tbuckley/cabot-search huggingface dataset:
Randomized Controlled Trial of Expressive Writing for Patients With Renal Cell Carcinoma
Authors: Kathrin Milbury, Amy Spelman, Christopher Wood, Surena F. Matin, Nizar Tannir, Eric Jonasch, Louis Pisters, Qi Wei, Lorenzo Cohen
Journal: Journal of Clinical Oncology (2014)

This randomized controlled trial examined the quality-of-life benefits of an expressive writing (EW) intervention for patients with renal cell carcinoma (RCC) and identified a potential underlying mechanism of intervention efficacy.Patients (N = 277) with stage I to IV RCC were randomly assigned to write about their deepest thoughts and feelings regarding their cancer (EW) or about neutral topics (neutral writing [NW]) on four separate occasions. Patients completed the Center for Epidemiologic Studies Depression Scale (CES-D), MD Anderson Symptom Inventory (MDASI), Brief Fatigue Inventory (BFI), Pittsburgh Sleep Quality Index (PSQI), Medical Outcomes Study Short Form-36 (SF-36), and Impact of Event Scale (IES) at baseline and 1, 4, and 10 months after the intervention.The mean age of participants (28% stage IV; 41% female) was 58 years. Multilevel modeling analyses, using a Bonferroni-corrected α = .021 for six outcomes adjusted for the correlation among outcomes, revealed that, relative to the NW group, patients in the EW group reported significantly lower MDASI scores (P = .003) and higher physical component summary scores on the SF-36 (P = .019) at 10 months after the intervention. Mediation analyses revealed that significant group differences for MDASI scores at 10 months were mediated by lower IES scores at 1 month after the intervention in the EW group (P = .042). No significant group differences were observed in the BFI, CES-D, PSQI, and mental component summary of the SF-36.EW may reduce cancer-related symptoms and improve physical functioning in patients with RCC. Evidence suggests that this effect may occur through short-term improvements in cognitive processing.
Darbepoetin Alfa for the Treatment of Chemotherapy-Induced Anemia: Disease Progression and Survival Analysis From Four Randomized, Double-Blind, Placebo-Controlled Trials
Authors: Michael Hedenus, Johan Vansteenkiste, Dusan Kotasek, Matthew Austin, Rafael G. Amado
Journal: Journal of Clinical Oncology (2005)

To determine the effect of darbepoetin alfa (DA) on progression-free survival (PFS) and overall survival (OS) in patients with chemotherapy-induced anemia (CIA).Two 16-week randomized, double-blind, placebo-controlled phase III studies of weekly DA in anemic patients with lung cancer (n = 314) or lymphoproliferative malignancies (LPMs; n = 344) undergoing chemotherapy were analyzed with prospectively defined long-term PFS and OS end points. Short-term effects of DA on PFS and OS were analyzed by including two additional 16-week dose-finding, double-blind, placebo-controlled studies in anemic patients with multiple tumor types (n = 405) and LPMs (n = 66).Median follow-up is 15.8 months (lung cancer) and 32.6 months (LPM). Median duration of PFS was comparable between DA and placebo: 5.1 months (95% CI, 4.1 to 6.9 months) versus 4.4 months (95% CI, 3.7 to 5.3 months) for lung cancer and 14.2 months (95% CI, 12.2 to 17.5 months) versus 15.9 months (95% CI, 13.1 to 19.0 months) for LPMs. The estimated hazard ratio (HR) of death related to DA use for lung cancer was 0.77 (95% CI, 0.59 to 1.01) and 1.26 (95% CI, 0.92 to 1.71) for LPMs. In the pooled analyses of all four studies (n = 1,129), no differences in PFS or OS were observed between DA and placebo (HR = 0.92; 95% CI, 0.78 to 1.07; and HR = 0.95; 95% CI, 0.78 to 1.16, respectively).Treatment with DA does not seem to influence PFS or OS in patients with CIA. Prospective, randomized clinical trials will provide additional insights into the effects of DA on PFS and OS in specific tumor types.
Injury patterns in Swedish elite athletics: annual incidence, injury types and risk factors
Authors: Jenny Jacobsson, Toomas Timpka, Jan Kowalski, Sverker Nilsson, Joakim Ekberg, Örjan Dahlström, Per A Renström
Journal: British Journal of Sports Medicine (2013)

Objective To estimate the incidence, type and severity of musculoskeletal injuries in youth and adult elite athletics athletes and to explore risk factors for sustaining injuries. Design Prospective cohort study conducted during a 52-week period. Setting Male and female youth and adult athletics athletes ranked in the top 10 in Sweden (n=292). Results 199 (68%) athletes reported an injury during the study season. Ninety-six per cent of the reported injuries were non-traumatic (associated with overuse). Most injuries (51%) were severe, causing a period of absence from normal training exceeding 3 weeks. Log-rank tests revealed risk differences with regard to athlete category (p=0.046), recent previous injury (&gt;3 weeks time-loss; p=0.039) and training load rank index (TLRI; p=0.019). Cox proportional hazards regression analyses showed that athletes in the third (HR 1.79; 95% CI 1.54 to 2.78) and fourth TLRI quartiles (HR 1.79; 95% CI 1.16 to 2.74) had almost a twofold increased risk of injury compared with their peers in the first quartile and interaction effects between athlete category and previous injury; youth male athletes with a previous serious injury had more than a fourfold increased risk of injury (HR=4.39; 95% CI 2.20 to 8.77) compared with youth females with no previous injury. Conclusions The injury incidence among both youth and adult elite athletics athletes is high. A training load index combing hours and intensity and a history of severe injury the previous year were predictors for injury. Further studies on measures to quantify training content and protocols for safe return to athletics are warranted.
Influence of anthropometry on race performance in extreme endurance triathletes: World Challenge Deca Iron Triathlon 2006
Authors: Beat Knechtle, Patrizia Knechtle, Jorge Luis Andonie, Götz Kohler
Journal: British Journal of Sports Medicine (2007)

Objective: To investigate the influence of anthropometric variables on race performance in ultra-endurance triathletes in an ultra-triathlon. Design: Descriptive field study. Setting: The “World Challenge Deca Iron Triathlon 2006” in Monterrey, Mexico, in which everyday for 10 consecutive days athletes had to perform the distance of one Ironman triathlon of 3.8 km swimming, 180 km cycling and 42.195 km running. Subjects: Eight male ultra-endurance athletes (mean (SD) age 40.6 (10.7) years, weight 76.4 (8.4) kg, height 175 (4) cm and body mass index (BMI) 24.7 (2.2) kg/m 2 ). Interventions: None. Main outcome measures: Direct measurement of body mass, height, leg length, skinfold thicknesses, limb circumference and calculation of BMI, skeletal muscle mass (SM), percentage SM (%SM) and percentage body fat (%BF) in order to correlate measured and calculated anthropometric variables with race performance. Results: Race time was not significantly (p&gt;0.05) influenced by the directly measured variables, height, leg length, body mass, average skinfold thicknesses, or circumference of thigh, calf or upper arm. Furthermore, no significant (p&gt;0.05) correlation was observed between race time and the calculated variables, BMI, %SM and %BF. Conclusions: In a multistage ultra-triathlon over 10 Ironman triathlon distances in 10 consecutive days, there was no effect of body mass, height, leg length, skinfold thicknesses, limb circumference, BMI, %SM or %BF on race performance in the only eight finishers.
Sphingosylphosphorylcholine potentiates vasoreactivity and voltage-gated Ca2+ entry via NOX1 and reactive oxygen species
Authors: Yasin Shaifta, Vladimir A. Snetkov, Jesus Prieto-Lloret, Greg A. Knock, Sergey V. Smirnov, Philip I. Aaronson, Jeremy P.T. Ward
Journal: Cardiovascular Research (2015)

AimsSphingosylphosphorylcholine (SPC) elicits vasoconstriction at micromolar concentrations. At lower concentrations (≤1 µmol/L), however, it does not constrict intrapulmonary arteries (IPAs), but strongly potentiates vasoreactivity. Our aim was to determine whether this also occurs in a systemic artery and to delineate the signalling pathway.
An Eicosapentaenoic Acid Supplement Versus Megestrol Acetate Versus Both for Patients With Cancer-Associated Wasting: A North Central Cancer Treatment Group and National Cancer Institute of Canada Collaborative Effort
Authors: Aminah Jatoi, Kendrith Rowland, Charles L. Loprinzi, Jeff A. Sloan, Shaker R. Dakhil, Neil MacDonald, Bruno Gagnon, Paul J. Novotny, James A. Mailliard, Teresita I.L. Bushey, Suresh Nair, Brad Christensen
Journal: Journal of Clinical Oncology (2004)

Purpose Studies suggest eicosapentaenoic acid (EPA), an omega-3 fatty acid, augments weight, appetite, and survival in cancer-associated wasting. This study determined whether an EPA supplement—administered alone or with megestrol acetate (MA)—was more effective than MA. Patients and Methods Four hundred twenty-one assessable patients with cancer-associated wasting were randomly assigned to an EPA supplement 1.09 g administered bid plus placebo; MA liquid suspension 600 mg/d plus an isocaloric, isonitrogenous supplement administered twice a day; or both. Eligible patients reported a 5-lb, 2-month weight loss and/or intake of less than 20 calories/kg/d. Results A smaller percentage taking the EPA supplement gained ≥ 10% of baseline weight compared with those taking MA: 6% v 18%, respectively (P = .004). Combination therapy resulted in weight gain of ≥ 10% in 11% of patients (P = .17 across all arms). The percentage of patients with appetite improvement (North Central Cancer Treatment Group Questionnaire) was not statistically different: 63%, 69%, and 66%, in EPA-, MA-, and combination-treated arms, respectively (P = .69). In contrast, 4-week Functional Assessment of Anorexia/Cachexia Therapy scores suggested MA-containing arms experienced superior appetite stimulation compared with the EPA arm, with scores of 40, 55, and 55 in EPA-, MA-, and combination-treated arms, respectively (P = .004). Survival was not significantly different among arms. Global quality of life was not significantly different among groups. With the exception of increased impotence in MA-treated patients, toxicity was comparable. Conclusion This EPA supplement, either alone or in combination with MA, does not improve weight or appetite better than MA alone.
Genome-Wide Analysis of MEF2 Transcriptional Program Reveals Synaptic Target Genes and Neuronal Activity-Dependent Polyadenylation Site Selection
Authors: Steven W. Flavell, Tae-Kyung Kim, Jesse M. Gray, David A. Harmin, Martin Hemberg, Elizabeth J. Hong, Eirene Markenscoff-Papadimitriou, Daniel M. Bear, Michael E. Greenberg
Journal: Neuron (2008)
Chronic Progressive Panencephalitis Due to Rubella Virus Simulating Subacute Sclerosing Panencephalitis
Authors: Marvin L. Weil, Hideo H. Itabashi, Natalie E. Cremer, Lyndon S. Oshiro, Edwin H. Lennette, Laurence Carnay
Journal: New England Journal of Medicine (1975)

Late-onset chronic progressive panencephalitis developed in a 12-year-old boy with congenital rubella syndrome from whose brain rubella virus was isolated. Progressive dementia began at eight, and ataxia, choreiform movements, myoclonic seizures, and fine perimacular pigmentation appeared at 11 years of age. The cerebrospinal fluid was minimally pleocytotic and had a total protein of 156 mg per deciliter, of which 52 per cent was gamma globulin. Electroencephalography demonstrated generalized medium and occasional high-voltage slowing without burst suppression. The antibody titer to rubella virus (hemagglutination inhibition) was 1:8192 in serum and 1:256 in cerebrospinal fluid. Antibody titer to measles virus (complement fixation) was less than 1:8 in serum. Microscopical study of biopsied brain tissue at the age of 11 disclosed panencephalitis similar to subacute sclerosing panencephalitis, but with perivascular deposits and without inclusion bodies. Rubella virus was isolated from the brain by cocultivation with CV-1 cells.
Duration of Breastfeeding Modulates the Effect of Filaggrin Variants on the Risk of Eczema Early in Life: Results from the Isle of Wight Birth Cohort
Authors: Ali H. Ziyab, Wilfried Karmaus, Hongmei Zhang, John W. Holloway, Susan L. Ewart, Syed H. Arshad
Journal: Journal of Allergy and Clinical Immunology (2015)
Blockade of Interferon‐γ Normalizes Interferon‐Regulated Gene Expression and Serum CXCL10 Levels in Patients With Systemic Lupus Erythematosus
Authors: Andrew A. Welcher, Michael Boedigheimer, Alan J. Kivitz, Zahir Amoura, Jill Buyon, Alla Rudinskaya, Kevin Latinis, Kit Chiu, Kelly S. Oliner, Michael A. Damore, Gregory E. Arnold, Winnie Sohn, Narendra Chirmule, Lovely Goyal, Christopher Banfield, James B. Chung
Journal: Arthritis & Rheumatology (2015)

Objective To assess the safety and immunologic impact of inhibiting interferon‐γ (IFNγ) with AMG 811, a human IgG1 monoclonal antibody against IFNγ, in patients with systemic lupus erythematosus (SLE). Methods Twenty‐six patients with mild‐to‐moderate, stable SLE were administered placebo or a single dose of AMG 811, ranging from 2 mg to 180 mg subcutaneously or 60 mg intravenously. Results Similar to results previously reported following inhibition of type I IFNs, treatment of SLE patients with AMG 811 led to a dose‐dependent modulation of the expression of genes associated with IFN signaling, as assessed by microarray analysis of the whole blood. The list of impacted genes overlapped with that identified by stimulating human whole blood with IFNγ and with those gene sets reported in the literature to be differentially expressed in SLE patients. Serum levels of IFNγ‐induced chemokines, including IFNγ‐inducible protein 10 (IP‐10), were found to be elevated at baseline in SLE patients as compared to healthy volunteers. In contrast to previously reported results from studies using type I IFN–blocking agents, treatment with AMG 811 led to dose‐related reductions in the serum levels of CXCL10 (IP‐10). Conclusion The scope and nature of the biomarkers impacted by AMG 811 support targeting of IFNγ as a therapeutic strategy for SLE.
Bispecific Antibody to ErbB2 Overcomes Trastuzumab Resistance through Comprehensive Blockade of ErbB2 Heterodimerization
Authors: Bohua Li, Yanchun Meng, Lei Zheng, Xunmin Zhang, Qing Tong, Wenlong Tan, Shi Hu, Hui Li, Yang Chen, Jinjing Song, Ge Zhang, Lei Zhao, Dapeng Zhang, Sheng Hou, Weizhu Qian, Yajun Guo
Journal: Cancer Research (2013)

The anti-ErbB2 antibody trastuzumab has shown significant clinical benefits in metastatic breast cancer. However, resistance to trastuzumab is common. Heterodimerization between ErbB2 and other ErbBs may redundantly trigger cell proliferation signals and confer trastuzumab resistance. Here, we developed a bispecific anti-ErbB2 antibody using trastuzumab and pertuzumab, another ErbB2-specific humanized antibody that binds to a distinct epitope from trastuzumab. This bispecific antibody, denoted as TPL, retained the full binding activities of both parental antibodies and exhibited pharmacokinetic properties similar to those of a conventional immunoglobulin G molecule. Unexpectedly, TPL showed superior ErbB2 heterodimerization-blocking activity over the combination of both parental monoclonal antibodies, possibly through steric hindrance and/or inducing ErbB2 conformational change. Further data indicated that TPL potently abrogated ErbB2 signaling in trastuzumab-resistant breast cancer cell lines. In addition, we showed that TPL was far more effective than trastuzumab plus pertuzumab in inhibiting the growth of trastuzumab-resistant breast cancer cell lines, both in vitro and in vivo. Importantly, TPL treatment eradicated established trastuzumab-resistant tumors in tumor-bearing nude mice. Our results suggest that trastuzumab-resistant breast tumors remain dependent on ErbB2 signaling and that comprehensive blockade of ErbB2 heterodimerization may be an effective therapeutic avenue. The unique potential of TPL to overcome trastuzumab resistance warrants its consideration as a promising treatment in the clinic.
High-intensity knee extensor training restores skeletal muscle function in COPD patients
Authors: Eivind Brønstad, Øivind Rognmo, Arnt Erik Tjonna, Hans Henrich Dedichen, Idar Kirkeby-Garstad, Asta K. Håberg, Charlotte Bjørk Ingul, Ulrik Wisløff, Sigurd Steinshamn
Journal: European Respiratory Journal (2012)

Improving reduced skeletal muscle function is important for optimising exercise tolerance and quality of life in chronic obstructive pulmonary disease (COPD) patients. By applying high-intensity training to a small muscle group, we hypothesised a normalisation of muscle function. Seven patients with COPD performed 6 weeks (3 days·week −1 ) of high-intensity interval aerobic knee extensor exercise training. Five age-matched healthy individuals served as a reference group. Muscle oxygen uptake and mitochondrial respiration of the vastus lateralis muscle were measured before and after the 6-week training programme. Initial peak work and maximal mitochondrial respiration were reduced in COPD patients and improved significantly after the training programme. Peak power and maximal mitochondrial respiration in vastus lateralis muscle increased to the level of the control subjects and were mainly mediated via improved complex I respiration. Furthermore, when normalised to citrate synthase activity, no difference in maximal respiration was found either after the intervention or compared to controls, suggesting normal functioning mitochondrial complexes. The present study shows that high-intensity training of a restricted muscle group is highly effective in restoring skeletal muscle function in COPD patients.
Results From a European Multicenter Randomized Trial of Physical Activity and/or Healthy Eating to Reduce the Risk of Gestational Diabetes Mellitus: The DALI Lifestyle Pilot
Authors: David Simmons, Judith G.M. Jelsma, Sander Galjaard, Roland Devlieger, Andre van Assche, Goele Jans, Rosa Corcoy, Juan M. Adelantado, Fidelma Dunne, Gernot Desoye, Jürgen Harreiter, Alexandra Kautzky-Willer, Peter Damm, Elisabeth R. Mathiesen, Dorte M. Jensen, Lise Lotte Andersen, Annunziata Lapolla, Maria Dalfra, Alessandra Bertolotto, Ewa Wender-Ozegowska, Agnieszka Zawiejska, David Hill, Pablo Rebollo, Frank J. Snoek, Mireille N.M. van Poppel
Journal: Diabetes Care (2015)

OBJECTIVE Ways to prevent gestational diabetes mellitus (GDM) remain unproven. We compared the impact of three lifestyle interventions (healthy eating [HE], physical activity [PA], and both HE and PA [HE+PA]) on GDM risk in a pilot multicenter randomized trial. RESEARCH DESIGN AND METHODS Pregnant women at risk for GDM (BMI ≥29 kg/m2) from nine European countries were invited to undertake a 75-g oral glucose tolerance test before 20 weeks' gestation. Those without GDM were randomized to HE, PA, or HE+PA. Women received five face-to-face and four optional telephone coaching sessions, based on the principles of motivational interviewing. A gestational weight gain (GWG) &amp;lt;5 kg was targeted. Coaches received standardized training and an intervention toolkit. Primary outcome measures were GWG, fasting glucose, and insulin sensitivity (HOMA) at 35–37 weeks. RESULTS Among the 150 trial participants, 32% developed GDM by 35–37 weeks and 20% achieved GWG &amp;lt;5 kg. HE women had less GWG (−2.6 kg [95% CI −4.9, −0.2]; P = 0.03) and lower fasting glucose (−0.3 mmol/L [−0.4, −0.1]; P = 0.01) than those in the PA group at 24–28 weeks. HOMA was comparable. No significant differences between HE+PA and the other groups were observed. CONCLUSIONS An antenatal HE intervention is associated with less GWG and lower fasting glucose compared with PA alone. These findings require a larger trial for confirmation but support the use of early HE interventions in obese pregnant women.
<i>In vitro</i> Procoagulant Activity Induced in Endothelial Cells by Chemotherapy and Antiangiogenic Drug Combinations: Modulation by Lower-Dose Chemotherapy
Authors: Li Ma, Giulio Francia, Alicia Viloria-Petit, Daniel J. Hicklin, Jeanne du Manoir, Janusz Rak, Robert S. Kerbel
Journal: Cancer Research (2005)

Abstract One of the emerging problems concerning the use of antiangiogenic drugs, when used in combination with certain chemotherapy regimens, is enhanced rates and severity of adverse clotting events. For as yet unknown reasons, certain drugs and particular combinations can induce an elevated incidence of thromboembolic events in treated cancer patients [e.g., SU5416, a vascular endothelial cell growth factor receptor-2 (VEGFR-2) antagonist, when combined with gemcitabine and cisplatin (CDDP)]. Such results highlight the need to develop assays capturing the essence of enhanced clot formation under such combination treatment and which may have predictive potential as well. Here, we report the possibility of such an assay (i.e., the ratio of tissue factor over tissue factor pathway inhibitor expression or activity in cultured human endothelial cells calculated as a coagulation index). A marked increase in coagulation index was observed after exposure to SU5416 and the CDDP/gemcitabine chemotherapy combination in contrast to either of these treatments used alone. Substitution of SU5416 with any one of ZD6474, SU6668, IMC-1121, a monoclonal antibody to VEGFR-2, or an antibody to VEGF (bevacizumab) did not cause a marked increase in the coagulation index, nor did the combination of SU5416 with 5-fluorouracil and leucovorin. Finally, we noted that reducing the concentrations of gemcitabine and CDDP (i.e., use of “metronomic dosing” in vitro) significantly attenuated the coagulation index increase induced by these drugs, suggesting that use of low-dose chemotherapy regimens might be an approach to consider for reducing the incidence of adverse clotting events associated with chemotherapy alone or in conjunction with antiangiogenic drug combination therapies.
Inflammatory obstruction of oesophageal tubes.
Authors: T Philp, A J Gunning, M K Bennett
Journal: Gut (1983)

Two patients, intubated for inoperable carcinoma of the oesophagus, recently presented with their tubes blocked by granulation tissue. This complication has not been previously reported. The tissue macroscopically resembled normal mucosa in one and recurrent tumour in the other. The presentation, aetiology, and significance of this granulation tissue is discussed.
Alternative Cyclin D1 Splice Forms Differentially Regulate the DNA Damage Response
Authors: Zhiping Li, Xuanmao Jiao, Chenguang Wang, L. Andrew Shirley, Hany Elsaleh, Olav Dahl, Min Wang, Evi Soutoglou, Erik S. Knudsen, Richard G. Pestell
Journal: Cancer Research (2010)

The DNA damage response (DDR) activates downstream pathways including cell cycle checkpoints. The cyclin D1 gene is overexpressed or amplified in many human cancers and is required for gastrointestinal, breast, and skin tumors in murine models. A common polymorphism in the human cyclin D1 gene is alternatively spliced, resulting in cyclin D1a and D1b proteins that differ in their carboxyl terminus. Cyclin D1 overexpression enhances DNA damage-induced apoptosis. The role of cyclin D1 and the alternative splice form in regulating the DDR is not well understood. Herein cyclin D1a overexpression enhanced the DDR as characterized by induction of γH2AX phosphorylation, the assembly of DNA repair foci, specific recruitment of DNA repair factors to chromatin, and G(2)-M arrest. Cyclin D1 deletion in fibroblasts or small interfering RNA-mediated reduction of endogenous cyclin D1 in colon cancer cells reduced the 5-fluorouracil-mediated DDR. Mechanistic studies showed that cyclin D1a, like DNA repair factors, elicited the DDR when stably associated with chromatin.