tbuckley/cabot-search huggingface dataset:
Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas: North American Brain Tumor Consortium trial 04-02
Authors: P. Y. Wen, S. M. Chang, K. R. Lamborn, J. G. Kuhn, A. D. Norden, T. F. Cloughesy, H. I. Robins, F. S. Lieberman, M. R. Gilbert, M. P. Mehta, J. Drappatz, M. D. Groves, S. Santagata, A. H. Ligon, W. K. A. Yung, J. J. Wright, J. Dancey, K. D. Aldape, M. D. Prados, K. L. Ligon
Journal: Neuro-Oncology (2014)

Inhibition of epidermal growth factor receptor (EGFR) and the mechanistic target of rapamycin (mTOR) may have synergistic antitumor effects in high-grade glioma patients. We conducted a phase I/II study of the EGFR inhibitor erlotinib (150 mg/day) and the mTOR inhibitor temsirolimus. Patients initially received temsirolimus 50 mg weekly, and the dose adjusted based on toxicities. In the phase II component, the primary endpoint was 6-month progression-free survival (PFS6) among glioblastoma patients. Twenty-two patients enrolled in phase I, 47 in phase II. Twelve phase I patients treated at the maximum tolerated dosage were included in the phase II cohort for analysis. The maximum tolerated dosage was 15 mg temsirolimus weekly with erlotinib 150 mg daily. Dose-limiting toxicities were rash and mucositis. Among 42 evaluable glioblastoma patients, 12 (29%) achieved stable disease, but there were no responses, and PFS6 was 13%. Among 16 anaplastic glioma patients, 1 (6%) achieved complete response, 1 (6%) partial response, and 2 (12.5%) stable disease, with PFS6 of 8%. Tumor levels of both drugs were low, and posttreatment tissue in 3 patients showed no reduction in the mTOR target phosphorylated (phospho-)S6S235/236 but possible compensatory increase in phospho-AktS473. Presence of EGFR variant III, phospho-EGFR, and EGFR amplification did not correlate with survival, but patients with elevated phospho–extracellular signal-regulated kinase or reduced phosphatase and tensin homolog protein expression had decreased progression-free survival at 4 months. Because of increased toxicity, the maximum tolerated dosage of temsirolimus in combination with erlotinib proved lower than expected. Insufficient tumor drug levels and redundant signaling pathways may partly explain the minimal antitumor activity noted.
Effect of Internet Therapeutic Intervention on A1C Levels in Patients With Type 2 Diabetes Treated With Insulin
Authors: Hugh D. Tildesley, Adel B. Mazanderani, Stuart A. Ross
Journal: Diabetes Care (2010)

To assess the effect of an Internet-based glucose monitoring system (IBGMS) on A1C levels in patients with type 2 diabetes treated with insulin.This trial involved 50 patients randomly assigned to receive either conventional treatment alone or with additional follow-up through an IBGMS for 6 months. Patients randomized to the intervention group uploaded blood glucose readings every 2 weeks to a secure Web site for review and receipt of feedback from their endocrinologist. A1C and laboratory test results were collected at 0, 3, and 6 months.The baseline parameters were not significantly different. Over a 6-month follow-up, A1C dropped from 8.8 to 7.6% (P < 0.001) in the intervention group compared with 8.5 to 8.4% (P = 0.51) in the control group.The use of IBGMS significantly improved A1C levels in patients with type 2 diabetes treated with insulin.
Harnessing Technology to Improve Clinical Trials: Study of Real-Time Informatics to Collect Data, Toxicities, Image Response Assessments, and Patient-Reported Outcomes in a Phase II Clinical Trial
Authors: M. Catherine Pietanza, Ethan M. Basch, Alex Lash, Lawrence H. Schwartz, Michelle S. Ginsberg, Binsheng Zhao, Marwan Shouery, Mary Shaw, Lauren J. Rogak, Manda Wilson, Aaron Gabow, Marcia Latif, Kai-Hsiung Lin, Qinfei Wu, Samantha L. Kass, Claire P. Miller, Leslie Tyson, Dyana K. Sumner, Alison Berkowitz-Hergianto, Camelia S. Sima, Mark G. Kris
Journal: Journal of Clinical Oncology (2013)

Purpose In clinical trials, traditional monitoring methods, paper documentation, and outdated collection systems lead to inaccuracies of study information and inefficiencies in the process. Integrated electronic systems offer an opportunity to collect data in real time. Patients and Methods We created a computer software system to collect 13 patient-reported symptomatic adverse events and patient-reported Karnofsky performance status, semi-automated RECIST measurements, and laboratory data, and we made this information available to investigators in real time at the point of care during a phase II lung cancer trial. We assessed data completeness within 48 hours of each visit. Clinician satisfaction was measured. Results Forty-four patients were enrolled, for 721 total visits. At each visit, patient-reported outcomes (PROs) reflecting toxicity and disease-related symptoms were completed using a dedicated wireless laptop. All PROs were distributed in batch throughout the system within 24 hours of the visit, and abnormal laboratory data were available for review within a median of 6 hours from the time of sample collection. Manual attribution of laboratory toxicities took a median of 1 day from the time they were accessible online. Semi-automated RECIST measurements were available to clinicians online within a median of 2 days from the time of imaging. All clinicians and 88% of data managers felt there was greater accuracy using this system. Conclusion Existing data management systems can be harnessed to enable real-time collection and review of clinical information during trials. This approach facilitates reporting of information closer to the time of events, and improves efficiency, and the ability to make earlier clinical decisions.
Functional dissection of the ash2 and ash1 transcriptomes provides insights into the transcriptional basis of wing phenotypes and reveals conserved protein interactions
Authors: Sergi Beltran, Mireia Angulo, Miguel Pignatelli, Florenci Serras, Montserrat Corominas
Journal: Genome biology (2007)

The trithorax group (trxG) genes absent, small or homeotic discs 1 (ash1) and 2 (ash2) were isolated in a screen for mutants with abnormal imaginal discs. Mutations in either gene cause homeotic transformations but Hox genes are not their only targets. Although analysis of double mutants revealed that ash2 and ash1 mutations enhance each other's phenotypes, suggesting they are functionally related, it was shown that these proteins are subunits of distinct complexes. The analysis of wing imaginal disc transcriptomes from ash2 and ash1 mutants showed that they are highly similar. Functional annotation of regulated genes using Gene Ontology allowed identification of severely affected groups of genes that could be correlated to the wing phenotypes observed. Comparison of the differentially expressed genes with those from other genome-wide analyses revealed similarities between ASH2 and Sin3A, suggesting a putative functional relationship. Coimmunoprecipitation studies and immunolocalization on polytene chromosomes demonstrated that ASH2 and Sin3A interact with HCF (host-cell factor). The results of nucleosome western blots and clonal analysis indicated that ASH2 is necessary for trimethylation of the Lys4 on histone 3 (H3K4). The similarity between the transcriptomes of ash2 and ash1 mutants supports a model in which the two genes act together to maintain stable states of transcription. Like in humans, both ASH2 and Sin3A bind HCF. Finally, the reduction of H3K4 trimethylation in ash2 mutants is the first evidence in Drosophila regarding the molecular function of this trxG gene.
Catheter Ablation for Atrial Fibrillation
Authors: Pierre Jaïs, Dipen C. Shah, Michel Haïssaguerre, Meleze Hocini, Jing Tian Peng, Jacques Clémenty
Journal: Annual Review of Medicine (2000)

▪ Abstract Atrial fibrillation is frequently disabling and resistant to antiarrhythmic drugs. Curative treatment by catheter-based ablation has been shown to be feasible either by achieving long linear lesions, mainly in the left atrium, or by targeting the initiating focus, most frequently in the pulmonary veins. This paper reviews the different ablation approaches, their results, potential complications, and relative merits.
Indirect Regulation of PTH by Estrogens May Require FGF23
Authors: Natalia Carrillo-López, Pablo Román-García, Ana Rodríguez-Rebollar, José Luis Fernández-Martín, Manuel Naves-Díaz, Jorge B. Cannata-Andía
Journal: Journal of the American Society of Nephrology (2009)

The mechanisms by which estrogens modulate PTH are controversial, including whether or not estrogen receptors (ERs) are present in the parathyroid glands. To explore these mechanisms, we combined a rat model of CKD with ovariectomy and exogenous administration of estrogens. We found that estrogen treatment significantly decreased PTH mRNA and serum levels. We did not observe ERalpha or ERbeta mRNA or protein in the parathyroids, suggesting an indirect action of estrogens on PTH regulation. Estrogen treatment significantly decreased serum 1,25(OH)(2) vitamin D(3) and phosphorus levels. In addition, estrogens significantly increased fibroblast growth factor 23 (FGF23) mRNA and serum levels. In vitro, estrogens led to transcriptional and translational upregulation of FGF23 in osteoblast-like cells in a time- and concentration-dependent manner. These results suggest that estrogens regulate PTH indirectly, possibly through FGF23.
Has Dialysis Payment Reform Led to Initial Racial Disparities in Anemia and Mineral Metabolism Management?
Authors: Marc N. Turenne, Elizabeth L. Cope, Shannon Porenta, Purna Mukhopadhyay, Douglas S. Fuller, Jeffrey M. Pearson, Claudia Dahlerus, Brett Lantz, Francesca Tentori, Bruce M. Robinson
Journal: Journal of the American Society of Nephrology (2014)

Implementation of the Medicare ESRD prospective payment system (PPS) and changes to dosing guidelines for erythropoiesis-stimulating agents (ESAs) in 2011 appear to have influenced use of injectable medications among dialysis patients. Given historically higher ESA and vitamin D use among black patients, we assessed the effect of these policy changes on racial disparities in the management of anemia and mineral metabolism. Analyses used cross-sectional monthly cohorts for a period-prevalent sample of 7384 maintenance hemodialysis patients at 132 facilities from the Dialysis Outcomes and Practice Patterns Study (DOPPS) Practice Monitor. Linear splines with knots at each policy change were used in survey-weighted regressions to estimate time trends in hemoglobin (Hgb), erythropoietin (EPO) dose, intravenous (IV) iron dose, ferritin, transferrin saturation (TSAT) concentration, parathyroid hormone (PTH), IV vitamin D dose, cinacalcet use, and phosphate binder use. From August 2010 to December 2011, mean Hgb declined from 11.5 to 11.0 g/dl (P<0.001), mean EPO dose declined from 20,506 to 14,777 U/wk (P<0.001), and mean serum PTH increased from 340 to 435 pg/ml (P<0.001). No meaningful differences by race were observed regarding the rates of change of management practices or laboratory measures (all P>0.21). Mean EPO and vitamin D dose and serum PTH levels remained higher in blacks. Despite evidence that anemia and mineral metabolism management practices have changed significantly over time, there was no immediate indication of racial disparities resulting from implementation of the PPS or ESA label change. Further studies are needed to examine effects among patient and facility subgroups.
Critically Ill Patients With 2009 Influenza A(H1N1) in Mexico
Authors: Guillermo Domínguez-Cherit
Journal: JAMA (2009)

In March 2009, novel 2009 influenza A(H1N1) was first reported in the southwestern United States and Mexico. The population and health care system in Mexico City experienced the first and greatest early burden of critical illness.To describe baseline characteristics, treatment, and outcomes of consecutive critically ill patients in Mexico hospitals that treated the majority of such patients with confirmed, probable, or suspected 2009 influenza A(H1N1).Observational study of 58 critically ill patients with 2009 influenza A(H1N1) at 6 hospitals between March 24 and June 1, 2009. Demographic data, symptoms, comorbid conditions, illness progression, treatments, and clinical outcomes were collected using a piloted case report form.The primary outcome measure was mortality. Secondary outcomes included rate of 2009 influenza (A)H1N1-related critical illness and mechanical ventilation as well as intensive care unit (ICU) and hospital length of stay.Critical illness occurred in 58 of 899 patients (6.5%) admitted to the hospital with confirmed, probable, or suspected 2009 influenza (A)H1N1. Patients were young (median, 44.0 [range, 10-83] years); all presented with fever and all but 1 with respiratory symptoms. Few patients had comorbid respiratory disorders, but 21 (36%) were obese. Time from hospital to ICU admission was short (median, 1 day [interquartile range {IQR}, 0-3 days]), and all patients but 2 received mechanical ventilation for severe acute respiratory distress syndrome and refractory hypoxemia (median day 1 ratio of Pao(2) to fraction of inspired oxygen, 83 [IQR, 59-145] mm Hg). By 60 days, 24 patients had died (41.4%; 95% confidence interval, 28.9%-55.0%). Patients who died had greater initial severity of illness, worse hypoxemia, higher creatine kinase levels, higher creatinine levels, and ongoing organ dysfunction. After adjusting for a reduced opportunity of patients dying early to receive neuraminidase inhibitors, neuraminidase inhibitor treatment (vs no treatment) was associated with improved survival (odds ratio, 8.5; 95% confidence interval, 1.2-62.8).Critical illness from 2009 influenza A(H1N1) in Mexico occurred in young individuals, was associated with severe acute respiratory distress syndrome and shock, and had a high case-fatality rate.
Reduced eosinophil apoptosis in induced sputum correlates with asthma severity
Authors: C.J.A. Duncan, A. Lawrie, M.G. Blaylock, J.G. Douglas, G.M. Walsh
Journal: European Respiratory Journal (2003)

This study was carried out to investigate the relationship between induced sputum eosinophil apoptosis and clinical severity score, airway obstruction and symptom scores in patients with chronic stable asthma. Altogether, 41 chronic stable asthmatic subjects of varying severity defined by Aas score and 17 control subjects underwent spirometry, symptom questionnaire and successful sputum induction. Sputum was processed and cytospins prepared for light microscopy to determine normal and apoptotic eosinophils. Mild asthmatic subjects had a significantly lower percentage sputum eosinophils and a significantly higher eosinophil apoptotic ratio (AR) than moderate or chronic severe asthmatics. Severe asthmatic subjects had a significantly greater age, duration of asthma and sputum eosinophil count x mL(-1) than mild asthmatic subjects. Asthmatic subjects' symptom scores, severity scores and age inversely correlated with AR and the percentage of sputum eosinophils. Baseline forced expiratory volume in one second inversely correlated with percentage sputum eosinophils and positively correlated with AR. The study demonstrates a relationship between reduced sputum eosinophil apoptosis and increased clinical severity of chronic stable asthma, providing additional evidence that eosinophil apoptosis may be important in the resolution of eosinophilic airway inflammation in asthma.
Gemcitabine for relapsed or resistant lymphoma
Authors: D.G. Savage, S.A. I Rule, M. Tighe, T.J. Garrett, W.M. Oster, R.T. Lee, J. Ruiz, D. Heitjan, M.L. Keohan, M. Flamm, S.A. Johnson
Journal: Annals of Oncology (2000)
The preventive effect of verapamil on ethanol-induced cardiac depression: phosphorus-31 nuclear magnetic resonance and high-pressure liquid chromatographic studies of hamsters.
Authors: S Wu, R White, J Wikman-Coffelt, R Sievers, M Wendland, J Garrett, C B Higgins, T James, W W Parmley
Journal: Circulation (1987)

Alcoholic depression of left ventricular function was produced in normal hamsters by the administration of increasing concentrations of alcohol in drinking water (up to 50%) for 6 months. The result was assessed by phosphorus-31 nuclear magnetic resonance of isolated perfused hearts and high-pressure liquid chromatography of freeze-clamped tissues. Hemodynamic data and myocardial oxygen consumption were also monitored. Alcoholic hamsters had significantly higher inorganic phosphate and lower ATP levels, while maintaining normal intracellular pH, phosphocreatine, and creatine. Although coronary flow and oxygen consumption were maintained at normal levels, hamsters ingesting 50% ethanol had significantly lower left ventricular developed pressure and dP/dt. Treatment with verapamil during long-term ethanol consumption prevented the development of these metabolic and functional abnormalities. It is hypothesized that alcohol produces membrane abnormalities leading to adverse ion flux, and that these are largely prevented by concurrent administration of verapamil.
Dealing with metastatic breast cancer in elderly women: results from a French study on a large cohort carried out by the ‘Observatory on Elderly Patients’
Authors: G. Freyer, A.-C. Braud, P. Chaibi, M. Spielmann, J.-P. Martin, G. Vilela, D. Guerin, L. Zelek
Journal: Annals of Oncology (2005)
Multivariable Analysis: A Primer for Readers of Medical Research
Authors: Mitchell H. Katz
Journal: Annals of Internal Medicine (2003)

Many clinical readers, especially those uncomfortable with mathematics, treat published multivariable models as a black box, accepting the author's explanation of the results. However, multivariable analysis can be understood without undue concern for the underlying mathematics. This paper reviews the basics of multivariable analysis, including what multivariable models are, why they are used, what types exist, what assumptions underlie them, how they should be interpreted, and how they can be evaluated. A deeper understanding of multivariable models enables readers to decide for themselves how much weight to give to the results of published analyses.
Treatment of subungual exostoses by elective day case surgery
Authors: D A R De Berker, J Langtry
Journal: British Journal of Dermatology (1999)

Twenty-one patients (11 female, 10 male: mean age 21.3 years) with subungual exostoses were treated with elective surgery under local anaesthetic in a dermatology day case theatre over a period of 8 years. Fifteen (71%) tumours affected the great toe, four (19%) affected other toes and two (10%) affected fingers. All received local excision with great care to remove all tumour residue from the terminal phalanx. Wounds were allowed to heal by secondary intention. Attention was paid to preoperative antiseptic procedure and postoperative analgesia. During follow-up of between 6 and 36 months (mean 17 months), there were two relapses (10%) in the first 12 months, seen in two of the younger subjects aged 9 and 13 years. One required further surgery. One further case suffered long-term dystrophy due to perioperative damage to nail matrix. Conservative and thorough treatment of this pathology can be achieved using the appropriate tools in a dermatology day case theatre.
Effects of cholecystectomy on the kinetics of primary and secondary bile acids.
Authors: F Berr, F Stellaard, E Pratschke, G Paumgartner
Journal: Journal of Clinical Investigation (1989)

Removal of the gallbladder is thought to increase formation and pool size of secondary bile acids, mainly deoxycholic acid (DCA), by increased exposure of primary bile acids (cholic acid [CA], chenodeoxycholic acid [CDCA]) to bacterial dehydroxylation in the intestine. We have tested this hypothesis by simultaneous determination of pool size and turnover of DCA, CA, and CDCA in nine women before and at various intervals after removal of a functioning gallbladder. An isotope dilution technique using marker bile acids labeled with stable isotopes (2H4-DCA, 13C-CA, 13C-CDCA) was used. After cholecystectomy, concentration and output of bile acids relative to bilirubin increased (P less than 0.02) in fasting duodenal bile and cholesterol saturation decreased by 27% (P less than 0.05) consistent with enhanced enterohepatic cycling of bile acids. Three months after removal of the gallbladder bile acid kinetics were in a new steady state: pool size and turnover of CDCA were unchanged. Synthesis of CA, the precursor of DCA, was diminished by 37% (P = 0.05), probably resulting from feedback inhibition by continuous transhepatic flux of bile acids. The fraction of CA transferred after 7 alpha-dehydroxylation to the DCA pool increased from 46 +/- 16 to 66 +/- 32% (P less than 0.05). However, this enhanced transfer did not lead to increased input or size of the DCA pool, because synthesis of the precursor CA had decreased.
Effectiveness of a Mental Health Court in Reducing Criminal Recidivism and Violence
Authors: Dale E McNiel, Renée L Binder
Journal: American Journal of Psychiatry (2007)

In response to the large-scale involvement of people with mental disorders in the criminal justice system, many communities have created specialized mental health courts in recent years. However, little research has been done to evaluate the criminal justice outcomes of such courts. This study evaluated whether a mental health court can reduce the risk of recidivism and violence by people with mental disorders who have been arrested.A retrospective observational design was used to compare the occurrence of new criminal charges for 170 people who entered a mental health court after arrest and 8,067 other adults with mental disorders who were booked into an urban county jail after arrest during the same interval. A matching strategy based on propensity scores was used to adjust analyses for nonrandom selection into mental health court.Propensity-weighted Cox regression analysis, controlling for other potential confounding variables (demographic characteristics, clinical variables, and criminal history), showed that participation in the mental health court program was associated with longer time without any new criminal charges or new charges for violent crimes. Successful completion of the mental health court program was associated with maintenance of reductions in recidivism and violence after graduates were no longer under supervision of the mental health court.The results indicate that a mental health court can reduce recidivism and violence by people with mental disorders who are involved in the criminal justice system.