bluuebunny/crossref_metadata_2025_split huggingface dataset:
Severe acute liver injury associated with lumiracoxib
Authors: Pillans Peter I , Ghiculescu Razvan A , Lampe Guy , Wilson Robert , Wong Richard , Macdonald Graeme A 
Published: December 2011

AbstractBackgound and Aim:  Significant elevations in liver transaminases were noted in some patients during pre‐marketing clinical trials with lumiracoxib, a selective COX‐2 inhibitor. It was withdrawn from the Australian market in August 2007, because of an association with severe liver injury. We describe in detail three cases of severe liver injury in patients taking lumiracoxibMethods:  Three patients admitted to our hospital with severe liver injury and taking lumiracoxib are described in detail, together with information on a further six cases reported to the Australian Therapeutics Goods Administration (TGA), none of whom had pre‐existing liver disease or obvious risk factors for liver disease.Results:  Liver histology showed severe hepatic necrosis. One patient required liver transplantation and another died. Autoantibodies were detected in all three patients. As with the other six cases reported to the TGA, all were females who had been taking lumiracoxib 200–400 mg daily, typically for a few months, for osteoarthritis.Conclusions:  Lumiracoxib can be associated with severe liver injury. The presence of a variety of positive auto‐antibodies suggests an altered immune response may be contributory.
Bone marrow cells: Important role on neovascularization of hepatocellular carcinoma
Authors: Zhu Haitao , Shao Qianwen , Sun Xitai , Deng Zhengming , Yuan Xianwen , Zhou Xiang , Ding Yitao 
Published: December 2011

AbstractBackground and Aim:  Present antivascular therapies including embolization to hepatocellular carcinoma (HCC) were not as satisfying as expected. The aim was to explore whether or not bone marrow cells (BMCs) played an important role on neovascularization in HCC.Methods:  Bone marrow‐GFP+ orthotropic HCC mice model was used. In controls and HCC mice, the dynamic change of circulating BMCs and serum vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF) were measured by flow cytometry and enzyme linked immunosorbent assay, respectively. Intrahepatic distribution of BMCs was evaluated using immunofluorescent and realtime polymerase chain reaction protocols. BMCs' intrahepatic differentiation and proportion in vessels was investigated by immunofluorescent methods. Immunohistochemistry and western blotting were performed to examine the expression of adhesion molecule in tumor tissues and tumor free tissues.Results:  Compared with controls, the frequency of circulating BMCs and serum VEGF, PDGF were much higher in HCC mice. The number of BMCs and the level of CD133 gene in tumor increased significantly relative to the tumor free zone. Since the early stage of HCC, BMCs have been mobilized, recruited into tumor and incorporated into different types of vessels of the liver. Besides into endothelial cells, BMCs also differentiated into vascular fibroblast and hepatic stellate cells. Moreover with tumor growth, the proportion of BMCs in vessels increased gradually.Conclusion:  Mobilized BMCs played an important role in tumor vasculogenesis of HCC. Combined blockading of bone marrow‐mediated vasculogenesis may improve the efficacy of current therapy to HCC patients.
Is the pleth variability index a surrogate for pulse pressure variation in a pediatric population undergoing spine fusion?
Authors: Feldman Jeffrey M. , Sussman Emily , Singh Devika , Friedman Ben J. 
Published: December 2011

SummaryObjective:  To compare simultaneous measurements of pulse pressure variation (PPV) and pleth variability index (PVI) in patients undergoing spinal fusion.Aims:  To determine if PVI can be used as a surrogate for PPV and also the influence of the prone position on these measurements.Background:  Spine fusion is an involved surgical procedure requiring attention to fluid administration. Dynamic indices for assessing fluid responsiveness like PPV have proven useful to guide fluid administration. Plethysmographic waveform variation like PVI is an appealing surrogate for measurements like PPV that require invasive arterial pressure measurement. Spine fusion patients are unique and the potential of either PPV or PVI to guide fluid therapy has not been studied.Methods:  Patients undergoing spine fusion for scoliosis were studied. In addition to the usual monitors including direct arterial pressure measurement, a multi‐wavelength pulse co‐oximeter was applied to measure PVI. Paired measurements of PPV and PVI were obtained and limits of agreement determined using the method of Bland and Altman. PPV and PVI in prone and supine positions were compared by paired t‐test.Results:  The bias between PVI and PPV measurements was −0.56% with 95% limits of agreement of +21.67% to −20.55%. There was no significant difference between the prone and supine measurements at the P = 0.05 level (Table 1).

Demographics of subjects and case information. Subjects 5 and 8 were excluded due to lack of data in the supine position

Subject
Age (years)
Wt (kg)
ASA
Sex
Duration (h)
EBL (ml)
Average TV (ml)
Average PIP (cmH2O)
IV Fluid (ml)
Blood (ml)

001
12
43.7
2
M
5.33
1000
401
19
4000
150

002
17
62.2
1
M
7.63
1250
518
20
4000
275

003
16
50
2
F
6.9
1700
355
19
4500
881

004
16
71.3
2
F
6.67
500
524
18
4500
0

006
17
62.3
2
F
6.15
600
490
17
3500
600

007
18
54
2
M
6.12
600
419
15
4200
0

009
11
52.4
1
F
7.27
300
348
29
3000
0

010
14
24.5
3
F
8.37
600
290
18
3500
380

011
18
72.1
2
M
7.02
400
397
15
3100
0

012
16
64.1
1
M
8.9
850
411
20
3300
120

013
13
39.2
3
F
5.33
1100
261
17
5250
739

014
13
49.6
2
M
8.3
1500
376
17
5000
885

015
14
45.2
2
M
6.43
600
350
18
3200
0

016
11
64.6
2
F
6.48
325
468
18
3000
0

017
18
62.1
2
M
8.37
1400
440
21
4000
0

018
13
44
1
F
11.4
400
297
16
4900
0

019
17
67.7
2
M
7.07
600
472
18
4400
100

020
14
47
2
F
4.53
200
351
18
3400
200

021
15
69.3
2
M
6.28
800
570
17
5000
150

022
18
62.5
1
M
7.82
1100
471
17
3250
1100

023
16
56
2
M
6.48
800
370
19
4000
800

024
14
37.8
3
M
8.62
900
342
17
4000
200

EBL, estimated blood loss; TV, tidal volume; PIP, peak inspiratory pressure.

Conclusions:  Our data indicate that PVI is not a surrogate for PPV. PVI measurements were not influenced by changing from the supine to prone position and therefore may prove useful for patients undergoing spine surgery.
A Participatory Approach to Healing and Transformation in South Africa
Authors: Morkel Elize 
Published: December 2011

In this article I describe my personal journey from working as private practitioner to participating in the wider South African society. Post‐apartheid South African society struggles with overwhelming problems related to poverty, illness, violence, sexism, and racism. Moreover, in those communities where the trauma is most severe, professional resources are scarce. I propose a participatory approach which invites therapists to respond to these socio‐economic and political challenges and the problems that arise from them by thinking and acting outside the constraints of their consultation rooms and of traditional therapeutic conversations, into active participation in ways that might support healing and social transformation. I use two examples to illustrate and discuss the participatory approach with which I have engaged for over 10 years. The illustrative examples show how a participatory approach can create ripples that impact communities in healing and transformative ways.
A Social Capital Basis for Environmental Concern: Evidence from Northern New England*
Authors: Macias Thomas , Nelson Elysia 
Published: December 2011

AbstractThis study, based on a random‐digit‐dialing telephone survey of adults in Maine, New Hampshire, and Vermont, uses ordinary least squares regression to examine a relatively neglected element in the sociological literature on environmental concern, namely, the influence of an individual's social capital on the formation of environmental attitudes. We argue that it is those individuals with a greater diversity of social connections who are most likely to be influenced by ecological perspectives grounded in conservation and environmental protection. Controlling for other theoretically relevant variables, we regress an index of environmental concern that gives special emphasis to environmental‐economic trade‐offs on our measures of relational and community social capital. While confirming much of the earlier work in this area, our model provides evidence that connections to other people play an important role in determining individual concern for the environment. Specifically, the number of respondents' “weak ties”—that is, not their closest relationships—and the average occupational status of respondents' social ties, in general, were both positively correlated with environmental concern. Additionally, one of our three measures of community social capital, the number of visits from friends over the past month, was statistically significant and negatively correlated with environmental concern.
Proton therapy for lung cancer
Authors: Nichols Jr. Romaine C. , Henderson Randal H. , Huh Soon , Flampouri Stella , Li Zuofeng , Bajwa Abubakr A. , D'Agostino Harry J , Pham Dat C. , Mendenhall Nancy P. , Hoppe Bradford S. 
Published: December 2011

AbstractProton therapy is an emerging radiotherapy technology with the potential to improve the therapeutic index in the treatment of lung cancer patients. Since charged particles, such as protons, have a penetration length that can be modified by using different energies, protons offer the clinician the ability to modulate radiation dose deposition along the beam path. This facilitates an increase of the dose to the tumor target while minimizing the volume of normal tissue irradiation. Such precise delivery is particularly relevant in the setting of lung cancer where the targeted tissues are in close proximity to moderately radiation‐sensitive organs like the spinal cord, heart, and esophagus, but are also effectively surrounded by the normal lung, which is extremely sensitive to radiation damage. Proton therapy has been investigated for the treatment of surgically curable yet medically inoperable patients as well as patients with regionally advanced disease.
Hematopoietic Stem-Progenitor Cells Restore Immunoreactivity and Improve Survival in Late Sepsis
Authors: Brudecki Laura , Ferguson Donald A. , Yin Deling , Lesage Gene D. , McCall Charles E. , El Gazzar Mohamed 
Published: December 2011

ABSTRACTSepsis progresses from an early/acute hyperinflammatory to a late/chronic hypoinflammatory phase with immunosuppression. As a result of this phenotypic switch, mortality in late sepsis from persistent primary infection or opportunistic new infection often exceeds that in acute sepsis. Emerging data support that persistence of the hypoinflammatory (hyporesponsive) effector immune cells during late sepsis might involve alterations in myeloid differentiation/maturation that generate circulating repressor macrophages that do not readily clear active infection. Here, we used a cecal ligation and puncture (CLP) murine model of prolonged sepsis to show that adoptive transfer of CD34+hematopoietic stem-progenitor cells after CLP improves long-term survival by 65%. CD34+cell transfer corrected the immunosuppression of late sepsis by (i) producing significantly higher levels of proinflammatory mediators uponex vivostimulation with the Toll-like receptor 4 (TLR4) agonist lipopolysaccharide, (ii) enhancing phagocytic activity of peritoneal macrophages, and (iii) clearing bacterial peritonitis. Improved immunity by CD34+cell transfer decreased inflammatory peritoneal exudate of surviving late-sepsis mice. Cell tracking experiments showed that the transferred CD34+cells first appeared in the bone marrow and then homed to the spleen and peritoneum. Because CD34+cells did not affect the early-phase hyperinflammatory response, it is likely that the newly incorporated pluripotent CD34+cells differentiated into competent immune cells in blood and tissue, thereby reversing or replacing the hyporesponsive endotoxin-tolerant cells that occur and persist after the initiation of early sepsis.
Stem Cell Pathways Contribute to Clinical Chemoresistance in Ovarian Cancer
Authors: Steg Adam D. , Bevis Kerri S. , Katre Ashwini A. , Ziebarth Angela , Dobbin Zachary C. , Alvarez Ronald D. , Zhang Kui , Conner Michael , Landen Charles N. 
Published: December 2011

Abstract
Purpose: Within heterogeneous tumors, subpopulations often labeled cancer stem cells (CSC) have been identified that have enhanced tumorigenicity and chemoresistance in ex vivo models. However, whether these populations are more capable of surviving chemotherapy in de novo tumors is unknown.
Experimental Design: We examined 45 matched primary/recurrent tumor pairs of high-grade ovarian adenocarcinomas for expression of CSC markers ALDH1A1, CD44, and CD133 using immunohistochemistry. Tumors collected immediately after completion of primary therapy were then laser capture microdissected and subjected to a quantitative PCR array examining stem cell biology pathways (Hedgehog, Notch, TGF-β, and Wnt). Select genes of interest were validated as important targets using siRNA-mediated downregulation.
Results: Primary samples were composed of low densities of ALDH1A1, CD44, and CD133. Tumors collected immediately after primary therapy were more densely composed of each marker, whereas samples collected at first recurrence, before initiating secondary therapy, were composed of similar percentages of each marker as their primary tumor. In tumors collected from recurrent platinum-resistant patients, only CD133 was significantly increased. Of stem cell pathway members examined, 14% were significantly overexpressed in recurrent compared with matched primary tumors. Knockdown of genes of interest, including endoglin/CD105 and the hedgehog mediators Gli1 and Gli2, led to decreased ovarian cancer cell viability, with Gli2 showing a novel contribution to cisplatin resistance.
Conclusions: These data indicate that ovarian tumors are enriched with CSCs and stem cell pathway mediators, especially at the completion of primary therapy. This suggests that stem cell subpopulations contribute to tumor chemoresistance and ultimately recurrent disease. Clin Cancer Res; 18(3); 869–81. ©2011 AACR.
GSK-3β regulates cell growth, migration, and angiogenesis via Fbw7 and USP28-dependent degradation of HIF-1α
Authors: Flügel Daniela , Görlach Agnes , Kietzmann Thomas 
Published: December 2011

AbstractThe hypoxia-inducible transcription factor-1α (HIF-1α) is a major regulator of angiogenesis, carcinogenesis, and various processes by which cells adapt to hypoxic conditions. Therefore, the identification of critical players regulating HIF-1α is not only important for the understanding of angiogenesis and different cancer phenotypes, but also for unraveling new therapeutic options. We report a novel mechanism by which HIF-1α is degraded after glycogen synthase kinase-3 (GSK-3)–induced phosphorylation and recruitment of the ubiquitin ligase and tumor suppressor F-box and WD protein Fbw7. Further, experiments with GSK-3β and Fbw7-deficient cells revealed that GSK-3β and Fbw7-dependent HIF-1α degradation can be antagonized by ubiquitin-specific protease 28 (USP28). In agreement with this, Fbw7 and USP28 reciprocally regulated cell migration and angiogenesis in an HIF-1α–dependent manner. Therefore, we have identified a new pathway that could be targeted at the level of GSK-3, Fbw7, or USP28 to influence HIF-1α–dependent processes like angiogenesis and metastasis.
Synthesis of an antiviral drug precursor from chitin using a saprophyte as a whole-cell catalyst
Authors: Steiger Matthias G , Mach-Aigner Astrid R , Gorsche Rita , Rosenberg Erwin E , Mihovilovic Marko D , Mach Robert L 
Published: December 2011

Abstract

Background
Recent incidents, such as the SARS and influenza epidemics, have highlighted the need for readily available antiviral drugs. One important precursor currently used for the production of Relenza, an antiviral product from GlaxoSmithKline, is N-acetylneuraminic acid (NeuNAc). This substance has a considerably high market price despite efforts to develop cost-reducing (biotechnological) production processes. Hypocrea jecorina (Trichoderma reesei) is a saprophyte noted for its abundant secretion of hydrolytic enzymes and its potential to degrade chitin to its monomer N-acetylglucosamine (GlcNAc). Chitin is considered the second most abundant biomass available on earth and therefore an attractive raw material.

Results
In this study, we introduced two enzymes from bacterial origin into Hypocrea, which convert GlcNAc into NeuNAc via N-acetylmannosamine. This enabled the fungus to produce NeuNAc from the cheap starting material chitin in liquid culture. Furthermore, we expressed the two recombinant enzymes as GST-fusion proteins and developed an enzyme assay for monitoring their enzymatic functionality. Finally, we demonstrated that Hypocrea does not metabolize NeuNAc and that no NeuNAc-uptake by the fungus occurs, which are important prerequisites for a potential production strategy.

Conclusions
This study is a proof of concept for the possibility to engineer in a filamentous fungus a bacterial enzyme cascade, which is fully functional. Furthermore, it provides the basis for the development of a process for NeuNAc production as well as a general prospective design for production processes that use saprophytes as whole-cell catalysts.
Desmin expression in colorectal cancer stroma correlates with advanced stage disease and marks angiogenic microvessels
Authors: Arentz Georgia , Chataway Tim , Price Timothy J , Izwan Zaipul , Hardi Gemma , Cummins Adrian G , Hardingham Jennifer E 
Published: December 2011

Abstract

Introduction
Biomarkers that improve stratification of colorectal cancer patients for adjuvant therapy versus resection alone, or that are predictive of response to therapeutic agents, have the potential to greatly improve patient selection for such therapies. The aim was to determine proteins differentially expressed within the malignant epithelial glands and closely associated stromal elements compared to matched normal mucosa, and to characterise the over-expression of one such protein as a potential biomarker.

Methods
Protein from laser microdissected tumor and normal mucosa was analysed by two dimensional difference gel electrophoresis (2D DIGE) and mass spectrometry to determine differentially over expressed tumor proteins. Tumor over-expression of one such protein, desmin, was quantified using immunofluorescence staining in a larger cohort. Dual staining for desmin and vimentin, or desmin and von Willebrand factor, was performed to determine the cell type of interest.

Results
Desmin expression was significantly increased between stage I and III tumors, (P < 0.0001), and stage II and III tumors, (P < 0.0001). Strong focal desmin expression was found in stroma directly adjacent to carcinomatous glands and microvessels. These cells showed co-localisation of desmin and vimentin in close association with cells expressing VWF, indicating they were pericytes. Significantly higher levels of desmin-positive pericytes were observed in late stage tumors, consistent with increased angiogenesis.

Conclusion
Pericyte coverage of vasculature is a marker of vessel maturation, hence desmin expression may have use as a marker for microvessel maturation. Clinical trials will be needed to determine its use in identifying tumors that will be less responsive to anti-angiogenic therapy.
Differences of Structures and Electronic Properties in the Triplet States between Dibromo and Dichloro Mononuclear Polypyridine Iridium(III) Complexes
Authors: Yoshikawa Naokazu , Yamabe Shinichi , Kanehisa Nobuko , Inoue Tsuyoshi , Takashima Hiroshi , Tsukahara Keiichi 
Published: December 2011

Abstract
Emission and electronic properties of eight iridium(III)-centered polypyridine complexes were studied systematically. A crystal structure of [IrBr2(phen)2]PF6 was obtained by X-ray diffraction study, where phen is 1,10-phenanthroline. Those in the triplet states were also determined by DFT calculations to investigate the source of emission spectra. Two triplet structures of [IrX2(bpy)2]+ and [IrX2(phen)2]+ and the transition state of interconversion were obtained with X− = Cl− and Br−. Here, bpy is 2,2′-bipyridine. For the chloro complexes, two triplet species have nonequivalent bpy and phen ligands through pseudo-Jahn–Teller geometric distortion. The dichloro complexes with asymmetric spin density distributions were found to correspond to stronger emission spectra than those for the dibromo compounds. Energies (Eem’s) corresponding to the observed emission wavelengths (λem’s) are in good agreement with the theoretical S0–T1 energy differences (ΔE’s). For [IrBr2(bpy)2]+, Eem = 2.29 eV and ΔE = 2.26 eV. For [IrCl2(bpy)2]+, Eem = 2.29 eV and ΔE = 2.33 eV. For [IrBr2(phen)2]+, Eem = 2.26 eV and ΔE = 2.28 eV. For [IrCl2(phen)2]+, Eem = 2.28 eV and ΔE = 2.34 eV. For all the four complexes, 1A, 1B, 3A, and 3B, DFT calculations indicate Ir–N bond rupture. Tc with a small S0–T1 energy-gap would undergo nonradiative relaxation. Tc indicates a triplet state which is a five-coordinate species with triplet metal-centered character. Coexistence of the triplet state species are discussed in terms of their electronic structures.
The Promotion of Particulate Matter Oxidation by Oxide Ion Conductors, Zr–Y–O and Zr–Nd–O
Authors: Harada Koichiro , Yamada Hiroshi , Takami Akihide 
Published: December 2011

Abstract
Catalytic particulate matter oxidation and its promotion by high oxide ion conductors, Zr–Y–O and Zr–Nd–O, has been studied. Zr-Based oxides show higher particulate matter oxidation activity by O2 compared to a Ce-based conventional catalyst using Pt-loaded oxide coated on a DPF substrate. Isotopic tracer methods involving 18O indicate Zr-based oxides release a large amount of lattice oxygen during carbon oxidation. Also, unique to the Zr-based oxides is an electron and electromotive force generation between carbon-deposited sites and carbon-free sites during carbon oxidation. Zr-Based oxides appear to have the capability to effectively generate oxide ions well suited for carbon oxidation.