tbuckley/cabot-search huggingface dataset:
Efficacy of Cognitive Behavioral Therapy and Physical Exercise in Alleviating Treatment-Induced Menopausal Symptoms in Patients With Breast Cancer: Results of a Randomized, Controlled, Multicenter Trial
Authors: Saskia F.A. Duijts, Marc van Beurden, Hester S.A. Oldenburg, Myra S. Hunter, Jacobien M. Kieffer, Martijn M. Stuiver, Miranda A. Gerritsma, Marian B.E. Menke-Pluymers, Peter W. Plaisier, Herman Rijna, Alexander M.F. Lopes Cardozo, Gertjan Timmers, Suzan van der Meij, Henk van der Veen, Nina Bijker, Louise M. de Widt-Levert, Maud M. Geenen, Gijsbert Heuff, Eric J. van Dulken, Epie Boven, Neil K. Aaronson
Journal: Journal of Clinical Oncology (2012)

The purpose of our study was to evaluate the effect of cognitive behavioral therapy (CBT), physical exercise (PE), and of these two interventions combined (CBT/PE) on menopausal symptoms (primary outcome), body image, sexual functioning, psychological well-being, and health-related quality of life (secondary outcomes) in patients with breast cancer experiencing treatment-induced menopause.Patients with breast cancer reporting treatment-induced menopausal symptoms (N=422) were randomly assigned to CBT (n=109), PE (n=104), CBT/PE (n=106), or to a waiting list control group (n=103). Self-report questionnaires were completed at baseline, 12 weeks, and 6 months. Multilevel procedures were used to compare the intervention groups with the control group over time.Compared with the control group, the intervention groups had a significant decrease in levels of endocrine symptoms (Functional Assessment of Cancer Therapy-Endocrine Symptoms; P<.001; effect size, 0.31-0.52) and urinary symptoms (Bristol Female Lower Urinary Tract Symptoms Questionnaire; P=.002; effect size, 0.29-0.33), and they showed an improvement in physical functioning (36-Item Short Form Health Survey physical functioning subscale; P=.002; effect size, 0.37-0.46). The groups that included CBT also showed a significant decrease in the perceived burden of hot flashes and night sweats (problem rating scale of the Hot Flush Rating Scale; P<.001; effect size, 0.39-0.56) and an increase in sexual activity (Sexual Activity Questionnaire habit subscale; P=.027; effect size, 0.65). Most of these effects were observed at both the 12-week and 6-month follow-ups.CBT and PE can have salutary effects on endocrine symptoms and, to a lesser degree, on sexuality and physical functioning of patients with breast cancer experiencing treatment-induced menopause. Future work is needed to improve the design and the planning of these interventions to improve program adherence.
Apoptosis and Caspases in Neurodegenerative Diseases
Authors: Robert M. Friedlander
Journal: New England Journal of Medicine (2003)

A form of cell death called apoptosis is a prominent feature in a broad spectrum of neurodegenerative diseases, ranging from stroke to Huntington's disease. Hypoxia, toxic cytokines, damage to mitochondria, and noxious peptides are capable of inducing apoptosis; each of these mechanisms can account for the death of specific types of neurons in neurodegenerative diseases. Pharmacologic interference with the induction or completion of apoptosis holds promise for the treatment of these disorders, and clinical trials with one such agent are already under way.
Helicobacter bilis triggers persistent immune reactivity to antigens derived from the commensal bacteria in gnotobiotic C3H/HeN mice
Authors: A. E Jergens, J. H Wilson-Welder, A. Dorn, A. Henderson, Z. Liu, R. B Evans, J. Hostetter, M. J Wannemuehler
Journal: Gut (2006)

Infection with Helicobacter species has been associated with the development of mucosal inflammation and inflammatory bowel disease (IBD) in several mouse models. However, consensus regarding the role of Helicobacter as a model organism to study microbial-induced IBD is confounded by the presence of a complex colonic microbiota.To investigate the kinetics and inflammatory effects of immune system activation to commensal bacteria following H bilis colonisation in gnotobiotic mice.C3H/HeN mice harbouring an altered Schaedler flora (ASF) were selectively colonised with H bilis and host responses were investigated over a 10-week period. Control mice were colonised only with the defined flora (DF). Tissues were analysed for gross/histopathological lesions, and bacterial antigen-specific antibody and T-cell responses.Gnotobiotic mice colonised with H bilis developed mild macroscopic and microscopic lesions of typhlocolitis beginning 3 weeks postinfection. ASF-specific IgG responses were demonstrable within 3 weeks, persisted throughout the 10-week study, and presented as a mixed IgG1:IgG2a profile. Lymphocytes recovered from the mesenteric lymph node of H bilis-colonised mice produced increased levels of interferon gamma, tumour necrosis factor alpha (TNFalpha), interleukin 6 (IL6) and IL12 in response to stimulation with commensal- or H bilis-specific bacterial lysates. In contrast, DF mice not colonised with H bilis did not develop immune responses to their resident flora and remained disease free.Colonisation of gnotobiotic C3H/HeN mice with H bilis perturbs the host's response to its resident flora and induces progressive immune reactivity to commensal bacteria that contributes to the development of immune-mediated intestinal inflammation.
Bevacizumab Combined With Chemotherapy for Platinum-Resistant Recurrent Ovarian Cancer: The AURELIA Open-Label Randomized Phase III Trial
Authors: Eric Pujade-Lauraine, Felix Hilpert, Béatrice Weber, Alexander Reuss, Andres Poveda, Gunnar Kristensen, Roberto Sorio, Ignace Vergote, Petronella Witteveen, Aristotelis Bamias, Deolinda Pereira, Pauline Wimberger, Ana Oaknin, Mansoor Raza Mirza, Philippe Follana, David Bollag, Isabelle Ray-Coquard
Journal: Journal of Clinical Oncology (2014)

In platinum-resistant ovarian cancer (OC), single-agent chemotherapy is standard. Bevacizumab is active alone and in combination. AURELIA is the first randomized phase III trial to our knowledge combining bevacizumab with chemotherapy in platinum-resistant OC.Eligible patients had measurable/assessable OC that had progressed < 6 months after completing platinum-based therapy. Patients with refractory disease, history of bowel obstruction, or > two prior anticancer regimens were ineligible. After investigators selected chemotherapy (pegylated liposomal doxorubicin, weekly paclitaxel, or topotecan), patients were randomly assigned to single-agent chemotherapy alone or with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until progression, unacceptable toxicity, or consent withdrawal. Crossover to single-agent bevacizumab was permitted after progression with chemotherapy alone. The primary end point was progression-free survival (PFS) by RECIST. Secondary end points included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes.The PFS hazard ratio (HR) after PFS events in 301 of 361 patients was 0.48 (95% CI, 0.38 to 0.60; unstratified log-rank P < .001). Median PFS was 3.4 months with chemotherapy alone versus 6.7 months with bevacizumab-containing therapy. RECIST ORR was 11.8% versus 27.3%, respectively (P = .001). The OS HR was 0.85 (95% CI, 0.66 to 1.08; P < .174; median OS, 13.3 v 16.6 months, respectively). Grade ≥ 2 hypertension and proteinuria were more common with bevacizumab. GI perforation occurred in 2.2% of bevacizumab-treated patients.Adding bevacizumab to chemotherapy statistically significantly improved PFS and ORR; the OS trend was not significant. No new safety signals were observed.
Current Status of Sentinel Lymph Node Surgery for Breast Cancer
Authors: D. Krag
Journal: JNCI Journal of the National Cancer Institute (1999)

The purpose of this review is to critically evaluate the collective epidemiologic evidence that a history of breastfeeding may decrease the risk of breast cancer.Original data for inclusion were identified through a MEDLINE® search of the English language literature from 1966 through 1998.To date, virtually all epidemiologic data regarding breastfeeding and breast cancer risk are derived from case-control studies, which vary according to classification of breastfeeding history.Overall, the evidence with respect to "ever" breast-feeding remains inconclusive, with results indicating either no association or a rather weak protective effect against breast cancer.An inverse association between increasing cumulative duration of breast-feeding and breast cancer risk among parous women has been reported in some, but not all, studies; the failure to detect an association in some Western populations may be due to the low prevalence of prolonged breast-feeding.It appears that the protective effect, if any, of long-term breast-feeding is stronger among, or confined to, premenopausal women.It has been hypothesized that an apparently protective effect of breast-feeding may be due to elevated breast cancer risk among women who discontinue breast-feeding or who take medication to suppress lactation; however, the evidence is limited and should be interpreted with caution.The biology underlying a protective effect of breast-feeding and why this should be restricted to premenopausal women remain unknown, although several mechanisms have been postulated (hormonal changes, such as reduced estrogen; removal of estrogens through breast fluid; excretion of carcinogens from breast tissue through breast-feeding; physical changes in the mammary epithelial cells, reflecting maximal differentiation; and delay of the re-establishment of ovulation).While breastfeeding is a potentially modifiable behavior, the practical implication of reduced breast cancer risk among premenopausal women with prolonged durations of breast-feeding may be of marginal importance, particularly in Western societies.[
Endothelial cells stimulated with tumor necrosis factor-alpha express varying amounts of tissue factor resulting in inhomogenous fibrin deposition in a native blood flow system. Effects of thrombin inhibitors.
Authors: D Kirchhofer, T B Tschopp, P Hadváry, H R Baumgartner
Journal: Journal of Clinical Investigation (1994)

TNF-alpha induces changes in endothelial cell functions, such as upregulation of tissue factor, resulting in endothelial procoagulant activity which may play a role in disseminated intravascular coagulation. The procoagulant activity of TNF-alpha-stimulated endothelial cell monolayers was studied in a human ex vivo native (nonanticoagulated) blood flow system using the three thrombin inhibitors recombinant hirudin, Ro 46-6240, and heparin. Under venous blood flow conditions (shear rate 65 s-1) recombinant hirudin, Ro 46-6240, and heparin inhibited fibrin deposition on the endothelial cells by 50% at concentrations of 14, 28, and 412 ng/ml, respectively. The highest tested concentrations of the thrombin inhibitors reduced the postchamber fibrinopeptide A levels from 713 +/- 69 to < 70 ng/ml. Surprisingly, even at relatively high inhibitor concentrations, some local fibrin deposits were found on TNF-alpha-stimulated cells, suggesting that some endothelial cells possess higher procoagulant activity than others. Therefore, the surface expression pattern of tissue factor, the primary initiator of coagulation in this system, was examined by immunogold-silver staining. The results showed that the tissue factor density on the cell surface varied strongly among TNF-alpha-stimulated endothelial cells. Using TNF receptor-selective agonistic mutants of TNF-alpha, it was demonstrated further that the heterogenous surface expression of tissue factor was mediated entirely by the 55-kD TNF receptor and did not involve the 75-kD TNF receptor. We conclude that in this system TNF-alpha induces heterogenous tissue factor expression which may lead to a high local thrombin concentration, such that even in the presence of thrombin inhibitors focal fibrin deposition occurs.
Analysis of the aerobic-anaerobic transition in elite cyclists during incremental exercise with the use of electromyography.
Authors: A Lucía, O Sánchez, A Carvajal, J L Chicharro
Journal: British Journal of Sports Medicine (1999)

OBJECTIVES: To investigate the validity and reliability of surface electromyography (EMG) as a new non-invasive determinant of the metabolic response to incremental exercise in elite cyclists. The relation between EMG activity and other more conventional methods for analysing the aerobic-anaerobic transition such as blood lactate measurements (lactate threshold (LT) and onset of blood lactate accumulation (OBLA)) and ventilatory parameters (ventilatory thresholds 1 and 2 (VT1 and VT2)) was studied. METHODS: Twenty eight elite road cyclists (age 24 (4) years; VO2MAX 69.9 (6.4) ml/kg/min; values mean (SD)) were selected as subjects. Each of them performed a ramp protocol (starting at 0 W, with increases of 5 W every 12 seconds) on a cycle ergometer (validity study). In addition, 15 of them performed the same test twice (reliability study). During the tests, data on gas exchange and blood lactate levels were collected to determine VT1, VT2, LT, and OBLA. The root mean squares of EMG signals (rms-EMG) were recorded from both the vastus lateralis and the rectus femoris at each intensity using surface electrodes. RESULTS: A two threshold response was detected in the rms-EMG recordings from both muscles in 90% of subjects, with two breakpoints, EMGT1 and EMGT2, at around 60-70% and 80-90% of VO2MAX respectively. The results of the reliability study showed no significant differences (p &gt; 0.05) between mean values of EMGT1 and EMGT2 obtained in both tests. Furthermore, no significant differences (p &gt; 0.05) existed between mean values of EMGT1, in the vastus lateralis and rectus femoris, and VT1 and LT (62.8 (14.5) and 69.0 (6.2) and 64.6 (6.4) and 68.7 (8.2)% of VO2MAX respectively), or between mean values of EMGT2, in the vastus lateralis and rectus femoris, and VT2 and OBLA (86.9 (9.0) and 88.0 (6.2) and 84.6 (6.5) and 87.7 (6.4)% of VO2MAX respectively). CONCLUSION: rms-EMG may be a useful complementary non-invasive method for analysing the aerobic-anaerobic transition (ventilatory and lactate thresholds) in elite cyclists.
Human epididymis protein 4 in association with Annexin II promotes invasion and metastasis of ovarian cancer cells
Authors: Huiyu Zhuang, Mingzi Tan, Juanjuan Liu, Zhenhua Hu, Dawo Liu, Jian Gao, Liancheng Zhu, Bei Lin
Journal: Molecular Cancer (2014)

The objective of the present study was to identify human epididymis protein 4 (HE4) interacting proteins and explore the mechanisms underlying their effect on ovarian cancer cell invasion and metastasis. HE4 interacting proteins were identified by mass spectrometry and validated by co-immunoprecipitation and pull-down assays. The scratch test, the Transwell assay and animal experiments were used to assess the invasive and metastatic abilities of ovarian cancer cells before and after transfection and HE4 protein treatment. HE4 and annexin II protein expression in epithelial ovarian tissues was detected by immunohistochemistry, and the relation between their expression levels was examined. Annexin II was identified as an HE4 interacting protein. HE4 and annexin II binding interaction promoted ovarian cancer cell invasion and metastasis. HE4 and annexin II expression levels were significantly higher in malignant epithelial ovarian tissues than in benign and normal epithelial ovarian tissues, and they were higher in tissues with lymph node metastases than in those without. HE4 gene interference downregulated the expression of MAPK and the FOCAL adhesion signaling pathway-associated molecules MKNK2 and LAMB2, and HE4 protein supplementation reversed this effect. The binding interaction between HE4 and annexin II activates the MAPK and FOCAL adhesion signaling pathways, promoting ovarian cancer cell invasion and metastasis.
Visceral Fat Accumulation Is Associated With Circadian Blood Pressure in Japanese Patients With Impaired Glucose Tolerance
Authors: Takayuki Masaki, Futoshi Anan, Hironobu Yoshimatsu
Journal: Diabetes Care (2011)

A central pattern of body fat distribution is generally considered to play an important role in the metabolic syndrome, which involves insulin resistance and hypertension (1). The patients of hypertension, especially nondippers, are at increased risk of hypertension associated with cardiovascular events compared with dippers patients whose nocturnal blood pressure is reduced (2). An increased visceral fat accumulation (VFA) is also a risk factor for cardiovascular disease, however, no studies have examined a relationship between VFA and 24-h ambulatory blood pressure (ABP). In the current study, therefore, we analyzed the VFA and 24-h ABP in patients with impaired glucose tolerance (IGT).

The blood pressure monitoring program recruited 255 consecutive subjects (139 men and 116 women, aged between 48 and 66 years). …
Histone Acetylase and Deacetylase Activity in Alveolar Macrophages and Blood Mononocytes in Asthma
Authors: Borja G. Cosío, Buphinder Mann, Kazuhiro Ito, Elen Jazrawi, Peter J. Barnes, K. Fan Chung, Ian M. Adcock
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Histone acetylation status is a key factor in the regulation of inflammatory gene transcription. We investigated the activity of histone acetylases (HAT) and deacetylases (HDAC), and the effect of glucocorticoids in alveolar macrophages (AM) and peripheral blood mononuclear cells (PBMC) from subjects with asthma. Bronchoalveolar lavage was performed in 10 patients with intermittent asthma, 8 with persistent asthma, and 10 healthy control subjects. PBMCs and granulocytes were isolated from six patients with mild and severe asthma, before and after a 7-day course of prednisolone (30 mg/day). AMs were isolated for HDAC assay or incubated with dexamethasone (1 μM). HAT activity was increased (1.43 ± 0.1 vs. 1.01 ± 0.1 standard units/10 μg, p < 0.05), and HDAC activity was reduced (3,031 ± 243 vs. 5,004 ± 164 arbitrary fluorescence units/10 μg, p < 0.001) in AMs of subjects with asthma compared with control subjects. Dexamethasone suppressed LPS-induced granulocyte macrophage-colony stimulating factor, tumor necrosis factor-α, and interleukin-8 release by 83 ± 1%, 51 ± 7% and 20 ± 9% (p < 0.001), respectively. Similar effects were seen on nuclear factor-κB inhibition, and interleukin-8 release was further reduced by the HDAC enhancer, theophylline (37 ± 6%). Prednisolone increased HDAC activity in PBMCs from subjects with mild asthma. The increased inflammatory response in asthma may be due to reduced HDAC and enhanced HAT activity. Glucocorticoids and theophylline may downregulate the inflammatory response by modulating HAT and HDAC activity, and nuclear factor-κB activation.
I-kappa-kinase-2 (IKK-2) inhibition potentiates vincristine cytotoxicity in non-Hodgkin's lymphoma
Authors: Ayad Al-Katib, Alan A Arnold, Amro Aboukameel, Angela Sosin, Peter Smith, Anwar N Mohamed, Frances W Beck, Ramzi M Mohammad
Journal: Molecular Cancer (2010)

IKK-2 is an important regulator of the nuclear factor-κB (NF-κB) which has been implicated in survival, proliferation and apoptosis resistance of lymphoma cells. In this study, we investigated whether inhibition of IKK-2 impacts cell growth or cytotoxicity of selected conventional chemotherapeutic agents in non-Hodgkin's lymphoma. Two established model systems were used; Follicular (WSU-FSCCL) and Diffuse Large Cell (WSU-DLCL2) Lymphoma, both of which constitutively express p-IκB. A novel, selective small molecule inhibitor of IKK-2, ML120B (N-[6-chloro-7-methoxy-9H-β-carbolin-8-yl]-2-methylnicotinamide) was used to perturb NF-κB in lymphoma cells. The growth inhibitory effect of ML120B (M) alone and in combination with cyclophosphamide monohydrate (C), doxorubicin (H) or vincristine (V) was evaluated in vitro using short-term culture assay. We also determined efficacy of the combination in vivo using the SCID mouse xenografts. ML120B down-regulated p-IκBα protein expression in a concentration dependent manner, caused growth inhibition, increased G0/G1 cells, but did not induce apoptosis. There was no significant enhancement of cell kill in the M/C or M/H combination. However, there was strong synergy in the M/V combination where the vincristine concentration can be lowered by a hundred fold in the combination for comparable G2/M arrest and apoptosis. ML120B prevented vincristine-induced nuclear translocation of p65 subunit of NF-κB. In vivo, ML120B was effective by itself and enhanced CHOP anti-tumor activity significantly (P = 0.001) in the WSU-DLCL2-SCID model but did not prevent CNS lymphoma in the WSU-FSCCL-SCID model. For the first time, this study demonstrates that perturbation of IKK-2 by ML120B leads to synergistic enhancement of vincristine cytotoxicity in lymphoma. These results suggest that disruption of the NF-κB pathway is a useful adjunct to cytotoxic chemotherapy in lymphoma.
AUDITORY STUDIES IN SCHIZOPHRENIA
Authors: ARNOLD M. LUDWIG, BENJAMIN S. WOOD, MARION P. DOWNS
Journal: American Journal of Psychiatry (1962)

A pilot study was undertaken to evaluate some quantitative and qualitative aspects of schizophrenics' auditory behavior by means of 5 auditory tests. It was found that schizophrenics displayed completely normal auditory acuity on the pure tone and speech reception threshold tests, whereas they displayed significantly more abnormalities than controls on the tone decay, delayed auditory feedback and signal-to-noise ratio tests. There were no significant correlations between abnormal test function and other variables analyzed. The possibility of a peripheral neural inhibition working in conjunction with psychic denial was discussed as possible mechanisms accounting for these findings.
Advantage of MIDAM Protocol in Treatment of Elderly Patients With Refractory and Relapsing Acute Myeloid Leukemia
Authors: Kalman Filanovsky, Lev Shvidel, Mordechai Shtalrid
Journal: Journal of Clinical Oncology (2010)

regarding treatment of refractory and relapsing acute myeloid leuke-mia (AML) with the intermediate-dose cytarabine and mitoxantrone(MIDAM) regimen. As is well known, the complete response rates(CRR) for these patients are low and the remission duration is short.The MIDAM regimen consisting of cytarabine 1g/m
Reconciling Phylodynamics with Epidemiology: The Case of Dengue Virus in Southern Vietnam
Authors: David A. Rasmussen, Maciej F. Boni, Katia Koelle
Journal: Molecular Biology and Evolution (2013)

Coalescent methods are widely used to infer the demographic history of populations from gene genealogies. These approaches—often referred to as phylodynamic methods—have proven especially useful for reconstructing the dynamics of rapidly evolving viral pathogens. Yet, population dynamics inferred from viral genealogies often differ widely from those observed from other sources of epidemiological data, such as hospitalization records. We demonstrate how a modeling framework that allows for the direct fitting of mechanistic epidemiological models to genealogies can be used to test different hypotheses about what ecological factors cause phylodynamic inferences to differ from observed dynamics. We use this framework to test different hypotheses about why dengue serotype 1 (DENV-1) population dynamics in southern Vietnam inferred using existing phylodynamic methods differ from hospitalization data. Specifically, we consider how factors such as seasonality, vector dynamics, and spatial structure can affect inferences drawn from genealogies. The coalescent models we derive to take into account vector dynamics and spatial structure reveal that these ecological complexities can substantially affect coalescent rates among lineages. We show that incorporating these additional ecological complexities into coalescent models can also greatly improve estimates of historical population dynamics and lead to new insights into the factors shaping viral genealogies.