bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful coil embolization of a large right coronary artery-coronary sinus fistula causing a significant left-to-right shunt: a case report
Authors: El Nihum Lamees I , Thakkar Akanksha N , Chinnadurai Ponraj , Lin C Huie 
Published: May 2021

Abstract

Background
This case reviews a challenging but successful transcatheter coil embolization of a large congenital coronary artery fistula (CAF) causing a significant left-to-right shunt.

Case summary
A 51-year-old female with no significant prior history presented with symptoms of dyspnoea and chest discomfort. Extensive evaluation revealed a large CAF between a tortuous right coronary artery (RCA) and the coronary sinus (CS) composed of three aneurysmal pseudochambers. Closure of the RCA-CS fistula was attempted through coil deployment into the fistula neck. However, due to the brisk flow through the fistula, both coils embolized into the fistula sac. An alternative location was subsequently identified on three-dimensional rendering of a computed tomography angiography scan, which revealed a sharp bend in the RCA prior to the fistula neck and distal to the posterior descending artery (PDA) takeoff. Repeat attempt at embolization was accomplished using a telescoping system to reach and occlude the targeted bend. The coil mass remained stable and angiography demonstrated reduced flow through the fistula and preserved patency of the PDA. The decreased residual flow through the fistula secondary to the initial embolization attempt likely aided the successful deployment of coils in the second and final attempt. At 1 year, the patient was doing well with resolution of her symptoms and no clinical symptoms of coronary ischaemia.

Discussion
We suggest that an initial unsuccessful attempt at transcatheter embolization of a CAF should not preclude subsequent attempts for closure when there exists an appropriate indication.
Toward a Stable Global Noctuidae (Lepidoptera) Taxonomy
Authors: Keegan Kevin L , Rota Jadranka , Zahiri Reza , Zilli Alberto , Wahlberg Niklas , Schmidt B Christian , Lafontaine J Donald , Goldstein Paul Z , Wagner David L 
Published: May 2021

AbstractNoctuidae are one of the world’s most diverse, ecologically successful, and economically important animal lineages with over 12,000 species in ~1,150 genera. We inferred a phylogeny using eight protein-coding genes for the global fauna, greatly expanding upon previous attempts to stabilize Noctuidae higher classification by sampling 341 genera (nearly half represented by their type species) representing 70/76 widely recognized family-group taxa: 20/21 subfamilies, 32/35 tribes, and 18/20 subtribes. We evaluated 17 subfamily-level taxa in detail, discussing adult and larval morphology, life histories, and taxonomic implications of our results. We significantly alter concepts of Acontiinae, Condicinae, Eustrotiinae, Metoponiinae, and Stiriinae. Our results supported recognition of two new subfamilies: Cobubathinae Wagner & Keegan, 2021 subf. nov. and Cropiinae Keegan & Wagner, 2021 subf. nov. Other nomenclatural changes we made are as follows. We moved: ‘Acontia’ viridifera (Hampson, 1910), ‘Azenia’ virida Barnes and McDunnough, 1916, Aleptinoides, Austrazenia, Chalcoecia, Megalodes, and Trogotorna to Chamaecleini in Acontiinae; Apaustis to, and reinstated Emmelia as a valid genus in Acontiinae; Allophyes and Meganephria to Cuculliinae; ‘Plagiomimicus’ navia (Harvey, 1875), Airamia, Alvaradoia, Hypoperigea, Neotarache, and Mesotrosta to Condicinae; Axenus, Azenia, Metaponpneumata, Sexserrata, and Tristyla to Metoponiinae; ‘Paramiana’ canoa (Barnes, 1907) to Noctuinae; Aucha, Cobubatha, and Tripudia to Cobubathinae; Anycteola and Supralathosea to Oncocnemidinae; Cropia to Cropiinae; Desmoloma to Dyopsinae; Eviridemas and Gloanna to Bryophilinae; Fota and Stilbia to Stiriinae; and Copibryophila, Homolagoa, and Tyta to Noctuidae incertae sedis. We conclude with discussion of instances where current understanding of noctuid biogeography and life histories were changed by our results.
Breast Imaging Radiologists’ Role in Value Pathways
Authors: Golding Lauren P , Nicola Gregory N 
Published: May 2021

Abstract
The Merit-Based Incentive Payment System (MIPS) has fallen short of its intended goal to substantially transform the delivery of healthcare by tying clinician payments to quality and cost reduction. Policy makers made changes to the program over its first five years in efforts to address concerns about complexity and lack of meaningful impact on outcomes for our patients. One of these changes, the creation of MIPS Value Pathways (MVPs), aims to streamline reporting of increasingly aligned measures and serve as a stepping-stone for the transition to alternative payment models. As MIPS continues to evolve, these value pathways will provide new opportunities for breast imaging radiologists to participate in value-based care.
Is transverse screw fixation really necessary in PAO?—A comparative in vivo study
Authors: Leopold Vincent J , Conrad Juana , Hipfl Christian , Müllner Maximilian , Khakzad Thilo , Perka Carsten , Hardt Sebastian 
Published: May 2021

Abstract
The optimal fixation technique in periacetabular osteotomy (PAO) remains controversial. This study aims to assess the in vivo stability of fixation in PAO with and without the use of a transverse screw. We performed a retrospective study to analyse consecutive patients who underwent PAO between January 2015 and June 2017. Eighty four patients (93 hips) of which 79% were female were included. In 54 cases, no transverse screw was used (group 1) compared with 39 with transverse screw (group 2). Mean age was 26.5 (15–44) in group 1 and 28.4 (16–45) in group 2. Radiological parameters relevant for DDH including lateral center edge angle of Wiberg (LCEA), Tönnis angle (TA) and femoral head extrusion index (FHEI) were measured preoperatively, post-operatively and at 3-months follow-up. All patients were mobilized with the same mobilization regimen. Post-operative LCEA, TA and FHEI were improved significantly in both groups for all parameters (P ≤ 0.0001). Mean initial correction for LCEA (P = 0.753), TA (P = 0.083) and FHEI (P = 0.616) showed no significant difference between the groups. Final correction at follow-up of the respective parameters was also not significantly different between both groups for LCEA (P = 0.447), TA (P = 0.100) and FHEI (P = 0.270). There was no significant difference between initial and final correction for the respective parameters. Accordingly, only minimal loss of correction was measured, showing no difference between the two groups for LCEA (P = 0.227), TA (P = 0.153) and FHEI (P = 0.324). Transverse screw fixation is not associated with increased fragment stability in PAO. This can be taken into account by surgeons when deciding on the fixation technique of the acetabular fragment in PAO.
Transcription factor allosteric regulation through substrate coordination to zinc
Authors: Almeida Beatriz C , Kaczmarek Jennifer A , Figueiredo Pedro R , Prather Kristala L J , Carvalho Alexandra T P 
Published: May 2021

AbstractThe development of new synthetic biology circuits for biotechnology and medicine requires deeper mechanistic insight into allosteric transcription factors (aTFs). Here we studied the aTF UxuR, a homodimer of two domains connected by a highly flexible linker region. To explore how ligand binding to UxuR affects protein dynamics we performed molecular dynamics simulations in the free protein, the aTF bound to the inducer D-fructuronate or the structural isomer D-glucuronate. We then validated our results by constructing a sensor plasmid for D-fructuronate in Escherichia coli and performed site-directed mutagenesis. Our results show that zinc coordination is necessary for UxuR function since mutation to alanines prevents expression de-repression by D-fructuronate. Analyzing the different complexes, we found that the disordered linker regions allow the N-terminal domains to display fast and large movements. When the inducer is bound, UxuR can sample an open conformation with a more pronounced negative charge at the surface of the N-terminal DNA binding domains. In opposition, in the free and D-glucuronate bond forms the protein samples closed conformations, with a more positive character at the surface of the DNA binding regions. These molecular insights provide a new basis to harness these systems for biological systems engineering.
Tidally perturbed oblique pulsations in the hierarchical triple system V1031 Orionis
Authors: Lee Jae Woo 
Published: May 2021

Abstract
We present Transiting Exoplanet Survey Satellite (TESS) photometry of the triple star system V1031 Ori (AB)C, which exhibits short-period oscillations superimposed on an eclipsing light curve.The high-quality data were analyzed in detail and combined with the published spectroscopic measurements to obtain the fundamental stellar parameters of the program target. The masses and radii of the eclipsing pair (AB) were determined to about $0.5\%$ and $0.7\%$ precision, respectively. We found 23 significant frequencies in two ranges of &lt;2 d−1 and 10.9–12.7 d−1 from the eclipse-subtracted residuals. Among them, 16 in the gravity (g)-mode region may be aliases and artefacts due to imperfect removal of the systematic trends and the binary effects from the TESS data. Seven frequencies in the pressure (p)-mode region were separated by the orbital frequency and split by an average offset of 0.042 ± 0.003 d−1 from their adjacent harmonics. Further, the pulsation amplitudes are clearly modulated with the binary star orbit. The results indicate that the p-mode frequencies are tidally perturbed pulsations from the secondary component and the pulsation axis could be aligned with the tidal axis.
002 Daridorexant, a dual orexin receptor antagonist, improves age-related insomnia in rats
Authors: Roch Catherine , Fischer Cédric , Jenck Francois , Steiner Michel 
Published: May 2021

Abstract

Introduction
Sleep disturbances develop with age, and prevalence of insomnia is higher in the elderly. Daridorexant is a new medication in development for the treatment of insomnia. Our aim was to investigate whether an insomnia-like phenotype develops in old rats, and then to assess the effect of repeated administration of daridorexant in these animals.

Methods
We recorded the electroencephalogram and electromyogram of freely moving male Wistar rats implanted with telemetry transmitters. Time spent sleeping during the inactive phase was measured at the ages of 4 (n=50), 6 (n=55), 8 (n=37), 12 (n=44), 18 (n=22) and 24 (n=9) months. The age at which the rats’ time spent sleeping started to be significantly reduced compared to that of 4-month-old rats was when the insomnia-like phenotype would start to occur. The impact of 100 mg/kg daridorexant, given orally at the beginning of the inactive phase, was evaluated in 16-month-old rats (n=8). Rats were consecutively treated daily for 6 days with vehicle (baseline period), for 3 weeks with daridorexant, and again for 1 week with vehicle (wash-out period).

Results
The total time spent sleeping during the 12-h inactive period decreased from 51.3±1.1% (mean ± SEM) at 4-months old to 39.3±4.4% at 24-months, with a significant decrease starting from 8-months (p&lt;0.05). Whereas the time spent in rapid-eye-movement (REM) sleep (~10%) was not affected by age (p=0.64), the time spent in non-REM sleep decreased from 41.7±0.8% at 4 months to 28.7±3.2% at 24 months (p&lt;0.001). In 16-month-old rats daridorexant increased the time spent in non-REM sleep over the first 6-h following administration (p&lt;0.001). The time spent in REM sleep was unaffected (p=0.47). The average time spent in non-REM sleep over those 6h was 37.2±2.5% at baseline, and 43.8±2.4%, 44.6±2.7% and 44.5±3.0% in the 1st (p&lt;0.05 vs baseline), 2nd (p&lt;0.001) and 3rd (p&lt;0.01) week of treatment, respectively. During the wash-out period, the non-REM sleep time returned to baseline levels (35.6±2.7%; p=0.06).

Conclusion
In rats, an insomnia-like phenotype, characterized by reduced non-REM sleep time, develops with age. Daridorexant improves this phenotype and its effect is maintained upon repeated administration over three weeks.

Support (if any)
Funded by Idorsia Pharmaceuticals Ltd
003 Treatment of Sleep Disordered Breathing with Leptin Loaded Exosomes
Authors: Freire Carla , Pho Huy , Ramsey Jacob , Streeter Stone , Kojima Ryo , Berger Slava , Fleury-Curado Thomaz , Sokolsky Marina , Batrakova Elena , Kabanov Alexander , Polotsky Vsevolod 
Published: May 2021

Abstract

Introduction
Obstructive sleep apnea (OSA) is characterized by recurrent periods of upper airway obstruction. The prevalence of OSA exceeds 50% in obese individuals and in 10–20% of obese patients OSA coexists with obesity hypoventilation syndrome (OHS) defined as daytime hypercapnia and hypoventilation during sleep attributed to the depressed control of breathing. There is no effective pharmacotherapy for OSA and OHS. Leptin is a potent respiratory stimulant and a potential therapeutic candidate. However, diet-induced obesity (DIO) results in reduced permeability of the blood-brain barrier (BBB) for leptin. Previous studies have shown that the BBB can be penetrated by exosomes, natural nanoparticles that can be used as drug delivery vehicles. In this study, we aimed to determine if exosomes overcome the BBB and treat OSA and OHS in DIO mice.

Methods
o examine the ability of exosomes to cross the BBB, male, lean (n=5) and DIO (n=5) C57BL/6J mice were injected with fluorescent exosomes or saline into the lateral tail vein. After 4h fluorescent exosomes biodistribution was evaluated by an in vitro imaging system (IVIS). Saline injected mice images were used for background adjustment. A separate subgroup of male, DIO (n=10) and lean (n=10) mice were headmounted with EEG and nuchal EMG leads. Sleep studies were performed in a plethysmography chamber and mice received saline, empty exosomes, free leptin, or leptin-loaded exosomes in a crossover manner.

Results
Exosomes were successfully delivered to the brain and the transport across the BBB was more efficient in DIO mice with 2-times greater relative fluorescence units measured in DIO when compared to lean mice (p&lt;0.005). In DIO mice, exosomal leptin induced dramatic 1.7-2.2-fold increases in minute ventilation and 1.5-2.0-fold increases in maximal inspiratory flow during both flow-limited (upper airway/sleep apnea) and non-flow limited breathing (control of breathing) (p&lt;0.05). In contrast, free leptin had no effect. Lean mice did not present significant sleep disordered breathing and no differences were observed between groups.

Conclusion
We demonstrated that exosomes overcome the BBB and that leptin-loaded exosomes treat OSA and OHS in DIO mice.

Support (if any)
R01HL 128970, R01HL 138932, R61 HL156240, U18 DA052301, FAPESP 2018/08758-3
007 NLRP3 inflammasomes contribute to dysregulated sleep and electroencephalogram delta power after mild and moderate TBI in mice
Authors: Zielinski Mark , Gibbons Allison , Lakis Gabrielle , Kaplan Gary 
Published: May 2021

Abstract

Introduction
Most traumatic brain injuries (TBI) are mild to moderate and can cause persistent dysregulated sleep, although the mechanisms are not well understood. Interleukin-1 beta (IL-1β) is a pro-inflammatory molecule that is activated in the cortex after waking activity and pathogenic challenge and alters non-rapid eye movement (NREM) sleep and electroencephalogram (EEG) delta power. Nucleotide-binding domain leucine rich family pyrin containing 3 (NLRP3) inflammasomes sense changes in their local environment to stimulate caspase-1 to activate IL-1β into its mature form. We previously found that NLRP3 inflammasomes are increased in the cortex after acute sleep loss and contribute to increased NREM sleep and EEG delta power after sleep loss and toxin challenge. We aimed to determine if NLRP3 inflammasomes contribute to the persistent dysregulated sleep caused by TBI.

Methods
Using 2-3-month-old mice lacking NLRP3 and C57BL/6J wild-type control mice, we assessed sleep states and sleep state episode durations and frequencies prior to TBI, and 24 h, 2-weeks, and 2 months after mild or moderate TBI using polysomnography. TBI occurred in the frontal cortex from a controlled cortical impact device. Additional mice received identical treatments serving as a TBI procedural control but received a craniectomy without the TBI.

Results
Similar sleep findings were observed between the craniectomy control group and baseline measures. However, when compared to baseline values, mice lacking NLRP3 had attenuations in the significant increased amounts of NREM sleep and EEG delta power occurring 24 h after TBI and the significant reductions in NREM sleep and EEG delta power seen 2 months after TBI that were observed in wild-type mice. These effects were similar in moderate and mild TBI groups. Mice lacking NLRP3 were not found to exhibit the fragmented sleep after mild or moderate TBI that was found to persist from 24 h to 2 months post-TBI in the wild-type mice. These effects were evident by significant increased frequencies of waking episodes induced by the TBIs.

Conclusion
Our findings suggest that NLRP3 inflammasomes contribute to dysregulated sleep occurring acutely or more persistently after TBI.

Support (if any)
Career Development Award IBX002823 (MZ) and Merit Review Award I01RX001144 (GK) from the United States Department of Veterans Affairs
009 Self-Reported Sleep Efficiency and Duration are Associated with Systemic Bioenergetic Function in Community-Dwelling Adults
Authors: Lehrer H Matthew , Chu Lauren , Hall Martica , Murdock Kyle 
Published: May 2021

Abstract

Introduction
Sleep is important for aging, health, and disease, but its cellular role in these outcomes is poorly understood. Basic research suggests that disturbed and insufficient sleep impair mitochondrial bioenergetics, which is involved in numerous aging-related chronic conditions. However, the relationship between sleep and bioenergetics has not been examined in humans. We examined associations of self-reported sleep with systemic bioenergetic function in peripheral blood mononuclear cells (PBMCs) of community-dwelling adults.

Methods
N = 43 adults (79% female) ages 48–70 (M = 61.63, SD = 5.99) completed the Pittsburgh Sleep Quality Index (PSQI) from which key components of sleep (satisfaction, alertness, timing, efficiency, and duration) were calculated. Participants provided blood samples from which PBMCs were isolated and measured for bioenergetics using extracellular flux analysis. Associations of sleep components with bioenergetic parameters, including the Bioenergetic Health Index (BHI), were examined.

Results
In bivariate analyses, lower sleep efficiency was associated with lower maximal respiration, spare capacity, and BHI (ps &lt; 0.05). Longer sleep duration was associated with lower BHI (p &lt; 0.01) and later sleep timing was associated with higher basal respiration, ATP-linked respiration, maximal respiration, spare capacity, and non-mitochondrial respiration (ps &lt; 0.05). After adjustment for age, sex, and body mass index, lower sleep efficiency (β = 0.52, p &lt; 0.01) and longer sleep duration (β = -0.43, p &lt; 0.01) were associated with lower BHI.

Conclusion
Self-reported indices of sleep efficiency and duration are related to systemic bioenergetic function in humans, suggesting a possible cellular pathway linking sleep to health.

Support (if any)
T32HL082610
010 Association between Objective Sleep Duration and DNA methylation in Adolescents
Authors: Larsen Michael , He Fan , Imamura Yuka , Berg Arthur , Vgontzas Alexandros , Liao Duanping , Bixler Edward , Gehrman Philip , Fernandez-Mendoza Julio 
Published: May 2021

Abstract

Introduction
Insufficient sleep and circadian misalignment are highly prevalent in adolescents and have been associated with physical and mental health disorders. Several genome wide association studies (GWAS) in adults have identified genes that may be involved in the regulation of sleep and circadian traits. However, little is known regarding the epigenetic basis and significance of short sleep duration in adolescence, a critical developmental period.

Methods
To investigate the association between objective sleep duration, as measured by 9-hour in-lab polysomnography (PSG), and DNA methylation in GWAS-informed sleep-related genes, data from 263 adolescents of the Penn State Child Cohort (12-23y, 55.9% male, 23.2% racial/ethnic minorities) were analyzed. Using DNA extracted from peripheral leukocytes, epigenome-wide and GWAS-informed single nucleotide resolution of DNA methylation in cytosine-phosphate-guanine (CpG) sites and surrounding regions were obtained. Multivariable-adjusted linear regression models assessed the association between PSG sleep duration and site-specific methylation levels. Covariates in these models included sex, age, race/ethnicity, body mass index percentile, and psychoactive medication use (i.e., stimulants, anti-depressants, anxiolytics, sedatives, and/or anti-psychotics). P-values were adjusted using the Benjamini & Hochberg method to correct for false discovery rate and, thus, q-values are reported.

Results
PSG sleep duration was associated with differential methylation at 162 intragenic sites in the epigenome-wide analysis with a q&lt;0.05. In GWAS-informed analysis, five genes were associated with altered DNA methylation, by which shorter PSG sleep duration was associated with hypermethylation in MAD1L1 (q=0.02), MAP2K1 (q=0.03), and RBM19 (q=0.01) and with hypomethylation in Brain Enriched Guanylate Kinase Associated (BEGAIN; q=0.0005) and SLC39A8 (q=0.02).

Conclusion
Objective sleep duration in adolescents is associated with altered DNA methylation in genes previously identified in adult GWAS of sleep and circadian traits. Importantly, our data also provides evidence for a potential epigenetic link between objective short sleep duration and genes involved in postsynaptic density (BEGAIN), circadian regulation (MAP2K1/RBM19) as well as internalizing (MAD1L1) and psychotic (SLC38A8) disorders.

Support (if any)
NIH Awards Number R01HL136587, R01MH118308, R01HL97165, R01HL63772, UL1TR000127