bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracorporeal life support following out-of-hospital refractory cardiac arrest
Authors: Le Guen Morgan , Nicolas-Robin Armelle , Carreira Serge , Raux Mathieu , Leprince Pascal , Riou Bruno , Langeron Olivier 
Published: January 2011

Abstract
Introduction
Extracorporeal life support (ECLS) has recently shown encouraging results in the resuscitation of in-hospital (IH) refractory cardiac arrest. We assessed the use of ECLS following out-of-hospital (OH) refractory cardiac arrest.

Methods
We evaluated 51 consecutive patients who experienced witnessed OH refractory cardiac arrest and received automated chest compression and ECLS upon arrival in the hospital. Patients with preexisting severe hypothermia who experienced IH cardiac arrest were excluded. A femorofemoral ECLS was set up on admission to the hospital by a mobile cardiothoracic surgical team.

Results
Fifty-one patients were included (mean age, 42 ± 15 years). The median delays from cardiac arrest to cardiopulmonary resuscitation and ECLS were, respectively, 3 minutes (25th to 75th interquartile range, 1 to 7) and 120 minutes (25th to 75th interquartile range, 102-149). Initial rhythm was ventricular fibrillation in 32 patients (63%), asystole in 15 patients (29%) patients and pulseless rhythm in 4 patients (8%). ECLS failed in 9 patients (18%). Only two patients (4%) (95% confidence interval, 1% to 13%) were alive at day 28 with a favourable neurological outcome. There was a significant correlation (r = 0.36, P = 0.01) between blood lactate and delay between cardiac arrest and onset of ECLS, but not with arterial pH or blood potassium level. Deaths were the consequence of multiorgan failure (n = 43; 47%), brain death (n = 10; 20%) and refractory hemorrhagic shock (n = 7; 14%), and most patients (n = 46; 90%) died within 48 hours.

Conclusions
This poor outcome suggests that the use of ECLS should be more restricted following OH refractory cardiac arrest.
Red blood cell transfusion in patients with subarachnoid hemorrhage: a multidisciplinary North American survey
Authors: Kramer Andreas H , Diringer Michael N , Suarez Jose I , Naidech Andrew M , Macdonald Loch R , Le Roux Peter D 
Published: January 2011

Abstract
Introduction
Anemia is associated with poor outcomes in patients with aneurysmal subarachnoid hemorrhage (SAH). It remains unclear whether this association can be modified with more aggressive use of red blood cell (RBC) transfusions. The degree to which restrictive thresholds have been adopted in neurocritical care patients remains unknown.

Methods
We performed a survey of North American academic neurointensivists, vascular neurosurgeons and multidisciplinary intensivists who regularly care for patients with SAH to determine hemoglobin (Hb) concentrations which commonly trigger a decision to initiate transfusion. We also assessed minimum and maximum acceptable Hb goals in the context of a clinical trial and how decision-making is influenced by advanced neurological monitoring, clinician characteristics and patient-specific factors.

Results
The survey was sent to 531 clinicians, of whom 282 (53%) responded. In a hypothetical patient with high-grade SAH (WFNS 4), the mean Hb concentration at which clinicians administered RBCs was 8.19 g/dL (95% CI, 8.07 to 8.30 g/dL). Transfusion practices were comparatively more restrictive in patients with low-grade SAH (mean Hb 7.85 g/dL (95% CI, 7.73 to 7.97 g/dL)) (P < 0.0001) and more liberal in patients with delayed cerebral ischemia (DCI) (mean Hb 8.58 g/dL (95% CI, 8.45 to 8.72 g/dL)) (P < 0.0001). In each setting, there was a broad range of opinions. The majority of respondents expressed a willingness to study a restrictive threshold of ≤8 g/dL (92%) and a liberal goal of ≥10 g/dl (75%); in both cases, the preferred transfusion thresholds were significantly higher for patients with DCI (P < 0.0001). Neurosurgeons expressed higher minimum Hb goals than intensivists, especially for patients with high-grade SAH (β = 0.46, P = 0.003), and were more likely to administer two rather than one unit of RBCs (56% vs. 19%; P < 0.0001). Institutional use of transfusion protocols was associated with more restrictive practices. More senior clinicians preferred higher Hb goals in the context of a clinical trial. Respondents were more likely to transfuse patients with brain tissue oxygen tension values <15 mmHg and lactate-to-pyruvate ratios >40.

Conclusions
There is widespread variation in the use of RBC transfusions in SAH patients. Practices are heavily influenced by the specific dynamic clinical characteristics of patients and may be further modified by clinician specialty and seniority, the use of protocols and advanced neurological monitoring.
Application and comparison of scoring indices to predict outcomes in patients with healthcare-associated pneumonia
Authors: Fang Wen-Feng , Yang Kuang-Yao , Wu Chieh-Liang , Yu Chong-Jen , Chen Chang-Wen , Tu Chih-Yen , Lin Meng-Chih 
Published: January 2011

Abstract
Introduction
Healthcare-associated pneumonia (HCAP) is a relatively new category of pneumonia. It refers to infections that occur prior to hospital admission in patients with specific risk factors following contact or exposure to a healthcare environment. There is currently no scoring index to predict the outcomes of HCAP patients. We applied and compared different community acquired pneumonia (CAP) scoring indices to predict 30-day mortality and 3-day and 14-day intensive care unit (ICU) admission in patients with HCAP.

Methods
We conducted a retrospective cohort study based on an inpatient database from six medical centers, recruiting a total of 444 patients with HCAP between 1 January 2007 and 31 December 2007. Pneumonia severity scoring indices including PSI (pneumonia severity index), CURB 65 (confusion, urea, respiratory rate, blood pressure, age 65), IDSA/ATS (Infectious Diseases Society of America/American Thoracic Society), modified ATS rule, SCAP (severe community acquired pneumonia), SMART-COP (systolic blood pressure, multilobar involvement, albumin, respiratory rate, tachycardia, confusion, oxygenation, pH), SMRT-CO (systolic blood pressure, multilobar involvement, respiratory rate, tachycardia, confusion, oxygenation), and SOAR (systolic blood pressure, oxygenation, age, respiratory rate) were calculated for each patient. Patient characteristics, co-morbidities, pneumonia pathogen culture results, length of hospital stay (LOS), and length of ICU stay were also recorded.

Results
PSI (>90) has the highest sensitivity in predicting mortality, followed by CURB-65 (≥2) and SCAP (>9) (SCAP score (area under the curve (AUC): 0.71), PSI (AUC: 0.70) and CURB-65 (AUC: 0.66)). Compared to PSI, modified ATS, IDSA/ATS, SCAP, and SMART-COP were easy to calculate. For predicting ICU admission (Day 3 and Day 14), modified ATS (AUC: 0.84, 0.82), SMART-COP (AUC: 0.84, 0.82), SCAP (AUC: 0.82, 0.80) and IDSA/ATS (AUC: 0.80, 0.79) performed better (statistically significant difference) than PSI, CURB-65, SOAR and SMRT-CO.

Conclusions
The utility of the scoring indices for risk assessment in patients with healthcare-associated pneumonia shows that the scoring indices originally designed for CAP can be applied to HCAP.
Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis
Authors: Mahony Shaun , Mazzoni Esteban O , McCuine Scott , Young Richard A , Wichterle Hynek , Gifford David K 
Published: January 2011

Abstract
Background
Among its many roles in development, retinoic acid determines the anterior-posterior identity of differentiating motor neurons by activating retinoic acid receptor (RAR)-mediated transcription. RAR is thought to bind the genome constitutively, and only induce transcription in the presence of the retinoid ligand. However, little is known about where RAR binds to the genome or how it selects target sites.

Results
We tested the constitutive RAR binding model using the retinoic acid-driven differentiation of mouse embryonic stem cells into differentiated motor neurons. We find that retinoic acid treatment results in widespread changes in RAR genomic binding, including novel binding to genes directly responsible for anterior-posterior specification, as well as the subsequent recruitment of the basal polymerase machinery. Finally, we discovered that the binding of transcription factors at the embryonic stem cell stage can accurately predict where in the genome RAR binds after initial differentiation.

Conclusions
We have characterized a ligand-dependent shift in RAR genomic occupancy at the initiation of neurogenesis. Our data also suggest that enhancers active in pluripotent embryonic stem cells may be preselecting regions that will be activated by RAR during neuronal differentiation.
Strong functional patterns in the evolution of eukaryotic genomes revealed by the reconstruction of ancestral protein domain repertoires
Authors: Zmasek Christian M , Godzik Adam 
Published: January 2011

Abstract
Background
Genome size and complexity, as measured by the number of genes or protein domains, is remarkably similar in most extant eukaryotes and generally exhibits no correlation with their morphological complexity. Underlying trends in the evolution of the functional content and capabilities of different eukaryotic genomes might be hidden by simultaneous gains and losses of genes.

Results
We reconstructed the domain repertoires of putative ancestral species at major divergence points, including the last eukaryotic common ancestor (LECA). We show that, surprisingly, during eukaryotic evolution domain losses in general outnumber domain gains. Only at the base of the animal and the vertebrate sub-trees do domain gains outnumber domain losses. The observed gain/loss balance has a distinct functional bias, most strikingly seen during animal evolution, where most of the gains represent domains involved in regulation and most of the losses represent domains with metabolic functions. This trend is so consistent that clustering of genomes according to their functional profiles results in an organization similar to the tree of life. Furthermore, our results indicate that metabolic functions lost during animal evolution are likely being replaced by the metabolic capabilities of symbiotic organisms such as gut microbes.

Conclusions
While protein domain gains and losses are common throughout eukaryote evolution, losses oftentimes outweigh gains and lead to significant differences in functional profiles. Results presented here provide additional arguments for a complex last eukaryotic common ancestor, but also show a general trend of losses in metabolic capabilities and gain in regulatory complexity during the rise of animals.
Network analysis of skin tumor progression identifies a rewired genetic architecture affecting inflammation and tumor susceptibility
Authors: Quigley David A , To Minh D , Kim Il Jin , Lin Kevin K , Albertson Donna G , Sjolund Jonas , Pérez-Losada Jesús , Balmain Allan 
Published: January 2011

Abstract
Background
Germline polymorphisms can influence gene expression networks in normal mammalian tissues and can affect disease susceptibility. We and others have shown that analysis of this genetic architecture can identify single genes and whole pathways that influence complex traits, including inflammation and cancer susceptibility. Whether germline variants affect gene expression in tumors that have undergone somatic alterations, and the extent to which these variants influence tumor progression, is unknown.

Results
Using an integrated linkage and genomic analysis of a mouse model of skin cancer that produces both benign tumors and malignant carcinomas, we document major changes in germline control of gene expression during skin tumor development resulting from cell selection, somatic genetic events, and changes in the tumor microenvironment. The number of significant expression quantitative trait loci (eQTL) is progressively reduced in benign and malignant skin tumors when compared to normal skin. However, novel tumor-specific eQTL are detected for several genes associated with tumor susceptibility, including IL18 (Il18), Granzyme E (Gzme), Sprouty homolog 2 (Spry2), and Mitogen-activated protein kinase kinase 4 (Map2k4).

Conclusions
We conclude that the genetic architecture is substantially altered in tumors, and that eQTL analysis of tumors can identify host factors that influence the tumor microenvironment, mitogen-activated protein (MAP) kinase signaling, and cancer susceptibility.
Identification of fusion genes in breast cancer by paired-end RNA-sequencing
Authors: Edgren Henrik , Murumagi Astrid , Kangaspeska Sara , Nicorici Daniel , Hongisto Vesa , Kleivi Kristine , Rye Inga H , Nyberg Sandra , Wolf Maija , Borresen-Dale Anne-Lise , Kallioniemi Olli 
Published: January 2011

Abstract
Background
Until recently, chromosomal translocations and fusion genes have been an underappreciated class of mutations in solid tumors. Next-generation sequencing technologies provide an opportunity for systematic characterization of cancer cell transcriptomes, including the discovery of expressed fusion genes resulting from underlying genomic rearrangements.

Results
We applied paired-end RNA-seq to identify 24 novel and 3 previously known fusion genes in breast cancer cells. Supported by an improved bioinformatic approach, we had a 95% success rate of validating gene fusions initially detected by RNA-seq. Fusion partner genes were found to contribute promoters (5' UTR), coding sequences and 3' UTRs. Most fusion genes were associated with copy number transitions and were particularly common in high-level DNA amplifications. This suggests that fusion events may contribute to the selective advantage provided by DNA amplifications and deletions. Some of the fusion partner genes, such as GSDMB in the TATDN1-GSDMB fusion and IKZF3 in the VAPB-IKZF3 fusion, were only detected as a fusion transcript, indicating activation of a dormant gene by the fusion event. A number of fusion gene partners have either been previously observed in oncogenic gene fusions, mostly in leukemias, or otherwise reported to be oncogenic. RNA interference-mediated knock-down of the VAPB-IKZF3 fusion gene indicated that it may be necessary for cancer cell growth and survival.

Conclusions
In summary, using RNA-sequencing and improved bioinformatic stratification, we have discovered a number of novel fusion genes in breast cancer, and identified VAPB-IKZF3 as a potential fusion gene with importance for the growth and survival of breast cancer cells.
A novel informatics concept for high-throughput shotgun lipidomics based on the molecular fragmentation query language
Authors: Herzog Ronny , Schwudke Dominik , Schuhmann Kai , Sampaio Julio L , Bornstein Stefan R , Schroeder Michael , Shevchenko Andrej 
Published: January 2011

AbstractShotgun lipidome profiling relies on direct mass spectrometric analysis of total lipid extracts from cells, tissues or organisms and is a powerful tool to elucidate the molecular composition of lipidomes. We present a novel informatics concept of the molecular fragmentation query language implemented within the LipidXplorer open source software kit that supports accurate quantification of individual species of any ionizable lipid class in shotgun spectra acquired on any mass spectrometry platform.
Pralatrexate in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results From the Pivotal PROPEL Study
Authors: O'Connor Owen A. , Pro Barbara , Pinter-Brown Lauren , Bartlett Nancy , Popplewell Leslie , Coiffier Bertrand , Jo Lechowicz Mary , Savage Kerry J. , Shustov Andrei R. , Gisselbrecht Christian , Jacobsen Eric , Zinzani Pier Luigi , Furman Richard , Goy Andre , Haioun Corinne , Crump Michael , Zain Jasmine M. , Hsi Eric , Boyd Adam , Horwitz Steven 
Published: January 2011

Purpose Peripheral T-cell lymphoma (PTCL) is a poor prognosis subtype of non-Hodgkin's lymphoma with no accepted standard of care. This study evaluated the efficacy and tolerability of pralatrexate, a novel antifolate with promising activity. Patients and Methods Patients with independently confirmed PTCL who progressed following ≥ 1 line of prior therapy received pralatrexate intravenously at 30 mg/m2/wk for 6 weeks in 7-week cycles. Primary assessment of response was made by independent central review using the International Workshop Criteria. The primary end point was overall response rate. Secondary end points included duration of response, progression-free survival (PFS), and overall survival (OS). Results Of 115 patients enrolled, 111 were treated with pralatrexate. The median number of prior systemic therapies was three (range, 1 to 12). The response rate in 109 evaluable patients was 29% (32 of 109), including 12 complete responses (11%) and 20 partial responses (18%), with a median DoR of 10.1 months. Median PFS and OS were 3.5 and 14.5 months, respectively. The most common grade 3/4 adverse events were thrombocytopenia (32%), mucositis (22%), neutropenia (22%), and anemia (18%). Conclusion To our knowledge, PROPEL (Pralatrexate in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma) is the largest prospective study conducted in patients with relapsed or refractory PTCL. Pralatrexate induced durable responses in relapsed or refractory PTCL irrespective of age, histologic subtypes, amount of prior therapy, prior methotrexate, and prior autologous stem-cell transplant. These data formed the basis for the US Food and Drug Administration approval of pralatrexate, the first drug approved for this disease.
Histopathologic-Based Prognostic Factors of Colorectal Cancers Are Associated With the State of the Local Immune Reaction
Authors: Mlecnik Bernhard , Tosolini Marie , Kirilovsky Amos , Berger Anne , Bindea Gabriela , Meatchi Tchao , Bruneval Patrick , Trajanoski Zlatko , Fridman Wolf-Herman , Pagès Franck , Galon Jérôme 
Published: January 2011

PurposeThe prognosis of patients with colorectal cancer has sometimes proved uncertain; thus, the prognostic significance of immune criteria was compared with that of the tumor extension criteria using the American Joint Committee on Cancer/International Union Against Cancer–TNM (AJCC/UICC-TNM) staging system.Patients and MethodsWe studied the intratumoral immune infiltrates in the center of the tumor and in the invasive margin of 599 specimens of stage I to IV colorectal cancers from two independent cohorts. We analyzed these findings in relation to the degree of tumor extension and to the frequency of recurrence.ResultsGrowth of the primary tumor and metastatic spread were associated with decreased intratumoral immune T-cell densities. Sixty percent of patients with high densities of CD8+cytotoxic T-lymphocyte infiltrate presented with stage Tis/T1 tumor, whereas no patients with low densities presented with such early-stage tumor. In patients who did not relapse, the density of CD8 infiltrates was inversely correlated with T stage. In contrast, in patients whose tumor recurred, the number of CD8 cells was low regardless of the T stage of the tumor. Univariate analysis showed that the immune score was significantly associated with differences in disease-free, disease-specific, and overall survival (hazard ratio [HR], 0.64, 0.60, and 0.70, respectively; P < .005). Time-dependent receiver operating characteristic curve analysis illustrated the predictive accuracy of the immune parameters (c-index = 65.3%, time-dependent c-index [Cτ] = 66.5%). A final stepwise model for Cox multivariate analysis supports the advantage of the immune score (HR, 0.64; P < .001; Cτ = 67.9%) compared with histopathologic features in predicting recurrence as well as survival.ConclusionAssessment of CD8+cytotoxic T lymphocytes in combined tumor regions provides an indicator of tumor recurrence beyond that predicted by AJCC/UICC-TNM staging.
Parent Reports of Quality of Life for Pediatric Patients With Cancer With No Realistic Chance of Cure
Authors: Tomlinson Deborah , Hinds Pamela S. , Bartels Ute , Hendershot Eleanor , Sung Lillian 
Published: January 2011

Purpose To compare quality of life of children with cancer with no reasonable chance of cure reported by parents 6 months or fewer versus more than 6 months before death. Patients and Methods This cross-sectional study included children between the ages of 2 and 18 years with cancer and no reasonable chance of cure at The Hospital for Sick Children, Toronto, Ontario, Canada. Parents reported quality of life on behalf of their children. Outcomes were the PedsQL 4.0 Generic Core Scales, Acute Cancer Module, and Multidimensional Fatigue Scale. Results Seventy-three parents of children participated. Compared with children who survived more than 6 months (n = 43), those who died at 6 months or fewer (n = 30) had significantly worse physical health (mean difference, 15.9; 95% CI, 1.8 to 30.0; P = .028), more pain and hurt (mean difference, 15.5; 95% CI, 0.9 to 30.0; P = .037), and worse general fatigue (mean difference, 15.8; 95% CI, 2.4 to 29.1; P = .021) and sleep/rest fatigue (mean difference, 16.0; 95% CI, 3.5 to 28.5; P = .013). Among the entire cohort, those with leukemia/lymphoma had worse physical and psychosocial quality of life compared with those with solid or brain tumors. Recent stem-cell transplantation was associated with worse psychosocial health. Conclusion Parents of children with cancer reported worse physical health, pain, and fatigue proximal to death. Those with leukemia/lymphoma were at higher risk for impaired quality of life. This knowledge can help in the design of targeted interventions to improve quality of life for children dying as a result of cancer.
Human cardiomyopathy mutations induce myocyte hyperplasia and activate hypertrophic pathways during cardiogenesis in zebrafish
Authors: Becker Jason R. , Deo Rahul C. , Werdich Andreas A. , Panàkovà Daniela , Coy Shannon , MacRae Calum A. 
Published: January 2011

SUMMARYTo assess the effects during cardiac development of mutations that cause human cardiomyopathy, we modeled a sarcomeric gene mutation in the embryonic zebrafish. We designed morpholino antisense oligonucleotides targeting the exon 13 splice donor site in the zebrafish cardiac troponin T (tnnt2) gene, in order to precisely recapitulate a human TNNT2 mutation that causes hypertrophic cardiomyopathy (HCM). HCM is a disease characterized by myocardial hypertrophy, myocyte and myofibrillar disarray, as well as an increased risk of sudden death. Similar to humans with HCM, the morphant zebrafish embryos displayed sarcomere disarray and there was a robust induction of myocardial hypertrophic pathways. Microarray analysis uncovered a number of shared transcriptional responses between this zebrafish model and a well-characterized mouse model of HCM. However, in contrast to adult hearts, these embryonic hearts developed cardiomyocyte hyperplasia in response to this genetic perturbation. The re-creation of a human disease-causing TNNT2 splice variant demonstrates that sarcomeric mutations can alter cardiomyocyte biology at the earliest stages of heart development with distinct effects from those observed in adult hearts despite shared transcriptional responses.
Information Goods vs. Industrial Goods: Cost Structure and Competition
Authors: Jones Roy , Mendelson Haim 
Published: January 2011

We study markets for information goods and find that they differ significantly from markets for traditional industrial goods. Markets for information goods in which products are vertically differentiated lack the segmentation inherent in markets for industrial goods. As a result, a monopoly will offer only a single product. Competition leads to highly concentrated information-good markets, with the leading firm behaving almost like a monopoly even with free entry and without network effects. We study how the structure of the firms' cost functions drives our results. This paper was accepted by Barrie R. Nault, information systems.