bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic alteration of ferredoxin NADP+-reductase or cysteine desulfurase in piperaquine-resistant Plasmodium berghei restores susceptibility to lumefantrine and abolishes the impact of probenecid, verapamil, and cyproheptadine
Authors: Bara Fagdéba David , Ndung’u Loise , Onchieku Noah Machuki , Irungu Beatrice , Karou Simplice Damintoti , Kimani Francis , Matoke-Muhia Damaris , Mwitari Peter , Magoma Gabriel , Nzila Alexis , Kiboi Daniel
Published: November 2019

Chemotherapy remains central in the control of malaria; however, resistance has consistently thwarted these efforts. Currently, lumefantrine (LM), and piperaquine (PQ) drugs, are essential components in the mainstay artemisinin-based therapies used for the treatment of malaria globally. Using LM and PQ-resistant Plasmodium berghei, we measured the effect of known chemosensitizers: probenecid, verapamil, or cyproheptadine on the activity of LM or PQ. Using PlasmoGEM vectors, we then evaluated the impact of deleting cysteine desulfurase (SufS) or over-expressing Ferredoxin NADP+ reductase (FNR), genes that mediate drug action. Our data showed that, only cyproheptadine at 5mgkg−1 restored LM activity by above 65% against the LM-resistant parasites (LMR) but failed to reinstate PQ activity against the PQ-resistant parasites (PQR). Whereas the PQR had lost significant susceptibility to LM, the three chemosensitizers; cyproheptadine, probenecid, and verapamil, restored LM potency against the PQR by above 70%, 60%, and 55% respectively. We thus focused on LM resistance in PQR. Deletion of the SufS or overexpression of the FNR genes in the PQR abolished the impact of the chemosensitizers on the LM activity, and restored the susceptibility of the PQR parasites to LM. Taken together, we demonstrate the association between SufS or FNR genes with the action of LM and chemosensitizers in PQR parasites. There is, however, need to interrogate the impact of the chemosensitizers and the role of SufS or FNR genes on LM action in the human malaria parasite, Plasmodium falciparum.
BeamDelta: simple alignment tool for optical systems
Authors: Hall Nicholas J. , Pinto David Miguel Susano , Dobbie Ian M.
Published: November 2019

BeamDelta is a tool to help align optical systems. It greatly assists in assembling bespoke optical systems by providing a live view of the current laser beam position and a reference position.

Even a simple optical setup has multiple degrees of freedom that affect the alignment of beam paths. These degrees of freedom rise exponentially with the complexity of the system. The process of aligning all the optical components for a specific system is often esoteric and poorly documented, if it is documented at all.

Alignment methods used often rely on visual inspection of beams impinging on pinholes in the beam path. Typically requiring an experienced operator staring at diffuse reflections for extended periods of time. This can lead to a decline in accuracy due to eye strain, flash blindness as well as symptoms such as headaches and, possibly, more serious retinal damage.

Here we present BeamDelta a simple alignment tool and accompanying software interface which allows users to obtain accurate alignment as well as removing the necessity of staring at diffuse laser reflections. BeamDelta is a robust alignment tool as it doesn’t require any precise alignment itself.
MicroRNA 1253 regulation of WAVE2 and its relevance to health disparities in hypertension
Authors: Arkorful Mercy A. , Hooten Nicole Noren , Zhang Yongqing , Hewitt Amirah N. , Sanchez Lori Barrientos , Evans Michele K. , Dluzen Douglas F.
Published: November 2019

The prevalence of hypertension among African Americans (AAs) in the US is among the highest of any demographic and affects over two-thirds of AA women. Previous data from our laboratory suggests substantial differential gene expression (DGE) of mRNAs and microRNAs (miRNAs) exists within peripheral blood mononuclear cells (PBMCs) isolated from AA and white women with or without hypertension. We hypothesized that DGE by race may contribute to racial differences in hypertension. We found that the Wiskott-Aldrich syndrome protein Verprolin homologous-2 (WAVE2) is differentially-expressed in AA women with hypertension, along with several other members of the actin cytoskeleton signaling pathway that plays a role in cell shape and branching of actin filaments. We performed an in silico miRNA target prediction analysis that suggested miRNA miR-1253 regulates WAVE2. Transfection of miR-1253 mimics into human umbilical vein endothelial cells (HUVECs) and human aortic endothelial cells (HAECs) significantly repressed WAVE2 mRNA and protein levels (P<0.05), and a luciferase reporter assay confirmed that miR-1253 regulates the WAVE2 3’ UTR (P<0.01). miR-1253 over-expression in HUVECs significantly increased HUVEC lamellipodia formation (P<0.01), suggesting the miR-1253/WAVE2 interaction may play a role in endothelial cell shape and actin cytoskeleton function. Together, we have identified novel roles for miR-1253 and WAVE2 in a hypertension-related disparities context. This may ultimately lead to the discovery of additional actin-related genes which are important in the vascular-related complications of hypertension and influence the disproportionate susceptibility to hypertension among AAs in general and AA women in particular.
Serine and glycine are essential for human muscle progenitor cell population expansion
Authors: Gheller Brandon J. , Blum Jamie E. , Bender Erica L. , Gheller Mary E. , Lim Esther W. , Handzlik Michal K. , Stover Patrick J. , Field Martha S. , Cosgrove Benjamin D. , Metallo Christian M. , Thalacker-Mercer Anna E.
Published: November 2019

Skeletal muscle regeneration is reliant on a population of muscle specific adult stem cells (muscle progenitor cells; MPCs). During regeneration, the MPC population undergoes a transient and rapid period of population expansion, which is necessary to repair damaged myofibers and restore muscle homeostasis. Much research has focused on the age-related accumulation of negative regulators of regeneration, while the age-related decline of nutrient and metabolic determinants of the regenerative process needs examination. We hypothesized that older individuals, a population that is at risk for protein malnutrition, have diminished availability of amino acids that are necessary for MPC function. Here, we identified that levels of the non-essential amino acid serine are reduced in the skeletal muscle of healthy, older individuals. Furthermore, using stable-isotope tracing studies, we demonstrate that primary, human MPCs (hMPCs) exhibit a limited capacity forde novobiosynthesis of serine and the closely related amino acid glycine. We identified that serine and glycine are essential forhMPC proliferation and, therefore, population expansion. Serine and glycine were necessary to support synthesis of the intracellular antioxidant glutathione, and restriction of serine and glycine was sensed in an EIF2α-dependent manner resulting in cell cycle arrest in G0/G1. In conclusion, we elucidate that, despite an absolute requirement of serine/glycine forhMPC proliferation, availability of serine in the skeletal muscle microenvironment is limited to thehMPCs of healthy older adults and is a likely underlying mechanism for impaired skeletal muscle regeneration with advancing age.

Graphical Abstract
A Germinal Center-Associated Microenvironmental Signature Reflects Malignant Phenotype and Outcome of Diffuse Large B-cell Lymphoma
Authors: Miyawaki Kohta , Kato Koji , Sugio Takeshi , Sasaki Kensuke , Miyoshi Hiroaki , Semba Yuichiro , Kikushige Yoshikane , Mori Yasuo , Kunisaki Yuya , Iwasaki Hiromi , Miyamoto Toshihiro , Kuo Frank C. , Aster Jon C. , Ohshima Koichi , Maeda Takahiro , Akashi Koichi
Published: November 2019

Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell malignancy with varying prognosis after the gold standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Several prognostic models have been established by focusing primarily on characteristics of lymphoma cells themselves including cell-of-origin, genomic alterations, and gene/protein expressions. However, the prognostic impact of lymphoma microenvironment and its association with characteristics of lymphoma cells are not fully understood. Using highly-sensitive transcriptome profiling of untreated DLBCL tissues, we here assess the clinical impact of lymphoma microenvironment on the clinical outcomes and pathophysiological, molecular signatures in DLBCL. The presence of normal germinal center (GC)-microenvironmental cells, including follicular T cells, macrophage/dendritic cells, and stromal cells, in lymphoma tissue indicates a positive therapeutic response. Our prognostic model, based on quantitation of transcripts from distinct GC-microenvironmental cell markers, clearly identified patients with graded prognosis independently of existing prognostic models. We observed increased incidences of genomic alterations and aberrant gene expression associated with poor prognosis in DLBCL tissues lacking GC-microenvironmental cells relative to those containing these cells. These data suggest that the loss of GC-associated microenvironmental signature dictates clinical outcomes of DLBCL patients reflecting the accumulation of “unfavorable” molecular signatures.
Unspecific binding but specific disruption of the group I intron by the StpA chaperone
Authors: Reinharz Vladimir , Tlusty Tsvi
Published: November 2019

Chaperone proteins — the most disordered among all protein groups — help RNAs fold into their functional structure by destabilizing misfolded configurations or stabilizing the functional ones. But disentangling the mechanism underlying RNA chaperoning is challenging, mostly due to inherent disorder of the chaperones and the transient nature of their interactions with RNA. In particular, it is unclear how specific the interactions are and what role is played by amino acid charge and polarity patterns. Here, we address these questions in the RNA chaperone StpA. By adapting direct coupling analysis (DCA) to treat in tandem sequences written in two alphabets, nucleotides and amino acids, we could analyze StpA-RNA interactions and identify a two-pronged mechanism: StpA disrupts specific positions in the group I intron while globally and loosely binding to the entire structure. Moreover, the interaction is governed by the charge pattern: negatively charged regions in the destabilizing StpA N-terminal affect a few specific positions in the RNA, located in stems and in the pseudoknot. In contrast, positive regions in the C-terminal contain strongly coupled amino acids that promote non-specific or weakly-specific binding to the RNA. The present study opens new avenues to examine the functions of disordered proteins and to design disruptive proteins based on their charge patterns.
Conformational heterogeneity in apo and drug-bound structures of Toxoplasma gondii prolyl-tRNA synthetase
Authors: Mishra Siddhartha , Malhotra Nipun , Kumari Shreya , Sato Mizuki , Kikuchi Haruhisa , Yogavel Manickam , Sharma Amit
Published: November 2019

Prolyl-tRNA synthetase (PRS) is a member of the aminoacyl-tRNA synthetase family that drives protein translation in cells. The apicomplexan PRSs are validated targets of febrifugine (FF) and its halogenated derivative halofuginone (HF). PRSs are of great interest for drug development against Plasmodium falciparum and Toxoplasma gondii. In this study, structures of apo and FF-bound T. gondii (TgPRS) are revealed and the dynamic nature of the conformational changes that occur upon FF binding is unraveled. In addition, this study highlights significant conformational plasticity within two different crystal structures of apo PRSs but not within drug-bound PRSs. The apo PRSs exist in multi-conformational states and manifest pseudo-dimeric structures. In contrast, when FF is bound the PRS dimer adopts a highly symmetrical architecture. It is shown that TgPRS does not display extant fold switching, in contrast to P. falciparum PRS, despite having over 65% sequence identity. Finally, structure-comparison analyses suggest the utility of r.m.s.d. per residue (r.m.s.d./res) as a robust tool to detect structural alterations even when the r.m.s.d. is low. Apo TgPRS reveals FF/HF-induced rigidity and this work has implications for drug-design studies that rely on the apo structures of target proteins.
Field work supervision through open and distance learning: an Indian perspective
Authors: Guin Sayantani
Published: November 2019

Purpose

The purpose of this paper is to highlight the method of field work supervision in BSW and MSW programmes offered through open and distance learning (ODL) at the Indira Gandhi National Open University (IGNOU). The key argument of the paper will focus on the fact that despite various challenges, field work supervision through ODL provides lot of scope and flexibility to students, generating a cadre of trained social work professionals.

Design/methodology/approach

The paper adopts a case study approach in presenting the various methods employed for field work supervision by the University. This section will highlight the achievements in terms of developing indigenous theory course and the best practices adopted by IGNOU to train social work professionals through adequate and timely supervision in the ODL mode.

Findings

Field work supervision in the ODL mode poses many challenges, especially when compared to that in the conventional universities. Some of these include irregular meeting of supervisor and student, inability of students to meet supervisor due to several reasons like remote location, poor economic background, lack of leave for working professionals, etc.

Research limitations/implications

There is a need for developing a mechanism to regularly orient field work supervisors in supervising students in the ODL mode. It is recommended that regular field work practicum workshops be conducted for supervisors and students. Viva for field work could be made mandatory at different regional centres. Field work supervision could be enhanced through the use of technology, namely, Skype, e-mail, WhatsApp, etc.

Originality/value

The paper describes the various nuances of field work supervision through ODL system. It is an original work and is of great value in understanding the challenges and difficulties encountered by learners and academic counsellors throughout the process of supervision. The paper highlights important recommendations by the stakeholders themselves in mitigating the challenges faced during field work supervision through ODL.
Travel destination choice: does perception of food safety risk matter?
Authors: Yeung Ruth M.W. , Yee Wallace M.S.
Published: November 2019

Purpose

The purpose of this paper is to explore the relationship between risk characteristics, risk perception and future travel intention in the context of food safety risk.

Design/methodology/approach

This research used a structured questionnaire administered to a convenience sample of 715 participants. By using structural equation modelling method, a travel intention framework was successfully developed to test the impact of characteristics of food safety risk on perception of risk, and subsequently on travel intention. In addition, the framework was also tested and compared with different demographic groups.

Findings

The research confirms that the characteristics of risk have impact on the two dimensions of perception of risk, namely, likelihood of occurrence and consequence of occurrence in turn travel intention. Furthermore, characteristics of risk affect demographic groups differently.

Research limitations/implications

The finding of this study offers insight into the distinct effects between the two dimensions, namely, likelihood and consequence of risk perception and each dimension consists of different loss components and has different effect on travel intention.

Practical implications

The framework provides insight to the government and travel industry that risk perception is a paramount issue for travellers when making destination decision. As such, the government and travel industry should take action to prevent the occurrence of food risk and to reduce the severity consequence of the risk when it occurs.

Originality/value

This research is one of the few studies generating new insights into perception of food safety risk in international tourism from the social science and marketing perspective.
Integrated project delivery implementation framework for water and wastewater treatment plant projects
Authors: Andary Elie Georges , Abi Shdid Caesar , Chowdhury Arindam , Ahmad Irtishad
Published: November 2019

Purpose

The public nature of water and wastewater construction capital projects has rendered design-bid-build (DBB) as the delivery method of choice for such projects over the past years. Shortcomings inherent to DBB have had a negative effect on the key performance indicators (KPIs) of these projects. Numerous studies have been published about the benefits offered by integrated project delivery (IPD) in improving the delivery of DBB projects. Links correlating IPD principles to improvements in KPIs of DBB construction projects have not been established scientifically, thus leaving owners with no guidance on which IPD principle(s) to implement in order to improve a particular project KPI. The paper aims to discuss this issue.

Design/methodology/approach

Actual data were collected from 43 water and wastewater construction projects – including two control projects with full implementation of selective IPD principles – and used to compute major projects KPIs. Regression analysis and a focus group are then utilized to determine the effect of each implemented IPD principle on various project KPIs.

Findings

Implementation of open communication was found to have a significant effect on reducing project cost overrun, and the co-location of teams significantly reduced the time to respond to RFIs. Collaborative decision making significantly reduced the cost of field rework. Other IPD principles showed less-significant effects on project KPIs and were concluded to be ineffective at improving the projects’ performance.

Practical implications

An implementation framework is developed that can guide utility owners on which IPD principle(s) to implement in order to improve specific project KPIs.

Originality/value

This study demonstrates that not all IPD principles will result in performance improvement of a project. A selective and cost-effective implementation of certain IPD principle will have to be based on the nature of the project and the particular KPIs targeted for improvement.
Fragmented time and domiciliary care quality
Authors: Atkinson Carol , Crozier Sarah
Published: November 2019

Purpose

The purpose of this paper is to examine the marketization of domiciliary care, its consequences for employment practice, specifically fragmented time, and the implications for care quality.

Design/methodology/approach

Focus groups and face-to-face or telephone interviews were conducted with care commissioners, service providers and care workers across Wales. There were 113 participants in total.

Findings

These demonstrate fragmented time’s negative consequences for service providers, care workers and, ultimately, care quality.

Research limitations/implications

No care recipients were interviewed and care quality was explored through the perceptions of other stakeholders.

Social implications

For policy makers, tensions are evidenced between aspirations for high-quality care and commissioning practice that mitigates against it. Current care commissioning practices need urgent review.

Originality/value

The research extends the definition of fragmented time and integrates with a model of care quality to demonstrate its negative consequences. Links between employment practice and care quality have only previously been hinted at.
How do suppliers address stringent environmental requirements from buyers? An exploratory study in the Bangladesh ready-made garment industry
Authors: Shumon Rezaul , Halim Zaheed , Rahman Shams , Ahsan Kamrul
Published: November 2019

Purpose

Stakeholders such as customers, governments and environmental organisations are more concerned than ever about the impact of supply chain practices on the environment, leading firms to introduce environmental requirements into their supply contracts. While the extant literature on supply chains acknowledges this trend, it fails to inform comprehensively on the concept of “stringent environmental requirement” and its consequences. The purpose of this paper is to investigate this concept and explore how such requirements may translate into supplier environmental performance.

Design/methodology/approach

Qualitative methodology was adopted by the study and data were collected through conducting eight case studies in the Bangladesh ready-made garment (RMG) industry.

Findings

A number of factors were found to be influencing suppliers’ perception of stringency, such as uncertainty relating to the newness and deadline of buyers’ environmental requirements, the complexity of implementing the requirements, and the use of buyer-specific frameworks. The research also shows that suppliers’ efforts in building environmental capability play a vital role in dealing with stringent environmental requirements.

Research limitations/implications

The case studies are limited to the Bangladesh RMG industry. Given that environmental regulations vary across different countries and industries, the data may not reflect all the possible variations in stringent environmental requirements.

Practical implications

The new insight proposed by this research can guide firms to further understand how supplier environmental performance and the sustainability of their supply chain can be achieved. The research provides broad insight into how suppliers can address stringent environmental requirements and improve their environmental performance.

Originality/value

This research establishes evidence for the relatively new phenomenon of “stringent environmental requirements”, and develops a theoretical framework to demonstrate the relationships among the critical determinants relevant to this phenomenon.
Application of business model innovation for new enterprises
Authors: Panda Bijaya Kumar
Published: November 2019

Purpose

The purpose of this paper is to study the details of new age digital business using a freemium business model.

Design/methodology/approach

Study of the various prospects of various digital business firms like revenues, customer base, share price, ranks. Uses of freemium business model to hold on to existing customers and attract new customers.

Findings

Innovative service or product offerings and growth strategy is the base of this business model. So businesses must assess innovation strategy before deciding whether to opt the freemium business model or not. Retaining the existing user and constant addition of new users are the founding stone of the freemium business model. So, the value offerings have to be well perceived by the customer so that switching costs will be increased for them and the customer will remain loyal.

Originality/value

Analyzing consumer behavior with recent analytical tools and techniques such as web analytics, bigdata analytics are required in order to get deeper market knowledge. It is crucial to get the knowledge of recent trends of markets, the perception of customer and customer’s journey mapping in order to run a business with freemium model.
Examining performance change and its drivers in Irish ports 2000-2016
Authors: O'Connor Eamonn , Hynes Stephen , Vega Amaya , Evers Natasha
Published: November 2019

Purpose

The purpose of this paper is to examine performance change in the Irish state-owned port sector over the 2000-2016 period using a case study approach.

Design/methodology/approach

For analysis, qualitative sources are used to construct an explanatory account for the quantitative measures of productivity, profitability and traffic shift-share change across the major ports within the system.

Findings

The results show that overall change in performance largely follows that of the macro-economic performance of the region, characterised by pre-recession growth, decline during the recession and post-recession recovery. Across the ports, however, there was a notable divergence in performance post-recession. Identified factors affecting performance change across the period include demand-side structural change, labour rationalisation and degree of private sector participation.

Originality/value

This study addresses a gap in the formal evaluation of port performance in Ireland. The study further demonstrates the potential of in-depth case study analysis for uncovering insights into the drivers of performance across a number of dimensions, thus allowing for the contextualisation of results. The study of a small number of cases enables the use of rich qualitative sources to create strong narratives, which combined with quantitative measures of performance, can lead to new insights.
Does environmental disclosure have an auditing effect?
Authors: Yao Sheng , Pan Lingling , Zhang Zhipeng
Published: November 2019

Purpose

The purpose of this paper is to investigate whether firms with high environmental disclosure have a low possibility of non-standard audit opinions and audit fees and whether this trend is more obvious after than prior to the Measures for the Disclosure of Environmental Information (Measure) implemented in 2008.

Design/methodology/approach

Based on the Measures implemented in 2008, the authors select data for the listed manufacturing firms from 2004 to 2006 (Pre-Measure) and from 2009 to 2011 (Post-Measure) as research samples to investigate the relationships between environmental disclosures, audit opinions and audit fees with difference in difference models. In addition, we also consider the influence of media attention, the polluting industry and internal control on the audit effect of environmental disclosure.

Findings

The results show that the level of environmental disclosure is significantly negatively correlated with the possibility of issuing non-standard audit opinions and audit fees after measure is implemented, especially hard environmental information. Further evidence indicates that the auditing effect of environmental disclosures is stronger on firms that receive less media attention, in firms with better internal controls, and in firms belonging to industries with heavy pollution.

Originality/value

In the Chinese setting, a high level of environmental information disclosures can effectively reduce the audit risk and lead to a high possibility of standard audit opinions and low audit fees. This effect is pronounced after issuing Measure. The conclusions suggest that measure and increasing environmental disclosure have an obvious positive audit effect and that firms should be forced or encouraged to disclose more environmental information from the perspective of auditors in China.
Increasing customer loyalty through customer engagement in the retail banking industry
Authors: Monferrer Diego , Moliner Miguel Angel , Estrada Marta
Published: November 2019

Purpose

This study aims to determine the main antecedents of customer engagement (market orientation, satisfaction, emotions and self-brand connection) and the relationship between customer engagement and customer loyalty in the retail-banking context.

Design/methodology/approach

A theoretical model of effects is tested using dyadic methodology, based on 225 dyads (bank branch manager–average of five branch customers). The authors use structural equation modelling (EQS 6.1) to test the relationships.

Findings

The results reveal a strong relationship between customer engagement and customer loyalty. Satisfaction is the main antecedent of customer engagement. Self-brand connection and emotions during the service also have a significant influence. Finally, branch market orientation has a positive influence on satisfaction and emotions.

Research limitations/implications

The first concerns the transversal data used. Geographical context is the second limitation. Third, the study sample only included customers with experience of the financial services of a specific bank (online customers are not included). Finally, the dyads are based on the opinion of the branch manager, on one hand, and an average of five customers per branch, on the other.

Practical implications

The combination of the branding strategy at the corporate level and the relationship marketing strategy at branch office level creates a situation in which customer engagement and customer loyalty can thrive. The communication campaigns designed to promote the brand image and associate brand values with the personality of the banks’ current and potential customers help to create an emotional bond that represents a switching cost for the customer. The moments of truth in branch offices are crucial aspects in the retail bank strategy.

Originality/value

First, from the conceptual perspective, it establishes a direct relationship between customer engagement and customer loyalty. Second, it empirically tested Pansari and Kumar’s (2017) customer engagement framework, which establishes customer satisfaction and customer emotions as the antecedents of customer engagement. Third, the study took an innovative step in establishing two levels of customer emotions in the retail bank context: emotions generated by corporate branding and emotions that arise during the experience of purchase and consuming. Fourth, the study shows that the market orientation adopted not at the macro corporate level but at the individual branch level is crucial to the generation of positive relational outcomes in the service the customer receives. The fifth contribution is related to the fact that the research streams associated with market orientation and relationship quality have traditionally been studied in isolation.
Drug survival of biologic agents for psoriatic patients in a real‐world setting in Japan
Authors: Kishimoto Megumi , Komine Mayumi , Kamiya Koji , Sugai Junichi , Mieno Makiko , Ohtsuki Mamitaro
Published: November 2019

This is a Japanese retrospective single‐center study carried out between 1 January 2010 and 21 November 2018 at the Department of Dermatology in Jichi Medical University Hospital. The drug survival rate for six biologic agents used for the treatment of psoriasis was investigated. We reviewed the clinical records of 315 treatment series of 205 patients with moderate to severe psoriasis treated with adalimumab (103 cases), infliximab (70 cases), ustekinumab (66 cases), secukinumab (38 cases), brodalumab (12 cases) and ixekizumab (26 cases). In our study, ustekinumab revealed a trend towards higher drug survival among the six biologic agents. Ustekinumab had a higher drug survival rate than infliximab and secukinumab with significant differences by log–rank test among all patients and among biologic‐naive (bio‐naive) patients. There was no significant difference in drug survival between bio‐naive and biologic‐experienced (non‐naive) patients in the treatment courses with adalimumab, infliximab, ustekinumab, secukinumab and ixekizumab. The dose augmentation therapy in infliximab‐treated patients was associated with longer drug survival. Of all patients, 25 cases with generalized pustular psoriasis (GPP) were included, who functioned as the negative predictor for drug persistence with a hazard ratio of 1.87 (95% confidence interval, 1.12–3.11;P = 0.016). Our results reveal that ustekinumab had a superior drug survival, which is supported by the previous studies. Further studies are needed to clarify the efficacy of biologic agents on patients with GPP.
Application of surface‐wave tomography to mineral exploration: a case study from Siilinjärvi, Finland
Authors: Da Col Federico , Papadopoulou Myrto , Koivisto Emilia , Sito Łukasz , Savolainen Mikko , Socco Laura Valentina
Published: November 2019

In order to assess the feasibility and validity of surface‐wave tomography as a tool for mineral exploration, we present an active seismic three‐dimensional case study from the Siilinjärvi mine in Eastern Finland. The aim of the survey is to identify the formation carrying the mineralization in an area south of the main pit, which will be mined in the future. Before acquiring the data, we performed an accurate survey design to maximize data coverage and minimize the time for deployment and recollection of the equipment. We extract path‐averaged Rayleigh‐wave phase‐velocity dispersion curves by means of a two‐station method. We invert them using a computationally efficient tomographic code which does not require the computation of phase‐velocity maps and inverts directly for one‐dimensional S‐wave velocity models. The retrieved velocities are in good agreement with the data from a borehole in the vicinity, and the pseudo three–dimensional S‐wave velocity volume allows us to identify the geological contact between the formation hosting most of the mineralization and the surrounding rock. We conclude that the proposed method is a valid tool, given the small amount of equipment used and the acceptable amount of time required to process the data.
Semantic fluency difficulties in developmental dyslexia and developmental language disorder (DLD): poor semantic structure of the lexicon or slower retrieval processes?
Authors: Mengisidou Maria , Marshall Chloë R. , Stavrakaki Stavroula
Published: November 2019

Background

Children with dyslexia and/or developmental language disorder (hereafter children with DDLD) have been reported to retrieve fewer words than their typically developing (TD) peers in semantic fluency tasks. It is not known whether this retrieval difficulty can be attributed to the semantic structure of their lexicon being poor or, alternatively, to words being retrieved more slowly despite semantic structure being intact.

Aims

To test two theoretical models that could potentially account for retrieval difficulties in semantic fluency tasks, namely, the Poor Lexical–Semantic Structure Model and the Slow‐Retrieval Model. Both models predict that children with DDLD will retrieve fewer items compared with TD children. However, while the Poor Lexical–Semantic Structure Model predicts a less sophisticated network of semantic connections between words in the lexicon, as evidenced by smaller clusters of related items in children with DDLD, the Slow‐Retrieval Model predicts intact inter‐item associations in the lexicon, as evidenced by the two groups’ clusters being of a similar size. The groups’ semantic fluency performance was therefore compared. How semantic fluency performance related to children's language, literacy, and phonological skills was also investigated.

Methods & Procedures

A total of 66 children with DDLD aged 7–12 years and 83 TD children aged 6–12 years, all monolingual Greek speakers, were tested on semantic fluency, using the categories ‘animals’, ‘foods’ and ‘objects from around the house’. The numbers of correct and incorrect responses, clusters and switches, and the average cluster size were computed. Children were also assessed on non‐verbal IQ, language, literacy and phonological tasks.

Outcomes & Results

In both groups, productivity in semantic fluency tasks correlated strongly with the numbers of clusters and switches, but not with average cluster size. The DDLD group produced significantly fewer correct responses and fewer clusters compared with the TD group, but the two groups showed similar switching and average cluster size. Children's language, literacy and phonological skills significantly predicted the number of correct responses produced, beyond the significant effect of age.

Conclusions & Implications

We conclude that poorer semantic fluency performance in children with DDLD results not from a lexicon with poor semantic structure, but rather from slower retrieval processes from a lexicon with intact semantic structure. The underlying causes of slow lexical retrieval still need further investigation.
Energy flux controls tetraether lipid cyclization in Sulfolobus acidocaldarius
Authors: Zhou Alice , Weber Yuki , Chiu Beverly K. , Elling Felix J. , Cobban Alec B. , Pearson Ann , Leavitt William D.
Published: November 2019

Microorganisms regulate the composition of their membranes in response to environmental cues. Many Archaea maintain the fluidity and permeability of their membranes by adjusting the number of cyclic moieties within the cores of their glycerol dibiphytanyl glycerol tetraether (GDGT) lipids. Cyclized GDGTs increase membrane packing and stability, which has been shown to help cells survive shifts in temperature and pH. However, the extent of this cyclization also varies with growth phase and electron acceptor or donor limitation. These observations indicate a relationship between energy metabolism and membrane composition. Here we show that the average degree of GDGT cyclization increases with doubling time in continuous cultures of the thermoacidophile Sulfolobus acidocaldarius (DSM 639). This is consistent with the behavior of a mesoneutrophile, Nitrosopumilus maritimus SCM1. Together, these results demonstrate that archaeal GDGT distributions can shift in response to electron donor flux and energy availability, independent of pH or temperature. Paleoenvironmental reconstructions based on GDGTs thus capture the energy available to microbes, which encompasses fluctuations in temperature and pH, as well as electron donor and acceptor availability. The ability of Archaea to adjust membrane composition and packing may be an important strategy that enables survival during episodes of energy stress.
The Declining Value of Revolving‐Door Lobbyists: Evidence from the American States
Authors: Strickland James M.
Published: November 2019

‘‘Revolving‐door” lobbyists are individuals who transition from governmental positions into lobbying for private entities. Such lobbyists thrive on the insider connections and political knowledge that they developed while in government. These assets afford former lawmakers more access to and influence over incumbent lawmakers. The value of their connections and knowledge, however, is contingent on former colleagues remaining within the legislature. As new legislators enter the assembly, the connections and knowledge of former members expire and lose value. Whereas increases in turnover or assembly size generate more former lawmakers who might lobby, such increases negatively affect former members’ value as lobbyists. Interest groups accordingly hire fewer former legislators to lobby. Other factors, such as longer cooling‐off periods or increased legislative staff resources, produce slight or no substantive effects on rates of revolving. Legislative characteristics mostly determine rates of revolving for former lawmakers.
Review article: bacteriophages in gastroenterology—from biology to clinical applications
Authors: Sabino João , Hirten Robert P. , Colombel Jean‐Frederic
Published: November 2019

Background

The gut microbiota plays an important role in the pathogenesis of several gastrointestinal diseases. Its composition and function are shaped by host‐microbiota and intra‐microbiota interactions. Bacteriophages (phages) are viruses that target bacteria and have the potential to modulate bacterial communities.

Aims

To summarise phage biology and the clinical applications of phages in gastroenterology

Methods

PubMed was searched to identify relevant studies.

Results

Phages induce bacterial cell lysis, integration of viral DNA into the bacteria and/or coexistence in a stable equilibrium. Bacteria and phages have co‐evolved and their dynamic interactions are yet to be fully understood. The increasing need to modulate microbial communities (e.g., gut microbiota, multidrug‐resistant bacteria) has been a strong stimulus for research in phages as an antibacterial therapy. In gastroenterology, phage therapy has been mainly studied in infectious diseases such as cholera. However, it is currently being explored in several other circumstances such as treating Clostridioides difficile colitis, targeting adherent‐invasive Escherichia coli in Crohn's disease or eradicating Fusobacterium nucleatum in colorectal cancer. Overall, phage therapy has a favourable and acceptable safety profile. Presently, trials with phage therapy are ongoing in Crohn's disease.

Conclusions

Phage therapy is a promising therapeutic tool against pathogenic bacteria in the fields of infectious diseases and gastroenterology. Randomised, placebo‐controlled trials with phage therapy for gastroenterological diseases are ongoing.
Ectogestation ethics: The implications of artificially extending gestation for viability, newborn resuscitation and abortion
Authors: Di Stefano Lydia , Mills Catherine , Watkins Andrew , Wilkinson Dominic
Published: November 2019

Recent animal research suggests that it may soon be possible to support the human fetus in an artificial uterine environment for part of a pregnancy. A technique of extending gestation in this way (“ectogestation”) could be offered to parents of extremely premature infants (EPIs) to improve outcomes for their child. The use of artificial uteruses for ectogestation could generate ethical questions because of the technology’s potential impact on the point of “viability”—loosely defined as the stage of pregnancy beyond which the fetus may survive external to the womb. Several medical decisions during the perinatal period are based on the gestation at which infants are considered viable, for example decisions about newborn resuscitation and abortion, and ectogestation has the potential to impact on these. Despite these possible implications, there is little existing evidence or analysis of how this technology would affect medical practice. In this paper, we combine empirical data with ethical analysis. We report a survey of 91 practicing Australian obstetricians and neonatologists; we aimed to assess their conceptual understanding of “viability,” and what ethical consequences they envisage arising from improved survival of EPIs. We also assess what the ethical implications of extending gestation should be for newborn and obstetric care. We analyze the concept of viability and argue that while ectogestation might have implications for the permissibility of neonatal life‐prolonging treatment at extremely early gestation, it should not necessarily have implications for abortion policy. We compare our ethical findings with the results of the survey.
Improving the justice‐based argument for conducting human gene editing research to cure sickle cell disease
Authors: Chan Berman
Published: November 2019

In a recent article, Marilyn Baffoe‐Bonnie offers three arguments that conducting CRISPR/Cas9 biotechnology research to cure sickle cell disease (SCD) would help address historical and current injustices in SCD research and care. I will grant that the first argument is sound, but show that the second and third arguments suffer from roughly the same defect, which is that they really argue for something else rather than for conducting CRISPR/Cas9 research to cure SCD. I conclude that a better justice‐based argument would use only Baffoe‐Bonnie’s first argument.
Social cognition in post‐traumatic stress disorder: A systematic review
Authors: Couette Maryline , Mouchabac Stéphane , Bourla Alexis , Nuss Philippe , Ferreri Florian
Published: November 2019

Objectives

Post‐traumatic stress disorder (PTSD) is a common psychiatric condition. Patients with PTSD have marked symptoms that significantly impair their social and emotional abilities, and numerous studies have explored this issue. We hypothesized that impairment of social cognition takes part in functional disability of individuals with PTSD.

Methods

We conducted a systematic review by querying PubMed database for the titles of articles published up to February 2018 with the terms [PTSD] [Post traumatic disorder] AND [Emotion recognition] OR [Facial expression of emotion] OR [Facial expression perception] OR [Empathy] OR [Affective empathy] OR [Mentalizing] OR [Social cognition] OR [Theory of Mind] OR [Mental state attribution] OR [Cognitive empathy] OR [Emotional empathy] OR [Social behaviour deficits].

Results

Our results suggest that affective and cognitive aspect of theory of mind is comprehensively disturbed in patients with PTSD, showing a significant impairment in their ability to predict what others feel, think, or believe. They could also be massively altered in their perception of basic emotional expressions whether it is an expression of threat or happiness. Their affective empathy appears to be systematically disturbed and correlated to verbal and/or physical aggressive behaviour.

Conclusions

Social cognition is disturbed in PTSD and should be regarded as an important symptom. Damages in social cognition seem to take part in the functional disability of people with PTSD. We highlight the interest of a systematic assessment of social cognition in the care of patients with PTSD and suggest which tests could be the most relevant for this evaluation.

Practitioner points

PTSD is no longer regarded as a subtype of anxiety disorder, but as part of a new category in the DSM‐5.

In clinical practice, symptoms tied to alterations in arousal and reactivity – such as irritability and vigilance – and to the disturbance of cognition and mood, are particularly closely correlated with poorer quality of life.

Impaired social cognition clearly impacts the functional disability of people with PTSD.

There are potential benefits of individualized cognitive remediation based on empathy and the emotional component of ToM (cognitive remediation, cognitive–behavioural therapy, therapeutic education, etc.) in PTSD people.
Platelet biology of the rapidly failing lung
Authors: Washington A. Valance , Esponda Omar , Gibson Angelia
Published: November 2019

Acute respiratory distress syndrome (ARDS) is characterized by a rapid‐onset respiratory failure with a mortality rate of approximately 40%. This physiologic inflammatory process is mediated by disruption of the alveolar‐vascular interface, leading to pulmonary oedema and impaired oxygen exchange, which often warrants mechanical ventilation to increase survival in the acute setting. One of the least understood aspects of ARDS is the role of the platelets in this process. Platelets, which protect vascular integrity, play a pivotal role in the progression and resolution of ARDS. The recent substantiation of the age‐old theory that megakaryocytes are found in the lungs has rejuvenated interest in and raised new questions about the importance of platelets for pulmonary function. In addition to primary haemostasis, platelets provide a myriad of inflammatory functions that are poised to aid the innate immune system. This review focuses on the evidence for regulatory roles of platelets in pulmonary inflammation, with an emphasis on two receptors, CLEC‐2 and TLT‐1. Studies of these receptors identify novel pathways through which platelets may regulate vascular integrity and inflammation in the lungs, thereby influencing the development of ARDS.