bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mendelian Randomization: How It Can—and Cannot—Help Confirm Causal Relations between Nutrition and Cancer
Authors: Schatzkin Arthur , Abnet Christian C. , Cross Amanda J. , Gunter Marc , Pfeiffer Ruth , Gail Mitchell , Lim Unhee , Davey-Smith George 
Published: January 2009

AbstractObservational epidemiologic studies of nutrition and cancer have faced formidable methodologic obstacles, including dietary measurement error and confounding. We consider whether Mendelian randomization can help surmount these obstacles. The Mendelian randomization strategy, building on both the accuracy of genotyping and the random assortment of alleles at meiosis, involves searching for an association between a nutritional exposure–mimicking gene variant (a type of “instrumental variable”) and cancer outcome. Necessary assumptions are that the gene is independent of cancer, given the exposure, and also independent of potential confounders. An allelic variant can serve as a proxy for diet and other nutritional factors through its effects on either metabolic processes or consumption behavior. Such a genetic proxy is measured with little error and usually is not confounded by nongenetic characteristics. Examples of potentially informative genes include LCT (lactase), ALDH2 (aldehyde dehydrogenase), and HFE (hemochromatosis), proxies, respectively, for dairy product intake, alcoholic beverage drinking, and serum iron levels. We show that use of these and other genes in Mendelian randomization studies of nutrition and cancer may be more complicated than previously recognized and discuss factors that can invalidate the instrumental variable assumptions or cloud the interpretation of these studies. Sample size requirements for Mendelian randomization studies of nutrition and cancer are shown to be potentially daunting; strong genetic proxies for exposure are necessary to make such studies feasible. We conclude that Mendelian randomization is not universally applicable, but, under the right conditions, can complement evidence for causal associations from conventional epidemiologic studies.
Changing Hormone Levels during the Menstrual Cycle Affect Knee Laxity and Stiffness in Healthy Female Subjects
Authors: Park Sang-Kyoon , Stefanyshyn Darren J. , Loitz-Ramage Barbara , Hart David A. , Ronsky Janet L. 
Published: January 2009

Background Whether knee laxity varies throughout the menstrual cycle remains controversial. As increased laxity may be a risk factor for anterior cruciate ligament (ACL) injury, further research is warranted. Hypothesis Variation in estradiol and progesterone levels during the menstrual cycle influences knee laxity and stiffness. Study Design Case control study; Level of evidence, 3. Methods The serum estradiol and progesterone levels of 26 healthy female subjects were recorded in the follicular phase, ovulation, and the luteal phase. Knee joint laxity was assessed using a standard knee arthrometer at the same intervals. Stiffness changes in the load-displacement curve were determined. Hormone levels across the cycle were compared between responders and nonresponders, defined by whether changes in knee laxity at 89 N occurred. Results Greater laxity at 89 N during ovulation was observed (ovulation: 5.13 ± 1.70 mm vs luteal: 4.55 ± 1.54 mm, P =. 012). In knee laxity testing at manual maximum load, greater laxity was noticed during ovulation (14.43 ± 2.60 mm, P =. 018), as compared with the follicular phase (13.35 ± 2.53 mm). A reduction in knee stiffness of approximately 17% (ovulation: 12.48 ± 5.46 N/mm vs luteal: 15.02 ± 7.71 N/mm, P =. 042) during ovulation was observed. However, there were no differences in hormone levels between responders and nonresponders at 89 N. Conclusion Female hormone levels are related to increased knee joint laxity and decreased stiffness at ovulation. To understand subject variations in knee joint laxity during the menstrual cycle in female athletes, further investigation is warranted.
‘It's like talking to a brick wall’
Authors: Whittall Jonathan 
Published: January 2009

For the purpose of this article, humanitarian diplomacy is defined as: the use of International Law and the humanitarian imperative as complimentary levers to facilitate the delivery of assistance or to promote the protection of civilians in a complex political emergency. Based on field research in the occupied Palestinian territory in 2007, this article demonstrates that the external reality of a US global superpower overly reliant on hard power, combined with its strategic alliance with Israel in the Middle East, creates an operating environment that severely constrains the use of humanitarian diplomacy. Whilst United Nations (UN) agencies implement technically sound interventions, the political realities prevent the effective use of International Law. The UN field staff are evoking Palestinian's humanitarian needs as a lever to promote protection, but this is fundamentally missing the point. The situation in the West Bank is a human rights issue – borne from a political crisis. The protection of Palestinians is undermined by an aversion to the use of International Law because of the political realities of an unchallenged occupation.
Layout as punctuation of semiosis: some examples from Israeli schoolbooks
Authors: Peled-Elhanan Nurit 
Published: January 2009

This article examines the function of layout in the representation of the Palestinian—Israeli conflict in three history textbooks used in Israeli schools. The analysis elaborates on two concepts of Kress and Van Leeuwen — `ideological layout' and `punctuation of semiosis'. The author argues that layout may `punctuate' semiosis in two different senses: first, in the sense of `bringing (conventional—official) semiosis to a temporary standstill in textual form'; and, second, in the sense of `piercing a hole' in the conventional or official semiosis it presents, and thereby criticizing it. In both cases, layout creates new complex signs that either support or contradict the verbal and visual texts it presents. This study suggests that layout analysis may help answer larger questions concerning `the transformation of social practices into discourses about social practices in specific institutional contexts' (Van Leeuwen, 1996). The discussion of the means by which these punctuations are achieved and the messages they convey is followed by reflections upon the difficulties students and teachers may have in reading such multimodal texts.
Dendritic cell homeostasis
Authors: Merad Miriam , Manz Markus G. 
Published: January 2009

AbstractDendritic cells (DCs) are a heterogeneous fraction of rare hematopoietic cells that coevolved with the formation of the adaptive immune system. DCs efficiently process and present antigen, move from sites of antigen uptake to sites of cellular interactions, and are critical in the initiation of immune responses as well as in the maintenance of self-tolerance. DCs are distributed throughout the body and are enriched in lymphoid organs and environmental contact sites. Steady-state DC half-lives account for days to up to a few weeks, and they need to be replaced via proliferating hematopoietic progenitors, monocytes, or tissue resident cells. In this review, we integrate recent knowledge on DC progenitors, cytokines, and transcription factor usage to an emerging concept of in vivo DC homeostasis in steady-state and inflammatory conditions. We furthermore highlight how knowledge of these maintenance mechanisms might impact on understanding of DC malignancies as well as posttransplant immune reactions and their respective therapies.
Prediction of protein-protein interaction types using association rule based classification
Authors: Park Sung Hee , Reyes José A , Gilbert David R , Kim Ji Woong , Kim Sangsoo 
Published: January 2009

Abstract

Background
Protein-protein interactions (PPI) can be classified according to their characteristics into, for example obligate or transient interactions. The identification and characterization of these PPI types may help in the functional annotation of new protein complexes and in the prediction of protein interaction partners by knowledge driven approaches.

Results
This work addresses pattern discovery of the interaction sites for four different interaction types to characterize and uses them for the prediction of PPI types employing Association Rule Based Classification (ARBC) which includes association rule generation and posterior classification. We incorporated domain information from protein complexes in SCOP proteins and identified 354 domain-interaction sites. 14 interface properties were calculated from amino acid and secondary structure composition and then used to generate a set of association rules characterizing these domain-interaction sites employing the APRIORI algorithm. Our results regarding the classification of PPI types based on a set of discovered association rules shows that the discriminative ability of association rules can significantly impact on the prediction power of classification models. We also showed that the accuracy of the classification can be improved through the use of structural domain information and also the use of secondary structure content.

Conclusion
The advantage of our approach is that we can extract biologically significant information from the interpretation of the discovered association rules in terms of understandability and interpretability of rules. A web application based on our method can be found at http://bioinfo.ssu.ac.kr/~shpark/picasso/
Bioelectrical impedance phase angle in clinical practice: implications for prognosis in stage IIIB and IV non-small cell lung cancer
Authors: Gupta Digant , Lammersfeld Carolyn A , Vashi Pankaj G , King Jessica , Dahlk Sadie L , Grutsch James F , Lis Christopher G 
Published: January 2009

Abstract

Background
A frequent manifestation of advanced lung cancer is malnutrition, timely identification and treatment of which can lead to improved patient outcomes. Bioelectrical impedance analysis (BIA) is an easy-to-use and non-invasive technique to evaluate changes in body composition and nutritional status. We investigated the prognostic role of BIA-derived phase angle in advanced non-small cell lung cancer (NSCLC).

Methods
A case series of 165 stages IIIB and IV NSCLC patients treated at our center. The Kaplan Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of phase angle, independent of stage at diagnosis and prior treatment history.

Results
93 were males and 72 females. 61 had stage IIIB disease at diagnosis while 104 had stage IV. The median phase angle was 5.3 degrees (range = 2.9 – 8). Patients with phase angle <= 5.3 had a median survival of 7.6 months (95% CI: 4.7 to 9.5; n = 81), while those with > 5.3 had 12.4 months (95% CI: 10.5 to 18.7; n = 84); (p = 0.02). After adjusting for age, stage at diagnosis and prior treatment history we found that every one degree increase in phase angle was associated with a relative risk of 0.79 (95% CI: 0.64 to 0.97, P = 0.02).

Conclusion
We found BIA-derived phase angle to be an independent prognostic indicator in patients with stage IIIB and IV NSCLC. Nutritional interventions targeted at improving phase angle could potentially lead to an improved survival in patients with advanced NSCLC.
Long-term effects of peroxisome proliferator-activated receptor ligand bezafibrate on N-terminal pro-B type natriuretic peptide in patients with advanced functional capacity impairment
Authors: Node Koichi , Inoue Teruo , Boyko Valentin , Goldberg Ilan , Fisman Enrique Z , Adler Yehuda , Schwammenthal Ehud , Matas Zipora , Behar Solomon , Tenenbaum Alexander 
Published: January 2009

Abstract

Background
The effects of pan-peroxisome proliferator-activated receptor (PPAR) ligand bezafibrate on N-terminal pro-B type natriuretic peptide (ProBNP) level in patients with coronary artery disease (CAD) is unknown. The current study aimed to investigate the long-term effects of bezafibrate on ProBNP level in patients with pre-existing CAD and advanced functional capacity impairment.

Methods
Metabolic and inflammatory parameters were analyzed from stored frozen serum samples obtained from 108 patients enrolled in the Bezafibrate Infarction Prevention (BIP) Study. They presented with New York Heart Association (NYHA) functional class III, comprising 58 patients in the bezafibrate group and 50 in the placebo groups, and completed a 2-year prospective, double-blind, placebo-controlled follow-up.

Results
During follow-up ProBNP level did not change significantly in the placebo group, whereas it increased slightly in the bezafibrate group, which was older and with lower baseline ProBNP values. No significant differences between the groups were found for ProBNP levels after 2 year of follow-up. Analysis-of-covariance (ANCOVA) -taking into account age and baseline ProBNP level- showed that bezafibrate was not associated with longitudinal ProBNP changes during the follow-up period (p = 0.3).

Conclusion
Long-term treatment by bezafibrate was not associated with longitudinal ProBNP changes in patients with pre-existing CAD and advanced functional capacity impairment.
Implication of granulocyte-macrophage colony-stimulating factor induced neutrophil gelatinase-associated lipocalin in pathogenesis of rheumatoid arthritis revealed by proteome analysis
Authors: Katano Masayoshi , Okamoto Kazuki , Arito Mitsumi , Kawakami Yuki , Kurokawa Manae S , Suematsu Naoya , Shimada Sonoko , Nakamura Hiroshi , Xiang Yang , Masuko Kayo , Nishioka Kusuki , Yudoh Kazuo , Kato Tomohiro 
Published: January 2009

Abstract
Introduction
In rheumatoid arthritis (RA), synovial fluid (SF) contains a large number of neutrophils that contribute to the inflammation and destruction of the joints. The SF also contains granulocyte-macrophage colony-stimulating factor (GM-CSF), which sustains viability of neutrophils and activates their functions. Using proteomic surveillance, we here tried to elucidate the effects of GM-CSF on neutrophils.

Methods
Neutrophils stimulated by GM-CSF were divided into four subcellular fractions: cytosol, membrane/organelle, nuclei, and cytoskeleton. Then, proteins were extracted from each fraction and digested by trypsin. The produced peptides were detected using matrix-assisted laser desorption ionisation-time-of-flight mass spectrometry (MALDI-TOF MS).

Results
We detected 33 peptide peaks whose expression was upregulated by more than 2.5-fold in GM-CSF stimulated neutrophils and identified 11 proteins out of the 33 peptides using MALDI-TOF/TOF MS analysis and protein database searches. One of the identified proteins was neutrophil gelatinase-associated lipocalin (NGAL). We confirmed that the level of NGAL in SF was significantly higher in patients with RA than in those with osteoarthritis. We next addressed possible roles of the increased NGAL in RA. We analysed proteome alteration of synoviocytes from patients with RA by treatment with NGAL in vitro. We found that, out of the detected protein spots (approximately 3,600 protein spots), the intensity of 21 protein spots increased by more than 1.5-fold and the intensity of 10 protein spots decreased by less than 1 to 1.5-fold as a result of the NGAL treatment. Among the 21 increased protein spots, we identified 9 proteins including transitional endoplasmic reticulum ATPase (TERA), cathepsin D, and transglutaminase 2 (TG2), which increased to 4.8-fold, 1.5-fold and 1.6-fold, respectively. Two-dimensional electrophoresis followed by western blot analysis confirmed the upregulation of TERA by the NGAL treatment and, moreover, the western blot analysis showed that the NGAL treatment changed the protein spots caused by post-translational modification of TERA. Furthermore, NGAL cancelled out the proliferative effects of fibroblast growth factor (FGF)-2 and epidermal growth factor (EGF) on chondrocytes from a patient with RA and proliferative effect of FGF-2 on chondrosarcoma cells.

Conclusions
Our results indicate that GM-CSF contributes to the pathogenesis of RA through upregulation of NGAL in neutrophils, followed by induction of TERA, cathepsin D and TG2 in synoviocytes. NGAL and the upregulated enzymes may therefore play an important role in RA.
Tamoxifen induces pleiotrophic changes in mammary stroma resulting in extracellular matrix that suppresses transformed phenotypes
Authors: Hattar Rhonda , Maller Ori , McDaniel Shauntae , Hansen Kirk C , Hedman Karla J , Lyons Traci R , Lucia Scott , Wilson R Storey , Schedin Pepper 
Published: January 2009

Abstract
Introduction
The functional unit of the mammary gland has been defined as the epithelial cell plus its microenvironment, a hypothesis that predicts changes in epithelial cell function will be accompanied by concurrent changes in mammary stroma. To test this hypothesis, the question was addressed of whether mammary stroma is functionally altered by the anti-oestrogen drug tamoxifen.

Methods
Forty female rats at 70 days of age were randomised to two groups of 20 and treated with 1.0 mg/kg tamoxifen or vehicle subcutaneously daily for 30 days, followed by a three-day wash out period. Mammary tissue was harvested and effects of tamoxifen on mammary epithelium and stroma determined.

Results
As expected, tamoxifen suppressed mammary alveolar development and mammary epithelial cell proliferation. Primary mammary fibroblasts isolated from tamoxifen-treated rats displayed a three-fold decrease in motility and incorporated less fibronectin in their substratum in comparison to control fibroblasts; attributes indicative of fibroblast quiescence. Immunohistochemistry analysis of CD68, a macrophage lysosomal marker, demonstrated a reduction in macrophage infiltration in mammary glands of tamoxifen-treated rats. Proteomic analyses by mass spectrometry identified several extracellular matrix (ECM) proteins with expression levels with tamoxifen treatment that were validated by Western blot. Mammary tissue from tamoxifen-treated rats had decreased fibronectin and increased collagen 1 levels. Further, ECM proteolysis was reduced in tamoxifen-treated rats as detected by reductions in fibronectin, laminin 1, laminin 5 and collagen 1 cleavage fragments. Consistent with suppression in ECM proteolysis with tamoxifen treatment, matrix metalloproteinase-2 levels and activity were decreased. Biochemically extracted mammary ECM from tamoxifen-treated rats suppressed in vitro macrophage motility, which was rescued by the addition of proteolysed collagen or fibronectin. Mammary ECM from tamoxifen-treated rats also suppressed breast tumour cell motility, invasion and haptotaxis, reduced organoid size in 3-dimensional culture and blocked tumour promotion in an orthotopic xenograft model; effects which could be partially reversed by the addition of exogenous fibronectin.

Conclusions
These data support the hypothesis that mammary stroma responds to tamoxifen treatment in concert with the epithelium and remodels to a microenvironment inhibitory to tumour cell progression. Reduced fibronectin levels and reduced ECM turnover appear to be hallmarks of the quiescent mammary microenvironment. These data may provide insight into attributes of a mammary microenvironment that facilitate tumour dormancy.
Balance of Irgm protein activities determines IFN-γ-induced host defense
Authors: Henry Stanley C , Daniell Xiaoju G , Burroughs Ashley R , Indaram Maanasa , Howell David N , Coers Jörn , Starnbach Michael N , Hunn Julia P , Howard Jonathan C , Feng Carl G , Sher Alan , Taylor Gregory A 
Published: January 2009

AbstractThe immunity-related GTPases (IRG), also known as p47 GTPases, are a family of proteins that are tightly regulated by IFNs at the transcriptional level and serve as key mediators of IFN-regulated resistance to intracellular bacteria and protozoa. Among the IRG proteins, loss of Irgm1 has the most profound impact on IFN-γ-induced host resistance at the physiological level. Surprisingly, the losses of host resistance seen in the absence of Irgm1 are sometimes more striking than those seen in the absence of IFN-γ. In the current work, we address the underlying mechanism. We find that in several contexts, another protein in the IRG family, Irgm3, functions to counter the effects of Irgm1. By creating mice that lack Irgm1 and Irgm3, we show that several phenotypes important to host resistance that are caused by Irgm1 deficiency are reversed by coincident Irgm3 deficiency; these include resistance to Salmonella typhimurium in vivo, the ability to affect IFN-γ-induced Salmonella killing in isolated macrophages, and the ability to regulate macrophage adhesion and motility in vitro. Other phenotypes that are caused by Irgm1 deficiency, including susceptibility to Toxoplasma gondii and the regulation of GKS IRG protein expression and localization, are not reversed but exacerbated when Irgm3 is also absent. These data suggest that members of the Irgm subfamily within the larger IRG family possess activities that can be opposing or cooperative depending on the context, and it is the balance of these activities that is pivotal in mediating IFN-γ-regulated host resistance.
Effect of Transition-metal Oxide Additives for Water–Gas-shift Reaction over Supported Copper Catalyst
Authors: Sagata Kunimasa , Kawanishi Yusuke , Asamoto Makiko , Yamaura Hiroyuki , Yahiro Hidenori 
Published: January 2009

Abstract
The catalytic activities of the low-temperature water–gas-shift (LT-WGS) reaction were investigated for Al2O3-supported Cu catalysts containing CrOx, MnOx, FeOx, CoOx, NiOx, or ZnO. The catalytic activity of Cu/Al2O3 catalyst at 423 K was improved by the small addition of transition-metal oxide. In particular, Cu/Al2O3 with CoOx showed the highest activity among the supported Cu catalysts used in this study.
Preparation of Ultrathin Palladium Membrane Using Electrophoresis of Metallic Nanoparticles
Authors: Tominaga Aki , Nakagoe Osamu , Tanabe Shuji 
Published: January 2009

Abstract
A new procedure to prepare ultrathin membrane composed of nanoparticles was investigated. The nanoparticles were prepared in aqueous solution containing PdII ions by sonochemical reduction. Electrophoresis was used to fix the nanoparticles on a porous substrate disc. The ultrathin membrane was successfully prepared with the combination procedure, and the obtained Pd membrane showed high perm-selectivity for H2 and 3.85 of the separation factor of H2/N2 at room temperature.
Assembling into Chiral Crystal of Spin Crossover Iron(II) Complex
Authors: Sato Tetsuya , Iijima Seiichiro , Kojima Masaaki , Matsumoto Naohide 
Published: January 2009

Abstract
A new spin crossover iron(II) complex, [Fe(H2L2-Me)2]Cl2·2-PrOH·0.5H2O (1), has been prepared, where H2L2-Me = (2-methylimidazol-4-yl)methylidene)histamine. The complex is a chiral molecule due to octahedral coordinations of two tridentate ligands, they are linked by the hydrogen bonds of NH···Cl−···HN through Cl− ion into a chiral one-dimensional (1D) rod, and further the chiral rods with the same chirality are stacked to form a chiral crystal (conglomerate). The solvated sample showed a two-step SCO, and the desolvated sample showed an abrupt one-step SCO at T1⁄2=180 K.