bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation Survivors: Understanding and Exploiting the Phenotype following Fractionated Radiation Therapy
Authors: Makinde Adeola Y. , John-Aryankalayil Molykutty , Palayoor Sanjeewani T. , Cerna David , Coleman C. Norman 
Published: November 2012

Abstract
Radiation oncology modalities such as intensity-modulated and image-guided radiation therapy can reduce the high dose to normal tissue and deliver a heterogeneous dose to tumors, focusing on areas deemed at highest risk for tumor persistence. Clinical radiation oncology produces daily doses ranging from 1 to 20 Gy, with tissues being exposed to 30 or more daily fractions. Hypothesizing the cells that survive fractionated radiation therapy have a substantially different phenotype than the untreated cells, which might be exploitable for targeting with molecular therapeutics or immunotherapy, three prostate cancer cell lines (PC3, DU145, and LNCaP) and normal endothelial cells were studied to understand the biology of differential effects of multifraction (MF) radiation of 0.5, 1, and/or 2 Gy fraction to 10 Gy total dose, and a single dose of 5 and 10 Gy. The resulting changes in mRNA, miRNA, and phosphoproteome were analyzed. Significant differences were observed in the MF radiation exposures including those from the 0.5 Gy MF that produces little cell killing. As expected, p53 function played a major role in response. Pathways modified by MF include immune response, DNA damage, cell-cycle arrest, TGF-β, survival, and apoptotic signal transduction. The radiation-induced stress response will set forth a unique platform for exploiting the effects of radiation therapy as “focused biology” for cancer treatment in conjunction with molecular targeted or immunologically directed therapy. Given that more normal tissue is treated, albeit to lower doses with these newer techniques, the response of the normal tissue may also influence long-term treatment outcome. Mol Cancer Res; 11(1); 5–12. ©2012 AACR.
Hemodynamic Responses to Rapid Saline Loading
Authors: Fujimoto Naoki , Borlaug Barry A. , Lewis Gregory D. , Hastings Jeffrey L. , Shafer Keri M. , Bhella Paul S. , Carrick-Ranson Graeme , Levine Benjamin D. 
Published: November 2012

Background—
Hemodynamic assessment after volume challenge has been proposed as a way to identify heart failure with preserved ejection fraction. However, the normal hemodynamic response to a volume challenge and how age and sex affect this relationship remain unknown.

Methods and Results—

Sixty healthy subjects underwent right heart catheterization to measure age- and sex-related normative responses of pulmonary capillary wedge pressure and mean pulmonary arterial pressure to volume loading with rapid saline infusion (100–200 mL/min). Hemodynamic responses to saline infusion in heart failure with preserved ejection fraction (n=11) were then compared with those of healthy young (<50 years of age) and older (≥50 years of age) subjects. In healthy subjects, pulmonary capillary wedge pressure increased from 10±2 to 16±3 mm Hg after ~1 L and to 20±3 mm Hg after ~2 L of saline infusion. Older women displayed a steeper increase in pulmonary capillary wedge pressure relative to volume infused (16±4 mm Hg·L
−1
·m
2
) than the other 3 groups (
P
≤0.019). Saline infusion resulted in a greater increase in mean pulmonary arterial pressure relative to cardiac output in women compared with men regardless of age. Subjects with heart failure with preserved ejection fraction exhibited a steeper increase in pulmonary capillary wedge pressure relative to infused volume (25±12 mm Hg·L
−1
·m
2
) than healthy young and older subjects (
P
≤0.005).

Conclusions—
Filling pressures rise significantly with volume loading, even in healthy volunteers. Older women and patients with heart failure with preserved ejection fraction exhibit the largest increases in pulmonary capillary wedge pressure and mean pulmonary arterial pressure.
Health-Related Quality of Life, Disease Severity, and Anticipated Trajectory of Diabetes
Authors: Scollan-Koliopoulos Melissa , Bleich David , Rapp Kenneth J. , Wong Patrick , Hofmann Cynthia J. , Raghuwanshi Maya 
Published: November 2012

Purpose Adults hospitalized with diabetes are likely to have multiple comorbid conditions contributing to suboptimal health-related quality of life. The purpose of this study was to survey urban, very low-income, hospitalized adults with diabetes about disease severity, anticipated disease trajectory, and self-rated health-related quality of life. Methods Data were collected using the Brief Illness Perception Questionnaire, the 36-item Short Form Health Survey (SF-36), the comparative risk perception questionnaire, and glycosylated hemoglobin. Severity was defined by glycosylated hemoglobin level and current microvascular complications from diabetes. Findings Those with more severe disease who also anticipated the development of additional diabetes-related complications were likely to have suboptimal physical and mental functioning. The perception of diabetes as a health threat concurrent with having non-diabetes-related comorbid chronic conditions contributed uniquely to explaining scores in health-related quality of life. Conclusion Hospitalized adults with diabetes represent a population affected by chronic disease demands that contribute to suboptimal physical and mental functioning. Suboptimal quality of life may contribute to severity of diabetes and to a perception of having a threatening disease trajectory. Hospitalization provides an opportunity for clinicians to intervene in mental and physical functioning by assessing for threatening illness perceptions and employing interventions to promote acceptance of functional limitations.
Influences on the decision to prescribe or administer anticholinergic drugs to treat death rattle: A focus group study
Authors: Hirsch Christine A , Marriott John F , Faull Christina M 
Published: November 2012

Background: The evidence supporting pharmacological treatment of death rattle is poor; yet, anticholinergic drugs feature in end-of-life care pathways and guidelines worldwide as a treatment option. Aim: This qualitative arm of a wider study aimed to explore important issues which health-care professionals associated with decision-making to prescribe or administer anticholinergics at the end of life. Design: After purposive sampling, five focus groups were conducted. Discussions were audiotaped and transcribed verbatim. Setting: Thirty medical and nursing personnel working in inpatient and community settings from two specialist palliative care units in the United Kingdom took part in the study. Results: Thematic analysis of transcripts from audiotapes revealed perceived pressures to prescribe and/or administer anticholinergics from colleagues and carers, and drugs were often prescribed or administered in order to be seen to ‘do something’, although the benefit in terms of therapeutic response was considered minimal. Familiarity with drug regimens and dosing was often based on personal experience. The monitoring of side effects of anticholinergics at the end of life was recognised as problematic and had little influence on prescribing and administration. There was also an indication that patients and carers in the community were more likely to receive timely verbal preparation and explanation around death rattle than those cared for in an inpatient setting. Conclusion: The study raises questions about the routine inclusion of anticholinergic treatment in UK end of life care pathways for the treatment of death rattle.
Efficacy vs. effectiveness: Erlotinib in previously treated non-small-cell lung cancer
Authors: Sheikh Naureen , Chambers Carole R 
Published: November 2012

Background: A randomized trial carried out by Shepherd et al. in patients with advanced or metastatic non-small-cell lung cancer showed statistically significant benefit of erlotinib over placebo in prolonging overall survival and progression-free survival. Objectives: The primary outcome was to compare overall survival of patients treated with erlotinib for non-small-cell lung cancer at Alberta Health Services – Cancer Care to the overall survival seen in the pivotal trial. Secondary outcomes included comparing progression-free survival, overall response rate, and duration of response between the two patient populations. Methods: A retrospective review of charts was conducted for patients with locally advanced or metastatic non-small-cell lung cancer who received erlotinib therapy after failure of at least one prior chemotherapy regimen between 1 August 2006 and 31 July 2009. Survival data was analyzed using the Kaplan-Meier method. Results: Median overall survival and progression-free survival were 5.19 months and 2.46 months, respectively, in Alberta Health Services – Cancer Care patients. The rate of response was 11% (median duration of response, 6.7 months). The likelihood of a response to erlotinib was higher among nonsmokers ( p < 0.0001) and those with response to prior chemotherapy ( p = 0.0896). In multivariate analysis, good performance status ( p = 0.0109) and response to prior therapy ( p < 0.0001) were favorable factors for survival. Conclusions: In a clinical setting, erlotinib does not perform as well in terms of median overall survival as reported in the pivotal trial (5.19 vs. 6.70 months).
Physical inactivity is associated with low self efficacy and social support among patients with hypertension in Nigeria
Authors: Idowu OA , Adeniyi AF , Atijosan OJ , Ogwumike OO 
Published: November 2012

Background Physical inactivity is a major factor in the development of many chronic illnesses, including hypertension. Evidence highlighting links among physical activity participation and psychosocial constructs such as self efficacy, social support and perceived barriers among hypertensive patients in the Nigerian population is scarce. This study explored the associations between physical activity and each of self efficacy, social support and perceived barriers. Methods Two hundred and twelve patients receiving treatment in two tertiary health institutions located in Ekiti State, Nigeria were surveyed cross-sectionally. Physical activity level, self efficacy, social support and perceived barriers were measured with the International Physical Activity Questionnaire, Exercise Self-Efficacy Scale, Medical Outcomes Social Support Scale and Exercise Benefits and Barrier Scale respectively. Results Level of physical activity was significantly associated with self efficacy ( rs = 0.67, p < 0.01,  = 0.45) and social support ( rs = 0.80, p < 0.01,  = 0.64), with most participants (56.1%) being physically inactive. However, no association was found between physical activity level and perceived barriers ( rs = 0.07, p > 0.01,  = 0.005). Conclusion Most of the hypertensive patients presented with low levels of physical activity. Physical activity was associated with psychosocial constructs including self efficacy and social support but not with perceived barriers.
Rapid cytological analysis of endobronchial ultrasound-guided aspirates in sarcoidosis
Authors: Plit Marshall L. , Havryk Adrian P. , Hodgson Alan , James Daniel , Field Andrew , Carbone Sonia , Glanville Allan R. , Bashirzadeh Farzad , Chay Anna M. , Hundloe Justin , Pearson Rebecca , Fielding David 
Published: November 2012

Rapid on-site evaluation (ROSE) of endobronchial ultrasound-guided transbronchial needle aspirates (EBUS-TBNA) has not been compared to final detailed cytological analysis in patients with suspected sarcoidosis.To assess the diagnostic accuracy of EBUS-TBNA with ROSE in patients with suspected sarcoidosis, a prospective two-centre study performed EBUS-TBNA with ROSE of cellular material followed by transbronchial lung biopsy (TBLB) and endobronchial biopsy (EBB). The diagnostic accuracy of EBUS-TBNA with ROSE was compared to the final cytological assessment and to TBLB and EBB.Analysis confirmed 49 out of 60 cases of sarcoidosis. ROSE sensitivity was 87.8% (specificity 91%, positive predictive value 97.7%). ROSE slide interpretation in combination with the final fixed slide and cell block preparations had a sensitivity of 91.8% (specificity 100%, positive predictive value 100%). 67% of patients were confirmed as having sarcoidosis on TBLB and 29% on EBB. Interobserver agreement between cytotechnologists and pathologists was very good (κ=0.91, 95% CI 0.80–1.0 and κ=0.91, 95% CI 0.79–1.0, respectively).EBUS-TBNA with ROSE has high diagnostic accuracy and interobserver agreement and informs the bronchoscopist in theatre whether additional diagnostic procedures need to be undertaken. EBUS-TBNA with ROSE should therefore be considered as the first-line investigation of sarcoidosis.
MirSNP, a database of polymorphisms altering miRNA target sites, identifies miRNA-related SNPs in GWAS SNPs and eQTLs
Authors: Liu Chenxing , Zhang Fuquan , Li Tingting , Lu Ming , Wang Lifang , Yue Weihua , Zhang Dai 
Published: November 2012

Abstract

Background
Numerous single nucleotide polymorphisms (SNPs) associated with complex diseases have been identified by genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) studies. However, few of these SNPs have explicit biological functions. Recent studies indicated that the SNPs within the 3’UTR regions of susceptibility genes could affect complex traits/diseases by affecting the function of miRNAs. These 3’UTR SNPs are functional candidates and therefore of interest to GWAS and eQTL researchers.

Description
We developed a publicly available online database, MirSNP (http://cmbi.bjmu.edu.cn/mirsnp), which is a collection of human SNPs in predicted miRNA-mRNA binding sites. We identified 414,510 SNPs that might affect miRNA-mRNA binding. Annotations were added to these SNPs to predict whether a SNP within the target site would decrease/break or enhance/create an miRNA-mRNA binding site. By applying MirSNP database to three brain eQTL data sets, we identified four unreported SNPs (rs3087822, rs13042, rs1058381, and rs1058398), which might affect miRNA binding and thus affect the expression of their host genes in the brain. We also applied the MirSNP database to our GWAS for schizophrenia: seven predicted miRNA-related SNPs (p < 0.0001) were found in the schizophrenia GWAS. Our findings identified the possible functions of these SNP loci, and provide the basis for subsequent functional research.

Conclusion
MirSNP could identify the putative miRNA-related SNPs from GWAS and eQTLs researches and provide the direction for subsequent functional researches.
Enterococcus and Streptococcusspp. associated with chronic and self-medicated urinary tract infections in Vietnam
Authors: Poulsen Louise Ladefoged , Bisgaard Magne , Son Nguyen Thai , Trung Nguyen Vu , An Hoang Manh , Dalsgaard Anders 
Published: November 2012

Abstract

Background
Urinary tract infections (UTI) are one of the most common infections among women worldwide. E. coli often causes more than 75% of acute uncomplicated UTI, however, little is known about how recurrent UTIs and indiscriminate use of antimicrobials affect the aetiology of UTIs. This study aimed to establish the aetiology of UTI in a population of recurrent and self-medicated patients referred from pharmacies to a hospital in Hanoi, Vietnam and to describe genotypes and antimicrobial susceptibility of the associated bacterial pathogens. The aetiology of bacterial pathogens associated with UTI (defined as ≥ 104 CFU/ml urine) was established by phenotypic and molecular methods. Enterococcus faecalis isolates were typed by Multi Locus Sequence Typing (MLST), Pulsed-Field Gel Electrophoresis (PFGE) and antimicrobial susceptibility testing.

Methods
Urine samples from 276 patients suffering symptoms of urinary tract infection were collected and cultured on Flexicult agar® allowing for detection of the most common urine pathogens. Patients were interviewed about underlying diseases, duration of symptoms, earlier episodes of UTI, number of episodes diagnosed by doctors and treatment in relation to UTI. All tentative E. faecalis and E. faecium isolates were identified to species level by PCR, 16S rRNA and partial sequencing of the groEL gene. E. faecalis isolates were further characterized by Multi Locus Sequence Typing and antimicrobial susceptibility testing.

Results
Mean age of 49 patients was 48 yrs (range was 11–86 yrs) and included 94% women. On average, patients reported to have suffered from UTI for 348 days (range 3 days-10 years, and experienced 2.7 UTIs during the previous year). Cephalosporins were reported the second drug of choice in treatment of UTI at the hospital. E. faecalis (55.1%), E. coli (12.2%) and Streptococcus gallolyticus subsp. pasteurianus (8.2%) were main bacterial pathogens. MIC testing of E. faecalis showed susceptibility to ampicillin, penicillin and vancomycin, but high-level resistance against gentamicin (48.1%). MLST revealed 12 Sequence Types (ST) of which ST 16 made up 44.5% and showed closely related PFGE types.

Conclusion
The different aetiology of UTI compared with reports elsewhere, where E. coli dominates, may be a result of chronic and recurrent UTIs together with indiscriminate use of antimicrobials. The similar genotypes shown by epidemiologically unrelated ST 16 isolates in Vietnam and elsewhere, suggest that E. faecalis ST 16 might represent a globally distributed clone. Treatment of UTI with cephalosporins may select for E. faecalis as it is intrinsic resistant and further studies are needed to establish the source(s) and role of E. faecalis ST 16 in acute UTI.
Comparison of toxin removal outcomes in online hemodiafiltration and intra-dialytic exercise in high-flux hemodialysis: A prospective randomized open-label clinical study protocol
Authors: Maheshwari Vaibhav , Samavedham Lakshminarayanan , Rangaiah Gade Pandu , Loy Yijun , Ling Lieng Hsi , Sethi Sunil , Leong Titus Lau Wai 
Published: November 2012

Abstract

Background
Maintenance hemodialysis (HD) patients universally suffer from excess toxin load. Hemodiafiltration (HDF) has shown its potential in better removal of small as well as large sized toxins, but its efficacy is restricted by inter-compartmental clearance. Intra-dialytic exercise on the other hand is also found to be effective for removal of toxins; the augmented removal is apparently obtained by better perfusion of skeletal muscles and decreased inter-compartmental resistance. The aim of this trial is to compare the toxin removal outcome associated with intra-dialytic exercise in HD and with post-dilution HDF.

Methods/design
The main hypothesis of this study is that intra-dialytic exercise enhances toxin removal by decreasing the inter-compartmental resistance, a major impediment for toxin removal. To compare the HDF and HD with exercise, the toxin rebound for urea, creatinine, phosphate, and β2-microglobulin will be calculated after 2 hours of dialysis. Spent dialysate will also be collected to calculate the removed toxin mass. To quantify the decrease in inter-compartmental resistance, the recently developed regional blood flow model will be employed. The study will be single center, randomized, self-control, open-label prospective clinical research where 15 study subjects will undergo three dialysis protocols (a) high flux HD, (b) post-dilution HDF, (c) high flux HD with exercise. Multiple blood samples during each study session will be collected to estimate the unknown model parameters.

Discussion
This will be the first study to investigate the exercise induced physiological change(s) responsible for enhanced toxin removal, and compare the toxin removal outcome both for small and middle sized toxins in HD with exercise and HDF. Successful completion of this clinical research will give important insights into exercise effect on factors responsible for enhanced toxin removal. The knowledge will give confidence for implementing, sustaining, and optimizing the exercise in routine dialysis care. We anticipate that toxin removal outcomes from intra-dialytic exercise session will be comparable to that obtained by standalone HDF. These results will encourage clinicians to combine HDF with intra-dialytic exercise for significantly enhanced toxin removal.

Trial registration
ClinicalTrials.gov number, NCT01674153
A multi-centre qualitative study exploring the experiences of UK South Asian and White Diabetic Patients referred for renal care
Authors: Wilkinson Emma , Randhawa Gurch , Feehally John , Farrington Ken , Greenwood Roger , Choi Peter , Lightstone Liz 
Published: November 2012

Abstract

Background
An exploration of renal complications of diabetes from the patient perspective is important for developing quality care through the diabetic renal disease care pathway.

Methods
Newly referred South Asian and White diabetic renal patients over 16 years were recruited from nephrology outpatient clinics in three UK centres - Luton, West London and Leicester – and their experiences of the diabetes and renal care recorded.
A semi-structured qualitative interview was conducted with 48 patients. Interview transcripts were analysed thematically and comparisons made between the White and South Asian groups.

Results
23 South Asian patients and 25 White patients were interviewed. Patient experience of diabetes ranged from a few months to 35 years with a mean time since diagnosis of 12.1 years and 17.1 years for the South Asian and White patients respectively. Confusion emerged as a response to referral shared by both groups. This sense of confusion was associated with reported lack of information at the time of referral, but also before referral. Language barriers exacerbated confusion for South Asian patients.

Conclusions
The diabetic renal patients who have been referred for specialist renal care and found the referral process confusing have poor of awareness of kidney complications of diabetes. Healthcare providers should be more aware of the ongoing information needs of long term diabetics as well as the context of any information exchange including language barriers.
Development of a gene therapy strategy to target hepatocellular carcinoma based inhibition of protein phosphatase 2A using the α-fetoprotein promoter enhancer and pgk promoter: an in vitro and in vivo study
Authors: Li Wei , Li Dao-Ming , Chen Kai , Chen Zheng , Zong Yang , Yin Hong , Xu Ze-Kuan , Zhu Yi , Gong Fei-Ran , Tao Min 
Published: November 2012

Abstract

Background
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Current therapies are insufficient, making HCC an intractable disease. Our previous studies confirmed that inhibition of protein phosphatase 2A (PP2A) may provide a promising therapeutic strategy for cancer. Unfortunately, constitutive expression of PP2A in normal tissues limits the application of PP2A inhibition. Thus, a HCC-specific gene delivery system should be developed. The α-fetoprotein (AFP) promoter is commonly used in HCC-specific gene therapy strategies; however, the utility of this approach is limited due to the weak activity of the AFP promoter. It has been shown that linking the AFP enhancer with the promoter of the non-tissue-specific, human housekeeping phosphoglycerate kinase (pgk) gene can generate a strong and HCC-selective promoter.

Methods
We constructed a HCC-specific gene therapy system to target PP2A using the AFP enhancer/pgk promoter, and evaluated the efficiency and specificity of this system both in vitro and in vivo.

Results

AFP enhancer/pgk promoter-driven expression of the dominant negative form of the PP2A catalytic subunit α (DN-PP2Acα) exerted cytotoxic effects against an AFP-positive human hepatoma cell lines (HepG2 and Hep3B), but did not affect AFP-negative human hepatoma cells (SK-HEP-1) or normal human liver cells (L-02). Moreover, AFP enhancer/pgk promoter driven expression of DN-PP2Acα inhibited the growth of AFP-positive HepG2 tumors in nude mice bearing solid tumor xenografts, but did not affect AFP-negative SK-HEP-1 tumors.

Conclusions
The novel approach of AFP enhancer/pgk promoter-driven expression of DN-PP2Acα may provide a useful cancer gene therapy strategy to selectively target HCC.