bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression in local stroma reflects breast tumor states and predicts patient outcome
Authors: Bainer Russell , Frankenberger Casey , Rabe Daniel , An Gary , Gilad Yoav , Rosner Marsha Rich 
Published: December 2016

AbstractThe surrounding microenvironment has been implicated in the progression of breast tumors to metastasis. However, the degree to which metastatic breast tumors locally reprogram stromal cells as they disrupt tissue boundaries is not well understood. We used species-specific RNA sequencing in a mouse xenograft model to determine how the metastasis suppressor RKIP influences transcription in a panel of paired tumor and stroma tissues. We find that gene expression in metastatic breast tumors is pervasively correlated with gene expression in local stroma of both mouse xenografts and human patients. Changes in stromal gene expression elicited by tumors better predicts subtype and patient survival than tumor gene expression, and genes with coordinated expression in both tissues predict metastasis-free survival. These observations support the use of stroma-based strategies for the diagnosis and prognosis of breast cancer.
Incomplete DRB4-dependence of the DCL4-mediated antiviral defense
Authors: Zhang Xiaofeng , Zhang Xiuchun , Wu Kunxin , Liu Zhixin , Li Dawei , Qu Feng 
Published: December 2016

AbstractThe double-stranded RNA-binding protein DRB4 of Arabidopsis was shown previously to contribute to the DICER-LIKE 4 (DCL4)-mediated biogenesis of viral small interfering RNAs (vsiRNAs) of 21 nucleotides (nt) in size. However, it is unclear whether all 21-nt vsiRNAs are dependent on this DRB4-DCL4 partnership. To resolve this question, we generated dcl2drb4 and dcl4drb4 double knockout mutants, and subjected them to infections with CPB-CC-PDS, a turnip crinkle virus mutant capable of inducing silencing of the PHYTOENE DESATURASE gene. The dcl2drb4 double knockouts caused a far smaller loss of antiviral silencing than dcl2dcl4. In addition, although both drb4 and dcl4 single mutants permitted a consistent (but small) increase in viral RNA levels, the drb4 mutant correlated with a less pronounced reduction of 21-nt vsiRNAs. Therefore, a substantial subset of DCL4 antiviral activity is DRB4-independent, and may involve other DRB proteins that compensate for loss of DRB4.
Pharmacological and genetic reappraisals of protease and oxidative stress pathways in a mouse model of obstructive lung diseases
Authors: Shuto Tsuyoshi , Kamei Shunsuke , Nohara Hirofumi , Fujikawa Haruka , Tasaki Yukihiro , Sugahara Takuya , Ono Tomomi , Matsumoto Chizuru , Sakaguchi Yuki , Maruta Kasumi , Nakashima Ryunosuke , Kawakami Taisei , Suico Mary Ann , Kondo Yoshitaka , Ishigami Akihito , Takeo Toru , Tanaka Ken-ichiro , Watanabe Hiroshi , Nakagata Naomi , Uchimura Kohei , Kitamura Kenichiro , Li Jian-Dong , Kai Hirofumi 
Published: December 2016

AbstractProtease-antiprotease imbalance and oxidative stress are considered to be major pathophysiological hallmarks of severe obstructive lung diseases including chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), but limited information is available on their direct roles in the regulation of pulmonary phenotypes. Here, we utilized βENaC-transgenic (Tg) mice, the previously established mouse model of severe obstructive lung diseases, to produce lower-mortality but pathophysiologically highly useful mouse model by backcrossing the original line with C57/BL6J mice. C57/BL6J-βENaC-Tg mice showed higher survival rates and key pulmonary abnormalities of COPD/CF, including mucous hypersecretion, inflammatory and emphysematous phenotypes and pulmonary dysfunction. DNA microarray analysis confirmed that protease- and oxidative stress-dependent pathways are activated in the lung tissue of C57/BL6J-βENaC-Tg mice. Treatments of C57/BL6J-βENaC-Tg mice with a serine protease inhibitor ONO-3403, a derivative of camostat methylate (CM), but not CM, and with an anti-oxidant N-acetylcystein significantly improved pulmonary emphysema and dysfunction. Moreover, depletion of a murine endogenous antioxidant vitamin C (VC), by genetic disruption of VC-synthesizing enzyme SMP30 in C57/BL6J-βENaC-Tg mice, exaggerated pulmonary phenotypes. Thus, these assessments clarified that protease-antiprotease imbalance and oxidative stress are critical pathways that exacerbate the pulmonary phenotypes of C57/BL6J-βENaC-Tg mice, consistent with the characteristics of human COPD/CF.
IL-34 is associated with the presence and severity of renal dysfunction and coronary artery disease in patients with heart failure
Authors: Fan Qin , Yan Xiaoxiang , Zhang Hang , Lu Lin , Zhang Qi , Wang Fang , Xi Rui , Hu Jian , Chen Qiujing , Niu Wenquan , Shen Weifeng , Zhang Ruiyan , Tao Rong 
Published: December 2016

AbstractPro-inflammatory mediators are identified in patients with heart failure (HF), some of which may be used as biomarkers with diagnostic or prognostic value. As an additional ligand of Colony Stimulating Factor-1 Receptor (CSF-1R), interleukin-34 (IL-34) has been identified as a pro-inflammatory cytokine participating in chronic heart failure (CHF). However, the potential impact of IL-34 in CHF complications remains unknown. In order to determine the clinical significance of serum IL-34 in CHF patients, especially those with kidney dysfunction and coronary artery disease (CAD) comorbid conditions, serum IL-34 was measured in 510 consecutive patients with CHF in a cross-sectional study. The present study demonstrated that higher serum IL-34 levels were associated with poorer renal function and more severe anemia in patients with CHF. After adjusting for age, gender, conventional risk factors, and other significant covariates, IL-34 positively correlated with the presence and severity of renal dysfunction (as measured by eGFR and cystatin C) on multivariable linear and logistic regression analysis. IL-34 was also demonstrated to be an independent risk factor for CAD among HF patients. In conclusion, elevated serum IL-34 levels were demonstrated to be independently associated with renal insufficiency and CAD in patients with CHF, regardless of the systolic function.
Estrogen-induced SDF-1α production promotes the progression of ER-negative breast cancer via the accumulation of MDSCs in the tumor microenvironment
Authors: Ouyang Liquan , Chang Weilong , Fang Bin , Qin Jieting , Qu Xincai , Cheng Fanjun 
Published: December 2016

AbstractEstrogen plays a role in the processes of tumorigenesis, metastasis, and drug resistance in estrogen receptor (ER)-positive breast cancer (BC). Whether estrogen contributes to ER-negative BC is unclear. Here, we aimed to investigate whether estrogen could stimulate the secretion of stromal-derived factor-1 (SDF-1α) by cancer-associated fibroblasts (CAFs) to promote the progression of ER-negative BC. We transplanted ER-negative BC cells into ovariectomized mice, which was followed by continuous injection of estrogen, and found that estrogen promoted the tumorigenesis of BC. Furthermore, High levels of SDF-1α and tumor-infiltrating myeloid-derived suppressor cells (MDSCs) were detected in the estrogen treatment group. Estrogen stimulates secretion of SDF-1α by CAFs extracted from BC patients. Recombinant SDF-1α could recruit MDSCs isolated from bone marrow cells of mice. In addition, the co-culture of CAFs and MDSCs demonstrated that the recruitment of MDSCs was increased when CAFs were exposed to estrogen. Using AMD3100 to block the SDF-1α/CXCR4 axis or gemcitabine to delete MDSCs, we observed that both of these agents could neutralize the effect of estrogen on tumorigenesis. Together, these results suggest that estrogen may promote the progression of ER-negative BC by stimulating CAFs to secrete SDF-1α, which can recruit MDSCs to the tumor microenvironment to exert tumor-promoting effects.
The neural representation of competence traits: An fMRI study
Authors: Ma Ning , Wang Simin , Yang Quansen , Feng Tingyong , Van Overwalle Frank 
Published: December 2016

AbstractPrevious neuroimaging studies have revealed that a trait code is mainly represented in the ventral medial prefrontal cortex (vmPFC). However, those studies only investigated the neural code of warmth traits. According to the ‘Big Two’ model of impression formation, competence traits are the other major dimension when we judge others. The current study explored the neural representation of competence traits by using an fMRI repetition suppression paradigm, which is a rapid reduction of neuronal responses upon repeated presentation of the same implied trait. Participants had to infer an agent’s trait from brief behavioral descriptions that implied a competence trait. In each trial, the critical target sentence was preceded by a prime sentence that implied the same or opposite competence-related trait, or no trait. The results revealed robust repetition suppression from prime to target in the vmPFC and precuneus during trait conditions. Critically, the suppression effect was much stronger after being primed with a similar and opposite competence trait compared with a trait-irrelevant prime. This suppression pattern was found nowhere else in the brain. Consistent with previous fMRI studies, we suggest that the neural code of competence traits is represented in these two brain areas with different levels of abstraction.
Intensive Language Action Therapy in Chronic Aphasia: A Randomized Clinical Trial Examining Guidance by Constraint
Authors: Kurland Jacquie , Stanek, Edward J. , Stokes Polly , Li Minming , Andrianopoulos Mary 
Published: December 2016

Purpose
Intensive language action therapy (ILAT) can be effective in overcoming learned nonuse in chronic aphasia. It is suggested that all three guiding principles (constraint, communication embedding, massed practice) are essential to ILAT's success. We examined whether one of these, guidance by constraint, is critical.

Method
Twenty-four participants with aphasia (PWAs) were assigned to ILAT or a modified version of promoting aphasic communicative effectiveness (PACE) in a randomized block, single-blind, parallel-group treatment study. Blocking was by severity (mild/moderate, moderate to severe, severe). Both groups received intensive treatment in the context of therapeutic language action games. Whereas the ILAT group was guided toward spoken responses, the PACE group could choose any response modality.

Results
All participants, whether assigned to ILAT or PACE groups, improved on the primary outcome measure, picture naming. There was a Severity × Treatment interaction, with the largest effects estimated for PWAs with mild/moderate and moderate to severe aphasia. Regardless of severity, the ILAT group outperformed the PACE group on untrained pictures, suggesting some benefit of ILAT to generalization. However, this difference was not statistically significant.

Conclusion
Although the groups differed in subtle ways, including better generalization to untrained pictures for ILAT, the study was inconclusive on the influence of guidance by constraint.
Mere experience of low subjective socioeconomic status stimulates appetite and food intake
Authors: Cheon Bobby K. , Hong Ying-Yi 
Published: December 2016

Significance
Lower socioeconomic status (SES) has been linked to increased risk of obesity. This relationship is generally assumed to be a product of low financial resources or greater stress associated with low SES that promotes unhealthy diets and lifestyles. We demonstrate here that the mere subjective experience of being lower in SES relative to others is alone sufficient to causally elicit behaviors that may risk obesity (e.g., preference, selection, and intake of greater calories), independent of actual economic deprivation or stress from being subordinated. Among social species, the physiological/psychological systems regulating hunger may have been adapted to be sensitive to perceived deprivation of critical social, material, and symbolic resources that underlie social class in addition to caloric deprivation.
Structural and mutational analysis of the nonribosomal peptide synthetase heterocyclization domain provides insight into catalysis
Authors: Bloudoff Kristjan , Fage Christopher D. , Marahiel Mohamed A. , Schmeing T. Martin 
Published: December 2016

Significance
Nonribosomal peptide synthetases produce peptides with wide varieties of therapeutic and biological activities. Monomer substrates are typically linked by a condensation domain. However, in many modules, a heterocyclization (Cy) domain takes its place and performs both condensation and cyclodehydration of a cysteine, serine, or threonine to form a five-membered ring in the peptide backbone. Although studied for decades, the mechanisms of condensation and cyclodehydration by Cy domains were previously unknown. The crystal structure of a Cy domain, and accompanying mutagenic and bioinformatics analyses, uncover the importance of an aspartate and a threonine for the cyclodehydration reaction. This study provides insight into the catalysis of condensation by the Cy domain and enables the proposal of a reaction mechanism for cyclodehydration.
Impact of Abuse on Adjustment and Chronic Pain Disability
Authors: Mehta Swati , Rice Danielle , Chan Alan , Shapiro Allan P. , Sequeira Keith , Teasell Robert W. 
Published: December 2016

Introduction/Aim:
Sexual abuse, state and trait psychosocial factors, pain intensity, and pain-related disability have been shown to be correlated among individuals with chronic pain. However, the interacting relationships among these factors are poorly understood. The current study aims to test model which examines the effect of abuse, state and trait psychosocial factors, and pain intensity on pain-related disability among individuals with chronic pain.

Methods:
In total, 229 participants diagnosed with chronic pain were recruited from a specialist chronic pain hospital in London, Ontario. Participants completed self-report measures related to sexual abuse history, pain intensity, personality (anxiety sensitivity, experiential avoidance, perfectionism), and adjustment (depression, anxiety, disability, maladaptive worrying). A path analysis was used to test the relationship among these variables.

Results:
The model provided a close fit to the data (χ2
21=17.02; P=0.71; root-mean-square error of approximation=0.00; normal fit index=0.97; comparative fit index=1.0). The model demonstrates the direct and indirect effects of childhood sexual abuse on state and trait psychosocial factors among individuals with chronic pain. Pain anxiety, maladaptive worrying, and pain intensity were the main determinants of pain-related disability.

Discussion/Conclusions:
The current model has important implications in understanding the interplay of factors involved in adjustment of individuals with chronic pain. Sexual abuse did not have a direct effect on pain-related disability. However, indirect effects through other psychosocial factors were demonstrated.
Duloxetine as an Analgesic Reduces Opioid Consumption After Spine Surgery
Authors: Bedin Antonio , Caldart Bedin Rafael A. , Vieira Joaquim E. , Ashmawi Hazem A. 
Published: December 2016

Objectives:
Multimodal analgesia is widely advocated for the control of perioperative pain in an effort to reduce the use of opioid. Duloxetine is a selective inhibitor of serotonin and norepinephrine reuptake with efficacy for chronic pain conditions. The primary objective of this study was to evaluate the efficacy of two 60 mg oral doses of duloxetine in terms of fentanyl consumption during the postoperative period in patients undergoing elective spine surgery.

Materials and Methods:
This study was prospective, double-blind, randomized, and placebo controlled. Patients received either 60 mg duloxetine or an identical placebo 1 hour before surgery and again the following morning. The study participants were allocated into 2 groups: Group C (control) participants received the placebo and Group D (duloxetine) participants received 60 mg duloxetine. The total consumption of fentanyl 48 hours after surgery was measured. Secondary end points were pain scores and the presence or absence of adverse effects, such as headache, nausea, vomiting, itching, dizziness, and drowsiness.

Results:
Demographic characteristics did not differ between groups. There was a significant difference in fentanyl consumption in the first 24 hours between Groups C and D (mean difference, 223.11±39.32 µg; P<0.001). Fentanyl consumption also differed between Groups C and D after 48 hours (mean difference, 179.35±32.55 µg; P<0.000). The pain scores over 48 hours did not significantly differ between groups. The incidence of side-effects was similar in both groups.

Discussion:
Duloxetine was effective as an adjunct for postoperative analgesia and reduced opioid consumption.
Correlates of interorganizational relationship strategies among critical access hospitals
Authors: Hearld Larry R. , Carroll Nathaniel W. , Hearld Kristine R. , Opoku-Agyeman William 
Published: December 2016

Background:
Interorganizational relationships (IORs) between hospitals and other health care providers have many potential benefits for critical access hospitals (CAHs) that operate in resource-constrained environments. Given the potential benefits of IORs, especially for CAHs, it is important to identify the conditions that support or hinder IOR development. However, most research examining IORs isolates individual types of relationships while ignoring the practical reality that many hospitals participate in a portfolio of relationships simultaneously.

Purpose:
The aim of the study was to examine the IOR strategies of CAHs as a function of market and organizational characteristics.

Methodology:
The sample consisted of CAHs operating in the United States between the years 2002 and 2012. For each year, hospitals were assigned to one of four mutually exclusive IOR categories: (a) no IOR, (b) vertical IOR only, (c) horizontal IOR only, and (d) both vertical and horizontal IOR. Organizational characteristics were categorized as structural, operational, and financial. Environmental characteristics were categorized as sociodemographic, physical, and health delivery system-related. A multinomial logistic regression model was used to assess the relationship between IOR strategies and organizational and environmental characteristics, with results reported as average marginal effects.

Results:
Approximately 41% of the CAHs were pursuing a combined vertical and horizontal IOR strategy, 20% were pursuing a vertical IOR-only strategy, 18% were pursuing a horizontal IOR-only strategy, and 21% were not engaged in an IOR strategy. Among the organizational characteristics, the type of IOR strategy used by a hospital varied as a function of ownership, total margin, days cash on hand, number of community orientation activities, and census. In contrast, among the environmental characteristics, only the number of community health centers in the community was associated with the type of IOR strategy pursued.

Conclusion:
CAHs’ construction of IOR portfolios may be more dependent on organizational attributes than by environmental conditions.
Clinical assessment of the impact of pelvic pain on women
Authors: Chalmers K. Jane , Catley Mark J. , Evans Susan F. , Moseley G. Lorimer 
Published: December 2016

Abstract
We aimed to develop a questionnaire that assesses the impact of pelvic pain on women, regardless of diagnosis, that has high utility, sound psychometric performance, easy scoring, and high reliability. Two studies, with 3 separate cohorts, were undertaken. Both studies were completed online. Studies included women with self-reported pelvic pain. Women were eligible to participate regardless of whether their pelvic pain was undiagnosed, self-diagnosed, or diagnosed by a clinician. Study 1 used a 3-round “patient-as-expert” Delphi technique. These rounds defined the 10 aspects of life with the self-reported greatest impact on the lives of women with pelvic pain, which formed the questionnaire. Study 2 used Rasch analysis to assess the psychometric properties of the resultant 10-item questionnaire. To assess its reliability, a subgroup completed the questionnaire 3 times over a 3-week period. In study 1, 443 women with pelvic pain participated. The resultant 10-item questionnaire consisted of 8 Likert questions and 2 supplemental, nonscored questions. In study 2, 1203 women with pelvic pain completed the questionnaire. Rasch analysis showed that the questionnaire targeted the pelvic pain population well, had appropriate Likert categories, constituted a unidimensional scale, and showed internal consistency. Twenty-seven women with pelvic pain completed the reliability trial. Test–retest reliability was high (intraclass correlation coefficient 0.91, P < 0.001). The resultant Pelvic Pain Impact Questionnaire assesses the life impact of pelvic pain. It uses patient-generated language, is easily administered and scored, has very strong psychometric properties, and it is suitable for research and clinical settings across primary, secondary, and tertiary care.
Bifunctional peptide-based opioid agonist/nociceptin antagonist ligand for dual treatment of nociceptive and neuropathic pain
Authors: Lagard Camille , Chevillard Lucie , Guillemyn Karel , Risède Patricia , Laplanche Jean-Louis , Spetea Mariana , Ballet Steven , Mégarbane Bruno 
Published: December 2016

Abstract
Drugs able to treat both nociceptive and neuropathic pain effectively without major side effects are lacking. We developed a bifunctional peptide-based hybrid (KGNOP1) that structurally combines a mu-opioid receptor agonist (KGOP1) with antinociceptive activity and a weak nociceptin receptor antagonist (KGNOP3) with anti-neuropathic pain activity. We investigated KGNOP1-related behavioral effects after intravenous administration in rats by assessing thermal nociception, cold hyperalgesia in a model of neuropathic pain induced by chronic constriction injury of the sciatic nerve, and plethysmography parameters including inspiratory time (TI) and minute ventilation (VM) in comparison to the well-known opioid analgesics, tramadol and morphine. Time-course and dose-dependent effects were investigated for all behavioral parameters to determine the effective doses 50% (ED50). Pain-related effects on cold hyperalgesia were markedly increased by KGNOP1 as compared to KGNOP3 and tramadol (ED50: 0.0004, 0.32, and 12.1 μmol/kg, respectively), whereas effects on thermal nociception were significantly higher with KGNOP1 as compared to morphine (ED50: 0.41 and 14.7 μmol/kg, respectively). KGNOP1 and KGOP1 produced a larger increase in TI and deleterious decrease in VM in comparison to morphine and tramadol (ED50(TI): 0.63, 0.52, 12.2, and 50.9 μmol/kg; ED50(VM): 0.57, 0.66, 10.6, and 50.0 μmol/kg, respectively). Interestingly, the calculated ratios of anti-neuropathic pain/antinociceptive to respiratory effects revealed that KGNOP1 was safer than tramadol (ED50 ratio: 5.44 × 10−3 vs 0.24) and morphine (ED50 ratio: 0.72 vs 1.39). We conclude that KGNOP1 is able to treat both experimental neuropathic and nociceptive pain, more efficiently and safely than tramadol and morphine, respectively, and thus should be a candidate for future clinical developments.