bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapamycin Resistance Is Linked to Defective Regulation of Skp2
Authors: Totary-Jain Hana , Sanoudou Despina , Dautriche Cula N. , Schneller Hillary , Zambrana Lester , Marks Andrew R. 
Published: February 2012

Abstract
The mammalian target of rapamycin (mTOR) plays a role in controlling malignant cellular growth. mTOR inhibitors, including rapamycin (sirolimus), are currently being evaluated in cancer trials. However, a significant number of tumors are rapamycin resistant. In this study, we report that the ability of rapamycin to downregulate Skp2, a subunit of the ubiquitin protein ligase complex, identifies tumors that are sensitive to rapamycin. RNA interference (RNAi)–mediated silencing of Skp2 in human tumor cells increased their sensitivity to rapamycin in vitro and inhibited the growth of tumor xenografts in vivo. Our findings suggest that Skp2 levels are a key determinant of antitumor responses to mTOR inhibitors, highlighting a potentially important pharmacogenomic marker to predict sensitivity to rapamycin as well as Skp2 silencing strategies for therapeutic purposes. Cancer Res; 72(7); 1836–43. ©2012 AACR.
Dissection of T-cell Antigen Specificity in Human Melanoma
Authors: Andersen Rikke Sick , Thrue Charlotte Albæk , Junker Niels , Lyngaa Rikke , Donia Marco , Ellebæk Eva , Svane Inge Marie , Schumacher Ton N. , thor Straten Per , Hadrup Sine Reker 
Published: February 2012

Abstract
Tumor-infiltrating lymphocytes (TIL) isolated from melanoma patients and expanded in vitro by interleukin (IL)-2 treatment can elicit therapeutic response after adoptive transfer, but the antigen specificities of the T cells transferred have not been determined. By compiling all known melanoma-associated antigens and applying a novel technology for high-throughput analysis of T-cell responses, we dissected the composition of melanoma-restricted T-cell responses in 63 TIL cultures. T-cell reactivity screens against 175 melanoma-associated epitopes detected 90 responses against 18 different epitopes predominantly from differentiation and cancer-testis antigens. Notably, the majority of these responses were of low frequency and tumor-specific T-cell frequencies decreased during rapid expansion. A further notable observation was a large variation in the T-cell specificities detected in cultures established from different fragments of resected melanoma lesions. In summary, our findings provide an initial definition of T-cell populations contributing to tumor recognition in TILs although the specificity of many tumor-reactive TILs remains undefined. Cancer Res; 72(7); 1642–50. ©2012 AACR.
Estimating Causal Effects of Genetic Risk Variants for Breast Cancer Using Marker Data from Bilateral and Familial Cases
Authors: Dudbridge Frank , Fletcher Olivia , Walker Kate , Johnson Nichola , Orr Nick , dos Santos Silva Isabel , Peto Julian 
Published: February 2012

Abstract
Background: Cases with a family history are enriched for genetic risk variants, and the power of association studies can be improved by selecting cases with a family history of disease. However, in recent genome-wide association scans utilizing familial sampling, the excess relative risk for familial cases is less than predicted when compared with unselected cases. This can be explained by incomplete linkage disequilibrium between the tested marker and the underlying causal variant.
Methods: We show that the allele frequency and effect size of the underlying causal variant can be estimated by combining marker data from studies that ascertain cases based on different family histories. This allows us to learn about the genetic architecture of a complex trait, without having identified any causal variants. We consider several validated common marker alleles for breast cancer, using our own study of high risk, predominantly bilateral cases, cases preferentially selected to have at least two affected first- or second-degree relatives, and published estimates of relative risk from standard case–control studies.
Results: To obtain realistic estimates and to accommodate some prior beliefs, we use Bayesian estimation to infer that the causal variants are probably common, with minor allele frequency &gt;5%, and have small effects, with relative risk around 1.2.
Conclusion: These results strongly support the common disease common variant hypothesis for these specific loci associated with breast cancer.
Impact: Our results agree with recent assertions that synthetic associations of rare variants are unlikely to account for most associations seen in genome-wide studies. Cancer Epidemiol Biomarkers Prev; 21(2); 262–72. ©2011 AACR.
The Impact of Obesity on Follow-Up after an Abnormal Screening Mammogram
Authors: Schur Ellen A. , Elmore Joann E. , Onega Tracy , Wernli Karen J. , Sickles Edward A. , Haneuse Sebastien 
Published: February 2012

AbstractBackground: Effective breast cancer screening and early detection are crucial for obese women, who experience a higher incidence of the disease and present at later stages.Methods: We examined the association between body mass index (BMI) and timeliness of follow-up after 241,222 abnormal screening mammograms carried out on 201,470 women in the Breast Cancer Surveillance Consortium. Each mammogram had one of three recommendations for follow-up: short-interval follow-up, immediate additional diagnostic imaging, and biopsy/surgical consultation. We used logistic regression to estimate the adjusted effect of BMI on any recorded follow-up within 270 days of the recommendation; linear regression was used to model the mean follow-up time among those with recorded follow-up.Results: As compared with normal-weight women, higher BMI was associated with slightly increased odds of follow-up among women who received a recommendation for short-interval follow-up (ORs: 1.03–1.10; P = 0.04) or immediate additional imaging (ORs: 1.03–1.09; P = 0.01). No association was found for biopsy/surgical consultation recommendations (P = 0.90). Among those with recorded follow-up, higher BMI was associated with longer mean time to follow-up for both short-interval (3–10 days; P &lt; 0.001) and additional imaging recommendations (2–3 days; P &lt; 0.001) but not biopsy/surgical consultation (P = 0.06). Regardless of statistical significance, actual differences in days to follow-up across BMI groups were small and unlikely to be clinically significant.Conclusions: Once obese women access screening mammography, their follow-up after abnormal results is similar to that of normal-weight women.Impact: Efforts to improve early detection of breast cancer in obese women should focus elsewhere, such as improving participation in screening mammography. Cancer Epidemiol Biomarkers Prev; 21(2); 327–36. ©2011 AACR.
Use of Metformin Is Not Associated with a Decreased Risk of Colorectal Cancer: A Case–Control Analysis
Authors: Bodmer Michael , Becker Claudia , Meier Christian , Jick Susan S. , Meier Christoph R. 
Published: February 2012

Abstract
Background: To explore the association between use of metformin or other antidiabetic drugs and the risk of colorectal cancer.
Methods: Using the United Kingdom–based General Practice Research Database (GPRD), we conducted a nested case–control analysis in patients with diabetes mellitus. Cases had an incident diagnosis of colorectal cancer, and up to 6 controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the GPRD prior to the index date. Results were adjusted for multiple potential confounders.
Results: We identified 920 diabetic patients with colorectal cancer. Mean age ± SD was 70.2 ± 8.6 years and 63.3% were male. Extensive use (≥50 prescriptions) of metformin was associated with a slightly increased risk of colorectal cancer (adjusted OR = 1.43, 95% CI: 1.08–1.90) as compared with non use, with an adjustment of OR = 1.81 (95% CI: 1.25–2.62) in men and of 1.00 (95% CI: 0.63–1.58) in women. Neither extensive use of sulfonylureas (adjusted OR = 0.79, 95% CI: 0.60–1.03) nor insulin (adjusted OR = 0.90, 95% CI: 0.63–1.28) were associated with an increased risk of colorectal cancer. A long-term history of diabetes (&gt;10 years) was not associated with a materially increased risk of colorectal cancer compared with short-term diabetes duration (&lt;2 years; adjusted OR = 1.14, 95% CI: 0.90–1.46).
Conclusion: Use of metformin was linked to an increased risk of colorectal cancer in men. Use of sulfonylureas or insulin was not associated with an altered risk of colorectal cancer.
Impact: Metformin does not prevent colorectal cancer. Cancer Epidemiol Biomarkers Prev; 21(2); 280–6. ©2011 AACR.
"GOLD or lower limit of normal definition? a comparison with expert-based diagnosis of chronic obstructive pulmonary disease in a prospective cohort-study"
Authors: Güder Gülmisal , Brenner Susanne , Angermann Christiane E , Ertl Georg , Held Matthias , Sachs Alfred P , Lammers Jan-Willem , Zanen Pieter , Hoes Arno W , Störk Stefan , Rutten Frans H 
Published: February 2012

Abstract

Background
The Global initiative for chronic Obstructive Lung Disease (GOLD) defines COPD as a fixed post-bronchodilator ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) below 0.7. Age-dependent cut-off values below the lower fifth percentile (LLN) of this ratio derived from the general population have been proposed as an alternative. We wanted to assess the diagnostic accuracy and prognostic capability of the GOLD and LLN definition when compared to an expert-based diagnosis.

Methods
In a prospective cohort study, 405 patients aged ≥ 65 years with a general practitioner's diagnosis of COPD were recruited and followed up for 4.5 (median; quartiles 3.9; 5.1) years. Prevalence rates of COPD according to GOLD and three LLN definitions and diagnostic performance measurements were calculated. The reference standard was the diagnosis of COPD of an expert panel that used all available diagnostic information, including spirometry and bodyplethysmography.

Results
Compared to the expert panel diagnosis, 'GOLD-COPD' misclassified 69 (28%) patients, and the three LLNs misclassified 114 (46%), 96 (39%), and 98 (40%) patients, respectively. The GOLD classification led to more false positives, the LLNs to more false negative diagnoses. The main predictors beyond the FEV1/FVC ratio for an expert diagnosis of COPD were the FEV1 % predicted, and the residual volume/total lung capacity ratio (RV/TLC). Adding FEV1 and RV/TLC to GOLD or LLN improved the diagnostic accuracy, resulting in a significant reduction of up to 50% of the number of misdiagnoses. The expert diagnosis of COPD better predicts exacerbations, hospitalizations and mortality than GOLD or LLN.

Conclusions
GOLD criteria over-diagnose COPD, while LLN definitions under-diagnose COPD in elderly patients as compared to an expert panel diagnosis. Incorporating FEV1 and RV/TLC into the GOLD-COPD or LLN-based definition brings both definitions closer to expert panel diagnosis of COPD, and to daily clinical practice.
Developing community-based preventive interventions in Hong Kong: a description of the first phase of the family project
Authors: Stewart Sunita M , Fabrizio Cecilia S , Hirschmann Malia R , Lam Tai Hing 
Published: February 2012

Abstract

Background
This paper describes the development of culturally-appropriate family-based interventions and their relevant measures, to promote family health, happiness and harmony in Hong Kong. Programs were developed in the community, using a collaborative approach with community partners. The development process, challenges, and the lessons learned are described. This experience may be of interest to the scientific community as there is little information currently available about community-based development of brief interventions with local validity in cultures outside the West.

Methods
The academic-community collaborative team each brought strengths to the development process and determined the targets for intervention (parent-child relationships). Information from expert advisors and stakeholder discussion groups was collected and utilized to define the sources of stress in parent-child relationships.

Results
Themes emerged from the literature and discussion groups that guided the content of the intervention. Projects emphasized features that were appropriate for this cultural group and promoted potential for sustainability, so that the programs might eventually be implemented at a population-wide level. Challenges included ensuring local direction, relevance and acceptability for the intervention content, engaging participants and enhancing motivation to make behavior changes after a brief program, measurement of behavior changes, and developing an equal partner relationship between academic and community staff.

Conclusions
This work has public health significance because of the global importance of parent-child relationships as a risk-factor for many outcomes in adulthood, the need to develop interventions with strong evidence of effectiveness to populations outside the West, the potential application of our interventions to universal populations, and characteristics of the interventions that promote dissemination, including minimal additional costs for delivery by community agencies, and high acceptability to participants.
Systemic air embolism during percutaneous core needle biopsy of the lung: frequency and risk factors
Authors: Freund Martin C , Petersen Johannes , Goder Katharina C , Bunse Tillmann , Wiedermann Franz , Glodny Bernhard 
Published: February 2012

Abstract

Background
Detection of risk factors for an air embolism in the left atrium, left ventricle, or systemic circulation (systemic air embolism, SAE) during a percutaneous core needle biopsy (PCNB) of the thorax.

Methods
In a retrospective observational study, all PCNBs of the thorax in 610 patients between 2007 and 2009 were analyzed. The SmartStep™ technique (General Electric) was used for the biopsy, with which the examiner can prepare a batch of three 1.25-mm or 2.5-mm collimated slices within a second using a foot switch in the CT room to check the needle position. The image data thus generated and the control CT scans that followed were examined retrospectively for the presence of intravascular air. Intravascular air was defined as two or more adjacent voxels with absorption values of < -200 HU in the left atrium, left ventricle, aorta, or arteries during or after the procedure. The univariate statistical analysis of categorical variables was made using 2 by 2 tables and the Fisher test. The groups were compared using the Mann-Whitney test. Finally, a multivariate logistic regression analysis was used to identify independent risk factors for the occurrence of an SAE.

Results
The radiological incidence of an SAE during a PCNB was 3.8% (23/610 patients), whereas the clinically apparent incidence was 0.49%. Two patients developed clinical symptoms consisting of transient hemiplegia or transient amaurosis; one died due to a fatal SAE of the coronary arteries. The mortality was thus 0.16%. The depth of the needle in the lesion (Wald: 6.859), endotracheal anesthesia (Wald: 5.721), location of the lesion above the level of the left atrium (Wald: 5.159), and prone position of the patients (Wald: 4.317) were independent risk factors for the incidence of an SAE (p < 0.05 each). Using explorative criteria, the acute angle of the needle to the tumor surface, and the transition of ventilated lung were independent factors. The frequency of biopsies, needle penetration depth, and tumor location near the diaphragm or in the lower lobe also played a subordinate role, not however, the needle penetration depth through the lung.

Conclusion
If possible, the PCNB should be performed under local anesthesia. We recommend avoiding endotracheal anesthesia and prone position. Whenever possible, patients should be positioned on the back in such a way that the tumor is lower than the left atrium. The tip of the needle should be within the tumor during the biopsy procedure.
Radiographic knee osteoarthritis in ex-elite table tennis players
Authors: Rajabi Reza , Johnson Gillian M , Alizadeh Mohammad H , Meghdadi Nazanin 
Published: February 2012

Abstract

Background
Table tennis involves adoption of the semi-flexed knee and asymmetrical torsional trunk movements creating rotational torques on the knee joint which may predispose players to osteoarthritis (OA) of the knee. This study aims to compare radiographic signs of knee OA and associated functional levels in ex-elite male table tennis players and control subjects.

Methods
Study participants were 22 ex-elite male table tennis players (mean age 56.64 ± 5.17 years) with 10 years of involvement at the professional level and 22 non-athletic males (mean age 55.63 ± 4.08 years) recruited from the general population. A set of three radiographs taken from each knee were evaluated by an experienced radiologist using the Kellgren and Lawrence (KL) scale (0-4) to determine radiographic levels of OA severity. The intercondylar distance was taken as a measure of lower limb angulation. Participants also completed the pain, stiffness, and physical function categories of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) 3.1 questionnaire.

Results
The results showed 78.3% of the ex-elite table tennis players and 36.3% of controls had varying signs of radiographic knee OA with a significant difference in the prevalence levels of definite radiographic OA (KL scale > 2) found between the two groups (P ≤ 0.001). Based on the WOMAC scores, 68.2% of the ex-elite table tennis players reported symptoms of knee pain compared with 27.3% of the controls (p = 0.02) though no significant differences were identified in the mean physical function or stiffness scores between the two groups. In terms of knee alignment, 73.7% of the ex-elite athletes and 32% of the control group had signs of altered lower limb alignment (genu varum) (p = 0.01). Statistical differences were found in subjects categorized as having radiographic signs of OA and altered lower limb alignment (p = 0.03).

Conclusions
Ex-elite table tennis players were found to have increased levels of radiological signs of OA in the knee joint though this did not transpire through to altered levels of physical disability or knee stiffness in these players when compared with subjects from the general population suggesting that function in these players is not severely impacted upon.
A direct detection of Escherichia coli genomic DNA using gold nanoprobes
Authors: Bakthavathsalam Padmavathy , Rajendran Vinoth Kumar , Baquir Mohammed Jaffar Ali 
Published: February 2012

AbstractBackgroundIn situation like diagnosis of clinical and forensic samples there exists a need for highly sensitive, rapid and specific DNA detection methods. Though conventional DNA amplification using PCR can provide fast results, it is not widely practised in diagnostic laboratories partially because it requires skilled personnel and expensive equipment. To overcome these limitations nanoparticles have been explored as signalling probes for ultrasensitive DNA detection that can be used in field applications. Among the nanomaterials, gold nanoparticles (AuNPs) have been extensively used mainly because of its optical property and ability to get functionalized with a variety of biomolecules.ResultsWe report a protocol for the use of gold nanoparticles functionalized with single stranded oligonucleotide (AuNP- oligo probe) as visual detection probes for rapid and specific detection ofEscherichia coli. The AuNP- oligo probe on hybridization with target DNA containing complementary sequences remains red whereas test samples without complementary DNA sequences to the probe turns purple due to acid induced aggregation of AuNP- oligo probes. The color change of the solution is observed visually by naked eye demonstrating direct and rapid detection of the pathogenicEscherichia colifrom its genomic DNA without the need for PCR amplification. The limit of detection was ~54 ng for unamplified genomic DNA. The method requires less than 30 minutes to complete after genomic DNA extraction. However, by using unamplified enzymatic digested genomic DNA, the detection limit of 11.4 ng was attained. Results of UV-Vis spectroscopic measurement and AFM imaging further support the hypothesis of aggregation based visual discrimination. To elucidate its utility in medical diagnostic, the assay was validated on clinical strains of pathogenicEscherichia coliobtained from local hospitals and spiked urine samples. It was found to be 100% sensitive and proves to be highly specific without any cross reaction with non-Escherichia colistrains.ConclusionThis work gives entry into a new class of DNA/gold nanoparticles hybrid materials which might have optical property that can be controlled for application in diagnostics. We note that it should be possible to extend this strategy easily for developing new types of DNA biosensor for point of care detection. The salient feature of this approach includes low-cost, robust reagents and simple colorimetric detection of pathogen.
Characterization of the seminal plasma proteome in men with prostatitis by mass spectrometry
Authors: Kagedan Daniel , Lecker Irene , Batruch Ihor , Smith Christopher , Kaploun Ilia , Lo Kirk , Grober Ethan , Diamandis Eleftherios P , Jarvi Keith A 
Published: February 2012

Abstract

Background
Prostatitis is an inflammation of the prostate gland which affects approximately 10% of men. Despite its frequency, diagnosing prostatitis and monitoring patient response to treatment remains frustrating. As the prostate contributes a substantial percentage of proteins to seminal plasma, we hypothesized that a protein biomarker of prostatitis might be found by comparing the seminal plasma proteome of patients with and without prostatitis.

Results
Using mass spectrometry, we identified 1708 proteins in the pooled seminal plasma of 5 prostatitis patients. Comparing this list to a previously published list of seminal plasma proteins in the pooled seminal plasma of 5 healthy, fertile controls yielded 1464 proteins in common, 413 found only in the control group, and 254 found only in the prostatitis group. Applying a set of criteria to this dataset, we generated a high-confidence list of 59 candidate prostatitis biomarkers, 33 of which were significantly increased in prostatitis as compared to control, and 26 of which were decreased. The candidates were analyzed using Gene Ontology and Ingenuity Pathway analysis to delineate their subcellular localizations and functions.

Conclusions
Thus, in this study, we identified 59 putative biomarkers in seminal plasma that need further validation for diagnosis and monitoring of prostatitis.