bluuebunny/crossref_metadata_2025_split huggingface dataset:
An evaluation of some assumptions underpinning the bidomain equations of electrophysiology
Authors: Whiteley Jonathan P 
Published: August 2019

Abstract
Tissue level cardiac electrophysiology is usually modelled by the bidomain equations, or the monodomain simplification of the bidomain equations. One assumption made when deriving the bidomain equations is that both the intracellular and extracellular spaces are in electrical equilibrium. This assumption neglects the disturbance of this equilibrium in thin regions close to the cell membrane known as Debye layers. We first demonstrate that the governing equations at the cell, or microscale, level may be adapted to take account of these Debye layers with little additional complexity, provided the permittivity within the Debye layers satisfies certain conditions that are believed to be satisfied for biological cells. We then homogenize the microscale equations using a technique developed for an almost periodic microstructure. Cardiac tissue is usually modelled as sheets of cardiac fibres stacked on top of one another. A common assumption is that an orthogonal coordinate system can be defined at each point of cardiac tissue, where the first axis is in the fibre direction, the second axis is orthogonal to the first axis but lies in the sheet of cardiac fibres and the third axis is orthogonal to the cardiac sheet. It is assumed further that both the intracellular and extracellular conductivity tensors are diagonal with respect to these axes and that the diagonal entries of these tensors are constant across the whole tissue. Using the homogenization technique we find that this assumption is usually valid for cardiac tissue, but highlight situations where the assumption may not be valid.
Development and Implementation of a Cloud-Based Meningitis Surveillance and Specimen Tracking System in Burkina Faso, 2018
Authors: Diallo Alpha Oumar , Kiemtoré Tanga , Bicaba Brice Wilfried , Medah Isaïe , Tarbangdo Tiga Félix , Sanou Simon , Soeters Heidi M , Novak Ryan T , Aké Honoré Flavien 
Published: August 2019

Abstract
Nationwide case-based meningitis surveillance was established in Burkina Faso following the introduction of meningococcal serogroup A conjugate vaccine in 2010. However, timely tracking and arrival of cerebrospinal fluid specimens for confirmation at national reference laboratories remained suboptimal. To better understand this gap and identify bottlenecks, the Burkina Faso Ministry of Health, along with key partners, developed and implemented a cloud-based System for Tracking Epidemiological Data and Laboratory Specimens (STELAB), allowing for timely nationwide data reporting and specimen tracking using barcodes. STELAB was adapted to Burkina Faso’s infrastructure to ensure suitability, functionality, flexibility, and sustainability. We describe the design, development, and implementation of STELAB. In addition, we discuss strategies used to promote sustainability, lessons learned during the first year of implementation, and future directions. STELAB’s novel design and country-driven approach has the potential to achieve sustainable real-time data reporting and specimen tracking for the first time in sub-Saharan Africa.
Non-interlacing peakon solutions of the Geng–Xue equation
Authors: Shuaib Budor , Lundmark Hans 
Published: August 2019

AbstractThe aim of the present article is to derive explicit formulas for arbitrary non-overlapping pure peakon solutions of the Geng–Xue (GX) equation, a two-component generalization of Novikov’s cubically non-linear Camassa–Holm type equation. By performing limiting procedures on the previously known formulas for so-called interlacing peakon solutions, where the peakons in the two component occur alternatingly, we turn some of the peakons into zero-amplitude ‘ghostpeakons’, in such a way that the remaining ordinary peakons occur in any desired configuration. A novel feature compared to the interlacing case is that the Lax pairs for the GX equation do not provide all the constants of motion necessary for the integration of the system. We also study the large-time asymptotics of the non-interlacing solutions. As in the interlacing case, the peakon amplitudes grow or decay exponentially, and their logarithms display phase shifts similar to those for the positions. Moreover, within a group of adjacent peakons in one component, all peakons but one have the same asymptotic velocity. A curious phenomenon occurs when the number of such peakon groups is odd, namely that the sets of incoming and outgoing velocities are unequal.
Calcium to phosphorus ratio requirement of 26- to 127-kg pigs fed diets with or without phytase1,2
Authors: Vier Carine M , Dritz Steve S , Tokach Mike D , DeRouchey Joel M , Goodband Robert D , Gonçalves Márcio A D , Orlando Uislei A D , Bergstrom Jon R , Woodworth Jason C 
Published: August 2019

Abstract
Two experiments were conducted to determine the effects of calcium to phosphorus (Ca:P) ratio in diets adequate in standardized total tract digestible (STTD) P on performance of 26- to 127-kg pigs fed diets with or without phytase. Pens of pigs (n = 1,134 in Exp. 1 and n = 1,215 in Exp. 2, initially 26.3 and 25.3 kg) were blocked by body weight (BW) and allotted to treatments in a randomized complete block design. There were 27 pigs per pen with 7 and 9 replicates per treatment in Exp. 1 and Exp. 2, respectively. Treatments were formulated to contain 0.75:1, 1.00:1, 1.25:1, 1.50:1, 1.75:1, and 2.00:1 analyzed Ca:P ratios in Exp. 1, and 0.75:1, 1.00:1, 1.25:1, 1.50:1, and 2.00:1 analyzed Ca:P ratios in Exp. 2. These correspond to a range of 0.96:1 to 2.67:1 and 0.95:1 to 2.07:1 STTD Ca:STTD P ratios in Exp. 1 and Exp. 2, respectively. Experiment 2 diets contained 1,000 phytase units of Ronozyme HiPhos 2500 (DSM Nutritional Products, Inc., Parsippany, NJ) with release values of 0.132% STTD P, 0.144% total Ca, and 0.096% STTD Ca. Diets contained 122% of NRC (2012) STTD P estimates for the weight range across 4 phases. In Exp. 1, increasing Ca:P ratio increased (quadratic, P < 0.05) average daily gain (ADG) and average daily feed intake (ADFI). Feed efficiency (G:F) worsened (quadratic, P < 0.05) at the highest ratio. Hot carcass weight (HCW) and bone ash increased (quadratic, P < 0.05) while carcass yield decreased (linear, P < 0.10) with increasing Ca:P ratio. The maximum responses in ADG, HCW, and bone ash were estimated at 1.38:1, 1.25:1, and 1.93:1 analyzed Ca:P and at 1.82:1, 1.64:1, and 2.57:1 STTD Ca:STTD P, respectively. In Exp. 2, increasing Ca:P ratio increased (quadratic, P < 0.05) ADG and bone ash, and improved G:F (linear, P < 0.05). There was a quadratic increase (P < 0.05) in HCW and decrease in carcass yield (P < 0.10). The maximum responses in ADG, HCW, and bone ash were estimated at 1.63:1, 1.11:1 to 1.60:1, and 1.25:1 analyzed Ca:P and at 1.75:1, 1.28:1 to 1.71:1, and 1.40:1 STTD Ca:STTD P, respectively. Expressing ADG on a STTD Ca:STTD P basis provided a more consistent estimate of the ideal Ca:P ratio among the 2 studies than analyzed Ca to analyzed P ratio. A STTD Ca:STTD P ratio between 1.75:1 to 1.82:1 can be used for 26- to 127-kg pigs that are fed diets adequate in STTD P with or without added phytase to maximize growth rate without reducing bone ash.
International Obligations Concerning Disarmament and the Cessation of the Nuclear Arms Race: Justiciability over Justice in the Marshall Islands Cases at the International Court of Justice
Authors: Black-Branch Jonathan 
Published: August 2019

Abstract
The International Court of Justice rulings in cases from the Marshall Islands against India, Pakistan and the UK not only failed to answer important questions regarding obligations to negotiate a nuclear cessation treaty and to disarm, but also raise new questions relating to the existence of a dispute under general international law. The Respondents objected to the Court’s jurisdiction to hear the case on the grounds that there was no justiciable dispute between them and the Marshall Islands, arguing that the issues should not be adjudicated within this forum. The Court agreed, finding there was not sufficient evidence of a dispute, per se, and consequently did not have jurisdiction to hear these cases on their merits as the Respondents were not aware of contentious issues. In the case of the UK, in particular, it was decided by a narrow majority, raising important questions about the Court’s strictly formalistic, and more importantly, unprecedented, approach regarding the existence of a dispute under international law. More significantly, the ruling avoided answering important questions relating to long-standing international obligations regarding disarmament and negotiations toward a treaty to cease the arms race pursuant to Article VI of the Nuclear Non-Proliferation Treaty, 1968. This article provides an overview and analysis of the Marshall Islands cases, examining the main legal issues and arguments, focusing on the Court’s reasoning and highlighting the division within the Court on substantive matters pertaining to obligations of nuclear-armed states.
Out of sight, out of mind
Authors: Dohe Sebastian , Falk Malve Anna 
Published: August 2019

Abstract
The grand-ducal gallery of Oldenburg is a forgotten collection today, though once it enjoyed international fame. In less than a century, the dukes of Oldenburg in Lower Saxony collected an exemplary gallery of Old Masters that attracted the attention and the praise of international connoisseurs and art historians like Wilhelm Bode, Abraham Bredius and Tancred Borenius. Then, after the end of the First World War, the collection fell apart. In 1919, it was disassembled and its masterpieces were sold, once again generating international attention, this time from art dealers, museums and collectors eager to have their share of the plunder. The protests over this sell-out added impetus to the passing of a Kulturgutschutzgesetz, the first German law aimed at the protection of works of art of national value. This article reviews the history of the gallery and presents the results of a recent research project.
Optical counterparts of an ultraluminous X-Ray Source X-1 in NGC 2500
Authors: Aksaker N , Akyuz A , Avdan S , Avdan H 
Published: August 2019

ABSTRACT
We present the results of a search for optical counterparts of ultraluminous X-ray source (ULX) X-1 in the nearby galaxy NGC 2500 by using archival images taken with the Hubble Space Telescope Wide Field Camera (WFC3)/UVIS. We identified four optical sources as possible counterparts within the 2σ error radius of 0$^{\prime \prime }_{.}$3 in the images. However, only two of them were investigated as candidates for counterparts due to their point-like features and their identification in various filters. These two faint candidates have absolute magnitudes of MV ≈ −3.4 and −3.7. The spectral energy distributions of two candidates were modelled by a power-law spectrum with a photon index (α) ∼1.5, but the spectrum of one candidate shows a deviation. This may suggest that at least two components are responsible for the optical emission. The red part of the spectrum could arise from the companion star and the blue part could be interpreted as an evidence of reprocessing of the X-rays from the disc.
Tumoricidal stem cell therapy enables killing in novel hybrid models of heterogeneous glioblastoma
Authors: Satterlee Andrew B , Dunn Denise E , Lo Donald C , Khagi Simon , Hingtgen Shawn 
Published: August 2019

Abstract

Background
Tumor-homing tumoricidal neural stem cell (tNSC) therapy is a promising new strategy that recently entered human patient testing for glioblastoma (GBM). Developing strategies for tNSC therapy to overcome intratumoral heterogeneity, variable cancer cell invasiveness, and differential drug response of GBM will be essential for efficacious treatment response in the clinical setting. The aim of this study was to create novel hybrid tumor models and investigate the impact of GBM heterogeneity on tNSC therapies.

Methods
We used organotypic brain slice explants and distinct human GBM cell types to generate heterogeneous models ex vivo and in vivo. We then tested the efficacy of mono- and combination therapy with primary NSCs and fibroblast-derived human induced neural stem cells (iNSCs) engineered with tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) or enzyme-prodrug therapy.

Results
Optical imaging, molecular assays, and immunohistochemistry revealed that the hybrid models recapitulated key aspects of patient GBM, including heterogeneity in TRAIL sensitivity, proliferation, migration patterns, hypoxia, blood vessel structure, cancer stem cell populations, and immune infiltration. To explore the impact of heterogeneity on tNSC therapy, testing in multiple in vivo models showed that tNSC-TRAIL therapy potently inhibited tumor growth and significantly increased survival across all paradigms. Patterns of tumor recurrence varied with therapeutic (tNSC-TRAIL and/or tNSC–thymidine kinase), dose, and route of administration.

Conclusions
These studies report new hybrid models that accurately capture key aspects of GBM heterogeneity which markedly impact treatment response while demonstrating the ability of tNSC mono- and combination therapy to overcome certain aspects of heterogeneity for robust tumor kill.
Integrated clinical, histopathological, and molecular data analysis of 190 central nervous system germ cell tumors from the iGCT Consortium
Authors: Takami Hirokazu , Fukuoka Kohei , Fukushima Shintaro , Nakamura Taishi , Mukasa Akitake , Saito Nobuhito , Yanagisawa Takaaki , Nakamura Hideo , Sugiyama Kazuhiko , Kanamori Masayuki , Tominaga Teiji , Maehara Taketoshi , Nakada Mitsutoshi , Kanemura Yonehiro , Asai Akio , Takeshima Hideo , Hirose Yuichi , Iuchi Toshihiko , Nagane Motoo , Yoshimoto Koji , Matsumura Akira , Kurozumi Kazuhiko , Nakase Hiroyuki , Sakai Keiichi , Tokuyama Tsutomu , Shibui Soichiro , Nakazato Yoichi , Narita Yoshitaka , Nishikawa Ryo , Matsutani Masao , Ichimura Koichi 
Published: August 2019

Abstract

Background
We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management.

Methods
Data from the Intracranial Germ Cell Tumor Genome Analysis (iGCT) Consortium were reviewed. A total of 190 cases were classified as primary germ cell tumors (GCTs) based on central pathological reviews.

Results
All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker positive and 6.1% of non-germinomatous GCTs were marker negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better progression-free survival than those at atypical sites (P = 0.03). A molecular clinical association study revealed frequent mitogen-activated protein kinase (MAPK) pathway mutations in males (51.4% vs 14.3%, P = 0.007), and phosphatidylinositol-3 kinase/mammalian target of rapamycin (PI3K/mTOR) pathway mutations in basal ganglia cases (P = 0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance.

Conclusions
The in-depth findings of this study regarding clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.
Nonsense-Mediated mRNA Decay Deficiency Affects the Auxin Response and Shoot Regeneration in Arabidopsis
Authors: Chiam Nyet-Cheng , Fujimura Tomoyo , Sano Ryosuke , Akiyoshi Nobuhiro , Hiroyama Ryoko , Watanabe Yuichiro , Motose Hiroyasu , Demura Taku , Ohtani Misato 
Published: August 2019

AbstractPlants generally possess a strong ability to regenerate organs; for example, in tissue culture, shoots can regenerate from callus, a clump of actively proliferating, undifferentiated cells. Processing of pre-mRNA and ribosomal RNAs is important for callus formation and shoot regeneration. However, our knowledge of the roles of RNA quality control via the nonsense-mediated mRNA decay (NMD) pathway in shoot regeneration is limited. Here, we examined the shoot regeneration phenotypes of the low-beta-amylase1 (lba1)/upstream frame shift1-1 (upf1-1) and upf3-1 mutants, in which the core NMD components UPF1 and UPF3 are defective. These mutants formed callus from hypocotyl explants normally, but this callus behaved abnormally during shoot regeneration: the mutant callus generated numerous adventitious root structures instead of adventitious shoots in an auxin-dependent manner. Quantitative RT-PCR and microarray analyses showed that the upf mutations had widespread effects during culture on shoot-induction medium. In particular, the expression patterns of early auxin response genes, including those encoding AUXIN/INDOLE ACETIC ACID (AUX/IAA) family members, were significantly affected in the upf mutants. Also, the upregulation of shoot apical meristem-related transcription factor genes, such as CUP-SHAPED COTYLEDON1 (CUC1) and CUC2, was inhibited in the mutants. Taken together, these results indicate that NMD-mediated transcriptomic regulation modulates the auxin response in plants and thus plays crucial roles in the early stages of shoot regeneration.
Persistent eosinophilia among 21 historic cases of Strongyloides stercoralis infection: a case for routine follow-up and repeat treatment
Authors: Arkell Paul , Cosgrove Catherine , Riley Peter 
Published: August 2019

Abstract

Background
Strongyloidasis affects more than 100 million people worldwide and causes persisting infection.

Methods
We retrospectively reviewed 21 cases of parasitologically confirmed Strongyloides stercoralis infection at our centre.

Results
We found four individuals who had eosinophilia (>0.5x109/litre) more than 6 mo after treatment.

Conclusions
This may represent ongoing or relapsed infection. Our data support the need for continued follow-up of treated individuals, particularly those with abnormal host defences who are at risk of severe forms of the disease.
Sociodemographic Characteristics and the Stigmatization of Prescription Opioid Addiction
Authors: Goodyear Kimberly , Chavanne David 
Published: August 2019

Objectives:
The aim of this study was to investigate the relationship between participants’ sociodemographic characteristics and the degree to which they stigmatize people with an opioid addiction.

Methods:
A randomized, between-subjects case vignette study (n = 2605) was conducted with a nationwide online survey. We investigated how the stigmatization toward a hypothetical individual who misused prescription opioids differed across participants’ sociodemographic factors (ie, age, gender, education, race, and income).

Results:
Our results showed that study participants who were male, white, low-income, college graduates, and younger rated the hypothetical individual with an opioid addiction with lower stigma. In addition, we showed that participant gender moderated the relationship between information given about initiation of opioid use (received prescription opioids from a doctor vs took prescription opioids from a friend) and opioid stigma perceptions.

Conclusions:
Our results support previous findings that stigmatizing attitudes towards drug use vary across participant sociodemographic characteristics. The findings from our study provide a better understanding of how stigmatizing attitudes towards prescription opioid use differ across sociodemographic characteristics and can serve to improve negative perceptions of those with an opioid addiction.
Diagnosis and treatment of myasthenia gravis
Authors: Mantegazza Renato , Cavalcante Paola 
Published: August 2019

Purpose of reviewThis article provides an update on the most recent advances in diagnostic procedures and therapeutic approaches for myasthenia gravis, spanning from autoantibody and neuroelectrophysiological tests as diagnostic tools, to innovative and promising treatments based on biological drugs.Recent findingsNovel studies performed by cell-based assays (CBAs) indicate an improvement in the chance of identifying serum autoantibodies in myasthenic patients. Clinical trials on the use of biological drugs were recently concluded, providing important data on safety and efficacy of eculizumab, efgartigimod and amifampridine phosphate: the first, a complement blocker, showed long-term safety and efficacy in acetylcholine receptor (AChR)-positive myasthenic patients with refractory generalized disease; the second, the neonatal Fc receptor blocker, was well tolerated and clinically effective in both AChR-specific and muscle-specific kinase receptor (MuSK)-positive patients; the third, a blocker of presynaptic potassium channels, was found to be well tolerated and effective in MuSK-positive patients.SummaryCBAs can lead to a significant reduction of seronegative patients, improving myasthenia gravis diagnostic process. New biological drugs offer innovative approaches to treat myasthenic patients with generalized disease, promising to change the paradigm of treatment and to significantly enhance therapeutic success within a precision medicine framework.