bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity Profile of Members of an Online Health Community After Articular Cartilage Repair of the Knee
Authors: Hambly Karen 
Published: March 2011

Background: Articular cartilage repair (ACR) procedures aim to alleviate pain and restore function for individuals with chondral defects. Rehabilitation is lengthy, and there are limited data on return to sports and exercise activities after ACR in non-elite-athlete populations. The Internet is a growing source of health-related information for patients, and it has resulted in the emergence of online health communities. Purpose: To establish a postoperative activity profile of users of an online health community who have undergone ACR of the knee and to compare this profile with those from the same community who have undergone initial anterior cruciate ligament reconstruction (ACLR). Study Design: Cross-sectional. Methods: Tegner Activity Scale ratings were collected via a self-reported online questionnaire from 201 participants of an online health community who had undergone tibiofemoral and/or patellofemoral ACR (n = 75) or ACLR (n = 126). Results: A higher Tegner activity level was significantly correlated to time from surgery for ACR (P < 0.005) and ACLR (P < 0.01). At a minimum of 24 months’ follow-up, the ACR group had a median postoperative Tegner score of 3, compared with 6 for the ACLR group. Tegner score was significantly negatively correlated with age at time of surgery for ACLR (P < 0.05) but not for ACR. Men demonstrated significantly higher Tegner activity levels than did women for both ACLR and ACR (P < 0.05). Conclusions: Activity levels after ACR in this population increased with postoperative time but remained lower than expected when compared with current published clinical and normative data. Clinical Relevance: Engagement with an online health community may influence expectations regarding return to sports and exercise activities. Reporting of activity-level data within clinical studies should be differentiated on the basis of sex. Further research is needed to elucidate factors that determine return to sports and exercise activities after ACR.
Heme regulates B-cell differentiation, antibody class switch, and heme oxygenase-1 expression in B cells as a ligand of Bach2
Authors: Watanabe-Matsui Miki , Muto Akihiko , Matsui Toshitaka , Itoh-Nakadai Ari , Nakajima Osamu , Murayama Kazutaka , Yamamoto Masayuki , Ikeda-Saito Masao , Igarashi Kazuhiko 
Published: March 2011

AbstractHeme binds to proteins to modulate their function, thereby functioning as a signaling molecule in a variety of biologic events. We found that heme bound to Bach2, a transcription factor essential for humoral immunity, including antibody class switch. Heme inhibited the DNA binding activity of Bach2 in vitro and reduced its half-life in B cells. When added to B-cell primary cultures, heme enhanced the transcription of Blimp-1, the master regulator of plasma cells, and skewed plasma cell differentiation toward the IgM isotype, decreasing the IgG levels in vitro. Intraperitoneal injection of heme in mice inhibited the production of antigen-specific IgM when heme was administered simultaneously with the antigen but not when it was administered after antigen exposure, suggesting that heme also modulates the early phase of B-cell responses to antigen. Heme oxygenase-1, which is known to be regulated by heme, was repressed by both Bach2 and Bach1 in B cells. Furthermore, the expression of genes for heme uptake changed in response to B-cell activation and heme administration. Our results reveal a new function for heme as a ligand of Bach2 and as a modulatory signal involved in plasma cell differentiation.
Epitope characterization and crystal structure of GA101 provide insights into the molecular basis for type I/II distinction of CD20 antibodies
Authors: Niederfellner Gerhard , Lammens Alfred , Mundigl Olaf , Georges Guy J. , Schaefer Wolfgang , Schwaiger Manfred , Franke Andreas , Wiechmann Kornelius , Jenewein Stefan , Slootstra Jerry W. , Timmerman Peter , Brännström Annika , Lindstrom Frida , Mössner Ekkehard , Umana Pablo , Hopfner Karl-Peter , Klein Christian 
Published: March 2011

Abstract
CD20 is a cell-surface marker of normal and malignant B cells. Rituximab, a monoclonal antibody targeting CD20, has improved the treatment of malignant lymphomas. Therapeutic CD20 antibodies are classified as either type I or II based on different mechanisms of killing malignant B cells. To reveal the molecular basis of this distinction, we fine-mapped the epitopes recognized by both types. We also determined the first X-ray structure of a type II antibody by crystallizing the obinutuzumab (GA101) Fab fragment alone and in complex with a CD20 cyclopeptide. Despite recognizing an overlapping epitope, GA101 binds CD20 in a completely different orientation than type I antibodies. Moreover, the elbow angle of GA101 is almost 30° wider than in type I antibodies, potentially resulting in different spatial arrangements of 2 CD20 molecules bound to a single GA101 or rituximab molecule. Using protein tomography, different CD20 complexes were found to be associated with the 2 antibodies, and confocal microscopy showed different membrane compartmentalization of these subpopulations of the cellular CD20 pool. Our findings offer a possible molecular explanation for the different cellular responses elicited by type I and II antibodies.
Initiatives to shorten duration of untreated psychosis: systematic review
Authors: Lloyd-Evans Brynmor , Crosby Michelle , Stockton Sarah , Pilling Stephen , Hobbs Lorna , Hinton Mark , Johnson Sonia 
Published: March 2011

BackgroundLong duration of untreated psychosis (DUP) is common and associated with poor outcomes. Strategies to enhance early detection of first-episode psychosis have been advocated.AimsTo evaluate initiatives for early detection of psychosis.MethodSystematic review of available evidence on the effectiveness of early detection initiatives to reduce the DUP.ResultsThe review included 11 studies which evaluated 8 early detection initiatives. Evidence suggests that general practitioner education campaigns and dedicated early intervention services do not by themselves reduce DUP or generate more treated cases. Evidence for multifocus initiatives is mixed: intensive campaigns targeting the general public as well as relevant professionals may be needed. No studies evaluated initiatives targeting young people or professionals from non-health organisations.ConclusionsHow early detection can be achieved is not clear. Evidence is most promising for intensive public awareness campaigns: these require organisation and resourcing at a regional or national level. More good-quality studies are needed to address gaps in knowledge.
Childhood eating disorders: British national surveillance study
Authors: Nicholls Dasha E. , Lynn Richard , Viner Russell M. 
Published: March 2011

BackgroundThe incidence of eating disorders appears stable overall, but may be increasing in younger age groups. Data on incidence, clinical features and outcome of early-onset eating disorders are sparse.AimsTo identify new cases of early-onset eating disorders (<13 years) presenting to secondary care over 1 year and to describe clinical features, management and 1-year outcomes.MethodSurveillance over 14 months through the established British Paediatric Surveillance System, and a novel child and adolescent psychiatry surveillance system set up for this purpose.ResultsOverall incidence was 3.01/100 000 (208 individuals). In total, 37% met criteria for anorexia nervosa; 1.4% for bulimia nervosa; and 43% for eating disorder not otherwise specified. Nineteen per cent showed determined food avoidance and underweight without weight/shape concerns. Rates of comorbidity were 41%; family history of psychiatric disorder 44%; and early feeding difficulties 21%. Time to presentation was >8 months. A total of 50% were admitted to hospital, typically soon after diagnosis. Outcome data were available for 76% of individuals. At 1 year, 73% were reported improved, 6% worse and 10% unchanged (11% unknown). Most were still in treatment, and seven were hospital in-patients for most of the year.ConclusionsChildhood eating disorders represent a significant clinical burden to paediatric and mental health services. Efforts to improve early detection are needed. These data provide a baseline to monitor changing trends in incidence.
The Madrid Declaration: why we need a coordinated Europe-wide effort in mental health research
Authors: Ayuso-Mateos José L. , Wykes Til , Arango Celso 
Published: March 2011

SummaryThe Madrid Declaration is being promoted by representatives from seven nationally funded mental health research networks, along with leaders of ongoing European Union-funded mental health projects. It advocates the creation of a Network of Excellent Networks, based on a dynamic and adaptive cross-European network of distinctly qualified research centres.
Phase III, Open-Label, Randomized Study Comparing Concurrent Gemcitabine Plus Cisplatin and Radiation Followed by Adjuvant Gemcitabine and Cisplatin Versus Concurrent Cisplatin and Radiation in Patients With Stage IIB to IVA Carcinoma of the Cervix
Authors: Dueñas-González Alfonso , Zarbá Juan J. , Patel Firuza , Alcedo Juan C. , Beslija Semir , Casanova Luis , Pattaranutaporn Pittayapoom , Hameed Shahid , Blair Julie M. , Barraclough Helen , Orlando Mauro 
Published: March 2011

Purpose To determine whether addition of gemcitabine to concurrent cisplatin chemoradiotherapy and as adjuvant chemotherapy with cisplatin improves progression-free survival (PFS) at 3 years compared with current standard of care in locally advanced cervical cancer. Patients and Methods Eligible chemotherapy- and radiotherapy-naive patients with stage IIB to IVA disease and Karnofsky performance score ≥ 70 were randomly assigned to arm A (cisplatin 40 mg/m2 and gemcitabine 125 mg/m2 weekly for 6 weeks with concurrent external-beam radiotherapy [XRT] 50.4 Gy in 28 fractions, followed by brachytherapy [BCT] 30 to 35 Gy in 96 hours, and then two adjuvant 21-day cycles of cisplatin, 50 mg/m2 on day 1, plus gemcitabine, 1,000 mg/m2 on days 1 and 8) or to arm B (cisplatin and concurrent XRT followed by BCT only; dosing same as for arm A). Results Between May 2002 and March 2004, 515 patients were enrolled (arm A, n = 259; arm B, n = 256). PFS at 3 years was significantly improved in arm A versus arm B (74.4% v 65.0%, respectively; P = .029), as were overall PFS (log-rank P = .0227; hazard ratio [HR], 0.68; 95% CI, 0.49 to 0.95), overall survival (log-rank P = .0224; HR, 0.68; 95% CI, 0.49 to 0.95), and time to progressive disease (log-rank P = .0012; HR, 0.54; 95% CI, 0.37 to 0.79). Grade 3 and 4 toxicities were more frequent in arm A than in arm B (86.5% v 46.3%, respectively; P < .001), including two deaths possibly related to treatment toxicity in arm A. Conclusion Gemcitabine plus cisplatin chemoradiotherapy followed by BCT and adjuvant gemcitabine/cisplatin chemotherapy improved survival outcomes with increased but clinically manageable toxicity when compared with standard treatment.
Prospective Study of Breast Cancer Incidence in Women With a BRCA1 or BRCA2 Mutation Under Surveillance With and Without Magnetic Resonance Imaging
Authors: Warner Ellen , Hill Kimberley , Causer Petrina , Plewes Donald , Jong Roberta , Yaffe Martin , Foulkes William D. , Ghadirian Parviz , Lynch Henry , Couch Fergus , Wong John , Wright Frances , Sun Ping , Narod Steven A. 
Published: March 2011

Purpose The sensitivity of magnetic resonance imaging (MRI) for breast cancer screening exceeds that of mammography. If MRI screening reduces mortality in women with a BRCA1 or BRCA2 mutation, it is expected that the incidence of advanced-stage breast cancers should be reduced in women undergoing MRI screening compared with those undergoing conventional screening. Patients and Methods We followed 1,275 women with a BRCA1 or BRCA2 mutation for a mean of 3.2 years. In total, 445 women were enrolled in an MRI screening trial in Toronto, Ontario, Canada, and 830 were in the comparison group. The cumulative incidences of ductal carcinoma in situ (DCIS), early-stage, and late-stage breast cancers were estimated at 6 years in the cohorts. Results There were 41 cases of breast cancer in the MRI-screened cohort (9.2%) and 76 cases in the comparison group (9.2%). The cumulative incidence of DCIS or stage I breast cancer at 6 years was 13.8% (95% CI, 9.1% to 18.5%) in the MRI-screened cohort and 7.2% (95% CI, 4.5% to 9.9%) in the comparison group (P = .01). The cumulative incidence of stages II to IV breast cancers was 1.9% (95% CI, 0.2% to 3.7%) in the MRI-screened cohort and 6.6% (95% CI, 3.8% to 9.3%) in the comparison group (P = .02). The adjusted hazard ratio for the development of stages II to IV breast cancer associated with MRI screening was 0.30 (95% CI, 0.12 to 0.72; P = .008). Conclusion Annual surveillance with MRI is associated with a significant reduction in the incidence of advanced-stage breast cancer in BRCA1 and BRCA2 carriers.
Phase I Trials of Molecularly Targeted Agents: Should We Pay More Attention to Late Toxicities?
Authors: Postel-Vinay Sophie , Gomez-Roca Carlos , Molife L. Rhoda , Anghan Bhavesh , Levy Antonin , Judson Ian , De Bono Johann , Soria Jean-Charles , Kaye Stan , Paoletti Xavier 
Published: March 2011

Purpose Phase I trials traditionally aim at determining the recommended phase II dose (RP2D) using grade ≥ 3 toxicity data from cycle 1 (C1) only. This design dates from the era of conventional chemotherapy and may not be relevant for new molecularly targeted agents (MTAs) usually administered in a chronic fashion and for which late or moderate toxicities may deserve particular attention. Patients and Methods All consecutive patients treated in phase I trials of MTAs at the Royal Marsden Hospital and Institut Gustave Roussy between January 2005 and July 2008 were included. Gastrointestinal, skin, and clinical renal toxicities of any grade and grades 3 to 4 toxic events of any type occurring at any cycle on treatment were recorded. Doses administered, treatment interruptions, dose modifications, and prescription of comedications were analyzed. Results A total of 445 patients (1,566 cycles; median treatment duration, 55 days) were included in 36 eligible trials; 790 toxicities (590, grade 1; 176, grade, 2; 24 grades, 3 to 4) and 1,819 toxicities (1,521, grade 1; 265, grade 2; 33, grades 3 to 4) were recorded during and after C1, respectively; 57% of the grades 3 to 4 toxicities occurred after C1; 50% of patients presented their worst-grade toxicity after C1. The risk of grades 3 to 4 toxicity was 3% in cycles 1 to 6 and was almost null afterwards. No cumulative toxicities were observed. Median toxicity duration was 15 days, with comedication administered in 68% of events. Conclusion Moderate and severe toxicities occur regularly after the first cycle in phase I trials of MTAs and may deserve increased attention in the RP2D process for these agents.
Bilateral Negative Sentinel Nodes Accurately Predict Absence of Lymph Node Metastasis in Early Cervical Cancer: Results of the SENTICOL Study
Authors: Lécuru Fabrice , Mathevet Patrice , Querleu Denis , Leblanc Eric , Morice Philipe , Daraï Emile , Marret Henri , Magaud Laurent , Gillaizeau Florence , Chatellier Gilles , Dargent Daniel 
Published: March 2011

Purpose Sentinel lymph node (SLN) biopsy may be used to target lymph node metastases in patients with early cervical cancer. Whether SLN biopsy only is acceptable in the staging and surgical management of early cervical cancer remains unknown. This prospective multicenter study (SENTICOL [Ganglion Sentinelle dans le Cancer du Col]) assessed the sensitivity and negative predictive value (NPV) of SLN biopsy. Patients and Methods Adults with cervical carcinoma who met the International Federation of Gynecology and Obstetrics criteria for stage IA1 with lymphovascular space invasion to stage IB1 underwent technetium 99 lymphoscintigraphy and Patent Blue injection followed by laparoscopic lymph node mapping, SLN removal, and lymph node dissection. Only surgeons trained in SLN biopsy in cervical carcinoma participated in the study. SLNs and nonsentinel lymph nodes underwent routine staining. Negative SLNs were subjected to ultrastaging. The reference method was pelvic and/or para-aortic lymphadenectomy with histologic examination of all nodes. Results One hundred forty-five patients were enrolled, and 139 were included in a modified intention-to-diagnose analysis. Intraoperative radioisotope-blue dye mapping detected at least one SLN in 136 patients (97.8%; 95% CI, 93.8% to 99.6%), 23 of whom had true-positive results and two who had false-negative results, yielding 92.0% sensitivity (23 of 25; 95% CI, 74.0% to 99.0%) and 98.2% NPV (111 of 113; 95% CI, 74.0% to 99.0%) for node metastasis detection. No false-negative results were observed in the 104 patients (76.5%) in whom SLN were identified bilaterally. Conclusion Combined labeling for node mapping was associated with high rates of SLN detection and with high sensitivity and NPV for metastasis detection. However, SLN biopsy was fully reliable only when SLNs were detected bilaterally.
Shortening Infusion Time for High-Dose Methotrexate Alters Antileukemic Effects: A Randomized Prospective Clinical Trial
Authors: Mikkelsen Torben S. , Sparreboom Alex , Cheng Cheng , Zhou Yinmei , Boyett James M. , Raimondi Susana C. , Panetta John C. , Bowman W. Paul , Sandlund John T. , Pui Ching-Hon , Relling Mary V. , Evans William E. 
Published: March 2011

PurposeTo determine whether shortening the infusion duration of high-dose methotrexate (HDMTX; 1 g/m2) affects the in vivo accumulation of active methotrexate polyglutamates (MTXPG1-7) in leukemia cells and whether this differs among major acute lymphoblastic leukemia (ALL) subtypes.MethodsFrom June 2000 through October 2007, 356 children with ALL were randomly assigned to receive initial single-agent treatment with HDMTX (1 g/m2) as either a 24-hour infusion or a 4-hour infusion at two pediatric hospitals in the United States. The primary outcome measures were the accumulation of MTXPG1-7in leukemia cells and the antileukemic effects (eg, inhibition of de novo purine synthesis in bone marrow ALL cells, and decrease in circulating ALL cells).ResultsThe 24-hour infusion resulted in significantly higher amounts of MTXPG1-7in bone marrow leukemia cells (median: 1,695 v 1,150 pmol/109cells, P = .0059), and better antileukemic effects. The 24-hour infusion had the greatest effect on MTXPG1-7accumulation in hyperdiploid ALL (median: 3,919 v 2,417 pmol/109cells, P = .0038); T-cell ALL exhibited smaller differences in MTXPG1-7but greater antileukemic effects with the longer infusion (median decrease in leukemia cells: 88.4% v 51.8%, P = .0075). In contrast, infusion duration had no significant impact on MTXPG1-7accumulation or antileukemic effects in ALL with the t(12;21)/(ETV6-RUNX1) chromosomal translocation.ConclusionShortening the infusion time of HDMTX reduces accumulation of active methotrexate in leukemia cells and decreases antileukemic effects, with differing consequences among major ALL subtypes.
Conventional-Dose Versus High-Dose Chemotherapy As First Salvage Treatment in Male Patients With Metastatic Germ Cell Tumors: Evidence From a Large International Database
Authors: Lorch Anja , Bascoul-Mollevi Caroline , Kramar Andrew , Einhorn Lawrence , Necchi Andrea , Massard Christophe , De Giorgi Ugo , Fléchon Aude , Margolin Kim , Lotz Jean-Pierre , Germà-Lluch Jose Ramon , Powles Thomas , Kollmannsberger Christian , Beyer Jörg 
Published: March 2011

Purpose Conventional-dose chemotherapy (CDCT) and high-dose chemotherapy (HDCT) may both be successfully used as salvage treatment for patients with metastatic germ cell tumors (GCTs) who experience progression with first-line treatment. Patients and Methods Data on 1,984 patients with GCTs who experienced progression after at least three cisplatin-based cycles and were treated with either cisplatin-based CDCT or carboplatin-based HDCT chemotherapy were collected from 38 centers or groups worldwide. Of 1,984 patients, 1,594 (80%) were eligible, and among the eligible patients, 1,435 (90%) could reliably be classified into one of the following five prognostic categories based on prior prognostic classification: very low (n = 76), low (n = 257), intermediate (n = 646), high (n = 351), and very high risk (n = 105). Within each of the five categories, the progression-free survival (PFS) and overall survival (OS) after CDCT and HDCT were compared using the Cox model adjusted for significant distributional differences between important variables. Results Overall, 773 patients received CDCT, and 821 patients received HDCT. Both treatment modalities were used with similar frequencies within each prognostic category. The hazard ratio for PFS was 0.44 (95% CI, 0.39 to 0.51) stratified on prognostic category, and the hazard ratio for OS was 0.65 (95% CI, 0.56 to 0.75), favoring HDCT. These results were consistent within each prognostic category except among low-risk patients, for whom similar OS was observed between the two treatment groups. Conclusion This retrospective analysis suggests a benefit from HDCT given as intensification of first salvage treatment in male patients with GCTs and emphasizes the need for another prospective randomized trial comparing CDCT to HDCT in this patient population.
Chemical speciation of environmentally significant metals with inorganic ligands. Part 4: The Cd2+ + OH–, Cl–, CO32–, SO42–, and PO43– systems (IUPAC Technical Report)
Authors: Powell Kipton J. , Brown Paul L. , Byrne Robert H. , Gajda Tamás , Hefter Glenn , Leuz Ann-Kathrin , Sjöberg Staffan , Wanner Hans 
Published: March 2011

The numerical modeling of CdIIspeciation amongst the environmental inorganic ligands Cl–, OH–, CO32–, SO42–, and PO43–requires reliable values for the relevant stability (formation) constants. This paper compiles and provides a critical review of these constants and related thermodynamic data. It recommends values of log10βp,q,r° valid atIm= 0 mol kg–1and 25 °C (298.15 K), along with the equations and empirical reaction ion interaction coefficients, ∆&epsilon;, required to calculate log10βp,q,rvalues at higher ionic strengths using the Brønsted–Guggenheim–Scatchard specific ion interaction theory (SIT). Values for the corresponding reaction enthalpies, ∆rH, are reported where available. Unfortunately, with the exception of the CdII-chlorido system and (at low ionic strengths) the CdII-sulfato system, the equilibrium reactions for the title systems are relatively poorly characterized. In weakly acidic fresh water systems (–log10{[H+]/c°} &lt; 6), in the absence of organic ligands (e.g., humic substances), CdIIspeciation is dominated by Cd2+(aq), with CdSO4(aq) as a minor species. In this respect, CdIIis similar to CuII[2007PBa] and PbII[2009PBa]. However, in weakly alkaline fresh water solutions, 7.5 &lt; –log10{[H+]/c°} &lt; 8.6, the speciation of CdIIis still dominated by Cd2+(aq), whereas for CuII[2007PBa] and PbII[2009PBa] the carbonato- species MCO3(aq) dominates. In weakly acidic saline systems (–log10{[H+]/cϒ} &lt; 6; –log10{[Cl–]/c°} &lt; 2.0) the speciation is dominated by CdCln(2–n)+complexes, (n= 1–3), with Cd2+(aq) as a minor species. This is qualitatively similar to the situation for CuIIand PbII. However, in weakly alkaline saline solutions, including seawater, the chlorido- complexes still dominate the speciation of CdIIbecause of the relatively low stability of CdCO3(aq). In contrast, the speciation of CuII[2007PBa] and PbII[2009PBa] in seawater is dominated by the respective species MCO3(aq). There is scope for additional high-quality measurements in the Cd2++ H++ CO32–system as the large uncertainties in the stability constants for the Cd2+-carbonato complexes significantly affect the speciation calculations.