bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polymorphisms cMyc-N11S and p27-V109G and breast cancer risk and prognosis
Authors: Figueiredo Jane C , Knight Julia A , Cho Stewart , Savas Sevtap , Onay U Venus , Briollais Laurent , Goodwin Pamela J , McLaughlin John R , Andrulis Irene L , Ozcelik Hilmi 
Published: June 2007

AbstractBackgroundcMyc and p27 are key genes implicated in carcinogenesis. Whether polymorphisms in these genes affect breast cancer risk or prognosis is still unclear. In this study, we focus on a rare non-synonymous polymorphism in cMyc (N11S) and a common polymorphism in p27 (V109G) and determine their role in risk and prognosis using data collected from the Ontario Breast Cancer Family Registry.MethodsRisk factor data was collected at baseline on a large group of women (cases = 1,115 and population-based controls = 710) and clinical data (including treatment and follow-up) were collected prospectively by periodic review of medical records for a subset of cases (N = 967) for nearly a decade. A centralized pathology review was conducted. Unconditional logistic regression was used to determine the association of polymorphisms with breast cancer risk and the Cox proportional hazards model was used to determine their association with survival.ResultsOur results suggest that while cMyc-N11S can be considered a putatively functional polymorphism located in the N-terminal domain, it is not associated with risk, tumor characteristics or survival. The p27-G109 allele was associated with a modest protective effect in adjusted analyses and higher T stage. We found no evidence to suggest that p27-V109G alone or in combination with cMyc-N11S was associated with survival. Age at onset and first-degree family history of breast or ovarian cancer did not significantly modify the association of these polymorphisms with breast cancer risk.ConclusionFurther work is recommended to understand the potential functional role of these specific non-synonymous amino acid changes and a larger, more comprehensive investigation of genetic variation in these genes (e.g., using a tagSNP approach) in combination with other relevant genes is needed as well as consideration for treatment effects when assessing their potential role in prognosis.
Crystal structure of Saccharomyces cerevisiae 6-phosphogluconate dehydrogenase Gnd1
Authors: He Weiwei , Wang Yi , Liu Wei , Zhou Cong-Zhao 
Published: June 2007

Abstract

Background
As the third enzyme of the pentose phosphate pathway, 6-phosphogluconate dehydrogenase (6PGDH) is the main generator of cellular NADPH. Both thioredoxin reductase and glutathione reductase require NADPH as the electron donor to reduce oxidized thioredoxin or glutathione (GSSG). Since thioredoxin and GSH are important antioxidants, it is not surprising that 6PGDH plays a critical role in protecting cells from oxidative stress. Furthermore the activity of 6PGDH is associated with several human disorders including cancer and Alzheimer's disease. The 3D structural investigation would be very valuable in designing small molecules that target this enzyme for potential therapeutic applications.

Results
The crystal structure of 6-phosphogluconate dehydrogenase (6PGDH/Gnd1) from Saccharomyces cerevisiae has been determined at 2.37 Å resolution by molecular replacement. The overall structure of Gnd1 is a homodimer with three domains for each monomer, a Rossmann fold NADP+ binding domain, an all-α helical domain contributing the majority to hydrophobic interaction between the two subunits and a small C-terminal domain penetrating the other subunit. In addition, two citrate molecules occupied the 6PG binding pocket of each monomer. The intact Gnd1 had a Km of 50 ± 9 μM for 6-phosphogluconate and of 35 ± 6 μM for NADP+ at pH 7.5. But the truncated mutants without the C-terminal 35, 39 or 53 residues of Gnd1 completely lost their 6PGDH activity, despite remaining the homodimer in solution.

Conclusion
The overall tertiary structure of Gnd1 is similar to those of 6PGDH from other species. The substrate and coenzyme binding sites are well conserved, either from the primary sequence alignment, or from the 3D structural superposition. Enzymatic activity assays suggest a sequential mechanism of catalysis, which is in agreement with previous studies. The C-terminal domain of Gnd1 functions as a hook to further tighten the dimer, but it is not necessary for the dimerization. This domain also works as a lid on the substrate binding pocket to control the binding of substrate and the release of product, so it is indispensable for the 6PGDH activity. Moreover, the co-crystallized citrate molecules, which mimic the binding mode of the substrate 6-phosphogluconate, provided us a novel strategy to design the 6PDGH inhibitors.
Why, and how, mixed methods research is undertaken in health services research in England: a mixed methods study
Authors: O'Cathain Alicia , Murphy Elizabeth , Nicholl Jon 
Published: June 2007

Abstract
Background
Recently, there has been a surge of international interest in combining qualitative and quantitative methods in a single study – often called mixed methods research. It is timely to consider why and how mixed methods research is used in health services research (HSR).

Methods
Documentary analysis of proposals and reports of 75 mixed methods studies funded by a research commissioner of HSR in England between 1994 and 2004. Face-to-face semi-structured interviews with 20 researchers sampled from these studies.

Results
18% (119/647) of HSR studies were classified as mixed methods research. In the documentation, comprehensiveness was the main driver for using mixed methods research, with researchers wanting to address a wider range of questions than quantitative methods alone would allow. Interviewees elaborated on this, identifying the need for qualitative research to engage with the complexity of health, health care interventions, and the environment in which studies took place. Motivations for adopting a mixed methods approach were not always based on the intrinsic value of mixed methods research for addressing the research question; they could be strategic, for example, to obtain funding. Mixed methods research was used in the context of evaluation, including randomised and non-randomised designs; survey and fieldwork exploratory studies; and instrument development. Studies drew on a limited number of methods – particularly surveys and individual interviews – but used methods in a wide range of roles.

Conclusion
Mixed methods research is common in HSR in the UK. Its use is driven by pragmatism rather than principle, motivated by the perceived deficit of quantitative methods alone to address the complexity of research in health care, as well as other more strategic gains. Methods are combined in a range of contexts, yet the emerging methodological contributions from HSR to the field of mixed methods research are currently limited to the single context of combining qualitative methods and randomised controlled trials. Health services researchers could further contribute to the development of mixed methods research in the contexts of instrument development, survey and fieldwork, and non-randomised evaluations.
Postoperative outcome of caesarean sections and other major emergency obstetric surgery by clinical officers and medical officers in Malawi
Authors: Chilopora Garvey , Pereira Caetano , Kamwendo Francis , Chimbiri Agnes , Malunga Eddie , Bergström Staffan 
Published: June 2007

Abstract

Background
Clinical officers perform much of major emergency surgery in Malawi, in the absence of medical officers. The aim of this study was to validate the advantages and disadvantages of delegation of major obstetric surgery to non-doctors.

Methods
During a three month period, data from 2131 consecutive obstetric surgeries in 38 district hospitals in Malawi were collected prospectively. The interventions included caesarean sections alone and those that were combined with other interventions such as subtotal and total hysterectomy repair of uterine rupture and tubal ligation. All these surgeries were conducted either by clinical officers or by medical officers.

Results
During the study period, clinical officers performed 90% of all straight caesarean sections, 70% of those combined with subtotal hysterectomy, 60% of those combined with total hysterectomy and 89% of those combined with repair of uterine rupture. A comparable profile of patients was operated on by clinical officers and medical officers, respectively. Postoperative outcomes were almost identical in the two groups in terms of maternal general condition – both immediately and 24 hours postoperatively – and regarding occurrence of pyrexia, wound infection, wound dehiscence, need for re-operation, neonatal outcome or maternal death.

Conclusion
Clinical officers perform the bulk of emergency obstetric operations at district hospitals in Malawi. The postoperative outcomes of their procedures are comparable to those of medical officers. Clinical officers constitute a crucial component of the health care team in Malawi for saving maternal and neonatal lives given the scarcity of physicians.
Differential vascular dysfunction in response to diets of differing macronutrient composition: a phenomenonological study
Authors: Fatani Sameer , Pickavance Lucy C , Sadler Claire J , Harrold Joanne A , Cassidy Roslyn , Wilding John PH , Naderali Ebrahim K 
Published: June 2007

Abstract

Background
Vascular dysfunction can develop from consumption of an energy-rich diet, even prior to the onset of obesity. However, the roles played by different dietary components remain uncertain. While attempting to develop models of obesity in a separate study, we observed that two high-energy diets of differing macronutrient compositions affected vascular function differently in overweight rats.

Methods
Male Wistar rats (n = 6/group) were fed diets providing varying percentages of energy from fat and carbohydrate (CHO). For 10 weeks, they were fed either chow, as control diet (10% of energy from fat; 63% from CHO), chow supplemented with chocolate biscuit (30% fat; 56% CHO) or a high-fat diet (45% fat; 35% CHO). Blood concentrations of biochemical markers of obesity were measured, and epididymal fat pads weighed as a measure of adiposity. Mesenteric arteries were dissected and their contractile and relaxant properties analysed myographically. Data were tested by analysis of variance (ANOVA).

Results
Weight gain and plasma concentrations of glucose, insulin and leptin were similar in all groups. However, biscuit-fed animals showed increased food intake (+27%; p < 0.01) and elevated concentrations of TGs and NEFAs (+41% and +17%; both p < 0.05). High-fat-fed animals showed an increase only in NEFAs (+38%; p < 0.01). Arterial vasoconstriction in response to NA and KCl increased only in biscuit-fed rats (both p < 0.01), while vasorelaxation in response to CCh and SNP, but not histamine, was attenuated in both groups (both p < 0.01). Furthermore, whereas the effect of the high-fat diet was most pronounced in endothelium-dependent vasorelaxation, the biscuit diet had the greater effect on endothelium-independent vasorelaxation.

Conclusion
Vascular dysfunction resulting from consumption of a high-fat or combined relatively high-fat/high-CHO diet occurs through different physiological processes, which may be attributable to their differing macronutrient compositions. Combining potentially atherogenic macronutrients induces more extensive vascular impairment than that of high-fat alone, and may be attributable to the more marked dyslipidaemia observed with such a diet. Thus, these findings help clarify the role of dietary components in vascular impairment, which has implications for clinical approaches to preventing cardiovascular disease.
Celsius: a community resource for Affymetrix microarray data
Authors: Day Allen , Carlson Marc RJ , Dong Jun , O'Connor Brian D , Nelson Stanley F 
Published: June 2007

AbstractCelsius is a data warehousing system to aggregate Affymetrix CEL files and associated metadata. It provides mechanisms for importing, storing, querying, and exporting large volumes of primary and pre-processed microarray data. Celsius contains ten billion assay measurements and affiliated metadata. It is the largest publicly available source of Affymetrix microarray data, and through sheer volume it allows a sophisticated, broad view of transcription that has not previously been possible.
LongSAGE profiling of nine human embryonic stem cell lines
Authors: Hirst Martin , Delaney Allen , Rogers Sean A , Schnerch Angelique , Persaud Deryck R , O'Connor Michael D , Zeng Thomas , Moksa Michelle , Fichter Keith , Mah Diana , Go Anne , Morin Ryan D , Baross Agnes , Zhao Yongjun , Khattra Jaswinder , Prabhu Anna-Liisa , Pandoh Pawan , McDonald Helen , Asano Jennifer , Dhalla Noreen , Ma Kevin , Lee Stephanie , Ally Adrian , Chahal Neil , Menzies Stephanie , Siddiqui Asim , Holt Robert , Jones Steven , Gerhard Daniela S , Thomson James A , Eaves Connie J , Marra Marco A 
Published: June 2007

AbstractTo facilitate discovery of novel human embryonic stem cell (ESC) transcripts, we generated 2.5 million LongSAGE tags from 9 human ESC lines. Analysis of this data revealed that ESCs express proportionately more RNA binding proteins compared with terminally differentiated cells, and identified novel ESC transcripts, at least one of which may represent a marker of the pluripotent state.
Neurokinin-1 receptor antagonist treatment protects mice against lung injury in polymicrobial sepsis
Authors: Hegde Akhil , Zhang Huili , Moochhala Shabbir M , Bhatia Madhav 
Published: June 2007

AbstractEarlier work from our laboratory has suggested a role for the neuropeptide substance P (SP) in inducing lung injury in sepsis. In that study, mice lacking the preprotachykinin-A gene, which encodes for SP, were protected against lung injury in sepsis. To further substantiate the role of SP in sepsis and to study its mchanism, we have evaluated the effect of SR140333, a SP receptor antagonist, on lung injury in sepsis, which was induced in male Swiss mice by cecal ligation and puncture (CLP). Sham-operated animals received the same surgical procedure, except CLP. Vehicle or SR140333 (1 mg/kg, s.c.) was administered to CLP mice 30 min before or 1 h after the CLP. Eight hours after surgery, lung tissue was collected and analyzed for myeloperoxidase (MPO) activity, chemokines, cytokines, and adhesion molecules. The CLP procedure alone caused a significant increase in the lung levels of MIP-2, MCP-1, IL-1β, IL-6, ICAM-1, E- and P-selectin, and MPO activity when compared with sham-operated mice. SR140333 injected 30 min before or 1 h after CLP significantly attenuated the increased lung MPO activity and levels of MIP-2, MCP-1, IL-1β, IL-6, ICAM-1, and E- and P-selectin compared with CLP-operated mice injected with the vehicle. Histological evaluation of the lung sections further supported the beneficial effect of SR140333 on lung inflammation. Therefore, SP receptor antagonism can be a potential therapeutic target in polymicrobial sepsis, and this effect is brought about via reduction in leukocyte recruitment.
The Elder Patient with Suspected Acute Coronary Syndromes in the Emergency Department
Authors: Han Jin H. , Lindsell Christopher J. , Hornung Richard W. , Lewis Timothy , Storrow Alan B. , Hoekstra James W. , Hollander Judd E. , Miller Chadwick D. , Peacock W. Frank , Pollack Charles V. , Gibler W. Brian 
Published: June 2007

ObjectivesTo describe the evaluation and outcomes of elder patients with suspected acute coronary syndromes (ACS) presenting to the emergency department (ED). MethodsThis was a post hoc analysis of the Internet Tracking Registry for Acute Coronary Syndromes (i∗trACS) registry, which had 17,713 ED visits for suspected ACS. First visits from the United States with nonmissing patient demographics, 12‐lead electrocardiogram results, and clinical history were included in the analysis. Those who used cocaine or amphetamines or left the ED against medical advice were excluded. Elder was defined as age 75 years or older. ACS was defined by 30‐day revascularization, Diagnosis‐related Group codes, or death within 30 days with positive cardiac biomarkers at index hospitalization. Multivariable logistic regression analyses were performed to determine the association between being elder and 1) 30‐day all‐cause mortality, 2) ACS, 3) diagnostic tests ordered, and 4) disposition. Multivariable logistic regression was also performed to determine which clinical variables were associated with ACS in elder and nonelder patients. ResultsA total of 10,126 patients with suspected ACS presenting to the ED were analyzed. For patients presenting to the ED, being elder was independently associated with ACS and all‐cause 30‐day mortality, with adjusted odds ratios of 1.8 (95% confidence interval [CI] = 1.5 to 2.2) and 2.6 (95% CI = 1.6 to 4.3), respectively. Elder patients were more likely to be admitted to the hospital (adjusted odds ratio, 2.2; 95% CI = 1.8 to 2.6), but there were no differences in the rates of cardiac catheterization and noninvasive stress cardiac imaging. Different clinical variables were associated with ACS in elder and nonelder patients. Chest pain as chief complaint, typical chest pain, and previous history of coronary artery disease were significantly associated with ACS in nonelder patients but were not associated with ACS in elder patients. Male gender and left arm pain were associated with ACS in both elder and nonelder patients. ConclusionsElder patients who present to the ED with suspected ACS represent a population at high risk for ACS and 30‐day mortality. Elders are more likely to be admitted to the hospital, but despite an increased risk for adverse events, they have similar odds of receiving a diagnostic test, such as stress cardiac imaging or cardiac catheterization, compared with nonelder patients. Different clinical variables are associated with ACS, and clinical prediction rules utilizing presenting symptoms should consider the effect modification of age.
In Vitro Fertilization Improves Childhood Growth and Metabolism
Authors: Miles Harriet L. , Hofman Paul L. , Peek John , Harris Mark , Wilson Dyanne , Robinson Elizabeth M. , Gluckman Peter D. , Cutfield Wayne S. 
Published: June 2007

Abstract
Background: There is limited information regarding the long-term outcome of children born after in vitro fertilization (IVF), although an increase in rare imprinted gene disorders such as Beckwith-Wiedemann syndrome has been reported.
Methods: We recruited healthy, prepubertal children born at term after singleton pregnancy. The children in the study group were conceived using IVF with fresh embryo transfer, whereas controls were naturally conceived. Anthropometric measurements, bone age, dual-energy x-ray absorptiometry, fasting serum glucose, insulin, lipid profile, IGF-I and -II, and IGF-binding proteins 1, 2, and 3 were performed.
Results: There were 69 IVF children aged 5.9 ± 0.2 yr and 71 control children aged 6.9 yr. IVF children were taller than controls when corrected for parents’ heights (height sd score of 1.05 ± 0.1 vs. 0.51 ± 0.11, P = 0.001) with higher levels of serum IGF-II (850 ± 24 vs. 773 ± 24 μg/liter, P = 0.03), higher IGF-I to IGF-binding protein 3 ratio (P = 0.04), and a trend toward higher IGF-I (105 ± 4 vs. 92 ± 4 μg/liter, P = 0.06). IVF children had higher high-density lipoprotein (1.67 ± 0.04 mmol/liter vs. 1.53 ± 0.04 mmol/liter, P = 0.02), lower triglycerides (0.65 ± 0.04 mmol/liter vs. 0.78 ± 0.04 mmol/liter, P = 0.02), and a lower total to high-density lipoprotein cholesterol ratio (2.58 vs. 2.86, P = 0.01). There were no differences in body composition.
Conclusions: IVF children are taller with higher IGF-I and IGF-II levels and have a slightly more favorable lipid profile. We speculate that IVF results in epigenetic change through altered methylation of genes involved in growth and metabolism. IVF programs should consider long-term longitudinal follow-up of IVF offspring.
Association of Prostaglandin E Synthase 2 (PTGES2) Arg298His Polymorphism with Type 2 Diabetes in Two German Study Populations
Authors: Nitz Inke , Fisher Eva , Grallert Harald , Li Yun , Gieger Christian , Rubin Diana , Boeing Heiner , Spranger Joachim , Lindner Inka , Schreiber Stefan , Rathmann Wolfgang , Gohlke Henning , Döring Angela , Wichmann H.-Erich , Schrezenmeir Jürgen , Döring Frank , Illig Thomas 
Published: June 2007

AbstractContext: On the basis of its chromosomal localization and its role in the synthesis of the antilipolytic compound prostaglandin E2, the prostaglandin E synthase 2 (PTGES2) is a candidate gene for type 2 diabetes.Objective: The aim of the present study was to investigate whether genetic variants in the PTGES2 gene are associated with type 2 diabetes.Results: Sequencing of the PTGES2 gene revealed one nonsynonymous coding single-nucleotide polymorphism (SNP) (Arg298His, rs13283456) and a previously unknown promoter SNP g.-417G&gt;T. Both SNPs and additional haplotype tagging SNPs (rs884115, rs10987883, rs4837240) were genotyped in a nested case-control study of 192 incident type 2 diabetes subjects and 384 controls (European Prospective Investigation into Cancer and Nutrition-Potsdam). Carriers of the minor allele of Arg298His had a lower risk to develop the disease [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.41–0.97, P = 0.04], compared with homozygous individuals with the common allele. The PTGES2 Arg298His polymorphism was reinvestigated in a population-based cross-sectional study (Cooperative Health Research in the Augsburg Region) consisting of 239 individuals with impaired glucose tolerance, 226 with type 2 diabetes, and 863 normoglycemic controls. In this study population, the Arg298His polymorphism was significantly associated with impaired glucose tolerance (OR 0.68, 95% CI 0.50–0.93, P = 0.007) and type 2 diabetes (OR 0.61, 95% CI 0.43–0.86, P = 0.004). A pooled analysis of data from both study populations revealed reduced risk of type 2 diabetes (OR 0.62, 95% CI 0.47–0.81, P = 0.0005) in PTGES2 298His allele carriers.Conclusion: We obtained evidence from two Caucasian study populations that the His298-allele of PTGES2 Arg298His confers to reduced risk of type 2 diabetes.