bluuebunny/crossref_metadata_2025 huggingface dataset:
RETrace: simultaneous retrospective lineage tracing and methylation profiling of single cells
Authors: Wei Christopher Jen-Yue , Zhang Kun
Published: March 2020

Retrospective lineage tracing harnesses naturally occurring mutations in cells to elucidate single cell development. Common single-cell phylogenetic fate mapping methods have utilized highly mutable microsatellite loci found within the human genome. Such methods were limited by the introduction of in vitro noise through polymerase slippage inherent in DNA amplification, which we characterized to be approximately 10–100× higher than the in vivo replication mutation rate. Here, we present RETrace, a method for simultaneously capturing both microsatellites and methylation-informative cytosines to characterize both lineage and cell type, respectively, from the same single cell. An important unique feature of RETrace was the introduction of linear amplification of microsatellites in order to reduce in vitro amplification noise. We further coupled microsatellite capture with single-cell reduced representation bisulfite sequencing (scRRBS), to measure the CpG methylation status on the same cell for cell type inference. When compared to existing retrospective lineage tracing methods, RETrace achieved higher accuracy (88% triplet accuracy from an ex vivo HCT116 tree) at a higher cell division resolution (lowering the required number of cell division difference between single cells by approximately 100 divisions). Simultaneously, RETrace demonstrated the ability to capture on average 150,000 unique CpGs per single cell in order to accurately determine cell type. We further formulated additional developments that would allow high-resolution mapping on microsatellite-stable cells or tissues with RETrace. Overall, we present RETrace as a foundation for multi-omics lineage mapping and cell typing of single cells.
Implementing IFRS in Saudi Arabia: evidence from publicly traded companies
Authors: Nurunnabi Mohammad , Jermakowicz Eva K. , Donker Han
Published: March 2020

Purpose

The Saudi Organization for Certified Public Accountants (SOCPA) requires that International Financial Reporting Standards (IFRS), as endorsed in Saudi Arabia, be used by all listed and unlisted companies. This study aims to provide insight into IFRS implementation problems, based on a survey sent to Saudi Arabian companies listed on Tadawul, the Saudi stock market (i.e. financial hub in the Middle East).

Design/methodology/approach

The survey focused on the impact that IFRS conversion has had on companies, their accounting and their finance strategies. The benefits and challenges of the adoption of IFRS are analyzed, including matters pertaining to the level of understanding and experience with IFRS, perceptions about the quality of IFRS and the impact of adoption of IFRS on consolidated equity and net income.

Findings

The survey had a response rate of 72 per cent. The results indicate a majority of respondents support conversion to IFRS as it results in higher quality financial reporting; the most important expected benefits of adopting IFRS include greater reporting transparency and improved comparability with other businesses; other expected benefits include harmonization of internal and external reporting, and increased cross-border investment opportunities; the IFRS process is costly and ties up resources because of its complexity and training needed and companies expect increased volatility in reported financial results that will impact share option plans and/or other incentive plans tied to profits. However, the authors find strong support among preparers of the financial statements for IFRS, as evidenced by higher agreement among respondents to the survey on the benefits of adopting IFRS, rather than on the costs of its adoption. Furthermore, the analysis shows that the likelihood of Saudi Arabian firms that are in favor of adopting IFRS decreases if the audit firm is one of the Big 4. The reason for this negative relationship could be that the cost of transition toward IFRS will be high. Therefore, Saudi Arabian firms will not favor a transition toward IFRS when their audit firm belongs to the Big 4. Most difficult to implement IFRS, as listed by respondents, include those on financial instruments, revenue, leases and employee benefits.

Originality/value

The authors show how economic and environmental factors play a critical role in the IFRS implementation process. This study should be important to all countries worldwide that are in the process of adopting IFRS.
Legal basis for the fraud exception in letters of credit under English Law
Authors: Aladwan Zaid
Published: March 2020

Purpose

This paper aims to analyse the status of the bank’s knowledge and the hardship related to the clear evidence requirement with regard to establish the fraud exception rule in English courts.

Design/methodology/approach

Traditional analysis method and critical legal thinking.

Findings

To trigger such an exception in England, two conditions, bank’s knowledge and clear evidence, must be met to establish the fraud rule, which will be applied only if it appears in documents. The bank’s knowledge condition, the awareness of the fraud that the bank should have before the payment, is material to determine whether if the fraud rule will trigger in most of the English cases. However, if the bank is not aware of the fraud, they must honour the credit if the documents are compliant, meaning the paying bank is protected if the documents against which it made payment are tainted with fraud, even if it is not aware of the fraud. Moreover, it is not a bank’s responsibility to investigate allegations of fraud. Nonetheless, there are some reservations regarding the bank’s knowledge and clear evidence conditions, as explained above. In short, such an approach does not lead to fairness and justice for the applicant.

Originality/value

English courts focus more on evidence of the fraud rather than making unnecessary distinctions pertinent to the fraud exception scope. The absence of such evidence will not trigger the exception rule. Conversely, injunctions are not easily granted in England where the requirement for heavy evidence and proof of the bank’s knowledge will be obstacles. That is to say, banks are more protected in England simply because the courts want to uphold the integrity of the banking system when affirming the autonomy principle. In a case where the applicant becomes aware of the fraud, there is no other option for the applicant except to ask for an injunction from the court, which is not easy to gain under English courts. In addition, it is unclear how the court will prove that the bank is aware if there is fraud in the presented documents. In addition, the question arises as to whether the same strict standard will be required by both the applicant and the party who notified the fraud.
The influence of organizational learning on performance and innovation: a literature review
Authors: Patky Jahnavi
Published: March 2020

Purpose

The study addresses four vital issues in the area of organizational learning (OL) literature. The purpose of this study is to elucidate the following: definition of OL, accepted dimensions of OL, antecedents and consequences of OL and the link between OL and performance and innovation.

Design/methodology/approach

The study presents a systematic literature review and concept analysis of OL, along with a focused discussion on the association of OL with performance and innovation.

Findings

After articulating multiple perspectives, OL can be defined as the process by which organizational knowledge base and insights are developed via associations between past actions, the effect of those and future operations. OL has two widely acknowledged dimensions, namely, exploratory learning and exploitative learning. Moreover, the study presented a conceptual analysis of OL along with a comprehensive framework for precursors and outcomes of OL.

Originality/value

This study probes the issues and the pattern in the literature of OL domain. The presented conceptual analysis gives direction to the future endeavours of researchers in the field of OL.
Can usage be used for scholars’ evaluation in the construction of smart libraries?
Authors: Liu Yunmei , Li Changling , Gao Zichun
Published: March 2020

Purpose

With the development of Web2.0 and publishing digitalization, traditional libraries and evaluation citation system can no longer indicate academic paper influence validly. Therefore, it is necessary to construct smart library and find the evaluation effect of Internet metrics-Usage.

Design/methodology/approach

This study puts forward four indexes of scholars’ evaluation based on Usage (total Usage (U), average Usage rate (U/N), hu-index and pu-index), which refer to citation indexes, takes the 35 high-output scholars in the field of library and information science in the WoS database as examples, analyzes performance of different scholars evaluation indexes based on Usage and compares the differences and correlations between “citation indicators” and “usage indicators.”

Findings

This study results show that pu-index is the strongest index to evaluate scholars. Second, there is a high correlation and strong mechanism based on time dependence and interactions between Usage and citation. Third, compared to “citation indicators”, the “usage indicators” has a larger numerical value and wider measurement range, which can break the time limitation of citation, and scientifically evaluate young scholars and newly published paper by scholars.

Originality/value

This paper proposes the pu-index – a relatively superior mathematical model for Usage and provides reference for the scholars’ evaluation policy of the smart library. This model can not only provide fair evaluation conditions for young scientists but also shorten the evaluation effect of the time lag of cited indicators. In addition, the “usage indicators” in this paper are new scientific evaluation indicators generated in the network environment. Applying it to the academic evaluation system will make the research papers widely accepted by the public and will also encourage scientists to follow the development of the Internet age and pursue research with equal emphasis on quantity and quality.
Analyzing critical success factors for a successful transition towards circular economy through DANP approach
Authors: Khan Shahbaz , Maqbool Annayath , Haleem Abid , Khan Mohd Imran
Published: March 2020

Purpose

The successful transition towards the circular economy is a requirement of this technological era. The objective of this study is to identify critical success factors behind the successful transition to the circular economy.

Design/methodology/approach

A systematic literature review and experts' inputs are used to identify the major critical success factors of a successful transition towards a circular economy. Further, DANP is applied to discover the interrelationships among the critical success factors dimensions by analyzing causal relations between the relevant critical success factors. Additionally, the ranking of significant critical success factors for the successful transition towards the circular economy is determined.

Findings

This study has used the DANP methodology to understand the relationships among the five dimensions and the twenty-two critical success factors and identified the key influencing critical success factors through their global weights. Research findings suggest that “vision regard to a circular economy” has the highest weights, followed by “financial sustainability” which is regarded as the most important CSF.

Research limitations/implications

The outcomes of this work may help organizations on issues related to the transition of the linear economy towards circular economy, in understanding the degree of importance of the each critical success factors, based on which the organizations can formulate an effective strategy to systematically emphasize critical success factors as per their importance for the successful transition towards circular economy.

Originality/value

This study tries to explore and analyze critical success factors of the transition from the linear economy to a circular economy. Further, the finding of this study provides deeper insights into academia and mangers that helps to formulate their action plan for moving towards the circular economy.
Psychological detachment
Authors: Ghosh Debjani , Sekiguchi Tomoki , Fujimoto Yuka
Published: March 2020

Purpose

The purpose of this paper is to develop an additional perspective on when and why intrinsic motivation predicts employee engagement by presenting a contextual boundary of psychological detachment in relation to the relationship between intrinsic motivation, employee creativity and employee engagement of workers.

Design/methodology/approach

Data were collected from 288 full-time Japanese workers using an online survey. The study used a bootstrap method (Preacher and Hayes, 2008) to test mediation, and a Hayes method (2013) to test moderation and a first-stage moderated mediation model.

Findings

Employee creativity mediated the relationship between intrinsic motivation and employee engagement, and the relationship between intrinsic motivation and creativity was moderated by psychological detachment. Additionally, the indirect effect of intrinsic motivation on employee engagement via creativity was moderated by psychological detachment.

Research limitations/implications

The cross-sectional design may have limited the empirical inferences; however, the proposed model was based on robust theoretical contentions, and the study included an unrelated “marker variable” (neuroticism) as an effective means of identifying common method variance (CMV), thus mitigating the limitation of the design.

Practical implications

This study has shown that intrinsically motivated employees who practice psychological detachment from work achieve higher creativity and stronger employee engagement.

Originality/value

Based on the unconscious thought theory (UTT), job demand resource theory (JD-R), recovery processes (i.e. effort-recovery model) and self-determination theory (SDT), this paper adds to the literature by demonstrating the mediating and moderating mechanisms driving intrinsic motivation and employee engagement relationship.
River dams and the stability of bird communities: A hierarchical Bayesian analysis in a tropical hydroelectric power plant
Authors: Abreu Tarcísio L. S. , Berg Sandro B. , de Faria Iubatã P. , Gomes Leonardo P. , Marinho‐Filho Jader S. , Colli Guarino R.
Published: March 2020

The effects of anthropogenic disturbance upon the stability of wildlife communities depend on the heterogeneity and connectivity of habitat remnants on multiple scales. The number of hydroelectric dams in biodiversity hotspots (Africa, South America and Asia) is growing rapidly. To establish their environmental impact, it is essential to understand the dynamics of wildlife communities before and following the establishment of dams.

We evaluated the impacts of the filling of the Serra do Facão hydroelectric reservoir in the São Marcos river, central Brazil, on the bird community. Using data from 1,145 surveys across 20 sampling sites over 8 years, 2 years before and 6 years after the filling of the reservoir, we assessed the resistance, i.e. maintenance close to an equilibrium state during the disturbance, and resilience, i.e. ability to return to the original state following the disturbance, of the bird community. We used spatiotemporal hierarchical Bayesian models to assess the effects of reservoir filling on five community parameters: abundance, richness, phylogenetic diversity, functional diversity and species composition.

In the period subsequent to reservoir filling, there was (a) a marked reduction in bird abundance, richness, phylogenetic diversity and functional diversity, and (b) a reduction in the proportion of forest species, coupled with an increase in the proportion of savanna species. Except for bird abundance, none of the other community attributes returned to their original levels, even after 6 years. Our findings indicate that Cerrado bird communities have both low resistance and low resilience to habitat loss associated with the establishment of hydroelectric reservoirs.

Synthesis and applications. The environmental costs of hydroelectric dams are still underestimated or neglected in Brazil. A new paradigm in the assessment of their environmental impacts is warranted, incorporating (a) models of spatiotemporal variations based on long‐term monitoring with surveys initiated before disturbances and (b) measures of functional and phylogenetic diversity, such that society can understand the costs and benefits of the establishment of new hydroelectric dams and make informed decisions. Biodiversity loss could be minimized by ensuring the preservation and connectivity of alluvial habitats, capable of maintaining the supply of resources and the functional and phylogenetic attributes of bird communities associated with such habitats.
The influence of ecological traits and environmental factors on the co‐occurrence patterns of birds on islands worldwide
Authors: Sato Eri , Kusumoto Buntarou , Şekercioğlu Çağan H. , Kubota Yasuhiro , Murakami Masashi
Published: March 2020

To understand the mechanisms shaping global species diversity patterns, we focused on species assembly of bird communities on islands, which are ideal for detecting ecological and historical processes. We tested the hypotheses that species traits and island environments interactively shape the phylogenetic structure of island bird assemblages through a variety of ecological processes: habitat filtering, in‐situ speciation, extinction, dispersal limitation and competitive exclusion. We assessed the effects of species ecological traits and environment factors on the phylogenetic fields, which defined as phylogenetic distance between individual bird species and co‐occurred species within each island, using phylogenetic generalized linear mixed models. Climate and isolation were the most important factors driving the co‐occurrence patterns of island bird species: the species' phylogenetic fields were significantly clustered on tropical and/or isolated islands. We also found that the phylogenetic fields strongly correlated with the ecological traits especially for the diet and habitat preferences: the phylogenetic fields tended to over‐disperse for granivores and species inhabiting in wetlands or coasts, while frugivores showed clustered phylogenetic fields. Moreover, mobility and body size had substantial effects on species assemblages: long‐distance dispersers had clustered phylogenetic fields and small‐bodied species showed overdispersed phylogenetic fields.
MARTIN Has Its Place: A Macroeconometric Model of the Australian Economy
Authors: Ballantyne Alexander , Cusbert Tom , Evans Richard , Guttmann Rochelle , Hambur Jonathan , Hamilton Adam , Kendall Elizabeth , McCririck Rachael , Nodari Gabriela , Rees Daniel M.
Published: March 2020

This paper introduces MARTIN, the Reserve Bank of Australia's new model of the Australian economy. MARTIN is an economy‐wide model used for forecasting and counterfactual scenario analysis. In contrast to other models used at the Bank (and at many other central banks) which adhere to a narrow theoretical view of how the economy operates, MARTIN is a macroeconometric model that consists of a system of reduced‐form equations built to strike a balance between theoretical rigour and empirical realism. We provide an overview of the model, describe its main equations and demonstrate its responses to various scenarios.
Antivirulence properties and related mechanisms of spice essential oils: A comprehensive review
Authors: Zhang Dan , Gan Ren‐You , Zhang Jia‐Rong , Farha Arakkaveettil Kabeer , Li Hua‐Bin , Zhu Fan , Wang Xiao‐Hong , Corke Harold
Published: March 2020

In recent decades, reduced antimicrobial effectiveness, increased bacterial infection, and newly emerged microbial resistance have become global public issues, leading to an urgent need to find effective strategies to counteract these problems. Strategies targeting bacterial virulence factors rather than bacterial survival have attracted increasing interest, since the modulation of virulence factors may prevent the development of drug resistance in bacteria. Spices are promising natural sources of antivirulence compounds owing to their wide availability, diverse antivirulence phytochemical constituents, and generally favorable safety profiles. Essential oils are the predominant and most important antivirulence components of spices. This review addresses the recent efforts of using spice essential oils to inhibit main bacterial virulence traits, including the quorum sensing system, biofilm formation, motility, and toxin production, with an intensive discussion of related mechanisms. We hope that this review can provide a better understanding of the antivirulence properties of spice essential oils, which have the potential to be used as antibiotic alternatives by targeting bacterial virulence.
Health‐related quality of life in patients with esophageal cancer or precancerous lesions assessed by EQ‐5D: A multicenter cross‐sectional study
Authors: Wang Youqing , Shi Jufang , Du Lingbin , Huang Huiyao , Wang Le , Zhu Juan , Li Huizhang , Bai Yana , Liao Xianzhen , Mao Ayan , Liu Guoxiang , Ren Jiansong , Sun Xiaojie , Gong Jiyong , Zhou Qi , Mai Ling , Zhu Lin , Xing Xiaojing , Liu Yuqin , Ren Ying , Song Bingbing , Lan Li , Zhou Jinyi , Lou Peian , Sun Xiaohua , Qi Xiao , Wu Shouling , Wei Wenqiang , Zhang Kai , Dai Min , Chen Wanqing , He Jie
Published: March 2020

Background

We aimed to obtain a set of health state utility scores of patients with esophageal cancer (EC) and precancerous lesions in China, and to explore the influencing factors of health‐related quality of life (HRQoL).

Methods

A hospital‐based multicenter cross‐sectional study was conducted. From 2013 to 2014, patients with EC or precancerous lesions were enrolled. HRQoL was assessed using a European quality of life‐5 dimension (EQ‐5D‐3L) instrument. Multivariable linear regression analysis was performed to explore the influencing factors of the EQ‐5D utility scores.

Results

A total of 2090 EC patients and 156 precancer patients were included in the study. The dimension of pain/discomfort had the highest rate of self‐reported problems, 60.5% in EC and 51.3% in precancer patients. The mean visual analog scale (VAS) score for EC and precancer patients were 68.4 ± 0.7 and 64.5 ± 3.1, respectively. The EQ‐5D utility scores for EC and precancer patients were estimated as 0.748 ± 0.009 and 0.852 ± 0.022, and the scores of EC at stage I, stage II, stage III, and stage IV were 0.693 ± 0.031, 0.747 ± 0.014, 0.762 ± 0.015, and 0.750 ± 0.023, respectively. According to the multivariable analyses, the factors of region, occupation, household income in 2012, health care insurance type, pathological type, type of therapy, and time points of the survey were statistically associated with the EQ‐5D utility scores of EC patients.

Conclusions

There were remarkable decrements of utility scores among esophageal cancer patients, compared with precancer patients. The specific utility scores of EC would support further cost‐utility analysis in populations in China.
Surgical management of perianal abscess in neonates and infants
Authors: Tan Tanny Sharman P. , Wijekoon Naveen , Nataraja Ramesh M. , Lynch Amiria , Pacilli Maurizio
Published: March 2020

Background

The optimal management of perianal abscess in neonates and infants remains unclear, including the need for laying open of the fistula and the role of microscopy and culture studies (MCS). We aimed to report the recurrence rate following incision and drainage alone (I&D) compared to incision and drainage with laying open of the fistula (I&DF) and to determine the value of MCS in perianal abscess management.

Methods

Following ethical approval (16326Q), a 10‐year (2007–2017) review of children younger than 1 year presenting with a perianal abscess was performed. Presence of a fistula was sought in all patients. Data are presented as number of cases (%), median (range) and analysed using Fisher's exact test and Mann–Whitney U‐test. P‐values of <0.05 were considered significant.

Results

We identified 108 patients (107 (99.1%) males) with 111 abscesses (three bilateral); 26 in I&D group and 85 in I&DF group. Initial abscess occurred to the right of midline in 64 cases (58%) and to the left of midline in 47 cases (42%). Twenty‐two (20%) recurred after 30 (6–372) days. Sixty‐five (59%) had MCS performed. Recurrence was higher in I&D group (9/26) versus I&DF group (13/85) (P = 0.04 (relative risk 2.2, 95% confidence interval 1.0–4.5)). There was no difference in recurrence within each group between patients with or without MCS (I&D group, P = 0.1; I&DF group, P = 0.3).

Conclusion

The recurrence of surgically managed perianal abscess is lower when a fistula is identified and laid open at the initial operation. There is little value of MCS in the management of paediatric perianal abscess.
Randomised clinical trial: transabdominal interferential electrical stimulation vs sham stimulation in women with functional constipation
Authors: Moore Judith S. , Gibson Peter R. , Burgell Rebecca E.
Published: March 2020

Background

Managing chronic constipation is challenging as patients frequently remain dissatisfied with laxative treatments. Novel studies using transabdominal electrical interferential therapy in children have shown benefit but there are inadequate adult studies.

Aim

To examine the effects of transabdominal interferential stimulation on bowel symptoms and quality of life in women with refractory constipation.

Methods

In a single‐blind, randomised, sham‐controlled pilot study, women aged ≥18 years with refractory constipation were randomised to receive interferential stimulation (with crossing of electric currents) or a novel sham stimulation (with no crossing of currents) for 1 hour a day for 6 weeks. Primary outcome was the number of patients with ≥3 spontaneous bowel movements/week. Secondary endpoints included change in PAC‐SYM (Patient Assessment of Constipation‐SYMptoms), PAC‐QOL (Patient Assessment of Constipation‐Quality of Life) and an overall symptom severity score (measured at baseline, mid time point of stimulation, end of treatment and 3 months after cessation of treatment).

Results

Interferential therapy (n = 17) met the primary outcome in 9(53%) compared with 2(12%) with sham therapy (n = 16) (P = 0.02). Interferential therapy resulted in reductions in PAC‐SYM (P = 0.03) and overall symptom scores (P = 0.05). Laxative use more than halved in 66% with interferential therapy compared with 14% with sham therapy (P = 0.01). Significant improvements in symptom outcomes were maintained at 3 months. There were no treatment‐related adverse effects.

Conclusion

Transabdominal interferential electrical stimulation is effective in reducing constipation in adult women. Three months after therapy, response is maintained and quality of life improved. Not allowing currents to cross intra‐abdominally was an effective placebo.

(Australianclinicaltrials.gov.au ACTRN12614000736640).
The effects of CEO activism on employees person‐organization ideological misfit: A conceptual model and research agenda
Authors: Brown Lee Warren , Manegold Jennifer G. , Marquardt Dennis J.
Published: March 2020

Research has found many positive benefits to person‐organization (PO) fit, for both individuals and the organization. However, PO misfit has received far less attention in the literature. In this article, we look specifically at PO misfit caused by the differing political values and beliefs of the CEO and employee. We argue that CEO activism influences employee perceptions of ideological misfit (IM), whereby differing political beliefs between employees and their activist CEO can impact workplace outcomes. We consider how peer group reactions, ethical climate, external needs fulfillment, and moral identity serve as boundary conditions for perceptions of PO misfit and related organizational outcomes. We also examine antecedents of CEO activism. Drawing on academic literature from both the micro and macro perspectives of management research, we introduce a conceptual model and discuss implications for the firm and its employees.
How does public spending affect technical efficiency? Some evidence from 15 European countries
Authors: Auci Sabrina , Castellucci Laura , Coromaldi Manuela
Published: March 2020

The relationship between government size and economic growth has been widely debated. Revisiting the subject from a distinct angle with respect to the mainstream approach, we provide an empirical analysis of the impact of government size on technical efficiency. The aim of this paper is to estimate the impact of public sector's size and of public expenditure components on 15 European countries’ technical efficiency from 1996 to 2014 by using a True Random Effect model. Using the total public expenditure as a proxy for the government size we estimate simultaneously national optimal production function and technical efficiency by controlling for income distribution and institutional quality. Our main findings show that the effect of public sector's size on efficiency is positive while the type of public expenditures may have both positive and negative impact. In more details, results suggest that education and health expenditures have a positive effect on technical efficiency, while others have a negative impact.
Achieving concurrency in cloud‐orchestrated Internet of Things for resource sharing through multiple concurrent access
Authors: Xu Xuedong , Sun Wei , G. N. Vivekananda , Shankar Achyut
Published: March 2020

Cloud‐orchestrated Internet of Things (IoT) facilitates proper utilization of network resources and placating user demands in smart communications. Multiple concurrent access (MCA) techniques designed for cloud‐assisted communication helps to achieve better resource sharing features with fault tolerance ability. A multi‐objective resource allocation and sharing (RAS) for balancing MCA in cloud‐orchestrated IoT is presented in this article. The RAS constraints are modeled through linear programming (LP) as an optimization approach. The constraints are resolved using genetic representations (GR) for reducing the unserviced requests and failed resource allocations. Conventional genetic stages are inherited by the LP model to solve resource allocation and access issues reducing latency. The combined LP and GR jointly resolve resource allocation and MCA stagnation in cloud network. A fair outcome of LP‐GR is estimation using the metrics response latency, resource utilization, request handled, and average latency.
Hereditäres Angioödem in einer Familie mit spezifischen Mutationen sowohl im Plasminogen‐ als auch im SERPING1‐Gen
Authors: Bork Konrad , Zibat Arne , Ferrari David M. , Wollnik Bernd , Schön Michael P. , Wulff Karin , Lippert Undine
Published: March 2020

Hintergrund

Die Bezeichnung hereditäres Angioödem (HAE) steht für eine Gruppe genetischer Erkrankungen mit rezidivierenden, schmerzhaften und potenziell lebensbedrohlichen Gewebeschwellungen. Die häufigste Variante des HAE entsteht durch Mutationen im SERPING1‐Gen, die zu einer eingeschränkten Funktion des Komplement‐1‐Inhibitors (C1‐INH) führen. Seltenere Formen mit normaler Funktion des C1‐INH können durch Mutationen im Gen für den Gerinnungsfaktor F12 ausgelöst werden, oft ist der genetische Hintergrund jedoch nicht bekannt. Vor kurzem wurde eine neue HAE‐Mutation im Plasminogen (PLG)‐Gen nachgewiesen.

Patienten und Methodik

Wir untersuchten die unterschiedlichen klinischen Manifestationen des HAE bei 14 verwandten Patienten mit Hilfe von klinischen Befunden, biochemischen Analysen für C1‐INH und C4 sowie der Gensequenzanalyse.

Ergebnisse

Die Symptome der Patienten konnten zwei verschiedenen Varianten des HAE zugeordnet werden. Bei zehn Patienten mit Schwellungen von Lippen und Zunge ohne Beteiligung der Extremitäten fanden wir eine Mutation des PLG‐Gens (c.988A>G). Bei vier der 14 Patienten mit Schwellungen im Gastrointestinaltrakt und an den Extremitäten konnten wir eine Mutation im SERPING1‐Gen identifizieren (c.1480C>T). In zweien dieser Fälle bestand zusätzlich eine c.988A>G‐Mutation im PLG‐Gen.

Schlussfolgerungen

Dieser bisher einmalige Befund von zwei verschiedenen HAE‐spezifischen Mutationen in einer Großfamilie liefert nicht nur eine Erklärung für die divergierenden Phänotypen, sondern legt nahe, dass eine Korrelation zwischen Genotyp und Phänotyp besteht. Abdominale Schübe und Schwellungen an den Extremitäten sind bei HAE‐C1‐INH häufig, bei HAE‐PLG jedoch ungewöhnlich.
S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma – short version, part 1: diagnosis, interventions for actinic keratoses, care structures and quality‐of‐care indicators
Authors: Heppt Markus V. , Leiter Ulrike , Steeb Theresa , Amaral Teresa , Bauer Andrea , Becker Jürgen C. , Breitbart Eckhard , Breuninger Helmut , Diepgen Thomas , Dirschka Thomas , Eigentler Thomas , Flaig Michael , Follmann Markus , Fritz Klaus , Greinert Rüdiger , Gutzmer Ralf , Hillen Uwe , Ihrler Stephan , John Swen Malte , Kölbl Oliver , Kraywinkel Klaus , Löser Christoph , Nashan Dorothée , Noor Seema , Nothacker Monika , Pfannenberg Christina , Salavastru Carmen , Schmitz Lutz , Stockfleth Eggert , Szeimies Rolf‐Markus , Ulrich Claas , Welzel Julia , Wermker Kai , Berking Carola , Garbe Claus
Published: March 2020

Actinic keratoses (AK) are common lesions in light‐skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence‐based framework for clinical decision making, the guideline “actinic keratosis and cutaneous squamous cell carcinoma” was developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guideline is aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office‐based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AK and cSCC. The guideline is also aimed at affected patients, their relatives, policy makers and insurance funds. In the first part, we will address aspects relating to diagnosis, interventions for AK, care structures and quality‐of‐care indicators.
Do not touch the locking system of Hot Axios during handling of the stent deployment hub
Authors: Ishii Tatsuya , Hayashi Tsuyoshi , Katanuma Akio
Published: March 2020

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Efficacy and safety of once‐monthly efpeglenatide in patients with type 2 diabetes: Results of a phase 2 placebo‐controlled, 16‐week randomized dose‐finding study
Authors: Del Prato Stefano , Kang Jahoon , Trautmann Michael E. , Stewart John , Sorli Christopher H. , Derwahl Michael , Soto Alfonso , Yoon Kun‐Ho
Published: March 2020

Aims

To determine the optimal dose(s) of once‐monthly administration of efpeglenatide, a long‐acting glucagon‐like peptide‐1 receptor agonist (GLP‐1RA), in patients with type 2 diabetes (T2D) inadequately controlled on metformin.

Materials and methods

In this phase 2, randomized, placebo‐controlled, double‐blind trial (NCT02081118), patients were randomized 1:1:1:1 to subcutaneous efpeglenatide (8, 12 or 16 mg once monthly; n = 158) or placebo (n = 51). The 16‐week treatment period included a 4‐week titration phase with once‐weekly efpeglenatide 4 mg, followed by one dose of efpeglenatide 8 mg once monthly and two doses of the assigned once‐monthly dose. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to week 17.

Results

All efpeglenatide doses significantly reduced HbA1c versus placebo (P < 0.0001 for all). Overall, the least squares mean difference in HbA1c reductions between efpeglenatide and placebo was −7.7 mmol/mol (−0.71%; baseline to week 17). At week 17, a significantly greater proportion of efpeglenatide patients had an HbA1c level <53 mmol/mol (<7%) versus placebo (48.7% vs. 30.6%; P = 0.0320). Significant body weight loss occurred across all efpeglenatide doses (placebo‐corrected reduction −2.0 kg [efpeglenatide overall]; P = 0.0003). The safety profile was consistent with GLP‐1RAs, with gastrointestinal (GI) disorders being the most common treatment‐emergent adverse events. Fluctuations in effects on glucose levels and rates of GI events occurred between peak and trough efpeglenatide concentrations.

Conclusions

Efpeglenatide once monthly (following once‐weekly titration) has significant benefits with regard to HbA1c and weight reduction versus placebo in patients with T2D. Further studies are needed to evaluate the long‐term efficacy and safety of efpeglenatide once monthly.
Inflammatory markers in saliva for diagnosis of sepsis of hospitalizes patients
Authors: Galhardo Luciana Freitas , Ruivo Gilson Fernandes , de Oliveira Luciane Dias , Parize Graziele , Santos Silvana Soléo Ferreira Dos , Pallos Debora , Leão Mariella Vieira Pereira
Published: March 2020

Background

Inflammatory/immunological serum markers are useful for the early detection of organ dysfunction, helping the diagnosis of sepsis. Although the detection of blood biomarkers is a standard practice, the use of noninvasive samples (eg saliva) would be beneficial.

Aim

To investigate the saliva of hospitalized patients with and without sepsis and identify the levels of inflammatory markers such as C‐reactive protein (CRP), procalcitonin (PCT), interleukin 6 (IL‐6) and nitric oxide (NO).

Methods

Saliva samples were collected from 26 patients in intensive care unit with diagnosis of sepsis and from 26 without sepsis (control). The levels of CRP were determined by using latex agglutination test, whereas those of procalcitonin and IL‐6 by ELISA and NO by the Griess reaction.

Results

Of 26 patients with sepsis, 14 were males (54%) with a mean age of 63.81 ± 3.48 years. The control group had the same distribution for gender, with mean age 65.04 ± 4.07 years. Sepsis group showed higher salivary concentrations of CRP, PCT, IL‐6 and NO, with only levels of IL‐6 being statistically different (P = .0001).

Conclusions

Patients with sepsis had significantly higher levels of IL‐6 in their saliva, suggesting that this biological sample could be useful in the diagnosis of this condition.
Linguistic determinants of formal thought disorder in first episode psychosis
Authors: Mackinley Michael , Chan Jenny , Ke Hanna , Dempster Kara , Palaniyappan Lena
Published: March 2020

Aim

Thought disorder is a core feature of schizophrenia but assessment of disordered thinking is challenging, which may contribute to the paucity of mechanistic understanding of disorganization in early psychosis. We studied the use of linguistic connectives in relation to clinically quantified dimensions of thought disorder using automated speech analysis in untreated, first episode psychosis (FEPs) and healthy controls (HCs).

Methods

39 treatment‐naïve, actively psychotic FEPs and 23 group matched HCs were recruited. Three one‐minute speech samples were induced in response to photographs from the Thematic Apperception Test and speech was analysed using COH‐METRIX software. Five connectives variables from the Coh‐Metrix software were reduced using principle component analysis, resulting in two linguistic connectives factors. Thought disorder was assessed using the Thought Language Index (TLI) and the PANSS‐8.

Results

Connective factors predicted disorganization, but not impoverishment suggesting aberrant use of connectives is specific to positive thought disorder. An independent t test comparing low and high disorganization FEPs showed higher load of acausal temporal connectives in high disorganization FEPs compared to low disorganization FEPs (mean [SD] in high vs low disorganization FEPs = 0.64 (1.1) vs ‐0.37 (1.02); t = 2.91, P = .006). Acausal‐temporal connectives were not correlated with severity of symptoms or cognition suggesting connective use is a specific index of disorganized thinking rather than overall illness status.

Conclusions

Clinical assessment of disorganization in psychosis is likely linked to the aberrant use of connectives resulting in an intuitive sense of incoherence. In early psychosis, thought disorder may be reliably quantifiable using automated syntax analysis.
Test performance study for detection of Ralstonia solanacearum and Clavibacter sepedonicus in potato tubers with TaqMan PCR
Authors: Vreeburg R. A. M. , Nas M. , De Paepe B. , Dreo T. , Gottsberger R. A. , Fornefeld E. , Fraser K. , Leonard S. , Le Roux A. C. , Meekes E. T. M. , Rivoal C. , Smits‐Mastebroek L. , van Vaerenbergh J.
Published: March 2020

A test performance study (TPS) was organized in 2018 with ten official testing laboratories to evaluate the performance of different real‐time PCR tests for the detection of Clavibacter sepedonicus and/or Ralstonia solanacearum in potato tubers. Participants were sent spiked potato extracts with low (0.8–1.2 × 104 cfu mL‐1), medium (1.6–2.4 × 105 cfu mL‐1) and high (1.6–2.4 × 107 cfu mL‐1) bacterial loads, DNA extracts thereof and heel‐end cores from symptomatic potato tubers. The four real‐time PCR tests in this TPS for detection of C. sepedonicus were considered fit for purpose as principal screening methods. Two real‐time PCRs in this TPS were considered fit for purpose as principal screening methods for detection of R. solanacearum. A third real‐time PCR missed 23% of the DNA samples from low‐level R. solanacearum spikes and is considered not fit for purpose as a principal screening method. Correct identification of spiked samples was lower when DNA extraction from the spiked samples was performed by the participating laboratories, highlighting the importance of appropriate DNA extraction protocols.
SPIB promotes anoikis resistance via elevated autolysosomal process in lung cancer cells
Authors: Zhang Hua , Wang Guobin , Zhou Ruimin , Li Xiaobo , Sun Yanan , Li Yanzhe , Du Wei , Yan Xiaojie , Yang Jie , Chang Xinzhong , Liu Zhe , Ma Zhenyi
Published: March 2020

Anoikis (detachment‐induced cell death) is a specific type of programmed cell death which occurs in response to the loss of the correct extracellular matrix connections. Anoikis resistance is an important mechanism in cancer invasiveness and metastatic behavior. Autophagy, on the other hand, involves the degradation of damaged organelles and the recycling of misfolded proteins and intracellular components. However, the intersection of these two cellular responses in lung cancer cells has not been extensively studied. Here, we identified that upon matrix deprivation, the lymphocyte lineage‐specific Ets transcription factor SPIB was activated and directly enhanced SNAP47 transcription in certain lung cancer cells. Loss of attachment‐induced autophagy significantly increased anoikis resistance by SPIB activation. Consistent with this function, SPIB depletion by short hairpin RNA abrogated SNAP47 transcriptional activation upon matrix deprivation. Therefore, these data delineate an important role of SPIB in autophagy‐mediated anoikis resistance in lung cancer cells. Accordingly, these findings suggest that manipulating SPIB‐regulated pathways in vivo and evaluating the impact of anoikis resistance warrant further investigation.

Database

RNA sequencing and ChIP sequencing data are available in Gene Expression Omnibus database under the accession numbers GSE106592 and GSE125561, respectively.
Integrated Hydrologic Modeling to Untangle the Impacts of Water Management During Drought
Authors: Thatch Lauren M. , Gilbert James M. , Maxwell Reed M.
Published: March 2020

Over the past century, groundwater levels in California's San Joaquin Valley have dropped by more than 30 m in some areas mostly due to excessive groundwater extraction used to irrigate agricultural lands and sustain a growing population. Between 2012 and 2015, California experienced the worst drought in its recorded history, depleting surface water supplies and further exacerbating groundwater depletion in the region. Due to a lack of groundwater regulation, exact quantities of extracted groundwater in California are unknown and hard to quantify. Recent adoption of the Sustainable Groundwater Management Act has intensified efforts to identify sustainable groundwater use. However, understanding sustainable use in a highly productive agricultural system with an extremely complex surface water allocation system, variable groundwater use, and spatially extensive and diverse irrigation practices is no easy task. Using an integrated hydrologic model coupled with a land surface model, we evaluated how water management activities, specifically a suite of irrigation and groundwater pumping scenarios, impact surface water–groundwater fluxes and storage components and how those activities and the relationships between them change during drought. Results showed that groundwater pumping volume had the most significant impact on long‐term water storage changes. A comparison with total water storage anomaly (TWSA) estimates from NASA's Gravity Recover and Climate Experiment (GRACE) provided some insight regarding which combinations of pumping and irrigation matched the GRACE TWSA estimates, lending credibility to these scenarios. In addition, the majority of long‐term water storage changes during the recent drought occurred in groundwater storage in the deeper subsurface.
Importance of Spatial Resolution in Global Groundwater Modeling
Authors: Reinecke Robert , Wachholz Alexander , Mehl Steffen , Foglia Laura , Niemann Christoph , Döll Petra
Published: March 2020

Global‐scale gradient‐based groundwater models are a new endeavor for hydrologists who wish to improve global hydrological models (GHMs). In particular, the integration of such groundwater models into GHMs improves the simulation of water flows between surface water and groundwater and of capillary rise and thus evapotranspiration. Currently, these models are not able to simulate water table depth adequately over the entire globe. Unsatisfactory model performance compared to well observations suggests that a higher spatial resolution is required to better represent the high spatial variability of land surface and groundwater elevations. In this study, we use New Zealand as a testbed and analyze the impacts of spatial resolution on the results of global groundwater models. Steady‐state hydraulic heads simulated by two versions of the global groundwater model G3M, at spatial resolutions of 5 arc‐minutes (9 km) and 30 arc‐seconds (900 m), are compared with observations from the Canterbury region. The output of three other groundwater models with different spatial resolutions is analyzed as well. Considering the spatial distribution of residuals, general patterns of unsatisfactory model performance remain at the higher resolutions, suggesting that an increase in model resolution alone does not fix problems such as the systematic overestimation of hydraulic head. We conclude that (1) a new understanding of how low‐resolution global groundwater models can be evaluated is required, and (2) merely increasing the spatial resolution of global‐scale groundwater models will not improve the simulation of the global freshwater system.