bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity at the HLA-DRB1 allelic variation locus does not influence multiple sclerosis disease severity, brain atrophy or cognition
Authors: Van der Walt Anneke , Stankovich J , Bahlo M , Taylor BV , Van der Mei IAF , Foote SJ , Rubio JP , Kilpatrick TJ , Butzkueven H 
Published: December 2010

Background: HLA-DRB1*1501 (DR15) and other HLA class II alleles increase the risk of developing multiple sclerosis (MS). However, the contribution of genetic heterogeneity to the clinical course of MS remains controversial. We examined the influence of DR15 and other common DRB1 alleles (DRB1*01 (DR1), DRB1*03 (DR3) and DRB1*04 (DR4) on MS severity in a large, Australian, population-based cohort. Methods: We studied the association between common HLA-DRB1 alleles and genotypes and age of onset as well as three clinical disease severity descriptors: Multiple Sclerosis Severity Score, progression index), and the interval between the first and second attack in 978 patients with relapsing remitting MS and secondary progressive MS. We assessed cognition using the Symbol Digit Modalities Test in 811 patients and brain atrophy using the linear magnetic resonance imaging marker, the intercaudate ratio, in 745 patients. Results: Carrying DR15 significantly decreased the age of MS onset by 3.2 years in homozygotes and 1.3 years in heterozygotes. Carrying the HLA-DR15, -DR1, -DR3 or -DR4 alone or in combination did not affect clinical disease severity, cognition or cerebral atrophy. Conclusions: This study confirms that heterogeneity of HLA-DRB1 does not influence disease outcome in relapsing MS patients, with the exception of a younger age of onset in HLA-DR15 carriers.
Arthroscopic Posterior Cruciate Ligament Tibial Inlay Reconstruction
Authors: Salata Michael J. , Sekiya Jon K. 
Published: December 2010

Context: The reconstruction of isolated complete posterior cruciate ligament (PCL) injuries remains a controversial topic. Proponents for reconstruction cite the premature development of arthritis in the medial and patellofemoral compartments as a compelling reason to offer reconstruction. Currently, no consensus exists about which technique should be used to reconstruct the PCL. Type of Study: Surgical technique. Evidence Acquisition: A MEDLINE and PUBMED search was performed using the following combination of keywords for the years 1985-2009: PCL, posterior cruciate ligament, and rehabilitation. The reviewed articles were those that addressed rehabilitation of the PCL after reconstruction and were written in the English language. Results: This PCL reconstruction technique may be more inherently stable and allow a more progressive rehabilitation program. Conclusion: There are unique features of all-arthroscopic, double-bundle, allograft reconstruction of the PCL that allow a more aggressive approach in PCL reconstruction rehabilitation. The stability afforded by the anatomic press-fit tibial plug and the augmented tibial and augmented femoral fixation are a plus. The anatomic position of the tibial insertion avoids the “killer turn” of the transtibial approach, limiting concerns for graft abrasion with range of motion and resultant elongation. The outside-in method for the femoral tunnels also minimizes the abrasion that can occur at the “critical corner.”
Lower Body Stiffness and Muscle Activity Differences Between Female Dancers and Basketball Players During Drop Jumps
Authors: Ambegaonkar Jatin P. , Shultz Sandra J. , Perrin David H. , Schmitz Randy J. , Ackerman Terry A. , Schulz Mark R. 
Published: December 2010

Background: Anterior cruciate ligament (ACL) injuries often occur during landing, with female athletes at higher injury risk than male athletes. Interestingly, female dancers have lower ACL injury rates than do female athletes in general. Hypothesis: Female dancers will have earlier and greater lower extremity muscle activity and higher sagittal knee joint and leg stiffness than will female basketball players. Study Design: Cross-sectional group comparison. Methods: Fifty-five healthy female athletes (35 dancers, 20 basketball players) performed 5 double-leg drop jumps from a 45-cm box. Surface electromyography (onsets and amplitudes; prelanding and postlanding) was recorded from the lateral gastrocnemius, medial and lateral hamstrings, lateral quadriceps muscles with a 3-dimensional electromagnetic tracking system, and forceplates recording biomechanics (leg spring stiffness and knee joint stiffness). Results: Compared with basketball players, dancers had greater leg spring stiffness ( P = 0.047) but similar knee joint stiffness ( P = 0.44). Although no significant differences were observed in overall muscle onset times ( P = 0.22) or activation amplitudes (prelanding, P = 0.60; postlanding, P = 0.78), small to moderate effect sizes (ESs) suggest trends in dancers toward earlier (ES = 0.53) and higher medial hamstrings activation pre- (ES = 0.55) and post- (ES = 0.41) landing and lower lateral quadriceps (ES = 0.30) and higher gastrocnemius (ES = 0.33) postlanding muscle activation. Conclusions: In dancers, the higher leg spring stiffness and trends toward higher hamstrings prelanding and postlanding, as well as lower quadriceps and higher gastrocnemius activation postlanding with similar knee joint stiffness, indicate lower extremity neuromechanical differences across other joints. Clinical Relevance: Female dancers may have lower extremity neuromechanics that are different from those of basketball players during drop jumps. If dancers use ACL-protective strategies during activity, then their training routines should be further investigated to improve ACL injury prevention programs.
Pathophysiology of Sports-Related Concussion
Authors: Giza Christopher C. , DiFiori John P. 
Published: December 2010

Context: Concussions that occur during participation in athletic events affect millions of individuals each year. Although our understanding of the pathophysiology of concussion has grown considerably in recent years, much remains to be elucidated. This article reviews basic science and relevant translational clinical research regarding several aspects of concussion. Evidence Acquisition: A literature search was conducted using PubMed from 1966 to 2010, with an emphasis on work published within the past 10 years. Additional articles were identified from the bibliography of recent reviews. Results: Basic science and clinical data both indicate that there is a period of increased vulnerability to repeated injury following a concussion and that its duration is variable. Growing evidence indicates that postinjury activity is likely to affect recovery from brain injury. Data suggest that long-term sequelae may result from prior concussion—particularly, repeated injuries. The unique aspects of cerebral development may account for differences in the effects of concussion in children and adolescents when compared with adults. Conclusions: The available pathophysiologic data from basic science and clinical studies have increased the evidence base for concussion management strategies—the approaches to which may differ between young athletes and adults.
Monocytic cells derived from human embryonic stem cells and fetal liver share common differentiation pathways and homeostatic functions
Authors: Klimchenko Olena , Di Stefano Antonio , Geoerger Birgit , Hamidi Sofiane , Opolon Paule , Robert Thomas , Routhier Mélanie , El-Benna Jamel , Delezoide Anne-Lise , Boukour Siham , Lescure Bernadette , Solary Eric , Vainchenker William , Norol Françoise 
Published: December 2010

AbstractThe early emergence of macrophages and their large pattern of tissue distribution during development suggest that they may play a critical role in the initial steps of embryogenesis. In the present study, we show that monocytic cells derived from human embryonic stem cells (hESCs) and from fetal liver follow a differentiation pathway different to that of adult cells, leading to specific functions. Embryonic and fetal monocytic cells differentiated from a CD14lowCD16− precursor to form CD14highCD16+ cells without producing the CD14highCD16− cell population that predominates in adult peripheral blood. Both demonstrated an enhanced expression of genes encoding tissue-degrading enzymes, chemokines, and scavenger receptors, as was previously reported for M2 macrophages. Compared with adult blood monocytes, embryonic and fetal monocytic cells secreted high amounts of proteins acting on tissue remodeling and angiogenesis, and most of them expressed the Tie2 receptor. Furthermore, they promoted vascular remodeling in xenotransplanted human tumors. These findings suggest that the regulation of human fetal and embryonic monocytic cell differentiation leads to the generation of cells endowed mainly with anti-inflammatory and remodeling functions. Trophic and immunosuppressive functions of M2-polarized macrophages link fetus and tumor development, and hESCs offer a valuable experimental model for in vitro studies of mechanisms sustaining these processes.
Therapeutic levels of fetal hemoglobin in erythroid progeny of β-thalassemic CD34+ cells after lentiviral vector-mediated gene transfer
Authors: Wilber Andrew , Hargrove Phillip W. , Kim Yoon-Sang , Riberdy Janice M. , Sankaran Vijay G. , Papanikolaou Eleni , Georgomanoli Maria , Anagnou Nicholas P. , Orkin Stuart H. , Nienhuis Arthur W. , Persons Derek A. 
Published: December 2010

Abstract
β-Thalassemia major results from severely reduced or absent expression of the β-chain of adult hemoglobin (α2β2;HbA). Increased levels of fetal hemoglobin (α2γ2;HbF), such as occurs with hereditary persistence of HbF, ameliorate the severity of β-thalassemia, raising the potential for genetic therapy directed at enhancing HbF. We used an in vitro model of human erythropoiesis to assay for enhanced production of HbF after gene delivery into CD34+ cells obtained from mobilized peripheral blood of normal adults or steady-state bone marrow from patients with β-thalassemia major. Lentiviral vectors encoding (1) a human γ-globin gene with or without an insulator, (2) a synthetic zinc-finger transcription factor designed to interact with the γ-globin gene promoters, or (3) a short-hairpin RNA targeting the γ-globin gene repressor, BCL11A, were tested. Erythroid progeny of normal CD34+ cells demonstrated levels of HbF up to 21% per vector copy. For β-thalassemic CD34+ cells, similar gene transfer efficiencies achieved HbF production ranging from 45% to 60%, resulting in up to a 3-fold increase in the total cellular Hb content. These observations suggest that both lentiviral-mediated γ-globin gene addition and genetic reactivation of endogenous γ-globin genes have potential to provide therapeutic HbF levels to patients with β-globin deficiency.
Dose Finding Study for the Use of Subcutaneous Recombinant Interleukin-2 to Augment Natural Killer Cell Numbers in an Outpatient Setting for Stage 4 Neuroblastoma After Megatherapy and Autologous Stem-Cell Reinfusion
Authors: Ladenstein Ruth , Pötschger Ulrike , Siabalis Dimitris , Garaventa Alberto , Bergeron Christophe , Lewis Ian J. , Stein Jerry , Kohler Janice , Shaw Peter J. , Holter Wolfgang , Pistoia Vito , Michon Jean 
Published: December 2010

Purpose To establish a safe dose of subcutaneous (SC) recombinant interleukin 2 (rIL-2) in an outpatient setting for children with stage 4 neuroblastoma after megatherapy (MGT) and autologous stem-cell reinfusion (ASCR) that is able to sustain an increase of natural-killer cells (NKCs) above the level previously reported for immunomodulatory potency. Patients and Methods Between August 1997 and November 2000, 33 patients with stage 4 neuroblastoma entered the study from six countries after receiving MGT/ASCR according to national protocols. Dose levels of 3, 6, and 9 × 106 U rIL-2/m2 were given SC in six 5-day cycles every 2 weeks. Results Median age at registration was 4.1 years (range, 1.8 to 7.4). Median observation time was 5 years (range, 4 to 9.8). Increase of NKCs was achieved in 89% of courses, with more than 100% increase over baseline and/or more than 1,000 NKCs/μL in 58%. On the basis of outpatient dose-limiting toxicity at dose level 3, dose level 2 was chosen for the confirmation stage. At dose level 2, the median increase in absolute NKCs was 1,180 cells/μL for all 83 cycles, corresponding to a median relative NKC increase over baseline of 711%. Fever was frequent but controllable with adequate supportive care; 6.5% of patients were hospitalized. Localized pain was moderate and acceptable. Event-free and overall survival rates at 5 years were 45% (± 9 standard deviation [SD]) and 48% (± 9 SD), respectively. Conclusion The low toxicity profile and ability to sustain an increase in NKCs of IL-2 at 6 × 106 U/m2 SC allows its integration in an outpatient setting.
Prophylaxis of Graft-Versus-Host Disease in Unrelated Donor Transplantation With Pentostatin, Tacrolimus, and Mini-Methotrexate: A Phase I/II Controlled, Adaptively Randomized Study
Authors: Parmar Simrit , Andersson Borje S. , Couriel Daniel , Munsell Mark F. , Fernandez-Vina Marcelo , Jones Roy B. , Shpall Elizabeth J. , Popat Uday , Anderlini Paolo , Giralt Sergio , Alousi Amin , Cano Pedro , Bosque Doyle , Hosing Chitra , Silva Leandro de Padua , Westmoreland Michael , Wathen J. Kyle , Berry Donald , Champlin Richard E. , de Lima Marcos J. 
Published: December 2010

Purpose Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after matched unrelated, related, or mismatched related donor hematopoietic stem-cell transplantation (HSCT). Improved GVHD prevention methods are needed. Pentostatin, an adenosine deaminase inhibitor, leads to lymphocyte depletion with low risk of myelosuppression. We hypothesized that addition of pentostatin to GVHD prophylaxis with tacrolimus and mini-methotrexate may improve outcomes, and we conducted a Bayesian adaptively randomized, controlled, dose-finding study, taking into account toxicity and efficacy. Patients and Methods Success was defined as the patient being alive, engrafted, in remission, without GVHD 100 days post-HSCT and no grade ≥ 3 GVHD at any time. Patients were randomly assigned to pentostatin doses of 0, 0.5, 1.0, 1.5, and 2.0 mg/m2 with drug administered on HSCT days 8, 15, 22, and 30. Eligible patients were recipients of mismatched related (n = 10) or unrelated (n = 137) donor HSCT. Results Median age was 47 years. Thirty-seven, 10, 29, 61, and 10 patients were assigned to the control and four treatment groups, respectively, with comparable baseline characteristics. Pentostatin doses of 1.0 and 1.5 mg/m2 had the highest success rates (69.0% and 70.5%) versus control (54.1%). The posterior probabilities that the success rates were greater with 1.5 mg/m2 or 1.0 mg/m2 versus control are 0.944 and 0.821, respectively. Hepatic aGVHD rates were 0%, 17.2%, and 11.1%, respectively, for 1.5 mg/m2, 1.0 mg/m2, and control groups. No grades 3 to 4 aGVHD occurred in 11 HLA-mismatched recipients in the 1.5 mg/m2 group. Conclusion Pentostatin increased the likelihood of success as defined here, and should be further investigated in larger randomized, confirmatory studies.
Induction of CD8+T-Cell Responses Against Novel Glioma–Associated Antigen Peptides and Clinical Activity by Vaccinations With α-Type 1 Polarized Dendritic Cells and Polyinosinic-Polycytidylic Acid Stabilized by Lysine and Carboxymethylcellulose in Patients With Recurrent Malignant Glioma
Authors: Okada Hideho , Kalinski Pawel , Ueda Ryo , Hoji Aki , Kohanbash Gary , Donegan Teresa E. , Mintz Arlan H. , Engh Johnathan A. , Bartlett David L. , Brown Charles K. , Zeh Herbert , Holtzman Matthew P. , Reinhart Todd A. , Whiteside Theresa L. , Butterfield Lisa H. , Hamilton Ronald L. , Potter Douglas M. , Pollack Ian F. , Salazar Andres M. , Lieberman Frank S. 
Published: December 2010

PurposeA phase I/II trial was performed to evaluate the safety and immunogenicity of a novel vaccination with α-type 1 polarized dendritic cells (αDC1) loaded with synthetic peptides for glioma-associated antigen (GAA) epitopes and administration of polyinosinic-polycytidylic acid [poly(I:C)] stabilized by lysine and carboxymethylcellulose (poly-ICLC) in HLA-A2+patients with recurrent malignant gliomas. GAAs for these peptides are EphA2, interleukin (IL)-13 receptor-α2, YKL-40, and gp100.Patients and MethodsTwenty-two patients (13 with glioblastoma multiforme [GBM], five with anaplastic astrocytoma [AA], three with anaplastic oligodendroglioma [AO], and one with anaplastic oligoastrocytoma [AOA]) received at least one vaccination, and 19 patients received at least four vaccinations at two αDC1 dose levels (1 × or 3 × 107/dose) at 2-week intervals intranodally. Patients also received twice weekly intramuscular injections of 20 μg/kg poly-ICLC. Patients who demonstrated positive radiologic response or stable disease without major adverse events were allowed to receive booster vaccines. T-lymphocyte responses against GAA epitopes were assessed by enzyme-linked immunosorbent spot and HLA-tetramer assays.ResultsThe regimen was well-tolerated. The first four vaccines induced positive immune responses against at least one of the vaccination-targeted GAAs in peripheral blood mononuclear cells in 58% of patients. Peripheral blood samples demonstrated significant upregulation of type 1 cytokines and chemokines, including interferon-α and CXCL10. Nine (four GBM, two AA, two AO, and one AOA) achieved progression-free status lasting at least 12 months. One patient with recurrent GBM demonstrated sustained complete response. IL-12 production levels by αDC1 positively correlated with time to progression.ConclusionThese data support safety, immunogenicity, and preliminary clinical activity of poly-ICLC-boosted αDC1-based vaccines.
Urinary stone composition in pediatric patients: a retrospective study of 205 cases
Authors: Alaya Akram , Nouri Abdellatif , Najjar Mohamed Fadhel 
Published: December 2010

AbstractBackground:Stone composition has changed substantially over the past decades in developed countries. We studied urinary stone composition in Tunisian children.Methods:We studied 205 children ranging from 3 months to 16 years old age and who were diagnosed as having urinary stones (122 boys and 83 girls). Stone analysis was performed respectively using a stereomicroscope and by infrared spectroscopy to determine, respectively, the morphological type and molecular composition of each.Results:Of 205 stones analysed, 77 (37.5%) were composed of a single constituent. Calcium oxalate (CaOx) stone were predominant, being a constituent of 54.7% of stones, followed by calcium phosphate and purines; 14.6% of cases. Calcium oxalate monohydrate was more frequently seen in girls (p<0.01), while struvite was more common in boys (p<0.001). Teenagers were more affected by whewellite stones compared with infants (p<0.05). Purine stones were predominant in 20% of cases, but its prevalence decreased with age.Conclusions:The increase in calcium oxalate stones in school age children and the decrease of struvite and purines stones confirm the change in the etiology of urolithiasis with respect to age.
Full-scan mass spectral evidence for 3-epi-25-hydroxyvitamin D3 in serum of infants and adults
Authors: Stepman Hedwig C.M. , Vanderroost An , Stöckl Dietmar , Thienpont Linda M. 
Published: December 2010

Abstract

Background: Since the introduction of liquid chromatography-mass spectrometry (LC/MS) for assessing vitamin D status, it has been shown that the C-3 epimer can account for a significant proportion of circulating 25-hydroxyvitamin D3 (25OHD3) concentrations in infants. However, some question whether monitoring a single MS transition at a chromatographic retention time typical for 3-epi-25OHD3 sufficiently warrants conclusions about the identity of the substance generating the signal. Therefore, we aimed to substantiate the evidence for 3-epi-25OHD3 in infants by collision induced dissociation (CID)-MS/MS product ion scans. A second objective was mass spectrometric investigation of the presence and prevalence of the 3-epi metabolite in serum from adults.

Methods: Serum samples from six infants and 32 adults were studied using an ultra performance LC/tandem MS (UPLC/MS/MS) method designed to separate the 3-epi-25OHD3 from 25OHD3. Samples were submitted to liquid/liquid extraction and Sephadex LH-20 fractionation, prior to column-switching UPLC with MS/MS recording of CID product ion spectra of the [M+H]+ precursor ion. The respective standards were analyzed under identical UPLC/MS/MS conditions for comparison.

Results: In the chromatograms of all samples, two peaks eluted with retention characteristics and spectra closely matching those observed for the 25OHD3 and the 3-epi standards. The percentage of the 3-epi metabolite relative to 25OHD3 in infants ranged from 15% to 41%, and in adults from 2.5% to 17%.

Conclusions: This preliminary finding suggests that the prevalence of 3-epi-25OHD3 in serum of infants is considerable, and that even in adults the concentrations of this form should not be neglected.
Rapid microwave digestion and microplate reading format method for urinary iodine determination
Authors: Hedayati Mehdi , Khazan Marjan , Yaghmaee Parichehr , Yeghaneh Marjan Zarif , Behdadfar Leila , Daneshpour Maryam Sadat 
Published: December 2010

Abstract

Background: High temperature and long heating time can be considered the main drawbacks of the conventional digestion methods of urinary iodine determination. The aim of this study was to assess the usefulness of a microwave for digestion and decomposition of urine interfering substances. It may help for shortening the time and increasing the safety of the method.

Methods: In this study, two digestion methods were tested on urine samples. Random urine samples were processed by conventional electrical heat as well as new microwave digestion methods. The urine samples were digested using the two methods mentioned, and then urinary iodine was determined using a colorimetric reaction according to the Sandell-Kolthoff reaction. In order to increase speed and precision of the test, a microplate ELISA reader was used. Sensitivity, precision, and comparison of the results were assessed in both of the methods.

Results: In the case of microwave digestion, only a 10-min period was needed for complete digestion of urine samples. The precision and recovery of the new digestion step was acceptable. Furthermore, comparison of final results of iodine content obtained using the microwave and conventional method showed good correlation.

Conclusions: These results show that a microwave method for urine digestion is advantageous due to its safety and ease of use, and quick preparation of urine samples to eliminate interfering substances and release iodine. Thus, it can replace the conventional electrical heat digestion method.