bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-Wide Study of Hypomethylated and Induced Genes in Patients with Liver Cancer Unravels Novel Anticancer Targets
Authors: Stefanska Barbara , Cheishvili David , Suderman Matthew , Arakelian Ani , Huang Jian , Hallett Michael , Han Ze-Guang , Al-Mahtab Mamun , Akbar Sheikh Mohammad Fazle , Khan Wasif Ali , Raqib Rubhana , Tanvir Imrana , Khan Haseeb Ahmed , Rabbani Shafaat A. , Szyf Moshe 
Published: April 2014

Abstract
Purpose: We utilized whole-genome mapping of promoters that are activated by DNA hypomethylation in hepatocellular carcinoma (HCC) clinical samples to shortlist novel targets for anticancer therapeutics. We provide a proof of principle of this approach by testing six genes short-listed in our screen for their essential role in cancer growth and invasiveness.
Experimental Design: We used siRNA- or shRNA-mediated depletion to determine whether inhibition of these genes would reduce human tumor xenograft growth in mice as well as cell viability, anchorage-independent growth, invasive capacities, and state of activity of nodal signaling pathways in liver, breast, and bladder cancer cell lines.
Results: Depletion of EXOSC4, RNMT, SENP6, WBSCR22, RASAL2, and NENF effectively and specifically inhibits cancer cell growth and cell invasive capacities in different types of cancer, but, remarkably, there is no effect on normal cell growth, suggesting a ubiquitous causal role for these genes in driving cancer growth and metastasis. Depletion of RASAL2 and NENF in vitro reduces their growth as explants in vivo in mice. RASAL2 and NENF depletion interferes with AKT, WNT, and MAPK signaling pathways as well as regulation of epigenetic proteins that were previously demonstrated to drive cancer growth and metastasis.
Conclusion: Our results prove that genes that are hypomethylated and induced in tumors are candidate targets for anticancer therapeutics in multiple cancer cell types. Because these genes are particularly activated in cancer, they constitute a group of targets for specific pharmacologic inhibitors of cancer and cancer metastasis. Clin Cancer Res; 20(12); 3118–32. ©2014 AACR.
Overexpression of Sirt7 Exhibits Oncogenic Property and Serves as a Prognostic Factor in Colorectal Cancer
Authors: Yu Hongyan , Ye Wen , Wu Jiangxue , Meng Xiangqi , Liu Ran-yi , Ying Xiaofang , Zhou Yi , Wang Hui , Pan Changchuan , Huang Wenlin 
Published: April 2014

Abstract
Purpose: Sirtuins play an important role in cancer development. Sirt7, as a member of this family, is frequently overexpressed in certain carcinomas, but the oncogenic mechanism is seldom reported. In this study, Sirt7 was characterized for its role in colorectal cancer aggressiveness and underlying molecular mechanisms.
Experimental Design: Quantitative PCR, Western blotting, and immunohistochemistry were performed to study Sirt7 expression in a cohort of colorectal cancer tissues and non-tumor tissues and cells. A series of in vitro and in vivo assays was performed to elucidate the function of Sirt7 in colorectal cancer and its underlying mechanisms. Association between the Sirt7 signature and survival was examined using Kaplan–Meier analysis and log-rank tests.
Results: The Sirt7 protein level significantly correlated with tumor stage (P = 0.029), lymph node metastasis (P = 0.046), and poor patient survival (P &lt; 0.05). Sirt7 knockdown significantly inhibited colorectal cancer cell proliferation, colony formation, and motility. Ectopic Sirt7 expression promoted colony formation, induced a more invasive phenotype, and accelerated cell growth both in vitro and in vivo. Moreover, Sirt7 enhanced MAPK pathway activity concomitantly with p-ERK and p-MEK upregulation. In Sirt7-overexpressing cells, the mesenchymal markers vimentin and fibronectin were upregulated, and the epithelial markers E-cadherin and β-catenin were downregulated, which was linked to enhanced invasion by colorectal cancer cells.
Conclusion: Our findings suggest that Sirt7 plays an important role in the development and progression of human colorectal cancer and functions as a valuable marker of colorectal cancer prognosis. Clin Cancer Res; 20(13); 3434–45. ©2014 AACR.
FGFR1 mRNA and Protein Expression, not Gene Copy Number, Predict FGFR TKI Sensitivity across All Lung Cancer Histologies
Authors: Wynes Murry W. , Hinz Trista K. , Gao Dexiang , Martini Michael , Marek Lindsay A. , Ware Kathryn E. , Edwards Michael G. , Böhm Diana , Perner Sven , Helfrich Barbara A. , Dziadziuszko Rafal , Jassem Jacek , Wojtylak Szymon , Sejda Aleksandra , Gozgit Joseph M. , Bunn Paul A. , Camidge D. Ross , Tan Aik-Choon , Hirsch Fred R. , Heasley Lynn E. 
Published: April 2014

Abstract
Purpose: FGFR1 gene copy number (GCN) is being evaluated as a biomarker for FGFR tyrosine kinase inhibitor (TKI) response in squamous cell lung cancers (SCC). The exclusive use of FGFR1 GCN for predicting FGFR TKI sensitivity assumes increased GCN is the only mechanism for biologically relevant increases in FGFR1 signaling. Herein, we tested whether FGFR1 mRNA and protein expression may serve as better biomarkers of FGFR TKI sensitivity in lung cancer.
Experimental Design: Histologically diverse lung cancer cell lines were submitted to assays for ponatinib sensitivity, a potent FGFR TKI. A tissue microarray composed of resected lung tumors was submitted to FGFR1 GCN, and mRNA analyses and the results were validated with The Cancer Genome Atlas (TCGA) lung cancer data.
Results: Among 58 cell lines, 14 exhibited ponatinib sensitivity (IC50 values ≤ 50 nmol/L) that correlated with FGFR1 mRNA and protein expression, but not with FGFR1 GCN or histology. Moreover, ponatinib sensitivity associated with mRNA expression of the ligands, FGF2 and FGF9. In resected tumors, 22% of adenocarcinomas and 28% of SCCs expressed high FGFR1 mRNA. Importantly, only 46% of SCCs with increased FGFR1 GCN expressed high mRNA. Lung cancer TCGA data validated these findings and unveiled overlap of FGFR1 mRNA positivity with KRAS and PIK3CA mutations.
Conclusions: FGFR1 dependency is frequent across various lung cancer histologies, and FGFR1 mRNA may serve as a better biomarker of FGFR TKI response in lung cancer than FGFR1 GCN. The study provides important and timely insight into clinical testing of FGFR TKIs in lung cancer and other solid tumor types. Clin Cancer Res; 20(12); 3299–309. ©2014 AACR.
Base Excision Repair Defects Invoke Hypersensitivity to PARP Inhibition
Authors: Horton Julie K. , Stefanick Donna F. , Prasad Rajendra , Gassman Natalie R. , Kedar Padmini S. , Wilson Samuel H. 
Published: April 2014

Abstract
PARP-1 is important for the recognition of both endogenous and exogenous DNA damage, and binds to DNA strand breaks including intermediates of base excision repair (BER). Once DNA-bound, PARP-1 becomes catalytically activated synthesizing PAR polymers onto itself and other repair factors (PARylation). As a result, BER repair proteins such as XRCC1 and DNA polymerase β (pol β) are more efficiently and rapidly recruited to sites of DNA damage. In the presence of an inhibitor of PARP activity (PARPi), PARP-1 binds to sites of DNA damage, but PARylation is prevented. BER enzyme recruitment is hindered, but binding of PARP-1 to DNA is stabilized, impeding DNA repair and leading to double-strand DNA breaks (DSB). Deficiencies in pol β−/− and Xrcc1−/− cells resulted in hypersensitivity to the PARP inhibitor 4-AN and reexpression of pol β or XRCC1, in these contexts, reversed the 4-AN hypersensitivity phenotype. BER deficiencies also showed evidence of replication defects that lead to DSB-induced apoptosis upon PARPi treatment. Finally, the clinically relevant PARP inhibitors olaparib and veliparib also exhibited hypersensitivity in both pol β−/− and Xrcc1−/− BER-deficient cells. These results reveal heightened sensitivity to PARPi as a function of BER deficiency.
Implications: BER deficiency represents a new therapeutic opportunity to enhance PARPi efficacy.
Visual Overview: http://mcr.aacrjournals.org/content/12/8/1128/F1.large.jpg.
Mol Cancer Res; 12(8); 1128–39. ©2014 AACR.
The H2.0-Like Homeobox Transcription Factor Modulates Yolk Sac Vascular Remodeling in Mouse Embryos
Authors: Prahst Claudia , Kasaai Bahar , Moraes Filipa , Jahnsen Espen D. , Larrivee Bruno , Villegas David , Pardanaud Luc , Pibouin-Fragner Laurence , Zhang Feng , Zaun Hans C. , Eichmann Anne , Jones Elizabeth A.V. 
Published: April 2014

Objective—
The H2.0-like homeobox transcription factor (HLX) plays an essential role in visceral organogenesis in mice and has been shown to regulate angiogenic sprouting in vitro and in zebrafish embryos. We therefore examined the role of HLX in vascular development in mouse and avian embryos.

Approach and Results—

In situ hybridization showed that
Hlx
is expressed in a subset of sprouting blood vessels in postnatal mouse retinas and embryos.
Hlx
expression was conserved in quail embryos and upregulated in blood vessels at the onset of circulation. In vitro assays showed that
Hlx
is dynamically regulated by growth factors and shear stress alterations. Proangiogenic vascular endothelial growth factor induces
Hlx
expression in cultured endothelial cells, whereas signals that induce stalk cell identity lead to a reduction in
Hlx
expression. HLX was also downregulated in embryos in which flow was ablated, whereas injection of a starch solution, which increases blood viscosity and therefore shear stress, causes an upregulation in HLX. HLX knockdown in vitro resulted in a reduction in tip cell marker expression and in reduced angiogenic sprouting, but
Hlx
−/−
embryos showed no defect in vascular sprouting at E8.5, E9.5, or E11.5 in vivo. Vascular remodeling of the capillary plexus was altered in
Hlx
−/−
embryos, with a modestly enlarged venous plexus and reduction of the arterial plexus.

Conclusions—

Our findings indicate not only that
Hlx
regulates sprouting in vitro, but that its role in sprouting is nonessential in vivo. We find HLX is regulated by shear stress and a subtle defect in vascular remodeling is present in knockout embryos.
Inter-Relationship Between Electrocardiographic Left Ventricular Hypertrophy and QT Prolongation as Predictors of Increased Risk of Mortality in the General Population
Authors: Soliman Elsayed Z. , Shah Amit J. , Boerkircher Andrew , Li Yabing , Rautaharju Pentti M. 
Published: April 2014

Background—
Prolonged-QT commonly coexists in the ECG with left ventricular hypertrophy (ECG-LVH). However, it is unclear whether to what extent QT prolongation coexisting with ECG-LVH can explain the prognostic significance of ECG-LVH, and whether prolonged-QT coexisting with ECG-LVH should be considered as an innocent consequence of ECG-LVH.

Methods and Results—
The study population consisted of 7506 participants (mean age, 59.4±13.3 years; 49% whites; and 47% men) from the US Third National Health and Nutrition Examination Survey. ECG-LVH was defined by Cornell voltage criteria. Prolonged heart-rate–adjusted QT (prolonged-QTa) was defined as QTa≥460 ms in women or 450 ms in men. Cox proportional hazards analysis was used to calculate the hazard ratios with 95% confidence intervals for the risk of all-cause mortality for various combinations of ECG-LVH and prolonged-QTa. ECG-LVH was present in 4.2% (N=312) of the participants, of whom 16.4% had prolonged-QTa. In a multivariable-adjusted model and compared with the group without ECG-LVH or prolonged-QTa, mortality risk was highest in the group with concomitant ECG-LVH and prolonged-QTa (hazard ratio, 1.63; 95% confidence interval, 1.12–2.36), followed by isolated ECG-LVH (1.48; 1.24–1.77), and then isolated prolonged-QTa (1.27; 1.12–1.46). In models with similar adjustment where ECG-LVH and prolonged-QTa were entered as 2 separate variables and subsequently additionally adjusted for each other, the mortality risk was essentially unchanged for both variables.

Conclusions—
Although prolonged-QT commonly coexists with LVH, both are independent markers of poor prognosis. Concomitant presence of prolonged-QT and ECG-LVH carries a higher risk than either predictor alone.
Number Needed to Entrain
Authors: Maruyama Mitsunori , Yamamoto Teppei , Abe Junko , Yodogawa Kenji , Seino Yoshihiko , Atarashi Hirotsugu , Shimizu Wataru 
Published: April 2014

Background—
Measuring postpacing intervals (PPIs) is the standard maneuver for localizing reentrant tachycardia circuits. However, changes or termination of the tachycardia during entrainment pacing, or difficulties in defining the correct local activity, limit the use of PPIs.

Methods and Results—

We hypothesized that the number of pacing stimuli needed to entrain (NNE) was useful for mapping intra-atrial reentrant tachycardias. First, 10 patients with typical atrial flutter were studied to characterize the NNE. Next, 317 entrainment attempts in 30 patients with 76 intra-atrial reentrant tachycardias were analyzed to determine the efficacy of the NNE. The NNE was small at sites within the reentrant circuit (median 2) and large at remote sites during typical atrial flutter. The NNE depended on the pacing cycle length and coupling interval of the initial paced beat, where the NNE became smaller at shorter pacing cycle lengths and coupling intervals. The NNE highly correlated with the difference between the PPI and tachycardia cycle length (
r
= 0.906;
P
<0.001). When the pacing cycle length and coupling interval were 16 to 30 ms below the tachycardia cycle length, a NNE ≤2 and >3 predicted a PPI−tachycardia cycle length ≤20 and >20 ms, respectively, with 100% accuracy. Thirty-six (11%) entrainment attempts changed or terminated intra-atrial reentrant tachycardia. Importantly, the NNE remained valid in those cases. Furthermore, the NNE provided additional information in cases with some difficulties with PPI measurements.

Conclusions—
The NNE is a simple and reliable criterion, which facilitates mapping intra-atrial reentrant tachycardia.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT001747.
Epidermal Growth Factor and Erythropoietin Infusion Accelerate Functional Recovery in Combination With Rehabilitation
Authors: Jeffers Matthew S. , Hoyles Amy , Morshead Cindi , Corbett Dale 
Published: April 2014

Background and Purpose—
Rehabilitation is the only treatment option for chronic stroke deficits, but unfortunately, it often provides incomplete recovery. In this study, a novel combination of growth factor administration and rehabilitation therapy was used to facilitate functional recovery in a rat model of cortical stroke.

Methods—
Ischemia was induced via injection of endothelin-1 into the sensorimotor cortex. This was followed by either a 2-week infusion of epidermal growth factor and erythropoietin or artificial cerebrospinal fluid into the ipsilateral lateral ventricle. Two weeks after ischemia, animals began an 8-week enriched rehabilitation program. Functional recovery was assessed after ischemia using the Montoya staircase-reaching task, beam-traversing, and cylinder test of forelimb asymmetry.

Results—
The combination of growth factor infusion and rehabilitation led to a significant acceleration in recovery in the staircase task. When compared with controls, animals receiving the combination treatment attained significant recovery of function at 4 weeks after stroke, whereas those receiving rehabilitation alone did not recover until 10 weeks. Significant recovery was also observed on the beam-traversing and cylinder tasks.

Conclusions—
Combining behavioral rehabilitation with growth factor infusion accelerates motor recovery. These data suggest a promising new avenue of combination therapies that may have the potential to reduce the rehabilitation time necessary to recover from sensorimotor deficits arising from stroke.
Migration and Indigenous Communities in the Southern States of Oaxaca and Chiapas, Mexico
Authors: Wohlgemuth Neusa Hidalgo-Monroy 
Published: April 2014

AbstractGlobalization has increased the mobility of labor, product of lower fertility rates and working age populations in developed nations that creates a demand for migrant workers to sustain national economic growth. According to the United Nations Population Fund in 2010, three percent of the world’s population lived outside their country of origin. Migration is an important force in development and it also has become an important factor in social change processes. Perceived as a force that can contribute to development, migration has become a focus of state-level policy-making planning policies creating a growing interest in the political and economic consequences of migration for both receiving and sending communities.This paper offers an overview of the different factors that are leading to migration out of Oaxaca and Chiapas, and the consequences to local indigenous societies. The paper also presents viable existing alternatives to rural development that have been developed by local small-scale farmers that can help reduce the massive exodus of people and consequently destruction of communities.
Ibn Barraǧān and Ibn ʿArabī on the Prediction of the Capture of Jerusalem in 583/1187 by Saladin
Authors: Bellver Jose 
Published: April 2014

Abstract
During the celebration of the capture of Aleppo by Saladin on ṣafar 18th, 579/June 11th, 1183, the qāḍī Muḥyī l-Dīn b. Zakī l-Dīn al-Dimašqī recited a poem in which he ventured the possibility of conquering Jerusalem in the month of raǧab, as this was the case four years later in 583/1187. Muḥyī l-Dīn b. al-Zakī was asked about the source of his prediction and he answered that he found it in Ibn Barraǧān’s Commentary of the Koran in the beginning of sura al-Rūm (Kor 30, 1-4), where the predicted year of the capture was also right. Even though the prediction became well-known, there is no account of the particular way it was obtained, except for the text in Ibn Barraǧān’s Koranic commentary. Instead, we only have later authors stating that Ibn Barraǧān based his analysis upon astrology. Some time later, in his al-Futūḥāt al-makkiyya, Ibn ʿArabī considered twice Ibn Barraǧān’s prediction and drew the same result by applying the science of letters to the same Koranic verses. However, Ibn ʿArabī pointed out that Ibn Barraǧān had committed an error and that his prediction was right by chance. This paper is devoted to the study of Ibn Barraǧān and Ibn ʿArabī’s methods applied to draw the prediction of the Muslim capture of Jerusalem in 583/1187. It supplies the translations of Ibn Barraǧān’s text in his Commentary of the Koran and those of Ibn ʿArabī in al-Futūḥāt al-Makkiyya.
The Sudanese Elements in the Sīrat Sayf b. Ḏī Yazan
Authors: Crudu Andrea 
Published: April 2014

Abstract
Sayf b. Ḏī Yazan is the central character of three main traditions: the original one, its partially historical Yemeni saga; the claim of the Sayfuwa rulers of Kanem-Bornu to be his descendants, and the related corpus of traditions; the Sīrat Sayf b. Ḏī Yazan, a popular epic originally composed in Egypt before the 16th century. The paper tries to demonstrate that the Sīra, in its later, much altered version, has been heavily influenced by sudanese stories, legends and traditions originally coming from the African region long dominated by the Sayfuwa dynasty. The aim is primarily to show this influence and to describe how it interacted with the Sīra. As for the questions regarding when, where and why this took place, only extremely hypothetical conjectures can be advanced at the present state of knowledge.
Gods and/or Ancestors: Practicing Lineage in Contemporary Singapore
Authors: Koh Khee Heong , Ong Chang Woei 
Published: April 2014

AbstractThis paper attempts to examine the roles and functions that lineages play in the social and cultural experiences of certain segments of Singapore’s Chinese community. Since Maurice Freedman argued over half a century ago that beyond the nuclear families and their immediate kin, the Chinese in Singapore normally did not organize themselves according to the ideal of lineage, researches on Chinese voluntary associations in Singapore have by and large overlooked the fact that the practice of organizing kinsmen around the ideas of lineage has persisted up to the present day. The paper looks at two cases — the Wengshan Hongs and the Bangtou Bais — of lineage practices in contemporary Singapore. The former highlights an intangible display of kinship consciousness in a religious space. Gods, rather than ancestors, are symbols that help to bind its kinsmen together. By comparison, the Bangtou Bai lineage is very explicit in the display of their common ancestry identity. The common surname association, the religious space, and the lineage space have been converged. It is the contention of the authors of this paper that the two cases can represent two major strategies of combining religious affiliations and memories of ancestors in a fast-developing urban environment.
Making the “Invisible” a “Visible Problem” — The Representation of Chinese Illegal Immigrants in U.S. Newspapers
Authors: Zhu Zheng 
Published: April 2014

AbstractIn this essay, I critically examined how the Chinese illegal immigrants were represented by theu.s.newspapers between the years 2000 and 2010. Four themes were unearthed. These four themes are 1) New Discourse of Racial Binary in Illegal Immigration, 2) Illegalizing “the Other”, 3) Victims of Chinese Culture, Politics and “Compatriots”, 4) Representation of Authentic Chinese Culture. The critical elaboration of these four themes demonstrated how the news discourse constructed Chinese illegal immigrants as the “outsiders within”. Ultimately, this project served two purposes. One was to “fill” the missing gap left unattended by the prior studies on Chinese immigrants. The other was to re-conceptualize the media representation of the “other” as a “contested and multilayered” process of excluding “the displaced outsiders”, who are struggling along the lines of social and national margins. It is through the critical exploration of the multiple theoretical perspectives and the ideological assumptions supported by the news texts that enables the disclosure of the dominant cultural discourse and politics of the host society.
(Re) imaginings of Hong Kong: Voices from the Hong Kong Diaspora and Their Children
Authors: Tang Winnie 
Published: April 2014

AbstractThis paper explores the (re)imaginings of the past by Chinese Americans and their families who came as part of the Hong Kong Chinese diaspora before 1997. Hong Kong is a locale often described as being conflicted with “the politics of disappearance”, but the Hong Kong Chinese diaspora provides a rich perspective into complex and nuanced tensions between central and peripheral linguistic and cultural imperialistic fields across time. Drawing upon the sociological work of transnational migration and belonging in Hong Kong, this research explores the discourses of Hong Kong émigrés and their young adult and adult children as they discuss their immigration stories, imaginings, and reimaginings of a colonial and post-colonial Hong Kong. The paper focuses on intergenerational conveyance of imagined identities across contexts and languages.