bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trend for decreasing Multiple Sclerosis Severity Scores (MSSS) with increasing calendar year of enrollment into the New York State Multiple Sclerosis Consortium
Authors: Kister Ilya , Chamot Eric , Bacon Joshua H , Cutter Gary , Herbert Joseph 
Published: January 2011

Background: Although the natural history of multiple sclerosis has been charted extensively, it is still not known whether the trajectory of disability accumulation has changed in the era of disease-modifying therapies (DMTs). Objective: The objective of this study was to examine trends in Multiple Sclerosis Severity Score (MSSS) with regard to calendar year of enrollment into the New York State MS Consortium (NYSMSC). Methods: Distributions of MSSS were calculated for each year of enrollment, from 1996 to 2007. Quantile regression was used in a multivariable analysis to model for conditional distribution of MSSS quantiles as functions of potential confounders. Results: The cohort consisted of 6238 patients. Mean age at enrollment was 38 years (SD = 10) and mean disease duration was 10.1 years (SD = 7.3); 57% were on DMTs. The quantile regression model of trends in MSSS between 1996 and 2007 controlled for age, sex, ethnicity, diagnostic delay, and disease duration and demonstrated a robust trend toward lower MSSS with increasing year of enrollment. The model-predicted median MSSS at enrollment in 1996 was 5.04 (95% CI, 4.86–5.21), and in 2007 was 3.78 (95%CI, 3.36–4.20; p < 0.001). The downward trend in MSSS during the enrollment period was confirmed by analysis of Expanded Disability Status Scale (EDSS) distributions, adjusted for disease duration, in successive years of enrollment. Conclusions: The recent enrollees into the NYSMSC had lower MSSSs compared to the earlier enrollees. The apparent slowing in disability accumulation is likely due to a complex combination of factors: advent of DMTs and improvements in MS care, as well as selection, migration, and recall biases.
Challenges in the design and conduct of controlled clinical effectiveness trials in schizophrenia
Authors: Rosenheck Robert A , Krystal John H , Lew Robert , Barnett Paul G , Thwin Soe Soe , Fiore Louis , Valley Danielle , Huang Grant D , Neal Carla , Vertrees Julia E , Liang Matthew H ,   for the CSP 555 Research Group
Published: January 2011

Background The introduction of antipsychotic medication has been a major advance in the treatment of schizophrenia and allows millions of people to live outside of institutions. It is generally believed that long-acting intramuscular antipsychotic medication is the most effective approach to increasing medication adherence and thereby reduce relapse in high-risk patients with schizophrenia, but the data are scant. Purpose To report the design of a study to assess the effect of long-acting injectable risperidone in unstable patients and under more realistic conditions than previously studied and to evaluate the effect of this medication on psychiatric inpatient hospitalization, schizophrenia symptoms, quality of life, medication adherence, side effects, and health care costs. Methods The trial was an open randomized clinical comparative effectiveness trial in patients with schizophrenia or schizo-affective disorders in which parenteral risperidone was compared to an oral antipsychotic regimen selected by each control patient’s psychiatrist. Participants had unstable psychiatric disease defined by recent hospitalization or exhibition of unusual need for psychiatric services. The primary endpoint was hospitalization for psychiatric indications; the secondary endpoint was psychiatric symptoms. Results Overall, 382 patients were randomized. Determination of a persons’ competency to understand the elements of informed consent was addressed. The use of a closed-circuit TV interview for psychosocial measures provided an economical, high quality, reliable means of collecting data. A unique method for insuring that usual care was optimal was incorporated in the follow-up of all subjects. Limitations Patients with schizophrenia or schizo-affective disorders and with the common co-morbid illnesses seen in the VA are a challenging group of subjects to study in long-term trials. Some techniques unique in the VA and found useful may not be generalizable or applicable in other research or treatment settings. Conclusions The trial tested a new antipsychotic medication early in its adoption in the Veterans Health Administration. The VA has a unique electronic medical record and database which can be used to identify the endpoint, that is, first hospitalization due to a psychiatric problem, with complete ascertainment. Several methodologic solutions addressed competency to understand elements of consent, the costs and reliability of collecting interview data gathering, and insuring usual care.
Planning and core analyses for periodic aggregate safety data reviews
Authors: Xia H Amy , Crowe Brenda J , Schriver Robert C , Oster Manfred , Hall David B 
Published: January 2011

Background In 2009, the Safety Planning, Evaluation and Reporting Team gave detailed recommendations for a well-planned and systematic approach for safety data collection and analysis. Important aspects of this approach included regular reviews of aggregate data by a multidisciplinary team focusing on safety. Purpose This article provides information to facilitate the planning and implementation of aggregate data reviews. Methods Our recommendations are based on experience of the authors and review of relevant literature. Results We present information regarding the planning of aggregate data reviews as well as examples of data displays that are useful for many different compounds. A subset of these data displays could form a set of ‘core’ analyses to be generated for aggregate data reviews.
Deficiency of SATB1 expression in Sézary cells causes apoptosis resistance by regulating FasL/CD95L transcription
Authors: Wang Yang , Su Mingwan , Zhou Liang L. , Tu Ping , Zhang Xuejun , Jiang Xiaoyan , Zhou Youwen 
Published: January 2011

AbstractSézary syndrome (SS) is an aggressive subtype of cutaneous T-cell lymphoma that is characterized by circulating leukemic Sézary cells. The accumulation of these malignant cells has been shown to be the result of the resistance to apoptosis, in particular, activation-induced cell death. However, the mechanism of apoptosis resistance remains unknown. By characterizing the gene transcription profiles of purified CD4+CD7− Sézary cells from patients with SS and cultured Sézary cells, it was found that Sézary cells are deficient in the expression of special AT-rich region binding protein 1 (SATB1), a key regulator of T-cell development and maturation. Retrovirus-mediated gene transduction revealed that SATB1 restoration in cultured Sézary cells (Hut78) triggered spontaneous cell death and sensitized Hut78 cells to activation-induced cell death, with associated activation of caspase 8 and caspase 3. Furthermore, endogenous expression of FasL in Sézary cells was increased in transcriptional and translational levels on restoration of SATB1 expression in cultured Sézary cells. These results suggest that deficiency in SATB1 expression in Sézary cells plays an important role in SS pathogenesis by causing apoptosis resistance. Thus, restoration of SATB1 expression may represent a potential molecular targeted therapy for SS, which does not have a cure at present.
Definition and characterization of the systemic T-cell dysregulation in untreated indolent B-cell lymphoma and very early CLL
Authors: Christopoulos Petros , Pfeifer Dietmar , Bartholomé Kilian , Follo Marie , Timmer Jens , Fisch Paul , Veelken Hendrik 
Published: January 2011

Abstract
Epidemiologic data show that the immune system may control or promote the emergence and growth of neoplastic lymphomatous clones. Conversely, systemic lymphomas, especially myeloma and chronic lymphocytic leukemia (CLL), are associated with clinical immunodeficiency. This prospective controlled study demonstrates substantially reduced circulating T helper cells, predominantly naive CD4+ cells, in patients with nonleukemic follicular lymphoma and extranodal marginal zone lymphoma, but not in monoclonal gammopathy and early CLL. These changes were correlated with a preactivated phenotype, hyperreactivity in vitro, presenescence, and a T helper 2 shift of peripheral T helper cells. No prominent alterations existed in the regulatory T-cell compartment. Gene expression profiling of in vitro–stimulated CD4+ cells revealed an independent second alteration of T helper cell physiology, which was most pronounced in early CLL but also detectable in follicular lymphoma/extranodal marginal zone lymphoma. This pattern consisted of down-regulation of T-cell receptor signaling cascades and globally reduced cytokine secretion. Both types of T-cell dysfunction may contribute to significant immunodeficiency in nonleukemic indolent B-cell lymphomas as demonstrated by unresponsiveness to hepatitis B vaccination. The precise definition of systemic T-cell dysfunction serves as the basis to study its prognostic impact, its relationship to the established influence of the lymphoma microenvironment, and its therapeutic manipulation.
Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse
Authors: Levis Mark , Ravandi Farhad , Wang Eunice S. , Baer Maria R. , Perl Alexander , Coutre Steven , Erba Harry , Stuart Robert K. , Baccarani Michele , Cripe Larry D. , Tallman Martin S. , Meloni Giovanna , Godley Lucy A. , Langston Amelia A. , Amadori Sergio , Lewis Ian D. , Nagler Arnon , Stone Richard , Yee Karen , Advani Anjali , Douer Dan , Wiktor-Jedrzejczak W. , Juliusson Gunnar , Litzow Mark R. , Petersdorf Stephen , Sanz Miguel , Kantarjian Hagop M. , Sato Takashi , Tremmel Lothar , Bensen-Kennedy Debra M. , Small Donald , Smith B. Douglas 
Published: January 2011

AbstractIn a randomized trial of therapy for FMS-like tyrosine kinase-3 (FLT3) mutant acute myeloid leukemia in first relapse, 224 patients received chemotherapy alone or followed by 80 mg of the FLT3 inhibitor lestaurtinib twice daily. Endpoints included complete remission or complete remission with incomplete platelet recovery (CR/CRp), overall survival, safety, and tolerability. Correlative studies included pharmacokinetics and analysis of in vivo FLT3 inhibition. There were 29 patients with CR/CRp in the lestaurtinib arm and 23 in the control arm (26% vs 21%; P = .35), and no difference in overall survival between the 2 arms. There was evidence of toxicity in the lestaurtinib-treated patients, particularly those with plasma levels in excess of 20μM. In the lestaurtinib arm, FLT3 inhibition was highly correlated with remission rate, but target inhibition on day 15 was achieved in only 58% of patients receiving lestaurtinib. Given that such a small proportion of patients on this trial achieved sustained FLT3 inhibition in vivo, any conclusions regarding the efficacy of combining FLT3 inhibition with chemotherapy are limited. Overall, lestaurtinib treatment after chemotherapy did not increase response rates or prolong survival of patients with FLT3 mutant acute myeloid leukemia in first relapse. This study is registered at www.clinicaltrials.gov as #NCT00079482.
Comparative analysis and supragenome modeling of twelve Moraxella catarrhalis clinical isolates
Authors: Davie Jeremiah J , Earl Josh , de Vries Stefan PW , Ahmed Azad , Hu Fen Z , Bootsma Hester J , Stol Kim , Hermans Peter WM , Wadowsky Robert M , Ehrlich Garth D , Hays John P , Campagnari Anthony A 
Published: January 2011

Abstract

Background

M. catarrhalis is a gram-negative, gamma-proteobacterium and an opportunistic human pathogen associated with otitis media (OM) and exacerbations of chronic obstructive pulmonary disease (COPD). With direct and indirect costs for treating these conditions annually exceeding $33 billion in the United States alone, and nearly ubiquitous resistance to beta-lactam antibiotics among M. catarrhalis clinical isolates, a greater understanding of this pathogen's genome and its variability among isolates is needed.

Results
The genomic sequences of ten geographically and phenotypically diverse clinical isolates of M. catarrhalis were determined and analyzed together with two publicly available genomes. These twelve genomes were subjected to detailed comparative and predictive analyses aimed at characterizing the supragenome and understanding the metabolic and pathogenic potential of this species. A total of 2383 gene clusters were identified, of which 1755 are core with the remaining 628 clusters unevenly distributed among the twelve isolates. These findings are consistent with the distributed genome hypothesis (DGH), which posits that the species genome possesses a far greater number of genes than any single isolate. Multiple and pair-wise whole genome alignments highlight limited chromosomal re-arrangement.

Conclusions

M. catarrhalis gene content and chromosomal organization data, although supportive of the DGH, show modest overall genic diversity. These findings are in stark contrast with the reported heterogeneity of the species as a whole, as wells as to other bacterial pathogens mediating OM and COPD, providing important insight into M. catarrhalis pathogenesis that will aid in the development of novel therapeutic regimens.
Characterization of the past and current duplication activities in the human 22q11.2 region
Authors: Guo Xingyi , Freyer Laina , Morrow Bernice , Zheng Deyou 
Published: January 2011

Abstract

Background
Segmental duplications (SDs) on 22q11.2 (LCR22), serve as substrates for meiotic non-allelic homologous recombination (NAHR) events resulting in several clinically significant genomic disorders.

Results
To understand the duplication activity leading to the complicated SD structure of this region, we have applied the A-Bruijn graph algorithm to decompose the 22q11.2 SDs to 523 fundamental duplication sequences, termed subunits. Cross-species syntenic analysis of primate genomes demonstrates that many of these LCR22 subunits emerged very recently, especially those implicated in human genomic disorders. Some subunits have expanded more actively than others, and young Alu SINEs, are associated much more frequently with duplicated sequences that have undergone active expansion, confirming their role in mediating recombination events. Many copy number variations (CNVs) exist on 22q11.2, some flanked by SDs. Interestingly, two chromosome breakpoints for 13 CNVs (mean length 65 kb) are located in paralogous subunits, providing direct evidence that SD subunits could contribute to CNV formation. Sequence analysis of PACs or BACs identified extra CNVs, specifically, 10 insertions and 18 deletions within 22q11.2; four were more than 10 kb in size and most contained young AluY s at their breakpoints.

Conclusions
Our study indicates that AluY s are implicated in the past and current duplication events, and moreover suggests that DNA rearrangements in 22q11.2 genomic disorders perhaps do not occur randomly but involve both actively expanded duplication subunits and Alu elements.
Analysis of nucleosome positioning determined by DNA helix curvature in the human genome
Authors: Liu Hongde , Duan Xueye , Yu Shuangxin , Sun Xiao 
Published: January 2011

Abstract

Background
Nucleosome positioning has an important role in gene regulation. However, dynamic positioning in vivo casts doubt on the reliability of predictions based on DNA sequence characteristics. What role does sequence-dependent positioning play? In this paper, using a curvature profile model, nucleosomes are predicted in the human genome and patterns of nucleosomes near some key sites are investigated.

Results
Curvature profiling revealed that in the vicinity of a transcription start site, there is also a nucleosome-free region. Near transcription factor binding sites, curvature profiling showed a trough, indicating nucleosome depletion. The trough of the curvature profile corresponds well to the high binding scores of transcription factors. Moreover, our analysis suggests that nucleosome positioning has a selective protection role. Target sites of miRNAs are occupied by nucleosomes, while single nucleotide polymorphism sites are depleted of nucleosomes.

Conclusions
The results indicate that DNA sequences play an important role in nucleosome positioning, and the positioning is important not only in gene regulation, but also in genetic variation and miRNA functions.
Distinctive mitochondrial genome of Calanoid copepod Calanus sinicus with multiple large non-coding regions and reshuffled gene order: Useful molecular markers for phylogenetic and population studies
Authors: Minxiao Wang , Song Sun , Chaolun Li , Xin Shen 
Published: January 2011

AbstractBackgroundCopepods are highly diverse and abundant, resulting in extensive ecological radiation in marine ecosystems.Calanus sinicusdominates continental shelf waters in the northwest Pacific Ocean and plays an important role in the local ecosystem by linking primary production to higher trophic levels. A lack of effective molecular markers has hindered phylogenetic and population genetic studies concerning copepods. As they are genome-level informative, mitochondrial DNA sequences can be used as markers for population genetic studies and phylogenetic studies.ResultsThe mitochondrial genome ofC. sinicusis distinct from other arthropods owing to the concurrence of multiple non-coding regions and a reshuffled gene arrangement. Further particularities in the mitogenome ofC. sinicusinclude low A + T-content, symmetrical nucleotide composition between strands, abbreviated stop codons for several PCGs and extended lengths of the genesatp6andatp8relative to other copepods. The monophyletic Copepoda should be placed within the Vericrustacea. The close affinity between Cyclopoida and Poecilostomatoida suggests reassigning the latter as subordinate to the former. Monophyly of Maxillopoda is rejected. Within the alignment of 11C. sinicusmitogenomes, there are 397 variable sites harbouring three 'hotspot' variable sites and three microsatellite loci.ConclusionThe occurrence of thecircular subgenomic fragmentduring laboratory assays suggests that special caution should be taken when sequencing mitogenomes using long PCR. Such a phenomenon may provide additional evidence of mitochondrial DNA recombination, which appears to have been a prerequisite for shaping the present mitochondrial profile ofC. sinicusduring its evolution. The lack of synapomorphic gene arrangements among copepods has cast doubt on the utility of gene order as a useful molecular marker for deep phylogenetic analysis. However, mitochondrial genomic sequences have been valuable markers for resolving phylogenetic issues concerning copepods. The variable site maps ofC. sinicusmitogenomes provide a solid foundation for population genetic studies.
AtRabD2b and AtRabD2c have overlapping functions in pollen development and pollen tube growth
Authors: Peng Jianling , Ilarslan Hilal , Wurtele Eve Syrkin , Bassham Diane C 
Published: January 2011

Abstract

Background
Rab GTPases are important regulators of endomembrane trafficking, regulating exocytosis, endocytosis and membrane recycling. Many Rab-like proteins exist in plants, but only a subset have been functionally characterized.

Results
Here we report that AtRabD2b and AtRabD2c play important roles in pollen development, germination and tube elongation. AtrabD2b and AtrabD2c single mutants have no obvious morphological changes compared with wild-type plants across a variety of growth conditions. An AtrabD2b/2c double mutant is also indistinguishable from wild-type plants during vegetative growth; however its siliques are shorter than those in wild-type plants. Compared with wild-type plants, AtrabD2b/2c mutants produce deformed pollen with swollen and branched pollen tube tips. The shorter siliques in the AtrabD2b/2c double mutant were found to be primarily due to the pollen defects. AtRabD2b and AtRabD2c have different but overlapping expression patterns, and they are both highly expressed in pollen. Both AtRabD2b and AtRabD2c protein localize to Golgi bodies.

Conclusions
These findings support a partially redundant role for AtRabD2b and AtRabD2c in vesicle trafficking during pollen tube growth that cannot be fulfilled by the remaining AtRabD family members.
Image-guided intensity modulated radiotherapy with helical tomotherapy for postoperative treatment of high-risk oral cavity cancer
Authors: Hsieh Chen-Hsi , Kuo Ying-Shiung , Liao Li-Jen , Hu Kawang-Yu , Lin Shih-Chiang , Wu Le-Jung , Lin Yu-Chin , Chen Yu-Jen , Wang Li-Ying , Hsieh Yen-Ping , Lin Shoei Long , Chen Chun-Yi , Chen Chien-An , Shueng Pei-Wei 
Published: January 2011

Abstract

Background
The aim of this study was to assess the treatment results and toxicity profiles of helical tomotherapy (HT) for postoperative high-risk oral cavity cancer.

Methods
From December 6, 2006 through October 9, 2009, 19 postoperative high-risk oral cavity cancer patients were enrolled. All of the patients received HT with (84%) or without (16%) chemotherapy.

Results
The median follow-up time was 17 months. The 2-year overall survival, disease-free survival, locoregional control, and distant metastasis-free rates were 94%, 84%, 92%, and 94%, respectively. The package of overall treatment time > 13 wk, the interval between surgery and radiation ≤ 6 wk, and the overall treatment time of radiation ≤ 7 wk was 21%, 84%, and 79%, respectively. The percentage of grade 3 mucositis, dermatitis, and leucopenia was 42%, 5% and 5%, respectively.

Conclusions
HT achieved encouraging clinical outcomes for postoperative high-risk oral cavity cancer patients with high compliance. A long-term follow-up study is needed to confirm these preliminary findings.
Mortality from suicide and other external cause injuries in China: a prospective cohort study
Authors: Rebholz Casey M , Gu Dongfeng , Yang Wenjie , Chen Jing , Wu Xigui , Huang Jian-feng , Chen Ji-chun , Chen Chung-Shiuan , Kelly Tanika N , Duan Xiufang , Bazzano Lydia A , He Jiang 
Published: January 2011

Abstract

Background
Premature death from suicide is a leading cause of death worldwide. However, the pattern and risk factors for suicide and other external cause injuries are not well understood. This study investigates mortality from suicide and other injuries and associated risk factors in China.

Methods
A prospective cohort study of 169,871 Chinese adults aged 40 years and older was conducted. Mortality due to suicide or other external cause injuries was recorded.

Results
Mortality from all external causes was 58.7/100,000 (72.3 in men and 44.4 in women): 14.1/100,000 (14.2 in men and 14.2 in women) for suicide and 44.6/100,000 (58.1 in men and 30.2 in women) for other external cause injuries. Transport accidents (17.2/100,000 overall, 23.4 in men and 10.8 in women), accidental poisoning (7.5/100,000 overall, 10.2 in men and 4.8 in women), and accidental falls (5.7/100,000 overall, 6.5 in men and 5.0 in women) were the three leading causes of death from other external cause injuries in China. In the multivariable analysis, male sex (relative risk [RR] 1.56, 95% confidence interval [CI] 1.03-2.38), age 70 years and older (2.27, 1.29-3.98), living in north China (1.68, 1.20-2.36) and rural residence (2.82, 1.76-4.51) were associated with increased mortality from suicide. Male sex (RR 2.50, 95% CI 1.95-3.20), age 60-69 years (1.93, 1.45-2.58) and 70 years and older (3.58, 2.58-4.97), rural residence (2.29, 1.77-2.96), and having no education (1.56, 1.00-2.43) were associated with increased mortality from other external cause injuries, while overweight (0.60, 0.43-0.83) was associated with decreased risk of mortality from other external cause injuries.

Conclusions
External cause mortality has become a major public health problem in China. Developing an integrated national program for the prevention of mortality due to external cause injuries in China is warranted.