tbuckley/cabot-search huggingface dataset:
Health-Related Quality of Life Among 5-Year Survivors of Esophageal Cancer Surgery: A Prospective Population-Based Study
Authors: Maryam Derogar, Pernilla Lagergren
Journal: Journal of Clinical Oncology (2012)

To clarify whether health-related quality of life (HRQL) can be restored in 5-year survivors of esophageal cancer surgery.The nationwide Swedish prospective and population-based cohort for this study consisted of patients with esophageal cancer who were treated surgically between 2001 and 2005 and were alive 5 years after surgery. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and EORTC QLQ-OES18 (the disease site-specific module for esophageal cancer) were used to assess HRQL 6 months, 3 years, and 5 years postoperatively. Paired t tests were used to evaluate changes in HRQL over time. Patients' HRQL was classified as improved, stable, or deteriorated. Multivariable linear regression was used to calculate mean score difference in HRQL with 95% CIs between patients and a background population according to HRQL category.Among 153 eligible patients alive after 5 years, 117 (76%) answered all HRQL assessments. Among a random sample of 6,969 Swedish adults representing the corresponding background population, 4,910 (70.5%) participated. For most patients, HRQL remained stable or improved over time, and their HRQL was comparable to that of the background population. Patients who deteriorated over time reported large and clinically significant mean score differences for all measures. For example, 5 years after surgery, physical function was stable or improved in 86% of patients and their mean score (87) was similar to that of the background population (88), but the 14% who deteriorated had a substantially lower mean score of 56.HRQL recovers to a level comparable to that in the background population in most patients who survive 5 years after esophagectomy for cancer, although a subgroup of patients has substantially worse HRQL.
Risk of cancer with metal-on-metal hip replacements: population based study
Authors: K. T. Makela, T. Visuri, P. Pulkkinen, A. Eskelinen, V. Remes, P. Virolainen, M. Junnila, E. Pukkala
Journal: BMJ (2012)

<b>Objective</b> To assess the risk of cancer associated with modern primary metal-on-metal hip replacements. <b>Design</b> Population based study. <b>Setting</b> Nationwide retrospective comparative register. <b>Participants</b> 10 728 patients who underwent metal-on-metal total hip arthroplasty and 18 235 patients who underwent conventional metal-on-polyethylene, ceramic-on-polyethylene, and ceramic-on-ceramic total hip arthroplasty (the non-metal-on-metal cohort) in the Finnish Arthroplasty Register 2001-10. Data on cancer cases up to 2010 for these cohorts were extracted from the Finnish Cancer Registry. <b>Main outcome measures</b> The relative risk of cancer was expressed as the ratio of observed to expected number of cases from the Finnish population—that is, the standardised incidence ratio. The relative risk of cancer in the metal-on-metal cohort compared with the non-metal-on-metal cohort was estimated with analyses of these ratios and Poisson regression. <b>Results</b> The overall risk of cancer in patients with metal-on-metal hip implants was similar to that in the Finnish population (378 observed <i>v</i> 400 expected, standardised incidence ratio 0.95, 95% confidence interval 0.85 to 1.04). The overall risk of cancer in patients with metal-on-metal hip implants was also no higher than in patients who had received non-metal-on-metal hip implants (relative risk 0.92, 0.81 to 1.05). <b>Conclusions</b> Metal-on-metal hip replacements are not associated with an increased overall risk of cancer during a mean follow-up of four years.
Hypertriglyceridemic HyperapoB in Type 2 Diabetes
Authors: Allan D. Sniderman, Benoit Lamarche, Jessica Tilley, David Seccombe, Jiri Frohlich
Journal: Diabetes Care (2002)

Much less attention has been paid to LDL in type 2 diabetes than to VLDL or HDL. In particular, there are few data on apoB levels in these patients. Moreover, most reports have focused on mean lipoprotein levels and consequently there is little information on the frequencies of the various dyslipidemic phenotypes.Plasma and lipoprotein lipids, apoB and apoA1 were measured by standardized methods. LDL particle size was determined by PAGE. The total cohort was divided into phenotypes by two different methods. The first was based on triglycerides (> or = or <1.5 mmol/l) and LDL cholesterol (> or = or <4 mmol/l), whereas the second was based on triglycerides (> or = or <1.5 mmol/l) and apoB (> or = or <120 mg/dl).For the overall cohort, plasma triglycerides were elevated (2.13 +/- 1.6 mmol/l), total and LDL cholesterol were normal (5.34 +/- 1.1 and 3.28 +/- 0.88 mmol/l, respectively), and peak LDL size was reduced (252.9 +/- 5.8 A). HDL cholesterol was between the 25th and 50th percentiles of the general population (1.12 +/- 0.36 mmol/l). The average level of apoB was 114 +/- 29 mg/dl, a value that is between the 50th and 75th percentiles of the general population and is higher than that for LDL cholesterol, which was between the 25th and the 50th percentiles of the population. The results of the phenotyping analysis were as follows. Using the conventional approach, only 23% has abnormal LDL, i.e., an elevated LDL cholesterol level. Using the new approach, almost 40% has an elevated apoB and therefore an elevated LDL particle number. Only 12.8% has combined hyperlipidemia based on the conventional approach, whereas almost one-third had the equivalent, hypertriglyceridemic hyperapoB-based on the new algorithm. The severity of the dyslipoproteinemia in this group was noteworthy. Although the average LDL cholesterol was 3.91 mmol/l, a value just below the 75th percentile of the general population, the average apoB was 145 mg/dl, a value that approximates the 95th percentile of the population.The dyslipidemic profile of patients with type 2 diabetes is not uniform. A substantial group have normal lipids and normal LDL particle number and size whereas others have markedly abnormal profiles. Diagnosis based on triglycerides and apoB rather than triglycerides and LDL cholesterol revealed that more than one in five had hypertriglyceridemic hyperapoB, which is characterized by hypertriglyceridemia, marked elevation of LDL particle number, small dense LDL, and low HDL, a constellation of abnormalities that is associated with markedly accelerated atherogenesis and therefore justifies intensive medical therapy.
Clinical Staging for Cutaneous T-Cell Lymphoma
Authors: STANFORD I. LAMBERG
Journal: Annals of Internal Medicine (1984)

The Mycosis Fungoides Cooperative Group has been following patients with cutaneous T-cell lymphoma, including mycosis fungoides and the Sézary syndrome variant. Previous analyses identified the extent of skin involvement and the number of sites of clinically enlarged lymph nodes as important prognostic variables. These two variables were used to classify 340 patients into four clinical stages. Repeat analysis based on additional follow-up data shows the usefulness of this clinical staging system for identifying patients with differing survival experience. An alternative grouping suggested by fitting a survival model to the data also has been studied. Staging systems based only on skin involvement and lymph nodes are recommended for general use because the information needed is readily available, requiring only physical examination.
Gastroesophageal Hypercontracting Sphincter
Authors: J. Marshall Garrett
Journal: JAMA (1969)

Eleven of 381 patients who underwent diagnostic esophageal-motility tests were found to have a "hypercontracting sphincter" characterized by prolonged and powerful contractions of the gastroesophageal sphincter. Other motility disturbances included esophageal motor incoordination, diffuse spasm of the esophagus in two patients, and pressure changes of hiatal hernia, which were present in six patients. Substernal pain, occasionally thought to be of cardiac origin, and dysphagia were prominent complaints in nine of the patients, while two patients had no gastrointestinal-tract symptoms. Reassurance, symptomatic treatment, and medical management of hiatal hernia were generally effective, but because of incapacitating pain in two patients, esophagomyotomy was performed and provided excellent relief of symptoms. A hypercontracting gastroesophageal sphincter should be considered in patients with unexplained chest pain, since the diagnosis, made only by manometry, will allow appropriate and effective treatment.
Role of platelet chemokines, PF-4 and CTAP-III, in cancer biology
Authors: Katerina Pilatova, Kristina Greplova, Regina Demlova, Beatrix Bencsikova, Giannoula Lakka Klement, Lenka Zdrazilova-Dubska
Journal: Journal of Hematology & Oncology (2013)

Abstract With the recent addition of anti-angiogenic agents to cancer treatment, the angiogenesis regulators in platelets are gaining importance. Platelet factor 4 (PF-4/CXCL4) and Connective tissue activating peptide III (CTAP-III) are two platelet-associated chemokines that modulate tumor angiogenesis, inflammation within the tumor microenvironment, and in turn tumor growth. Here, we review the role of PF-4 and CTAP-III in the regulation of tumor angiogenesis; the results of clinical trial using recombinant PF-4 (rPF-4); and the use of PF-4 and CTAP-III as cancer biomarkers.
The epidemiology and prevention of injuries in American Flag Football (AFF)
Authors: Y Kaplan
Journal: British Journal of Sports Medicine (2011)

Background Although AFF is considered a non-tackle sport, many moderate-serious contact-type injuries have been reported. There are no studies describing neither the epidemiology nor the prevention of injuries in this international sporting activity. Objective To conduct a 2- season prospective injury-exploratory study in the AFF league, followed by a 2-season prevention trial. Design All time-loss injuries sustained in game sessions were recorded by the off-the-field medical personnel. This was followed up by a more detailed phone questionnaire by the author, 7–14 days following the injury. Setting American Flag Football league in Israel. Participants Male and female amateur league players. Main outcome measurements Epidemiological data. Results 1791 players participated in 1005 games over the two seasons. Athlete-exposures=1799955. There were 179 injuries recorded, with an injury rate=0.099 per 1000 athlete-exposures (95% CI 0.08 to 0.11). 98% of the injuries were traumatic in nature. Over 75% of injuries were caused by contact with the ground. 30% of the contact injuries were to the fingers, thumb and wrist. Many of the finger injuries occurred as a direct result of the player's fingers being caught in the pockets of the opposing player. 20% of the injuries were to the knee, 16% to the head and face and 12% to the ankle. Conclusion As a result of the epidemiological study, a two- season (2010–2012) prospective, longitudinal, randomised controlled injury prevention trial will be conducted, where the players will be randomly divided into those teams that will make up the experimental group (n=+180) and those in the control group (n=+180). The experimental group will be instructed to wear mouth guards and air casts. The control group will be instructed to wear pocket less pants. Following the data collection, the results will be analyzed, conclusions drawn and recommendations suggested for inclusion in future league games.
A call for more dialogue and more details
Authors: J. Cooper Cutting
Journal: Behavioral and Brain Sciences (2004)

Pickering & Garrod (P&G) argue that contemporary models of language use are inadequate. This has resulted largely because of an experimental focus on monologue rather than dialogue. I agree with the need for increased experimentation that focuses on the interplay between production and comprehension. However, I have some concerns about the Interactive Alignment model that the authors propose.
rILYd4, a Human CD59 Inhibitor, Enhances Complement-Dependent Cytotoxicity of Ofatumumab against Rituximab-Resistant B-cell Lymphoma Cells and Chronic Lymphocytic Leukemia
Authors: Xiaowen Ge, Lin Wu, Weiguo Hu, Stacey Fernandes, Chun Wang, Xu Li, Jennifer R. Brown, Xuebin Qin
Journal: Clinical Cancer Research (2011)

Ofatumumab is an anti-CD20 antibody recently approved for treatment of fludarabine and alemtuzumab refractory chronic lymphocytic leukemia (CLL); it mediates much stronger complement-dependent cytotoxicity (CDC) than rituximab. Human CD59, a key membrane complement regulator that inhibits CDC, is highly expressed in B-cell malignancies and its upregulation is an important determinant of the sensitivity of B-cell malignancies to rituximab treatment. Previously, we have shown that the potent CD59 inhibitor rILYd4 sensitizes rituximab-resistant lymphoma cells to rituximab-mediated CDC. Here, we further investigated whether rILYd4 can sensitize B-cell malignancies to ofatumumab-mediated CDC and whether either ofatumumab-mediated CDC or rILYd4-enhanced ofatumumab-mediated CDC correlates with CD20 or CD59 expression, known biomarkers involved in rituximab activity.Rituximab-resistant cell lines and primary CLL cells were used to investigate the antitumor efficacy of the combination of rILYd4 with ofatumumab or rituximab. Propidium iodide staining or alamarBlue assay were used to evaluate the CDC effect. The levels of CD20 and CD59 on the cell membrane were analyzed by flow cytometry.rILYd4 enhanced CDC effects mediated by ofatumumab or rituximab on rituximab-resistant lymphoma cells and primary CLL cells in vitro. The sensitivity to CDC effects mediated by ofatumumab positively correlated with the ratio of CD20/CD59 and negatively correlated with CD59 levels on CLL cells. The degree to which rILYd4 enhanced CDC correlated positively with the CD59 levels on CLL cells.These data suggest that rILYd4 may enhance the anticancer activity of ofatumumab and rituximab in B-cell malignancies that have relapsed after prior antibody-based therapies.
Effects of 9-<i>cis</i>-Retinoic Acid on the Insulin-Like Growth Factor Axis in Former Smokers
Authors: Ho-Young Lee, Yoon Soo Chang, Ji-Youn Han, Diane D. Liu, J. Jack Lee, Reuben Lotan, Margaret R. Spitz, Waun Ki Hong
Journal: Journal of Clinical Oncology (2005)

Purpose Insulin-like growth factor (IGF) axis has been associated with the risk of lung cancer. 9-cis-retinoic acid (9-cis-RA) has shown potential chemopreventive activities in former smokers. This study was designed to evaluate the effects of 9-cis-RA on IGF axis in former smokers to identify any benefit the retinoid may have in preventing lung cancer. Patients and Methods Serum concentrations of IGF-I, IGF binding protein (IGFBP)-3, and their molar ratio (IGF-I/IGFBP-3) were measured with radioimmunoassay kits in stored blood samples from the participants of an original chemoprevention trial. The participants had ceased smoking for at least 12 months and were randomly assigned to receive 3 months of daily oral 9-cis-RA (100 mg) or placebo. All statistical tests were two-sided. Results A total of 111 samples from the study's baseline and 84 samples from the 3 months treatment were analyzed. The serum concentrations of IGF-I and IGF-I/IGFBP-3 at baseline were significantly lower in female than in male participants. After 3 months of treatment, the serum level of IGF-I and IGF-I/IGFBP-3 were significantly lower in the 9-cis-RA group than in the placebo group (P = .03 and P &lt; .01, respectively), but the IGFBP-3 level was significantly higher (P = .03). Conclusion 9-cis-RA treatment modulated the IGF axis in former smokers, suggesting that the IGF axis is a potential target for the chemopreventive activities of 9-cis-RA and that the serum concentrations of IGF, IGFBP-3, and IGF-I/IGFBP-3 could serve as surrogate end point biomarkers of 9-cis-RA treatment.
Gene Conversion Maintains Nonfunctional Transposable Elements in an Obligate Mutualistic Endosymbiont
Authors: R. Cordaux
Journal: Molecular Biology and Evolution (2009)

Long-term bacterial endosymbionts typically exhibit reduced genomes, lack genes encoding recombination functions and transposable elements, such as insertion sequences (ISs). In sharp contrast, I found that ISs constitute 2.4% of the genome of the obligate mutualistic endosymbiont Wolbachia wBm. Although no IS copy is transpositionally functional, I show that ISs persist in wBm because of frequent recombinational gene conversion (GC) homogenizing homologous IS sequences. These results not only indicate that there exists a functional recombination molecular machinery in wBm, but they also suggest that, by slowing down the rate of IS degradation and loss, GC may represent a major force influencing reductive evolution in wBm.
Assessment of short-, medium-, and long-term variations in arterial dimensions from computer-assisted quantitation of coronary cineangiograms.
Authors: J H Reiber, P W Serruys, C J Kooijman, W Wijns, C J Slager, J J Gerbrands, J C Schuurbiers, A den Boer, P G Hugenholtz
Journal: Circulation (1985)

A computer-assisted technique has been developed to assess absolute coronary arterial dimensions from 35 mm cineangiograms. The boundaries of optically magnified and video-digitized coronary segments and the intracardiac catheter are defined by automated edge-detection techniques. Contour positions are corrected for pincushion distortion. The accuracy and precision of the edge detection procedure as assessed from cinefilms of contrast-filled acrylate (Perspex) models were -30 and 90 micrometers, respectively. The variability of the analysis procedure itself in terms of absolute arterial dimensions was less than 0.12 mm, and in terms of percentage arterial narrowing for coronary obstructions less than 2.74%. Short-, medium-, and long-term variability measurements were assessed from repeated coronary angiographic examinations performed 5 min, 1 hr, and 90 days apart, respectively. For all studies the mean differences in absolute diameters were less than 0.13 mm. The variability in obstruction diameter ranged from 0.22 mm for the best-controlled study (medium-term) to 0.36 mm for the least-controlled study (long-term); variability in reference diameter ranged from 0.15 to 0.66 mm, respectively. It is concluded that the biological variations are a source of major concern and that further attempts toward standardization of the angiographic procedure are seriously needed.
Modification of HDL3 by mild oxidative stress increases ATP-binding cassette transporter 1-mediated cholesterol efflux
Authors: A PIRILLO, P UBOLDI, G PAPPALARDO, H KUHN, A CATAPANO
Journal: Cardiovascular Research (2007)

Elevated levels of high-density lipoprotein (HDL) cholesterol are inversely related to the risk of cardiovascular disease. The anti-atherosclerotic function of HDL is mainly ascribed to its role in reverse cholesterol transport, and requires the integrity of HDL structure. Experimental evidence suggests that the ability of HDL to promote removal of excess cholesterol from peripheral cells is impaired upon oxidation. On the other hand, tyrosylation of HDL enhances its protective function, suggesting that not all forms of modified lipoprotein may be atherogenic. In the present study we investigated the effect of a mild oxidation of HDL(3) on its function as cholesterol acceptor.A mild oxidative stress (induced by 15 min exposure of HDL(3) to 1 microM Cu(++) or to 15-lipoxygenase) caused the formation of pre-beta-migrating particles. Compared to native lipoprotein, mildly modified HDL(3) induced a significant ATP-binding cassette transporter 1 (ABCA1)-mediated increase of cholesterol and phospholipids efflux from J774 macrophages. This effect was abolished by an inhibitor of ABCA1-mediated lipid efflux (glyburide) and was absent in Tangier fibroblasts.A mild oxidative modification of HDL(3) may improve its function as cholesterol acceptor, increasing ABCA1-mediated lipid efflux from macrophages, a process that may reduce foam cell formation.
Amiodarone-induced hepatic phospholipidosis: A morphological alteration independent of pseudoalcoholic liver disease
Authors: Bernard Guigui, Sylvain Perrot, Jean Pierre Berry, Jocelyne Fleury-Feith, Nadine Martin, Jean Michel Métreau, Daniel Dhumeaux, Elie Serge Zafrani
Journal: Hepatology (1988)

In order to study the relationship between amiodarone-induced hepatic phospholipidosis and liver disease, liver biopsies obtained from 13 patients treated with amiodarone for 4 months to 15 years were investigated by light and electron microscopy. Light microscopy showed pseudoalcoholic liver lesions that were probably related to amiodarone in four cases, various alterations (i.e. cirrhosis, three cases; steatosis and fibrosis, two cases; chronic venous congestion, one case; acute hepatitis, one case) that could be explained by another cause than amiodarone in seven cases and normal liver in two cases. In all cases, electron microscopy showed intralysosomal myelin figures suggestive of phospholipidosis. These myelin figures were associated with intralysosomal electron-dense deposits. In the four cases in which analysis by electron microprobe was performed, it demonstrated large amounts of iodine in the electron-dense deposit-containing lysosomes, indicating the accumulation of amiodarone. These results show that hepatic phospholipidosis is constantly observed in amiodarone-treated patients, whether or not pseudoalcoholic liver lesions are present. This phospholipidosis, which could be only a morphological marker of intrahepatic accumulation of the drug, should not therefore be considered grounds for attributing liver disease to the drug.
An Integrated Genomic and Epigenomic Approach Predicts Therapeutic Response to Zebularine in Human Liver Cancer
Authors: Jesper B. Andersen, Valentina M. Factor, Jens U. Marquardt, Chiara Raggi, Yun-Han Lee, Daekwan Seo, Elizabeth A. Conner, Snorri S. Thorgeirsson
Journal: Science Translational Medicine (2010)

Epigenomic changes such as aberrant hypermethylation and subsequent atypical gene silencing are characteristic features of human cancer. Here, we report a comprehensive characterization of epigenomic modulation caused by zebularine, an effective DNA methylation inhibitor, in human liver cancer. Using transcriptomic and epigenomic profiling, we identified a zebularine response signature that classified liver cancer cell lines into two major subtypes with different drug responses. In drug-sensitive cell lines, zebularine caused inhibition of proliferation coupled with increased apoptosis, whereas drug-resistant cell lines showed up-regulation of oncogenic networks (for example, E2F1, MYC, and TNF) that drive liver cancer growth in vitro and in preclinical mouse models. Assessment of zebularine-based therapy in xenograft mouse models demonstrated potent therapeutic effects against tumors established from zebularine-sensitive but not zebularine-resistant liver cancer cells, leading to increased survival and decreased pulmonary metastasis. Integration of the zebularine gene expression and demethylation response signatures allowed differentiation of patients with hepatocellular carcinoma according to their survival and disease recurrence. This integrated signature identified a subclass of patients within the poor-survivor group that is likely to benefit from therapeutic agents that target the cancer epigenome.