tbuckley/cabot-search huggingface dataset:
Quantitation of Aurora Kinase A Gene Copy Number in Urine Sediments and Bladder Cancer Detection
Authors: Hong-Seok Park, Weon Seo Park, Jolanta Bondaruk, Noriyoshi Tanaka, Hiroshi Katayama, Sangkyou Lee, Philippe E. Spiess, Jordan R. Steinberg, Zhi Wang, Ruth L. Katz, Colin Dinney, Keren J. Elias, Yair Lotan, Rizwan C. Naeem, Keith Baggerly, Subrata Sen, H. Barton Grossman, Bogdan Czerniak
Journal: JNCI Journal of the National Cancer Institute (2008)

Chromosome missegregation and the resulting aneuploidy is a common change in neoplasia. The Aurora kinase A (AURKA) gene, which encodes a key regulator of mitosis, is frequently amplified and/or overexpressed in cancer cells, and the level of AURKA amplification is associated with the level of aneuploidy. We examined whether AURKA gene amplification is a biomarker for the detection of bladder cancer.The effect of ectopic expression of Aurora kinase A (AURKA) using an adenoviral vector in simian virus 40-immortalized urothelial cells (SV-HUC) on centrosome multiplication and chromosome copy number was measured in vitro by immunofluorescence and fluorescence in situ hybridization (FISH), respectively. The FISH test was also used to examine AURKA gene copy number in exfoliated cells in voided urine samples from 23 patients with bladder cancer and 7 healthy control subjects (training set), generating a model for bladder cancer detection that was subsequently validated in an independent set of voided urine samples from 100 bladder cancer patients and 148 control subjects (92 healthy individuals and 56 patients with benign urologic disorders). An AURKA gene score (the proportion of cells with three or more AURKA signals) was used to produce receiver operating characteristic (ROC) curves and to calculate the specificity and sensitivity of the AURKA FISH test. Differences between mean AURKA scores in different pathogenetic groups of bladder cancer stratified according to histological grade and stage were tested by unpaired Mann-Whitney t tests or one-way Wilcoxon tests. All statistical tests were two-sided.Forced overexpression of AURKA in urothelial cells induced amplification of centrosomes, chromosome missegregation, and aneuploidy, and natural overexpression was detectable in in situ lesions from patients with bladder cancer. The FISH test for the AURKA gene copy number performed on the validation set yielded a specificity of 96.6% (95% confidence interval [CI] = 92.3% to 98.5%) and sensitivity of 87% (95% CI = 79.0% to 92.2%) and an area under the ROC curve of 0.939 (95% CI = 0.906 to 0.971; P < .001).Overexpression of AURKA can cause aneuploidy in urothelial cells, and the AURKA gene copy number is a promising biomarker for detection of bladder cancer.
Return to play guidelines after anterior cruciate ligament surgery
Authors: G Myklebust, R Bahr
Journal: British Journal of Sports Medicine (2005)

Doctors should question whether return to high level pivoting sports is in the athlete’s best interest after ACL reconstruction

“When can I play again, Doc?” is the emotionally charged, quintessential question asked by nearly every athlete after anterior cruciate ligament (ACL) injury. Invariably, the same question is one of the first asked by parents, team mates, coaches, and—in the case of the high profile athlete—the media. This implies that, to meet the expectations of the athlete and his/her surroundings, swift surgical intervention and accelerated rehabilitation becomes a priority. Therefore it is not surprising if the time to return to play is the standard by which orthopaedic surgeons measure themselves and are measured in sports circles.

Measured by this standard, sports medicine has made giant advances in ACL treatment programmes during the previous decades. We have progressed from open surgery to arthroscopic surgery, from extended casting to short term bracing, from conservative to accelerated rehabilitation programmes, and from long hospital stays to outpatient surgery. When an athlete is injured today, it is expected that arthroscopic surgery will take place a few weeks after injury, that rehabilitation is started immediately, and that the patient is able to return to sport in four to nine months. The “best” surgeons and physiotherapists are rumoured to return players even sooner.

“Are there other criteria whereby we should measure treatment outcome than the time to return to sport?” 

Lost in the need to succeed and with the fear of defeat deeply embedded in our decision making processes, it is no wonder that we rarely ask: “Is it time to quit? Is it safe to return patients to pivoting sports? What are the long term results of our treatment programmes? Are there other criteria whereby we should measure treatment outcome than the time to return to sport?” …
Age-specific and sex-specific adult mortality risk in India in 2014: analysis of 0·27 million nationally surveyed deaths and demographic estimates from 597 districts
Authors: Usha Ram, Prabhat Jha, Patrick Gerland, Ryan J Hum, Peter Rodriguez, Wilson Suraweera, Kaushalendra Kumar, Rajesh Kumar, Rajesh Dikshit, Denis Xavier, Rajeev Gupta, Prakash C Gupta, Faujdar Ram
Journal: The Lancet Global Health (2015)

BackgroundAs child mortality decreases rapidly worldwide, premature adult mortality is becoming an increasingly important contributor to global mortality. Any possible worldwide reduction of premature adult mortality before the age of 70 years will depend on progress in India. Indian districts increasingly have responsibility for implementing public health programmes. We aimed to assess age-specific and sex-specific adult mortality risks in India at the district level.MethodsWe analysed data from five national surveys of 0·27 million adult deaths at an age of 15–69 years together with 2014 demographic data to estimate age-specific and sex-specific adult mortality risks for 597 districts. Cause of death data were drawn from the verbal autopsies in the Registrar General of India's ongoing Million Death Study.FindingsIn 2014, about two-fifths of India's men aged 15–69 years lived in the 253 districts where the conditional probability of a man dying at these ages exceeded 50%, and more than a third of India's women aged 15–69 years lived in the 222 districts where the conditional probability of a woman dying exceeded 40%. The probabilities of a man or woman dying by the age of 70 years in high-mortality districts was 62% and 54%, respectively, whereas the probability of a man or woman dying by the age of 70 years in low-mortality districts was 40% and 30%, respectively. The roughly 10-year survival gap between high-mortality and low-mortality districts was nearly as extreme as the survival gap between the entire Indian population and people living in high-income countries. Adult mortality risks at ages 15–69 years was highest in east India and lowest in west India, by contrast with the north–south divide for child mortality. Vascular disease, tuberculosis, malaria and other infections, and respiratory diseases accounted for about 60% of the absolute gap in adult mortality risk at ages 15–69 years between high-mortality and low-mortality districts. Most of the variation in adult mortality could not be explained by known determinants or risk factors for premature mortality.InterpretationIndia's large variation in adult mortality by district, notably the higher death rates in eastern India, requires further aetiological research, particularly to explore whether high levels of adult mortality risks from infections and non-communicable diseases are a result of historical childhood malnutrition and infection. Such research can be complemented by an expanded coverage of known effective interventions to reduce adult mortality, especially in high-mortality districts.FundingNational Institutes of Health, Canadian Institutes of Health Research, University of Toronto.
The three-dimensional dynamic geometry of the left ventricle in the conscious dog.
Authors: J S Rankin, P A McHale, C E Arentzen, D Ling, J C Greenfield, R W Anderson
Journal: Circulation Research (1976)

The dynamic geometry of the left ventricle was assessed with the use of chronically implanted pulse-transit ultrasonic dimension transducers. The orientation of the transducers allowed the measurement of left ventricular minor and major axis diameters and equatorial wall thickness in the conscious dog. The left ventricle was modeled as a three-dimensional, prolate ellipsoidal shell. Left ventricular and pleural pressures were measured with high fidelity micromanometers. Aortic blood flow was obtained with electromagnetic flow probes. To test the assumptions inherent in this technique, left ventricular mass, internal volume, stroke volume, and peak aortic flow were computed from the dimension data and compared to directly measured values. Correlation coefficients of 0.95 or greater were obtained for each of these comparisons. In addition, the calculated left ventricular mass was constant to within +/- 6% of the mean value throughout the cardiac cycle. We found that the dynamic contraction pattern of the left ventricle was dependent on the physiological state of the dog. Furthermore, in the conscious state, shortening of the minor axis diameter, lengthening of the major axis diameter, and slight thickening or thinning of the wall were noted during isovolumic contraction (isovolumic ellipticalization pattern). In the open-chested, anesthetized state, however, marked rearrangements in geometry were observed during isovolumic contraction manifested by lengthening of the minor axis diameter, and significant thickening of the wall (isovolumic sphericalization pattern). We also observed that left ventricular volume was significantly diminished in the open-chested state. The isovolumic contraction pattern in open-chested dogs could be changed from sphericalization to ellipticalization by increasing end-diastolic volume with the infusion of saline. During a vena caval occlusion in the conscious state, the contraction pattern changed from isovolumic ellipticalization to isovolumic sphericalization as the end-diastolic volume decreased. Thus, the exact pattern of left ventricular contraction was found to be a function of left ventricular volume.
Reprogramming Tumor-Associated Dendritic Cells <i>In Vivo</i> Using miRNA Mimetics Triggers Protective Immunity against Ovarian Cancer
Authors: Juan R. Cubillos-Ruiz, Jason R. Baird, Amelia J. Tesone, Melanie R. Rutkowski, Uciane K. Scarlett, Ana L. Camposeco-Jacobs, Jorge Anadon-Arnillas, Noah M. Harwood, Murray Korc, Steven N. Fiering, Lorenzo F. Sempere, Jose R. Conejo-Garcia
Journal: Cancer Research (2012)

Abstract Modulating the activity of miRNAs provides opportunities for novel cancer interventions. However, low bioavailability and poor cellular uptake are major challenges for delivering miRNA mimetics specifically to tumor cells. Here, we took advantage of the spontaneous enhanced endocytic activity of ovarian cancer-associated dendritic cells (DC) to selectively supplement the immunostimulatory miRNA miR-155. In vivo processing of nanoparticles carrying oligonucleotide duplexes mimicking the bulged structure of endogenous pre-miRNA (but not siRNA-like oligonucleotides) dramatically augmented miR-155 activity without saturating the RNA-induced silencing complex. Endogenous processing of synthetic miR-155 favored Ago2 and, to a lesser extent, Ago4 loading, resulting in genome-wide transcriptional changes that included silencing of multiple immunosuppressive mediators. Correspondingly, tumor-infiltrating DCs were transformed from immunosuppressive to highly immunostimulatory cells capable of triggering potent antitumor responses that abrogated the progression of established ovarian cancers. Our results show both the feasibility and therapeutic potential of supplementing/replenishing miRNAs in vivo using nonviral approaches to boost protective immunity against lethal tumors. Thus, we provide a platform, an optimized design, and a mechanistic rationale for the clinical testing of nonviral miRNA mimetics. Cancer Res; 72(7); 1683–93. ©2012 AACR.
Wireless connectivity for health and sports monitoring: a review
Authors: S Armstrong
Journal: British Journal of Sports Medicine (2007)

This is a review of health and sports monitoring research that uses or could benefit from wireless connectivity. New, enabling wireless connectivity standards are evaluated for their suitability, and an assessment of current exploitation of these technologies is summarised. An example of the application is given, highlighting the capabilities of a network of wireless sensors. Issues of timing and power consumption in a battery-powered system are addressed to highlight the benefits networking can provide, and a suggestion of how monitoring different biometric signals might allow one to gain additional information about an athlete or patient is made.
COMPARISON OF THE PROGNOSTIC VALUE OF PEAK CK-MB AND TROPONIN LEVELS AMONG PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Authors: Chee Tang Chin, Tracy Y. Wang, Shuang Li, Eric D. Peterson, Stephen D. Wiviott, James A. deLemos, Michael C. Kontos, Matthew T. Roe
Journal: Journal of the American College of Cardiology (2010)
Wall Tissue Remodeling Regulates Longitudinal Tension in Arteries
Authors: Zane S. Jackson, Avrum I. Gotlieb, B. Lowell Langille
Journal: Circulation Research (2002)

Changes in blood pressure or flow induce arterial remodeling that normalizes mechanical loads that are imposed on arterial tissue. Arteries are also under substantial longitudinal stretch (axial strain) that may be altered by growth or atrophy of tissues to which they are attached. We therefore tested whether axial strain is also regulated in a negative feedback manner through arterial remodeling. Axial strain in rabbit carotid arteries was increased from 62±2% to 97±2% without altering other mechanical loads on wall tissues. Strain was reduced within 3 days and completely normalized by 7 days. Remodeling involved tissue elaboration, endothelial cell replication rates were increased by &gt;50-fold and smooth muscle cell replication rates were increased by &gt;15-fold, and substantially elevated DNA, elastin, and collagen contents were recorded. Also, increased rates of apoptosis were indicated by degradation of DNA into oligonucleosomes, and matrix remodeling was reflected in enlarged fenestrae in the internal elastic lamina and increased expression and activation of gelatinases, especially matrix metalloproteinase-2. Intriguingly, reduced axial strain was not normalized, presumably because remodeling processes, apart from cell contraction, are ineffective in decreasing strain, and arterial smooth muscle orientation precludes large effects of contraction on axial strain.
Discharge coordinator intervention prevents hospitalisations in patients with COPD: A randomized controlled trial
Authors: Mitja Lainscak, Sasa Kadivec, Mitja Kosnik, Barbara Benedik, Marjana Bratkovic, Tatjana Jakhel, Robert Marcun, Petra Miklosa, Barbara Stalc, Jerneja Farkas
Journal: European Respiratory Journal (2012)

Background. Discharge planning is key element in the healthcare continuum that seeks to bridge the gap between hospital and patient home environment. As limited data is available for COPD, we conceived this study to determine the effectiveness of discharge coordinator intervention in reducing the risk for COPD hospitalisation.  Methods. This was a randomized, controlled trial that compared discharge coordinator intervention with usual care. Patients were enrolled within 48 hours following admission due to COPD exacerbation. Discharge coordinator intervention included educational and self-management sessions with patients and caregivers and liaison with health and social care providers in patient home environment. Patients in control group received standard management.  Results. Of the 253 eligible patients (71±9 years, 72% men, 87% GOLD III/IV), 118 were assigned to intervention and 135 to usual care group. During follow-up of 180 days, fewer patients receiving intervention were hospitalized due to COPD (14% vs 31%, p=0.002). In time to event analysis, intervention was associated with lower rates of COPD hospitalisations (p=0.001). Cox model of proportional hazards adjusted for sex, age, GOLD stage, heart failure, cancer, and long term oxygen treatment demonstrated that intervention reduced risk of COPD hospitalisation (hazard ratio 0.43, 95% confidence interval 0.24-0.77, p=0.002).  Conclusions. Among patients hospitalized for COPD exacerbation, discharge coordinator intervention reduced COPD hospitalisations. Hospital management programs should consider discharge planning to improve outcome in patients with COPD.
Estrogen Plus Progestin and Risk of Venous Thrombosis
Authors: Mary Cushman
Journal: JAMA (2004)

VENOUS THROMBOSIS (VT), INcluding deep vein thrombosis (DVT) and pulmonary embolus (PE), is a common disorder with an incidence of about 1 to 2 per 1000 person-years among adults. 1][10][11][12][13][14][15] To prevent VT among women considering hormone therapy use, it is important to define the most susceptible subgroups and whether any factors might attenuate the risk.In studies to date, it appears that the presence of factor V Leiden increases the risk of VT associated with estrogen use to approximately 15-fold. 16,17Clarification is needed on the effects of postmenopausal hormone therapy on thrombo-sis in the presence of other VT risk factors, especially age, obesity, and purported protective factors, such as aspirin or statin use. 14,18
HLA-DR<sup>high</sup>/CD27<sup>high</sup> plasmablasts indicate active disease in patients with systemic lupus erythematosus
Authors: A M Jacobi, H Mei, B F Hoyer, I M Mumtaz, K Thiele, A Radbruch, G-R Burmester, F Hiepe, T Dörner
Journal: Annals of the Rheumatic Diseases (2009)

Monitoring of peripheral B-cell subsets in patients with systemic lupus erythematosus (SLE) revealed an activity-related expansion of CD27(++)CD20(-)CD19(dim) Ig-secreting cells. A similar subset has also been identified 6-8 days after tetanus/diphtheria vaccination in normal individuals and in patients with infectious disease.This subset was analysed further focussing on the HLA-DR surface expression in a cohort of 25 patients with SLE.This study revealed that 86% (range 59-97%) of CD27(++)CD20(-)CD19(dim) cells express high levels of HLA-DR, are also expanded in the bone marrow, and represent plasmablasts enriched with anti-dsDNA secreting cells. The remaining CD27(++)CD20(-)CD19(dim) cells were HLA-DR(low) and represent mature plasma cells. Importantly, HLA-DR(high) plasmablasts showed a closer correlation with lupus activity and anti-dsDNA levels than the previously identified CD27(++)CD20(-)CD19(dim) cells.HLA-DR(high)CD27(++)CD20(-)CD19(dim) plasmablasts represent a more precise indicator of lupus activity and suggest that there is an overproduction or lack of negative selection of these cells in SLE.
BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas
Authors: Stefan Pfister, Wibke G. Janzarik, Marc Remke, Aurélie Ernst, Wiebke Werft, Natalia Becker, Grischa Toedt, Andrea Wittmann, Christian Kratz, Heike Olbrich, Rezvan Ahmadi, Barbara Thieme, Stefan Joos, Bernhard Radlwimmer, Andreas Kulozik, Torsten Pietsch, Christel Herold-Mende, Astrid Gnekow, Guido Reifenberger, Andrey Korshunov, Wolfram Scheurlen, Heymut Omran, Peter Lichter
Journal: Journal of Clinical Investigation (2008)

The molecular pathogenesis of pediatric astrocytomas is still poorly understood. To further understand the genetic abnormalities associated with these tumors, we performed a genome-wide analysis of DNA copy number aberrations in pediatric low-grade astrocytomas by using array-based comparative genomic hybridization. Duplication of the BRAF protooncogene was the most frequent genomic aberration, and tumors with BRAF duplication showed significantly increased mRNA levels of BRAF and a downstream target, CCND1, as compared with tumors without duplication. Furthermore, denaturing HPLC showed that activating BRAF mutations were detected in some of the tumors without BRAF duplication. Similarly, a marked proportion of low-grade astrocytomas from adult patients also had BRAF duplication. Both the stable silencing of BRAF through shRNA lentiviral transduction and pharmacological inhibition of MEK1/2, the immediate downstream phosphorylation target of BRAF, blocked the proliferation and arrested the growth of cultured tumor cells derived from low-grade gliomas. Our findings implicate aberrant activation of the MAPK pathway due to gene duplication or mutation of BRAF as a molecular mechanism of pathogenesis in low-grade astrocytomas and suggest inhibition of the MAPK pathway as a potential treatment.
Hamstring muscle injuries in professional football: the correlation of MRI findings with return to play
Authors: Jan Ekstrand, Jeremiah C Healy, Markus Waldén, Justin C Lee, Bryan English, Martin Hägglund
Journal: British Journal of Sports Medicine (2011)

Background Hamstring injury is the single most common injury in professional football. MRI is commonly used to confirm the diagnosis and provide a prognosis of lay-off time. Objective To evaluate the use of MRI as a prognostic tool for lay-off after hamstring injuries in professional football players and to study the association between MRI findings and injury circumstances. Methods Prospective cohort study where 23 European professional teams, were followed between 2007 and 2011. Team medical staffs recorded individual player exposure and time-loss injuries. Radiological grading was performed using a modified Peetrons classification into four grades where grades 2 and 3 represent fibre disruption. Results In total, 516 hamstring injuries occurred and 58% of these were examined by MRI. Thirteen per cent were grade 0 injuries, 57% grade 1, 27% of grade 2 and 3% of grade 3. Grade 0 and 1 injuries accounted for 56% (2141/3830 days) of the total lay-off. The lay-off time differed between all four radiological grades of injury (8±3, 17±10, 22±11 and 73±60 days, p&lt;0.0001). Eighty-three per cent of injuries affected the biceps femoris while 11% and 5% occurred to the semimembranosus and semitendinosus, respectively. Re-injuries (N=34/207) constituted 16% of injuries. All re-injuries occurred to the biceps femoris. Conclusion MRI can be helpful in verifying the diagnosis of a hamstring injury and to prognosticate lay-off time. Radiological grading is associated with lay-off times after injury. Seventy per cent of hamstring injuries seen in professional football are of radiological grade 0 or 1, meaning no signs of fibre disruption on MRI, but still cause the majority of absence days.