bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current therapeutic landscape in multiple sclerosis: an evolving treatment paradigm
Authors: Cree Bruce A.C. , Mares Jan , Hartung Hans-Peter 
Published: April 2019

Purpose of review
To critically assess the current landscape of disease-modifying agents for multiple sclerosis (MS). Treatment algorithms will be discussed and studies for new agents in late development or recently approved are analyzed in terms of their impact on current treatment strategies.

Recent findings
A real-world study from Wales suggests that early initiation of highly effective therapy may provide more benefit that an escalation approach in relapsing MS. A study from the MSBase dataset found evidence that early treatment with highly effective therapies decreased the risk of developing secondary progressive MS. Ocrelizumab is highly efficacious in relapsing MS and in a group of patients with primary progressive MS. Another CD20 directed mAb, ofatumumab, is in phase 3. A large study examining extended interval dosing of natalizumab in an attempt to decrease the risk of developing progressive multifocal leukoencephalopathy is underway. Cladribine and alemtuzumab may work by immune reconstitution. Siponimod was recently approved by United States Federal Drug Administration for relapsing MS and active secondary progressive MS. Other S1P receptor modulators are being studied in phase 3 trials for relapsing MS. Cladribine received FDA approval as treatment for relapsing and active secondary progressive MS. Autologous hematopoetic stem-cell transplantation may be an option for treatment-refractory MS.

Summary
Development of disease-modifying agents in MS continues to be successful. Treatment algorithms need to take new developments into account.
Fourth Nerve Palsy Due to Neurocysticercosis
Authors: Hong Bennett Yau-Bun , Bean Andrew , Vickers Aroucha , Cykowski Matthew , Lee Andrew G. 
Published: April 2019

Abstract:
Neurocysticercosis is the most common disease of the nervous system caused by a parasite. Ophthalmological manifestations of cysticercosis typically are due to direct intraorbital or intraocular involvement, parenchymal brainstem involvement, or secondary to hydrocephalus or increased intracranial pressure. We describe a patient with a unilateral fourth nerve palsy, a rare presentation of neurocyticercosis.
A backward encoding approach to recover subcortical auditory activity
Authors: Schmidt Fabian , Demarchi Gianpaolo , Geyer Florian , Weisz Nathan 
Published: April 2019

1.AbstractSeveral subcortical nuclei along the auditory pathway are involved in the processing of sounds. One of the most commonly used methods of measuring the activity of these nuclei is the auditory brainstem response (ABR). Due to its low signal-to-noise ratio, ABR’s have to be derived by averaging over thousands of artificial sounds such as clicks or tone bursts. This approach cannot be easily applied to natural listening situations (e.g. speech, music), which limits auditory cognitive neuroscientific studies to investigate mostly cortical processes.We propose that by training a backward encoding model to reconstruct evoked ABRs from high-density electrophysiological data, spatial filters can be tuned to auditory brainstem activity. Since these filters can be applied (i.e. generalized) to any other data set using the same spatial coverage, this could allow for the estimation of auditory brainstem activity from any continuous sensor level data. In this study, we established a proof-of-concept by using a backward encoding model generated using a click stimulation rate of 30 Hz to predict ABR activity recorded using EEG from an independent measurement using a stimulation rate of 9 Hz. We show that individually predicted and measured ABR’s are highly correlated (r ∼ 0.7). Importantly these predictions are stable even when applying the trained backward encoding model to a low number of trials, mimicking a situation with an unfavorable signal-to-noise ratio. Overall, this work lays the necessary foundation to use this approach in more interesting listening situations.
Taxonomic variability over functional stability in the microbiome of Cystic Fibrosis patients chronically infected by Pseudomonas aeruginosa
Authors: Bacci Giovanni , Taccetti Giovanni , Dolce Daniela , Armanini Federica , Segata Nicola , Di Cesare Francesca , Lucidi Vincenzina , Fiscarelli Ersilia , Morelli Patrizia , Casciaro Rosaria , Negroni Anna , Mengoni Alessio , Bevivino Annamaria 
Published: April 2019

AbstractAlthough the cystic fibrosis (CF) lung microbiome has been characterized in several studies, little is still known about the functions harboured by those bacteria, and how they change with disease status and antibiotic treatment. The aim of this study was to investigate the taxonomic and functional temporal dynamics of airways microbiome in a cohort of CF patients. Multiple sputum samples were collected over 15 months from 22 patients with chronic P. aeruginosa infection, for a total of 79 samples. DNA extracted from samples was subjected to shotgun metagenomic sequencing allowing either strain-level taxonomic profiling and assessment of the functional metagenomic repertoire. High inter-patient taxonomic heterogeneity was found with short-term compositional changes during exacerbations and following antibiotic treatment. Each patient exhibited distinct sputum microbial communities at the taxonomic level, and strain-specific colonization of traditional CF pathogens, including P. aeruginosa, and emerging pathogens. Sputum microbiome was found to be extraordinarily resilient following antibiotic treatment, with rapid recovery of taxa and metagenome-associated gene functions. In particular, a large core set of genes, including antibiotic resistance genes, were shared across patients despite observed differences in clinical status or antibiotic treatment, and constantly detected in the lung microbiome of all subjects independently from known antibiotic exposure, suggesting an overall microbiome-associated functions stability despite taxonomic fluctuations of the communities.IMPORTANCEWhile the dynamics of CF sputum microbial composition were highly patient-specific, the overall sputum metagenome composition was stable, showing a high resilience along time and antibiotic exposure. The high degree of redundancy in the CF lung microbiome could testifies ecological aspects connected to the disease that were never considered so far, as the large core-set of genes shared between patients despite observed differences in clinical status or antibiotic treatment. Investigations on the actual functionality (e.g. by metatranscriptomics) of the identified core-set of genes could provide clues on genetic function of the microbiome to be targeted in future therapeutic treatments.
Streptococcus pyogenescapsule promotes microcolony-independent biofilm formation
Authors: Matysik Artur , Kline Kimberly A. 
Published: April 2019

ABSTRACTBiofilms play an important role in the pathogenesis of Group A Streptococcus (GAS), a gram-positive pathogen responsible for a wide range infections and significant public health impact. Although most GAS serotypes are able to form biofilms, there is large heterogeneity between individual strains in biofilm formation, as measured by standard crystal violet assays. It is generally accepted that biofilm formation includes initial adhesion of bacterial cells to a surface, followed by microcolony formation, biofilm maturation, and extensive production of extracellular matrix that links together proliferating cells and provides a scaffold for the three-dimensional biofilm structure. However, our studies show that for GAS strain JS95, microcolony formation is not an essential step in static biofilm formation, and instead, biofilm can be effectively formed from slow-growing or non-replicating late exponential or early stationary planktonic cells, via sedimentation and fixation of GAS chains into biofilms. In addition, we show that the GAS capsule specifically contributes to the alternative, sedimentation-initiated biofilms. Microcolony-independent, sedimentation biofilms are similar in morphology and 3-D structure to biofilms initiated by actively dividing planktonic bacteria. We conclude that GAS can form biofilms by an alternate, non-canonical mechanism that does not require transition from microcolony formation to biofilm maturation, and which may be obscured by biofilm phenotypes that arise via the classical biofilm maturation processes.IMPORTANCEThe static biofilm assay is a common tool for easy biomass quantification of biofilm forming bacteria. However,S. pyogenesbiofilm formation as measured by the static assay is strain dependent and yields heterogeneous results for different strains of the same serotype. In this study, we show that two independent mechanisms, for which the protective capsule contributes opposing functions, may contribute to static biofilm formation. We propose that separation of these mechanisms for biofilm formation might uncover previously unappreciated biofilm phenotypes that may otherwise be masked in the classic static assay.
Robust Reconstruction of CRISPR and Tumor Lineage Using Depth Metrics
Authors: Sugino Ken , Lee Tzumin 
Published: April 2019

SummaryLineage reconstruction using CRISPR edited barcodes are becoming wide-spread and methods robust against noise are in need. Neighbor-Joining (NJ) algorithm is a robust distance based algorithm extensively used in phylogeny field. NJ is also used for CRISPR-encoded-lineage (CEL) reconstruction with proper re-rooting since NJ is unrooted algorithm. However, we found NJ works without re-rooting for reconstructing CEL when the lineage contains multiple trees but not for a single tree. Examining why this is the case leads to the idea of “depth metrics”. The notion of depth metrics also naturally explains why Russell-Rao metric, previously found best metric for CEL reconstruction, works well. Furthermore, based on the probabilistic model of CEL, we constructed a new metric that performs better than Russell-Rao metric. We also propose inferring ancestral code during reconstruction instead of using a linkage method. These, together with Nearest-Neighbor-Interchange resulted in a new robust method for reconstructing CEL or tumor-cell-lineages which share same assumptions as CEL.
Transmission of prion infectivity from blood by peptoid-conjugated beads
Authors: Hornemann Simone , Schwarz Petra , Rushing Elisabeth J. , Connolly Michael D. , Zuckermann Ronald N. , Yam Alice Y. , Aguzzi Adriano 
Published: April 2019

AbstractPrions cause transmissible infectious diseases in humans and animals and have been found to be transmissible by blood transfusion even in the presymptomatic stage. However, the concentration of prions in body fluids such as blood and urine is extremely low, and therefore direct diagnostic tests on such specimens often yield false-negative results. Quantitative preanalytical prion enrichment may significantly improve the sensitivity of prion assays by concentrating trace amounts of prions from large volumes of body fluids. Here we show that beads conjugated to positively charged peptoids not only captured PrP aggregates from plasma of prion-infected hamsters, but also adsorbed prion infectivity in both the symptomatic and preclinical stages of the disease. Bead absorbed prion infectivity efficiently transmitted disease to transgenic indicator mice. We found that the readout of the peptoid-based misfolded protein assay (MPA) correlates closely with prion infectivity in vivo, thereby validating the MPA as a simple, quantitative, and sensitive surrogate indicator of the presence of prions. The reliable and sensitive detection of prions in plasma will enable a wide variety of applications in basic prion research and diagnostics.
Use of an automated pyrosequencing technique for confirmation of Sickle Cell Disease
Authors: Martino CC , Alencar CS , Loureiro P , Carneiro-Proietti AB , Máximo CA , Mota RA , Rodrigues DOW , Gaburo N , Kelly S , Sabino EC ,   for the International Component of the NHLBI Recipient Epidemiology and Donor Evaluation Study (REDS-III)
Published: April 2019

ABSTRACTBackgroundThe diagnosis of sickle cell disease (SCD) is made by hemoglobin assays such as high-performance liquid chromatography (HPLC), isoelectric focusing and cellulose acetate or citrate agar electrophoresis. These assays are easy to perform and used in large-scale newborn screening in many countries. These tests however may not easily differentiate Sβ0 thalassemia from SS or identify other hemoglobin variants, and in this case, hemoglobin (HBB) gene sequencing may be necessary.ObjectivesTo develop a high throughput DNA based confirmatory assay for SCD and to detect mutations in the HBB gene.MethodsWe developed an automated pyrosequencing technique (PyS) based on QIAGEN technology (Hilden, Germany) to detect homozygous or heterozygous hemoglobin S mutations as well as hemoglobin C mutations. The technique was tested on 2,748 samples from patients enrolled in a multi-center SCD cohort in Brazil. Patients were previously tested using HPLC to diagnose SCD as part of routine clinical care. Any subjects with discrepant results between HPLC and PyS or with heterozygous hemoglobin S detected had Sanger sequencing of the HBB gene.ResultsWe identified 168 samples with discrepant results between HPLC and PyS and 100 with concordant HPLC and PyS= heterozygous S, which would suggest Sβ-thalassemia or other hemoglobin S variants. The PyS assay correctly identified 1906 (98.7%) of the 1930 HbSS and 628 (98.7%) of the 636 HbSC samples. Of the 179 remaining samples, PyS correctly indicated S heterozygosis in 165 (92.2%). Of the 165 heterozygous S samples confirmed by Sanger as consistent with Sβ thalassemia genotype, 84 samples were classified as Sβ0 thalassemia and 81 as Sβ+ thalassemia. The most frequent beta thalassemia mutations of Sβ0 and Sβ+ were HBB: c.118C>T (Gln40Stop) and HBB c.92 + 6T> C, respectively.DiscussionThe PyS proved to be satisfactory for large-scale confirmatory testing of hemoglobin mutation. Moreover, with this study we were able to describe the most common β+ and β0 mutations in SCD patients with Sβ-thalassemia in a large multi-institutional SCD cohort in Brazil.
Mck1 defines a key S-phase checkpoint effector in response to various degrees of replication threats
Authors: Li Xiaoli , Jin Xuejiao , Sharma Sushma , Liu Xiaojing , Zhang Jiaxin , Niu Yanling , Li Jiani , Li Zhen , Zhang Jingjing , Cao Qinhong , Liu Beidong , Lou Huiqiang 
Published: April 2019

AbstractThe S-phase checkpoint plays an essential role in regulation of the ribonucleotide reductase (RNR) activity to maintain the dNTP pools. How eukaryotic cells respond appropriately to different levels of replication threats remains elusive. Here, we have identified that a conserved GSK-3 kinase Mck1 cooperates with Dun1 in regulating this process. DeletingMCK1sensitizesdun1Δ to hydroxyurea (HU) reminiscent ofmec1Δ orrad53Δ. As a kinase at the downstream of Rad53, Mck1 does not participate in the post-translational regulation of RNR as Dun1 does, but Mck1 can release the Crt1 repressor from the promoters ofRNR2/3/4by phosphorylation. Meanwhile, Hug1, an Rnr2 inhibitor, is induced to fine-tune the dNTP levels. When cells suffer a more severe threat, Mck1 can inhibit the transcription ofHUG1. Importantly, only a combined deletion ofHUG1andCRT1, can confer a dramatic boost of dNTP levels and the survival ofmck1Δdun1Δ ormec1Δ cells assaulted by a lethal dose of HU. These findings reveal the division-of-labor between Mck1 and Dun1 at the S-phase checkpoint pathway to fine-tune dNTP homeostasis.Author SummaryThe appropriate amount and balance of four dNTPs are crucial for all cells correctly copying and passing on their genetic material generation by generation. Eukaryotes have developed an alert and response system to deal with the disturbance. Here, we uncovered a second-level effector branch. It is activated by the upstream surveillance kinase cascade, which can induce the expression of dNTP-producing enzymes. It can also reduce the inhibitor of these enzymes to further boost their activity according to the degrees of threats. These findings suggest a multi-level response system to guarantee dNTP supply, which is essential to maintain genetic stability under various environmental challenges.
Tone of earnings announcements in sin industries
Authors: Luo Yan , Zhou Linying 
Published: April 2019

Purpose
The purpose of this paper is to investigate the empirical association between the tone of earnings announcements and a company’s membership in a sin industry.

Design/methodology/approach
This study constructs a model of the determinants of earnings announcement tone to examine the impact of sin industry membership on earnings announcement tone. An interaction term between CEO power (CEO–chairman duality) and sin industry membership is used to test whether CEO power moderates the strength of the association. The earnings announcements tone is measured using the spread in the proportion of positive and negative words. The category of sin industry includes not only industries such as tobacco, gambling and alcohol, but also industries associated with emerging environmental, social, and ethical issues (i.e. firearms, oil and cement).

Findings
The analysis of a sample of US firms from the 1994 to 2013 period shows that the tone of earnings announcement is less optimistic for companies in sin industries, but this association is weaker for companies that are led by powerful CEOs. The results remain robust to alternative definitions of sin industry membership and CEO power (CEO tenure) and to alternative model specifications.

Originality/value
The findings suggest that although sin companies cannot change the nature of their business, the management of such companies, in general, uses a less aggressive tone in their earnings announcements. These results further investors’ understanding of sin companies’ reporting behavior.
How cross-culture affects the outcomes of co-creation
Authors: Grott Emily Mary , Cambra-Fierro Jesus , Perez Lourdes , Yani-de-Soriano Mirella 
Published: April 2019

Purpose
The aim of this study is two-fold. Firstly, to examine the outcomes of co-creation from a customer perspective using well-recognised customer management variables (customer satisfaction, loyalty and word-of-mouth (WOM). Secondly, to assess potential cross-cultural differences that may exist within the context of co-creation.

Design/methodology/approach
A questionnaire was completed in the banking services industry, and the final valid sample comprised individuals from the UK and Spain. Multi-sample analysis was carried out using PLS software.

Findings
Co-creation has a direct influence on customer satisfaction, customer loyalty and WOM; co-creation activities lead to cumulative customer satisfaction, which also affects customer loyalty and positive WOM. Furthermore, the results show that the direct relationships between co-creation and loyalty and WOM are more powerful for British consumers than Spanish consumers, who need to feel satisfied prior to demonstrating loyalty and engaging in positive WOM.

Practical implications
Firms can use co-creation as a strategic tool if they provide trustworthy collaboration spaces. Furthermore, firms need to adapt the way they interact, listen and respond to customers in different cultural contexts. Trustworthy collaboration spaces and adapting to cultural differences can result in customers who are more satisfied, loyal to the company and more likely to carry out positive WOM, which can ultimately lead to future business.

Originality/value
This study provides insights into co-creation from a customer perspective. Although much service research has examined the drivers of customer co-creation, literature that analyses the consequences of customer co-creation is still scarce. Moreover, this is the first study to provide empirical evidence of cross-cultural differences within the context of co-creation.
Inflation and income inequality in developed and developing countries
Authors: Siami-Namini Sima , Hudson Darren 
Published: April 2019

Purpose
The purpose of this paper is to investigate both linear and/or nonlinear effects of inflation on income inequality and to test the Kuznets hypothesis using panel data of 24 developed countries (DCs) and 66 developing countries (LDCs) observed over the period of 1990–2014.

Design/methodology/approach
This paper explores the short- and long-run Granger causality relationship between inflation and income inequality using the Toda and Yamamoto (1995) procedure and a Vector Error Correction Model (VECM) approach. The existence of a nonlinear relationship between inflation and income inequality is confirmed implying as inflation rises income inequality decreases. Income inequality then reaches a minimum and then starts rising again. The findings of this paper show the existence of Kuznets “U-shaped” hypothesis between income inequality and real GDP per capita in DCs group, and the existence of Kuznets’ inverted “U-shaped” hypothesis for LDCs group.

Findings
The results indicate that there is no bi-directional Granger causality between inflation and income inequality in the short-run, but, there is bi-directional Granger causality in the long-run for both the DCs and LDCs group. The results help us to assess the effectiveness of monetary policy in reducing income inequality in both the DCs and LDCs group. As a policy implication, monetary policy is often aimed at controlling the annual rate of inflation in the long-run with a short-run focus on reducing output gaps and creating employment. However, managing inflation may have implications for income inequality.

Originality/value
This is original research paper which analyzes the “U-shaped” and inverted “U-shaped” paths of income inequality and real GDP per capita for large sample of two group countries including developed and developing countries, respectively. Also, this paper analyzes the nonlinear relationship between inflation and income inequality in two groups. Furthermore, this paper investigates the short- and long-run relationship between variables. The results are important for policy makers.
The role of inclusive development and military expenditure in modulating the effect of terrorism on governance
Authors: Asongu Simplice , Nwachukwu Jacinta , le Roux Sara 
Published: April 2019

PurposeThe purpose of this paper is to investigate the role of inclusive human development and military expenditure in modulating the effect of terrorism on governance.Design/methodology/approachIt is based on 53 African countries for the period 1998–2012 and interactive generalised method of moments is employed. Six governance indicators from the World Bank and two terrorism variables are used, namely, domestic and transnational terrorism dynamics.FindingsThe following main findings are established. There is a negative net effect on governance (regulation quality and corruption-control) when inclusive human development is used to reduce terrorism. There is a positive net impact on governance (voice and accountability and rule of law) when military expenditure is used to reduce domestic terrorism.Originality/valueThe authors have complemented the sparse literature on the use of policy variables to mitigate the effect of policy syndromes on macroeconomic outcomes.