bluuebunny/crossref_metadata_2025 huggingface dataset:
Parallel processing of sensory cue and spatial information in the Dentate Gyrus
Authors: Tuncdemir Sebnem N. , Grosmark Andres D. , Turi Gergely F. , Shank Amei , Bowler Jack , Ordek Gokhan , Losonczy Attila , Hen Rene , Lacefield Clay
Published: February 2020

During exploration, animals form an internal map of an environment by combining information about specific sensory cues or landmarks with the animal’s motion through space, a process which critically depends on the mammalian hippocampus. The dentate gyrus (DG) is the first stage of the hippocampal trisynaptic circuit where self-motion and sensory cue information are integrated, yet it remains unknown how neurons within the DG encode both cue related (“what”) and spatial (“where”) information during cognitive map formation. Using two photon calcium imaging in head fixed mice running on a treadmill, along with on-line sensory cue manipulation at specific track locations, we have identified robust sensory cue responses in DG granule cells largely independent of spatial location. Granule cell cue responses are stable for long periods of time, selective for the modality of the stimulus and accompanied by strong inhibition of the firing of other active neurons. At the same time, there is a smaller fraction of neurons whose firing is spatially tuned but insensitive to the presentation of nearby cues, similar to traditional place cells. These results demonstrate the existence of “cue cells” in addition to the better characterized “place cells” in the DG, an important heterogeneity that has been previously overlooked. We hypothesize that the granule cell population may support multiple channels of spatial and non-spatial information that contribute distinctly to local and down-stream computations and impact the role of the dentate gyrus in spatial navigation and episodic memory.
The BRPF1 bromodomain is a molecular reader of di-acetyllysine
Authors: Obi Juliet O. , Lubula Mulu Y. , Cornilescu Gabriel , Henrickson Amy , McGuire Kara , Evans Chiara M. , Phillips Margaret , Boyson Samuel P. , Demeler Borries , Markley John L. , Glass Karen C.
Published: February 2020

Bromodomain-containing proteins are often part of chromatin-modifying complexes, and their activity can lead to altered expression of genes that drive cancer, inflammation and neurological disorders in humans. Bromodomain-PHD finger protein 1 (BRPF1) is part of the MOZ (monocytic leukemic zinc-finger protein) HAT (histone acetyltransferase) complex, which is associated with chromosomal translocations known to contribute to the development of acute myeloid leukemia (AML). BRPF1 contains a unique combination of chromatin reader domains including two plant homeodomain (PHD) fingers separated by a zinc knuckle (PZP domain), a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain. BRPF1 is known to recruit the MOZ HAT complex to chromatin by recognizing acetylated lysine residues on the N-terminal histone tail region through its bromodomain. However, histone proteins can contain several acetylation modifications on their N-terminus, and it is unknown how additional marks influence bromodomain recruitment to chromatin. Here, we identify the BRPF1 bromodomain as a selective reader of di-acetyllysine modifications on histone H4. We used ITC assays to characterize the binding of di-acetylated histone ligands to the BRPF1 bromodomain and found that the domain binds preferentially to histone peptides H4K5acK8ac and H4K5acK12ac. Analytical ultracentrifugation (AUC) experiments revealed that the monomeric state of the BRPF1 bromodomain coordinates di-acetylated histone ligands. NMR chemical shift perturbation studies, along with binding and mutational analyses, revealed non-canonical regions of the bromodomain-binding pocket that are important for histone tail recognition. Together, our findings provide critical information on how the combinatorial action of post-translational modifications can modulate BRPF1 bromodomain binding and specificity.
“Just be there”
Authors: Karampela Maria , Lacka Ewelina , McLean Graeme
Published: February 2020

Purpose

In business-to-business (B2B) settings, research on social media sites (SMS) has primarily examined the benefits and challenges relating to their use, as well as factors driving their adoption. Recently, attention has turned to the consequences of using SMS in B2B markets. The purpose of this paper is to extend this line of research by investigating the impact of B2B brands’ social media presence, interactivity and responsiveness on customers’ perceptions of four indicators of brand relationship strength (commitment, intimacy, satisfaction and partner quality).

Design/methodology/approach

Data from an online survey (N = 200) with customers of UK-based B2B firms were analysed using structural equation modelling.

Findings

The study reveals that a supplier’s presence on Twitter, LinkedIn and Facebook has a positive impact on all four brand relationship strength indicators; interactivity enhances perceived partner quality, while responsiveness positively influences commitment. Differences across the three SMS are also observed.

Research limitations/implications

The research was conducted on a sample of UK-based firms with varying degrees of SMS use that may influence the impact on B2B brand relationship strength.

Practical implications

This study indicates that B2B brands ought to focus primarily on presence on SMS, given its positive impact on brand relationship strength. At the same time, however, B2B brands should be active in responding to customers’ queries on SMS, as well as interacting with them to enhance commitment and perceived partner quality, respectively.

Originality/value

This study contributes to the digital marketing and B2B relationships interface and is the first to examine the role of B2B brands’ presence, interactivity and responsiveness on SMS in enhancing relationships with customers.
Group development model and Lean Six Sigma project team outcomes
Authors: Guttenberg Jamie L.
Published: February 2020

Purpose

The purpose of this study is to examine if there is a difference between service-sector Lean Six Sigma (LSS) project teams that progress through Tuckman’s group development model and those that do not in terms of the number of completed projects, the number of projects completed on time, the length of time to complete the projects and the total cost savings and avoidance because of the projects.

Design/methodology/approach

The research consisted of a quantitative, descriptive methodology. The design included a sample from a service-sector LSS practitioner population, a survey instrument, one independent construct with two levels, four dependent constructs and a multivariate analysis of variance (MANOVA).

Findings

The progression of service-sector LSS teams through Tuckman’s group development model, as measured with the group process questionnaire, significantly influences the teams in terms of the number of completed projects, the number of projects completed on time, the length of time to complete the projects and the total cost savings and avoidance because of the projects.

Research limitations/implications

A limitation of the study is there may be other factors not related to Tuckman’s group development model that can influence the outcomes of LSS projects. These variables may include senior executive buy-in, number of LSS practitioners in the organization, the robustness of LSS training programs, level of talent and other factors not related to Tuckman’s group development model. Another limitation of the study encompassed using a sample of convenience instead of a random sample.

Practical implications

The recommendation for practice is binate. First, service-sector LSS project teams should ensure they progress through the stages of Tuckman’s group development model to enjoy the significantly improved project outcomes. Second, LSS practitioners and trainers should ensure that Tuckman’s group development model is part of the training curriculum.

Social implications

The study demonstrates that all groups should attempt to progress through the stages of Tuckman and Jensen (2010) group development model to enjoy the benefits of working in a cohesive, task-focused team.

Originality/value

This study adds to the body of knowledge because, prior to this study, there was not prior research involving Tuckman’s group development model and LSS team outcomes.
A lean manufacturing road map using fuzzy-DEMATEL with case-based analysis
Authors: Seleem Sameh N. , Attia El-Awady , Karam Ahmed , El-Assal Ahmed
Published: February 2020

Purpose

This paper aims to develop a lean manufacturing road map for industrial firms by selecting the appropriate lean tools relying on the predefined strategic objectives and the firm constraints. It also illustrates how to prioritize these tools considering their interrelationship.

Design/methodology/approach

Relying on the predefined strategic objectives, operational objectives can be set by using the balanced scorecard (BSC). Afterwards, the theory of constraints (TOC) is introduced to investigate the manufacturing system and to determine its constraints. For these constraints, the principle of fault tree analysis (FTA) is used to determine their root causes. Consequently, lean manufacturing tools/initiatives can be proposed. Finally, the fuzzy-decision making trial and evaluation laboratory (fuzzy-DEMATEL) method is implemented to prioritize these initiatives and to construct a suitable lean road map by managing experts’ knowledge.

Findings

The practical results indicate that diagnosing the manufacturing system and managing experts’ knowledge to select the appropriate lean initiatives, and prioritizing these initiatives relying on the understanding of their interrelationship could support achieving the strategic targets without consuming extra time or resources.

Research limitations/implications

The study is limited to manufacturing firms. Besides, it reinforces the need for investigating the effectiveness of the proposed approach on service sectors.

Practical implications

The study provides a methodology with a real application, to manage experts’ knowledge for developing an effective lean improvement road map. The methodology could be adopted by any manufacturing firm.

Originality/value

The study supports decision makers of a firm to select the improvement initiatives by an original structural approach, which integrates BSC, TOC, FTA and fuzzy-DEMATEL. Besides, the interrelationships among the selected lean initiatives are considered, and results show the importance of analysing these interrelationships during the construction of the lean improvement plan. Moreover, its effectiveness and applicability are validated via a practical case study.
Thermo-mechanical analysis of train wheel-rail contact using a novel finite-element model
Authors: Yang Liuqing , Hu Ming , Zhao Deming , Yang Jing , Zhou Xun
Published: February 2020

Purpose

The purpose of this paper is to develop a novel method for analyzing wheel-rail (W-R) contact using thermo-mechanical measurements and study the effects of heating on the characteristics of W-R contact under different creepages.

Design/methodology/approach

This study developed an implicit-explicit finite element (FE) model which could solve both partial slip and full sliding problems by setting different angular velocities on the wheels. Based on the model, four material types under six different creepages were simulated.

Findings

The results showed that frictional heating significantly affected the residual stress distribution under large creepage conditions. As creepage increased, the temperature of the wheel tread and rail head rose and the peak value was located at the trailing edge of the contact patch.

Originality/value

The proposed FE model could reduce computational time and thus cost to about one-third of the amount commonly found in previous literature. Compared to other studies, these results are in good agreement and offer a reasonable alternative method for analyzing W-R contact under various conditions.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-07-2019-0298
Innovation within networks – patent strategies for blockchain technology
Authors: Dehghani Milad , Mashatan Atefeh , Kennedy Ryan William
Published: February 2020

Purpose

Understanding a technology’s patent landscape, including patent strategies, helps organizations position themselves regarding their innovation and provides insight about a technology’s future direction. This study aims to provide an overview of the blockchain technology patenting trends and outlines an exploratory framework of patenting strategies for blockchain.

Design/methodology/approach

A total of 3,234 registered patents are analyzed to determine the geographical distribution and identify key actors patenting around the globe. In addition, an empirical study consisting of multiple case studies in the form of ten in-depth interviews with owners/managers of organizations based in North America was conducted to understand organizations’ strategies for patenting the blockchain technology.

Findings

Several novel insights regarding the strategies are used for blockchain technology patenting. For example, the existence of strong anti-patent sentiment which results in a lack of patenting by start-up organizations or has led to a form of open source patenting strategy. Larger organizations appear to be patenting defensively, and small to medium organizations are primarily patenting to defend their competitive advantage.

Practical implications

Start-up organizations harboring anti-patent sentiment should consider the open-source patenting strategy to ensure that the collaborative innovation network can continue. They should also consider collaborating with other actors within the network to have a competitive position in the market.

Originality/value

To the authors’ knowledge, this paper is the first to conduct an empirical study with organizations currently using the blockchain technology to understand patenting strategies used for blockchain.
Biocybernetic model for the diagnosis and treatment of chronic pain
Authors: Hormazabal Fernando , Lavanderos Leonardo , Malpartida Alejandro
Published: February 2020

Purpose

The biopsychosocial model (BPSM) on chronic pain is an interactive psychophysiological behavior pattern that cannot be separated into different independent components. However, the epistemological analysis of the classic BPSM, based on “biopsychosocial factors,” can be reduced to a list of biological, psychological and social factors, which can be addressed simultaneously, but independently, where simultaneity is seen as relationality. The purpose of this paper is to achieve a systemic and transdisciplinary vision of the idea of simultaneity and multidisciplinarity of the BPSM and propose a new model for the diagnosis and treatment of chronic pain.

Design/methodology/approach

Based on the following conceptual triad, co-autonomy, centralization and non-requisite variety, to constitute systemic indicators, the authors design a new conceptual model of cohesion, communication, conduction and coordination (CO4) model to deal with the relational system of chronic pain patients.

Findings

The indicators of the CO4 system as transdisciplinary structure create and focus a completely new relationship regarding the relational system of the chronic pain patients. This new conceptual framework transcends the objects and frameworks of each discipline separately, going beyond the multidisciplinary model.

Originality/value

The CO4 model allows a diagnostic and therapeutic standardization as a new model on chronic pain, improving therapeutic efficiency, resource use and laying the foundation for a common language in future chronic pain research.
Courageous leadership: delivering results in turbulent times
Authors: Phillips Jack J. , Phillips Patti P.
Published: February 2020

Purpose

In uncertain times, courageous leaders must be in place, stepping forward to take action to drive results. Because there is really no such thing as a natural-born leader, the organization must constantly develop current and new leaders. Leadership skills and leader behavior are shaped and molded over time, but also can be dramatically changed and improved with a variety of effective leadership development programs. The perplexing issue about leaders and leadership development is the negative press it often receives. The root cause of this problem is not necessarily the content of leadership development programs or even the way that they are delivered, it is the definition of leadership success and the success of leadership development.

Design/methodology/approach

The purpose of this paper is to illustrate the success of a courageous leader does not occur until impact is achieved in the organization.

Findings

The courageous leader is one who can deliver on all levels of outcomes in the face of many difficulties, challenges and uncertainties in ambiguous environments.

Originality/value

Great leaders deliver great results, including the impact they have on their organizations or spheres of influence. Without impact, leaders are ineffective. To achieve success in these turbulent times requires leaders to be effective in delivering on five levels of outcomes, including impact and ROI. The courageous leader is one who can deliver on all levels of outcomes in the face of many difficulties, challenges and uncertainties in ambiguous environments.
Converting strategic ambiguity to competitive advantage: How Philips Lighting solved the challenge of LED technology disruption
Authors: Schoemaker Paul J.H. , Day George S. , Rao Govi
Published: February 2020

Purpose

The case of Philips Lighting shows how management coped with the ambiguous but real threats and opportunities of a highly disruptive emerging technology using three insight-producing approaches: 10; 10;∙9; Probe and learn widely. 10;∙9; Explore creative hypotheses. 10;∙9; Develop multiple scenarios. 10;

Design/methodology/approach

The case shows how leadership teams can effectively respond when confronted with ambiguous but potentially disruptive signals.

Findings

When assessing a potential digital disruption, leaders can begin by probing the latent needs of current as well as potential customers more thoroughly. Once ‘probe and learn’ approaches have surfaced new perspectives and strategic possibilities, the organization should generate context-expanding hypotheses about the meaning and consequences of various weak signals.

Practical implications

A limited number of disparate scenarios, clearly organized around a few pivotal uncertainties, provide leaders with a strategic context for interpreting ambiguous signals.

Originality/value

In the current VUCA environmen, when turbulence is high or major disruption is feared, all leaders need to examine at least one scenario that directly challenges the organization’s current mindset.
Underworked and overpaid
Authors: Lilly Juliana
Published: February 2020

Theoretical basis

The purpose of this paper is to help readers better understand the psychological impact of employees feeling underutilized in the workplace.

Research methodology

The case is based on primary data collected from Jonathan and describes his actual experience in the workplace. Mark also provided input on the situation. Because Jonathan and Mark are still employed in the same institution, the names have been disguised to protect their identity.

Case overview/synopsis

Jonathan is a highly motivated and successful employee who was promoted into a position that had no real responsibility. His manager would not restructure the job to make it more challenging or rewarding, so after three years of frustration, Jonathan has to decide if he should keep trying to fix the job, coast until retirement or resign.

Complexity academic level

This case is applicable for undergraduate business courses in organizational behavior, principles of management, principles of human resource management or leadership.
Reasons for and outcome of occupational therapy consultation and treatment in the context of multidisciplinary cancer rehabilitation; a historical cohort study
Authors: Rijpkema Corine , Duijts Saskia F. A. , Stuiver Martijn M.
Published: February 2020

Introduction

The aim of this study was to investigate reasons why people consulted an occupational therapist following cancer treatment, and to examine the outcome of occupational therapy interventions, in the context of multidisciplinary rehabilitation.

Methods

Data from 181 patients were collected retrospectively. The International Classification of Human Functioning and Health (ICF) was used to describe the reasons for occupational therapy consultation. Patients had completed the Canadian Occupational Performance Measurement (COPM) before and after the occupational therapy intervention. Change scores were calculated with a 95% confidence interval and a two‐sided p‐value obtained from a paired t‐test.

Results

The reasons for occupational therapy consultation were predominantly within the ICF domain “Activities and Participation”. On average, patients improved 3.0 points (95% CI 2.8–3.2) on the performance scale of the COPM, and 3.4 points (95% CI 3.2–3.7) on the satisfaction scale (both: p = <.001).

Conclusion

The result of this study supports the added value of occupational therapy to cancer rehabilitation, and emphasise the positive effect of occupational therapy on everyday functioning. Controlled clinical studies are needed to strengthen the evidence.
Associations between Medicaid expansion and nurse staffing ratios and hospital readmissions
Authors: Tarazi Wafa W.
Published: February 2020

Objective

To examine the associations between Medicaid expansion and nurse staffing ratios and hospital‐wide readmission rates.

Data sources

Secondary data from the 2011‐2016 Healthcare Cost Report Information System, the American Hospital Association Annual Survey, and the Hospital Compare data.

Study design

Difference‐in‐difference models are used to compare outcomes in hospitals located in states that expanded Medicaid with those located in nonexpansion states. The changes in nurse staffing ratios and hospital‐wide readmission rates are calculated in each one of the postexpansion years (2014, 2015, and 2016), compared to pre‐expansion.

Principal findings

Results indicate that nurse staffing ratios increased, whereas hospital‐wide readmission rates declined in expansion states relative to nonexpansion states. Nurse staffing ratios increased by 0.33, 0.42, and 0.46 registered nurses hours per adjusted patient days in 2014, 2015, and 2016 in hospitals located in expansion states, compared with hospitals in nonexpansion states after expansion. This increase was statistically significant (P < .001) in 2015 and 2016, but marginally significant (P = .016) in 2014. Hospital‐wide readmission rates statistically significantly decreased by 9, 16, and 18 per 10 000 patients (P < .001) in 2014, 2015, and 2016, respectively, in expansion vs nonexpansion states hospitals after expansion.

Conclusions

Medicaid expansion was associated with gradually improved hospitals' nurse staffing ratios and hospital‐wide readmission rates from 2014 through 2016. The continued monitoring of quality measures of hospitals can help assess the impact of Medicaid expansion over a longer period of time.
Point‐of‐care creatinine measurements to predict acute kidney injury
Authors: Vaara Suvi T. , Glassford Neil , Eastwood Glenn M. , Canet Emmanuel , Mårtensson Johan , Bellomo Rinaldo
Published: February 2020

Background

Plasma creatinine (Cr) is a marker of kidney function and typically measured once daily. We hypothesized that Cr measured by point‐of‐care technology early after ICU admission would be a good predictor of acute kidney injury (AKI) the next day in critically ill patients.

Methods

We conducted a retrospective database audit in a single tertiary ICU database. We included patients with normal first admission Cr (CrF) and identified a Cr value (CrP) obtained within 6‐12 hours from ICU admission. We used their difference converted into percentage (delta‐Cr‐%) to predict subsequent AKI (based on Cr and/or need for renal replacement therapy) the next day. We assessed predictive value by calculating area under the receiver characteristic curve (AUC), logistic regression models for AKI with and without delta‐Cr‐%, and the category‐free net reclassifying index (cfNRI).

Results

We studied 780 patients. Overall, 70 (9.0%) fulfilled the Cr AKI definition by CrP measurement. On day 2, 148 patients (19.0%) were diagnosed with AKI. AUC (95% CI) for delta‐Cr‐% to predict AKI on day 2 was 0.82 (95% CI 0.78‐0.86), and 0.74 (95% CI 0.69‐0.80) when patients with AKI based on the CrP were excluded. Using a cut‐off of 17% increment, the positive likelihood ratio (95% CI) for delta‐Cr‐% to predict AKI was 3.5 (2.9‐4.2). The cfNRI was 90.0 (74.9‐106.1).

Conclusions

Among patients admitted with normal Cr, early changes in Cr help predict AKI the following day.
Interactions Between Alcohol and the Endocannabinoid System
Authors: Kunos George
Published: February 2020

Endocannabinoids are lipid mediators that interact with the same cannabinoid receptors that recognize Δ9‐tetrahydrocannabinol (THC), the psychoactive constituent of marijuana, to induce similar effects in the brain and periphery. Alcohol and THC are both addictive substances whose acute use elicits rewarding effects that can lead to chronic and compulsive use via engaging similar signaling pathways in the brain. In the liver, both alcohol and endocannabinoids activate lipogenic gene expression leading to fatty liver disease. This review focuses on evidence accumulated over the last 2 decades to indicate that both the addictive neural effects of ethanol and its organ toxic effects in the liver and elsewhere are mediated, to a large extent, by endocannabinoids signaling via cannabinoid‐1 receptors (CB1R). The therapeutic potential of CB1R blockade globally or in peripheral tissues only is also discussed.
Morphological variation and sexual dimorphism in the Aspidoscelis gularis complex (Squamata: Teiidae) from Mexico
Authors: Esquivel‐Ramírez Anahí , Hornung‐Leoni Claudia T. , Manríquez‐Morán Norma L.
Published: February 2020

Morphological variation can be promoted by ecological factors and the evolutionary history of the taxa. The Aspidoscelis gularis complex is one of the groups of whiptail lizards that exhibits one of the widest distributions in North America, occupying a great variety of environments. Its members are similar in morphology, which has contributed to the taxonomic uncertainty in the group. In this study, variation in size and head shape was analysed considering a phylogenetic hypothesis based on the Cytb and ND2 mitochondrial genes. Six evolutionarily significant units were found, of which the morphological patterns were analysed. Eleven morphological characters and two landmark configurations of the head were used. Analysis of size revealed a pattern of sexual dimorphism, while geometric morphometrics suggested that there is no dimorphism in head shape. Neither size nor shape shows unique patterns of morphological variation between the evolutionarily significant units, which could be attributed to morphological conservatism and recurrent hybridization in whiptails.
Exosomes mediate intercellular transfer of non–autonomous tolerance to proteasome inhibitors in mixed‐lineage leukemia
Authors: Ge Maolin , Qiao Zhi , Kong Yan , Lu Hui , Liu Han
Published: February 2020

Proteasome inhibitors significantly improve cancer outcomes, but their use is eventually followed by proteasome inhibitor resistance and relapse. Current understanding of proteasome inhibitor resistance is limited to cell‐autonomous mechanisms; whether non–autonomous mechanisms can be implicated in the development of proteasome inhibitor resistance is unclear. Here, we show that proteasome inhibitor tolerance can be transmitted non–autonomously through exosome‐mediated intercellular interactions. We revealed that reversible proteasome inhibitor resistance can be transmitted from cells under therapy stress to naïve sensitive cells through exosome‐mediated cell cycle arrest and enhanced stemness in mixed‐lineage leukemia cells. Integrated multi‐omics analysis using the Tied Diffusion through Interacting Events algorithm identified several candidate exosomal proteins that may serve as predictors for proteasome inhibitor resistance and potential therapeutic targets for treating refractory mixed‐lineage leukemia. Furthermore, inhibiting the secretion of exosomes is a promising strategy for reversing proteasome inhibitor resistance in vivo, which provides a novel proof of principle for the treatment of other refractory or relapsed cancers.
Genetic basis of neurodevelopmental disorders in 103 Jordanian families
Authors: Froukh Tawfiq , Nafie Omar , Al Hait Sana' A. S. , Laugwitz Lucia , Sommerfeld Julia , Sturm Marc , Baraghiti Aya , Issa Tala , Al‐Nazer Anis , Koch Philipp A. , Hanselmann Johannes , Kootz Beate , Bauer Peter , Al‐Ameri Wael , Abou Jamra Rami , Alfrook Ayman J. , Hamadallah Moath , Sofan Linda , Riess Angelika , Haack Tobias B. , Riess Olaf , Buchert Rebecca
Published: February 2020

We recruited 103 families from Jordan with neurodevelopmental disorders (NDD) and patterns of inheritance mostly suggestive of autosomal recessive inheritance. In each family, we investigated at least one affected individual using exome sequencing and an in‐house diagnostic variant interpretation pipeline including a search for copy number variation. This approach led us to identify the likely molecular defect in established disease genes in 37 families. We could identify 25 pathogenic nonsense and 11 missense variants as well as 3 pathogenic copy number variants and 1 repeat expansion. Notably, 11 of the disease‐causal variants occurred de novo. In addition, we prioritized a homozygous frameshift variant in PUS3 in two sisters with intellectual disability. To our knowledge, PUS3 has been postulated only recently as a candidate disease gene for intellectual disability in a single family with three affected siblings. Our findings provide additional evidence to establish loss of PUS3 function as a cause of intellectual disability.
Impact of Vancomycin‐Induced Changes in the Intestinal Microbiota on the Pharmacokinetics of Simvastatin
Authors: Sunwoo Jung , Ji Sang Chun , Kim Andrew HyoungJin , Yu Kyung‐Sang , Cho Joo‐Youn , Jang In‐Jin , Lee SeungHwan
Published: February 2020

The pharmacokinetic (PK) properties of drugs are affected in several ways by interactions with microbiota. The aim of this study was to investigate the effects of oral vancomycin on the gut microbiota and, consequently, on the PKs of simvastatin. An open‐label, single arm, sequential crossover study was conducted in six healthy Korean male subjects. After 6 days on a control diet, simvastatin 40 mg was orally administered to the subjects before and after 1 week of oral vancomycin treatment. Blood samples for PK analysis and fecal samples for metagenomic and metabolomic analyses were collected. After vancomycin treatment, the richness of microbiota considerably decreased, and the composition was altered. In particular, the relative abundance of Bacteroidetes decreased, whereas that of proteobacteria increased. In addition, changes in fecal metabolites, including D‐glucuronic acid, were observed. However, systemic exposure of simvastatin was not changed whereas that of hydroxysimvastatin showed a tendency to increase. The relationship between the change of PKs of simvastatin and the change of gut microbiota and fecal metabolites were not clearly observed.
Inorganic polyphosphate controls cyclophilin B‐mediated collagen folding in osteoblast‐like cells
Authors: Khong Mei Li , Li Lina , Solesio Maria E. , Pavlov Evgeny V. , Tanner Julian A.
Published: February 2020

Evidence is emerging that inorganic polyphosphate (polyP) is a fundamental molecule involved in a wide range of biological processes. In higher eukaryotes, polyP is abundant in osteoblasts but questions remain as to its functions. Here, we find that polyP is particularly enriched in endoplasmic reticulum (ER) where it colocalizes with cyclophilin B (CypB) using osteoblastic SaOS‐2 model cell line. PolyP binds directly and specifically to CypB, inhibiting its peptidyl‐prolyl cis‐trans isomerase activity which is critical for collagen folding. PolyP sequestration by spermine and ER‐specific polyP reduction by polyphosphatase expression in cells reduced collagen misfolding and confirmed that endogenous polyP acts as a molecular control of CypB‐mediated collagen folding. We propose that polyP is a previously unrecognized critical regulator of protein homeostasis in ER.
The End of Abstraction and the Beginning of the People: On Law and Representation in Arnold Schoenberg's Moses und Aron
Authors: Nester Adi
Published: February 2020

This essay links the crisis of representation in modernist art with the problem of political representation in Arnold Schoenberg's unfinished opera Moses und Aron. It reads the opera in light of Schoenberg's unpublished political drafts concerning the nature of democracy as well as against the writings of political theorists such as Schmitt, Hobbes, and Rousseau, and proposes an understanding of the opera‐fragment as Schoenberg's own attempt to study the concepts “Law” and “the People” as abstract ideas whose particularized representation involves an inevitable corruption of the ideas behind the representation. Thus the compulsion to represent that which cannot be represented in the opera is translated into two separate problems: the embodiment of an abstract law through its interpretation in particular cases, and the question of representing a heterogeneous group through a unified concept like the People as well as the group's diverse demands as the general will.
Arabische Märchen zwischen Berlin und München. Migrantenautorschaft, Gender und Stereotypisierung in Abbas Khiders Der falsche Inder (2008)1
Authors: Barthold Willi
Published: February 2020

Abbas Khiders teilweise autobiographischer Roman Der falsche Inder (2008) porträtiert die strapaziöse Reise eines irakischen Flüchtlings, dem es schließlich gelingt, eine neue Identität als Autor in Deutschland zu finden. Dieser Essay untersucht die Formen der literarischen Inszenierung von Autorschaft, die der Text vor dem Hintergrund vorherrschender migrations‐ und islamfeindlicher Stereotype in der deutschen Öffentlichkeit entwickelt. Khiders Protagonist erkämpft sich diskursive Handlungsfähigkeit nicht nur durch eine spielerische Aneignung der deutschen Literaturtradition, sondern auch durch eine Konfrontation von Stereotypisierungen und Formen kultureller Ausgrenzung, die mit Hilfe einer selbstreflexiven Ironie und kreativer Mechanismen der Umkehr funktioniert. So kann der Text Machtstrukturen offenlegen, die den Zugang zum deutschen literarischen Diskurs regulieren. Zudem werden im Roman anhand eines Geflüchteten und seiner öffentlichen Wahrnehmung Tendenzen der geschlechtlichen Diskriminierung, die den medialen Migrationsdiskurs der letzten Jahre prägten, einer kritischen Reflexion unterzogen, sodass zugleich ein Hinterfragen von in der westlichen Gesellschaft präsenten Formen von Sexismus möglich wird.
Associations between corrected serum calcium and phosphorus levels and outcome in dialysis patients in the Kumamoto Prefecture
Authors: Sueta Daisuke , Tabata Noriaki , Tanaka Motoko , Hanatani Shinsuke , Arima Yuichiro , Sakamoto Kenji , Yamamoto Eiichiro , Izumiya Yasuhiro , Kaikita Koichi , Arizono Kenji , Matsui Kunihiko , Tsujita Kenichi
Published: February 2020

Introduction

Mortality in hemodialysis patients is relatively high; thus, its risk stratification is very important. There are insufficient data describing the current status of the management of serum phosphate and calcium levels.

Methods

We conducted a multicenter, prospective, registry study throughout the Kumamoto Prefecture in Japan. We enrolled 1993 patients at 58 facilities with complete explanatory data, including serum phosphate, corrected calcium, and intact parathyroid hormone levels. We categorized subjects into nine categories according to low, normal, and high levels of phosphate and corrected calcium levels. The endpoint was all‐cause mortality.

Results

Of the total number of subjects, 56.1% of the patients were in the normal phosphate and calcium category, and 72% and 77.1% had controlled serum phosphate and calcium levels, respectively. Two hundred twenty‐six deaths occurred during the follow‐up period. In the nine categories, the highest mortality rates were observed in the highest corrected calcium and lowest phosphate categories. Stepwise backward multivariate regression analyses identified the serum corrected calcium level (OR, 1.38; 95% CI, 1.06–1.79; P = 0.016) and the serum phosphate level (OR, 1.26; 95% CI, 1.08–1.48; P = 0.003) as significant and independent predictors of all‐cause mortality.

Conclusions

The corrected serum calcium and phosphate levels are associated with mortality in our dialysis population, with poorest survival in patients with high corrected serum calcium and low serum phosphorus.
Signage as an intervention on a general medicine ward to reduce unnecessary testing
Authors: Wiens Evan J. , Supel Izabella , Gallardo Justine , Seifer Colette M.
Published: February 2020

Background

Up to 30% of medical spending in developed countries is unnecessary. Unnecessary testing is not only wasteful economically, but can be injurious to patients. Studies have shown that interventions such as education, auditing, and restrictive ordering can reduce unnecessary testing. However, these interventions are time‐ and resource‐intensive. We conducted a study to determine if the passive intervention of placing signs on clinicians' computers was effective in reducing unnecessary testing.

Aims

To determine the effectiveness of signage on physicians' computers to limit unnecessary testing.

Methods

We identified two acute medicine wards on which all orders are placed via computer. On one ward (Ward A), we placed signs outlining recommendations regarding responsible test‐ordering. Ward B acted as a control. Data was collected during a 6‐month study period to determine whether test‐ordering practices differed.

Results

A total of 1645 patients accounting for 17 786 patient‐days were included in the study. Fewer tests were ordered on Ward A than Ward B (7.38 vs 8.20 tests/patient‐day; P < 0.01). Additionally, significantly fewer patients on Ward B received ≥1 complete blood count/day (36.1% vs 42.5%, P = 0.04). This effect was most pronounced among patients admitted for 7–30 days.

Conclusion

The passive intervention of placing signs on clinicians' computers significantly reduced unnecessary testing.
Fabrication of high‐fracture‐strength and gas‐tightness PDC films via PIP process for pressure sensor application
Authors: Yu Yuxi , Liu Yixin , Zhang Zhihao , Zhang Jibin
Published: February 2020

High‐fracture‐strength and high‐gas‐tightness thin‐film gas‐pressure sensors were fabricated using a silicon oxycarbonitride polymer‐derived‐ceramic (SiCNO‐PDC) material via a multiple polymer‐infiltration‐pyrolysis (PIP) process. To obtain dense SiCNO ceramic films, two types of liquid polyvinylsilazane (PVSZ) precursors were chosen; a high‐ceramic‐yield precursor with high viscosity (PVSZ‐1) was designed to construct the skeleton of ceramic film, whereas a relatively high‐ceramic‐yield precursor with low viscosity (PVSZ‐2) was designed to infiltrate in ceramic defects. The results confirmed that the PVSZ‐2 can effectively fill both intergranular and intragranular defects of ceramic films pyrolyzed by the PVSZ‐1, and produce the sponge‐like structures with nanosized pores. Although the density of the ceramic films only increased by 2.2%‐5.2% after PIP process, the gas tightness was fundamentally improved, and all ceramic films after PIP process could keep gas‐tight condition without loss of pressure after 72 hours. Similarly, the fracture strengths of the ceramic films after PIP cycles have also been improved, and the value could reach 108 MPa after only three PIP cycles. In addition, because a linear relationship among the load, resonant frequency, and deflection was detected in our ceramic films, the wireless passive gas‐pressure sensors with high‐sensitivity and high‐temperature resistance have been fabricated. It strongly indicates that the ceramic films obtained by our PIP process have real potential to be used as thin‐film gas‐pressure sensing elements in high‐temperature and high‐pressure fields.
The effects of ABRACADABRA on reading outcomes: An updated meta‐analysis and landscape review of applied field research
Authors: Abrami Philip C. , Lysenko Larysa , Borokhovski Eugene
Published: February 2020

ABRACADABRA (ABRA) is an evidence‐based suite of interactive multimedia that engages learners in the development of core reading skills. This meta‐analysis presents an update of the research evidence about the effectiveness of ABRA for elementary students. It reports 91 effect sizes in six reading‐related outcomes for a sample of 7,388 students. Regardless of context and measurement type, the studies yielded positive effects of ABRA, ranging in magnitude from g+ = 0.080 for Vocabulary Knowledge to g+ = 0.378 for Phonemic Awareness and reaching statistical significance in four outcome categories. This meta‐analysis adds to our understanding of the effectiveness of ABRA‐based reading instruction by exploring factors of research design, ABRA design and implementation contexts, and various student characteristics and offers implications for instructional practice.
Gut microbiota ofSpodoptera frugiperda(J.E. Smith) larvae as revealed by metatranscriptomic analysis
Authors: Rozadilla Gaston , Cabrera Natalia A. , Virla Eduardo G. , Greco Nancy M. , McCarthy Christina B.
Published: February 2020

The invasive fall armyworm,Spodoptera frugiperda(J.E. Smith; Lepidoptera: Noctuidae), is considered one of the most harmful pests in corn, rice and cotton crops and has developed resistance to the most widespread methods used to control it, chemical insecticides and transgenic crops based onBttoxins. On the other hand, gut microbiota plays an important role in the insect's fitness, and metatranscriptomic analyses of the insect host are an invaluable tool for identifying new pest control targets. Notwithstanding, there are extremely few reports on the functionally active profile of the gut microbiota in insects, especially in lepidopterans. Moreover, most studies have only described the bacterial community even though all the components of the microbiota, Bacteria, Archaea, fungi, protozoa and viruses, influence different physiological aspects of the insect host. This is the first time an unbiased and comprehensive metatranscriptomic approach has been used to describe the taxonomic and functional profile of the gut microbiota ofS. frugiperdalarvae, both bacterial and non‐bacterial. We identified novel and very active components which were putatively playing an important nutritional role, such as ammonia‐oxidizing Archaea and Bacteria, and a xylan‐ and hemicellulose‐degrading Actinobacteria. This analysis also allowed us to identify potential biocontrol agents.
The composition of the microbial community associated with Macrobrachium rosenbergii zoeae varies throughout larval development
Authors: Ma Rongrong , Wang Yuan , Zhao Shu , Yin Menghe , Fang Wenhong
Published: February 2020

The giant river prawn, Macrobrachium rosenbergii, is an economically important freshwater prawn. The cultivation of zoea larvae is crucial for the success of the M. rosenbergii industry. In this study, we surveyed the microbial community diversity and structure associated with M. rosenbergii zoeae at different stages of larval development. Samples of zoea larvae from different developmental stages were collected and subjected to high‐throughput DNA sequencing. Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria were the dominant phyla in all six sample groups. At the genus level, the relative abundance of Bacillus decreased, and that of Enterobacter increased with the growth of the zoeae. This may have been related to the intestinal development of the zoea larvae. The microbial diversity of M. rosenbergii zoea larvae decreased significantly with development. The beta diversity analysis showed that the closer the developmental stage of M. rosenbergii, the more similar the structure of the associated bacterial communities.
Spatio‐temporal variations in mortality during the seawater production phase of Atlantic salmon (Salmo salar) in Norway
Authors: Bang Jensen Britt , Qviller Lars , Toft Nils
Published: February 2020

In a sustainable production of animals, monitoring and minimizing mortality must be a top priority. Systematic measuring of mortality over time can be used to evaluate the impact of changes in management and production strategies in Norway. To aid understanding of the potential for reducing mortality, we have used data from 2014 to 2018 to investigate the spatio‐temporal patterns of mortality, by descriptive analyses and statistical modelling of possible determinants of mortality. The results show large differences in mortality across different production zones and between years. The areas with the highest density of farmed salmon are also the ones with highest mortality. The total cumulated mortality of farmed salmon increased from 32.3 million in 2014 to 35.2 million in 2018, corresponding to 14.3% and 15.8% of the standing stock. An initial higher mortality was observed during the first 3 months after stocking (mean: 1.5% [0.9%–8.6%] mortality/month). This was followed by a period of stability and lower mortality (mean: 0.8% [0.9%–3.1%] mortality/month), until month 10, when mortality started to increase again. The month of first stocking, the year of slaughter, production zone and number of months at sea were all found to be statistically significant determinants for mortality, with p‐values < 1e−15.
CRH receptor antagonists from Pulsatilla chinensis prevent CRH‐induced premature catagen transition in human hair follicles
Authors: Nam You Jin , Lee Eun Young , Choi Eun‐Ju , Kang Sangjin , Kim Jinwan , Choi Yong‐Soo , Kim Dong Hyun , An Ji Hae , Han Inbo , Lee Sunghou , Lee Min Ho , Kim Young Ho , Chung Ji Hyung
Published: February 2020

Background

There is a growing interest in the relationship among stress hormones, neuroendocrine signaling, and skin diseases, including hair loss. Previous reports showed that stress hormones inhibit human hair growth and induce early catagen transition. Moreover, a CRH receptor antagonist reversed CRH‐induced alopecia in a mouse model, suggesting that antagonization of the CRH receptor is a key clinical strategy to treat stress‐induced hair loss.

Objectives

The aim of this study was to investigate the protective effect of CRH receptor antagonists from Pulsatilla chinensis on human hair follicles (hHFs) and human dermal papilla cells (hDPCs).

Methods

hHFs were observed and scored by hair cycle. The levels of cAMP, a second messenger, were measured in each group. In addition, the mRNA and protein levels of factors related to the hair cycle were measured. Furthermore, the expression levels of various members of the mitogen‐activated protein kinase (MAPK) signaling pathway related to stress were measured.

Results

CRH induced early catagen transition in an ex vivo hair organ culture model. In addition, CRH downregulated the levels of alkaline phosphatase (ALP) and hair anagen‐related cytokines in cultured hDPCs. Moreover, CRH induced the phosphorylation of JNK, c‐Jun, p38, ERK, and Akt in cultured hDPCs. CRH receptor antagonists isolated from P chinensis reversed these CRH‐induced modulations in both ex vivo hair follicles (HFs) and cultured hDPCs.

Conclusions

These results indicate that P chinensis effectively blocks CRH receptor function and that saponin derivatives from P chinensis could be a pharmaceutical and cosmetic approach to treat stress‐induced hair loss.