bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional assays to determine the significance of two common XPC 3'UTR variants found in bladder cancer patients
Authors: Qiao Boling , Scott Gina B , Elliott Faye , Vaslin Laurence , Bentley Johanne , Hall Janet , Bishop D Timothy , Knowles Margaret A , Kiltie Anne E 
Published: June 2011

Abstract

Background

XPC is involved in the nucleotide excision repair of DNA damaged by carcinogens known to cause bladder cancer. Individuals homozygous for the variant allele of XPC c.1496C > T (p.Ala499Val) were shown in a large pooled analysis to have an increased bladder cancer risk, and we found two 3'UTR variants, *611T > A and c.*618A > G, to be in strong linkage disequilibrium with c.1496T. Here we determined if these two 3'UTR variants can affect mRNA stability and assessed the impact of all three variants on mRNA and protein expression.

Methods

In vitro mRNA stability assays were performed and mRNA and protein expression measured both in plasmid-based assays and in lymphocytes and lymphoblastoid cell lines from bladder and breast cancer patients.

Results
The two 3'UTR variants were associated with reduced protein and mRNA expression in plasmid-based assays, suggesting an effect on mRNA stability and/or transcription/translation. A near-significant reduction in XPC protein expression (p = 0.058) was detected in lymphoblastoid cell lines homozygous for these alleles but no differences in mRNA stability in these lines was found or in mRNA or protein levels in lymphocytes heterozygous for these alleles.

Conclusion
The two 3'UTR variants may be the variants underlying the association of c.1496C > T and bladder cancer risk acting via a mechanism modulating protein expression.
Down-regulation of NKD1 increases the invasive potential of non-small-cell lung cancer and correlates with a poor prognosis
Authors: Zhang Sheng , Wang Yan , Dai Shun-Dong , Wang En-Hua 
Published: June 2011

Abstract

Background
As a negative modulator of the canonical Wnt signaling pathway, Naked1 (NKD1) is widely expressed in many normal tissues. However, the expression pattern and clinicopathological significance of NKD1 in patients with non-small-cell lung cancer (NSCLC) is still unclear.

Methods
Immunohistochemical studies were performed on 35 cases of normal lung tissues and 100 cases of NSCLC, including 66 cases with complete follow-up records. The NKD1 protein and mRNA expressions were detected by western blot and Real-time PCR, respectively. To examine the effect of NKD1 on the invasiveness of lung cancer cells, NKD1 was down-regulated by siRNA in lung cancer cell lines and the invasive ability was then evaluated by the Matrigel invasion assay. In addition, the expressions of Dishevelled-1 and β-catenin proteins, as well as MMP mRNA were also examined in NKD1 knockdown cells.

Results
In 35 fresh lung cancer tissues examined, 27(79%) of them exhibited lower levels of NKD1 protein in comparison with their corresponding normal tissue (P = 0.009). However, the NKD1 mRNA level was significantly higher in cancerous lung tissues, compared with the adjacent normal tissues. In 100 NSCLC tissues, NKD1 was significantly lower in 78 cases (78%) than in the normal specimens, determined by immunohistochemical staining. The reduced NKD1 expression was correlated with histological type (P = 0.003), poor differentiation (P = 0.004), lymph node metastasis (P = 0.013), TNM stage (P = 0.002) and poor survival (62.88 ± 3.23 versus 23.61 ± 2.18 months, P = 0.03). In addition, NKD1 knockdown could up-regulate Dishevelled-1 and β-catenin protein levels, as well as increased MMP-7 transcription and the invasive ability of lung cancer cells. Furthermore, when the NKD1-knockdown cells were treated with Dishevelled-1 antibody, their invasive potential was significantly reduced.

Conclusion
NKD1 protein is reduced but NKD1 mRNA is elevated in NSCLC. Reduced NKD1 protein expression correlates with a poor prognosis in NSCLC. NKD1 might inhibit the activity of the canonical Wnt pathway through Dishevelled-1.
Psychological treatment of depressive symptoms in Chinese elderly inpatients with significant medical comorbidity: A meta-analysis
Authors: Dai Bibing , Li Juan , Cuijpers Pim 
Published: June 2011

Abstract

Background
As it is uncertain whether psychological treatments for depressive symptoms are effective in elderly inpatients with significant medical comorbidity, we aimed to assess the treatment effectiveness not only on depressive symptoms but also on somatic symptoms in these inpatients.

Methods
We performed a meta-analysis of randomized controlled studies assessing the effects of psychological treatments in Chinese older inpatients with significant medical comorbidity based upon extensive searches of the most comprehensive computerized Chinese academic database.

Results
The overall effect size for depressive symptoms of twelve studies which compared psychological treatments with a care-as-usual control group was d = 0.80 (95% Confidence Intervals (CI) = 0.60-0.99; p < 0.001). The relative risk of psychological intervention of being effective or not, compared to control condition, was 1.52 (95% CI = 1.25-1.85; p < 0.001).

Conclusions
We conclude that psychological treatments of depressive symptoms are effective for Chinese elderly inpatients with significant medical comorbidity which should receive more attention in medical settings.
Cross-sectional evaluation of the periapical status as related to quality of root canal fillings and coronal restorations in a rural adult male population of Turkey
Authors: Gündüz Kaan , Avsever Hakan , Orhan Kaan , Demirkaya Kadriye 
Published: June 2011

Abstract

Background
To determine the prevalence of periapical lesions in root canal-treated teeth in a rural, male adult, Turkish population and to investigate the influence of the quality of root canal fillings on prevalence of periapical lesions.

Methods
The sample for this cross-sectional study consisted of 552 adult male patients, 18-32 years of age, presenting consecutively as new patients seeking routine dental care at the Dental Sciences of Gulhane Military Medicine, Ankara. The radiographs of the 1014 root canal-treated teeth were evaluated. The teeth were grouped according to the radiographic quality of the root canal filling and the coronal restoration. The criteria used for the examination were slightly modified from those described by De Moor. Periapical status was assessed by the Periapical Index scores (PAI) proposed by Orstavik.

Results
The overall success rate of root canal treatment was 32.1%. The success rates of adequately root canal treatment were significantly higher than inadequately root canal treatment, regardless of the quality or presence of the coronal restoration (P < .001). In addition, the success rate of inadequate root canal treatment was also significantly affected by the quality of coronal restorations.

Conclusions
Our results revealed a high prevalence of periapical lesions in root canal treatment, which is comparable to that reported in other methodologically compatible studies from diverse geographical locations. In addition, the results from the present study confirm the findings of other studies that found the quality of the root canal treatment to be a key factor for prognosis with or without adequate coronal restoration.
The interleukin-6 and noradrenaline mediated inflammation-stress feedback mechanism is dysregulated in metabolic syndrome: Effect of exercise
Authors: Martín-Cordero Leticia , García Juan J , Hinchado Maria D , Ortega Eduardo 
Published: June 2011

Abstract

Background
Metabolic syndrome (MS) is a metabolic disorder associated with obesity, type-II diabetes, and "low grade inflammation", with the concomitant increased risk of cardiovascular events. Removal of the inflammatory mediator signals is a promising strategy to protect against insulin resistance, obesity, and other problems associated with MS such as cardiovascular disease. The aim of the present investigation was to determine the "inflammatory and stress status" in an experimental model of MS, and to evaluate the effect of a program of habitual exercise and the resulting training-induced adaptation to the effects of a single bout of acute exercise.

Methods
Obese Zucker rats (fa/fa) were used as the experimental model of MS, and lean Zucker rats (Fa/fa) were used for reference values. The habitual exercise (performed by the obese rats) consisted of treadmill running: 5 days/week for 14 weeks, at 35 cm/s for 35 min in the last month. The acute exercise consisted of a single session of 25-35 min at 35 cm/s. Circulating concentrations of IL-6 (a cytokine that regulates the inflammatory and metabolic responses), CRP (a systemic inflammatory marker), and corticosterone (CTC) (the main glucocorticoid in rats) were determined by ELISA, and that of noradrenaline (NA) was determined by HPLC. Glucose was determined by standard methods.

Results
The genetically obese animals showed higher circulating levels of glucose, IL-6, PCR, and NA compared with the control lean animals. The habitual exercise program increased the concentration of IL-6, PCR, NA, and glucose, but decreased that of CTC. Acute exercise increased IL-6, CRP, and NA in the sedentary obese animals, but not in the trained obese animals. CTC was increased after the acute exercise in the trained animals only.

Conclusion
Animals with MS present a dysregulation in the feedback mechanism between IL-6 and NA which can contribute to the systemic low-grade inflammation and/or hyperglycaemia of MS. An inappropriate exercise intensity can worsen this dysregulation, contributing to the metabolic, inflammatory, and stress disorders associated with MS. Habitual exercise (i.e., training) induces a positive adaptation in the response to acute exercise.
Heterogeneous decrease in malaria prevalence in children over a six-year period in south-western Uganda
Authors: De Beaudrap Pierre , Nabasumba Carolyn , Grandesso Francesco , Turyakira Eleanor , Schramm Birgit , Boum Yap , Etard Jean-François 
Published: June 2011

Abstract

Background
Malaria is a major public health problem, especially for children. However, recent reports suggest a decline in the malaria burden. The aim of this study was to assess the change in the prevalence of malaria infection among children below five years of age between 2004 and 2010 in a mesoendemic area of Uganda and to analyse the risk factors of malaria infection.

Methods
Two cross-sectional surveys were conducted in 2004 and in 2010 at the end of the rainy and dry seasons to measure the prevalence of P. falciparum infection among children less than five years of age. Rapid diagnostic tests and blood smears were used to diagnose malaria infection. In 2010, sampling was stratified by urban and rural areas. In each selected household, knowledge of malaria and bed nets, and bed net ownership and use, were assessed.

Results
In 2004 and 2010, respectively, a total of 527 and 2,320 (999 in the urban area and 1,321 in rural areas) children less than five years old were enrolled. Prevalence of malaria infection declined from 43% (95% CI: 34-52) in 2004, to 23% (95% CI: 17-30) in rural areas in 2010 and 3% (95% CI: 2-5) in the urban area in 2010. From the rainy to dry season in 2010, prevalence decreased from 23% to 10% (95% CI: 6-14) in rural areas (P = 0.001) and remained stable from 3% to 4% (95% CI: 1-7) in the urban area (P = 0.9). The proportion of households reporting ownership and use of at least one bed net increased from 22.9% in 2004 to 64.7% in the urban area and 44.5% in rural areas in 2010 (P < 0.001). In 2010, the risk of malaria infection was consistently associated with child age and household wealth. In rural areas, malaria infection was also associated with geographic factors.

Conclusions
This study reports a significant drop in the prevalence of malaria infection among children below five years of age, paralleled by an uptake in bed-net use. However, prevalence remains unacceptably high in rural areas and is strongly associated with poverty.
Dietary red palm oil supplementation decreases infarct size in cholesterol fed rats
Authors: Szucs Gergo , Bester Dirk J , Kupai Krisztina , Csont Tamas , Csonka Csaba , Esterhuyse Adriaan J , Ferdinandy Peter , Van Rooyen Jacques 
Published: June 2011

Abstract

Background and Aims
The effect of red palm oil (RPO) supplementation on infarct size after ischaemia/reperfusion in a cholesterol enriched diet-induced hyperlipidemic animal model has not been reported. Previous studies reported results on the effect of RPO in a normal diet, whilst evidence of protection has been linked to improved functional recovery, prosurvival kinase, anti-apoptosis and NO-cGMP. Therefore, we aimed to investigate the effects of dietary RPO supplementation in a cholesterol-enriched diet-induced hyperlipidemic rat model and to investigate the involvement of matrix metalloproteinase 2 (MMP2) inhibition as a possible mechanism of protection.

Materials and Methods
Male Wistar rats were fed either a standard rat chow diet (Norm) or a 2% cholesterol-enriched diet (Chol) for nine weeks. Additionally, two more groups received the same treatment, however, at the week 4, diet was supplemented with RPO for the last five weeks (Norm+RPO and Chol+RPO), respectively. After the feeding period hearts were isolated, perfused according to Langendorff and subjected to 30 minutes of normothermic global ischaemia followed by two hours of reperfusion. Infarct size was measured by 2,3,5-triphenyltetrazolium chloride staining at the end of reperfusion.

Results
Cholesterol-enriched diet increased myocardial infarct size from 23.5 ± 3.0% to 37.2 ± 3.6% (p < 0.05) when compared to normal diet. RPO supplementation significantly reduced infarct size either in Norm+RPO or in Chol+RPO (to 9.2 ± 1.0% and 26.9 ± 3.0%), respectively. Infarct size in Chol+RPO was comparable to the Norm group. MMP2 activity before ischaemia was significantly reduced in the Chol+RPO group when compared to the Chol group. However, the MMP2 activity of the hearts of the RPO fed rats was significantly increased when compared to the normal diet group after ischaemia.

Conclusions
For the first time it was shown that dietary RPO supplementation attenuated the increased susceptibility of the hearts in cholesterol fed rats to ischaemia/reperfusion injury. This was shown by reduced infarct size. For the first time we also show that red palm oil supplementation altered pre-ischaemic levels of MMP-2, which may indicate that myocardial MMP2 may be implicated as a possible role player in RPO mediated protection against ischaemia/reperfusion injury in hearts of cholesterol supplemented rats.
Peritoneal carcinomatosis from ovarian cancer: chemosensitivity test and tissue markers as predictors of response to chemotherapy
Authors: Arienti Chiara , Tesei Anna , Verdecchia Giorgio Maria , Framarini Massimo , Virzì Salvatore , Grassi Antonio , Scarpi Emanuela , Turci Livia , Silvestrini Rosella , Amadori Dino , Zoli Wainer 
Published: June 2011

Abstract

Background
Platinum-based regimens are the treatments of choice in ovarian cancer, which remains the leading cause of death from gynecological malignancies in the Western world. The aim of the present study was to compare the advantages and limits of a conventional chemosensitivity test with those of new biomolecular markers in predicting response to platinum regimens in a series of patients with peritoneal carcinomatosis from ovarian cancer.

Methods
Fresh surgical biopsy specimens were obtained from 30 patients with primary or recurrent peritoneal carcinomatosis from ovarian cancer. ERCC1, GSTP1, MGMT, XPD, and BRCA1 gene expression levels were determined by Real-Time RT-PCR. An in vitro chemosensitivity test was used to define a sensitivity or resistance profile to the drugs used to treat each patient.

Results

MGMT and XPD expression was directly and significantly related to resistance to platinum-containing treatment (p = 0.036 and p = 0.043, respectively). Significant predictivity in terms of sensitivity and resistance was observed for MGMT expression (75.0% and 72.5%, respectively; p = 0.03), while high predictivity of resistance (90.9%) but very low predictivity of sensitivity (37.5%) (p = 0.06) were observed for XPD. The best overall and significant predictivity was observed for chemosensitivity test results (85.7% sensitivity and 91.3% resistance; p = 0.0003).

Conclusions
The in vitro assay showed a consistency with results observed in vivo in 27 out of the 30 patients analyzed. Sensitivity and resistance profiles of different drugs used in vivo would therefore seem to be better defined by the in vitro chemosensitivity test than by expression levels of markers.
Long- term outcome of paediatric patients with ANCA vasculitis
Authors: Arulkumaran Nishkantha , Jawad Susan , Smith Stuart W , Harper Lorraine , Brogan Paul , Pusey Charles D , Salama Alan D 
Published: June 2011

Abstract

Background
Primary systemic vasculitis presenting in childhood is an uncommon but serious condition. As these patients transfer to adult clinics for continuing care, defining long term outcomes with emphasis on disease and treatment- related morbidity and mortality is important. The aim of this study is to describe the long- term clinical course of paediatric patients with ANCA vasculitis.

Methods
The adult patients in our vasculitis clinics who had presented in childhood, with a follow up time of greater than 10 years were included. We also reviewed the literature for articles describing the clinical outcome of paediatric patients with ANCA vasculitis.

Results
We describe the clinical course of 8 adults who presented in childhood with ANCA vasculitis. 7 patients had Wegener's granulomatosis and 1 had microscopic polyangiitis. The median age at presentation was 11.5 years, and follow up time ranged form 11 to 30 years. Induction therapy for all patients was steroids and/or cyclophosphamide. Maintenance therapy was with azathioprine or mycophenolate mofetil. Biological agents were used in 3 patients for relapsed disease in adulthood only.
Seven patients achieved complete remission. All patients experienced disease relapse, with a median of 4 episodes. Kidney function was generally well preserved, with median eGFR 76 ml/min. Only one patient developed end-stage renal failure and one patient died after 25 years of disease. Treatment-related morbidity rates were high; 7 suffered from infections, 4 were infertile, 2 had skeletal complications, and 1 developed malignancy.

Conclusion
Close long- term follow up of paediatric patients with ANCA vasculitis is imperative, as this patient cohort is likely to live long enough to develop significant treatment and disease- related morbidities. Prospective cohort studies with novel therapies including paediatric patients are crucial to help us determine the best approach to managing this complex group of patients. In addition, although not yet observed in our series, late cardiovascular morbidity remains a major longer-term potential concern for adult survivors of paediatric vasculitis.
Resistance to thyroid hormone associated with a novel mutation of the thyroid β receptor gene in a four-year-old female
Authors: Canadas Karina T , Rivkees Scott A , Udelsman Robert , Breuer Christopher K 
Published: June 2011

Abstract
Resistance to thyroid hormone (RTH) is a rare syndrome of reduced responsiveness of target tissues to thyroid hormone and is caused mutation in the thyroid β receptor gene. We report a novel mutation, E445X, causing RTH in a 4-year old girl. The patient exhibited extreme signs and symptoms of RTH at an early age, and had a large compressive goiter. Following total extracapsular thyroidectomy, upper airway compression was relieved and symptoms of hyperthyroidism improved. This case appears to be the youngest child recorded to have undergone total thyroidectomy for RTH. Post-operative TSH elevations were managed with every-other-day triiodothyronine therapy.
Interactomes, manufacturomes and relational biology: analogies between systems biology and manufacturing systems
Authors: Rietman Edward A , Colt John Z , Tuszynski Jack A 
Published: June 2011

AbstractBackgroundWe review and extend the work of Rosen and Casti who discuss category theory with regards to systems biology and manufacturing systems, respectively.ResultsWe describe anticipatory systems, or long-range feed-forward chemical reaction chains, and compare them to open-loop manufacturing processes. We then close the loop by discussing metabolism-repair systems and describe the rationality of the self-referential equationf=f(f). This relationship is derived from some boundary conditions that, in molecular systems biology, can be stated as the cardinality of the following molecular sets must be about equal: metabolome, genome, proteome. We show that this conjecture is not likely correct so the problem of self-referential mappings for describing the boundary between living and nonliving systems remains an open question. We calculate a lower and upper bound for the number of edges in the molecular interaction network (the interactome) for two cellular organisms and for two manufacturomes for CMOS integrated circuit manufacturing.ConclusionsWe show that the relevant mapping relations may not be Abelian, and that these problems cannot yet be resolved because the interactomes and manufacturomes are incomplete.
Identification of serum biomarkers for aging and anabolic response
Authors: Banerjee Camellia , Ulloor Jagadish , Dillon Edgar L , Dahodwala Qusai , Franklin Brittani , Storer Thomas , Sebastiani Paola , Sheffield-Moore Melinda , Urban Randall J , Bhasin Shalender , Montano Monty 
Published: June 2011

AbstractObjectiveWith the progressive aging of the human population, there is an inexorable decline in muscle mass, strength and function. Anabolic supplementation with testosterone has been shown to effectively restore muscle mass in both young and elderly men. In this study, we were interested in identifying serum factors that change with age in two distinct age groups of healthy men, and whether these factors were affected by testosterone supplementation.MethodsWe measured the protein levels of a number of serum biomarkers using a combination of banked serum samples from older men (60 to 75 years) and younger men (ages 18 to 35), as well as new serum specimens obtained through collaboration. We compared baseline levels of all biomarkers between young and older men. In addition, we evaluated potential changes in these biomarker levels in association with testosterone dose (low dose defined as 125 mg per week or below compared to high dose defined as 300 mg per week or above) in our banked specimens.ResultsWe identified nine serum biomarkers that differed between the young and older subjects. These age-associated biomarkers included: insulin-like growth factor (IGF1), N-terminal propeptide of type III collagen (PIIINP), monokine induced by gamma interferon (MIG), epithelial-derived neutrophil-activating peptide 78 (ENA78), interleukin 7 (IL-7), p40 subunit of interleukin 12 (IL-12p40), macrophage inflammatory protein 1β (MIP-1β), platelet derived growth factor β (PDGFβ) and interferon-inducible protein 10 (IP-10). We further observed testosterone dose-associated changes in some but not all age related markers: IGF1, PIIINP, leptin, MIG and ENA78. Gains in lean mass were confirmed by dual energy X-ray absorptiometry (DEXA).ConclusionsResults from this study suggest that there are potential phenotypic biomarkers in serum that can be associated with healthy aging and that some but not all of these biomarkers reflect gains in muscle mass upon testosterone administration.