bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statin therapy and multiple sclerosis disability in a population-based cohort
Authors: Soldán M Mateo Paz , Pittock Sean J , Weigand Stephen D , Yawn Barbara P , Rodriguez Moses 
Published: September 2011

Background: Axonal damage and inflammatory demyelination both occur in multiple sclerosis (MS). Some studies suggest that statins, through pleiotropic effects, reduce inflammatory episodes and protect neurons. However, other studies suggest statins have disparate impacts on these pathologic processes. Objective: The objective of this study was to assess disability progression in MS patients receiving statin therapy. Methods: We performed a retrospective medical record review of an established population-based MS prevalence cohort in Olmsted County, Minnesota, comparing disability progression between patients receiving statins and controls. Results: Duration of statin use ranged from 1.9 to 20.3 years with a mean and standard deviation of 6.8 ± 4 years. Years between assessments ranged from 0.6 to 8.2 (75% of patients having intervals >6.4 years). The median (interquartile range) absolute change of disability among the statin group was 0 (0 to +1), compared with +0.5 (0, +1) in the no-statin group. Distributions were not significantly different ( p = 0.39). The mean (standard deviation) absolute change of disability scores among the statin group was +0.69 (+1.49), not significantly different from +0.61 (+1.31) in the no-statin group. Likewise, annualized disability scores did not differ significantly ( p = 0.23). Eighteen (40%) patients worsened by 1.0 or more on Expanded Disability Status Scale (EDSS) in the statin group and 36 (40%) in the no-statin group ( p = 0.85, chi-squared test). Conclusions: In this cohort, disability progression did not differ between those receiving statin therapy and controls. These findings support the hypothesis that statins, in doses currently prescribed for hyperlipidemia, do not affect the long-term course of MS.
A novel pro-lymphangiogenic function for Th17/IL-17
Authors: Chauhan Sunil K. , Jin Yiping , Goyal Sunali , Lee Hyun Soo , Fuchsluger Thomas A. , Lee Hyung Keun , Dana Reza 
Published: September 2011

AbstractTh17 cells, in addition to their proinflammatory functions, have been recognized as potent inducers of angiogenesis in autoimmune diseases and malignancies. In the present study, we demonstrate distinct mechanisms by which IL-17 induces lymphangiogenesis. Using the mouse cornea micropocket and cell culture assays, our data demonstrate that IL-17 directly promotes growth of lymphatic vessels by inducing increased expression of prolymphangiogenic VEGF-D and proliferation of lymphatic endothelial cells. However, IL-17–induced growth of blood vessels is primarily mediated through IL-1β secretion by IL-17–responsive cells. Furthermore, in vivo blockade of IL-17 in a preclinical model of Th17-dominant autoimmune ocular disease demonstrates a significant reduction in the corneal lymphangiogenesis and in the progression of clinical disease. Taken together, our findings demonstrate a novel prolymphangiogenic function for Th17/IL-17, indicating that IL-17 can promote the progression and amplification of immunity in part through its induction of lymphangiogenesis.
Enhanced levels of both the membrane-bound and soluble forms of IgM Fc receptor (FcμR) in patients with chronic lymphocytic leukemia
Authors: Li Fu Jun , Kubagawa Yoshiki , McCollum Matthew K. , Wilson Landon , Motohashi Tomoko , Bertoli Luigi F. , Barton James C. , Barnes Stephen , Davis Randall S. , Kubagawa Hiromi 
Published: September 2011

AbstractThe association of an IgM-Fc receptor (FcμR) with chronic lymphocytic leukemia (CLL) was suggested more than 30 years ago, but its authenticity has never been formally addressed. We examined the expression of the recently identified FcμR by B and T cells in CLL patients using receptor-specific monoclonal antibodies. CLL B cells (CD5+/CD19+) expressed much higher levels of FcμR on their cell surface than B cells from healthy donors. Such enhanced expression was more evident in immunoglobulin heavy chain variable region (IGHV)–mutated, CD38− or early Rai-stage CLL than in IGHV-unmutated, CD38+, or advanced Rai-stage CLL. Intriguingly, surface FcμR levels also were significantly elevated in the non-CLL B cells (CD5−/CD19+) and T cells (CD5+/CD19−), especially in IGHV-mutated CLL. CLL patients also had high serum titers of FcμR compared with healthy donors, and serum FcμR levels correlated significantly with circulating lymphocyte numbers but not with the IGHV mutation status or Rai stage. The serum FcμR was resolved as an ∼ 40-kDa protein, distinct from the cell surface FcμR of ∼ 60 kDa, and it was produced by both CLL B and non-CLL B cells. Mass spectrometric analysis revealed that the serum FcμR is a soluble form of the receptor encoded by an alternatively spliced FcμR transcript. These findings indicate enhanced levels of both membrane-bound and soluble forms of FcμR in CLL patients.
Major histocompatibility complex class II expression deficiency caused by a RFXANK founder mutation: a survey of 35 patients
Authors: Ouederni Monia , Vincent Quentin B. , Frange Pierre , Touzot Fabien , Scerra Sami , Bejaoui Mohamed , Bousfiha Aziz , Levy Yves , Lisowska-Grospierre Barbara , Canioni Danielle , Bruneau Julie , Debré Marianne , Blanche Stéphane , Abel Laurent , Casanova Jean-Laurent , Fischer Alain , Picard Capucine 
Published: September 2011

AbstractInherited deficiency of major histocompatibility complex (MHC) class II molecules impairs antigen presentation to CD4+ T cells and results in combined immunodeficiency (CID). Autosomal-recessive mutations in the RFXANK gene account for two-thirds of all cases of MHC class II deficiency. We describe here the genetic, clinical, and immunologic features of 35 patients from 30 unrelated kindreds from North Africa sharing the same RFXANK founder mutation, a 26-bp deletion called I5E6-25_I5E6 + 1), and date the founder event responsible for this mutation in this population to approximately 2250 years ago (95% confidence interval [CI]: 1750-3025 years). Ten of the 23 patients who underwent hematopoietic stem cell transplantation (HSCT) were cured, with the recovery of almost normal immune functions. Five of the patients from this cohort who did not undergo HSCT had a poor prognosis and eventually died (at ages of 1-17 years). However, 7 patients who did not undergo HSCT (at ages of 6-32 years) are still alive on Ig treatment and antibiotic prophylaxis. RFXANK deficiency is a severe, often fatal CID for which HSCT is the only curative treatment. However, some patients may survive for relatively long periods if multiple prophylactic measures are implemented.
Quaternary organization of GPIb-IX complex and insights into Bernard-Soulier syndrome revealed by the structures of GPIbβ and a GPIbβ/GPIX chimera
Authors: McEwan Paul A. , Yang Wenjun , Carr Katherine H. , Mo Xi , Zheng Xiaofeng , Li Renhao , Emsley Jonas 
Published: September 2011

AbstractPlatelet GPIb-IX receptor complex has 3 subunits GPIbα, GPIbβ, and GPIX, which assemble with a ratio of 1:2:1. Dysfunction in surface expression of the complex leads to Bernard-Soulier syndrome. We have crystallized the GPIbβ ectodomain (GPIbβE) and determined the structure to show a single leucine-rich repeat with N- and C-terminal disulphide-bonded capping regions. The structure of a chimera of GPIbβE and 3 loops (a,b,c) taken from the GPIX ectodomain sequence was also determined. The chimera (GPIbβEabc), but not GPIbβE, forms a tetramer in the crystal, showing a quaternary interface between GPIbβ and GPIX. Central to this interface is residue Tyr106 from GPIbβ, which inserts into a pocket generated by 2 loops (b,c) from GPIX. Mutagenesis studies confirmed this interface as a valid representation of interactions between GPIbβ and GPIX in the full-length complex. Eight GPIbβ missense mutations identified from patients with Bernard-Soulier syndrome were examined for changes to GPIb-IX complex surface expression. Two mutations, A108P and P74R, were found to maintain normal secretion/folding of GPIbβE but were unable to support GPIX surface expression. The close structural proximity of these mutations to Tyr106 and the GPIbβE interface with GPIX indicates they disrupt the quaternary organization of the GPIb-IX complex.
Mouse models of MYH9-related disease: mutations in nonmuscle myosin II-A
Authors: Zhang Yingfan , Conti Mary Anne , Malide Daniela , Dong Fan , Wang Aibing , Shmist Yelena A. , Liu Chengyu , Zerfas Patricia , Daniels Mathew P. , Chan Chi-Chao , Kozin Elliot , Kachar Bechara , Kelley Michael J. , Kopp Jeffrey B. , Adelstein Robert S. 
Published: September 2011

AbstractWe have generated 3 mouse lines, each with a different mutation in the nonmuscle myosin II-A gene, Myh9 (R702C, D1424N, and E1841K). Each line develops MYH9-related disease similar to that found in human patients. R702C mutant human cDNA fused with green fluorescent protein was introduced into the first coding exon of Myh9, and D1424N and E1841K mutations were introduced directly into the corresponding exons. Homozygous R702C mice die at embryonic day 10.5-11.5, whereas homozygous D1424N and E1841K mice are viable. All heterozygous and homozygous mutant mice show macrothrombocytopenia with prolonged bleeding times, a defect in clot retraction, and increased extramedullary megakaryocytes. Studies of cultured megakaryocytes and live-cell imaging of megakaryocytes in the BM show that heterozygous R702C megakaryocytes form fewer and shorter proplatelets with less branching and larger buds. The results indicate that disrupted proplatelet formation contributes to the macrothrombocytopenia in mice and most probably in humans. We also observed premature cataract formation, kidney abnormalities, including albuminuria, focal segmental glomerulosclerosis and progressive kidney disease, and mild hearing loss. Our results show that heterozygous mice with mutations in the myosin motor or filament-forming domain manifest similar hematologic, eye, and kidney phenotypes to humans with MYH9-related disease.
Gut flora enhance bacterial clearance in lung through toll-like receptors 4
Authors: Tsay Tzyy-Bin , Yang Ming-Chieh , Chen Pei-Hsuan , Hsu Ching-Mei , Chen Lee-Wei 
Published: September 2011

AbstractBackgroundThe influence of the gut flora on lung inflammatory reaction against bacterial challenge remains undefined. This study was designed to investigate whether gut flora enhances lung defense againstE.colipneumonia through TLR4 signaling.MethodsC3H/HeN (WT) mice and C3H/HeJ (TLR4 deficient) mice were treated with antibiotics in drinking water for 4 weeks to deplete gut commensal microflora. At week 3, drinking water was supplemented with lipopolysaccharide (LPS); a ligand for TLR4, to trigger TLRs in intestinal tract. At the end of 4thweek,E.coliwas injected to trachea to induceE.colipneumonia.ResultsWe found that commensal depletion by antibiotic pretreatment beforeE.colipneumonia challenge induced a 30% decrease of MPO activity in the lung, a significant decrease of bacterial killing activity of alveolar macrophage, and bacterial counts in C3H/HeN mice but not in C3H/HeJ (TLR4 deficient) mice. LPS, a TLR4 ligand, supplementation during antibiotic pretreatment reversed these effects and decreasedE.colipneumonia-induced mortality in C3H/HeN mice. Furthermore, commensal depletion induced a suppression of NF-κB DNA binding activity and an increase of KC, MIP-2, IL-1β expression in the lung in C3H/HeN mice but not in C3H/HeJ mice.ConclusionsTaken together with that commensal depletion increasedE.colipneumonia-induced mortality and LPS supplementation decreased it, we conclude that gut flora enhances bacterial clearance againstE.colipneumonia through TLR4.
High frequency chest wall oscillation for asthma and chronic obstructive pulmonary disease exacerbations: a randomized sham-controlled clinical trial
Authors: Mahajan Amit K , Diette Gregory B , Hatipoğlu Umur , Bilderback Andrew , Ridge Alana , Harris Vanessa Walker , Dalapathi Vijay , Badlani Sameer , Lewis Stephanie , Charbeneau Jeff T , Naureckas Edward T , Krishnan Jerry A 
Published: September 2011

Abstract

Background
High frequency chest wall oscillation (HFCWO) is used for airway mucus clearance. The objective of this study was to evaluate the use of HFCWO early in the treatment of adults hospitalized for acute asthma or chronic obstructive pulmonary disease (COPD).

Methods
Randomized, multi-center, double-masked phase II clinical trial of active or sham treatment initiated within 24 hours of hospital admission for acute asthma or COPD at four academic medical centers. Patients received active or sham treatment for 15 minutes three times a day for four treatments. Medical management was standardized across groups. The primary outcomes were patient adherence to therapy after four treatments (minutes used/60 minutes prescribed) and satisfaction. Secondary outcomes included change in Borg dyspnea score (≥ 1 unit indicates a clinically significant change), spontaneously expectorated sputum volume, and forced expired volume in 1 second.

Results
Fifty-two participants were randomized to active (n = 25) or sham (n = 27) treatment. Patient adherence was similarly high in both groups (91% vs. 93%; p = 0.70). Patient satisfaction was also similarly high in both groups. After four treatments, a higher proportion of patients in the active treatment group had a clinically significant improvement in dyspnea (70.8% vs. 42.3%, p = 0.04). There were no significant differences in other secondary outcomes.

Conclusions
HFCWO is well tolerated in adults hospitalized for acute asthma or COPD and significantly improves dyspnea. The high levels of patient satisfaction in both treatment groups justify the need for sham controls when evaluating the use of HFCWO on patient-reported outcomes. Additional studies are needed to more fully evaluate the role of HFCWO in improving in-hospital and post-discharge outcomes in this population.

Trial Registration
ClinicalTrials.gov: NCT00181285
A global view of porcine transcriptome in three tissues from a full-sib pair with extreme phenotypes in growth and fat deposition by paired-end RNA sequencing
Authors: Chen Congying , Ai Huashui , Ren Jun , Li Wanbo , Li Pinghua , Qiao Ruimin , Ouyang Jing , Yang Ming , Ma Junwu , Huang Lusheng 
Published: September 2011

Abstract

Background
Elucidation of the pig transcriptome is essential for interpreting functional elements of the genome and understanding the genetic architecture of complex traits such as fat deposition, metabolism and growth.

Results
Here we used massive parallel high-throughput RNA sequencing to generate a high-resolution map of the porcine mRNA and miRNA transcriptome in liver, longissimus dorsi and abdominal fat from two full-sib F2 hybrid pigs with segregated phenotypes on growth, blood physiological and biochemical parameters, and fat deposition. We obtained 8,508,418-10,219,332 uniquely mapped reads that covered 78.0% of the current annotated transcripts and identified 48,045-122,931 novel transcript fragments, which constituted 17,085-29,499 novel transcriptional active regions in six tested samples. We found that about 18.8% of the annotated genes showed alternative splicing patterns, and alternative 3' splicing is the most common type of alternative splicing events in pigs. Cross-tissue comparison revealed that many transcriptional events are tissue-differential and related to important biological functions in their corresponding tissues. We also detected a total of 164 potential novel miRNAs, most of which were tissue-specifically identified. Integrated analysis of genome-wide association study and differential gene expression revealed interesting candidate genes for complex traits, such as IGF2, CYP1A1, CKM and CES1 for heart weight, hemoglobin, pork pH value and serum cholesterol, respectively.

Conclusions
This study provides a global view of the complexity of the pig transcriptome, and gives an extensive new knowledge about alternative splicing, gene boundaries and miRNAs in pigs. Integrated analysis of genome wide association study and differential gene expression allows us to find important candidate genes for porcine complex traits.
Serotype and genotype analysis of dengue virus by sequencing followed by phylogenetic analysis using samples from three mini outbreaks-2007-2009 in Pakistan
Authors: Fatima Zareen , Idrees Muhammad , Bajwa Mohammad A , Tahir Zarfishan , Ullah Obaid , Zia Muhammad Q , Hussain Abrar , Akram Madiha , Khubaib Bushra , Afzal Samia , Munir Saira , Saleem Sana , Rauff Bisma , Badar Sadaf , Naudhani Mahrukh , Butt Sadia , Aftab Mahwish , Ali Liaqat , Ali Muhammad 
Published: September 2011

Abstract

Background
Since the first reported outbreak of dengue hemorrhagic fever in Pakistan, several mini outbreaks have erupted in the region. Dengue virus serotype 3 (DEN-3) was first documented in 2005 outbreak in Karachi. Reports show that serotype 3 is prevalent in Lahore since 2008. Serotype 2 (DEN-2) is the major circulating serotype in Pakistan as it is documented since 1994. We have conducted a detailed study of three outbreaks of dengue virus infection that occurred in years 2007, 2008 and 2009 in Lahore by using molecular techniques such as PCR and nucleotide sequencing of the C-prM gene junction of Dengue virus.

Results
Through the analysis of 114 serum samples collected over the period of three years (2007-2009), total 20 patients were found to be infected with dengue virus. In year 2007, four were positive for serotype 2 and one sample was positive for serotype DEN-3. In 2008, five samples had concurrent infection with serotypes DEN-2 and DEN-3 while three samples were infected only with serotype DEN-2. In year 2009, one sample had concurrent infection with serotypes DEN-2 and DEN-3 while six were positive for serotype DEN-2 only.

Conclusions
Our study showed that serotype DEN-2 was dominant in positive samples of dengue virus infection collected during the period of three years (2007-2009). The other serotype present was serotype DEN-3. Genotypes of serotype DEN-2 and serotype DEN-3 were subtype IV and subtype III, respectively.
A preliminary investigation assessing the viability of classifying hand postures in seniors
Authors: Tavakolan Mojgan , Xiao Zhen Gang , Menon Carlo 
Published: September 2011

AbstractBackgroundFear of frailty is a main concern for seniors. Surface electromyography (sEMG) controlled assistive devices for the upper extremities could potentially be used to augment seniors' force while training their muscles and reduce their fear of frailty. In fact, these devices could both improve self confidence and facilitate independent leaving in domestic environments. The successful implementation of sEMG controlled devices for the elderly strongly relies on the capability of properly determining seniors' actions from their sEMG signals. In this research we investigated the viability of classifying hand postures in seniors from sEMG signals of their forearm muscles.MethodsNineteen volunteers, including seniors (70 years old in average) and young people (27 years old in average), participated in this study and sEMG signals from four of their forearm muscles (i.e. Extensor Digitorum, Palmaris Longus, Flexor Carpi Ulnaris and Extensor Carpi Radialis) were recorded. The feature vectors were built by extracting features from each channel of sEMG including autoregressive (AR) model coefficients, waveform length and root mean square (RMS). Multi-class support vector machines (SVM) was used as a classifier to distinguish between fifteen different essential hand gestures including finger pinching.ResultsClassification of hand gestures both in the pronation and supination positions of the arm was possible. Classified hand gestures were: rest, ulnar deviation, radial deviation, grasp and four different finger pinching configurations. The obtained average classification accuracy was 90.6% for the seniors and 97.6% for the young volunteers.ConclusionsThe obtained results proved that the pattern recognition of sEMG signals in seniors is feasible for both pronation and supination positions of the arm and the use of only four EMG channel is sufficient. The outcome of this study therefore validates the hypothesis that, although there are significant neurological and physical changes occurring in humans while ageing, sEMG controlled hand assistive devices could potentially be used by the older people.
Characteristics of Chinese patients with cough in primary care centre
Authors: Hong Qunying , Bai Chunxue , Wang Xiangdong 
Published: September 2011

Abstract

Background
Cough is one of the most common respiratory symptoms and is well characterized in specialized cough clinics with high success rates of diagnosis and treatment. However, there is a paucity of data regarding cough in primary care settings. The present study aimed at investigating clinical epidemiology of cough through a national study of two questionnaire surveys sent to primary care physicians in China.

Methods
Approximately 18,000 subjects recruited were having daytime or night symptoms of cough and diagnoses of respiratory disease from February 2005 to April 2006 as Survey 1 and from June 2007 to December 2007 as Survey 2. Patients suffering from respiratory malignancy, hyperthyroidism, hypertension, heart disease, diabetes, severe hypohepatia or renal dysfunction, pregnancy, possible pregnancy or lactation, neutropenia were not eligible. Information regarding demography, history of allergies, symptomatic profile, treatment and curative effects for cough was elicited.

Results
8216 questionnaires were collected in Survey 1 and 9711 in Survey 2. The mean values of ages were 25.7 and 22.3 years old, respectively. Symptoms included expectoration (74% and 76%), wheeze (59% and 74%), breathlessness (22% and 26%), chest pain (9% and 13%) and fever (15% and 18%). About 15% and 23% patients had hypersusceptibility, of whom 6% to 17% had a family history. More than 50% of the cases had histories of allergic rhinitis, asthma, conjunctivitis or atopic dermatitis. Asthma, COPD, and bronchitis were dominant etiologies of cough. Procaterol or the combination of antibiotics and steroids were used as the treatment.

Conclusion
Causes and outcomes of cough differed with ages and time in this particular national study, while successful and precise diagnosis and management of cough in primary care settings need to be further improved in China.
A Cost Effective Triaxial Test Method for Unsaturated Soils
Authors: Burrage R. E. , Anderson J. B. , Pando M. A. , Ogunro V. O. , Cottingham M. A. 
Published: September 2011

AbstractThis paper describes a test method to measure the shear strength of unsaturated soils using standard triaxial equipment with minor, low-cost modifications. The method is based on using the axis translation technique in a standard triaxial testing apparatus with a base pedestal slightly modified to accommodate a high-air-entry ceramic disk. The testing apparatus and procedure are described. The aim of the proposed test setup was to limit the modifications of the standard triaxial setup within a reasonable budget to make the method accessible and attractive to researchers and practitioners that may otherwise not be able to afford the testing devices commonly used in the field of unsaturated soil mechanics. Thus, the paper discusses the effectiveness of the proposed test method, and also discusses the potential limitations that may exist due to some of the simplifications used in this methodology. The proposed methodology was used to evaluate the shear strength of residual soils at the Auburn National Geotechnical Experimentation Site. The shear strength parameters obtained for the Auburn unsaturated soils were compared to previous tests conducted in similar soils and proved to be reasonably accurate.