bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of early recurrence among postmenopausal women with estrogen receptor‐positive early breast cancer treated with adjuvant tamoxifen
Authors: Kennecke Hagen , McArthur Heather , Olivotto Ivo A. , Speers Caroline , Bajdik Chris , Chia Stephen K. , Ellard Susan , Norris Brian , Hayes Malcolm , Barnett Jeff , Gelmon Karen A. 
Published: February 2008

AbstractBACKGROUNDAdjuvant aromatase inhibitors (AIs), instead of or after tamoxifen, are effective in decreasing recurrence in postmenopausal women with estrogen receptor (ER)‐positive breast cancer. An understanding of which patients are at risk of early recurrence while they are receiving tamoxifen may improve clinical decision making.METHODSThe patients who were included in this study were women aged ≥50 years with early‐stage, ER‐positive breast cancer diagnosed between 1986 and 1999 and had been treated with tamoxifen. Characteristics of the patients with early recurrences (within 2.5 years of diagnosis), late recurrences (between 2.5 years and 5 years) and no recurrence within 5 years were compared. Logistic regression analyses were conducted to identify which groups were at risk of early recurrence.RESULTSAmong 3844 women, 304 women (7.9%) developed disease recurrence within 2.5 years. Higher than average rates of recurrence within 2.5 years were observed in cohorts with lymph node (N)‐positive tumors (11.5%), grade 3 histology (14.3%), or low‐positive ER levels, ie, 10–49 fmol/mg or 10%–20% staining (14.9%). In multivariate analyses, only pathologically N‐positive tumors (1–3 vs 0 positive lymph nodes: odds ratio [OR], 1.6; 4–9 vs 0 positive lymph nodes: OR, 2.23 [P = .03]) and low‐positive ER status (OR, 2.04; P = .01) were associated with recurrence within 2.5 years compared with recurrence between 2.5 years and 5 years. Other clinical and pathologic variables were not predictive of early recurrence.CONCLUSIONSSubgroups of women with early ER‐positive breast cancer may be identified who are at increased risk of recurrence within 2.5 years of diagnosis despite tamoxifen. It remains to be proven whether upfront AI therapy results in an advantage to these women. Cancer 2008. © 2008 American Cancer Society.
Imprinted tumor suppressor genes ARHI and PEG3 are the most frequently down‐regulated in human ovarian cancers by loss of heterozygosity and promoter methylation
Authors: Feng Weiwei , Marquez Rebecca T. , Lu Zhen , Liu Jinsong , Lu Karen H. , Issa Jean‐Pierre J. , Fishman David M. , Yu Yinhua , Bast Robert C. 
Published: February 2008

AbstractBACKGROUNDImprinted tumor suppressor genes may be particularly important in the pathogenesis of ovarian cancer. Two imprinted genes, paternally expressed 3 (PEG3) and aplasia Ras homologue member I (ARHI), are the most frequently down‐regulated in ovarian cancers on gene expression arrays.METHODSPEG3 and ARHI expression levels were evaluated with real‐time reverse‐transcriptase polymerase chain reaction (PCR) analysis. Promoter methylation was measured by pyrosequencing, and loss of heterozygosity (LOH) was detected by PCR‐LOH assays.RESULTSPEG3 was down‐regulated in 75% and ARHI was down‐regulated in 88% of 40 ovarian cancers. ARHI CpG islands I and II were hypermethylated in 13 of 42 ovarian cancers (31%) and in 5 of 42 ovarian cancers (12%), respectively, and hypermethylation was associated with reduced ARHI expression in all 18 samples of ovarian cancer with CpG island hypermethylation. PEG3 was hypermethylated in 11 of 42 ovarian cancers (26%), and PEG3 expression was down‐regulated in 10 of those 11 cancers. LOH was detected in 8 of 35 informative cases for ARHI (23%) and in 5 of 25 informative cases for PEG3 (20%). PEG3 and ARHI expression was highly correlated in human ovarian cancers (correlation coefficient [R] = 0.69; P < .0001). PEG3 and ARHI also were methylated concordantly in ovarian cancers (R = 0.36; P = .019). Re‐expression of PEG3, similar to that of ARHI, markedly inhibited ovarian cancer growth. ARHI and PEG3 expression could be restored by treatment with 5‐aza‐2′‐deoxycytidine and trichostatin A, consistent with the importance of promoter methylation and histone acetylation in regulating expression of both genes.CONCLUSIONSLoss of expression of the growth‐inhibitory imprinted genes ARHI and PEG3 through promoter methylation, LOH, and other mechanisms may stimulate clonogenic growth and contribute to the pathogenesis of a majority of ovarian cancers. Cancer 2008. © 2008 American Cancer Society.
Gemcitabine and vinorelbine in pemetrexed‐pretreated patients with malignant pleural mesothelioma
Authors: Zucali Paolo A. , Ceresoli Giovanni L. , Garassino Isabella , De Vincenzo Fabio , Cavina Raffaele , Campagnoli Elisabetta , Cappuzzo Federico , Salamina Silvia , Soto Parra Hector J. , Santoro Armando 
Published: February 2008

AbstractBACKGROUNDPemetrexed‐cisplatin chemotherapy is the standard of care in the first‐line treatment of unresectable malignant pleural mesothelioma (MPM). Second‐line cytotoxic therapy is considered for a growing group of patients, but the optimal treatment has not been defined to date. Gemcitabine and vinorelbine have shown activity in the first‐line setting. The objective of this study was to evaluate the activity and toxicity of the gemcitabine‐vinorelbine combination in pemetrexed‐pretreated patients with MPM.METHODSFrom January 2004 to September 2006, 30 consecutive patients who were pretreated with pemetrexed with or without a platinum‐derivative were enrolled. Gemcitabine 1000 mg/m2 and vinorelbine 25 mg/m2 were administered intravenously on Days 1 and 8 every 3 weeks. Treatment was repeated for a maximum of 6 cycles or until progression or unacceptable toxicity.RESULTSA partial response was observed in 3 patients (10%; 95% confidence interval [CI], 2.1–26.5%), and 10 patients (33.3%; 95% CI, 17.3–52.8%) had stable disease after treatment. Overall, 13 patients (43.3%; 95% CI, 25.5–62.6%) achieved disease control. The median time to progression was 2.8 months (range, 0.6–12.1 months), and the median survival was 10.9 months (range, 0.8–25.3 months). Hematologic toxicity was acceptable, with grade 3 or 4 neutropenia occurring in 11% of patients and thrombocytopenia occurring in 4% of patients; no case of febrile neutropenia was observed. Nonhematologic toxicity generally was mild.CONCLUSIONSThe gemcitabine and vinorelbine combination was moderately active and had an acceptable toxicity profile in pemetrexed‐pretreated patients with MPM. The role of second‐line treatment in MPM needs to be evaluated in prospective trials in large series of patients who are stratified according to previous treatment and prognostic factors. Cancer 2008. © 2008 American Cancer Society.
Alkali Metal Complexes of the Dipeptides PheAla and AlaPhe: IRMPD Spectroscopy
Authors: Polfer Nick C. , Oomens Jos , Dunbar Robert C. 
Published: February 2008

AbstractComplexes of PheAla and AlaPhe with alkali metal ions Na+ and K+ are generated by electrospray ionization, isolated in the Fourier‐transform ion cyclotron resonance (FT–ICR) ion trapping mass spectrometer, and investigated by infrared multiple‐photon dissociation (IRMPD) using light from the FELIX free electron laser over the mid‐infrared range from 500 to 1900 cm−1. Insight into structural features of the complexes is gained by comparing the obtained spectra with predicted spectra and relative free energies obtained from DFT calculations for candidate conformers. Combining spectroscopic and energetic results establishes that the metal ion is always chelated by the amide carbonyl oxygen, whilst the C‐terminal hydroxyl does not complex the metal ion and is in the endo conformation. It is also likely that the aromatic ring of Phe always chelates the metal ion in a cation‐π binding configuration. Along with the amide CO and ring chelation sites, a third Lewis‐basic group almost certainly chelates the metal ion, giving a threefold chelation geometry. This third site may be either the C‐terminal carbonyl oxygen, or the N‐terminal amino nitrogen. From the spectroscopic and computational evidence, a slight preference is given to the carbonyl group, in an ROaOt chelation pattern, but coordination by the amino group is almost equally likely (particularly for K+PheAla) in an ROaNt chelation pattern, and either of these conformations, or a mixture of them, would be consistent with the present evidence. (R represents the π ring site, Oa the amide oxygen, Ot the terminal carbonyl oxygen, and Nt the terminal nitrogen.) The spectroscopic findings are in better agreement with the MPW1PW91 DFT functional calculations of the thermochemistry compared with the B3LYP functional, which seems to underestimate the importance of the cation–π interaction.
Photodissociation of Hydrated Hydrogen Iodide Clusters
Authors: Lee Han Myoung , Kolaski Maciej , Kim Kwang S. 
Published: February 2008

AbstractUsing high‐level ab initio calculations and excited state ab initio molecular dynamics simulations, we show that hydrated iodic acids release hydrogen radicals and/or hydrogen molecules as well as iodine radicals upon excitation. Its photoreaction process involving charge transfer to the solvent takes place in four steps: 1) hydration of the acid, 2) charge transfer to water upon excitation of hydrated acid, 3) detachment of the neutral iodine atom, and 4) detachment of the hydrogen radical. The iodine detachment process from excited hydrated hydro–iodic acids is exothermic and the detachment of hydrogen radicals from hydrated hydronium radicals is spontaneous if the initial kinetic energy of the cluster is high enough to get over the activation barrier of the detachment. The complete release of the radicals can be understood in terms of kinetics. This study shows how the hydrogen and halogen radicals are dissociated and released from their hydrated acids. Simple experiments corroborate our predicted mechanism for the release of hydrogen molecules from iodic acid in water by ultraviolet light.
Light Harvesting and Energy Transfer in Multiporphyrin‐Modified CdSe Nanoparticles
Authors: Kang Soonchul , Yasuda Masakazu , Miyasaka Hiroshi , Hayashi Hironobu , Kawasaki Mitsuo , Umeyama Tomokazu , Matano Yoshihiro , Yoshida Kaname , Isoda Seiji , Imahori Hiroshi 
Published: February 2008

AbstractMultiporphyrin‐modified CdSe nanoparticles (CdSe‐H2P) were prepared to elucidate the interaction between chromophores and luminescent semiconducting nanoparticles in the excited and ground states. The CdSe‐H2P nanoparticles were obtained by place‐exchange reactions of hexadecylamine‐thiophenol‐modified CdSe nanoparticles with porphyrin alkanethiols in toluene. The number of porphyrin molecules on the surface of a single CdSe nanoparticle increased with increasing reaction time to reach a saturated maximum of 21. The porphyrins as well as the core in CdSe‐H2P can absorb UV/Vis radiation. Steady‐state emission and emission‐lifetime measurements reveal efficient energy transfer from the CdSe excited state to the porphyrins in the CdSe‐H2P nanoparticles. The resulting porphyrin excited singlet state is not quenched by the CdSe core. These unique properties are in sharp contrast with those of multiporphyrin‐modified metal and silica nanoparticles. Thus, semiconducting nanoparticle–multiporphyrin composites are highly promising as novel artificial photosynthetic materials.
Early adolescents show enhanced acute cocaine‐induced locomotor activity in comparison to late adolescent and adult rats
Authors: Badanich Kimberly A. , Maldonado Antoniette M. , Kirstein Cheryl L. 
Published: February 2008

AbstractInitiation of drug use during adolescence is associated with an increased probability to develop a drug addiction. The present study examined dose–response effects of cocaine (0, 5, 10, or 20 mg/kg, i.p.) on locomotor activity in early adolescent (postnatal day (PND) 35), late adolescent (PND 45), and young adults (PND 60) by measuring total distance moved (TDM) and frequency of start–stops. In response to 20 mg/kg cocaine, early adolescents showed the greatest cocaine‐induced increase in TDM in comparison to late adolescent and adult rats. At this same dose, early adolescents showed the greatest cocaine‐induced attenuation of start–stops relative to older rats. Results suggest that early adolescents engage in more cocaine‐induced locomotor activity and less stationary behavior indicating that early adolescents are more sensitive to locomotor activating effects of high dose cocaine than older rats. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 127–133, 2008.
Therapeutic effects of complex rearing or bFGF after perinatal frontal lesions
Authors: Comeau Wendy , Gibb Robbin , Hastings Erica , Cioe Jan , Kolb Bryan 
Published: February 2008

AbstractWe investigated the effects of an enriched environment and/or basic fibroblast growth factor (bFGF) on recovery from neonatal frontal injury in rats. Rats received medial frontal lesions, or sham surgery, on postnatal day (P) 2/3. In the first set of experiments (Experiments 1 and 2), rats were housed in enriched environments that consisted of a large enclosure with multiple objects (or standard housing) for 90 days beginning at weaning (P22) or in adulthood (P110). In Experiment 3, the rats either received 7 days of subcutaneous bFGF beginning on the day after surgery or bFGF plus enriched housing beginning at weaning. After the 90‐day housing period, the animals were tested on a spatial navigation task and a skilled reaching task. Early lesions of the medial frontal cortex caused severe impairments in spatial learning but this deficit was markedly reduced with enriched housing, bFGF, or a combination of both, with the latter being most effective. The housing effects varied with age, however: the earlier the experience began, the better the outcome. Enriched housing increased dendritic length in cortical pyramidal neurons, an effect that was greater in the lesion than the control animals, and enriched housing reversed the lesion‐induced decrease in spine density. Enriched environment increased the thickness of the cortical mantle in both lesion and controls whereas bFGF had no effect. Experience thus can affect functional and anatomical outcome after early brain injury but the effects vary with age at experience and may be facilitated by treatment with bFGF. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 134–146, 2008.
Physiological responses to social and physical challenges in children: Quantifying mechanisms supporting social engagement and mobilization behaviors
Authors: Heilman Keri J. , Bal Elgiz , Bazhenova Olga V. , Sorokin Yevgeniya , Perlman Susan B. , Hanley Mary C. , Porges Stephen W. 
Published: February 2008

AbstractPhysiological response patterns to laboratory‐based social and physical challenges were investigated in 37 typically‐developing 3‐ to 5‐year‐old children. The study was conducted to determine whether the response profiles during each challenge were similar and whether individual differences in the response profiles to the challenges were correlated. Results demonstrated challenge specific physiological response strategies. In response to the social challenge, respiratory sinus arrhythmia and heart period increased and motor activity decreased. In contrast, in response to the physical challenge, respiratory sinus arrhythmia and heart period decreased and motor activity increased. Neither challenge reliably elicited changes in salivary cortisol. Only heart period responses were correlated between the challenges. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 171–182, 2008.
Understanding language and cognitive deficits in very low birth weight children
Authors: Ortiz‐Mantilla Silvia , Choudhury Naseem , Leevers Hilary , Benasich April A. 
Published: February 2008

AbstractVery‐low‐birth‐weight infants are at much higher risk for cognitive and language delays but the nature of such deficits is not clearly understood. Given increasing rates of prematurity and infants born very‐low‐birth‐weight, examination of mechanisms that underlie poorer developmental outcome is essential. We investigated language and cognitive abilities in very‐low and normal birth‐weight infants to determine whether performance differences were due to poorer global cognitive performance or to deficits in specific processing abilities. Thirty‐two very‐low and 32 normal birth‐weight infants received visual and auditory‐visual habituation recognition‐memory tasks, and standardized language and cognitive assessments. Very‐low‐birth‐weight infants performed more poorly on visual and auditory‐visual habituation tasks and scored lower than controls on cognitive and language measures. These findings suggest that differences in language abilities in very‐low‐birth‐weight children may be part of a global deficit that impacts many areas of cognitive functioning rather than a specific impairment in rapid auditory processing. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 107–126, 2008.
Adrenocortical and behavioral attunement in parents with 1‐year‐old infants
Authors: van Bakel Hedwig J. A. , Riksen‐Walraven J. Marianne 
Published: February 2008

AbstractSethre‐Hofstad et al. [2002, Psychoneuroendocrinology 27:731–747] found that behaviorally well‐attuned or sensitive parents showed better physiological attunement with their 2‐ to 4‐year‐old toddlers' adrenocortical responses to a potentially challenging task than less sensitive parents. In the present study we aimed to replicate this finding in a sample of 83 parents with 15‐month‐old infants. Parental and infant cortisol responses were assessed using saliva samples collected before and 21 min after the child's confrontation with a stranger and a moving robot. Infant behaviors reflecting distress/uncertainty during the stranger‐robot session were rated from videotape. Parental sensitivity was observed during a parent–infant teaching episode. Our findings replicate those of Sethre‐Hofstad et al. [2002, Psychoneuroendocrinology 27:731–747] by showing correlated parent–infant cortisol responses for sensitive parents but not for less sensitive parents. Furthermore, sensitive parents cortisol responses were associated with their children's distress/uncertainty during the stranger‐robot episode, whereas this was not true for less sensitive parents. Results indicate an important connection between behavior and physiology in parent–infant interactions that deserve more research. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 196–201, 2008.
Preobesity in the infant OLETF rat: The role of suckling
Authors: Schroeder Mariana , Lavi‐Avnon Yael , Zagoory‐Sharon Orna , Moran Timothy H. , Weller Aron 
Published: February 2008

AbstractThe Otsuka Long Evans Tokushima Fatty (OLETF) rat model of obesity, which lacks CCK1 receptors, has been extensively investigated over the last decade. We have recently focused on the early developmental stages of this strain, finding that OLETF pups are heavier than controls from birth and hyperphagic already from postnatal (PN) Day 2. OLETF mothers present differential maternal behavior patterns and increased nursing time and frequency, which might contribute to the preobese characteristics of the pups. The present investigation examined the pups' ability to gain weight from the nursing episodes. First, we measured the pups' weight gain from one nursing bout from their own dam. Next we examined the pups' weight gain after a feeding competition test with control pups from foster dams of both strains. OLETF pups gained more weight than controls from their own dams on PN Week 1 due to a higher suckling rate (and/or efficacy) and on PN Week 3 due to increased nursing time. When competing with control pups, OLETF pups gained significantly more weight after the same nursing bout, regardless of the strain of the mother. Body mass index (BMI) was significantly higher in OLETF pups compared to controls. The maternal parameters assessed from the experiment were latencies to pup retrieval and to nursing, and nursing duration; differences were only observed in nursing time. OLETF dams increased their average nursing time over the PN weeks, while control dams decreased their nursing time toward weaning. The results suggest an important contribution of OLETF pups toward their own preobese development. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 202–202, 2008.
IRAK‐4 kinase activity is required for IRAK‐4‐dependent innate and adaptive immune responses
Authors: Lye Elizabeth , Dhanji Salim , Calzascia Thomas , Elford Alisha R. , Ohashi Pamela S. 
Published: February 2008

AbstractInterleukin‐1 receptor‐associated kinase (IRAK)‐4 is a serine‐threonine kinase that plays an important role in innate and adaptive immune responses. While the requirement of IRAK‐4 kinase activity has been studied in the context of IL‐1R signaling, it is not clear whether IRAK‐4 requires its kinase function for all of its roles in the immune system. IRAK‐4 kinase‐dead knock‐in (IRAK‐4KD/KD) mice were generated to further elucidate whether IRAK‐4 kinase activity is required for IRAK‐4 to induce cytokine production. IRAK‐4KD/KD mice were impaired in their ability to produce cytokines in response to in vivo challenge with lipopolysaccharide (LPS), a potent TLR4 ligand. Cytokine production was also reduced in macrophages and dendritic cells from IRAK‐4KD/KD mice in response to LPS and other TLR ligands. In addition, adaptive immune responses were impaired in IRAK‐4KD/KD mice. Although in vitro T cell proliferation in response to TCR activation was unaffected in IRAK‐4‐deficient mice, in vivo T cell responses to lymphocytic choriomeningitits virus infection were significantly impaired in IRAK‐4‐knockout mice or mice expressing the kinase‐dead mutant of IRAK‐4. Collectively, these results indicate that IRAK‐4 kinase activity is required for IRAK‐4‐dependent signaling in innate and adaptive immunity.
Tripeptidyl peptidase II is dispensable for the generation of both proteasome‐dependent and proteasome‐independent ligands of HLA‐B27 and other class I molecules
Authors: Marcilla Miguel , Villasevil Eugenia M. , de Castro José Antonio López 
Published: February 2008

AbstractA significant fraction of the HLA‐B27‐bound peptide repertoire is resistant to proteasome inhibitors. The possible implication of tripeptidyl peptidase II (TPPII) in generating this subset was analyzed by quantifying the surface re‐expression of HLA‐B*2705 after acid stripping in the presence of two TPPII inhibitors, butabindide and Ala‐Ala‐Phe‐chloromethylketone. Neither decreased HLA‐B27 re‐expression under conditions in which TPPII activity was largely inhibited. This was in contrast to a significant effect of the proteasome inhibitor epoxomicin. The failure of TPPII inhibition to decrease surface re‐expression was not limited to HLA‐B27, since it was also observed in several HLA‐B27‐negative cell lines, including Mel JuSo. Actually, HLA class I re‐expression in Mel JuSo cells increased as a function of butabindide concentration, which is consistent with an involvement of TPPII in destroying HLA class I ligands. Inhibition of TPPII with small interfering RNA also failed to decrease the surface expression of HLA class I molecules on 143B cells. Our results indicate that TPPII is dispensable for the generation of proteasome‐dependent HLA class I ligands and, without excluding its role in producing some individual epitopes, this enzyme is not involved to any quantitatively significant extent, in generating the proteasome‐independent HLA‐B27‐bound peptide repertoire.See accompanying commentary: http://dx.doi.org/10.1002/eji.200838181