bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastro oesophageal reflux disease (GORD)-related symptoms and its association with mood and anxiety disorders and psychological symptomology: a population-based study in women
Authors: Sanna Livia , Stuart Amanda L , Berk Michael , Pasco Julie A , Girardi Paolo , Williams Lana J 
Published: July 2013

AbstractBackgroundPsychopathology seems to play a role in reflux pathogenesis and vice versa, yet few population-based studies have systematically investigated the association between gastro-oesophageal reflux disease (GORD) and psychopathology. We thus aimed to investigate the relationship between GORD-related symptoms and psychological symptomatology, as well as clinically diagnosed mood and anxiety disorders in a randomly selected, population-based sample of adult women.MethodsThis study examined data collected from 1084 women aged 20-93 yr participating in the Geelong Osteoporosis Study. Mood and anxiety disorders were identified using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID-I/NP), and psychological symptomatology was assessed using the General Health Questionnaire (GHQ-12). GORD-related symptoms were self-reported and confirmed by medication use where possible and lifestyle factors were documented.ResultsCurrent psychological symptomatology and mood disorder were associated with increased odds of concurrent GORD-related symptoms (adjusted OR 2.1, 95% CI 1.3-3.5, and OR 3.0, 95% CI 1.7-5.6, respectively). Current anxiety disorder also tended to be associated with increased odds of current GORD-related symptoms (p = 0.1). Lifetime mood disorder was associated with a 1.6-fold increased odds of lifetime GORD-related symptoms (adjusted OR 1.6, 95% CI 1.1-2.4) and lifetime anxiety disorder was associated with a 4-fold increased odds of lifetime GORD-related symptoms in obese but not non-obese participants (obese, age-adjusted OR 4.0, 95% CI 1.8-9.0).ConclusionsThese results indicate that psychological symptomatology, mood and anxiety disorders are positively associated with GORD-related symptoms. Acknowledging this common comorbidity may facilitate recognition and treatment, and opens new questions as to the pathways and mechanisms of the association.
Decreased APOE-containing HDL subfractions and cholesterol efflux capacity of serum in mice lacking Pcsk9
Authors: Choi Seungbum , Aljakna Aleksandra , Srivastava Ujala , Peterson Blake R , Deng Bin , Prat Annik , Korstanje Ron 
Published: July 2013

Abstract

Background
Studies in animals showed that PCSK9 is involved in HDL metabolism. We investigated the molecular mechanism by which PCSK9 regulates HDL cholesterol concentration and also whether Pcsk9 inactivation might affect cholesterol efflux capacity of serum and atherosclerotic fatty streak volume.

Methods
Mass spectrometry and western blot were used to analyze the level of apolipoprotein E (APOE) and A1 (APOA1). A mouse model overexpressing human LDLR was used to test the effect of high levels of liver LDLR on the concentration of HDL cholesterol and APOE-containing HDL subfractions. Pcsk9 knockout males lacking LDLR and APOE were used to test whether LDLR and APOE are necessary for PCSK9-mediated HDL cholesterol regulation. We also investigated the effects of Pcsk9 inactivation on cholesterol efflux capacity of serum using THP-1 and J774.A1 macrophage foam cells and atherosclerotic fatty streak volume in the aortic sinus of Pcsk9 knockout males fed an atherogenic diet.

Results
APOE and APOA1 were reduced in the same HDL subfractions of Pcsk9 knockout and human LDLR transgenic male mice. In Pcsk9/Ldlr double-knockout mice, HDL cholesterol concentration was lower than in Ldlr knockout mice and higher than in wild-type controls. In Pcsk9/Apoe double-knockout mice, HDL cholesterol concentration was similar to that of Apoe knockout males. In Pcsk9 knockout males, THP-1 macrophage cholesterol efflux capacity of serum was reduced and the fatty streak lesion volume was similar to wild-type controls.

Conclusions
In mice, LDLR and APOE are important factors for PCSK9-mediated HDL regulation. Our data suggest that, although LDLR plays a major role in PCSK9-mediated regulation of HDL cholesterol concentration, it is not the only mechanism and that, regardless of mechanism, APOE is essential. Pcsk9 inactivation decreases the HDL cholesterol concentration and cholesterol efflux capacity in serum, but does not increase atherosclerotic fatty streak volume.
Existence of periodic solutions of a p-Laplacian-Neumann problem
Authors: Hameed Raad Awad , Sun Jiebao , Wu Boying 
Published: July 2013

Abstract
In this paper, we study a periodic p-Laplacian equation with nonlocal terms and Neumann boundary conditions. We establish the existence of time periodic solutions of the p-Laplacian-Neumann problem by the theory of Leray-Schauder degree.
Identification of the feline foamy virus Bet domain essential for APOBEC3 counteraction
Authors: Lukic Dragana Slavkovic , Hotz-Wagenblatt Agnes , Lei Janet , Räthe Ann-Mareen , Mühle Michael , Denner Joachim , Münk Carsten , Löchelt Martin 
Published: July 2013

Abstract

Background
APOBEC3 (A3) proteins restrict viral replication by cytidine deamination of viral DNA genomes and impairing reverse transcription and integration. To escape this restriction, lentiviruses have evolved the viral infectivity factor (Vif), which binds A3 proteins and targets them for proteolytic degradation. In contrast, foamy viruses (FVs) encode Bet proteins that allow replication in the presence of A3, apparently by A3 binding and/or sequestration, thus preventing A3 packaging into virions and subsequent restriction. Due to a long-lasting FV-host coevolution, Bet proteins mainly counteract restriction by A3s from their cognate or highly related host species.

Results
Through bioinformatics, we identified conserved motifs in Bet, all localized in the bel2 exon. In line with the localization of these conserved motifs within bel2, this part of feline FV (FFV) Bet has been shown to be essential for feline A3 (feA3) inactivation and feA3 protein binding. To study the function of the Bet motifs in detail, we analyzed the ability of targeted deletion, substitution, and chimeric FFV-PFV (prototype FV) Bet mutants to physically bind and/or inactivate feA3. Binding of Bet to feA3Z2b is sensitive to mutations in the first three conserved motifs and N- and C-terminal deletions and substitutions across almost the complete bel2 coding sequence. In contrast, the Bel1 (also designated Tas) domain of Bet is dispensable for basal feA3Z2b inactivation and binding but mainly increases the steady state level of Bet. Studies with PFV Bel1 and full-length FFV Bel2 chimeras confirmed the importance of Bel2 for A3 inactivation indicating that Bel1 is dispensable for basal feA3Z2b inactivation and binding but increases Bet stability. Moreover, the bel1/tas exon may be required for expression of a fully functional Bet protein from a spliced transcript.

Conclusions
We show that the Bel2 domain of FV Bet is essential for the inactivation of APOBEC3 cytidine deaminase restriction factors. The Bel1/Tas domain increases protein stability and can be exchanged by related sequence. Since feA3 binding and inactivation by Bet are highly correlated, the data support the view that FV Bet prevents A3-mediated restriction of viral replication by creating strong complexes with these proteins.
Neural stem cell sparing by linac based intensity modulated stereotactic radiotherapy in intracranial tumors
Authors: Oehler Julia , Brachwitz Tim , Wendt Thomas G , Banz Nico , Walther Mario , Wiezorek Tilo 
Published: July 2013

Abstract

Background
Neurocognitive decline observed after radiotherapy (RT) for brain tumors in long time survivors is attributed to radiation exposure of the hippocampus and the subventricular zone (SVZ). The potential of sparing capabilities for both structures by optimized intensity modulated stereotactic radiotherapy (IMSRT) is investigated.

Methods
Brain tumors were irradiated by stereotactic 3D conformal RT or IMSRT using m3 collimator optimized for PTV and for sparing of the conventional OARs (lens, retina, optic nerve, chiasm, cochlea, brain stem and the medulla oblongata). Retrospectively both hippocampi and SVZ were added to the list of OAR and their dose volume histograms were compared to those from two newly generated IMSRT plans using 7 or 14 beamlets (IMSRT-7, IMSRT-14) dedicated for optimized additional sparing of these structures. Conventional OAR constraints were kept constant. Impact of plan complexity and planning target volume (PTV) topography on sparing of both hippocampi and SVZ, conformity index (CI), the homogeneity index (HI) and quality of coverage (QoC) were analyzed. Limits of agreement were used to compare sparing of stem cell niches with either IMSRT-7 or IMSRT-14. The influence of treatment technique related to the topography ratio between PTV and OARs, realized in group A-D, was assessed by a mixed model.

Results
In 47 patients CI (p ≤ 0.003) and HI (p < 0.001) improved by IMSRT-7, IMSRT-14, QoC remained stable (p ≥ 0.50) indicating no compromise in radiotherapy. 90% of normal brain was exposed to a significantly higher dose using IMSRT. IMSRT-7 plans resulted in significantly lower biologically effective doses at all four neural stem cell structures, while contralateral neural stem cells are better spared compared to ipsilateral. A further increase of the number of beamlets (IMSRT-14) did not improve sparing significantly, so IMSRT-7 and IMSRT-14 can be used interchangeable. Patients with tumors contacting neither the subventricular zone nor the cortex benefit most from IMSRT (p < 0.001).

Conclusion
The feasibility of neural stem cell niches sparing with sophisticated linac based inverse IMSRT with 7 beamlets in an unselected cohort of intracranial tumors in relation to topographic situation has been demonstrated. Clinical relevance testing neurotoxicity remains to be demonstrated.
Biogas production from wheat straw: community structure of cellulose-degrading bacteria
Authors: Sun Li , Müller Bettina , Schnürer Anna 
Published: July 2013

Abstract

Background
Wheat straw is one of the most abundant crop residues produced in the world, making it highly interesting as a substrate for biogas production. However, due to the complex structure, its degradability and gas yield are low. The degradability can be improved by pre-treatment, making the material more accessible to microbial degradation.

Methods
To investigate the microbial response to straw as a feed stock for biogas production, this study examined the community structure of cellulose-degrading bacteria in lab-scale biogas digesters operating with manure, alone or in co-digestion with straw, with and without pre-treatment (steam-explosion) at different temperatures. The community was studied by targeting the functional gene encoding glycoside hydrolases of families 5 and 48 using T-RFLP, clone libraries and qPCR.

Results
In general, bacteria belonging to the phyla Firmicutes and Bacteroidetes dominated the cellulose-degrading bacteria community in all digesters. The degree of similarity to the characterised bacteria was often low, and some clones were more closely related to the uncultured bacteria. The addition of straw, pre-treatment of straw and increasing operating temperature all affected the cellulose-degrading community structure, with differing responses in the cel48 and cel5 communities. Both communities changed in response to temperature, while only the cel5 community was affected by the addition of straw and cel48 community by straw pre-treatment.

Conclusions
The addition of straw, pre-treatment of straw and operating temperature all affected the cellulose-degrading community in biogas digesters, but there were no major differences in the digester performance and gas yield.
Natriuretic peptide receptors regulate cytoprotective effects in a human ex vivo 3D/bioreactor model
Authors: Peake Nicholas , Su Nyan , Ramachandran Manoj , Achan Pramod , Salter Donald M , Bader Dan L , Moyes Amie J , Hobbs Adrian J , Chowdhury Tina T 
Published: July 2013

Abstract
Introduction
The present study examined the effect of C-type natriuretic peptide (CNP) and biomechanical signals on anabolic and catabolic activities in chondrocyte/agarose constructs.

Methods
Natriuretic peptide (Npr) 2 and 3 expression were compared in non-diseased (grade 0/1) and diseased (grade IV) human cartilage by immunofluoresence microscopy and western blotting. In separate experiments, constructs were cultured under free-swelling conditions or subjected to dynamic compression with CNP, interleukin-1β (IL-1β), the Npr2 antagonist P19 or the Npr3 agonist cANF4-23. Nitric oxide (NO) production, prostaglandin E2 (PGE2) release, glycosaminoglycan (GAG) synthesis and CNP concentration were quantified using biochemical assays. Gene expression of Npr2, Npr3, CNP, aggrecan and collagen type II were assessed by real-time qPCR. Two-way ANOVA and a post hoc Bonferroni-corrected t-test were used to analyse the data.

Results
The present study demonstrates increased expression of natriuretic peptide receptors in diseased or older cartilage (age 70) when compared to non-diseased tissue (age 60) which showed minimal expression. There was strong parallelism in the actions of CNP on cGMP induction resulting in enhanced GAG synthesis and reduction of NO and PGE2 release induced by IL-1β. Inhibition of Npr2 with P19 maintained catabolic activities whilst specific agonism of Npr3 with cANF4-23 had the opposite effect and reduced NO and PGE2 release. Co-stimulation with CNP and dynamic compression enhanced anabolic activities and inhibited catabolic effects induced by IL-1β. The presence of CNP and the Npr2 antagonist abolished the anabolic response to mechanical loading and prevented loading-induced inhibition of NO and PGE2 release. In contrast, the presence of the Npr3 agonist had the opposite effect and increased GAG synthesis and cGMP levels in response to mechanical loading and reduced NO and PGE2 release comparable to control samples. In addition, CNP concentration and natriuretic peptide receptor expression were increased with dynamic compression.

Conclusions
Mechanical loading mediates endogenous CNP release leading to increased natriuretic peptide signalling. The loading-induced CNP/Npr2/cGMP signalling route mediates anabolic events and prevents catabolic activities induced by IL-1β. The CNP pathway therefore represents a potentially chondroprotective intervention for patients with OA, particularly when combined with physiotherapeutic approaches to stimulate biomechanical signals.
Obesity enhances nongenomic estrogen receptor crosstalk with the PI3K/Akt and MAPK pathways to promote in vitro measures of breast cancer progression
Authors: Bowers Laura W , Cavazos David A , Maximo Ilane XF , Brenner Andrew J , Hursting Stephen D , deGraffenried Linda A 
Published: July 2013

Abstract
Introduction
Epidemiological and clinical studies indicate that obesity is associated with a worse postmenopausal breast cancer prognosis and an increased risk of endocrine therapy resistance. However, the mechanisms mediating these effects remain poorly understood. Here we investigate the molecular pathways by which obesity-associated circulating factors in the blood enhance estrogen receptor alpha (ERα) positive breast cancer cell viability and growth.

Methods
Blood serum was collected from postmenopausal breast cancer patients and pooled by body mass index (BMI) category (Control: 18.5 to 24.9 kg/m2; Obese: ≥30.0 kg/m2). The effects of patient sera on MCF-7 and T47D breast cancer cell viability and growth were examined by MTT and colony formation assays, respectively. Insulin-like growth factor receptor 1(IGF-1R), Akt, and ERK1/2 activation and genomic ERα activity were assessed to determine their possible contribution to obese patient sera-induced cell viability and growth. To further define the relative contribution of these signaling pathways, cells grown in patient sera were treated with various combinations of ERα, PI3K/Akt and MAPK targeted therapies. Comparisons between cells exposed to different experimental conditions were made using one-way analysis of variance (ANOVA) and Student's t test.

Results
Cells grown in media supplemented with obese patient sera displayed greater cell viability and growth as well as IGF-1R, Akt and ERK1/2 activation relative to control sera. Despite the lack of a significant difference in genomic ERα activity following growth in obese versus control patient sera, we observed a dramatic reduction in cell viability and growth after concurrent inhibition of the ERα and PI3K/Akt signaling pathways. Further, we demonstrated that ERα inhibition was sufficient to attenuate obese serum-induced Akt and ERK1/2 activation. Together, these data suggest that obesity promotes greater ERα positive breast cancer cell viability and growth through enhanced crosstalk between nongenomic ERα signaling and the PI3K/Akt and MAPK pathways.

Conclusions
Circulating factors in the serum of obese postmenopausal women stimulate ERα positive breast cancer cell viability and growth by facilitating non-genomic ERα crosstalk with the PI3K/Akt and MAPK signaling pathways. These findings provide valuable insight into one mechanism by which obesity may promote ERα positive postmenopausal breast cancer progression and endocrine therapy resistance.
Cardiac index and oxygen delivery during low and high tidal volume ventilation strategies in patients with acute respiratory distress syndrome: a crossover randomized clinical trial
Authors: Natalini Giuseppe , Minelli Cosetta , Rosano Antonio , Ferretti Pierluigi , Militano Carmine R , De Feo Carlo , Bernardini Achille 
Published: July 2013

Abstract
Introduction
The beneficial effect of low tidal volume (TV) ventilation strategy on mortality in patients with acute respiratory distress syndrome (ARDS) has been attributed to the protective effect on ventilator-induced lung injury, and yet its effect on cardiovascular function might also play an important role. The aim of this study was to assess whether low TV ventilation improves cardiac output and oxygen delivery compared with high TV ventilation strategy in patients with ARDS.

Methods
In this crossover randomized clinical trial 16 ARDS patients were recruited in an intensive care unit at a university-affiliated hospital. Each patient was ventilated for 30 min with low (6 mL/kg) and 30 min with high (12 mL/kg) TV. The two experimental periods, applied in random order and with allocation concealment, were separated by 30 min of basal ventilation. Minute ventilation was constantly maintained by appropriate respiratory rate changes.

Results
Compared with high TV ventilation, low TV ventilation showed decreased pH (7.37 vs. 7.41, P = 0.001) and increased PaCO2 (49 vs. 43 mmHg; P = 0.002). Cardiac index and oxygen delivery index were increased with low compared with high TV ventilation (3.9 vs. 3.5 L.min-1.m-2, P = 0.012, and 521 vs. 463 mL.min-1.m-2, P = 0.002, respectively), while oxygen extraction ratio decreased (0.36 vs. 0.44, P = 0.027). In four patients oxygen extraction ratio was >0.5 during high TV but not during low TV strategy. The magnitude of the change in cardiac index was positively associated with PaCO2 variation (P = 0.004), while it was unrelated to the magnitude of changes in TV and airway pressure. The decrease of cardiac index was predicted by PaCO2 reduction, with and area under ROC curve of 0.72.

Conclusions
Our findings suggest that a low TV ventilation strategy increases cardiac index and oxygen delivery, thus supporting the hypothesis that the beneficial effect of low TV ventilation in patients with ARDS could be partially explained by hemodynamic improvement. In other words, low tidal volume ventilation could be protective also for the cardiovascular system and not only for the lung. The slight increase of PaCO2 during low TV ventilation seems to predict the increase of cardiac index.

Trial registration
ClinicalTrials.gov: NCT00713713
Factors predicting the use of therapeutic hypothermia and survival in unconscious out-of-hospital cardiac arrest patients admitted to the ICU
Authors: Lindner TW , Langørgen J , Sunde K , Larsen AI , Kvaløy JT , Heltne JK , Draegni T , Søreide E 
Published: July 2013

Abstract
Introduction
Therapeutic hypothermia (TH) after out-of-hospital cardiac arrest (OHCA) was adopted early in Norway. Since 2004 the general recommendation has been to cool all unconscious OHCA patients treated in the intensive care unit (ICU), but the decision to cool individual patients was left to the responsible physician. We assessed factors that were associated with use of TH and predicted survival.

Method
We conducted a retrospective observational study of prospectively collected cardiac arrest and ICU registry data from 2004 to 2008 at three university hospitals.

Results
A total of 715 unconscious patients older than 18 years of age, who suffered OHCA of both cardiac and non-cardiac causes, were included. With an overall TH use of 70%, the survival to discharge was 42%, with 90% of the survivors having a favourable cerebral outcome. Known positive prognostic factors such as witnessed arrest, bystander cardio pulmonary resuscitation (CPR), shockable rhythm and cardiac origin were all positive predictors of TH use and survival. On the other side, increasing age predicted a lower utilisation of TH: Odds Ratio (OR), 0.96 (95% CI, 0.94 to 0.97); as well as a lower survival: OR 0.96 (95% CI, 0.94 to 0.97). Female gender was also associated with a lower use of TH: OR 0.65 (95% CI, 0.43 to 0.97); and a poorer survival: OR 0.57 (95% CI, 0.36 to 0.92). After correcting for other prognostic factors, use of TH remained an independent predictor of improved survival with OR 1.91 (95% CI 1.18-3.06; P <0.001). Analysing subgroups divided after initial rhythm, these effects remained unchanged for patients with shockable rhythm, but not for patients with non-shockable rhythm where use of TH and female gender lost their predictive value.

Conclusions
Although TH was used in the majority of unconscious OHCA patients admitted to the ICU, actual use varied significantly between subgroups. Increasing age predicted both a decreased utilisation of TH as well as lower survival. Further, in patients with a shockable rhythm female gender predicted both a lower use of TH and poorer survival. Our results indicate an underutilisation of TH in some subgroups. Hence, more research on factors affecting TH use and the associated outcomes in subgroups of post-resuscitation patients is needed.