bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone marrow lesions from osteoarthritis knees are characterized by sclerotic bone that is less well mineralized
Authors: Hunter David J , Gerstenfeld Lou , Bishop Gavin , Davis A David , Mason Zach D , Einhorn Tom A , Maciewicz Rose A , Newham Pete , Foster Martyn , Jackson Sonya , Morgan Elise F 
Published: January 2009

Abstract
Introduction
Although the presence of bone marrow lesions (BMLs) on magnetic resonance images is strongly associated with osteoarthritis progression and pain, the underlying pathology is not well established. The aim of the present study was to evaluate the architecture of subchondral bone in regions with and without BMLs from the same individual using bone histomorphometry.

Methods
Postmenopausal female subjects (n = 6, age 48 to 90 years) with predominantly medial compartment osteoarthritis and on a waiting list for total knee replacement were recruited. To identify the location of the BMLs, subjects had a magnetic resonance imaging scan performed on their study knee prior to total knee replacement using a GE 1.5 T scanner with a dedicated extremity coil. An axial map of the tibial plateau was made, delineating the precise location of the BML. After surgical removal of the tibial plateau, the BML was localized using the axial map from the magnetic resonance image and the lesion excised along with a comparably sized bone specimen adjacent to the BML and from the contralateral compartment without a BML. Cores were imaged via microcomputed tomography, and the bone volume fraction and tissue mineral density were calculated for each core. In addition, the thickness of the subchondral plate was measured, and the following quantitative metrics of trabecular structure were calculated for the subchondral trabecular bone in each core: trabecular number, thickness, and spacing, structure model index, connectivity density, and degree of anisotropy. We computed the mean and standard deviation for each parameter, and the unaffected bone from the medial tibial plateau and the bone from the lateral tibial plateau were compared with the affected BML region in the medial tibial plateau.

Results
Cores from the lesion area displayed increased bone volume fraction but reduced tissue mineral density. The samples from the subchondral trabecular lesion area exhibited increased trabecular thickness and were also markedly more plate-like than the bone in the other three locations, as evidenced by the lower value of the structural model index. Other differences in structure that were noted were increased trabecular spacing and a trend towards decreased trabecular number in the cores from the medial location as compared with the contralateral location.

Conclusions
Our preliminary data localize specific changes in bone mineralization, remodeling and defects within BMLs features that are adjacent to the subchondral plate. These BMLs appear to be sclerotic compared with unaffected regions from the same individual based on the increased bone volume fraction and increased trabecular thickness. The mineral density in these lesions, however, is reduced and may render this area to be mechanically compromised, and thus susceptible to attrition.
Profiling RE1/REST-mediated histone modifications in the human genome
Authors: Zheng Deyou , Zhao Keji , Mehler Mark F 
Published: January 2009

Abstract
Background
The transcriptional repressor REST (RE1 silencing transcription factor, also called NRSF for neuron-restrictive silencing factor) binds to a conserved RE1 motif and represses many neuronal genes in non-neuronal cells. This transcriptional regulation is transacted by several nucleosome-modifying enzymes recruited by REST to RE1 sites, including histone deacetylases (for example, HDAC1/2), demethylases (for example, LSD1), and methyltransferases (for example, G9a).

Results
We have investigated a panel of 38 histone modifications by ChIP-Seq analysis for REST-mediated changes. Our study reveals a systematic decline of histone acetylations modulated by the association of RE1 with REST (RE1/REST). By contrast, alteration of histone methylations is more heterogeneous, with some methylations increased (for example, H3K27me3, and H3K9me2/3) and others decreased (for example, H3K4me, and H3K9me1). Furthermore, the observation of such trends of histone modifications in upregulated genes demonstrates convincingly that these changes are not determined by gene expression but are RE1/REST dependent. The outcomes of REST binding to canonical and non-canonical RE1 sites were nearly identical. Our analyses have also provided the first direct evidence that REST induces context-specific nucleosome repositioning, and furthermore demonstrate that REST-mediated histone modifications correlate with the affinity of RE1 motifs and the abundance of RE1-bound REST molecules.

Conclusions
Our findings indicate that the landscape of REST-mediated chromatin remodeling is dynamic and complex, with novel histone modifying enzymes and mechanisms yet to be elucidated. Our results should provide valuable insights for selecting the most informative histone marks for investigating the mechanisms and the consequences of REST modulated nucleosome remodeling in both neural and non-neural systems.
Association of headache with childhood adversity and mental disorder: cross-national study
Authors: Lee Sing , Tsang Adley , Von Korff Michael , de Graaf Ron , Benjet Corina , Haro Josep Maria , Angermeyer Matthias , Demyttenaere Koen , de Girolamo Giovanni , Gasquet Isabelle , Merikangas Kathleen , Posada-Villa José , Takeshima Tadashi , Kessler Ronald C. 
Published: January 2009

BackgroundCommunity studies about the association of headache with both childhood family adversities and depression/anxiety disorders are limited.AimsTo assess the independent and joint associations of childhood family adversities and early-onset depression and anxiety disorders with risks of adult-onset headache.MethodData were pooled from cross-sectional community surveys conducted in ten Latin and North American, European and Asian countries (n=18 303) by using standardised instruments. Headache and a range of childhood family adversities were assessed by self-report.ResultsThe number of childhood family adversities was associated with adult-onset headache after adjusting for gender, age, country and early-onset depression/anxiety disorder status (for one adversity, hazard ratio (HR)=1.22–1.6; for two adversities, HR=1.19–1.67; for three or more adversities, HR=1.37–1.95). Early and current onset of depression/anxiety disorders were independently associated (HR=1.42–1.89) with adult-onset headache after controlling for number of childhood family adversities.ConclusionsThe findings call for a broad developmental perspective concerning risk factors for development of headache.
Trends in the administration of electroconvulsive therapy in England
Authors: Bickerton David , Worrall Adrian , Chaplin Robert 
Published: January 2009

Aims and MethodWe measured the use of electroconvulsive therapy (ECT) over 3 months in England in 2006 and compared that with studies from 1999 and 2002. Questionnaires were completed by hospital ECT staff and returned by post with data collected prospectively on ECT use from National Health Service organisations.ResultsTwo-thirds (56 of 76) of the trusts providing ECT at 109 clinics responded. the number of clinics providing ECT and the number of patients receiving ECT has declined. There has been an increase in the proportion of people receiving ECT when detained under the Mental Health Act 1983.Clinical ImplicationsThe number of ECT clinics is likely to continue to decrease and psychiatrists may have decreasing experience of treating patients with ECT.
Poor Survival for Infants WithMYCN-Amplified Metastatic Neuroblastoma Despite Intensified Treatment: The International Society of Paediatric Oncology European Neuroblastoma Experience
Authors: Canete Adela , Gerrard Mary , Rubie Hervé , Castel Victoria , Di Cataldo Andrea , Munzer Caroline , Ladenstein Ruth , Brichard Bénédicte , Bermúdez José D. , Couturier Jerôme , de Bernardi Bruno , Pearson Andrew J. , Michon Jean 
Published: January 2009

PurposeTo report the results of a prospective, nonrandomized European study on infants with neuroblastoma and MYCN gene amplification.Patients and MethodsInfants with neuroblastoma (stage 2, 3, 4, and 4s) and MYCN gene amplification who were diagnosed between 1999 and 2004 were eligible for enrollment onto the study. After diagnosis, staging, and mandatory biologic studies, induction chemotherapy (IC) with conventional drugs was administered, followed by delayed surgery, megatherapy (busulfan-melphalan as a conditioning regimen), and local radiotherapy.ResultsOf the 46 infants enrolled onto the study, 35 infants were eligible; of these 35 infants, 97% had metastatic spread (24 infants had stage 4, and 10 infants had stage 4s). Two-year overall survival (OS) was 30% (SE, 0.08), with median survival time of 12 months, and 23 deaths due to disease. Two-year, event-free survival (EFS) was 29% (SE, 0.07). The treatment was well tolerated with no deaths as a result of toxicity or severe toxicity. Despite protocol adherence, 30% of the patients who were assessable for response to IC experienced disease progression or did not respond. Stage and high lactate dehydrogenase reached significance in the univariate analysis (P = .028 and .039, respectively for OS; and P = .05 and .031 respectively, for EFS). Ten of 16 patients who received megatherapy are still alive.ConclusionAlthough treatment was well tolerated, survival was poor and our IC failed to achieve a satisfactory response in 30% of our patients. New therapeutic approaches and more intense world-wide collaboration are needed to achieve a cure in this population.
Iodine-131—Metaiodobenzylguanidine Double Infusion With Autologous Stem-Cell Rescue for Neuroblastoma: A New Approaches to Neuroblastoma Therapy Phase I Study
Authors: Matthay Katherine K. , Quach Alekist , Huberty John , Franc Benjamin L. , Hawkins Randall A. , Jackson Hollie , Groshen Susan , Shusterman Suzanne , Yanik Gregory , Veatch Janet , Brophy Patricia , Villablanca Judith G. , Maris John M. 
Published: January 2009

Purpose Iodine-131—metaiodobenzylguanidine (131I-MIBG) provides targeted radiotherapy with more than 30% response rate in refractory neuroblastoma, but activity infused is limited by radiation safety and hematologic toxicity. The goal was to determine the maximum-tolerated dose of 131I-MIBG in two consecutive infusions at a 2-week interval, supported by autologous stem-cell rescue (ASCR) 2 weeks after the second dose. Patients and Methods The 131I-MIBG dose was escalated using a 3 + 3 phase I trial design, with levels calculated by cumulative red marrow radiation index (RMI) from both infusions. Using dosimetry, the second infusion was adjusted to achieve the target RMI, except at level 4, where the second infusion was capped at 21 mCi/kg. Results Twenty-one patients were enrolled onto the study at levels 1 to 4, with 18 patients assessable for toxicity and 20 patients assessable for response. Cumulative 131I-MIBG given to achieve the target RMI ranged from 22 to 50 mCi/kg, with cumulative RMI of 3.2 to 8.92 Gy. No patient had a dose-limiting toxicity. Reversible grade 3 nonhematologic toxicity occurred in six patients at level 4, establishing the recommended cumulative dose as 36 mCi/kg. The median time to absolute neutrophil count more than 500/μL after ASCR was 13 days (4 to 27 days) and to platelet independence was 17 days (6 to 47 days). Responses included two partial responses, eight mixed responses, three stable disease, and seven progressive disease. Responses by semiquantitative MIBG score occurred in eight patients, soft tissue responses occurred in five of 11 patients, but bone marrow responses occurred in only two of 13 patients. Conclusion The lack of toxicity with this approach allowed dramatic dose intensification of 131I-MIBG, with minimal toxicity and promising activity.
Phase I Study of Lapatinib in Combination With Chemoradiation in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck
Authors: Harrington Kevin J. , El-Hariry Iman A. , Holford Clare S. , Lusinchi Antoine , Nutting Christopher M. , Rosine Dominique , Tanay Mary , Deutsch Eric , Matthews Jennifer , D'Ambrosio Consuelo , Turner Simon J. , Pandeshwara Jagannatha S. , Bourhis Jean 
Published: January 2009

Purpose This study (EGF100262) sought to establish the recommended phase II dose of lapatinib with chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Patients and Methods Patients were enrolled onto cohorts of escalating lapatinib dose (500, 1,000, and 1,500 mg/d). Patients received 1 week of lapatinib alone followed by 6.5 to 7 weeks of the same dose of lapatinib plus radiotherapy 66 to 70 Gy and cisplatin 100 mg/m2 on days 1, 22, and 43 of radiotherapy. End points included safety/tolerability and clinical activity. Results Thirty-one patients were enrolled (seven patients in each of the 500- and 1,000-mg cohorts and three in the 1,500-mg cohort; an additional 14 patients were enrolled at 1,500 mg in a safety cohort). Dose-limiting toxicities (DLTs) included perforated ulcer in one patient in the 500-mg cohort and transient elevation of liver enzymes in one patient in the 1,000-mg cohort. No DLTs were observed in the 1,500-mg cohort. Therefore, the recommended phase II dose was defined as lapatinib 1,500 mg/d with chemoradiotherapy. The most common grade 3 to 4 adverse events were radiation mucositis, radiation dermatitis, lymphopenia, and neutropenia. No patients experienced drug-related symptomatic cardiotoxicity, and no interstitial pneumonitis was reported. The overall response rate was 81% (65% at the recommended phase II dose). Conclusion The recommended phase II dose is lapatinib 1,500 mg/d with chemoradiotherapy in patients with LA SCCHN; this regimen is associated with an acceptable tolerability profile. Given these findings, randomized phase II and III studies of lapatinib plus chemoradiotherapy have been initiated.
Phase I Trial of Oral Irinotecan and Temozolomide for Children With Relapsed High-Risk Neuroblastoma: A New Approach to Neuroblastoma Therapy Consortium Study
Authors: Wagner Lars M. , Villablanca Judith G. , Stewart Clinton F. , Crews Kristine R. , Groshen Susan , Reynolds C. Patrick , Park Julie R. , Maris John M. , Hawkins Randall A. , Daldrup-Link Heike E. , Jackson Hollie A. , Matthay Katherine K. 
Published: January 2009

Purpose Irinotecan and temozolomide have single-agent activity and schedule-dependent synergy against neuroblastoma. Because protracted administration of intravenous irinotecan is costly and inconvenient, we sought to determine the maximum-tolerated dose (MTD) of oral irinotecan combined with temozolomide in children with recurrent/resistant high-risk neuroblastoma. Patients and Methods Patients received oral temozolomide on days 1 through 5 combined with oral irinotecan on days 1 through 5 and 8 through 12 in 3-week courses. Daily oral cefixime was used to reduce irinotecan-associated diarrhea. Results Fourteen assessable patients received 75 courses. Because neutropenia and thrombocytopenia were initially dose-limiting, temozolomide was reduced from 100 to 75 mg/m2/d for subsequent patients. Irinotecan was then escalated from 30 to 60 mg/m2/d. First-course grade 3 diarrhea was dose-limiting in one of six patients treated at the irinotecan MTD of 60 mg/m2/d. Other toxicities were mild and reversible. The median SN-38 lactone area under the plasma concentration versus time curve at this dose was 72 ng · hr/mL. One patient with bulky soft tissue disease had a complete response through six courses. Six additional patients received a median of seven courses (range, three to 22 courses) before progression. Conclusion This all-oral regimen was feasible and well tolerated in heavily pretreated children with resistant neuroblastoma, and seven (50%) of 14 assessable patients had response or disease stabilization for three or more courses in this phase I trial. SN-38 lactone exposures were similar to those reported with protracted intravenous irinotecan. The dosages recommended for further study in this patient population are temozolomide 75 mg/m2/d plus irinotecan 60 mg/m2/d when given with cefixime.
Safety of Ovarian Preservation in Premenopausal Women With Endometrial Cancer
Authors: Wright Jason D. , Buck Adam M. , Shah Monjri , Burke William M. , Schiff Peter B. , Herzog Thomas J. 
Published: January 2009

Purpose Oophorectomy is commonly performed in premenopausal women with endometrial cancer who undergo hysterectomy. The benefits of oophorectomy in this setting are unknown, and the procedure subjects women to the long-term sequelae of estrogen deprivation. We examined the safety of ovarian preservation in young women with endometrial cancer who underwent hysterectomy. Patients and Methods Women ≤ 45 years of age with stage I endometrial cancer recorded from 1988 to 2004 in the Surveillance, Epidemiology, and End Results Database were examined. We developed Cox proportional hazards models and Kaplan-Meier curves to compare women who underwent oophorectomy with those who had ovarian preservation. Results A total of 3,269 women, including 402 patients (12%) who had ovarian preservation, were identified. Younger age (P < .0001), later year of diagnosis (P = .04), residence in the eastern United States (P = .02), and low tumor grade (P < .0001) were associated with ovarian preservation. In a multivariate Cox model, ovarian preservation had no effect on either cancer-specific (hazard ratio [HR] = 0.58; 95% CI, 0.14 to 2.44) or overall (HR = 0.68; 95% CI, 0.34 to 1.35) survival. The findings were unchanged when women who received pelvic radiotherapy were excluded. Conclusion Ovarian preservation in premenopausal women with early-stage endometrial cancer may be safe and not associated with an increase in cancer-related mortality.
Androgen-Induced Progression of Arterial Calcification in Apolipoprotein E-Null Mice Is Uncoupled from Plaque Growth and Lipid Levels
Authors: McRobb L. , Handelsman D. J. , Heather A. K. 
Published: January 2009

Arterial calcification has prognostic significance for cardiovascular outcomes, but its pathogenesis remains unclear. Calcification increases with age, but its prevalence in men suggests hormonal influence. In this study we analyzed the effect of exogenous androgens on calcification of advanced atherosclerotic lesions in the arterial tree of gonadally intact 34-wk-old male and female apolipoprotein E-null mice. Testosterone (T) increased calcification 3- to 4-fold (P &lt; 0.05) in lesions of the innominate artery and aortic sinus. A nonaromatizable androgen, dihydrotestosterone, also increased lesion calcification in the innominate artery (2.4-fold, P &lt; 0.05) but not the aortic sinus. The androgen-induced effects were independent of sex and occurred despite corresponding reductions in plaque area, the latter correlating inversely with increased serum high-density lipoprotein cholesterol levels. Androgen-induced calcification in the innominate artery was observed with up-regulation of local androgen receptor (AR) expression in response to T and dihydrotestosterone for both males and females but neither androgen influenced innominate artery estrogen receptor (ER)-α or -β expression in either sex. Conversely, T-induced calcification in the aortic sinus was associated with down-regulation of ERα but not ERβ expression in both sexes, whereas androgen-induced AR expression was increased in female but decreased in male mice. This study demonstrates for the first time that calcification of advanced atherosclerotic lesions is an androgen-sensitive process and postulates potential roles for both AR- and ER-mediated pathways in androgen-induced vascular calcification. We demonstrate a novel direct link between vascular calcification and the major male hormone, T, uncoupled from conventional relationships with plaque growth and lipid levels.
Calcification of advanced atherosclerotic lesions is an androgen-sensitive process whereby testosterone uncouples conventional relationships between plaque growth and lipid levels.
Interaction of visual and odour cues in the mushroom body of the hawkmothManduca sexta
Authors: Balkenius Anna , Bisch-Knaden Sonja , Hansson Bill 
Published: January 2009

SUMMARYThe responses to bimodal stimuli consisting of odour and colour were recorded using calcium-sensitive optical imaging in the mushroom bodies of the hawkmoth Manduca sexta. The results show that the activity in the mushroom bodies is influenced by both olfaction and vision. The interaction between the two modalities depends on the odour and the colour of the visual stimulus. A blue stimulus suppressed the response to a general flower scent(phenylacetaldehyde). By contrast, the response to a green leaf scent(1-octanol) was enhanced by the presence of the blue stimulus. A green colour had no influence on these odours but caused a marked increase in the response to an odour component (benzaldehyde) of the hawkmoth-pollinated Petunia axillaris.
Inconsistencies in children's recall of witnessed events: The role of age, question format and perceived reason for question repetition
Authors: Howie Pauline , Kurukulasuriya Nadezhda , Nash Laura , Marsh Annabel 
Published: January 2009

Purpose. Children's inconsistencies when answering repeated questions about past events are a source of concern in forensic, educational, and other contexts. Theoretical accounts of these inconsistencies have predominantly assumed that children shift because they infer adult dissatisfaction with their initial answer. This study aimed to test this account via examination of the effects of question format on shifting, as well as via direct questioning of children.Method. Four‐, five‐, and seven‐year‐olds (N = 226) were asked 17 recall questions about a recent classroom activity, with eight target questions repeated in one of four formats: no‐correct (mildly misleading questions to which the correct answer was ‘no’), yes‐correct (mildly misleading questions to which the correct answer was ‘yes’), specific open wh‐ questions, and forced‐choice questions. They were then asked about the adult's reasons for repetition. Accuracy, shifting, and interpretations of question repetition were examined.Results. Shifting from accuracy decreased with age, and was affected by question format in 4‐year‐olds only, who shifted more to no‐correct than to forced‐choice questions. Shifting towards accuracy was more common in forced‐choice questions than either no‐correct or open questions, but there were no significant age differences. First‐answer‐unsatisfactory interpretations of question repetition were rare, especially in the two younger groups. The oldest group offered a wider range of interpretations and also showed some evidence of an association between first‐answer‐unsatisfactory interpretations and shifting.Conclusions. Overall, our findings present a challenge to first‐answer‐unsatisfactory explanations of young children's shifting in recall settings, at least where overt pressure to shift is low. Forensic implications are considered.