bluuebunny/crossref_metadata_2025_split huggingface dataset:
Follicular dendritic cell–dependent drug resistance of non-Hodgkin lymphoma involves cell adhesion–mediated Bim down-regulation through induction of microRNA-181a
Authors: Lwin Tint , Lin Jianhong , Choi Yong Sung , Zhang Xinwei , Moscinski Lynn C. , Wright Kenneth L. , Sotomayor Eduardo M. , Dalton William S. , Tao Jianguo 
Published: September 2010

AbstractFollicular dendritic cells (FDCs), an essential component of the lymph node microenvironment, regulate and support B-lymphocyte differentiation, survival, and lymphoma progression. Here, we demonstrate that adhesion of mantle cell lymphoma and other non-Hodgkin lymphoma cells to FDCs reduces cell apoptosis and is associated with decreased levels of the proapoptotic protein, Bim. Bim down-regulation is posttranscriptionally regulated via up-regulation of microRNA-181a (miR-181a). miR-181a overexpression decreases, whereas miR-181a inhibition increases Bim levels by directly targeting Bim. Furthermore, we found that cell adhesion–up-regulated miR-181a contributes to FDC-mediated cell survival through Bim down-regulation, implicating miR-181a as an upstream effector of the Bim-apoptosis signaling pathway. miR-181a inhibition and Bim upregulation significantly suppressed FDC-mediated protection against apoptosis in lymphoma cell lines and primary lymphoma cells. Thus, FDCs protect B-cell lymphoma cells against apoptosis, in part through activation of a miR-181a–dependent mechanism involving down-regulation of Bim expression. We demonstrate, for the first time, that cell-cell contact controls tumor cell survival and apoptosis via microRNA in mantle cell and other non-Hodgkin lymphomas. Regulation of microRNAs by B-cell–FDC interaction may support B-cell survival, representing a novel molecular mechanism for cell adhesion–mediated drug resistance and a potential therapeutic target in B-cell lymphomas.
A novel form of human STAT1 deficiency impairing early but not late responses to interferons
Authors: Kong Xiao-Fei , Ciancanelli Michael , Al-Hajjar Sami , Alsina Laia , Zumwalt Timothy , Bustamante Jacinta , Feinberg Jacqueline , Audry Magali , Prando Carolina , Bryant Vanessa , Kreins Alexandra , Bogunovic Dusan , Halwani Rabih , Zhang Xin-Xin , Abel Laurent , Chaussabel Damien , Al-Muhsen Saleh , Casanova Jean-Laurent , Boisson-Dupuis Stéphanie 
Published: September 2010

Abstract
Autosomal recessive STAT1 deficiency is associated with impaired cellular responses to interferons and susceptibility to intracellular bacterial and viral infections. We report here a new form of partial STAT1 deficiency in 2 siblings presenting mycobacterial and viral diseases. Both carried a homozygous missense mutation replacing a lysine with an asparagine residue at position 201 (K201N) of STAT1. This mutation causes the abnormal splicing out of exon 8 from most STAT1 mRNAs, thereby decreasing (by ∼ 70%) STAT1 protein levels. The mutant STAT1 proteins are not intrinsically deleterious, in terms of tyrosine phosphorylation, dephosphorylation, homodimerization into γ-activating factor and heterotrimerization into ISGF-3, binding to specific DNA elements, and activation of the transcription. Interestingly, the activation of γ-activating factor and ISGF3 was impaired only at early time points in the various cells from patient (within 1 hour of stimulation), whereas sustained impairment occurs in other known forms of complete and partial recessive STAT1 deficiency. Consequently, delayed responses were normal; however, the early induction of interferon-stimulated genes was selectively and severely impaired. Thus, the early cellular responses to human interferons are critically dependent on the amount of STAT1 and are essential for the appropriate control of mycobacterial and viral infections.
BAALC and ERG expression levels are associated with outcome and distinct gene and microRNA expression profiles in older patients with de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study
Authors: Schwind Sebastian , Marcucci Guido , Maharry Kati , Radmacher Michael D. , Mrózek Krzysztof , Holland Kelsi B. , Margeson Dean , Becker Heiko , Whitman Susan P. , Wu Yue-Zhong , Metzeler Klaus H. , Powell Bayard L. , Kolitz Jonathan E. , Carter Thomas H. , Moore Joseph O. , Baer Maria R. , Carroll Andrew J. , Caligiuri Michael A. , Larson Richard A. , Bloomfield Clara D. 
Published: September 2010

AbstractBAALC and ERG expression levels are prognostic markers in younger (< 60 years) cytogenetically normal acute myeloid leukemia (CN-AML) adults; their prognostic impact in older (≥ 60 years) patients requires further investigation. We evaluated pretreatment expression of BAALC and ERG in 158 de novo patients treated on cytarabine/daunorubicin-based protocols. The patients were also characterized for other established molecular prognosticators. Low BAALC and ERG expression levels were associated with better outcome in univariable and multivariable analyses. Expression levels of both BAALC and ERG were the only factors significantly associated with overall survival upon multivariable analysis. To gain biological insights, we derived gene expression signatures associated with BAALC and ERG expression in older CN-AML patients. Furthermore, we derived the first microRNA expression signatures associated with the expression of these 2 genes. In low BAALC expressers, genes associated with undifferentiated hematopoietic precursors and unfavorable outcome predictors were down-regulated, whereas HOX genes and HOX-gene–embedded microRNAs were up-regulated. Low ERG expressers presented with down-regulation of genes involved in the DNA-methylation machinery, and up-regulation of miR-148a, which targets DNMT3B. We conclude that in older CN-AML patients, low BAALC and ERG expression associates with better outcome and distinct gene and microRNA expression signatures that could aid in identifying new targets and novel therapeutic strategies for older patients.
Stimulus and mechanisms of exercise-induced bronchoconstriction
Authors: Anderson S.D. , Kippelen P. 
Published: September 2010

Educational aimsTo describe the stimulus for exercise-induced bronchoconstriction.To describe the different mechanisms whereby this stimulus may act to cause the airways to narrow in asthmatics and athletes.To describe the relevance of the stimulus and mechanism to protocols to diagnose exercise-induced bronchoconstriction.To describe the inflammatory mediators involved in exercise-induced bronchoconstriction.To describe how and why airway injury could contribute to the pathogenesis of airway hyperresponsiveness and exercise-induced bronchoconstriction in athletes.SummaryThe stimulus for exercise-induced bronchoconstriction (EIB) is the loss of water by humidifying large volumes of air during exercise. The mechanism for EIB relates to the thermal and osmotic effects of water loss. The thermal theory proposes that EIB is a vascular event comprising vasoconstriction during exercise followed by rapid rewarming and a reactive hyperaemia at the end of exercise. The osmotic theory proposes that water loss induces an increase in osmolarity in the airways, which causes the release of mediators that cause bronchial smooth muscle to contract. Increased vascular permeability and leakage are common to both theories.
Field and laboratory exercise challenges for identifying exercise-induced bronchoconstriction
Authors: Rundell K.W. , Sue-Chu M. 
Published: September 2010

Educational aimsTo define necessary conditions for a successful exercise challenge.To provide operational procedures for performing an exercise challenge in the laboratory or the field for the identification of exercise-induced bronchoconstriction.To compare positive and negative attributes of each challenge.To provide spirometric cut-off criteria for positive challenge tests.SummaryExercise challenge tests are often used for identification of exercise-induced bronchoconstriction (EIB). Optimal test conditions are: absolute humidity of <10 mg H2O per L; exercise intensity resulting in a sustained increase in minute ventilation to 14–21 times the forced expiratory volume in 1 s or heart rate (HR) to 80–90% of the estimated maximal HR; and exercise duration of 6–8 min. Variability in fitness level and age necessitate individualisation of the exercise protocol. Field tests are subject to variability in test conditions and may have poorer repeatability than laboratory tests that require expensive equipment. However, either challenge test can be employed for the diagnosis of EIB in conjunction with a critical clinical assessment.
Global transcriptional profiles of beating clusters derived from human induced pluripotent stem cells and embryonic stem cells are highly similar
Authors: Gupta Manoj K , Illich Damir J , Gaarz Andrea , Matzkies Matthias , Nguemo Filomain , Pfannkuche Kurt , Liang Huamin , Classen Sabine , Reppel Michael , Schultze Joachim L , Hescheler Jürgen , Šarić Tomo 
Published: September 2010

Abstract

Background
Functional and molecular integrity of cardiomyocytes (CMs) derived from induced pluripotent stem (iPS) cells is essential for their use in tissue repair, disease modelling and drug screening. In this study we compared global transcriptomes of beating clusters (BCs) microdissected from differentiating human iPS cells and embryonic stem (ES) cells.

Results
Hierarchical clustering and principal component analysis revealed that iPS-BCs and ES-BCs cluster together, are similarly enriched for cardiospecific genes and differ in expression of only 1.9% of present transcripts. Similarly, sarcomeric organization, electrophysiological properties and calcium handling of iPS-CMs were indistinguishable from those of ES-CMs. Gene ontology analysis revealed that among 204 genes that were upregulated in iPS-BCs vs ES-BCs the processes related to extracellular matrix, cell adhesion and tissue development were overrepresented. Interestingly, 47 of 106 genes that were upregulated in undifferentiated iPS vs ES cells remained enriched in iPS-BCs vs ES-BCs. Most of these genes were found to be highly expressed in fibroblasts used for reprogramming and 34% overlapped with the recently reported iPS cell-enriched genes.

Conclusions
These data suggest that iPS-BCs are transcriptionally highly similar to ES-BCs. However, iPS-BCs appear to share some somatic cell signature with undifferentiated iPS cells. Thus, iPS-BCs may not be perfectly identical to ES-BCs. These minor differences in the expression profiles may occur due to differential cellular composition of iPS-BCs and ES-BCs, due to retention of some genetic profile of somatic cells in differentiated iPS cell-derivatives, or both.
Epstein-Barr virus-encoded EBNA1 enhances RNA polymerase III-dependent EBER expression through induction of EBER-associated cellular transcription factors
Authors: Owen Thomas J , O'Neil John D , Dawson Christopher W , Hu Chunfang , Chen Xiaoyi , Yao Yunhong , Wood Victoria HJ , Mitchell Louise E , White Robert J , Young Lawrence S , Arrand John R 
Published: September 2010

Abstract

Background
Epstein-Barr Virus (EBV)-encoded RNAs (EBERs) are non-polyadenylated RNA molecules transcribed from the EBV genome by RNA polymerase III (pol III). EBERs are the most abundant viral latent gene products, although the precise mechanisms by which EBV is able to achieve such high levels of EBER expression are not fully understood. Previously EBV has been demonstrated to induce transcription factors associated with EBER expression, including pol III transcription factors and ATF-2. We have recently demonstrated that EBV-encoded nuclear antigen-1 (EBNA1) induces cellular transcription factors, and given these findings, we investigated the role of EBNA1 in induction of EBER-associated transcription factors.

Results
Our data confirm that in epithelial cells EBNA1 can enhance cellular pol III transcription. Transient expression of EBNA1 in Ad/AH cells stably expressing the EBERs led to induction of both EBER1 and EBER2 and conversely, expression of a dominant negative EBNA1 led to reduced EBER expression in EBV-infected Ad/AH cells. EBNA1 can induce transcription factors used by EBER genes, including TFIIIC, ATF-2 and c-Myc. A variant chromatin precipitation procedure showed that EBNA1 is associated with the promoters of these genes but not with the promoters of pol III-transcribed genes, including the EBERs themselves. Using shRNA knock-down, we confirm the significance of both ATF-2 and c-Myc in EBER expression. Further, functional induction of a c-Myc fusion protein led to increased EBER expression, providing c-Myc binding sites upstream of EBER1 were intact. In vivo studies confirm elevated levels of the 102 kD subunit of TFIIIC in the tumour cells of EBV-positive nasopharyngeal carcinoma biopsies.

Conclusions
Our findings reveal that EBNA1 is able to enhance EBER expression through induction of cellular transcription factors and add to the repertoire of EBNA1's transcription-regulatory properties.
Hepatitis C virus infection in Brazilian long-distance truck drivers
Authors: Freitas Nara R , Teles Sheila A , Matos Marcos A , Lopes Carmen LR , Reis Nádia RS , Espírito-Santo Márcia P , Lampe Elisabeth , Martins Regina MB 
Published: September 2010

AbstractHepatitis C virus (HCV) infection is a global public health problem. Long-distance truck drivers live apart from their family for long periods of time, a lifestyle that favors at-risk behaviors such as unprotected sex with multiple partners and illicit drug use. As data concerning HCV infection in this population are still rare, this paper aims to investigate the prevalence, genotypes/subtypes, and the factors associated with HCV infection in long-distance truck drivers in Brazil. A cross-sectional survey was carried out with 641 Brazilian long-truck drivers who were recruited at a major truck stop located at kilometer 1,296 of the BR-153 highway, which is considered to be one of the longest roads in Brazil. All individuals were interviewed, and their serum samples were tested for the presence of antibodies to HCV (anti-HCV) by ELISA and immunoblot. Anti-HCV positive samples were tested for HCV RNA by PCR amplification of the 5' NC and NS5B regions and were genotyped using the LiPA assay and nucleotide sequencing, respectively. Factors associated with HCV infection were identified with logistic regression. The prevalence of HCV infection was 1.4% (95% CI: 0.7-2.8). History of blood transfusion, sharing of personal hygiene tools, illicit drug use and HBV status were factors independently associated with HCV infection in the study population. HCV RNA was detected in 8/9 anti-HCV positive samples, in which genotypes 1 (n = 3), 2 (n = 2), and 3 (n = 3) were determined by LiPA. Using phylogenetic tree analysis of the NS5B region, subtypes 1a (n = 1), 1b (n = 2), 2b (n = 2) and 3a (n = 3) were identified. These data show that the prevalence of HCV infection among Brazilian truck drivers was similar to that observed for the general population. History of blood transfusion, sharing of personal hygiene tools, illicit drug use and HBV status were predictors of HCV infection. The HCV genotypes/subtypes identified in the study population are consistent with those circulating in Brazil.
Laparoscopic treatment of biliary peritonitis following nonoperative management of blunt liver trauma
Authors: Marzano Ettore , Rosso Edoardo , Oussoultzoglou Elie , Collange Olivier , Bachellier Philippe , Pessaux Patrick 
Published: September 2010

Abstract

Introduction
Nonoperative management (NOM) of hemodynamically stable patients with blunt hepatic injuries is considered the current standard of care. However, it is associated with several in-hospital complications. In selected cases laparoscopy could be proposed as diagnostic and therapeutic means.

Case report
A 28 years-old male was admitted in the Emergency Unit following a motor vehicle crash. CT-scan showed an isolated stade II hepatic injury at the level of the segment IV. Firstly a NOM was decided. Laparoscopic exploration was then performed at day 4 due to a biliary peritonitis. Intraoperative trans-cystic duct cholangiography showed a biliary leaks of left hepatic biliary tract, involving sectioral pedicle to segment III. Cholecystectomy, trans-cystic biliary drainage, application of surgical tissue sealing patch and abdominal drainage were performed. Postoperative outcome was uneventful, with fast patient recovery.

Conclusion
Laparoscopy has gained a role as diagnostic and therapeutic means in treatment of complications following NOM of blunt liver trauma. This approach seems feasible and safety, with satisfactory postoperative outcome.
First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer
Authors: Yin Yong-Mei , Geng Yi-Ting , Shao Yong-Feng , Hu Xiao-Li , Li Wei , Shu Yong-Qian , Wang Zhao-Xia 
Published: September 2010

Abstract

Background
Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK) inhibitor of epidermal growth factor receptor (EGFR), displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC) in Chinese population are not sufficient.

Purpose
To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC), a study of single agent treatment with gefitinib in Chinese patients was conducted.

Methods
45 patients with advanced NSCLC were treated with gefitinib (250 mg daily) until the disease progression or intolerable toxicity.

Results
Among the 45 patients, 15 patients achieved partial response (PR), 17 patients experienced stable disease (SD), and 13 patients developed progression disease (PD). None of the patients achieved complete response (CR). The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively). The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively). In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively).

Conclusions
Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.
A case‐series study to explore the efficacy of foot orthoses in treating first metatarsophalangeal joint pain
Authors: Welsh Brian J , Redmond Anthony C , Chockalingam Nachiappan , Keenan Anne‐Maree 
Published: September 2010

AbstractBackgroundFirst metatarsophalangeal (MTP) joint pain is a common foot complaint which is often considered to be a consequence of altered mechanics. Foot orthoses are often prescribed to reduce 1st MTP joint pain with the aim of altering dorsiflexion at propulsion. This study explores changes in 1st MTP joint pain and kinematics following the use of foot orthoses.MethodsThe effect of modified, pre‐fabricated foot orthoses (X‐line®) were evaluated in thirty‐two patients with 1st MTP joint pain of mechanical origin. The primary outcome was pain measured at baseline and 24 weeks using the pain subscale of the foot function index (FFI). In a small sub‐group of patients (n = 9), the relationship between pain and kinematic variables was explored with and without their orthoses, using an electromagnetic motion tracking (EMT) system.ResultsA significant reduction in pain was observed between baseline (median = 48 mm) and the 24 week endpoint (median = 14.50 mm, z = ‐4.88, p < 0.001). In the sub‐group analysis, we found no relationship between pain reduction and 1st MTP joint motion, and no significant differences were found between the 1st MTP joint maximum dorsiflexion or ankle/subtalar complex maximum eversion, with and without the orthoses.ConclusionsThis observational study demonstrated a significant decrease in 1st MTP joint pain associated with the use of foot orthoses. Change in pain was not shown to be associated with 1st MTP joint dorsiflexion nor with altered ankle/subtalar complex eversion. Further research into the effect of foot orthoses on foot function is indicated.
Intensive care diaries reduce new onset post traumatic stress disorder following critical illness: a randomised, controlled trial
Authors: Jones Christina , Bäckman Carl , Capuzzo Maurizia , Egerod Ingrid , Flaatten Hans , Granja Cristina , Rylander Christian , Griffiths Richard D ,   the RACHEL group
Published: September 2010

Abstract
Introduction
Patients recovering from critical illness have been shown to be at risk of developing Post Traumatic Stress disorder (PTSD). This study was to evaluate whether a prospectively collected diary of a patient's intensive care unit (ICU) stay when used during convalescence following critical illness will reduce the development of new onset PTSD.

Methods
Intensive care patients with an ICU stay of more than 72 hours were recruited to a randomised controlled trial examining the effect of a diary outlining the details of the patients ICU stay on the development of acute PTSD. The intervention patients received their ICU diary at 1 month following critical care discharge and the final assessment of the development of acute PTSD was made at 3 months.

Results
352 patients were randomised to the study at 1 month. The incidence of new cases of PTSD was reduced in the intervention group compared to the control patients (5% versus 13%, P = 0.02).

Conclusions
The provision of an ICU diary is effective in aiding psychological recovery and reducing the incidence of new PTSD.

Trial registration
NCT00912613.
The Impact of Continuing Professional Development Versus Traditional Continuing Pharmacy Education on Pharmacy Practice
Authors: McConnell Karen J , Newlon Carey L , Delate Thomas 
Published: September 2010

Background: The Institute of Medicine states that the new vision for continuing education (CE) for health-care professionals will be based on continuing professional development (CPD); however, information on the utility of CPD is lacking. Objective: To assess the effect of CPD, compared with that of traditional continuing pharmacy education (CPE), on perceptions of factors related to pharmacy practice. Methods: This 10-month, nonblinded, randomized controlled study recruited licensed pharmacists employed at a health maintenance organization (HMO). After completing a basic CPD course, participants were randomized to the intervention or control group. The control group was instructed to continue with traditional CPE. The intervention group participants completed 3 CPD workshops and were instructed to utilize the CPD approach for their learning needs. At baseline and follow-up, all participants completed a study questionnaire on perceptions of their pharmacy practices. The outcome measures were comparisons on follow-up and changes from baseline to follow-up in responses to the study questionnaire. Results: One hundred pharmacists were enrolled. The intervention (n = 44, 7 lost to follow-up) and control (n = 47, 2 lost to follow-up) groups were similar at baseline. At follow-up, a higher percentage of intervention participants reported that they had better interactions with other health-care providers (always/frequently 32% vs 6%, respectively) and initiated practice/work changes (always/frequently 21% vs 0%, respectively) (both p < 0.01) as a result of their education activities. Compared with control participants at follow-up, intervention participants reported that their education activities improved patient care changes (46% vs 23%), professional knowledge (34% vs 6%), skills (48% vs 17%), and attitudes/values (43% to 11%) (all p < 0.05). However, intervention participants reported more often that time was a barrier to completing education activities (75% vs 32%, p < 0.001). Conclusions: Pharmacists who participated in CPD reported more often that their perceptions of various aspects of their pharmacy practice improved as a result of their education activities compared with pharmacists who participated in traditional CPE.