bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emotional and Temporal Aspects of Situation Model Processing during Text Comprehension: An Event-Related fMRI Study
Authors: Ferstl Evelyn C. , Rinck Mike , Cramon D. Yves von 
Published: April 2005

Abstract
Language comprehension in everyday life requires the continuous integration of prior discourse context and general world knowledge with the current utterance or sentence. In the neurolinguistic literature, these so-called situation model building processes have been ascribed to the prefrontal cortex or to the right hemisphere. In this study, we use whole-head event-related fMRI to directly map the neural correlates of narrative comprehension in context. While being scanned using a spin-echo sequence, 20 participants listened to 32 short stories, half of which contained globally inconsistent information. The inconsistencies concerned either temporal or chronological information or the emotional status of the protagonist. Hearing an inconsistent word elicited activation in the right anterior temporal lobe. The comparison of different information aspects revealed activation in the left precuneus and a bilateral frontoparietal network for chronological information. Emotional information elicited activation in the ventromedial prefrontal cortex and the extended amygdaloid complex. In addition, the integration of inconsistent emotional information engaged the dorsal frontomedial cortex (Brodmann's area 8/9), whereas the integration of inconsistent temporal information required the lateral prefrontal cortex bilaterally. These results indicate that listening to stories can elicit activation reflecting content-specific processes. Furthermore, updating of the situation model is not a unitary process but it also depends on the particular requirements of the text. The right hemisphere contributes to language processing in context, but equally important are the left medial and bilateral prefrontal cortices.
Under-reporting of inpatient services utilisation in household surveys – a population-based study in Hong Kong
Authors: Tsui Eva LH , Leung Gabriel M , Woo Pauline PS , Choi Sarah , Lo Su-Vui 
Published: April 2005

Abstract
Background
Recognising that household interviews may produce biased estimates of health services utilisation, we examined for under- and over-reporting of hospitalisation episodes in three recent, consecutive population-based household surveys in Hong Kong.

Methods
Territory-wide inpatient service utilisation volumes as estimated from the 1999, 2001 and 2002 Thematic Household Surveys (THS) were benchmarked against corresponding statistics derived from routine administrative databases. Between-year differences on net under-reporting were quantified by Cohen's d effect size. To assess the potential for systematic biases in under-reporting, age- and sex-specific net under-reporting rates within each survey year were computed and the F-test was performed to evaluate differences between demographic subgroups. We modelled the effects of age and sex on the likelihood of ever hospitalisation through logistic regression to compare the odds ratios respectively derived from survey and administrative data.

Results
The extent of net under-reporting was moderately large in all three years amounting to about one-third of all inpatient episodes. However, there did not appear to be significant systematic biases in the degree of under-reporting by age or sex on stratified analyses and logistic regression modelling.

Conclusion
Under-reporting was substantial in Hong Kong's THS. Recall bias was likely most responsible for such reporting inaccuracies. A proper full-design record-check study should be carried out to confirm the present findings.
Dietary omega-3 fatty acids and ionizing irradiation on human breast cancer xenograft growth and angiogenesis
Authors: Hardman W Elaine , Sun LuZhe , Short Nicholas , Cameron Ivan L 
Published: April 2005

Abstract

Background
The effects of an omega-3 (n-3) fatty acid enriched diet alone and in combination with gamma irradiation (IR) therapy in nude mice bearing a human MDA-MB231 breast cancer xenograft were tested. The cancer cells were injected into the mammary fat pad of young female mice. Six weeks later, mice were randomly divided into two diet groups: 1) mice with 10% corn oil (rich in omega 6 fatty acids) in their food, 2) mice consuming a 10% fat diet that was enriched in n-3 fatty acids. After two weeks on the diet, treatment with 200 cGy of IR every second day for four treatments (total 800 cGy) was initiated on half of the mice from each diet group. Some mice in each of the 4 groups were euthanized 24 hours after the end of IR while the remaining mice were followed for 3 additional weeks. Tumor sections were stained for endothelial cells with CD31 and PAS and for hypoxia inducible factor 1α (HIF-α).

Results
The tumor cortex within 100 microns of the well-vascularized capsule had little vascularization. Blood vessels, capillaries, and endothelial pseudopods were found at areas greater than 100 microns from the capsule (subcortex). Mice on the corn oil diet and treated with IR 24 hours previously or non-irradiated mice fed the n-3 diet had tumors with fewer blood vessels in the subcortex and more endothelial pseudopods projecting into hypoxic (HIF- α positive) areas than did mice from the non-irradiated corn oil fed group. The tumor growth rate of mice that received IR or that were fed the n-3 fatty acid enriched diet was significantly slower than in the mice fed the 10% corn oil diet. Harmful side effects were found only in the IR treated mice.

Conclusion
The omega-3 fatty acid enriched diet proved to be a safe means for retarding tumor growth and vascularization.
Adoptive T cell therapy: Addressing challenges in cancer immunotherapy
Authors: Yee Cassian 
Published: April 2005

AbstractAdoptive T cell therapy involves the ex vivo selection and expansion of effector cells for the treatment of patients with cancer. In this review, the advantages and limitations of using antigen-specific T cells are discussed in counterpoint to vaccine strategies. Although vaccination strategies represent more readily available reagents, adoptive T cell therapy provides highly selected T cells of defined phenotype, specificity and function that may influence their biological behavior in vivo. Adoptive T cell therapy offers not only translational opportunities but also a means to address fundamental issues in the evolving field of cancer immunotherapy.
Differential expression of CCR3 and CXCR3 by human lung and bone marrow-derived mast cells: implications for tissue mast cell migration
Authors: Brightling Christopher E , Kaur Davinder , Berger Patrick , Morgan Angela J , Wardlaw Andrew J , Bradding Peter 
Published: April 2005

AbstractThe selective microlocalization of mast cells within specific airway structures, such as the airway smooth muscle and submucosal glands, in asthma is important in the pathophysiology of inflammatory lung disease. Chemokines are likely candidates mediating mast cell migration into these tissue compartments. In this study, we have defined the chemokine receptor profile of human lung mast cells (HLMC) compared with mast cells derived from human bone marrow (BM) and the human mast cell line HMC-1. CXC chemokine receptor 3 (CXCR3) was the most highly expressed chemokine receptor on ex vivo HLMC analyzed by flow cytometry, and CXCR3 expression by mast cells in the bronchial mucosa was confirmed by immuno-histochemistry. CXCR3 was functional, inducing a rise in cytosolic-free Ca2+, actin reorganization, and chemotaxis in response to the CXC ligands CXCL9, -10, and -11. CXCR3 activation did not induce degranulation or cytokine synthesis. In addition, more than 10% of ex vivo HLMC expressed CC chemokine receptor 3, CXCR1, and CXCR4. It is interesting that CXCR3 was not expressed by human BM-derived mast cells, suggesting its expression is induced during tissue maturation. As CXCR3 ligands are elevated in many pulmonary diseases, CXCR3 may be important for determining the anatomical microlocalization of mast cells within the human lung.
Lipopolysaccharide stimulation converts vigorously washed dendritic cells (DCs) to nonexhausted DCs expressing CD70 and evoking long-lasting type 1 T cell responses
Authors: Iwamoto Sanju , Ishida Makoto , Takahashi Keiko , Takeda Ken , Miyazaki Akira 
Published: April 2005

AbstractA great variety of in vitro culture protocols for human monocyte-derived dendritic cells (mo-DCs) has been used to generate DCs suitable for use in immunotherapy. It is thought that activated DCs undergo one-way differentiation into “exhausted” DCs. In the present study, we contrived an in vitro method for facilitating expression of CD70 by mature DCs. This was achieved by vigorous washing of mo-DCs before exposure to lipopolysaccharide (LPS). Unexpectedly, these mature DCs retain expression of some interleukin (IL)-12 family members after extended periods and maintain their ability to stimulate type 1 T cell responses. In contrast, DCs exposed to IL-4 before LPS stimulation or LPS-stimulated DCs not exposed to washing stress before activation failed to express CD70 and did differentiate into exhausted DCs. It is interesting that DCs expressing CD70 (CD70+ DCs) induced interferon-γ production from purified, allogeneic CD8+ T cells through a direct CD27-CD70 interaction. This is evidence for a pathway resulting in generation of CD8 T effectors by B7-independent mechanisms. These data suggest that exposure of immature DCs to LPS stimulation contributes to their terminal differentiation into CD70+ DCs, which have potent ability to prolong type 1 T cell responses through alternative pathways.
Enhanced TLR4 reactivity following injury is mediated by increased p38 activation
Authors: Maung Adrian A , Fujimi Satoshi , Miller Marissa L , MacConmara Malcolm P , Mannick John A , Lederer James A 
Published: April 2005

AbstractSevere injury primes the innate-immune system for increased Toll-like receptor 4 (TLR4)-induced proinflammatory cytokine production by macrophages. In this study, we examined changes in TLR4 signaling pathways in splenic macrophages from burn-injured or sham mice to determine the molecular mechanism(s) responsible for the increased TLR4 responsiveness. Using flow cytometry and specific antibodies, we first looked for injury-induced changes in the expression levels of several TLR-associated signaling molecules. We found similar levels of myeloid differentiation primary-response protein 88 (MyD88) and interleukin-1 receptor-associated kinase-M (IRAK-M) and somewhat lower levels of total p38, extracellular signal-regulated kinase (ERK), and stress-activated protein kinase (SAPK)/c-jun N-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs) in burn compared with sham macrophages. However, with the use of antibodies specific for the phosphorylated (activated) forms of the three MAPKs, we found that macrophages from burn mice showed a twofold increase in purified lipopolysaccharide (LPS)-stimulated p38 activation as compared with cells from sham mice on days 1 and 7 post-injury, whereas ERK and SAPK/JNK activation was increased by burn injury only on day 1. Using the specific p38 inhibitor (SB203580), we confirmed that the increase in tumor necrosis factor α production by LPS-stimulated burn macrophages requires p38 activation. Although we demonstrated that injury increases macrophage TLR4 mRNA expression and intracellular expression of TLR4-myeloid differentiation protein-2 (MD-2) protein, macrophage cell-surface expression of TLR4-MD-2 was not changed by burn injury. Our results suggest that the injury-induced increase in TLR4 reactivity is mediated, at least in part, by enhanced activation of the p38 signaling pathway.
Systematic Review of Barriers to the Recruitment of Older Patients With Cancer Onto Clinical Trials
Authors: Townsley Carol A. , Selby Rita , Siu Lillian L. 
Published: April 2005

Purpose Older patients are significantly underrepresented in cancer clinical trials. A literature review was undertaken to identify the barriers that impede the accrual of this vulnerable population onto clinical trials and to determine what specific strategies are needed to improve the representation of older patients in research studies. Methods A systematic literature search was undertaken using several different strategies to identify relevant articles. Results Nine of 31 relevant papers from 159 citations were included. Age is a significant barrier to recruitment; only a quarter to one third of potentially eligible older patients are enrolled onto trials. Physicians' perceptions, protocol eligibility criteria with restrictions on comorbid conditions, and functional status to optimize treatment tolerability are the most important reasons resulting in the exclusion of older patients. Other barriers include the lack of social support and the need for extra time and resources to enroll these patients. Conversely, older patients do not view their age as an important reason for refusing trials. Conclusion Specific clinical trials confined to older patients should be conducted to evaluate tumor biology, treatment tolerability, and the effect of comorbid conditions. Protocol designs need to stratify for age and be less restrictive with respect to exclusions on functional status, comorbidity, and previous cancers, such that results are generalizable to older patients. Physician education to dispel unfounded perceptions, improved access to available clinical trials, and provision of personnel and resources to accommodate the unique requirements of an older population are possible solutions to remove the barriers of ageism.
TGFBR1☆6A May Contribute to Hereditary Colorectal Cancer
Authors: Bian Yansong , Caldes Trinidad , Wijnen Juul , Franken Patrick , Vasen Hans , Kaklamani Virginia , Nafa Khédoudja , Peterlongo Paolo , Ellis Nathan , Baron John A. , Burn John , Moeslein Gabriela , Morrison Patrick J. , Chen Yu , Ahsan Habibul , Watson Patrice , Lynch Henry T. , de la Chapelle Albert , Fodde Riccardo , Pasche Boris 
Published: April 2005

Purpose TGFBR1☆6A is a tumor susceptibility gene that increases breast, colon, and ovarian cancer risk. Fourteen percent of the general population carries TGFBR1☆6A, and TGFBR1☆6A homozygotes have a greater than 100% increased colon cancer risk compared with noncarriers. Low-penetrance genes such as TGFBR1☆6A may account for a sizable proportion of familial colorectal cancer occurrences. To test this hypothesis, we determined whether TGFBR1☆6A contributes to a proportion of mismatch repair (MMR) gene mutation–negative hereditary nonpolyposis colorectal cancer (HNPCC) patients. Patients and Methods A case-case study was performed of 208 index patients with HNPCC meeting the Amsterdam criteria. Patients were examined for mutations and genomic rearrangements in the MLH1, MSH2, and MSH6 genes and genotyped for TGFBR1☆6A. Tumor microsatellite instability status was available for 95 patients. Results A total of 144 patients (69.2%) carried a deleterious mutation and were classified as positive for MMR gene mutation; 64 patients (30.8%) had no evidence of mutations and were classified as MMR negative. TGFBR1☆6A allelic frequency was significantly higher among MMR-negative patients (0.195) than among MMR-positive patients (0.104; P = .011). The proportion of TGFBR1☆6A homozygotes was nine-fold higher among MMR-negative (6.3%) than among MMR-positive patients (0.7%; P = .032). The highest TGFBR1☆6A allelic frequency was found among MMR-negative patients with tumors exhibiting no microsatellite instability (0.211), and the lowest frequency was found among MMR-positive patients with tumors exhibiting microsatellite instability (0.121); the difference was not statistically significant (P = .17). Conclusion TGFBR1☆6A may be causally responsible for a proportion of HNPCC occurrences.
Expression ofInterleukin-10Splicing Variants Is a Positive Prognostic Feature in Relapsed Childhood Acute Lymphoblastic Leukemia
Authors: Wu Shuling , Geβner Reinhard , Taube Tillmann , von Stackelberg Arend , Henze Günter , Seeger Karl 
Published: April 2005

PurposeBiologic features of hematologic malignancies have prognostic implications and are essential elements in the design of current therapeutic trials. This study aimed to determine the expression of a splicing-derived variant of interleukin (IL) -10 in leukemic cells and its clinical relevance in children with acute lymphoblastic leukemia (ALL) at first relapse.Patients and MethodsBetween January 1997 and December 2001, bone marrow (BM) samples were collected from 98 children with first relapse of ALL at diagnosis. These patients were enrolled in the relapse trial ALL-REZ BFM (ALL-Relapse Berlin-Frankfurt-Münster) 95 and 96. The detection of IL-10 isoforms in leukemic cells of BM samples were performed by conventional reverse transcriptase polymerase chain reaction and by immunoblotting.ResultsIL-10 was detected in 93.9% BM samples. In addition to expressing full-length IL-10, a new splicing-derived IL-10 variant (termed IL-10δ3) that lacked the entire exon 3 was identified in leukemic cells. The IL-10δ3 variant was found in 80.4% of BM samples. Most importantly, expression of IL-10δ3 was associated with a significantly better response to chemotherapy (P = .001) and probability of event-free survival (P = .01) at 5 years.ConclusionThese results indicate that splicing-derived IL-10 isoforms may modulate IL-10–mediated biologic effects and therapeutic efficacy in lymphatic disease, and expression of IL-10δ3 is a positive prognostic feature in relapsed childhood ALL.
Results of the Dutch National Study of the Palliative Effect of Irradiation Using Two Different Treatment Schemes for Non–Small-Cell Lung Cancer
Authors: Kramer Gijsbert W.P.M. , Wanders Stofferinus L. , Noordijk Ed M. , Vonk Ernest J.A. , van Houwelingen Hans C. , van den Hout Wilbert B. , Geskus Ronald B. , Scholten Mirjam , Leer Jan-Willem H. 
Published: April 2005

Purpose A national multicenter randomized study compared the efficacy of 2 × 8 Gy versus our standard 10 × 3 Gy in patients with inoperable stage IIIA/B (with an Eastern Cooperative Oncology Group score of 3 to 4 and/or substantial weight loss) and stage IV non–small-cell lung cancer. Patients and Methods Between January 1999 and June 2002, 297 patients were eligible and randomized to receive either 10 × 3 Gy or 2 × 8 Gy by external-beam irradiation. The primary end point was a patient-assessed score of treatment effect on seven thoracic symptoms using an adapted Rotterdam Symptom Checklist. Study sample size was determined based on an average total symptom score difference of more than one point over the initial 39 weeks post-treatment. The time course of symptom scores were also evaluated, and other secondary end points were toxicity and survival. Results Both treatment arms were equally effective, as the average total symptom score over the initial 39 weeks did not differ. However, the pattern in time of these scores differed significantly (P < .001). Palliation in the 10 × 3-Gy arm was more prolonged (until week 22) with less worsening symptoms than in 2 × 8-Gy. Survival in the 10 × 3-Gy arm was significantly (P = .03) better than in the 2 × 8-Gy arm with 1-year survival of 19.6% (95%CI, 14.1% to 27.3%) v 10.9% (95%CI, 6.9% to 17.3%). Conclusion The 10 × 3-Gy radiotherapy schedule is preferred over the 2 × 8-Gy schedule for palliative treatment, as it improves survival and results in a longer duration of the palliative response.
Patterns and Correlates of Local Therapy for Women With Ductal Carcinoma-In-Situ
Authors: Katz Steven J. , Lantz Paula M. , Janz Nancy K. , Fagerlin Angela , Schwartz Kendra , Liu Lihua , Deapen Dennis , Salem Barbara , Lakhani Indu , Morrow Monica 
Published: April 2005

Purpose Concerns have been raised about the quality of treatment for women with ductal carcinoma-in-situ (DCIS) because persistent high rates of mastectomy suggest overtreatment, whereas lower than expected rates of radiation therapy after breast-conserving surgery (BCS) suggest undertreatment. Patients and Methods All women with DCIS diagnosed in 2002 and who reported to the Detroit and Los Angeles Surveillance, Epidemiology, and End Results (SEER) registries were identified and surveyed shortly after receipt of surgery (response rate, 79.7%; n = 817). Analyses were restricted to patients with DCIS (n = 659) indicated by SEER stage data. Results Only 14.0% of patients at lowest risk of recurrence (based on tumor size and histologic grade) received a mastectomy compared with 22.8% and 52.6% of patients at intermediate and highest risk (P < .001). Only 13.1% of patients who were not influenced or slightly influenced by concerns about recurrence received mastectomy compared with 48.8% of women who were greatly influenced by this concern (P < .001). A between-geographic site difference in receipt of radiation after BCS was observed for the lowest risk group (38.9% in Los Angeles v 70.5% in Detroit) but not for the highest risk group (80.2% in Los Angeles v 85.9% in Detroit, P = .006 for site and risk group differences). Between-site differences in receipt of radiation after BCS were consistent with patient recall of surgeon discussions about treatment. Conclusion Surgeons are tailoring their recommendations for local therapy options for DCIS based on important clinical factors. Patient attitudes also play an important role in treatment decisions. The substantial influence of both surgeon opinion and patient attitudes should temper concerns about the quality of treatment for women with DCIS.
Randomized Trial of Hyperthermia and Radiation for Superficial Tumors
Authors: Jones Ellen L. , Oleson James R. , Prosnitz Leonard R. , Samulski Thaddeus V. , Vujaskovic Zeljko , Yu Daohai , Sanders Linda L. , Dewhirst Mark W. 
Published: April 2005

Purpose Randomized clinical trials have demonstrated hyperthermia (HT) enhances radiation response. These trials, however, generally lacked rigorous thermal dose prescription and administration. We report the final results of a prospective randomized trial of superficial tumors (≤ 3 cm depth) comparing radiotherapy versus HT combined with radiotherapy, using the parameter describing the number of cumulative equivalent minutes at 43°C exceeded by 90% of monitored points within the tumor (CEM 43°C T90) as a measure of thermal dose. Methods This trial was designed to test whether a thermal dose of more than 10 CEM 43°C T90 results in improved complete response and duration of local control compared with a thermal dose of ≤ 1 CEM 43°C T90. Patients received a test dose of HT ≤ 1 CEM 43°C T90 and tumors deemed heatable were randomly assigned to additional HT versus no additional HT. HT was given using microwave spiral strip applicators operating at 433 MHz. Results One hundred twenty-two patients were enrolled; 109 (89%) were deemed heatable and were randomly assigned. The complete response rate was 66.1% in the HT arm and 42.3% in the no-HT arm. The odds ratio for complete response was 2.7 (95% CI, 1.2 to 5.8; P = .02). Previously irradiated patients had the greatest incremental gain in complete response: 23.5% in the no-HT arm versus 68.2% in the HT arm. No overall survival benefit was seen. Conclusion Adjuvant hyperthermia with a thermal dose more than 10 CEM 43°C T90 confers a significant local control benefit in patients with superficial tumors receiving radiation therapy.