bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia induces differential translation of enolase/MBP-1
Authors: Sedoris Kara C , Thomas Shelia D , Miller Donald M 
Published: April 2010

AbstractBackgroundHypoxic microenvironments in tumors contribute to transformation, which may alter metabolism, growth, and therapeutic responsiveness. The α-enolase gene encodes both a glycolytic enzyme (α-enolase) and a DNA-binding tumor suppressor protein, c-myc binding protein (MBP-1). These divergent α-enolase gene products play central roles in glucose metabolism and growth regulation and their differential regulation may be critical for tumor adaptation to hypoxia. We have previously shown that MBP-1 and its binding to the c-myc P2promoter regulates the metabolic and cellular growth changes that occur in response to altered exogenous glucose concentrations.ResultsTo examine the regulation of α-enolase and MBP-1 by a hypoxic microenvironment in breast cancer, MCF-7 cells were grown in low, physiologic, or high glucose under 1% oxygen. Our results demonstrate that adaptation to hypoxia involves attenuation of MBP-1 translation and loss of MBP-1-mediated regulation of c-myc transcription, evidenced by decreased MBP-1 binding to the c-myc P2promoter. This allows for a robust increase in c-myc expression, "early c-myc response", which stimulates aerobic glycolysis resulting in tumor acclimation to oxidative stress. Increased α-enolase mRNA and preferential translation/post-translational modification may also allow for acclimatization to low oxygen, particularly under low glucose concentrations.ConclusionsThese results demonstrate that malignant cells adapt to hypoxia by modulating α-enolase/MBP-1 levels and suggest a mechanism for tumor cell induction of the hyperglycolytic state. This important "feedback" mechanism may help transformed cells to escape the apoptotic cascade, allowing for survival during limited glucose and oxygen availability.
Atypical/Nor98 scrapie in the Basque Country: a case report of eight outbreaks
Authors: Rodríguez-Martínez Ana B , Garrido Joseba M , Maza Sonia , Benedicto Leyre , Geijo Mariví , Gómez Nieves , Minguijón Esmeralda , Benestad Sylvie L , Juste Ramón A 
Published: April 2010

Abstract

Background
Since 2002, an active surveillance program for transmissible spongiform encephalopathy in small ruminants in European Union countries allowed identification of a considerable number of atypical cases with similarities to the previously identified atypical scrapie cases termed Nor98.

Case presentation
Here we report molecular and neuropathological features of eight atypical/Nor98 scrapie cases detected between 2002 and 2009. Significant features of the affected sheep included: their relatively high ages (mean age 7.9 years, range between 4.3 and 12.8), their breed (all Latxa) and their PRNP genotypes (AFRQ/ALRQ, ALRR/ALRQ, AFRQ/AFRQ, AFRQ/AHQ, ALRQ/ALRH, ALRQ/ALRQ). All the sheep were confirmed as atypical scrapie by immunohistochemistry and immunoblotting. Two cases presented more PrP immunolabelling in cerebral cortex than in cerebellum.

Conclusions
This work indicates that atypical scrapie constitutes the most common small ruminant transmissible spongiform encephalopathy form in Latxa sheep in the Spanish Basque Country. Moreover, a new genotype (ALRQ/ALRH) was found associated to atypical scrapie.
Building and analyzing protein interactome networks by cross-species comparisons
Authors: Wiles Amy M , Doderer Mark , Ruan Jianhua , Gu Ting-Ting , Ravi Dashnamoorthy , Blackman Barron , Bishop Alexander JR 
Published: April 2010

AbstractBackgroundA genomic catalogue of protein-protein interactions is a rich source of information, particularly for exploring the relationships between proteins. Numerous systems-wide and small-scale experiments have been conducted to identify interactions; however, our knowledge of all interactions for any one species is incomplete, and alternative means to expand these network maps is needed. We therefore took a comparative biology approach to predict protein-protein interactions across five species (human, mouse, fly, worm, and yeast) and developed InterologFinder for research biologists to easily navigate this data. We also developed a confidence score for interactions based on available experimental evidence and conservation across species.ResultsThe connectivity of the resultant networks was determined to have scale-free distribution, small-world properties, and increased local modularity, indicating that the added interactions do not disrupt our current understanding of protein network structures. We show examples of how these improved interactomes can be used to analyze a genome-scale dataset (RNAi screen) and to assign new function to proteins. Predicted interactions within this dataset were tested by co-immunoprecipitation, resulting in a high rate of validation, suggesting the high quality of networks produced.ConclusionsProtein-protein interactions were predicted in five species, based on orthology. An InteroScore, a score accounting for homology, number of orthologues with evidence of interactions, and number of unique observations of interactions, is given to each known and predicted interaction. Our websitehttp://www.interologfinder.orgprovides research biologists intuitive access to this data.
Evaluation of a low-cost, portable imaging system for early detection of oral cancer
Authors: Rahman Mohammed S , Ingole Nilesh , Roblyer Darren , Stepanek Vanda , Richards-Kortum Rebecca , Gillenwater Ann , Shastri Surendra , Chaturvedi Pankaj 
Published: April 2010

Abstract

Background
There is an important global need to improve early detection of oral cancer. Recent reports suggest that optical imaging technologies can aid in the identification of neoplastic lesions in the oral cavity; however, there is little data evaluating the use of optical imaging modalities in resource limited settings where oral cancer impacts patients disproportionately. In this article, we evaluate a simple, low-cost optical imaging system that is designed for early detection of oral cancer in resource limited settings. We report results of a clinical study conducted at Tata Memorial Hospital (TMH) in Mumbai, India using this system as a tool to improve detection of oral cancer and its precursors.

Methods
Reflectance images with white light illumination and fluorescence images with 455 nm excitation were obtained from 261 sites in the oral cavity from 76 patients and 90 sites in the oral cavity from 33 normal volunteers. Quantitative image features were used to develop classification algorithms to identify neoplastic tissue, using clinical diagnosis of expert observers as the gold standard.

Results
Using the ratio of red to green autofluorescence, the algorithm identified tissues judged clinically to be cancer or clinically suspicious for neoplasia with a sensitivity of 90% and a specificity of 87%.

Conclusions
Results suggest that the performance of this simple, objective low-cost system has potential to improve oral screening efforts, especially in low-resource settings.
Frailty, Serum Androgens, and the CAG Repeat Polymorphism: Results from the Massachusetts Male Aging Study
Authors: Travison Thomas G. , Shackelton Rebecca , Araujo Andre B. , Morley John E. , Williams Rachel E. , Clark Richard V. , McKinlay John B. 
Published: April 2010

AbstractContext: The CAG repeat polymorphism in the androgen receptor, denoted (CAG)n, is thought to (inversely) index androgen sensitivity. We hypothesized that (CAG)n would exhibit a modifying influence on the association between circulating total and calculated free testosterone (TT and FT) and physical frailty in aging men.Objective: The objective of the study was to establish the influence of (CAG)n on the relation between circulating TT, FT, LH, SHBG, and frailty.Design: This was a prospective cohort study of health and endocrine functioning in randomly selected men, with a baseline (T1: 1987–89) and two follow-up (T2: 1995–1997; T3: 2002–2004) visits.Setting: This was an observational study of men residing in greater Boston, MA.Participants: A total of 624 subjects aged 50–86 yr were retained.Main Outcome Measures: The frailty phenotype was measured at T3. Components included weight loss, exhaustion, low physical activity, weakness, and slowness. Subjects exhibiting two of these five components were considered to be in an intermediate state, and those exhibiting three or more were considered frail.Results: (CAG)n was positively associated with TT and FT. Multivariable regression analyses revealed no influence of CAG on longitudinal within-subject changes in hormone levels or cross-sectional (T3) associations between hormone concentrations and the prevalence of intermediate frailty or frailty. Models incorporating subjects’ history of hormone decline produced similar negative results.Conclusions: This population-based study does not support the hypothesis that interindividual differences in (CAG)n can account for a lack of association between circulating androgens and the frailty phenotype. Longitudinal analyses are needed to confirm these conclusions.
Evaluation of international recruitment of health professionals in England
Authors: Young Ruth , Noble Jenny , Mahon Ann , Maxted Mairead , Grant Janet , Sibbald Bonnie 
Published: April 2010

Objectives: To explore whether a period of intensive international recruitment by the English National Health Service (NHS) achieved its objectives of boosting workforce numbers and to set this against the wider costs, longer-term challenges and questions arising. Methods: A postal survey of all pre-2006 NHS providers, Strategic Health Authorities and Deans of Postgraduate Medical Education obtained information on 284 (45%) organizations (142 completed questionnaires). Eight subsequent case studies (74 interviews) covered medical consultant, general practitioner, nurse, midwife and allied health professional recruitment. Results: Most respondents had undertaken or facilitated international recruitment between 2001 and 2006 and believed that it had enabled them to address immediate staff shortages. Views on longer-term implications, such as recruit retention, were more equivocal. Most organizations had made only a limited value-for-money assessment, balancing direct expenditure on overseas recruitment against savings on temporary staff. Other short and long-term transaction and opportunity costs arose from pressures on existing staff, time spent on induction/pastoral support, and human resource management and workforce planning challenges. Though recognized, these extensive ‘hidden costs’ for NHS organizations were harder to assess as were the implications for source countries and migrant staff. Conclusions: The main achievement of the intensive international recruitment period from a UK viewpoint was that such a major undertaking was seen through without major disruption to NHS services. The wider costs and challenges meant, however, that large-scale international recruitment was not sustainable as a solution to workforce shortages. Should such approaches be attempted in future, a clearer upfront appraisal of all the potential costs and implications will be vital.
Circle configurations in strictly convex normed planes
Authors: Spirova Margarita 
Published: April 2010

AbstractWe present extensions of results of P. J. Kelly [Amer. Math. Monthly 57: 677–678, 1950] on the so-called re-entrant property of circles in strictly convex normed (or Minkowski) planes, and also further properties of circles, well known for the Euclidean plane, are generalized for all strictly convex Minkowski planes. More precisely, we present “Minkowskian analogues” of the philosophical symbol Yin-Yang, of the Arbelos, a special case of the famous Apollonius problem on circles touching each other, and one of the Sangaku-circles problems (coming from the Japanese Temple Geometry). The latter is remarkable since the consideration of this type of problems in the Euclidean plane requires the use of inversion or of the Pythagorean Theorem (i.e., of tools having no analogues in normed planes). Finally we observe that a strictly convex normed plane which, in addition, is smooth can be considered as a flat Möbius plane where, for example, Apollonius' problem is solved.
Cardiovascular and Metabolic Effects of Medroxyprogesterone Acetate versus Conjugated Equine Estrogen After Premenopausal Hysterectomy with Bilateral Ovariectomy
Authors: Kalyan Shirin , Hitchcock Christine L. , Sirrs Sandra , Pudek Morris , Prior Jerilynn C. 
Published: April 2010

Study Objective. To compare the cardiovascular and metabolic effects of medroxyprogesterone acetate (MPA) with those of conjugated equine estrogen (CEE) as single‐hormone therapies in women who underwent hysterectomy with bilateral ovariectomy.Design. Secondary analysis of a 12–month, double‐blind, randomized, parallel‐therapy trial.Setting. Four teaching hospitals and one community hospital in Vancouver, Canada.Participants. Thirty‐three healthy women who underwent premenopausal hysterectomy with bilateral ovariectomy.Intervention. Subjects received either MPA 10 mg/day (18 women) or CEE 0.6 mg/day (15 women) for 12 months, started immediately after hysterectomy with bilateral ovariectomy.Measurements and Main Results. Lipid profiles (high‐density lipoprotein cholesterol [HDL], total cholesterol, apolipoprotein B, and triglyceride levels), homeostatic measures (hemoglobin A1c and fasting blood glucose level), hormone levels (free and bioavailable testosterone, cortisol, sex hormone‐binding globulin [SHBG], and dehydroepiandrosterone sulfate), inflammatory markers (C‐reactive protein [CRP] and serum albumin levels), and anthropometric measures (body mass index [BMI], truncal fat, and total body fat) were assessed over the 12–month period. After 12 months, the women assigned to MPA had lesser increases in BMI (p=0.04), triglyceride (p=0.003), HDL (p<0.0005), SHBG (p<0.0005), total testosterone (p=0.003), and CRP values (p=0.01) and higher serum albumin levels (p<0.0005) compared with the women receiving CEE.Conclusion. Therapy with CEE, but not MPA, after surgical menopause appears to predispose healthy women to low‐grade inflammation, as evidenced by its independent associations with elevated CRP and reduced albumin levels. In women treated with MPA, the favorable levels of inflammatory markers, BMI, and triglyceride levels need to be confirmed in larger controlled trials, as progesterone therapy may provide a safe and effective alternative to estrogen for vasomotor symptoms in women with surgical menopause.
The Road Not Taken and Choices in Radiation Oncology
Authors: Coleman C. Norman , Glatstein Eli 
Published: April 2010

Abstract
Accomplishments and contributions in a career in radiation oncology, and in medicine in general, involve individual choices that impact the direction of a specialty, decisions in patient care, consequences of treatment outcome, and personal satisfaction. Issues in radiation oncology include: the development and implementation of new radiation treatment technology; the use of multimodality and biologically based therapies; the role of nonradiation “energy” technologies, often by other medical specialties, including the need for quality assurance in treatment and data reporting; and the type of evidence, including appropriate study design, analysis, and rigorous long-term follow-up, that is sought before widespread implementation of a new treatment. Personal choices must weigh: the pressure from institutions—practices, departments, universities, and hospitals; the need to serve society and the underserved; the balance between individual reward and a greater mission; and the critical role of personal values and integrity, often requiring difficult and “life-defining” decisions. The impact that each of us makes in a career is perhaps more a result of character than of the specific details enumerated on one's curriculum vitae. The individual tapestry weaved by choosing the more or less traveled paths during a career results in many pathways that would be called success; however, the one path for which there is no good alternative is that of living and acting with integrity.
The Transcription Factor Rfx3 Regulates β-Cell Differentiation, Function, and Glucokinase Expression
Authors: Ait-Lounis Aouatef , Bonal Claire , Seguín-Estévez Queralt , Schmid Christoph D. , Bucher Philipp , Herrera Pedro L. , Durand Bénédicte , Meda Paolo , Reith Walter 
Published: April 2010

OBJECTIVE
Pancreatic islets of perinatal mice lacking the transcription factor Rfx3 exhibit a marked reduction in insulin-producing β-cells. The objective of this work was to unravel the cellular and molecular mechanisms underlying this deficiency.

RESEARCH DESIGN AND METHODS
Immunofluorescence studies and quantitative RT-PCR experiments were used to study the emergence of insulin-positive cells, the expression of transcription factors implicated in the differentiation of β-cells from endocrine progenitors, and the expression of mature β-cell markers during development in Rfx3−/− and pancreas-specific Rfx3-knockout mice. RNA interference experiments were performed to document the consequences of downregulating Rfx3 expression in Min6 β-cells. Quantitative chromatin immunoprecipitation (ChIP), ChIP sequencing, and bandshift experiments were used to identify Rfx3 target genes.

RESULTS
Reduced development of insulin-positive cells in Rfx3−/− mice was not due to deficiencies in endocrine progenitors or β-lineage specification, but reflected the accumulation of insulin-positive β-cell precursors and defective β-cells exhibiting reduced insulin, Glut-2, and Gck expression. Similar incompletely differentiated β-cells developed in pancreas-specific Rfx3-deficient embryos. Defective β-cells lacking Glut-2 and Gck expression dominate in Rfx3-deficent adults, leading to glucose intolerance. Attenuated Glut-2 and glucokinase expression, and impaired glucose-stimulated insulin secretion, were also induced by RNA interference–mediated inhibition of Rfx3 expression in Min6 cells. Finally, Rfx3 was found to bind in Min6 cells and human islets to two well-known regulatory sequences, Pal-1 and Pal-2, in the neuroendocrine promoter of the glucokinase gene.

CONCLUSIONS
Our results show that Rfx3 is required for the differentiation and function of mature β-cells and regulates the β-cell promoter of the glucokinase gene.
Reliability of Shoulder Internal Rotation Passive Range of Motion Measurements in the Supine Versus Sidelying Position
Authors: Lunden Jason B. , Muffenbier Mike , Giveans M. Russell , Cieminski Cort J. 
Published: April 2010

Study Design Clinical measurement, reliability. Objective To compare intrarater and interrater reliability of shoulder internal rotation (IR) passive range of motion measurements utilizing a standard supine position and a sidelying position. Background Glenohumeral IR range of motion deficits are often noted in patients with shoulder pathology. Excellent intrarater reliability has been found when measuring this motion. However, interrater reliability has been reported as poor to fair. Some clinicians currently use a sidelying position for IR stretching with patients who have shoulder pathology. However, no objective data exist for IR passive range of motion measured in this sidelying position, either in terms of reliability or normative values. Methods Seventy subjects (mean age, 36.8 years), with (n = 19) and without (n = 51) shoulder pathology, were included in this study. Shoulder IR passive range of motion of the dominant shoulder or involved shoulder was measured by 2 investigators in 2 positions: (1) a standard supine position, with the shoulder at 90° of abduction, and (2) in sidelying on the tested side, with the shoulder flexed to 90°. Results Intrarater reliability for supine measurements was good to excellent (ICC3,1 = 0.70–0.93) and for sidelying measurements was excellent (ICC3,1 = 0.94–0.98). Interrater reliability was fair to good for the supine measurement (ICC2,2 = 0.74–0.81) and good to excellent for the sidelying measurement (ICC2,2 = 0.88–0.96). The mean (range) value of the dominant shoulder sidelying IR passive range of motion was 40° (11° to 69°) for healthy subjects and 25° (−16° to 49°) for subjects with shoulder pathology. Conclusions For subjects with shoulder pathology, measurements of shoulder IR made in the sidelying position had superior intrarater and interrater reliability compared to those in the standard supine position. J Orthop Sports Phys Ther 2010;40(9):589–594. doi:10.2519/jospt.2010.3197
Differential Diagnosis and Physical Therapy Management of a Patient With Radial Wrist Pain of 6 Months' Duration: A Case Report
Authors: González-Iglesias Javier , Huijbregts Peter , Fernández-De-Las-Peñas César , Cleland Joshua A. 
Published: April 2010

Study Design Case report. Background Differential diagnosis for patients with radial wrist pain requires consideration of systemic disease, referred pain to the radial aspect of the wrist, and local dysfunction. The list of possible local dysfunctions should include De Quervain syndrome, as well as entrapment neuropathy of the superficial radial nerve. Case Description The patient was a 57-year-old man with right radial wrist pain of 6 months' duration. The referral diagnosis was De Quervain syndrome, but a previous course of electrophysical agents-based physical therapy management had been unsuccessful. The physical examination ruled out the cervical, shoulder, elbow, and wrist joints as possible sources of pain. In this case, the diagnosis of entrapment neuropathy of the superficial radial nerve, rather than De Quervain syndrome, was primarily based on the symptom provocation resulting from a modified radial bias upper limb nerve tension test. Based on this diagnosis, treatment consisted of active and passive exercises using neurodynamic techniques. Outcomes After 1 treatment session, the patient noted changes with regard to current pain intensity and function that exceeded the minimal clinically important difference and the minimal detectable change, respectively. After only 2 treatment sessions, the patient reported a complete resolution of symptoms and a full return to work. Discussion This case report critically evaluates the diagnostic process for patients with radial wrist pain and suggests neuropathy of the superficial sensory branch of the radial nerve as a differential diagnostic option. Level of Evidence Therapy, level 4. J Orthop Sports Phys Ther 2010;40(6):361–368. doi:10.2519/jospt.2010.3210