bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental Modeling Supports a Role for MyBP-HL as a Novel Myofilament Component in Arrhythmia and Dilated Cardiomyopathy
Authors: Barefield David Y. , Puckelwartz Megan J. , Kim Ellis Y. , Wilsbacher Lisa D. , Vo Andy H. , Waters Emily A. , Earley Judy U. , Hadhazy Michele , Dellefave-Castillo Lisa , Pesce Lorenzo L. , McNally Elizabeth M. 
Published: August 2017

Background:
Cardiomyopathy and arrhythmias are under significant genetic influence. Here, we studied a family with dilated cardiomyopathy and associated conduction system disease in whom prior clinical cardiac gene panel testing was unrevealing.

Methods:

Whole-genome sequencing and induced pluripotent stem cells were used to examine a family with dilated cardiomyopathy and atrial and ventricular arrhythmias. We also characterized a mouse model with heterozygous and homozygous deletion of
Mybphl
.

Results:

Whole-genome sequencing identified a premature stop codon, R255X, in the
MYBPHL
gene encoding MyBP-HL (myosin-binding protein-H like), a novel member of the myosin-binding protein family.
MYBPHL
was found to have high atrial expression with low ventricular expression. We determined that MyBP-HL protein was myofilament associated in the atria, and truncated MyBP-HL protein failed to incorporate into the myofilament. Human cell modeling demonstrated reduced expression from the mutant
MYBPHL
allele. Echocardiography of
Mybphl
heterozygous and null mouse hearts exhibited a 36% reduction in fractional shortening and an increased diastolic ventricular chamber size. Atria weight normalized to total heart weight was significantly increased in
Mybphl
heterozygous and null mice. Using a reporter system, we detected robust expression of
Mybphl
in the atria, and in discrete puncta throughout the right ventricular wall and septum, as well. Telemetric electrocardiogram recordings in
Mybphl
mice revealed cardiac conduction system abnormalities with aberrant atrioventricular conduction and an increased rate of arrhythmia in heterozygous and null mice.

Conclusions:

The findings of reduced ventricular function and conduction system defects in
Mybphl
mice support that
MYBPHL
truncations may increase risk for human arrhythmias and cardiomyopathy.
Subclinical Atrial Fibrillation in Older Patients
Authors: Healey Jeff S. , Alings Marco , Ha Andrew , Leong-Sit Peter , Birnie David H. , de Graaf Jacob J. , Freericks Michel , Verma Atul , Wang Jia , Leong Darryl , Dokainish Hisham , Philippon Francois , Barake Walid , McIntyre William F. , Simek Kim , Hill Michael D. , Mehta Shamir R. , Carlson Mark , Smeele Frank , Pandey A. Shekhar , Connolly Stuart J. 
Published: August 2017

Background:
Long-term continuous electrocardiographic monitoring shows a substantial prevalence of asymptomatic, subclinical atrial fibrillation (SCAF) in patients with pacemakers and patients with cryptogenic stroke. Whether SCAF is also common in other patients without these conditions is unknown.

Methods:

We implanted subcutaneous electrocardiographic monitors (St. Jude CONFIRM-AF) in patients ≥65 years of age attending cardiovascular or neurology outpatient clinics if they had no history of atrial fibrillation but had any of the following: CHA
2
DS
2
-VASc score of ≥2, sleep apnea, or body mass index >30 kg/m
2
. Eligibility also required either left atrial enlargement (≥4.4 cm or volume ≥58 mL) or increased (≥290 pg/mL) serum NT-proBNP (N-terminal pro–B-type natriuretic peptide). Patients were monitored for SCAF lasting ≥5 minutes.

Results:

Two hundred fifty-six patients were followed up for 16.3±3.8 months. Baseline age was 74±6 years; mean CHA
2
DS
2
-VASc score was 4.1±1.4; left atrial diameter averaged 4.7±0.8 cm; and 48% had a prior stroke, transient ischemic attack, or systemic embolism. SCAF ≥5 minutes was detected in 90 patients (detection rate, 34.4%/y; 95% confidence interval [CI], 27.7–42.3). Baseline predictors of SCAF were increased age (hazard ratio [HR] per decade, 1.55; 95% CI, 1.11–2.15), left atrial dimension (HR per centimeter diameter, 1.43; 95% CI, 1.09–1.86), and blood pressure (HR per 10 mm Hg, 0.87; 95% CI, 0.78–0.98), but not prior stroke. The rate of occurrence of SCAF in those with a history of stroke, systemic embolism, or transient ischemic attack was 39.4%/y versus 30.3%/y without (
P
=0.32). The cumulative SCAF detection rate was higher (51.9%/y) in those with left atrial volume above the median value of 73.5 mL.

Conclusions:
SCAF is frequently detected by continuous electrocardiographic monitoring in older patients without a history of atrial fibrillation who are attending outpatient cardiology and neurology clinics. Its clinical significance is unclear.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01694394.
Birth Weight, Postnatal Weight Gain, and Childhood Adiposity in Relation to Lipid Profile and Blood Pressure During Early Adolescence
Authors: Hulst Andraea Van , Barnett Tracie A. , Paradis Gilles , Roy‐Gagnon Marie‐Hélène , Gomez‐Lopez Lilianne , Henderson Mélanie 
Published: August 2017

Background

Different pathways likely underlie the association between early weight gain and cardiovascular disease risk. We examined whether birth weight for length relationship and weight gain up to 2 years of age are associated with lipid profiles and blood pressure (
BP
) in early adolescence and determined whether childhood adiposity mediates these associations.

Methods and Results

Data from QUALITY (Quebec Adipose and Lifestyle Investigation in Youth), a cohort of white children with parental history of obesity, were analyzed (n=395). Sex‐specific weight for length
z
scores from birth to 2 years were computed. Rate of postnatal weight gain was estimated using individual slopes of weight for length
z
‐score measurements. Percentage of body fat was measured at 8 to 10 years. Fasting lipids and
BP
were measured at 10 to 12 years. Using path analysis, we found indirect effects of postnatal weight gain, through childhood adiposity, on all outcomes: Rate of postnatal weight for length gain was positively associated with childhood adiposity, which in turn was associated with unfavorable lipid and
BP
levels in early adolescence. In contrast, small beneficial direct effects on diastolic
BP
z
scores, independent of weight at other time points, were found for birth weight for length (β=−0.05, 95%
CI
, −0.09 to −0.002) and for postnatal weight gain (β=−0.02, 95%
CI
, −0.03 to −0.002).

Conclusions

Among children with at least 1 obese parent, faster postnatal weight gain leads to cardiovascular risk factors in early adolescence through its effect on childhood adiposity. Although heavier newborns may have lower
BP
in early adolescence, this protective direct effect could be offset by a deleterious indirect effect linking birth weight to later adiposity.
ALDH2 modulated changes in cytokine levels and cognitive function in bipolar disorder: A 12-week follow-up study
Authors: Lee Sheng-Yu , Wang Tzu-Yun , Chen Shiou-Lan , Chang Yun-Hsuan , Chen Po-See , Huang San-Yuan , Tzeng Nian-Sheng , Wang Liang-Jen , Lee I-Hui , Chen Kao-Chin , Yang Yen Kuang , Yang Yi-Hsin , Chen Cheng-Sheng , Lu Ru-Band 
Published: August 2017

Objectives: We investigated the association of the aldehyde dehydrogenase 2 ( ALDH2) polymorphism (rs671), which is involved with the dopaminergic function, and with changes in cytokine levels and cognitive function, in a 12-week follow-up study in patients with bipolar disorder. Methods: Patients with a first diagnosis of bipolar disorder were recruited. Symptom severity and levels of plasma cytokines (tumor necrosis factor α, C-reactive protein, interleukin 6 and transforming growth factor β1) were examined during weeks 0, 1, 2, 4, 8 and 12. Neurocognitive function was evaluated at baseline and endpoint. The ALDH2 polymorphism genotype was determined. Results: A total of 541 patients with bipolar disorder were recruited, and 355 (65.6%) completed the 12-week follow-up. A multiple linear regression analysis showed a significant ( p = 0.000226) association between the ALDH2 polymorphism and changes in C-reactive protein levels. Different aspects of cognitive function improved in patients with different ALDH2 genotypes. Only patients with the ALDH2*1*1 genotype showed significant correlations between improvement of cognitive function and increased transforming growth factor -β1. Conclusion: The ALDH2 gene might influence changes in cytokine levels and cognitive performance in patients with bipolar disorder. Additionally, changes in cytokine levels and cognitive function were correlated only in patients with specific ALDH2 genotypes.
Novel nonsense gain-of-function NFKB2 mutations associated with a combined immunodeficiency phenotype
Authors: Kuehn Hye Sun , Niemela Julie E. , Sreedhara Karthik , Stoddard Jennifer L. , Grossman Jennifer , Wysocki Christian A. , de la Morena M. Teresa , Garofalo Mary , Inlora Jingga , Snyder Michael P. , Lewis David B. , Stratakis Constantine A. , Fleisher Thomas A. , Rosenzweig Sergio D. 
Published: August 2017

Key Points
NFKB2 GOF mutations are associated with CID without endocrine or ectodermal manifestations. As most autosomal-dominant primary immunodeficiencies, NFKB2 GOF changes have incomplete penetrance and variable expressivity.
Restless Legs Syndrome and Sleep-Related Movement Disorders
Authors: Trotti Lynn Marie 
Published: August 2017

ABSTRACT

Purpose of Review: This article provides an update on six sleep-related movement disorders: restless legs syndrome (RLS), periodic limb movement disorder, sleep-related leg cramps, bruxism, rhythmic movement disorder, and propriospinal myoclonus, with an emphasis on RLS.

Recent Findings: RLS is a common sensorimotor disorder that impairs quality of life. RLS is frequently comorbid to neurologic, psychiatric, vascular, and inflammatory diseases. Accumulating evidence implicates the pathophysiology of RLS as a state of dopamine dysfunction and iron deficiency that occurs on a background of genetic susceptibility conferred by 6 gene polymorphisms. Multiple treatments approved by the US Food and Drug Administration (FDA) are available. Dopamine agonists and α2δ calcium channel ligands are considered first-line treatments, but these treatments have very different side effect profiles that should be taken into consideration.

Summary: Sleep-related movement disorders are frequently encountered in clinical practice. For some disorders, particularly RLS and periodic limb movement disorder, our understanding of biology, epidemiology, and treatment is advanced. For others, much work is needed to determine optimal treatment strategies.
Rapid Eye Movement Sleep Behavior Disorder and Other Rapid Eye Movement Sleep Parasomnias
Authors: Ho¨gl Birgit , Iranzo Alex 
Published: August 2017

ABSTRACT

Purpose of Review: The most common rapid eye movement (REM) parasomnia encountered by neurologists is REM sleep behavior disorder (RBD), and nightmares are so frequent that every neurologist should be able to differentiate them from the dream enactment of RBD. Isolated sleep paralysis is relatively common and is often mistaken for other neurologic disorders. This article summarizes the current state of the art in the diagnosis of RBD, discusses the role of specific questionnaires and polysomnography in the diagnosis of RBD, and reviews recent studies on idiopathic RBD as an early feature of a synucleinopathy, secondary RBD, and its management. Recent diagnostic criteria and implications of nightmares and isolated sleep paralysis are also reviewed.

Recent Findings: Idiopathic RBD can now be considered as part of the prodromal stage of a synucleinopathy. Therefore, an accurate diagnosis is mandatory, and this implies detection of REM sleep without atonia. The polysomnography montage, including EMG of the submentalis and flexor digitorum superficialis muscles, provides a high sensitivity and specificity for the diagnosis. The exact diagnosis is important for patient counseling and for future neuroprotective trials.

Summary: REM parasomnias include RBD, sleep paralysis, and nightmares, which have distinct clinical characteristics and different implications regarding diagnostic procedures, management, and prognosis.
Driving Safety and Fitness to Drive in Sleep Disorders
Authors: Tippin Jon , Dyken Mark Eric 
Published: August 2017

ABSTRACT
Driving an automobile while sleepy increases the risk of crash-related injury and death. Neurologists see patients with sleepiness due to obstructive sleep apnea, narcolepsy, and a wide variety of neurologic disorders. When addressing fitness to drive, the physician must weigh patient and societal health risks and regional legal mandates. The Driver Fitness Medical Guidelines published by the National Highway Traffic Safety Administration (NHTSA) and the American Association of Motor Vehicle Administrators (AAMVA) provide assistance to clinicians. Drivers with obstructive sleep apnea may continue to drive if they have no excessive daytime sleepiness and their apnea-hypopnea index is less than 20 per hour. Those with excessive daytime sleepiness or an apnea-hypopnea index of 20 per hour or more may not drive until their condition is effectively treated. Drivers with sleep disorders amenable to pharmaceutical treatment (eg, narcolepsy) may resume driving as long as the therapy has eliminated excessive daytime sleepiness. Following these guidelines, documenting compliance to recommended therapy, and using the Epworth Sleepiness Scale to assess subjective sleepiness can be helpful in determining patients’ fitness to drive.
Narcolepsy and Other Central Hypersomnias
Authors: Dauvilliers Yves , Barateau Lucie 
Published: August 2017

ABSTRACT

Purpose of Review: This article focuses on the clinical presentation, pathophysiology, diagnosis, differential diagnosis, and management of narcolepsy type 1 and narcolepsy type 2, idiopathic hypersomnia, Kleine-Levin syndrome, and other central disorders of hypersomnolence, as defined in the International Classification of Sleep Disorders, Third Edition (ICSD-3).

Recent Findings: In ICSD-3, the names of some central disorders of hypersomnolence have been changed: narcolepsy with cataplexy and narcolepsy without cataplexy have been renamed narcolepsy type 1 and narcolepsy type 2, respectively. A low level of hypocretin-1/orexin-A in the CSF is now theoretically sufficient to diagnose narcolepsy type 1, as it is a highly specific and sensitive biomarker. Conversely, other central hypersomnias are less well-defined disorders with variability in the phenotype, and few reliable biomarkers have been discovered so far. The epidemiologic observation that influenza A (H1N1) infection and vaccination are potential triggering factors of narcolepsy type 1 (discovered during the 2009 H1N1 pandemic) has increased interest in this rare disease, and progress is being made to better understand the process (highly suspected to be autoimmune) responsible for the destruction of hypocretin neurons. Treatment of narcolepsy remains largely symptomatic, usually initially with modafinil or armodafinil or with higher-potency stimulants such as methylphenidate or amphetamines. Several newer wake-promoting agents and psychostimulants have also been developed, including sodium oxybate, which has a role in the treatment of cataplexy and as an adjunctive wake-promoting agent, and pitolisant, a selective histamine H3 receptor inverse agonist that is currently only available in Europe.

Summary: Although far less common than many other sleep disorders, central hypersomnias are among the most severe and disabling diseases in the field of sleep medicine, and their early recognition is of major importance for patients, especially children, to maximize their quality of life and functioning in activities of daily living.
Shared Medical Decision Making in Consideration of Opioid Therapy in a Patient With Restless Legs Syndrome
Authors: Rubin Michael 
Published: August 2017

ABSTRACT
Treating patients with restless legs syndrome (RLS) may pose a significant challenge to the clinician if those with intractable disease worsen with chronic treatment. Opioids are established as effective treatment for refractory RLS; however, some patients may be reluctant to try opioids because of the risk of dependency. Understanding the physician’s duty to the patient through the framework of a shared decision-making model allows the neurologist to propose opioid therapy despite possible initial reluctance by the patient when the neurologist believes that this therapy is the most medically reasonable approach to optimizing the patient’s well-being.
Comorbid Sleep Disturbances in Neurologic Disorders
Authors: Ju Yo-El S. , Videnovic Aleksandar , Vaughn Bradley V. 
Published: August 2017

ABSTRACT

Purpose of Review: This article provides a review of disturbances of sleep comorbid with common neurologic disorders.

Recent Findings: A wide variety of neurologic disorders are frequently complicated by comorbid sleep disturbances. In many cases, a bidirectional relationship appears to occur between sleep function and the neurologic disease, such that treatment of comorbid sleep disturbances may improve the symptoms of the neurologic disease.

Summary: Neurologic disorders are often associated with abnormalities of sleep. Sleep influences the severity of both epilepsy and headache, and treatment of comorbid sleep disorders may improve seizure and headache frequency. Alzheimer disease is characterized by circadian phase delay and poor nighttime sleep and is strongly associated with obstructive sleep apnea. Parkinson disease is associated with several sleep disorders, including insomnia, restless legs syndrome, rapid eye movement (REM) sleep behavior disorder, daytime hypersomnia, and sleep-disordered breathing. Hypoventilation in amyotrophic lateral sclerosis and other neuromuscular disorders often presents initially with sleep problems, and treatment with noninvasive ventilation improves survival and quality of life.
A GEF activity-independent function for nuclear Net1 in Nodal signal transduction and mesendoderm formation
Authors: Wei Shi , Ning Guozhu , Li Linwei , Yan Yifang , Yang Shuyan , Cao Yu , Wang Qiang 
Published: August 2017

ABSTRACT
Net1 is a well-characterized oncoprotein with RhoA-specific GEF activity. Oncogenic Net1, which lacks the first 145 amino acids, is present in the cytosol and contributes to the efficient activation of RhoA and the formation of actin stress fibers in a number of tumor cell types. Meanwhile, wild-type Net1 is predominantly localized in the nucleus at steady state due to its N-terminal nuclear localization sequences, where the function of nuclear Net1 has not been fully determined. Here, we find that zebrafish net1 is expressed specifically in mesendoderm precursors during gastrulation. Endogenous Net1 is located in the nucleus during early embryonic development. Gain- and loss-of-function experiments in zebrafish embryos and mammalian cells demonstrate that, regardless of its GEF activity, nuclear Net1 is critical for zebrafish mesendoderm formation and Nodal signal transduction. Detailed analyses of protein interactions reveal that Net1 associates with Smad2 in the nucleus in a GEF-independent manner, and then promotes Smad2 activation by enhancing recruitment of p300 (also known as EP300) to the transcriptional complex. These findings describe a novel genetic mechanism by which nuclear Net1 facilitates Smad2 transcriptional activity to guide mesendoderm development.
Troubles with mycorrhizal mushroom identification where morphological differentiation lags behind barcode sequence divergence
Authors: Bazzicalupo Anna L. , Buyck Bart , Saar Irja , Vauras Jukka , Carmean David , Berbee Mary L. 
Published: August 2017

AbstractSpecies of Russula (Russulaceae), a large, cosmopolitan, ectomycorrhizal fungal genus are notoriously difficult to identify. To delimit species and to evaluate their morphology, we sequenced the ~400 bp ITS2 ribosomal DNA region from 713 Pacific Northwest Russula specimens from Benjamin Woo’s exceptional collection. As a topological constraint for analysis of the ITS2, we sequenced and inferred a phylogeny from the ITS, LSU, RPB2 and EF1-a regions from 50 European and North American specimens of major clades in Russula. We delimited 72 candidate species from Woo's collection’s ITS2 sequences using ABGD, GMYC, PTP, and mothur software. To guide application of names, we sequenced a ~200 bp portion of the ITS from 18 American type specimens. Of the 72 delimited species, 28 matched a type or a currently barcoded European species. Among the remaining 44 are poorly known or undescribed species. We tested the congruence of morphology with delimitations for 23 species represented by 10 or more specimens each. No morphological character alone was consistently diagnostic across all specimens of any of the 23 candidate species. Ordination of combined field characters followed by pairwise multivariate analysis of variance showed that centroids were significantly different in 221 of 253 species pair comparisons. Ordination also showed that specimens from the same species were widely dispersed, overlapping with specimens from other species. This explains why only 48.5% of specimens were correctly assigned to their species in a canonical variates analysis of combined field and spore characters. Based on sequence comparisons, we contribute to correcting the broad and confusing misapplications of European names that have long obscured patterns of Russula’s geographical distribution and diversification. Our evidence suggests that morphology in Russula diverges slowly, and that phenotypic plasticity, convergence, or retention of ancestral polymorphisms blur the distinctions among recently derived species.
Typification of 18th Century names in Carex sect. Rhynchocystis (Cyperaceae): Carex pendula and allies
Authors: Jiménez-Mejías Pedro , Míguez Mónica , Spencer Mark A. , Jarvis Charles E. , Martín-Bravo Santiago 
Published: August 2017

AbstractAccording to recent molecular and morphological studies, the apparently homogeneous Carex pendula has been shown to include two different species. One species is distributed across western Europe and the Mediterranean, whereas the other ranges from central and eastern Europe to the Caucasus and northern Iran. Three different names have been considered synonyms of C. pendula: C. agastachys, C. maxima, and C. mutabilis. Here C. pendula is shown to apply to the western taxon, and C. agastachys to be the oldest name for the eastern taxon. An epitype is designated for C. pendula given the insufficient level of detail provided by the previously designated neotype.