bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel transcriptional profile in wrist muscles from cerebral palsy patients
Authors: Smith Lucas R , Pontén Eva , Hedström Yvette , Ward Samuel R , Chambers Henry G , Subramaniam Shankar , Lieber Richard L 
Published: July 2009

Abstract

Background
Cerebral palsy (CP) is an upper motor neuron disease that results in a progressive movement disorder. Secondary to the neurological insult, muscles from CP patients often become spastic. Spastic muscle is characterized by an increased resistance to stretch, but often develops the further complication of contracture which represents a prominent disability in children with CP. This study's purpose is to characterize alterations of spastic muscle on the transcriptional level. Increased knowledge of spastic muscle may lead to novel therapies to improve the quality of life for children with CP.

Method
The transcriptional profile of spastic muscles were defined in children with cerebral palsy and compared to control patients using Affymetrix U133A chips. Expression data were verified using quantitative-PCR (QPCR) and validated with SDS-PAGE for select genes. Significant genes were determined using a 2 × 2 ANOVA and results required congruence between 3 preprocessing algorithms.

Results
CP patients clustered independently and 205 genes were significantly altered, covering a range of cellular processes. Placing gene expression in the context of physiological pathways, the results demonstrated that spastic muscle in CP adapts transcriptionally by altering extracellular matrix, fiber type, and myogenic potential. Extracellular matrix adaptations occur primarily in the basal lamina although there is increase in fibrillar collagen components. Fiber type is predominately fast compared to normal muscle as evidenced by contractile gene isoforms and decrease in oxidative metabolic gene transcription, despite a paradoxical increased transcription of slow fiber pathway genes. We also found competing pathways of fiber hypertrophy with an increase in the anabolic IGF1 gene in parallel with a paradoxical increase in myostatin, a gene responsible for stopping muscle growth. We found evidence that excitation-contraction coupling genes are altered in muscles from patients with CP and may be a significant component of disease.

Conclusion
This is the first transcriptional profile performed on spastic muscle of CP patients and these adaptations were not characteristic of those observed in other disease states such as Duchenne muscular dystrophy and immobilization-induced muscle atrophy. Further research is required to understand the mechanism of muscle adaptation to this upper motor neuron lesion that could lead to the development of innovative therapies.
Neuropathic and nociceptive pain in head and neck cancer patients receiving radiation therapy
Authors: Epstein Joel B , Wilkie Diana J , Fischer Dena J , Kim Young-Ok , Villines Dana 
Published: July 2009

Abstract

Background
Pain is common in head and neck cancer (HNC) patients and may be attributed to the malignancy and/or cancer treatment. Pain mechanisms and patient report of pain in HNC are expected to include both nociceptive and neuropathic components. The purpose of this study was to assess the trajectory of orofacial and other pain during and following treatment, using patient reports of neuropathic pain and nociceptive pain and pain impact.

Methods
124 consecutive HNC patients receiving radiation therapy (RT) (95 men, 29 women; mean age: 54.7 ± 12.3 years) participated in a patient-reported outcome (PRO) assessment. Patients completed the McGill Pain Questionnaire three times during therapy and 3 months following study entry.

Results
The majority of patients related their pain to the tumor and/or cancer treatment. Whereas 59% reported their pain to be less severe than they expected, 29% were not satisfied with their level of pain despite pain management during cancer therapy. Worst pain was 3.0 ± 1.3 on a 0- to 5-point verbal descriptor scale. Pain intensity was present at entry, highest at 2-week follow-up, declining towards the end of treatment and persisting at 3-month follow-up. The most common neuropathic pain descriptors chosen were aching (20%) and burning (27%); nociceptive words chosen were dull (22%), sore (32%), tender (35%), and throbbing (23%), and affective/evaluative descriptors were tiring (25%) and annoying (41%). 57% of patients reported continuous pain, and combined continuous and intermittent pain was reported by 79% of patients.

Discussion
This study provides evidence that patients with HNC experience nociceptive and neuropathic pain during RT despite ongoing pain management. The affective and evaluative descriptors chosen for head and neck pain indicate considerable impact on quality of life even with low to moderate levels of pain intensity. These findings suggest that clinicians should consider contemporary management for both nociceptive and neuropathic pain in head and neck cancer patients.
Bronchoalveoloar lavage fluid cytokines and chemokines as markers and predictors for the outcome of interstitial lung disease in systemic sclerosis patients
Authors: Schmidt Katrin , Martinez-Gamboa Lorena , Meier Susan , Witt Christian , Meisel Christian , Hanitsch Leif G , Becker Mike O , Huscher Doerte , Burmester Gerd R , Riemekasten Gabriela 
Published: July 2009

Abstract
Introduction
Interstitial lung disease (ILD) is a frequent manifestation of systemic sclerosis (SSc), and cytokines can contribute to the disease pathology. The aim of the current study was to identify specific changes in cytokine levels that may serve as disease markers and possible targets for therapy.

Methods
Cytokines were measured with bioplex analysis in 38 bronchoalveolar fluids (BALFs) from 32 SSc patients (27 with alveolitis and 11 without alveolitis) and 26 control patients. In the case of SSc patients, cytokines were correlated with the respective bronchoalveolar lavage (BAL) cell differentiation, lung function, and thoracic HR-CT score. For 35 BALF samples derived from 29 SSc patients, follow-up investigations of clinical data, lung-function parameter, or thoracic HR-CT scans were available to evaluate the predictive capacity of BALF cytokines and chemokines.

Results
High IL-7 levels were characteristic of SSc-associated interstitial lung disease (ILD) and, in addition, when compared with ILD-negative SSc patients, ILD-positive SSc patients revealed higher IL-4, IL-6, IL-8, and CCL2 (MCP-1) BALF levels. High CCL2 and IL-8 BALF concentrations were associated with neutrophilic and mixed alveolitis. Cytokine levels of IL-4, IL-8, and CCL2 correlated negatively with lung-function parameters; CCL2 concentrations also correlated with HR-CT scores. High concentrations of several cytokines were associated with the progress of ILD and end-stage ILD. Univariate analyses revealed high IL-2 and tumor necrosis factor-alpha (TNF-α) levels as the best predictors for progressive disease, together with lung-function parameters, young age, and neutrophilic alveolitis. Multivariate analyses partially confirmed these results but did not sufficiently converge because of the limited number of patients.

Conclusions
The association of BALF cytokines with lung fibrosis and its progress suggests that cytokines contribute to the pathogenesis of ILD and hence could be regarded as potential therapeutic targets.
Changes in regional distribution of lung sounds as a function of positive end-expiratory pressure
Authors: Lev Shaul , Glickman Yael A , Kagan Ilya , Dahan David , Cohen Jonathan , Grinev Milana , Shapiro Maury , Singer Pierre 
Published: July 2009

Abstract
Introduction
Automated mapping of lung sound distribution is a novel area of interest currently investigated in mechanically ventilated, critically ill patients. The objective of the present study was to assess changes in thoracic sound distribution resulting from changes in positive end-expiratory pressure (PEEP). Repeatability of automated lung sound measurements was also evaluated.

Methods
Regional lung sound distribution was assessed in 35 mechanically ventilated patients in the intensive care unit (ICU). A total of 201 vibration response imaging (VRI) measurements were collected at different levels of PEEP between 0 and 15 cmH2O. Findings were correlated with tidal volume, oxygen saturation, airway resistance, and dynamic compliance. Eighty-two duplicated readings were performed to evaluate the repeatability of the measurement.

Results
A significant shift in sound distribution from the apical to the diaphragmatic lung areas was recorded when increasing PEEP (paired t-tests, P < 0.05). In patients with unilateral lung pathology, this shift was significant in the diseased lung, but not as pronounced in the other lung. No significant difference in lung sound distribution was encountered based on level of ventilator support needed. Decreased lung sound distribution in the base was correlated with lower dynamic compliance. No significant difference was encountered between repeated measurements.

Conclusions
Lung sounds shift towards the diaphragmatic lung areas when PEEP increases. Lung sound measurements are highly repeatable in mechanically ventilated patients with various lung pathologies. Further studies are needed in order to fully appreciate the contribution of PEEP increase to diaphragmatic sound redistribution.
Dosage compensation on the active X chromosome minimizes transcriptional noise of X-linked genes in mammals
Authors: Yin Shanye , Wang Ping , Deng Wenjun , Zheng Hancheng , Hu Landian , Hurst Laurence D , Kong Xiangyin 
Published: July 2009

Abstract
Background
Theory predicts that haploid-expressed genes should have noisier expression than comparable diploid-expressed ones with the same expression level. However, in mammals there are several classes of gene that are monoallelically expressed, including X-linked genes, imprinted genes and some other autosomal genes. Does it follow that the evolution of X chromosomes in eukaryotes comes at the cost of increased transcriptional noise in the heterogametic sex? Moreover, is escaping X-inactivation in mammalian females associated with an increase in transcriptional variation? To address these questions, we analyze gene expression variation between replicate samples of diverse mammalian cell lines in steady-state using microarray data.

Results
We observe that transcriptional variation of X-linked genes is no different to that of autosomal genes both before and after control for transcript abundance. By contrast, autosomal genes subject to allelic exclusion do have unusually high noise levels even allowing for their low transcript abundance. The prior theory we suggest was insufficient, at least as regards X-chromosomes, as it failed to appreciate the regulatory complexity of gene expression, not least the effects of genomic neighborhood.

Conclusions
These results suggest that high noise is not a necessary consequence of haploid expression and emphasize the primacy of expression level as a determinant of noise. The latter has consequences for understanding the etiology of haplo-insufficiency and the evolution of gene expression levels. Given the coupling between expression level and noise on the X-chromosome, we suggest that part of the selective advantage of dosage compensation is noise abatement of X-linked genes.
Obstacles to the successful development of an efficacious T cell-inducing HIV-1 vaccine
Authors: Haut Larissa Herkenhoff , Ertl Hildegund C J 
Published: July 2009

Abstract
Preclinical and clinical HIV-1 cell vaccine development continues to be hampered by the lack of validated preclinical animal models: a discussion about way forward.
An efficacious vaccine to HIV-1 is direly needed to stem the global pandemic. Immunogens that elicit broadly cross-neutralizing antibodies to HIV-1 remain elusive, and thus, most HIV-1 vaccine efforts are focusing on induction of T cells. The notion that T cells can mediate protection against HIV-1 has been called into question by the failure of the STEP trial, which was designed to test this concept by the use of an E1-deleted Ad vaccine carrier. Lack of efficacy of the STEP trial vaccine underscores our limited knowledge about correlates of immune protection against HIV-1 and stresses the need for an enhanced commitment to basic research, including preclinical and clinical vaccine studies. In this review, we discuss known correlates of protection against HIV-1 and different vaccine strategies that have been or are being explored to induce such correlates, focusing on T cell-inducing vaccines and particularly on Ad vectors.
Higher Incidence of Relapse With Peripheral Blood Rather Than Marrow As a Source of Stem Cells in Adults With Acute Myelocytic Leukemia Autografted During the First Remission
Authors: Gorin Norbert-Claude , Labopin Myriam , Blaise Didier , Reiffers Josy , Meloni Giovanna , Michallet Mauricette , de Witte Theo , Attal Michel , Rio Bernard , Witz Francois , Fouillard Loic , Willemze Roel , Rocha Vanderson 
Published: July 2009

Purpose The cell source for autologous stem cell transplantation has shifted from bone marrow (BM) to peripheral blood (PB). In acute myelocytic leukemia (AML), for patients who receive transplants during first complete remission (CR1), no prospective randomized study has compared relapse incidence (RI) to cell source. Patients and Methods We analyzed 2,165 patients who received autografts (1,607 PB and 558 BM) from 1994 to 2006 and were reported to the European Cooperative Group for Blood and Marrow Transplantation with complete research data. Relative to the time of CR1, PB transplants were performed earlier than BM transplants. Because a poorer outcome was associated with a shorter interval from CR1 to transplantation, patients were divided into three groups: BM, early PB (≤ 80 days after CR1), and late PB (> 80 days after CR1) transplantation. Results In a multivariate analysis adjusted for differences between groups and center, RI was higher with both early PB (56% ± 3%; hazard ratio [HR], 1.45; 95% CI, 1.11 to 1.9; P = .006) and late PB transplantation (46% ± 2%; HR, 1.3; 95% CI, 1.06 to 1.59; P = .01) as compared with BM transplantation (39% ± 2%). This translated into a significantly worse leukemia-free survival (LFS) for early PB transplantation (36% ± 3%; HR, 0.75; 95% CI, 0.58 to 0.96; P = .02) and a trend for a poorer LFS for late PB (46% ± 2%; HR, 0.84; 95% CI, 0.7 to 1.01; P = .06) as compared with BM (52% ± 2%). Conclusion For patients with AML in CR1, risk of relapse is greater with PB transplantation rather than BM, independent of the interval from CR1 to transplantation.
Efficacy and Safety of Axitinib in Patients With Advanced Non–Small-Cell Lung Cancer: Results From a Phase II Study
Authors: Schiller Joan H. , Larson Timothy , Ou S.-H. Ignatius , Limentani Steven , Sandler Alan , Vokes Everett , Kim Sinil , Liau Katherine , Bycott Paul , Olszanski Anthony J. , von Pawel Joachim 
Published: July 2009

Purpose This phase II study evaluated efficacy and safety of single-agent axitinib, an oral, potent, selective inhibitor of vascular endothelial growth factor receptors (VEGFR) -1, -2, and -3, in patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods This was an open-label, single-arm, multicenter, phase II study with a Simon two-stage minimax design. Patients received a starting dose of axitinib 5 mg orally BID. The primary end point was Response Evaluation Criteria in Solid Tumors (RECIST) –defined objective response rate. Secondary end points included safety and tolerability, overall survival (OS), and progression-free survival (PFS). Results Thirty-two patients were enrolled, with a median age of 66.5 years. The majority of patients (75%) had adenocarcinoma. Nine patients (28%) had received no prior chemotherapy for metastatic disease, and 23 (72%) had received ≥ one regimen. Three patients (9%) had a RECIST investigator-assessed, confirmed partial response (PR); disease control rate (PR + stable disease) was 41%. Median PFS was 4.9 months overall (95% CI, 3.6 to 7.0 months). Median OS was 14.8 months (95% CI, 10.7 months to not estimable) overall and 14.8 months (95% CI, 12.5 months to not estimable) in patients receiving first-line axitinib. One-year survival rates for patients with or without prior therapy for metastatic disease were 57% and 78%, respectively. Grade 3 treatment-related adverse events in ≥ 5% of patients comprised fatigue (22%), hypertension (9%), and hyponatremia (9%). Conclusion Axitinib demonstrated single-agent activity in patients with advanced NSCLC. Therapy was well tolerated with manageable toxicities. Further investigation of this VEGFR inhibitor in NSCLC is of interest.
Subcutaneous Alemtuzumab in Fludarabine-Refractory Chronic Lymphocytic Leukemia: Clinical Results and Prognostic Marker Analyses From the CLL2H Study of the German Chronic Lymphocytic Leukemia Study Group
Authors: Stilgenbauer Stephan , Zenz Thorsten , Winkler Dirk , Bühler Andreas , Schlenk Richard F. , Groner Silja , Busch Raymonde , Hensel Manfred , Dührsen Ulrich , Finke Jürgen , Dreger Peter , Jäger Ulrich , Lengfelder Eva , Hohloch Karin , Söling Ulrike , Schlag Rudolf , Kneba Michael , Hallek Michael , Döhner Hartmut 
Published: July 2009

PurposeThe phase II CLL2H trial evaluated safety and efficacy of subcutaneous alemtuzumab in patients with fludarabine-refractory chronic lymphocytic leukemia (CLL). Clinical and biologic markers were evaluated for their impacts on outcome.Patients and MethodsOne hundred nine patients were enrolled, and 103 received at least one dose of alemtuzumab. After dose escalation, alemtuzumab was administered subcutaneously at 30 mg three times weekly for up to 12 weeks. Response was assessed every 4 weeks during treatment and quarterly thereafter.ResultsThe overall response rate was 34% (complete response, 4%; partial response, 30%). The median progression-free survival was 7.7 months, and the median overall survival (OS) was 19.1 months. Grades 3 to 4 neutropenia, thrombocytopenia, and anemia occurred in 56%, 57%, and 49% of patients, respectively. Grades 3 to 4 noncytomegalovirus and cytomegalovirus infections occurred in 29% and 8% of patients, respectively. Injection-site skin reactions were generally mild. Efficacy did not vary significantly in subgroups defined by genetic parameters (in particular, in 17p deletion, 11q deletion, mutated TP53, and unmutated VH), but efficacy was inferior in patients with increased β2-microglobulin (β2-MG) and thymidine kinase (TK). In multivariate analysis of clinical and biologic variables, age, performance status, β2-MG, and TK were independent prognostic factors for OS.ConclusionSubcutaneous alemtuzumab appears as effective and safe as intravenous alemtuzumab in fludarabine-refractory CLL. Subcutaneous administration should be the preferred delivery route because of its efficacy, convenience, improved adverse effect profile, and cost savings. In contrast to chemotherapy-based therapy, alemtuzumab treatment overcomes the adverse prognostic impact of VH mutation status, TP53 mutation, and genomic aberrations.
Dynamics and kinematics of ant locomotion: do wood ants climb on level surfaces?
Authors: Reinhardt Lars , Weihmann Tom , Blickhan Reinhard 
Published: July 2009

SUMMARYThe biomechanics of running in small animals have remained poorly characterized because of the difficulty of recording three-dimensional ground reaction forces. Available techniques limit investigations to animals with a body mass above 1 g. Here we present, for the first time, single-leg ground reaction forces of ants (body mass 10 mg), measured with a custom-built miniature force plate. We investigated forces and high-speed kinematics for straight level runs (average speed: 8.4 cm s–1) of Formica polyctena workers. The major finding was that the time course of ground reaction forces strongly differed from previous observations of larger insects. Maximum vertical force was reached during the first third of the tripod contact phase. During this period the body was decelerated predominantly by the front legs. Subsequently, the front legs pulled and accelerated the body. This `climbing' type of stride may be useful on the bumpy and unstable substrates that the animals face in their natural habitats,and may therefore also occur on level ground. Propulsive forces were generated predominantly by the front and hind legs. Dragging of the gaster on the substrate resulted in a breaking momentum, which was compensated by the legs. Future investigations will reveal, whether the identified pattern is due to specialization.
Aversion- vs fear-inducing properties of 2,4,5-trimethyl-3-thiazoline, a component of fox odor, in comparison with those of butyric acid
Authors: Endres Thomas , Fendt Markus 
Published: July 2009

SUMMARY
2,4,5-trimethyl-3-thiazoline (TMT), a component of fox feces, is a widely used odorant to induce innate fear behavior in rats and mice. However, based on the slight acrid smell it was argued that the observed behavioral effects are a result of the aversive and not of the fear-inducing properties of TMT. In the present study, we tried to directly compare the aversive and fear-inducing properties of TMT with those of the aversive control odor butyric acid. We first identified concentrations of butyric acid and TMT that induce similar amounts of avoidance behavior in rats, indicating that these concentrations have similar aversive properties. In a second experiment, these two concentrations were then tested for their ability to induce freezing, a species-specific defensive response. Only TMT but not butyric acid induced freezing in the rats. This supports the hypothesis that TMT indeed has specific fear-inducing properties and that the observed behavioral effects could not simply be reduced to the aversive properties of TMT.
Adaptation of Western measures of cognition for assessing 5‐year‐old semi‐urban Ugandan children
Authors: Nampijja M. , Apule B. , Lule S. , Akurut H. , Muhangi L. , Elliott A. M. , Alcock K. J. 
Published: July 2009

BackgroundThe majority of available psychometric tests originates from the Western World and was designed to suit the culture, language, and socio‐economic status of the respective populations. Few tests have been validated in the developing world despite the growing interest in examining effects of biological and environmental factors on cognitive functioning of children in this setting.AimsThe present study aimed at translating and adapting Western measures of working memory, general cognitive ability, attention, executive function, and motor ability in order to obtain a cognitive instrument suitable for assessing 5‐year‐old semi‐urban Ugandan children. This population represents a particular assessment challenge as school enrolment is highly variable at this age in this setting and many children are unused to a formal educational setting.MethodsMeasures of the above domains were selected, translated, and modified to suit the local culture, education, and socio‐economic background of the target population.The measures were piloted and then administered to semi‐urban Ugandan children aged 4;6–5;6, who included children who had started and not yet started school.ResultsAnalysis of validity and reliability characteristics showed that 8 (at least one from each domain) out of the 11 measures were successfully adapted on the basis that they showed adequate task comprehension, optimum levels of difficulty to demonstrate individual and group differences in abilities, sensitivity to effects of age and education, and good internal as well as test–retest reliability.ConclusionTranslation and adaptation are realistic and worthwhile strategies for obtaining valid and reliable cognitive measures in a resource‐limited setting.