tbuckley/cabot-search huggingface dataset:
Has the athlete trained enough to return to play safely? The acute:chronic workload ratio permits clinicians to quantify a player's risk of subsequent injury
Authors: Peter Blanch, Tim J Gabbett
Journal: British Journal of Sports Medicine (2015)

The return to sport from injury is a difficult multifactorial decision, and risk of reinjury is an important component. Most protocols for ascertaining the return to play status involve assessment of the healing status of the original injury and functional tests which have little proven predictive ability. Little attention has been paid to ascertaining whether an athlete has completed sufficient training to be prepared for competition. Recently, we have completed a series of studies in cricket, rugby league and Australian rules football that have shown that when an athlete's training and playing load for a given week (acute load) spikes above what they have been doing on average over the past 4 weeks (chronic load), they are more likely to be injured. This spike in the acute:chronic workload ratio may be from an unusual week or an ebbing of the athlete's training load over a period of time as in recuperation from injury. Our findings demonstrate a strong predictive (R(2)=0.53) polynomial relationship between acute:chronic workload ratio and injury likelihood. In the elite team setting, it is possible to quantify the loads we are expecting athletes to endure when returning to sport, so assessment of the acute:chronic workload ratio should be included in the return to play decision-making process.
Exploring competency in endobronchial ultrasonography (EBUS): Correlation between experience, self-assessment, theoretical knowledge, and technical performance
Authors: Lars Konge, Mona Savran, Paul Clementsen, Valentina Minddal, Jouke Annema
Journal: European Respiratory Journal (2014)

Background  EBUS is the new gold standard for mediastinal sampling, but is difficult to learn and very operator-dependent. Competency is currently established based on experience (number of performed procedures), self-assessment (the physician9s own judgment), or the subjective opinion of a supervisor.  Aims and objectives  The aim of the study was to explore to what degree experience, self-assessment, and theoretical knowledge could predict the quality of an EBUS procedure. Our hypothesis was that experience would correlate better with actual performance than self-assessment and theoretical knowledge.  Methods  Thirty-one international physicians filled out a questionnaire regarding number of performed EBUS procedures and self-assessment of competency. Theoretical knowledge was assessed by administering a validated test with 46 questions. All participants performed an EBUS procedure including two biopsies on a virtual-reality simulator and previously validated simulator metrics were used for objective assessment of quality.  Results  Surprisingly, the number of correct answers on the theoretical test was the best predictor of technical performance (Pearson correlation=0.52, p=0.004). Experience and self-assessment were weak, insignificant predictors (Pearson correlations=0.01, p=0.59 and 0.18, p=0.35, respectively).  Conclusions  Caution has to be used when establishing basic competency in endosonography based on number of performed procedures or the perception of the physician. We propose to develop an evidence-based credentialing system consisting of theoretical and practical tests.
Quality of life (QOL) with sunitinib versus interferon-alfa (IFN-α) as first-line therapy in patients with metastatic renal cell carcinoma (mRCC): Final results
Authors: D. Cella, M. D. Michaelson, J. C. Cappelleri, A. G. Bushmakin, C. Charbonneau, S. T. Kim, J. Z. Li, R. J. Motzer
Journal: Journal of Clinical Oncology (2009)

6529 Background: In an international, randomized phase 3 trial (Figlin et al, ASCO. 2008), sunitinib showed superior progression-free survival (the primary endpoint) and objective response rate over IFN-α (11 vs. 5 mo and 47% vs. 12%, respectively; p &lt; 0.000001) as first-line mRCC therapy, with a median overall survival of more than 2 years. Here, we report the final health-related QOL results from this trial. Methods: 750 treatment-naïve mRCC patients were randomized 1:1 to receive sunitinib 50 mg orally once-daily in recurring cycles of 4 weeks on drug and 2 weeks off or IFN-α 9 MU subcutaneously thrice-weekly. QOL was measured by the Functional Assessment of Cancer Therapy-General (FACT-G), which has 4 subscales, the FACT-Kidney Symptom Index-15 item (FKSI-15), which includes a Disease-Related Symptoms (FKSI-DRS) subscale, and the EQ-5D questionnaire's utility index (EQ-5D Index) and visual analog scale (EQ-VAS). The primary QOL endpoint was FKSI-DRS. Higher scores indicated better outcomes. Patients completed questionnaires on days 1 and 28 of each cycle. Data were analyzed for the intent-to-treat population using mixed-effects models (MM), supplemented with pattern-mixture models (PMM). We also compared QOL of patients in the United States (US) with patients in the European Union (EU; France, Germany, Italy, Poland, Spain and United Kingdom). Results: Patients on sunitinib reported better FKSI-15 and FKSI-DRS scores than those on IFN-α, with a significant difference in the overall means across cycles (4.06 and 2.36, respectively; p &lt; 0.0001; MM). Similarly, differences in means for FACT-G (and all subscales), EQ-5D Index, and EQ-VAS all significantly favored sunitinib (p &lt; 0.05). Based on pre-set, required minimum score differences, between-treatment differences in the mean scores were clinically meaningful for FKSI-15, FKSI-DRS, FACT-G, and the FACT-G functional well-being subscale. Between-treatment differences were similar for both the US and EU populations. Across all analyses, results from PMM were similar to those from MM. Conclusions: Sunitinib provides superior QOL over IFN-α, in addition to superior efficacy, as first-line mRCC therapy. [Table: see text]
Onwards and upwards: BASEM provides a smorgasbord of practical, convenient educational opportunities for practitioners of sport and exercise medicine
Authors: Eleanor J Tillett
Journal: British Journal of Sports Medicine (2015)

Welcome to the British Association of Sport and Exercise Medicine (BASEM) 2015 issue of BJSM . As I am writing this, I am starting to ‘Hear the Dragon Roar’ calling us to Cardiff—one of the proud hosts of the year's Rugby World Cup. Hopefully by the time this issue arrives on your doorstops (cyber or otherwise) we will all be reflecting on a fantastic few weeks of rugby showing sport and sports medicine at its best. Our annual congress this year, once again joint with the Faculty of Sport and Exercise Medicine, is following hot on the heels of the Rugby World Cup. It will also take place in Cardiff as we continue to take BASEM conference locations on a tour of Great Britain; hopefully one will be appearing near you soon.

Whether you like your sports medicine elite or …
Finding the right balance: aOX40 immunotherapy enhances effector T cell function without impairing regulatory T cells intrinsic suppressive capacity in mouse tumor models
Authors: Amy Moran, Fanny Polesso, Minhazur Sarker, David Parker, Susan E Murray, Andrew Weinberg
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Expression of the co-stimulatory molecule OX40 is induced after TCR ligation on conventional T cells and the importance of OX40 in promoting proliferation, effector function, and survival of activated T cells are illustrated in multiple disease models. Paradoxically, CD4+Foxp3+
Abstract P036: Poor Nutritional Intake and Malnutrition in Obese Patients with Heart Failure
Authors: Lorraine Evangelista, Marjan Motie, Terry A Lennie
Journal: Circulation (2014)

Introduction: Poor nutritional status and unintentional cachexia have been shown to have a strong association with survival in patients with heart failure (HF). However, there is currently a paucity of research describing the dietary patterns of obese patients with chronic HF. Objective: This study was done to identify the food and nutrient intake of the Pro-HEART trial participants and compare participant intake to national guidelines. Methods: Pro-HEART is a clinical trial designed to evaluate the short-term and long-term effects of a high protein vs. standard protein diet on body weight and adiposity and other health outcomes in overweight and obese patients with HF, complicated with diabetes and/or metabolic syndrome. Baseline food consumption of 77 participants was analyzed using a validated 3-Day Food Record. Results: On average, the participants were 58.1±10.3 years, male (74%), married (65%), Caucasian (49%). The average energy intake was 1358.6 ± 478.9; 58% exceeded the recommended amount of percent calories from fat, 73% exceeded the saturated fat recommendation (of 10% of daily calories), and 92% consumed too much sodium. Only 40% consumed the recommended amount of daily calories from carbohydrates. On average, participants consumed 0.68 ± 0.21 gm/kg of protein; only 9% consumed at least 1 gm/kg of protein as recommended. Less than 50% met the minimum recommended servings for folate, vitamin E, calcium and sodium (see Table). Conclusions: Our findings showed that overweight and obese patients with HF exceeded recommended intake of fat, saturated fats, and sodium. Likewise, data suggest that overweight and obese patients with HF are at risk for poor nutritional intake of key micronutrients and minerals essential for reducing the inflammatory and metabolic abnormalities associated with HF and confirm that patients who do not appear cachectic may still be at risk for malnutrition. Thus, the risk for poor nutritional intake should be considered in all HF patients, regardless of whether they appear malnourished or not.
Host Cell-Modified T-Antigen in Membranes of Simian Virus 40-Transformed Hamster Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: R Schmidt-Ullrich, S J Kahn, W S Thompson, D F Wallach
Journal: JNCI Journal of the National Cancer Institute (1980)

Highly purified plasma membranes of simian virus 40 (SV40)-transformed hamster and mouse cells were subjected to indirect immunoprecipitation and bidimensional isoelectric focusing-immunoelectrophoresis with high-titer (≥512) sera against SV40 T-antigen. An SV40-specific protein of approximately 100,000 daltons and pH-4.7 isoelectric point cross-reacted immunologically with T-antigen, which indicated the presence of a T-antigen species. However, this protein appeared to be host cell modified because of its low isoelectric point and its reactivity with heterologous antisera containing antibodies specific for neuraminidase- and trypsin-sensitive carbohydrate and/or peptide moieties lacking nuclear T-antigen. Another protein specific for the membranes of SV40-transformed cells had a molecular mass near 60,000 daltons and an isoelectric point at pH 4.5 and appeared closely associated with membrane T-antigen. It copre-cipitated with membrane T-antigen upon indirect immunoprecipitation with anti-T serum. However, when this protein was dissociated from membrane T-antigen by isoelectric focusing in the presence of Triton X-100 and urea, its reactivity with anti-T serum was lost. This suggested that the protein was not encoded in the SV40 genome.
Lung function defects in treated pulmonary tuberculosis patients
Authors: Deepak Aggarwal, Vivek KU, Ashok K. Janmeja
Journal: European Respiratory Journal (2015)

In their study, Amaral et al. [1] have nicely demonstrated the association of obstructive and restrictive lung function defects in patients with a past history of tuberculosis (TB). However, a few points regarding these tubercular sequelae need to be discussed in order for the results to be fully understood. Healed pulmonary TB often presents with residual lung function defects which may require further treatment <http://ow.ly/TXfLm>
Long-Term Follow-Up Evaluation After Sirolimus-Eluting Stent Implantation by Optical Coherence Tomography
Authors: Masamichi Takano, Masanori Yamamoto, Shigenobu Inami, Daisuke Murakami, Koji Seimiya, Takayoshi Ohba, Yoshihiko Seino, Kyoichi Mizuno
Journal: Journal of the American College of Cardiology (2008)
Part 5: Acute Coronary Syndromes
Authors: Michelle Welsford, Nikolaos I. Nikolaou, Farzin Beygui, Leo Bossaert, Chris Ghaemmaghami, Hiroshi Nonogi, Robert E. O’Connor, Daniel R. Pichel, Tony Scott, Darren L. Walters, Karen G. H. Woolfrey, Abdulaziz S. Ali, Chi Keong Ching, Michael Longeway, Catherine Patocka, Vincent Roule, Simon Salzberg, Anthony V. Seto
Journal: Circulation (2015)
Hospital Incidence and Outcomes of the Acute Respiratory Distress Syndrome Using the Kigali Modification of the Berlin Definition
Authors: Elisabeth D. Riviello, Willy Kiviri, Theogene Twagirumugabe, Ariel Mueller, Valerie M. Banner-Goodspeed, Laurent Officer, Victor Novack, Marguerite Mutumwinka, Daniel S. Talmor, Robert A. Fowler
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Estimates of the incidence of the acute respiratory distress syndrome (ARDS) in high- and middle-income countries vary from 10.1 to 86.2 per 100,000 person-years in the general population. The epidemiology of ARDS has not been reported for a low-income country at the level of the population, hospital, or intensive care unit (ICU). The Berlin definition may not allow identification of ARDS in resource-constrained settings.To estimate the incidence and outcomes of ARDS at a Rwandan referral hospital using the Kigali modification of the Berlin definition: without requirement for positive end-expiratory pressure, hypoxia cutoff of SpO2/FiO2 less than or equal to 315, and bilateral opacities on lung ultrasound or chest radiograph.We screened every adult patient for hypoxia at a public referral hospital in Rwanda for 6 weeks. For every patient with hypoxia, we collected data on demographics and ARDS risk factors, performed lung ultrasonography, and evaluated chest radiography when available.Forty-two (4.0%) of 1,046 hospital admissions met criteria for ARDS. Using various prespecified cutoffs for the SpO2/FiO2 ratio resulted in almost identical hospital incidence values. Median age for patients with ARDS was 37 years, and infection was the most common risk factor (44.1%). Only 30.9% of patients with ARDS were admitted to an ICU, and hospital mortality was 50.0%. Using traditional Berlin criteria, no patients would have met criteria for ARDS.ARDS seems to be a common and fatal syndrome in a hospital in Rwanda, with few patients admitted to an ICU. The Berlin definition is likely to underestimate the impact of ARDS in low-income countries, where resources to meet the definition requirements are lacking. Although the Kigali modification requires validation before widespread use, we hope this study stimulates further work in refining an ARDS definition that can be consistently used in all settings.
Role of slug in TGF-β1 mediated MMP-9 expression in human oral squamous cell cancer
Authors: M. J. Joseph, V. Ananthanarayanan, M. E. Diamond, L. Sun, H. G. Munshi
Journal: Journal of Clinical Oncology (2007)

21000 Background: Oral squamous cell cancer (OSCC) causes significant morbidity and mortality as a result of loco-regional invasion and distant metastasis. Invasive OSCC tumors demonstrate increased expression of matrix metalloproteinases (MMPs), including MMP-9. TGF-β1, which promotes MMP-dependent invasion, is also frequently overexpressed in OSCC. Recent reports indicate that TGF-β1 can signal through Snail family of transcription factors, including Slug, which are key regulators of epithelial to mesenchymal transition. Methods: To examine the relationship between TGF-β1 and MMP-9 in human OSCC tumors, phospho-Smad2 and MMP-9 expression was quantified in an oral cancer tissue microarray, and then the relationship determined using Pearson correlation coefficient. To understand the role of Slug in TGF-β1-mediated MMP-9 expression, premalignant oral keratinocyte cell lines (OKF4 and OKF6) and malignant OSCC lines (SCC25 and UMSCC1) were treated with TGF-β1 (10 ng/ml) and analyzed for Slug and MMP-9 expression at the message and protein levels. The specific role of Slug was determined by transfecting OSCC cells with Slug specific siRNA or control siRNA, treating with TGF-β1 for 24h, and determining the effect on MMP-9 expression. Results: There was a statistically significant correlation between phospho-Smad2 and MMP- 9 expression in human OSCC samples, with a Pearson correlation coefficient of 0.4392 (p=0.0007). In vitro, treatment of premalignant and OSCC cells with TGF-β1 induced both Slug and MMP-9 expression at the message and protein level. Interestingly, transfection of Slug siRNA in OKF4 and OKF6 cells increased both basal and TGF-β1-mediated MMP-9 expression, while transfection of Slug siRNA in SCC25 and UMSCC1 cells decreased basal and TGF-β1-mediated MMP-9 expression. Conclusions: Overall, our data indicate that TGF-β1 may regulate MMP-9 expression in human oral squamous cell cancer. Additionally, our data indicate a role for Slug in TGF-β1-mediated MMP-9 expression in oral cancer cells. Future experiments will examine the mechanism by which Slug differentially regulates MMP-9 expression in premalignant and malignant OSCC cells. No significant financial relationships to disclose.
Screening for tuberculosis in patients with rheumatic diseases commencing anti-TNF-α treatment: A regional survey
Authors: Elena Karampini, Ramamurthy Sathyamoorthy
Journal: European Respiratory Journal (2012)

Introduction:  The increase in active tuberculosis (TB) associated with anti-tumor necrosis factor α (anti-TNF-α) treatment has led to screening for active/latent TB before anti-TNF-α is given. Marked variation in TB incidence has been noted depending on patients9 ethnicity, country of birth and, for those not born in the UK, the length of time since their first entry. We aimed to evaluate our risk assessment mechanism.  Method:  Retrospective study of 227 patients (F 65.2%, M 34.8%; median age: 53 yrs) with rheumatic diseases receiving anti-TNF-α (infliximab, etanercept, adalimumab) in 2001-2009. This sample represents a particularly multiethnic patient population.  Results:  1 patient (0.44% of the total) underwent tuberculin skin testing (TST). All patients were on additional immunosuppressants interfering with the accuracy of TST. No patients underwent interferon-gamma assay testing for latent TB. 9 patients (4% of the total) received chemoprophylaxis prior to anti-TNF-α. 2 patients (0.88% of the total) who had not received chemoprophylaxis developed active TB. The first was on etanercept & adalimumab prior to developing miliary TB. The second was on adalimumab & infliximab prior to TB diagnosis. Both patients recovered with quadruple anti-TB therapy. Both patients were born in the Indian subcontinent and had been in the UK for over 5 years. The TB incidence rate was 196.8 per 100,000 patient-years.  Conclusion:  TB screening prior to starting anti-TNF-α can be improved so as to facilitate appropriate chemoprophylaxis targeting. Interferon-gamma assays could be a useful tool in the diagnosis of latent TB when patients are already on immunosuppressants.
Abstract IA04: Understanding tumor heterogeneity in glioblastoma
Authors: Simon Tavaré, Andrea Sottoriva, Sara Piccirillo, Inma Spiteri, Anestis Touloumis, John C. Marioni, Christina N. Curtis, Colin Watts
Journal: Cancer Research (2015)

Abstract Glioblastoma (GB) is advanced at the time of clinical presentation and response to treatment may be confounded by clonal heterogeneity and differential patterns of resistance in spatially distinct parts of the same tumor. However, we do not understand how this complex environment evolves. Accumulating evidence suggests that intra-tumor heterogeneity is likely to be the key to understanding treatment failure, however the dynamics of such heterogeneity are still poorly understood. Using a Fluorescence-Guided Multiple Sampling technique we obtained samples from the tumor mass, the sub-ependymal zone and the non-fluorescent tumor margin. We performed an integrated genomic analysis to develop a spatial reconstruction of tumor evolution in individual patients. Temporal analysis was performed using patient-derived xenografts obtained by serial transplantation of tumor cells in immuno-suppressed mice. Phylogenetic reconstruction of the fragments from each GB identifies copy number alterations in EGFR and CDKN2A/B/p14ARF as early evolutionary events while aberrations in PDGFRA and PTEN occur later in the disease progression. Transcriptional profiling reveals that many patients display multiple GB subtypes within their tumor while deconstruction of the clonal organization of each tumor fragment at single-molecule level identified multiple coexisting cell lineages. Ancestral tumor precursors that gave rise to the tumor mass were found in the sub-ependymal zone of a subset of GB patients. When used in in vivo experiments, tumor cells show variable competitive capacity for disease propagation and further genetic diversification, suggesting that GB evolves through complex dynamics of sub-clonal fitness advantage and acquisitions of mutations and copy number alterations. Our integrated genomic analysis addresses the evolution of GB in individual patients across multiple spatial scales. Our data reveal early clonal diversification generating a genetically complex and highly evolved disease environment at clinical presentation. We propose that these fundamental patient-specific tumor evolutionary dynamics underlie clinical phenotypic heterogeneity and may have implications for the emergence of resistant disease. Citation Format: Simon Tavaré, Andrea Sottoriva, Sara Piccirillo, Inma Spiteri, Anestis Touloumis, John C. Marioni, Christina N. Curtis, Colin Watts. Understanding tumor heterogeneity in glioblastoma. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr IA04.
In vivo targeting of leukemia stem cells by directing parthenolide-loaded nanoparticles to the bone marrow niche
Authors: H Zong, S Sen, G Zhang, C Mu, Z F Albayati, D G Gorenstein, X Liu, M Ferrari, P A Crooks, G J Roboz, H Shen, M L Guzman
Journal: Leukemia (2015)
Knockdown of TNF-α by DNAzyme gold nanoparticles as an anti-inflammatory therapy for myocardial infarction
Authors: Inthirai Somasuntharam, Kevin Yehl, Sheridan L. Carroll, Joshua T. Maxwell, Mario D. Martinez, Pao-Lin Che, Milton E. Brown, Khalid Salaita, Michael E. Davis
Journal: Biomaterials (2015)