tbuckley/cabot-search huggingface dataset:
Consensus statement on injury definitions and data collection procedures in studies of football (soccer) injuries
Authors: C W Fuller, J Ekstrand, A Junge, T E Andersen, R Bahr, J Dvorak, M Hägglund, P McCrory, W H Meeuwisse
Journal: British Journal of Sports Medicine (2006)

Variations in definitions and methodologies have created differences in the results and conclusions obtained from studies of football (soccer) injuries, making interstudy comparisons difficult. Therefore an Injury Consensus Group was established under the auspices of Fédération Internationale de Football Association Medical Assessment and Research Centre. A nominal group consensus model approach was used. A working document on definitions, methodology, and implementation was discussed by the group. Iterative draft statements were prepared and circulated to members of the group for comment before the final consensus statement was produced. Definitions of injury, recurrent injury, severity, and training and match exposures in football together with criteria for classifying injuries in terms of location, type, diagnosis, and causation are proposed. Proforma for recording players’ baseline information, injuries, and training and match exposures are presented. Recommendations are made on how the incidence of match and training injuries should be reported and a checklist of issues and information that should be included in published reports of studies of football injuries is presented.
Pro-inflammatory human Th17 cells selectively express P-glycoprotein and are refractory to glucocorticoids
Authors: Radha Ramesh, Lina Kozhaya, Kelly McKevitt, Ivana M. Djuretic, Thaddeus J. Carlson, Maria A. Quintero, Jacob L. McCauley, Maria T. Abreu, Derya Unutmaz, Mark S. Sundrud
Journal: The Journal of Experimental Medicine (2014)

IL-17A–expressing CD4+ T cells (Th17 cells) are generally regarded as key effectors of autoimmune inflammation. However, not all Th17 cells are pro-inflammatory. Pathogenic Th17 cells that induce autoimmunity in mice are distinguished from nonpathogenic Th17 cells by a unique transcriptional signature, including high Il23r expression, and these cells require Il23r for their inflammatory function. In contrast, defining features of human pro-inflammatory Th17 cells are unknown. We show that pro-inflammatory human Th17 cells are restricted to a subset of CCR6+CXCR3hiCCR4loCCR10−CD161+ cells that transiently express c-Kit and stably express P-glycoprotein (P-gp)/multi-drug resistance type 1 (MDR1). In contrast to MDR1− Th1 or Th17 cells, MDR1+ Th17 cells produce both Th17 (IL-17A, IL-17F, and IL-22) and Th1 (IFN-γ) cytokines upon TCR stimulation and do not express IL-10 or other anti-inflammatory molecules. These cells also display a transcriptional signature akin to pathogenic mouse Th17 cells and show heightened functional responses to IL-23 stimulation. In vivo, MDR1+ Th17 cells are enriched and activated in the gut of Crohn’s disease patients. Furthermore, MDR1+ Th17 cells are refractory to several glucocorticoids used to treat clinical autoimmune disease. Thus, MDR1+ Th17 cells may be important mediators of chronic inflammation, particularly in clinical settings of steroid resistant inflammatory disease.
Whole-Exome Sequencing Reveals <i>TopBP1</i> as a Novel Gene in Idiopathic Pulmonary Arterial Hypertension
Authors: Vinicio A. de Jesus Perez, Ke Yuan, Maria A. Lyuksyutova, Frederick Dewey, Mark E. Orcholski, Eric M. Shuffle, Maya Mathur, Luke Yancy, Vanessa Rojas, Caiyun Grace Li, Aiqin Cao, Tero-Pekka Alastalo, Nayer Khazeni, Karlene A. Cimprich, Atul J. Butte, Euan Ashley, Roham T. Zamanian
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disorder characterized by progressive loss of pulmonary microvessels. Although mutations in the bone morphogenetic receptor 2 (BMPR2) are found in 80% of heritable and ∼15% of patients with IPAH, their low penetrance (∼20%) suggests that other unidentified genetic modifiers are required for manifestation of the disease phenotype. Use of whole-exome sequencing (WES) has recently led to the discovery of novel susceptibility genes in heritable PAH, but whether WES can also accelerate gene discovery in IPAH remains unknown.To determine whether WES can help identify novel gene modifiers in patients with IPAH.Exome capture and sequencing was performed on genomic DNA isolated from 12 unrelated patients with IPAH lacking BMPR2 mutations. Observed genetic variants were prioritized according to their pathogenic potential using ANNOVAR.A total of nine genes were identified as high-priority candidates. Our top hit was topoisomerase DNA binding II binding protein 1 (TopBP1), a gene involved in the response to DNA damage and replication stress. We found that TopBP1 expression was reduced in vascular lesions and pulmonary endothelial cells isolated from patients with IPAH. Although TopBP1 deficiency made endothelial cells susceptible to DNA damage and apoptosis in response to hydroxyurea, its restoration resulted in less DNA damage and improved cell survival.WES led to the discovery of TopBP1, a gene whose deficiency may increase susceptibility to small vessel loss in IPAH. We predict that use of WES will help identify gene modifiers that influence an individual's risk of developing IPAH.
End-Digit Preference and the Quality of Blood Pressure Monitoring in Diabetic Adults
Authors: Esther S.H. Kim, T. Alafia Samuels, Hsin-Chieh Yeh, Marcela Abuid, Spyridon S. Marinopoulos, Jeanne M. McCauley, Frederick L. Brancati
Journal: Diabetes Care (2007)

Although tight blood pressure (BP) control is proven to reduce diabetes-related cardiovascular risk, it has been difficult to achieve in practice, perhaps in part because of low-quality monitoring data. We hypothesized that low-quality BP data, reflected in end-digit preference (EDP), remains common in primary care of diabetic adults.Data were abstracted from the charts of 404 adults with type 2 diabetes seen at 16 academically affiliated clinics from 1999 to 2001. End-digits of systolic and diastolic BPs taken with nonautomated sphygmomanometers were extracted, and prevalence of EDP for zero was calculated. Associations between EDP and selected patient characteristics were determined using multiple logistic regressions.EDP was highly prevalent in the BP measurements taken by nonphysicians (4,333 BPs; 50% of systolic, 50% of diastolic readings ended in zero; P < 0.001) and physicians (1,347 BPs; 69% of systolic, 64% of diastolic readings ended in zero; P < 0.001). In multivariate analysis, nonphysicians showed greater EDP for systolic BP in older patients (odds ratio [OR] 1.07 per 5 years) and women (OR 1.36 vs. men) and for diastolic BP in African-Americans (OR 1.25 vs. whites; all P < 0.05); physicians showed greater EDP for diastolic BP in less obese patients (OR 0.97 per 5 kg/m2 increment in BMI; P = 0.02).Low-quality BP measurement is common in primary care of diabetic adults. Procedural and technological improvements to BP measurement deserve attention as part of an overall strategy to tighten BP control and reduce cardiovascular risk.
Long-term follow-up of patients with primary biliary cirrhosis on colchicine therapy
Authors: Abraham Zifroni, Fenton Schaffner
Journal: Hepatology (1991)

We followed up a group of patients with primary biliary cirrhosis who participated in a 4-yr prospective, double-blind controlled trial of colchicine therapy for 4 additional years. All were placed on open label colchicine (0.6 mg twice daily) after the trial was concluded. Of the original group of 28 patients treated with colchicine, 8 died and 5 received transplants (3 of the 5 died). Of the original placebo control group eight patients died and six received transplants (1 of the 6 died). Surviving patients on long-term colchicine therapy (mean period = 8.1 yr, range = 5.3 to 9.1) showed reduction of mean serum alkaline phosphatase from 5.1 times the upper limit of normal values to 1.9 times (p less than 0.01). Mean ALT fell from 1.8 to 1.2 times the upper limit of normal (p = 0.05), and mean serum total bilirubin remained stable (1.6 mg/dl vs. 1.5 mg/dl). Major complications of cirrhosis developed in four patients in the colchicine group and five patients in the original control group. The only side effect of colchicine was diarrhea, which was noted in three patients. The diarrhea resolved with reduction in the dose of colchicine. Colchicine is a safe and inexpensive drug for the long-term treatment of primary biliary cirrhosis. The biochemical parameters of disease activity (alkaline phosphatase and ALT) remain improved after long-term follow-up, and bilirubin values remain stable. However, complications of cirrhosis, deaths and transplantations were not prevented. The clinical usefulness of colchicine in the treatment of primary biliary cirrhosis seems to be limited.
Erythropoietin Activates Cell Survival Pathways in Breast Cancer Stem–like Cells to Protect Them from Chemotherapy
Authors: Matilde Todaro, Alice Turdo, Monica Bartucci, Flora Iovino, Rosanna Dattilo, Marco Biffoni, Giorgio Stassi, Giulia Federici, Ruggero De Maria, Ann Zeuner
Journal: Cancer Research (2013)

Recombinant erythropoietin (EPO) analogs [erythropoiesis-stimulating agents (ESA)] are clinically used to treat anemia in patients with cancer receiving chemotherapy. After clinical trials reporting increased adverse events and/or reduced survival in ESA-treated patients, concerns have been raised about the potential role of ESAs in promoting tumor progression, possibly through tumor cell stimulation. However, evidence is lacking on the ability of EPO to directly affect cancer stem-like cells, which are thought to be responsible for tumor progression and relapse. We found that breast cancer stem-like cells (BCSC) isolated from patient tumors express the EPO receptor and respond to EPO treatment with increased proliferation and self-renewal. Importantly, EPO stimulation increased BCSC resistance to chemotherapeutic agents and activated cellular pathways responsible for survival and drug resistance. Specifically, the Akt and ERK pathways were activated in BCSC at early time points following EPO treatment, whereas Bcl-xL levels increased at later times. In vivo, EPO administration counteracted the effects of chemotherapeutic agents on BCSC-derived orthotopic tumor xenografts and promoted metastatic progression both in the presence and in the absence of chemotherapy treatment. Altogether, these results indicate that EPO acts directly on BCSC by activating specific survival pathways, resulting in BCSC protection from chemotherapy and enhanced tumor progression.
Lung Cancer—Where Are We Today?
Authors: Stephen G. Spiro, Joanna C. Porter
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Lung cancer remains the commonest cause of cancer death in both men and women in the developed world, although mortality rates for men are dropping. Spiral computed tomography (CT) of the chest in middle-aged, smoking subjects may identify two to four times more lung cancers than a chest X-ray, with more than 70% of tumors being Stage I. The incidence of benign nodules is high, making interpretation difficult. Randomized controlled trials are required to determine whether spiral CT detects lung cancer early enough to improve mortality. Preoperative staging has relied on CT scans, but positron emission tomography scanning has greater sensitivity, specificity, and accuracy than CT and is recommended as the final confirmatory investigation when the CT shows resectable disease. In locally advanced non-small cell lung cancer, there is a small advantage for the addition of chemotherapy to radiotherapy, but no advantage for postoperative radiotherapy. Chemotherapy gives no benefit when given as neoadjuvant or adjuvant treatment around surgery. In advanced disease, newer cytotoxic agents confer a small survival advantage over older combinations, but the advantage in median survival over best supportive care remains a few months with modest improvements in quality of life. Survival with small cell lung cancer has shown little increase over the last 15 years despite multiple attempts to manipulate the timing, dose intensity of chemotherapy, and the potential of radiotherapy. Novel therapies are urgently needed for all cell types of lung cancer.
Signal Transducers and Activators of Transcription 5b Activation Enhances Hepatocellular Carcinoma Aggressiveness through Induction of Epithelial-Mesenchymal Transition
Authors: Terence K. Lee, Kwan Man, Ronnie T.P. Poon, Chung Mau Lo, Anthony P. Yuen, Irene O. Ng, Kevin T. Ng, Warren Leonard, Sheung Tat Fan
Journal: Cancer Research (2006)

Abstract Poor prognosis of hepatocellular carcinoma (HCC) is associated with a high potential of vascular invasion and metastasis. Epithelial-mesenchymal transition (EMT) is a key event in the tumor invasion process. Recently, signal transducers and activators of transcription 5 (STAT5) has been linked to tumor progression by EMT induction. However, the precise roles of STAT5 genes (STAT5a and STAT5b) in human epithelial cancers have not been elucidated clearly. The aim of this study is to analyze the roles of STAT5 isoforms in HCC progression using HCC clinical samples. We showed that activation of STAT5b, but not STAT5a, was found in HCC clinical samples and its expression was significantly associated with younger age (P = 0.037), advanced tumor stages (P = 0.003), venous infiltration (P = 0.016), microsatellite formation (P = 0.024), multiple tumor nodules (P = 0.02), and poor patient survival. To specifically investigate the mechanism underlying constitutive activation of STAT5b in HCC, EGFP-HBX was introduced into Huh-7 cells. STAT5b activation in HCC is at least partially mediated by HBX activation. Ectopic STAT5b transfection conferred increased HCC cell motility and invasiveness by induction of EMT changes. In conclusion, STAT5b activation enhanced HCC aggressiveness by induction of EMT, which was possibly mediated by HBX activation. STAT5b could serve as a novel molecular target for HCC treatment. (Cancer Res 2006; 66(20): 9948-56)
Chronic Idiopathic Axonal Polyneuropathy Is Associated With the Metabolic Syndrome
Authors: Nora A. Visser, Alexander F.J.E. Vrancken, Yvonne T. van der Schouw, Leonard H. van den Berg, Nicolette C. Notermans
Journal: Diabetes Care (2012)

This study aims to investigate the association between chronic idiopathic axonal polyneuropathy (CIAP) and the metabolic syndrome or its individual components.A total of 249 patients with CIAP and 709 controls underwent fasting laboratory studies, and blood pressure and waist circumference were measured. The metabolic syndrome was diagnosed if three or more of the following Adult Treatment Panel III criteria were present: impaired fasting glucose, hypertension, abdominal obesity, reduced HDL cholesterol, and hypertriglyceridemia. Subgroup analysis was performed for patients with a painful predominantly sensory CIAP, because this phenotype is most similar to diabetic polyneuropathy. Statistical analysis was performed with adjustment for age and gender.Fifty-five percent of all patients fulfilled the metabolic syndrome criteria compared with 34% of controls (odds ratio 2.2 [95% CI 1.7-3.0]). Multivariate analysis shows hypertension (2.9 [1.7-4.9]) and abdominal obesity (3.3 [2.4-4.6]) to be significantly more prevalent in patients than in controls. Of the patients classified as having a painful predominantly sensory CIAP, 62% fulfilled the metabolic syndrome criteria (3.1 [2.0-4.8]). In this subgroup, hypertension and abdominal obesity also were significantly more prevalent compared with controls.Abdominal obesity and hypertension seem to be the most consistent contributing components of the metabolic syndrome in patients with CIAP. Evaluation and appropriate treatment of these risk factors in patients with CIAP would be advocated.
Therapy for Osteosarcoma in Dogs With Intravenous Injection of Liposome-Encapsulated Muramyl Tripeptide
Authors: E G. MacEwen, I. D. Kurzman, R. C. Rosenthal, B. W. Smith, P. A. Manley, J. K. Roush, P. E Howard
Journal: JNCI Journal of the National Cancer Institute (1989)

Canine osteosarcoma is a spontaneous malignancy in dogs, characterized by micrometastasis to pulmonary and extrapulmonary tissues at the time of diagnosis. Standard treatment involves amputation of the affected leg, but median survival time is 3–4 months with death due to metastasis. A randomized double-blind trial was conducted to evaluate liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (liposome/MTP-PE) as a treatment for metastasis in dogs undergoing amputation for osteosarcoma. Fourteen dogs were treated with liposome/MTP-PE, and 13 were treated with empty liposomes. Median survival time was 222 days for dogs treated with liposome/MTP-PE, compared to 77 days for dogs treated with empty liposomes (P<.002). In the liposome< MTP-PE-treated group there were still four dogs alive and free of metastasis at >1 year post surgery. Treatment was well tolerated; no significant toxic effects were noted except for mild elevations in body temperature (1–2 °C) for 2–6 hours post injection. [J Natl Cancer Inst 81:935-938, 1989]
Effects of prostaglandin F2α on intracellular pH, intracellular calcium, cell shortening and L-type calcium currents in rat myocytes
Authors: S Fong Yew
Journal: Cardiovascular Research (1998)

Objective: We have studied the mechanisms underlying the positive inotropic action of prostaglandin F2α (PGF2α) by monitoring intracellular calcium transients, intracellular pH, L-type calcium currents and cell shortening in isolated ventricular myocytes. Methods: Rat myocytes were loaded with fura-2AM for intracellular calcium measurements, or BCECF-AM for pH measurements. Cell shortening was recorded using an edge detection system, and L-type calcium currents measured using whole cell patch clamping. Results: PGF2α(3 nmol l−1–3 μmol l−1) increased single myocyte shortening and reduced resting cell length in a concentration-dependent manner. While myocyte shortening was increased by PGF2α, this was not associated with any change in the amplitude of intracellular calcium transients, diastolic calcium, or L-type calcium currents. However, the same myocytes were capable of responding to catecholamines with increases in calcium transient amplitude and L-type calcium currents. PGF2α (3 μmol l−1) caused a reversible rise in intracellular pH of 0.08±0.01 pH units (n=5, p<0.05). The Na+–H+ exchanger inhibitor, HOE 694 (10 μmol l−1), abolished the PGF2α-induced rise in pH and the increase in cell shortening. PGF2α-induced increases in cell shortening and intracellular pH were also attenuated by the protein kinase C (PKC) inhibitor, chelerythrine (2 μmol l−1). Conclusion: The positive inotropic action of PGF2α appears to be mediated via activation of the Na+–H+ exchanger with the possible involvement of PKC. This suggests that PGF2α_produces intracellular alkalosis, which then sensitizes cardiac myofilaments to calcium.
Late intervention with a myeloperoxidase inhibitor prevents emphysema and small airway remodeling in the guinea pig
Authors: Andrew Churg, Caroline Marshall, Don Sin, Elaine Cadogan, Matt Soars, Sarah Bolton, Justine Maltby, Philip Mallinder, Joanne Wright
Journal: European Respiratory Journal (2011)

Considerable evidence links both inflammation and oxidative stress to the pathogenesis of COPD. Myeloperoxidase (MPO), a neutrophil product, plays a major role in bacterial killing via production of the powerful oxidant, HOCl. However, oxidants generated by MPO can damage tissue and MPO exerts a variety of other effects that drive inflammation. We examined the effects of an MPO inhibitor, AZ11938920 on chronic (6 month) cigarette smoke-induced lesions in the guinea pig. One group of animals received compound from smoking day 1 (prophylactic arm), whereas another group was only treated after 3 months of smoke exposure (therapeutic arm). Analysis of lavage fluid showed that both treatments abolished smoke-induced increases in lavage inflammatory cells. Both treatments prevented smoke-induced increases in airspace size (emphysema) and small airway remodeling. Physiologically, both treatments largely reversed smoke-induced shifts of the pressure-volume and flow-volume curves and returned resistance to control values. Both treatments prevented muscularization of the small intrapulmonary arteries, but only partially ameliorated smoke-induced pulmonary hypertension. Immunohistochemical staining for the oxidation product, dityrosine, was increased in smoke-exposed animals and this effect was largely reversed by both treatments. We conclude that a myeloperoxidase inhibitor is able to prevent the development of emphysema and small airway remodeling and to partially protect against pulmonary hypertension, even when treatment starts after 3 months of smoke exposure. This protection appears to be related to prevention of oxidant damage and suppression of inflammation.
Merkel cell polyomavirus DNA detection in lesional and nonlesional skin from patients with Merkel cell carcinoma or other skin diseases
Authors: V. Foulongne, O. Dereure, N. Kluger, J.P. Molès, B. Guillot, M. Segondy
Journal: British Journal of Dermatology (2009)

Background A novel polyomavirus, the Merkel cell polyomavirus (MCPyV), has recently been identified in Merkel cell carcinoma (MCC). Objectives To investigate the specificity of this association through the detection, quantification and analysis of MCPyV DNA in lesional and nonlesional skin biopsies from patients with MCC or with other cutaneous diseases, as well as in normal skin from clinically healthy individuals. Methods DNA was extracted from lesional and nonlesional skin samples of patients with MCC or with other cutaneous diseases and from normal-appearing skin of clinically healthy subjects. MCPyV DNA was detected by polymerase chain reaction (PCR) and quantified by real-time PCR. Additionally, the T antigen coding region was sequenced in eight samples from seven patients. Results MCPyV DNA was detected in 14 of 18 (78%) patients with MCC, five of 18 (28%) patients with other skin diseases (P = 0.007) and one of six (17%) clinically healthy subjects. In patients with MCC, viral DNA was detected in nine of 11 (82%) tumours and in 10 of 14 (71%) nontumoral skin samples (P = 0.66). MCPyV DNA levels were higher in MCC tumours than in nontumoral skin from patients with MCC, and than in lesional or nonlesional skin from patients with other cutaneous disorders. Signature mutations in the T antigen gene were not identified in the two MCC tumour specimens analysed. Conclusions High prevalence and higher levels of MCPyV DNA in MCC supports a role for MCPyV in tumorigenesis. However, the high prevalence of MCPyV in the nontumoral skin and in subjects without MCC suggests that MCPyV is a ubiquitous virus.