tbuckley/cabot-search huggingface dataset:
Can Oral Bisphosphonates Really Reduce the Risk of Breast Cancer in Healthy Women?
Authors: Michael Gnant
Journal: Journal of Clinical Oncology (2010)

cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: Three year results. J Natl Cancer Inst 92: 699-708, 2000 19. Stanislaus R, Carey M, Deus HF, et al: RPPAML/RIMS: A metadata format and an information management system for reverse phase protein arrays. BMC Bioinformatics 9:555, 2008 20. Zhang L, Wei Q, Mao L, et al: Serial dilution curve: A new method for analysis of reverse phase protein array data. Bioinformatics 25:650-654, 2009 21. Wong KK, Tsang YTM, Zu Z, et al: Insulin growth factor 1 pathway is a potential therapeutic target for low-grade ovarian cancers. Gynecol Oncol (in press) 22. Burger RA, Sill MW, Monk BJ, et al: Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: A Gynecologic Oncology Group study. J Clin Oncol 25:5165-5171, 2007 23. Cannistra SA, Matulonis UA, Penson RT, et al: Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol 25:5180-5186, 2007 24. Ahmed A, Le XF, Lu Z, et al. Kinase regulated microtubule stabilization correlates with paclitaxel response in a target specific siRNA kinome screen. Proc Am Assoc Cancer Res 50, 2009 (abstr 3869) 25. Ahmed A, Jacomo RO, Lu Z, et al: The salt inducible kinase 2 (SIK2) is required for centrosome separation at the onset of mitosis. Proc Am Assoc Cancer Res 50, 2009 (abstr LB-43) 26. Ahmed AA, Le X-F, Lu Z, et al: Loss of CDK5 sensitizes cells to paclitaxel by enhancing intracellular retention. Proc Am Assoc Cancer Res 57, 2010 (abstr 1585) 27. Whitehurst AW, Bodemann BO, Cardenas J, et al: Synthetic lethal screen identification of chemosensitizer loci in cancer cells. Nature 446:815-819, 2007 28. Landen CN Jr, Chavez-Reyes A, Bucana C, et al: Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery. Cancer Res 65:6910-6918, 2005
Good Glycemic Control With Flexibility in Timing of Basal Insulin Supply
Authors: Eberhard Standl, Stephan Maxeiner, Sotirios Raptis, Zahra Karimi-Anderesi, Matthias Axel Schweitzer
Journal: Diabetes Care (2005)

The early initiation of insulin therapy to achieve good metabolic control is being increasingly considered in type 2 diabetes (1), but barriers, including fear of hypoglycemia, need to be overcome to achieve target glycemic control (2).

Insulin glargine (glargine; Lantus) is a once-daily, basal human insulin analog. The 24-h duration and flat time-action profile of glargine (3) should give flexibility to patients in terms of the injection time despite targeting fasting blood glucose (FBG) close to normal: administration should be possible at any time of day provided it is at the same time each day. Previously, we have demonstrated similar levels of nocturnal hypoglycemia but better glycemic control with morning versus bedtime glargine plus three milligrams glimepiride (4).

The study objective was to compare the frequency of nocturnal hypoglycemia following morning …
Strategies to Prevent “Bad Luck” in Cancer
Authors: Adriana Albini, Silvio Cavuto, Giovanni Apolone, Douglas M. Noonan
Journal: JNCI Journal of the National Cancer Institute (2015)

It is impossible to predict exactly who will develop a cancer and who will not. We know that several "risk factors" may increase the chance of getting cancer and that risk increases with age. However, even with that in mind we seem to be able to explain only a certain number of cancers. Recently, Tomasetti and Vogelstein published a provocative article in Science stating that a large percentage of cancers may be due to "bad luck" (stochastic mutation events during DNA replication) and only a few to carcinogens, pathogens, or inherited genes and that this should impact public health policies. However, their intriguing analysis has numerous limitations, some of which have already been commented upon, including the likely biased subset of cancers and that finding a correlation does not signify a cause-effect mechanism. Here, we point out that there may also be an alternative explanation for the data, the cancer stem cell hypothesis, which postulates that cancers are derived from tissue stem cells and not from somatic differentiated cells. We also highlight the importance of the tissue microenvironment in the growth of transformed cells and outline a table of concurrent factors for several cancers. The message communicated to the public should not be one of helplessness in avoiding cancers, particularly given the now extensive knowledge of known risk factors and several agents/behaviors that can lower risk for specific cancers. While some tumors will still be due to chance, prevention should still be a primary goal for public health policies.
Auditory hallucinations, network connectivity, and schizophrenia
Authors: Ralph E. Hoffman, Maxine Varanko, Thomas H. McGlashan, Michelle Hampson
Journal: Behavioral and Brain Sciences (2004)

Multidisciplinary studies indicate that auditory hallucinations may arise from speech perception neurocircuitry without disrupted theory of mind capacities. Computer simulations of excessive pruning in speech perception neural networks provide a model for these hallucinations and demonstrate that connectivity reductions just below a “psychotogenic threshold” enhance information processing. These data suggest a process whereby vulnerability to schizophrenia is maintained in the human population despite reproductive disadvantages of this illness.
Systematic analysis of gene expression in human brains before and after death.
Authors: Henriette Franz, Claudia Ullmann, Albert Becker, Margaret Ryan, Sabine Bahn, Thomas Arendt, Matthias Simon, Svante Pääbo, Philipp Khaitovich
Journal: Genome biology (2005)

Numerous studies have employed microarray techniques to study changes in gene expression in connection with human disease, aging and evolution. The vast majority of human samples available for research are obtained from deceased individuals. This raises questions about how well gene expression patterns in such samples reflect those of living individuals.Here, we compare gene expression patterns in two human brain regions in postmortem samples and in material collected during surgical intervention. We find that death induces significant expression changes in more than 10% of all expressed genes. These changes are non-randomly distributed with respect to their function. Moreover, we observe similar expression changes due to death in two distinct brain regions. Consequently, the pattern of gene expression differences between the two brain regions is largely unaffected by death, although the magnitude of differences is reduced by 50% in postmortem samples. Furthermore, death-induced changes do not contribute significantly to gene expression variation among postmortem human brain samples.We conclude that postmortem human brain samples are suitable for investigating gene expression patterns in humans, but that caution is warranted in interpreting results for individual genes.
Nutritional status modulates box C/D snoRNP biogenesis by regulated subcellular relocalization of the R2TP complex
Authors: Yoshito Kakihara, Taras Makhnevych, Liang Zhao, Weiwen Tang, Walid A Houry
Journal: Genome biology (2014)

Box C/D snoRNPs, which are typically composed of box C/D snoRNA and the four core protein components Nop1, Nop56, Nop58, and Snu13, play an essential role in the modification and processing of pre-ribosomal RNA. The highly conserved R2TP complex, comprising the proteins Rvb1, Rvb2, Tah1, and Pih1, has been shown to be required for box C/D snoRNP biogenesis and assembly; however, the molecular basis of R2TP chaperone-like activity is not yet known.Here, we describe an unexpected finding in which the activity of the R2TP complex is required for Nop58 protein stability and is controlled by the dynamic subcellular redistribution of the complex in response to growth conditions and nutrient availability. In growing cells, the complex localizes to the nucleus and interacts with box C/D snoRNPs. This interaction is significantly reduced in poorly growing cells as R2TP predominantly relocalizes to the cytoplasm. The R2TP-snoRNP interaction is mainly mediated by Pih1.The R2TP complex exerts a novel regulation on box C/D snoRNP biogenesis that affects their assembly and consequently pre-rRNA maturation in response to different growth conditions.
Cubical Shape Enhances the Interaction of Layer‐by‐Layer Polymeric Particles with Breast Cancer Cells
Authors: Jenolyn F. Alexander, Veronika Kozlovskaya, Jun Chen, Thomas Kuncewicz, Eugenia Kharlampieva, Biana Godin
Journal: Advanced Healthcare Materials (2015)

Blood‐borne objects display a nonspherical shape with in‐flow dimensions much larger than the vascular endothelial fenestrations, yet, at the diseased state, are able to traverse through these fenestrations owing to their elasticity. The role of physical parameters including shape and elasticity in the behavior of objects found in the tumor microenvironment needs to be understood to ultimately enhance chemotherapy and minimize its side effects. In this study, sphere‐ and cube‐shaped biocompatible elastic microparticles (EM) made via layer‐by‐layer assembly of hydrogen‐bonded tannic acid/poly( N ‐vinylpyrrolidone) (TA/PVPON) as hollow polymer shells and their rigid core‐shell precursors (RM) are explored. In contrast to rigid five‐bilayer (TA/PVPON) core shells, hollow elastic shells are unrecognized by J774A.1 macrophages, yet interact with endothelial and breast cancer cells. Internalization of cubical shells is fivefold more efficient by HMVEC (human microvascular endothelial cells) and sixfold and 2.5‐fold more efficient by MDA‐MB‐231 and by SUM159 (breast cancer cells), respectively, compared to spherical shells. The interaction of cubical (TA/PVPON) 5 shells with endothelial cells is similar under 10 s −1 (characteristic of tumor vasculature) and 100 s −1 shear rate (normal vasculature) while it is decreased at 100 s −1 shear rate for the spherical shells. Our data suggest that cubical geometry promotes interaction of particles with breast cancer cells, while elasticity prevents engulfment by phagocytic cells in the tumor microenvironment.
Deriving a germinal center lymphocyte migration model from two-photon data
Authors: Marc Thilo Figge, Alexandre Garin, Matthias Gunzer, Marie Kosco-Vilbois, Kai-Michael Toellner, Michael Meyer-Hermann
Journal: The Journal of Experimental Medicine (2008)

Recently, two-photon imaging has allowed intravital tracking of lymphocyte migration and cellular interactions during germinal center (GC) reactions. The implications of two-photon measurements obtained by several investigators are currently the subject of controversy. With the help of two mathematical approaches, we reanalyze these data. It is shown that the measured lymphocyte migration frequency between the dark and the light zone is quantitatively explained by persistent random walk of lymphocytes. The cell motility data imply a fast intermixture of cells within the whole GC in approximately 3 h, and this does not allow for maintenance of dark and light zones. The model predicts that chemotaxis is active in GCs to maintain GC zoning and demonstrates that chemotaxis is consistent with two-photon lymphocyte motility data. However, the model also predicts that the chemokine sensitivity is quickly down-regulated. On the basis of these findings, we formulate a novel GC lymphocyte migration model and propose its verification by new two-photon experiments that combine the measurement of B cell migration with that of specific chemokine receptor expression levels. In addition, we discuss some statistical limitations for the interpretation of two-photon cell motility measurements in general.
Impact of the European paediatric legislation in paediatric rheumatology: past, present and future
Authors: Nicolino Ruperto, Richard Vesely, Agnes Saint-Raymond, Alberto Martini
Journal: Annals of the Rheumatic Diseases (2013)

Conducting clinical trials in paediatric rheumatology has been difficult mainly because of the lack of funding for academic studies and the lack of interest by pharmaceutical companies in the small and non-rewarding paediatric market. The situation changed dramatically a few years ago with the introduction of the Best Pharmaceuticals for Children Act in the USA and of specific legislation for the development of paediatric medicines (Paediatric Regulation) in the European Union (EU). The EU Paediatric Regulation had a positive impact in paediatric rheumatology-in particular, on the development of new treatments for children with juvenile idiopathic arthritis (JIA). Some problems remain, however, such as greater harmonisation of the regulatory aspects of medicines, how to handle me-too agents, how to conduct adequate pharmacokinetic studies and develop age-appropriate formulations, ethical problems in study review and implementation, and a change in the current JIA classification. The introduction of specific legislation, coupled with the existence of large international networks such as the Pediatric Rheumatology Collaborative Study Group (PRCSG at http://www.prcsg.org), covering North America, and the Paediatric Rheumatology International Trials Organisation (PRINTO at http://www.printo.it), covering more than 50 countries, has led to great advances in paediatric rheumatology. Future changes might increase the possibility of conducting trials with similar approaches in other paediatric rheumatological conditions and provide evidence-based treatments for children affected by rheumatic diseases.
A prediction rule for elderly primary-care patients with lower respiratory tract infections
Authors: J. Bont, E. Hak, A. W. Hoes, M. Schipper, F. G. Schellevis, T. J. M. Verheij
Journal: European Respiratory Journal (2007)

Prognostic scores for lower respiratory tract infections (LRTI) have been mainly derived in a hospital setting. The current authors have developed and validated a prediction rule for the prognosis of acute LRTI in elderly primary-care patients. Data including demographics, medication use, healthcare use and comorbid conditions from 3,166 episodes of patients aged > or =65 yrs visiting the general practitioner (GP) with LRTI were collected. Multiple logistic regression analysis was used to construct a predictive model. The main outcome measure was 30-day hospitalisation or death. The Second Dutch Survey of GPs was used for validation. The following were independent predictors of 30-day hospitalisation or death: increasing age; previous hospitalisation; heart failure; diabetes; use of oral glucocorticoids; previous use of antibiotics; a diagnosis of pneumonia; and exacerbation of chronic obstructive pulmonary disease. A prediction rule based on these variables showed that the outcome increased directly with increasing scores: 3, 10 and 31% for scores of <2 points, 3-6 and > or =7 points, respectively. Corresponding figures for the validation cohort were 3, 11 and 26%, respectively. This simple prediction rule can help the primary-care physician to differentiate between high- and low-risk patients. As a possible consequence, low-risk patients may be suitable for home treatment, whereas high-risk patients might be monitored more closely in a homecare or hospital setting. Future studies should assess whether information on signs and symptoms can further improve this prediction rule.
How valid is a self reported 12 month sports injury history?: Figure 1
Authors: B J Gabbe, C F Finch, K L Bennell, H Wajswelner
Journal: British Journal of Sports Medicine (2003)

A past injury history is one of the most commonly cited risk factors for sports injury. Often, injury history data are collected by self report surveys, with the potential for recall bias.To assess the accuracy of a 12 month injury history recall in a population of 70 community level Australian football players.The retrospective, self reported injury histories of 70 community level Australian football players were compared with prospective injury surveillance records for the same 12 month period. The accuracy of the players' recall of the number of injuries, injured body regions, and injury diagnosis was assessed.Recall accuracy declined as the level of detail requested increased. All players could recall whether or not they were injured during the previous year. Almost 80% were able to accurately recall the number of injuries and body regions injured, but not the diagnoses, whereas only 61% were able to record the exact number, body region, and diagnosis of each injury sustained.The findings of this study highlight the difficulty of using retrospectively collected injury data for research purposes. Any injury research relying on self reported injury history data to establish the relation between injury history and injury risk should consider the validity of the self report injury histories.
Abnormal oral mucosal light reflectance: a new clinical marker of high risk for colorectal cancer
Authors: C De Felice
Journal: Gut (2006)

<b>Background:</b> A familial predisposition to colorectal cancer (CRC) has been clearly established, consisting of familial clustering in 15–20% and clear hereditary aetiology in 5–10% of overall CRC cases. Early identification of families and individuals at high risk is essential as intensive surveillance has been demonstrated to reduce cancer incidence and overall mortality. In the present study, the value of oral mucosal light reflectance in identifying hereditary non-polyposis colorectal cancer (HNPCC) carriers was investigated. <b>Methods:</b> Twenty members of six different genetically unrelated HNPCC kindred and 30 genetically unrelated age and sex matched healthy controls were examined. Lower gingival and vestibular oral mucosal reflectance was measured using an imaging spectrophotometer. <b>Results:</b> HNPCC carriers showed significantly lower values in the 590–700 nm wavelength range (p⩽0.0004). A reflectance cut off value ⩽47.9% at the 700 nm wavelength discriminated between HNPCC carriers and controls, with 100% sensitivity and 100% specificity. <b>Conclusions:</b> These findings may provide an additional phenotypic sign in HNPCC carriers, which could be used in first level CRC population screening programmes.
Effect of Wheat Bran on Glycemic Control and Risk Factors for Cardiovascular Disease in Type 2 Diabetes
Authors: David J. A. Jenkins, Cyril W. C. Kendall, Livia S. A. Augustin, Margaret C. Martini, Mette Axelsen, Dorothea Faulkner, Edward Vidgen, Tina Parker, Herb Lau, Philip W. Connelly, Jerome Teitel, William Singer, Arthur C. Vandenbroucke, Lawrence A. Leiter, Robert G. Josse
Journal: Diabetes Care (2002)

OBJECTIVE—Cohort studies indicate that cereal fiber reduces the risk of diabetes and coronary heart disease (CHD). Therefore, we assessed the effect of wheat bran on glycemic control and CHD risk factors in type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 23 subjects with type 2 diabetes (16 men and 7 postmenopausal women) completed two 3-month phases of a randomized crossover study. In the test phase, bread and breakfast cereals were provided as products high in cereal fiber (19 g/day additional cereal fiber). In the control phase, supplements were low in fiber (4 g/day additional cereal fiber). RESULTS—Between the test and control treatments, no differences were seen in body weight, fasting blood glucose, HbA1c, serum lipids, apolipoproteins, blood pressure, serum uric acid, clotting factors, homocysteine, C-reactive protein, magnesium, calcium, iron, or ferritin. LDL oxidation in the test phase was higher than that seen in the control phase (12.1 ± 5.4%, P &amp;lt; 0.034). Of the subjects originally recruited, more dropped out of the study for health and food preference reasons from the control phase (16 subjects) than the test phase (11 subjects). CONCLUSIONS—High-fiber cereal foods did not improve conventional markers of glycemic control or risk factors for CHD in type 2 diabetes over 3 months. Possibly longer studies are required to demonstrate the benefits of cereal fiber. Alternatively, cereal fiber in the diet may be a marker for another component of whole grains that imparts health advantages or a healthy lifestyle.
Risk factors and costs associated with an asthma attack
Authors: G Hoskins
Journal: Thorax (2000)

<h3>BACKGROUND</h3> A study was undertaken to identify asthma patients at risk of an attack and to assess the economic impact of treatment strategies. <h3>METHODS</h3> A retrospective cohort analysis of a representative data set of 12 203 patients with asthma in the UK over a one year period was performed. Logistic multiple regression was used to model the probability of an attack occurring using a set of categorised predictor factors. Health service costs were calculated by applying published average unit costs to the patient resource data. The main outcome measures were attack incidence, health service resource use, drug treatment, and cost estimates for most aspects of asthma related health care. <h3>RESULTS</h3> Children under five years of age accounted for 597 patients (5%), 3362 (28%) were aged 5–15 years, 4315 (35%) 16–44, 3446 (28%) 45–74, and 483 (4%) were aged over 74 years. A total of 9016 patients (74%) were on some form of prophylactic asthma medication; 2653 (22%) experienced an attack in the year data collection occurred. Overall health care expenditure was estimated at £2.04 million. The average cost per patient who had an attack was £381 compared with £108 for those who did not, an increase of more than 3.5 times. In those aged under five and those over 75 years of age there were no significant markers to identify risk, but both groups were small in size. The level of treatment step in the British Thoracic Society (BTS) asthma guidelines was a statistically significant factor for all other age groups. Night time symptoms were significant in the 5–15, 16–44 and 45–74 age groups, exercise induced symptoms were only significant for the 5–15 age group, and poor inhaler technique in the 16–44 age group. <h3>CONCLUSIONS</h3> Patients at any treatment step of the BTS asthma guidelines are at risk of an asthma attack, the risk increasing as the treatment step increases. Poorly controlled asthma may have a considerable impact on health care costs. Appropriate targeting of preventive measures could therefore reduce overall health care costs and the growing pressures on hospital services associated with asthma management.
Recognition of Six-Transmembrane Epithelial Antigen of the Prostate–Expressing Tumor Cells by Peptide Antigen–Induced Cytotoxic T Lymphocytes
Authors: David A. Rodeberg, Rebecca A. Nuss, Sherine F. Elsawa, Esteban Celis
Journal: Clinical Cancer Research (2005)

Abstract The identification of novel markers and therapeutic targets in advanced cancer is critical for improving diagnosis and therapy. Six-transmembrane epithelial antigen of the prostate (STEAP) is expressed predominantly in human prostate tissue and in other common malignancies including prostate, bladder, colon, and ovarian carcinomas, and in Ewing's sarcoma, suggesting that it could function as an almost universal tumor antigen. We have used MHC peptide binding algorithms to predict potential STEAP sequences capable of stimulating in vitro naïve HLA-A2–restricted CTLs. Four of six peptides predicted by these algorithms were able to induce antigen-specific CTLs that killed peptide-pulsed HLA-A2 target cells. Two of these peptides, STEAP-292 (MIAVFLPIV) and a modification of this peptide STEAP-292.2L (MLAVFLPIV), were the most efficient in the induction of primary CTL responses. More importantly, these CTLs were able to respond to tumor cells that express HLA-A2 and STEAP (colon, bladder, prostate, Ewing's sarcoma, and melanoma). Our results provide strong evidence that STEAP-292 is naturally processed by many tumor types and is presented in the context of HLA-A2 in sufficient amounts to allow recognition by CTLs. Also because STEAP-292.2L is a more immunogenic peptide able to induce CTL recognition of these STEAP-containing tumors and may have potential as an antitumor peptide vaccine.