bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ubiquitin-mediated interaction of p210 BCR/ABL with β-catenin supports disease progression in a murine model for chronic myelogenous leukemia
Authors: Chen Ru , Hu Tinghui , Mahon Gwendolyn M. , Tala Ilona , Pannucci Nicole L. , Ozer Harvey L. , Whitehead Ian P. 
Published: August 2013

Key Points
p210 BCR/ABL interacts with β-catenin in the bone marrow transplantation model for chronic myelogenous leukemia. Loss of the interaction results in an altered disease phenotype, suggesting a role for β-catenin in chronic phase disease.
PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma
Authors: Richardson Paul G. , Schlossman Robert L. , Alsina Melissa , Weber Donna M. , Coutre Steven E. , Gasparetto Cristina , Mukhopadhyay Sutapa , Ondovik Michael S. , Khan Mahmudul , Paley Carole S. , Lonial Sagar 
Published: August 2013

Key PointsPanobinostat + bortezomib + dexamethasone recaptures responses in heavily pretreated, bortezomib-refractory multiple myeloma patients.
Domiciliary diurnal variation of exhaled nitric oxide fraction for asthma control
Authors: Saito Junpei , Gibeon David , Macedo Patricia , Menzies-Gow Andrew , Bhavsar Pankaj K. , Chung Kian Fan 
Published: August 2013

A major goal of asthma management is maintaining optimal control. Current assessment is based on symptoms and lung function.We evaluated whether domiciliary daily home exhaled nitric oxide fraction (FeNO) monitoring could be useful as an index of asthma control. 50 asthmatic subjects and 15 healthy volunteers with a range of asthma severity underwent asthma control questionnaire (ACQ), spirometry before and after salbutamol and sputum induction.FeNOand peak expiratory flow (PEF) were measured twice daily for 2 weeks. A record of exacerbations was obtained 3 months later.DiurnalFeNOvariation in uncontrolled asthmatics was significantly greater than in controlled asthmatics (p<0.01). PEF variation was not different. The daily variation ofFeNOlevels was also greater in uncontrolled asthmatics compared with controlled asthmatic and healthy subjects (p<0.01). 80% of uncontrolled asthmatics experienced at least one or more exacerbations over the 3 months after the enrolment. The combination of diurnalFeNOvariation ≥16.6% and ACQ scores ≥1.8 was best at predicting uncontrolled asthma (area under curve 0.91, 95% CI 0.86–0.97; p<0.001).Diurnal variation inFeNOcan be used as a biomarker of asthma control and as a predictor of the risk of future exacerbation. Prospective studies are warranted.
Severely reduced diffusion capacity in idiopathic pulmonary arterial hypertension: patient characteristics and treatment responses
Authors: Trip Pia , Nossent Esther J. , de Man Frances S. , van den Berk Inge A.H. , Boonstra Anco , Groepenhoff Herman , Leter Edward M. , Westerhof Nico , Grünberg Katrien , Bogaard Harm-Jan , Vonk-Noordegraaf Anton 
Published: August 2013

A subgroup of patients with idiopathic pulmonary arterial hypertension (IPAH) has severely reduced diffusing capacity of the lung for carbon monoxide (DLCO) and poor prognosis. Their characteristics are currently unknown. The aim of this study is to contrast clinical characteristics and treatment responses of IPAH-patients with a severely reduced and more preservedDLCO.Retrospectively, 166 IPAH patients were included and grouped based on aDLCOcut-off value of 45% pred (IPAH<45%and IPAH≥45%). Clinical characteristics, treatment responses and survival were compared.IPAH<45%were older, more often male, had a more frequent history of coronary disease and a higher tobacco exposure. Forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity, total lung capacity and alveolar volume values were slightly lower and computed tomography scan abnormalities more prevalent in patients with a lowDLCO. Age and number of pack years were independently associated withDLCO<45% pred. IPAH<45%showed no different haemodynamic profile, yet worse exercise performance and a worse survival rate, which were both related to age, sex and the presence of coronary disease.To conclude, a severely reducedDLCOin IPAH is associated with advanced age and a greater tobacco exposure. These patients have a worse exercise performance despite a similar hemodynamic profile. We confirm the decreased survival in this patient group and now show that this poor outcome is related to age, sex and the presence of coronary disease.
Risks for HIV and other sexually transmitted infections among Asian men who have sex with men in Vancouver, British Columbia: a cross-sectional survey
Authors: Maung Maung Thiha , Chen Becky , Moore David M , Chan Keith , Kanters Steve , Michelow Warren , Hogg Robert S , Nakamura Nadine , Robert Wayne , Gustafson Reka , Gilbert Mark ,   The ManCount Study Team
Published: August 2013

Abstract

Background
Individuals of Asian heritage represent the largest ethnic minority in Canada. Approximately 10% of the new HIV diagnoses in men in British Columbia occur among Asian-Canadians. However, the HIV risk patterns of Asian men who have sex with men (MSM) have not been extensively studied.

Methods
Participants aged ≥ 19 years were enrolled in a venue-based HIV serobehavioural survey of MSM in Vancouver, Canada. We compared the demographic characteristics, risk behaviours, and prevalence of HIV and other sexual and blood borne infections between Asian and non-Asian MSM using bivariate analysis and logistic regression confounder modelling.

Results
Amongst 1132 participants, 110 (9.7%) self-identified as Asian. Asian participants were younger than non-Asian participants (median age 29 vs. 32 years; p < 0.001), but otherwise did not differ from other study participants. HIV prevalence was lower among Asian MSM compared to Non-Asian MSM (3.7% vs 19.0%, p <0.001). Among men who self-reported as HIV negative or unknown we found no differences in unprotected anal intercourse (UAI) with a discordant or unknown serostatus partner in the previous six months (11 vs. 13%; p = 0.503). However, Asian MSM were less likely to report ever using injection drugs (10.8% vs. 19.2%; p = 0.043) or using alcohol before having sex (52% vs. 64.4%; p = 0.017).

Conclusions
Asian MSM in our study reported similar rates of UAI as non-Asian MSM, but had a lower prevalence of HIV infection. Other factors, such as the use of drugs and alcohol, in relation to sex, may partly explain these differences. However this requires further investigation.
Correlation between B7-H3 expression and matrix metalloproteinases 2 expression in pancreatic cancer
Authors: Xu Lihua , Ding Xiangmin , Tan Huo , Qian Jianjun 
Published: August 2013

Abstract

Background
B7-H3 and matrix metalloproteinases 2 (MMP-2) are reported highly expressed in malignant tumor, we investigate the relationship between B7-H3 expression and MMP-2 on malignant behavior and prognosis predictable value in pancreatic cancer.

Methods
We tested the expressions of B7-H3 and MMP-2 protein in 45 pancreatic surgical resected cancer samples; meanwhile, the clinicopathological data of enrolled patients were obtained for correlation analysis to obtain their relationship with pancreatic cancer progress.

Results
The expression of B7-H3 was up-regulated with infiltrating depth, lymph node metastasis and TNM stage (P < 0.01). Positive expression rate of MMP-2 in pancreatic cancer tissues was 44.35%, whereas negative in normal pancreatic tissues. Multivariate analysis of Logistic regression showed B7-H3 and MMP-2 expressions were hazardous makers correlated with infiltrating depth (P < 0.05).

Conclusion
Our study showed combined detections of B7-H3 and MMP2 protein expression could identify patients at high risk in disease recurrence and prognosis more efficiently.
Promoting universal financial protection: contracting faith-based health facilities to expand access – lessons learned from Malawi
Authors: Chirwa Maureen L , Kazanga Isabel , Faedo Giulia , Thomas Stephen 
Published: August 2013

Abstract

Background
Public-private collaborations are increasingly being utilized to universalize health care. In Malawi, the Ministry of Health contracts selected health facilities owned by the main faith-based provider, the Christian Health Association of Malawi (CHAM), to deliver care at no fee to the most vulnerable and underserved populations in the country through Service Level Agreements (SLAs). This study examined the features of SLAs and their effectiveness in expanding universal coverage. The study involved a policy analysis focusing on key stakeholders around SLAs as well as a case study approach to analyse how design and implementation of SLAs affect efficiency, equity and sustainability of services delivered by SLAs.

Methods
The study employed both qualitative and quantitative research methods to address the research questions and was conducted in five CHAM health facilities: Mulanje Mission, Holy Family, and Mtengowanthenga Hospitals, and Mabiri and Nkope Health Centres. National and district level decision makers were interviewed while providers and clients associated with the health facilities were surveyed on their experiences. A total of 155 clients from an expected 175 were recruited in the study.

Results
The study findings revealed key aspects of how SLAs were operating, the extent to which their objectives were being attained and why. In general, the findings demonstrated that SLAs had the potential to improve health and universal health care coverage, particularly for the vulnerable and underserved populations. However, the findings show that the performance of SLAs in Malawi were affected by various factors including lack of clear guidelines, non-revised prices, late payment of bills, lack of transparency, poor communication, inadequate human and material resources, and lack of systems to monitor performance of SLAs, amongst others.

Conclusions
There was strong consensus and shared interest between the government and CHAM regarding SLAs. It was clear that free services provided by SLAs had a great impact on the impoverished locals that used the facilities. However, lack of supporting systems, inadequate infrastructure and shortage of health care providers affected SLA performance. The paper provides recommendations to policy makers for the replication and strengthening of SLA implementation in the roll-out of universalization policy.
TBX6, LHX1 and copy number variations in the complex genetics of Müllerian aplasia
Authors: Sandbacka Maria , Laivuori Hannele , Freitas Érika , Halttunen Mervi , Jokimaa Varpu , Morin-Papunen Laure , Rosenberg Carla , Aittomäki Kristiina 
Published: August 2013

AbstractBackgroundMüllerian aplasia (MA) is a congenital disorder of the female reproductive tract with absence of uterus and vagina with paramount impact on a woman’s life. Despite intense research, no major genes have been found to explain the complex genetic etiology.Methods and ResultsWe have used several genetic methods to study 112 patients with MA. aCGH identified CNVs in 8/50 patients (16%), including 16p11.2 and 17q12 deletions previously associated with MA. Subsequently, another four patients were shown to carry the ~0.53 Mb deletion in 16p11.2. More importantly, sequencing ofTBX6,residing within 16p11.2, revealed two patients carrying a splice site mutation.Two previously reportedTBX6variants in exon 4 and 6 were shown to have a significantly higher frequency in patients (8% and 5%, respectively) than in controls (2% each). We also sequencedLHX1and found three apparently pathogenic missense variants in 5/112 patients. Altogether, we identified either CNVs or variations inTBX6orLHX1in 30/112 (26.8%) MA patients. CNVs were found in 12/112 (10.7%), patients, novel variants inTBX6orLHX1in 7/112 (6.3%), and rare variants inTBX6in 15/112 (13.4%) patients. Furthermore, four of our patients (4/112, 3.6%) were shown to carry variants in bothTBX6andLHX1or a CNV in combination withTBX6variants lending support to the complex genetic etiology of MA.ConclusionsWe have identifiedTBX6as a new gene associated with MA. Our results also support the relevance ofLHX1and CNVs in the development of this congenital malformation.
The pathogenic intestinal spirochaete Brachyspira pilosicoli forms a diverse recombinant species demonstrating some local clustering of related strains and potential for zoonotic spread
Authors: Neo Eugene , La Tom , Phillips Nyree Dale , Alikani Mohammad Yousef , Hampson David J 
Published: August 2013

Abstract

Background

Brachyspira pilosicoli is an anaerobic spirochaete that can colonizes the large intestine of many host species. Infection is particularly problematic in pigs and adult poultry, causing colitis and diarrhea, but it is also known to result in clinical problems in human beings. Despite the economic importance of the spirochaete as an animal pathogen, and its potential as a zoonotic agent, it has not received extensive study.

Methods
A multilocus sequence typing (MLST) method based on the scheme used for other Brachyspira species was applied to 131 B. pilosicoli isolates originating from different host species and geographical areas. A variety of phylogenetic trees were constructed and analyzed to help understand the data.

Results
The isolates were highly diverse, with 127 sequence types and 123 amino acid types being identified. Large numbers (50-112) of alleles were present at each locus, with all loci being highly polymorphic. The results of Shimodaira-Hasegawa tests identified extensive genetic recombination, although the calculated standardized index of association value (0.1568; P <0.0005) suggested the existence of some clonality. Strains from different host species and geographical origins generally were widely distributed throughout the population, although in nine of the ten cases where small clusters of related isolates occurred these were from the same geographical areas or farms/communities, and from the same species of origin. An exception to the latter was a cluster of Australian isolates originating from pigs, chickens and a human being, suggesting the likelihood of relatively recent transmission of members of this clonal group between species.

Conclusions
The strongly recombinant population structure of B. pilosicoli contrasts to the more highly clonal population structures of the related species Brachyspira hyodysenteriae and Brachyspira intermedia, both of which are specialized enteric pathogens of pigs and poultry. The genomic plasticity of B. pilosicoli may help to explain why it has been able to adapt to colonize the large intestines of a wider range of hosts compared to other Brachyspira species. The identification of a clonal group of isolates that had been recovered from different host species, including a human being, suggests that zoonotic transmission by B. pilosicoli may occur in nature. Evidence for local transmission between the same host species also was obtained.
MOLE 2.0: advanced approach for analysis of biomacromolecular channels
Authors: Sehnal David , Svobodová Vařeková Radka , Berka Karel , Pravda Lukáš , Navrátilová Veronika , Banáš Pavel , Ionescu Crina-Maria , Otyepka Michal , Koča Jaroslav 
Published: August 2013

Abstract

Background
Channels and pores in biomacromolecules (proteins, nucleic acids and their complexes) play significant biological roles, e.g., in molecular recognition and enzyme substrate specificity.

Results
We present an advanced software tool entitled MOLE 2.0, which has been designed to analyze molecular channels and pores. Benchmark tests against other available software tools showed that MOLE 2.0 is by comparison quicker, more robust and more versatile. As a new feature, MOLE 2.0 estimates physicochemical properties of the identified channels, i.e., hydropathy, hydrophobicity, polarity, charge, and mutability. We also assessed the variability in physicochemical properties of eighty X-ray structures of two members of the cytochrome P450 superfamily.

Conclusion
Estimated physicochemical properties of the identified channels in the selected biomacromolecules corresponded well with the known functions of the respective channels. Thus, the predicted physicochemical properties may provide useful information about the potential functions of identified channels. The MOLE 2.0 software is available at http://mole.chemi.muni.cz.
Rare coding variants of the adenosine A3 receptor are increased in autism: on the trail of the serotonin transporter regulome
Authors: Campbell Nicholas G , Zhu Chong-Bin , Lindler Kathryn M , Yaspan Brian L , Kistner-Griffin Emily ,   NIH ARRA Consortium, Hewlett William A , Tate Christopher G , Blakely Randy D , Sutcliffe James S 
Published: August 2013

Abstract

Background
Rare genetic variation is an important class of autism spectrum disorder (ASD) risk factors and can implicate biological networks for investigation. Altered serotonin (5-HT) signaling has been implicated in ASD, and we and others have discovered multiple, rare, ASD-associated variants in the 5-HT transporter (SERT) gene leading to elevated 5-HT re-uptake and perturbed regulation. We hypothesized that loci encoding SERT regulators harbor variants that impact SERT function and/or regulation and therefore could contribute to ASD risk. The adenosine A3 receptor (A3AR) regulates SERT via protein kinase G (PKG) and other signaling pathways leading to enhanced SERT surface expression and catalytic activity.

Methods
To test our hypothesis, we asked whether rare variants in the A3AR gene (ADORA3) were increased in ASD cases vs. controls. Discovery sequencing in a case-control sample and subsequent analysis of comparison exome sequence data were conducted. We evaluated the functional impact of two variants from the discovery sample on A3AR signaling and SERT activity.

Results
Sequencing discovery showed an increase of rare coding variants in cases vs. controls (P=0.013). While comparison exome sequence data did not show a significant enrichment (P=0.071), combined analysis strengthened evidence for association (P=0.0025). Two variants discovered in ASD cases (Leu90Val and Val171Ile) lie in or near the ligand-binding pocket, and Leu90Val was enriched individually in cases (P=0.040). In vitro analysis of cells expressing Val90-A3AR revealed elevated basal cGMP levels compared with the wildtype receptor. Additionally, a specific A3AR agonist increased cGMP levels across the full time course studied in Val90-A3AR cells, compared to wildtype receptor. In Val90-A3AR/SERT co-transfections, agonist stimulation elevated SERT activity over the wildtype receptor with delayed 5-HT uptake activity recovery. In contrast, Ile171-A3AR was unable to support agonist stimulation of SERT. Although both Val90 and Ile171 were present in greater numbers in these ASD cases, segregation analysis in families showed incomplete penetrance, consistent with other rare ASD risk alleles.

Conclusions
Our results validate the hypothesis that the SERT regulatory network harbors rare, functional variants that impact SERT activity and regulation in ASD, and encourages further investigation of this network for other variation that may impact ASD risk.
Clinical evidence for allergy in orofacial granulomatosis and inflammatory bowel disease
Authors: Patel Pritash , Brostoff Jonathan , Campbell Helen , Goel Rishi M , Taylor Kirstin , Ray Shuvra , Lomer Miranda , Escudier Michael , Challacombe Stephen , Spencer Jo , Sanderson Jeremy 
Published: August 2013

AbstractBackgroundOrofacial granulomatosis (OFG) causes chronic, disfiguring, granulomatous inflammation of the lips and oral mucosa. A proportion of cases have co‐existing intestinal Crohn's disease (CD). The pathogenesis is unknown but has recently been linked to dietary sensitivity. Although allergy has been suggested as an aetiological factor in OFG there are few published data to support this link. In this study, we sought clinical evidence of allergy in a series of patients with OFG and compared this to a series of patients with inflammatory bowel disease (IBD) without oral involvement and to population control estimates.MethodsPrevalence rates of allergy and oral allergy syndrome (OAS) were determined in 88 patients with OFG using questionnaires, skin prick tests, total and specific serum IgE levels. Allergy was also determined in 117 patients with IBD without evidence of oral involvement (79 with CD and 38 with ulcerative colitis (UC)).ResultsPrevalence rates of allergy in patients with OFG were significantly greater than general population estimates (82% versus 22% respectively p = <0.0005). Rates of allergy were also greater in those with CD (39%) and, interestingly, highest in those with OFG and concurrent CD (87%). Conversely, whist OAS was common in allergic OFG patients (35%) rates of OAS were significantly less in patients with concomitant CD (10% vs 44% with and without CD respectively p = 0.006). Amongst CD patients, allergy was associated with perianal disease (p = 0.042) but not with ileal, ileocolonic or colonic disease location. Allergy in UC (18%) was comparable to population estimates.ConclusionWe provide compelling clinical evidence for the association of allergy with OFG whether occurring alone or in association with CD. The presence of gut CD increases this association but, conversely, reduces the expression of OAS in those with atopy. Interestingly, there is no evidence of increased allergy in UC.
Protective effects of decay-accelerating factor on blast-induced neurotrauma in rats
Authors: Li Yansong , Chavko Mikulas , Slack Jessica L , Liu Bin , McCarron Richard M , Ross James D , Dalle Lucca Jurandir J 
Published: August 2013

Abstract

Background
Blast-induced neurotrauma (BINT) is the signature life threatening injury of current military casualties. Neuroinflammation is a key pathological occurrence of secondary injury contributing to brain damage after blast injury. We have recently demonstrated that blast-triggered complement activation and cytokine release are associated with BINT. Here, we evaluated if administration of the complement inhibitor recombinant human decay-accelerating factor (rhDAF) is beneficial on neuroinflammation and neurodegeneration in a rat model of moderate BINT. Administration of rhDAF after exposure to moderate blast overpressure (BOP, 120 kPa) mitigated brain injury characterized by neuronal degeneration. rhDAF treatment reduced complement hemolytic activity at 3 hours and tissue complement deposition at 3, 24, and 48 hours as well as systemic and local cytokine release at 24 hours post BOP. Furthermore, rhDAF protected blood–brain barrier (BBB) integrity and reduced cytotoxic edema. Interaction between complement cleavage component, C3a and C3a receptor and tau phosphorylation were also attenuated in rhDAF treated animals at 3 and 24 hours after BOP. These novel findings suggest early complement targeted inhibition as a new therapeutic strategy to decrease neuroinflammation and neurodegeneration after blast TBI.

Result
Administration of rhDAF after exposure to moderate blast overpressure (BOP, 120 kPa) mitigated brain injury characterized by neuronal degeneration. rhDAF treatment reduced complement hemolytic activity at 3 hours and tissue complement deposition at 3, 24, and 48 hours as well as systemic and local cytokine release at 24 hours post BOP. Furthermore, rhDAF protected blood–brain barrier (BBB) integrity and reduced cytotoxic edema. Interaction between complement cleavage component, C3a and C3a receptor and tau phosphorylation were also attenuated in rhDAF treated animals at 3 and 24 hours after BOP.

Conclusion
These novel findings suggest early complement targeted inhibition as a new therapeutic strategy to decrease neuroinflammation and neurodegeneration after blast TBI.