bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reliability of a Computerized Version of the Pediatric Canadian Triage and Acuity Scale
Authors: Gravel Jocelyn , Gouin Serge , Bailey Benoit , Roy Michel , Bergeron Sylvie , Amre Devendra 
Published: August 2007

Background: The use of a standardized triage tool allows better comparison of the patients; a computerized version could theoretically improve its reliability.Objectives: To compare the interrater agreement of the Pediatric Canadian Triage and Acuity Scale (PedCTAS) and a computerized version (Staturg).Methods: A two‐phase experimental study was conducted to compare the interrater agreement between nurses assigning triage level to written case scenarios using either traditional PedCTAS or Staturg. Participants were nurses with at least one year of experience in pediatric emergency medicine and trained at triage. Each of the 54 scenarios was evaluated first by all nurses using either one of the strategies. Four weeks later, they evaluated the same scenarios using the other tool. The primary outcome was the interrater agreement measured using κ score.Results: Eighteen of the 29 eligible nurses participated in the study. The computerized triage tool showed a better interrater agreement, with a Staturg κ score of 0.55 (95% confidence interval = 0.53 to 0.57) versus a PedCTAS κ score of 0.51 (95% confidence interval = 0.49 to 0.53). The computerized version was also associated with higher agreements for scenarios describing patients with the highest severity of triage (κ score of 0.72 vs. 0.55 for level 1; κ score of 0.70 vs. 0.51 for level 2).Conclusions: A computerized version of the PedCTAS showed a statistically significant improvement in the interrater agreement for nurses evaluating the triage level of 54 clinical scenarios, but this difference has probably small clinical significance.
Evaluating the Effectiveness of Dispatch‐assisted Cardiopulmonary Resuscitation Instructions
Authors: Vaillancourt Christian , Verma Aikta , Trickett John , Crete Denis , Beaudoin Tammy , Nesbitt Lisa , Wells George A. , Stiell Ian G. 
Published: August 2007

Objectives: To determine the frequency of agonal breathing during cardiac arrest (CA), its impact on the ability of 9‐1‐1 dispatchers to identify CA, and the impact of dispatch‐assisted cardiopulmonary resuscitation (CPR) instructions on bystander CPR rates.Methods: A before‐after observational study enrolling out‐of‐hospital adult CA patients where resuscitation was attempted in a single city with basic life support with defibrillation/advanced life support tiered emergency medical services. Victim, caller, and system characteristics were measured during two successive nine‐month periods before (control group) and after (intervention group) the introduction of dispatch‐assisted CPR instructions.Results: There were 529 CAs between July 1, 2003, and December 31, 2004. Victim characteristics were similar in the control (n= 295) and intervention (n= 234) period; mean age was 68.3 years; 66.7% were male; 50.1% of CAs were witnessed; call‐to‐vehicle stop was 6 minutes, 37 seconds; ventricular fibrillation/ventricular tachycardia occurred in 29.9%; and the survival rate was 4.0%. Dispatchers identified 56.3% (95% confidence interval [CI] = 48.9% to 63.0%) of CA cases; agonal breathing was present in 37.0% (95% CI = 30.1% to 43.9%) of all CA cases and accounted for 50.0% (95% CI = 39.1% to 60.9%) of missed diagnoses. Callers provided ventilations in 17.2% and chest compressions in 8.3% of cases as a result of the intervention. Long time intervals were observed between call to diagnosis (2 minutes, 38 seconds) and during ventilation instructions (2 minutes, 5 seconds). Bystander CPR rates increased from 16.7% in the control phase to 26.4% in the intervention phase (absolute rate, 9.7%; 95% CI = 8.5% to 11.3%; p = 0.006).Conclusions: This trial demonstrates an increase in bystander CPR rate after the introduction of dispatch‐assisted CPR. Agonal breathing occurred frequently and had a negative impact on the recognition of CA. There were long time intervals between call initiation and diagnosis of CA and during mouth‐to‐mouth ventilation instructions.
Brain Structure and Function Differences in Monozygotic Twins: Possible Effects of Breast Cancer Chemotherapy
Authors: Ferguson Robert J. , McDonald Brenna C. , Saykin Andrew J. , Ahles Tim A. 
Published: August 2007

Purpose Adjuvant chemotherapy has been associated with mild cognitive decline among a subset of breast cancer survivors. Late cognitive effects after chemotherapy can have a deleterious impact on survivor quality of life and functional health; however, the etiology of chemotherapy-related cognitive dysfunction remains unknown. Patients and Methods We present a case of monozygotic twins who are discordant for breast cancer and chemotherapy exposure (ie, one twin contracted breast cancer and underwent chemotherapy, and the other had no breast cancer). As part of a larger study, each was evaluated with standardized, self-report measures of cognitive function, standard neuropsychological tests, and structural and functional magnetic resonance imaging (MRI). Results Results indicated small differences in neuropsychological test performance but striking contrasts in self-reported cognitive complaints and structural and functional MRI images. Specifically, the twin who underwent chemotherapy had substantially more subjective cognitive complaints, more white matter hyperintensities on MRI, and an expanded spatial extent of brain activation during working memory processing than her nonaffected twin. Conclusion This case illustrates possible physiologic mechanisms that could produce long-term cognitive complaints among chemotherapy recipients and help formulate hypotheses for further empirical study in the area of chemotherapy-associated cognitive dysfunction.
Clinical Implications of CYP2D6 Genotypes Predictive of Tamoxifen Pharmacokinetics in Metastatic Breast Cancer
Authors: Lim Hyeong-Seok , Ju Lee Han , Seok Lee Keun , Sook Lee Eun , Jang In-Jin , Ro Jungsil 
Published: August 2007

Purpose The CYP3A and CYP2D6 enzymes play a major role in converting tamoxifen to its active metabolites. CYP3A is a highly inducible enzyme, regulated mainly by pregnane X receptor (PXR). This study assessed the association between genetic polymorphisms of CYP2D6 and PXR, and tamoxifen pharmacokinetics (PK) and clinical outcomes in patients with breast cancer. Patients and Methods Plasma concentrations of tamoxifen and its metabolites were measured. Common alleles of CYP2D6 and PXR were identified in 202 patients treated with tamoxifen 20 mg daily for more than 8 weeks. Twelve of the 202 patients and an additional nine patients with metastatic breast cancer receiving tamoxifen were assessed for clinical outcome in correlation with genotypes. Results Patients carrying CYP2D6*10/*10 (n = 49) demonstrated significantly lower steady-state plasma concentrations of 4-hydroxy-N-desmethyltamoxifen and 4-hydroxytamoxifen than did those with other genotypes (n = 153; 4-hydroxy-N-desmethyltamoxifen: 7.9 v 18.9 ng/mL, P < .0001; 4-hydroxytamoxifen: 1.5 v 2.6 ng/mL, P < .0001), whereas no difference by PXR genotypes was found. CYP2D6*10/*10 was significantly more frequent among nonresponders with MBC (100% v 50%, P = .0186). In Cox proportional hazard analysis, CYP2D6 genotype and number of disease sites were significant factors affecting time to progression (TTP). The median TTP for patients receiving tamoxifen was shorter in those carrying CYP2D6*10/*10 than for others (5.0 v 21.8 months, P = .0032) Conclusion CYP2D6*10/*10 is associated with lower steady-state plasma concentrations of active tamoxifen metabolites, which could possibly influence the clinical outcome by tamoxifen in Asian breast cancer patients.
Phase III Double-Blind, Placebo-Controlled Study of Thalidomide in Extensive-Disease Small-Cell Lung Cancer After Response to Chemotherapy: An Intergroup Study FNCLCC cleo04–IFCT 00-01
Authors: Pujol Jean Louis , Breton Jean Luc , Gervais Radj , Tanguy Marie-Laure , Quoix Elisabeth , David Philippe , Janicot Henri , Westeel Virginie , Gameroff Sabine , Genève Jean , Maraninchi Dominique 
Published: August 2007

Purpose This randomized, double-blind, placebo-controlled phase III study aimed to determine whether thalidomide prolongs survival of patients with extensive-disease small-cell lung cancer (SCLC). Patients and Methods One hundred nineteen patients received two courses of etoposide, cisplatin, cyclophosphamide, and 4′-epidoxorubicin (PCDE). Responder patients who had recovered from chemotherapy toxicity were randomly assigned to receive four additional PCDE cycles plus thalidomide (400 mg daily) or placebo. Results After the first two PCDE cycles, objective response rate was 81.5%, and 92 patients were randomly assigned to placebo (n = 43) or thalidomide (n = 49). Median exposure duration to placebo was 4.5 months, and median exposure to thalidomide was 4.9 months. Patients treated with thalidomide had a longer survival compared with patients who received placebo, although the difference was not statistically significant (minimal follow-up, 3 years; median survival time, 11.7 v 8.7 months, respectively; log-rank test: hazard ratio [HR] = 0.74; 95% CI, 0.49 to 1.12; P = .16). Patients with a performance status (PS) of 1 or 2 who received thalidomide had a significantly longer survival (HR = 0.59; 95% CI, 0.37 to 0.92; P = .02). The disease also progressed slower in patients with PS of 1 or 2 receiving thalidomide (HR = 0.54; 95% CI, 0.36 to 0.87; P = .02), whereas the difference did not reach statistical significance for the whole population (HR = 0.74; 95% CI, 0.49 to 1.12; P = .15). Neuropathy occurred more frequently in the thalidomide group compared with the placebo group (33% v 12%, respectively). Conclusion Treatment with thalidomide was not associated with a significant improvement in survival of SCLC patients. There was pronounced heterogeneity in survival outcomes between groups of patients. Some benefit was observed among patients with a PS of 1 or 2 (exploratory analyses), deserving further studies targeting angiogenesis in this disease.
Phase II Study of Lapatinib in Recurrent or Metastatic Epidermal Growth Factor Receptor and/or erbB2 Expressing Adenoid Cystic Carcinoma and Non–Adenoid Cystic Carcinoma Malignant Tumors of the Salivary Glands
Authors: Agulnik Mark , Cohen Ezra W.E. , Cohen Roger B. , Chen Eric X. , Vokes Everett E. , Hotte Sebastien J. , Winquist Eric , Laurie Scott , Hayes D. Neil , Dancey Janet E. , Brown Shirley , Pond Gregory R. , Lorimer Ian , Daneshmand Manijeh , Ho James , Tsao Ming-Sound , Siu Lillian L. 
Published: August 2007

Purpose Expression of erbB2 and/or epidermal growth factor receptor (EGFR) is associated with biologic aggressiveness and poor prognosis in malignant salivary gland tumors (MSGTs). This phase II study was conducted to determine the antitumor activity of lapatinib, a dual inhibitor of EGFR and erbB2 tyrosine kinase activity, in MSGTs. Patients and Methods Patients with progressive, recurrent, or metastatic adenoid cystic carcinoma (ACC) immunohistochemically expressing at least 1+ EGFR and/or 2+ erbB2 were treated with lapatinib 1,500 mg daily, in a two-stage cohort. Patients with non-ACC MSGTs were treated as a separate single-stage cohort. Results Of 62 patients screened, 29 of 33 (88%) ACC and 28 of 29 (97%) non-ACC patients expressed EGFR and/or erbB2. Forty patients with progressive disease were enrolled onto the study. Among 19 assessable ACC patients, there were no objective responses, 15 patients (79%) had stable disease (SD), nine patients (47%) had SD ≥ 6 months, and four patients (21%) had progressive disease (PD). For 17 assessable non-ACC patients, there were no objective responses, eight patients (47%) had SD, four patients (24%) had SD ≥ 6 months, and nine patients (53%) had PD. The most frequent adverse events were grade 1 to 2 diarrhea, fatigue, and rash. Eight paired tumor biopsies for correlative studies were procured; results did not correlate with clinical outcome. Conclusion Although no responses were observed, lapatinib was well tolerated, with prolonged tumor stabilization of ≥ 6 months in 36% (95% CI, 21% to 54%) of assessable patients. The antitumor effects of lapatinib in MGSTs appear mainly cytostatic, hence evaluation of other molecular targeted agents, or combinations with lapatinib, may be considered. Continued efforts should be made to gain better understanding into the biology of this heterogeneous group of malignancies.
Primary Fallopian Tube Malignancies in BRCA-Positive Women Undergoing Surgery for Ovarian Cancer Risk Reduction
Authors: Callahan Michael J. , Crum Christopher P. , Medeiros Fabiola , Kindelberger David W. , Elvin Julia A. , Garber Judy E. , Feltmate Colleen M. , Berkowitz Ross S. , Muto Michael G. 
Published: August 2007

Purpose To review the frequency and location of malignancies detected after prophylactic salpingo-oophorectomy in women with BRCA mutations. Methods Medical records and pathology findings were reviewed from BRCA-positive women undergoing prophylactic surgery for ovarian cancer risk reduction who underwent complete examination of the adnexa. Patients undergoing this procedure between January 1999 and January 2007 were identified. Results From January 1999 to January 2007, 122 BRCA-positive patients underwent prophylactic surgery in the Division of Gynecologic Oncology at Brigham and Women's Hospital. The median age was 46.5 years (range, 33 to 76 years). Seven (5.7%) were found to have an early malignancy in the upper genital tract and all patients were age ≥ 44 years at diagnosis. Of seven consecutive cancers culled between January 1999 and January 2007, all (100%) originated in the fimbrial or ampullary region of the tube; six had an early (intraepithelial) component. Two were associated with surface implants on the ovary and two required repeated sectioning to detect microscopic carcinomas in the fimbria. Conclusion The distal fallopian tube seems to be the dominant site of origin for early malignancies detected in approximately 6% of women undergoing ovarian cancer risk-reduction surgery. The greatest proportion of serous cancer risk in BRCA mutation–positive women should be assigned to the fimbria rather than the ovary, and future clinical and research protocols should employ thorough examination of the fimbria, including multiple sections from each tissue block, to maximize detection of early malignancies in this population.
Tumor Suppressor LKB1 Inhibits Activation of Signal Transducer and Activator of Transcription 3 (STAT3) by Thyroid Oncogenic Tyrosine Kinase Rearranged in Transformation (RET)/Papillary Thyroid Carcinoma (PTC)
Authors: Kim Dong Wook , Chung Hyo Kyun , Park Ki Cheol , Hwang Jung Hwan , Jo Young Suk , Chung Jongkyeong , Kalvakolanu Dhananjaya V. , Resta Nicoletta , Shong Minho 
Published: August 2007

AbstractThe tumor suppressor LKB1 (STK11) is a cytoplasmic/nuclear serine/threonine kinase, defects in which cause Peutz-Jeghers syndrome (PJS) in humans and animals. Recent studies showed that loss of function of LKB1 is associated with sporadic forms of lung, pancreatic, and ovarian cancer. In cancer cells, LKB1 is inactivated by two mechanisms: mutations in its central kinase domain or complete loss of LKB1 expression. Inactivation of LKB1 is associated with progression of PJS and transformation of benign polyps into malignant tumors. This study examines the effect of LKB1 on regulation of STAT3 and expression of transcriptional targets of STAT3. The results show that LKB1 inhibits rearranged in transformation (RET)/papillary thyroid carcinoma (PTC)-dependent activation of signal transducer and activator of transcription 3 (STAT3), which is mediated by phosphorylation of STAT3 tyrosine 705 by RET/PTC. Suppression of STAT3 transactivation by LKB1 requires the kinase domain but not the kinase activity of LKB1. The centrally located kinase domain of LKB1 is an approximately 260-amino-acid region that binds to the linker domain of STAT3. Chromatin immunoprecipitation studies indicate that expression of LKB1 reduces the binding of STAT3 to its target promoters and suppresses STAT3-mediated expression of Cyclin D1, VEGF, and Bcl-xL. Knockdown of LKB1 by specific small interfering RNA led to an increase in STAT3 transactivation activity and promoted cell proliferation in the presence of RET/PTC. Thus, this study suggests that LKB1 suppresses tumor growth by inhibiting RET/PTC-dependent activation of oncogenic STAT3.
Serotonin and nitric oxide interaction in the control of bioluminescence in northern krill, Meganyctiphanes norvegica (M. Sars)
Authors: Krönström Jenny , Dupont Samuel , Mallefet Jerome , Thorndyke Michael , Holmgren Susanne 
Published: August 2007

SUMMARY
The role of nitric oxide (NO) in the control of bioluminescence (light production) in the crustacean Meganyctiphanes norvegica (krill) was investigated using pharmacological and immunohistochemical methods. All nitrergic drugs tested failed to induce bioluminescence per se but modulated light production stimulated by 5-hydroxytryptamine (5-HT). NO donors[sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP)]injected in live specimens significantly reduced light production stimulated by 5-HT, whereas inhibition of the enzyme NO synthase (NOS) with l-NAME (NG-nitro-l-arginine methyl ester)resulted in an enhancement of the 5-HT response. The effects of NO do not seem to be mediated via production of cGMP as injections of a cGMP analogue (8-Bromoguanosine 3′,5′-cyclic monophosphate) gave inconclusive effects on the 5-HT-stimulated light response. Inhibition of cGMP production with ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) did not affect the light response. Moreover, a few individuals showed a considerably higher response to 5-HT in April and June compared with specimens collected in the autumn and winter. Furthermore, both NOS-like and 5-HT-like materials were detected by immunohistochemistry inside the light organs. NOS-like immunoreactivity was primarily observed in structures associated with vessels inside the light organs, whereas 5-HT-like material was abundant in nerve fibres throughout the whole light organ. The results suggest that NO has a modulatory role at several levels in the control of light production in M. norvegica and that NO and 5-HT interact in this regulation.
Larval desperation and histamine: how simple responses can lead to complex changes in larval behaviour
Authors: Swanson R. L. , Marshall D. J. , Steinberg P. D. 
Published: August 2007

SUMMARY
Some marine invertebrate larvae expand the range of settlement cues to which they will respond as they age. How do relatively simple larvae achieve such complex changes in behaviour? Larvae of the Australian sea urchin Holopneustes purpurascens settle and metamorphose specifically in response to a settlement cue, dissolved histamine, produced by the host alga Delisea pulchra. Older H. purpurascens larvae appear to accept a wider range of host algae, which contain far less histamine than D. pulchra, than newly competent larvae. We tested the hypothesis that older H. purpurascens larvae accept a greater range of host algae by metamorphosing in response to lower concentrations of histamine. We compared the response of newly competent and older larvae to a range of histamine concentrations in settlement assays. Larval age strongly affected the minimum concentration of histamine that induced metamorphosis in H. purpurascens, with older larvae responding to lower concentrations of histamine than newly competent larvae. Older larvae were more sensitive to lower concentrations of histamine yet still maintained a stringent requirement for exposure to histamine in order to metamorphose. In addition, older larvae metamorphosed after shorter exposure periods to histamine than did younger larvae. By using histamine concentration as a proxy for specific habitat cues, H. purpurascens larvae appear to expand their range of settlement preferences with age by simply changing their sensitivity to a single settlement cue. Overall, our results show that marine invertebrate larvae can exhibit surprisingly complex changes in behaviour via simple changes in their response to a single cue.
Escape performance decreases during ontogeny in wild crickets
Authors: Dangles O. , Pierre D. , Christides J. P. , Casas J. 
Published: August 2007

SUMMARY
Increasing the ecological relevance of studies relating to the performance of organisms has been a central issue for functional biologists over the last few years. Of particular concern are changes in performance throughout the life cycle as selective forces act differently on various life stages. We addressed this issue experimentally by following ontogenic variations in the escape performance of crickets threatened by artificial predatory signals. We measured their performance under natural settings, which is a necessary approach yet one that is undocumented in insects. We analysed numeric film sequences obtained using a high-speed video camera at 1000 frames s–1 to quantify wild cricket performance and behaviour in the field. We detected significant differences in cricket escape performance throughout ontogeny. Escape performances were higher in juvenile crickets than older instars. Complementary behavioural measurements for escaping crickets suggest that these variations may be related to the lower predatory risk perceived by large adults than by juveniles. We expect that our analysis of size-refuge will also improve our understanding in the development of performance, given its importance in community and population ecology theories.
p38 MAPK is a likely component of the signal transduction pathway triggering rapid cold hardening in the flesh fly Sarcophaga crassipalpis
Authors: Fujiwara Yoshihiro , Denlinger David L. 
Published: August 2007

SUMMARY
Rapid cold hardening (RCH) is an adaptation enabling insects to quickly respond to low temperature, but little is known about the molecular events that trigger this response. In this study of the flesh fly Sarcophaga crassipalpis, we explore a possible role for mitogen-activated protein kinases (MAPKs) in the low temperature signaling that elicits RCH. We report that p38 MAPK from S. crassipalpis, which shows high cDNA sequence homology to p38 MAPKs from other insects and mammals, is rapidly activated at temperatures around 0°C, temperatures that are most effective for inducing RCH. By contrast, low temperature does not activate either extracellular signal-regulated kinase (ERK) or Jun N-terminal kinase (JNK). An increase in phospho-p38 MAPK was observed within 10 min following exposure to 0°C and reached its maximum level in 2 h. When flies were transferred from 0 to 25°C, the level of phospho-p38 MAPK decreased immediately and reached trace levels by 3 h. Nondiapausing flies were much more responsive to p38 MAPK activation than cold-hardy diapausing pupae. Thus, p38 MAPK activation and RCH both show the same narrow ranges of temperature sensitivity, temporal profiles of activation and decay, and developmental specificity. These correlations suggest that p38 MAPK plays a potential role in regulating the induction of RCH. The p38 MAPK response was not dependent upon the brain, as evidenced by high activation in isolated abdomens exposed to low temperature.