bluuebunny/crossref_metadata_2025 huggingface dataset:
PLATELET-DEPENDENT ACTIVATION AND AMPLIFICATION OF THE POLYMORPHONUCLEAR LEUKOCYTES LYSOSOMAL ENZYME RELEASE
Authors: Maschio A Del , Corvazier E , Maillet F , Kazatchkine M , Maclouf J
Published: August 2018

The degranulatlon of human PMNs by opsonlsed zymosan (OpZ) was studied In the presence or In the absence of platelet alone or after stimulation by thrombin. Evidence Is presented that the presence of platelets Increased the extent of the liberation of lysozyme from PMNs stimulated by OpZ with a maximal intensity when they were stimulated by thrombin. The extent of the amplification was higher when the PMNs trigger was lower (i.e. 0.5 x 108 particles/ml as compared to 3.0 x 108 particles). This effect was dependent on the platelet concentration (from 10-80 platelets/PMN). Platelets stimulated by thrombin could alsoactivate the resting PMNs with a maximum obtained ata thrombin concentration of 0.1 U/ml, corresponding to the maximal release by these cells of products stored In their granules. However, the substitution ofplatelet suspensions by the released products found In their supernatant after stimulation by thrombin, resulted In a comparable stimulation only at platelet concentrations above the ones for coincubation experiments. These findings suggest that the presence of platelets themselves or In combination with their released products are responsible for this amplification. The use of zymosan alone or coated with IgG, C3b1, C3b or OpZ did not reveal any specificity of the Inducer for this amplification suggesting that platelets and/or platelet products acted by enhancing acommon step of PMNs activation Independent of the stimulus carried by the particles. Additionally, It could be noted that the maximal effect of the amplification by platelets occurred when the level of stimulation of the PMNs alone was the weakest.
EFFECT OF ATRIAL NATRIURETIC POLYPEPTIDES ON PLATELET FUNCTION
Authors: Asaji T , Murakami E , Takekoshi N , Matsui S , Imaoka T
Published: August 2018

Atrial natriuretic polypeptides (ANP) have been shown to possess a potent diuretic and natriuretic activity, and medicated to patients with heart insufficiency as a drug to be mediated by cGMPaccumulation in glomeruli. A existence of receptors for ANP have recently beenreported in human platelet. But, whether ANP has a direct effect on platelet function remains to be known.

Single stimulation of ANP in any concentration did not induce aggregation in neither platelet rich plasma, nor washed platelets. Also no effect of pretreatment with ANP was observed against aggregation triggered by known mediators of platelet activation (Thrombin, ADP, Epinephrine, Collagen) using platelet rich plasma and washed platelets.

Therefore, biochemical parameters such as cyclic nucleotides (cAMP, cGMP), phosphatidylinositol hydrolysis and protein phosphorylation, leading to the early stage of platelet activation were examined to investigate the effect of ANP in receptor linked transducing mechanism. Neither cyclic nucleotides accumulation nor [32 P] phosphatidic acid production were detected in platelets treated with ANP. ANP caused a small increase of 32P incorporation into M 30K protein, but no change on the level of phosphorylation of 47K, 20K protein (Imaoka, T. and Haslam, R.J., J.Biol.Chem.258,11404, 1983) was observed.

These results clearly suggested thatANP binding with membrane receptor was not linked with adenylate cyclase, ganulate cyclase and phosphatidylinositol phosphate turnover in human platelet, maybe because of too few numbers of ANP receptor. Mechanism of 30K protein phosphorylation and Ca++ mobilization are important subjects for future study, (supported by MESC of Japan)
HEREDITARY PLATELET FUNCTION DISORDERS IN JAPAN
Authors: Yasunaga K
Published: August 2018

Nationwide surveys of hereditary platelet function disorders in Japan were carried out in 1976, 1981, and 1986. Information on 271 cases received in the 1986 survey was analyzed with that for 103 other cases reported in earlier surveys but not in 1986, making a total of 374 cases. The mortality rate was 6.8% of 162 cases in 1976, 6.6% of 213 cases in 1981, and 5.9% of 374 cases in 1986. Bleeding symptoms appeared at age 12 years in 56.8% of patients and the most common were epistaxis and purpura. Of the 295 cases 49.5% were isolated cases, 20.3% had siblings with confirmed bleeding tendencies, and 30.2% had other kin with bleeding tendencies, suggestings autosomal tnansmission. Consanguineous marriage was reported by 11.9% of patients.

Of the 374 cases in 1986, 59.4% were thrombasthenia (TA), 11.5% Bernard-Soulier symdrome (BSS), 22.5% release abnormalities (PRA), 1.3% other, and 5.3% unclassified. Of the 84 cases of PRA, 60 were storage pool deficiency, 18 release mechanism abnormalities, and 6 undecided between the two types. The resultsof laboratory tests were as follows
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PLATELET DYSFUNCTION INDUCED BY TETRAHYDROCANNABINOL
Authors: Patel R , Bick R
Published: August 2018

Many drugs and other agents have been reported to induce platelet dysfunction and clinical bleedability; however, tetrahydrocannabinol (marijuana) has thus far not been reported. The patient herein described is a 28-year-old Caucasian female who wasreferred for evaluation of easy and spontaneous bruising. On history, the patient related that for a three-month period she had been developing spontaneous ecchymoses of the extremities and torso. She denied any medication other than heavy marijuana use. Hemostasis evaluation revealed her to have a normal prothrombin time, partial thromboplastin time (PTT), Factor VIII coagulant activity (Factor VIII:C), Factor VIII related antigen (Factor VIII:RAg), and ristocetincofactor activity. Platelet aggregation was performed which revealed abnormal aggregation to epinephrine, adenosine diphosphate (ADP) and abnormal release but normal aggregation toristocetin. She was asked to refrainfrom marijuana and was reaggregated revealing normal aggregation and release to epinephrine, ADP, collagen and arachidonic acid; however, ADP release induced by ristocetin remainedmoderately abnormal, even though aggregation was normal. In addition, with cessation of marijuana use, her clinical bruising abated.

Following this, she again indulged in marijuana and she was reaggregated, revealing delayed aggregation and release to epinephrine with abnormal aggregation to ADP. Additionally, ristocetin release and adenosine triphosphate (ATP) release remained abnormal but aggregation remained normal and arachidonic acid aggregationremained normal.

In summary, we herein describe a young female who demonstrated aggregation abnormalities and clinically significant spontaneous bruising during periods of using marijuana; the defect disappeared upon cessation of marijuana and reappeared upon resumption of marijuana use. The defect atpresent appears to be that of a membrane-type defect with no evidence that marijuana interferes with the prostaglandin pathway.
PLATELET FUNCTION AND ENDOCRINE STRESS RESPONSE DURING EPIDURAL AND GENERAL ANAESTHESIA FOR MINOR SURGERY OF THE LOWER LIMBS
Authors: Nielsen T H , Nielsen H K , Husted S E , Husegaard H C , Hansen S L , Fieldborg N
Published: August 2018

Postoperative frequency of deep venous thrombosis(DVT) is high, reported to be 13-59$ after abdominalsurgery and as high as 73$ after total hip replacement. Epidural anaesthesia can reduce the frequency ofDVT and pulmonary embolism. Platelet aggregation (PA) is supposed to play an important role in formationof DVT. In a randomized study twenty patients admitted to transarthroscopic meniscectomy were allocated to epidural or general anaesthesia. All operations were carried out in blood less field using a thigh tourniquet. S-cortisol, thromboxane-B2 (TxB2) and PAwere measured before premedication, before Itart of the operation and finally before and lo min after exsufflation of the tourniquet. Aggregability was measured in platelet -rich plasma and expressed as the treshold concentration of collagen and ADP. S-cortisol and TxB2 were measured by RIA. Collagen induced TxB2-synthesis in platelet-rich plasma was significanthigher during general as compared with epidural anaesthesia (p<o.o5). Furthermore, s-cortisol significantly decreased in the epidural and increased in thegeneral anaesthesia group (p<o.o5). Treshold concentration of collagen and ADP did not differbetween the two groups, and removal of the thigh tourniquet did not influence any of the measured variables. It is concluded, thatthe adrenocortical system is activatedduring general and inhibited duringepidural anaesthesia. As a possible concequence the platelet function is enhanced during general anaesthesia, increasingthe risk of thromboembolic complications
MULTITHERAPY PRETREATMENT IMPROVES HEMODYNAMIC FUNCTION IN EXPERIMENTAL ENDOTOXEMIA
Authors: Pillgram-Larsen J , Ruud T E , Stadaas J O , Aasen A O
Published: August 2018

To evaluate the cardiopulmonary response to a newregimen of therapy in endotoxemia, ten pigs were infused with endotoxin 0.01 mg/kg over three hours. Five animals (treatment group) received therapy starting 30 min prior to endotoxin infusion consisting of repeated doses of protease inhibitor concentrates (C1esterase inhibitor 2000 IU, antithrombin III 500 IU,aprotinin 2 mill KIU), methylprednisolone 100 mg/kg, antihistamine(promethazin 1 mg/kg), a serotonin antagonist (ketanserine 2 mg/kg) and an opiate antagonist (naloxone 0.06 mg/kg). Five animals were untreated.Eight animals (control group) were anaesthetized and observed without endotoxin or treatment. The observation time was five hours. Two untreated animals receiving endotoxin died. Endotoxin caused a decrease in cardiac function with decreased left ventricular stroke work (LVSW). Endotoxin resulted in a marked increase in pulmonary vascular resistance (PVR) and oxygenation was impaired. With multiherapy cardiac output increased. Systemic vascular resistence was decreased in the treatment group while it increased steadily in the untreated group. LVSW was significantlybetter maintained in the treated animals. Pulmonary vascular resistence was unaltered in the treatment group. Pulmonary gas exchange was not different between the endotoxin infused groups. Endotoxin infusion caused no metabolic changes in this short time modelas oxygen consumption was not different between the three groups. Overall cardiopulmonary function was improved in treated animals compared to both untreated endotoxin infused animals and controls as mixed venous oxygen saturation was higher in the treatment group.
Multitherapy has a protective effect on cardiopulmonary functions in experimental endotoxemia.
EFFECTS OF INTRAVENOUS ADMINISTRATIONOF A TISSUE-TYPE PLASMINOGEN ACTIVATOR (AK-124) IN ACUTE MYOCARDIAL INFARCTION, INCLUDING CHANGES IN BLOOD COAGULATION AND FIBRINOLYTIC ACTIVITY.- PRELIMINARY REPORT
Authors: Honda T , Aosaki M , Tanaka T , Aosaki M , Uchida T , Kimata S , Hirosawa K , Horikawa Y , Ishizuka S , Ohki K
Published: August 2018

We administered a tissue-type plasminogen activator (t-PA) intravenously to 10 patients with acute myocardial infarction (AMI), within 6 hours after the onset of symptoms, and then examined the state of reperfusion by coronary arterio graphy (CAG), and observed changes in blood coagulation and fibrinolytic activity to evaluate the drug effects. AK-124 (produced by Asahi Chemical Industry and Kowa Co., Ltd.in collaboration), a t-PA produced the by tissue cultureof normal human lung cells, was given in a dosage of48,000_576,000 A.K. units by intravenous infusionover 30_45 minutes. In 7 patients who received t-PA, areflow or improved flow was detected on CAG. In t-PAtreated patients, euglobulin lysis activity clearly increased, euglobulin lysis time clearly shortened, and D-dimer increased. After t-PA treatment, the levels of circulating fibrinogen and a2-plasmin inhibitor decreased by an average of 12%, and 14% of base-line values respectively, but plasminogen showed no detectable change. A hematoma at the site of the catheter insertion was observed in one patient. These observations suggest that t-PA has a higher specificity for fibrin bound plasminogen than for plasma plasminogen, and produces coronary thrombolysis without causing systemic fibrinolysis, at least with the above dosage.
Recent Developments in Clinical Terminologies — SNOMED CT, LOINC, and RxNorm
Authors: Bodenreider Oliver , Cornet Ronald , Vreeman Daniel
Published: August 2018

Objective: To discuss recent developments in clinical terminologies. SNOMED CT (Systematized Nomenclature of Medicine Clinical Terms) is the world's largest clinical terminology, developed by an international consortium. LOINC (Logical Observation Identifiers, Names, and Codes) is an international terminology widely used for clinical and laboratory observations. RxNorm is the standard drug terminology in the U.S.

Methods and results: We present a brief review of the history, current state, and future development of SNOMED CT, LOINC and RxNorm. We also analyze their similarities and differences, and outline areas for greater interoperability among them.

Conclusions: With different starting points, representation formalisms, funding sources, and evolutionary paths, SNOMED CT, LOINC, and RxNorm have evolved over the past few decades into three major clinical terminologies supporting key use cases in clinical practice. Despite their differences, partnerships have been created among their development teams to facilitate interoperability and minimize duplication of effort.
Algorithmen und Leitlinien zur Behandlung der akuten Depression
Authors: Adli M. , Bschor T. , Seemüller F.
Published: August 2018

Therapiealgorithmen stellen explizite und systematische Behandlungsprotokolle dar, welche standardisierte Handlungsanweisungen für therapeutische Entscheidungen beinhalten. Die wichtigsten nationalen und internationalen Leitlinien werden im Hinblick auf die Empfehlungen zur medikamentösen Akuttherapie der unipolaren depressiven Episode verglichen und Unterschiede sowie Gemeinsamkeiten herausgearbeitet. Von den meisten Leitlinien wird für die mittelschwere Depression eine Monotherapie mit einem Antidepressivum und bei einer psychotischen Depression die Kombination aus einem Antipsychotikum und einem Antidepressivum empfohlen. Bei initialer Non-Response empfiehlt die S3-Leitlinie, therapeutisches Drugmonitoring, Dosiserhöhung, Augmentation mit Lithium und Quetiapin oder eine Kombinationstherapie von TZA, SSRI und SNRI mit entweder Mianserin oder Mirtazapin. Bei den internationalen Leitlinien zeigt sich in diesem Fall die größte Übereinstimmung für eine Augmentation des initialen Antidepressivums mit einem Antipsychotikum der zweiten Generation.
Ketamin in der Behandlung depressiver Episoden
Authors: Deuschle M. , Gilles M.
Published: August 2018

Ketamin, ein hochaffiner nicht kompetitiver Antagonist am glutamatergen N-Methyl-D-Aspartat (NMDA-)Rezeptor zeigt potente und schnell wirksame antidepressive Effekte bei Patienten mit therapieresistenter unipolarer und bipolarer Depression. Dieser rasch einsetzende antidepressive Effekt konnte seit 2000 in vielen, wenn auch meist mit kleiner Fallzahl, randomisiert kontrollierten Studien gezeigt werden. Bis heute ist die Ketamingabe zur Behandlung depressiver Störungen eine Off-label-Behandlung. Behandlungsrichtlinien und -algorithmen im klinischen Umfeld sind ebenso wie mehr Forschung bezüglich der Beobachtung möglicher (nachteiliger) klinischer Langzeitwirkungen und Sicherheitsdaten von wiederholten Ketamingaben und -erhaltungstherapie nötig.
Uniform electric field enabled multi-needles electrospinning head based on trapezoid arrangement
Authors: Zhu Ziming , Xu Guojie , Chen Rouxi , Wang Zhifeng , Huang Jiaxu , Chen Xindu , Zeng Jun , Liang Feng , Fang Feiyu , Wang Han , Wu Peixuan , He Yunbo , Zhao Yixiang , Li Yang
Published: August 2018

The electrospinning electric field is the main factor responsible for the jet stretching force. Previous studies showed that nonhomogeneous electric field would affect the jets formed during the multi-needles electrospinning. Therefore, a multitude of methods were explored to optimize the electric field in multi-needles electrospinning, such as adjusting the supplied voltage on each needle, varying the space of the needles and spatial distribution of the needles. In this paper, three categories of needles distribution were explored for a homogeneous electric field and the design of a higher needles density of electrospinning head. The theoretical and experimental results showed that the homogeneous electric field formed with the trapezoidal head at 15mm distance while the others’ head required over 30mm. Hence, the trapezoidal arrangement is a better multi-needles distribution for electrospinning head, and has much more significance for high yield of electrospinning nanofibers.
Localization of current-induced degradation effects in (InAlGa)N-based UV-B LEDs
Authors: Ruschel J. , Glaab J. , Brendel M. , Rass J. , Stölmacker C. , Lobo-Ploch N. , Kolbe T. , Wernicke T. , Mehnke F. , Enslin J. , Einfeldt S. , Weyers M. , Kneissl M.
Published: August 2018

The degradation behavior of ultraviolet-B light emitting diodes (UV-B LEDs) emitting near 310 nm has been investigated and a method to localize the degradation effects is presented. Measurements of the electro-optical characteristics of UV-B LEDs, during a 200 h constant-current degradation study, showed an initial fast decrease in the optical power accompanied by a decrease in the drive voltage and an increase in the capacitance. Furthermore, by using a specially designed contact geometry, it was possible to separate the degradation of the electrical properties of the p-layers and p-contacts from the degradation of the active region and n-side of the LED heterostructure. Our investigations show that the initial changes in capacitance and voltage can be attributed to changes in the p-side and at the p-contact of the LED, which can be explained by an activation of Mg dopants.
A momentum flux measuring instrument with the variable-range for exhaust plume
Authors: Weng Huiyan , Cai Guobiao , Liu Lihui , Zheng Hongru , Shang Shengfei , He Bijiao
Published: August 2018

A momentum flux measuring instrument (MFMI), which ranges from 1 mN∼300 N, is designed to measure the parameters related to the momentum flux of exhaust plume of attitude and orbit control thrusters covered electric and chemical thrusters. A MFMI with the variable-range provides an efficient and economy way to study the exhaust plume of both electric and chemical thrusters. The flexural pivots, replaceable strain gauge, replaceable target plate, and force arm with the variable length make it possible. The designed MFMI with the non-displacement measurement can reduce the influence of pipelines and test lines, especially the elastic force and friction due to displacement. The designed MFMI system with the range of 0∼100 mN and 0∼15 N was calibrated separately. The target indirect measurement method is a simple and economical option for measuring the thrust of electric thrusters, and is employed to measure the thrust of the LIPS-200 ion thruster using the designed MFMI. Research indicates that the sputtering contributes to the momentum transfer of plasma-surface interactions. In addition, the high-speed charged ions from the thruster will experience a charge-exchange (CEX) collision with the slow neutral background. Therefore, the influence of the sputtering and CEX on target indirect measurement method is derived in detail, and then the measured thrust is corrected. The measured average thrust, which is 40.1 mN, demonstrates that the designed MFMI is effective. The designed MFMI can also be employed as a thrust stand by directly mounting the thrusters on torsional arm, and a maximum of three thrusters can be installed on the MFMI at the same time.
Numerical study on uniform-shear flow over a circular disk at low Reynolds numbers
Authors: Yang Jianzhi , Liu Minghou , Wang Changjian , Zhu Xiaowei , Zhang Aifeng
Published: August 2018

Uniform shear flows over a circular disk of aspect ratio 10 (thickness/diameter) at low Reynolds numbers are numerically investigated with the main focus on the effect of inlet shear on the wake evolutions. The Reynolds numbers considered are Re = 140, 160, and 180 based on the inlet center velocity uc and disk diameter d. The non-dimensional shear rate k(=∇ud/uc) is varied from 0 to 0.09. The bifurcations leading to unsteady states with hairpin vortex shedding occur much earlier in uniform shear. In most cases, wake evolutions occurring as the shear rate increases in uniform shear are similar to those as the Reynolds number increases in uniform flow. A new wake mode termed as dragonfly-wings (DW) mode is captured at Re = 180 and k = 0.01 and 0.03. At DW mode, hairpin vortex structures are shed from diametrically opposite orientations, but with irregularity in strength and shape, i.e., three different vortex loops are observed in the wake, and produce three peaks at low frequencies in the frequency spectrum of the drag. The planar-symmetry plane for standing-wave and zig-zig modes is determined by both the initial conditions and the direction of the uniform shear. It is found that with increasing inlet shear rate, the non-dimensional shedding frequency remains nearly constant for the low shear rates (k < 0.1). Time-averaged drag and lift coefficients slightly increase with increasing inlet shear rate. Finally, the hysteretic property of the DW mode transition is examined and further investigated using the Landau mode, indicating that DW mode transition is non-hysteretic (supercritical).
On the motion of the 3D compressible micropolar fluids with time periodic external forces
Authors: Tan Zhong , Xu Qiuju
Published: August 2018

This paper analyzes the time periodic solutions to the three-dimensional equations modeling the compressible micropolar fluids under some smallness and structure conditions on time periodic forces. By adopting a regularized approximation scheme and using the topological degree theory, we prove the existence of time periodic solutions in a bounded domain. Furthermore, via a limiting process, the existence result can be obtained in the whole space R3.
Passive charged-particle radiation detection using pn junction in a diamond semiconductor
Authors: DeJarnette Drew
Published: August 2018

Utilization of a new pn junction in a high-purity diamond semiconductor enables high-fidelity detection of alpha particles under zero bias voltage, which is possible due to the high built-in electric field.
Light shed on shedding droplets
Authors: Johnson-Groh Mara
Published: August 2018

New work on the shedding of multiple droplets from a surface may improve airplane anti-icing, fuel cell performance, and removing impurities in biological samples.
A novel approach for estimating densities of secretive species from road-survey and spatial-movement data
Authors: Willson John D. , Pittman Shannon E. , Beane Jeffrey C. , Tuberville Tracey D.
Published: August 2018

Context
Accurate estimates of population density are a critical component of effective wildlife conservation and management. However, many snake species are so secretive that their density cannot be determined using traditional methods such as capture–mark–recapture. Thus, the status of most terrestrial snake populations remains completely unknown.

Aim
We developed a novel simulation-based technique for estimating density of secretive snakes that combined behavioural observations of snake road-crossing behaviour (crossing speed), effort-corrected road-survey data, and simulations of spatial movement patterns derived from radio-telemetry, without relying on mark–recapture.

Methods
We used radio-telemetry data to parameterise individual-based movement models that estimate the frequency with which individual snakes cross roads and used information on survey vehicle speed and snake crossing speed to determine the probability of detecting a snake, given that it crosses the road transect during a survey. Snake encounter frequencies during systematic road surveys were then interpreted in light of detection probabilities and simulation model results to estimate snake densities and to assess various factors likely to affect abundance estimates. We demonstrated the broad applicability of this approach through a case study of the imperiled southern hognose snake (Heterodon simus) in the North Carolina (USA) Sandhills.

Key results
We estimated that H. simus occurs at average densities of 0.17 ha–1 in the North Carolina Sandhills and explored the sensitivity of this estimate to assumptions and variation in model parameters.

Conclusions
Our novel method allowed us to generate the first abundance estimates for H. simus. We found that H. simus exists at low densities relative to congeners and other mid-sized snake species, raising concern that this species may not only have declined in geographic range, but may also occur at low densities or be declining in their strongholds, such as the North Carolina Sandhills.

Implications
We present a framework for estimating density of species that have traditionally been considered too secretive to study at the population level. This method will greatly enhance our ability to study and manage a wide variety of snake species and could be applied to other secretive wildlife species that are most frequently encountered during road surveys.
Mineralocorticoid Receptor and Cardiovascular Disease
Authors: Buonafine Mathieu , Bonnard Benjamin , Jaisser Frédéric
Published: August 2018

Activation of the mineralocorticoid receptor (MR) in the distal nephron by its ligand, aldosterone, plays an important role in sodium reabsorption and blood pressure regulation. However, expression of the MR goes beyond the kidney. It is expressed in a variety of other tissues in which its activation could lead to tissue injury. Indeed, MR activation in the cardiovascular (CV) system has been shown to promote hypertension, fibrosis, and inflammation. Pharmacological blockade of the MR has protective effects in several animal models of CV disease. Furthermore, the use of MR antagonists is beneficial for heart failure patients, preventing mortality and morbidity. A better understanding of the implications of the MR in the setting of CV diseases is critical for refining treatments and improving patient care. The mechanisms involved in the deleterious effects of MR activation are complex and include oxidative stress, inflammation, and fibrosis. This review will discuss the pathological role of the MR in the CV system and the major mechanisms underlying it.
Synergizing CRISPR/Cas9 off-target predictions for ensemble insights and practical applications
Authors: Zhang Shixiong , Li Xiangtao , Lin Qiuzhen , Wong Ka-Chun
Published: August 2018

Motivation

The RNA-guided CRISPR/Cas9 system has been widely applied to genome editing. CRISPR/Cas9 system can effectively edit the on-target genes. Nonetheless, it has recently been demonstrated that many homologous off-target genomic sequences could be mutated, leading to unexpected gene-editing outcomes. Therefore, a plethora of tools were proposed for the prediction of off-target activities of CRISPR/Cas9. Nonetheless, each computational tool has its own advantages and drawbacks under diverse conditions. It is hardly believed that a single tool is optimal for all conditions. Hence, we would like to explore the ensemble learning potential on synergizing multiple tools with genomic annotations together to enhance its predictive abilities.

Results

We proposed an ensemble learning framework which synergizes multiple tools together to predict the off-target activities of CRISPR/Cas9 in different combinations. Interestingly, the ensemble learning using AdaBoost outperformed other individual off-target predictive tools. We also investigated the effect of evolutionary conservation (PhyloP and PhastCons) and chromatin annotations (ChromHMM and Segway) and found that only PhyloP can enhance the predictive capabilities further. Case studies are conducted to reveal ensemble insights into the off-target predictions, demonstrating how the current study can be applied in different genomic contexts. The best prediction predicted by AdaBoost is up to 0.9383 (AUC) and 0.2998 (PRC) that outperforms other classifiers. This is ascribable to the fact that AdaBoost introduces a new weak classifier (i.e. decision stump) in each iteration to learn the DNA sequences that were misclassified as off-targets until a small error rate is reached iteratively.

Availability and implementation

The source codes are freely available on GitHub at https://github.com/Alexzsx/CRISPR.

Supplementary information

Supplementary data are available at Bioinformatics online.
HitPickV2: a web server to predict targets of chemical compounds
Authors: Hamad Sabri , Adornetto Gianluca , Naveja J Jesús , Chavan Ravindranath Aakash , Raffler Johannes , Campillos Mónica
Published: August 2018

Motivation

The identification of protein targets of novel compounds is essential to understand compounds’ mechanisms of action leading to biological effects. Experimental methods to determine these protein targets are usually slow, costly and time consuming. Computational tools have recently emerged as cheaper and faster alternatives that allow the prediction of targets for a large number of compounds.

Results

Here, we present HitPickV2, a novel ligand-based approach for the prediction of human druggable protein targets of multiple compounds. For each query compound, HitPickV2 predicts up to 10 targets out of 2739 human druggable proteins. To that aim, HitPickV2 identifies the closest, structurally similar compounds in a restricted space within a vast chemical–protein interaction area, until 10 distinct protein targets are found. Then, HitPickV2 scores these 10 targets based on three parameters of the targets in such space: the Tanimoto coefficient (Tc) between the query and the most similar compound interacting with the target, a target rank that considers Tc and Laplacian-modified naïve Bayesian target models scores and a novel parameter introduced in HitPickV2, the number of compounds interacting with each target (occur). We present the performance results of HitPickV2 in cross-validation as well as in an external dataset.

Availability and implementation

HitPickV2 is available in www.hitpickv2.com.

Supplementary information

Supplementary data are available at Bioinformatics online.
NanoShaper–VMD interface: computing and visualizing surfaces, pockets and channels in molecular systems
Authors: Decherchi Sergio , Spitaleri Andrea , Stone John , Rocchia Walter
Published: August 2018

NanoShaper is a program specifically aiming the construction and analysis of the molecular surface of nanoscopic systems. It uses ray-casting for parallelism and it performs analytical computations whenever possible to maximize robustness and accuracy of the approach. Among the other features, NanoShaper provides volume, surface area, including that of internal cavities, for any considered molecular system. It identifies pockets via a very intuitive definition based on the concept of probe radius, intrinsic to the definition of the solvent excluded surface. We show here that, with a suitable choice of the parameters, the same approach can also permit the visualisation of molecular channels. NanoShaper has now been interfaced with the widely used molecular visualization software VMD, further enriching its already well furnished toolset.

Availability and implementation

VMD is available at http://www.ks.uiuc.edu/Research/vmd/. NanoShaper, its documentation, tutorials and supporting programs are available at http://concept.iit.it/downloads.

Supplementary information

Supplementary data are available at Bioinformatics online.
RNAdetect: efficient computational detection of novel non-coding RNAs
Authors: Chen Chun-Chi , Qian Xiaoning , Yoon Byung-Jun
Published: August 2018

Motivation

Non-coding RNAs (ncRNAs) are known to play crucial roles in various biological processes, and there is a pressing need for accurate computational detection methods that could be used to efficiently scan genomes to detect novel ncRNAs. However, unlike coding genes, ncRNAs often lack distinctive sequence features that could be used for recognizing them. Although many ncRNAs are known to have a well conserved secondary structure, which provides useful cues for computational prediction, it has been also shown that a structure-based approach alone may not be sufficient for detecting ncRNAs in a single sequence. Currently, the most effective ncRNA detection methods combine structure-based techniques with a comparative genome analysis approach to improve the prediction performance.

Results

In this paper, we propose RNAdetect, a computational method incorporating novel features for accurate detection of ncRNAs in combination with comparative genome analysis. Given a sequence alignment, RNAdetect can accurately detect the presence of functional ncRNAs by incorporating novel predictive features based on the concept of generalized ensemble defect (GED), which assesses the degree of structure conservation across multiple related sequences and the conformation of the individual folding structures to a common consensus structure. Furthermore, n-gram models (NGMs) are used to extract features that can effectively capture sequence homology to known ncRNA families. Utilization of NGMs can enhance the detection of ncRNAs that have sparse folding structures with many unpaired bases. Extensive performance evaluation based on the Rfam database and bacterial genomes demonstrate that RNAdetect can accurately and reliably detect novel ncRNAs, outperforming the current state-of-the-art methods.

Availability and implementation

The source code for RNAdetect and the benchmark data used in this paper can be downloaded at https://github.com/bjyoontamu/RNAdetect.
The challenges and contradictions of state-funded community organizing
Authors: Grimshaw Lucy , Mates Lewis , Reynolds Andie
Published: August 2018

The UK coalition government introduced the Community Organisers Programme in 2010, providing state funding to train community organizers in England for the first time. This article presents a case study in the north of England, exploring the implementation of the programme. It illustrates the challenges and contradictions faced by trainee community organizers and suggests lessons for community practitioners and policymakers of all political complexions in the United Kingdom and other countries.
Centrality and Partial Correlation Coefficient-Based Assortativity Analysis of Real-World Networks
Authors: Meghanathan Natarajan
Published: August 2018

The assortativity index (A. Index) of a complex network has been hitherto computed as the Pearson’s correlation coefficient of the remaining degree centrality (R-DEG) of the first-order neighbors (i.e. end vertices of the edges) in the network. In this paper, we seek to evaluate the assortativity of real-world networks with respect to prototypical centrality metrics (in addition to R-DEG) such as eigenvector centrality (EVC), betweenness centrality (BWC) and closeness centrality (CLC). Unlike R-DEG, the centrality values of the vertices with respect to these three metrics are influenced by the centrality values of the vertices in the neighborhood. We propose to use the notion of ‘Partial Correlation Coefficient’ to nullify the influence of the second-order neighbors (i.e. vertices that are two hops away) and quantify the assortativity of the first-order neighbors with respect to a particular centrality metric (such as EVC, BWC and CLC). We conduct an exhaustive assortativity analysis on a suite of 70 real-world networks of diverse degree distributions. We observe real-world networks to be more assortative (A. Index > 0) with respect to CLC and EVC and relatively more dissortative (A. Index < 0) with respect to BWC and R-DEG.
On the Question of Genericity of Hyperbolic Knots
Authors: V Malyutin Andrei
Published: August 2018

A well-known conjecture in knot theory says that the proportion of hyperbolic knots among all of the prime knots of $n$ or fewer crossings approaches $1$ as $n$ approaches infinity. In this article, it is proved that this conjecture contradicts several other plausible conjectures, including the 120-year-old conjecture on additivity of the crossing number of knots under connected sum and the conjecture that the crossing number of a satellite knot is not less than that of its companion.
Deformations of Lie Groupoids
Authors: Crainic Marius , Mestre João Nuno , Struchiner Ivan
Published: August 2018

We study deformations of Lie groupoids by means of the cohomology which controls them. This cohomology turns out to provide an intrinsic model for the cohomology of a Lie groupoid with values in its adjoint representation. We prove several fundamental properties of the deformation cohomology including Morita invariance, a van Est theorem, and a vanishing result in the proper case. Combined with Moser’s deformation arguments for groupoids, we obtain several rigidity and normal form results.
Resource-based view on safety culture’s influence on hospital performance: The moderating role of electronic health record implementation
Authors: Upadhyay Soumya , Weech-Maldonado Robert , Lemak Christy H. , Stephenson Amber , Mehta Tapan , Smith Dean G.
Published: August 2018

Background:

Patient safety and safety culture have received increasing attention from agencies such as the Agency of Healthcare Research and Quality and the Institute of Medicine. Safety culture refers to the fundamental values, attitudes, and perceptions that provide a unique source of competitive advantage to improve performance. This study contributes to the literature and expands understanding of safety culture and hospital performance outcomes when considering electronic health record (EHR) usage.

Purpose:

Based on the resource-based view of the firm, this study examined the association between safety culture and hospital quality and financial performance in the presence of EHR.

Methodology/Approach:

Data consist of the 2016 Hospital Survey on Patient Safety, Hospital Compare, American Hospital Association’s annual survey, and the American Hospital Association’s Information Technology supplement. Our final analytic sample consisted of 154 hospitals. We used a two-part nested regression model approach.

Results/Conclusion:

Safety culture has a direct positive relationship with financial performance (operating margin). Furthermore, having basic EHR as compared to not having EHR further enhances this positive relationship. On the other hand, safety culture does not have a direct association with quality performance (readmissions) in most cases. However, safety culture coupled with basic EHR functionalities, compared to not having EHR, is associated with lower readmissions.

Practice Implications:

Hospitals should strive to improve patient safety culture as part of their strategic plan for quality improvement. In addition, hospital managers should consider implementing EHR as a resource that can support safety culture’s effect on outcomes such as financial and quality performance indicators. Future studies can examine the differences between basic and advanced EHR presence in relation to safety culture.
Cognitive Performance of Severely Hearing-impaired Older Adults Before and After Cochlear Implantation: Preliminary Results of a Prospective, Longitudinal Cohort Study Using the RBANS-H
Authors: Claes Annes J. , Van de Heyning Paul , Gilles Annick , Van Rompaey Vincent , Mertens Griet
Published: August 2018

Objective:

To evaluate cognitive change in severely hearing-impaired older adults after cochlear implantation.

Study Design:

Prospective, longitudinal cohort study with assessments before, and at 6 and 12 months after implantation.

Patients:

Twenty older adults (median age: 71.5 yr).

Main Outcome Measures:

Change in the Repeatable Battery for the Assessment of Neuropsychological Status for Hearing-impaired individuals (RBANS-H) total score and subdomain scores were used to assess cognitive evolution. In addition, change in best-aided speech audiometry in quiet (monosyllabic words) and in noise (Leuven Intelligibility Sentences Test [LIST]) was examined, as well as patient-reported measures of health-related quality of life (Nijmegen Cochlear Implant Questionnaire [NCIQ]), self-perceived hearing disability (Speech, Spatial, and Qualities of hearing Scale—12 [SSQ12]), sound quality (Hearing Implant Sound Quality Index—19 [HISQUI19]), and states of anxiety and depression (Hospital Anxiety and Depression Scale [HADS]).

Results:

The RBANS-H total scores improved significantly after 12 months cochlear implant (CI) usage (p < 0.001). At subdomain level, significant improvements were observed in the immediate and delayed memory domain (p = 0.005 and p = 0.002, respectively), and to a lesser extent also in the attention domain (p = 0.047). Furthermore, speech perception in quiet and in noise improved significantly after 6 months and remained stable after 12 months. Similarly, a significant improvement was observed on all patient-reported measures after 6 months of CI usage. These results remained stable after 12 months, except for the HADS.

Conclusions:

A significant improvement in overall cognition after 12 months of CI usage was established. However, future research is imperative to further disentangle possible practice effects from the effects of the cochlear implantation. The significant, positive effect of cochlear implantation on speech perception and patient-reported measures was confirmed.
Pediatric headache: overview
Authors: Kelly Meaghan , Strelzik Jeffrey , Langdon Raquel , DiSabella Marc
Published: August 2018

Purpose of review

Headache is a common medical complaint in children and adolescents with the majority having experienced some type of headache by their teenage years. Pediatric headache presentations often differ compared to adults, and children may have difficulty describing their symptoms. Thus, a thorough understanding of the approach to the pediatric headache patient is essential to ensure appropriate diagnosis, evaluation, and management.

Recent findings

In the following article we will review the components of a comprehensive pediatric headache assessment, as well as discuss primary and secondary headache types seen in children with focus on clinical pearls and ‘red flags’ necessitating diagnostic testing.

Headaches in children may be due to primary or secondary etiologies. Common primary headache types include migraine or tension-type headache. Secondary headache causes are broad and include infections, trauma, vascular disorders, substance use/withdrawal, and psychiatric conditions. Current American Academy of Neurology (AAN) guidelines recommend against routine lab studies, lumbar puncture, electro-encephalogram (EEG), or neuroimaging in patients with no headache red flags by history and a normal neurologic examination.
Factors Influencing Patient Satisfaction in Plastic Surgery: A Nationwide Analysis
Authors: Chen Kevin , Congiusta Susan , Nash Ira S. , Coppa Gene F. , Smith Mark L. , Kasabian Armen K. , Thorne Charles , Tanna Neil
Published: August 2018

Background:

Patient satisfaction surveys are an increasingly important part of health care, influencing the practice of physicians. Press Ganey has developed tools to assess physician and department performance that are used by 50 percent of hospitals in the United States and over 10,000 health care organizations. The authors sought to evaluate the factors that influence patient satisfaction in plastic surgery patients both locally and nationally.

Methods:

A 24-item Press Ganey survey was distributed to patients of 686 participating plastic surgeons nationwide, including those at the authors’ home institution. The responses from January to December of 2016 were analyzed retrospectively with Pearson correlation coefficients. The items “likelihood to recommend provider” and “likelihood to recommend practice” were correlated to all other items of the survey, as these items have been shown to be surrogates for overall satisfaction.

Results:

There were 411 survey responses from patients in the Northwell Health System and 36,836 responses from patients nationally. Items that were not well correlated (r < 0.5) with “likelihood to recommend practice” or “provider” were items such as wait time and courtesy of registration staff. The items that were best correlated (r > 0.8) with “likelihood to recommend practice” or “provider” were the patient’s confidence in the care provider and the provider’s concern for questions. All correlations were statistically significant (p < 0.001).

Conclusion:

In an evolving patient centric culture, the patient’s confidence and trust of the provider is more important than perception of the provider’s office environment to maintaining patient loyalty and market share.
Increased Skeletal Muscle FDG Uptake Due to Sexual Activity on PET/CT in a Middle Age Woman
Authors: Wang Wei , Kan Ying , Liu Jie , Yuan Leilei , Yang Jigang
Published: August 2018

A 48-year-old woman with gradually growing left lung nodule underwent FDG PET/CT scan, which demonstrated mild 18F-FDG uptake in the nodule of the left lobe, suggestive of malignancy. Unexpectedly, increased FDG uptake in bilateral gluteus medius, gluteus minimus, and piriformis was shown. She described having sexual activity in missionary position the night prior. The case emphasizes the importance of avoiding sexual activity before the FDG PET/CT study.
Pulmonary Hypertension Parameters Assessment by Electrocardiographically Gated Computed Tomography
Authors: Zhu Yinsu , Tang Xin , Wang Zhiyue , Wei Yongyue , Zhu Xiaomei , Liu Wangyan , Xu Yi , Tang Lijun , Shi Haibin
Published: August 2018

Purpose:

Pulmonary hypertension (PH) parameters such as pulmonary artery or right ventricular size can be measured easily on computed tomography (CT). However, there are limited data on electrocardiographically (ECG) gated CT. We sought to determine age-specific and sex-specific normal reference values for PH parameters normalized by body surface area (BSA) using ECG-gated cardiac CT in a Chinese population.

Materials and Methods:

In total, we enrolled 519 non-PH patients undergoing ECG-gated CT coronary angiography and measured PH parameters, including main pulmonary artery (MPA) and right pulmonary artery (RPA) diameters and distension, the ratio of MPA to ascending aorta (AAO) diameter (MPA/AAO), and the ratio of right ventricular to left ventricular diameter (RV/LV). Maximum MPA and RPA diameters were also normalized to BSA (nMPA, nRPA).

Results:

Age, sex, BSA, and body mass index (BMI) were variably associated with PH parameters. Age was an independent predictor of all PH parameters. The maximum MPA diameter (26.5±2.7 mm), maximum RPA diameter (20.9±3.0 mm), nMPA (15.8±2.0 mm/m2), nRPA (12.4±2.0 mm/m2), and RV/LV (0.85±0.11) increased with age. MPA/AAO (0.80±0.10), MPA, and RPA distension (25.4%±7.1%; 23.3%±6.7%) correlated negatively with age. Although absolute MPA and RPA diameters were slightly larger in men, women had significantly larger nMPA and nRPA values. MPA and RPA sizes and RV/LV were correlated positively with BSA and BMI.

Conclusions:

Using ECG-gated cardiac CT, we determined the normal reference values of PH parameters for non-PH adult Chinese patients, and these values were variably influenced by age, sex, BSA, and BMI.