bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of the Circadian Clock Gene Bmal1 Increases Sensitivity to Oxaliplatin in Colorectal Cancer
Authors: Zeng Zhao-lei , Luo Hui-yan , Yang Jing , Wu Wen-jing , Chen Dong-liang , Huang Peng , Xu Rui-hua 
Published: November 2013

Abstract
Purpose: The circadian clock gene Bmal1 is involved in cancer cell proliferation and DNA damage sensitivity. The aim of this study was to explore the effect of Bmal1 on oxaliplatin sensitivity and to determine its clinical significance in colorectal cancer.
Experimental Design: Three colorectal cancer cell lines, HCT116, THC8307 and HT29, were used. The Bmal1-mediated control of colorectal cancer cell proliferation was tested in vitro and in vivo. MTT and colony formation assays were performed to determine the sensitivity of colorectal cancer cells to oxaliplatin. Flow cytometry was used to examine changes in the cell-cycle distribution and apoptosis rate. Proteins expressed downstream of Bmal1 upon its overexpression were determined by Western blotting. Immunohistochemistry was used to analyze Bmal1 expression in 82 archived colorectal cancer tumors from patients treated with oxaliplatin-based regimens.
Results: Bmal1 overexpression inhibited colorectal cancer cell proliferation and increased colorectal cancer sensitivity to oxaliplatin in three colorectal cancer cell lines and HCT116 cells model in vivo. Furthermore, the overall survival of patients with colorectal cancer with high Bmal1 levels in their primary tumors was significantly longer than that of patients with low Bmal1 levels (27 vs. 19 months; P = 0.043). The progression-free survival of patients with high Bmal1 expression was also significantly longer than that of patients with low Bmal1 expression (11 vs. 5 months; P = 0.015). Mechanistically, the effect of Bmal1 was associated with its ability to regulate G2–M arrest by activating the ATM pathway.
Conclusion: Bmal1 shows the potential as a novel prognostic biomarker and may represent a new therapeutic target in colorectal cancer. Clin Cancer Res; 20(4); 1042–52. ©2013 AACR.
SC-60, a Dimer-Based Sorafenib Derivative, Shows a Better Anti–Hepatocellular Carcinoma Effect than Sorafenib in a Preclinical Hepatocellular Carcinoma Model
Authors: Tai Wei-Tien , Shiau Chung-Wai , Li Yong-Shi , Chen Yao-Li , Chu Pei-Yi , Huang Jui-Wen , Hsu Cheng-Yi , Hsu Yi-Chieh , Chen Pei-Jer , Chen Kuen-Feng 
Published: November 2013

Abstract
Sorafenib is the first approved targeted therapeutic reagent for hepatocellular carcinoma. Here, we report that SC-60, a dimer-based sorafenib derivative, overcomes the resistance of sorafenib and shows a better anti-hepatocellular carcinoma effect in vitro and in vivo. SC-60 substantially increased SH2 domain-containing phosphatase 1 (SHP-1) phosphatase activity in hepatocellular carcinoma cells and purified SHP-1 proteins, suggesting that SC-60 affects SHP-1 directly. Molecular docking and truncated mutants of SHP-1 further confirmed that SC-60 interferes with the inhibitory N-SH2 domain to relieve the closed catalytic protein tyrosine phosphatase domain of SHP-1. Deletion of N-SH2 domain (dN1) or point mutation (D61A) of SHP-1 abolished the effect of SC-60 on SHP-1, p-STAT3, and apoptosis. Importantly, SC-60 exhibited significant survival benefits compared with sorafenib in a hepatocellular carcinoma orthotopic model via targeting the SHP-1/STAT3–related signaling pathway. In summary, dimer derivative of sorafenib, SC-60, is a SHP-1 agonist and may be a potent reagent for hepatocellular carcinoma–targeted therapy. Mol Cancer Ther; 13(1); 27–36. ©2013 AACR.
Tumor Subtype-Specific Cancer–Testis Antigens as Potential Biomarkers and Immunotherapeutic Targets for Cancers
Authors: Yao Jun , Caballero Otavia L. , Yung W.K. Alfred , Weinstein John N. , Riggins Gregory J. , Strausberg Robert L. , Zhao Qi 
Published: November 2013

Abstract
Cancer–testis (CT) antigens are potential targets for cancer immunotherapy because of their restricted expression in immune-privileged germ cells and various malignancies. Current application of CT-based immunotherapy has been focused on CT expression–rich tumors such as melanoma and lung cancers. In this study, we surveyed CT expression using The Cancer Genome Atlas (TCGA) datasets for ten common cancer types. We show that CT expression is specific and enriched within certain cancer molecular subtypes. For example, HORMAD1, CXorf61, ACTL8, and PRAME are highly enriched in the basal subtype of breast cancer; MAGE and CSAG are most frequently activated in the magnoid subtype of lung adenocarcinoma; and PRAME is highly upregulated in the ccB subtype of clear cell renal cell carcinoma. Analysis of CT gene expression and DNA methylation indicates that some CTs are regulated epigenetically, whereas others are controlled primarily by tissue- and subtype-specific transcription factors. Our results suggest that although for some CT expression is associated with patient outcome, not many are independent prognostic markers. Thus, CTs with shared expression pattern are heterogeneous molecules with distinct activation modes and functional properties in different cancers and cancer subtypes. These data suggest a cancer subtype–orientated application of CT antigen as biomarkers and immunotherapeutic targets. Cancer Immunol Res; 2(4); 371–9. ©2013 AACR.
Effect of Sleep Apnea and Continuous Positive Airway Pressure on Cardiac Structure and Recurrence of Atrial Fibrillation
Authors: Neilan Tomas G. , Farhad Hoshang , Dodson John A. , Shah Ravi V. , Abbasi Siddique A. , Bakker Jessie P. , Michaud Gregory F. , van der Geest Rob , Blankstein Ron , Steigner Michael , John Roy M. , Jerosch‐Herold Michael , Malhotra Atul , Kwong Raymond Y. 
Published: November 2013

Background

Sleep apnea (
SA
) is associated with an increased risk of atrial fibrillation (
AF
). We sought to determine the effect of
SA
on cardiac structure in patients with
AF
, whether therapy for
SA
was associated with beneficial cardiac structural remodelling, and whether beneficial cardiac structural remodelling translated into a reduced risk of recurrence of
AF
after pulmonary venous isolation (
PVI
).

Methods and Results

A consecutive group of 720 patients underwent a cardiac magnetic resonance study before
PVI
. Patients with
SA
(n=142, 20%) were more likely to be male, diabetic, and hypertensive and have an increased pulmonary artery pressure, right ventricular volume, atrial dimensions, and left ventricular mass. Treated
SA
was defined as duration of continuous positive airway pressure therapy of >4 hours per night. Treated
SA
patients (n=71, 50%) were more likely to have paroxysmal
AF
, a lower blood pressure, lower ventricular mass, and smaller left atrium. During a follow‐up of 42 months,
AF
recurred in 245 patients. The cumulative incidence of
AF
recurrence was 51% in patients with
SA
, 30% in patients without
SA
, 68% in patients with untreated
SA
, and 35% in patients with treated
SA
. In a multivariable model, the presence of
SA
(
hazard ratio
2.79,
CI
1.97 to 3.94,
P<
0.0001) and untreated
SA
(
hazard ratio
1.61,
CI
1.35 to 1.92,
P<
0.0001) were highly associated with
AF
recurrence.

Conclusions

Patients with
SA
have an increased blood pressure, pulmonary artery pressure, right ventricular volume, left atrial size, and left ventricular mass. Therapy with
continuous positive airway pressure
is associated with lower blood pressure, atrial size, and ventricular mass, and a lower risk of
AF
recurrence after
PVI
.
Assessing Legal Advocacy to Advance Roma Health in Macedonia, Romania, and Serbia
Authors: Abdikeeva Alphia , Ezer Tamar , Covaci Alina 
Published: November 2013

Abstract
Across Europe, Roma suffer extreme marginalisation, negatively impacting their health. Many cannot access healthcare at all. For others, the health system is a hostile place. At the same time, good legal frameworks are in place to protect health rights, and there is increasing recognition of systemic violations experienced by Roma. Essential to building on this momentum and closing the gap between standards and implementation is Roma ability to conduct legal advocacy. Since 2010, the Open Society Foundations has supported Roma engagement in Macedonia, Romania and Serbia in the following advocacy strategies: i) legal empowerment, ii) documentation and advocacy, iii) media advocacy, and iv) strategic litigation. This article presents a framework developed to evaluate the effectiveness of these efforts and a baseline against which outcomes can be measured in a few years. The evaluation framework provides a qualitative assessment of Roma capacity, accountability for violations, changes in law and practice, and impact on communities. Findings reveal that that presently Roma lack knowledge of their rights and rarely challenge violations. Accountability in healthcare is practically non-existent. However, where legal advocacy has been used, violations decrease, and power dynamics shift. As healthcare becomes more responsive to communities, it also better serves non-Roma citizens.
Epidemiology of Primary Anterior Shoulder Dislocation Requiring Closed Reduction in Ontario, Canada
Authors: Leroux Timothy , Wasserstein David , Veillette Christian , Khoshbin Amir , Henry Patrick , Chahal Jaskarndip , Austin Peter , Mahomed Nizar , Ogilvie-Harris Darrell 
Published: November 2013

Background: There is a lack of high-quality population-based literature describing the epidemiology of primary anterior shoulder dislocation. Purpose: To (1) calculate the incidence density rate (IDR) of primary anterior shoulder dislocation requiring closed reduction (CR; “index event”) in the general population and demographic subgroups, and (2) determine the rate of and risk factors for repeat shoulder CR. Study Design: Cohort study (prognosis); Level of evidence, 2. Methods: All patients who underwent shoulder CR by a physician in Ontario between April 2002 and September 2010 were identified with administrative databases. Exclusion criteria included age <16 and >70 years, posterior dislocation, and prior shoulder dislocation or surgery. Index event IDR was calculated for all populations/subgroups, and IDR comparisons were made. Repeat shoulder CR was sought until September 2012. Risk factors for repeat shoulder CR were identified with a Prentice, Williams, and Peterson proportional hazards model. Results: There were 20,719 persons (median age, 35 years; 74.3% male) who underwent a shoulder CR after a primary anterior shoulder dislocation (23.1/100,000 person-years). The IDR was highest among young males (98.3/100,000 person-years). A total of 3940 (19%) patients underwent repeat shoulder CR after a median of 0.9 years, of which 41.7% were ≤20 years of age. Less than two-thirds of all first repeat shoulder CR events occurred within 2 years; in fact, 95% occurred within 5 years. The risk of repeat shoulder CR was lowest if the primary reduction had been performed by an orthopaedic surgeon (hazard ratio [HR], 0.76; 95% CI: 0.64, 0.90; P = .002) or was associated with a humeral tuberosity fracture (HR, 0.71; CI, 0.53, 0.95; P = .02). Older age (HR, 0.97; CI, 0.97, 0.98; P < .0001) and higher medical comorbidity score (HR, 0.92; CI, 0.87, 0.98; P = .009) were also protective. Risk was highest among males (HR, 1.26; CI, 1.16, 1.36; P < .0001) and patients from low-income neighborhoods (HR, 1.23; CI, 1.13, 1.34; P < .0001). Conclusion: Young male patients have the highest incidence of primary anterior shoulder dislocation requiring CR and the greatest risk of repeat shoulder CR. Patient, provider, and injury factors all influence repeat shoulder CR risk. A comprehensive understanding of the epidemiology of primary anterior shoulder dislocation will aid management decisions and injury prevention initiatives.
Protective effect of vanadyl sulfate on skin injury in streptozotocin-induced diabetic rats
Authors: Tunali S , Yanardag R 
Published: November 2013

The aim of the present study was to investigate the effect of vanadyl sulfate supplementation on the skin tissues of diabetic and control rats. In this study, 6–6.5 months old male Swiss albino rats were used. The animals were randomly divided into the following four groups: group I, control (nondiabetic intact animals); group II, vanadyl sulfate control; group III, streptozotocin (STZ)-diabetic animals and group IV, STZ-diabetic animals given vanadyl sulfate. The animals were made diabetic by intraperitoneal injection of a single dose of 65 mg/kg STZ in 0.01 M citrate buffer (pH = 4.5). From day 1 to day 60, 100 mg/kg vanadyl sulfate was given daily by gavage technique to one of the control and diabetic groups. Body weights and blood glucose levels were estimated on experimental days 0, 1 and 60. On the 60th day, skin tissue samples were taken, glutathione (GSH), lipid peroxidation (LPO), nonenzymatic glycosylation (NEG) and protein levels, catalase (CAT), superoxide dismutase (SOD) and glutathione- S-transferase (GST) activities were determined. Blood glucose, skin LPO and NEG levels increased, but skin GSH levels and CAT, SOD and GST activities decreased in the STZ group. Treatment with vanadyl sulfate reversed these effects. The present study showed that vanadyl sulfate exerted antioxidant properties and may prevent skin damage caused by diabetes.
Activation of the inflammatory transcription factor nuclear factor interleukin-6 during inflammatory and psychological stress in the brain
Authors: Fuchs Franziska , Damm Jelena , Gerstberger Rüdiger , Roth Joachim , Rummel Christoph 
Published: November 2013

Abstract

Background
The transcription factor nuclear factor interleukin 6 (NF-IL6) is known to be activated by various inflammatory stimuli in the brain. Interestingly, we recently detected NF-IL6-activation within the hypothalamus-pituitary-adrenal (HPA)-axis of rats after systemic lipopolysaccharide (LPS)-injection. Thus, the aim of the present study was to investigate whether NF-IL6 is activated during either, inflammatory, or psychological stress in the rat brain.

Methods
Rats were challenged with either the inflammatory stimulus LPS (100 μg/kg, i.p.) or exposed to a novel environment. Core body temperature (Tb) and motor activity were monitored using telemetry, animals were killed at different time points, brains and blood removed, and primary cell cultures of the anterior pituitary lobe (AL) were investigated. Analyses were performed using immunohistochemistry, RT-PCR, and cytokine-specific bioassays.

Results
Stress stimulation by a novel environment increased NF-IL6-immunoreactivity (IR) in the pituitary’s perivascular macrophages and hypothalamic paraventricular cells and a rise in Tb lasting approximately 2 h. LPS stimulation lead to NF-IL6-IR in several additional cell types including ACTH-IR-positive corticotrope cells in vivo and in vitro. Two other proinflammatory transcription factors, namely signal transducer and activator of transcription (STAT)3 and NFκB, were significantly activated and partially colocalized with NF-IL6-IR in cells of the AL only after LPS-stimulation, but not following psychological stress. In vitro NF-IL6-activation was associated with induction and secretion of TNFα in folliculostellate cells, which could be antagonized by the JAK-STAT-inhibitor AG490.

Conclusions
We revealed, for the first time, that NF-IL6 activation occurs not only during inflammatory LPS stimulation, but also during psychological stress, that is, a novel environment. Both stressors were associated with time-dependent activation of NF-IL6 in different cell types of the brain and the pituitary. Moreover, while NF-IL6-IR was partially linked to STAT3 and NFκB activation, TNFα production, and ACTH-IR after LPS stimulation; this was not the case after exposure to a novel environment, suggesting distinct underlying signaling pathways. Overall, NF-IL6 can be used as a broad activation marker in the brain and might be of interest for therapeutic approaches not only during inflammatory but also psychological stress.
Knowledge, use and management of native wild edible plants from a seasonal dry forest (NE, Brazil)
Authors: Cruz Margarita Paloma , Peroni Nivaldo , Albuquerque Ulysses Paulino 
Published: November 2013

Abstract

Background
Despite being an ancient practice that satisfies basic human needs, the use of wild edible plants tends to be forgotten along with associated knowledge in rural communities. The objective of this work is to analyze existing relationships between knowledge, use, and management of native wild edible plants and socioeconomic factors such as age, gender, family income, individual income, past occupation and current occupation.

Methods
The field work took place between 2009 and 2010 in the community of Carão, Altinho municipality, in the state of Pernambuco in northeastern Brazil. We conducted semi-structured interviews with 39 members of the community regarding knowledge, use and management of 14 native wild edible plants from the Caatinga region, corresponding to 12 vegetable species. In parallel, we documented the socioeconomic aspects of the interviewed population (age, gender, family income, individual income, past occupation and current occupation).

Results
Knowledge about edible plants was related to age but not to current occupation or use. Current use was not associated with age, gender or occupation. The association between age and past use may indicate abandonment of these resources.

Conclusion
Because conservation of the species is not endangered by their use but by deforestation of the ecosystems in which these plants grow, we suggest that the promotion and consumption of the plants by community members is convenient and thereby stimulates the appropriation and consequent protection of the ecosystem. To promote consumption of these plants, it is important to begin by teaching people about plant species that can be used for their alimentation, disproving existing myths about plant use, and encouraging diversification of use by motivating the invention of new preparation methods. An example of how this can be achieved is through events like the “Preserves Festival”.
Immune responses to stress after stress management training in patients with rheumatoid arthritis
Authors: de Brouwer Sabine JM , van Middendorp Henriët , Kraaimaat Floris W , Radstake Timothy RDJ , Joosten Irma , Donders A Rogier T , Eijsbouts Agnes , Koulil Saskia Spillekom-van , van Riel Piet LCM , Evers Andrea WM 
Published: November 2013

Abstract
Introduction
Psychological stress may alter immune function by activating physiological stress pathways. Building on our previous study, in which we report that stress management training led to an altered self-reported and cortisol response to psychological stress in patients with rheumatoid arthritis (RA), we explored the effects of this stress management intervention on the immune response to a psychological stress task in patients with RA.

Methods
In this study, 74 patients with RA, who were randomly assigned to either a control group or a group that received short stress management training, performed the Trier Social Stress Test (TSST) 1 week after the intervention and at a 9-week follow-up. Stress-induced changes in levels of key cytokines involved in stress and inflammatory processes (for example, interleukin (IL)-6 and IL-8) were assessed.

Results
Basal and stress-induced cytokine levels were not significantly different in patients in the intervention and control groups one week after treatment, but stress-induced IL-8 levels were lower in patients in the intervention group than in the control group at the follow-up assessment.

Conclusions
In line with our previous findings of lower stress-induced cortisol levels at the follow-up of stress management intervention, this is the first study to show that relatively short stress management training might also alter stress-induced IL-8 levels in patients with RA. These results might help to determine the role of immunological mediators in stress and disease.

Trial registration
The Netherlands National Trial Register (NTR1193)
Impact of Wait Times on Survival for Women With Uterine Cancer
Authors: Elit Lorraine M. , O'Leary Erin M. , Pond Gregory R. , Seow Hsien-Yeang 
Published: November 2013

Purpose To determine whether wait time from histologic diagnosis of uterine cancer to time of definitive surgery by hysterectomy had an impact on all-cause survival. Patients and Methods Women in Ontario with a confirmed histopathologic diagnosis of uterine cancer between April 1, 2000, and March 31, 2009, followed by surgery were identified in the Ontario Cancer Registry. Survival was calculated by using the Kaplan-Meier method. Factors were evaluated for their prognostic effect on survival by using Cox proportional hazards regression. Wait time was evaluated in a multivariable model after adjusting for other significant factors. Results The final study population included 9,417 women; 51.9% had surgery by a gynecologist, and 69.9% had endometrioid adenocarcinoma. Five-year survival for women with wait times of 0.1 to 2, 2.1 to 6, 6.1 to 12, or more than 12 weeks was 71.1%, 81.8%, 79.5%, and 71.9%, respectively. Wait times of ≤ 2 weeks were adversely prognostic for survival after adjusting for other significant factors in the multivariable model, and patients with wait times of more than 12 weeks had worse survival than those who had wait times between 2.1 and 12.0 weeks. Conclusion To the best of our knowledge, this is the first report in a large population-based cohort demonstrating that longer wait times from diagnosis of uterine cancer to definitive surgery have a negative impact on overall survival.
Dimethyl sulfide control of the clean summertime Arctic aerosol and cloud
Authors: Leaitch W. Richard , Sharma Sangeeta , Huang Lin , Toom-Sauntry Desiree , Chivulescu Alina , Macdonald Anne Marie , von Salzen Knut , Pierce Jeffrey R. , Bertram Allan K. , Schroder Jason C. , Shantz Nicole C. , Chang Rachel Y.-W. , Norman Ann-Lise 
Published: November 2013

Abstract
One year of aerosol particle observations from Alert, Nunavut shows that new particle formation (NPF) is common during clean periods of the summertime Arctic associated with attendant low condensation sinks and with the presence of methane sulfonic acid (MSA), a product of the atmospheric oxidation of dimethyl sulfide (DMS). The clean aerosol time periods, defined using the distribution of refractory black carbon number concentrations, increase in frequency from June through August as the anthropogenic influence dwindles. During the clean periods, the number concentrations of particles that can act as cloud condensation nuclei (CCN) increase from June through August suggesting that DMS, and possibly other oceanic organic precursors, exert significant control on the Arctic summertime submicron aerosol, a proposition supported by simulations from the GEOS-Chem-TOMAS global chemical transport model with particle microphysics. The CCN increase for the clean periods across the summer is estimated to be able to increase cloud droplet number concentrations (CDNC) by 23–44 cm-3, comparable to the mean CDNC increase needed to yield the current global cloud albedo forcing from industrial aerosols. These results suggest that DMS may contribute significantly to modification of the Arctic summer shortwave cloud albedo, and they offer a reference for future changes in the Arctic summer aerosol.
Explicit and Implicit Difference Methods for Quasilinear First Order Partial Functional Differential Equations
Authors: Kamont Zdzisław , Szafrańska Anna 
Published: November 2013

Abstract.

Initial boundary value problems of the Dirichlet type for quasilinear functional differential equations are considered.
Explicit difference schemes of the Euler type and implicit difference methods are investigated.
Sufficient conditions for the convergence of approximate solutions
are given and comparisons of the methods are presented.
It is proved that assumptions on the regularity of given functions
are the same for both classes of the methods. It is shown that conditions on the mesh for explicit
difference schemes are more
restrictive than suitable assumptions for implicit
methods.
Error estimates for both methods are presented.
Interpolating operators corresponding to functional variables are constructed.