bluuebunny/crossref_metadata_2025_split huggingface dataset:
MADS+: discovery of differential splicing events from Affymetrix exon junction array data
Authors: Shen Shihao , Warzecha Claude C. , Carstens Russ P. , Xing Yi 
Published: November 2009

Abstract
Motivation: The Affymetrix Human Exon Junction Array is a newly designed high-density exon-sensitive microarray for global analysis of alternative splicing. Contrary to the Affymetrix exon 1.0 array, which only contains four probes per exon and no probes for exon–exon junctions, this new junction array averages eight probes per probeset targeting all exons and exon–exon junctions observed in the human mRNA/EST transcripts, representing a significant increase in the probe density for alternative splicing events. Here, we present MADS+, a computational pipeline to detect differential splicing events from the Affymetrix exon junction array data. For each alternative splicing event, MADS+ evaluates the signals of probes targeting competing transcript isoforms to identify exons or splice sites with different levels of transcript inclusion between two sample groups. MADS+ is used routinely in our analysis of Affymetrix exon junction arrays and has a high accuracy in detecting differential splicing events. For example, in a study of the novel epithelial-specific splicing regulator ESRP1, MADS+ detects hundreds of exons whose inclusion levels are dependent on ESRP1, with a RT-PCR validation rate of 88.5% (153 validated out of 173 tested).
Availability: MADS+ scripts, documentations and annotation files are available at http://www.medicine.uiowa.edu/Labs/Xing/MADSplus/.
Contact: yi-xing@uiowa.edu
mimiRNA: a microRNA expression profiler and classification resource designed to identify functional correlations between microRNAs and their targets
Authors: Ritchie William , Flamant Stephane , Rasko John E. J. 
Published: November 2009

Abstract
Motivation: microRNAs (miRNAs) are short non-coding RNAs that regulate gene expression by inhibiting target mRNA genes. Their tissue- and disease-specific expression patterns have immense therapeutic and diagnostic potential. To understand these patterns, a reliable compilation of miRNA and mRNA expression data is required to compare multiple tissue types. Moreover, with the appropriate statistical tools, such a resource could be interrogated to discover functionally related miRNA–mRNA pairs.
Results:We have developed mimiRNA, an online resource that integrates expression data from 1483 samples and permits visualization of the expression of 635 human miRNAs across 188 different tissues or cell types. mimiRNA incorporates a novel sample classification algorithm, ExParser, that groups identical miRNA or mRNA experiments from separate sources. This enables mimiRNA to provide reliable expression profiles and to discover functional relations between miRNAs and mRNAs such as miRNA targets. Additionally, mimiRNA incorporates a decision tree algorithm to discover distinguishing miRNA features between two tissue or cell types. We validate the efficacy of our resource on independent experimental data and through biologically relevant analyses.
Availability: http://mimirna.centenary.org.au
Contact: j.rasko@centenary.org.au
Supplementary information: Supplementary data are available at Bioinformatics online.
Bridging the gap in heart failure prevention: rationale and design of the Nurse‐led Intervention for Less Chronic Heart Failure (NIL‐CHF) Study
Authors: Carrington Melinda J. , Stewart Simon ,   on behalf of the NIL‐CHF Study Investigators
Published: November 2009

AimsThe primary objective of the Nurse‐led Intervention for Less Chronic Heart Failure (NIL‐CHF) Study is to develop a programme of care that cost‐effectively prevents the development of chronic heart failure (CHF).MethodsNIL‐CHF is a randomized controlled trial of a hybrid, home‐ and clinic‐based, nurse‐led multidisciplinary intervention targeting hospitalized patients at risk of developing CHF. A target of 750 patients aged ≥45 years will be exposed to usual post‐discharge care or the NIL‐CHF intervention. The composite primary endpoint is all‐cause mortality or CHF‐related admission during 3–5 years of follow‐up. After 12 months recruitment, ∼300 eligible patients (40% of target) have been randomized. Overall, 73% are male and the mean age is 65 ± 10 years. The most common antecedents for CHF thus far are hypertension (70%, 95% CI, 64–75%), coronary artery disease (51%, 95% CI, 31–41%), and type 2 diabetes (26%, 95% CI, 21–31%), whereas 76% (95% CI, 69–82%) of patients have diastolic dysfunction, 29% (95% CI, 23–36%) left ventricular hypertrophy, 71% (95% CI, 64–78%) mitral valve dysfunction, and 7% (95% CI, 4–12%) have a left ventricular ejection fraction ≤45%.ConclusionAs one of the largest randomized studies of its kind, NIL‐CHF will ultimately provide important insights into the potential to prevent CHF via prolonged and intensive disease management.
Sevoflurane Ameliorates Gas Exchange and Attenuates Lung Damage in Experimental Lipopolysaccharide-induced Lung Injury
Authors: Voigtsberger Stefanie , Lachmann Robert A. , Leutert Anik C. , Schläpfer Martin , Booy Christa , Reyes Livia , Urner Martin , Schild Julia , Schimmer Ralph C. , Beck-Schimmer Beatrice 
Published: November 2009

Background
Acute lung injury is a common complication in critically ill patients. Several studies suggest that volatile anesthetics have immunomodulating effects. The aim of the current study was to assess possible postconditioning with sevoflurane in an in vivo model of endotoxin-induced lung injury.

Methods
Rats were anesthetized, tracheotomized, and mechanically ventilated. Lipopolysaccharide (saline as control) was administered intratracheally. Upon injury after 2 h of propofol anesthesia, general anesthesia was continued with either sevoflurane or propofol for 4 h. Arterial blood gases were measured every 2 h. After 6 h of injury, bronchoalveolar lavage was performed and lungs were collected. Total cell count, albumin content, concentrations of the cytokines cytokine-induced neutrophil chemoattractant-1 and monocyte chemoattractant protein-1, and phospholipids were analyzed in bronchoalveolar lavage fluid. Expression of messenger RNA for the two cytokines and for surfactant protein B was determined in lung tissue. Histopathologic examination of the lung was performed.

Results
Significant improvement of the ratio of oxygen tension to inspired oxygen fraction was shown with sevoflurane (mean + or - SD: 243 + or - 94 mmHg [32.4 kPa]) compared with propofol (88 + or - 19 mmHg [11.7 kPa]). Total cell count representing effector cell recruitment as well as albumin content as a measure of lung permeability were significantly decreased in the sevoflurane-lipopolysaccharide group compared with the propofol-lipopolysaccharide group in bronchoalveolar lavage fluid. Expression of the cytokines protein in bronchoalveolar lavage fluid as well as messenger RNA in lung tissue was significantly lower in the sevoflurane-lipopolysaccharide group compared with the propofol-lipopolysaccharide group.

Conclusions
Postconditioning with sevoflurane attenuates lung damage and preserves lung function in an in vivo model of acute lung injury.
Differential Role of Pim-1 Kinase in Anesthetic-induced and Ischemic Preconditioning against Myocardial Infarction
Authors: Stumpner Jan , Redel Andreas , Kellermann Anna , Lotz Christopher A. , Blomeyer Christoph A. , Smul Thorsten M. , Kehl Franz , Roewer Norbert , Lange Markus 
Published: November 2009

Background
Ischemic preconditioning (IPC) and anesthetic-induced preconditioning against myocardial infarction are mediated via protein kinase B. Pim-1 kinase acts downstream of protein kinase B and was recently shown to regulate cardiomyocyte survival. The authors tested the hypothesis that IPC and anesthetic-induced preconditioning are mediated by Pim-1 kinase.

Methods
Pentobarbital-anesthetized male C57Black/6 mice were subjected to 45 min of coronary artery occlusion and 3 h of reperfusion. Animals received no intervention, Pim-1 kinase inhibitor II (10 microg/g intraperitoneally), its vehicle dimethyl sulfoxide (10 microl/g intraperitoneally), or 1.0 minimum alveolar concentration desflurane alone or in combination with Pim-1 kinase inhibitor II (10 microg/g intraperitoneally). IPC was induced by three cycles of 5 min ischemia-reperfusion each, and animals received IPC either alone or in combination with Pim-1 kinase inhibitor II (10 microg/g intraperitoneally). Infarct size was determined with triphenyltetrazolium chloride, and area at risk was determined with Evans blue (Sigma-Aldrich, Taufkirchen, Germany). Protein expression of Pim-1 kinase, Bad, phospho-Bad, and cytosolic content of cytochrome c were measured using Western immunoblotting.

Results
Infarct size in the control group was 47 + or - 2%. Pim-1 kinase inhibitor II (44 + or - 2%) had no effect on infarct size. Desflurane (17 + or - 3%) and IPC (19 + or - 2%) significantly reduced infarct size compared with control (both P < 0.05 vs. control). Blockade of Pim-1 kinase completely abrogated desflurane-induced preconditioning (43 + or - 3%), whereas IPC (35 + or - 3%) was blocked partially. Desflurane tended to reduce cytosolic content of cytochrome c, which was abrogated by Pim-1 kinase inhibitor II.

Conclusion
These data suggest that Pim-1 kinase mediates at least in part desflurane-induced preconditioning and IPC against myocardial infarction in mice.
Neuroprotection against Spinal Cord Ischemia–Reperfusion Injury Induced by Different Ischemic Postconditioning Methods
Authors: Jiang Xiaojing , Ai Chunyu , Shi Enyi , Nakajima Yoshiki , Ma Hong 
Published: November 2009

Background
The authors compared the neuroprotective effects induced by two ischemic postconditioning methods and sought to determine the roles of phosphatidylinositol 3-kinase-Akt and extracellular signal-regulated kinase (ERK) in this neuroprotection.

Methods
Spinal cord ischemia was induced in rabbits by occlusion of the infrarenal aorta with a balloon catheter for 25 min. Postconditioning was accomplished by either five cycles of 1-min occlusion and 1-min reperfusion (standard postconditioning) or control of the perfusion pressure between 45 and 55 mmHg at the first 10 min of reperfusion (modified postconditioning). Motor function was assessed with the Tarlov score during a 28-day observation period. Histologic examination of lumbar spinal cords was performed. Expressions of Akt and ERK in the spinal cord were evaluated by Western blot.

Results
Compared with the controls, the two postconditioning methods markedly increased Tarlov scores 1, 3, 7, and 28 days after spinal cord ischemia and number of intact motor neurons in the lumbar spinal cord. No significant difference in Tarlov scores and number of intact motor neurons was detected between the two postconditioning method groups. The two postconditioning methods enhanced the expressions of phospho-Akt and phospho-ERK in spinal cords. The neuroprotective effects and the increases in phospho-Akt and phospho-ERK were abolished by administration of phosphatidylinositol 3-kinase-Akt inhibitor LY-294002 or ERK inhibitor PD-98059.

Conclusions
The two postconditioning methods possess comparable neuroprotective effects on the spinal cord and share a common molecular mechanism, in which phosphatidylinositol 3-kinase and ERK pathways play crucial roles.
Pain Assessment Is Associated with Decreased Duration of Mechanical Ventilation in the Intensive Care Unit
Authors: Payen Jean-Francois , Bosson Jean-Luc , Chanques Gérald , Mantz Jean , Labarere José 
Published: November 2009

Background
Critically ill patients frequently experience pain, but assessment rates remain below 40% in mechanically ventilated patients. Whether pain assessment affects patient outcomes is largely unknown.

Methods
As part of a prospective cohort study of mechanically ventilated patients who received analgesia on day 2 of their stay in the intensive care unit (ICU), the investigators performed propensity-adjusted score analysis to compare the duration of ventilator support and duration of ICU stay between 513 patients who were assessed for pain and 631 patients who were not assessed for pain.

Results
Patients assessed for pain on day 2 were more likely to receive sedation level assessment, nonopioids, and dedicated analgesia during painful procedures than patients whose pain was not assessed. They also received fewer hypnotics and lower daily doses of midazolam. Patients with pain assessment had a shorter duration of mechanical ventilation (8 vs. 11 days; P < 0.01) and a reduced duration of stay in the ICU (13 vs. 18 days; P < 0.01). In propensity-adjusted score analysis, pain assessment was associated with increased odds of weaning from the ventilator (odds ratio, 1.40; 95% confidence interval, 1.00-1.98) and of discharge from the ICU (odds ratio, 1.43; 95% confidence interval, 1.02-2.00).

Conclusions
Pain assessment in mechanically ventilated patients is independently associated with a reduction in the duration of ventilator support and of duration of ICU stay. This might be related to higher concomitant rates of sedation assessments and a restricted use of hypnotic drugs when pain is assessed.
Susceptibility to Fraud in Systematic Reviews
Authors: Marret Emmanuel , Elia Nadia , Dahl Jørgen B. , McQuay Henry J. , Møiniche Steen , Moore R Andrew , Straube Sebastian , Tramèr Martin R. 
Published: November 2009

Background
Dr. Scott Reuben allegedly fabricated data. The authors of the current article examined the impact of Reuben reports on conclusions of systematic reviews.

Methods
The authors searched in ISI Web of Knowledge systematic reviews citing Reuben reports. Systematic reviews were grouped into one of three categories: I, only cited but did not include Reuben reports; II, retrieved and considered, but eventually excluded Reuben reports; III, included Reuben reports. For quantitative systematic reviews (i.e., meta-analyses), a relevant difference was defined as a significant result becoming nonsignificant (or vice versa) by excluding Reuben reports. For qualitative systematic reviews, each author decided independently whether noninclusion of Reuben reports would have changed conclusions.

Results
Twenty-five systematic reviews (5 category I, 6 category II, 14 category III) cited 27 Reuben reports (published 1994-2007). Most tested analgesics in surgical patients. One of 6 quantitative category III reviews would have reached different conclusions without Reuben reports. In all 6 (30 subgroup analyses involving Reuben reports), exclusion of Reuben reports never made any difference when the number of patients from Reuben reports was less than 30% of all patients included in the analysis. Of 8 qualitative category III reviews, all authors agreed that one would certainly have reached different conclusions without Reuben reports. For another 4, the authors' judgment was not unanimous.

Conclusions
Carefully performed systematic reviews proved robust against the impact of Reuben reports. Quantitative systematic reviews were vulnerable if the fraudulent data were more than 30% of the total. Qualitative systematic reviews seemed at greater risk than quantitative.
A generalized Coleman–Noll procedure for the exploitation of the entropy principle
Authors: Cimmelli V. A. , Sellitto A. , Triani V. 
Published: November 2009

A generalization of the classical Coleman–Noll procedure for the exploitation of second law of thermodynamics in the presence of first-order non-local constitutive functions is proposed. The local balance of entropy is regarded as a differential inequality constrained by the governing equations for the set of the unknown fields as well as by their gradient extensions. The thermodynamic compatibility of such a class of materials is achieved without any modification of the basic thermodynamic laws. The results so obtained are applied to model nonlinear heat conduction in solids, in the presence of a dynamical semi-empirical temperature scale.
Plasticity of Arabidopsis Root Gravitropism throughout a Multidimensional Condition Space Quantified by Automated Image Analysis
Authors: Durham Brooks Tessa L. , Miller Nathan D. , Spalding Edgar P. 
Published: November 2009

AbstractPlant development is genetically determined but it is also plastic, a fundamental duality that can be investigated provided large number of measurements can be made in various conditions. Plasticity of gravitropism in wild-type Arabidopsis (Arabidopsis thaliana) seedling roots was investigated using automated image acquisition and analysis. A bank of computer-controlled charge-coupled device cameras acquired images with high spatiotemporal resolution. Custom image analysis algorithms extracted time course measurements of tip angle and growth rate. Twenty-two discrete conditions defined by seedling age (2, 3, or 4 d), seed size (extra small, small, medium, or large), and growth medium composition (simple or rich) formed the condition space sampled with 1,216 trials. Computational analyses including dimension reduction by principal components analysis, classification by k-means clustering, and differentiation by wavelet convolution showed distinct response patterns within the condition space, i.e. response plasticity. For example, 2-d-old roots (regardless of seed size) displayed a response time course similar to those of roots from large seeds (regardless of age). Enriching the growth medium with nutrients suppressed response plasticity along the seed size and age axes, possibly by ameliorating a mineral deficiency, although analysis of seeds did not identify any elements with low levels on a per weight basis. Characterizing relationships between growth rate and tip swing rate as a function of condition cast gravitropism in a multidimensional response space that provides new mechanistic insights as well as conceptually setting the stage for mutational analysis of plasticity in general and root gravitropism in particular.
OsKu70 Is Associated with Developmental Growth and Genome Stability in Rice
Authors: Hong Jong-Pil , Byun Mi Young , An Kyungsook , Yang Sae-Jun , An Gynheung , Kim Woo Taek 
Published: November 2009

Abstract
The cellular functions of Ku70 in repair of DNA double-stranded breaks and telomere regulation have been described in a wide range of organisms. In this study, we identified the rice (Oryza sativa) Ku70 homolog (OsKu70) from the rice genome database. OsKu70 transcript was detected constitutively in every tissue and developmental stage examined and also in undifferentiated callus cells in rice. Yeast two-hybrid and in vitro pull-down experiments revealed that OsKu70 physically interacts with OsKu80. We obtained loss-of-function osku70 T-DNA knockout mutant lines and constructed transgenic rice plants that overexpress the OsKu70 gene in the sense (35S:OsKu70) or antisense (35S:anti-OsKu70) orientation. The homozygous G2 osku70 mutant lines were more sensitive than wild-type plants to a DNA-damaging agent (0.01%–0.05% methyl-methane sulfonate), consistent with the notion that OsKu70 participates in the DNA repair mechanism. Terminal restriction fragment analysis revealed that telomeres in homozygous G2 osku70 mutants were markedly longer (10–20 kb) than those in wild-type plants (5–10 kb), whereas telomere length in heterozygous G2 osku70 mutant and T2 OsKu70-overexpressing transgenic (35S:OsKu70) rice resembled that of the wild-type plant. In contrast to what was observed in Arabidopsis (Arabidopsis thaliana) atku70 mutants, homozygous G2 osku70 rice plants displayed severe developmental defects in both vegetative and reproductive organs under normal growth conditions, resulting in sterile flowers. Analysis of meiotic progression in pollen mother cells demonstrated that up to 11.1% (seven of 63) of G2 mutant anaphase cells displayed one or more chromosomal fusions. These results suggest that OsKu70 is required for the maintenance of chromosome stability and normal developmental growth in rice plants.
Incidence and survival trends for childhood cancer in Osaka, Japan, 1973–2001
Authors: Baba Sachiko , Ioka Akiko , Tsukuma Hideaki , Noda Hiroyuki , Ajiki Wakiko , Iso Hiroyasu 
Published: November 2009

(Cancer Sci 2010; 101: 787–792)Mortality for childhood cancer has declined in Osaka, as well as all over Japan, since the 1970s, but whether this decline can be explained by trends of incidence or survival of childhood cancer has not been examined. A total of 5960 malignant tumors diagnosed between 1973 and 2001 in children <15 years of age were registered at the Osaka Cancer Registry in Japan. The time trends for childhood cancer were analyzed over 29 years for incidence and 20 years for survival. Leukemia was the most common among childhood cancer for both sexes and accounted for one‐third of all cases. The age‐standardized annual incidence rate of all tumors was highest in 1988–1992: 155.1 per million for males and 135.9 for females. Five‐year survival for all tumors improved from 50.1% in 1978–1982 to 73.0% in 1993–1997 for males and from 52.3% to 76.3% for females. Thus, the constant decline in mortality in childhood cancer was primarily due to improved survival between the 1970s and 1980s and reduced incidence after the 1990s.
hTERT‐promoter‐dependent oncolytic adenovirus enhances the transduction and therapeutic efficacy of replication‐defective adenovirus vectors in pancreatic cancer cells
Authors: Onimaru Manabu , Ohuchida Kenoki , Mizumoto Kazuhiro , Nagai Eishi , Cui Lin , Toma Hiroki , Takayama Koichi , Matsumoto Kunio , Hashizume Makoto , Tanaka Masao 
Published: November 2009

(Cancer Sci 2010; 101: 735–742)Adenovirus‐mediated gene therapy shows promise for cancer therapy, but transgene expression of replication‐defective adenovirus may be low and transient in clinical settings. Recent reports have shown that the use of a conditionally replication‐competent adenovirus (CRAd) enhanced the gene transduction of a replication‐defective adenovirus vector. The control of tumor–stromal interactions has also been determined to be important in cancer therapy. In this study, we investigated the effect of the human telomerase reverse transcriptase (hTERT)‐CRAd, Ad5/3hTERTE1, which possesses the tumor‐specific hTERT promoter with the chimeric fiber 5/3, on the transgene expression and therapeutic efficacy of a replication‐defective adenovirus vector expressing NK4 under the control of the CMV promoter, Ad‐NK4. In addition, we established a new strategy to target both cancer cells and cancer–stromal interactions. Human pancreatic cancer cells were infected with Ad‐NK4 and either Ad5/3hTERTE1 (CRAd‐combination group) or Ad5/3hTERTLuc (control‐combination group). In the CRAd‐combination group, Ad‐NK4‐delivered transgene expression was increased, leading to an enhanced inhibitory effect on the invasion of cancer cells. In in vivo experiments, NK4 expression within tumors and its inhibitory effect on tumor growth, angiogenesis, and metastasis were enhanced in the CRAd‐combination group. These results suggest that hTERT‐CRAd enhances the transgene expression and therapeutic efficacies of Ad‐NK4, possibly through the in‐trans replication of Ad‐NK4 induced by adenovirus E1 derived from co‐infected hTERT‐CRAd. This approach may be a promising combination therapy against advanced pancreatic cancer.