bluuebunny/crossref_metadata_2025_split huggingface dataset:
CANDID: a flexible method for prioritizing candidate genes for complex human traits
Authors: Hutz Janna E. , Kraja Aldi T. , McLeod, Howard L. , Province Michael A. 
Published: July 2008

AbstractGenomewide studies and localized candidate gene approaches have become everyday study designs for identifying polymorphisms in genes that influence complex human traits. Yet, in general, the number of significant findings and the need to focus on smaller regions require a prioritization of genes for further study. Some candidate gene identification algorithms have been proposed in recent years to attempt to streamline this prioritization, but many suffer from limitations imposed by the source data or are difficult to use and understand. CANDID is a prioritization algorithm designed to produce impartial, accurate rankings of candidate genes that influence complex human traits. CANDID can use information from publications, protein domain descriptions, cross‐species conservation measures, gene expression profiles and protein‐protein interactions in its analysis. Additionally, users may supplement these data sources with results from linkage, association and other studies. CANDID was tested on well‐known complex trait genes using data from the Online Mendelian Inheritance in Man database. Additionally, CANDID was evaluated in a modeled gene discovery environment, where it ranked genes whose trait associations were published after CANDID's databases were compiled. In all settings, CANDID exhibited high sensitivity and specificity, indicating an improvement upon previously published algorithms. Its accuracy and ease of use make CANDID a highly useful tool in study design and analysis for complex human traits. Genet. Epidemiol. 2008. © 2008 Wiley‐Liss, Inc.
Comparative gene expression profiling of olfactory ensheathing glia and Schwann cells indicates distinct tissue repair characteristics of olfactory ensheathing glia
Authors: Franssen Elske H.P. , De Bree Freddy M. , Essing Anke H.W. , Ramon‐Cueto Almudena , Verhaagen Joost 
Published: July 2008

AbstractOlfactory ensheathing glia (OEG) are a specialized type of glia that support the growth of primary olfactory axons from the neuroepithelium in the nasal cavity to the brain. Transplantation of OEG in the injured spinal cord promotes sprouting of injured axons and results in reduced cavity formation, enhanced axonal and tissue sparing, remyelination, and angiogenesis. Gene expression analysis may help to identify the molecular mechanisms underlying the ability of OEG to recreate an environment that supports regeneration in the central nervous system. Here, we compared the transcriptome of cultured OEG (cOEG) with the transcriptomes of cultured Schwann cells (cSCs) and of OEG directly obtained from their natural environment (nOEG), the olfactory nerve layer of adult rats. Functional data mining by Gene Ontology (GO)‐analysis revealed a number of overrepresented GO‐classes associated with tissue repair. These classes include “response to wounding,” “blood vessel development,” “cell adhesion,” and GO‐classes related to the extracellular matrix and were overrepresented in the set of differentially expressed genes between both comparisons. The current screening approach combined with GO‐analysis has identified distinct molecular properties of OEG that may underlie their efficacy and interaction with host tissue after implantation in the injured spinal cord. These observations can form the basis for studies on the function of novel target molecules for therapeutic intervention after neurotrauma. © 2008 Wiley‐Liss, Inc.
Glial TLR4 receptor as new target to treat neuropathic pain: Efficacy of a new receptor antagonist in a model of peripheral nerve injury in mice
Authors: Bettoni Isabella , Comelli Francesca , Rossini Clara , Granucci Francesca , Giagnoni Gabriella , Peri Francesco , Costa Barbara 
Published: July 2008

AbstractNeuropathic pain remains a prevalent clinical problem because it is often poorly responsive to the currently used analgesics, thus it is crucial the identification of new potential targets and drugs. Recent evidence indicated that microglial cells in the spinal cord are critically involved in the development and maintenance of neuropathic pain, with a pivotal role of toll‐like receptor 4 (TLR4). Binding of an endogenous ligand to TLR4 might be considered an important step in the regulation of microglia activity in pain facilitation, suggesting that a mechanism aimed to inhibit such a binding could be effective against neuropathic pain. We have synthesized new ligands to TLR4 with antagonistic activity. In the present work we evaluated the efficacy of the most potent TLR4 antagonist synthesized by us (FP‐1), administered in mice with painful neuropathy. The repeated treatment of neuropathic mice with FP‐1 (5–10 mg/kg, i.p.) evoked a relief of both thermal hyperalgesia and mechanical allodynia, whereas the administration of the highest dose to TLR4 knockout neuropathic mice revealed that in the absence of TLR4 receptor, the compound lost its efficacy. As consequence of TLR4 binding, the repeated treatment with FP‐1 prevented the activation of the transcription factor NF‐kB and the TNFα overproduction in the spinal cord. Together, our findings support the previous evidence indicative for a contribution of glial TLR4 to the initiation of neuropathic pain, suggest it as potential innovative target to treat this debilitating disease, and propose FP‐1 as lead compound for the development of new effective drugs. © 2008 Wiley‐Liss, Inc.
The four‐and‐a‐half‐LIM protein 2 (FHL2) is overexpressed in gliomas and associated with oncogenic activities
Authors: Li Ming , Wang Jide , Ng Samuel S. M. , Chan Chu‐Yan , Chen Amy C. , Xia Hong Ping , Yew David T. , Wong Benjamin C. Y. , Chen Zhu , Kung Hsiang‐Fu , Lin Marie Chia‐Mi 
Published: July 2008

AbstractFour‐and‐a‐half‐LIM protein 2 (FHL2) is a member of FHL protein family, which plays a crucial role in regulating gene expression, cell survival, and migration. Although its function in oncogenesis appears to be tumor type‐specific, its roles in glioma formation and development are yet to be elucidated. In the present study, we demonstrated that the mRNA level of FHL2 was elevated in both low‐ and high‐grade glioma samples. Overexpression of FHL2 stimulated the proliferation, anchorage‐independent growth, and migration of human glioblastoma cells. Conversely, FHL2 knockdown by short hairpin RNA (shRNA‐FHL2) inhibited glioblastoma cell proliferation and migration. Overexpression of FHL2 increased the tumorigenicity of glioblastoma cells in nude mice and decreased the mRNA levels of p53 and its downstream proapoptotic genes, including p21, Bcl2‐associated protein X (Bax), and p53‐upregulated modulator of apoptosis. It also enhanced the promoter activities of activator protein‐1 (AP‐1), human telomerase reverse transcriptase, and survivin genes. Together, these results provide the first evidence that FHL2 contributes to glioma carcinogenesis. © 2008 Wiley‐Liss, Inc.
Morphogenesis and regulation of Bergmann glial processes during Purkinje cell dendritic spine ensheathment and synaptogenesis
Authors: Lippman Jocelyn J. , Lordkipanidze Tamar , Buell Margaret E. , Yoon Sung Ok , Dunaevsky Anna 
Published: July 2008

AbstractAstrocytes have an important role in synaptic formation and function but how astrocytic processes become associated with synaptic structures during development is not well understood. Here we analyzed the pattern of growth of the processes extending off the main Bergmann glial (BG) shafts during synaptogenesis in the cerebellum. We found that during this period, BG process outgrowth was correlated with increased ensheathment of dendritic spines. In addition, two‐photon time‐lapse imaging revealed that BG processes were highly dynamic, and processes became more stable as the period of spine ensheathment progressed. While process motility was dependent on actin polymerization, activity of cytoskeletal regulators Rac1 and RhoG did not play a role in glial process dynamics or density, but was critical for maintaining process length. We extended this finding to probe the relationship between process morphology and ensheathment, finding that shortened processes result in decreased coverage of the spine. Furthermore, we found that areas in which BG expressed dn‐Rac1, and therefore had a lower level of synaptic ensheathment, showed an overall increase in synapse number. These analyses reveal how BG processes grow to surround synaptic structures, elucidate the importance of BG process structure for proper development of synaptic ensheathment, and reveal a role for ensheathment in synapse formation. © 2008 Wiley‐Liss, Inc.
Cross‐country disparities in health‐care expenditure: a factor decomposition
Authors: Alcalde‐Unzu Jorge , Ezcurra Roberto , Pascual Pedro 
Published: July 2008

AbstractThis note investigates the sources of international differences in the levels of per capita health‐care expenditure, using data on the OECD countries between 1975 and 2003. To that end, we use Theil's second measure of inequality for decomposing cross‐country disparities in per capita health‐care expenditure into the contributions of various factors: health‐care expenditure expressed as a share of GDP, labour productivity, employment rate, activity rate and the ratio of working‐age population to total population. Our results show that cross‐country differences in the share of GDP devoted to health‐care expenditure and labour productivity are the main determinants of the level of dispersion in per capita health‐care expenditure. On the contrary, existing disparities in the remaining explanatory factors considered play a less relevant role in this context. In any event, the analysis performed reveals that the overall inequality in per capita health‐care expenditure decreased throughout the study period. This was due to the process of international convergence observed in most of the factors used to break down the level of per capita health‐care expenditure. Copyright © 2008 John Wiley & Sons, Ltd.
Physician labour supply in Canada: a cohort analysis
Authors: Crossley Thomas F. , Hurley Jeremiah , Jeon Sung‐Hee 
Published: July 2008

AbstractThis paper employs a cohort analysis to examine the relative importance of different factors in explaining changes in the number of hours spent in direct patient care by Canadian general/family practitioners (GPs) over the period 1982–2003. Cohorts are defined by year of graduation from medical school. The results for male GPs indicate that there is little age effect on hours of direct patient care, especially among physicians aged 35–55, there is no strong cohort effect on hours of direct patient care, but there is a secular decline in hours of direct patient care over the period. The results for female GPs indicate that female physicians on average work fewer hours than male physicians, there is a clear age effect on hours of direct patient care, there is no strong cohort effect, and there has been little secular change in average hours of direct patient care. The changing behaviour of male GPs accounted for a greater proportion of the overall decline in hours of direct patient care from the 1980s through the mid‐1990s than did the growing proportion of female GPs in the physician stock. Copyright © 2008 John Wiley & Sons, Ltd.
Parental response to health risk information: experimental results on willingness‐to‐pay for safer infant milk formula
Authors: Goldberg Isabell , Roosen Jutta , Nayga Rodolfo M. 
Published: July 2008

AbstractEnterobacter sakazakii, a pathogen that can be found in powdered infant milk formula, can cause adverse health effects on infants. Using Vickrey auction, this study examines parents' willingness to pay (WTP) for a quality assurance label on powdered infant milk formula. The influence of ambiguity with the incidence rate information and provision of safe‐handling information on WTP are also evaluated using three experimental treatments. Our findings generally imply that parents significantly value a quality assurance label. The mean price premium parents are willing to pay for the safer and quality assurance labelled powdered infant milk formula ranges from 61 to 133 Eurocents per 100 grams (53–116% of the base price per 100 grams) depending on the treatment. While no ambiguity effects are generally found, provision of safe‐handling information significantly reduced WTP to 39–69 Eurocents per 100 grams depending on the treatment. Copyright © 2008 John Wiley & Sons, Ltd.
Potential for efficacy of the oncolytic Herpes simplex virus 1716 in patients with oral squamous cell carcinoma
Authors: Mace Alastair T. M. , Ganly Ian , Soutar David S. , Brown S. Moira 
Published: July 2008

AbstractBackground.Herpes simplex virus (HSV) 1716 is a selectively replicating oncolytic virus. Our objective was to assess the potential efficacy of HSV1716 in patients with oral squamous cell carcinoma (SCC) by intratumoral injection.Methods.Twenty patients with oral SCC had a single intratumoral injection of HSV1716 at a dose of 105 pfu (plaque forming unit) or 5 × 105 pfu. Injections were done at 1, 3, or 14 days before surgical resection. The tumors were assessed for evidence of viral replication and necrosis. Immunologic response to virus and toxicity was also assessed.Results.Intratumoral injections were well tolerated with no adverse effects. Evidence of biological activity was lacking, with no increase in detectable virus in tumor samples.Conclusion.Intratumoral injection of HSV1716 is safe but with little evidence for viral replication or efficacy. Further studies at higher doses are required to determine the potential efficacy of this virus in head and neck cancer. © 2008 Wiley Periodicals, Inc. Head Neck 2008
Definitive radiation therapy for squamous cell carcinoma of the soft palate
Authors: Chera Bhishamjit S. , Amdur Robert J. , Hinerman Russell W. , Morris Christopher G. , Villaret Douglas B. , Werning John W. , Mendenhall William M. 
Published: July 2008

AbstractBackground.We report the University of Florida experience with soft‐palate carcinoma treated with radiotherapy alone or combined with adjuvant chemotherapy and/or neck dissection for residual disease in the neck.Methods.A total of 145 patients treated with curative intent from 1963 to 2004 were included. Potential follow‐up was ≥2 years.Results.Local control rates at 5 years were: T1, 90%; T2, 91%; T3, 67%; T4, 57%. Nodal control rates at 5 years were: N0, 90%; N1, 82%; N2, 68%; N3, 71%. Ultimate local‐regional control rates at 5 years were: stage I, 89%; stage II, 88%; stage III, 96%; stage IVA, 63%; stage IVB, 43%. In multivariate analysis, overall treatment time significantly affected local and ultimate local‐regional control, and nodal stage significantly affected overall survival. Overall survival rate at 5 years was 44%. Cause‐specific survival rate at 5 years was 73%.Conclusions.The likelihood of cure after definitive radiotherapy is relatively high and is impacted by disease extent and overall treatment time. © 2008 Wiley Periodicals, Inc. Head Neck 2008
A 20-year single-center experience with acute liver failure during pregnancy: Is the prognosis really worse?
Authors: Bhatia Vikram , Singhal Amit , Panda Subrat Kumar , Acharya Subrat Kumar 
Published: July 2008

Abstract

Pregnant patients with acute liver failure (ALF) are believed to have a worse outcome than nonpregnant women and men with ALF. However objective data supporting this supposition are scant. Therefore, the current study compared the outcome, complications, and causes of ALF among pregnant women and girls with age-matched nonpregnant women and girls and men and boys with ALF. One thousand fifteen consecutive ALF patients in the reproductive age group, admitted at the All India Institute of Medical Sciences, New Delhi, from January 1986 to December 2006, were included in the study. A total of 249 (38.5%) women were pregnant. They were compared with 341 nonpregnant women and girls and 425 men and boys, aged 15 to 45 years. The mortality rate of pregnant women and girls (53.8%) was similar to age-matched nonpregnant women and girls (57.2%), and men and boys (57.9%);

P

= 0.572.The clinical and biochemical features, disease severity, and complications were also similar in the three groups. A significantly higher proportion of ALF was attributable to hepatitis E virus (HEV) among women and girls who were pregnant (59.4%), as compared with both nonpregnant women and girls (30.4%), and men and boys (23.1%);

P

< 0.001. However, the outcome of HEV-related ALF was independent of the sex and pregnancy status of the patients (

P

= 0.103). Mortality in HEV-ALF and non–HEV-ALF patients in pregnant women and girls was 51% (74/145) and 54.7% (52/95)(

P

> 0.1), respectively. The outcome of pregnant ALF patients was also unrelated to the trimester of pregnancy. The mortality of non–HEV-related ALF among the pregnant women and girls (54.7%), age-matched nonpregnant women and girls (61.7%), and men and boys (62.8%) were also similar (

P

> 0.1).

Conclusion:

The mortality of pregnant patients with ALF is similar to that of nonpregnant women and girls and men and boys and is independent of the cause or trimester. Pregnancy

per se

should not be regarded as a poor prognostic factor for a patient with ALF. (Hepatology 2008.)
Differentiation therapy of hepatocellular carcinoma in mice with recombinant adenovirus carrying hepatocyte nuclear factor-4α gene
Authors: Yin Chuan , Lin Yong , Zhang Xin , Chen Yue-Xiang , Zeng Xin , Yue Hai-Yan , Hou Jun-Liang , Deng Xing , Zhang Jun-Ping , Han Ze-Guang , Xie Wei-Fen 
Published: July 2008

Abstract

Previous studies have shown that hepatocyte nuclear factor-4α (HNF4α) is a central regulator of differentiated hepatocyte phenotype and forced expression of HNF4α could promote reversion of tumors toward a less invasive phenotype. However, the effect of HNF4α on cancer stem cells (CSCs) and the treatment of hepatocellular carcinoma (HCC) with HNF4α have not been reported. In this study, an adenovirus-mediated gene delivery system, which could efficiently transfer and express HNF4α, was generated to determine its effect on hepatoma cells (Hep3B and HepG2)

in vitro

and investigate the anti-tumor effect of HNF4α in mice. Our results demonstrated that forced re-expression of HNF4α induced the differentiation of hepatoma cells into hepatocytes, dramatically decreased “stemness” gene expression and the percentage of CD133+ and CD90+ cells, which are considered as cancer stem cells in HCC. Meanwhile, HNF4α reduced cell viability through inducing apparent apoptosis in Hep3B, while it induced cell cycle arrest and cellular senescence in HepG2. Moreover, infection of hepatoma cells by HNF4α abolished their tumorigenesis in mice. Most interestingly, systemic administration of adenovirus carrying the HNF4α gene protected mice from liver metastatic tumor formation, and intratumoral injection of HNF4α also displayed significant antitumor effects on transplanted tumor models.

Conclusion:

The striking suppression effect of HNF4α on tumorigenesis and tumor development is attained by inducing the differentiation of hepatoma cells—especially CSCs—into mature hepatocytes, suggesting that differentiation therapy with HNF4α may be an effective treatment for HCC patients. Our study also implies that differentiation therapy may present as one of the best strategies for cancer treatment through the induction of cell differentiation by key transcription factors. (Hepatology 2008.)
Evaluation of previously nonscreened hereditary hemorrhagic telangiectasia patients shows frequent liver involvement and early cardiac consequences
Authors: Gincul Rodica , Lesca Gaetan , Gelas-Dore Bénédicte , Rollin Nathalie , Barthelet Martine , Dupuis-Girod Sophie , Pilleul Franck , Giraud Sophie , Plauchu Henri , Saurin Jean-Christophe 
Published: July 2008

Abstract

Hereditary hemorrhagic telangiectasia (HHT) is a genetic disease characterized by cutaneous, mucosal, and sometimes visceral arteriovenous malformations. Severe hepatic manifestations have been characterized in a subgroup of patients, but few data are available in previously nonscreened patients. We prospectively evaluated liver involvement and its cardiac consequences in such patients. Between 2000 and 2005, we prospectively evaluated the clinical, biological, and hepatic Doppler sonography (DS) characteristics of 102 consecutive HHT patients (mean age, 52.5 years; range, 19-88; 80.4%) with an identified genetic mutation. Patients were segregated into three different severity groups according to DS values. Factors predictive of an abnormal DS, according to predetermined criteria, and of a high cardiac index were identified by logistic and linear regression analysis, respectively. Abnormal liver biology and clinical signs of hepatic involvement were present in 35.3% and 27.5% of cases, respectively. Abnormal DS (defined as at least enlargement of the main hepatic artery) was observed in 56 (54.9%) cases, and direct or indirect signs of significant fistulas were present in 26 (25.5%) cases. Abnormal liver biology and a mutation involving the

ACVRL1

gene were predictive of hepatic ultrasound (US) abnormalities. The diameter of the main hepatic artery and the presence of focal nodular hyperplasia (FNH) were predictive of a higher cardiac index.

Conclusion:

This large prospective series of previously nonscreened HHT patients identified a subgroup at risk of liver involvement (patients with abnormal liver biology and

ACVRL1

mutations) and a subgroup with a higher cardiac index: future studies will show whether such patients would benefit from systematic DS screening and long-term cardiac surveillance. (Hepatology 2008;48:1570–1576.)
Leptin induces phagocytosis of apoptotic bodies by hepatic stellate cells via a Rho guanosine triphosphatase–dependent mechanism
Authors: Jiang Joy X. , Mikami Kenichiro , Shah Vijay H. , Torok Natalie J. 
Published: July 2008

Abstract

Leptin, a profibrogenic cytokine, plays an important role in the development of non-alcoholic steatohepatitis. Leptin also regulates immune responses, including macrophage phagocytic activity. Stellate cells are key elements in liver fibrogenesis, and previously we have demonstrated that phagocytosis of apoptotic bodies by stellate cells is profibrogenic. To study the effects of leptin on the phagocytic activity of hepatic stellate cells, we exposed both LX-2 cells and primary stellate cells to leptin, and we have observed increased phagocytic activity. In stellate cells isolated from Zucker (

fa

/

fa

) rats, the rate of phagocytosis was significantly decreased. To investigate the mechanism by which leptin induces phagocytosis, we focused on the role of Rho-guanosine triphosphate (GTP)-ases. We found that leptin induced the PI3K-dependent activation of Rac1, and that nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase activation was also implicated in this process. Leptin also induced RhoA activation and translocation to the phagosomes. Expression of the constitutive active Rac1 and RhoA both increased the phagocytic rate, whereas inhibition of the Rho-dependent kinase decreased the phagocytic activity.

Conclusion:

We describe a novel role of leptin in the fibrogenic process, the induction of phagocytosis of apoptotic bodies by hepatic stellate cells. The data provide strong evidence of a Rho-GTPase–mediated regulation of the cytoskeleton during stellate cell phagocytosis. Leptin-mediated phagocytic activity of stellate cells therefore could be an important mechanism responsible for progression of fibrosis in non-alcoholic steatohepatitis. (Hepatology 2008.)