bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic dissection of blood lipid traits by integrating genome-wide association study and gene expression profiling in a porcine model
Authors: Chen Congying , Yang Bin , Zeng Zhijun , Yang Hui , Liu Chenlong , Ren Jun , Huang Lusheng 
Published: December 2013

Abstract

Background
Serum concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) are highly heritable traits that are used clinically to evaluate risk for cardiovascular disease in humans. In this study, we applied a genome-wide association study (GWAS) in 1,075 pigs from two populations and gene expression studies on 497 liver samples to dissect the genetic basis of serum lipids in a pig model.

Results
We totally identified 8, 5, 2 and 3 genomic loci harboring 109 SNPs that were significantly associated with LDL-C, TC, TG and the ratio of HDL-C/LDL-C in two experimental populations, respectively. In the F2 population, the most prominent SNP was identified at the SSC3: 124,769,847 bp where APOB is the well-known candidate gene. However, in the Sutai population, the most number of significant SNPs was identified at SSC2: 64.97-82.22 Mb where LDLR was identified as the candidate gene. Furthermore, we firstly reported 4 novel genomic loci in pigs harboring the LDL-C-associated SNPs. We also observed obvious population heterogeneity in the two tested populations. Through whole-genome gene expression analysis, we detected 718 trait-correlated expressions. Many of these transcripts correspond to candidate genes for blood lipids in humans. The GWAS mapped 120 cis-eQTLs and 523 trans-eQTLs for these transcripts. One gene encoding the transcript gnl|UG|Ssc#S35330332 stands out to be an important candidate gene for LDL-C by an integrative analysis of GWAS, eQTL and trait-associated expression.

Conclusions
We identified the genomic regions or candidate genes associated with blood lipids by an integrative analysis of GWAS, QTT and eQTL mapping in pigs. The findings would benefit the further identification of the causative genes for blood lipid traits in both pigs and humans.
Heterozygous FA2H mutations in autism spectrum disorders
Authors: Scheid Isabelle , Maruani Anna , Huguet Guillaume , Leblond Claire S , Nygren Gudrun , Anckarsäter Henrik , Beggiato Anita , Rastam Maria , Amsellem Fréderique , Gillberg I Carina , Elmaleh Monique , Leboyer Marion , Gillberg Christopher , Betancur Catalina , Coleman Mary , Hama Hiroko , Cook Edwin H , Bourgeron Thomas , Delorme Richard 
Published: December 2013

Abstract

Background
Widespread abnormalities in white matter development are frequently reported in cases of autism spectrum disorders (ASD) and could be involved in the disconnectivity suggested in these disorders. Homozygous mutations in the gene coding for fatty-acid 2-hydroxylase (FA2H), an enzyme involved in myelin synthesis, are associated with complex leukodystrophies, but little is known about the functional impact of heterozygous FA2H mutations. We hypothesized that rare deleterious heterozygous mutations of FA2H might constitute risk factors for ASD.

Methods
We searched deleterious mutations affecting FA2H, by genotyping 1256 independent patients with ASD genotyped using Genome Wide SNP arrays, and also by sequencing in independent set of 186 subjects with ASD and 353 controls. We then explored the impact of the identified mutations by measuring FA2H enzymatic activity and expression, in transfected COS7 cells.

Results
One heterozygous deletion within 16q22.3-q23.1 including FA2H was observed in two siblings who share symptoms of autism and severe cognitive impairment, axial T2-FLAIR weighted MRI posterior periventricular white matter lesions. Also, two rare non-synonymous mutations (R113W and R113Q) were reported. Although predictive models suggested that R113W should be a deleterious, we did not find that FA2H activity was affected by expression of the R113W mutation in cultured COS cells.

Conclusions
While our results do not support a major role for FA2H coding variants in ASD, a screening of other genes related to myelin synthesis would allow us to better understand the role of non-neuronal elements in ASD susceptibility.
Fixed point theorems for α-Geraghty contraction type maps in metric spaces
Authors: Cho Seong-Hoon , Bae Jong-Sook , Karapınar Erdal 
Published: December 2013

Abstract
In this paper, we introduce a notion of α-Geraghty contraction type maps in the setting of a metric space. We also establish some fixed point theorems for such maps and give an example to illustrate our results. Finally, we discuss the application of our main results in the research fields of ordinary differential equations.

MSC:47H10, 54H25.
Global dynamics of some systems of higher-order rational difference equations
Authors: Khan Abdul Qadeer , Qureshi Muhammad Naeem , Din Qamar 
Published: December 2013

Abstract
In the present work, we study the qualitative behavior of two systems of higher-order rational difference equations. More precisely, we study the local asymptotic stability, instability, global asymptotic stability of equilibrium points and rate of convergence of positive solutions of these systems. Our results considerably extend and improve some recent results in the literature. Some numerical examples are given to verify our theoretical results.

MSC:39A10, 40A05.
Evans syndrome associated with sterile inflammation of the central nervous system: a case report
Authors: Simon Ole Jan , Kuhlmann Tanja , Bittner Stefan , Müller-Tidow Carsten , Weigt Jochen , Wiendl Heinz , Meuth Sven G 
Published: December 2013

Abstract

Introduction
Evans syndrome is a rare hematological disease commonly defined as Coombs-positive hemolytic anemia and immune thrombocytopenia. Pathophysiology of this disease involves decreased cluster of differentiation (CD)4+ T-helper cell counts, increased CD8+ T-suppressor cell counts, a decreased CD4/CD8 ratio, and reduced serum immunoglobulin G, M and A levels - indicating a complex immune dysregulation. Association with other autoimmune diseases has been described although involvement of the central nervous system has not been reported so far.

Case presentation
We here present a case of a 28-year-old woman of Turkish origin with progressive, disseminated, partly mass-forming lymphoplasmacellular infiltration (CD3+ and CD138+ cells) of the brain in association with Evans syndrome. No other central nervous system disorder could be identified on neuropathological evaluation. Although treatment with rituximab was effective to normalize erythrocyte and thrombocyte levels in her peripheral blood, it failed to dampen the inflammation in her central nervous system or prevent clinical progression. Initiation of treatment with cyclophosphamide resulted in stabilization of her central nervous system inflammation and the disease course.

Conclusions
The complex immune dysregulation resulting in the antibody-mediated pathologies that can be regarded as the cause of both lymphoplasmacellular encephalitis and Evans syndrome renders this association to be of clinical relevance for both neurologists and hematologists. Our experience also sheds light on the effectiveness of different treatments for both disorders and we advise clinicians to take a closer look when encountering a combination of peripheral blood diseases with affection of the central nervous system.
Comparison between laparotomy first versus angiographic embolization first in patients with pelvic fracture and hemoperitoneum: a nationwide observational study from the Japan Trauma Data Bank
Authors: Katsura Morihiro , Yamazaki Shin , Fukuma Shingo , Matsushima Kazuhide , Yamashiro Toshimitsu , Fukuhara Shunichi 
Published: December 2013

Abstract

Background
A common dilemma in the management of pelvic fractures is recognizing the presence of associated abdominal injury. The purpose of this study was to determine the association between initial therapeutic intervention (laparotomy or transcatheter arterial embolization (TAE)) and mortality.

Methods
This was a cohort study using the Japan Trauma Data Bank between 2004 and 2010, including blunt trauma patients with pelvic fractures and positive Focused Assessment with Sonography in Trauma (FAST) results. Eligible patients were restricted to those who underwent laparotomy or TAE/angiography as the initial therapeutic intervention. Crude and adjusted odds ratio (AOR) for in-hospital mortality were compared between the laparotomy first and TAE first groups (reference group). Multiple logistic regression analysis and propensity score adjusted analysis were used to adjust for clinically relevant confounders, including the severity of injury.

Results
Of the 317 participants, 123 patients underwent laparotomy first and 194 patients underwent TAE first. The two groups were similar in terms of age, although the laparotomy first group had higher mean Injury Severity Scores (ISS) and higher mean scores based on the abdominal Abbreviated Injury Scale (AIS), as well as lower mean pelvic AIS and systolic blood pressure (SBP). Half of the patients who were hypotensive (SBP < 90 mmHg) on arrival underwent TAE first. The laparotomy first group had a significantly higher crude in-hospital mortality (41% vs. 27%; P < 0.01). After adjusting for confounders, the choice of initial therapeutic intervention did not affect the in-hospital mortality (AOR, 1.20; 95% Confidence Interval (CI), 0.61-2.39). Even in the limited subgroup of hypotensive patients (SBP 66–89 mmHg and SBP < 65 mmHg subgroup), the effect was similar (AOR, 1.50; 95% CI, 0.56-4.05 and AOR, 1.05; 95% CI, 0.44-3.03).

Conclusions
In Japan, laparotomy and TAE are equally chosen as the initial therapeutic intervention regardless of hemodynamic status. No significant difference was seen between the laparotomy first and TAE first groups regarding in-hospital mortality.
Dynamic Kisspeptin Receptor Trafficking Modulates Kisspeptin-Mediated Calcium Signaling
Authors: Min Le , Soltis Kathleen , Reis Ana Claudia S. , Xu Shuyun , Kuohung Wendy , Jain Manisha , Carroll Rona S. , Kaiser Ursula B. 
Published: December 2013

AbstractKisspeptin receptor (KISS1R) signaling plays a critical role in the regulation of reproduction. We investigated the role of kisspeptin-stimulated KISS1R internalization, recycling, and degradation in the modulation of KISS1R signaling. Kisspeptin stimulation of Chinese hamster ovary or GT1–7 cells expressing KISS1R resulted in a biphasic increase in intracellular Ca2+ ([Ca2+]i), with a rapid acute increase followed by a more sustained second phase. In contrast, stimulation of the TRH receptor, another Gq/11-coupled receptor, resulted in a much smaller second-phase [Ca2+]i response. The KISS1R-mediated second-phase [Ca2+]i response was abolished by removal of kisspeptin from cell culture medium. Notably, the second-phase [Ca2+]i response was also inhibited by dynasore, brefeldin A, and phenylarsine oxide, which inhibit receptor internalization and recycling, suggesting that KISS1R trafficking contributes to the sustained [Ca2+]i response. We further demonstrated that KISS1R undergoes dynamic ligand-dependent and -independent recycling. We next investigated the fate of the internalized kisspeptin-KISS1R complex. Most internalized kisspeptin was released extracellularly in degraded form within 1 hour, suggesting rapid processing of the internalized kisspeptin-KISS1R complex. Using a biotinylation assay, we demonstrated that degradation of cell surface KISS1R was much slower than that of the internalized ligand, suggesting dissociated processing of the internalized kisspeptin-KISS1R complex. Taken together, our results suggest that the sustained calcium response to kisspeptin is dependent on the continued presence of extracellular ligand and is the result of dynamic KISS1R trafficking.
Speed of Invasion of an Expanding Population by a Horizontally Transmitted Trait
Authors: Venegas-Ortiz Juan , Allen Rosalind J , Evans Martin R 
Published: December 2013

AbstractRange expansions are a ubiquitous phenomenon, leading to the spatial spread of genetic, ecological, and cultural traits. While some of these traits are advantageous (and hence selected), other, nonselected traits can also spread by hitchhiking on the wave of population expansion. This requires us to understand how the spread of a hitchhiking trait is coupled to the wave of advance of its host population. Here, we use a system of coupled Fisher-Kolmogorov-Petrovsky-Piskunov (F-KPP) equations to describe the spread of a horizontally transmitted hitchhiking trait within a population as it expands. We extend F-KPP wave theory to the system of coupled equations to predict how the hitchhiking trait spreads as a wave within the expanding population. We show that the speed of this trait wave is controlled by an intricate coupling between the tip of the population and trait waves. Our analysis yields a new speed selection mechanism for coupled waves of advance and reveals the existence of previously unexpected speed transitions.
Environmental Risk Factors by Gender Associated With Attention-Deficit/Hyperactivity Disorder
Authors: Silva Desiree , Colvin Lyn , Hagemann Erika , Bower Carol 
Published: December 2013

BACKGROUND:
Early environmental risk factors associated with attention-deficit/hyperactivity disorder (ADHD) have been increasingly suggested. Our study investigates the maternal, pregnancy, and newborn risk factors by gender for children prescribed stimulant medication for treatment of ADHD in Western Australia.

METHODS:
This is a population-based, record linkage case–control study. The records of all non-Aboriginal children and adolescents born in Western Australia and aged &lt;25 years who were diagnosed with ADHD and prescribed stimulant medication (cases = 12 991) were linked to the Midwives Notification System (MNS) to obtain maternal, pregnancy, and birth information. The control population of 30 071 children was randomly selected from the MNS.

RESULTS:
Mothers of children with ADHD were significantly more likely to be younger, be single, have smoked in pregnancy, have labor induced, and experience threatened preterm labor, preeclampsia, urinary tract infection in pregnancy, or early term delivery irrespective of the gender of the child, compared with the control group. In the fully adjusted model, a novel finding was of a possible protective effect of oxytocin augmentation in girls. Low birth weight, postterm pregnancy, small for gestational age infant, fetal distress, and low Apgar scores were not identified as risk factors.

CONCLUSIONS:
Smoking in pregnancy, maternal urinary tract infection, being induced, and experiencing threatened preterm labor increase the risk of ADHD, with little gender difference, although oxytocin augmentation of labor appears protective for girls. Early term deliveries marginally increased the risk of ADHD. Studies designed to disentangle possible mechanisms, confounders, or moderators of these risk factors are warranted.
Identifying Potential Kidney Donors Among Newborns Undergoing Circulatory Determination of Death
Authors: Hanley Heather , Kim Sunhwa , Willey Erin , Castleberry Dana , Mathur Mudit 
Published: December 2013

BACKGROUND:
Over 96 000 patients await kidney transplantation in the United States, and 35 000 more are wait-listed annually. The demand for donor kidneys far outweighs supply, resulting in significant waiting list morbidity and mortality. We sought to identify potential kidney donors among newborns because en bloc kidney transplantation donation after circulatory determination of death (DCDD) may broaden the donor pool.

METHODS:
We reviewed discharges from our 84-bed NICU between November 2002 and October 2012 and identified all deaths. The mode of death among potential organ donors (weight ≥1.8 kg) was recorded. Patients undergoing withdrawal of life support were further evaluated for DCDD potential. After excluding patients with medical contraindications, those with warm ischemic time (WIT) less than 120 minutes were characterized as potential kidney donors.

RESULTS:
There were 11 201 discharges. Of 609 deaths, 359 patients weighed ≥1.8 kg and 159 died after planned withdrawal of life support. The exact time of withdrawal could not be determined for 2 patients, and 100 had at least 1 exclusion criterion. Of the remaining patients, 42 to 57 infants were potential en bloc kidney donors depending on acceptance threshold for WIT. Applying a 40% to 70% consent rate range would yield 1.7 to 4 newborn DCDD donors per year.

CONCLUSIONS:
A neonatal DCDD kidney program at our institution could provide 2 to 4 paired kidneys for en bloc transplantation each year. Implementing a DCDD kidney donation program in NICUs could add a new source of donors and increase the number of kidneys available for transplantation.
Bronchiolitis Management Before and After the AAP Guidelines
Authors: Parikh Kavita , Hall Matthew , Teach Stephen J. 
Published: December 2013

BACKGROUND AND OBJECTIVES:
Evidence-based practice guidelines for bronchiolitis management published by the American Academy of Pediatrics in 2006 recommend supportive care with limited diagnostic testing and treatment. We sought to determine the impact of these guidelines on the treatment of hospitalized children.

METHODS:
We analyzed data on inpatients with bronchiolitis aged 1 to 24 months from the Pediatric Health Information System, an administrative billing database, from November 1, 2004 to March 31, 2012. We compared trends in use of diagnostic and treatment resources before and after the publication of the guidelines by using segmented time series.

RESULTS:
A total of 41 pediatric hospitals contributed data to yield 130 262 patients; 58% were male, and 59% were publicly insured. Median age was 4.0 months (interquartile range, 2–9). Unadjusted analysis showed improvement in utilization rates before and after guidelines for diagnostic tests and for medications; however, there was no decreased use of antibiotics. A segmented regression analysis also demonstrated differences in rates of change before and after guidelines, with significant improvement for chest radiography, steroids, and bronchodilators (P &lt; .0001).

CONCLUSIONS:
In a nationally representative cohort of pediatric hospitals, publication of the 2006 American Academy of Pediatrics bronchiolitis guidelines was associated with significant reductions in the use of diagnostic and therapeutic resources.
Costimulation Modulation With Abatacept in Patients With Recent-Onset Type 1 Diabetes: Follow-up 1 Year After Cessation of Treatment
Authors: Orban Tihamer , Bundy Brian , Becker Dorothy J. , DiMeglio Linda A. , Gitelman Stephen E. , Goland Robin , Gottlieb Peter A. , Greenbaum Carla J. , Marks Jennifer B. , Monzavi Roshanak , Moran Antoinette , Peakman Mark , Raskin Philip , Russell William E. , Schatz Desmond , Wherrett Diane K. , Wilson Darrell M. , Krischer Jeffrey P. , Skyler Jay S. ,   the Type 1 Diabetes TrialNet Abatacept Study Group
Published: December 2013

OBJECTIVE
We previously reported that 2 years of costimulation modulation with abatacept slowed decline of β-cell function in recent-onset type 1 diabetes (T1D). Subsequently, abatacept was discontinued and subjects were followed to determine whether there was persistence of effect.

RESEARCH DESIGN AND METHODS
Of 112 subjects (ages 6–36 years) with T1D, 77 received abatacept and 35 received placebo infusions intravenously for 27 infusions over 2 years. The primary outcome—baseline-adjusted geometric mean 2-h area under the curve (AUC) serum C-peptide during a mixed-meal tolerance test (MMTT) at 2 years—showed higher C-peptide with abatacept versus placebo. Subjects were followed an additional year, off treatment, with MMTTs performed at 30 and 36 months.

RESULTS
C-peptide AUC means, adjusted for age and baseline C-peptide, at 36 months were 0.217 nmol/L (95% CI 0.168–0.268) and 0.141 nmol/L (95% CI 0.071–0.215) for abatacept and placebo groups, respectively (P = 0.046). The C-peptide decline from baseline remained parallel with an estimated 9.5 months’ delay with abatacept. Moreover, HbA1c levels remained lower in the abatacept group than in the placebo group. The slightly lower (nonsignificant) mean total insulin dose among the abatacept group reported at 2 years was the same as the placebo group by 3 years.

CONCLUSIONS
Costimulation modulation with abatacept slowed decline of β-cell function and improved HbA1c in recent-onset T1D. The beneficial effect was sustained for at least 1 year after cessation of abatacept infusions or 3 years from T1D diagnosis.
Paradoxical Reduction in HDL-C With Fenofibrate and Thiazolidinedione Therapy in Type 2 Diabetes: The ACCORD Lipid Trial
Authors: Linz Peter E. , Lovato Laura C. , Byington Robert P. , O’Connor Patrick J. , Leiter Lawrence A. , Weiss Daniel , Force Rex W. , Crouse John R. , Ismail-Beigi Faramarz , Simmons Debra L. , Papademetriou Vasilios , Ginsberg Henry N. , Elam Marshall B. 
Published: December 2013

OBJECTIVE
To determine the occurrence of extremely low HDL cholesterol (HDL-C) among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial and to examine the relationship of this finding with treatment with fenofibrate and thiazolidinedione (TZD).

RESEARCH DESIGN AND METHODS
The ACCORD Lipid Trial was a randomized, double-blind, placebo-controlled study conducted in patients with type 2 diabetes at 77 clinical centers across the U.S. and Canada in a 5,518-patient subset of the larger 10,251 ACCORD Glycemia Trial. Patients were enrolled from 11 January 2001 to 29 October 2005 and followed until the end of study visits between 1 March and 30 June 2009. Follow-up in the ACCORD Lipid Trial was 4–8 years (mean 4.7 years). Patients were treated with blinded fenofibrate or placebo on a background of simvastatin therapy. The main outcome measures for these descriptive, post hoc analyses was the occurrence of extremely low HDL-C (defined as &lt;25 mg/dL [0.647 mmol/L]) during the trial.

RESULTS
Among ACCORD Lipid Trial participants, the occurrence of extremely low HDL-C ever during study follow-up was 106% higher among those randomized to fenofibrate (10.1% fenofibrate vs. 4.9% placebo, P &lt; 0.001). The occurrence of low HDL-C was associated with concurrent treatment with fenofibrate and TZD (7.0% for both vs. 2.2% for neither at 48 months postrandomization).

CONCLUSIONS
Idiosyncratic and marked reduction in HDL-C can occur in some patients treated with both fenofibrate and TZD. Practitioners should recognize this important potential idiosyncratic reaction and take appropriate corrective action.