bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression profiles of alveolar type II cells of chronic obstructive pulmonary disease: a case–control study
Authors: Fujino Naoya , Ota Chiharu , Takahashi Toru , Suzuki Takaya , Suzuki Satoshi , Yamada Mitsuhiro , Nagatomi Ryouichi , Kondo Takashi , Yamaya Mutsuo , Kubo Hiroshi 
Published: November 2012

ObjectivesThe aim of this study was to identify the gene expression pattern specific in alveolar epithelial type II cells (ATII cells) isolated from patients with chronic obstructive pulmonary disease (COPD).DesignCase control.SettingTwo hospitals in Japan.ParticipantsThree patients without COPD and three patients with COPD in microarray analyses. Five smokers without COPD and nine smokers with COPD in the following analyses.Primary and secondary outcome measuredPrimary outcome included identification of differentially expressed genes and activated or inhibited pathways in ATII cells of the patients with COPD, compared to those of the patients without COPD, using Affymetrix gene expression arrays. Secondary outcome included validation of the results of microarray analyses by quantitative reverse transcription-PCR.ResultsWe isolated ATII cells from COPD and non-COPD lungs using fluorescence-activated cell sorting. We performed Affymetrix gene expression arrays on both types of ATII cells. Gene set enrichment analyses revealed that two major gene sets were enriched in ATII cells from COPD lungs: interferon-responsive gene sets and gene sets associated with cell cycle progression. Gene ontology term enrichment analyses indicated that among the interferon-stimulated genes, ATII cells in COPD expressed genes such asPSMB8,PSMB9,TAP1andTAP2associated with the antigen processing and presentation pathway. We validated the results of the microarray analyses using quantitative reverse transcriptase-PCR. In addition, FACS analysis indicated that the percentage of ATII cells to CD45-negative lung cells isolated from COPD lungs were significantly increased more than that from non-COPD lungs.ConclusionsOur study demonstrated that interferon-stimulated genes involved in the antigen processing and presentation pathway and genes involved in cell cycle progression were enriched in ATII cells of the patients with COPD. These pathways might alter phenotypes of ATII cells in COPD lungs.
Observational Research in Childhood Infectious Diseases (ORChID): a dynamic birth cohort study
Authors: Lambert Stephen Bernard , Ware Robert S , Cook Anne L , Maguire Frances A , Whiley David M , Bialasiewicz Seweryn , Mackay Ian M , Wang David , Sloots Theo P , Nissen Michael D , Grimwood Keith 
Published: November 2012

IntroductionEven in developed economies infectious diseases remain the most common cause of illness in early childhood. Our current understanding of the epidemiology of these infections is limited by reliance on data from decades ago performed using low-sensitivity laboratory methods, and recent studies reporting severe, hospital-managed disease.Methods and analysisThe Observational Research in Childhood Infectious Diseases (ORChID) study is an ongoing study enrolling a dynamic birth cohort to document the community-based epidemiology of viral respiratory and gastrointestinal infections in early childhood. Women are recruited antenatally, and their healthy newborn is followed for the first 2 years of life. Parents keep a daily symptom diary for the study child, collect a weekly anterior nose swab and dirty nappy swab and complete a burden diary when a child meets pre-defined illness criteria. Specimens will be tested for a wide range of viruses by real-time PCR assays. Primary analyses involves calculating incidence rates for acute respiratory illness (ARI) and acute gastroenteritis (AGE) for the cohort by age and seasonality. Control material from children when they are without symptoms will allow us to determine what proportion of ARIs and AGE can be attributed to specific pathogens. Secondary analyses will assess the incidence and shedding duration of specific respiratory and gastrointestinal pathogens.Ethics and disseminationThis study is approved by The Human Research Ethics Committees of the Children's Health Queensland Hospital and Health Service, the Royal Brisbane and Women's Hospital and The University of Queensland.Trial registrationclinicaltrials.govNCT01304914.
A post-collision slab-breakoff model for the orgin of the Middle Eocene magmatic rocks of the Armutlu–Almacık belt, NW Turkey and its regional implications
Authors: Gülmez Fatma , Genç Ş. Can , Keskİn Mehmet , Tüysüz Okan 
Published: November 2012

Abstract

Middle Eocene magmatic rocks (MEMR) (49.3±2 to 38.1±1.9 Ma) formed an east–west trending belt after continental collision and rest unconformably on pre-Middle Eocene units as a common cover. The origin and tectonic setting of MEMR are controversial as both arc and post-collisional settings are proposed. We present new geological and petrological data from the western part of the belt, between the Armutlu Peninsula and the Almacık Mountains. The MEMR are represented by basic to intermediate volcanic rocks, dykes and coeval granites. The lavas exhibit a continuous trend from basalt to dacite. The MEMR as a whole display low- to medium-K subalkaline (to rarely mildly alkaline) affinities and a calc-alkaline trend. On N-type Mid Ocean Ridge Basalt-normalized spidergrams these rocks display relative enrichment in large ion lithophile elements, slight enrichment in light rare earth elements, but depletion in Ta and Nb. Geochemical data and Sr, Nd, Pb and δ
18
O isotope compositions, coupled with εNd
(T)
values, reveal that the MEMR magma was of hybrid type, with both depleted sub-continental lithospheric mantle and crustal components. We conclude that the MEMR was produced in a post-collisional setting, and we favour a slab-breakoff mechanism to explain this as it is consistent with the known Middle Eocene tectonic evolution of northwestern Turkey.
PNUTS Functions as a Proto-Oncogene by Sequestering PTEN
Authors: Kavela Sridhar , Shinde Swapnil R. , Ratheesh Raman , Viswakalyan Kotapalli , Bashyam Murali D. , Gowrishankar Swarnalata , Vamsy Mohana , Pattnaik Sujit , Rao Subramanyeshwar , Sastry Regulagadda A. , Srinivasulu Mukta , Chen Junjie , Maddika Subbareddy 
Published: November 2012

Abstract
PTEN is a well-defined tumor suppressor gene that antagonizes the PI3K/Akt pathway to regulate a multitude of cellular processes, such as survival, growth, motility, invasiveness, and angiogenesis. While the functions of PTEN have been studied extensively, the regulation of its activity during normal and disease conditions still remains incompletely understood. In this study, we identified the protein phosphatase-1 nuclear targeting subunit PNUTS (PPP1R10) as a PTEN-associated protein. PNUTS directly interacted with the lipid-binding domain (C2 domain) of PTEN and sequestered it in the nucleus. Depletion of PNUTS leads to increased apoptosis and reduced cellular proliferation in a PTEN-dependent manner. PNUTS expression was elevated in certain cancers compared with matched normal tissues. Collectively, our studies reveal PNUTS as a novel PTEN regulator and a likely oncogene. Cancer Res; 73(1); 205–14. ©2012 AACR.
SpliceArray Profiling of Breast Cancer Reveals a Novel Variant of NCOR2/SMRT That Is Associated with Tamoxifen Resistance and Control of ERα Transcriptional Activity
Authors: Zhang Luduo , Gong Chun , Lau Samantha L.Y. , Yang Nan , Wong Oscar G.W. , Cheung Annie N.Y. , Tsang Janice W.H. , Chan Kelvin Y.K. , Khoo Ui-Soon 
Published: November 2012

Abstract
Gene expression profiling aimed at classifying and prognosing breast cancer has yielded signatures with little, if any, concordance. However, expression arrays used in these studies do not discriminate alternate RNA splice isoforms that vary widely in cancer and may resolve this problem. In this study, we profiled splice isoforms in a panel of tamoxifen-sensitive and -resistant cell lines, defining a novel variant (BQ323636.1) of the nuclear receptor corepressor 2 (NCOR2) that was associated with tamoxifen resistance. Overexpression of this variant in a tamoxifen-sensitive cell line induced its resistance to tamoxifen. We confirmed our initial findings from cell lines in 77 breast tumors from a Chinese cohort, where BQ323636.1 expression was higher in tamoxifen-resistant patients than tamoxifen-sensitive patients. For patients who were estrogen receptor (ER)-positive and had received tamoxifen treatment, higher BQ323636.1 expression level correlated with distant metastasis. High expression level of BQ323636.1 was found to be associated with poorer overall and disease-free survival for patients who had received tamoxifen treatment. Notably, higher BQ323636.1 versus NCOR2 wild-type ratio was also associated with negative ER and progesterone receptor (PR) status, and triple-negative status (ER−/PR−/HER2− receptor status). Mechanistic investigations showed that under conditions of tamoxifen exposure, BQ323636.1 suppressed the transcriptional activity of ERα, exhibiting promoter-regulating functions. Our findings highlight a novel splice variant of the ERα corepressor NCOR2 as a candidate biomarker in breast cancer that not only predicts tamoxifen response but may be targeted to overcome tamoxifen resistance. Cancer Res; 73(1); 246–55. ©2012 AACR.
Identification of an Aurora Kinase Inhibitor Specific for the Aurora B Isoform
Authors: Xie Hua , Lee Mee-Hyun , Zhu Feng , Reddy Kanamata , Peng Cong , Li Yan , Lim Do Young , Joon Kim Dong , Li Xiang , Kang Soouk , Li Haitao , Ma Weiya , Lubet Ronald A. , Ding Jian , Bode Ann M. , Dong Zigang 
Published: November 2012

Abstract
Aurora kinases play an important role in chromosome alignment, segregation, and cytokinesis during mitosis. In the present study, we used a ligand docking method to explore the novel scaffold of potential Aurora B inhibitors. One thousand compounds from our in-house compound library were screened against the Aurora B structure and one compound, (E)-3-((E)-4-(benzo[d][1,3]dioxol-5-yl)-2-oxobut-3-en-1-ylidene)indolin-2-one (designated herein as HOI-07) was selected for further study. HOI-07 potently inhibited in vitro Aurora B kinase activity in a dose-dependent manner, without obvious inhibition of another 49 kinases, including Aurora A. This compound suppressed Aurora B kinase activity in lung cancer cells, evidenced by the inhibition of the phosphorylation of histone H3 on Ser10 in a dose- and time-dependent manner. This inhibition resulted in apoptosis induction, G2–M arrest, polyploidy cells, and attenuation of cancer cell anchorage-independent growth. Moreover, knocking down the expression of Aurora B effectively reduced the sensitivity of cancer cells to HOI-07. Results of an in vivo xenograft mouse study showed that HOI-07 treatment effectively suppressed the growth of A549 xenografts, without affecting the body weight of mice. The expression of phospho-histone H3, phospho-Aurora B, and Ki-67 was also suppressed in the HOI-07 treatment group. Taken together, we identified HOI-07 as a specific Aurora B inhibitor, which deserves further investigation. Cancer Res; 73(2); 716–24. ©2012 AACR.
Production of Gastrointestinal Tumors in Mice by Modulating Latent TGF-β1 Activation
Authors: Shibahara Kotaro , Ota Mitsuhiko , Horiguchi Masahito , Yoshinaga Keiji , Melamed Jonathan , Rifkin Daniel B. 
Published: November 2012

Abstract
TGF-β and its signaling pathways are important mediators in the suppression of cancers of the gastrointestinal tract. TGF-β is released from cells in a latent complex consisting of TGF-β, the TGF-β propeptide [latency associated protein (LAP)], and a latent TGF-β binding protein (LTBP). We previously generated mice in which the LTBP-binding cysteine residues in LAP TGF-β1 were mutated to serine precluding covalent interactions with LTBP. These Tgfb1C33S/C33S mice develop multiorgan inflammation and tumors consistent with reduced TGF-β1 activity. To test whether further reduction in active TGF-β levels would yield additional tumors and a phenotype more similar to Tgfb1−/− mice, we generated mice that express TGF-β1C33S and are deficient in either integrin β8 or TSP-1, known activators of latent TGF-β1. In addition, we generated mice that have one mutant allele and one null allele at the Tgfb1 locus, reasoning that these mice should synthesize half the total amount of TGF-β1 as Tgfb1C33S/C33S mice, and the amount of active TGF-β1 would be correspondingly decreased compared with Tgfb1C33S/C33S mice. These compound-mutant mice displayed more severe inflammation and higher tumor numbers than the parental Tgfb1C33S/C33S animals. The level of active TGF-β1 in compound mutant mice seemed to be decreased compared with Tgfb1C33S/C33S mice as determined from analyses of surrogate markers of active TGF-β, such as P-Smad2, C-Myc, KI-67, and markers of cell-cycle traverse. We conclude that these mutant mice provide a useful system for modulating TGF-β levels in a manner that determines tumor number and inflammation within the gastrointestinal tract. Cancer Res; 73(1); 459–68. ©2012 AACR.
Synergistic Adaptations to Exercise in the Systemic and Coronary Circulations That Underlie the Warm-Up Angina Phenomenon
Authors: Lockie Timothy P.E. , Rolandi M. Cristina , Guilcher Antoine , Perera Divaka , De Silva Kalpa , Williams Rupert , Asrress Kaleab N. , Patel Kiran , Plein Sven , Chowienczyk Phil , Siebes Maria , Redwood Simon R. , Marber Michael S. 
Published: November 2012

Background—
The mechanisms of reduced angina on second exertion in patients with coronary arterial disease, also known as the warm-up angina phenomenon, are poorly understood. Adaptations within the coronary and systemic circulations have been suggested but never demonstrated in vivo. In this study we measured central and coronary hemodynamics during serial exercise.

Methods and Results—

Sixteen patients (15 male, 61±4.3 years) with a positive exercise ECG and exertional angina completed the protocol. During cardiac catheterization via radial access, they performed 2 consecutive exertions (Ex1, Ex2) using a supine cycle ergometer. Throughout exertions, distal coronary pressure and flow velocity were recorded in the culprit vessel using a dual sensor wire while central aortic pressure was recorded using a second wire. Patients achieved a similar workload in Ex2 but with less ischemia than in Ex1 (
P
<0.01). A 33% decline in aortic pressure augmentation in Ex2 (
P
<0.0001) coincided with a reduction in tension time index, a major determinant of left ventricular afterload (
P
<0.001). Coronary stenosis resistance was unchanged. A sustained reduction in coronary microvascular resistance resulted in augmented coronary flow velocity on second exertion (both
P
<0.001). These changes were accompanied by a 21% increase in the energy of the early diastolic coronary backward-traveling expansion, or suction, wave on second exercise (
P
<0.05), indicating improved microvascular conductance and enhanced left ventricular relaxation.

Conclusions—
On repeat exercise in patients with effort angina, synergistic changes in the systemic and coronary circulations combine to improve vascular–ventricular coupling and enhance myocardial perfusion, thereby potentially contributing to the warm-up angina phenomenon.
Institutional contexts contribute to the low priority given to developing self-care independence in a rehabilitation ward: a qualitative study
Authors: Chang Ling-Hui , Wang Jye 
Published: November 2012

Objectives: To examine the institutional contexts that contribute to the low priority given to the development of self-care independence in a rehabilitation ward. Design: Research was guided by ethnographic principles of Martyn Hammersley and Paul Atkinson (2007). Individual in-depth interviews were completed. Participant observation was done daily during the rehabilitation stay of the patients. Patients: Six men and three women with neurological impairments and their caregivers. Results: Patients’ daily routines on a rehabilitation ward in Taiwan are described. Four prominent themes emerged from the data: (1) the attitudes of patients, caregivers, and staff facilitated extended rehabilitation stays within the first year after disability, (2) attending therapy sessions was the most important activity, (3) pragmatic considerations, such as ‘faster and easier’, outweighed the value of developing self-care independence, and (4) strategic organization of daily routines to keep therapy the priority was critical for daily activity. Conclusion: Multiple institutional factors jeopardize the development of self-care independence in a rehabilitation ward. The factors include the primacy of biomedical-oriented rehabilitation ideology, insurance reimbursement policies, and cultural values associated with family caregiving. They legitimize the low priority given to developing self-care independence. Therapists need to include a critical review of daily routines (what and how activities are carried out inside and outside of therapy clinics) as part of therapy regime to identify opportunities and institutional constraints to the development of self-care independence.
Long-term effects of new progressive group balance training for elderly people with increased risk of falling – a randomized controlled trial
Authors: Halvarsson Alexandra , Franzén Erika , Farén Elin , Olsson Elisabeth , Oddsson Lars , Ståhle Agneta 
Published: November 2012

Objective: To evaluate the long-term effects of a progressive and specific balance group-based program in healthy elderly individuals with increased risk of falling. Design: Follow-up of a randomized controlled trial at nine and 15 months on a population that has previously been described at three months. Setting: The study was conducted in Stockholm, Sweden. Subjects: 59 community-dwelling elderly (age 67–93 years), recruited by advertisement, were randomly allocated to training or to serve as controls. Intervention: Group balance training three times per week during 12 weeks with a 15 month follow-up time. Main measures: Participants were assessed at baseline, three, nine, and 15 months thereafter for gait function (preferred and fast walking), rapid step execution (single and dual task), fear of falling, and likelihood of depression. Results: Fast gait speed ( p = 0.004), dual task step execution ( p = 0.006) and fear of falling ( p = 0.001) were still improved in the training group at nine months follow-up. Only self-perceived fear of falling remained significantly improved ( p = 0.012) at 15 months follow-up. Although fast gait speed had decreased to baseline level in the training group (1.49 m/s) it remained significantly higher than in the control group (1.37 m/s) at the end of the study, a difference between the groups that was not seen at baseline. Conclusion: This training program provided important positive short and long-term benefits to gait, balance function, and fear of falling.
Does social support impact depression in caregivers of adults ageing with spinal cord injuries?
Authors: Rodakowski Juleen , Skidmore Elizabeth R , Rogers Joan C , Schulz Richard 
Published: November 2012

Objective: The objective of this study was to examine the role of social support in predicting depression in caregivers of adults aging with spinal cord injuries. Design: Cross-sectional secondary data analyses were conducted for this study. Setting: Participants were recruited from multiple community locations in Pittsburgh, PA and Miami, FL. Subjects: Community-dwelling caregivers of aging adults with spinal cord injuries ( N = 173) were interviewed as part of a multisite randomized controlled trial. Main measures: The Center for Epidemiological Studies Depression Scale measured caregiver depression symptom levels. A hierarchical multiple regression analysis examined the effect of social support (social integration, received social support, and negative social interactions) on depressive symptom levels for the caregivers of adults aging with spinal cord injuries, controlling for demographic characteristics, and caregiving characteristics. Results: Caregivers were, on average, 53 years old (SD = 15) and care-recipients were 55 years old (SD = 13). Average Center for Epidemiological Studies Depression Scale scores indicated that 69 (40%) of caregivers had significant depressive symptoms (mean 8.69, SD = 5.5). Negative social interactions ([Formula: see text] = 0.27, P< 0.01) and social integration ([Formula: see text] = −0.25, P< 0.01) were significant independent predictors of depressive symptom levels in caregivers of adults aging with spinal cord injuries. Conclusions: Findings demonstrate that negative social interactions and social integration are associated with the burden in caregivers of adults aging with spinal cord injuries. Negative social interactions and social integration should be investigated in assessments and interventions intended to target caregiver depressive symptom levels.
A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD)
Authors: Oehen Peter , Traber Rafael , Widmer Verena , Schnyder Ulrich 
Published: November 2012

Psychiatrists and psychotherapists in the US (1970s to 1985) and Switzerland (1988–1993) used MDMA legally as a prescription drug, to enhance the effectiveness of psychotherapy. Early reports suggest that it is useful in treating trauma-related disorders. Recently, the first completed pilot study of MDMA-assisted psychotherapy for PTSD yielded encouraging results. Designed to test the safety and efficacy of MDMA-assisted psychotherapy in patients with treatment-resistant PTSD; our randomized, double-blind, active-placebo controlled trial enrolled 12 patients for treatment with either low-dose (25 mg, plus 12.5 mg supplemental dose) or full-dose MDMA (125 mg, plus 62.5 mg supplemental dose). MDMA was administered during three experimental sessions, interspersed with weekly non-drug-based psychotherapy sessions. Outcome measures used were the Clinician-Administered PTSD Scale (CAPS) and the Posttraumatic Diagnostic Scale (PDS). Patients were assessed at baseline, three weeks after the second and third MDMA session (end of treatment), and at the 2-month and 1-year follow-ups. We found that MDMA-assisted psychotherapy can be safely administered in a clinical setting. No drug-related serious adverse events occurred. We did not see statistically significant reductions in CAPS scores ( p = 0.066), although there was clinically and statistically significant self-reported (PDS) improvement ( p = 0.014). CAPS scores improved further at the 1-year follow-up. In addition, three MDMA sessions were more effective than two ( p = 0.016).