bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acceleration of cutaneous healing by electrical stimulation: Degenerate electrical waveform down‐regulates inflammation, up‐regulates angiogenesis and advances remodeling in temporal punch biopsies in a human volunteer study
Authors: Sebastian Anil , Syed Farhatullah , Perry Donna , Balamurugan Vinayagapriya , Colthurst James , Chaudhry Iskander H. , Bayat Ardeshir 
Published: October 2011

AbstractWe previously demonstrated the beneficial effect of a novel electrical stimulation (ES) waveform, degenerate wave (DW) on skin fibroblasts, and now hypothesize that DW can enhance cutaneous wound healing in vivo. Therefore, a punch biopsy was taken from the upper arm of 20 volunteers on day 0 and repeated on day 14 (NSD14). A contralateral upper arm biopsy was taken on day 0 and treated with DW for 14 days prior to a repeat biopsy on day 14 (ESD14). A near‐completed inflammatory stage of wound healing in ESD14, compared to NSD14 was demonstrated by up‐regulation of interleukin‐10 and vasoactive intestinal peptide using quantitative real time polymerase chain reaction and down‐regulation of CD3 by immunohistochemistry (IHC) (p < 0.05). In addition to up‐regulation (p < 0.05) of mRNA transcripts for re‐epithelialization and angiogenesis, IHC showed significant overexpression (p < 0.05) of CD31 (15.5%), vascular endothelial growth factor (66%), and Melan A (8.6 cells/0.95 mm2) in ESD14 compared to NSD14 (9.5%, 38% and 4.3 cells/0.95 mm2, respectively). Furthermore, granulation tissue formation (by hematoxylin and eosin staining), and myofibroblastic proliferation demonstrated by alpha‐smooth muscle actin (62.7%) plus CD3+ T lymphocytes (8.1%) showed significant up‐regulation (p < 0.05) in NSD14. In the remodeling stage, mRNA transcripts for fibronectin, collagen IV (by IHC, 14.1%) and mature collagen synthesis (by Herovici staining, 71.44%) were significantly up‐regulated (p < 0.05) in ESD14. Apoptotic (TUNEL assay) and proliferative cells (Ki67) were significantly up‐regulated (p < 0.05) in NSD14 (5.34 and 11.9 cells/0.95 mm2) while the proliferation index of ESD14 was similar to normal skin. In summary, cutaneous wounds receiving DW electrical stimulation display accelerated healing seen by reduced inflammation, enhanced angiogenesis and advanced remodeling phase.
Multiplexed molecular descriptors of pressure ulcers defined by imaging mass spectrometry
Authors: Taverna Domenico , Nanney Lillian B. , Pollins Alonda C. , Sindona Giovanni , Caprioli Richard 
Published: October 2011

AbstractThe pathogenesis of impaired healing within pressure ulcers remains poorly characterized and rarely examined. We describe the results of a pilot study that applies matrix‐assisted laser desorption/ionization imaging mass spectrometry technology for direct tissue analysis to evaluate proteomic signatures ranging from 2 to 20 kDa and phospholipids from 300–1,200 Da in focal regions within the wound microenvironment. Distinguishing molecular differences were apparent between upper vs. lower regions of ulcers and further contrasted against adjacent dermis and epidermal margins using protein profiles, ion density maps, principal component analysis and significant analysis of microarrays. Several proteins previously uncharacterized in pressure ulcers, the α‐defensins (human neutrophil peptide [HNP]‐1, ‐2, ‐3), are potential markers indicating whether the wound status is improving or being prolonged in a deleterious, chronic state. Thymosin β4 appears to be a favorable protein marker showing higher relative levels in adjacent dermis and maturing areas of the wound bed. Lipidomic examination revealed the presence of major lipid classes: glycerophosphocholines, glycerophosphoglycerols, glycerophosphoinositols, and triacylglycerols. Our pilot data examined from either a global perspective using proteomic or lipidomic signatures or as individual distributions reveal that imaging mass spectrometry technology can be effectively used for discovery and spatial mapping of molecular disturbances within the microenvironment of chronic wounds.
Non‐surgical periodontal therapy improves oral health‐related quality of life
Authors: Wong Ruby M. S. , Ng Sam K. S. , Corbet Esmonde F. , Keung Leung W. 
Published: October 2011

AbstractAimThe influence of non‐surgical periodontal therapy on oral health‐related quality of life (OHQoL) was investigated.Materials and MethodsSixty‐five Chinese adults (25 men, mean 47.4 years) with moderate‐to‐advanced chronic periodontitis were recruited. All received oral hygiene instructions (OHI) and non‐surgical periodontal treatment in a quadrant‐wise approach, followed by recalls at 1, 3, 6, 9 and 12 months post treatment, when OHI and prophylaxis were repeated. Clinical parameters were recorded, and oral health impact profile short‐form (OHIP‐14S) was administered at all time points.ResultsModerate‐to‐deep sites (≥4 mm) decreased from 31.0% to 3.0% at 12 months post treatment (p < 0.005) which corresponded well with reductions in plaque, 72.8% to 25.4% (p < 0.005) and bleeding on probing, 86.3% to 32.0% (p < 0.005). Median OHIP‐14S scores gradually reduced from 17 at baseline to 14 over the first 6 months and remained plateaued at 12‐month post treatment (p < 0.005). Improvements in subdomains of physical pain, psychological discomfort and psychological disability accounted for the changes.ConclusionThis study demonstrates that OHQoL, in particular, pain and psychological subdomains, improvement was associated with non‐surgical periodontal therapy responses. Clinicians could capitalize upon the positive psychological OHQoL impacts of mechanical periodontal treatment for subsequent patient‐centred motivation during maintenance therapy.
A γ‐aminobutyrate type A receptor‐associated protein involved in the immune response of Eriocheir sinensis
Authors: Zhou Z. , Wang L. , Kong P. , Qiu L. , Zhang H. , Gao Y. , Yang J. , Song L. 
Published: October 2011

SummaryThe γ‐aminobutyrate type A receptor‐associated protein (GABARAP) is a ubiquitin‐like modifier, which is implicated in membrane trafficking and fusion events of γ‐aminobutyrate type A receptor, autophagy and apoptosis. In the present study, the gene encoding GABARAP (designated EsGABARAP) was cloned from Chinese mitten crab Eriocheir sinensis by using rapid amplification of cDNA ends approach and expression sequence tag (EST) analysis. The full‐length cDNA of EsGABARAP was of 457 bp, containing a 5′ untranslated region (UTR) of 77 bp, a 3′ UTR of 32 bp with a poly(A) tail and an open reading frame (ORF) of 348 bp encoding a polypeptide of 116 amino acids with the predicted molecular weight of 13.81 kDa and theoretical isoelectric point of 8.73. The deduced amino acid sequence of EsGABARAP shared higher similarity (91.8–97.4%) with those of other GABARAPs, and it contained a conserved MAP1_LC3 domain. In the phylogenetic tree, EsGABARAP was firstly clustered with GABARAPs from other animals and then gathered together with the same family proteins of GABARAP. The mRNA expression level of EsGABARAP in six tissues and its temporal expression level in haemocytes of crabs challenged with Listonella anguillarum were determined by quantitative real‐time RT‐PCR. The mRNA transcripts of EsGABARAP could be detected ubiquitously in the examined tissues, including haemocytes, hepatopancreas, muscle, gill, heart and gonad, with the highest expression level in hepatopancreas. The expression level of EsGABARAP mRNA in haemocytes was up‐regulated after L. anguillarum challenge and reached 6.58‐fold of that in blank group at 24 h (P < 0.05) and 7.52‐fold at 48 h (P < 0.05). The increasing transcripts in haemocytes after L. anguillarum challenge gave the preliminary evidence for the involvement of EsGABARAP as a part of immune response against bacteria challenge in crabs.
Daily Light–Dark Cycles Influence Hypoxia‐Inducible Factor 1 and Heat Shock Protein Levels in the Pacemakers of Crayfish
Authors: Velázque‐Amado Rosa María , Escamilla‐Chimal Elsa G. , Fanjul‐Moles María Luisa 
Published: October 2011

AbstractIt has been proposed that at moderate concentrations, reactive oxygen species (ROS) play an important role as regulatory mediators in signaling processes. Many of the ROS‐mediated responses, such as those mediated by the glutathione (GSH) system, protect cells against oxidative stress and reestablish “redox homeostasis.” The response to stress is controlled by specific transcription factors, such as hypoxia‐inducible factor 1 (HIF‐1), which interacts with chaperones such as heat shock proteins (HSP) that stabilize intracellular components. We have reported that the oxidation produced by extreme light cycles was coupled to cellular fluctuations in the production of free radicals and ROS in crayfish. Herein, we investigated whether ROS resulting from light–dark cycles (20:4 LD) with a long photoperiod activated HIF‐1α in the putative pacemakers of crayfish. Our results indicate that both the light resulting from equatorial and extreme daily light cycles and the constant darkness‐induced HIF‐1α and heat shock protein 70 (HSP70) appeared to regulate each other. The interaction between these proteins and the ability of crayfish to shift from the oxidative to glycolytic pathways, thereby synchronizing to extreme illumination conditions and maintaining a rhythmic predictive relationship with the environment, suggest HIF‐1 as a key factor in these rhythmic metabolic interactions.
Examining the influence of insurance and moral hazard on the utilisation of practitioner‐based complementary and alternative medicine
Authors: Bohm Josef 
Published: October 2011

AbstractMoral hazard (excess consumption of clinical services) is representative of consumer behaviour associated with the utilisation of services reimbursed from third‐party payers. Within the USA, CAM is supported by numerous commercial and public insurance programmes. The objective of this article is to assess the utilisation of CAM when paid for by third‐party payers. Data from the 2007 US National Health Interview Survey were examined to measure the relationship between insurance coverage and the utilisation of practitioner‐based alternative medicine. Participant use of chiropractic, osteopathic manipulation and acupuncture was compared with health insurance coverage. The analysis applied standard epidemiological risk ratios to the data in order to calculate the effect of insurance coverage on CAM and moral hazard. The presence of health insurance was a strong facilitator of utilisation, with up to a 40% increase in utilisation when reimbursement mechanisms were introduced. The finding suggests that market‐based strategies for dealing with moral hazard have little influence when applied to practitioner‐based CAM, while insurance coverage plays a significant role in its delivery. Consequently, factors related to behavioural economics and agency modelling may undermine efficient utilisation and payment for CAM services.
JAGUC — A SOFTWARE PACKAGE FOR ENVIRONMENTAL DIVERSITY ANALYSES
Authors: NEBEL MARKUS E. , WILD SEBASTIAN , HOLZHAUSER MICHAEL , HÜTTENBERGER LARS , REITZIG RAPHAEL , SPERBER MATTHIAS , STOECK THORSTEN 
Published: October 2011

Background: The study of microbial diversity and community structures heavily relies on the analyses of sequence data, predominantly taxonomic marker genes like the small subunit of the ribosomal RNA (SSU rRNA) amplified from environmental samples. Until recently, the "gold standard" for this strategy was the cloning and Sanger sequencing of amplified target genes, usually restricted to a few hundred sequences per sample due to relatively high costs and labor intensity. The recent introduction of massive parallel tag sequencing strategies like pyrosequencing (454 sequencing) has opened a new window into microbial biodiversity research. Due to its swift nature and relatively low expense, this strategy produces millions of environmental SSU rDNA sequences granting the opportunity to gain deep insights into the true diversity and complexity of microbial communities. The bottleneck, however, is the computational processing of these massive sequence data, without which, biologists are hardly able to exploit the full information included in these sequence data. Results: The freely available standalone software package JAGUC implements a broad regime of different functions, allowing for efficient and convenient processing of a huge number of sequence tags, including importing custom-made reference data bases for basic local alignment searches, user-defined quality and search filters for analyses of specific sets of sequences, pairwise alignment-based sequence similarity calculations and clustering as well as sampling saturation and rank abundance analyses. In initial applications, JAGUC successfully analyzed hundreds of thousands of sequence data (eukaryote SSU rRNA genes) from aquatic samples and also was applied for quality assessments of different pyrosequencing platforms. Conclusions: The new program package JAGUC is a tool that bridges the gap between computational and biological sciences. It enables biologists to process large sequence data sets in order to infer biological meaning from hundreds of thousands of raw sequence data. JAGUC offers advantages over available tools which are further discussed in this manuscript.
HB-EGF and PDGF Mediate Reciprocal Interactions of Carcinoma Cells with Cancer-Associated Fibroblasts to Support Progression of Uterine Cervical Cancers
Authors: Murata Takuya , Mizushima Hiroto , Chinen Ichino , Moribe Hiroki , Yagi Shigeo , Hoffman Robert M. , Kimura Tadashi , Yoshino Kiyoshi , Ueda Yutaka , Enomoto Takayuki , Mekada Eisuke 
Published: October 2011

Abstract
Tumor stroma drives the growth and progression of cancers. A heparin-binding epidermal growth factor–like growth factor, HB-EGF, is an EGF receptor ligand that stimulates cell growth in an autocrine or paracrine fashion. While elevated expression of HB-EGF in cancer cells and its contribution to tumor progression are well documented, the effects of HB-EGF expression in the tumor stroma have not been clarified. Here, we show that HB-EGF is expressed in stromal fibroblasts where it promotes cancer cell proliferation. In uterine cervical cancers, HB-EGF was detected immunohistochemically in the stroma proximal to the cancer epithelium. Proliferation of cervical cancer cells in vitro was enhanced by coculture with fibroblasts isolated from tumor tissues of patients with cervical cancer. Inhibition of HB-EGF function or treatment with platelet–derived growth factor (PDGF) inhibitors abrogated cancer cell growth enhanced by cervical cancer–associated fibroblast (CCF) coculture. Furthermore, tumor formation in a mouse xenograft model was enhanced by cotransplantation of CCF or mouse embryonic fibroblasts, but not with embryonic fibroblasts from HB-EGF–deficient mice. Conversely, conditioned medium from cancer cells induced HB-EGF expression in CCF. Mechanistic investigations established that PDGF was the primary factor responsible. Together, our findings indicate that HB-EGF and PDGF reciprocally mediate the interaction of cancer cells with cancer-associated fibroblasts, promoting cancer cell proliferation in a paracrine manner that has implications for novel combinatorial cancer therapies. Cancer Res; 71(21); 6633–42. ©2011 AACR.
PAR-1 and Thrombin: The Ties That Bind the Microenvironment to Melanoma Metastasis
Authors: Zigler Maya , Kamiya Takafumi , Brantley Emily C. , Villares Gabriel J. , Bar-Eli Menashe 
Published: October 2011

Abstract
Progression of melanoma is dependent on cross-talk between tumor cells and the adjacent microenvironment. The thrombin receptor, protease-activated receptor-1 (PAR-1), plays a key role in exerting this function during melanoma progression. PAR-1 and its activating factors, which are expressed on tumor cells and the surrounding stroma, induce not only coagulation but also cell signaling, which promotes the metastatic phenotype. Several adhesion molecules, cytokines, growth factors, and proteases have recently been identified as downstream targets of PAR-1 and have been shown to modulate interactions between tumor cells and the microenvironment in the process of melanoma growth and metastasis. Inhibiting such interactions by targeting PAR-1 could potentially be a useful therapeutic modality for melanoma patients. Cancer Res; 71(21); 6561–6. ©2011 AACR.
Wnt Inhibitor Screen Reveals Iron Dependence of β-Catenin Signaling in Cancers
Authors: Song Siyuan , Christova Tania , Perusini Stephen , Alizadeh Solmaz , Bao Ren-Yue , Miller Bryan W. , Hurren Rose , Jitkova Yulia , Gronda Marcela , Isaac Methvin , Joseph Babu , Subramaniam Ratheesh , Aman Ahmed , Chau Anh , Hogge Donna E. , Weir Scott J. , Kasper James , Schimmer Aaron D. , Al-awar Rima , Wrana Jeff L. , Attisano Liliana 
Published: October 2011

Abstract
Excessive signaling from the Wnt pathway is associated with numerous human cancers. Using a high throughput screen designed to detect inhibitors of Wnt/β-catenin signaling, we identified a series of acyl hydrazones that act downstream of the β-catenin destruction complex to inhibit both Wnt-induced and cancer-associated constitutive Wnt signaling via destabilization of β-catenin. We found that these acyl hydrazones bind iron in vitro and in intact cells and that chelating activity is required to abrogate Wnt signaling and block the growth of colorectal cancer cell lines with constitutive Wnt signaling. In addition, we found that multiple iron chelators, desferrioxamine, deferasirox, and ciclopirox olamine similarly blocked Wnt signaling and cell growth. Moreover, in patients with AML administered ciclopirox olamine, we observed decreased expression of the Wnt target gene AXIN2 in leukemic cells. The novel class of acyl hydrazones would thus be prime candidates for further development as chemotherapeutic agents. Taken together, our results reveal a critical requirement for iron in Wnt signaling and they show that iron chelation serves as an effective mechanism to inhibit Wnt signaling in humans. Cancer Res; 71(24); 7628–39. ©2011 AACR.
Molecular Determinants of Retinoic Acid Sensitivity in Pancreatic Cancer
Authors: Gupta Sonal , Pramanik Dipankar , Mukherjee Radha , Campbell Nathaniel R. , Elumalai Sathyanarayanan , de Wilde Roeland F. , Hong Seung-Mo , Goggins Michael G. , De Jesus-Acosta Ana , Laheru Daniel , Maitra Anirban 
Published: October 2011

Abstract
Purpose: To identify a predictive molecular “signature” for sensitivity to retinoic acid in pancreatic cancer.
Experimental Design: Fourteen patient-derived, low-passage pancreatic ductal adenocarcinoma (PDAC) lines with varied expression of fatty acid–binding protein 5 (FABP5) and cellular retinoic acid–binding protein 2 (CRABP2) were used to evaluate the response to all-trans retinoic acid (ATRA). Cell proliferation, apoptosis, and migration/invasion assays were used to measure the in vitro response. Tumor growth was monitored in subcutaneous xenografts in athymic nude mice for 4 weeks.
Results: Response to ATRA was observed to be dependent upon differential expression of FABP5 versus CRABP2. Thus, elevated FABP5 expression was associated with minimal cytotoxicity and tumor growth inhibition and a paradoxical increase in migration and invasion. Conversely, CRABP2 expression in the absence of FABP5 was associated with significant tumor growth inhibition with ATRA, even in gemcitabine-resistant tumors. The ATRA-resistant phenotype of FABP5highCRABP2null cells could be circumvented by ectopic expression of CRABP2. Alternatively, reexpression of endogenous CRABP2 could be enabled in FABP5highCRABP2null PDAC lines by exposure to decitabine and trichostatin A, thereby relieving epigenetic silencing of the CRABP2 gene promoter. Immunohistochemical staining for FABP5 in archival human tissue microarrays identifies a subset of cases (13 of 63, ∼20%) which are negative for FABP5 expression and might be candidates for ATRA therapy.
Conclusions: The widely used agent ATRA deserves a “second look” in PDAC, but needs to be targeted to patient subsets with biopsy-proven FABP5-negative tumors, or be combined with a chromatin-modifying agent to reexpress endogenous CRABP2. Clin Cancer Res; 18(1); 280–9. ©2011 AACR.
Forty Years of Translational Cancer Research
Authors: Hait William N. 
Published: October 2011

Abstract
Forty years after the signing of the National Cancer Act, we have produced a stunning repository of scientific information that is being translated into better therapies for patients. Although challenges remain, many solutions have been adopted, leading to early signs of progress against some of humankind's most dreadful diseases. This Prospective attempts to highlight some of the approaches that have been successful and analyze some that have not, and peers into a future in which renewal of the investment in cancer research will produce further benefits for patients. Cancer Discovery; 1(5): 383–90. ©2011 AACR.
The Prospects of HPV Vaccination in Cervical Cancer Prevention: Results of a New Independent Trial
Authors: Bosch F. Xavier , de Sanjose Silvia , Castellsague Xavier 
Published: October 2011

Abstract
Herrero and colleagues show that in a phase III randomized trial in Guanacaste, Costa Rica, the use of a human papillomavirus type 16 (HPV16) and HPV18 ASO4-adjuvanted vaccine (Cervarix) resulted in complete efficacy against 12-month persistent HPV16 and HPV18 infections and partial protection against HPV31, 33, and 45 in HPV-naïve young women ages 18 to 25. Cancer Discovery; 1(5): 377–80. ©2011 AACR.
Commentary on Herrero et al., p. 408.
Resource Use Among Adult Congenital Heart Surgery Admissions in Pediatric Hospitals
Authors: Kim Yuli Y. , Gauvreau Kimberlee , Bacha Emile A. , Landzberg Michael J. , Benavidez Oscar J. 
Published: October 2011

Background—
Pediatric hospitals frequently perform congenital heart surgery in adults with congenital heart disease. The impact of these admissions on pediatric hospital resources is unknown. Our goals were to examine resource use by adults undergoing congenital heart surgery in pediatric hospitals, explore the association between high resource use (HRU) and inpatient death, and identify HRU risk factors.

Methods and Results—

We obtained inpatient data from 42 pediatric hospitals from 2000 to 2008 and selected adult congenital heart (ACH) surgery admissions. We defined HRU admissions as those exceeding the 90th percentile for total hospital charges. We performed multivariable analyses using generalized estimating equations to identify risk factors for HRU. Of 97 563 congenital heart surgery admissions to pediatric hospitals, 3061 (3.1%) were adults, accounting for 2.2% of total hospital charges. The threshold for HRU was total hospital charges ≥$213 803. Although HRU admissions comprised 10% of admissions, they accounted for 34% of charges for all ACH surgery admissions. Mortality rate was 16% for HRU admissions and 0.7% for others (
P
<0.001). Multivariable analysis demonstrated higher case complexity: risk category 2 (adjusted odds ratio [AOR], 3.6;
P
=0.02), risk category 3 (AOR, 13.7;
P
<0.001), and risk category 4+ (AOR, 30.7;
P
<0.001) as compared with risk category 1; DiGeorge syndrome (AOR, 4.2;
P
=0.006); depression (AOR, 3.1;
P
<0.001); weekend admission (AOR, 2.6;
P
<0.001); and government insurance (AOR, 2.0;
P
<0.001) as risk factors for HRU.

Conclusions—
High resource use ACH surgery admissions are associated with significantly greater mortality rates. ACH admissions with greater surgical complexity, government insurance, DiGeorge syndrome, weekend admission, and depression were more likely to result in HRU.