bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-CPAP therapies in obstructive sleep apnoea
Authors: Randerath W.J. , Verbraecken J. , Andreas S. , Bettega G. , Boudewyns A. , Hamans E. , Jalbert F. , Paoli J.R. , Sanner B. , Smith I. , Stuck B.A. , Lacassagne L. , Marklund M. , Maurer J.T. , Pepin J.L. , Valipour A. , Verse T. , Fietze I. 
Published: March 2011

In view of the high prevalence and the relevant impairment of patients with obstructive sleep apnoea syndrome (OSAS) lots of methods are offered which promise definitive cures for or relevant improvement of OSAS.This report summarises the efficacy of alternative treatment options in OSAS.An interdisciplinary European Respiratory Society task force evaluated the scientific literature according to the standards of evidence-based medicine.Evidence supports the use of mandibular advancement devices in mild to moderate OSAS. Maxillomandibular osteotomy seems to be as efficient as continuous positive airway pressure (CPAP) in patients who refuse conservative treatment. Distraction osteogenesis is usefully applied in congenital micrognathia or midface hypoplasia. There is a trend towards improvment after weight reduction. Positional therapy is clearly inferior to CPAP and long-term compliance is poor. Drugs, nasal dilators and apnoea triggered muscle stimulation cannot be recommended as effective treatments of OSAS at the moment. Nasal surgery, radiofrequency tonsil reduction, tongue base surgery, uvulopalatal flap, laser midline glossectomy, tongue suspension and genioglossus advancement cannot be recommended as single interventions. Uvulopalatopharyngoplasty, pillar implants and hyoid suspension should only be considered in selected patients and potential benefits should be weighed against the risk of long-term side-effects. Multilevel surgery is only a salvage procedure for OSA patients.
Effect of different asthma treatments on risk of cold-related exacerbations
Authors: Reddel H.K. , Jenkins C. , Quirce S. , Sears M.R. , Bateman E.D. , O’Byrne P.M. , Humbert M. , Buhl R. , Harrison T. , Brusselle G.G. , Thorén A. , Sjöbring U. , Peterson S. , Östlund O. , Eriksson G.S. 
Published: March 2011

Common colds often trigger asthma exacerbations. The present study compared cold-related severe exacerbations during budesonide/formoterol maintenance and reliever therapy, and different regimens of maintenance inhaled corticosteroids (ICS), with or without long-acting β2-agonists (LABA), and with as-needed short-acting β2-agonists (SABA) or LABA.Reported colds and severe exacerbations (defined by oral corticosteroid use and/or hospitalisation/emergency room visit) were assessed for 12,507 patients during 6–12 months of double-blind treatment. Exacerbations occurring ≤14 days after onset of reported colds were analysed by a Poisson model.The incidence of colds was similar across treatments. Asthma symptoms and reliever use increased during colds. Budesonide/formoterol maintenance and reliever therapy reduced severe cold-related exacerbations by 36%versuspooled comparators plus SABA (rate ratio (RR) 0.64; p=0.002), and for individual treatment comparisons, by 52%versusthe same maintenance dose of ICS/LABA (RR 0.48; p<0.001); there were nonsignificant reductionsversushigher maintenance doses of ICS or ICS/LABA (RR 0.83 and 0.72, respectively). As-needed LABA did not reduce cold-related exacerbationsversusas-needed SABA (RR 0.96).Severe cold-related exacerbations were reduced by budesonide/formoterol maintenance and reliever therapy compared with ICS with or without LABA and with as-needed SABA. Subanalyses suggested the importance of the ICS component in reducing cold-related exacerbations. Future studies should document the cause of exacerbations, in order to allow identification of different treatment effects.
TGFβ1 enhances MAD1 expression and stimulates promoter-bound Pol II phosphorylation: basic functions of C/EBP, SP and SMAD3 transcription factors
Authors: Hein Nadine , Jiang Kan , Cornelissen Christian , Lüscher Bernhard 
Published: March 2011

Abstract

Background
The MAD1 protein, a member of the MYC/MAX/MAD network of transcriptional regulators, controls cell proliferation, differentiation and apoptosis. MAD1 functions as a transcriptional repressor, one direct target gene being the tumor suppressor PTEN. Repression of this gene is critical to mediate the anti-apoptotic function of MAD1. Under certain conditions it also antagonizes the functions of the oncoprotein MYC. Previous studies have demonstrated that MAD1 expression is controlled by different cytokines and growth factors. Moreover we have recently demonstrated that the MAD1 promoter is controlled by the cytokine granulocyte colony-stimulating factor (G-CSF) through the activation of STAT3, MAP kinases and C/EBP transcription factors.

Results
We observed that in addition to G-CSF, the cytokine transforming growth factor β (TGFβ1) rapidly induced the expression of MAD1 mRNA and protein in promyelocytic tumor cells. Moreover we found that C/EBP and SP transcription factors cooperated in regulating the expression of MAD1. This cooperativity was dependent on the respective binding sites in the proximal promoter, with the CCAAT boxes being bound by C/EBPα/β heterodimers. Both C/EBP and SP transcription factors bound constitutively to DNA without obvious changes in response to TGFβ1. In addition SMAD3 stimulated the MAD1 reporter, cooperated with C/EBPα and was bound to the core promoter region. Thus SMAD3 appears to be a potential link between TGFβ1 signaling and C/EBP regulated promoter activity. Moreover TGFβ1 stimulated the phosphorylation of polymerase II at serine 2 and its progression into the gene body, consistent with enhanced processivity.

Conclusions
Our findings suggest that C/EBP and SP factors provide a platform of transcription factors near the core promoter of the MAD1 gene that participate in mediating signal transduction events emanating from different cytokine receptors. SMAD3, a target of TGFβ1 signaling, appears to be functionally relevant. We suggest that a key event induced by TGFβ1 at the MAD1 promoter is the recruitment or activation of cofactors, possibly in complex with C/EBP, SP, and SMAD3 transcriptional regulators, that control polymerase activity.
Introgression potential between safflower (Carthamus tinctorius) and wild relatives of the genus Carthamus
Authors: Mayerhofer Marion , Mayerhofer Reinhold , Topinka Deborah , Christianson Jed , Good Allen G 
Published: March 2011

Abstract

Background
Safflower, Carthamus tinctorius, is a thistle that is grown commercially for the production of oil and birdseed and recently, as a host for the production of transgenic pharmaceutical proteins. C. tinctorius can cross with a number of its wild relatives, creating the possibility of gene flow from safflower to weedy species. In this study we looked at the introgression potential between different members of the genus Carthamus, measured the fitness of the parents versus the F1 hybrids, followed the segregation of a specific transgene in the progeny and tried to identify traits important for adaptation to different environments.

Results
Safflower hybridized and produced viable offspring with members of the section Carthamus and species with chromosome numbers of n = 10 and n = 22, but not with n = 32. The T-DNA construct of a transgenic C. tinctorius line was passed on to the F1 progeny in a Mendelian fashion, except in one specific cross, where it was deleted at a frequency of approximately 21%. Analyzing fitness and key morphological traits like colored seeds, shattering seed heads and the presence of a pappus, we found no evidence of hybrid vigour or increased weediness in the F1 hybrids of commercial safflower and its wild relatives.

Conclusion
Our results suggest that hybridization between commercial safflower and its wild relatives, while feasible in most cases we studied, does not generate progeny with higher propensity for weediness.
Anal infections with concomitant Chlamydia trachomatisgenotypes among men who have sex with men in Amsterdam, the Netherlands
Authors: Quint Koen D , Bom Reinier JM , Quint Wim GV , Bruisten Sylvia M , van der Loeff Maarten F Schim , Morré Servaas A , de Vries Henry JC 
Published: March 2011

Abstract

Background
Lymphogranuloma venereum (LGV) proctitis is caused by Chlamydia trachomatis (Ct) genotype L and is endemic among men who have sex with men (MSM) in western society. Genotype L infections need to be distinguished from non-LGV (genotypes A-K) Ct infections since they require prolonged antibiotic treatment. For this purpose, an in-house developed pmpH based LGV polymerase chain reaction (PCR) test is used at the Amsterdam STI outpatient clinic. We investigated retrospectively the anal Ct genotype distribution, and the frequency of concomitant genotype infections in MSM infected with LGV and non-LGV Ct infections. To detect concomitant Ct genotype infections, the pmpH LGV PCR and genoTyping Reverse Hybridization Assay (Ct-DT RHA) were used.

Methods
A total of 201 Ct positive rectal swabs from MSM were selected, which were previously diagnosed as either LGV (n = 99) or non-LGV Ct infection (n = 102) according to the algorithm of Ct detection by the commercially available Aptima Combo 2 assay followed by an in-house pmpH LGV PCR. The samples were retested with the commercially available Ct-DT RHA, which differentiates between 14 major genotypes and is able to detect concomitant Ct genotypes.

Results
Excellent genotyping agreement was observed between the Ct-DT RHA and the pmpH LGV PCR (Kappa = 0.900, 95%CI = 0.845-0.955, McNemar's p = 1.000). A concomitant non-LGV genotype was detected in 6/99 (6.1%) LGV samples. No additional LGV infections were observed with the Ct-DT RHA among the non-LGV Ct group. In the non-LGV group genotype G/Ga (34.3%) was seen most frequent, followed by genotype D/Da (22.5%) and genotype J (13.7%). All LGV infections were caused by genotype L2.

Conclusions
Concomitant non-LGV genotypes do not lead to missed LGV proctitis diagnosis. The pmpH LGV PCR displayed excellent agreement with the commercially available Ct-DT genotyping RHA test. The genotypes G/Ga, D/Da and J were the most frequent non-LGV Ct strains in MSM.
Inhibin B and anti-Müllerian hormone as markers of gonadal function after hematopoietic cell transplantation during childhood
Authors: Laporte Sylvie , Couto-Silva Ana-Claudia , Trabado Séverine , Lemaire Pierre , Brailly-Tabard Sylvie , Espérou Hélène , Michon Jean , Baruchel André , Fischer Alain , Trivin Christine , Brauner Raja 
Published: March 2011

Abstract

Background
It is difficult to predict the reproductive capacity of children given hematopoietic cell transplantation (HCT) before pubertal age because the plasma concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are not informative and no spermogram can be done.

Methods
We classified the gonadal function of 38 boys and 34 girls given HCT during childhood who had reached pubertal age according to their pubertal development and FSH and LH and compared this to their plasma inhibin B and anti-Müllerian hormone (AMH).

Results
Ten (26%) boys had normal testicular function, 16 (42%) had isolated tubular failure and 12 (32%) also had Leydig cell failure. All 16 boys given melphalan had tubular failure. AMH were normal in 25 patients and decreased in 6, all of whom had increased FSH and low inhibin B.
Seven (21%) girls had normal ovarian function, 11 (32%) had partial and 16 (47%) complete ovarian failure. 7/8 girls given busulfan had increased FSH and LH and 7/8 had low inhibin B. AMH indicated that ovarian function was impaired in all girls.
FSH and inhibin B were negatively correlated in boys (P < 0.0001) and girls (P = 0.0006). Neither the age at HCT nor the interval between HCT and evaluation influenced gonadal function.

Conclusion
The concordance between FSH and inhibin B suggests that inhibin B may help in counselling at pubertal age. In boys, AMH were difficult to use as they normally decrease when testosterone increases at puberty. In girls, low AMH suggest that there is major loss of primordial follicles.
Targeting of human interleukin-12B by small hairpin RNAs in xenografted psoriatic skin
Authors: Bak Rasmus O , Stenderup Karin , Rosada Cecilia , Petersen Line B , Moldt Brian , Dagnæs-Hansen Frederik , Jakobsen Maria , Kamp Søren , Jensen Thomas G , Dam Tomas N , Mikkelsen Jacob Giehm 
Published: March 2011

Abstract

Background
Psoriasis is a chronic inflammatory skin disorder that shows as erythematous and scaly lesions. The pathogenesis of psoriasis is driven by a dysregulation of the immune system which leads to an altered cytokine production. Proinflammatory cytokines that are up-regulated in psoriasis include tumor necrosis factor alpha (TNFα), interleukin-12 (IL-12), and IL-23 for which monoclonal antibodies have already been approved for clinical use. We have previously documented the therapeutic applicability of targeting TNFα mRNA for RNA interference-mediated down-regulation by anti-TNFα small hairpin RNAs (shRNAs) delivered by lentiviral vectors to xenografted psoriatic skin. The present report aims at targeting mRNA encoding the shared p40 subunit (IL-12B) of IL-12 and IL-23 by cellular transduction with lentiviral vectors encoding anti-IL12B shRNAs.

Methods
Effective anti-IL12B shRNAs are identified among a panel of shRNAs by potency measurements in cultured cells. The efficiency and persistency of lentiviral gene delivery to xenografted human skin are investigated by bioluminescence analysis of skin treated with lentiviral vectors encoding the luciferase gene. shRNA-expressing lentiviral vectors are intradermally injected in xenografted psoriatic skin and the effects of the treatment evaluated by clinical psoriasis scoring, by measurements of epidermal thickness, and IL-12B mRNA levels.

Results
Potent and persistent transgene expression following a single intradermal injection of lentiviral vectors in xenografted human skin is reported. Stable IL-12B mRNA knockdown and reduced epidermal thickness are achieved three weeks after treatment of xenografted psoriatic skin with lentivirus-encoded anti-IL12B shRNAs. These findings mimick the results obtained with anti-TNFα shRNAs but, in contrast to anti-TNFα treatment, anti-IL12B shRNAs do not ameliorate the psoriatic phenotype as evaluated by semi-quantitative clinical scoring and by immunohistological examination.

Conclusions
Our studies consolidate the properties of lentiviral vectors as a tool for potent gene delivery and for evaluation of mRNA targets for anti-inflammatory therapy. However, in contrast to local anti-TNFα treatment, the therapeutic potential of targeting IL-12B at the RNA level in psoriasis is questioned.
Oxaliplatin long-circulating liposomes improved therapeutic index of colorectal carcinoma
Authors: Yang Chuang , Liu Hai Z , Fu Zhong X , Lu Wei D 
Published: March 2011

Abstract

Background
Cytotoxic drugs are non-selective between normal and pathological tissue, and this poses a challenge regarding the strategy for treatment of tumors. To achieve sufficient antitumor activity for colorectal carcinoma, optimization of the therapeutic regimen is of great importance. We investigated the ability of oxaliplatin long-circulating liposomes (PEG-liposomal L-oHP) to provide an improved therapeutic index of colorectal carcinoma.

Results
We determined that PEG- liposomes conjugated with cells at 2 h, with a mean fluorescence intensity that was enhanced upon extended induction time. The PEG-liposomal L-oHP induced a significant apoptotic response as compared with free L-oHP, 23.21% ± 3.38% vs. 16.85% ± 0.98%, respectively. Fluorescence imaging with In-Vivo Imaging demonstrated that PEG- liposomes specifically targeted tumour tissue. After intravenous injections of PEG-liposomal L-oHP or free L-oHP, the tumour volume suppression ratio was 26.08% ± 12.43% and 18.19% ± 7.09%, respectively, the percentage increased life span (ILS%) was 45.36% and 76.19%, respectively, and Bcl-2, Bax mRNA and protein expression in tumour tissue was 0.27-fold vs. 0.88-fold and 1.32-fold vs. 1.61-fold compared with free L-oHP, respectively.

Conclusion
The PEG-liposomal L-oHP exhibited a tendency to target tumour tissue and demonstrated a significantly greater impact on apoptosis compared to free oxaliplatin.
Delayed β-cell response and glucose intolerance in young women with Turner syndrome
Authors: Hjerrild Britta E , Holst Jens J , Juhl Claus B , Christiansen Jens S , Schmitz Ole , Gravholt Claus H 
Published: March 2011

Abstract

Background
To investigate glucose homeostasis in detail in Turner syndrome (TS), where impaired glucose tolerance (IGT) and type 2 diabetes are frequent.

Methods
Cross sectional study of women with Turner syndrome (TS)(n = 13) and age and body mass index matched controls (C) (n = 13), evaluated by glucose tolerance (oral and intravenous glucose tolerance test (OGTT and IVGTT)), insulin sensitivity (hyperinsulinemic, euglycemic clamp), beta-cell function (hyperglycaemic clamp, arginine and GLP-1 stimulation) and insulin pulsatility.

Results
Fasting glucose and insulin levels were similar. Higher glucose responses was seen in TS during OGTT and IVGTT, persisting after correction for body weight or muscle mass, while insulin responses were similar in TS and C, despite the higher glucose level in TS, leading to an insufficient increase in insulin response during dynamic testing. Insulin sensitivity was comparable in the two groups (TS vs. control: 8.6 ± 1.8 vs. 8.9 ± 1.8 mg/kg*30 min; p = 0.6), and the insulin responses to dynamic β-cell function tests were similar. Insulin secretion patterns examined by deconvolution analysis, approximate entropy, spectral analysis and autocorrelation analysis were similar. In addition we found low IGF-I, higher levels of cortisol and norepinephrine and an increased waist-hip ratio in TS.

Conclusions
Young normal weight TS women show significant glucose intolerance in spite of normal insulin secretion during hyperglycaemic clamping and normal insulin sensitivity. We recommend regularly testing for diabetes in TS.

Trial Registration
Registered with http://clinicaltrials.com, ID nr: NCT00419107
Short-chain fatty acid level and field cancerization show opposing associations with enteroendocrine cell number and neuropilin expression in patients with colorectal adenoma
Authors: Yu Danny CW , Bury Jonathan P , Tiernan James , Waby Jennifer S , Staton Carolyn A , Corfe Bernard M 
Published: March 2011

Abstract

Background
Previous reports have suggested that the VEGF receptor neuropilin-1 (NRP-1) is expressed in a singly dispersed subpopulation of cells in the normal colonic epithelium, but that expression becomes dysregulated during colorectal carcinogenesis, with higher levels in tumour suggestive of a poor prognosis. We noted that the spatial distribution and morphology if NRP-1 expressing cells resembles that of enteroendocrine cells (EEC) which are altered in response to disease state including cancer and irritable bowel syndrome (IBS). We have shown that NRP-1 is down-regulated by butyrate in colon cancer cell lines in vitro and we hypothesized that butyrate produced in the lumen would have an analogous effect on the colon mucosa in vivo. Therefore we sought to investigate whether NRP-1 is expressed in EEC and how NRP-1 and EEC respond to butyrate and other short-chain fatty acids (SCFA - principally acetate and propionate). Additionally we sought to assess whether there is a field effect around adenomas.

Methodology
Biopsies were collected at the mid-sigmoid, at the adenoma and at the contralateral wall (field) of 28 subjects during endoscopy. Samples were fixed for IHC and stained for either NRP-1 or for chromogranin A (CgA), a marker of EEC. Stool sampling was undertaken to assess individuals' butyrate, acetate and propionate levels.

Result
NRP-1 expression was inversely related to SCFA concentration at the colon landmark (mid-sigmoid), but expression was lower and not related to SCFA concentration at the field. Likewise CgA+ cell number was also inversely related to SCFA at the landmark, but was lower and unresponsive at the field. Crypt cellularity was unaltered by field effect. A colocalisation analysis showed only a small subset of NRP-1 localised with CgA. Adenomas showed extensive, weaker staining for NRP-1 which contrastingly correlated positively with butyrate level. Field effects cause this relationship to be lost. Adenoma tissue shows dissociation of the co-regulation of NRP-1 and EEC.

Conclusion
NRP-1 is inversely associated with levels of butyrate and other SCFA in vivo and is expressed in a subset of CgA expressing cells. EEC number is related to butyrate level in the same way.
B cells Can Modulate the CD8 Memory T Cell after DNA Vaccination Against Experimental Tuberculosis
Authors: Almeida Luciana P , Trombone Ana PF , Lorenzi Julio CC , Rocha Carolina D , Malardo Thiago , Fontoura Isabela C , Gembre Ana F , Silva Ricardo LL , Silva Célio L , Castelo Ademilson P , Coelho-Castelo Arlete AM 
Published: March 2011

Abstract

Background
Although B cells are important as antigen presenting cells (APC) during the immune response, their role in DNA vaccination models is unknown.

Methods
In this study in vitro and in vivo experiments were performed to evaluate the ability of B cells to protect mice against Mycobacterium tuberculosis challenge.

Results

In vitro and in vivo studies showed that B cells efficiently present antigens after naked plasmid pcDNA3 encoding M. leprae 65-kDa heat shock protein (pcDNA3-Hsp65) internalization and protect B knock-out (BKO) mice against Mycobacterium tuberculosis infection. pcDNA3-Hsp65-transfected B cells adoptively transferred into BKO mice rescued the memory phenotypes and reduced the number of CFU compared to wild-type mice.

Conclusions
These data not only suggest that B cells play an important role in the induction of CD8 T cells but also that they improve bacterial clearance in DNA vaccine model.
Effect of Peierls transition in armchair carbon nanotube on dynamical behaviour of encapsulated fullerene
Authors: Poklonski Nikolai A , Vyrko Sergey A , Kislyakov Eugene F , Hieu Nguyen Ngoc , Bubel' Oleg N , Popov Andrei M , Lozovik Yurii E , Knizhnik Andrey A , Lebedeva Irina V , Viet Nguyen Ai 
Published: March 2011

AbstractThe changes of dynamical behaviour of a single fullerene molecule inside an armchair carbon nanotube caused by the structural Peierls transition in the nanotube are considered. The structures of the smallest C20 and Fe@C20 fullerenes are computed using the spin-polarized density functional theory. Significant changes of the barriers for motion along the nanotube axis and rotation of these fullerenes inside the (8,8) nanotube are found at the Peierls transition. It is shown that the coefficients of translational and rotational diffusions of these fullerenes inside the nanotube change by several orders of magnitude. The possibility of inverse orientational melting, i.e. with a decrease of temperature, for the systems under consideration is predicted.