tbuckley/cabot-search huggingface dataset:
Symptoms and QOL as Predictors of Chemoprevention Adherence in NRG Oncology/NSABP Trial P-1
Authors: Stephanie R. Land, Farzana L. Walcott, Qing Liu, D. Lawrence Wickerham, Joseph P. Costantino, Patricia A. Ganz
Journal: JNCI Journal of the National Cancer Institute (2015)

Tamoxifen provides a 50% reduction in the incidence of breast cancer (BC) among high-risk women, yet many do not adhere to the five-year course of therapy. Using the prospective double-blind National Surgical Adjuvant Breast and Bowel Project P-1 study, we evaluated whether participant-reported outcomes were associated with drug adherence and whether baseline behavioral risk factors modified those associations. P-1 participants were randomly assigned to placebo vs tamoxifen (20mg/day). Mixed effects logistic regression was used to evaluate whether baseline or three-month SF-36 quality of life (QOL) mental and physical component summaries (MCS, PCS), and participant-reported symptoms (gynecologic, vasomotor, sexual, and other) predicted 12-month drug adherence (76–100% of assigned medication). The evaluation accounted for age, treatment, estimated breast cancer risk, education, baseline smoking, alcohol consumption, and obesity. All statistical tests were two-sided. Participants enrolled at least three years before trial unblinding and without medically indicated discontinuation before 12 months were eligible for the present analyses (n = 10 576). At 12 months, 84.3% were adherent. Statistically significant predictors of adherence were: three-month MCS (odds ratio [OR] = 1.15 per 10 points, 95% confidence interval [CI] = 1.06 to 1.25); three-month gynecologic symptoms among moderate alcohol drinkers (OR = .79, 95% CI = 0.72 to 0.88); baseline vasomotor symptoms among participants assigned tamoxifen (OR = .88, 95% CI = 0.80 to 0.97); and three-month sexual symptoms among younger participants (OR = .89 at age 41 years, 95% CI = 0.80 to 0.99). The strongest association was with three-month other symptoms (OR = .77, 95% CI = 0.63 to 0.93). PCS was not associated with adherence. Symptom and QOL associations were not modified by smoking or obesity. Promoting QOL and managing symptoms early in therapy may be important strategies to improve adherence.
Autophagy, Metabolism, and Cancer
Authors: Eileen White, Janice M. Mehnert, Chang S. Chan
Journal: Clinical Cancer Research (2015)

Abstract Macroautophagy (autophagy hereafter) captures intracellular proteins and organelles and degrades them in lysosomes. The degradation breakdown products are released from lysosomes and recycled into metabolic and biosynthetic pathways. Basal autophagy provides protein and organelle quality control by eliminating damaged cellular components. Starvation-induced autophagy recycles intracellular components into metabolic pathways to sustain mitochondrial metabolic function and energy homeostasis. Recycling by autophagy is essential for yeast and mammals to survive starvation through intracellular nutrient scavenging. Autophagy suppresses degenerative diseases and has a context-dependent role in cancer. In some models, cancer initiation is suppressed by autophagy. By preventing the toxic accumulation of damaged protein and organelles, particularly mitochondria, autophagy limits oxidative stress, chronic tissue damage, and oncogenic signaling, which suppresses cancer initiation. This suggests a role for autophagy stimulation in cancer prevention, although the role of autophagy in the suppression of human cancer is unclear. In contrast, some cancers induce autophagy and are dependent on autophagy for survival. Much in the way that autophagy promotes survival in starvation, cancers can use autophagy-mediated recycling to maintain mitochondrial function and energy homeostasis to meet the elevated metabolic demand of growth and proliferation. Thus, autophagy inhibition may be beneficial for cancer therapy. Moreover, tumors are more autophagy-dependent than normal tissues, suggesting that there is a therapeutic window. Despite these insights, many important unanswered questions remain about the exact mechanisms of autophagy-mediated cancer suppression and promotion, how relevant these observations are to humans, and whether the autophagy pathway can be modulated therapeutically in cancer. Clin Cancer Res; 21(22); 5037–46. ©2015 AACR. See all articles in this CCR Focus section, “Cell Death and Cancer Therapy.”
The Iodine Deficiency Disorders: Their Nature and Prevention
Authors: B S Hetzel, J T Dunn
Journal: Annual Review of Nutrition (1989)

The Iodine Deficiency Disorders: Their Nature and Prevention, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/nutr/9/1/annurev.nu.09.070189.000321-1.gif
Interactions Between Retinal Ganglion Cells During the Development of the Mammalian Visual System
Authors: C J Shatz, D W Sretavan
Journal: Annual Review of Neuroscience (1986)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Phase I and pharmacokinetic evaluation of all-trans-retinoic acid in pediatric patients with cancer.
Authors: M A Smith, P C Adamson, F M Balis, J Feusner, L Aronson, R F Murphy, M E Horowitz, G Reaman, G D Hammond, R M Fenton
Journal: Journal of Clinical Oncology (1992)

PURPOSE Recent reports of the dramatic antitumor effect of all-trans-retinoic acid (RA) in patients with acute promyelocytic leukemia (APL) have renewed interest in the oncologic indications for retinoids. Furthermore, a variety of pediatric tumors are responsive to RA in vitro, which provides additional rationale for a phase I evaluation of RA in children with cancer that is refractory to standard therapy. PATIENTS AND METHODS A phase I trial of RA administered orally twice daily for 28-day treatment courses was performed. Cohorts of at least three pediatric cancer patients were entered at successive RA dose levels (from 45 to 80 mg/m2/d) until dose-limiting toxicity (DLT) was consistently observed. RESULTS The maximum-tolerated dose (MTD) of RA was 60 mg/m2/d. Three of eight patients at the 80-mg/m2/d dose level developed reversible pseudotumor cerebri that necessitated discontinuation of the agent. Both patients with APL achieved complete remission (CR), whereas no patients with solid tumors had objective responses. Pharmacokinetic studies demonstrated a relatively short terminal half-life for RA (45 minutes), with diminution in plasma levels after chronic dosing. CONCLUSIONS The MTD and recommended phase II dose for RA in children is 60 mg/m2/d given twice daily. Reversible CNS toxicity related to RA-induced pseudotumor cerebri is dose-limiting. Two children with APL achieved a CR to RA, which supports the inclusion of pediatric patients in clinical trials that evaluate the use of RA for patients with APL.
Evaluating equality in psoriasis healthcare: a cohort study of the impact of age on prescription of biologics
Authors: K. Geale, M. Henriksson, M. Schmitt-Egenolf
Journal: British Journal of Dermatology (2015)

Summary Background Inequality in healthcare has been identified in many contexts. To the best of our knowledge, this is the first study investigating age inequality in the form of prescription patterns of biologics in psoriasis care. Objectives To determine whether patients with psoriasis have equal opportunities to receive biological medications as they age. If patients did not receive equal treatment, a subsequent objective was to determine the magnitude of the disparity. Methods A cohort of biologic-naive patients with psoriasis was analysed using Cox proportional hazards models to measure the impact of each additional year of life on the likelihood of initiating biological treatment, after controlling for sex, body mass index, comorbidities, disease activity and educational level. A supporting analysis used a nonparametric graphical method to study the proportion of patients initiating biological treatment as age increased, after controlling for the same covariates. Results The Cox proportional hazards model resulted in hazard ratios of a 1-year increase in age of 0·96–0·97 depending on calendar-year stratification, which implies that an increase in age of 30 years corresponds to a reduced likelihood of initiating biological treatment by 61·3–67·6%. The estimated proportion of patients initiating biological medication always decreased as age increased, at a statistically significant level. Conclusions Patients with psoriasis have fewer opportunities to access biological medications as they age. This result was shown to be applicable at all stages in a patient's life course and was not only restricted to the elderly, although it implies greater disparities as the age difference between patients increases. These results show that inequality in access to biological treatments due to age is prevalent in clinical practice today. Further research is needed to investigate the extent to which this result is influenced by patient preferences.
Epistatic Interactions in the Arabinose<i>Cis</i>-Regulatory Element
Authors: Mato Lagator, Claudia Igler, Anaísa B. Moreno, Călin C. Guet, Jonathan P. Bollback
Journal: Molecular Biology and Evolution (2015)

Changes in gene expression are an important mode of evolution; however, the proximate mechanism of these changes is poorly understood. In particular, little is known about the effects of mutations within cis binding sites for transcription factors, or the nature of epistatic interactions between these mutations. Here, we tested the effects of single and double mutants in two cis binding sites involved in the transcriptional regulation of the Escherichia coli araBAD operon, a component of arabinose metabolism, using a synthetic system. This system decouples transcriptional control from any posttranslational effects on fitness, allowing a precise estimate of the effect of single and double mutations, and hence epistasis, on gene expression. We found that epistatic interactions between mutations in the araBAD cis-regulatory element are common, and that the predominant form of epistasis is negative. The magnitude of the interactions depended on whether the mutations are located in the same or in different operator sites. Importantly, these epistatic interactions were dependent on the presence of arabinose, a native inducer of the araBAD operon in vivo, with some interactions changing in sign (e.g., from negative to positive) in its presence. This study thus reveals that mutations in even relatively simple cis-regulatory elements interact in complex ways such that selection on the level of gene expression in one environment might perturb regulation in the other environment in an unpredictable and uncorrelated manner.
Heterogeneous cell origin of <i>Helicobater pylori</i>-dependent high-grade gastric lymphomas.
Authors: Sung Hsin Kuo, Li-Tzong Chen, Chung-Wu Lin, Kun-Huei Yeh, Hui-Jen Tsai, Hsiao-Wei Lee, Ming-Shiang Wu, Ping-Ning Hsu, Ann-Lii Cheng
Journal: Journal of Clinical Oncology (2015)

e19520 Background: We recently showed that gastric “pure” diffuse large B-cell lymphoma (DLBCL) as well as DLBCL with histologic evidence of mucosa-associated lymphoid tissue (DLBCL[MALT]) remains Helicobater pylori (HP)-dependent, and can be cured by HP eradication (HPE) therapy. Since HP-related low-grade gastric lymphomas are of homogeneous marginal-zone B cell origin, we intended to explore if this holds true for HP-dependent high-grade gastric lymphoma. Methods: Lymphoma biopsies from 11 “pure’ DLBCL, 16 DLBCL(MALT), and 18 MALT lymphoma of stomach patients who achieved complete pathologic remission after HPE were included. We used immunohistochemistry to measure the expression of CD10, BCL6, and MUM-1, and used Hans algorithm to define germinal center B-cell (GCB) and non-GCB origin. Eight gastric “pure” DLBCLs were further examined by Agilent Whole Human Genome microarray to discriminate GCB and non-GCB signatures. Results: By Hans algorithm, all 18 low-grade MALT lymphomas were of non-GCB phenotype, compatible with marginal-zone B cell origin. Surprisingly, 7 (58.3%) of 12 gastric “pure” DLBCLs and 8 (50.0%) of 16 DLBCL (MALT)s were of GCB phenotype. By further gene expression assay in 8 cases of “pure” DLBCL, 4 (80.0%) of 5 patients with GCB by Hans algorithm had GCB signatures, whereas 2 (66.7%) of 3 patients with non-GCB by Hans algorithm had non-GCB signatures. Conclusions: These findings suggest that a substantial portion of HP-dependent large B-cell lymphoma of the stomach may not be of marginal B-cell origin. Whether HP can also transform GCB into large cell lymphoma warrants further investigation.
Costs of blood transfusion: a process-flow analysis.
Authors: S B Cantor, D V Hudson, B Lichtiger, E B Rubenstein
Journal: Journal of Clinical Oncology (1998)

PURPOSE To determine the cost of transfusing 2 units (U) of packed RBCs at a comprehensive cancer center. METHODS We performed a process-flow analysis to identify all costs of transfusing 2 U of allogeneic packed RBCs on an outpatient basis to patients with either (1) solid tumor who did not undergo bone marrow transplantation (BMT), (2) solid tumor who underwent BMT, (3) hematologic malignancy who did not undergo BMT, (4) hematologic malignancy who underwent allogeneic BMT, or (5) hematologic malignancy who underwent autologous BMT. We conducted structured interviews to determine the personnel time used and physical resources necessary at all steps of the transfusion process. RESULTS The mean cost of a 2-U transfusion of allogeneic packed RBCs was $548, $565, $569, $569, and $566 for patients with non-BMT solid tumor, BMT solid tumor, non-BMT hematologic malignancy, allogeneic BMT hematologic malignancy, and autologous BMT hematologic malignancy, respectively. Sensitivity analysis showed that total transfusion costs were sensitive to variations in the amount of clinician compensation and overhead costs, but were relatively insensitive to reasonable variations in the direct costs of blood tests and the blood itself, or the probability or extent of transfusion reaction. CONCLUSION The costs of the transfusion of packed RBCs are greater than previously analyzed, particularly in the cancer care setting.
Peripheral neuropathy after high-dose cytosine arabinoside, daunorubicin, and asparaginase consolidation for acute nonlymphocytic leukemia.
Authors: B L Powell, R L Capizzi, E S Lyerly, M R Cooper
Journal: Journal of Clinical Oncology (1986)

Two patients with acute nonlymphocytic leukemia (ANLL) developed peripheral motor and sensory neuropathies after consolidation chemotherapy with high-dose cytosine arabinoside (ara-C), daunorubicin, and asparaginase. Evidence for ara-C and daunorubicin-induced peripheral neuropathies is reported. Despite the frequent use of these agents, only two cases of peripheral neuropathy after systemic therapy have been previously described; neurotoxic effects may be potentiated and become clinically important when the three drugs are used in combination.
The CKD-EPI equation for eGFR predicted adverse outcomes after PCI better than other equations
Authors: Sean A. Hebert, Donald A. Molony
Journal: Annals of Internal Medicine (2015)

Source Citation Parsh J, Seth M, Aronow H, et al. Choice of estimated glomerular filtration rate equation impacts drug-dosing recommendations and risk stratification in patients with chronic kidney disease undergoing percutaneous coronary interventions. J Am Coll Cardiol. 2015;65:2714-23. 26112195
Cognition as the tip of the emotional iceberg: A neuro-evolutionary perspective
Authors: Peter A. Bos, Eddie Brummelman, David Terburg
Journal: Behavioral and Brain Sciences (2015)

Abstract We emphasize the importance of a neuroevolutionary perspective in moving beyond the cognition-emotion dichotomy. Cognitive behavior depends on cortical structures firmly rooted in the emotional brain from which they have evolved. As such, there cannot be cognition without emotion. Endocrine regulation of amygdala connectivity, a neural “switch” between impulsivity and deliberation, further underscores the phylogenetic impossibility of a cognition-emotion dichotomy.
Liver Enzymes Changes and Safety Profile of Deferasirox Iron Chelator in Omani Children with Thalassemia Major
Authors: Surekha Tony Mevada, Abdaluziz Sulieman AlDhuli, A.Hakim Al-Rawas, Murtadha K. Al-Khabori, Hanan Nazir, Mathew Zachariah, Prof. Yasser Wali
Journal: Blood (2014)
Drug points: Acute dissection of the aorta with amphetamine misuse
Authors: W C Dihmis, P Ridley, J P Dhasmana, J D Wisheart
Journal: BMJ (1997)

Objective: To test the efficacy of a graded aerobic exercise programme in the chronic fatigue syndrome.Design: Randomised controlled trial with control treatment crossover after the first follow up examination.Setting: Chronic fatigue clinic in a general hospital department of psychiatry.Subjects: 66 patients with the chronic fatigue syndrome who had neither a psychiatric disorder nor appreciable sleep disturbance.Interventions: Random allocation to 12 weeks of either graded aerobic exercise or flexibility exercises and relaxation therapy.Patients who completed the flexibility programme were invited to cross over to the exercise programme afterwards.Main outcome measure: The self rated clinical global impression change score, "very much better" or "much better" being considered as clinically important.Results: Four patients receiving exercise and three receiving flexibility treatment dropped out before completion.16 of 29 patients rated themselves as better after completing exercise treatment compared with eight of 30 patients who completed flexibility treatment.Analysis by intention to treat gave similar results (17/33 v 9/33 patients better).Fatigue, functional capacity, and fitness were significantly better after exercise than after flexibility treatment.12 of 22 patients who crossed over to exercise after flexibility treatment rated themselves as better after completing exercise treatment.32 of 47 patients rated themselves as better three months after completing supervised exercise treatment.35 of 47 patients rated themselves as better one year after completing supervised exercise treatment.Conclusion: These findings support the use of appropriately prescribed graded aerobic exercise in the management of patients with the chronic fatigue syndrome.
Combined modality therapy with radiotherapy, chemotherapy, and immunotherapy in limited small-cell carcinoma of the lung: a Phase III cancer and Leukemia Group B Study.
Authors: L H Maurer, T Pajak, W Eaton, R Comis, P Chahinian, C Faulkner, P M Silberfarb, E Henderson, V B Rege, P E Baldwin
Journal: Journal of Clinical Oncology (1985)

Patients with limited-stage small-cell carcinoma of the lung (SCCL) were randomly assigned to a four-drug chemotherapy program consisting of methotrexate, doxorubicin, cyclophosphamide, and CCNU (MACC) or to a regimen consisting of cyclophosphamide, CCNU, and vincristine alternated with Adriamycin (Adria Laboratories, Columbus, Ohio) and vincristine (CCV/AV). All patients received 4,500 cGy, in a split course, to the primary tumor, mediastinum, and supraclavicular lymph node drainage areas and 3,000 cGy to the whole brain. After four cycles of chemotherapy, patients were randomly assigned to chemotherapy plus methanol extractable residue of BCG (MER-BCG) or no MER-BCG. The complete response frequencies were similar for the two regimens (54% and 48%) as were the median survivals (12.0 and 11.5 months) and the two-year survival rates (15% and 17%). Immunotherapy with MER-BCG did not prolong the time to disease progression or improve survival. Women had a greater chance of achieving a complete remission independent of performance status. There was a complex interaction between sex and the chemotherapy regimens that may have important implications for the design and stratification of future trials in SCCL.
Early High-Frequency Oscillatory Ventilation in Pediatric Acute Respiratory Failure. A Propensity Score Analysis
Authors: Scot T. Bateman, Santiago Borasino, Lisa A. Asaro, Ira M. Cheifetz, Shelley Diane, David Wypij, Martha A. Q. Curley
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: The use of high-frequency oscillatory ventilation (HFOV) for acute respiratory failure in children is prevalent despite the lack of efficacy data.Objectives: To compare the outcomes of patients with acute respiratory failure managed with HFOV within 24–48 hours of endotracheal intubation with those receiving conventional mechanical ventilation (CMV) and/or late HFOV.Methods: This is a secondary analysis of data from the RESTORE (Randomized Evaluation of Sedation Titration for Respiratory Failure) study, a prospective cluster randomized clinical trial conducted between 2009 and 2013 in 31 U.S. pediatric intensive care units. Propensity score analysis, including degree of hypoxia in the model, compared the duration of mechanical ventilation and mortality of patients treated with early HFOV matched with those treated with CMV/late HFOV.Measurements and Main Results: Among 2,449 subjects enrolled in RESTORE, 353 patients (14%) were ever supported on HFOV, of which 210 (59%) had HFOV initiated within 24–48 hours of intubation. The propensity score model predicting the probability of receiving early HFOV included 1,064 patients (181 early HFOV vs. 883 CMV/late HFOV) with significant hypoxia (oxygenation index ≥8). The degree of hypoxia was the most significant contributor to the propensity score model. After adjusting for risk category, early HFOV use was associated with a longer duration of mechanical ventilation (hazard ratio, 0.75; 95% confidence interval, 0.64–0.89; P = 0.001) but not with mortality (odds ratio, 1.28; 95% confidence interval, 0.92–1.79; P = 0.15) compared with CMV/late HFOV.Conclusions: In adjusted models including important oxygenation variables, early HFOV was associated with a longer duration of mechanical ventilation. These analyses make supporting the current approach to HFOV less convincing.
Dose Escalation in Stage III Non–Small-Cell Lung Cancer
Authors: David Cella
Journal: JAMA Oncology (2015)

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A simple, robust and highly predictive prognostic index for the determination of risk directed therapy in acute myeloid leukaemia (AML) derived from the United Kingdom medical research council (MRC) AML10 trial.
Authors: K. Wheatley, Alan Kenneth Burnett, A. H. Goldstone, I. M. Hann, R. C. Stevens, J. K. Rees, R. G. Gray
Journal: Blood (1995)