bluuebunny/crossref_metadata_2025_split huggingface dataset:
Common variants in the ATM, BRCA1, BRCA2, CHEK2 and TP53 cancer susceptibility genes are unlikely to increase breast cancer risk
Authors: Baynes Caroline , Healey Catherine S , Pooley Karen A , Scollen Serena , Luben Robert N , Thompson Deborah J , Pharoah Paul DP , Easton Douglas F , Ponder Bruce AJ , Dunning Alison M ,   the SEARCH breast cancer study
Published: April 2007

Abstract
Introduction
Certain rare, familial mutations in the ATM, BRCA1, BRCA2, CHEK2 or TP53 genes increase susceptibility to breast cancer but it has not, until now, been clear whether common polymorphic variants in the same genes also increase risk.

Methods
We have attempted a comprehensive, single nucleotide polymorphism (SNP)- and haplotype-tagging association study on each of these five genes in up to 4,474 breast cancer cases from the British, East Anglian SEARCH study and 4,560 controls from the EPIC-Norfolk study, using a two-stage study design. Nine tag SNPs were genotyped in ATM, together with five in BRCA1, sixteen in BRCA2, ten in CHEK2 and five in TP53, with the aim of tagging all other known, common variants. SNPs generating the common amino acid substitutions were specifically forced into the tagging set for each gene.

Results
No significant breast cancer associations were detected with any individual or combination of tag SNPs.

Conclusion
It is unlikely that there are any other common variants in these genes conferring measurably increased risks of breast cancer in our study population.
Effects of epinephrine and vasopressin on end-tidal carbon dioxide tension and mean arterial blood pressure in out-of-hospital cardiopulmonary resuscitation: an observational study
Authors: Mally Stefan , Jelatancev Alina , Grmec Stefek 
Published: April 2007

Abstract
Introduction
Clinical data considering vasopressin as an equivalent option to epinephrine in cardiopulmonary resuscitation (CPR) are limited. The aim of this prehospital study was to assess whether the use of vasopressin during CPR contributes to higher end-tidal carbon dioxide and mean arterial blood pressure (MAP) levels and thus improves the survival rate and neurological outcome.

Methods
Two treatment groups of resuscitated patients in cardiac arrest were compared: in the epinephrine group, patients received 1 mg of epinephrine intravenously every three minutes only; in the vasopressin/epinephrine group, patients received 40 units of arginine vasopressin intravenously only or followed by 1 mg of epinephrine every three minutes during CPR. Values of end-tidal carbon dioxide and MAP were recorded, and data were collected according to the Utstein style.

Results
Five hundred and ninety-eight patients were included with no significant demographic or clinical differences between compared groups. Final end-tidal carbon dioxide values and average values of MAP in patients with restoration of pulse were significantly higher in the vasopressin/epinephrine group (p < 0.01). Initial (odds ratio [OR]: 18.65), average (OR: 2.86), and final (OR: 2.26) end-tidal carbon dioxide values as well as MAP at admission to the hospital (OR: 1.79) were associated with survival at 24 hours. Initial (OR: 1.61), average (OR: 1.47), and final (OR: 2.67) end-tidal carbon dioxide values as well as MAP (OR: 1.39) were associated with improved hospital discharge. In the vasopressin group, significantly more pulse restorations and a better rate of survival at 24 hours were observed (p < 0.05). Subgroup analysis of patients with initial asystole revealed a higher hospital discharge rate when vasopressin was used (p = 0.04). Neurological outcome in discharged patients was better in the vasopressin group (p = 0.04).

Conclusion
End-tidal carbon dioxide and MAP are strong prognostic factors for the outcome of out-of-hospital cardiac arrest. Resuscitated patients treated with vasopressin alone or followed by epinephrine have higher average and final end-tidal carbon dioxide values as well as a higher MAP on admission to the hospital than patients treated with epinephrine only. This combination vasopressor therapy improves restoration of spontaneous circulation, short-term survival, and neurological outcome. In the subgroup of patients with initial asystole, it improves the hospital discharge rate.
Cortisol levels in cerebrospinal fluid correlate with severity and bacterial origin of meningitis
Authors: Holub Michal , Beran Ondřej , Džupová Olga , Hnyková Jarmila , Lacinová Zdenka , Příhodová Jana , Procházka Bohumír , Helcl Miroslav 
Published: April 2007

Abstract
Introduction
Outcomes following bacterial meningitis are significantly improved by adjunctive treatment with corticosteroids. However, little is known about the levels and significance of intrathecal endogenous cortisol. The aim of this study was to assess cortisol as a biological and diagnostic marker in patients with bacterial meningitis.

Methods
Forty-seven consecutive patients with bacterial meningitis and no prior treatment were evaluated. For comparison, a group of 37 patients with aseptic meningitis and a group of 13 healthy control individuals were included.

Results
The mean age of the bacterial meningitis patients was 42 years, and the mean Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation II, and Sequential Organ Failure Assessment scores on admission were 12, 13 and 4, respectively. Altogether, 40 patients (85%) were admitted to the intensive care unit, with a median (interquartile range) length of stay of 8 (4 to 15) days. A bacterial etiology was confirmed in 35 patients (74%). The median (interquartile range) cortisol concentration in cerebrospinal fluid (CSF) was 133 (59 to 278) nmol/l. CSF cortisol concentrations were positively correlated with serum cortisol levels (r = 0.587, P < 0.001). Furthermore, CSF cortisol levels correlated with Acute Physiology and Chronic Health Evaluation II score (r = 0.763, P < 0.001), Sequential Organ Failure Assessment score (r = 0.650, P < 0.001), Glasgow Coma Scale score (r = -0.547, P < 0.001) and CSF lactate levels (r = 0.734, P < 0.001). CSF cortisol was only weakly associated with intrathecal levels of IL-6 (r = 0.331, P = 0.02) and IL-8 (r = 0.296, P < 0.05). CSF cortisol levels in bacterial and aseptic meningitis significantly differed (P < 0.001). The CSF cortisol concentration of 46.1 nmol/l was found to be the optimal cutoff value for diagnosis of bacterial meningitis.

Conclusion
CSF cortisol levels in patients with bacterial meningitis are highly elevated and correlate with disease severity. Moreover, our findings also suggest that intrathecal cortisol may serve as a valuable marker in discriminating between bacterial and aseptic meningitis.
The concentration of oxygen, lactate and glucose in the central veins, right heart, and pulmonary artery: a study in patients with pulmonary hypertension
Authors: Gutierrez Guillermo , Venbrux Anthony , Ignacio Elizabeth , Reiner Jonathan , Chawla Lakhmir , Desai Anish 
Published: April 2007

Abstract
Introduction
Decreases in oxygen saturation (SO2) and lactate concentration [Lac] from superior vena cava (SVC) to pulmonary artery have been reported. These gradients (ΔSO2 and Δ[Lac]) are probably created by diluting SVC blood with blood of lower SO2 and [Lac]. We tested the hypothesis that ΔSO2 and Δ[Lac] result from mixing SVC and inferior vena cava (IVC) blood streams.

Methods
This was a prospective, sequential, observational study of hemodynamically stable individuals with pulmonary artery hypertension (n = 9) who were about to undergo right heart catheterization. Catheters were advanced under fluoroscopic guidance into the IVC, SVC, right atrium, right ventricle, and pulmonary artery. Samples were obtained at each site and analyzed for SO2, [Lac], and glucose concentration ([Glu]). Analysis of variance with Tukey HSD test was used to compare metabolite concentrations at each site.

Results
There were no differences in SO2 or [Lac] between IVC and SVC, both being greater than their respective pulmonary artery measurements (P < 0.01 for SO2 and P < 0.05 for [Lac]). SO2 and [Lac] in right atrium, right ventricle, and pulmonary artery were similar. ΔSO2 was 4.4 ± 1.4% (mean ± standard deviation) and Δ[Lac] was 0.16 ± 0.11 mmol/l (both > 0; P < 0.001). Δ[Glu] was -0.19 ± 0.31 mmol/l, which was not significantly different from zero, with SVC [Glu] being less than IVC [Glu].

Conclusion
Mixing of SVC with IVC blood does not account for the development of ΔSO2 and Δ[Lac] in hemodynamically stable individuals with pulmonary artery hypertension. An alternate mechanism is mixing with coronary sinus blood, implying that ΔSO2 and Δ[Lac] may reflect changes in coronary sinus SO2 and [Lac] in this patient population.
Premortem clinical diagnoses and postmortem autopsy findings: discrepancies in critically ill cancer patients
Authors: Pastores Stephen M , Dulu Alina , Voigt Louis , Raoof Nina , Alicea Margarita , Halpern Neil A 
Published: April 2007

Abstract
Introduction
Limited data are available regarding the relationship of premortem clinical diagnoses and postmortem autopsy findings in cancer patients who die in an oncologic intensive care unit (ICU). The purposes of this study were to compare the premortem clinical and postmortem diagnoses of cancer patients who died in the ICU and to analyze any discrepancies between them.

Methods
This is a retrospective review of medical records and autopsy reports of all cancer patients who died in a medical-surgical ICU and had an autopsy performed between 1 January 1999 and 30 September 2005 at a tertiary care cancer center. Premortem clinical diagnoses were compared with the postmortem findings. Major missed diagnoses were identified and classified, according to the Goldman criteria, into class I and class II discrepancies.

Results
Of 658 deaths in the ICU during the study period, 86 (13%) autopsies were performed. Of the 86 patients, 22 (26%) had 25 major missed diagnoses, 12 (54%) patients had class I discrepancies, 7 (32%) had class II discrepancies, and 3 (14%) had both class I and class II discrepancies. Class I discrepancies were due to opportunistic infections (67%) and cardiac complications (33%), whereas class II discrepancies were due to cardiopulmonary complications (70%) and opportunistic infections (30%).

Conclusion
There was a discrepancy rate of 26% between premortem clinical diagnoses and postmortem findings in cancer patients who died in a medical-surgical ICU at a tertiary care cancer center. Our findings underscore the need for enhanced surveillance, monitoring, and treatment of infections and cardiopulmonary disorders in critically ill cancer patients.
Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis
Authors: Bozza Fernando A , Salluh Jorge I , Japiassu André M , Soares Marcio , Assis Edson F , Gomes Rachel N , Bozza Marcelo T , Castro-Faria-Neto Hugo C , Bozza Patrícia T 
Published: April 2007

Abstract
Introduction
The current shortage of accurate and readily available, validated biomarkers of disease severity in sepsis is an important limitation when attempting to stratify patients into homogeneous groups, in order to study pathogenesis or develop therapeutic interventions. The aim of the present study was to determine the cytokine profile in plasma of patients with severe sepsis by using a multiplex system for simultaneous detection of 17 cytokines.

Methods
This was a prospective cohort study conducted in four tertiary hospitals. A total of 60 patients with a recent diagnosis of severe sepsis were included. Plasma samples were collected for measurement of cytokine concentrations. A multiplex analysis was performed to evaluate levels of 17 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, interferon-γ, granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor, monocyte chemoattractant protein [MCP]-1, macrophage inflammatory protein-1 and tumour necrosis factor-α). Cytokine concentrations were related to the presence of severe sepsis or septic shock, the severity and evolution of organ failure, and early and late mortality.

Results
Concentrations of IL-1β, IL-6, IL-7, IL-8, IL-10, IL-13, interferon-γ, MCP-1 and tumour necrosis factor-α were significantly higher in septic shock patients than in those with severe sepsis. Cytokine concentrations were associated with severity and evolution of organ dysfunction. With regard to the severity of organ dysfunction on day 1, IL-8 and MCP-1 exhibited the best correlation with Sequential Organ Failure Assessment score. In addition, IL-6, IL-8 and G-CSF concentrations during the first 24 hours were predictive of worsening organ dysfunction or failure of organ dysfunction to improve on day three. In terms of predicting mortality, the cytokines IL-1β, IL-4, IL-6, IL-8, MCP-1 and G-CSF had good accuracy for predicting early mortality (< 48 hours), and IL-8 and MCP-1 had the best accuracy for predicting mortality at 28 days. In multivariate analysis, only MCP-1 was independently associated with prognosis.

Conclusion
In this exploratory analysis we demonstrated that use of a multiple cytokine assay platform allowed identification of distinct cytokine profiles associated with sepsis severity, evolution of organ failure and death.
The metabolic and renal effects of adrenaline and milrinone in patients with myocardial dysfunction after coronary artery bypass grafting
Authors: Heringlake Matthias , Wernerus Marit , Grünefeld Julia , Klaus Stephan , Heinze Hermann , Bechtel Matthias , Bahlmann Ludger , Poeling Jochen , Schön Julika 
Published: April 2007

Abstract
Introduction
Myocardial dysfunction necessitating inotropic support is a typical complication after on-pump cardiac surgery. This prospective, randomized pilot study analyzes the metabolic and renal effects of the inotropes adrenaline and milrinone in patients needing inotropic support after coronary artery bypass grafting (CABG).

Methods
During an 18-month period, 251 patients were screened for low cardiac output upon intensive care unit (ICU) admission after elective, isolated CABG surgery. Patients presenting with a cardiac index (CI) of less than 2.2 liters/minute per square meter upon ICU admission – despite adequate mean arterial (titrated with noradrenaline or sodium nitroprusside) and filling pressures – were randomly assigned to 14-hour treatment with adrenaline (n = 7) or milrinone (n = 11) to achieve a CI of greater than 3.0 liters/minute per square meter. Twenty patients not needing inotropes served as controls. Hemodynamics, plasma lactate, pyruvate, glucose, acid-base status, insulin requirements, the urinary excretion of alpha-1-microglobuline, and creatinine clearance were determined during the treatment period, and cystatin-C levels were determined up to 48 hours after surgery (follow-up period).

Results
After two to four hours after ICU admission, the target CI was achieved in both intervention groups and maintained during the observation period. Plasma lactate, pyruvate, the lactate/pyruvate ratio, plasma glucose, and insulin doses were higher (p < 0.05) in the adrenaline-treated patients than during milrinone or control conditions. The urinary excretion of alpha-1-microglobuline was higher in the adrenaline than in the control group 6 to 14 hours after admission (p < 0.05). No between-group differences were observed in creatinine clearance, whereas plasma cystatin-C levels were significantly higher in the adrenaline than in the milrinone or the control group after 48 hours (p < 0.05).

Conclusion
This suggests that the use of adrenaline for the treatment of postoperative myocardial dysfunction – in contrast to treatment with the PDE-III inhibitor milrinone – is associated with unwarranted metabolic and renal effects.
Clinical trials registration: ClinicalTrials.gov NCT00446017.
CAGE-TSSchip: promoter-based expression profiling using the 5'-leading label of capped transcripts
Authors: Katayama Shintaro , Kanamori-Katayama Mutsumi , Yamaguchi Kazumi , Carninci Piero , Hayashizaki Yoshihide 
Published: April 2007

AbstractCap analysis gene expression (CAGE) technology has revealed numerous transcription start sites (TSSs) in mammals and has suggested complex promoter-based patterns of regulation. We developed the CAGE-TSSchip to detect promoter-based transcriptional activity. The CAGE-TSSchip is a customized oligonucleotide array that targets known TSSs identified by CAGE. A new labeling method, labeling capped transcripts from the 5'-end, had to be developed. The CAGE-TSSchip is accurate and sensitive, and represents the activity of each TSS.
Genome mapping and expression analyses of human intronic noncoding RNAs reveal tissue-specific patterns and enrichment in genes related to regulation of transcription
Authors: Nakaya Helder I , Amaral Paulo P , Louro Rodrigo , Lopes André , Fachel Angela A , Moreira Yuri B , El-Jundi Tarik A , da Silva Aline M , Reis Eduardo M , Verjovski-Almeida Sergio 
Published: April 2007

Abstract
Background
RNAs transcribed from intronic regions of genes are involved in a number of processes related to post-transcriptional control of gene expression. However, the complement of human genes in which introns are transcribed, and the number of intronic transcriptional units and their tissue expression patterns are not known.

Results
A survey of mRNA and EST public databases revealed more than 55,000 totally intronic noncoding (TIN) RNAs transcribed from the introns of 74% of all unique RefSeq genes. Guided by this information, we designed an oligoarray platform containing sense and antisense probes for each of 7,135 randomly selected TIN transcripts plus the corresponding protein-coding genes. We identified exonic and intronic tissue-specific expression signatures for human liver, prostate and kidney. The most highly expressed antisense TIN RNAs were transcribed from introns of protein-coding genes significantly enriched (p = 0.002 to 0.022) in the 'Regulation of transcription' Gene Ontology category. RNA polymerase II inhibition resulted in increased expression of a fraction of intronic RNAs in cell cultures, suggesting that other RNA polymerases may be involved in their biosynthesis. Members of a subset of intronic and protein-coding signatures transcribed from the same genomic loci have correlated expression patterns, suggesting that intronic RNAs regulate the abundance or the pattern of exon usage in protein-coding messages.

Conclusion
We have identified diverse intronic RNA expression patterns, pointing to distinct regulatory roles. This gene-oriented approach, using a combined intron-exon oligoarray, should permit further comparative analysis of intronic transcription under various physiological and pathological conditions, thus advancing current knowledge about the biological functions of these noncoding RNAs.
Normalization of two-channel microarrays accounting for experimental design and intensity-dependent relationships
Authors: Dabney Alan R , Storey John D 
Published: April 2007

AbstractIn normalizing two-channel expression arrays, the ANOVA approach explicitly incorporates the experimental design in its model, and the MA plot-based approach accounts for intensity-dependent biases. However, both approaches can lead to inaccurate normalization in fairly common scenarios. We propose a method called efficient Common Array Dye Swap (eCADS) for normalizing two-channel microarrays that accounts for both experimental design and intensity-dependent biases. Under reasonable experimental designs, eCADS preserves differential expression relationships and requires only a single array per sample pair.
Deafblindness in French Canadians from Quebec: a predominant founder mutation in the USH1Cgene provides the first genetic link with the Acadian population
Authors: Ebermann Inga , Lopez Irma , Bitner-Glindzicz Maria , Brown Carolyn , Koenekoop Robert Karel , Bolz Hanno Jörn 
Published: April 2007

Abstract
Background
Usher syndrome type 1 (USH1) is the leading cause of deafblindness. In most populations, many private mutations are distributed across the five known USH1 genes. We investigated patients from the French Canadian population of Quebec (approximately 6 million people) that descends from about 8,500 French settlers who colonized the St Lawrence River valley between 1608 and 1759. We hypothesized that founder mutations in USH1 genes exist in this population.

Results
We have genetically characterized 15 patients from different regions of Quebec who were clinically diagnosed as USH1. Of these cases, 60% carried mutations of the USH1C gene, a genetic subtype that is rare outside the Acadian population. We have discovered a founder effect of the c.216G>A mutation, which has previously been designated the 'Acadian allele' because it accounts for virtually all Acadian USH1 cases. It represents 40% of disease alleles in Quebec, and a carrier of c.216G>A was identified in the general population. Mutations in other genes, except CDH23, are very rare.

Conclusion
Based on our findings, approximately 0.5% of congenitally deaf children in Quebec are at risk of developing retinal degeneration due to homozygosity for c.216G>A. Although the Acadians and French Canadians from Quebec are descended from French ancestors, they have always been considered genetically distinct. The genetic conditions common in Quebec are generally not found in Acadians, or they are due to different mutations. Our results, however, show that carriers of the c.216G>A allele haplotype belonged to the early founders of both the Acadian and the Quebec population.
Integration of Arabidopsis thaliana stress-related transcript profiles, promoter structures, and cell-specific expression
Authors: Ma Shisong , Bohnert Hans J 
Published: April 2007

Abstract
Background
Arabidopsis thaliana transcript profiles indicate effects of abiotic and biotic stresses and tissue-specific and cell-specific gene expression. Organizing these datasets could reveal the structure and mechanisms of responses and crosstalk between pathways, and in which cells the plants perceive, signal, respond to, and integrate environmental inputs.

Results
We clustered Arabidopsis transcript profiles for various treatments, including abiotic, biotic, and chemical stresses. Ubiquitous stress responses in Arabidopsis, similar to those of fungi and animals, employ genes in pathways related to mitogen-activated protein kinases, Snf1-related kinases, vesicle transport, mitochondrial functions, and the transcription machinery. Induced responses to stresses are attributed to genes whose promoters are characterized by a small number of regulatory motifs, although secondary motifs were also apparent. Most genes that are downregulated by stresses exhibited distinct tissue-specific expression patterns and appear to be under developmental regulation. The abscisic acid-dependent transcriptome is delineated in the cluster structure, whereas functions that are dependent on reactive oxygen species are widely distributed, indicating that evolutionary pressures confer distinct responses to different stresses in time and space. Cell lineages in roots express stress-responsive genes at different levels. Intersections of stress-responsive and cell-specific profiles identified cell lineages affected by abiotic stress.

Conclusion
By analyzing the stress-dependent expression profile, we define a common stress transcriptome that apparently represents universal cell-level stress responses. Combining stress-dependent and tissue-specific and cell-specific expression profiles, and Arabidopsis 5'-regulatory DNA sequences, we confirm known stress-related 5' cis-elements on a genome-wide scale, identify secondary motifs, and place the stress response within the context of tissues and cell lineages in the Arabidopsis root.