bluuebunny/crossref_metadata_2025_split huggingface dataset:
T-cell autoreactivity to citrullinated autoantigenic peptides in rheumatoid arthritis patients carrying HLA-DRB1 shared epitope alleles
Authors: Law Soi Cheng , Street Shayna , Yu Chien-Hsiung Alan , Capini Christelle , Ramnoruth Sakoontalla , Nel Hendrik J , van Gorp Eline , Hyde Claire , Lau Kim , Pahau Helen , Purcell Anthony W , Thomas Ranjeny 
Published: May 2012

Abstract
Introduction
Anti-citrullinated peptide antibodies are found in rheumatoid arthritis (RA) patients with HLA-DRβ chains encoding the shared epitope (SE) sequence. Citrullination increases self-antigen immunogenicity, through increased binding affinity to SE-containing HLA-DR molecules. To characterise T-cell autoreactivity towards citrullinated self-epitopes, we profiled responses of SE+ healthy controls and RA patients to citrullinated and unmodified epitopes of four autoantigens.

Methods
We compared T-cell proliferative and cytokine responses to citrullinated and native type II collagen 1,237 to 1,249, vimentin 66 to 78, aggrecan 84 to 103 and fibrinogen 79 to 91 in six SE+ healthy controls and in 21 RA patients with varying disease duration. Cytokine-producing cells were stained after incubation with peptide in the presence of Brefeldin-A.

Results
Although proliferative responses were low, IL-6, IL-17 and TNF were secreted by CD4+ T cells of SE+ RA patients and healthy controls, as well as IFNγ and IL-10 secreted by RA patients, in response to citrullinated peptides. Of the epitopes tested, citrullinated aggrecan was most immunogenic. Patients with early RA were more likely to produce IL-6 in response to no epitope or to citrullinated aggrecan, while patients with longstanding RA were more likely to produce IL-6 to more than one epitope. Cytokine-producing CD4+ T cells included the CD45RO+ and CD45RO- and the CD28+ and CD28- subsets in RA patients.

Conclusion
Proinflammatory cytokines were produced by CD4+ T cells in SE+ individuals in response to citrullinated self-epitopes, of which citrullinated aggrecan was most immunogenic. Our data suggest that the T-cell response to citrullinated self-epitopes matures and diversifies with development of RA.
The role of angiogenic factors in predicting clinical outcome in severe bacterial infection in Malawian children
Authors: Mankhambo Limangeni A , Banda Daniel L ,   The IPD Study Group, Jeffers Graham , White Sarah A , Balmer Paul , Nkhoma Standwell , Phiri Happy , Molyneux Elizabeth M , Hart C Anthony , Molyneux Malcolm E , Heyderman Robert S , Carrol Enitan D 
Published: May 2012

Abstract
Introduction
Severe sepsis is a disease of the microcirculation, with endothelial dysfunction playing a key role in its pathogenesis and subsequent associated mortality. Angiogenesis in damaged small vessels may ameliorate this dysfunction. The aim of the study was to determine whether the angiogenic factors (vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and angiopoietin-1 (Ang-1) and -2 (Ang-2)) are mortality indicators in Malawian children with severe bacterial infection.

Methods
In 293 children with severe bacterial infection, plasma VEGF, PDGF, FGF, and Ang-1 and Ang-2 were measured on admission; in 50 of the children with meningitis, VEGF, PDGF, and FGF were also measured in the CSF. Healthy controls comprised children from some of the villages of the index cases. Univariable and multivariable logistic regression analyses were performed to develop a prognostic model.

Results
The median age was 2.4 years, and the IQR, 0.7 to 6.0 years. There were 211 children with bacterial meningitis (72%) and 82 (28%) with pneumonia, and 154 (53%) children were HIV infected. Mean VEGF, PDGF, and FGF concentrations were higher in survivors than in nonsurvivors, but only PDGF remained significantly increased in multivariate analysis (P = 0.007). Mean Ang-1 was significantly increased, and Ang-2 was significantly decreased in survivors compared with nonsurvivors (6,000 versus 3,900 pg/ml, P = 0.03; and 7,700 versus 11,900 pg/ml, P = 0.02, respectively). With a logistic regression model and controlling for confounding factors, only female sex (OR, 3.95; 95% CI, 1.33 to 11.76) and low Ang-1 (OR, 0.23; 95% CI, 0.08 to 0.69) were significantly associated with mortality. In children with bacterial meningitis, mean CSF VEGF, PDGF, and FGF concentrations were higher than paired plasma concentrations, and mean CSF, VEGF, and FGF concentrations were higher in nonsurvivors than in survivors (P = 0.02 and 0.001, respectively).

Conclusions
Lower plasma VEGF, PDGF, FGF, and Ang-1 concentrations and higher Ang-2 concentrations are associated with an unfavorable outcome in children with severe bacterial infection. These angiogenic factors may be important in the endothelial dysregulation seen in severe bacterial infection, and they could be used as biomarkers for the early identification of patients at risk of a poor outcome.
Surgical intensive care unit clinician estimates of the adequacy of communication regarding patient prognosis
Authors: Aslakson Rebecca A , Wyskiel Rhonda , Shaeffer Dauryne , Zyra Marylou , Ahuja Nita , Nelson Judith E , Pronovost Peter J 
Published: May 2012

Abstract
Introduction
Intensive care unit (ICU) patients and family members repeatedly note accurate and timely communication from health care providers to be crucial to high-quality ICU care. Practice guidelines recommend improving communication. However, few data, particularly in surgical ICUs, exist on health care provider opinions regarding whether communication is effective.

Methods
To evaluate ICU clinician perceptions regarding adequacy of communication regarding prognosis, we developed a survey and administered it to a cross section of surgical ICU nurses, surgical ICU physicians, nurse practitioners (NPs), and surgeons.

Results
Surgeons had a high satisfaction with communication regarding prognosis for themselves (90%), ICU nurses (85%), and ICU physicians and NPs (85%). ICU nurses noted high satisfaction with personal (82%) and ICU physician and NP (71%) communication, but low (2%) satisfaction with that provided by surgeons. ICU physicians and NPs noted high satisfaction with personal (74%) and ICU nurse (88%) communication, but lower (23%) satisfaction with that provided by surgeons. ICU nurses were the most likely (75%) to report speaking to patients and patient families regarding prognosis, followed by surgeons (40%), and then ICU physicians and NPs (33%). Surgeons noted many opportunities to speak to ICU nurses and ICU physicians and NPs about patient prognosis and noted that comments were often valued. ICU physicians and NPs and ICU nurses noted many opportunities to speak to each other but fewer opportunities to communicate with surgeons. ICU physicians and NPs thought that their comments were valued by ICU nurses but less valued by surgeons. ICU nurses thought that their comments were less valued by ICU physicians and NPs and surgeons.

Conclusions
ICU nurses, surgeons, and ICU intensivists and NPs varied widely in their satisfaction with communication relating to prognosis. Clinician groups also varied in whether they thought that they had opportunities to communicate prognosis and whether their concerns were valued by other provider groups. These results hint at the nuanced and complicated relationships present in surgical ICUs. Further validation studies and further evaluations of patient and family member perspectives are needed.
Genome-wide patterns of carbon and nitrogen regulation of gene expression validate the combined carbon and nitrogen (CN)-signaling hypothesis in plants
Authors: Palenchar Peter M , Kouranov Andrei , Lejay Laurence V , Coruzzi Gloria M 
Published: May 2012

Abstract
Background
Carbon and nitrogen are two signals that influence plant growth and development. It is known that carbon- and nitrogen-signaling pathways influence one another to affect gene expression, but little is known about which genes are regulated by interactions between carbon and nitrogen signaling or the mechanisms by which the different pathways interact.

Results
Microarray analysis was used to study global changes in mRNA levels due to carbon and nitrogen in Arabidopsis thaliana. An informatic analysis using InterAct Class enabled us to classify genes on the basis of their responses to carbon or nitrogen treatments. This analysis provides in vivo evidence supporting the hypothesis that plants have a carbon/nitrogen (CN)-sensing/regulatory mechanism, as we have identified over 300 genes whose response to combined CN treatment is different from that expected from expression values due to carbon and nitrogen treatments separately. Metabolism, energy and protein synthesis were found to be significantly affected by interactions between carbon and nitrogen signaling. Identified putative cis-acting regulatory elements involved in mediating CN-responsive gene expression suggest multiple mechanisms for CN responsiveness. One mechanism invokes the existence of a single CN-responsive cis element, while another invokes the existence of cis elements that promote nitrogen-responsive gene expression only when present in combination with a carbon-responsive cis element.

Conclusion
This study has allowed us to identify genes and processes regulated by interactions between carbon and nitrogen signaling and take a first step in uncovering how carbon- and nitrogen-signaling pathways interact to regulate transcription.
Identification, characterization and comparative genomics of chimpanzee endogenous retroviruses
Authors: Polavarapu Nalini , Bowen Nathan J , McDonald John F 
Published: May 2012

Abstract
Background
Retrotransposons, the most abundant and widespread class of eukaryotic transposable elements, are believed to play a significant role in mutation and disease and to have contributed significantly to the evolution of genome structure and function. The recent sequencing of the chimpanzee genome is providing an unprecedented opportunity to study the functional significance of these elements in two closely related primate species and to better evaluate their role in primate evolution.

Results
We report here that the chimpanzee genome contains at least 42 separate families of endogenous retroviruses, nine of which were not previously identified. All but two (CERV 1/PTERV1 and CERV 2) of the 42 families of chimpanzee endogenous retroviruses were found to have orthologs in humans. Molecular analysis (PCR and Southern hybridization) of CERV 2 elements demonstrates that this family is present in chimpanzee, bonobo, gorilla and old-world monkeys but absent in human, orangutan and new-world monkeys. A survey of endogenous retroviral positional variation between chimpanzees and humans determined that approximately 7% of all chimpanzee-human INDEL variation is associated with endogenous retroviral sequences.

Conclusion
Nine families of chimpanzee endogenous retroviruses have been transpositionally active since chimpanzees and humans diverged from a common ancestor. Seven of these transpositionally active families have orthologs in humans, one of which has also been transpositionally active in humans since the human-chimpanzee divergence about six million years ago. Comparative analyses of orthologous regions of the human and chimpanzee genomes have revealed that a significant portion of INDEL variation between chimpanzees and humans is attributable to endogenous retroviruses and may be of evolutionary significance.
Constructing a fish metabolic network model
Authors: Li Shuzhao , Pozhitkov Alexander , Ryan Rachel A , Manning Charles S , Brown-Peterson Nancy , Brouwer Marius 
Published: May 2012

AbstractWe report the construction of a genome-wide fish metabolic network model, MetaFishNet, and its application to analyzing high throughput gene expression data. This model is a stepping stone to broader applications of fish systems biology, for example by guiding study design through comparison with human metabolism and the integration of multiple data types. MetaFishNet resources, including a pathway enrichment analysis tool, are accessible at http://metafishnet.appspot.com.
Quake: quality-aware detection and correction of sequencing errors
Authors: Kelley David R , Schatz Michael C , Salzberg Steven L 
Published: May 2012

AbstractWe introduce Quake, a program to detect and correct errors in DNA sequencing reads. Using a maximum likelihood approach incorporating quality values and nucleotide specific miscall rates, Quake achieves the highest accuracy on realistically simulated reads. We further demonstrate substantial improvements in de novo assembly and SNP detection after using Quake. Quake can be used for any size project, including more than one billion human reads, and is freely available as open source software from http://www.cbcb.umd.edu/software/quake.
Genome-wide functional analysis of human 5' untranslated region introns
Authors: Cenik Can , Derti Adnan , Mellor Joseph C , Berriz Gabriel F , Roth Frederick P 
Published: May 2012

Abstract
Background
Approximately 35% of human genes contain introns within the 5' untranslated region (UTR). Introns in 5'UTRs differ from those in coding regions and 3'UTRs with respect to nucleotide composition, length distribution and density. Despite their presumed impact on gene regulation, the evolution and possible functions of 5'UTR introns remain largely unexplored.

Results
We performed a genome-scale computational analysis of 5'UTR introns in humans. We discovered that the most highly expressed genes tended to have short 5'UTR introns rather than having long 5'UTR introns or lacking 5'UTR introns entirely. Although we found no correlation in 5'UTR intron presence or length with variance in expression across tissues, which might have indicated a broad role in expression-regulation, we observed an uneven distribution of 5'UTR introns amongst genes in specific functional categories. In particular, genes with regulatory roles were surprisingly enriched in having 5'UTR introns. Finally, we analyzed the evolution of 5'UTR introns in non-receptor protein tyrosine kinases (NRTK), and identified a conserved DNA motif enriched within the 5'UTR introns of human NRTKs.

Conclusions
Our results suggest that human 5'UTR introns enhance the expression of some genes in a length-dependent manner. While many 5'UTR introns are likely to be evolving neutrally, their relationship with gene expression and overrepresentation among regulatory genes, taken together, suggest that complex evolutionary forces are acting on this distinct class of introns.
Mucin5B expression by lung alveolar macrophages is increased in long-term smokers
Authors: Sepper Ruth , Prikk Kaiu , Metsis Madis , Sergejeva Svetlana , Pugatsjova Natalia , Bragina Olga , Marran Sirje , Fehniger Thomas E 
Published: May 2012

AbstractMucin5B is expressed in alveolar macrophages in long-term smokers who have developed smoking associated lung diseases.This study investigated the expression of MUC5B by AMs in the lungs of cigarette smokers and nonsmokers. We analyzed MUC5B expression by measuring the levels of apomucin and mRNA in human BALF cells from 50 subjects (20 nonsmokers, 17 patients with CB, and 13 patients with COPD). apoMUC5B was observed in BALF mononuclear cells in 60% of all subjects, but a significantly higher frequency of apoMUC5B+ cells was found in subjects with CB (95% CI, 4.5–24.9) or COPD (95% CI, 6.2–39.6) than in nonsmokers (95% CI, 0.5-2.5). apoMUC5B+ mononuclear cells showed strong expression of CD163, confirming their identity as AMs. MUC5B mRNA expression was detected by ISH in AMs of subjects investigated, and real-time qPCR analysis confirmed MUC5B mRNA expression. In conclusion, MUC5B is expressed in a subset of lung AMs and long-term cigarette smoking may increase the level of MUC5B produced by these cells.
Differential expression of CD14-dependent and independent pathways for chemokine induction regulates neutrophil trafficking in infection
Authors: Metkar Shalaka , Kim Kwang Sik , Silver Jack , Goyert Sanna M 
Published: May 2012

Abstract
Harnessing the CD14-independent pathway for chemokine induction in severe infection leads to early neutrophil recruitment to the site of infection, enhanced bacterial clearance, and survival.
Previous studies have shown that CD14−/− mice are resistant to peritoneal infection with some clinical isolates of Escherichia coli and that this resistance is accompanied by an enhanced ability to clear the bacteria; in contrast, normal mice expressing CD14 fail to clear the bacteria, causing severe sepsis and death. The enhanced clearance in CD14−/− mice is dependent on early neutrophil recruitment to the local foci of infection in the PC. The studies described show that neutrophil recruitment in CD14−/− mice occurs as a result of the local induction of the CXCL1 and CXCL2 chemokines, KC and MIP-2. Although local induction of these chemokines also occurs in normal mice, their effects on neutrophil recruitment to the PC appear to be counterbalanced by very high levels of these chemokines in the blood of normal, but not CD14−/−, mice. Neutrophil recruitment to the PC is also inhibited in normal mice in response to LPS, which also induces high chemokine levels in the blood of normal, but not CD14−/−, mice. However, MPLA, a monophosphorylated derivative of LPS, is able to induce early neutrophil recruitment in normal mice; this is because MPLA, unlike LPS or E. coli, induces MIP-2 and KC in the PC but not in the blood of normal mice. The pretreatment of normal mice with MPLA is able to protect them from a lethal E. coli infection. Thus, stimulation of a local CD14-independent chemokine induction pathway without triggering a systemic CD14-dependent chemokine pathway can protect against severe E. coli infections.
Analysis of incidental focal hypermetabolic uptake in the breast as detected by 18F-FDG PET/CT: clinical significance and differential diagnosis
Authors: Chae Eun Young , Cha Joo Hee , Kim Hak Hee , Shin Hee Jung , Kim Hyun Ji , Oh Ha Yeun , Koh Young Hwan , Moon Dae Hyuk 
Published: May 2012

Background With the widespread use of PET/CT, incidental hypermetabolic foci unrelated to the known malignancy have been described with increasing frequency. Purpose To determine the frequency and clinical significance of incidental focal hypermetabolic uptake in the breast as detected by 18F-FDG PET/CT, and to explore factors differentiating benign and malignant breast uptake. Material and Methods From January 2005 to June 2010, a total of 51,971 whole-body FDG PET/CT examinations were performed in our clinic. After excluding 7254 sets of PET/CT data from patients known to have breast cancer, we retrospectively identified patients showing incidental focal hypermetabolic activity in the breast. Of 44,717 PET/CT examinations conducted on 32,988 patients, we identified 131 patients with no previous known or suspected benign and malignant breast disease. The etiology, mean SUVmax, and diameter of breast lesions were assessed. We also compared the presentation of the lesions on CT, mammography, and ultrasonography. Results Of the 131 patients, 60 were histologically diagnosed with breast lesions, including 32 with malignant and 28 with benign lesions. An additional 11 patients were followed-up for more than 2 years and were clinically considered to have benign lesions. The remaining 60 patients who had neither histologic confirmation nor followed-up for more than 2 years were excluded. Therefore, 71 patients were finally included. The mean SUVmax of 39 benign lesions and 32 malignant lesions were 2.02 ± 1.52 and 3.71 ± 3.83, respectively ( P = 0.0001). At a cut-off value of 2.3, the rate of malignancy and specificity of the mean SUVmax for differentiating benign and malignant breast lesions were 61.3%, 76.3, respectively. The CT data from PET/CT revealed that the mean diameters of benign and malignant lesions were 1.19 ± 0.97 cm and 2.26 ± 1.96 cm, respectively ( P = 0.0009). Conclusion Incidental focal 18F-FDG uptake in the breast as detected by PET/CT was indicative of malignancy in 45% of patients. Both mean SUVmax and diameter were greater for malignant than benign lesions.
Charge Carrier TransportMechanism of ð-Conjugated Organic Materials
Authors: Kim Seong Hyun , Yang Yong Suk , Lee Jung Hun , Lim Sang Chul , Zyung Taehyoung 
Published: May 2012

AbstractThe complex dielectric constants of several π-conjugated materials were measured, and generalized Langevin equation was used to analyze the dielectric behavior in the frequency domain. From the results of the fitting the experimental data using the generalized Langevin equation, we suggest that the charge carriers are electrically screened by the neighboring charges through the structural relaxation, and the carriers are not interact each other. We confirmed that the generalized Langevin equation offers a very good approach to analyze and understand the transport properties of charge carriers in π-conjugated materials.
Community Health Worker Encounter Forms: A Tool to Guide and Document Patient Visits and Worker Performance
Authors: Lemay Celeste A. , Ferguson Warren J. , Hargraves J. Lee 
Published: May 2012

Objectives. We explored the benefits of using community health worker (CHW) encounter forms to collect data on patient interactions and assessed the effectiveness of these forms in guiding and directing interactions. Methods. A 1-page standardized encounter form was developed to document topics discussed during visits with diabetes patients. A portion of the form was designed to be used as a script to guide the interaction and assist patients in setting appropriate self-management goals. Data were also collected via CHW work logs and interviews with CHWs and their supervisors to validate findings. Results. Data were collected for 1198 interactions with 540 patients at 6 community health centers. Self-management goals were set during 62% of encounters. With respect to the most recent self-management goal set, patients who had set a challenging goal were more likely to be in the action stage of change than in other stages. Work logs revealed that CHWs engaged in a number of activities not involving direct patient interactions and thus not captured on encounter forms. Conclusions. Evaluating and monitoring CHWs’ daily activities has been challenging. Encounter forms have great potential for documenting the work of CHWs with patients.
Lessons Learned From a Community–Academic Initiative: The Development of a Core Competency–Based Training for Community–Academic Initiative Community Health Workers
Authors: Ruiz Yumary , Matos Sergio , Kapadia Smiti , Islam Nadia , Cusack Arthur , Kwong Sylvia , Trinh-Shevrin Chau 
Published: May 2012

Objectives. Despite the importance of community health workers (CHWs) in strategies to reduce health disparities and the call to enhance their roles in research, little information exists on how to prepare CHWs involved in community–academic initiatives (CAIs). Therefore, the New York University Prevention Research Center piloted a CAI–CHW training program. Methods. We applied a core competency framework to an existing CHW curriculum and bolstered the curriculum to include research-specific sessions. We employed diverse training methods, guided by adult learning principles and popular education philosophy. Evaluation instruments assessed changes related to confidence, intention to use learned skills, usefulness of sessions, and satisfaction with the training. Results. Results demonstrated that a core competency–based training can successfully affect CHWs’ perceived confidence and intentions to apply learned content, and can provide a larger social justice context of their role and work. Conclusions. This program demonstrates that a core competency–based framework coupled with CAI-research–specific skill sessions (1) provides skills that CAI–CHWs intend to use, (2) builds confidence, and (3) provides participants with a more contextualized view of client needs and CHW roles.