tbuckley/cabot-search huggingface dataset:
Variations in genes regulating tumor-associated macrophages (TAMs) to predict outcomes of bevacizumab-based treatment in patients with metastatic colorectal cancer: results from TRIBE and FIRE3 trials
Authors: Y. Sunakawa, S. Stintzing, S. Cao, V. Heinemann, C. Cremolini, A. Falcone, D. Yang, W. Zhang, Y. Ning, S. Stremitzer, S. Matsusaka, S. Yamauchi, A. Parekh, S. Okazaki, M.D. Berger, S. Graver, A. Mendez, S.J. Scherer, F. Loupakis, H.-J. Lenz
Journal: Annals of Oncology (2015)
Electron Microscopic Study of Spinal Ganglia From Vincristine-Treated Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: L. J. Journey, Jose Burdman, Audrey Whaley
Journal: JNCI Journal of the National Cancer Institute (1969)

A single intraperitoneal injection of vincristine sulfate (VCR) into mice produced severe neurotoxic symptoms and resulted in hind-limb paralysis at a dose of 5 mg/kg. Sensory nerve cell architecture was severely altered in the dorsal ganglia of VCR-treated mice. These changes included the production of extensive bands of filaments in neuronal soma with a concurrent diminution in neurotubular content, which thus suggested an interrelationship between these two cytoplasmic elements. Neurotubules were abundant in small axons, whereas neurofilaments predominated in the larger myelinated fibers of normal spinal ganglia. These axonal neurotubules appeared more resistant to disruption by VCR than those within the cell body. No specific alterations were noted in the satellite or Schwann cells of treated ganglia.
Abstract 250: Prehospital Teleconsultation in Acute Coronary Syndromes: Feasibility and Effects
Authors: Harold Fischermann, Max Skorning, Sebastian Bergrath, Stefan Krüger, Jörg Schröder, Christina Fitzner, Daniel Rörtgen, Stefan K Beckers, Rolf Rossaint
Journal: Circulation (2011)

BACKGROUND: Transmission of 12-lead ECG (ECG) to a specialist in acute coronary syndromes (ACS) is beneficial but not routinely integrated into Emergency Medical Services (EMS). Prehospital teleconsultation (TC) with comprehensive data transmission is a new approach. The feasibility and effects on emergency care of ACS were investigated. METHOD: TC was performed between one ambulance and a TC center including real time transmission of voice, ECG, vital data, pictures and video. Standard EMS with ECG transmission via fax served as control. Patients with suspected ACS from May 3 to September 30, 2010 on workdays were included. Primary outcomes: guideline coherent treatment (ECG performance, indicated oxygen and drug administration), time intervals, choice of appropriate facility, quality of prehospital diagnosis and hospital length of stay (LOS). Secondary outcomes: Information content of patient care reporting (PCR), system utilization and technical observations. RESULTS: Overall 939 patients were treated - 289 by the TC ambulance and 650 by standard EMS. Thereof 41 patients in the study group and 67 in the control group met the inclusion criteria. TC vs. control: Baseline data and guideline coherent treatment did not differ. On-scene time was prolonged in non-ST-elevation ACS (26 vs. 19 min, p&lt;0.0001) but not in ST-elevation myocardial infarction (22.5 vs. 20 min, p=0.45). Remaining time intervals, the quality of prehospital diagnosis and LOS showed no difference. Urgent percutaneous coronary intervention (PCI) was performed in 16 (76%) vs. 15 (45%) patients (p=0.047). One (9%) vs. 5 (25%) patients were transferred secondarily from a community hospital for PCI (p=0.38). Information content of PCR improved with TC (p&lt;0.0001). Utilization vs. dysfunction for single applications (%): voice 100 vs. 29; ECG 95 vs. 23; realtime vital data 100 vs. 24; pictures 61 vs. 12; video 35 vs. 14. CONCLUSION: The system is safe, feasible and without impairing effect on relevant time intervals. Treatment with TC was at least equivalent to a high level standard EMS with ECG transmission and led to improved mission documentation. TC holds the potential to optimize patient care, safety and information flow to the hospital. Trials Registration: ISRCTN83270177
Metabolic profile in women with polycystic ovary syndrome across adult life
Authors: Bárbara Echiburú, Nicolás Crisosto, Manuel Maliqueo, Francisco Pérez-Bravo, Amanda Ladron de Guevara, Paola Hernández, Gabriel Cavada, Catalina Rivas, Andrés Clavel, Teresa Sir-Petermann
Journal: Metabolism (2016)
Abstract P104: Reactivation of Embryonic Gene Program due to CUG Repeat RNA Expression in Myotonic Dystrophy
Authors: Auinash Kalsotra, Ravi Singh, Chad Creighton, Thomas Cooper
Journal: Circulation Research (2011)

Myotonic dystrophy type 1 (DM1) is a dominantly inherited disease that affects multiple organ systems. Cardiac involvement, which is characterized by conduction defects and arrhythmias, is the second leading cause of death in DM1 patients. The causative mutation is a CTG expansion in the 3' untranslated region of DMPK gene resulting in aberrant expression of CUG repeat RNA that accumulates into nuclear foci and causes misregulation in alternative splicing. Here we show that heart-specific and inducible expression of CUG repeat RNA in a DM1 mouse model results in global reactivation of embryonic gene expression program in adult heart that is distinct from a general hypertrophic stress response. Using q-PCR TaqMan arrays, we identified 54 miRNAs that were differentially expressed in DM1 mouse hearts one week following induction of CUG repeat RNA. Interestingly, 83% (45/54) of them exhibited a developmental shift in expression towards the embryonic pattern. Because over 90% (41/45) of them were down regulated within 72 hr after induction of repeat RNA and only 2/22 examined decreased in two unrelated mouse models of heart disease, we conclude their reduced expression is specific to DM1 and not simply a general response to cardiac injury. Microarray studies revealed a developmental switch not only in the miRNA expression patterns but also a pervasive shift in mRNA steady state levels of a number of genes to embryonic stage. Intriguingly, we found that loss of MBNL1 or gain of CELF1 activity, two major RNA binding proteins disrupted in DM1, are not driving the miRNA misregulation since their expression is indistinguishable between wild type, MBNL1 knock out and CELF1 over expressing mice. Moreover, comparable decrease in ten out of ten primary miRNA transcripts examined suggests loss of expression is not due to a processing defect. Instead, we discovered that adult-to-embryonic shift in expression of select micro- and messenger RNAs in DM1 heart occurs due to specific inactivation of a Mef2 transcriptional program. We are currently determining causal contributions of this Mef2-miRNA circuitry in the developmental reprogramming of gene expression in DM1 as well as its direct role in cardiac manifestations of this disease.
Are more genes better in clinical-genomic studies? A mathematical model to define identification power for clinically relevant genes
Authors: M. R. Crager, S. Shak
Journal: Journal of Clinical Oncology (2009)

e22136 Background: Modern molecular technologies that drive personalized medicine can generate expression data for thousands of candidate genes, or indeed, data for the “whole genome”. Clinical-genomic studies aim to identify genes that are truly associated with clinical outcome. We investigated the impact of large numbers of genes with little or no association with clinical outcome on the statistical power of studies to identify individual genes with strong association. Methods: We adapted Efron's (Ann Stat 2007) empirical Bayes approach to develop a method to calculate the identification power for individual genes in analyses that control the false discovery rate (FDR), the expected proportion of false positives. The identification power is the probability that a gene with a given true magnitude of association with clinical outcome will be identified when we control the FDR at a specified level. The identification power also depends on the proportion of genes studied that are not associated with outcome and the distribution of the degree of association among genes that are. Results: The identification power for clinically relevant genes decreases dramatically as the proportion of genes having no association with clinical outcome increases. For example, in a scenario in which 100 genes have some association with clinical outcome [median hazard ratio (HR) 1.125], increasing the number of genes having no association from 400 to 4000 decreases the identification power an individual gene having strong association (HR 1.42) from 80% to 36%. Similarly, when the number of genes having no association is 400 and the median HR among the 100 genes that have an association is decreased from 1.125 to 1.06, identification power for a gene with an association HR of 1.42 decreases from 80% to 62%. Conclusions: Identification power can be used to optimize strategies for gene finding and enable personalized medicine. Although technology allows the assay of ever-increasing numbers of genes, inclusion in a single study of many genes unrelated to clinical outcome is detrimental to the identification power for clinically relevant genes. Even with increased power, replication of results in independent studies will continue to be critically important. [Table: see text]
Abstract P207: Nonalcoholic Fatty Liver Disease Interacts With Diabetes Increasing The Risk Of Atherosclerosis In The Family Heart Study
Authors: Mary F Feitosa, Alexander P Reiner, Mary K Wojczynski, Kari E North, Michael A Province, Jeff J Carr, Ingrid B Borecki
Journal: Circulation (2012)

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and type 2 diabetes (T2D), which are risk factors for atherosclerosis. However, it is not clear whether NAFLD has an independent contribution to atherosclerosis. The burden of calcification in the coronary artery (CAC) can be measured by computed tomography (CT) and is a measure of atherosclerosis. CT measured liver attenuation (in Hounsfield Units) is inversely related to the amount of fat in the liver (FL), while elevated alanine aminotransferse (ALT, in U/L) levels indicate hepatic damage and is often used as a marker of NAFLD. We investigated whether NAFLD, defined by FL and ALT levels, is a significant predictor of the presence of CAC independent of insulin resistance (HOMA-IR: fasting glucose* fasting insulin/22.5) and overall obesity (BMI, kg/m 2 ) in 2,550 European-American individuals. We employed a linear mixed model to account for the non-independence of family members, and included age, age 2 , sex, current cigarette smoking (yes/no), alcohol intake (yes/no) and clinical center in each model. Heavy drinkers (men: ≥ 21 drinks/week, women: ≥ 14 drinks/week) and subjects who tested positive for hepatitis-C antibodies were excluded from the analyses. In the multivariate model including FL, ALT, BMI, HOMA-IR, and T2D, neither FL nor ALT was associated with CAC; while BMI (p&lt; 0.0001), HOMA-IR (p= 0.0150) and T2D (p= 0.0008) were significant. Also, we employed a similar multivariate regression model separately in subjects without T2D (not taking hypoglycemic medications and/or fasting glucose &lt;126 ml/dL) and with T2D (but excluding subject taking insulin medication). In subjects without T2D, we found that ALT (p=0.0385, OR=1.126, 95% CI:1.006–1.260) was a significant predictor of CAC together with BMI (p&lt; 0.0001) and HOMA-IR (p= 0.0082). In subjects with T2D, ALT (p=0.0376, OR= 0.590, 95% CI:0.361–0.964) was a significant predictor of CAC but not FL, BMI or HOMA-IR which may reflect the effect of other T2D medication. Further, we investigated whether T2D interacts with ALT modifying the risk of CAC independent of BMI and HOMA-IR. In the combined T2D and non-T2D subsets, we included the interaction term (T2D*ALT) in the multivariate model and found significant association of CAC with T2D*ALT (p= 0.0018, OR= 0.555, 95% CI: 0.0384–0.802), ALT (p= 0.0315, OR= 1.134, 95% CI: 1.011–1.271), and T2D (p=0.0001), together with BMI (p&lt;0.0001) and HOMA-IR (p= 0.0156). In summary, we found that: (i) the association of NAFLD steatosis (FL) with CAC is mediated by overall obesity (BMI) and insulin resistance (HOMA-IR); (ii) ALT, indicating hepatic damage, is a significant predictor of atherosclerosis independent of BMI and HOMA-IR; and (iii) having hepatic damage along with T2D augments the risk of atherosclerosis.
Ondansetron oral spray (Zensana) versus ondansetron oral tablets in a randomized, bioavailability study in adult subjects
Authors: W. Yates, G. I. Berk, M. Wolter, S. Nino, S. Kollipara, R. Chavira, J. Kisicki
Journal: Journal of Clinical Oncology (2006)

8622 Background: Zensana ondansetron oral spray (ZSN) is the first oral spray 5-HT 3 antagonist to deliver ondansetron, the most commonly prescribed anti-emetic for chemotherapy induced nausea and vomiting (CINV) through the oral cavity. ZSN achieves therapeutic drug levels by delivering small droplets of concentrated drug solution over the oral mucosa, which has a rich blood supply and has been shown to be an alternative drug delivery route. ZSN may offer certain advantages to patients experiencing CINV who have difficulty swallowing and holding down pills. Methods: This was a randomized, crossover, pharmacokinetic (PK) study where ZSN, administered as 4mg, 8mg, 12mg, and 8mg with a 30-sec hold before swallowing was evaluated in healthy subjects against an 8mg ondasetron (Zofran [ZFR]) tablet (reference). Treatments were separated by 48 hrs. PK samples were measured during the 24 hrs after dosing and were assayed using LC/MS/MS techniques. PK parameters were analyzed using a cross-over ANOVA model. Two treatments were concluded bioequivalent if the 90% CI of the geometric mean ratios for ln-transformed C max , AUC 0-t , and AUC 0-inf fell between the FDA guideline of 80% to 125%. Results: Thirty-two subjects (17 women, 15 men) received each of the 5 treatments, except for one man who did not receive the 12mg dose. The geometric mean ratios and the 90% CI for C max , AUC 0-t , and AUC 0-inf respectively, for each pair of treatments were as follows: ZSN 4mg vs 8mg tablet (TAB): 41%(39–43%); 45%(43–47%), and 47%(45–49%); ZSN 8mg vs 8mg TAB: 87%(83–91%), 98%(94–102%), and 99%(94–103%); ZSN 12mg vs 8mg TAB: 145%(138–152%), 157%(150–164%), and 157%(150–164%); and ZSN 8mg with a 30 sec hold vs 8mg TAB: 86%(82–90%), 99%(94–103%), and 99%(95–104%). There were no serious or unexpected adverse events (AE) and the safety profile was similar across all treatments. The most commonly reported AEs were constipation (11/32[34%]), headache (10/32[31%]), and dizziness (5/32[16%]) which were mild to moderate in severity. Conclusions: ZSN 8mg falls within the FDA criteria for bioequivalence, and is bioequivalent to an 8mg ZFR tablet. ZSN 4, 8, or 12mg has a similar safety profile as a ZFR 8 mg tablet. [Table: see text]
&lt;italic&gt;Brief Communication:&lt;/italic&gt; The Attacker: Target-Cell Ratio and Serum Effects on In Vitro Cell-Mediated Immunity
Authors: A Mantovani, A Veechi, F Spreafico
Journal: JNCI Journal of the National Cancer Institute (1975)

Sera collected from mice rejecting an allogeneic tumor and showing arming activity for normal splenocytes increased target-cell lysis by immune cells when low (≤25:1) attacker:target-cell ratios (A:T) were used but inhibited cytotoxicity at higher (100:1) A:T. The importance of this methodologic variable in studies of serum activity on cellular cytotoxicity is emphasized and the possible mechanisms are discussed.
Ototoxicity of preradiation cisplatin for children with central nervous system tumors.
Authors: C S Kretschmar, M P Warren, B L Lavally, S Dyer, N J Tarbell
Journal: Journal of Clinical Oncology (1990)

From March 1984 through March 1989 we performed 235 audiometric tests on 39 children with malignant brain tumors who were treated with cisplatin 100 mg/m2 every 3 weeks for three courses and vincristine weekly for 9 weeks followed by cranial irradiation. Twenty-eight of the 39 children had sufficient serial testing for evaluation of ototoxicity secondary to cisplatin. Following the third cisplatin treatment (300 mg/m2 cumulative dose), 20% of the assessable children had hearing loss limited to the high frequencies of 6,000 to 8,000 Hz, 16% had hearing loss beginning at 3,000 to 4,000 Hz, and three children (11%) had loss within the speech frequencies beginning at 1,000 to 2,000 Hz. Eighteen of 19 children (95%) who were evaluated comparatively at a median of 15 months following radiation showed no significant change from preradiation testing. There was no correlation between hearing loss and patient age. We conclude that cisplatin ototoxicity was acceptable and that radiation therapy does not increase the ototoxicity of cisplatin when the drug is given before, instead of following, cranial irradiation.
Malignant carcinoid syndrome: Survival in the octreotide LAR era
Authors: L. B. Anthony, T. Kang, Y. Shyr
Journal: Journal of Clinical Oncology (2005)

4084 Background: Somatostatin analogues (SMSA) (octreotide) are effective in controlling excess hormonal symptoms in the majority of patients (pts) with carcinoid syndrome. Octreotide long acting release (LAR) is a depot (intramuscular) formulation introduced 10 years after the immediate release (subcutaneous (SC)/intravenous) octreotide became commercially available in 1988. Monthly octreotide LAR provides continuous and predictable blood levels. Immediate release octreotide results in widely fluctuating blood levels and requires pts to comply with 2–4 daily injections for optimal control of symptoms. For carcinoid syndrome pts (elevated 5-HIAA), a median overall survival of 24 months (N=90) was reported by Z Davis, C Moertel, D McIlrath (Surg, Gyn & Obst 137:637, 1973) in the pre-SMSA era. Octreotide LAR's effect on survival is unknown. Methods: Consecutive carcinoid syndrome pts treated with SMSA SQ (N=90) between 1986–1995 were the control group. The investigational group consisted of consecutive carcinoid syndrome pts treated with octreotide LAR (N=145) between 1996–2004. Entry criteria included elevated 5-HIAA and/or blood chromogranin A and biopsy proven Stage IV carcinoid. Patient characteristics recorded were: age, race, gender, primary and metastatic disease sites, disease duration, concomitant therapies and SMSA or octreotide LAR dose. A Kaplan-Meier estimator and the Log rank-test were used to determine median survival and statistical significance, respectively. Results: The 2 groups were similar with regards to age, race, gender, biochemical marker elevation, primary (majority were midgut) and metastatic disease sites and concomitant therapies. The survival curves for the 2 groups were significantly different. The estimated overall median survival, p values and Hazard Ratio with 95% confidence interval (CI) from the time of metastatic disease diagnosis are: Control group (SMSA SQ) = 143 months Investigational group (octreotide LAR) = 229 months* *p < 0.0001; Hazard Ratio: 0.34 (95% CI of ratio: 0.18 to 0.54) Conclusions: Carcinoid syndrome pts receiving treatment with octreotide LAR have a 66% (range 46–82%) lower risk of death than pts receiving intermittent SMSA SQ therapy. (Supported in part by NIH-GCRC-RR00095). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis
Impact Of Ruxolitinib On The Natural History Of Patients With Primary Myelofibrosis: A Retrospective Comparison Of The DIPSS and The Comfort-2 Cohorts
Authors: Francesco Passamonti, Margherita Maffioli, Francisco Cervantes, Alessandro M. Vannucchi, Enrica Morra, Tiziano Barbui, Caramazza Domenica, Elisa Rumi, Gisslinger Heinz, Laurent Knoops, Barbara Mora, Norbert Hollaender, Margaret Squier, Cristiana Pascutto, Claire N Harrison, Mario Cazzola
Journal: Blood (2013)
Care, quality, and cost implications of the timing of palliative care consultation among patients with advanced cancer.
Authors: Colin Scibetta, Michael W. Rabow, Kathleen Kerr
Journal: Journal of Clinical Oncology (2014)

8 Background: ASCO recommends that early palliative care (PC) be offered alongside standard cancer care for patients with metastatic cancer and/or high symptom burden. There is limited data about how the timing of PC affects the quality, intensity, and cost of care at the end of life for patients with advanced cancer. Methods: We analyzed administrative and billing data to assess patterns of healthcare utilization for a cohort of patients at an academic comprehensive cancer center who died from cancer between Jan 1, 2010 and May 31, 2012. We examined the associations of early PC (&gt;90 days prior to death) versus late PC (&lt;90 days prior to death) with QOPI, NQF, and other established quality metrics and direct cost of medical care in last 6 months of life. Results: Among 978 decedents who received treatment at the cancer center, only 298 (30%) had specialty PC referrals. Of these patients, 94 (9.6% of decedents, 31.5% of referrals) had early PC while 204 (21% of decedents, 68.5% of referrals) had late PC. Patients who received early PC had a lower rate of inpatient admissions in the last month of life (33% vs. 66%, p=0.002), lower rates of ICU stay in last month of life (5% vs. 20%, p=0.0005), fewer ED visits in last month (34% vs. 54%, p=0.0002), fewer instances of hospice length of service &lt;3 days (7% vs. 20%, p=0.0001), and a lower rate of inpatient death (15% vs. 34%, p=0.0001). Most patients (84%) who received early PC were seen as outpatients, while late PC was mostly delivered in the hospital (82.4%). Of the late PC cohort, only 52 (25.4%) were ever seen in the outpatient PC clinic, but 170 (83%) had at least one oncology office visit 91-180 days prior to death. The direct cost of inpatient medical care in the last 6 months of life for patients with early PC was reduced when compared to patients who had late PC ($19k vs. $25.7k), while the direct cost of outpatient care was higher in the early PC compared to late PC population ($13k vs. $11.5k). Conclusions: Early PC is associated with less intensive medical care and improved quality outcomes at the EOL for patients with advanced cancer. Early PC results in a significant inpatient cost savings with a modest increase in outpatient costs. Early PC is likely best delivered in the outpatient setting.
춘계학술대회 : 포스터발표 ; 단일기관에서 경험한 급성 B형 간염의 임상상
Authors: 이태희, 김용문, 정승현, 김선문, 임의혁, 허규찬, 최용우, 강영우
Journal: Clinical and Molecular Hepatology (2005)

배경/목적: 한국에서의 급성 B형 간염은 1980년대만 하더라도 성인에서는 흔하지 않았으며, 5%미만에서만 만성화하고 대부분에서 자연 치유되는 것으로 알려져 있다. 최근 한국에서의 급성 B형 간염은 현저하게 감소하고 있으나, 성인에서의 빈도는 과거에 비해 늘어나는 췌이다. 연자들은 단일기관에서 경험한 급성 B형 간염의 임상양상 및 혈청학적 변화를 조사하였다. 대상 및 방법: 2000년 6월부터 2004년 12월까지 본원에서 급성 간염으로 입원하여 임상