bluuebunny/crossref_metadata_2025 huggingface dataset:
An optimized derivative of an endogenous CXCR4 antagonist prevents atopic dermatitis and airway inflammation
Authors: Harms Mirja , Habib Monica MW , Nemska Simona , Nicolò Antonella , Gilg Andrea , Preising Nico , Sokkar Pandian , Carmignani Sara , Raasholm Martina , Weidinger Gilbert , Kizilsavas Gönül , Wagner Manfred , Ständker Ludger , Abadi Ashraf , Jumaa Hassan , Kirchhoff Frank , Frossard Nelly , Sanchez-Garcia Elsa , Münch Jan
Published: August 2020

Background

Aberrant CXCR4/CXCL12 signaling is involved in many pathophysiological processes including chronic inflammatory diseases. Thus, the chemokine receptor CXCR4 is a promising target for the therapy of inflammatory disorders, such as atopic dermatitis or allergic asthma. A natural fragment of serum albumin, named EPI-X4, has previous been identified as endogenous peptide antagonist and inverse agonist of CXCR4. The endogenous CXCR4 antagonist provides a promising basis for the development of improved analogues for the therapy of inflammatory diseases.

Objective

To increase the anti-CXCR4 activity of EPI-X4 and to evaluate the therapeutic potential of optimized analogs in mouse models of atopic dermatitis and asthma.

Methods

Molecular docking analysis of the interaction of EPI-X4 with CXCR4 was performed to define critical interaction motifs and to rationally design analogs with increased activity. EPI-X4 derivatives were synthesized and CXCR4 binding and antagonizing activity determined in assays for antibody competition, inhibition of CXCR4-mediated HIV-1 infection, CXCL12-dependent Ca2+mobilization, ERK and AKT phosphorylation and cell migration. Toxicity of peptides was evaluated in zebrafish embryos. The therapeutic efficacy of the lead peptide EPI-X4 JM#21 was determined in mouse models of atopic dermatitis and asthma.

Results

Docking analysis identified key interaction motifs of EPI-X4/CXCR4. Rational drug design allowed to increase the anti-CXCR4 activity of EPI-X4 and resulted in the generation of the lead analog JM#21, which bound CXCR4 and suppressed CXCR4-tropic HIV-1 infection more efficiently than the clinically approved small molecule CXCR4 antagonist AMD3100. JM#21 did not exert toxic effects in zebrafish embryos and efficiently prevented inflammation of the skin in a mouse model of atopic dermatitis. Moreover, EPI-X4 and its improved derivative suppressed allergen-induced infiltration of eosinophils and other immune cells into the airways of animals in an asthma mouse model.

Conclusion

The rationally designed EPI-X4 derivative JM#21 is a potent antagonist of CXCR4 and the first CXCR4 inhibitor with therapeutic efficacy in atopic dermatitis. Further clinical development of this new class of CXCR4 antagonists for the therapy of atopic dermatitis, asthma and other CXCR4-associated diseases is highly warranted.

Graphical Abstract
Different evolutionary pathways of HIV-1 between fetus and mother perinatal transmission pairs indicate unique immune selection pressure in fetuses
Authors: Marichannegowda Manukumar Honnayakanahalli , Mengual Michael , Kumar Amit , Giorgi Elena E. , Tu Joshua J. , Martinez David R. , Li Xiaojun , Feng Liping , Permar Sallie R , Gao Feng
Published: August 2020

Study of evolution and selection pressure on HIV-1 in fetuses will lead to a better understanding of the role of immune responses in shaping virus evolution and vertical transmission. Detailed genetic analyses of HIV-1envgene from 12in uterotransmission pairs show that most infections (67%) occur within two months from childbirth. In addition, envsequences from long-term infected fetuses were highly divergent and formed separate phylogenetic lineages from their cognate maternal viruses. Host selection sites unique to infant viruses were identified in regions frequently targeted by broadly neutralizing antibodies and T cell immune responses. The identification of unique selection sites in theenvgene of fetal viruses indicates that the immune system in fetuses is capable of exerting selection pressure on viral evolution. Studying selection and evolution of HIV-1 or other viruses in fetuses can be an alternative approach to investigate adaptive immunity in fetuses.
Global BioID-based SARS-CoV-2 proteins proximal interactome unveils novel ties between viral polypeptides and host factors involved in multiple COVID19-associated mechanisms
Authors: Laurent Estelle M.N. , Sofianatos Yorgos , Komarova Anastassia , Gimeno Jean-Pascal , Tehrani Payman Samavarchi , Kim Dae-Kyum , Abdouni Hala , Duhamel Marie , Cassonnet Patricia , Knapp Jennifer J. , Kuang Da , Chawla Aditya , Sheykhkarimli Dayag , Rayhan Ashyad , Li Roujia , Pogoutse Oxana , Hill David E. , Calderwood Michael A. , Falter-Braun Pascal , Aloy Patrick , Stelzl Ulrich , Vidal Marc , Gingras Anne-Claude , Pavlopoulos Georgios A. , Van Der Werf Sylvie , Fournier Isabelle , Roth Frederick P. , Salzet Michel , Demeret Caroline , Jacob Yves , Coyaud Etienne
Published: August 2020

The worldwide SARS-CoV-2 outbreak poses a serious challenge to human societies and economies. SARS-CoV-2 proteins orchestrate complex pathogenic mechanisms that underlie COVID-19 disease. Thus, understanding how viral polypeptides rewire host protein networks enables better-founded therapeutic research. In complement to existing proteomic studies, in this study we define the first proximal interaction network of SARS-CoV-2 proteins, at the whole proteome level in human cells. Applying a proximity-dependent biotinylation (BioID)-based approach greatly expanded the current knowledge by detecting interactions within poorly soluble compartments, transient, and/or of weak affinity in living cells. Our BioID study was complemented by a stringent filtering and uncovered 2,128 unique cellular targets (1,717 not previously associated with SARS-CoV-1 or 2 proteins) connected to the N- and C-ter BioID-tagged 28 SARS-CoV-2 proteins by a total of 5,415 (5,236 new) proximal interactions. In order to facilitate data exploitation, an innovative interactive 3D web interface was developed to allow customized analysis and exploration of the landscape of interactions (accessible athttp://www.sars-cov-2-interactome.org/). Interestingly, 342 membrane proteins including interferon and interleukin pathways factors, were associated with specific viral proteins. We uncovered ORF7a and ORF7b protein proximal partners that could be related to anosmia and ageusia symptoms. Moreover, comparing proximal interactomes in basal and infection-mimicking conditions (poly(I:C) treatment) allowed us to detect novel links with major antiviral response pathway components, such as ORF9b with MAVS and ISG20; N with PKR and TARB2; NSP2 with RIG-I and STAT1; NSP16 with PARP9-DTX3L. Altogether, our study provides an unprecedented comprehensive resource for understanding how SARS-CoV-2 proteins orchestrate host proteome remodeling and innate immune response evasion, which can inform development of targeted therapeutic strategies.
Non-Refoldability is Pervasive Across theE. coliProteome
Authors: To Philip , Whitehead Briana , Tarbox Haley E. , Fried Stephen D.
Published: August 2020

The foundational paradigm of protein folding is that the primary sequence of a protein contains all the information needed for it to adopt a specific native structure1,2. This remarkable property is explained by Anfinsen’s thermodynamic hypothesis3,4, which asserts that because native states minimize the Gibbs free energy of a protein molecule under physiological conditions, proteins can reliably navigate to their native structures and remain in those states by ergodically sampling their free energy landscapes5. Most experiments of protein folding – conducted on purified, small, single-domain soluble proteins – follow the proportion of protein molecules that are folded as a function of time, temperature, denaturant concentration, or sequence6–8, and have yielded immense insight into the molecular determinants that underpin stable globular folds9,10. However, our reliance on the thermodynamic hypothesis as a ground truth to interpret these experiments has limited our ability to study the folding of complex proteins or to consider alternative non-thermodynamic scenarios11,12. Here, we introduce an experimental approach to probe protein refolding for whole proteomes. We accomplish this by first unfolding and refoldingE. colilysates, and then interrogating the resulting protein structures using a permissive protease that preferentially cleaves at flexible regions. Using mass spectrometry, we analyze the digestion patterns to globally assess structural differences between native and ‘refolded’ proteins. These studies reveal that following denaturation, many proteins are incapable of navigating back to their native structures. Our results signal a pervasive role for co-translational folding in shaping protein biogenesis, and suggest that the apparent stability of many native states derive fromkinetic persistencerather than thermodynamic stability.
The SARS-CoV-2 ORF10 is not essentialin vitroorin vivoin humans
Authors: Pancer Katarzyna , Milewska Aleksandra , Owczarek Katarzyna , Dabrowska Agnieszka , Branicki Wojciech , Sanak Marek , Pyrc Krzysztof
Published: August 2020

SARS-CoV-2 genome annotation revealed the presence of 10 open reading frames (ORFs), of which the last one (ORF10) is positioned downstream the N gene. It is a hypothetical gene, which was speculated to encode a 38 aa protein. This hypothetical protein does not share sequence similarity with any other known protein and cannot be associated with a function. While the role of this ORF10 was proposed, there is a growing evidence showing that the ORF10 is not a coding region.

Here, we identified SARS-CoV-2 variants in which the ORF10 gene was prematurely terminated. The disease was not attenuated, and the transmissibility between humans was not hampered. Alsoin vitro, the strains replicated similarly, as the related viruses with the intact ORF10. Altogether, based on clinical observation and laboratory analyses, it appears that the ORF10 protein is not essential in humans. This observation further proves that the ORF10 should not be treated as the protein-coding gene, and the genome annotations should be amended.
Shared heritability of face and brain shape distinct from cognitive traits
Authors: Naqvi Sahin , Sleyp Yoeri , Hoskens Hanne , Indencleef Karlijne , Spence Jeffrey P. , Bruffaerts Rose , Radwan Ahmed , Eller Ryan J. , Richmond Stephen , Shriver Mark D. , Shaffer John R. , Weinberg Seth M. , Walsh Susan , Thompson James , Pritchard Jonathan K. , Sunaert Stefan , Peeters Hilde , Wysocka Joanna , Claes Peter
Published: August 2020

Evidence from both model organisms and clinical genetics suggests close coordination between the developing brain and face1–8, but it remains unknown whether this developmental link extends to genetic variation that drives normal-range diversity of face and brain shape. Here, we performed a multivariate genome-wide association study of cortical surface morphology in 19,644 European-ancestry individuals and identified 472 genomic loci influencing brain shape at multiple levels. We discovered a substantial overlap of these brain shape association signals with those linked to facial shape variation, with 76 common to both. These shared loci include transcription factors with cell-intrinsic roles in craniofacial development, as well as members of signaling pathways involved in brain-face crosstalk. Brain shape heritability is equivalently enriched near regulatory regions active in either brain organoids or in facial progenitor cells. However, brain shape association signals shared with face shape are distinct from those shared with behavioral-cognitive traits or neuropsychiatric disorder risk. Together, we uncover common genetic variants and candidate molecular players underlying brain-face interactions. We propose that early in embryogenesis, the face and the brain mutually shape each other through a combination of structural effects and paracrine signaling, but this interplay may have little impact on later brain development associated with cognitive function.
Silicon Nitride Inactivates SARS-CoV-2in vitro
Authors: Lehman Caitlin W. , Flur Rafaela , Kehn-Hall Kylene , McEntire Bryan J. , Bal B. Sonny , Bock Ryan M.
Published: August 2020

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the COVID-19 pandemic, remains viable and therefore potentially infectious on several materials. One strategy to discourage the fomite-mediated spread of COVID-19 is the development of materials whose surface chemistry can spontaneously inactivate SARS-CoV-2. Silicon nitride (Si3N4), a material used in spine fusion surgery, is one such candidate because it has been shown to inactivate several bacterial species and viral strains. This study hypothesized that contact with Si3N4would inactivate SARS-CoV-2, while mammalian cells would remain unaffected.

Materials

SARS-CoV-2 virions (2×104PFU/mL diluted in growth media) were exposed to 5, 10, 15, and 20% (w/v) of an aqueous suspension of sintered Si3N4particles for durations of 1, 5, and 10 minutes, respectively. Before exposure to the virus, cytotoxicity testing of Si3N4alone was assessed in Vero cells at 24 and 48 hour post-exposure times. Following each exposure to Si3N4, the remaining infectious virus was quantitated by plaque assay.

Results

Vero cell viability increased at 5% and 10% (w/v) concentrations of Si3N4at exposure times up to 10 minutes, and there was only minimal impact on cell health and viability up to 20% (w/v). However, the SARS-CoV-2 titers were markedly reduced when exposed to all concentrations of Si3N4; the reduction in viral titers was between 85% - 99.6%, depending on the dose and duration of exposure.

Conclusions

Si3N4was non-toxic to the Vero cells while showing strong antiviral activity against SARS-CoV-2. The viricidal effect increased with increasing concentrations of Si3N4and longer duration of exposure. Surface treatment strategies based on Si3N4may offer novel methods to discourage SARS-CoV-2 persistence and infectivity on surfaces and discourage the spread of COVID-19.
Proximity labeling at non-centrosomal microtubule-organizing centers reveals VAB-10B and WDR-62 as distinct microtubule regulators
Authors: Sanchez Ariana D. , Branon Tess C. , Cote Lauren E. , Papagiannakis Alexandros , Liang Xing , Pickett Melissa A. , Shen Kang , Jacobs-Wagner Christine , Ting Alice Y. , Feldman Jessica L.
Published: August 2020

Reorganization of microtubules from the centrosome to non-centrosomal subcellular sites is central to cell differentiation. To identify components of non-centrosomal microtubule organizing centers in differentiated cells of a living organism, we developed the biotin ligase-based proximity labeling approach TurboID for use inC. elegans. We identified proteins proximal to the non-centrosomal microtubule minus end protein PTRN-1/Patronin at the apical membrane of epithelial cells, focusing on two conserved proteins: spectraplakin protein VAB-10B and WDR-62, a protein we identify as homologous to vertebrate primary microcephaly disease gene WDR62. We found that WDR-62 and VAB-10B independently regulate the growth and localization of non-centrosomal microtubules and the apical targeting of microtubule minus end proteins. This regulation occurs downstream of cell polarity and in conjunction with actin. Our data suggest a division of labor where microtubule growth and anchoring are regulated by distinct complexes and uncover novel functions of spectraplakins and WDR62 family proteins.
Endoderm Nitric Oxide Signals to Regulate Nascent Development of Cardiac Progenitors in Chicken Embryos
Authors: Shah Devan H. , Biswas Sujoy K. , Martin Adrian M. , Bianco Simone , Denetclaw Wilfred F.
Published: August 2020

Heart development in the chicken embryo is regulated by a concert of cardiogenic morphogens and signaling molecules, but the physiological signal molecule nitric oxide(NO) has not been studied in the context of heart formation. A dynamic investigation of endoderm NO formation demonstrates for the first time a correlation with the established development events of the cardiac heart fields and heart tube. Manipulation of endoderm NO signaling demonstrate a role of NO signaling in the differentiation and proliferation of cardiac progenitors for heart tube formation and cardiac heart field development. To investigate NO in the proliferation of myocardial cells in the heart tube embryos, a computer vision based artificial intelligence approach is followed to automate the long and tedious job of counting cells in a large image dataset. We document NO as an important signaling molecule in the regulation of nascent embryonic cardiogenesis whose effects on other early cardiogenic morphogens is unknown.
Microbial bioprospecting for lignocellulose degradation at a unique Greek environment
Authors: Georgiadou Daphne N. , Avramidis Pavlos , Ioannou Efstathia , Hatzinikolaou Dimitris G.
Published: August 2020

Bacterial systems have gained wide attention for depolymerization of lignocellulosic biomass, due to their high functional diversity and adaptability. To achieve the full microbial exploitation of lignocellulosic residues and the cost-effective production of bioproducts within a biorefinery, multiple metabolic pathways and enzymes of various specificities are required. In this work, highly diverse aerobic, mesophilic bacteria enriched from Keri Lake, a pristine marsh of increased biomass degradation and natural underground oil leaks, were explored for their metabolic versatility and enzymatic potential towards lignocellulosic substrates. A wide diversity ofPseudomonasspecies were obtained from enrichment cultures where organosolv lignin served as the sole carbon and energy source and were able to assimilate a range of lignin-associated aromatic compounds. Highly complex bacterial consortia were also enriched in cultures with xylan or carboxymethyl cellulose as sole carbon sources, belonging to Actinobacteria, Proteobacteria, Bacilli, Sphingobacteriia, and Flavobacteria. Numerous individual isolates could target diverse structural lignocellulose polysaccharides by expressing hydrolytic activities on crystalline or amorphous cellulose and xylan. Specific isolates showed increased potential for growth in lignin hydrolysates prepared from alkali pretreated agricultural wastes. The results suggest that Keri isolates represent a pool of effective lignocellulose degraders with significant potential for industrial applications in a lignocellulose biorefinery.
Release probability increases towards distal dendrites boosting high-frequency signal transfer
Authors: Jensen Thomas P. , Kopach Olga , Savchenko Leonid P. , Reynolds James P. , Rusakov Dmitri A.
Published: August 2020

Dendritic integration of synaptic inputs entangles their increased electrotonic attenuation at distal dendrites, which can be counterbalanced by the increased synaptic receptor density. However, during sustained network activity the influence of individual synapses depends on their release properties. How these properties are distributed along dendrites remains poorly understood. Here, we employed classical optical quantal analyses and a genetically encoded optical glutamate sensor in acute hippocampal slices to monitor release at CA3-CA1 synapses. We find that their release probability increases with greater distances from the soma. Similar-fidelity synapses tend to group together whereas release probability shows no trends regarding the within-branch position. Simulations with a realistic CA1 pyramidal cell hosting stochastic synapses suggest that the observed trends boost signal transfer fidelity, particularly at higher input frequencies. Because high-frequency bursting has been associated with learning, the release probability pattern we have found may play a key role in memory trace formation.
The connectome of the adultDrosophilamushroom body: implications for function
Authors: Li Feng , Lindsey Jack , Marin Elizabeth C. , Otto Nils , Dreher Marisa , Dempsey Georgia , Stark Ildiko , Bates Alexander Shakeel , Pleijzier Markus William , Schlegel Philipp , Nern Aljoscha , Takemura Shinya , Yang Tansy , Francis Audrey , Braun Amalia , Parekh Ruchi , Costa Marta , Scheffer Louis , Aso Yoshinori , Jefferis Gregory S. X. E. , Abbott L.F. , Litwin-Kumar Ashok , Waddell Scott , Rubin Gerald M.
Published: August 2020

Making inferences about the computations performed by neuronal circuits from synapse-level connectivity maps is an emerging opportunity in neuroscience. The mushroom body (MB) is well positioned for developing and testing such an approach due to its conserved neuronal architecture, recently completed dense connectome, and extensive prior experimental studies of its roles in learning, memory and activity regulation. Here we identify new components of the MB circuit inDrosophila, including extensive visual input and MB output neurons (MBONs) with direct connections to descending neurons. We find unexpected structure in sensory inputs, in the transfer of information about different sensory modalities to MBONs, and in the modulation of that transfer by dopaminergic neurons (DANs). We provide insights into the circuitry used to integrate MB outputs, connectivity between the MB and the central complex and inputs to DANs, including feedback from MBONs. Our results provide a foundation for further theoretical and experimental work.
A single cell trajectory of human archetypal pluripotent stem cell differentiation to trophoblast stem cells reveals induction of endogenous BMP5/7 and GATA3 without transitioning through a naive state
Authors: Tietze Ethan , Barbosa Andre Rocha , Silva Araujo Bruno Henrique , Euclydes Veronica , Cho Hyeon Jin , Lee Yong Kyu , Feltrin Arthur , Spiegelberg Bailey , Lorenzetti Alan , Leemput Joyce van de , Carlo Pasquale Di , Sawada Tomoyo , Ursini Gianluca , Benjamin Kynon J. , Brentani Helena , Kleinman Joel E. , Hyde Thomas M. , Weinberger Daniel R. , McKay Ronald , Shin Joo Heon , Paquola Apua C.M. , Erwin Jennifer A.
Published: August 2020

The human placenta is increasingly a focus of research related to early child development and the impact of maternal hyperimmune states. Primary human trophoblast stem cells (hTSC) and human pluripotent stem cells (hPSC) differentiated to hTSC can potentially model placental processesin vitro. Yet, it remains controversial how the differentiation of human pluripotent stem cells to trophectoderm relates toin vivodevelopment and the factors required for this differentiation. Here, we demonstrate that the primed pluripotent state retains potency to generate trophoblast stem cells by activating EGF and WNT and inhibiting TGFb, HDAC and ROCK signaling without exogenous BMP4 (named TS). We map this specification by temporal single cell RNAseq compared to activating BMP4 or activating BMP4 and inhibiting WNT. TS conditions generate a stable proliferating cell type that is highly similar to six-week placental cytotrophoblasts with activation of endogenous retroviral genes and without amnion expression. Multiple primed iPSC and ES lines differentiate to iPS-derived-TSCs that can be passaged for at least 30 passages and differentiate to pure populations of multinucleated syncytiotrophoblasts and extravillous trophoblast cells. Our findings establish that primed iPS cell specification to hTSC with TS conditions involves induction ofTMSB4X,BMP5/7, GATA3 andTFAP2Awithout transitioning through a naive state. Collectively, our results suggest that the primed state is on a continuum of potency and can differentiate to trophoblast stem cells via multiple paths.

Significance Statement

In the present study, we map the specification of primed induced pluripotent stem cells to trophoblast stem cells (TSC). Primed iPS-derived-TSC share transcriptional, morphological and functional characteristics with humanex vivocytotrophoblasts including capacity of self-renewal and the ability to differentiate to pure extravillous and syncytiotrophoblasts. iPS-derived TSC display a uniquely active transcriptional network of human endogenous retroviruses similar toin vivotrophoblast. In addition, the fast conversion of primed iPSC to TSC allows for modeling placental diseases from large pluripotent stem cell cohorts which are traditionally banked at the primed state. Collectively, our results suggest that the primed state is on a continuum of potency which can differentiate to trophoblast stem cells via multiple paths.
Determinants of oversubscription of SME IPOs in India: evidence from quantile regression
Authors: Arora Nischay , Singh Balwinder
Published: August 2020

Purpose

The study aims to measure the subscription level and examine the determinants of oversubscription of small and medium enterprise (SME) initial public offerings (IPOs) in India.

Design/methodology/approach

The study employs cross sectional data to analyze 403 SME IPOs issued from Feb 2012 to May 2018 and listed on Bombay Stock Exchange's small and medium enterprise (BSE SME) platform and National Stock Exchange (NSE) EMERGE to investigate the determinants of oversubscription of SME IPOs. Hence, the study makes use of ordinary least square regression and quantile regression to test the hypotheses formulated for the determinants of oversubscription.

Findings

The main findings unveil that while issue price, pricing mechanism, listing delay negatively influence oversubscription; firm size, underwriter reputation, hot market and underpricing have been divulged to positively influence oversubscription. However, issue size emerged out to be significant in quantile regression at 25th, 50th and 75th quantiles.

Research limitations/implications

The present study is confined to limited number of variables in understanding the factors impacting oversubscription. Future studies could include macroeconomic variables like gross domestic product (GDP), inflation rate, industry specific variable, i.e. technology/nontechnology industry, financial/nonfinancial industry for better understanding. Cross country analysis is suggested in future studies to validate the findings of current study. Future studies are advised to conduct the study examining the factors affecting oversubscription in light of COVID-19 pandemic.

Practical implications

The findings of the present study offer implications to academicians, investors, investment advisors and regulators. It provides useful insights to researchers by listing the factors that contribute to variation in subscription levels in emerging economy like India thereby, paving the way for future researches in SME IPOs in countries with different institutional settings. For investors, the study provides additional and novel information useful for IPO valuation and informed investment decisions. In addition, the findings put investment advisors in better place to guide potential investors regarding investment in good quality SME stocks (i.e. highly subscribed stocks) in more informative manner. Last but not the least, as this study would assist the regulators in handling future IPOs in a way that augments the chances of success of SME IPOs.

Originality/value

This study is a novel contribution in widening the IPO literature by examining the relationship between pre-IPO firm actions like issue price, pricing mechanism, issue size, firm size, listing delay, underwriter reputation, hot market, underpricing and oversubscription in unexplored settings of Indian SME IPOs.
Researcher perspective in the IS discipline: an empirical study of articles in the basket of 8 journals
Authors: Clarke Roger , Davison Robert M. , Jia Wanying
Published: August 2020

Purpose

The purpose of this paper is to explore the nature of “researcher perspective” in articles published in the AIS Basket of 8 journals.

Design/methodology/approach

Purposive sampling: descriptive analysis of 659 articles published in three complete years of each of the eight leading journals (2001, 2008, 2015).

Findings

When observing phenomena, IS researchers mostly adopt the perspective of one of the stakeholders in the activities, commonly that of the sponsor of the information system that is in focus. 96% of relevant articles adopted a single-perspective approach, and 93% of those were oriented towards the system sponsor.

Research limitations/implications

The discipline has not been exploiting opportunities to deliver greater value firstly through the adoption of perspectives other than that of the system sponsor, and secondly through dual- and multi-perspective research. Further, the ignoring of the viewpoints of other stakeholders is inconsistent with the requirements of the recently-adopted AIS Code of Ethics.

Practical implications

The dominance of single-perspective/system-sponsor-viewpoint research greatly constrains the benefits that IS research can deliver to IS practitioners and to the world at large.

Originality/value

The authors are not aware of any prior investigation into the nature of researcher perspective. We contend that an appreciation of the current bias is essential if IS research is to adapt, and thereby make far more useful contributions to practice.
Value creation in industrial clusters: the strategic nature of relationships with stakeholders and the policy environment
Authors: Chakrabarty Subrata
Published: August 2020

Purpose

Given that an industrial cluster contains a high concentration of numerous stakeholders, a firm in an industrial cluster often ends up forming relationships with many of the stakeholders. The research questions are as follows: Does stakeholder-based management always lead to greater value creation? What are the moderators in this association? This paper proposes that although relationships with stakeholders can act as a “catalyst” for value-creation, they can also act as a “retardant.” A combination of (1) the strategic nature of the relationships and (2) the policy environment determines whether the relationships with stakeholders act as catalysts or retardants.

Design/methodology/approach

Using relationship-focused theory, a conceptual framework that adopts a relational view of stakeholder theory is developed. Given the high concentration of stakeholders in industrial clusters, the conceptual framework uses stakeholders in industrial clusters as a setting. A firm can form relationships with a variety of stakeholders in an industrial cluster. The strategic nature of a relationship with a stakeholder is assessed in terms of variations in strategic intent and intellectual spillover.

Findings

The key argument is the following: whether a relationship with a stakeholder becomes a catalyst or a retardant for value creation is contingent on the fit between the strategic nature of the relationship and the policy environment. For instance, in a probusiness policy environment, relying on relationships with stakeholders that maximize intellectual spillover can act as a catalyst for value creation. In contrast, in an antibusiness environment, not having to rely on intellectual spillover is a safer option.

Originality/value

Whereas the literature implicitly assumes that stakeholder theory has relational essence, the conceptual framework developed in this paper adopts a relational view of stakeholder theory in a very explicit way. This paper applies relationship-focused theory by making explicit the different forms of stakeholder relationships. Such an explicitly relational approach in theorizing can help in more in-depth research on the link between stakeholder relationships and value creation. The conceptual framework will allow future research to analyze value creation in an industrial cluster, especially in terms of how stakeholder relationships can act as either catalysts or retardants.
Translation, cross‐cultural adaptation and validation of the Pain Catastrophizing Scale (PCS) into Bengali in patients with chronic non‐malignant musculoskeletal pain
Authors: Majumder Muhammad Shoaib Momen , Ahmed Shamim , Shazzad Nahiduzzamane , Hasan A. T. M. Tanveer , Haq Syed Atiqul , Rasker Johannes J.
Published: August 2020

Aim

To develop a culturally adapted and validated Bengali Pain Catastrophizing Scale (BePCS).

Methods

The English PCS was translated, adapted and back‐translated into and from Bengali, pre‐tested by 30 adult patients with chronic non‐malignant musculoskeletal pain. The BePCS was administered twice with 14 days interval to 90 patients. Convergent validity was measured by comparing the BePCS score with scores of the domains physical functioning and mental health of the Bengali Short Form 36, through Spearman's correlation coefficient. Test‐retest reliability was assessed by intraclass correlation coefficient (ICC) and Spearman's rank correlation coefficient and internal consistency by Cronbach's alpha. Content validity was assessed by index for content validity (ICV) and floor and ceiling effects.

Results

The BePCS was well accepted by the patients in the pre‐test. The content validity was excellent, both item ICV and scale ICV were 1. Construct validity: the convergent validity was −0.424 for physical functioning and −0.413 for mental health, indicating a moderate negative correlation. Total BePCS score showed excellent internal consistency with a mean Cronbach's α = 0.92. Internal consistency for subscales rumination, magnification and helplessness, were Cronbach's α 0.903, 0.72 and 0.872 respectively. The test‐retest reliability of total BePCS was 0.78 (P < .001) and for the subscales rumination 0.872 (P < .001), magnification 797 (P < .001) and helplessness 0.927 (P < .001), showing excellent test‐retest reliability.

Conclusions

The interviewer‐administered BePCS appears to be an acceptable, reliable and valid instrument for measuring health‐related quality of life in Bengali speaking patients with chronic non‐malignant musculoskeletal pain. Further evaluation in the general population and in different medical conditions should be done.
Affective Disruption During Forced Ethanol Abstinence in C57BL/6J and C57BL/6NJ Mice
Authors: Hartmann Matthew C. , Haney Megan M. , Smith Caitlin G. , Kumar Vivek , Rosenwasser Alan M.
Published: August 2020

Background

In alcohol‐dependent individuals, acute alcohol withdrawal results in severe physiological disruption, including potentially lethal central nervous system hyperexcitability. Although benzodiazepines successfully mitigate such symptoms, this treatment does not significantly reduce recidivism rates in postdependent individuals. Instead, persistent affective disturbances that often emerge weeks to months after initial detoxification appear to play a significant role in relapse risk; however, it remains unclear whether genetic predispositions contribute to their emergence, severity, and/or duration. Interestingly, significant genotypic and phenotypic differences have been observed among distinct C57BL/6 (B6) substrains, and, in particular, C57BL/6J (B6J) mice have been found to reliably exhibit higher voluntary ethanol (EtOH) intake and EtOH preference compared to several C57BL/6N (B6N)‐derived substrains. To date, however, B6 substrains have not been directly compared on measures of acute withdrawal severity or affective–behavioral disruption during extended abstinence.

Methods

Male and female B6J and B6NJ mice were exposed to either a 7‐day chronic intermittent EtOH vapor (CIE) protocol or to ordinary room air in inhalation chambers. Subsequently, blood EtOH concentrations and handling‐induced convulsions were evaluated during acute withdrawal, and mice were then tested weekly for affective behavior on the sucrose preference test, light–dark box test, and forced swim test throughout 4 weeks of (forced) abstinence.

Results

Despite documented differences in voluntary EtOH intake between these substrains, we found little evidence for substrain differences in either acute withdrawal or long‐term abstinence between B6J and B6NJ mice.

Conclusions

In B6J and B6NJ mice, both the acute and long‐term sequelae of EtOH withdrawal are dependent on largely nonoverlapping gene networks relative to those underlying voluntary EtOH drinking.
SLC Neurotransmitter Transporters as Therapeutic Targets for Alcohol Use Disorder: A Narrative Review
Authors: McColl Eliza R. , Piquette‐Miller Micheline
Published: August 2020

Alcohol use disorder (AUD) is 1 of the most prevalent of all substance use disorders and contributes significantly to global disease burden. Despite its prevalence, <10% of individuals with AUD receive treatment. A significant barrier to receiving treatment is a lack of effective pharmacotherapies. While 3 medications have been approved by the FDA for AUD (disulfiram, acamprosate, naltrexone), their efficacy remains low. Furthermore, a number of undesirable side effects associated with these drugs further reduce patient compliance. Thus, research into new effective pharmacotherapies for AUD is warranted. Due to their involvement in regulating synaptic neurotransmitter levels, solute carrier (SLC) transporters could be targeted for developing effective treatment strategies for AUD. Indeed, a number of studies have shown beneficial reductions in alcohol consumption through the use of drugs that target transporters of dopamine, serotonin, glutamate, glycine, and GABA. The purpose of this narrative review is to summarize preclinical and clinical studies from the last 2 decades targeting SLC neurotransmitter transporters for the treatment of AUD. Limitations, as well as future directions for expanding this field, are also discussed.
A systematic review exploring the patient decision‐making factors and attitudes towards pre‐implantation genetic testing for aneuploidy and gender selection
Authors: Bracewell‐Milnes Timothy , Saso Srdjan , Jones Benjamin , Cato Sarah , Parikh Riya , Thum Meen‐Yau , Johnson Mark , Almeida Paula , Norman‐Taylor Julian , Nikolaou Dimitrios
Published: August 2020

Introduction

Pre‐implantation genetic testing for aneuploidy (PGT‐A) is in high demand worldwide, with ongoing debate among medical societies as to which patient groups it should be offered. The psychological aspects for patients regarding its use, lag behind the genomic technological advances, leaving couples with limited decision‐making support. The development of this technology also leads to the possibility for its utilization in gender selection. Despite the controversy surrounding these issues, very few studies have investigated the psychological aspects of patients using PGT‐A.

Material and methods

This systematic review provides an up‐to‐date analysis of the psychosocial aspects surrounding PGT for aneuploidy and sex selection, as well as decision‐making factors. A systematic search of English peer‐reviewed journals of three computerized databases were undertaken following PRISMA guidelines. The qualitative data were extracted using thematic analysis. PROSPERO Registration number: CRD42019126439.

Results

The main outcome measures were patients’ motivations, decision‐making factors, attitudes and experiences surrounding the use of PGT for aneuploidy and sex selection. Ten studies were included, four for PGT‐A and six for sex selection. Attitudes towards PGT‐A were positive, with the main motivating factors being decreasing miscarriage rate, reducing the risk of termination of pregnancy and reducing the time to pregnancy. Consistently raised concerns regarding PGT‐A were the financial burden and moral beliefs. The vast majority of patients felt sufficiently knowledgeable to make the decision; however, studies did reveal that a minority mis‐interpreted certain potential benefits of PGT‐A. Studies investigating PGT for sex selection predominantly reported the main motivation was to achieve gender balance within the family dynamic, with most studies finding no difference between couples using PGT for gender selection to have male or female offspring.

Conclusions

Although this systematic review was limited by the small number of studies investigating this topic, a significant minority of patients appeared to misunderstand certain benefits and limitations of PGT‐A. Fertility clinics must ensure they provide adequate counseling to all patients using PGT‐A. With the use of PGT‐A on the rise globally, there is a need to develop decision support tools for couples who have an increasing number of genetic testing options becoming available to them.
Effect of supervised group exercise on psychological well‐being among pregnant women with or at high risk of depression (the EWE Study): A randomized controlled trial
Authors: Broberg Lotte , Tabor Ann , Rosthøj Susanne , Backhausen Mette , Frokjaer Vibe G. , Damm Peter , Hegaard Hanne K.
Published: August 2020

Introduction

Depression is expected to be the leading cause of disability worldwide by 2030. The prevalence is increasing and is two‐fold higher in women than in men, women being at particularly high risk during hormonal transition phases such as pregnancy and the postpartum period. The objective for this trial was to assess the effect of supervised group exercise on psychological well‐being and symptoms of depression among pregnant women with or at high risk of depression.

Material and methods

This study was undertaken at the Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, Denmark, from August 2016 to September 2018. Pregnant women with a current or previous history of depression and/or anxiety requiring treatment within the last 10 years, or use of antidepressants 3 months before or during pregnancy, were randomly assigned to 12 weeks of supervised group exercise from 17 to 22 weeks of gestation twice weekly, or to a control group. The primary outcome was self‐reported psychological well‐being at 29‐34 weeks of gestation, measured by the five‐item World Health Organization Well‐being Index (WHO‐5). Secondary outcomes included delivery outcomes and psychological well‐being (WHO‐5) 8 weeks postpartum.

Results

The intention‐to‐treat analysis showed no significant effect on psychological well‐being on the primary outcome. Mean WHO‐5 score in the intervention group was 2.0 (95% CI −1.3 to 5.2, P = .2) higher than in the control group. Per protocol analysis of women who attended ≥75% of the exercise sessions showed a statistically significant higher mean WHO‐5 score relative to the control group at gestational weeks 29‐34. Eight weeks postpartum the intervention group reported higher psychological well‐being than the control group, mean difference in WHO‐5 score of 5.5 (95% CI 1.0‐10.1, P = .04).

Conclusions

Supervised group exercise did not improve psychological well‐being for women with or at high risk of depression at 29‐34 weeks of gestation. Eight weeks postpartum the intervention group reported significantly higher psychological well‐being than the control group. Based on our results, supervised exercise in groups is a safe complementary course of treatment alongside the existing antenatal care.
Deconstructing the relationships between self‐esteem and paranoia in early psychosis: an experience sampling study
Authors: Monsonet Manel , Kwapil Thomas R. , Barrantes‐Vidal Neus
Published: August 2020

Background

No studies have examined the association between self‐esteem and paranoia developmentally across the critical stages of psychosis emergence. The present study fills this gap and extends previous research by examining how different dimensions, measures, and types of self‐esteem relate to daily‐life paranoia across at‐risk mental states for psychosis (ARMS) and first episode of psychosis (FEP) stages. Furthermore, the moderation effects of momentary anxiety and momentary perceived social support on the association between momentary self‐esteem and paranoia were examined.

Design

This study used a multilevel, cross‐sectional design.

Methods

One‐hundred and thirteen participants (74 ARMS and 39 FEP) were assessed repeatedly over seven consecutive days on levels of momentary paranoia, self‐esteem, anxiety and perceived social support using experience sampling methodology. Measures of trait and implicit self‐esteem were also collected.

Results

Global momentary and trait self‐esteem, and their positive and negative dimensions, were related to daily‐life paranoia in both ARMS and FEP groups. Conversely, implicit self‐esteem was not associated with daily‐life paranoia in either group. Anxiety negatively moderated the association between positive self‐esteem and lower paranoia, whereas both feeling close to others and feeling cared for by others strengthened this association. However, only feeling cared for by others moderated the association between negative self‐esteem and higher paranoia.

Conclusions

Different types, measures and dimensions of self‐esteem are differentially related to paranoia in early psychosis and are influenced by contextual factors in daily‐life. This yields a more complex picture of these associations and offers insights that might aid psychological interventions.

Practitioner points

Different measures (trait and momentary) and dimensions (positive and negative) of explicit self‐esteem are distinctly related to paranoia across risk and first‐episode stages of psychosis.

Explicit, but not implicit, self‐esteem is associated with real‐life paranoia in incipient psychosis.

Anxiety boosted the association of poor self‐esteem and paranoia ideation in daily‐life.

Social closeness, but feeling cared for by others in particular, interacts with self‐esteem tempering the expression of paranoia in real life.
The effect of 5‐azacytidine treatment delays and dose reductions on the prognosis of patients with myelodysplastic syndrome: how to optimize treatment results and outcomes
Authors: Diamantopoulos Panagiotis T. , Symeonidis Argiris , Pappa Vasiliki , Kotsianidis Ioannis , Galanopoulos Athanasios , Pontikoglou Charalampos , Anagnostopoulos Achilles , Vassilopoulos George , Zikos Panagiotis , Hatzimichael Eleftheria , Papaioannou Maria , Megalakaki Aekaterini , Repousis Panagiotis , Kotsopoulou Maria , Dimou Maria , Solomou Elena , Dryllis Georgios , Tsokanas Dimitrios , Papoutselis Menelaos‐Konstantinos , Papageorgiou Sotirios , Kyrtshonis Marie‐Christine , Kourakli Alexandra , Papadaki Helen , Panayiotidis Panayiotis , Viniou Nora‐Athina
Published: August 2020

The regimen of 5‐azacytidine for patients with myelodysplastic syndrome (MDS) has remained unchanged since its first approval. Although several modifications have since been made and delays and dose reductions are common especially during the first treatment cycles, there are minimal data on the prognostic effect of these modifications. In this study, based on data from 897 patients with MDS treated with 5‐azacytidine recorded in a national registry, the effect of treatment delays and dose reductions on response, transformation to acute myeloid leukaemia, and survival (after 5‐azacytidine initiation, OST) were analysed. Delays during the first two cycles were noted in 150 patients (16·7%) and were found to adversely affect OST independently of the International Prognostic Scoring System score [hazard ratio (HR), 1·368; P = 0·033] or pre‐existing neutropenia (HR, 1·42; P = 0·015). In patients achieving a response, delays before response achievement were correlated with its type (complete remission, 2·8 days/cycle; partial remission, 3·3 days/cycle; haematologic improvement, 5·6 days/cycle; P = 0·041), while delays after response achievement did not have any effect on retention of response or survival. Dose reductions were found to have no prognostic impact. Based on our results, treatment delays especially during the first cycles should be avoided, even in neutropenic patients. This strict strategy may be loosened after achieving a favourable response.