bluuebunny/crossref_metadata_2025 huggingface dataset:
S3V2-IDEAS: a package for normalizing, denoising and integrating epigenomic datasets across different cell types
Authors: Xiang Guanjue , Giardine Belinda M. , Mahony Shaun , Zhang Yu , Hardison Ross C
Published: September 2020

Epigenetic modifications reflect key aspects of transcriptional regulation, and many epigenomic data sets have been generated under many biological contexts to provide insights into regulatory processes. However, the technical noise in epigenomic data sets and the many dimensions (features) examined make it challenging to effectively extract biologically meaningful inferences from these data sets. We developed a package that reduces noise while normalizing the epigenomic data by a novel normalization method, followed by integrative dimensional reduction by learning and assigning epigenetic states. This package, called S3V2-IDEAS, can be used to identify epigenetic states for multiple features, or identify signal intensity states and a master peak list across different cell types for a single feature. We illustrate the outputs and performance of S3V2-IDEAS using 137 epigenomics data sets from the VISION project that providesValIdatedSystematicIntegratiONof epigenomic data in hematopoiesis.

Availability and implementation

S3V2-IDEAS pipeline is freely available as open source software released under an MIT license at:https://github.com/guanjue/S3V2_IDEAS_ESMP

Contact

rch8@psu.edu,gzx103@psu.edu

Supplementary information

S3V2-IDEAS-bioinfo-supplementary-materials.pdf
ETV5 expression positively correlates with promoter methylation and predicts response for 5-FU-based adjuvant therapy response in proximal colon cancer
Authors: Giri Anil K
Published: September 2020

Discovery of markers predictive for 5-Fluorouracil (5-FU)-based adjuvant chemotherapy (adjCTX) response in patients with locally advanced stage II and III colorectal cancer (CRC) is necessary for early identification of potential responders as only 20-65% of CRC patients benefit from the treatment. PEA3 subfamily of ETS transcription factors (ETV1, ETV4, and ETV5) are upregulated in multiple cancers including colon cancers. However, the underlying epigenetic mechanism regulating their overexpression and their role in predicting therapy response in colon cancer is largely unexplored. In this study, using gene expression and methylation data from The Cancer Genome Atlas (TCGA) project, we showed that promoter DNA methylation negatively correlates with ETV4 expression (ρ= -0.17, p=5.6×10−3) and positively correlates with ETV5 expression (ρ= 0.22, p=1.43×10−4) in colon cancer tissue. Further, our analysis in 662 colon cancer patients treated with 5-FU-based-adjCTX revealed that higher ETV5 expression associated with shorter relapse-free survival (RFS) of treated patients with proximal tumors (Hazard ratio = 3.30 - 6.22, p=0.005-0.02). We also observed higher expression of signaling molecules involved in cellular proliferation (e.g. GNB5, DUSP4, FYN) in patients with high ETV5 level, suggesting that the increased cellular proliferation due to overexpression of these genes could drive the therapy resistance. The present study suggests ETV5 expression as a strong predictive biomarker for 5-FU-based adjCTX response in stage II/III CRC patients with proximal tumors.
Evidence for conformational change-induced hydrolysis of β-tubulin-GTP
Authors: Paydar Mohammadjavad , Kwok Benjamin H.
Published: September 2020

Microtubules, protein polymers of α/β-tubulin dimers, form the structural framework for many essential cellular processes including cell shape formation, intracellular transport, and segregation of chromosomes during cell division. It is known that tubulin-GTP hydrolysis is closely associated with microtubule polymerization dynamics. However, the precise roles of GTP hydrolysis in tubulin polymerization and microtubule depolymerization, and how it is initiated are still not clearly defined. We report here that tubulin-GTP hydrolysis can be triggered by conformational change induced by the depolymerizing kinesin-13 proteins or by the stabilizing chemical agent paclitaxel. We provide biochemical evidence that conformational change precedes tubulin-GTP hydrolysis, confirming this process is mechanically driven and structurally directional. Furthermore, we quantitatively measure the average size of the presumptive stabilizing “GTP cap” at growing microtubule ends. Together, our findings provide the molecular basis for tubulin-GTP hydrolysis and its role in microtubule polymerization and depolymerization.
Conformational flexibility Of A Highly Conserved Helix Controls Cryptic Pocket Formation In FtsZ
Authors: Alnami Aisha , Norton Raymond S. , Pena Helena Perez , Haider Shozeb , Kozielski Frank
Published: September 2020

Mycobacterium tuberculosisis responsible for more than 1.6 million deaths per year. Overcoming failure from established therapies owing to multidrug resistance requires the identification of novel targets. One potential antibacterial target is filamentous temperature sensitive protein Z (FtsZ), which is the bacterial homologue of mammalian tubulin, a validated cancer target.M. tuberculosisFtsZ function is essential, with its inhibition leading to arrest of cell division, elongation of the bacterial cell and eventual cell death. However, the development of potent inhibitors against FtsZ has been a challenge due to the lack of structural information. Here we have solved multiple crystal structures ofM. tuberculosisFtsZ in complex with coumarin analogues. Coumarins bind exclusively to two novel cryptic pockets in nucleotide-free FtsZ but not to the binary FtsZ-GTP or GDP complexes. Our findings provide a detailed understanding of the molecular basis for cryptic pocket formation, controlled by the conformational flexibility of the H7 helix, and thus reveal an important structural and mechanistic rationale for coumarin’s antibacterial activity.
Effects of Healthy Aging on Right Ventricular Structure and Biomechanical Properties
Authors: Kia Danial Sharifi , Shen Yuanjun , Bachman Timothy N. , Goncharova Elena A. , Kim Kang , Simon Marc A.
Published: September 2020

Healthy aging has been associated with alterations in pulmonary vasculature and right ventricular (RV) hemodynamics, potentially leading to RV remodeling. Despite the current evidence suggesting an association between aging and alterations in RV function and higher prevalence of pulmonary hypertension in the elderly, limited data exist on age-related differences in RV structure and biomechanics. In this work we report our preliminary findings on the effects of healthy aging on RV structure, function, and biomechanical properties. Hemodynamic measurements, biaxial mechanical testing, constitutive modeling, and quantitative histological analysis were employed to study two groups of Sprague-Dawley rats: control (11 weeks) and aging (80 weeks).

Aging was associated with increases in RV peak pressures (≈↑17%, p=0.017), RV contractility (≈↑52%, p= 0.004), and RV wall thickness (≈↑34%, p=0.002). Longitudinal realignment of RV collagen (16.4°, p=0.013) and myofibers (14.6°, p=0.017) were observed with aging, accompanied by transmural cardiomyocyte loss and fibrosis. A bimodal alteration in biomechanical properties was noted, resulting in increased myofiber stiffness (≈↑158%, p=0.0006) and decreased effective collagen fiber stiffness (≈↓67%, p=0.031).

Our results demonstrate the potential of healthy aging to modulate RV remodeling via increased peak pressures, cardiomyocyte loss, fiber reorientation, and altered collagen/myofiber stiffness. Some similarities were observed between aging-induced remodeling patterns and those of RV remodeling in pressure overload.
Optogenetic activation of CA1 pyramidal neuronsin vivoinduces hypersynchronous and low voltage fast seizures
Authors: Huynh Trong D , Ashraf Omar , Craig Hayden , Larmeu Lana , Barker Benjemin , Stephenson Cade , Murcia Derrick , Howard Brady , Sun Hai
Published: September 2020

Increasing evidence supports the idea that the CA1 of the hippocampus plays an important role in the pathogenesis of temporal lobe epilepsy (TLE). There is however a lack of proof that the over-excitation of CA1 alone is sufficient in inducing seizuresin vivo. Furthermore, the relevance of the seizures induced from the over-excitation of CA1 to the pathophysiology of TLE is undetermined. Here, we employed optogenetics to activate pyramidal neurons (PNs) in CA1, which reliably induced generalized seizures in freely moving non-epileptic mice. We showed that repeated photostimulations had a kindling effect. In addition, seizures induced by over-active CA1 PNs were dominated by two distinctive onset patterns, i.e. hypersynchronous (HYP) and low voltage fast (LVF) activities, which are widely recorded in patients with and animal models of TLE. In our study, HYP seizures were predominantly associated with the first photostimulation and were entirely replaced by the LVF type afterwards. This phenomenon suggests that the activation of CA1 PNs, when occurring after the first seizure, could lead to the recruitment of GABAergic interneurons to participate in the seizure generation. These findings suggest that seizures induced from the over-excitation of CA1 PNs likely involved the same hippocampal networks and cellular mechanisms underlying TLE.
Glypican4 mediates Wnt transport between germ layers via signaling filopodia
Authors: Hu Bo , Balaraju Anurag Kakkerla , Rodriguez Juan J , Gao Yuanyuan , Nguyen Nhan T , Steen Heston , Suhaib Saeb , Chen Songhai , Lin Fang
Published: September 2020

Glypicans influence signaling pathways by regulating morphogen trafficking and reception. However, the underlying mechanisms in vertebrates are poorly understood. In zebrafish, Glypican 4 (Gpc4) is required for convergence and extension (C&E) of both the mesoderm and endoderm. Here we show that transgenic expression of GFP-Gpc4 in the endoderm ofgpc4mutants rescues C&E defects in all germ layers. The rescue of mesoderm was likely mediated by Wnt5b and Wnt11f2, and depended on signaling filopodia rather than on cleavage of the Gpc4 GPI anchor. Gpc4 bound Wnt5b and regulated formation of the filopodia that transport Wnt5b to neighboring cells. Blocking signaling filopodia that extend from endodermal cells suppressed this rescue. Thus, endodermal signaling filopodia that expressed GFP-Gpc4 transported Wnt5b, and likely Wnt11f2, to other germ layers, rescuing the C&E defects caused by agpc4deficiency. Our study reveals a new mechanism that could explainin vivomorphogen distribution involving Gpc4.
L-ascorbic acid (vitamin C) fermentation by the human pathogenVibrio cholerae
Authors: Rosenberger J.R. , McDonald N.D. , Boyd E.F.
Published: September 2020

L-ascorbic acid, commonly known as vitamin C, is a ubiquitous 6-carbon carbohydrate characterized by its ability to scavenge free radicals. In enteric bacteria, L-ascorbate can be utilized as a nutrient using the UlaABCDEF and UlaG-UlaRpathway under anaerobic conditions. In this study, we identified homologs of the Ula system withinVibrio choleraeand showed thatV. choleraeis able to utilize L-ascorbate as an energy source. Growth pattern assays of aulaGin-frame deletion mutant demonstrated thatulaGis essential for L-ascorbate fermentation. Expression analysis showed thatulacatabolism and transport genes were significantly induced in cells grown in the presence of L-ascorbate compared to glucose and these genes were also highly induced during growth on intestinal mucus. Inin vitrogrowth competition assays, theulaGmutant was outcompeted by wild type when grown in intestinal mucus suggesting the Ula system could be important for fitness. Within theulaoperon inV. choleraeand allVibriospecies a homology of ORF VCA0243 is present that encodes a pyridoxal phosphate (PLP) phosphatase. This enzyme inE. coli, converts the active form of vitamin B6PLP to its inactive form pyridoxal (PL). InV. splendidusand related species, the aerobic and anaerobic L-ascorbate pathway genes cluster together and both systems contain a PLP phosphatase. An in-frame deletion mutant ofvca0243resulted in a growth defect in L-ascorbate fermentation as well as additional carbon and amino acid sources indicating a role in cellular metabolism. Phylogenetic analysis of UlaG and UlaD suggested the region was acquired by horizontal gene transfer.

Importance

L-ascorbate is a carbohydrate present in the human intestine, available for microbial consumption and several enteric species have been shown to utilize this compound as an energy source. We demonstrated that L-ascorbate fermentation genes are also present among marine bacteria from the familyVibrionaceaeand that the human pathogenV. choleraecan ferment L-ascorbate as an energy source. Within the Ula operon in allVibrionaceae, a putative pyridoxal phosphate phosphatase was present that was required for L-ascorbate fermentation and cellular metabolism in general. The Ula system was present among a limited number of genera withinVibrionaceae; Vibrio, AliivibrioandPhotobacteriumand showed an evolutionary history consistent with horizontal transfer between genera and species.
Is There a Correlation Between Pulmonary Inflammation Index With COVID-19 Disease Severity And Outcome?
Authors: Hussein Aliae AR Mohamed , Galal Islam , Mohammed Mohammed M , Abd Elaal Howida K , Aly Karim
Published: September 2020

Rational

the radiologic pulmonary inflammatory index (PII) may be used as early predictor of inflammation as laboratory assessments in COVID-19 cases. The purpose of this study was to compare the clinical and radiological features between the cases of COVID-19 necessitating admittance to the intensive care unit (ICU) and those who did not, and to correlate the radiological pulmonary inflammation index (PII) with other inflammatory markers and outcome.

Patients and methods

This study included 72 patients consecutively admitted with confirmed COVID-19. Their electronic records of were retrospectively revised and the demographic, clinical, laboratory (complete blood count, C reactive protein, D dimer and serum ferritin), HRCT data, pulmonary inflammation index (PII) and the outcomes of the patients (ICU admission, death, recovery, and referral) were analyzed.

Results

They were 50/50% males/females, mean age was 47.1 ± 16.8 (median 47 years). During their stay, 15.3% necessitated ICU admittance, 49 (68%) cured and discharged, 9 cases referred and five cases (6.9%) died. The baseline lesions identified were ground glass opacification recognized in (93%), higher PII and >3 lobes affection were considerably recorded in those who required ICU admittance (P= 0.041 and 0.013). There were moderate positive correlations between PII with age (r=0.264, P=0.031) and other prognostic inflammatory indicators as ferritin (r=0.225, P=0.048), D Dimer (r=0.271, P=0.043) and serum creatinine.

Conclusions

The use of PII together with clinical and laboratory data may be valuable in defining the inflammatory state of COVID-19. It was correlated with other inflammatory indices as D dimer, ferritin even before clinical deterioration. This may allow clinicians to avoid the progression of the illness and improve cure rates by proper early intervention.
Emotional tagging retroactively promotes memory integration through rapid neural reactivation and reorganization
Authors: Zhu Yannan , Zhang Lingke , Zeng Yimeng , Chen Changming , Fernández Guillén , Qin Shaozheng
Published: September 2020

Neutral events preceding emotional experiences are thought to be better remembered by tagging them as significant to simulate future event predictions. Yet, the neurobiological mechanisms how emotion transforms initially mundane events into strong memories remain unclear. By two behavioral and one fMRI studies with adapted sensory preconditioning paradigm, we show rapid neural reactivation and reorganization underlying emotion-tagged retroactive memory enhancement. Behaviorally, emotional tagging enhanced initial memory for neutral associations across the three studies. Neurally, emotional tagging potentiated reactivation of overlapping neural traces in the hippocampus and stimulus-relevant neocortex. Moreover, it induced large-scale hippocampal-neocortical reorganization supporting such retroactive benefit, as characterized by enhanced hippocampal-neocortical coupling modulated by the amygdala during online processing, and a shift from stimulus-relevant neocortex to transmodal prefrontal-parietal areas during offline post-tagging rest. Together, emotional tagging retroactively promotes associations between past neutral events through stimulating rapid reactivation of overlapping representations and reorganizing related memories into an integrated network.
Structural basis for binding mechanism of human serum albumin complexed with cyclic peptide dalbavancin
Authors: Ito Sho , Senoo Akinobu , Nagatoishi Satoru , Ohue Masahito , Yamamoto Masaki , Tsumoto Kouhei , Wakui Naoki
Published: September 2020

Cyclic peptides, with unique structural features, have emerged as new candidates for drug discovery; their association with human serum albumin (HSA; long blood half-life), is crucial to improve drug delivery and avoid renal clearance. Here, we present the crystal structure of HSA complexed with dalbavancin, a clinically used cyclic peptide. SAXS and ITC experiments showed that the HSA-dalbavancin complex exists in a monomeric state; dalbavancin is only bound to the subdomain IA of HSA in solution. Structural analysis and MD simulation revealed that the swing of Phe70 and movement of the helix near dalbavancin were necessary for binding. The flip of Leu251 promoted the formation of the binding pocket with an induced-fit mechanism; moreover, the movement of the loop region including Glu60 increased the number of non-covalent interactions with HSA. These findings may support the development of new cyclic peptides for clinical use, particularly the elucidation of their binding mechanism to HSA.
Enhanced SARS-CoV-2 Neutralization by Secretory IgA in vitro
Authors: Wang Zijun , Lorenzi Julio C. C. , Muecksch Frauke , Finkin Shlomo , Viant Charlotte , Gaebler Christian , Cipolla Melissa , Hoffman Hans-Heinrich , Oliveira Thiago Y. , Oren Deena A. , Ramos Victor , Nogueira Lilian , Michailidis Eleftherios , Robbiani Davide F. , Gazumyan Anna , Rice Charles M. , Hatziioannou Theodora , Bieniasz Paul D. , Caskey Marina , Nussenzweig Michel C.
Published: September 2020

SARS-CoV-2 primarily infects cells at mucosal surfaces. Serum neutralizing antibody responses are variable and generally low in individuals that suffer mild forms of the illness. Although potent IgG antibodies can neutralize the virus, less is known about secretory antibodies such as IgA that might impact the initial viral spread and transmissibility from the mucosa. Here we characterize the IgA response to SARS-CoV-2 in a cohort of 149 individuals. IgA responses in plasma generally correlate with IgG responses and clones of IgM, IgG and IgA producing B cells that are derived from common progenitors are evident. Plasma IgA monomers are 2-fold less potent than IgG equivalents. However, IgA dimers, the primary form in the nasopharynx, are on average 15 times more potent than IgA monomers. Thus, secretory IgA responses may be particularly valuable for protection against SARS-CoV-2 and for vaccine efficacy.
Dissecting the heterogeneous subcortical brain volume of Autism spectrum disorder (ASD) using community detection
Authors: Li Ting , Hoogman Martine , Mota Nina Roth , Buitelaar Jan K. ,   the ENIGMA-ASD Working Group, Vasquez Alejandro Arias , Franke Barbara , van Rooij Daan
Published: September 2020

Structural brain alterations found in Autism Spectrum Disorder (ASD) have previously been very heterogeneous, with overall limited effect sizes for every region implicated. In this study, we aimed at exploring the existence of subgroups in ASD, based on neuroanatomic profiles; we hypothesized that effect sizes of case/control difference would be increased in defined subgroups. Using the dataset from the ENIGMA-ASD Working Group (n=2661), exploratory factor analysis (EFA) was applied on seven subcortical volumes of individuals with ASD and controls to uncover the underlying organization of subcortical structures. Based on earlier findings in ADHD patients and controls as well as data availability, we focused on three age groups: boys (aged 4-14 years), male adolescents (aged 14-22 years), and adult men (aged >=22 years). The resulting factor scores were used in a community detection (CD) analysis, to cluster participants into subgroups. Three factors were found in each sample, with the factor structure in adult men differing from that in boys and male adolescents. From the patterns in these factors, CD uncovered four distinct communities in boys and three communities in adolescents and adult men, irrespective of ASD diagnostic status. The effect sizes of case/control comparisons appeared more pronounced than in the whole sample in some communities. Based on subcortical volumes, we succeeded in stratifying our participants into more homogeneous subgroups with similar brain structural patterns. The stratification enhanced our ability to observe case/control differences of subcortical brain volumes in ASD, and may help explain some of the heterogeneity of previous findings in ASD.
Structural Genetics of circulating variants affecting the SARS-CoV-2 Spike / human ACE2 complex
Authors: Ortuso Francesco , Mercatelli Daniele , Guzzi Pietro Hiram , Giorgi Federico Manuel
Published: September 2020

SARS-CoV-2 entry in human cells is mediated by the interaction between the viral Spike protein and the human ACE2 receptor. This mechanism evolved from the ancestor bat coronavirus and is currently one of the main targets for antiviral strategies. However, there currently exist several Spike protein variants in the SARS-CoV-2 population as the result of mutations, and it is unclear if these variants may exert a specific effect on the affinity with ACE2 which, in turn, is also characterized by multiple alleles in the human population. In the current study, the GBPM analysis, originally developed for highlighting host-guest interaction features, has been applied to define the key amino acids responsible for the Spike/ACE2 molecular recognition, using four different crystallographic structures. Then, we intersected these structural results with the current mutational status, based on more than 295,000 sequenced cases, in the SARS-CoV-2 population. We identified several Spike mutations interacting with ACE2 and mutated in at least 20 distinct patients: S477N, N439K, N501Y, Y453F, E484K, K417N, S477I and G476S. Among these, mutation N501Y in particular is one of the events characterizing SARS-CoV-2 lineage B.1.1.7, which has recently risen in frequency in Europe. We also identified five ACE2 rare variants that may affect interaction with Spike and susceptibility to infection: S19P, E37K, M82I, E329G and G352V.

Significance Statement

We developed a method to identify key amino acids responsible for the initial interaction between SARS-CoV-2 (the COVID-19 virus) and human cells, through the analysis of Spike/ACE2 complexes. We further identified which of these amino acids show variants in the viral and human populations. Our results will facilitate scientists and clinicians alike in identifying the possible role of present and future Spike and ACE2 sequence variants in cell entry and general susceptibility to infection.
Determinants of Water Source Use, Quality of Water, Sanitation and Hygiene Perceptions among Urban Households in North-West Ethiopia: A Cross-Sectional Study
Authors: Gebremichael Shewayiref Geremew , Yismaw Emebet , Dejen Belete , Dires Adeladilew
Published: September 2020

Background

Clean water is an essential element for human health, wellbeing, and prosperity. Every human being has the right to access safe drinking water. But, in now day, due to rapid population growth, illiteracy, lack of sustainable development, and climate change; it still faces a global challenge for about one billion people in the developing nation. The discontinuity of drinking water supply puts in force households either to use unsafe water storage materials or to use water from unimproved sources. This study aimed to identify the determinants of water source types, use, quality of water, and sanitation perception of physical parameters among urban households in North-West Ethiopia.

Methods

A community-based cross-sectional study was conducted among households from February to March 2019. An interview-based pre-tested and structured questionnaire was used to collect the data. Data collection samples were selected randomly and proportional to each kebeles’ households. MS Excel and R Version 3.6.2 was used to enter and analyze the data; respectively. Descriptive statistics using frequencies and percentages were used to explain the sample data concerning the predictor variable. Both bivariate and multivariate logistic regressions were used to assess the association between the independent and the response variables.

Results

Four hundred eighteen (418) households have participated. Based on the study undertaken, 78.95% of households used improved and 21.05% of households used unimproved drinking water sources. Households drinking water sources are significantly associated with age of participant (x2= 20.392, df=3), educational status (x2= 19.358, df=4), source of income (x2= 21.777, df=3), monthly income (x2= 13.322, df=3), availability of additional facilities (x2= 98.144, df=7), cleanness status (x2=42.979, df=4), scarcity of water (x2= 5.1388, df=1) and family size (x2= 9.934, df=2). The logistic regression analysis also indicated as those factors are significantly determined (p 0.05) the water source types used by households. Factors such as availability of toilet facility, household member type, and sex of head of the household are not significantly associated with the drinking water sources.

Conclusion

The study showed that being an older age group of the head of the household, being government employer, merchant and self-employed, being a higher income group, the presence of all facilities in the area, lived in a clean surrounding and lower family size are the determinant factors of using drinking water from improved sources. Therefore; the local, regional, and national governments and other supporting organizations shall improve the accessibility and adequacy of drinking water from improved sources through short and long time plans for the well-being of the community in the area.
Steric-Free Bioorthogonal Labeling of Acetylation Substrates Based on a Fluorine-Thiol Displacement Reaction (FTDR)
Authors: Lyu Zhigang , Zhao Yue , Buuh Zakey Yusuf , Gorman Nicole , Goldman Aaron R. , Islam Md Shafiqul , Tang Hsin-Yao , Wang Rongsheng E.
Published: September 2020

We have developed a novel bioorthogonal reaction that can selectively displace fluorine substitutions alpha to amide bonds. This fluorine-thiol displacement reaction (FTDR) allows for fluorinated cofactors or precursors to be utilized as chemical reporters; hijacking acetyltransferase mediated acetylation both in vitro and in live cells, which cannot be achieved with azide- or al- kyne- based chemical reporters. The fluoroacetamide labels can be further converted to biotin or fluorophore tags using FTDR, enabling the general detection and imaging of acetyl substrates. This strategy may lead to a steric-free labeling platform for substrate proteins, expanding our chemical toolbox for functional annotation of post-translational modifications (PTMs) in a systematic manner.
The future of integrated reporting in an emerging market: an analysis of the disclosure conformity level
Authors: Adhariani Desi , Sciulli Nick
Published: September 2020

Purpose

This study provides an analysis of the possibility of companies in Indonesia to adopt integrated reporting (IR). This is undertaken by comparing the degree of conformity between current reporting disclosures with that of the IR framework.

Design/methodology/approach

A mixed-method approach is employed, which entailed using both quantitative and qualitative techniques to access data. For the quantitative analysis, a total of 64 companies are chosen, which represent companies with significant market capitalization included in the LQ45 index (an index for the 45 most liquid stocks) in 2016 and the non-LQ45 by publishing a sustainability report. These companies are selected on the basis of high levels of disclosure compared with other companies and serve as an appropriate benchmark for other listed companies. The level of disclosure conformity is employed using 39 principle disclosure indices and 76 content disclosure indices based on the IR framework. For the qualitative analysis, interviews were conducted with nine interviewees that are considered as experts in the field of IR. The interviews are conducted to assist in providing explanations for the findings.

Findings

The results indicate that approximately 60% of companies (mostly in the banking, finance and mining industries) have an adequate degree of conformity, reflecting their higher probability of voluntary compliance to apply the IR framework. However, the principles of conciseness and connectivity of information provide significant challenges for Indonesian firms when they will consider implementation. Further analysis using in-depth interviews with experts showed that several factors from various perspectives should be considered in shifting to IR.

Originality/value

This study provides empirical evidence on the current reporting landscape of Indonesian firms. Scant research is available on the possible adoption of IR in emerging markets such as Indonesia. Hence, this project raises further possible explanations for the challenges and pressures faced by Indonesian firms in an era of changing stakeholder expectations.
Work-based learning tools to inform the implementation of degree apprenticeships for the public sector in England
Authors: Garnett Jonathan
Published: September 2020

Purpose

The article identifies and examines key elements of a work-based learning framework to consider their use as part of the higher education response to the apprenticeship agenda for the public sector in England.

Design/methodology/approach

This article draws upon work-based learning academic literature and the authors 28 years’ experience of the development and implementation of work-based learning at higher education level in the UK and internationally.

Findings

The article suggests that while the experience of work-based learning at higher education level appears to offer many ready-made tools and approaches for the development and delivery of higher and degree apprenticeships, these should not be adopted uncritically and in some cases may require significant repurposing.

Research limitations/implications

This article is intended to inform practitioners developing degree apprenticeships. Given the degree apprenticeship is still at a relatively early stage in its implementation, this has limited the extent to which it has been possible to review entire degree implementation to the point of participant graduation.

Practical implications

The article draws upon real-life implementation of innovative curriculum design and is of direct practical relevance to the design and operation of work-based learning for degree apprenticeships.

Social implications

Degree apprenticeships have the potential to increase productivity and enhance social mobility. Effective design and implementation of degree apprenticeships in the public sector has the potential to make a significant impact on the quality of public services.

Originality/value

The article provides an informed and sustained examination of how degree apprenticeships, especially those designed for public sector employees, might build upon previous higher education experience in work-based learning.
Expected benefits of people interactions and guest experiences
Authors: Chen Ya-Ling , Chen Joseph , Liu Wan-Yu , Sharma Tanmay
Published: September 2020

Purpose

This research aims to grasp hotel guests' motives and potential benefits sought when interacting with other guests, service personnel and residents and examines how these benefits can contribute to the total guest experience.

Design/methodology/approach

Mixed methods are adopted for the purpose of this study comprising individual interviews and a questionnaire survey.

Findings

Five groups of advantages emerge from individual interviews, including friendliness in interaction, social benefits, information acquisition, curiosity gratification and hospitality services. In the survey, which gathers 326 questionnaires, this study reveals that the five types of benefits derived from hotel guests' interactions could be further categorized into two dimensions: civility (e.g. friendliness and social) and utility (e.g. information, curiosity and service). The study confirms that four out of five potential or expected benefits from this personal interaction is significantly associated with the total hotel experience.

Research limitations/implications

Respondents of this study are culturally homogenous; as a result, multi-cultural settings should be considered for future research.

Originality/value

Tourism and hospitality literature on people's interaction is mostly center around social aspects of interaction. The current study comprehensively explores all expected utilities of interaction, occurring in all sorts of interactions (e.g. customer-to-resident and customer-to-service personnel). Specifically, the findings of this study uncover the underlying factors which prompt the tourists to interact with other people in a lodging setting and examine the relative importance of those underlying factors to the total lodging experiences.
Seeing destinations through vlogs: implications for leveraging customer engagement behavior to increase travel intention
Authors: Cheng Yusi , Wei Wei , Zhang Lu
Published: September 2020

Purpose

This study aims to understand customers’ watching experience with travel vlogs and its impacts on one of the most prominent manifestations of customer engagement behaviors (CEBs) – word-of-mouth (WOM) – and their travel intention. Drawing upon the theory of resonance, this study incorporated both cognitive and emotional aspects of travel vlog watching experience.

Design/methodology/approach

Online survey data were collected from 352 participants who have watched travel vlogs over the past 12 months. Partial least squares structural equation modeling (PLS-SEM) was performed for hypotheses testing.

Findings

The study results reveal positive impacts of source credibility, inspiration, escapism and self-congruence on WOM, which further leads to travel intention. While source credibility is the strongest predictor of WOM, more factors representing the emotional resonance turn out to be the driving factors of WOM.

Research limitations/implications

This study pinpoints the value of investigating audiences’ vlogs watching experience from a CEB perspective within the tourism setting. Future research is encouraged to explore more types of CEBs in the intersection of social media consumption and travel behaviors.

Practical implications

Travel vloggers need to convey their intrinsic passion and enthusiasm to create an emotional connection with the audiences. Hospitality and tourism marketers are recommended to promote products and services by incentivizing audiences to engage with the travel vlogs.

Originality/value

No prior research integrated vlogs watching experiences, engagement behavior and future travel intention in a tourism setting. This study fills this gap and contributes to the literature on customer engagement, media consumption and marketing.
Corporate environmental accountability in Nigeria: an example of regulatory failure and regulatory capture
Authors: Noah Abdurafiu Olaiya , Adhikari Pawan , Ogundele Babafemi O. , Yazdifar Hassan
Published: September 2020

Purpose

The purpose of this study is to investigate how state regulations become ineffective in holding corporations accountable for environmental degradation in an emerging economy context, with a specific focus on oil and gas and cement industry in Nigeria.

Design/methodology/approach

The study draws on capture theory to bring out the factors that have rendered redundant the state intervention to make corporations accountable for their environmental activities. The research setting is the oil and gas and cement industry in Nigeria. Data for the study are derived from both documentary analysis and semi-structured interviews and analysed using a thematic technique.

Findings

The findings of the paper demonstrate a regulatory failure to hold corporations to account for their environmental activities. A lack of political will, outdated regulations and the manipulation of the regulators, all have played a part in preventing corporations from being accountable for their activities. In addition, the widespread elite corruption in the country has provided corporations with leeway to manipulate their environmental accountability practices. The study emphasises the need for continuous review of the regulations and efforts to reduce corruption in order to promote corporations' environmental accountability in Nigeria.

Research limitations/implications

The research is limited to Nigeria, oil and gas and cement industries. The theoretical lens can be used to address problem of capture of the regulations and institution in the country.

Practical implications

The practical implication is that it would enhance environmental regulations in Nigeria and emerging economies. It will also provide support from researchers emerging markets on the adoption of capture theory in future research.

Social implications

It will promote corporate best environmental practices in the country. It will reduce the issues surrounding environmental accountability practices and create awareness on environmental issues among the populace. It will create the impression that corporations will be held accountable for their environmental activities in the country and the need to have improved environmental regulations in the country.

Originality/value

The study adds to the debate on corporate environmental accountability practices engendering insights from the Nigerian oil and gas and cement industry. The paper demonstrates how companies in emerging economies can capture state regulations and how rendering environmental accountability becomes more of rhetoric than a reality with little impacts on the welfare of people and society.
Two cycles of neoadjuvant chemotherapy improves survival in patients with high‐risk upper tract urothelial carcinoma
Authors: Zennami Kenji , Sumitomo Makoto , Takahara Kiyoshi , Nukaya Takuhisa , Takenaka Masashi , Fukaya Kosuke , Ichino Manabu , Fukami Naohiko , Sasaki Hitomi , Kusaka Mamoru , Shiroki Ryoichi
Published: September 2020

Objectives

To assess the impact of two cycles of neoadjuvant chemotherapy (NAC) in patients who underwent nephroureterectomy for high‐risk cN0M0 upper tract urothelial carcinoma (UTUC), and to evaluate the efficacy of NAC in patients with localised disease (≤cT2).

Patients and Methods

We retrospectively analysed patients with high‐risk cN0M0 UTUC who received NAC followed by surgery, compared with a matched cohort who underwent initial surgery at Fujita Health University during 2005–2019. Baseline and tumour characteristics, overall survival (OS), cancer‐specific survival (CSS), and recurrence‐free survival (RFS) were compared between the cohorts. Cox proportional hazards models were used to identify predictors of survival.

Results

There were 117 and 67 patients in the study group and the control group, respectively. Significantly higher pathological downstaging (pDS) and lower lymphovascular invasion (LVI) were observed in the study group than in the control group (48% vs 22%, P = 0.008 and 29% vs 46%, P = 0.045, respectively). The NAC group had significantly better 5‐year OS (79% vs 53%, P = 0.003), 5‐year CSS (84% vs 66%, P = 0.008), and 5‐year RFS (80% vs 61%, P = 0.001) than the control group. The OS benefit of NAC was observed even in patients with localised (≤cT2) disease (P = 0.019). Patients with LVI showed significantly worse CSS both in pathologically locally advanced (≥pT3) and in localised (≤pT2) tumours (P = 0.048 and P = 0.018, respectively). Multivariate analysis identified LVI, NAC, and pDS as independent predictors of OS. Male sex and post‐NAC LVI were identified as predictors of worse survival in patients who underwent NAC.

Conclusions

Two cycles of NAC improved the survival of patients with high‐risk UTUC, even in patients with localised disease. Although two cycles of NAC appear to be effective in cN0M0 high‐risk UTUC including localised disease, additional larger sample size multicentre prospective studies comparing short‐course NAC regimens followed by surgery and surgery alone are required.
A dictionary for translation from natural to formal data model language
Authors: Šuman Sabrina , Jakupović Alen , Marinac Mladen
Published: September 2020

The paper describes our current research activities and results related to developing knowledge‐based systems to support the creation of entity‐relationship (ER) models. The authors based obtaining an ER model in textual form on translation from one language into another, that is, from an English controlled natural language into the formalized language of an ER data model. Our translation method consisted of creating translation rules of sentential form parts into ER model constructs based on the textual and character patterns detected in the business descriptions. To enable the computer analyses necessary for creating translation mechanisms, we created a linguistic corpus that contains lists of the business descriptions and the texts of other business materials. From the corpus, we then created a specific dictionary and linguistic rules to automate the business descriptions' translation into the ER data model language. Before that, however, the corpus was enriched by adding annotations to the words related to ER data model constructs. In this paper, we also present the main issues uncovered during the translation process and offer a possible solution with utility evaluation: applying information‐extraction performance measures to a set of sentences from the corpus.
Blood and cerebrospinal fluid immune cell profiles in patients with temporal lobe epilepsy of different etiologies
Authors: Langenbruch Lisa , Bleß Laurens , Schulte‐Mecklenbeck Andreas , Sundermann Benedikt , Brix Tobias , Elger Christian E. , Melzer Nico , Wiendl Heinz , Meuth Sven G. , Gross Catharina C. , Kovac Stjepana
Published: September 2020

Inflammation plays a role in the pathogenesis of immune‐mediated epilepsy, but also in epilepsy of other etiology such as hippocampal sclerosis. This study aimed to characterize immune cell signatures in the peripheral blood (PB) and cerebrospinal fluid (CSF) in temporal lobe epilepsy (TLE) of different etiologies. We retrospectively evaluated CSF routine parameters and immune cell profiles using flow cytometry in a cohort of 51 patients and 45 age‐matched controls with functional disorders. Groups were comprised of patients with nonlesional TLE (n = 26), TLE due to hippocampal sclerosis (n = 14), or limbic encephalitis with antibodies against the 65‐kDa isoform of glutamic acid decarboxylase (GAD65‐LE; n = 11). TLE patients showed increased proportions of human leukocyte antigen–DR isotype (HLA‐DR)‐expressing CD4+ T lymphocytes in the CSF. Furthermore, they were characterized by a shift in monocyte subsets toward immature CD14lowCD16+ cells in the PB and blood/CSF‐barrier dysfunction. Whereas TLE patients in general showed similar immune cell profiles, patients with GAD65‐LE differed from other TLE patients by increased proportions of HLA‐DR–expressing CD8+ T lymphocytes and type 2/3 oligoclonal bands. These findings point to a role of innate and adaptive immunity in TLE. CSF parameters may help to discriminate epilepsy patients from controls and different forms of TLE from each other.
Dermatological side effects rarely interfere with the continuation of checkpoint inhibitor immunotherapy for cancer
Authors: Rovers Jessica F. J. , Bovenschen H. Jorn
Published: September 2020

Background

Immunotherapy with checkpoint inhibitors (CPIs) is an emerging anticancer treatment strategy, which may cause a variety of skin reactions. In this study, we sought to analyze and classify the cutaneous side effects (CSE) of the CPIs nivolumab, pembrolizumab, and ipilimumab with respect to prevalence, type, and severity, and to review their potential interference with CPI immunotherapy.

Methods

In this retrospective analysis, medical records were analyzed with respect to incidence, type, and severity of CSE in patients on CPI immunotherapy for cancer. The implications for immunotherapy maintenance were scrutinized.

Results

From 2012 to 2019, 352 consecutive patients were treated with CPIs for cancer, of which 46 patients (13.1%) experienced CSE. The incidence of CSE was less with nivolumab (n = 16; 9.5%) and pembrolizumab monotherapy (n = 9; 9.6%) as compared to ipilimumab (n = 10; 23.3%) and combination therapy (n = 11; 23.9%); P < 0.05. Skin toxicity could be stratified by rash/eczema (n = 28; 60.9%), autoimmune (n = 8; 17.4%, vitiligo n = 5, lichen sclerosus n = 2, psoriasis guttata n = 1), lichenoid reaction (n = 5; 10.9%), pruritus (n = 4; 8.7%), and a miscellaneous group (n = 3; 6.5%). The limited severity grades of CSE caused immunotherapy disruption in only three (0.9%) cases. Interestingly, 80% of melanoma patients who developed vitiligo during immunotherapy had stable disease or disease remission.

Conclusion

CPIs in cancer patients may result in a distinct set of CSE, with drug rash and eczematous rash being the most common. CTLA‐4 blocker ipilimumab and combination therapy are more prone to elicit skin toxicity than the PD‐1 inhibitors nivolumab and pembrolizumab, although this rarely interferes with the continuation of immunotherapy.
FABP4 inhibitor BMS309403 protects against hypoxia‐induced H9c2 cardiomyocyte apoptosis through attenuating endoplasmic reticulum stress
Authors: Sun Fuqiang , Du Jiangchuan , Li Hongbin , Hao Shuang , Zhao Guochang , Lu Fanfan
Published: September 2020

Acute myocardial infarction is characterized by ischaemia‐induced cardiomyocyte apoptosis, in which the endoplasmic reticulum (ER) stress plays an important role. The fatty acid‐binding protein‐4 (FABP4) has been implicated in regulating ER stress and apoptosis. Yet, whether FABP4 is involved in modulating cardiomyocyte apoptosis remains unclarified. By applying an in vitro model of hypoxia‐induced apoptosis of H9c2 cardiomyocytes, we found that FABP4 expression was elevated upon hypoxia stimulation, which was further demonstrated to be transcriptionally activated by the hypoxia‐inducible factor 1a (HIF‐1α). In addition, the pharmacological inhibition of FABP4 with BMS309403 protected against hypoxia‐induced apoptosis in cardiomyocytes, indicating that FABP4 induction is detrimental for cardiomyocyte survival under hypoxic condition. Moreover, BMS309403 attenuated ER stress in cardiomyocytes exposed to hypoxia, which, however, was reversed by tunicamycin, an ER stress activator. More importantly, the protective effect of BMS309403 on cardiomyocytes vanished in the presence of tunicamycin. Thus, these observations establish that FABP4 inhibitor BMS309403 reduces hypoxia‐induced cardiomyocyte apoptosis through attenuating excessive ER stress, implying that FABP4 inhibition may be of clinical benefit for MI treatment.