bluuebunny/crossref_metadata_2025 huggingface dataset:
Multicentre pilot study evaluation of lung ultrasound for the management of paediatric pneumonia in low-resource settings: a study protocol
Authors: Lenahan Jennifer L , Volpicelli Giovanni , Lamorte Alessandro , Jehan Fyezah , Bassat Quique , Ginsburg Amy Sarah
Published: December 2018

Introduction

Pneumonia is the leading infectious cause of death among children under 5 years of age worldwide. However, pneumonia is challenging to diagnose. Lung ultrasound (LUS) is a promising diagnostic technology. Further evidence is needed to better understand the role of LUS as a tool for the diagnosis of childhood pneumonia in low-resource settings.

Methods and analysis

This study aims to pilot LUS in Mozambique and Pakistan and to generate evidence regarding the use of LUS as a diagnostic tool for childhood pneumonia. Children with cough <14 days with chest indrawing (n=230) and without chest indrawing (n=40) are enrolled. World Health Organization Integrated Management of Childhood Illness assessment is performed at enrolment, along with a chest radiograph and LUS examination. Respiratory and blood specimens are collected for viral and bacterial testing and biomarker assessment. Enrolled children are followed for 14 days (in person) and 30 days (phone call) post-enrolment with LUS examinations performed on Days 2, 6 and 14. Qualitative and quantitative data are also collected to assess feasibility, usability and acceptability of LUS among healthcare providers and caregivers. The primary outcome is LUS findings at enrolment with secondary outcomes including patient outcomes, repeat LUS findings, viral and bacterial test results, and patient status after 14 and 30 days of follow-up.

Ethics and dissemination

This trial was approved by the Western Institutional Review Board as well as local ethics review committees at each site. We plan to disseminate study results in peer-reviewed journals and international conferences.

Trial registration number

NCT03187067.
MYCNde novo gain-of-function mutation in a patient with a novel megalencephaly syndrome
Authors: Kato Kohji , Miya Fuyuki , Hamada Nanako , Negishi Yutaka , Narumi-Kishimoto Yoko , Ozawa Hiroshi , Ito Hidenori , Hori Ikumi , Hattori Ayako , Okamoto Nobuhiko , Kato Mitsuhiro , Tsunoda Tatsuhiko , Kanemura Yonehiro , Kosaki Kenjiro , Takahashi Yoshiyuki , Nagata Koh-ichi , Saitoh Shinji
Published: December 2018

Background

In this study, we aimed to identify the gene abnormality responsible for pathogenicity in an individual with an undiagnosed neurodevelopmental disorder with megalencephaly, ventriculomegaly, hypoplastic corpus callosum, intellectual disability, polydactyly and neuroblastoma. We then explored the underlying molecular mechanism.

Methods

Trio-based, whole-exome sequencing was performed to identify disease-causing gene mutation. Biochemical and cell biological analyses were carried out to elucidate the pathophysiological significance of the identified gene mutation.

Results

We identified a heterozygous missense mutation (c.173C>T; p.Thr58Met) in theMYCNgene, at the Thr58 phosphorylation site essential for ubiquitination and subsequent MYCN degradation. The mutant MYCN (MYCN-T58M) was non-phosphorylatable at Thr58 and subsequently accumulated in cells and appeared to induce CCND1 and CCND2 expression in neuronal progenitor and stem cells in vitro. Overexpression of Mycn mimicking the p.Thr58Met mutation also promoted neuronal cell proliferation, and affected neuronal cell migration during corticogenesis in mouse embryos.

Conclusions

We identified a de novo c.173C>T mutation inMYCNwhich leads to stabilisation and accumulation of the MYCN protein, leading to prolonged CCND1 and CCND2 expression. This may promote neurogenesis in the developing cerebral cortex, leading to megalencephaly. While loss-of-function mutations inMYCNare known to cause Feingold syndrome, this is the first report of a germline gain-of-function mutation inMYCNidentified in a patient with a novel megalencephaly syndrome similar to, but distinct from, CCND2-related megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome. The data obtained here provide new insight into the critical role of MYCN in brain development, as well as the consequences of MYCN defects.
In-vitro study of species-specific coagulation differences in animals and humans using rotational thromboelastometry (ROTEM)
Authors: Lechner Raimund , Helm M , Müller M , Wille T , Riesner H J , Friemert B
Published: December 2018

Animal tests are conducted in all fields of trauma research, but transferability of these data to humans is limited. For example, it is still unclear which animal species is most similar to humans in terms of physiology of blood coagulation. To improve transferability and raise awareness of the existing differences, we compared human coagulation to coagulation of different animals. Rotational thromboelastometry was used to analyse the blood of pigs, sheep, rabbits and dogs. Animal data were compared with human coagulation based on the number of significant differences of the test parameters and on a descriptive comparison of the extent of relative deviation of the single values. All animal species showed significant differences in coagulation properties when compared with humans. Coagulation parameters of dogs and sheep were on average most similar to humans. However, there is no animal which is most similar to humans concerning all aspects of coagulation. Differences in coagulation between humans and animals are significant. This must be taken into account when transferring animal test data to humans.
Dual loyalty in military medical ethics: a moral dilemma or a test of integrity?
Authors: Olsthoorn Peter
Published: December 2018

When militaries mention loyalty as a value they mean loyalty to colleagues and the organisation. Loyalty to principle, the type of loyalty that has a wider scope, plays hardly a role in the ethics of most armed forces. Where military codes, oaths and values are about the organisation and colleagues, medical ethics is about providing patient care impartially. Being subject to two diverging professional ethics can leave military medical personnel torn between the wish to act loyally towards colleagues, and the demands of a more outward looking ethic. This tension constitutes a test of integrity, not a moral dilemma.
Incidence of acute respiratory distress syndrome and associated mortality in a polytrauma population
Authors: van Wessem Karlijn J P , Leenen Luke P H
Published: December 2018

Background

The incidence of acute respiratory distress syndrome (ARDS) has decreased in the last decade by improvement in trauma and critical care. However, it still remains a major cause of morbidity and mortality. This study investigated the current incidence and mortality of ARDS in polytrauma patients.

Methods

A 4.5-year prospective study included consecutive trauma patients admitted to a level 1 trauma center intensive care unit (ICU). Isolated head injuries, drowning, asphyxiation, burns, and deaths <48 hours were excluded. Demographics, Injury Severity Score (ISS), physiologic parameters, resuscitation parameters, Denver Multiple Organ Failure scores, and ARDS data according to Berlin criteria were prospectively collected. Data are presented as median (IQR), and p<0.05 was considered significant.

Results

241 patients were included. The median age was 45 (27–59) years, 178 (74%) were male, the ISS was 29 (22–36), and 232 (96%) patients had blunt injuries. Thirty-one patients (13%) died. Fifteen patients (6%) developed ARDS. The median time to ARDS onset was 3 (2–5) days after injury. The median duration of ARDS was 2.5 (1–3.5) days. All patients with ARDS were male compared with 61% of non-ARDS patients (p=0.003). Patients who developed ARDS had higher ISS (30 vs. 25, p=0.01), lower Partial Pressure of Oxygen in arterial blood (PaO2) both in the emergency department and ICU, and higher Partial Pressure of Carbon Dioxide in arterial blood (PaCo2) in the ICU. Patients with ARDS needed more crystalloids <24 hours (8.7 vs. 6.8 L, p=0.03), received more fresh frozen plasma <24 hours (3 vs. 0 U, p=0.04), and more platelet <8 hours and <24 hours. Further, they stayed longer on the ventilator (11 vs. 2 days, p<0.001), longer in the ICU (12 vs. 3 days, p<0.001), and in the hospital (33 vs. 15 days, p=0.004). Patients with ARDS developed more often multiple organ dysfunction syndrome (40% vs. 3%, p<0.001) and died more often (20% vs. 3%, p=0.01). Only one patient with ARDS (7%) died of ARDS.

Discussion

In this polytrauma population mortality was predominantly caused by brain injury. The incidence of ARDS was low; its presentation was only early onset, during a short time period, and accompanied by low mortality.

Level of evidence

Level III.
Seasonal space use of transient and resident coyotes (Canis latrans) in North Carolina, USA
Authors: Sasmal Indrani , Moorman Christopher E. , Swingen Morgan B. , Datta Shubham , DePerno Christopher S.
Published: December 2018

Coyote (Canis latrans Say, 1823) is a recent immigrant into eastern United States and little is known about the species’ space use and movement in the region. We compared space use and movement of radio-collared coyotes among biological seasons. We captured and collared 30 coyotes from February through May 2011 and collected 85 386 GPS locations through October 2012 at Fort Bragg Military Installation. We defined four biological seasons according to coyote life history: breeding (December–February), gestation (March–May), pup-rearing (June–August), and dispersal (September–November). Out of 27 radio-collared individuals, we identified 10 as transient and 11 as resident based on home-range size and variability across seasons; 6 switched their status and were classified as intermediate. We observed low variability of core-area size across seasons for resident males and females, whereas we documented high variability for transient males. Movement rate of resident coyotes during spring (449.75 m/h) was greater than summer (295.33 m/h), whereas movement rates did not differ between any other seasons. For transient coyotes, movement rate during summer (283 m/h) was less than fall (374.73 m/h), spring (479.85 m/h), and winter (488.5 m/h). Some coyotes adjusted their residency status seasonally and other individuals dispersed large distances (>200 km).
Eastern Fence Lizards (Sceloporus undulatus) display an ontogenetic shift in relative consumption of native and invasive prey
Authors: Venable Cameron P. , Langkilde Tracy
Published: December 2018

Interactions between invasive prey and native predators can provide an opportunity to better understand predator–prey dynamics and how these may change through ontogeny. Eastern Fence Lizards (Sceloporus undulatus (Bosc and Daudin in Sonnini and Latreille, 1801)) are ant specialist, particularly as juveniles. Invasive red imported fire ants (Solenopsis invicta Buren, 1972) pose a lethal risk to S. undulatus that eat them, especially smaller-bodied juveniles. We examine ontogenetic shifts in S. undulatus consumption of toxic invasive fire ants versus palatable native pyramid ants (Dorymyrmex bureni (Trager, 1988)). We predicted that hatchlings should avoid eating fire ants in favor of native ants, whereas less-vulnerable adults should take advantage of both prey sources. However, when given the choice between fire ants and native ants, hatchlings consumed similar numbers of these species, whereas adults consumed nearly three times as many native ants as invasive fire ants. Increased consumption of fire ants in adulthood could be the result of lifetime experience, strategies to safely consume fire ants, ontogenetic shifts in the ability to distinguish between ants, or reduced costs to adults of eating venomous ants. Future research should aim to distinguish these alternative mechanisms and examine the long-term consequences of native species incorporating toxic invasive prey into their diets.
Renormalization of quantum field theory on Riemannian manifolds
Authors: Dang Nguyen Viet , Herscovich Estanislao
Published: December 2018

In this paper, we provide a simple pedagogical proof of the existence of covariant renormalizations in Euclidean perturbative quantum field theory on closed Riemannian manifolds, following the Epstein–Glaser philosophy. We rely on a local method that allows us to extend a distribution defined on an open set [Formula: see text] to the whole manifold [Formula: see text].
Fractional Matching Preclusion for (n,k)-Star Graphs
Authors: Ma Tianlong , Mao Yaping , Cheng Eddie , Wang Jinling
Published: December 2018

The matching preclusion number of a graph is the minimum number of edges whose deletion results in a graph that has neither perfect matchings nor almost perfect matchings. As a generalization, Liu and Liu introduced the concept of fractional matching preclusion number in 2017. The Fractional Matching Preclusion Number (FMP number) of G is the minimum number of edges whose deletion leaves the resulting graph without a fractional perfect matching. The Fractional Strong Matching Preclusion Number (FSMP number) of G is the minimum number of vertices and/or edges whose deletion leaves the resulting graph without a fractional perfect matching. In this paper, we obtain the FMP number and the FSMP number for (n, k)-star graphs. In addition, all the optimal fractional strong matching preclusion sets of these graphs are categorized.
Effect of Ni concentration on solderability, microstructure and hardness of SAC0705-xNi solder joints on Cu and graphene-coated Cu substrates
Authors: Cai Hongming , Liu Yang , Li Shengli , Zhang Hao , Sun Fenglian , Qi Junlei
Published: December 2018

In this paper, solderability, microstructure and hardness of SAC0705-xNi solder joints on Cu and graphene-coated Cu (G-Cu) substrates were studied. As Ni content increases in the solder, the solderability improves gradually on both the Cu and G-Cu substrates. The solderability of SAC0705-xNi is better on G-Cu substrate than that on Cu substrate. The increasing Ni content in the solder has a positive effect on the microstructure refinement of both the kinds of substrates. Such effect is more significant on G-Cu substrate than that on Cu substrate. With the increase of Ni content, the thickness of the interfacial intermetallic compound (IMC) shows an increasing trend first and then decreasing trend on the two kinds of substrates. Since the graphene layer works as a diffusion barrier, the IMC on G-Cu is thinner than that on Cu substrate. The addition of Ni leads to the strengthening of the microstructure and thus increases the hardness of the solder bulks.
Study of Grodzins relation of B(E2) with E(21+) in A = 130, 100 and 80 regions
Authors: Gupta J. B. , Katoch Vikas
Published: December 2018

The nuclei in the [Formula: see text] [Formula: see text] and [Formula: see text] regions, lying on both sides of the [Formula: see text]-stability line, continue to be of interest for their complex nuclear structures. The Grodzins product rule (GPR) viz. [Formula: see text], for the ground bands of even-[Formula: see text] even-[Formula: see text] nuclei provides a useful approach to study these structures. The utility of our method, displaying the linear relation of [Formula: see text] to [Formula: see text], is illustrated for the [Formula: see text] Zn to [Formula: see text] Cd series of isotopes. The spread of the data on the linear plots enables a quick view of the shape phase transitions. The role of the shells and the subshells, at spherical and deformed shell gaps for neutrons and protons, with their mutual re-inforcement and the shape phase transition are vividly visible on our plots. The development of collectivity in this region is also linked to the effective number of valence nucleons above the magic number of [Formula: see text], and 28 rather than [Formula: see text], for Mo to Cd isotopes for a microscopic calculation.
Distinguishing Vagueness from Ambiguity in Rough Set Approximations
Authors: Greco Salvatore , Matarazzo Benedetto , Słowiński Roman
Published: December 2018

In this paper we present a new approach to rough set approximations that permits to distinguish between two kinds of “imperfect” knowledge in a joint framework: on one hand, vagueness, due to imprecise knowledge and uncertainty typical of fuzzy sets, and on the other hand, ambiguity, due to granularity of knowledge originating from the coarseness typical of rough sets. The basic idea of our approach is that each concept is represented by an orthopair, that is, a pair of disjoint sets in the universe of knowledge. The first set in the pair contains all the objects that are considered as surely belonging to the concept, while the second set contains all the objects that surely do not belong to the concept. In this context, following some previous research conducted by us on the algebra of rough sets, we propose to define as rough approximation of the orthopair representing the considered concept another orthopair composed of lower approximations of the two sets in the first orthopair. We shall apply this idea to the classical rough set approach based on indiscernibility, as well as to the dominance-based rough set approach. We discuss also a variable precision rough approximation, and a fuzzy rough approximation of the orthopairs. Some didactic examples illustrate the proposed methodology.
Zsigmondy theorem for arithmetic dynamics induced by a drinfeld module
Authors: Zhao Zhengjun , Ji Qingzhong
Published: December 2018

Let [Formula: see text] be a Drinfeld [Formula: see text]-module defined over a global function field [Formula: see text] Let [Formula: see text] be a non-torsion point of [Formula: see text] with infinite [Formula: see text]-orbit. For each [Formula: see text] write the ideal [Formula: see text] as a quotient of relatively prime integral ideals. We establish an analogue of the classical Zsigmondy theorem for the ideal sequence [Formula: see text] i.e. for all but finitely many [Formula: see text] there exists a prime ideal [Formula: see text] such that [Formula: see text] and [Formula: see text] for all [Formula: see text]
Deception, identity, and security
Authors: Casey William , Kellner Ansgar , Memarmoshrefi Parisa , Morales Jose Andre , Mishra Bud
Published: December 2018

Classical mathematical game theory helps to evolve the emerging logic of identity in the cyber world.
Algorithms for Online Influencer Marketing
Authors: Lagrée Paul , Cappé Olivier , Cautis Bogdan , Maniu Silviu
Published: December 2018

Influence maximization is the problem of finding influential users, or nodes, in a graph so as to maximize the spread of information. It has many applications in advertising and marketing on social networks. In this article, we study a highly generic version of influence maximization, one of optimizing influence campaigns by sequentially selecting “spread seeds” from a set of
influencers
, a small subset of the node population, under the hypothesis that, in a given campaign, previously activated nodes remain persistently active. This problem is in particular relevant for an important form of online marketing, known as
influencer marketing
, in which the marketers target a sub-population of influential people, instead of the entire base of potential buyers. Importantly, we make no assumptions on the underlying diffusion model, and we work in a setting where neither a diffusion network nor historical activation data are available. We call this problem
online influencer marketing with persistence
(in short, OIMP). We first discuss motivating scenarios and present our general approach. We introduce an estimator on the influencers’
remaining potential
– the expected number of nodes that can still be reached from a given influencer – and justify its strength to rapidly estimate the desired value, relying on real data gathered from Twitter. We then describe a novel algorithm, GT-UCB, relying on probabilistic upper confidence bounds on the remaining potential. We show that our approach leads to high-quality spreads on both simulated and real datasets. Importantly, it is orders of magnitude faster than state-of-the-art influence maximization methods, making it possible to deal with large-scale online scenarios.
Imperfect forward secrecy
Authors: Adrian David , Bhargavan Karthikeyan , Durumeric Zakir , Gaudry Pierrick , Green Matthew , Halderman J. Alex , Heninger Nadia , Springall Drew , Thomé Emmanuel , Valenta Luke , VanderSloot Benjamin , Wustrow Eric , Zanella-Béguelin Santiago , Zimmermann Paul
Published: December 2018

We investigate the security of Diffie-Hellman key exchange as used in popular Internet protocols and find it to be less secure than widely believed. First, we present Logjam, a novel flaw in TLS that lets a man-in-the-middle downgrade connections to "export-grade" Diffie-Hellman. To carry out this attack, we implement the number field sieve discrete logarithm algorithm. After a week-long precomputation for a specified 512-bit group, we can compute arbitrary discrete logarithms in that group in about a minute. We find that 82% of vulnerable servers use a single 512-bit group, and that 8.4% of Alexa Top Million HTTPS sites are vulnerable to the attack. In response, major browsers have changed to reject short groups.

We go on to consider Diffie-Hellman with 768- and 1024-bit groups. We estimate that even in the 1024-bit case, the computations are plausible given nation-state resources. A small number of fixed or standardized groups are used by millions of servers; performing precomputation for a single 1024-bit group would allow passive eavesdropping on 18% of popular HTTPS sites, and a second group would allow decryption of traffic to 66% of IPsec VPNs and 26% of SSH servers. A close reading of published NSA leaks shows that the agency's attacks on VPNs are consistent with having achieved such a break. We conclude that moving to stronger key exchange methods should be a priority for the Internet community.
Face2Face
Authors: Thies Justus , Zollhöfer Michael , Stamminger Marc , Theobalt Christian , Nießner Matthias
Published: December 2018

Face2Face
is an approach for real-time facial reenactment of a monocular target video sequence (e.g., Youtube video). The source sequence is also a monocular video stream, captured live with a commodity webcam. Our goal is to animate the facial expressions of the target video by a source actor and re-render the manipulated output video in a photo-realistic fashion. To this end, we first address the under-constrained problem of facial identity recovery from monocular video by non-rigid model-based bundling. At run time, we track facial expressions of both source and target video using a dense photometric consistency measure. Reenactment is then achieved by fast and efficient deformation transfer between source and target. The mouth interior that best matches the re-targeted expression is retrieved from the target sequence and warped to produce an accurate fit. Finally, we convincingly re-render the synthesized target face on top of the corresponding video stream such that it seamlessly blends with the real-world illumination. We demonstrate our method in a live setup, where Youtube videos are reenacted in real time. This live setup has also been shown at SIGGRAPH Emerging Technologies 2016, by Thies et al. where it won the Best in Show Award.
Muscle contracture and passive mechanics in cerebral palsy
Authors: Lieber Richard L. , Fridén Jan
Published: December 2018

Skeletal muscle contractures represent the permanent shortening of a muscle-tendon unit, resulting in loss of elasticity and, in extreme cases, joint deformation. They may result from cerebral palsy, spinal cord injury, stroke, muscular dystrophy, and other neuromuscular disorders. Contractures are the prototypic and most severe clinical presentation of increased passive mechanical muscle force in humans, often requiring surgical correction. Intraoperative experiments demonstrate that high muscle passive force is associated with sarcomeres that are abnormally stretched, although otherwise normal, with fewer sarcomeres in series. Furthermore, changes in the amount and arrangement of collagen in the extracellular matrix also increase muscle stiffness. Structural light and electron microscopy studies demonstrate that large bundles of collagen, referred to as perimysial cables, may be responsible for this increased stiffness and are regulated by interaction of a number of cell types within the extracellular matrix. Loss of muscle satellite cells may be related to changes in both sarcomeres and extracellular matrix. Future studies are required to determine the underlying mechanism for changes in muscle satellite cells and their relationship (if any) to contracture. A more complete understanding of this mechanism may lead to effective nonsurgical treatments to relieve and even prevent muscle contractures.
Voluntary wheel running prevents salt-induced endothelial dysfunction: role of oxidative stress
Authors: Guers John J. , Kasecky-Lardner Lauren , Farquhar William B. , Edwards David G. , Lennon Shannon L.
Published: December 2018

Diets high in salt can lead to endothelial dysfunction, a nontraditional risk factor for cardiovascular disease (CVD). Exercise is known to reduce CVD risk; however, it remains unknown whether chronic physical activity can attenuate salt-induced endothelial dysfunction independent of blood pressure (BP) and whether these changes are due to an upregulation in endogenous antioxidants. Eight-week-old Sprague-Dawley rats were fed either a normal (NS; 0.49%)- or a high (HS; 4.0%)-salt diet and further divided into voluntary wheel running (NS-VWR, HS-VWR) and sedentary (NS, HS) groups for 6 wk. BP was measured weekly and remained unchanged within groups ( P = 0.373). Endothelium-dependent relaxation (EDR) was impaired in the femoral artery of HS compared with NS (38.6 ± 4.0% vs. 65.0 ± 3.6%; P = 0.013) animals, whereas it was not different between NS and HS-VWR (73.4 ± 6.4%; P = 0.273) animals. Incubation with the antioxidants TEMPOL ( P = 0.024) and apocynin ( P = 0.013) improved EDR in HS animals, indicating a role for reactive oxygen species (ROS). Wheel running upregulated the antioxidant superoxide dismutase-2 (SOD-2) ( P = 0.011) under HS conditions and lowered NOX4 and Gp91-phox, two subunits of NADPH oxidase. Wheel running elevated phosphorylated endothelial nitric oxide synthase (eNOS) ( P = 0.014) in HS-fed rats, demonstrating a role for physical activity and eNOS activity under HS conditions. Finally, there was a reduction in EDR ( P = 0.038) when femoral arteries from NS-VWR animals were incubated with TEMPOL or apocynin, suggesting there may be a critical level of ROS needed to maintain endothelial function. In summary, physical activity protected HS-fed rats from reductions in endothelial function, likely through increased SOD-2 levels and reduced oxidative stress.

NEW & NOTEWORTHY Our data suggest that voluntary wheel running can prevent impairments in endothelium-dependent relaxation in the femoral artery of rats fed a high-salt diet. This appears to be independent of blood pressure and mediated through a decrease in expression of NADPH oxidases as a result of physical activity. These data suggest that increased chronic physical activity can protect the vasculature from a diet high in salt, likely through a reduction in oxidative stress.
Molecular adaptations in human subcutaneous adipose tissue after ten weeks of endurance exercise training in healthy males
Authors: Riis Simon , Christensen Britt , Nellemann Birgitte , Møller Andreas Buch , Husted Anna Sofie , Pedersen Steen B. , Schwartz Thue W. , Jørgensen Jens Otto Lunde , Jessen Niels
Published: December 2018

Endurance exercise training induces adaptations in metabolically active organs, but adaptations in human subcutaneous adipose tissue (scAT) remains incompletely understood. On the basis of animal studies, we hypothesized that endurance exercise training would increase the expression of proteins involved in lipolysis and glucose uptake in scAT. To test these hypotheses, 19 young and healthy males were randomized to either endurance exercise training (TR; age 18–24 yr; BMI 19.0–25.4 kg/m2) or a nonexercising control group (CON; age 21–35 yr; BMI 20.5–28.8 kg/m2). Abdominal subcutaneous fat biopsies and blood were obtained at rest before and after intervention. By using Western blotting and PCR, we determined expression of lipid droplet-associated proteins, various proteins involved in substrate metabolism, and mRNA abundance of cell surface G protein-coupled receptors (GPCRs). Adipose tissue insulin sensitivity was determined from fasting plasma insulin and nonesterified fatty acids (adipose tissue insulin resistance index; Adipo-IR). Adipo-IR improved in TR compared with CON ( P = 0.03). This was accompanied by increased insulin receptor (IR) protein expression in scAT with a 1.54-fold (SD 0.79) change from baseline in TR vs. 0.85 (SD 0.30) in CON ( P = 0.007). Additionally, hexokinase II (HKII) and succinate dehydrogenase complex subunit A (SDHA) protein increased in TR compared with CON ( P = 0.006 and P = 0.04, respectively). We did not observe changes in lipid droplet-associated proteins or mRNA abundance of GPCRs. Collectively, 10 weeks of endurance exercise training improved adipose tissue insulin sensitivity, which was accompanied by increased IR, HKII, and SDHA protein expression in scAT. We suggest that these adaptations contribute to an improved metabolic flexibility.

NEW & NOTEWORTHY This study is the first to investigate the molecular adaptations in human subcutaneous adipose tissue (scAT) after endurance exercise training compared with a nonexercising control group. We show that endurance exercise training improves insulin sensitivity in human scAT, and this is accompanied by increased expression of insulin receptor, hexokinase II, and succinate dehydrogenase complex subunit A. Collectively, our data suggest that endurance exercise training induces molecular adaptations in human scAT, which may contribute to an improved metabolic flexibility.
Shake Table Study on the Efficiency of Seismic Base Isolation Using Natural Stone Pebbles
Authors: Banović Ivan , Radnić Jure , Grgić Nikola
Published: December 2018

The results of a shake table study of the efficiency of a seismic base isolation using a layer of natural stone pebbles are presented. Models of stiff and medium‐stiff buildings were tested. Case studies were conducted with the foundation of model on the rigid base and on four different layers of pebbles (thin and thick layer with small and large pebbles). Four different horizontal accelerograms were applied, and the characteristic displacements, accelerations, and strains were measured. Strains/stresses of the tested models remained in the elastic area. It was concluded that the effectiveness of the stone pebble layer under the foundation, i.e., the reduction in the seismic forces and stresses in the structure compared to the classical solution of foundation, significantly depends on the type of the applied excitation and depends relatively little on the layer thickness and pebble fraction. The results of the study showed that a layer of pebbles can significantly reduce the peak acceleration and strains/stresses of the model, with acceptable displacements. Further research is expected to confirm the effectiveness of this low‐cost and low‐tech seismic base isolation and to pave the way to its practical application.
Current and Emerging Evidence for Toll-Like Receptor Activation in Sjögren’s Syndrome
Authors: Kiripolsky Jeremy , Kramer Jill M.
Published: December 2018

While the importance of Toll-like receptor (TLR) signaling is well established in many autoimmune diseases, the role of TLR activation in Sjögren’s syndrome (SS) is poorly understood. Studies in mice and humans reveal that TLRs are potent mediators of inflammation in SS. TLRs are expressed and functional in salivary tissue, and TLRs in peripheral blood cells of SS patients are also upregulated and hyperresponsive to ligation. In this review, we will detail observations in mouse models regarding the importance of TLR activation in both local and systemic disease. We will then discuss studies in SS patients that provide evidence of the importance of TLR-mediated signaling in disease. While the ligands that activate TLRs in the context of SS are unknown, emerging data suggest that damage-associated molecular patterns (DAMPs) may be significant drivers of the chronic and unremitting inflammation that is characteristic of SS. We will discuss putative DAMPs that may be of clinical significance in disease. Therapies that target TLR signaling cascades will likely reduce both exocrine-specific and systemic manifestations of SS.
Potential Application of Yokukansan as a Remedy for Parkinson’s Disease
Authors: Jang Jung-Hee , Jung Kyungsook , Kim Joong-Sun , Jung Inchul , Yoo Horyong , Moon Changjong
Published: December 2018

Parkinson’s disease (PD), the second most common progressive neurodegenerative disorder, is characterized by complex motor and nonmotor symptoms. The clinical diagnosis of PD is defined by bradykinesia and other cardinal motor features, although several nonmotor symptoms are also related to disability, an impaired quality of life, and shortened life expectancy. Levodopa, which is used as a standard pharmacotherapy for PD, has limitations including a short half‐life, fluctuations in efficacy, and dyskinesias with long‐term use. There have been efforts to develop complementary and alternative therapies for incurable PD. Yokukansan (YKS) is a traditional herbal medicine that is widely used for treating neurosis, insomnia, and night crying in children. The clinical efficacy of YKS for treating behavioral and psychological symptoms, such as delusions, hallucinations, and impaired agitation/aggression subscale and activities of daily living scores, has mainly been investigated in the context of neurological disorders such as PD, Alzheimer’s disease, and other psychiatric disorders. Furthermore, YKS has previously been found to improve clinical symptoms, such as sleep disturbances, neuropsychiatric and cognitive impairments, pain, and tardive dyskinesia. Preclinical studies have reported that the broad efficacy of YKS for various symptoms involves its regulation of neurotransmitters including GABA, serotonin, glutamate, and dopamine, as well as the expression of dynamin and glutamate transporters, and changes in glucocorticoid hormones and enzymes such as choline acetyltransferase and acetylcholinesterase. Moreover, YKS has neuroprotective effects at various cellular levels via diverse mechanisms. In this review, we focus on the clinical efficacy and neuropharmacological effects of YKS. We discuss the possible mechanisms underpinning the effects of YKS on neuropathology and suggest that the multiple actions of YKS may be beneficial as a treatment for PD. We highlight the potential that YKS may serve as a complementary and alternative strategy for the treatment of PD.
A Network Pharmacology Approach to Uncover the Potential Mechanism of Yinchensini Decoction
Authors: Chen Guoming , Huang Chuyao , Liu Yunyun , Chen Tengyu , Huang Ruilan , Liang Miaozhen , Zhang Jie , Xu Hua
Published: December 2018

Objective. To predict and explore the potential mechanism of Yinchensini decoction (YCSND) based on systemic pharmacology. Method. TCMSP database was searched for the active constituents and related target proteins of YCSND. Cytoscape 3.5.1 was used to construct the active ingredient‐target interaction of YCSND and network topology analysis, with STRING online database for protein‐protein interaction (PPI) network construction and analysis; and collection from the UniProt database of target protein gene name, with the DAVID database for the gene ontology (GO) functional analysis, KEGG pathway enrichment analysis mechanism and targets of YCSND. Results. The results indicate the core compounds of YCSND, namely, kaempferol, 7‐Methoxy‐2‐methyl isoflavone, and formononetin. And its core targets are prostaglandin G/H synthase 2, estrogen receptor, Calmodulin, heat shock protein HSP 90, etc. PPI network analysis shows that the key components of the active ingredients of YCSND are JUN, TP53, MARK1, RELA, MYC, and so on. The results of the GO analysis demonstrate that extracellular space, cytosol, and plasma membrane are the main cellular components of YCSND. Its molecular functions are mainly acting on enzyme binding, protein heterodimerization activity, and drug binding. The biological process of YCSND is focused on response to drug, positive regulation of transcription from RNA polymerase II promoter, the response to ethanol, etc. KEGG results suggest that the pathways, including pathways in cancer, hepatitis B, and pancreatic cancer, play a key role in YCSND. Conclusion. YCSND exerts its drug effect through various signaling pathways and acts on kinds of targets. By system pharmacology, the potential role of drugs and the mechanism of action can be well predicted.
Gastropleural Fistula as a Rare Complication of Gastric Sleeve Surgery: A Case Report and Comprehensive Literature Review
Authors: Alghanim Fahad , Alkhaibary Ali , Alzakari Abdulmohsen , AlRumaih Abdullah
Published: December 2018

Gastropleural fistula (GPF) is a rare, life-threatening complication of gastric sleeve surgery. GPF is an uncommon differential diagnosis to consider in a patient presenting with a picture of pneumonia. As such, GPF should be suspected in a patient with a history of nonresolving pneumonia who recently underwent gastric sleeve surgery. To the best of our knowledge, only eight cases of gastropleural fistulas after bariatric surgery have been reported in the literature. Herein, we report a case of gastropleural fistula after gastric sleeve surgery and review the pertinent literature. A gastropleural fistula is an exceedingly rare and life-threatening complication postbariatric surgery. Nonsurgical conservative management (total parenteral nutrition, percutaneous drainage, and antibiotics with endoscopic stenting) can be considered.
Combined Therapy of Hypertensive Nephropathy with Breviscapine Injection and Antihypertensive Drugs: A Systematic Review and a Meta‐Analysis
Authors: Wu Lihua , Liu Ming , Fang Zhuyuan
Published: December 2018

Objective. To evaluate the beneficial and adverse effects of breviscapine injection in combination with antihypertensive drugs for treating hypertensive nephropathy in clinical practice. Methods. We searched PubMed, the Cochrane Library, Embase, CNKI, Sino Med, VIP, and Wanfang Data for relevant literature. The timeframe of retrieval was set from the founding date of each database to September 28, 2018. Results. Fourteen papers were included in this study. The quality of all the studies included was determined to be low. All studies were conducted with Chinese populations. Meta‐analysis showed that, compared with single‐use antihypertensive drugs, using breviscapine injection in combination with antihypertensive drugs to treat hypertensive nephropathy can reduce serum creatinine (Scr) [WMD = –35.16, 95% CI(–50.01, –20.31), P ≤ 0.001], blood urea nitrogen (BUN) [WMD = –2.00, 95% CI(–3.07, –0.94), P ≤ 0.001], 24‐hour urinary total protein (24 h UTP) [WMD = –0.04, 95% CI(–0.05, –0.02), P ≤ 0.001], and the beta‐2‐microglobulin (B2M) [WMD = –0.09, 95% CI(–0.11, –0.07), P ≤ 0.001], improve creatinine clearance rate (Ccr) [WMD = 7.84, 95% CI(5.20, 10.49), P ≤ 0.001], and increase the clinical efficacy [RR = 1.27, 95% CI(1.05, 1.53), P = 0.014], but does not lower systolic blood pressure (SBP) [WMD = –1.02, 95% CI(–2.88, 0.84), P = 0.281]. There was no significant difference in adverse events between experimental groups and control groups. Conclusion. Breviscapine injection in combination with antihypertensive drugs can improve clinical efficacy and Ccr and reduce Scr, BUN, 24 h UTP, and B2M in patients with hypertensive nephropathy. The present meta‐analysis indicated that breviscapine injection can serve as a renal protective effect to patients with hypertensive nephropathy. However, the evidence of methodological quality and sample sizes is weak, and thus, further standardized research is required.
Trichophytonas a Rare Cause of Postoperative Wound Infection Resistant to Standard Empiric Antimicrobial Therapy
Authors: Gaffar Sheema , Birknes John K. , Cunnion Kenji M.
Published: December 2018

Fungal infections are rare causes of acute surgical wound infections, butCandidais not an infrequent etiology in chronic wound infections.Trichophytonspecies is a common cause of tinea capitis but has not been reported as a cause of neurosurgical wound infection. We report a case ofTrichophyton tonsuranscausing a nonhealing surgical wound infection in a 14-year-old male after hemicraniectomy. His wound infection was notable for production of purulent exudate from the wound and lack of clinical improvement despite empiric treatment with multiple broad-spectrum antibiotics targeting typical bacterial causes of wound infection. Multiple wound cultures consistently grewTrichophytonfungus, and his wound infection clinically improved rapidly after starting terbinafine and discontinuing antibiotics.
On the Effects of Various Measures of Performance Selections on Simulation Model Calibration Performance
Authors: Wang Chen , Xu Chengcheng
Published: December 2018

Objective. This paper examines the effects of various measures of performance (MOP) selections on simulation model calibration performance, in terms of reflecting actual traffic conditions and vehicle interactions. Method. Two intersections in Shanghai were selected for simulation model calibration, one for testing and another for validation. Three effective MOPs were utilized, including average travel time (i.e., time passing the intersection), average queue length, and vehicle headway distribution. The counts of three types of traffic conflicts (i.e., crossing, rear-end, and lane change) were used as safety MOPs. Those MOPs, as calibration objectives, were examined and compared. Results. The results of the testing site showed that different effective MOPs had their own advantages: average travel time appeared to be the best in reflecting lane change and rear-end conflicts while headway distribution performed the best consistency between simulated and actual crossing conflicts. Compared to the safety MOPs, average travel time and headway distribution still performed better, in terms of resulting in more similar simulated conflict metrics (e.g., TTC, PET) to actual ones. A multicriteria calibration strategy based on average travel time and headway distribution generally had better performances in reflecting actual traffic conditions and vehicle interactions than using any single effective or safety MOP. Similar results were found for the validation site. Conclusion. To simulate actual traffic conditions and vehicle interactions, multiple effective MOPs could be simultaneously considered for model calibration, instead of using safety MOPs.
Flavonoid Productivity Optimized for Green and Red Forms of Perilla frutescens via Environmental Control Technologies in Plant Factory
Authors: Lu Na , Takagaki Michiko , Yamori Wataru , Kagawa Natsuko
Published: December 2018

Perilla frutescens (Lamiaceae) is a dietary staple in Asia. It is an abundant source of flavonoids that are bioactively beneficial to human health and fitness. The current popularity of plant-based consumption is being driven by the healthful benefits of bioactive nutrition, and the concentration of bioactive agents found in raw plant materials is an important factor in the assessment of food quality. To test the feasibility of promoting flavonoid productivity in perilla plants via environmental treatment, plant factory technology was applied to perilla plant cultivation. Apigenin (AG) and luteolin (LT) are two of the most potent anticarcinogenic flavonoids in perilla, and these are also found in many vegetables and fruits. Quantitative analysis of AG and LT was conducted on plants cultivated under nine environmental forms of treatment imposed by three levels of light intensity (100, 200, and 300 µmol·m−2·s−1) combined with three levels of nutrient-solution concentration (1.0, 2.0, and 3.0 dS·m−1) for hydroculture. The contents of AG in green and red perilla plant were increased by high nutrient-solution levels under the same light intensity. In green perilla, the highest concentration of AG (8.50 µg·g−1) was obtained under treatment of the highest level of nutrient-solution (3.0 dS·m−1) and 200 µmol·m−2·s−1 of light intensity, whereas in red perilla, the highest concentration of AG (6.38 µg·g−1) was achieved from the highest levels of both of these forms of treatment (300 µmol·m−2·s−1 and 3.0 dS·m−1). The increase in AG content per plant between the lowest and the highest levels was recorded by 6.4-fold and 8.6-fold in green and red perilla, respectively. The behavior of LT concentration differed between green and red forms of perilla. LT concentration in red perilla was enhanced under nutrient deficiency (1.0 dS·m−1) and affected by light intensity. Different responses were observed in the accumulations of AG and LT in red and green perilla during treatments, and this phenomenon was discussed in terms of biosynthetic pathways that involve the expressions of phenylpropanoids and anthocyanins. The total yield of flavonoids (AG and LT) was improved with the optimization of those forms of treatment, with the best total yields: 33.9 mg·plant−1 in green Perilla; 10.0 mg·plant−1 in red perilla, and a 4.9-fold and a 5.4-fold increase was recorded in green and red perilla, respectively. This study revealed that flavone biosynthesis and accumulation in perilla plants could be optimized via environmental control technologies, and this approach could be applicable to leafy vegetables with bioactive nutrition to produce a stable industrial supply of high flavonoid content.
A Novel Integrative Processing Technology for the Preparation of Rehmanniae Radix Slices
Authors: Bao Bei-hua , Qian Yan , Cheng Fang-fang , Chen Pei-dong , Cao Yu-dan , Yu Sheng , Shan Ming-qiu , Yao Wei-feng , Ding An-wei , Zhang Li
Published: December 2018

The traditional processing method for the slices preparation of Rehmanniae roots is time‐ and energy‐consuming and is prone to result in loss of active components during twice water‐treatment (once for wash and the other for softening) and drying steps. In this study, we firstly explored an integrative processing technique for Rehmanniae Radix by 2x3 factorial experiment based on the contents of catalpol and verbascoside as measured by HPLC. The potential differences between the traditional stepwise processing technique and the integrative processing technique for catalpol and verbascoside in the prepared slices were investigated. To further confirm the effectiveness of drugs using the integrative processing technique, some pharmacological variables, such as rectal temperature, hematologic parameters (RBC, HGB, HCT, and blood viscosity), and coagulation parameters (TT, APTT, PT and FIB), were detected in a blood‐heat and hemorrhage syndrome rat model. Two‐way ANOVA analysis showed that drying for 18 h at 50°C was considered as the best combination of process conditions. The mean catalpol and verbascoside contents in the integrative method‐processed samples (4.30% and 0.33%, respectively) were higher than those in the traditional method‐processed samples (2.61% and 0.21%, respectively). Significant increases in rectal temperature, and hematologic parameters, TT, APTT, and FIB, were observed in the model group rats, compared to the blank group animals (P<0.01). Both in the integrative groups and traditional groups, the extracts caused significant decreases in rectal temperature, RBC, HGB, and HCT with increased concentration compared to the model group animals. All coagulation parameters tested were shortened in model rats received two kind prepared slices. There were no significant therapeutic differences between the integrative and the traditional method‐processed slices on the hemostasis and hemorheological parameters in this blood‐heat and hemorrhage syndrome rat model, indicating that our integrative method may be a feasible technique for processing Rehmanniae Radix slices.