bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Amphotericin B Against Fusarium and Aspergillus in Corneal Storage Medium
Authors: Duncan Katherine , Parker Jeff , Hoover Caroline , Lindquist Thomas D. , Jeng Bennie H. 
Published: October 2018

Purpose:
The incidence of postkeratoplasty fungal infection is increasing in the United States, and our most commonly used corneal storage medium, Optisol-GS, contains antibiotics but no antifungal agents. We previously demonstrated the efficacy of amphotericin B additives in eliminating Candida albicans contaminants in Optisol-GS. The purpose of this study was to determine whether amphotericin B would also be efficacious against Fusarium solani and Aspergillus fumigatus.

Methods:
Vials of Optisol-GS were supplemented with 0.255 μg/mL of amphotericin B. Half of the vials were inoculated with F. solani and half with A. fumigatus. Positive control vials were inoculated with the fungi but no amphotericin B. The vials were refrigerated, sampled, and plated at different time points. The plates were then incubated at 36°C for 48 hr after which fungal colony counts were performed.

Results:
There was an average reduction in the growth of F. solani in the amphotericin B–supplemented vials of 44% on day 2, 79% on day 7, and 80% on day 14 when compared with the positive control vials. There was an average reduction in the growth of A. fumigatus in the amphotericin B–supplemented vials of 40% on day 2 and 14% on day 7 when compared with the positive control vials. Both amphotericin B–supplemented and control vials grew less than 2 colonies of A. fumigatus on day 14.

Conclusions:
This study suggests that amphotericin B additives in Optisol-GS reduce the growth of F. solani and A. fumigatus.
Trainee Performance in Loop Electrosurgical Excision Procedure (LEEP) After Simulation Training
Authors: Wilson Erin , Janssens Sarah , Ng Dora , Jolly Brian , Hewett David G. , Beckmann Michael 
Published: October 2018

Objective
The aim of the study was to review the performance of trainees in loop electrosurgical excision procedure (LEEP) procedures after the introduction of a simulation training program.

Materials and Method
A simulation training program was introduced in September 2016 for gynecology trainees at the study institution. Trainees were encouraged to perform at least 3 simulated LEEP procedures before operating. For a 12-month period after the introduction of training, data on operating time and specimen quality measures of clear margin status, adequate depth, and absence of fragmentation were reviewed. This was compared with a 12-month period before simulation training (from September 2014–September 2015). Trainees were surveyed for feedback on the training.

Results
In total, 135 LEEP procedures were reviewed: 68 before and 67 after simulator training. Trainee specimens after training were more likely to be nonfragmented (89.2% vs 55.9%, p = .003), have clear margins (72.2% vs 41.9%, p = .015), and meet “all criteria” (46% vs 20.6%, p = .043) than trainee specimens before training. There was no change in depth adequacy (70.3% vs 67.7%, p = .99). Median trainee procedure time reduced from 18 minutes (interquartile range = 11–24) before training to 8 minutes after training (interquartile range = 6–11) (p = <0.001). There was no significant change in operating time or specimen quality from LEEP procedures performed by attendings (who did not use the simulator). Trainee and attending procedural outcomes were similar after training. Trainees had mostly positive views on the training, though reported time constraints as a barrier to simulation.

Conclusions
After the introduction of an LEEP simulation training program, operative time and specimen quality from trainee procedures seemed to improve.
Direct-acting antiviral hepatitis C virus treatment perturbation of the metabolic milieu
Authors: Driedger Matt , Galanakis Chrissi , Doyle Mary-Anne , Cooper Curtis L. 
Published: October 2018

Objective
Hepatitis C virus (HCV), cirrhosis, and HCV medications including direct-acting antivirals (DAAs) ±ribavirin may all influence the metabolic milieu. While interferon-based regimens improve glucose tolerance, evidence is limited on DAAs. Cases of elevated lactate have recently been reported in patients treated with DAAs, and lactic acidosis is a known complication of antivirals used to treat hepatitis B virus and HIV.

Patients and methods
Measures were evaluated at baseline, week 4, end of treatment, and 12–24 weeks after treatment. Mixed-effects modeling was used to determine factors influencing glucose and lactate over time.

Results
In total, 442 patients were treated (mean age 56, 65% male, 72% genotype 1, 48% cirrhotic). Glucose did not change on or after DAA treatment from baseline (P=0.51) aside from those with untreated diabetes, which declined (P=0.02). Overall, there was a decline in lactate following HCV treatment (mean 2.4–2.1 mmol/l; P<0.001). Lactate initially increased on treatment and then decreased after treatment completion in male patients treated with ribavirin. This pattern was not observed in other groups. There was no evidence of lactic acidosis with HCV nucleotide use.

Conclusion
Distinct glucose and lactate trajectories were identified without evidence of DAA metabolic toxicity. HCV treatment does not improve random glucose levels aside from perhaps in untreated diabetic patients.
Xenotransplantation tolerance: applications for recent advances in modified swine
Authors: Llore Nathaly P. , Bruestle Karina A. , Griesemer Adam 
Published: October 2018

Purpose of review
The aim of this study was to review the recent progress in xenotransplantation achieved through genetic engineering and discuss the potential of tolerance induction to overcome remaining barriers to extended xenograft survival.

Recent findings
The success of life-saving allotransplantation has created a demand for organ transplantation that cannot be met by the supply of human organs. Xenotransplantation is one possible solution that would allow for a nearly unlimited supply of organs. Recent genetic engineering of swine has decreased the reactivity of preformed antibodies to some, but not all, potential human recipients. Experiments using genetically modified swine organs have now resulted in survival of life-supporting kidneys for over a year. However, the grafts show evidence of antibody-mediated rejection on histology, suggesting additional measures will be required for further extension of graft survival. Tolerance induction through mixed chimerism or thymic transplantation across xenogeneic barriers would be well suited for patients with a positive crossmatch to genetically modified swine or relatively negative crossmatches to genetically modified swine, respectively.

Summary
This review highlights the current understanding of the immunologic processes in xenotransplantation and describes the development and application of strategies designed to overcome them from the genetic modification of the source animal to the induction of tolerance to xenografts.
Anti-aquaporin-4 Antibody Positive Optic Neuritis Following Scrub Typhus in an Elderly Female
Authors: Bae Dae Woong , An Jae Young 
Published: October 2018

Introduction:
Aquaporin-4 antibody (AQP4-Ab) is specific for neuromyelitis optica spectrum disorder (NMOSD) and so is helpful to distinguish NMOSD from other autoimmune diseases. Several viral infections may play a role in the onset of NMOSD.

Case Report:
We describe a case of a previous healthy 82-year-old woman who presented with acute visual loss occurring 3 weeks after scrub typhus. Physical examination showed a relatively afferent pupillary defect in the right eye and ophthalmoscopy revealed edema of the right optic disc. Enhanced magnetic resonance imaging revealed enhancement of the right optic nerve. Serological testing showed AQP4-Ab. After methylprednisolone pulse therapy followed by oral tapering of prednisolone, visual dysfunction was improved. Subsequently she experienced no attacks for 5 years.

Conclusions:
Optic neuritis (ON) associated with scrub typhus is extremely rare. Our case support that scrub typhus could trigger ON in a lifelong asymptomatic patient with AQP4-Ab and AQP4-Ab should be considered in a very old age patient with suspected postinfectious inflammatory ON.
Thrombolysis After Protamine Reversal of Heparin for Acute Ischemic Stroke After Cardiac Catheterization
Authors: Warner Danielle S. , Schwartz Bryan G. , Babygirija Reji , Rovin Richard A. , Kassam Amin B. , Biddick Lindsay , Sajjad Rehan , Chohan Adil , Panichpisal Kessarin 
Published: October 2018

Background:
Patients with an acute ischemic stroke (AIS) following cardiac catheterization (CC) generally do not receive intravenous thrombolysis [intravenous tissue plasminogen activator (IV-tPA)] as it is contraindicated due to the coagulopathy related to the heparin used during the procedure. We report a case of AIS successfully treated with IV thrombolysis following protamine reversal of heparin effect.

Case report:
An 87-year-old man with diabetes mellitus, hypertension, neurofibromatosis, and hyperlipidemia underwent elective transradial CC following an abnormal stress test. He had 2 drug-eluting stents for severe stenosis of mid-circumflex and right coronary arteries and received heparin 13,000 IU during procedure. He developed acute left hemiparesis with initial NIH stroke scale (NIHSS) of 4. Computed tomographic scan of the brain and computed tomographic angiogram of head and neck were unremarkable. Bedside activated clotting time was 181. Protamine 40 mg was administered and 30 minutes later, the activated clotting time level was normalized. IV-tPA was administered at 4 hours 25 minutes from his last known well. Within 15 minutes, his NIHSS was 0. Magnetic resonance imaging of brain showed no acute infarction 24 hours after stroke.

Conclusions:
There are limited reports of protamine reversal of heparin before IV-tPA administration. To our knowledge, there are only 6 AIS cases including ours. Three cases received 0.6 mg/kg of tPA dose. All have favorable outcomes and no intracranial hemorrhage was reported. Protamine reversal of heparin for AIS after CC seems to be safe. Further studies are needed to confirm the therapeutic safety and efficacy of this strategy.
Moana: A robust and scalable cell type classification framework for single-cell RNA-Seq data
Authors: Wagner Florian , Yanai Itai 
Published: October 2018

AbstractSingle-cell RNA-Seq (scRNA-Seq) enables the systematic molecular characterization of heterogeneous tissues at an unprecedented resolution and scale. However, it is currently unclear how to establish formal cell type definitions, which impedes the systematic analysis of scRNA-Seq data across experiments and studies. To address this challenge, we have developed Moana, a hierarchical machine learning framework that enables the construction of robust cell type classifiers from heterogeneous scRNA-Seq datasets. To demonstrate Moana’s capabilities, we construct cell type classifiers for human immune cells that accurately distinguish between closely related cell types in the presence of experimental perturbations and systematic differences between scRNA-Seq protocols. We show that Moana is generally applicable and scales to datasets with more than ten thousand cells, thus enabling the construction of tissue-specific cell type atlases that can be directly applied to analyze new scRNASeq datasets. A Python implementation of Moana can be found at https://github.com/yanailab/moana.
Intersubject MVPD: Empirical Comparison of fMRI Denoising Methods for Connectivity Analysis
Authors: Li Yichen , Saxe Rebecca , Anzellotti Stefano 
Published: October 2018

AbstractNoise is a major challenge for the analysis of fMRI data in general and for connectivity analyses in particular. As researchers develop increasingly sophisticated tools to model statistical dependence between the fMRI signal in different brain regions, there is a risk that these models may increasingly capture artifactual relationships between regions, that are the result of noise. Thus, choosing optimal denoising methods is a crucial step to maximize the accuracy and reproducibility of connectivity models. Most comparisons between denoising methods require knowledge of the ground truth: of what is the ‘real signal’. For this reason, they are usually based on simulated fMRI data. However, simulated data may not match the statistical properties of real data, limiting the generalizability of the conclusions. In this article, we propose an approach to evaluate denoising methods using real (non-simulated) fMRI data. First, we introduce an intersubject version of multivariate pattern dependence (iMVPD) that computes the statistical dependence between a brain region in one participant, and another brain region in a different participant. iMVPD has the following advantages: 1) it is multivariate, 2) it trains and tests models on independent folds of the real fMRI data, and 3) it generates predictions that are both between subjects and between regions. Since whole-brain sources of noise are more strongly correlated within subject than between subjects, we can use the difference between standard MVPD and iMVPD as a ‘discrepancy metric’ to evaluate denoising techniques (where more effective techniques should yield smaller differences). As predicted, the difference is the greatest in the absence of denoising methods. Furthermore, a combination of removal of the global signal and CompCorr optimizes denoising (among the set of denoising options tested).
JHU-2545 Selectively Shields Salivary Glands and Kidneys during PSMA-Targeted Radiotherapy
Authors: Nedelcovych Michael T. , Dash Ranjeet P. , Wu Ying , Choi Eun Yong , Lapidus Rena S. , Majer Pavel , Abou Diane , Penet Marie-France , Nikolopoulou Anastasia , Amor-Coarasa Alex , Babich John , Thorek Daniel L. , Rais Rana , Kratochwil Clemens , Slusher Barbara S. 
Published: October 2018

ABSTRACTPURPOSEProstate-specific membrane antigen (PSMA) radiotherapy is a promising treatment for metastatic castration-resistant prostate cancer (mCRPC) with several beta or alpha particle-emitting radionuclide-conjugated small molecules showing efficacy in late stage patients. However, PSMA is also expressed in kidneys and salivary glands where specific uptake causes dose-limiting xerostomia and potential for nephrotoxicity. The PSMA inhibitor 2- (phosphonomethyl)pentanedioic acid (2-PMPA) can prevent kidney uptake in mice, but also blocks tumor uptake, precluding its clinical utility. Selective delivery of 2-PMPA to non-malignant tissues could improve the therapeutic window of PSMA radiotherapy.EXPERIMENTAL DESIGNA tri-alkoxycarbonyloxy alkyl (TrisPOC) prodrug of 2-PMPA, JHU-2545, was synthesized to enhance 2-PMPA delivery to non-malignant tissues. Preclinical pharmacokinetic and imaging experiments were conducted prior to assessment in 3 mCRPC patients receiving PSMA PET and radiotherapy.RESULTSJHU-2545 resulted in 3- and 53-fold greater exposure of 2-PMPA in rodent salivary glands (18.0 ± 0.97 h*nmol/g) and kidneys (359 ± 4.16 h*nmol/g) versus prostate tumor xenograft (6.79 ± 0.19 h*nmol/g). JHU-2545 also blocked rodent kidneys and salivary glands uptake of the PSMA PET tracers 68Ga-PSMA-11 and 18F-DCFPyL by up to 85% without effect on tumor. In a mCRPC patient, JHU-2545 treatment prior to 68Ga-PSMA-617 administration reduced kidney SUVmax by 76% without effect on metastatic lesions. When administered prior to injection of the beta emitter 177Lu-PSMA-617, JHU-2545 shielded both the salivary glands (72% Gy reduction) and kidneys (45% Gy reduction) without effect on metastases’ dose.CONCLUSIONSJHU-2545 pre-treatment raises the cumulative dose limit and improves the safety and efficacy profile of PSMA radiotherapy.STATEMENT OF TRANSLATIONAL RELEVANCEProstate Specific Membrane Antigen (PSMA) molecular radiotherapy has emerged as a promising treatment for metastatic castration-resistant prostate cancer (mCRPC), but endogenous expression of PSMA in kidneys and salivary glands causes uptake into these organs resulting in dose-limiting toxicities. We describe the discovery of JHU-2545, a PSMA inhibitor prodrug that selectively blocks kidney and salivary gland uptake of PSMA theranostics without altering tumor uptake in both preclinical models and in mCRPC patients. Pretreatment of JHU-2545 thereby improves the safety and efficacy profile of the multiple PSMA radiotherapies in development.
Deep reinforcement learning for the control of microbial co-cultures in bioreactors
Authors: Treloar Neythen J. , Fedorec Alexander J.H. , Ingalls Brian P. , Barnes Chris P. 
Published: October 2018

AbstractMulti-species microbial communities are widespread in natural ecosystems. When employed for biomanufacturing, engineered synthetic communities have shown increased productivity (in comparison with pure cultures) and allow for the reduction of metabolic load by compartmentalising bioprocesses between multiple sub-populations. Despite these benefits, co-cultures are rarely used in practice because control over the constituent species of an assembled community has proven challenging. Here we demonstrate,in silico, the efficacy of an approach from artificial intelligence – reinforcement learning – in the control of co-cultures within continuous bioreactors. We confirm that feedback via reinforcement learning can be used to maintain populations at target levels, and that model-free performance with bang-bang control can outperform traditional proportional integral controller with continuous control, when faced with infrequent sampling. Further, we demonstrate that a satisfactory control policy can be learned in one twenty-four hour experiment, by running five bioreactors in parallel. Finally, we show that reinforcement learning can directly optimise the output of a co-culture bioprocess. Overall, reinforcement learning is a promising technique for the control of microbial communities.
Economic theory innovation and China’s development practice
Authors: Huang Taiyan 
Published: October 2018

Purpose
The purpose of this paper is to promote the theoretical innovation of socialist economics with Chinese characteristics in these areas.

Design/methodology/approach
We must “excavate new materials, discover new problems, propose new ideas, and construct new theories from the practice of China’s reform and development.”

Findings
Giving full play to the government’s role in realizing optimal allocation of resources required for the public economy to better exert its control, influence and guidance, and at least assume the following three responsibilities. The first is to iron out the economic cycle. The second is to lead the industry to upgrade. The third is to ensure national economic security.

Originality/value
Some deep-rooted issues still need to be further studied in order to establish the scientific and practical nature of the socialist economics with Chinese characteristics. For instance, why is the theory of a socialist economy with Chinese characteristics summarized from the development practice in China a scientific theory?
Finite elements simulation of improvised explosively formed projectiles
Authors: Castedo Ricardo , Santos Anastasio Pedro , Yenes José Ignacio , Sanchidrián José Ángel , López Lina María , Segarra Pablo 
Published: October 2018

Purpose
The purpose of this paper is to investigate the applicability of the LS-DYNA software using a Lagrangian formulation in the jet formation, flight and penetration of improvised explosively formed projectiles (EFPs). Numerical results dealing with different properties of the EFPs have been validated with a significant number of field tests.

Design/methodology/approach
2D and 3D Lagrangian models, using different material definition, are developed to reproduce the field-measured characteristics of copper- and steel-made EFPs: projectile size and velocity. After validation, the model has been extended to analyse the penetration features. Two different plasticity models have been used to describe the steel target, Plastic-Kinematic and Johnson–Cook.

Findings
Despite the difficulty in characterizing a non-industrial artefact, the results show that both Lagrangian models (2D and 3D) are able to simulate the projectile size, velocity and penetration capability with errors less than 10 per cent when using the Johnson–Cook material model for both liner and target.

Practical implications
These data can be used to test the penetration ability of improvised EFP’s against different targets, i.e. light armoured vehicles.

Originality/value
There are no references that address the application of the Lagrangian simulation of non-industrial EFPs and its validation with field tests, including penetration assessment.
Model of the wheel motion state under path constraints based on the Darboux frame in 3D space
Authors: Zhang He , Yang Shaowei , Ma Zhengfeng 
Published: October 2018

Purpose
Existing three-dimensional (3D) road-surface models use approximation methods such as a set of discrete triangular patches and cannot accurately describe changes in the geometrically designed elements along the road. This paper aims to construct a 3D road-surface model with combinations of geometric design invariants and apply the proposed model to analyse the state of motion of a wheel’s centre.

Design/methodology/approach
In this paper, the 3D road surface is modelled as a continuous function with combinations of geometric design invariants. By introducing the theories of differential geometries and rigid body dynamics, a wheel-road model wherein a wheel fixed to a Darboux frame moves along a curved road surface is constructed, and the wheel time-dependent properties of the velocity, angular velocity and acceleration at an arbitrary point of the surface are described using road geometry design invariants.

Findings
This paper adopts the Darboux frame to study the instantaneous spin-rolling motion of a wheel. It is found that the magnitudes of the spin-rolling velocity, the acceleration and the geometric invariants of the road surface, including the geodesic curvature, the normal curvature and the geodesic torsion, determine the instantaneous states of motion of a wheel.

Originality/value
This work provides a theoretical foundation for future studies of wheel motion states, such as the relationship between road geometry design invariants and driving safety, vehicle lane changing and other vehicle microbehaviours. New insights are gained in the areas of road safety and vehicles incorporating artificial intelligence.
The impact of a leader’s demographic and professional characteristics on employee motivation
Authors: Campos-García Irene , Zúñiga-Vicente José Ángel 
Published: October 2018

PurposeBuilding on Upper Echelons Theory and prior research on strategic leadership, the purpose of this paper is to examine the possible effect on employee motivation of two sets of characteristics related to leaders: demographic (gender and age); and professional development (tenure, prior career experience in the organization and training).Design/methodology/approachThe empirical analysis is based on data from a survey of Spanish educational organizations (secondary schools). The hypotheses are tested using hierarchical multiple regression analysis estimations.FindingsThe results reveal that the characteristics linked to a leader’s professional development have a significant impact on employee (teacher) motivation. Specifically, a long tenure in office has a negative effect, while prior career experience in an organization and continuous training have a positive impact. However, none of the leader’s demographic characteristics considered in the study has a significant impact on teacher motivation.Practical implicationsSeveral lines of managerial and educational policy action are suggested for improving employee (teacher) motivation, especially in the specific case of the schools considered here.Originality/valueThis study is one of the first attempts to explore what impact certain leaders’ characteristics have on employee motivation.