bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent chemoradiotherapy with low dose weekly gemcitabine in stage III non-small cell lung cancer
Authors: Abacioglu Ufuk , Yumuk Perran F , Caglar Hale , Sengoz Meric , Turhal Nazim S 
Published: July 2005

Abstract

Background
Combined chemoradiotherapy (CRT) is the treatment of choice for stage III NSCLC. Gemcitabine (G) is a novel deoxycitidine analogue that has been proven to be a potent radiosensitizer. Twenty-two consecutive patients were treated with concurrent CRT to demonstrate the tolerability and efficacy of low dose G given weekly as radiosensitizer in stage III NSCLC.

Methods
Patients with KPS ≥70, adequate bone marrow reserve, with no prior radiotherapy (RT) and surgery were included. Eighteen patients had received prior induction chemotherapy (CT). G (75 mg/m2/week) was infused over 1 hour for 6 weeks. Thoracic RT was given two hours later over 6 weeks at 1.8 Gy/day fractions (total dose of 61.2 Gy). Pulmonary toxicity was evaluated with computed tomography scans in 6 weeks.

Results
Median age was 60 years (range, 48–75), median follow-up was 15 months (range, 2–40). Sixty-eight percent of patients were male and median KPS score was 90. Conformal 3D-RT planning was used in 64% of patients. G was given for a median of 5 weeks (range 1–9). Twelve patients (54.6%) received all planned CT. G was stopped because of intolerance in 6 and death in 2 patients. Seven patients (31.8%) had radiation pneumonitis. Twenty patients were evaluated for overall response, 1 patient (4.5%) had clinical CR, 81.8% had PR while 9.5% had SD. Median overall survival (OS) was 14 ± 5 months (95% CI 3–25). One- and 2-year OS rates were 55% and 38%. Sixteen patients died of disease-related events (6 with progression of primary tumor, 8 due to metastatic disease), 2 patients died of other causes. One- and 2-year progression-free survival and local control rates were 56%, 27% and 79%, 51%, respectively.

Conclusion
G might be used as radiosensitizer for patients with stage III NSCLC who could not receive full doses CT with concurrent RT.
Lung cancer symptoms and pulse oximetry in the prognostic assessment of patients with lung cancer
Authors: Martins Sandro J , Ho Nelson , Cavamura Sueli O , Harada Cecilia M , Yamamoto Crystina A , Takagaki Teresa Y 
Published: July 2005

Abstract
Background
Medical oncologists continue to use performance status as a proxy for quality of life (QOL) measures, as completion of QOL instruments is perceived as time consuming, may measure aspects of QOL not affected by cancer therapy, and interpretation may be unclear. The pulse oximeter is widely used in clinical practice to predict cardiopulmonary morbidity after lung resection in cancer patients, but little is known on its role outside the surgical setting. We evaluated whether the Lung Cancer Symptom Scale and pulse oximetry may contribute to the evaluation of lung cancer patients who received standard anticancer therapy.

Methods
We enrolled forty-one consecutive, newly diagnosed, patients with locally advanced or metastatic lung cancer in this study. We developed a survival model with the variables gender, age, histology, clinical stage, Karnofsky performance status, wasting, LCSS symptom scores, average symptom burden index, and pulse oximetry (SpO2).

Results
Patient and observer-rated scores were correlated, except for the fatigue subscale. The median SpO2 was 95% (range: 86 to 98), was unrelated to symptom scores, and was weakly correlated with observer cough scores. In a multivariate survival model, SpO2 > 90% and patient scores on the LCSS appetite and fatigue subscales were independent predictors of survival.

Conclusion
LCSS fatigue and appetite rating, and pulse oximetry should be studied further as prognostic factors in lung cancer patients.
Computer-aided dermoscopy for diagnosis of melanoma
Authors: Barzegari Masoomeh , Ghaninezhad Haiedeh , Mansoori Parisa , Taheri Arash , Naraghi Zahra S , Asgari Masood 
Published: July 2005

Abstract

Background
Computer-aided dermoscopy using artificial neural networks has been reported to be an accurate tool for the evaluation of pigmented skin lesions. We set out to determine the sensitivity and specificity of a computer-aided dermoscopy system for diagnosis of melanoma in Iranian patients.

Methods
We studied 122 pigmented skin lesions which were referred for diagnostic evaluation or cosmetic reasons. Each lesion was examined by two clinicians with naked eyes and all of their clinical diagnostic considerations were recorded. The lesions were analyzed using a microDERM® dermoscopy unit. The output value of the software for each lesion was a score between 0 and 10. All of the lesions were excised and examined histologically.

Results
Histopathological examination revealed melanoma in six lesions. Considering only the most likely clinical diagnosis, sensitivity and specificity of clinical examination for diagnosis of melanoma were 83% and 96%, respectively. Considering all clinical diagnostic considerations, the sensitivity and specificity were 100% and 89%. Choosing a cut-off point of 7.88 for dermoscopy score, the sensitivity and specificity of the score for diagnosis of melanoma were 83% and 96%, respectively. Setting the cut-off point at 7.34, the sensitivity and specificity were 100% and 90%.

Conclusion
The diagnostic accuracy of the dermoscopy system was at the level of clinical examination by dermatologists with naked eyes. This system may represent a useful tool for screening of melanoma, particularly at centers not experienced in the field of pigmented skin lesions.
Epidermal Growth Factor Receptor Gene Mutations and Increased Copy Numbers Predict Gefitinib Sensitivity in Patients With Recurrent Non–Small-Cell Lung Cancer
Authors: Takano Toshimi , Ohe Yuichiro , Sakamoto Hiromi , Tsuta Koji , Matsuno Yoshihiro , Tateishi Ukihide , Yamamoto Seiichiro , Nokihara Hiroshi , Yamamoto Noboru , Sekine Ikuo , Kunitoh Hideo , Shibata Tatsuhiro , Sakiyama Tokuki , Yoshida Teruhiko , Tamura Tomohide 
Published: July 2005

PurposeTo evaluate epidermal growth factor receptor (EGFR) mutations and copy number as predictors of clinical outcome in patients with non–small-cell lung cancer (NSCLC) receiving gefitinib.Patients and MethodsSixty-six patients with NSCLC who experienced relapse after surgery and received gefitinib were included. Direct sequencing of exons 18 to 24 of EGFR and exons 18 to 24 of ERBB2 was performed using DNA extracted from surgical specimens. Pyrosequencing and quantitative real-time polymerase chain reaction were performed to analyze the allelic pattern and copy number of EGFR.ResultsThirty-nine patients (59%) had EGFR mutations; 20 patients had deletional mutations in exon 19, 17 patients had missense mutations (L858R) in exon 21, and two patients had missense mutations (G719S or G719C) in exon 18. No mutations were identified in ERBB2. Response rate (82% [32 of 39 patients] v 11% [three of 27 patients]; P < .0001), time to progression (TTP; median, 12.6 v 1.7 months; P < .0001), and overall survival (median, 20.4 v 6.9 months; P = .0001) were significantly better in patients with EGFR mutations than in patients with wild-type EGFR. Increased EGFR copy numbers (≥ 3/cell) were observed in 29 patients (44%) and were significantly associated with a higher response rate (72% [21 of 29 patients] v 38% [14 of 37 patients]; P = .005) and a longer TTP (median, 9.4 v 2.6 months; P = .038). High EGFR copy numbers (≥ 6/cell) were caused by selective amplification of mutant alleles.ConclusionEGFR mutations and increased copy numbers were significantly associated with better clinical outcome in gefitinib-treated NSCLC patients.
Increased Epidermal Growth Factor Receptor Gene Copy Number Detected by Fluorescence In Situ Hybridization Associates With Increased Sensitivity to Gefitinib in Patients With Bronchioloalveolar Carcinoma Subtypes: A Southwest Oncology Group Study
Authors: Hirsch Fred R. , Varella-Garcia Marileila , McCoy Jason , West Howard , Xavier Ana Carolina , Gumerlock Paul , Bunn Paul A. , Franklin Wilbur A. , Crowley John , Gandara David R. 
Published: July 2005

Purpose Bronchioloalveolar carcinoma (BAC) and adenocarcinomas with BAC features seem to be increasing in incidence, particularly in younger, never-smoking women. Epidermal growth factor receptor (EGFR) inhibitors demonstrated response rates of 20% to 30% in patients with advanced BAC subtypes, but selection methods for patient therapy are not established. Patients and Methods EGFR and HER2 gene copy numbers were assessed by fluorescence in situ hybridization (FISH) in 81 patients treated with gefitinib 500 mg/d (Southwest Oncology Group protocol S0126) and were correlated to treatment outcome. Tumors were classified into two main strata: FISH-positive (high polysomy/gene amplification) and FISH-negative (disomy/low polysomy). Results In 81 patients, the median survival time for EGFR/FISH-negative patients was 8 months and not yet reached for FISH-positive patients (but approaching 18 months; hazard ratio [HR] = 2.02; P = .042). Median progression-free survival time for EGFR/FISH-positive patients was 9 months versus 4 months for the FISH-negative patients (HR = 1.67; P = .072). In multivariate analysis, EGFR copy number by FISH remained a significant predictive factor for survival after accounting for smoking status, sex, histology, and performance status. Fifty-five patients were evaluated for response using Response Evaluation Criteria in Solid Tumors Group, and 12 of 19 EGFR/FISH-positive patients (63%) demonstrated disease control versus 14 (39%) of 36 patients in the FISH-negative group (P = .087). No association was found between HER2 gene copy number and response (n = 39 patients) or survival (n = 56 patients; P > .10). Conclusion Increased EGFR gene copy number detected by FISH is associated with improved survival after gefitinib therapy in patients with advanced BAC, suggesting FISH methodology can be used to assess survival potential in patients treated with EGFR tyrosine kinase inhibitors.
Neoadjuvant Treatment of Postmenopausal Breast Cancer With Anastrozole, Tamoxifen, or Both in Combination: The Immediate Preoperative Anastrozole, Tamoxifen, or Combined With Tamoxifen (IMPACT) Multicenter Double-Blind Randomized Trial
Authors: Smith Ian E. , Dowsett Mitch , Ebbs Stephen R. , Dixon J. Michael , Skene Anthony , Blohmer J.-U. , Ashley Susan E. , Francis Stephen , Boeddinghaus Irene , Walsh Geraldine 
Published: July 2005

Purpose The Immediate Preoperative Anastrozole, Tamoxifen, or Combined With Tamoxifen (IMPACT) trial was designed to test the hypothesis that the clinical and/or biologic effects of neoadjuvant tamoxifen compared with anastrozole and with the combination of tamoxifen and anastrozole before surgery in postmenopausal women with estrogen receptor (ER) –positive, invasive, nonmetastatic breast cancer might predict for outcome in the Arimidex, Tamoxifen Alone or in Combination (ATAC) adjuvant therapy trial. Patients and Methods Postmenopausal women with ER-positive, invasive, nonmetastatic, and operable or locally advanced potentially operable breast cancer were randomly assigned to neoadjuvant tamoxifen (20 mg daily), anastrozole (1 mg daily), or a combination of tamoxifen and anastrozole for 3 months. The tumor objective response (OR) was assessed by both caliper and ultrasound. Comparisons were also made of clinical response with ultrasound response, actual and feasible surgery with feasible surgery at baseline, OR in human epidermal growth factor receptor 2 (HER2) –positive cancers, and tolerability. Results There were no significant differences in OR in the intent-to-treat population between patients receiving tamoxifen, anastrozole, or the combination. In patients who were assessed as requiring mastectomy at baseline (n = 124), 44% of patients received breast-conserving surgery (BCS) after anastrozole compared with 31% of patients after tamoxifen (P = .23); this difference became significant for patients who were deemed feasible for BCS by their surgeon (46% v 22%, respectively; P = .03). The OR for patients with HER2-positive cancer (n = 34) was 58% for anastrozole compared with 22% for tamoxifen (P = .18). All treatments were well tolerated. Conclusion Neoadjuvant anastrozole is as effective and well tolerated as tamoxifen in ER-positive operable breast cancer in postmenopausal women, but the hypothesis that clinical outcome might predict for long-term outcome in adjuvant therapy was not fulfilled.
Phase II Trial of Temsirolimus (CCI-779) in Recurrent Glioblastoma Multiforme: A North Central Cancer Treatment Group Study
Authors: Galanis Evanthia , Buckner Jan C. , Maurer Matthew J. , Kreisberg Jeffrey I. , Ballman Karla , Boni J. , Peralba Josep M. , Jenkins Robert B. , Dakhil Shaker R. , Morton Roscoe F. , Jaeckle Kurt A. , Scheithauer Bernd W. , Dancey Janet , Hidalgo Manuel , Walsh Daniel J. 
Published: July 2005

Background Temsirolimus (CCI-779) is a small-molecule inhibitor of the mammalian target of rapamycin (mTOR) and represents a rational therapeutic target against glioblastoma multiforme (GBM). Methods Recurrent GBM patients with ≤ 1 chemotherapy regimen for progressive disease were eligible. Temsirolimus was administered in a 250-mg intravenous dose weekly. Results Sixty-five patients were treated. The incidence of grade 3 or higher nonhematologic toxicity was 51%, and consisted mostly of hypercholesterolemia (11%), hypertriglyceridemia (8%), and hyperglycemia (8%). Grade 3 hematologic toxicity was observed in 11% of patients. Temsirolimus peak concentration (Cmax), and sirolimus Cmax and area under the concentration-time curve were decreased in patients receiving p450 enzyme–inducing anticonvulsants (EIACs) by 73%, 47%, and 50%, respectively, but were still within the therapeutic range of preclinical models. Twenty patients (36%) had evidence of improvement in neuroimaging, consisting of decrease in T2 signal abnormality +/− decrease in T1 gadolinium enhancement, on stable or reduced steroid doses. Progression-free survival at 6 months was 7.8% and median overall survival was 4.4 months. Median time to progression (TTP) for all patients was 2.3 months and was significantly longer for responders (5.4 months) versus nonresponders (1.9 months). Development of grade 2 or higher hyperlipidemia in the first two treatment cycles was associated with a higher percentage of radiographic response (71% v 31%; P = .04). Significant correlation was observed between radiographic improvement and high levels of phosphorylated p70s6 kinase in baseline tumor samples (P = .04). Conclusion Temsirolimus is well tolerated in recurrent GBM patients. Despite the effect of EIACs on temsirolimus metabolism, therapeutic levels were achieved. Radiographic improvement was observed in 36% of temsirolimus–treated patients, and was associated with significantly longer TTP. High levels of phosphorylated p70s6 kinase in baseline tumor samples appear to predict a patient population more likely to derive benefit from treatment. These findings should be validated in other studies of mTOR inhibitors.
Cognitive Science: The Newest Science of the Artificial*
Authors: Simon Herbert A. 
Published: July 2005

Cognitive science is, of course, not really a new discipline, but a recognition of a fundamental set of common concerns shared by the disciplines of psychology, computer science, linguistics, economics, epistemology, and the social sciences generally. All of these disciplines are concerned with information processing systems, and all of them are concerned with systems that are adaptive—that are what they are from being ground between the nether millstone of their physiology or hardware, as the case may be, and the upper millstone of a complex environment in which they exist. Systems that are adaptive may equally well be described as “artificial,” for as environments change, they can be expected to change too, as though they were deliberately designed to fit those environments (as indeed they sometimes are).The task of empirical science is to discover and verify invariants in the phenomena under study. The artificiality of information processing systems creates a subtle problem in defining empirical invariants in such systems. For observed regularities are very likely invariant only within a limited range of variation in their environments, and any accurate statement of the laws of such systems must contain reference to their relativity to environmental features. It is a common experience in experimental psychology, for example, to discover that we are studying sociology—the effects of the past histories of our subjects—when we think we are studying physiology—the effects of properties of the human nervous system. Similarly, business cycle economists are only now becoming aware of the extent to which the parameters of the system they are studying are dependent on the experiences of a population with economic events over the previous generation.In artificial sciences, the descriptive and the normative are never far apart. Thus, in economics, the “principle of rationality” is sometimes asserted as a descriptive invariant, sometimes as advice to decision makers. Similarly, in psychology, the processes of adaptation (learning) have always been a central topic, at one time a topic that dominated the whole field of research. Linguistics, too, has suffered its confusions between descriptive and normative attitudes towards its subject. But we must avoid the error, in studying information processing systems, of thinking that the adaptive processes themselves must be invariant; and we must be prepared to face the complexities of regression in the possibility that they themselves may be subject to improvement and adaptation.It might have been necessary a decade ago to argue for the commonality of the information processes that are employed by such disparate systems as computers and human nervous systems. The evidence for that commonality is now overwhelming, and the remaining questions about the boundaries of cognitive science have more to do with whether there also exist nontrivial commonalities with information processing in genetic systems than with whether men and machines both think.
Neurological Knowledge and Complex Behaviors
Authors: Geschwind Norman 
Published: July 2005

Some scholars believe thot Cognitive Science is the attempt to achieve in artificial systems what has already been achieved in the brain. Others, by contrast, argue that the study of ideal adaptive mechanisms could go on without reference to the brain. The author points out that the brain may not be the ideal cognitive device because of biological limitotions on its capacity. Although it may not be ideal, it is still of major interest to cognitive scientists because of the great interest in the human mind, and, in addition, because at this moment the brain is the most important single reservoir of odoptive mechanisms.The paper discusses several areas of neuroscience which are likely to shed light on mechanisms of adaptation. The study of simple nervous systems is likely to reveal important design principles of cognitive devices. The study of complex nervous systems will, of course, exert a major influence. The study of such systems leads to certain general principles concerning the neural circuits involved in complex odoptive behaviors: (1) There exist innate specialized systems for the learning of many specific behaviors that at first might appeor to be purely cultural. (2) There is no evidence for the existence of any all‐purpose computer in the brain. (3) There are many surprising dissociations manifested by the specialized systems in the brain, e.g., a special system for recognition of faces as against other visual patterns. (4) The study of the nervous system enables one to formulate more precise mechanisms for the role of emotion in cognitive function.(5) Some human behoviors con probably be understood poorly or not at all if the neural substrate is not considered. (6) The cognitive systems designed for dealing with ottentionol processes may be among the most complex neural structures which underlie behavior.There are certain other properties of brains that should be kept in mind by the cognitive scientists who are studying human behovior: (1) Brains differ from each other in structure, and it is very likely that the strategy for the solution of certain problems differs from person to person. (2) The presence of certain innate cognitive strategies in the brain may prevent that organism from employing other strategies which might be optimal for other problems. (3) Any theory about a particular cognitive strategy will have implications as to the particular mode of breakdown that might be expected after brain lesions. The study of disordered function from brain disease may thus be a valuable way to test certain cognitive theories.
Repair Theory: A Generative Theory of Bugs in Procedural Skills
Authors: Brown John Seely , VanLehn Kurt 
Published: July 2005

This paper describes a generative theory of bugs. It claims that all bugs of a procedural skill can be derived by a highly constrained form of problem solving acting on incomplete procedures. These procedures are characterized by formal deletion operations that model incomplete learning and forgetting. The problem solver and the deletion operator have been constrained to make it impossible to derive “star‐bugs”—algorithms that are so absurd that expert diagnosticians agree that the alogorithm will never be observed as a bug. Hence, the theory not only generates the observed bugs, it fails to generate star‐bugs.The theory has been tested on an extensive data base of bugs for multidigit subtraction that was collected with the aid of the diagnostic systems buggy and debuggy. In addition to predicting bug occurrence, by adoption of additional hypotheses, the theory also makes predictions about the frequency and stability of bugs, as well as the occurrence of certain latencies in processing time during testing. Arguments are given that the theory can be applied to domains other than subtraction and that it can be extended to provide a theory of procedural learning that accounts for bug acquisition. Lastly, particular care has been taken to make the theory principled so that it can not be tailored to fit any possible data.
A real‐world rational agent: unifying old and new AI
Authors: Verschure Paul F.M.J. , Althaus Philipp 
Published: July 2005

AbstractExplanations of cognitive processes provided by traditional artificial intelligence were based on the notion of the knowledge level. This perspective has been challenged by new AI that proposes an approach based on embodied systems that interact with the real‐world. We demonstrate that these two views can be unified. Our argument is based on the assumption that knowledge level explanations can be defined in the context of Bayesian theory while the goals of new AI are captured by using a well established robot based model of learning and problem solving, called Distributed Adaptive Control (DAC). In our analysis we consider random foraging and we prove that minor modifications of the DAC architecture renders a model that is equivalent to a Bayesian analysis of this task. Subsequently, we compare this enhanced, “rational,” model to its “non‐rational” predecessor and a further control condition using both simulated and real robots, in a variety of environments. Our results show that the changes made to the DAC architecture, in order to unify the perspectives of old and new AI, also lead to a significant improvement in random foraging.