bluuebunny/crossref_metadata_2025_split huggingface dataset:
Critical Roles of Notch and Wnt/β-Catenin Pathways in the Regulation of Hyperplasia and/or Colitis in Response to Bacterial Infection
Authors: Ahmed Ishfaq , Chandrakesan Parthasarathy , Tawfik Ossama , Xia Lijun , Anant Shrikant , Umar Shahid 
Published: June 2012

ABSTRACT

Notch and Wnt/β-catenin signals play essential roles in intestinal development and homeostasis.
Citrobacter rodentium
induces transmissible murine colonic hyperplasia (TMCH) and various degrees of inflammation, depending upon the genetic background. We aimed at delineating the role of the Notch and Wnt/β-catenin pathways in the regulation of colonic crypt hyperplasia and/or colitis following
C. rodentium
infection. During TMCH, relative levels of the Notch intracellular domain (NICD) increased significantly, along with increases in Jagged-1 and Hes-1 coinciding with the progression and regression phases of hyperplasia. Blocking of Notch signaling with dibenzazepine (DBZ) for 5 days before the onset of hyperplasia also blocked Wnt/β-catenin signaling. Targeting the Notch pathway for 5 days after the onset of hyperplasia failed to inhibit Wnt/β-catenin-regulated crypt hyperplasia. Chronic DBZ administration for 10 days blocked both Notch and Wnt signaling, disrupted the intestinal barrier, and induced colitis. Core-3
−/−
mice, which are defective in mucin secretion and are susceptible to experimental triggers of colitis, also exhibited significant colitis in response to
C. rodentium
plus DBZ. Chronic DBZ administration in these mice did not result in depletion of the putative stem cell marker doublecortin-like kinase-1 (DCLK1) in the crypts. Dietary bael (
Aegle marmelos
) extract (4%) and curcumin (4%) restored signaling via the Notch and Wnt/β-catenin pathways, thereby promoting crypt regeneration, and also replenished the mucus layer, leading to amelioration of
C. rodentium
- and DBZ-induced colitis in NIH:Swiss mice. Thus, the balancing act between cell proliferation and mucus production to restore barrier integrity seems to depend upon the interplay between the Wnt/β-catenin and Notch pathways in the TMCH model.
The Pseudomonas aeruginosa PhoP-PhoQ Two-Component Regulatory System Is Induced upon Interaction with Epithelial Cells and Controls Cytotoxicity and Inflammation
Authors: Gellatly Shaan L. , Needham Brittany , Madera Laurence , Trent M. Stephen , Hancock Robert E. W. 
Published: June 2012

ABSTRACT

The adaptation of
Pseudomonas aeruginosa
to its environment, including the host, is tightly controlled by its network of regulatory systems. The two-component regulatory system PhoPQ has been shown to play a role in the virulence and polymyxin resistance of
P. aeruginosa
as well as several other Gram-negative species. Dysregulation of this system has been demonstrated in clinical isolates, yet how it affects virulence of
P. aeruginosa
is unknown. To investigate this, an assay was used whereby bacteria were cocultured with human bronchial epithelial cells. The interaction of wild-type (WT) bacteria that had adhered to epithelial cells led to a large upregulation of the expression of the
oprH-phoP-phoQ
operon and its target, the
arn
lipopolysaccharide (LPS) modification operon, in a PhoQ-dependent manner, compared to cells in the supernatant that had failed to adhere. Relative to the wild type, a
phoQ
mutant cocultured on epithelial cells produced less secreted protease and lipase and, like the
phoQ
mutant,
piv
,
lipH
, and
lasB
mutants demonstrated reduced cytotoxicity toward epithelial cells. Mutation in
phoQ
also resulted in alterations to lipid A and to increased inflammatory LPS. These data indicate that mutation of
phoQ
results in a phenotype that is similar to the less virulent but more inflammatory phenotype of clinical strains isolated from chronic-stage cystic fibrosis lung infections.
ONTOTV: AN ONTOLOGY-BASED SYSTEM FOR THE MANAGEMENT OF INFORMATION ABOUT TELEVISION CONTENTS
Authors: REDONDO-GARCÍA JOSÉ LUIS , LOZANO-TELLO ADOLFO 
Published: June 2012

Nowadays, there are a huge number of digital television platforms and channels, so it is not easy for the viewer to decide what they want to watch. Some television providers offer information about the programs they broadcast, but this information is usually scarce and there is no possibility to perform advanced operations like recommendation ones. For this reason, viewers could benefit from a system that integrates all the available information about contents, and applies semantics methodologies in order to provide a better television watching experience. The main objective of this research is the design of a television content management system, called OntoTV, which retrieves television content information from various existing sources and represents all these data in the best way possible by using knowledge engineering and ontologies. These semantic computing techniques make it possible to offer the viewers more useful operations on the stored data than traditional systems do, and with a high degree of personalization. Additionally, OntoTV accomplishes all of this regardless of the TV platform installed and the client device used. The viewers' satisfaction when using this system has been also studied to prove its functionality.
Prognostic PET 18F-FDG Uptake Imaging Features Are Associated with Major Oncogenomic Alterations in Patients with Resected Non–Small Cell Lung Cancer
Authors: Nair Viswam S. , Gevaert Olivier , Davidzon Guido , Napel Sandy , Graves Edward E. , Hoang Chuong D. , Shrager Joseph B. , Quon Andrew , Rubin Daniel L. , Plevritis Sylvia K. 
Published: June 2012

AbstractAlthough 2[18F]fluoro-2-deoxy-d-glucose (FDG) uptake during positron emission tomography (PET) predicts post-surgical outcome in patients with non–small cell lung cancer (NSCLC), the biologic basis for this observation is not fully understood. Here, we analyzed 25 tumors from patients with NSCLCs to identify tumor PET-FDG uptake features associated with gene expression signatures and survival. Fourteen quantitative PET imaging features describing FDG uptake were correlated with gene expression for single genes and coexpressed gene clusters (metagenes). For each FDG uptake feature, an associated metagene signature was derived, and a prognostic model was identified in an external cohort and then tested in a validation cohort of patients with NSCLC. Four of eight single genes associated with FDG uptake (LY6E, RNF149, MCM6, and FAP) were also associated with survival. The most prognostic metagene signature was associated with a multivariate FDG uptake feature [maximum standard uptake value (SUVmax), SUVvariance, and SUVPCA2], each highly associated with survival in the external [HR, 5.87; confidence interval (CI), 2.49–13.8] and validation (HR, 6.12; CI, 1.08–34.8) cohorts, respectively. Cell-cycle, proliferation, death, and self-recognition pathways were altered in this radiogenomic profile. Together, our findings suggest that leveraging tumor genomics with an expanded collection of PET-FDG imaging features may enhance our understanding of FDG uptake as an imaging biomarker beyond its association with glycolysis. Cancer Res; 72(15); 3725–34. ©2012 AACR.
Molecular Pathways: MicroRNAs as Cancer Therapeutics
Authors: Melo Sonia A. , Kalluri Raghu 
Published: June 2012

Abstract
MicroRNAs (miRNA) are approximately 18 to 25 nucleotides in length and affect gene expression by silencing the translation of messenger RNAs. Because each miRNA regulates the expression of hundreds of different genes, miRNAs can function as master coordinators, efficiently regulating and coordinating multiple cellular pathways and processes. By coordinating the expression of multiple genes, miRNAs are responsible for fine-tuning the cell's most important processes, like the ones involved in cellular growth and proliferation. Dysregulation of miRNAs appears to play a fundamental role in the onset, progression and dissemination of many cancers, and replacement of downregulated miRNAs in tumor cells results in a positive therapeutic response. Thus, in theory, inhibition of a particular miRNA linked to cancer onset or progression can remove the inhibition of the translation of a therapeutic protein—and conversely, administration of a miRNA mimetic can boost the endogenous miRNA population repressing the translation of an oncogenic protein. Although several basic questions about their biologic principles still remain to be answered, and despite the fact that all data with respect to miRNAs and therapy are still at the preclinical level, many specific characteristics of miRNAs in combination with compelling therapeutic efficacy data have triggered the research community to start exploring the possibilities of using miRNAs as potential therapeutic candidates. Clin Cancer Res; 18(16); 4234–9. ©2012 AACR.
Molecular Pathways: Targeting the TGF-β Pathway for Cancer Therapy
Authors: Smith Anna L. , Robin Tyler P. , Ford Heide L. 
Published: June 2012

Abstract
TGF-β is a ubiquitous cytokine that plays an active role in many cellular processes. Nearly every cell type has the ability to secrete TGF-β, as well as the ability to respond to TGF-β via the presence of TGF-β receptors on the cell surface. Consequently, gain or loss of function of the TGF-β pathway and its components are known to lead to a variety of diseases, including cancer. In epithelial cells, TGF-β functions as a tumor suppressor, where it inhibits proliferation, induces apoptosis, and mediates differentiation. Conversely, in other contexts, TGF-β promotes tumor progression through increasing tumor cell invasion and metastasis. Thus, TGF-β can have opposing roles, likely dependent, in part, on whether the cancer is early or late stage. The effects of TGF-β on tumor suppression and promotion are not limited to the tumor cell itself; rather, these effects can also be mediated through the stroma and the immune system. The dichotomous role of TGF-β in cancer highlights our need to understand the contextual effects of this cytokine to better guide patient selection for the use of anti–TGF-β therapies currently in clinical trials. Clin Cancer Res; 18(17); 4514–21. ©2012 AACR.
FAS1 Domain Protein Inhibits VEGF165-Induced Angiogenesis by Targeting the Interaction between VEGFR-2 and αvβ3 Integrin
Authors: Nam Ju-Ock , Son Hye-Nam , Jun Eunsung , Cha Kiweon , Lee Byung-Heon , Park Rang-Woon , Kim In-San 
Published: June 2012

Abstract
It is known that VEGF receptors (VEGFR) and integrins interact with each other to regulate angiogenesis. We reported previously that the fasciclin 1 (FAS1) domain–containing protein, TGFBIp/βig-h3 (TGF-β–induced protein) is an angiogenesis regulator that inhibits both endothelial cell migration and growth via αvβ3 integrin. In an attempt to target the interaction between VEGFR-2 and αvβ3 integrin, we determined whether the FAS1 domain region of TGFBIp/βig-h3 (FAS1 domain protein) can block the interaction between the two receptors, leading to the suppression of angiogenesis. In this study, we showed that FAS1 domain protein inhibits VEGF165-induced endothelial cell proliferation and migration via αvβ3 integrin, resulting in the inhibition of VEGF165-induced angiogenesis. We also defined a molecular mechanism by which FAS1 domain protein blocks the association between αvβ3 integrin and VEGFR-2, showing that it binds to αvβ3 integrin but not to VEGFR-2. Blocking the association of these major angiogenic receptors with FAS1 domain protein inhibits signaling pathways downstream of VEGFR-2. Collectively, our results indicate that FAS1 domain protein, in addition to its inhibitory effect on αvβ3 integrin–mediated angiogenesis, also inhibits VEGF165-induced angiogenesis. Thus, FAS1 domain protein can be further developed into a potent anticancer drug that targets two principal angiogenic pathways. Mol Cancer Res; 10(8); 1010–20. ©2012 AACR.
Evaluation of a novel individualised communication-skills training intervention to improve doctors’ confidence and skills in end-of-life communication
Authors: Clayton Josephine M , Butow Phyllis N , Waters Amy , Laidsaar-Powell Rebekah C , O’Brien Angela , Boyle Frances , Back Anthony L , Arnold Robert M , Tulsky James A , Tattersall Martin HN 
Published: June 2012

Background: We developed a novel individualised training program regarding end-of-life communication, designed to be time effective for busy junior-doctors working in hospital settings. Aim: We aimed to pilot this brief individualised training program with junior-doctors to explore its acceptability, feasibility and effect on the doctors’ confidence, communication skills, attitudes towards psychosocial care and burnout. Design: The content of the training intervention was informed by a systematic literature review and evidence-based clinical practice guidelines regarding end-of-life communication. The intervention was based on sound educational principles and involved three one-hour teaching sessions over a three-week period, including two individual sessions with an expert facilitator and simulated patient/caregiver. In addition, participants received written and audiovisual take-home learning materials. Participants were videotaped consulting with a simulated patient/caregiver pre/post training to assess the impact of the course on their communication behaviours. Participants completed de-identified questionnaires pre/post training, including self-assessed confidence, attitudes to psychosocial care, and the Maslach Burnout inventory. Participants: Participants included 22 junior-doctors from a large teaching hospital in Sydney, Australia. Results: All participants reported that the training was useful, had been helpful for their communication with patients and that they would recommend the training to others. Significant improvements were found in participants’ communication skills (in seven out of 21 specific and all three global communication behaviours assessed, range P=0.02 to <0.001), confidence in communicating about relevant topics ( P<0.001), attitudes towards psychosocial care ( P=0.03) and sense of personal accomplishment ( P=0.043). There were no overall differences in participants’ burnout levels. Conclusion: This intervention shows promise and warrants further formal evaluation.
The complex actions of sumatriptan on rat dural afferents
Authors: Harriott Andrea M , Scheff Nicole N , Gold Michael S 
Published: June 2012

Aim To test the hypothesis that the clinical efficacy of triptans reflects convergent modulation of ion channels also involved in inflammatory mediator (IM)-induced sensitization of dural afferents. Methods Acutely dissociated retrogradely labeled rat dural afferents were studied with whole cell and perforated patch techniques in the absence and presence of sumatriptan and/or IM (prostaglandin E2, bradykinin, and histamine). Results Sumatriptan dose-dependently suppressed voltage-gated Ca2+ currents. Acute (2 min) sumatriptan application increased dural afferent excitability and occluded further IM-induced sensitization. In contrast, pre-incubation (30 min) with sumatriptan had no influence on dural afferent excitability and partially prevented IM-induced sensitization of dural afferents. The sumatriptan-induced suppression of voltage-gated Ca2+ currents and acute sensitization and pre-incubation-induced block of IM-induced sensitization were blocked by the 5-HT1D antagonist BRL 15572. Pre-incubation with sumatriptan failed to suppress the IM-induced decrease in action potential threshold and overshoot (which results from modulation of voltage-gated Na+ currents) and activation of Cl− current, and had no influence on the Cl− reversal potential. However, pre-incubation with sumatriptan caused a dramatic hyperpolarizing shift in the voltage dependence of K+ current activation. Discussion These results indicate that although the actions of sumatriptan on dural afferents are complex, at least two distinct mechanisms underlie the antinociceptive actions of this compound. One of these mechanisms, the shift in the voltage dependence of K+ channel activation, may suggest a novel strategy for future development of anti-migraine agents.
Intranasal ketorolac tromethamine (SPRIX®) containing 6% of lidocaine (ROX-828) for acute treatment of migraine: Safety and efficacy data from a phase II clinical trial
Authors: Pfaffenrath V , Fenzl E , Bregman D , Färkkila M 
Published: June 2012

Objective Ketorolac is a non-triptan, non-opioid, mixed cyclooxygenase (COX)1/2-inhibitor for short-term management of moderate-to-severe acute pain. This trial evaluated an intranasal formulation of ketorolac tromethamine (SPRIX®) containing 6% lidocaine (ROX-828) for the acute treatment of migraine with and without aura as defined by the International Headache Society. Methods Patients were randomly assigned 1:1 to self-treat with intranasal ROX-828 (31.5 mg ketorolac tromethamine/200 µL, containing 6% of lidocaine) or placebo (with 6% lidocaine) within four hours of a new migraine attack rated ≥ moderate in pain intensity. Assessments included headache intensity and associated migraine symptoms (nausea, vomiting, phonophobia, photophobia) measured at baseline and at regular intervals through 48 hours post-dosing, and global impression of efficacy (seven-point scale) measured at two hours. Results Randomized patients who had a migraine attack ( N = 140) were evaluable (ROX-828, N = 68; placebo, N = 72). Patients receiving ROX-828 showed a significant ( p < 0.05) improvement in pain relief at all time points except 0.5 and 24 hours compared with those who received placebo. More patients achieved pain-free status with ROX-828 than with placebo at 1.5, 3, 4, 24 and 48 hours ( p < 0.05); significance at the two-hour time point, which was the primary endpoint, was not met. Patients’ global impression of efficacy showed statistically significantly better results for patients receiving ROX-828 than for those receiving placebo. Associated migraine symptoms were significantly improved ( p < 0.05) with ROX-828 relative to placebo at several time points throughout the observation period. The most frequently reported adverse events in both groups were associated with nasal discomfort. Conclusion Self-administered intranasal ROX-828 was well tolerated. While the primary endpoint was not met, the results provide preliminary evidence that ROX-828 improves migraine pain.
T-cell suicide gene therapy prompts thymic renewal in adults after hematopoietic stem cell transplantation
Authors: Vago Luca , Oliveira Giacomo , Bondanza Attilio , Noviello Maddalena , Soldati Corrado , Ghio Domenico , Brigida Immacolata , Greco Raffaella , Lupo Stanghellini Maria Teresa , Peccatori Jacopo , Fracchia Sergio , Del Fiacco Matteo , Traversari Catia , Aiuti Alessandro , Del Maschio Alessandro , Bordignon Claudio , Ciceri Fabio , Bonini Chiara 
Published: June 2012

Abstract
The genetic modification of T cells with a suicide gene grants a mechanism of control of adverse reactions, allowing safe infusion after partially incompatible hematopoietic stem cell transplantation (HSCT). In the TK007 clinical trial, 22 adults with hematologic malignancies experienced a rapid and sustained immune recovery after T cell–depleted HSCT and serial infusions of purified donor T cells expressing the HSV thymidine kinase suicide gene (TK+ cells). After a first wave of circulating TK+ cells, the majority of T cells supporting long-term immune reconstitution did not carry the suicide gene and displayed high numbers of naive lymphocytes, suggesting the thymus-dependent development of T cells, occurring only upon TK+-cell engraftment. Accordingly, after the infusions, we documented an increase in circulating TCR excision circles and CD31+ recent thymic emigrants and a substantial expansion of the active thymic tissue as shown by chest tomography scans. Interestingly, a peak in the serum level of IL-7 was observed after each infusion of TK+ cells, anticipating the appearance of newly generated T cells. The results of the present study show that the infusion of genetically modified donor T cells after HSCT can drive the recovery of thymic activity in adults, leading to immune reconstitution.
A disease risk index for patients undergoing allogeneic stem cell transplantation
Authors: Armand Philippe , Gibson Christopher J. , Cutler Corey , Ho Vincent T. , Koreth John , Alyea Edwin P. , Ritz Jerome , Sorror Mohamed L. , Lee Stephanie J. , Deeg H. Joachim , Storer Barry E. , Appelbaum Frederick R. , Antin Joseph H. , Soiffer Robert J. , Kim Haesook T. 
Published: June 2012

Abstract
The outcome of allogeneic HSCT varies considerably by the disease and remission status at the time of transplantation. Any retrospective or prospective HSCT study that enrolls patients across disease types must account for this heterogeneity; yet, current methods are neither standardized nor validated. We conducted a retrospective study of 1539 patients who underwent transplantation at Dana-Farber Cancer Institute/Brigham and Women's Hospital from 2000 to 2009. Using multivariable models for overall survival, we created a disease risk index. This tool uses readily available information about disease and disease status to categorize patients into 4 risk groups with significantly different overall survival and progression-free survival on the basis of primarily differences in the relapse risk. This scheme applies regardless of conditioning intensity, is independent of comorbidity index, and was validated in an independent cohort of 672 patients from the Fred Hutchinson Cancer Research Center. This simple and validated scheme could be used to risk-stratify patients in both retrospective and prospective HSCT studies, to calibrate HSCT outcomes across studies and centers, and to promote the design of HSCT clinical trials that enroll patients across diseases and disease states, increasing our ability to study nondisease-specific outcomes in HSCT.
Vertebral derotation in adolescent idiopathic scoliosis causes hypokyphosis of the thoracic spine
Authors: Watanabe Kota , Nakamura Takayuki , Iwanami Akio , Hosogane Naobumi , Tsuji Takashi , Ishii Ken , Nakamura Masaya , Toyama Yoshiaki , Chiba Kazuhiro , Matsumoto Morio 
Published: June 2012

Abstract

Background
The purpose of this study was to test the hypothesis that direct vertebral derotation by pedicle screws (PS) causes hypokyphosis of the thoracic spine in adolescent idiopathic scoliosis (AIS) patients, using computer simulation.

Methods
Twenty AIS patients with Lenke type 1 or 2 who underwent posterior correction surgeries using PS were included in this study. Simulated corrections of each patient’s scoliosis, as determined by the preoperative CT scan data, were performed on segmented 3D models of the whole spine. Two types of simulated extreme correction were performed: 1) complete coronal correction only (C method) and 2) complete coronal correction with complete derotation of vertebral bodies (C + D method). The kyphosis angle (T5-T12) and vertebral rotation angle at the apex were measured before and after the simulated corrections.

Results
The mean kyphosis angle after the C + D method was significantly smaller than that after the C method (2.7 ± 10.0° vs. 15.0 ± 7.1°, p < 0.01). The mean preoperative apical rotation angle of 15.2 ± 5.5° was completely corrected after the C + D method (0°) and was unchanged after the C method (17.6 ± 4.2°).

Conclusions
In the 3D simulation study, kyphosis was reduced after complete correction of the coronal and rotational deformity, but it was maintained after the coronal-only correction. These results proved the hypothesis that the vertebral derotation obtained by PS causes hypokyphosis of the thoracic spine.
Existence of strong solutions for a class of semilinear evolution equations with nonlocal initial conditions
Authors: Chen Pengyu , Li Yongxiang , Fan Hongxia 
Published: June 2012

Abstract
This paper discusses the existence of strong solutions for a class of semilinear evolution equations with nonlocal initial conditions in Hilbert spaces. The discussion is based on analytic semigroups theory and fixed point theorem. An application to a partial differential equation with nonlocal condition is also considered.

Mathematics Subject Classification(2010): 34G20; 34K30; 35D35; 47D06.