bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural memory of the genioglossus muscle during sleep is stage‐dependent in healthy subjects and obstructive sleep apnoea patients
Authors: Taranto‐Montemurro Luigi , Sands Scott A. , Grace Kevin P. , Azarbarzin Ali , Messineo Ludovico , Salant Rebecca , White David P. , Wellman D. Andrew 
Published: July 2018

Key points
In most patients with obstructive sleep apnoea (OSA), there is a spontaneous resolution of the breathing disorders during slow wave sleep (SWS) for yet unknown reasons related to non‐anatomical factors.
Some recently identified forms of neural memory specific of upper airway muscles may play a role in this phenomenon.
In the present study, we show for the first time that a form of memory of the genioglossus (tongue) muscle is greatly enhanced during SWS compared to non‐rapid eye movement stage 2 sleep.
The present study represents a step forward in understanding the mechanisms responsible for the spontaneous development of stable breathing during SWS in OSA patients and may help the discovery of novel therapeutic strategies for this disease.
AbstractSeveral studies have shown that obstructive sleep apnoea (OSA) improves during slow wave sleep (SWS) for reasons that remain unclear. Recent studies have identified forms of neural memory such as short‐term potentiation or after‐discharge that can occur in response to upper airway obstruction. Neural memory may play a role in the development of stable breathing during SWS by increasing upper airway muscles activity in this sleep stage. We hypothesize that the after‐discharge of the genioglossus muscle following upper airway obstruction is enhanced during SWS compared to non‐rapid eye movement stage 2 (N2). During sleep, we performed five‐breath drops in continuous positive airway pressure (CPAP‐drop) to simulate obstructive events and reflexively activate the genioglossus. Immediately afterwards, CPAP was returned to an optimal level. Once the post‐drop ventilation returned to eupnoea, the genioglossus after‐discharge was measured as the time it took for genioglossus activity to return to baseline levels. In total, 171 CPAP‐drops were analysed from a group of 16 healthy subjects and 19 OSA patients. A mixed‐model analysis showed that after‐discharge duration during SWS was 208% (95% confidence interval = 112% to 387%, P = 0.022) greater than during N2 after adjusting for covariates (ventilatory drive, CPAP levels). There was also a non‐significant trend for a –35% reduction in after‐discharge duration following an arousal vs. no‐arousal from sleep (95% confidence interval = –59.5% to 5%, P = 0.08). Genioglossus after‐discharge is two‐fold greater in SWS vs. N2, which could partly explain the breathing stabilization described in OSA patients during this sleep stage.
Evaluation of the minimum age for consent to mental health treatment with the minimum age of criminal responsibility in children and adolescents: a global comparison
Authors: Noroozi Mona , Singh Ilina , Fazel Mina 
Published: July 2018

BackgroundIn many countries, a young person who seeks medical care is not authorised to consent to their own assessment and treatment, yet the same child can be tried for a criminal offence. The absence of child and adolescent mental health legislation in most countries exacerbates the issues young people face in independently accessing mental healthcare. Countries with existing legislation rarely define a minimum age for mental health consent (MAMHC). In stark contrast, nearly all 196 nations studied maintain legislation defining a minimum age of criminal responsibility (MACR).ObjectiveThis review highlights inconsistent developmental and legal perspectives in defined markers of competency across medical and judicial systems.MethodsA review of the MAMHC was performed and compared with MACR for the 52 countries for which policy data could be identified through publicly available sources.FindingsOnly 18% of countries maintain identifiable mental health policies specific to children’s mental health needs. Of those reviewed, only 11 nations maintained a defined MAMHC, with 7 of 11 having a MAMHC 2 years higher than the country’s legislated MACR.ConclusionsWith increasing scientific understanding of the influences on child and adolescent decision making, some investment in the evidence-base and reconciliation of the very different approaches to child and adolescent consent is needed.Clinical implicationsA more coherent approach to child and adolescent consent across disciplines could help improve the accessibility of services for young people and facilitate mental health professionals and services as well as criminal justice systems deliver optimal care.
Deducing the symmetry of the standard model from the automorphism and structure groups of the exceptional Jordan algebra
Authors: Todorov Ivan , Dubois-Violette Michel 
Published: July 2018

We continue the study undertaken in Ref. 16 of the exceptional Jordan algebra [Formula: see text] as (part of) the finite-dimensional quantum algebra in an almost classical space–time approach to particle physics. Along with reviewing known properties of [Formula: see text] and of the associated exceptional Lie groups we argue that the symmetry of the model can be deduced from the Borel–de Siebenthal theory of maximal connected subgroups of simple compact Lie groups.
The quaternary alloy on the Bethe lattice
Authors: Albayrak Erhan 
Published: July 2018

The quaternary alloy (QA) is simulated on the Bethe lattice (BL) in the form of ABpCqDr and its phase diagrams are calculated by using the exact recursion relations (ERR) for the coordination number z = 3. The QA is designed on the BL by placing A atoms (spin-1/2) on the odd shells and randomly placing B (spin-3/2), C (spin-5/2) or D (spin-1) atoms with probabilities p, q and r, respectively, on the even shells. A compact form of formulation for the QA is obtained in the standard-random approach which can easily be reduced to ternary alloy (TA) and mixed-spin models by the appropriate values of the random variables p, q and r. The phase diagrams are calculated on the temperature and ratio of bilinear interaction parameter planes for given values of probabilities.
Higher muscle fiber conduction velocity and early rate of torque development in chronically strength-trained individuals
Authors: Del Vecchio A. , Negro F. , Falla D. , Bazzucchi I. , Farina D. , Felici F. 
Published: July 2018

Strength-trained individuals (ST) develop greater levels of force compared with untrained subjects. These differences are partly of neural origin and can be explained by training-induced changes in the neural drive to the muscles. In the present study we hypothesize a greater rate of torque development (RTD) and faster recruitment of motor units with greater muscle fiber conduction velocity (MFCV) in ST compared with a control cohort. MFCV was assessed during maximal voluntary isometric explosive contractions of the elbow flexors in eight ST and eight control individuals. MFCV was estimated from high-density surface electromyogram recordings (128 electrodes) in intervals of 50 ms starting from the onset of the electromyogram. RTD and MFCV were computed and normalized to their maximal voluntary torque (MVT) values. The explosive torque of the ST was greater than in the control group in all time intervals analyzed ( P < 0.001). The absolute MFCV values were also greater for the ST than for controls at all time intervals ( P < 0.001). ST also achieved greater normalized RTD in the first 50 ms of contraction [887.6 (152) vs. 568.5 (148.66)%MVT/s, mean (SD), P < 0.001] and normalized MFCV before the rise in force compared with controls. We have shown for the first time that ST can recruit motor units with greater MFCV in a shorter amount of time compared with untrained subjects during maximal voluntary isometric explosive contractions. NEW & NOTEWORTHY Strength-trained individuals show neuromuscular adaptations. These adaptations have been partly related to changes in the neural drive to the muscles. Here, we show for the first time that during the initial phase of a maximal isometric explosive contraction, strength-trained individuals achieve higher levels of force and recruit motor units with greater conduction velocities.
Sex differences in large conducting airway anatomy
Authors: Dominelli Paolo B. , Ripoll Juan G. , Cross Troy J. , Baker Sarah E. , Wiggins Chad C. , Welch Brian T. , Joyner Michael J. 
Published: July 2018

Airway luminal area is the major determinant of resistance to airflow in the tracheobronchial tree. Women may have smaller central conducting airways than men; however, previous evidence is confounded by an indirect assessment of airway geometry and by subjects with prior smoking history. The purpose of this study was to examine the effect of sex on airway size in healthy nonsmokers. Using low-dose high-resolution computed tomography, we retrospectively assessed airway luminal area in healthy men ( n = 51) and women ( n = 73) of varying ages (19–86 yr). Subjects with a positive smoking history, cardiopulmonary disease, or a body mass index > 40 kg/m2 were excluded. Luminal areas of the trachea, right and left main bronchus, bronchus intermediate, left and right upper lobes, and the left lower lobe were analyzed at three discrete points. The luminal areas of the conducting airways were ~26%–35% smaller in women. The trachea had the largest differences in luminal area between men and women (298 ± 47 vs. 195 ± 28 mm2 or 35% smaller for men and women, respectively), whereas the left lower lobe had the smallest differences (57 ± 15 vs. 42 ± 9 mm2 or 26% smaller for men and women, respectively). When a subset of subjects was matched for height, the sex differences in airway luminal area persisted, with women being ~20%–30% smaller. With all subjects, there were modest relationships between height and airway luminal area ( r = 0.73–0.53, P < 0.05). Although there was considerable overlap between sexes, the luminal areas of the large conducting airways were smaller in healthy women than in men. NEW & NOTEWORTHY Previous evidence for sex differences in airway size has been confounded by indirect measures and/or cohorts with significant smoking histories or pathologies. We found that central airways in healthy women were significantly smaller (~26%–35%) than men. The significant sex-difference in airway size was attenuated (20%–30% smaller) but preserved in a subset of subjects matched for height. Over a range of ages, healthy women have smaller central airways than men.
Adrenoceptor blockade modifies regional cerebral blood flow responses to hyperbaric hyperoxia: protection against CNS oxygen toxicity
Authors: Gasier Heath G. , Demchenko Ivan T. , Zhilyaev Sergei Yu , Moskvin Alexander N. , Krivchenko Alexander I. , Piantadosi Claude A. 
Published: July 2018

Exposure to extreme hyperbaric oxygen (HBO2) >5–6 atmospheres absolute (ATA) produces baroreflex impairment, sympathetic hyperactivation, hypertension, tachycardia, and cerebral hyperemia, known as phase II, culminating in seizures. We hypothesized that attenuation of the effects of high sympathetic outflow would preserve regional cerebral blood flow (rCBF) and protect against HBO2-induced seizures. To explore this possibility, we tested four adrenoceptor antagonists in conscious and anesthetized rats exposed to HBO2at 5 and 6 ATA, respectively: phentolamine (nonselective α1and α2), prazosin (selective α1), propranolol (nonselective β1and β2), and atenolol (selective β1). In conscious rats, four drug doses were administered to rats before HBO2exposures, and seizure latencies were recorded. Drug doses that provided similar protection against seizures were administered before HBO2exposures in anesthetized rats to determine the effects of adrenoceptor blockade on mean arterial pressure, heart rate, rCBF, and EEG spikes. All four drugs modified cardiovascular and rCBF responses in HBO2that aligned with epileptiform discharges, but only phentolamine and propranolol effectively increased EEG spike latencies by ~20 and 36 min, respectively. When phentolamine and propranolol were delivered during HBO2at the onset of phase II, only propranolol led to sustained reductions in heart rate and rCBF, preventing the appearance of epileptiform discharges. The enhanced effectiveness of propranolol may extend beyond β-adrenoceptor blockade, i.e., membrane stability and reduced metabolic activity. These results indicate that adrenoceptor drug pretreatment will minimize the effects of excessive sympathetic outflow on rCBF and extend HBO2exposure time.NEW & NOTEWORTHY Blocking adrenergic receptors with phentolamine (nonselective α1and α2), prazosin (selective α1), propranolol (nonselective β1and β2), and atenolol (selective β1) modified cardiovascular and regional cerebral blood flow (rCBF) responses in hyperbaric oxygen (HBO2) at 6 atmospheres absolute (ATA); however, only phentolamine and propranolol extended EEG spike latencies. When these two agents were delivered at the onset of sympathetic hyperactivation, only propranolol reduced heart rate and rCBF throughout the exposure and prevented epileptiform discharges. These data validate the strong role of adrenergic control of cardiovascular function and rCBF in extreme HBO2and the potential use of antiadrenergic drugs to prevent seizures.
A Rare Missense Variant in TCF7L2 Associates with Colorectal Cancer Risk by Interacting with a GWAS-Identified Regulatory Variant in the MYC Enhancer
Authors: Chang Jiang , Tian Jianbo , Yang Yang , Zhong Rong , Li Jiaoyuan , Zhai Kan , Ke Juntao , Lou Jiao , Chen Wei , Zhu Beibei , Shen Na , Zhang Yi , Gong Yajie , Zhu Ying , Zou Danyi , Peng Xiating , Huang Kun , Miao Xiaoping 
Published: July 2018

Abstract
Genome-wide association studies (GWAS) of colorectal cancer have identified several common susceptible variants in gene regulatory regions. However, low-frequency or rare coding risk variants have not been systematically investigated in patients with colorectal cancer from Chinese populations. In this study, we performed an exome-wide association analysis with 1,062 patients with colorectal cancer and 2,184 controls from a Chinese population. Promising associations were further replicated in two replication sets: replication stage I with 2,478 cases and 3,880 controls, and replication stage II with 3,761 cases and 4,058 controls. We identified two variants significantly associated with colorectal cancer risk: a novel rare missense variant in TCF7L2 [rs138649767, OR = 2.08, 95% confidence interval (CI): 1.69–2.57, P = 5.66 × 10−12] and a previous European GWAS-identified 3′-UTR variant in ATF1 (rs11169571, OR = 1.18, 95% CI: 1.13–1.24, P = 1.65 × 10−12). We found a significant interaction between the TCF7L2 missense variant rs138649767 and a previous GWAS-identified regulatory variant rs6983267 in the MYC enhancer (Pinteraction = 0.0002). Functional analysis of this variant revealed that TCF7L2 with rs138649767-A allele harbored the ability to activate the MYC enhancer with rs6983267-G allele and enhance colorectal cancer cell proliferation. In addition, the ATF1 rs11169571 variant significantly correlated with ATF1 expression by affecting hsa-miR-1283 and hsa-miR-520d-5p binding. Further ChIP-seq and gene coexpression analyses showed that oncogenes NRAS and BRAF were activated by ATF1 in colorectal cancer. These results widen our understanding of the molecular basis of colorectal cancer risk and provide insight into pathways that might be targeted to prevent colorectal cancer.
Significance: Exome-wide association analysis identifies a rare missense variant in TCF7L2 and a common regulatory variant in ATF1 as susceptibility factors of colorectal cancer.
Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/17/5164/F1.large.jpg. Cancer Res; 78(17); 5164–72. ©2018 AACR.
Interaction Between Pannexin 1 and Caveolin-1 in Smooth Muscle Can Regulate Blood Pressure
Authors: DeLalio Leon J. , Keller Alexander S. , Chen Jiwang , Boyce Andrew K.J. , Artamonov Mykhaylo V. , Askew-Page Henry R. , Keller T.C. Stevenson , Johnstone Scott R. , Weaver Rachel B. , Good Miranda E. , Murphy Sara A. , Best Angela K. , Mintz Ellen L. , Penuela Silvia , Greenwood Iain A. , Machado Roberto F. , Somlyo Avril V. , Swayne Leigh Anne , Minshall Richard D. , Isakson Brant E. 
Published: July 2018

Objective—
Sympathetic nerve innervation of vascular smooth muscle cells (VSMCs) is a major regulator of arteriolar vasoconstriction, vascular resistance, and blood pressure. Importantly, α–adrenergic receptor stimulation, which uniquely couples with Panx1 (pannexin 1) channel-mediated ATP release in resistance arteries, also requires localization to membrane caveolae. Here, we test whether localization of Panx1 to Cav1 (caveolin-1) promotes channel function (stimulus-dependent ATP release and adrenergic vasoconstriction) and is important for blood pressure homeostasis.

Approach and Results—
We use in vitro VSMC culture models, ex vivo resistance arteries, and a novel inducible VSMC-specific Cav1 knockout mouse to probe interactions between Panx1 and Cav1. We report that Panx1 and Cav1 colocalized on the VSMC plasma membrane of resistance arteries near sympathetic nerves in an adrenergic stimulus-dependent manner. Genetic deletion of Cav1 significantly blunts adrenergic-stimulated ATP release and vasoconstriction, with no direct influence on endothelium-dependent vasodilation or cardiac function. A significant reduction in mean arterial pressure (total=4 mm Hg; night=7 mm Hg) occurred in mice deficient for VSMC Cav1. These animals were resistant to further blood pressure lowering using a Panx1 peptide inhibitor Px1IL2P, which targets an intracellular loop region necessary for channel function.

Conclusions—
Translocalization of Panx1 to Cav1-enriched caveolae in VSMCs augments the release of purinergic stimuli necessary for proper adrenergic-mediated vasoconstriction and blood pressure homeostasis.
Inhibiting Glycogen Synthase Kinase 3 Reverses Obesity-Induced White Adipose Tissue Inflammation by Regulating Apoptosis Inhibitor of Macrophage/CD5L-Mediated Macrophage Migration
Authors: Wang Li , Wang Yuan , Zhang Chao , Li Jingjing , Meng Yuan , Dou Man , Noguchi Constance Tom , Di Lijun 
Published: July 2018

Objective—
Obesity-induced inflammation in white adipose tissue, characterized by increased macrophage infiltration and associated with macrophage population shift from anti-inflammatory M2 to proinflammatory M1 macrophages, largely contributes to obesity-induced insulin resistance and influences type 2 diabetes mellitus pathogenesis. GSK3 (glycogen synthase kinase 3), a serine/threonine kinase, has been reported to participate in various cellular processes. We sought to examine the potential mechanism by which GSK3, a serine/threonine kinase implicated in various cellular processes, modulates obesity-induced visceral adipose tissue (VAT) inflammation.

Approach and Results—
Male C57BL/6J mice were fed a high-fat diet for 10 weeks while being treated with vehicle control or GSK3 inhibitors SB216763 or CHIR99021. RNA-sequencing results using VAT demonstrated that GSK3 inhibitor treatment reversed obesity-specific expression of genes associated with inflammation. Consistently, GSK3 inhibition reduced obesity-induced VAT inflammation as characterized by decreased proinflammatory M1 macrophages but increased anti-inflammatory M2 macrophages in the VAT and reduced circulatory inflammatory monocytes. These anti-inflammatory effects of GSK3 inhibition were found to be driven, at least in part, by inhibiting production of apoptosis inhibitor of macrophage in macrophages via inactivating STAT3 to reduce free fatty acid and chemokine level produced from VAT to suppress the migration/chemotaxis of macrophages and monocytes.

Conclusions—
Our findings suggest that GSK3 may act as an important regulator of obesity-induced inflammation and characterize the novel role of GSK3 in shifting macrophage polarization and reinforce its therapeutic potential for obesity-induced inflammation and its associated diabetes mellitus.
Dispute Settlement in the Law of the Sea: Survey for 2017
Authors: Churchill Robin 
Published: July 2018

Abstract
This is the latest in a series of annual surveys in this Journal reviewing dispute settlement in the law of the sea, both under the UN Convention on the Law of the Sea and outside the framework of the Convention. It covers developments in 2017. The most significant developments during the year were the judgment of the Special Chamber of the International Tribunal for the Law of the Sea in the Ghana/Côte d’Ivoire maritime boundary case and the final award of the tribunal in the Croatia/Slovenia arbitration. There were also a number of less significant developments.
Reintensification and Eyewall Formation in Strong Shear: A Case Study of Typhoon Noul (2015)
Authors: Shimada Udai , Horinouchi Takeshi 
Published: July 2018

Abstract
Strong vertical wind shear produces asymmetries in the eyewall structure of a tropical cyclone (TC) and is generally a hostile environment for TC intensification. Typhoon Noul (2015), however, reintensified and formed a closed eyewall despite 200–850-hPa vertical shear in excess of 11 m s−1. Noul’s reintensification and eyewall formation in strong shear were examined by using Doppler radar and surface observations. The evolution of the azimuthal-mean structure showed that the tangential wind at 2-km altitude increased from 30 to 45 m s−1 in only 5 h. During the first half of the reintensification, the azimuthal-mean inflow penetrated into the ~40-km radius, well inside the radius of maximum wind (RMW), at least below 4-km altitude, and reflectivity inside the RMW increased. As for the asymmetric evolution, vigorous convection, dominated by an azimuthal wavenumber-1 asymmetry, occurred in the downshear-left quadrant when shear started to increase and then moved upshear. A mesovortex formed inside the convective asymmetry on the upshear side. The direction of vortex tilt between the 1- and 5-km altitudes rotated cyclonically from the downshear-left to the upshear-right quadrant as the vortex was vertically aligned. In conjunction with the alignment, the amplitude of the wavenumber-1 convective asymmetry decreased and a closed eyewall formed. These features are consistent with the theory that a vortex can be vertically aligned through upshear precession. The analysis results suggest that the vortex tilt, vigorous convection, and subsequent intensification were triggered by the increase in shear in a convectively favorable environment.