bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide profiling identifies associations between lupus nephritis and differential methylation of genes regulating tissue hypoxia and type 1 interferon responses
Authors: Mok Amanda , Solomon Olivia , Nayak Renuka R , Coit Patrick , Quach Hong L , Nititham Joanne , Sawalha Amr H , Barcellos Lisa F , Criswell Lindsey A , Chung Sharon A 
Published: December 2016

ObjectivePrevious studies have shown that differential DNA methylation is associated with SLE susceptibility. How DNA methylation affects the clinical heterogeneity of SLE has not been fully defined. We conducted this study to identify differentially methylated CpG sites associated with nephritis among women with SLE.MethodsThe methylation status of 428 229 CpG sites across the genome was characterised for peripheral blood cells from 322 women of European descent with SLE, 80 of whom had lupus nephritis, using the Illumina HumanMethylation450 BeadChip. Multivariable linear regression adjusting for population substructure and leucocyte cell proportions was used to identify differentially methylated sites associated with lupus nephritis. The influence of genetic variation on methylation status was investigated using data from a genome-wide association study of SLE. Pathway analyses were used to identify biological processes associated with lupus nephritis.ResultsWe identified differential methylation of 19 sites in 18 genomic regions that was associated with nephritis among patients with SLE (false discovery rate q<0.05). Associations for four sites inHIF3A,IFI44andPRR4were replicated when examining methylation data derived from CD4+ T cells collected from an independent set of patients with SLE. These associations were not driven by genetic variation within or around the genomic regions. In addition, genes associated with lupus nephritis in a prior genome-wide association study were not differentially methylated in this epigenome-wide study. Pathway analysis indicated that biological processes involving type 1 interferon responses and the development of the immune system were associated with nephritis in patients with SLE.ConclusionsDifferential methylation of genes regulating the response to tissue hypoxia and interferon-mediated signalling is associated with lupus nephritis among women with SLE. These findings have not been identified in genetic studies of lupus nephritis, suggesting that epigenome-wide association studies can help identify the genomic differences that underlie the clinical heterogeneity of SLE.
Characteristics and Outcomes of Patients With Myocarditis Listed for Heart Transplantation
Authors: ElAmm Chantal A. , Al-Kindi Sadeer G. , Oliveira Guilherme H. 
Published: December 2016

Background—
Myocarditis can cause dilated cardiomyopathy resulting in end-stage heart failure requiring advanced therapies. There is little contemporary information on the clinical progression, need for mechanical circulatory support, and outcomes of orthotopic heart transplantation of these patients.

Methods and Results—

We queried the UNOS database (United Network for Organ Sharing) for all adults listed for orthotopic heart transplantation (2000–2015) with a listed diagnosis of myocarditis. Comparative and survival analyses were performed. Of 45 941 adults listed for orthotopic heart transplantation during this period, we identified 299 patients (0.7%) with the diagnosis of myocarditis. Compared with patients with nonischemic cardiomyopathy (NICM) and ischemic cardiomyopathy (ICM), myocarditis patients were younger (myocarditis 43.4±14.2 years, NICM 49.8±12.4 years, and ICM 57.5±8.0 years;
P
<0.001) and more frequently listed as status 1A (myocarditis 44% versus NICM 21% versus ICM 21%;
P
<0.001), with significantly higher need for mechanical ventilation (myocarditis 11% versus NICM 2% versus ICM 4%;
P
<0.001), biventricular mechanical circulatory support (myocarditis 19% versus NICM 2%, versus ICM 2%;
P
<0.001), and extracoroporeal membrane oxygenation (myocarditis 5% versus NICM 0.4% versus ICM 1%;
P
<0.001). Additionally, patients with myocarditis had higher likelihood of delisting for clinical improvement (hazard ratio, 2.49 [95% confidence interval, 1.63–3.79] versus ICM and hazard ratio, 2.12 [95% confidence interval, 1.40–3.22] versus NICM;
P
<0.001). Despite higher allosensitization, patients with myocarditis had similar post-transplant rejection, retransplantation, and survival rates compared with other groups.

Conclusions—
Patients with the diagnosis of myocarditis listed for orthotopic heart transplantation are younger, sicker, and recover more frequently but require more biventricular mechanical circulatory support. Heart transplantation survival is comparable to that of patients with other types of heart failure.
High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice
Authors: Marques Francine Z. , Nelson Erin , Chu Po-Yin , Horlock Duncan , Fiedler April , Ziemann Mark , Tan Jian K. , Kuruppu Sanjaya , Rajapakse Niwanthi W. , El-Osta Assam , Mackay Charles R. , Kaye David M. 
Published: December 2016

Background:
Dietary intake of fruit and vegetables is associated with lower incidence of hypertension, but the mechanisms involved have not been elucidated. Here, we evaluated the effect of a high-fiber diet and supplementation with the short-chain fatty acid acetate on the gut microbiota and the prevention of cardiovascular disease.

Methods:
Gut microbiome, cardiorenal structure/function, and blood pressure were examined in sham and mineralocorticoid excess–treated mice with a control diet, high-fiber diet, or acetate supplementation. We also determined the renal and cardiac transcriptome of mice treated with the different diets.

Results:

We found that high consumption of fiber modified the gut microbiota populations and increased the abundance of acetate-producing bacteria independently of mineralocorticoid excess. Both fiber and acetate decreased gut dysbiosis, measured by the ratio of Firmicutes to Bacteroidetes, and increased the prevalence of
Bacteroides acidifaciens
. Compared with mineralocorticoid-excess mice fed a control diet, both high-fiber diet and acetate supplementation significantly reduced systolic and diastolic blood pressures, cardiac fibrosis, and left ventricular hypertrophy. Acetate had similar effects and markedly reduced renal fibrosis. Transcriptome analyses showed that the protective effects of high fiber and acetate were accompanied by the downregulation of cardiac and renal
Egr1
, a master cardiovascular regulator involved in cardiac hypertrophy, cardiorenal fibrosis, and inflammation. We also observed the upregulation of a network of genes involved in circadian rhythm in both tissues and downregulation of the renin-angiotensin system in the kidney and mitogen-activated protein kinase signaling in the heart.

Conclusions:
A diet high in fiber led to changes in the gut microbiota that played a protective role in the development of cardiovascular disease. The favorable effects of fiber may be explained by the generation and distribution of one of the main metabolites of the gut microbiota, the short-chain fatty acid acetate. Acetate effected several molecular changes associated with improved cardiovascular health and function.
Elusive does not always equal rare: genetic assessment of a protected Gila monster (Heloderma suspectum) population in Saguaro National Park, Arizona
Authors: Farrar Victoria Sophia , Edwards Taylor , Bonine Kevin Edward 
Published: December 2016

Population genetic baselines for species perceived to be at-risk are crucial for monitoring population trends and making well-informed management decisions. We characterized the genetic status of a population of Gila monsters (Heloderma suspectum), a large venomous lizard native to deserts of the southwestern United States and northern Mexico, by sampling 100 individuals in Sonoran Desert upland habitat at Saguaro National Park, Arizona, USA. We used 18 microsatellite markers, along with 1195 bp of sequence data from the mitochondrial DNA 12S locus, to examine genetic diversity, estimate effective population size, and assess demographic history. Despite suburban development adjacent to the study area, we observed high genetic diversity with uninhibited gene flow within this protected population. We estimated effective population size (Ne) for the total sample area (80 km2) using the linkage disequilibrium method in NeEstimator to be 94 individuals (95% confidence interval: 80.7-111.2). In 2011, we used capture-recapture methods to estimate that 80 adult Gila monsters (95% CI = 37-225) inhabited the area along the 14-km transect that we surveyed most frequently; probability of detecting resident Gila monsters during surveys was <0.01, highlighting the challenges of studying the species. Despite being considered an elusive and thus potentially rare species, these data reveal that in this protected environment the population appears healthy and robust. The results provide an important genetic baseline for future studies and monitoring, and exemplify the success of protective population measures in National Parks and under Arizona state laws.
When cervical pain is actually migraine: An observational study in 207 patients
Authors: Viana Michele , Sances Grazia , Terrazzino Salvatore , Sprenger Till , Nappi Giuseppe , Tassorelli Cristina 
Published: December 2016

Introduction A large proportion of migraine patients remain undiagnosed or misdiagnosed in Italy. In our experience, many migraineurs self-diagnose their condition as “cervical pain attack” or “cervical pain syndrome” (CP), assuming cervical spine pathology as the cause. We aimed to phenotype and classify the headache of patients with self-diagnosed CP, and to describe this sample of patients. Methods Consecutive patients aged 18 to 75 years, referred to the Headache Center of the Mondino Institute (Pavia, Italy) for a first visit for headache, completed a questionnaire about CP and were subsequently examined by an experienced clinician. Results Out of 207 patients, 132 (64%) believed they suffered from CP. According to ICHD-IIIβ criteria, these patients suffered from migraine or probable migraine in 91% of cases. The great majority of patients who believed that they suffered from CP underwent unnecessary medical exams (including radiation exposure in 40% of cases) and used treatments that were inadequate for their real diagnosis. Conclusion The majority of patients with CP suffer from typical migraine. The misdiagnosis produces an economic burden (for patients and the health care system) and leads to impaired quality of life of patients.
Shift from intravenous or 16% subcutaneous replacement therapy to 20% subcutaneous immunoglobulin in patients with primary antibody deficiencies
Authors: Canessa Clementina , Iacopelli Jessica , Pecoraro Antonio , Spadaro Giuseppe , Matucci Andrea , Milito Cinzia , Vultaggio Alessandra , Agostini Carlo , Cinetto Francesco , Danieli Maria Giovanna , Gambini Simona , Marasco Carolina , Trizzino Antonino , Vacca Angelo , De Mattia Domenico , Martire Baldassarre , Plebani Alessandro , Di Gioacchino Mario , Gatta Alessia , Finocchi Andrea , Licciardi Francesco , Martino Silvana , De Carli Marco , Moschese Viviana , Azzari Chiara 
Published: December 2016

In patients with primary antibody deficiencies, subcutaneous administration of IgG (SCIG) replacement is effective, safe, well-tolerated, and can be self-administered at home. A new SCIG replacement at 20% concentration (Hizentra®) has been developed and has replaced Vivaglobin® (SCIG 16%). An observational prospective multi-centric open-label study, with retrospective comparison was conducted in 15 Italian centers, in order to investigate whether and to what extent switching to Hizentra® would affect frequency of infusions, number of infusion sites, patients’ satisfaction, and tolerability in patients previously treated with Vivaglobin® or intravenous immunoglobulins (IVIG). Any variations of dosage, frequency and duration of the infusions, and of number of infusion sites induced by Hizentra® with respect to the former treatment were recorded. Practical advantages and disadvantages of Hizentra®, with respect to the medicinal product formerly used, and the variations in patients’ therapy-related satisfaction were monitored by means of the TSQM (Treatment Satisfaction Questionnaire for Medication); number, frequency, and duration of infectious events and adverse effects were recorded. Eighty-two patients switched to Hizentra®: 19 (23.2%) from IVIG and 63 (76.8%) from Vivaglobin®. The mean interval between infusions was not affected by the shift (7.0 ± 2.0 days with previous treatment versus 7.1 ± 1.2 during Hizentra®). A decrease in the number of infusion sites with Hizentra® was recorded in 12 out of 56 patients for whom these data were available. At 6 months, 89.7% of patients were satisfied with Hizentra®; no difference in terms of effectiveness, side effects, convenience, and global satisfaction was observed. No difference in the incidence of adverse events was reported.
Validity of the Italian Code of Ethics for everyday nursing practice
Authors: Gobbi Paola , Castoldi Maria Grazia , Alagna Rosa Anna , Brunoldi Anna , Pari Chiara , Gallo Annamaria , Magri Miriam , Marioni Lorena , Muttillo Giovanni , Passoni Claudia , Torre Anna La , Rosa Debora , Carnevale Franco A 
Published: December 2016

Background: The research question for this study was as follows: Is the Code of Ethics for Nurses in Italy (Code) a valid or useful decision-making instrument for nurses faced with ethical problems in their daily clinical practice? Method: Focus groups were conducted to analyze specific ethical problems through 11 case studies. The analysis was conducted using sections of the Code as well as other relevant documents. Each focus group had a specific theme and nurses participated freely in the discussions according to their respective clinical competencies. Ethical considerations: The executive administrative committee of the local nursing licensing council provided approval for conducting this project. Measures were taken to protect the confidentiality of consenting participants. Findings: The answer to the research question posed for this investigation was predominantly positive. Many sections of the Code were useful for discussion and identifying possible solutions for the ethical problems presented in the 11 cases. Conclusion: We concluded that the Code of Ethics for Nurses in Italy can be a valuable aid in daily practice in most clinical situations that can give rise to ethical problems.
The cost–quality relationship in European hospitals: a systematic review
Authors: Søgaard Rikke , Enemark Ulrika 
Published: December 2016

Objective To determine the relationship between cost and quality in European hospitals. Methods Juran’s cost–quality curve served as a theoretical framework, linked to basic efficiency concepts. Based on systematic database searches, citation searches and cross-referencing, we identify 1093 empirical studies. After exclusion of studies from outside Europe (699), non-hospital settings (10 studies), lack of a cost parameter (194) or a quality parameter (27 studies), 22 studies (28 analyses) were assessed for direction of association and methodological heterogeneity. Results There was evidence of positive, negative, two-directional and no association between cost and quality. We examined whether diagnosis, procedure, type of quality measure and specification of the econometric model could explain the inconsistent evidence, but no clear explanation is identified. Despite the significant policy relevance, evidence on the relationship between costs and quality is limited. The literature is characterized by substantial methodological heterogeneity and lack of explicit definitions of the chosen cost and quality parameters, the econometric model and the underlying hypothesis for the cost–quality relationship. Conclusion It has been more than 60 years since Juran introduced the idea of failure costs, which implied that the marginal costs of quality could be non-constant. It seems imperative to acknowledge this idea in future studies.
Clinical correlation of anatomical location of non-thrombotic iliac vein lesion
Authors: Aurshina Afsha , Kheyson Borislav , Eisenberg Justin , Hingorani Anil , Ganelin Arkady , Ascher Enrico , Iadgarova Eleanor , Marks Natalie 
Published: December 2016

Objective Treatment of non-thrombotic iliac vein lesions is an active area of research. Intravascular ultrasound allows its localization. We chose intravascular ultrasound to clarify the exact anatomical location of non-thrombotic iliac vein lesions and correlate it with clinical findings. Materials and methods Over seven months, we performed ilio-femoral intravascular ultrasound studies on 217 patients, in 141 women and 76 men. The average age ± standard deviation was 68 ± 14 years. We used intravascular ultrasound intraoperatively to measure the ilio-femoral veins and compared it with adjacent non-stenotic ilio-femoral veins. If more than 50% area or diameter reduction was found, it was treated with appropriate balloon and stent. Results We identified 244 lesions, 124 in left lower extremity and 120 in the right lower extremity. The most common site was the proximal common iliac vein 38.7% (22.5% females and 16.12% males) in left lower extremity and middle external iliac vein 29.16% (18.33% females and 10.83% males) in right lower extremity. The least common site was the distal external iliac vein in 3.2% (all 3.2% females) and the distal external iliac vein 7.5% (5% females and 2.5% males) in right lower extremity. Clinical correlation was noted between laterality and location of the NIVL lesion ( p < 0.0001). Conclusion This analysis gives an insight into understanding the exact anatomical locations of the non-thrombotic iliac vein lesions helping clinicians and researchers guide their treatment and research.
Oesophageal candidiasis and squamous cell cancer in patients with gain‐of‐function STAT1 gene mutation
Authors: Koo Sara , Kejariwal Deepak , Al‐Shehri Tariq , Dhar Anjan , Lilic Desa 
Published: December 2016

BackgroundOesophageal candidiasis is a common, usually self‐limiting opportunistic infection, but long‐term infection with Candida is known to predispose to oral and oesophageal squamous cell cancer (SCC). Permissive factors that lead to immune deficiencies can underlie persistent or recurring candidiasis, called chronic mucocutaneous candidiasis (CMC). Secondary immune deficiencies are most often due to human immunodeficiency virus (HIV) infection, antibiotic use and immunosuppressive treatment (steroids, chemotherapy). Inborn errors of the immune system (primary immune deficiencies) can present with isolated CMC known as CMC disease (CMCD), which is most often found in patients with autoimmune polyendocrinopathy syndrome type 1 (APS1)/APECED or in patients with an underlying gain‐of‐function STAT1 mutation (GOF‐STAT1).ObjectiveTo describe a new form of inherited/familial CMC with a high risk for developing squamous cell carcinoma of the oesophagus, due to a gain‐of‐function mutation in the STAT1 gene.Methods and resultsThis report describes a family of patients with CMC with confirmed GOF‐STAT1 mutation. These patients usually present with CMCD in childhood, have severe oral and oesophageal candidiasis accompanied by severe difficulty swallowing, chest pain, heartburn, and are at risk of developing oral and/or oesophageal SCC. This case series describes six patients in three generations of the same family, two of whom developed and died of SCC. We recommend regular endoscopic surveillance to detect early oesophageal neoplasia in patients with CMCD as well as urgent endoscopy in symptomatic patients.ConclusionCMC is not a well‐recognised condition in gastroenterology practice and clinicians need to be aware of the genetics of the condition as well as the risk for oesophageal cancer so that they can counsel their patients and arrange surveillance appropriately.
The relationship between fatigability and sleep quality in people with multiple sclerosis
Authors: Aldughmi Mayis , Huisinga Jessie , Lynch Sharon G , Siengsukon Catherine F 
Published: December 2016

Background Perceived fatigue and fatigability are constructs of multiple sclerosis (MS)-related fatigue. Sleep disturbances lead to poor sleep quality, which has been found to be associated with perceived fatigue in people with MS (PwMS). However, the relationship between fatigability and sleep quality is unknown. Objective To explore the relationship between physical and cognitive fatigability with self-reported and objective measures of sleep quality in PwMS. Methods Fifty-one ambulatory PwMS participated in the study. Physical fatigability was measured by percent-change in meters walked on the six-minute walk test (6MWT) and in force exerted on a repeated maximal hand grip test. Cognitive fatigability was measured using response speed variability on the continuous performance test. Self-report sleep quality was measured using the Pittsburgh Sleep Quality Index, and objective sleep quality was measured using 1 week of actigraphy. Results Components of the Pittsburgh Sleep Quality Index and several actigraph parameters were significantly associated with physical fatigability and cognitive fatigability. However, controlling for depression eliminated the association between the sleep outcomes and cognitive fatigability and attenuated the association between the sleep outcomes and physical fatigability. Conclusion Poor sleep quality is related to fatigability in MS but depression appears to mediate these relationships.
Robust multi-group gene set analysis with few replicates
Authors: Mishra Pashupati P. , Medlar Alan , Holm Liisa , Törönen Petri 
Published: December 2016

Abstract
Background
Competitive gene set analysis is a standard exploratory tool for gene expression data. Permutation-based competitive gene set analysis methods are preferable to parametric ones because the latter make strong statistical assumptions which are not always met. For permutation-based methods, we permute samples, as opposed to genes, as doing so preserves the inter-gene correlation structure. Unfortunately, up until now, sample permutation-based methods have required a minimum of six replicates per sample group.

Results
We propose a new permutation-based competitive gene set analysis method for multi-group gene expression data with as few as three replicates per group. The method is based on advanced sample permutation technique that utilizes all groups within a data set for pairwise comparisons. We present a comprehensive evaluation of different permutation techniques, using multiple data sets and contrast the performance of our method, mGSZm, with other state of the art methods. We show that mGSZm is robust, and that, despite only using less than six replicates, we are able to consistently identify a high proportion of the top ranked gene sets from the analysis of a substantially larger data set. Further, we highlight other methods where performance is highly variable and appears dependent on the underlying data set being analyzed.

Conclusions
Our results demonstrate that robust gene set analysis of multi-group gene expression data is permissible with as few as three replicates. In doing so, we have extended the applicability of such approaches to resource constrained experiments where additional data generation is prohibitively difficult or expensive. An R package implementing the proposed method and supplementary materials are available from the website http://ekhidna.biocenter.helsinki.fi/downloads/pashupati/mGSZm.html.