bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Association Analyses Highlight
IL6
,
ALPL
, and
NAV1
As 3 New Susceptibility Genes Underlying Calcific Aortic Valve Stenosis
Authors: Thériault Sébastien , Dina Christian , Messika-Zeitoun David , Le Scouarnec Solena , Capoulade Romain , Gaudreault Nathalie , Rigade Sidwell , Li Zhonglin , Simonet Floriane , Lamontagne Maxime , Clavel Marie-Annick , Arsenault Benoit J. , Boureau Anne-Sophie , Lecointe Simon , Baron Estelle , Bonnaud Stéphanie , Karakachoff Matilde , Charpentier Eric , Fellah Imen , Roussel Jean-Christian , Philippe Verhoye Jean , Baufreton Christophe , Probst Vincent , Roussel Ronan , Redon Richard , Dagenais François , Pibarot Philippe , Mathieu Patrick , Le Tourneau Thierry , Bossé Yohan , Schott Jean-Jacques , Balkau B. , Ducimetière P. , Eschwège E. , Alhenc-Gelas F. , Girault A. , Fumeron F. , Marre M. , Bonnet F. , Bonnefond A. , Froguel P. , Rancière F. , Cogneau J. , Born C. , Caces E. , Cailleau M. , Lantieri O , Moreau J.G. , Rakotozafy F. , Tichet J. , Vol S. 
Published: October 2019

Background:

Calcific aortic valve stenosis (CAVS) is a frequent and life-threatening cardiovascular disease for which there is currently no medical treatment available. To date, only 2 genes,
LPA
and
PALMD
, have been identified as causal for CAVS. We aimed to identify additional susceptibility genes for CAVS.

Methods:
A GWAS (genome-wide association study) meta-analysis of 4 cohorts, totaling 5115 cases and 354 072 controls of European descent, was performed. A TWAS (transcriptome-wide association study) was completed to integrate transcriptomic data from 233 human aortic valves. A series of post-GWAS analyses were performed, including fine-mapping, colocalization, phenome-wide association studies, pathway, and tissue enrichment as well as genetic correlation with cardiovascular traits.

Results:

In the GWAS meta-analysis, 4 loci achieved genome-wide significance, including 2 new loci:
IL6
(interleukin 6) on 7p15.3 and
ALPL
(alkaline phosphatase) on 1p36.12. A TWAS integrating gene expression from 233 human aortic valves identified
NAV1
(neuron navigator 1) on 1q32.1 as a new candidate causal gene. The CAVS risk alleles were associated with higher mRNA expression of
NAV1
in valve tissues. Fine-mapping identified rs1800795 as the most likely causal variant in the
IL6
locus. The signal identified colocalizes with the expression of the
IL6
RNA antisense in various tissues. Phenome-wide association analyses in the UK Biobank showed colocalized associations between the risk allele at the
IL6
lead variant and higher eosinophil count, pulse pressure, systolic blood pressure, and carotid artery procedures, implicating modulation of the IL6 pathways. The risk allele at the
NAV1
lead variant colocalized with higher pulse pressure and higher prevalence of carotid artery stenosis. Association results at the genome-wide scale indicated genetic correlation between CAVS, coronary artery disease, and cardiovascular risk factors.

Conclusions:
Our study implicates 3 new genetic loci in CAVS pathogenesis, which constitute novel targets for the development of therapeutic agents.
Myocardial Fibrosis and Prognosis in Heart Transplant Recipients
Authors: Hughes Andrew , Okasha Osama , Farzaneh-Far Afshin , Kazmirczak Felipe , Nijjar Prabhjot S. , Velangi Pratik , Akçakaya Mehmet , Martin Cindy M. , Shenoy Chetan 
Published: October 2019

Background:
Myocardial fibrosis is a well-described histopathologic feature in heart transplant recipients. Whether myocardial fibrosis in heart transplant recipients is independently associated with clinical outcomes is unclear. We sought to determine whether myocardial fibrosis on late gadolinium enhancement cardiovascular magnetic resonance imaging in heart transplant recipients was independently associated with all-cause death or major adverse cardiac outcomes in the long-term.

Methods:
Using a cohort of consecutive heart transplant recipients that had cardiovascular magnetic resonance imaging, we determined the prevalence and the patterns of myocardial fibrosis and analyzed associations between myocardial fibrosis and a composite end point of all-cause death or major adverse cardiac events: retransplantation, nonfatal myocardial infarction, coronary revascularization, and heart failure hospitalization.

Results:

One hundred and fifty-two heart transplant recipients (age, 54±15 years; 29% women; 5.0±5.4 years after heart transplantation) were included. Myocardial fibrosis was present in 18% (37% infarct pattern, 41% noninfarct pattern, and 22% both). Its prevalence was positively associated with cardiac allograft vasculopathy grade. With a median follow-up of 2.6 years, myocardial fibrosis was independently associated with all-cause death or major adverse cardiac events (hazard ratio, 2.88; 95% CI, 1.59–5.23;
P
<0.001) after adjustment for cardiac allograft vasculopathy, history of rejection, time since transplantation, left ventricular ejection fraction, and indexed right ventricular end-diastolic volume. Every 1% increase in myocardial fibrosis was independently associated with a 6% higher hazard for all-cause death or major adverse cardiac events (hazard ratio, 1.06; 95% CI, 1.03–1.09;
P
<0.001). The addition of myocardial fibrosis variables to models with cardiac allograft vasculopathy, history of rejection, time since transplantation, left ventricular ejection fraction, and indexed right ventricular end-diastolic volume resulted in significant improvements in model fit, suggesting incremental prognostic value.

Conclusions:
In heart transplant recipients, myocardial fibrosis is seen on late gadolinium enhancement cardiovascular magnetic resonance imaging in 18%. Both the presence and the extent of myocardial fibrosis are independently associated with the long-term risk of all-cause death or major adverse cardiac events.
Bone Marrow-Derived Cells Restore Functional Integrity of the Gut Epithelial and Vascular Barriers in a Model of Diabetes and ACE2 Deficiency
Authors: Duan Yaqian , Prasad Ram , Feng Dongni , Beli Eleni , Li Calzi Sergio , Longhini Ana Leda F. , Lamendella Regina , Floyd Jason L. , Dupont Mariana , Noothi Sunil K. , Sreejit Gopalkrishna , Athmanathan Baskaran , Wright Justin , Jensen Amanda R. , Oudit Gavin Y. , Markel Troy A. , Nagareddy Prabhakara R. , Obukhov Alexander G. , Grant Maria B. 
Published: October 2019

Rationale:
There is incomplete knowledge of the impact of bone marrow cells on the gut microbiome and gut barrier function.

Objective:
We postulated that diabetes mellitus and systemic ACE2 (angiotensin-converting enzyme 2) deficiency would synergize to adversely impact both the microbiome and gut barrier function.

Methods and Results:

Bacterial 16S rRNA sequencing and metatranscriptomic analysis were performed on fecal samples from wild-type, ACE2
−/y
, Akita (type 1 diabetes mellitus), and ACE2
−/y
-Akita mice. Gut barrier integrity was assessed by immunofluorescence, and bone marrow cell extravasation into the small intestine was evaluated by flow cytometry. In the ACE2
−/y
-Akita or Akita mice, the disrupted barrier was associated with reduced levels of myeloid angiogenic cells, but no increase in inflammatory monocytes was observed within the gut parenchyma. Genomic and metatranscriptomic analysis of the microbiome of ACE2
−/y
-Akita mice demonstrated a marked increase in peptidoglycan-producing bacteria. When compared with control cohorts treated with saline, intraperitoneal administration of myeloid angiogenic cells significantly decreased the microbiome gene expression associated with peptidoglycan biosynthesis and restored epithelial and endothelial gut barrier integrity. Also indicative of diabetic gut barrier dysfunction, increased levels of peptidoglycan and FABP-2 (intestinal fatty acid-binding protein 2) were observed in plasma of human subjects with type 1 diabetes mellitus (n=21) and type 2 diabetes mellitus (n=23) compared with nondiabetic controls (n=23). Using human retinal endothelial cells, we determined that peptidoglycan activates a noncanonical TLR-2 (Toll-like receptor 2) associated MyD88 (myeloid differentiation primary response protein 88)-ARNO (ADP-ribosylation factor nucleotide-binding site opener)-ARF6 (ADP-ribosylation factor 6) signaling cascade, resulting in destabilization of p120-catenin and internalization of VE-cadherin as a mechanism of deleterious impact of peptidoglycan on the endothelium.

Conclusions:

We demonstrate for the first time that the defect in gut barrier function and dysbiosis in ACE2
−/y
-Akita mice can be favorably impacted by exogenous administration of myeloid angiogenic cells.
Associations Between Sleep Apnea and Subclinical Carotid Atherosclerosis
Authors: Zhao Ying Y. , Javaheri Sogol , Wang Rui , Guo Na , Koo Brian B. , Stein James H. , Korcarz Claudia E. , Redline Susan 
Published: October 2019

Background and Purpose—
Many health effects of sleep apnea (SA) may be mediated through accelerated atherosclerosis. We examined the associations of snoring and several measurements of SA with subclinical carotid atherosclerosis in a large multiethnic population sample.

Methods—
This analysis included 1615 participants (mean age, 68 years) from examination 5 (2010–2013) of the MESA study (Multi-Ethnic Study of Atherosclerosis). Sleep measures including SA (apnea-hypopnea index [4%], ≥15 events/hour) were derived from full in-home polysomnography. Carotid atherosclerosis was measured using high-resolution B-mode ultrasound. Multivariable linear and logistic regression models were used to evaluate the associations between sleep exposures with carotid intima-media thickness and the presence of carotid plaque, respectively. Effect modification by age, sex, and race/ethnicity was examined.

Results—

In multivariable analysis, SA was associated with an increased odds of carotid plaque presence in individuals aged <68 years (odds ratio, 1.47; 95% CI, 1.05–2.06) but not in older individuals (odds ratio, 0.95; 95% CI, 0.67–1.37;
P
interaction=0.078). Greater hypoxemia (sleep time <90% saturation) was associated with increasing carotid intima-media thickness in younger (0.028±0.014 mm) but not in older individuals (−0.001±0.013 mm;
P
interaction=0.106). Self-reported snoring was not associated with carotid atherosclerosis. In assessing race-specific outcomes, greater hypoxemia was associated with increased carotid intima-media thickness in blacks (0.049±0.017 mm;
P
interaction=0.033).

Conclusions—
In this large multiethnic population-based sample, sleep disturbances are associated with subclinical carotid atherosclerosis in both men and women, particularly in those <68 years of age. The mechanisms underlying the association between SA and carotid atherosclerosis may differ for carotid plaque and carotid intima-media thickness.
Association of Socioeconomic Status With Ischemic Stroke Survival
Authors: Vivanco-Hidalgo Rosa Maria , Ribera Aida , Abilleira Sònia 
Published: October 2019

Background and Purpose—
The aim of the study was to determine the impact of individuals’ socioeconomic status and their Primary Care Service Area Socioeconomic Index on survival after ischemic stroke.

Methods—
We conducted a nationwide population-based cohort study in Catalonia, Spain. We included all patients with first ischemic stroke admitted to a public hospital between January 1, 2015, and December 31, 2016. We measured both individual socioeconomic status (categorized as exempts, <€18 000 [$US 20 468] income per year, and >€18 000 income per year) and Primary Care Service Area Socioeconomic Index (from 0 to 100 categorized in quartiles).
We used mixed-effects logistic and survival models to estimate odds ratios and hazard ratios for the short- (30 days) and the long-term (3 years) all-cause case fatality rates by individuals’ socioeconomic status groups.

Results—
The cohort consisted of 16 344 ischemic stroke patients with 24 638 person-years of follow-up. We did not find an association between the lowest socioeconomic individual status and short-term survival (odds ratio, 1.03; 95% CI, 0.76–1.40), although we found it in patients with <€18 000 income/year (odds ratio, 1.26; 95% CI, 1.10–1.45). At long-term, after adjustment, we observed a gradient in mortality risk with decreasing individual socioeconomic status (hazard ratio, 1.52; 95% CI, 1.30–1.77). The Primary Care Service Area Socioeconomic Index had only an influence on short-term survival (odds ratio, 1.19; 95% CI, 1.03–1.37).

Conclusions—
Individuals’ socioeconomic status was associated with short- and long-term survival in patients with ischemic stroke. Conversely, Primary Care Service Area Socioeconomic Index measures had an influence only in short-term survival. A small fraction of this association is due to differences in comorbidity and cardiovascular risk factors. Interventions addressing both individuals’ and primary care service socioeconomic aspects might eventually affect differently short- and long-term survival.
Spike-Based Winner-Take-All Computation: Fundamental Limits and Order-Optimal Circuits
Authors: Su Lili , Chang Chia-Jung , Lynch Nancy 
Published: October 2019

Winner-take-all (WTA) refers to the neural operation that selects a (typically small) group of neurons from a large neuron pool. It is conjectured to underlie many of the brain's fundamental computational abilities. However, not much is known about the robustness of a spike-based WTA network to the inherent randomness of the input spike trains. In this work, we consider a spike-based [Formula: see text]–WTA model wherein [Formula: see text] randomly generated input spike trains compete with each other based on their underlying firing rates and [Formula: see text] winners are supposed to be selected. We slot the time evenly with each time slot of length 1 ms and model the [Formula: see text] input spike trains as [Formula: see text] independent Bernoulli processes. We analytically characterize the minimum waiting time needed so that a target minimax decision accuracy (success probability) can be reached. We first derive an information-theoretic lower bound on the waiting time. We show that to guarantee a (minimax) decision error [Formula: see text] (where [Formula: see text]), the waiting time of any WTA circuit is at least [Formula: see text]where [Formula: see text] is a finite set of rates and [Formula: see text] is a difficulty parameter of a WTA task with respect to set [Formula: see text] for independent input spike trains. Additionally, [Formula: see text] is independent of [Formula: see text], [Formula: see text], and [Formula: see text]. We then design a simple WTA circuit whose waiting time is [Formula: see text]provided that the local memory of each output neuron is sufficiently long. It turns out that for any fixed [Formula: see text], this decision time is order-optimal (i.e., it matches the above lower bound up to a multiplicative constant factor) in terms of its scaling in [Formula: see text], [Formula: see text], and [Formula: see text].
The Comprehension of STEM Graphics via a Multisensory Tablet Electronic Device by Students with Visual Impairments
Authors: Hahn Michael E. , Mueller Corrine M. , Gorlewicz Jenna L. 
Published: October 2019

Introduction: The current work probes the effectiveness of multimodal touch screen tablet electronic devices in conveying science, technology, engineering, and mathematics graphics via vibrations and sounds to individuals who are visually impaired (i.e., blind or low vision) and compares it with similar graphics presented in an embossed format. Method: A volunteer sample of 22 participants who are visually impaired, selected from a summer camp and local schools for blind students, were recruited for the current study. Participants were first briefly (∼30 min) trained on how to explore graphics via a multimodal touch screen tablet. They then explored six graphic types (number line, table, pie chart, bar chart, line graph, and map) displayed via embossed paper and tablet. Participants answered three content questions per graphic type following exploration. Results: Participants were only 6% more accurate when answering questions regarding an embossed graphic as opposed to a tablet graphic. A paired-samples t test indicated that this difference was not significant, t(14) = 1.91, p = .07. Follow-up analyses indicated that presentation medium did not interact with graphic type, F(5, 50) = 0.43, p = .83, nor visual ability, F(1, 13) = 0.00, p = .96. Discussion: The findings demonstrate that multimodal touch screen tablets may be comparable to embossed graphics in conveying iconographic science and mathematics content to individuals with visual impairments, regardless of the severity of impairment. The relative equivalence in response accuracy between mediums was unexpected, given that most students who participated were braille readers and had experience reading embossed graphics, whereas they were introduced to the tablet the day of testing. Implications for practitioners: This work illustrates that multimodal touch screen tablets may be an effective option for general education teachers or teachers of students with visual impairments to use in their educational practices. Currently, preparation of accessible graphics is time consuming and requires significant preparation, but such tablets provide solutions for offering “real-time” displays of these graphics for presentation in class.
Effects of Lifestyles of People with Visual Impairments on Cardiometabolic Risk Markers
Authors: Gawlik Krystyna , Zwierzchowska Anna , Rosołek Barbara 
Published: October 2019

Introduction: The aim of this study was to identify selected cardiometabolic risk markers and determine their correlation with lifestyles of adults with visual impairments. Methods: The study randomly selected 49 people with visual impairments (25 women and 24 men) aged 17–84 years (mean age 58.5 years). Body build, composition metrics, biochemical parameters, level of physical activity, and eating habits were evaluated. Results: Excessive body mass was found in 65% of respondents (72% women and 58% men). Above-typical blood total cholesterol levels were found in 52% of women and 42% of men, low-density lipoprotein (LDL) cholesterol levels in 33% of men and 20% of women, triglyceride levels in 16% of women and 17% of men and glucose in 56% of women and 42% of men. Reduced levels of high-density lipoprotein cholesterol were found in 25% of men and 20% of women. Results showed that 43% of respondents were not involved in physical activity at the recommended level. The use of nicotine was declared by 18% of respondents. No significant correlations were observed for the relationships between physical activity and somatic and biochemical parameters. Eating habits had a significant effect on the prevalence of above-typical LDL cholesterol levels, whereas smoking led to significant differences between study participants due to body mass index and fat percentage. Discussion: Lifestyles of individuals with visual impairments were not entirely healthy. Due to the characteristics of the disability, people with visual impairments are challenged with barriers to living healthy lifestyles. Implications for practitioners: The information obtained here can be used to implement adequate measures to provide equal opportunities for people who are blind or have low vision to lead healthy lifestyles and improve their quality of life.
Effect of Corticosteroid (Triamcinolone Acetonide) and Chlorhexidin on Chemotherapy-induced Oxidative Stress in Buccal Mucosa of Rats
Authors: Gümüş Sami , Yarιktaş Murat , Nazιroĝlu Mustafa , Uĝuz Abdülhadi Cihangir , Aynali Giray , Başpιnar Şirin 
Published: October 2019

Oral mucositis (OM) refers to erythematous and ulcerative lesions of the oral mucosa. This pathology can occur by various causes. Cancer therapy is one of the well-known causes of OM such as chemotherapy and/or with radiation therapy. It has been widely mentioned that oxidative stress parameters such as lipid peroxidation (LP) levels increase during cancer process. Glutathione (GSH) is one of the major intracellular enzymes to detoxify oxidant molecules. The aim of this study was to investigate and compare the effects of Triamcinolone Acetonide (TA), a synthetic steroid chlorhexidine (CHX), a chemical antiseptic, on 5-fluorouracil (5-FU), a chemotherapeutic agent and soft abrasion induced OM in buccal mucosa of rats. OM was induced in rats through a combination of 5-FU treatment and mild abrasion of the cheek pouch with a wire brush. Buccal mucosa lipid peroxidation (LP) levels were higher (p< 0.05) in 5-FU group than in control although LP levels were lower (p<0.05) in TA group than in control group. The reduced glutathione levels were lower (p<0.05) in 5-FU group than in the control group although its level was higher (p<0.05) in TA and CHX groups than in the 5-FU group. Glutathione peroxidase activity was also higher (p<0.05) in TA group than the 5-FU group. In histopathological analyses, treatment with TA reduced 5-FU induced inflammatory cell infiltration and ulceration (p<0.001) but not with CHX. In conclusion, we observed that TA and CHX treatment modulated chemotherapy induced oxidative injury in the rat OM. However, only TA histopathologically ameliorated the 5-FU induced OM of rats. These findings suggest that TA is a useful agent for management of experimental oxidative injury and OM caused by the chemotherapy.
Validation and comparison of two automated methods for quantifying brain white matter hyperintensities of presumed vascular origin
Authors: Waymont Jennifer M.J. , Petsa Chariklia , McNeil Chris J. , Murray Alison D. , Waiter Gordon D. 
Published: October 2019

Objectives White matter hyperintensities (WMH) are a common imaging finding indicative of cerebral small vessel disease. Lesion segmentation algorithms have been developed to overcome issues arising from visual rating scales. In this study, we evaluated two automated methods and compared them to visual and manual segmentation to determine the most robust algorithm provided by the open-source Lesion Segmentation Toolbox (LST). Methods We compared WMH data from visual ratings (Scheltens’ scale) with those derived from algorithms provided within LST. We then compared spatial and volumetric WMH data derived from manually-delineated lesion maps with WMH data and lesion maps provided by the LST algorithms. Results We identified optimal initial thresholds for algorithms provided by LST compared with visual ratings (Lesion Growth Algorithm (LGA): initial κ and lesion probability thresholds, 0.5; Lesion Probability Algorithm (LPA) lesion probability threshold, 0.65). LGA was found to perform better then LPA compared with manual segmentation. Conclusion LGA appeared to be the most suitable algorithm for quantifying WMH in relation to cerebral small vessel disease, compared with Scheltens’ score and manual segmentation. LGA offers a user-friendly, effective WMH segmentation method in the research environment.