bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain-wide functional networks associated with anatomically- and functionally-defined hippocampal subfields using ultrahigh-resolution fMRI
Authors: Chang Wei-Tang , Langella Stephanie K. , Tang Yichuan , Zhang Han , Yap Pew-Thian , Giovanello Kelly S. , Lin Weili
Published: December 2020

The hippocampus is critical for learning and memory and may be separated into anatomically-defined hippocampal subfields (aHPSFs). Many studies have shown that aHPSFs, and their respective functional networks, are differentially vulnerable to a variety of disorders. Hippocampal functional networks, particularly during resting state, are generally analyzed using aHPSFs as seed regions, with the underlying assumption that the function within a subfield is homogeneous, yet heterogeneous between subfields. However, several prior studies that have utilized aHPSFs and assessed brain-wide cortical connectivity have observed similar resting-state functional connectivity profiles between aHPSFs. Alternatively, data-driven approaches offer a means to investigate hippocampal functional organization without a priori assumptions. However, insufficient spatial resolution may lead to partial volume effects at the boundaries of hippocampal subfields, resulting in a number of caveats concerning the reliability of the results. Hence, we developed a functional Magnetic Resonance Imaging (fMRI) sequence on a 7T MR scanner achieving 0.94 mm isotropic resolution with a TR of 2s and brain-wide coverage to 1) investigate whether hippocampal functional segmentation with ultrahigh-resolution data demonstrate similar anatomical, lamellar structures in the hippocampus, and 2) define and compare the brain-wide FC associated with fine-grained aHPSFs and functionally-defined hippocampal subfields (fHPSFs). Using a spatially restricted hippocampal Independent Component Analysis (ICA) approach, this study showed that fHPSFs were arranged along the longitudinal axis of the hippocampus that were not comparable to the lamellar structures of aHPSFs. Contrary to the anatomically defined hippocampal subfields which are bilaterally symmetrical, 13 out of 20 fHPSFs were unilateral. For brain-wide FC, the fHPSFs rather than aHPSFs revealed that a number of fHPSFs connected specifically with some of the functional networks. The visual and sensorimotor networks preferentially connected with different portions of CA1, CA3 and CA4/DG. The DMN was also found to connect more extensively with posterior subfields rather than anterior subfields. Finally, the frontoparietal network (FPN) was anticorrelated with the head portion of CA1. The investigation of functional networks associated with the fHPSFs may enhance the sensitivity of biomarkers for a range of neurological disorders, as network-based approaches take into account disease-related alterations in brain-wide interconnections rather than measuring the regional changes of hippocampus.
Single-Cell Manifold Preserving Feature Selection (SCMER)
Authors: Liang Shaoheng , Mohanty Vakul , Dou Jinzhuang , Miao Qi , Huang Yuefan , Müftüoğlu Muharrem , Ding Li , Peng Weiyi , Chen Ken
Published: December 2020

1

Abstract

A key challenge in studying organisms and diseases is to detect rare molecular programs and rare cell populations (RCPs) that drive development, differentiation, and transformation. Molecular features such as genes and proteins defining RCPs are often unknown and difficult to detect from unenriched single-cell data, using conventional dimensionality reduction and clustering-based approaches.

Here, we propose a novel unsupervised approach, named SCMER, which performs UMAP style dimensionality reduction via selecting a compact set of molecular features with definitive meanings.

We applied SCMER in the context of hematopoiesis, lymphogenesis, tumorigenesis, and drug resistance and response. We found that SCMER can identify non-redundant features that sensitively delineate both common cell lineages and rare cellular states ignored by current approaches.

SCMER can be widely used for discovering novel molecular features in a high dimensional dataset, designing targeted, cost-effective assays for clinical applications, and facilitating multi-modality integration.
Lack of evidence of ACE2 expression and replicative infection by SARS-CoV-2 in human endothelial cells
Authors: McCracken Ian , Saginc Gaye , He Liqun , Huseynov Alik , Daniels Alison , Fletcher Sarah , Peghaire Claire , Kalna Viktoria , Andaloussi-Mäe Maarja , Muhl Lars , Craig Nicky M. , Griffiths Samantha J. , Haas Jürgen G. , Tait-Burkard Christine , Lendahl Urban , Birdsey Graeme M. , Betsholtz Christer , Noseda Michela , Baker Andrew , Randi Anna M.
Published: December 2020

A striking feature of severe COVID-19 is thrombosis in large as well as small vessels of multiple organs. This has led to the assumption that SARS-CoV-2 virus directly infects and damages the vascular endothelium. However, endothelial expression of ACE2, the cellular receptor for SARS-CoV-2, has not been convincingly demonstrated. Interrogating human bulk and single-cell transcriptomic data, we foundACE2expression in endothelial cells to be extremely low or absentin vivoand not upregulated by exposure to inflammatory agentsin vitro. Also, the endothelial chromatin landscape at theACE2locus showed presence of repressive and absence of activation marks, suggesting that the gene is inactive in endothelial cells. Finally, we failed to achieve infection and replication of SARS-CoV-2 in cultured human endothelial cells, which were permissive to productive infection by coronavirus 229E that uses CD13 as the receptor. Our data suggest that SARS-Cov-2 is unlikely to infect endothelial cells directly; these findings are consistent with a scenario where endothelial injury is indirectly caused by the infection of neighbouring epithelial cells and/or due to systemic effects mediated by immune cells, platelets, complement activation, and/or proinflammatory cytokines.
Thinking ahead: spontaneous prediction in context as a keystone of language in humans and machines
Authors: Goldstein Ariel , Zada Zaid , Buchnik Eliav , Schain Mariano , Price Amy , Aubrey Bobbi , Nastase Samuel A. , Feder Amir , Emanuel Dotan , Cohen Alon , Jansen Aren , Gazula Harshvardhan , Choe Gina , Rao Aditi , Kim Se Catherine , Casto Colton , Fanda Lora , Doyle Werner , Friedman Daniel , Dugan Patricia , Melloni Lucia , Reichart Roi , Devore Sasha , Flinker Adeen , Hasenfratz Liat , Levy Omer , Hassidim Avinatan , Brenner Michael , Matias Yossi , Norman Kenneth A. , Devinsky Orrin , Hasson Uri
Published: December 2020

Departing from traditional linguistic models, advances in deep learning have resulted in a new type of predictive (autoregressive) deep language models (DLMs). Using a self-supervised next-word prediction task, these models are trained to generate appropriate linguistic responses in a given context. We provide empirical evidence that the human brain and autoregressive DLMs share three fundamental computational principles as they process natural language: 1) both are engaged in continuous next-word prediction before word-onset; 2) both match their pre-onset predictions to the incoming word to calculate post-onset surprise (i.e., prediction error signals); 3) both represent words as a function of the previous context. In support of these three principles, our findings indicate that: a) the neural activity before word-onset contains context-dependent predictive information about forthcoming words, even hundreds of milliseconds before the words are perceived; b) the neural activity after word-onset reflects the surprise level and prediction error; and c) autoregressive DLM contextual embeddings capture the neural representation of context-specific word meaning better than arbitrary or static semantic embeddings. Together, our findings suggest that autoregressive DLMs provide a novel and biologically feasible computational framework for studying the neural basis of language.
Newfound coding potential of transcripts unveils missing members of human protein communities
Authors: Leblanc Sebastien , Brunet Marie A , Jacques Jean-François , Lekehal Amina M , Duclos Andréa , Tremblay Alexia , Bruggeman-Gascon Alexis , Samandi Sondos , Brunelle Mylène , Cohen Alan A , Scott Michelle S , Roucou Xavier
Published: December 2020

Recent proteogenomic approaches have led to the discovery that regions of the transcriptome previously annotated as non-coding regions (i.e. UTRs, open reading frames overlapping annotated coding sequences in a different reading frame, and non-coding RNAs) frequently encode proteins (termed alternative proteins). This suggests that previously identified protein-protein interaction networks are partially incomplete since alternative proteins are not present in conventional protein databases. Here we used the proteogenomic resource OpenProt and a combined spectrum- and peptide-centric analysis for the re-analysis of a high throughput human network proteomics dataset thereby revealing the presence of 280 alternative proteins in the network. We found 19 genes encoding both an annotated (reference) and an alternative protein interacting with each other. Of the 136 alternative proteins encoded by pseudogenes, 38 are direct interactors of reference proteins encoded by their respective parental gene. Finally, we experimentally validate several interactions involving alternative proteins. These data improve the blueprints of the human protein-protein interaction network and suggest functional roles for hundreds of alternative proteins.
A Robust Genome-Wide Association Study Uncovers Signature Genetic Alterations amongPseudomonas aeruginosaCystic Fibrosis Isolates
Authors: Hwang Wontae , Yong Ji Hyun , Min Kyung Bae , Lee Kang-Mu , Yoon Sang Sun
Published: December 2020

Pseudomonas aeruginosa(PA) is an opportunistic pathogen that causes diverse human infections such as chronic airway infection in cystic fibrosis (CF) patients. Although many sequenced genomes are available, a comprehensive comparison between genomes of CF versus non-CF PA isolates remains yet to be conducted. In order to gain a deeper understanding into the PA adaptation in the CF airway, we performed a Genome-Wide Association Study (GWAS) using a total of 1,001 PA genomes. Genetic variations uniquely identified among CF isolates were categorized into (i) alterations in protein-coding regions either large- or small-scale and (ii) polymorphic variations in intergenic regions. We introduced each CF-specific genetic alteration into the genome of PAO1, a prototype PA strain and experimentally validated their outcomes. Loci readily mutated among CF isolates include genes encoding a probable sulphatase and a probable TonB-dependent receptor (PA2332~PA2336), L-cysteine transporter (YecS, PA0313) and a probable transcriptional regulator (PA5438). A promoter region of heme/hemoglobin uptake outer membrane receptor (PhuR, PA4710) was similarly identified as meaningfully different between the CF and non-CF isolate groups. Our analysis, the first of its kind, highlights how PA evolves its genome to persist and survive within the context of chronic CF infection.
LL-37 fights SARS-CoV-2: The Vitamin D-Inducible Peptide LL-37 Inhibits Binding of SARS-CoV-2 Spike Protein to its Cellular Receptor Angiotensin Converting Enzyme 2In Vitro
Authors: Roth Annika , Lütke Steffen , Meinberger Denise , Hermes Gabriele , Sengle Gerhard , Koch Manuel , Streichert Thomas , Klatt Andreas R.
Published: December 2020

Objective

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the pathogen accountable for the coronavirus disease 2019 (COVID-19) pandemic. Viral entry via binding of the receptor binding domain (RBD) located within the S1 subunit of the SARS-CoV-2 Spike (S) protein to its target receptor angiotensin converting enzyme (ACE) 2 is a key step in cell infection. The efficient transition of the virus is linked to a unique protein called open reading frame (ORF) 8. As SARS-CoV-2 infections can develop into life-threatening lower respiratory syndromes, effective therapy options are urgently needed. Several publications propose vitamin D treatment, although its mode of action against COVID-19 is not fully elucidated. It is speculated that vitamin D’s beneficial effects are mediated by up-regulating LL-37, a well-known antimicrobial peptide with antiviral effects.

Methods

Recombinantly expressed SARS-CoV-2 S protein, the extended S1 subunit (S1e), the S2 subunit (S2), the receptor binding domain (RBD), and ORF8 were used for surface plasmon resonance (SPR) studies to investigate LL-37’s ability to bind to SARS-CoV-2 proteins and to localize its binding site within the S protein. Binding competition studies were conducted to confirm an inhibitory action of LL-37 on the attachment of SARS-CoV-2 S protein to its entry receptor ACE2.

Results

We could show that LL-37 binds to SARS-CoV-2 S protein (LL-37/SStrepKD= 410 nM, LL-37/SHisKD= 410 nM) with the same affinity, as SARS-CoV-2 binds to hACE2 (hACE2/SStrepKD= 370 nM, hACE2/SHisKD= 370 nM). The binding is not restricted to the RBD of the S protein, but rather distributed along the entire length of the protein. Interaction between LL-37 and ORF8 was detected with a KDof 290 nM. Further, inhibition of the binding of SStrep(IC50= 740 nM), S1e (IC50= 170 nM), and RBD (IC50= 130 nM) to hACE2 by LL-37 was demonstrated.

Conclusions

We have revealed a biochemical link between vitamin D, LL-37, and COVID-19 severity. SPR analysis demonstrated that LL-37 binds to SARS-CoV-2 S protein and inhibits binding to its receptor hACE2, and most likely viral entry into the cell. This study supports the prophylactic use of vitamin D to induce LL-37 that protects from SARS-CoV-2 infection, and the therapeutic administration of vitamin D for the treatment of COVID-19 patients. Further, our results provide evidence that the direct use of LL-37 by inhalation and systemic application may reduce the severity of COVID-19.
NMDAR-independent acetylcholine, serotonin, and norepinephrine mediated modulation of synaptic eligibility traces into LTD in mice visual cortex
Authors: Khan Shumsuzzaman
Published: December 2020

This manuscript has been withdrawn after a formal notification from Johns Hopkins University that it was submitted and made public without the appropriate approval
Trust transfer and the intention to use app-enabled carpooling service
Authors: Wu Minhua , Neill Stern
Published: December 2020

Purpose

In China, with the rapid dissemination of mobile communications technology along with congested traffic and increasingly expensive transportation costs, consumers are turning to smartphone-enabled, ride-sharing services. Sharing economy requires trust in strangers. Based on trust transfer theory and a dyadic conceptualization of trust from cognitive to affective, the purpose of this study is to examine trust building through the use of Didi, a third-party, ride-sharing platform that mediates exchanges among strangers.

Design/methodology/approach

Structural equation modeling (SEM) results based on 242 observations indicate that the platform functions as an important enabler of trust, which influences a consumer's behavioral intention.

Findings

Specifically, Didi's reputation and security assurance have a positive influence on passengers' cognitive trust in drivers. There is also evidence that the interaction as mediated by the app between passengers and drivers helps the formation of affective trust, while the results do not support a relationship between cognitive and affective trust.

Originality/value

The research findings address trust transference between participants in the sharing economy and its effects, which have significant theoretical and practical implications and offer opportunities for future research in other sectors of the sharing economy.
Preparing graduates with the employability skills for the unknown future: reflection on assessment practice during COVID-19
Authors: Dyki Matthew , Singorahardjo Maggie , Cotronei-Baird Valeria S.
Published: December 2020

Purpose

The purpose of this paper is to provide an authentic and relevant way of sharing our realisation of the significance of integrating employability skills in assessment practice. This is supported from the anecdotal evidence received from students, which show that the inclusion and assessment of employability skills has provided them with an artifact that demonstrates the employability skills required for the continually changing future and workplace. For staff, the ability to assess and give feedback on the acquisition of employability skills makes it a more enjoyable experience.

Design/methodology/approach

Due to the short rollout period and pivot to online learning, there has not been an opportunity to undertake a comprehensive and formal data collection. However, anecdotal evidence has been collected from students and staff on the experience of the student-created video assignment in a completely online environment.

Findings

This paper establishes how a student video assessment contributes to students’ acquisition, development and enhancement of employability skills, such as communication and teamwork skills, that are central for preparing students for continually evolving future and thus the “new normal” brought forward by COVID-19.

Practical implications

This paper enables the authors to share their experiences and provision of their resources so that other teaching academics are able to design their own assessment task that contributes to students’ acquisition, development and enhancement of employability skills.

Originality/value

The originality of this paper is the application of integrating employability skills in assessment practice and the associated rubric as way to build students’ employability skills in the post-COVID world.
Vasundhara's Appraisal
Authors: Vohra Neharika
Published: December 2020

Premal Seth, Head, Human Resources, of Technosol, sat in his Bengaluru office at 9 pm dreading the traffic he would have to negotiate if he stepped outside to catch a bite and equally dreading going up for coffee to the coffee shop 100 meters from his office. It was the first week of April (the week after the finalization of performance appraisals and ratings of all employees) and he would often bump into known and unknown people within the company who were disappointed, upset, sad, or plain angry at how the manager had ranked him/her or how unfair the performance management system was. Deciding not to get up at all, he focused on the various pending grievance emails. As he was going through them, an email from Vasundhara Rao, a senior subject matter expert, located in Ahmedabad, caught his attention (for details about the case characters, refer Exhibit 1).
An estimation model of construction project segmentation for optimum project pricing
Authors: Shiue Fang-Jye , Lee Hsin-Yun , Zheng Meng-Cong , Khitam Akhmad F.K. , Assefa Sintayehu
Published: December 2020

Purpose

For large projects, project segmentation and planning the size of contract packages in construction bids is a complex and critical issue. Due to the nature of construction projects, which frequently have large budgets, long durations and many activities with complex procedures, project segmentation involves complicated decision-making. To fill this gap, this study aims to develop an integrated model for planning project segmentation.

Design/methodology/approach

The proposed model integrates a simulation and multiple attribute decision-making method. The simulation is used to evaluate the bidding outcome of various project segmentations. The owner can then determine the bid-price behavior of contractors in response to varying work package sizes. The multiple attribute decision-making method is used to select the optimal segmentation solution from the simulated scenarios.

Findings

The proposed model is applied to a large road preservation project in Indonesia and incorporates bid participants and market conditions. The model provides seven scenarios for segmentation. The range of scenarios captures increasing competitiveness in the construction with the average bid price becoming gradually more beneficial for the owner. The model also utilizes a multiple attribute decision-making method to select the optimum scenario for the owner.

Originality/value

This study presents an applicable model for project segmentation that is useful for both project owners and contractors. By utilizing the proposed model, a project owner can segment a large project into smaller contract packages to create improved project pricing.
Factors affecting the intrusiveness and selection of real-site data collection methods in hot and humid climates: critical review
Authors: Moohialdin Ammar , Lamari Fiona , Miska Marc , Trigunarsyah Bambang
Published: December 2020

Purpose

Hot and humid climates (HHCs) are potential environmental hazards that directly affect construction workers' health and safety (HS) and negatively impact workers' productivity. Extensive research efforts have addressed the effects of HHCs. However, these efforts have been inconsistent in their approach for selecting factors influencing workers in such conditions. There are also increasing concerns about the drop-off in research interest to follow through intrusive and non-real-time measurements. This review aims to identify the major research gaps in measurements applied in previous research with careful attention paid to the factors that influence the intrusiveness and selection of the applied data collection methods.

Design/methodology/approach

This research integrates a manual subjective discussion with a thematic analysis of Leximancer software and an elaborating chronological, geographical and methodological review that yielded 701 articles and 76 peer-reviewed most related articles.

Findings

The literature included the physiological parameters as influencing factors and useful indicators for HHC effects and identified site activity intensity as the most influencing work-related factor. In total, three main gaps were identified: (1) the role of substantial individual and work-related factors; (2) managerial interventions and the application of the right time against the right symptoms, sample size and measurement intervals and (3) applied methods of data collection; particularly, the intrusiveness of the utilised sensors.

Practical implications

The focus of researchers and practitioners should be in applying nonintrusive, innovative and real-time methods that can provide crew-level measurements. In particular, methods that can represent the actual effects of allocated tasks are aligned with real-time weather measurements, so proactive HHC-related preventions can be enforced on time.

Originality/value

This review contributes to the field of construction workers' safety in HHCs and enables researchers and practitioners to identify the most influential individual and work-related factors in HHCs. This review also proposes a framework for future research with suggestions to cover the highlighted research gaps and contributes to a critical research area in the construction industry.
Analyzing attitudes of students toward the use of technology for learning: simplicity is the key to successful implementation in higher education
Authors: Naveh Gali , Shelef Amit
Published: December 2020

Purpose

Research has shown that the much-anticipated technology revolution in higher education has failed to come to fruition. The arrival of ‘digital natives’ millennial students to higher education was presume to present even greater challenge concerning technology use. In light of these gaps, this research aims to capture higher education students' choice, use and preferences of technology in learning and teaching.

Design/methodology/approach

A paper-based questionnaire was distributed to third and fourth year students of industrial engineering and management at an engineering college in Israel. The students were asked to indicate their use of devices and technologies for learning, their frequency of use and their purpose of using.

Findings

Students extensively use a variety of technologies for learning. They prefer to use the same technologies for learning that they use in their personal lives – mainstream, commercially available technologies – rather than those offered by the institute. They perceive technology as a learning tool more than as a logistic/administrative tool, they would like technology to be more easily accessible and that it not be used as a facilitator of pedagogical change.

Practical implications

The results indicate that technologies intended for use in teaching should be designed similar to commercially available alternatives that are simpler to use and more appealing.

Originality/value

This study provides an up-to-date view of students' perceptions of technology for learning that can be used to more effectively implement teaching technologies in higher education.
Understanding the influence of professional status and service feedback on patients' doctor choice in online healthcare markets
Authors: Yang Hualong , Du Helen S. , Shang Wei
Published: December 2020

Purpose

Despite the prevalent use of professional status and service feedback in online healthcare markets, the potential interaction relationship between two types of information is still unknown. This study used the signaling theory to examine the substitute relationship between professional status and service feedback in patients' doctor choice, as well as the moderating effect of illness severity.

Design/methodology/approach

To test the paper's hypotheses, we constructed a panel data model using 418 doctors' data collected over a period of six months from an online healthcare market in China. Then, according to the results of the Hausman test, we estimated a fixed-effects model of patients' choice in online healthcare markets.

Findings

The empirical results showed that the effect of a doctor's professional status and service feedback on a patient's doctor choice was substitutable. Moreover, patients' illness severity played a moderating role, in that the influence of professional status on a patient with high-severity illness was higher than that on a patient with low-severity illness, whereas the influence of service feedback on a patient with low-severity illness was higher than that of a patient with high-severity illness. In addition, we found that illness severity negatively moderated the substitute relationship between professional status and service feedback on a patient's choice.

Originality/value

These findings not only contribute to signaling theory and research on online healthcare markets, but also help us understand the importance of professional status and service feedback on a patient's choice when seeking a doctor online.
Reflections on public financial management in the Covid-19 pandemic
Authors: Ball Ian
Published: December 2020

Purpose

The purpose of this paper is to reflect on competence in the management of government, with a focus on the management of public finances. I also reflect on the role public financial management (PFM) can play in addressing the impact of the coronavirus (COVID-19) pandemic.

Design/methodology/approach

The approach in this paper is to document my thoughts and opinions on PFM in the context of the COVID-19 pandemic.

Findings

Competent bureaucrats and sound finances are the key drivers of an effective PFM system that enables and encourages decisions leading to high standards of financial performance and position.

Practical implications

Although this is purely a personal reflection on the issue covered, it may encourage other academics and practitioners to explore the idea further in various settings across the globe.

Originality/value

Having devoted my academic and professional career to the field of PFM, this personal, reflective essay considers the role of PFM systems in generating information that leads to better decisions, better financial performance and position and ultimately a greater ability to absorb shocks such as the COVID-19 pandemic.
The challenges faced by service providers on satellite mental health-care facilities in Yangon, Myanmar: a qualitative study
Authors: Lin Kyaw , Lin Sun , Sein Than Tun
Published: December 2020

Purpose

Myanmar has an insufficient number of mental health workers with few institutional facilities resulting in a significant treatment gap. Although few mental health services are integrated into primary health care (PHC), the challenges are unknown. This study aimed to assess the challenges perceived by providers in the service delivery of satellite mental health care (SMHC) in two sample townships in Yangon.

Design/methodology/approach

The research was based on a case study design by applying a qualitative approach using in-depth interviews (IDIs). In the three types of service providers, a total of six staff participated as interviewees. These consisted of two team leaders, two clinical specialists providing consultations to clients and two mental health nurses.

Findings

Providers perceived the following as major challenges in the provision of services: unstable financial resources and management, insufficient human resources and capacity of service providers, restricted outpatient services, the lack of a functional referral system, overcrowding, inadequate individual consultation time, long-waiting hours, finite opening days and hours and poor setting of infrastructure, resulting in lack of privacy.

Research limitations/implications

In the absence of similar studies in Myanmar, findings could not be placed in the context of the national literature for comparison. Further, the study involved a limited number of respondents, which may have affected the findings.

Originality/value

Although the challenges revealed were not uncommon in mental health services in developing countries, this study focused on a specific model of mental health care integrated into general healthcare settings in Myanmar. The findings offer a benchmark on efforts to develop decentralized mental health services in Myanmar and provide input for future in-depth studies.
Risks’ cross-contagion between shadow banks based on complex network theory: evidence from China
Authors: Jin Li
Published: December 2020

Purpose

The purpose of this paper is to analyze the network path and internal mechanism of risks’ cross-contagion between shadow banks and design strategies for preventing risk infection between shadow banks.

Design/methodology/approach

Using the complex network theory, analyze the mechanism of risks’ cross-contagion between shadow banks from the credit network, business relationship network (BRN) and social network (SN); the cross-contagion mechanism using the structural equation model on the basis of China’s shadow banks is tested; based on the three risk infection paths, the prevention and control strategies for risk infection using the mathematical models of epidemic diseases are designed.

Findings

There are three network risk contagion paths between shadow banks. One, the credit network, risks are infected crossly mainly through debt and equity relationships; two, the BRN, risks are infected crossly mainly through business network and macro policy transmission; three, investor SN, risks are infected crossly mainly through individual SN and fractal relationships. The following three strategies for preventing risk’s cross-contagion between shadow banks: one, the in advance preventing strategy is more effective than the ex post control strategy; two, increasing the risk management coefficient; three, reducing the number of risk-infected submarkets.

Originality/value

The research of this study, especially the strategies for preventing the risks’ cross-contagion, could provide theoretical and practical guidance for regulatory authorities in formulating risk supervision measures.
Does service failure criticality affect global travellers' service evaluations? An empirical analysis of online reviews
Authors: Dwesar Rishi , Sahoo Debajani
Published: December 2020

Purpose

Increased global air travel and competition in the airline industry entail better service delivery and failure management. This study examines how airline type, failure criticality and the traveller's culture influence travellers' airline evaluations of service failure.

Design/methodology/approach

The study uses a large data set of customers' online reviews and incorporates quantitative and qualitative feedback from 20 major airlines across the world. Semantic tagging, sentiment and multivariate analyses have been used to analyse the data.

Findings

Failure criticality and travellers' cultural backgrounds significantly affect airline evaluations after service failures. Moreover, failure criticality influences evaluations of travellers from individualistic cultures more severely. Contrary to expectations, full-service airlines were evaluated positively after less critical service failures.

Practical implications

The findings support that customers undergo different emotional states when they experience service failure. Understanding these internal emotional sensitivities and how services would be judged by travellers across cultures can help airlines to better manage their service recovery efforts and to strategise prioritisation of scarce resources.

Originality/value

Though airline service failure has been well researched, this study examines the role of culture in service failure evaluations. The study uses a novel method to analyse a large data set of both quantitative and qualitative traveller feedback useful in service recovery management.
Generating knowledge through micro-contradictions: the case of a nursing home for the elderly
Authors: Hofaidhllaoui Mahrane , Satouri Temna , Chouki Mourad , Smida Ali
Published: December 2020

Purpose

The purpose of this paper is to coordinate the different stages involved in designing a “CSR approach” in order to visualize and analyze micro-contradictions occurring between players in a multidisciplinary team.

Design/methodology/approach

This intervention research project was spread over three years and conducted within an establishment for dependent elderly people (EDE).

Findings

This research extends Engeström's work to highlight the micro-contradictions identified and their nature. These micro-contradictions are reduced and investigated through mediator artifacts incorporating new knowledge.

Research limitations/implications

The main limitation of the research study is that the authors were unable to completely validate Engeström's model, including the notion of instrument. The actors involved all belong to the same organization and use the same tools. This study would be worth repeating with a project team featuring actors from different organizations in order to grasp the concept of instruments used by individual actors.

Practical implications

On the managerial front, the authors draw managers' attention to the importance of collaborative construction of management tools, which can improve the governance of their organizations.

Originality/value

The originality of this paper is based on the opportunity for the long-term analysis of the relationship between potential disturbances and the generation of new knowledge during collaborative work involving a multidisciplinary team. This study is useful for this type of establishment, especially within the context of the current health crisis.
Standard renal replacement therapy combined with hemoadsorption in the treatment of critically ill septic patients
Authors: Popescu Mihai , Dima Simona , David Corina , Tudor Andrada , Simionescu Mihai , Tomescu Dana
Published: December 2020

The aim of the study was to assess clinical and paraclinical effects of hemoadsorption on organ dysfunction, severity scores, and 28‐day survival in septic patients. Fifty‐five septic patients admitted to a general intensive care unit of a university hospital were included in the present study. Each patient underwent three consecutive 24‐hour sessions of renal replacement therapy in combination with hemoadsorption. Clinical and paraclinical variables were measured after the treatment and severity scores were calculated. The use of hemoadsorption was associated with an increase in arterial partial pressure of oxygen/fraction of inspired oxygen ratio (P = .02), urine output (P = .01), and Glasgow Coma Score (P = .03) and a decrease in white blood cell count (P = .03), C‐reactive protein (P = .01), procalcitonin (P = .01) levels, and platelet count (P = .01). The use of hemoadsorption was associated with an improvement in neurological and renal functions and a decrease in inflammatory markers. Acute respiratory distress syndrome improved significantly based on relevant improvements in one‐third of the patients.
Reconstitution of a mini‐gene cluster combined with ribosome engineering led to effective enhancement of salinomycin production in Streptomyces albus
Authors: Li Dong , Tian Yuqing , Liu Xiang , Wang Wenxi , Li Yue , Tan Huarong , Zhang Jihui
Published: December 2020

Salinomycin, an FDA‐approved polyketide drug, was recently identified as a promising anti‐tumour and anti‐viral lead compound. It is produced by Streptomyces albus, and the biosynthetic gene cluster (sal) spans over 100 kb. The genetic manipulation of large polyketide gene clusters is challenging, and approaches delivering reliable efficiency and accuracy are desired. Herein, a delicate strategy to enhance salinomycin production was devised and evaluated. We reconstructed a minimized sal gene cluster (mini‐cluster) on pSET152 including key genes responsible for tailoring modification, antibiotic resistance, positive regulation and precursor supply. These genes were overexpressed under the control of constitutive promoter PkasO* or Pneo. The pks operon was not included in the mini‐cluster, but it was upregulated by SalJ activation. After the plasmid pSET152::mini‐cluster was introduced into the wild‐type strain and a chassis host strain obtained by ribosome engineering, salinomycin production was increased to 2.3‐fold and 5.1‐fold compared with that of the wild‐type strain respectively. Intriguingly, mini‐cluster introduction resulted in much higher production than overexpression of the whole sal gene cluster. The findings demonstrated that reconstitution of sal mini‐cluster combined with ribosome engineering is an efficient novel approach and may be extended to other large polyketide biosynthesis.
Comparison of adequacy between transbronchial lung cryobiopsy samples and endobronchial ultrasound‐guided transbronchial needle aspiration samples for next‐generation sequencing analysis
Authors: Tone Mari , Inomata Minoru , Awano Nobuyasu , Kuse Naoyuki , Takada Kohei , Minami Jonsu , Muto Yutaka , Fujimoto Kazushi , Kumasaka Toshio , Izumo Takehiro
Published: December 2020

Background

Most lung cancer patients present with lesions in both lung fields and lymphadenopathy. Thus, transbronchial lung cryobiopsy (TBLC) and endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) are commonly performed for diagnosing lung cancer. However, the adequacy of these samples for next‐generation sequencing (NGS) analysis remains unclear. This study aimed to compare the adequacy between TBLC and EBUS‐TBNA samples for NGS analysis.

Methods

This retrospective cohort study included patients whose lung samples were collected via TBLC or EBUS‐TBNA and analyzed using NGS. Out of 46 genes, the number of genes in TBNA and TBLC samples that could not be assessed via NGS analysis was mainly evaluated.

Results

A total of 37 patients were included and classified into two groups (TBLC group, n = 18 and TBNA group, n = 19). The mean number of genes that could not be evaluated via NGS analysis was significantly lower in the TBLC group than in the TBNA group (0.9 vs. 10.3, P = 0.024). The median total area of tumor cells in TBLC samples was significantly greater than that in TBNA samples (6.3 [1.6–4.2] vs. 2.6 [0.2–17.3] mm2, P < 0.01). In the TBNA group, there were two fully inadequate samples for NGS analysis with a high degree of cell crush or low tumor content, while there was no fully inadequate sample in the TBLC group.

Conclusions

TBLC is more effective in obtaining adequate samples for NGS analysis than EBUS‐TBNA. TBLC should be performed to obtain adequate samples for NGS analysis in lung cancer patients with target lesions in lung fields, even if they have lymphadenopathy.

Key points

Significant findings of the study

The mean number of genes that could not be evaluated was significantly lower in TBLC samples than in EBUS‐TBNA samples (0.9 vs. 10.3, P = 0.024). TBLC could obtain adequate samples with a high concentration of uncrushed tumor cells for NGS.

What this study adds

To obtain samples for NGS analysis, the use of TBLC should be aggressively considered in lung‐cancer patients with target lesions located in lung fields, even if they have lymphadenopathy.
Crystal–chemical and diffraction analyses of Maya blue suggesting a different provenance of the palygorskite found in Aztec pigments*
Authors: Sánchez del Río M. , García‐Rivas J. , Suárez M. , García‐Romero E.
Published: December 2020

Maya blue is a pigment found in different archaeological sites of different cultures from Mesoamerica, and also in colonial buildings in Mexico and Cuba. The pigment is made from a thermally treated mixture of indigo and palygorskite. Pigment samples from Aztec and non‐Aztec archaeological sites as well as reference Yucatecan palygorskites were studied in this paper to assess their differences. The characterization of the samples was carried out by a combination of a crystal–chemical‐point analyses using electron microscopy to obtain the structural formulae of the palygorskite crystals, and studied using high‐resolution X‐ray diffraction. The data show evidence that the palygorskite used by non‐Aztec cultures, such as the Maya, is compatible with palygorskite from known sources in the Yucatan Peninsula, while the palygorskite used by the Aztec culture is different in its structure and has an origin that is still unknown.
Recurrence‐ and progression‐free survival in intermediate‐risk non‐muscle‐invasive bladder cancer: the impact of conditional evaluation and subclassification
Authors: Kohada Yuki , Hayashi Tetsutaro , Hsi Ryan S. , Yukihiro Kazuma , Sentani Kazuhiro , Goto Keisuke , Inoue Shogo , Ohara Shinya , Teishima Jun , Kajiwara Mitsuru , Nishisaka Takashi , Yasui Wataru , Black Peter C. , Matsubara Akio
Published: December 2020

Objectives

To assess the change in rates of recurrence‐free survival (RFS) and progression‐free survival (PFS) based on the duration of survival without recurrence or progression among patients with intermediate‐risk (IR) non‐muscle‐invasive bladder cancer (NMIBC), and to examine the predictive factors for recurrence at different time points by assessing conditional RFS and PFS.

Participants and Methods

A cohort of 602 patients treated with transurethral resection of bladder tumour and histopathologically diagnosed with IR NMIBC was included in this retrospective study.

Results

The conditional RFS rate at 1, 2, 3, 4 and 5 years improved with increased duration of RFS; however, the conditional PFS rate did not improve over time. Multivariable analyses showed that recurrent tumour, multiple tumours, tumour size (>3 cm), immediate postoperative instillation of chemotherapy, and administration of BCG were independent predictive factors for recurrence at baseline. The predictive ability of these factors disappeared with increasing recurrence‐free survivorship. Subclassification of these patients with IR NMIBC into three groups using clinicopathological factors (recurrent tumour, multiple tumours, tumour size) demonstrated that the high IR group (two factors) had significantly worse RFS than the intermediate (one factor, P < 0.001) and low IR groups (no factor, P = 0.005) at baseline. This subclassification stratified conditional risk of RFS also at 1, 3 and 5 years, which provides the basis for distinct surveillance protocols among patients with IR NMIBC.

Conclusion

Conditional survival analyses of patients with IR NMIBC demonstrate that RFS changes over time, while PFS does not change. These data support distinct surveillance protocols based on the subclassification of IR NMIBC.
What makes an island a suitable refuge for an endemic lizard?
Authors: Escoriza Daniel
Published: December 2020

Aim

To identify and evaluate the environmental properties of the Mediterranean islands that make them a suitable habitat for their endemic lizards. This would represent an important improvement in our knowledge and would assist the conservation of these lizards, which are threatened by both the expansion of mainland species and the increasing intensity of human disturbance on these islands.

Location

Mediterranean Basin.

Methods

I assessed the environmental associations of 50 species of lizard (19 endemic) across 552 Mediterranean islands using outlying mean index analysis. The strength of the species responses was assessed using binomial generalized linear models.

Results

The presence of endemic species is positively correlated with the distance of the island from the mainland. Island connectivity is also positively correlated with an increased presence of endemic lizards, but not with an increased presence of mainland species (i.e. those with exclusive or mainly continental natural distribution). In addition, island size, temperature and vegetation productivity are positively correlated with the presence of mainland species. Outlying mean index (OMI) analysis showed that the endemic species occupy niche positions that are similar to the average environmental conditions in the archipelago, but frequently without using the entire range of niches. The mainland species usually occur in more peripheral positions in the environmental space, except for some highly expansive species.

Conclusions

Lizards that are endemic to the Mediterranean islands were found to be present on a large number of islands within an archipelago, but they quickly disappear as the conditions change, largely because of human activity. Large islands act as population reservoirs for mainland species, facilitating secondary colonization of peripheral islets.
Mechanism of action of Imeglimin: A novel therapeutic agent for type 2 diabetes
Authors: Hallakou‐Bozec Sophie , Vial Guillaume , Kergoat Micheline , Fouqueray Pascale , Bolze Sébastien , Borel Anne‐Laure , Fontaine Eric , Moller David E.
Published: December 2020

Imeglimin is an investigational first‐in‐class novel oral agent for the treatment of type 2 diabetes (T2D). Several pivotal phase III trials have been completed with evidence of statistically significant glucose lowering and a generally favourable safety and tolerability profile, including the lack of severe hypoglycaemia. Imeglimin's mechanism of action involves dual effects: (a) amplification of glucose‐stimulated insulin secretion (GSIS) and preservation of β‐cell mass; and (b) enhanced insulin action, including the potential for inhibition of hepatic glucose output and improvement in insulin signalling in both liver and skeletal muscle. At a cellular and molecular level, Imeglimin's underlying mechanism may involve correction of mitochondrial dysfunction, a common underlying element of T2D pathogenesis. It has been observed to rebalance respiratory chain activity (partial inhibition of Complex I and correction of deficient Complex III activity), resulting in reduced reactive oxygen species formation (decreasing oxidative stress) and prevention of mitochondrial permeability transition pore opening (implicated in preventing cell death). In islets derived from diseased rodents with T2D, Imeglimin also enhances glucose‐stimulated ATP generation and induces the synthesis of nicotinamide adenine dinucleotide (NAD+) via the ‘salvage pathway’. In addition to playing a key role as a mitochondrial co‐factor, NAD+ metabolites may contribute to the increase in GSIS (via enhanced Ca++ mobilization). Imeglimin has also been shown to preserve β‐cell mass in rodents with T2D. Overall, Imeglimin appears to target a key root cause of T2D: defective cellular energy metabolism. This potential mode of action is unique and has been shown to differ from that of other major therapeutic classes, including biguanides, sulphonylureas and glucagon‐like peptide‐1 receptor agonists.