bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased expression of miR-27 predicts poor prognosis and promotes tumorigenesis in human multiple myeloma
Authors: Che Feifei , Wan Chunqian , Dai Jingying , Chen Jiao
Published: March 2019

Multiple myeloma (MM) is an incurable hematological malignancy characterized by abnormal infiltration of plasma cells in the bone marrow. MicroRNAs (miRNAs) have emerged as crucial regulators in human tumorigenesis and tumor progression. miR-27, a novel cancer-related miRNA, has been confirmed to be implicated in multiple types of human tumors; however, its biological role in MM remains largely unknown. The present study aimed to characterize the biological role of miR-27 in MM and elucidate the potential molecular mechanisms. Here we found that miR-27 was significantly up-regulated in MM samples compared with normal bone marrow samples from healthy donors. Moreover, the log-rank test and Kaplan–Meier survival analysis displayed that MM patients with high miR-27 expression experienced a significantly shorter overall survival than those with low miR-27 expression. In the current study, we transfected MM cells with miR-27 mimics or miR-27 inhibitor to manipulate its expression. Functional studies demonstrated that miR-27 overexpression promoted MM cell proliferation, facilitated cell cycle progression, and expedited cell migration and invasion; whereas miR-27 knockdown inhibited cell proliferation, induced cell cycle arrest, and slowed down cell motility. Mechanistic studies revealed that Sprouty homolog 2 (SPRY2) was a direct target of miR-27 and that rescuing SPRY2 expression reversed the promoting effects of miR-27 on MM cell proliferation, migration, and invasion. Besides, miR-27 ablation suppressed tumorigenecity of MM cells in mouse xenograft models. Collectively, our data indicate that miR-27 exerts its oncogenic functions in MM by targetting SPRY2 and that miR-27 may be used as a promising candidate target in MM treatment.
Structural studies of plasmin inhibition
Authors: Wu Guojie , Quek Adam J. , Caradoc-Davies Tom T. , Ekkel Sue M. , Mazzitelli Blake , Whisstock James C. , Law Ruby H.P.
Published: March 2019

Plasminogen (Plg) is the zymogen form of the serine protease plasmin (Plm), and it plays a crucial role in fibrinolysis as well as wound healing, immunity, tissue remodeling and inflammation. Binding to the targets via the lysine-binding sites allows for Plg activation by plasminogen activators (PAs) present on the same target. Cellular uptake of fibrin degradation products leads to apoptosis, which represents one of the pathways for cross-talk between fibrinolysis and tissue remodeling. Therapeutic manipulation of Plm activity plays a vital role in the treatments of a range of diseases, whereas Plm inhibitors are used in trauma and surgeries as antifibrinolytic agents. Plm inhibitors are also used in conditions such as angioedema, menorrhagia and melasma. Here, we review the rationale for the further development of new Plm inhibitors, with a particular focus on the structural studies of the active site inhibitors of Plm. We compare the binding mode of different classes of inhibitors and comment on how it relates to their efficacy, as well as possible future developments.
Taxonomic research survey on vector controlled induction motor drives
Authors: Tripathi Saurabh Mani , Vaish Rachna
Published: March 2019

The increased demand of induction machines in industries motivated the researchers to carry out their research on induction motor (IM) drives with a clear focus to achieve the wide range consistent control of speed and torque, as well as the stable operation of the IM drives. Vector control has become the industrial standard for the IM drive since scalar control being inadequate to provide precise and wide range speed control. Also, the steady‐state and dynamic performances of the IM drive employing vector control have been observed better. In this study, intense analysis has been done on the methods available to implement vector control with their features, merits and demerits. Besides, the research trends and current status of researches have also been explored via the taxonomical listing of relevant research literature which, in the author's belief, would guide the researchers working in this area in finding out relevant references for their works.
Obstacle information aided target tracking algorithms for angle‐only tracking of a highly maneuverable target in three dimensions
Authors: Kim Jonghoek
Published: March 2019

This study considers the angle‐only target tracking problem, which is to estimate the target information (position and velocity) based on both the azimuth and the elevation angle of the target. Incorporating obstacle information into maneuvering target tracking algorithms can produce a better performance when the target's maneuver is caused by avoiding collision with obstacles. Incorporating obstacle information, the target tracking algorithms are developed to track a highly maneuverable target in three dimensions. This study demonstrates the effectiveness of the proposed obstacle information aided tracking algorithms using simulations.
Magnetic braking of supermassive stars through winds
Authors: Haemmerlé L. , Meynet G.
Published: March 2019

Context. Supermassive stars (SMSs) are candidates for being progenitors of supermassive quasars at high redshifts. However, their formation process requires strong mechanisms that would be able to extract the angular momentum of the gas that the SMSs accrete.

Aims. We investigate under which conditions the magnetic coupling between an accreting SMS and its winds can remove enough angular momentum for accretion to proceed from a Keplerian disc.

Methods. We numerically computed the rotational properties of accreting SMSs that rotate at the ΩΓ-limit and estimated the magnetic field that is required to maintain the rotation velocity at this limit using prescriptions from magnetohydrodynamical simulations of stellar winds.

Results. We find that a magnetic field of 10 kG at the stellar surface is required to satisfy the constraints on stellar rotation from the ΩΓ-limit.

Conclusions. Magnetic coupling between the envelope of SMSs and their winds could allow for SMS formation by accretion from a Keplerian disc, provided the magnetic field is at the upper end of present-day observed stellar fields. Such fields are consistent with primordial origins.
Oscillations in the Sun with SONG: Setting the scale for asteroseismic investigations
Authors: Fredslund Andersen M. , Pallé P. , Jessen-Hansen J. , Wang K. , Grundahl F. , Bedding T. R. , Roca Cortes T. , Yu J. , Mathur S. , Gacia R. A. , Arentoft T. , Régulo C. , Tronsgaard R. , Kjeldsen H. , Christensen-Dalsgaard J.
Published: March 2019

Context. We present the first high-cadence multiwavelength radial-velocity observations of the Sun-as-a-star, carried out during 57 consecutive days using the stellar échelle spectrograph at the Hertzsprung SONG Telescope operating at the Teide Observatory.

Aims. Our aim was to produce a high-quality data set and reference values for the global helioseismic parameters νmax, ⊙ and Δν⊙ of the solar p-modes using the SONG instrument. The obtained data set or the inferred values should then be used when the scaling relations are applied to other stars showing solar-like oscillations observed with SONG or similar instruments.

Methods. We used different approaches to analyse the power spectrum of the time series to determine νmax, ⊙: simple Gaussian fitting and heavy smoothing of the power spectrum. We determined Δν⊙ using the method of autocorrelation of the power spectrum. The amplitude per radial mode was determined using the method described in Kjeldsen et al. (2008, ApJ, 682, 1370).

Results. We found the following values for the solar oscillations using the SONG spectrograph: νmax, ⊙ = 3141 ± 12 μHz, Δν⊙ = 134.98 ± 0.04 μHz, and an average amplitude of the strongest radial modes of 16.6 ± 0.4 cm s−1. These values are consistent with previous measurements with other techniques.
Therapie der Hypercholesterinämie in der Primärprävention
Authors: Sanin Veronika , Koenig Wolfgang
Published: March 2019

Atherosclerotic cardiovascular disease is the leading cause of premature mortality and morbidity worldwide. Dyslipidemia is a commonly encountered clinical condition and is an important determinant of cardiovascular disease. The causality of plasma low-density lipoprotein-cholesterol (LDL-C) in the pathophysiology of cardiovascular disease has been established beyond any reasonable doubt. In this context, individual risk estimation, the determination of target values and lipid-lowering strategies represent an essential part and a challenge in the daily clinical practice to prevent cardiovascular events. Statins are recommended as first-line therapy for patients with hypercholesterolemia in secondary prevention. Controversies remain in the context of primary prevention, however, as to which kind of subjects to treat, the magnitude of the benefit, and potential harm. This article gives a brief overview of the current evidence, guideline recommendations and strategies for lowering of LDL-C in the primary prevention of cardiovascular disease.
Vascular Adaptation to Indoor Cycling Exercise in Premenopausal Women
Authors: Bjarnegård Niclas , Hedman Kristofer , Länne Toste
Published: March 2019

The early vascular adaptation to indoor cycling, a popular activity at many fitness centres, is incompletely evaluated. Forty two healthy women (21–45 years) underwent measurements of arterial wall properties and geometry as well as a maximal bicycle exercise test before and after a 3 months period during which 21 of the women joined indoor cycling classes at a gym 2–3 times per week, while 21 women served as time controls. Peak work load increased by in average 16% (p<0.001) and ascending aortic diameter by 4% (p<0.01) in the exercise group, while unchanged in control group. The exercise intervention had no significant influence on the local intima-media thickness, blood pressure or the pulse pressure wave configuration while the carotid artery distensibility (p<0.05) was higher after the intervention. There was a positive correlation between change in (Δ) peak work load and Δ-diameter of tubular ascending aorta (r=0.42, p<0.01) in the exercise group. In conclusion, after only 3 months of bicycle exercise training, signs of central arterial remodelling were seen in premenopausal women, which was associated to improvement in exercise capacity.
Fingeramputation nach Bagatellverletzung –
versicherungsrechtliche Aspekte in Deutschland und praktische
Herangehensweise
Authors: Wahl Uwe , Siemers Frank , Hofmann Gunther O. , Ernst Friedrich , Schröter Patrick
Published: March 2019

Die Begutachtung ist ein Bestandteil der ärztlichen Tätigkeit. Da die
Subspezialisierung in der Medizin stetig fortschreitet, sind die
Gutachterkollektive für spezielle gutachterliche Fragestellungen häufig klein.
Der ärztliche Gutachter hat Tatsachen im Vollbeweis und Zusammenhänge mit
hinreichender Wahrscheinlichkeit zu bewerten. In der Begutachtung für die
gesetzliche Unfallversicherung spielt in der Erörterung der Haftungsbegründung
die Frage nach Vorerkrankungen/Schadensanlage eine wesentliche Rolle.
Gelegenheitsursachen bzw. Bagatellverletzungen müssen erkannt werden, weil sich
daraus eine Versicherungsrelevanz ergibt.

Ein Versicherter mit einer akralen, nicht arteriosklerotischen
Durchblutungsstörung (Thrombangiitis obliterans) erlitt einen Arbeitsunfall mit
einem Haut-Weichteildefekt, in dessen Folge eine Fingeramputation erforderlich
wurde. Das Vorliegen einer Gelegenheitsursache konnte nach gefäßmedizinischer
Begutachtung widerlegt werden. Der handchirurgische Gutachter empfahl eine
Minderung der Erwerbsfähigkeit von 25 von 100. Der Unfallversicherungsträger
folgte der Entscheidung der ärztlichen Gutachter.
On the Court: A Comprehensive Analysis of Basketball Facial Trauma
Authors: Othman Sammy , Cohn Jason E. , McKinnon Brian
Published: March 2019

With basketball gradually becoming increasingly popular across the United States, it is necessary for health care providers to understand injuries associated with the sport. We aim to determine the incidence of basketball-related facial injuries and further describe their patterns with regard to age, mechanism of injury, and degree of injury. An analysis of emergency department visits under the National Electronic Injury Surveillance System was conducted from 2015 through 2017. Chi-squared testing (χ2) was performed to compare categorical variables. After a review of results, a total of 4,578 patients were included for analysis spanning a 3-year time period (2015-2017). Lacerations were the most common injury overall (57.9%). Nasal fractures were by far the most common fracture (76.1%), and elbows to the face and collisions with other players were the most common types of injury mechanisms (31 and 28.7%, respectively). Adolescents (aged 12-18 years) were the most frequently injured group (42.5%), although young adults (aged 19-34 years) were also frequently affected (30.1%). Basketball facial trauma remains a prominent issue. Our research, in correlation with previous research, shows that current precautions to injury are not widely observed or are ineffective to the extent of need for further reform. It thus becomes necessary to provide patient education and develop more practical methods for decreasing player injury.
Ultrasensitive and uniform surface-enhanced Raman scattering substrates for the methidathion detection
Authors: Lin Guanzhou , Zhu Jia , Wu Meizhang , Lu Peimin , Wu Wengang
Published: March 2019

In this paper, we proposed a rapid method of detecting Methidathion pesticides by surface enhanced Raman scattering (SERS). In the method, Ag nanoparticles (AgNPs) are synthesized by the modified Tollens technique and deposited on glass slides to become simple detection arrays for SERS detection. The AgNPs synthesis used in this research is environmentally friendly and does not produce harmful substances to the environment. Through measuring/investigating the SERS signals of Rhodamine 6G under different concentrations, the preparation process and process parameters of the detection substrate are determined. The Methidathion detection limit reaches 0.1 ppm based on the substrates. This work lays a foundation for preparation of large-scale SERS detection arrays in the future.
Giant non-volatile magnetoelectric effects via growth anisotropy in Co40Fe40B20 films on PMN-PT substrates
Authors: Wang J. , Pesquera D. , Mansell R. , van Dijken S. , Cowburn R. P. , Ghidini M. , Mathur N. D.
Published: March 2019

Uniaxial magnetic anisotropy was imposed on a CoFeB film by applying an in-plane magnetic field during growth. Electrically driven strain from a ferroelectric 0.68Pb(Mg1/3Nb2/3)O3-0.32PbTiO3 (011) substrate resulted in giant magnetoelectric effects, whose coupling constant peaked at a record value of ∼8.0 × 10−6 s m−1. These large magnetoelectric effects arose due to non-volatile 90° rotations of the magnetic easy axis, reflecting a competition between the fixed growth anisotropy and the voltage-controlled magnetoelastic anisotropy. In contrast to previous work, our non-volatile rotations did not require the assistance of an applied magnetic field or the setting of an in-plane substrate polarization prior to deposition.
Effects of subcavity in supersonic cavity flow
Authors: Panigrahi Chintan , Vaidyanathan Aravind , Nair Manoj T.
Published: March 2019

An experimental and numerical study is conducted on a rectangular open cavity with a length to depth ratio of 2 at Mach number 1.71 by placing a subcavity at different locations. The subcavity at the front wall has already been established as a passive control device experimentally. In addition, it has been observed that it can act as a passive resonator. However, in the current study, it is found that the location of the subcavity and its dimensions play a crucial role in determining the types of oscillations existing inside the cavity. Cavity models with a subcavity length to main cavity length of 0.2 (l/L = 0.20) were investigated by placing the subcavity at the front wall, aft wall, and simultaneously at both front and aft walls. High speed schlieren visualization revealed the presence of different shock features associated with the cavity flow field. Statistical techniques such as fast Fourier transform, spectrogram, coherence, and correlation are employed to analyze the unsteady pressure data. Numerical computations are carried out to validate the experimental results and also to explore the flow physics. The front wall subcavity acts as a passive control device with a maximum reduction of 34.1 dB in the sound pressure level for the most dominant tone, and there is also a notable reduction in the overall sound pressure level by 11.7 dB. In the case of front wall subcavity, the acoustic wave gets inclined as it interacts with the subcavity, thereby displacing the shear layer to form a dome-shaped structure. The aft wall subcavity acts as a passive resonator with distinct fluid-resonant oscillations and the respective modal frequencies differ widely from those predicted using Rossiter’s expression. The shear layer interacts with a recirculation region formed inside the subcavity at the aft wall, thereby mitigating the effect due to direct impingement of the shear layer on the aft wall. The subcavity at both walls acts as a passive suppression device with a reduction of 34.9 dB in the sound pressure level for the most dominant mode and also with a reduction of 14.5 dB in the overall sound pressure level.
PbSnSe/PbSrSe quantum well materials for thermophotovoltaic devices
Authors: Khodr Majed , Chakraburtty Manisha , McCann Patrick J.
Published: March 2019

Multiple quantum well (MQW) materials composed of Pb0.81Sn0.19Se wells and Pb0.80Sr0.20Se barriers with intersubband energy gaps of 343 meV and 450 meV were modeled for thermophotovoltaic (TPV) device performance. The effect of L-valley degeneracy removal in these (111)-oriented IV-VI semiconductor quantum wells was evaluated. Degeneracy splitting reduces the effective densities of states in both the valence and conduction bands. Thermally generated intrinsic charge carrier concentrations are smaller by a factor of three as compared to bulk materials with the same bandgap energies. A current-matched dual junction TPV cell made from these MQW materials in a generator with a 1215°C radiator is predicted to have a power density of 2.34 W/cm2, 49% better than the power density generated by a cell made from bulk materials with the same bandgap energies.
Core structure and secondary breakdown of an exploding wire in the current-pause regime
Authors: Romanova V. M. , Mingaleev A. R. , Ter-Oganesyan A. E. , Shelkovenko T. A. , Ivanenkov G. V. , Pikuz S. A.
Published: March 2019

The results of experiments with rapidly exploding thin conductors in the current-pause regime are presented. Copper wires 25 μm in diameter and 12 mm in length serve as loads for a GVP pulsed generator based on a low-inductance capacitor. The generator produces current pulses of up to 10 kA with dI/dt up to 50 A/ns. A 100–800-ns current-pause regime is obtained for charging voltages of 10–15 kV. The discharge channel structure is studied by shadow photography using 0.53-μm, 10-ns second-harmonic pulses from a Nd3+:YAG laser. In the experiments, three types of secondary breakdown are observed, with different symmetry types, different current-pause durations, and different dependences on the energy deposited into the wire during its resistive heating. All of these breakdown types develop inside a tubular core that is produced in the current-pause stage and that remains almost undamaged by the breakdown.
The role of UV photolysis and molecular transport in the generation of reactive species in a tissue model with a cold atmospheric pressure plasma jet
Authors: Ghimire Bhagirath , Szili Endre J. , Lamichhane Pradeep , Short Robert D. , Lim Jun Sup , Attri Pankaj , Masur Kai , Weltmann Klaus-Dieter , Hong Sung-Ha , Choi Eun Ha
Published: March 2019

Cold atmospheric pressure plasma jets (plasma) operated in ambient air provide a rich source of reactive oxygen and nitrogen species (RONS), which are known to influence biological processes important in disease. In the plasma treatment of diseased tissue such as subcutaneous cancer tumors, plasma RONS need to first traverse an interface between the plasma-skin surface and second be transported to millimeter depths in order to reach deep-seated diseased cells. However, the mechanisms in the plasma generation of RONS within soft tissues are not understood. In this study, we track the plasma jet delivery of RONS into a tissue model target and we delineate two processes: through target delivery of RONS generated (primarily) in the plasma jet and in situ RONS generation by UV photolysis within the target. We demonstrate that UV photolysis promotes the rapid generation of RONS in the tissue model target's surface after which the RONS are transported to millimeter depths via a slower molecular process. Our results imply that the flux of UV photons from plasma jets is important for delivering RONS through seemingly impenetrable barriers such as skin. The findings have implications not only in treatments of living tissues but also in the functionalization of soft hydrated biomaterials such as hydrogels and extracellular matrix derived tissue scaffolds.
Effects of magnetic nanoparticles on mixing in droplet-based microfluidics
Authors: Maleki Mohammad Amin , Soltani M. , Kashaninejad Navid , Nguyen Nam-Trung
Published: March 2019

High-throughput, rapid and homogeneous mixing of microdroplets in a small length scale such as that in a microchannel is of great importance for lab-on-a-chip applications. Various techniques for mixing enhancement in microfluidics have been extensively reported in the literature. One of these techniques is the mixing enhancement with magnetofluidics using ferrofluid, a liquid with dispersed magnetic nanoparticles. However, a systematic study exploring the mixing process of ferrofluid and its influencing parameters is lacking. This study numerically examines the effect of key parameters including magnetic field, mean velocity, and size of a microdroplet on the mixing process. A microfluidic double T-junction with droplets in merging regime is considered. One of the dispersed phases is a ferrofluid containing paramagnetic nanoparticles, while the other carried neutral species. Under an applied magnetic field, the ferrofluid experiences a magnetic force that in turn induces a secondary bulk flow called magnetoconvection. The combination of the induced magnetoconvection and shear-driven circulating flow within a moving droplet improves the mixing efficiency remarkably. Mixing enhancement is maximized for a specific ratio between the magnetic force and the shear force. The dominance of either force would deteriorate the mixing performance. On the other hand, using a magnetic force and a shear force with comparable order of magnitude leads to an effective manipulation of vortices inside the droplet and subsequently causes an optimized particle distribution over the entire droplet. Furthermore, the smaller the droplets, the better the mixing.
Assessing aquatic ecosystem health through the analysis of plankton biodiversity
Authors: Shao N. F. , Yang S. T. , Sun Y. , Gai Y. , Zhao C. S. , Wang F. , Yin X. , Dong B.
Published: March 2019

Healthy plankton communities are the foundation of many freshwater food webs. Their biodiversity is often used to directly reflect the health of the rivers. Globally, river ecosystem restoration is a critical issue and many freshwater ecosystems, especially in cities, are degraded because of intensive human activities. This is true for Jinan, China’s first pilot city for the Water Ecological Civilisation Project. The outcomes of aquatic ecosystem restoration in the city will directly affect the success or failure of the construction of aquatic ecological civilisations across the entire country; therefore, there is an urgent need for research on the assessment of river health in Jinan based on plankton biodiversity. As such, this study gathered data on the distribution of plankton (phytoplankton and zooplankton) in Jinan by collecting three sets of samples from 59 aquatic ecosystem monitoring stations in spring, summer and autumn of 2015. In all, 104 species of phytoplankton and 56 species of zooplankton were identified. Diatoms, Chlorophyta, and Cyanophyta accounted for 50, 31 and 15% respectively of phytoplankton, and rotifers, Protozoa and cladocerans accounted for 39, 31 and 17% respectively of zooplankton. We constructed a plankton health assessment model based on the Shannon–Wiener diversity index for analysis of the temporal and spatial distribution. According to the overall health distribution diagram, spatially health status was significantly better in north and south Jinan than in the city centre; temporally, spring water ecosystem health was better than in summer and autumn. These conclusions provide a theoretical basis and direction for the restoration of aquatic ecosystems in Jinan, and the methods used in this study can serve as a reference for aquatic ecosystem evaluation in developing countries.
Physical immobilization of particles inspired by pollination
Authors: Santos Lúcia F. , Silva A. Sofia , Correia Clara R. , Mano João F.
Published: March 2019

Significance

Honey bees present a peculiar hairy structure that covers the surface of their body, which is able to transport large quantities of pollen particles for pollination purposes. Inspired by this natural phenomenon and to overcome the current problems associated with drug patches with passive delivery, we propose the concept of a micropatterned surface featuring micropillars with defined spacing and height to mimic the hair of bees for the entrapment of a large quantity of microparticles. We believe that such substrates could be extended to diverse applications that require reversible immobilization of solid particulate objects. In particular, high drug content is required for obtaining more effective drug patches, enabling more sustained and targeted release of the drug.
Dynamics of bed bug infestations and control under disclosure policies
Authors: Xie Sherrie , Hill Alison L. , Rehmann Chris R. , Levy Michael Z.
Published: March 2019

Bed bugs have reemerged in the United States and worldwide over recent decades, presenting a major challenge to both public health practitioners and housing authorities. A number of municipalities have proposed or initiated policies to stem the bed bug epidemic, but little guidance is available to evaluate them. One contentious policy is disclosure, whereby landlords are obligated to notify potential tenants of current or prior bed bug infestations. Aimed to protect tenants from leasing an infested rental unit, disclosure also creates a kind of quarantine, partially and temporarily removing infested units from the market. Here, we develop a mathematical model for the spread of bed bugs in a generalized rental market, calibrate it to parameters of bed bug dispersion and housing turnover, and use it to evaluate the costs and benefits of disclosure policies to landlords. We find disclosure to be an effective control policy to curb infestation prevalence. Over the short term (within 5 years), disclosure policies result in modest increases in cost to landlords, while over the long term, reductions of infestation prevalence lead, on average, to savings. These results are insensitive to different assumptions regarding the prevalence of infestation, rate of introduction of bed bugs from other municipalities, and the strength of the quarantine effect created by disclosure. Beyond its application to bed bugs, our model offers a framework to evaluate policies to curtail the spread of household pests and is appropriate for systems in which spillover effects result in highly nonlinear cost–benefit relationships.
Transcranial alternating current stimulation entrains single-neuron activity in the primate brain
Authors: Krause Matthew R. , Vieira Pedro G. , Csorba Bennett A. , Pilly Praveen K. , Pack Christopher C.
Published: March 2019

Significance

Neurostimulation is a common therapy for a variety of neurological disorders, but the most effective stimulation approaches are often highly invasive, requiring electrodes to be implanted deep within brain structures like the hippocampus and basal ganglia. Here, we show that transcranial electrical stimulation (tES), a neuromodulatory technique that uses electrodes placed outside the scalp, can also affect patterns of neural activity in these areas. We find that tES can reliably control the timing, but not the rate, of spikes in individual neurons. Because changes in spike timing are thought to play a key role in many brain functions, the data shown here suggest that tES may be a valuable tool for clinical and fundamental studies of the human brain.
RIP1 kinase inhibitor halts the progression of an immune-induced demyelination disease at the stage of monocyte elevation
Authors: Zhang Sitao , Su Yaning , Ying Zhengxin , Guo Dejia , Pan Chenjie , Guo Jia , Zou Ziye , Wang Lei , Zhang Ze , Jiang Zhaodi , Zhang Zhiyuan , Wang Xiaodong
Published: March 2019

Significance

Myelin sheaths insulate the neuronal axons and speed the transmission of electrical impulses. The demyelination process occurs in many human diseases, including multiple sclerosis (MS). Using multiple mouse models of MS, we demonstrate in this study the role of MLKL, a protein known to function in a form of regulated necrosis (necroptosis), in facilitating demyelination in a necroptosis-independent manner in the central nervous system. An RIP1 kinase inhibitor was shown to block the progression of MS in an immune-induced demyelination model, and it does so at the stage after antibody generation but before breakdown of the blood–brain barrier, at a likely step of monocyte elevation. These findings provide insights into the demyelination process and potential new therapeutic agents for MS.
Patterns of genome-wide allele-specific expression in hybrid rice and the implications on the genetic basis of heterosis
Authors: Shao Lin , Xing Feng , Xu Conghao , Zhang Qinghua , Che Jian , Wang Xianmeng , Song Jiaming , Li Xianghua , Xiao Jinghua , Chen Ling-Ling , Ouyang Yidan , Zhang Qifa
Published: March 2019

Significance

Utilization of heterosis has greatly increased productivity of many crops globally. Allele-specific expression (ASE) has been suggested as a mechanism for causing heterosis. We performed a genome-wide analysis of ASE in three tissues of an elite rice hybrid grown under four conditions. The analysis identified 3,270 genes showing various patterns of ASE in response to developmental and environmental cues, which provides a glimpse of the ASE landscape in the hybrid genome. We showed that the ASE patterns may have distinct implications in the genetic basis of heterosis, especially in light of the classical dominance and overdominance hypotheses. The genes showing ASE provide the candidates for future studies of the genetic and molecular mechanism of heterosis.
AAV
cis
-regulatory sequences are correlated with ocular toxicity
Authors: Xiong Wenjun , Wu David M. , Xue Yunlu , Wang Sean K. , Chung Michelle J. , Ji Xuke , Rana Parimal , Zhao Sophia R. , Mai Shuyi , Cepko Constance L.
Published: March 2019

Significance

Adeno-associated viral (AAV) gene therapy is becoming an important therapeutic modality, especially for ocular diseases, due to its efficiency of gene delivery and relative lack of pathogenicity. However, AAV sometimes can cause inflammation and toxicity. We explored such effects using injections into the mouse eye. We found a strong correlation of toxicity and inflammation with the use of promoters that were broadly active, or specifically active in the retinal pigment epithelium. AAVs with photoreceptor-specific promoters were found to be nontoxic at all doses tested. These studies reveal that safer vectors can be designed if assays for relevant and specific cell types are developed and tested with a range of vectors with different genomic elements.
Renal control of disease tolerance to malaria
Authors: Ramos Susana , Carlos Ana Rita , Sundaram Balamurugan , Jeney Viktoria , Ribeiro Ana , Gozzelino Raffaella , Bank Claudia , Gjini Erida , Braza Faouzi , Martins Rui , Ademolue Temitope Wilson , Blankenhaus Birte , Gouveia Zélia , Faísca Pedro , Trujillo Damian , Cardoso Sílvia , Rebelo Sofia , del Barrio Laura , Zarjou Abolfazl , Bolisetty Subhashini , Agarwal Anupam , Soares Miguel P.
Published: March 2019

Significance

Malaria, the disease caused by
Plasmodium
spp. infection, remains a major global cause of morbidity and mortality, claiming the lives of over ∼4.5 × 10
5
individuals per year. Paradoxically, however, up to 98% of infected individuals survive the infection, establishing disease tolerance to malaria. We found that this host defense strategy, which does not target
Plasmodium
directly, relies on the capacity of renal proximal tubule epithelial cells to detoxify labile heme, a pathologic by-product of hemolysis that accumulates in plasma and urine during the blood stage of infection. This defense strategy prevents the onset of acute kidney injury, a clinical hallmark of severe malaria.
Time-dependent manufacturing processes lead to a new class of inverse problems
Authors: Axinte Dragos , Billingham John
Published: March 2019

The control of time-dependent, energy beam manufacturing processes has been achieved in the past through trial-and-error approaches. We identify key research gaps and generic challenges related to inverse problems for these processes that require a multidisciplinary problem-solving approach to tackle them. The generic problems that we identify have a wide range of applications in the algorithmic control of modern manufacturing processes.
Tetraspanin‐decorated extracellular vesicle‐mimetics as a novel adaptable reference material
Authors: Lozano‐Andrés Estefanía , Libregts Sten F. , Toribio Victor , Royo Félix , Morales Sara , López‐Martín Soraya , Valés‐Gómez Mar , Reyburn Hugh T. , Falcón‐Pérez Juan Manuel , Wauben Marca H. , Soto Manuel , Yáñez‐Mó María
Published: March 2019

Features like small size, low refractive index and polydispersity pose challenges to the currently available detection methods for Extracellular Vesicles (EVs). In addition, the lack of appropriate standards to set up the experimental conditions makes it difficult to compare analyses obtained by different technical approaches. By modifying synthetic nanovesicles with recombinant antigenic regions of EV‐enriched tetraspanins, we aimed to construct an EV‐mimetic that can be used as a suitable standard for EV analyses.

To this end, the sequences of the large extracellular loops of the tetraspanins CD9, CD63 and CD81 were tagged with a target sequence for the biotin ligase BirA, and co‐transformed with a BirA expression plasmid into Escherichia coli. GST fusion proteins were then isolated by affinity chromatography and released using thrombin. Biotinylated recombinant tetraspanin‐loops were then coupled to (strept)avidin‐coated synthetic nanovesicles and analysed and characterised by Dot‐blot, Western‐blot, Nanoparticle Tracking Analysis, Flow Cytometry and Transmission Electron Microscopy.

With this method, we were able to efficiently produce tetraspanin‐domain decorated nanovesicles that share biophysical properties with natural EVs, can be detected using specific antibodies against common EV markers such as tetraspanins, and can be used as robust reference materials for detection techniques that are often used in the EV field.
When Conflict Cannot be Avoided: Relative Contributions of Early Selection and Frontal Executive Control in Mitigating Stroop Conflict
Authors: Itthipuripat Sirawaj , Deering Sean , Serences John T
Published: March 2019

When viewing familiar stimuli (e.g., common words), processing is highly automatized such that it can interfere with the processing of incompatible sensory information. At least two mechanisms may help mitigate this interference. Early selection accounts posit that attentional processes filter out distracting sensory information to avoid conflict. Alternatively, late selection accounts hold that all sensory inputs receive full semantic analysis and that frontal executive mechanisms are recruited to resolve conflict. To test how these mechanisms operate to overcome conflict induced by highly automatized processing, we developed a novel version of the color-word Stroop task, where targets and distractors were simultaneously flickered at different frequencies. We measured the quality of early sensory processing by assessing the amplitude of steady-state visually evoked potentials (SSVEPs) elicited by targets and distractors. We also indexed frontal executive processes by assessing changes in frontal theta oscillations induced by color-word incongruency. We found that target- and distractor-related SSVEPs were not modulated by changes in the level of conflict whereas frontal theta activity increased on high compared to low conflict trials. These results suggest that frontal executive processes play a more dominant role in mitigating cognitive interference driven by the automatic tendency to process highly familiar stimuli.
Dynamic Causal Modeling of the Relationship between Cognition and Theta–alpha Oscillations in Adults with Down Syndrome
Authors: Hamburg Sarah , Rosch Richard , Startin Carla Marie , Friston Karl John , Strydom André
Published: March 2019

Individuals with Down syndrome (DS) show high inter-subject variability in cognitive ability and have an ultra-high risk of developing dementia (90% lifetime prevalence). Elucidating factors underlying variability in cognitive function can inform us about intellectual disability (ID) and may improve our understanding of factors associated with later cognitive decline. Increased neuronal inhibition has been posited to contribute to ID in DS. Combining electroencephalography (EEG) with dynamic causal modeling (DCM) provides a non-invasive method for investigating excitatory/inhibitory mechanisms. Resting-state EEG recordings were obtained from 36 adults with DS with no evidence of cognitive decline. Theta–alpha activity (4–13 Hz) was characterized in relation to general cognitive ability (raw Kaufmann’s Brief Intelligence Test second Edition (KBIT-2) score). Higher KBIT-2 was associated with higher frontal alpha peak amplitude and higher theta–alpha band power across distributed regions. Modeling this association with DCM revealed intrinsic self-inhibition was the key network parameter underlying observed differences in 4–13 Hz power in relation to KBIT-2 and age. In particular, intrinsic self-inhibition in right V1 was negatively correlated with KBIT-2. Results suggest intrinsic self-inhibition within the alpha network is associated with individual differences in cognitive ability in adults with DS, and may provide a potential therapeutic target for cognitive enhancement.
Incident anaemia in older adults with heart failure: rate, aetiology, and association with outcomes
Authors: Ambrosy Andrew P , Gurwitz Jerry H , Tabada Grace H , Artz Andrew , Schrier Stanley , Rao Sunil V , Barnhart Huiman X , Reynolds Kristi , Smith David H , Peterson Pamela N , Sung Sue Hee , Cohen Harvey Jay , Go Alan S ,   RBC HEART Investigators
Published: March 2019

Aims

Limited data exist on the epidemiology, evaluation, and prognosis of otherwise unexplained anaemia of the elderly in heart failure (HF). Thus, we aimed to determine the incidence of anaemia, to characterize diagnostic testing patterns for potentially reversible causes of anaemia, and to evaluate the independent association between incident anaemia and long-term morbidity and mortality.

Methods and results

Within the Cardiovascular Research Network (CVRN), we identified adults age ≥65 years with diagnosed HF between 2005 and 2012 and no anaemia at entry. Incident anaemia was defined using World Health Organization (WHO) haemoglobin thresholds (<13.0 g/dL in men; <12.0 g/dL in women). All-cause death and hospitalizations for HF and any cause were identified from electronic health records. Among 38 826 older HF patients, 22 163 (57.1%) developed incident anaemia over a median (interquartile range) follow-up of 2.9 (1.2–5.6) years. The crude rate [95% confidence interval (CI)] per 100 person-years of incident anaemia was 26.4 (95% CI 26.0–26.7) and was higher for preserved ejection fraction (EF) [29.2 (95% CI 28.6–29.8)] compared with borderline EF [26.5 (95% CI 25.4–27.7)] or reduced EF [26.6 (95% CI 25.8–27.4)]. Iron indices, vitamin B12 level, and thyroid testing were performed in 20.9%, 14.9%, and 40.2% of patients, respectively. Reduced iron stores, vitamin B12 deficiency, and/or hypothyroidism were present in 29.7%, 3.2%, and 18.6% of tested patients, respectively. In multivariable analyses, incident anaemia was associated with excess mortality [hazard ratio (HR) 2.14, 95% CI 2.07–2.22] as well as hospitalization for HF (HR 1.80, 95% CI 1.72–1.88) and any cause (HR 1.77, 95% CI 1.72–1.83).

Conclusion

Among older adults with HF, incident anaemia is common and independently associated with substantially increased risks of morbidity and mortality. Additional research is necessary to clarify the value of routine evaluation and treatment of potentially reversible causes of anaemia.
Accounting for missing data in statistical analyses: multiple imputation is not always the answer
Authors: Hughes Rachael A , Heron Jon , Sterne Jonathan A C , Tilling Kate
Published: March 2019

Background

Missing data are unavoidable in epidemiological research, potentially leading to bias and loss of precision. Multiple imputation (MI) is widely advocated as an improvement over complete case analysis (CCA). However, contrary to widespread belief, CCA is preferable to MI in some situations.

Methods

We provide guidance on choice of analysis when data are incomplete. Using causal diagrams to depict missingness mechanisms, we describe when CCA will not be biased by missing data and compare MI and CCA, with respect to bias and efficiency, in a range of missing data situations. We illustrate selection of an appropriate method in practice.

Results

For most regression models, CCA gives unbiased results when the chance of being a complete case does not depend on the outcome after taking the covariates into consideration, which includes situations where data are missing not at random. Consequently, there are situations in which CCA analyses are unbiased while MI analyses, assuming missing at random (MAR), are biased. By contrast MI, unlike CCA, is valid for all MAR situations and has the potential to use information contained in the incomplete cases and auxiliary variables to reduce bias and/or improve precision. For this reason, MI was preferred over CCA in our real data example.

Conclusions

Choice of method for dealing with missing data is crucial for validity of conclusions, and should be based on careful consideration of the reasons for the missing data, missing data patterns and the availability of auxiliary information.
Impact of Treatment Interruption on HIV Reservoirs and Lymphocyte Subsets in Individuals Who Initiated Antiretroviral Therapy During the Early Phase of Infection
Authors: Huiting Erin D , Gittens Kathleen , Justement J Shawn , Shi Victoria , Blazkova Jana , Benko Erika , Kovacs Colin , Wender Paul A , Moir Susan , Sneller Michael C , Fauci Anthony S , Chun Tae-Wook
Published: March 2019

Therapeutic strategies for achieving sustained virologic remission are being explored in human immunodeficiency virus (HIV)–infected individuals who began antiretroviral therapy (ART) during the early phase of infection. In the evaluation of such therapies, clinical protocols should include analytical treatment interruption (ATI); however, the immunologic and virologic impact of ATI in individuals who initiated ART early has not been fully delineated. We demonstrate that ATI causes neither expansion of HIV reservoirs nor immunologic abnormalities following reinitiation of ART. Our findings support the use of ATI to determine whether sustained virologic remission has been achieved in clinical trials of individuals who initiated ART early during HIV infection.
The Happiness of Refugees in the United States: Evidence from Utica, NY
Authors: Hagstrom Paul , Pereira Javier , Wu Stephen
Published: March 2019

We study determinants of happiness—a subjective measure of wellbeing—for roughly 600 refugees from over 30 different countries currently residing in Utica, NY. For refugees from the former Soviet Union, the former Yugoslavia and Southeast Asia, having many friends from one’s own ethnic group is strongly positively correlated with happiness in Utica, while, for African refugees, English-language skills are a strong determinant of happiness with living in their local area. Income is only modestly related to the happiness of refugees in general, though the results vary by group. We do find strong evidence that those with children are happier than those without. These last two results represent departures from much of the broader literature on happiness in the United States.
“Choose Physical Therapy” for Neonatal Abstinence Syndrome: Clinical Management for Infants Affected by the Opioid Crisis
Authors: McCarty Dana B , Peat Jennifer R , O'Donnell Shannon , Graham Elisabeth , Malcolm William F
Published: March 2019

In response to the opioid crisis, the American Physical Therapy Association has strongly advocated for physical therapy as a safe alternative to pharmacological pain management through the “#ChoosePT” campaign and the dedication of a PTJ special issue to the nonpharmacological management of pain. Physical therapists not only play an important role in the rehabilitation of the nearly 2 million adolescents and adults addicted to prescription opioids but also provide care to infants born to mothers with various drug addictions. This Perspective article explores the incidence, pathophysiology, and risk factors for neonatal abstinence syndrome and describes the clinical presentations of withdrawal and neurotoxicity in infants. Discipline-specific recommendations for the physical therapist examination and plan of care, including pharmacological management considerations, are outlined. Nonpharmacological management, including supportive care, feeding, parent education, social aspects of care, and follow-up services, are discussed from a physical therapy perspective. Finally, this article reviews developmental outcomes in infants with neonatal abstinence syndrome and reflects on challenges and future directions of research in this area.
Post-traumatic stress disorder among Syrian adolescent refugees in Jordan
Authors: Beni Yonis Othman , Khader Yousef , Jarboua Alaa , Al-Bsoul Maariyha Majed , Al-Akour Nemeh , Alfaqih Mahmoud A , Khatatbeh Moawiah M , Amarneh Basil
Published: March 2019

Objective

Studies among Syrian refugees in Turkey, Lebanon and Germany showed high prevalence rates of post-traumatic stress disorder (PTSD). However, data on PTSD among Syrian adolescent refugees in Jordan are scarce. Therefore, this study aimed to assess the prevalence and severity of PTSD, and its associated factors among Syrian schoolchildren refugees resettled in Jordan.

Methods

This cross-sectional study was conducted among Syrian schoolchildren refugees aged 12–18 years. A stratified cluster random sample was used to select male and female schoolchildren in four cities with the highest density of Syrian refugees. The Child Post-Traumatic Stress Disorder Symptom Scale (CPSS) was used to measure PTSD severity.

Results

The prevalence of moderate to severe PTSD among Syrian schoolchildren refugees in Jordan was 31%. This prevalence was higher in female adolescents compared with males (P = 0.001), and in children who had one or both parents died compared with those whose parents were living together (P = 0.006). The prevalence was lower in those living in Sahab city compared with Mafraq city (P = 0.006).

Conclusion

PTSD is a common condition among Syrian adolescent refugees, especially among females, and those who lost one or both parents. Screening for PTSD and other mental health illnesses is highly recommended. Gender-specific psychosocial support and educational programs should be implemented.