tbuckley/cabot-search huggingface dataset:
Abstract 240: Teaching Basic Life Support: Controlled Study with a 2-Stage Versus the Standard 4-Stage Approach
Authors: Sasa Sopka, Henning Biermann, Matthieu Ott, Max Skorning, Rolf Rossaint, Stefan K Beckers
Journal: Circulation (2012)

Introduction Quality of external chest compressions (ECC) is of paramount relevance within Basic Life Support (BLS). Recent guidelines describe the so called 4-Stage-Approach for teaching practical skills within resuscitation training. However, this methodology was questioned in recent studies when used for simple skills teaching. Hypothesis To observe whether a structured 2-Stage-Approach leads to sufficient practical performance in BLS-Training compared to the standard 4-Stage-Approach. Methods Overall 270 Laypersons were trained in BLS after randomization either to the standard method group using a 4-Stage-Approach (4S) or a modified 2-Stage-Approach-group (2S) lasting the same course duration. All participants were tested on a manikin (Skillreporter ResusciAnne® with PC SkillReporting Software (Version 1.3.0), Laerdal, Stavanger, Norway) in the same cardiac arrest mock scenario prior to the BLS-course and after one week with each time 2 min of continuous ECC each. Practical Endpoints: mean compression rate; mean compression depth. Results Data from 255 subjects (4S: n=127; 2S: n=128) was analyzed. The standard group (4S) as well as the intervention group (2S) improved significantly compared to baseline testing after one week concerning compression depth (4S: 47.8±10.4 mm to 52.4±7.6 mm, p&lt;0.0001; 2S: 47.7±10.7 mm to 55.8±5.4 mm; p&lt;0.0001) and compression rate (4S: 116.1±23.4 min-1 to 118.7±16.0 min-1, p&lt;0.0001; 2S: 114.1±22.8 min-1 to 119.6±13.8 min-1; p&lt;0.0001). The participants trained with the 2-Stage-Approach showed superior performance one week after training in respect of the mean compression depth (4S: 52.4±7.6 mm vs. 2S: 55.8±5.4 mm; p&lt;0.0001). Conclusions Teaching ECC within BLS is sufficiently accomplished with a structured 2-Stage-Approach. Compared to the standard 4-Stage-Approach this methodology leads to comparable skill performance with significantly improved compression depth. Therefore this approach should be further evaluated and offers the option to standardize instructors performance more easily.
Use of DNA microarrays to determine estrogen and HER-2 receptor status in breast cancer
Authors: W. F. Symmans, C. Sotiriou, K. S. Anderson, V. Valero, D. J. Booser, K. R. Hess, J. S. Ross, M. Piccart, G. N. Hortobagyi, L. Pusztai
Journal: Journal of Clinical Oncology (2005)

546 Purpose: To evaluate whether estrogen receptor (ER) and HER-2 receptor status in breast cancer is accurately determined using gene expression profiles. Patients and Methods: Gene expression profiles were obtained from 82 fine needle aspiration (FNA) samples and 40 frozen tissue samples in 122 patients with newly diagnosed breast cancer. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were used to define ER and HER-2 status. The cohorts of FNA and tissue samples were evaluated in two laboratories using Affymetrix U133A GeneChip technology and all expression data were normalized using a single digital standard (dCHIP software). Thresholds of gene expression to determine ER and HER-2 status were defined in the cohort of 82 FNAs and then tested in the 40 tissue samples. Results: ER gene expression (probe ESR1 205225) ≥ 500 (arbitrary units) defined ER-positive status (IHC ≥ 10%) in 82 FNAs with 96% overall accuracy (95% CI, 90%–99%), and was validated with 90% overall accuracy (95% CI, 76%–97%) in 40 tissues. Considering ER IHC > 0% as positive, the overall accuracies were 98% (FNA) and 100% (tissue). ER reporter genes (55 probes) were identified by co-expression with ER (ESR1) (Spearman correlation, R ≥ 0.7) in the 82 FNAs, and their mean expression in the 40 tissue samples was correlated with ER (ESR1) expression (R = 0.84) and ER IHC status (p < 0.0001). HER-2 gene expression (probe ERBB2 216836) expression ≥ 1500 defined clinical HER-2-positive status (IHC = 3 and/or FISH ratio ≥ 2) in 82 FNAs with 96% overall accuracy (95% CI, 90%–99%), and was validated with 100% overall accuracy (95% CI, 91%–100%) in 40 tissues. Conclusion: Expression values of ESR1, ERBB2, and a set of ER reporter genes from Affymetrix GeneChips accurately determined ER and HER-2 status, and were comparable in FNA and tissue samples from two independent laboratories. DNA microarrays could be become a single assay to report ER and HER-2 status included with other clinically relevant predictions. No significant financial relationships to disclose.
Randomized phase II study of neoadjuvant chemotherapy and trastuzumab for operable breast cancer with overexpression of HER2
Authors: N. Masuda, M. Ando, K. Aogi, H. Ino, H. Iwata, Y. Tokuda, S. Nakamura, N. Yamamoto, Y. Fujiwara
Journal: Journal of Clinical Oncology (2009)

565 Background: Achievement of pathological complete response (pCR) by primary systemic therapy (PST) correlates with improved survival in operable breast cancer patients. Based on data of the higher pCR rate with concomitant chemotherapy and trastuzumab (H) reported by some clinical trials, we performed a multi-center, prospective randomized phase II study to evaluate the efficacy of adding H to standard chemotherapy and to determine more effective agent which will show higher pCR by the comparison between weekly paclitaxel (P) and tri-weekly docetaxel (D) in neo-adjuvant setting for HER-2+ pts. Methods: Generally, the concomitant combination with anthracycline and H is not recommended because of the increasing cardiac toxicity. PST regimen was scheduled as the sequential chemotherapy with 4 cycles of CEF (cyclophosphamide, epirubicin 100 mg/m 2 , 5FU) followed by 4 cycles of q3w H with qw P 80 mg/m 2 (HP) or q3w D 75 mg/m 2 (HD). The primary objective was designed to evaluate the pCR, defined as no evidence of residual invasive cancer in axilla and breast. The inclusion criteria was pts with Stage II or IIIA, HER-2 overexpression, under 65-yo, adequate cardiac function (EF&gt;=60%) and a written informed consent. The sample size was estimated to detect the difference of pCR rate &gt;=10% from 30% baseline, as at least 100 pts. The pathological response was evaluated by central review. Results: From March 2007 to June 2008, 102 pts were enrolled and randomized as well balance in the same number, median age (51yo), and the same distribution of clinical stage. 88 pts (86%) was successful on complete treatment course. Pre-matured data was available for 60 pts whom central review had been completed: there was no significantly difference in pCR rate between two groups, 53% (95%CI: 35.4–71.1%) on HP and 47% (28.8–64.5%) on HD. Out of 30 pts with pCR, 13 pts had component of DCIS. Serious adverse events were reported on 13 cases; mainly febrile neutropenia was experienced on 6 pts. One after the HP course had experienced the cardiac failure to fall in LVEF to 39%. Conclusions: In HER-2+ pts, PST with CEF followed by HP or HD might be equally active and achieving high pCR without significant toxicity. The final reviewed results will be established until May 2009, and presented at the ASCO meeting. No significant financial relationships to disclose.
Single-Cell Transcriptome Study as Big Data
Authors: Pingjian Yu, Wei Lin
Journal: Genomics Proteomics & Bioinformatics (2016)

The rapid growth of single-cell RNA-seq studies (scRNA-seq) demands efficient data storage, processing, and analysis. Big-data technology provides a framework that facilitates the comprehensive discovery of biological signals from inter-institutional scRNA-seq datasets. The strategies to solve the stochastic and heterogeneous single-cell transcriptome signal are discussed in this article. After extensively reviewing the available big-data applications of next-generation sequencing (NGS)-based studies, we propose a workflow that accounts for the unique characteristics of scRNA-seq data and primary objectives of single-cell studies.
Activity of docetaxel plus trabectedin in recurrent or persistent ovarian and primary peritoneal cancer: A phase II study of the Gynecologic Oncology Group (GOG).
Authors: B. J. Monk, M. Sill, J. L. Walker, P. Hanjani, R. P. Edwards, J. Rotmensch, K. De Geest, A. J. Bonebrake
Journal: Journal of Clinical Oncology (2010)

5046 Background: To estimate the activity of docetaxel 60 mg/m2 IV over 1 hr followed by trabectedin 1.1 mg/m2 over 3 hrs with filgrastim, pegfilgrastim, or sargramostim every 3 weeks (one cycle) until disease progression or adverse effects prohibit further therapy. Methods: Patients with recurrent and measurable disease, acceptable organ function, and PS ≤ 2 were eligible. The number of prior cytotoxic regimens was limited to 3 (including no more than 1 non-platinum, non-taxane regimen). Patients receiving only 1 prior cytotoxic regimen (platinum-based regimen for management of primary disease) must have had a platinum-free interval of < 12 mo. A two-stage design was utilized with a target sample size of 35 subjects per stage. Another GOG study within the same protocol queue involving a single agent taxane yielded 8 responses (16%) among 49 subjects (90% CI 8.6-28.5%) and served as a historical control for direct comparison. The current study was designed to determine if the current regimen increased the probability of response by 20% with 90% power while limiting the probability of declaring regimens with similar activity as the historical control as being interesting to 10%. The minimum number of responses to declare the regimen interesting was 21. Results: 71 patients were enrolled with 70 being eligible and evaluable at this time (prior regimens:1 = 29%, 2 = 51%, 3 = 20%). The median number of cycles was 6 (396 total cycles). The number of patients responding was 21 (30%; 90% CI 21-40%). The odds ratio for responding was 2.2 (90% 1-sided CI 1.09–Infinity). The median progression-free survival and overall survival was 4.4 mo and 12.5 mo, respectively. The median response duration was 8.4 mo. Numbers of subjects with grade 3/4 toxicity included: neutropenia 6/14; constitutional 8/0; GI (excluding nausea/vomiting) 10/0; metabolic 9/1; pain 6/0. There were no treatment related deaths nor cases of liver failure. Conclusions: This combination is well tolerated and appears more active than single agent taxane therapy in those with recurrent ovarian and peritoneal cancer after failing multiple lines of chemotherapy. Further study is warranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Johnson & Johnson Johnson & Johnson Johnson & Johnson Johnson & Johnson
Population pharmacokinetic (PPK) analysis of recombinant human Apo2L/TRAIL (rhApo2L/TRAIL) in a Phase 1a Study in advanced cancer and lymphoma
Authors: Y. Xin, T. M. Tohnya, R. S. Herbst, D. S. Mendelson, S. G. Eckhardt, P. J. O'Dwyer, W. Novotny, D. E. Allison, B. L. Lum, N. Jumbe
Journal: Journal of Clinical Oncology (2008)

2525 Background: rhApo2L/TRAIL induces apoptosis through binding to the pro-apoptotic receptors DR4 and DR5. This drug selectively induces apoptosis in many cancer cell lines derived from various malignancies, while sparing most normal cells in preclinical models. Preclinically, clearance of this molecule was highly correlated with glomerular filtration rate (GFR), suggesting that the kidney could play a critical role in elimination. Body weight-normalized doses were selected for the first-in-human study. This population PK analysis (PPK) and covariate analysis was conducted to: 1) describe the PK of rhApo2L/TRAIL using a non-linear mixed effects modeling approach and 2) identify covariates as potential predictors of PK variability. Methods: The NONMEM analysis was performed using 1034 serum concentration samples from 67 patients receiving rhApo2L/TRAIL at doses ranging from 0.5–30 mg/kg. Potentially clinically relevant covariates were evaluated. Results: A one-compartment model with linear clearance best described rhApo2L/TRAIL concentration data. After the inclusion of the statistically significant covariates (CRCL on CL and weight on Vd), the typical parameter estimates (percent of standard error of estimation) of rhApo2L/TRAIL clearance (CL) and volume of distribution (Vd) were 116 L/day (3.85%) and 4.28 L (3.69%), respectively. The inter-patient variability (IIV) for CL and Vd was 32.6% (19.3%) and 27.9% (28.6%), respectively. Creatinine clearance explained the IIV of CL by 26.4% and weight explained the IIV of Vd by 25%. Gender, age, race, albumin, alkaline phosphatase, and aspartate aminotransferase had no effect on rhApo2L/TRAIL PK. Conclusions: A one-compartment model with linear clearance accurately described rhApo2L/TRAIL PK disposition in patients in this trial. Creatinine clearance and weight marginally reduced inter-individual variability of rhApo2L/TRAIL. Further assessments of additional variables likely to play a role in clearance and the necessity of weight-based dosing are ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology Genentech™ BioOncology Genentech™ BioOncology Genentech™ BioOncology Genentech™ BioOncology Genentech™ BioOncology
포스터발표 : 그랜드볼룸 ; 한국인에서 자가면역성 간염을 진단하기 위한 Revised Original Scoring System과 Simplified Scoring System의 진단 일치율에 관한 연구 (초)
Authors: 이윤나, 김영석, 김상균, 임재희, 문종호, 이문성, 김부성, 김희경
Journal: Clinical and Molecular Hepatology (2010)
Pathologic complete response (pCR) to neoadjuvant chemoradiation (CRT) of uT2uN0 rectal cancer (RC) treated by local excision (LE): Results of the ACOSOG Z6041 trial.
Authors: J. Garcia-Aguilar, Q. Shi, C. R. Thomas, E. Chan, P. Cataldo, J. Marcet, D. Medich, A. Pigazzi, S. Oommen, M. Posner
Journal: Journal of Clinical Oncology (2010)

3510 Background: LE alone is an effective treatment for selected T1 RCs, however, for T2 RCs it results in unacceptable local recurrence and survival. The Z6041 phase II trial investigates the efficacy of CRT and LE for treating T2N0 RC. Methods: Patients (pts) with ultrasound-staged T2N0 RC and ECOG PS ≤ 2 were treated with capecitabine (825 mg/m2 days 1-14 and 22-35) and oxaliplatin (50 mg/m2 weeks 1, 2, 4 and 5) during radiation (RT) (total dose 54 Gy) followed by LE. Due to toxicity, the dose of RT was reduced to 50.4 Gy and capecitabine to 725 mg/m2 (5 days/week/5 weeks). Pts were evaluated for clinical and pathologic response. pCR was defined as ypT0N0. The association between pCR rate and pre-treatment pt and tumor characteristics were assessed by logistic regression. The agreement between clinical and pathologic assessment of response was evaluated by sensitivity and specificity. Results: Of the 90 pts accrued (66% male; age [mean ± SD], 63 ± 11; 83% ECOG PS 0, and 89% white), 6 pts did not receive treatment per protocol, 1 did not have surgery due to toxicity, 2 pts are unevaluable (data pending). For the 81 pts with available data, 57 treated with the original and 27 with the revised regimen, the average tumor diameter was 2.9 ± 0.8 cm and distance from anal verge, 5.0 ± 2.0 cm. Chemotherapy and RT were completed per protocol in 81% and 89% of pts, respectively. A total of 36 pts achieved pCR (44%; 95% CI, 33%, 55%), 26 (46%) in the original and 10 (40%) in the revised regimen. Overall, 52 (64%) tumors were downstaged (ypT0-1), and 5 pts (6%) had ypT3 tumors. Five LE specimens contained lymph nodes; only one with a T3 tumor had a positive node. Resection margins were negative in 98% of pts. No pre-treatment tumor characteristic or treatment variable was associated with pCR. A complete clinical response was concordant with pCR in 31 of 36 pts (sensitivity 86%, specificity 70%). Conclusions: The pCR rate with capecitabine and oxaliplatin-based CRT for early stage RC is higher than for stage II-III tumors, and is one of the highest reported in a cooperative group setting. Resection margins were negative in all but 1 pt. The ability of surgeons to predict a pCR was higher than previously reported. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis Roche, sanofi-aventis
Randomized phase II parallel evaluation of OSI-211 (liposomal lurtotecan) and topotecan in women with relapsed epithelial ovarian cancer (EOC)
Authors: C. J. Poole, H. Thomas, M. Gore, G. Dark, P. Vasey, N. Bailey, T. Cameron, C. van Duym, M. Ptaszynski
Journal: Journal of Clinical Oncology (2005)

5017 Background: OSI-211 is a liposomal formulation of lurtotecan, a topoisomerase-I inhibitor. In a previous randomised dose ranging/feasibility trial a day 1, 2, and 3 q 3/52 regimen was chosen for further evaluation. We present here a randomized phase II, parallel evaluation of OSI-211 and topotecan (TOP) to better estimate the drug’s efficacy and safety using this schedule, standardised for occult pt. selection factors, and to guide a decision whether to proceed with an appropriately powered, randomised phase III trial. Methods: Entry criteria comprised pts. with relapsed EOC, treated with 1 or 2 prior regimens (at least 1 platinum containing) & measurable disease. Pts were randomized to receive OSI-211 1.8 mg/m2 daily x 3 or TOP 1.5 mg/m2 daily x 5, q 3/52 & stratified according to number of prior regimens (1 or 2) and time from last chemotherapy (< 6mos vs. ≥ 6mos). Objective response rate (ORR) was measured using RECIST; toxicity with NCI CTC v2.0. Results: 82 pts of median age 59 yrs (34–82) were randomized, 40 to OSI -211 and 42 to TOP (1 never treated). Treatment groups were well balanced with for interval from last chemotherapy, number of prior regimens, histology and PS. A total of 200 cycles of OSI-211 (range: 1–18) and 176 cycles of TOP (range: 1–8) were administered, with a median of 5 for each arm. Toxicity was comparable for both (G3/4: OSI-211 43% TOP 41%) with asthenia (70% vs. 63%), nausea (50% vs. 51%), vomiting (30% vs. 39%) and diarrhea (20 vs.20%) being the most frequently reported non-hematological toxicity for OSI-211 and TOP. Grade 3/4 febrile neutropenia, G3 thrombocytopenia and sepsis were reported in 3% vs. 12%, 10% vs. 0% and 5% each, in the OSI-211 and TOP pts respectively. The ORR for OSI-211 was 13% (95%CI: 4–27; 5 PR) and 12% for TOP (CI: 4–26; 1CR, 4PR), predominantly in sensitive pts (last chemotherapy ≥ 6mos), with a disease control rate (ORR+SD) of 70% and 71% for OSI-211 and TOP respectively. Median TTP & survival for OSI-211 & TOP was 26 vs. 29 wks & 12 vs. 11mos. Conclusions: OSI-211 is an active agent in relapsed EOC with ostensibly similar efficacy and toxicity to the standard regimen of TOP in this non-comparative study, but with the benefit of a reduced number of dosing days. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration OSI OSI
Interim analysis of the randomized PATSGO trial evaluating the prolongation of adjuvant temozolomide in newly diagnosed glioblastoma patients.
Authors: J. Baurain, T. Boterberg, D. Devriendt, F. Hammouch, G. Cosnard, N. Whenham, P. M. Clement, C. Mitine, L. Renard
Journal: Journal of Clinical Oncology (2010)

2044 Background: The standard treatment of GBM is curently maximal surgical resection followed by 6 weeks of radiochemotherapy and 6 months of adjuvant temozolomide (TMZ). Nevertheless, nearly half of the patients who have completed this treatment will relapse within 6 months. In some cases where TMZ was continued beyond 6 months, a further clinical and radiologic improvement has been observed. Therefore some physicians propose to extend adjuvant TMZ, although this approach is not validated by a trial demonstrating a clinical benefit. Methods: Progression-free patients were randomized after completion of the 6 cycles adjuvant TMZ in a Belgian academic multicenter phase II trial. In the experimental arm, treatment was continued until progression (TMZ Arm). The patients randomized in the observation arm discontinued TMZ and were retreated upon progression. The presence of residual tumor and MGMT status were used as stratification factors. 42 patients out of the 62 planned are included. Tumor evaluation was performed by MRI every 3 months and centrally reviewed. An interim analysis was planned and performed 6 months after the inclusion of the twentieth patient. Results: Half of the patients included in this interim analysis were randomized in the TMZ arm. The well-known prognostic factors were equally balanced between the TMZ arm and the observation arm: median age 55 vs. 56 yrs, Karnovsky index 84 vs. 92%, residual tumor 8 vs. 9 pts, and steroids use 5 vs. 2 pts. The median follow-up was 12.3 and 6.5 months, respectively. The progression-free survival (PFS) at 6 months was 70% vs 57%, respectively. The median number of TMZ cycles received in the TMZ arm was 6 and 4 patients progressed. In the observation arm, 5 patients were rechallenged and 3 cycles were given without any response. The toxicities of TMZ were limited to grade 1-2 and 3 patients with an asymptomatic grade 3 lymphopenia. Conclusions: Continued treatment with TMZ is well tolerated in this selected population. The interim analysis is in line with a potential benefit of the experimental arm in terms of PFS. Accrual continues and the final analysis will be reported later. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough
Early sex education in relationship to later coital and reproductive behavior: evidence from Jamaican women
Authors: E B Brody, F Ottey, J Lagranade
Journal: American Journal of Psychiatry (1976)

In a group of 150 working-class Jamaican women, lack of information from their mothers about sex coupled with chronic resentment was associated with having had more sexual partners, impregnators, and children. In contrast to age at first coitus, age at first pregnancy did not seem related to the early availability of information about sex, and it was less significantly correlated with overall education.