self-management of diabetes and perhaps of other chronic diseases.
Identifying and managing performance concerns in community pharmacists in the UK
Authors: Jacobs Sally , Hassell Karen , Seston Elizabeth , Potter Helen , Schafheutle Ellen 
Published: April 2013

Objectives To explore current arrangements for identifying and managing performance concerns in community pharmacists in the UK. Methods Semi-structured qualitative telephone interviews were conducted with 20 senior managers from community pharmacies and locum agencies. Results A strong emphasis was placed on business performance alongside other aspects of professional performance in the identification of performance concerns in pharmacists. The majority of concerns were identified reactively, through customer complaints, peer- or self-referral, or following a dispensing error. Community pharmacies sought to manage performance concerns internally where possible, but only the larger organizations had the infrastructure to provide their own training or other remedial support. Several challenges to identifying and managing performance concerns were identified. There were few mechanisms for identifying and supporting locum pharmacists with performance issues. Conclusions Being ‘for-profit’ organizations, community pharmacies may prioritize business performance over ensuring the professional performance of pharmacists, the responsibility for which would be left to the individual pharmacist. This may be detrimental to the quality of care provided. With the growth of independent sector providers more widely, these findings may have implications for the regulation of other health care professionals’ performance.
Patient-derived induced pluripotent stem cells recapitulate hematopoietic abnormalities of juvenile myelomonocytic leukemia
Authors: Gandre-Babbe Shilpa , Paluru Prasuna , Aribeana Chiaka , Chou Stella T. , Bresolin Silvia , Lu Lin , Sullivan Spencer K. , Tasian Sarah K. , Weng Julie , Favre Helene , Choi John K. , French Deborah L. , Loh Mignon L. , Weiss Mitchell J. 
Published: April 2013

Key Points
Patient-derived iPSCs recapitulate juvenile myelomonocytic leukemia. MEK inhibition normalizes GM-CSF independence and hypersensitivity in myeloid precursors from JMML iPSCs.
Early responses predict better outcomes in patients with newly diagnosed chronic myeloid leukemia: results with four tyrosine kinase inhibitor modalities
Authors: Jain Preetesh , Kantarjian Hagop , Nazha Aziz , O’Brien Susan , Jabbour Elias , Romo Carlos Guillermo , Pierce Sherry , Cardenas-Turanzas Marylou , Verstovsek Srdan , Borthakur Gautam , Ravandi Farhad , Quintás-Cardama Alfonso , Cortes Jorge 
Published: April 2013

Key Points
This analysis demonstrates the universality of the early response in CML, regardless of the treatment modality used. Factors correlating with poor cytogenetic responses at 3-mo assessment in a multivariate analysis across all 4 TKIs.
A new characterization of Mathieu-groups by the order and one irreducible character degree
Authors: Xu Haijing , Yan Yanxiong , Chen Guiyun 
Published: April 2013

Abstract
The main aim of this article is to characterize the finite simple groups by less character quantity. In fact, we show that each Mathieu-group G can be determined by their largest and second largest irreducible character degrees.

MSC:20C15.