bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling Clinical Trial Attrition Using Machine Intelligence: A driver analytics case study using 1,325 trials representing one million patients
Authors: Hutchison Emmette , Zhang Youyi , Nampally Sreenath , Neelufer Imran Khan , Malkov Vlad , Weatherall Jim , Khan Faisal , Shameer Khader
Published: November 2021

The amount of time and resources invested in bringing novel therapeutics to market has increased year over year with fewer successful treatments reaching patients. In the lifecycle of drug development, the clinical phase is a major contributor to this decreasing efficiency in the development of clinical trials. One major barrier to the successful execution of a randomized control trial (RCT) is the attrition of patients who no longer participate in a trial either following enrollment or randomization. To address this problem, we have assembled a unique dataset by integrating multiple public databases including ClinicalTrials.gov and Aggregate Analysis of ClincalTrials.gov (AACT) to assemble a trial sponsor-independent dataset. This data spans 20 years of clinical trials and over 1 million patients (3,175 cohorts consisting of 1,020,085 patients and 79 curated features) in the respiratory domain and enabled a data-driven approach to identify top features influencing patient attrition in a trial. Top Features included Duration of Trial, Duration of Treatment, Indication, and Number of Adverse Events. We evaluated multiple machine learning models and found the best performance on the Test Set with Random Forest (Test subset: n=637 cohorts; RMSE 6.64). We envisage that our work will enable clinical trial sponsors to optimize trial run time by better anticipating and correcting for potential patient attrition using patient-centric strategies to improve patient engagement, thus enabling new therapies to be delivered to patients more quickly.
Pulmonary thromboembolism in COVID-19 Patients on CT Pulmonary Angiography - A Single-Centre Retrospective Cohort Study in the United Arab Emirates
Authors: Saeed Ghufran Aref , Gaba Waqar H , Kareem Adi Abd Al , Marshoodi Reima Al , Mazrouei Safaa Al , Shah Asad R
Published: November 2021

Purpose

Our aim is to identify the prevalence and distribution of pulmonary thromboembolism in COVID-19 infected patients in our hospital.

Materials and Methods

Data of all patients with COVID-19 infection either on RT-PCR testing or non-contrast high resolution CT(HRCT) who had CT pulmonary angiography (CTPA) from April to June 2020 were included. 133 patients were initially included in the study, 7 were excluded leaving a total number of 126 patients.

Results

Twenty (15.8%) patients had evidence of pulmonary embolism (PE) on CTPA with mean age of 50 years (ranging 31-85) with 95% males. The mean D-dimer was 5.61mcg/mL among the PE-negative and 14.49 mcg/mL in the PE-positive groups respectively. Among the patients with evidence of pulmonary embolism on CTPA almost half required admission to intensive care unit in comparison to only one-fifth with negative CTPA. One-fourth died among the PE positive group with only 5% died among the PE negative group. There was a 33% reduction in the development of PE in the COVID-19 patients who had received low molecular weight heparin (LMWH) prior to their CTPA study versus those who had not.

Conclusion

D dimers correlate well with the incidence of pulmonary embolism among COVID-19 patients. Our data suggest that majority of our patients, developed pulmonary embolisms within 5 days into their hospital stay, accounting to almost two thirds of all positive cases diagnosed by CTPA. Those with PE among COVID-19 patients have high chances of ICU admission and mortality. Use of thromboprophylaxis early on might reduce the incidence of PE.
Knowledge awareness and practice with antimicrobial stewardship programmes among healthcare providers in a Ghanaian Tertiary Hospital
Authors: Kpokiri Eneyi E. , Ladva Misha , Dodoo Cornelius C. , Orman Emmanuel , Alalbila Thelma , Mensah Adelaide , Jato Jonathan , Mfoafo Kwadwo A. , Folitse Isaac , Hutton-Nyameaye Araba , Okon-Ben Inemesit , Mensah-Kane Paapa , Sarkodie Emmanuel , Awadzi Benedict , Jani Yogini
Published: November 2021

Antimicrobial resistance (AMR) is a significant problem in global health today, particularly in Low- and Middle-Income Countries (LMICs) where antimicrobial stewardship programmes are yet to be successfully implemented. We established a partnership between AMR pharmacists leads from a UK NHS hospital and in Ho Teaching Hospital with the aim to by enhance antimicrobial stewardship knowledge and practice among healthcare providers through an educational intervention. We employed a mixed method approach including an initial before and after training survey on knowledge and awareness, followed by qualitative interviews with healthcare providers conducted six months after delivery of training. This study was carried out in Ho teaching hospital with 18 healthcare professionals including pharmacists, medical doctors, nurses and medical laboratory scientists. Ethical approval was obtained prior to data collection. In the first phase, we surveyed 50 health care providers including nurses (33%), pharmacists (29%) and biomedical scientists (23%). Of these, 58% of participants had engaged in continuous professional development on AMR/AMS, and above 95% demonstrated good knowledge on the general use of antibiotics. A total of 18 participants, which included 4 medical doctors, 5 pharmacists, 4 nurses, 2 midwives and 3 biomedical scientists, were interviewed in the second stage and demonstrated greater awareness of AMS practices, particularly the role of education for patients as well as healthcare professionals. We found that knowledge and practice with AMS was markedly improved six months after the training session. There is limited practice of AMS in LMICs, however through AMR focused training we demonstrate improved AMS skills and practice among health care providers in Ho Teaching hospital. There is need for continuous AMR training sessions for health care professionals in resource limited settings.
Estimation of R0 for the spread of SARS-CoV-2 in Germany from Excess Mortality
Authors: Prada Juan Pablo , Maag Luca Estelle , Siegmund Laura , Bencurova Elena , Chunguang Liang , Koutsilieri Eleni , Dandekar Thomas , Scheller Carsten
Published: November 2021

For SARS-CoV-2, R0 calculations report usually 2-3, biased by PCR testing increases. Covid-19-induced excess mortality is less biased.

We used data from Robert Koch Institute on Covid incidence, deaths, and PCR tests and excess mortality to determine early, policy-free R0 estimates with a serial interval of 4.7 days.

The PCR-based R0 value was 2.56 (95% CI 2.52-2.60) for Covid-19 cases and 2.03 (95%CI 1.96-2.10) for Covid-19-related deaths. As the number of PCR tests increased, R0 values were corrected accordingly, yielding 1.86 for Covid-19 cases and 1.47 for Covid-19 deaths, excess deaths were 1.34 (95% CI 1.32-1.37).

R0 is much lower than previously thought. This fits the observed seasonal pattern of infection across Europe in 2020-2021, including emergence of more contagious escape variants such as delta.

One-Sentence Summary

Excess mortality reveals infection speed in Covid-19 is surprisingly low with seasonal infection patterns and escape variants.
Human genetic evidence supports MAP3K15 inhibition as a therapeutic strategy for diabetes
Authors: Nag Abhishek , Dhindsa Ryan S. , Harper Andrew R. , Vitsios Dimitrios , Ahnmark Andrea , Bilican Bilada , Madeyski-Bengtson Katja , Zarrouki Bader , Wang Quanli , Smith Katherine , Smith Dave , Challis Benjamin , Paul Dirk S. , Bohlooly-Y Mohammad , Snowden Mike , Baker David , Fritsche-Danielson Regina , Pangalos Menelas N. , Petrovski Slavé
Published: November 2021

Diabetes mellitus is a chronic health condition that can result in significant end-organ complications and is estimated to impact at least 8.5% of the global adult population. Here, we performed gene-level collapsing analysis on exome sequences from 454,796 multi-ancestry UK Biobank participants to detect genetic associations with diabetes. Rare non-synonymous variants in GCK, GIGYF1, HNF1A, and HNF4A were significantly associated (P<1×10-8) with increased risk of diabetes, whereas rare non-synonymous variants in MAP3K15 were significantly associated with reduced risk of diabetes. Recessive carriers of rare non-synonymous variants in the X chromosome gene MAP3K15 had a 30% reduced risk of diabetes (OR=0.70, 95% CI: [0.62,0.79], P=5.7×10-10), along with reduced blood glucose (beta=-0.13, 95% CI: [-0.15,-0.10], P=5.5×10-18) and reduced glycosylated haemoglobin levels (beta=-0.14, 95% CI: [-0.16,-0.11], P=1.1×10-24). Hemizygous males carrying protein-truncating variants (PTVs) in MAP3K15 demonstrated a 40% reduced risk of diabetes (OR=0.60, 95% CI: [0.45,0.81], P=0.0007). These findings were independently replicated in FinnGen, with a MAP3K15 PTV associating with decreased risk of both type 1 diabetes (T1DM) and type 2 diabetes (T2DM) (p<0.05). The effect of MAP3K15 loss on diabetes was independent of body mass index, suggesting its protective effect is unlikely to be mediated via the insulin resistance pathway. Tissue expression profile of MAP3K15 indicates a possible involvement of pancreatic islet cell or stress response pathways. No safety concerns were identified among heterozygous or recessive MAP3K15 PTV carriers across over 15,719 studied endpoints in the UK Biobank. Human population genetic evidence supports MAP3K15 inhibition as a novel therapeutic target for diabetes.
Genome-wide H3K9 Acetylation Level Increases with Age-Dependent Senescence of Flag Leaf in Rice (Oryza sativa)
Authors: Zhang Yu , Li Yanyun , Zhang Yuanyuan , Zhang Zeyu , Zhang Deyu , Wang Xiaonan , Lai Binfan , Huang Dandan , Gu Lianfeng , Xie Yakun , Miao Ying
Published: November 2021

Flag leaf senescence is an important biological process that drives the remobilization of nutrients to the growing organs of rice. Leaf senescence is controlled by genetic information via gene expression and epigenetic modification, but the precise mechanism is as of yet unclear. Here, we analyzed genome-wide acetylated lysine residue 9 of histone H3 (H3K9ac) enrichment by chromatin immunoprecipitation-sequencing (ChIP-seq) and examined its association with transcriptomes by RNA-seq during flag leaf aging in rice (Oryza sativa). We found that genome-wide H3K9 acetylation levels increased with age-dependent senescence in rice flag leaf, and there was a positive correlation between the density and breadth of H3K9ac and gene expression and transcript elongation. A set of 1,249 up-regulated, differentially expressed genes (DEGs) and 996 down-regulated DEGs showing a strong relationship between temporal changes in gene expression and gain/loss of H3K9ac was observed during rice flag leaf aging. We produced a landscape of H3K9 acetylation-modified gene expression targets that includes known senescence-associated genes, metabolism-related genes, as well as miRNA biosynthesis-related genes. Our findings reveal a complex regulatory network of metabolism- and senescence-related pathways mediated by H3K9ac and also elucidate patterns of H3K9ac-mediated regulation of gene expression during flag leaf aging in rice.

Significance statement

Genome-wide H3K9 acetylation levels increased with age-dependent senescence in rice flag leaf, and positively correlation the density and breadth of H3K9ac with transcript elongation and expression. Identified numerous H3K9 acetylation-modified gene expression targets reveal a complex regulatory network and metabolism-mediated senescence network that are associated with H3K9ac during leaf aging in rice.
Structure-activity studies ofStreptococcus pyogenesenzyme SpyCEP reveal high affinity for CXCL8 in the SpyCEP C-terminal
Authors: Pearson Max , Haslam Carl , Fosberry Andrew , Jones Emma J , Reglinski Mark , Edwards Robert J. , Lawrenson Richard Ashley , Brown Jonathan C , Mossakowska Danuta , Pease James Edward , Sriskandan Shiranee
Published: November 2021

TheStreptococcus pyogenescell envelope protease (SpyCEP) is vital to streptococcal pathogenesis and disease progression. Despite its strong association with invasive disease, little is known about enzymatic function beyond the ELR+CXC chemokine substrate range. As a serine protease, SpyCEP has a catalytic triad consisting of aspartate (D151), histidine (H279), and serine (S617) residues which are all thought to be mandatory for full activity. We utilised a range of SpyCEP constructs to investigate the protein domains and catalytic residues necessary for enzyme function. We designed a high-throughput mass spectrometry assay to measure CXCL8 cleavage and applied this for the first time to study the enzyme kinetics of SpyCEP.

Results revealed a remarkably low Michaelis-Menton constant (KM) of 82 nM and a turnover of 1.65 molecules per second. We found that an N-terminally-truncated SpyCEP C-terminal construct containing just the catalytic dyad of H279 and S617 was capable of cleaving CXCL8 with a similar KMof 55 nM, albeit with a reduced substrate turnover of 2.7 molecules per hour, representing a 2,200- fold reduction in activity. We conclude that the SpyCEP C-terminus plays a key role in high affinity substrate recognition and binding, but that the N-terminus is required for full catalytic activity.
Hypoxia classifier for transcriptome datasets
Authors: Puente-Santamaría Laura , Sanchez-Gonzalez Lucia , Ramos-Ruiz Ricardo , del Peso Luis
Published: November 2021

Molecular gene signatures are useful tools to characterize the physiological state of cell populations, but most have developed under a narrow range of conditions and cell types and are often restricted to a set of gene identities.

Focusing on the transcriptional response to hypoxia, we aimed to generate widely applicable classifiers sourced from the results of a meta-analysis of 69 differential expression datasets which included 425 individual RNA-seq experiments from 33 different human cell types exposed to different degrees of hypoxia (0.1-5%O2) for 2-48h.

The resulting decision trees include both gene identities and quantitative boundaries, allowing for easy classification of individual samples without control or normoxic reference. Each tree is composed by 3-5 genes mostly drawn from a small set of just 8 genes (EGLN1, MIR210HG, NDRG1, ANKRD37, TCAF2, PFKFB3, BHLHE40, and MAFF). In spite of their simplicity, these classifiers achieve over 95% accuracy in cross validation and over 80% accuracy when applied to additional challenging datasets. Our results indicate that the classifiers are able to identify hypoxic tumor samples from bulk RNAseq and hypoxic regions within tumor from spatially resolved transcriptomics datasets. Moreover, application of the classifiers to histological sections from normal tissues suggest the presence of a hypoxic gene expression pattern in the kidney cortex not observed in other normoxic organs. Finally, tree classifiers described herein outperform traditional hypoxic gene signatures when compared against a wide range of datasets. This work describes a set of hypoxic gene signatures, structured as simple decision tress, that identify hypoxic samples and regions with high accuracy and can be applied to a broad variety of gene expression datasets and formats.
Cdc6p modulates the structure and DNA binding activity of the origin recognition complex in vitro
Authors: Mizushima Tohru , Takahashi Naoko , Stillman Bruce
Published: November 2021

An interaction between the origin recognition complex (ORC) and Cdc6p is the first and a key step in the initiation of chromosomal DNA replication. We describe the assembly of an origin-dependent complex containing ORC and Cdc6p from Saccharomyces cerevisiae. Cdc6p increases the DNA binding specificity of ORC by inhibiting non-specific DNA binding of ORC. Cdc6p induces a concomitant change in the conformation of ORC and mutations in the Cdc6p Walker A and Walker B motifs, or ATP-γ-S inhibited these activities of Cdc6p. These data suggest that Cdc6p modifies ORC function at DNA replication origins. On the basis of these results in yeast, we propose that Cdc6p may be an essential determinant of origin specificity in metazoan species.
Long palindromes formed in Streptomyces by nonrecombinational intra-strand annealing
Authors: Qin Zhongjun , Cohen Stanley N.
Published: November 2021

Long inverted repeats (palindromes) are ubiquitous among prokaryotic and eukaryotic genomes. Earlier work has implicated both DNA breaks and short inverted repeats (IRs) in the formation of long palindromes in yeast and Tetrahymena by a proposed mechanism of intramolecular recombination. Here we report that long-palindromic linear plasmids are formed in Streptomyces following double strand DNA breakage by a nonrecombinational intra-strand annealing process that also involves IRs. By modification of palindrome-generating linear plasmids and development of a novel procedure that enables the sequencing of palindrome junctions, we show that long-palindrome formation occurs by unimolecular intra-strand annealing of IRs followed by 3′ extension of the resulting DNA fold-back. The consequent hairpin structures serve as templates for synthesis of duplex linear plasmids containing long palindromes. We suggest that this model for long-palindrome formation in Streptomyces may represent a generally applicable mechanism for generating DNA palindromes.
RecE/RecT and Redα/Redβ initiate double-stranded break repair by specifically interacting with their respective partners
Authors: Muyrers Joep P.P. , Zhang Youming , Buchholz Fraenk , Stewart A. Francis
Published: November 2021

The initial steps of double-stranded break (DSB) repair by homologous recombination mediated by the 5′–3′ exonuclease/annealing protein pairs, RecE/RecT and Redα/Redβ, were analyzed. Recombination was RecA-independent and required the expression of both components of an orthologous pair, even when the need for exonuclease activity was removed by use of preresected substrates. The required orthologous function correlated with a specific protein–protein interaction, and recombination was favored by overexpression of the annealing protein with respect to the exonuclease. The need for both components of an orthologous pair was observed regardless of whether recombination proceeded via a single-strand annealing or a putative strand invasion mechanism. The DSB repair reactions studied here are reminiscent of the RecBCD/RecA reaction and suggest a general mechanism that is likely to be relevant to other systems, including RAD52 mediated recombination.
A cell cycle-dependent protein serves as a template-specific translation initiation factor
Authors: Pilipenko Evgeny V. , Pestova Tatyana V. , Kolupaeva Victoria G. , Khitrina Elena V. , Poperechnaya Angela N. , Agol Vadim I. , Hellen Christopher U.T.
Published: November 2021

Cap-independent translation initiation on picornavirus mRNAs is mediated by an internal ribosomal entry site (IRES) in the 5′ untranslated region (5′ UTR) and requires both eukaryotic initiation factors (eIFs) and IRES-specific cellulartrans-acting factors (ITAFs). We show here that the requirements fortrans-acting factors differ between related picornavirus IRESs and can account for cell type-specific differences in IRES function. The neurovirulence of Theiler's murine encephalomyelitis virus (TMEV; GDVII strain) was completely attenuated by substituting its IRES by that of foot-and-mouth disease virus (FMDV). Reconstitution of initiation using fully fractionated translation components indicated that 48S complex formation on both IRESs requires eIF2, eIF3, eIF4A, eIF4B, eIF4F, and the pyrimidine tract-binding protein (PTB) but that the FMDV IRES additionally requires ITAF45, also known as murine proliferation-associated protein (Mpp1), a proliferation-dependent protein that is not expressed in murine brain cells. ITAF45did not influence assembly of 48S complexes on the TMEV IRES. Specific binding sites for ITAF45, PTB, and a complex of the eIF4G and eIF4A subunits of eIF4F were mapped onto the FMDV IRES, and the cooperative function of PTB and ITAF45in promoting stable binding of eIF4G/4A to the IRES was characterized by chemical and enzymatic footprinting. Our data indicate that PTB and ITAF45act as RNA chaperones that control the functional state of a particular IRES and that their cell-specific distribution may constitute a basis for cell-specific translational control of certain mRNAs.
Mechanisms of Hox gene colinearity: transposition of the anterior Hoxb1 gene into the posterior HoxD complex
Authors: Kmita Marie , van der Hoeven Frank , Zákány József , Krumlauf Robb , Duboule Denis
Published: November 2021

Transposition of Hoxd genes to a more posterior (5′) location within the HoxD complex suggested that colinearity in the expression of these genes was due, in part, to the existence of a silencing mechanism originating at the 5′ end of the cluster and extending towards the 3′ direction. To assess the strength and specificity of this repression, as well as to challenge available models on colinearity, we inserted a Hoxb1/lacZtransgene within the posterior HoxD complex, thereby reconstructing a cluster with a copy of the most anterior gene inserted at the most posterior position. Analysis of Hoxb1 expression after ectopic relocation revealed that Hoxb1-specific activity in the fourth rhombomere was totally abolished. Treatment with retinoic acid, or subsequent relocations toward more 3′ positions in theHoxD complex, did not release this silencing in hindbrain cells. In contrast, however, early and anterior transgene expression in the mesoderm was unexpectedly not suppressed. Furthermore, the transgene induced a transient ectopic activation of the neighboringHoxd13 gene, without affecting other genes of the complex. Such a local and transient break in colinearity was also observed after transposition of the Hoxd9/lacZ reporter gene, indicating that it may be a general property of these transgenes when transposed at an ectopic location. These results are discussed in the context of existing models, which account for colinear activation of vertebrate Hox genes.
ATR disruption leads to chromosomal fragmentation and early embryonic lethality
Authors: Brown Eric J. , Baltimore David
Published: November 2021

Although a small decrease in survival and increase in tumor incidence was observed in ATR+/−mice, ATR−/− embryos die early in development, subsequent to the blastocyst stage and prior to 7.5 days p.c. In culture, ATR−/−blastocysts cells continue to cycle into mitosis for 2 days but subsequently fail to expand and die of caspase-dependent apoptosis. Importantly, caspase-independent chromosome breaks are observed inATR−/− cells prior to widespread apoptosis, implying that apoptosis is caused by a loss of genomic integrity. These data show that ATR is essential for early embryonic development and must function in processes other than regulation of p53.
An aminoacylation-dependent nuclear tRNA export pathway in yeast
Authors: Grosshans Helge , Hurt Ed , Simos George
Published: November 2021

Yeast Los1p, the homolog of human exportin-t, mediates nuclear export of tRNA. Using fluorescence in situ hybridization, we could show that the export of some intronless tRNA species is not detectably affected by the disruption of LOS1. To find other factors that facilitate tRNA export, we performed a suppressor screen of a synthetically lethal los1 mutant and identified the essential translation elongation factor eEF-1A. Mutations in eEF-1A impaired nuclear export of all tRNAs tested, which included both spliced and intronless species. An even stronger defect in nuclear exit of tRNA was observed under conditions that inhibited tRNA aminoacylation. In all cases, inhibition of tRNA export led to nucleolar accumulation of mature tRNAs. Our data show that tRNA aminoacylation and eEF-1A are required for efficient nuclear tRNA export in yeast and suggest coordination between the protein translation and the nuclear tRNA processing and transport machineries.
Ku complex interacts with and stimulates the Werner protein
Authors: Cooper Marcus P. , Machwe Amrita , Orren David K. , Brosh Robert M. , Ramsden Dale , Bohr Vilhelm A.
Published: November 2021

Werner syndrome (WS) is the hallmark premature aging disorder in which affected humans appear older than their chronological age. The protein WRNp, defective in WS, has helicase function, DNA-dependent ATPase, and exonuclease activity. Although WRNp functions in nucleic acid metabolism, there is little or no information about the pathways or protein interactions in which it participates. Here we identify Ku70 and Ku86 as proteins that interact with WRNp. Although Ku proteins had no effect on ATPase or helicase activity, they strongly stimulated specific exonuclease activity. These results suggest that WRNp and the Ku complex participate in a common DNA metabolic pathway.
Leptin-specific patterns of gene expression in white adipose tissue
Authors: Soukas Alexander , Cohen Paul , Socci Nicholas D. , Friedman Jeffrey M.
Published: November 2021

Leptin is a hormone that regulates body weight by decreasing food intake and increasing energy expenditure. ob/obmice carry leptin mutations and are obese and hyperphagic. Leptin administration to lean and ob/ob mice activates a novel metabolic program that depletes adipose tissue. Although this response is physiologically distinct from that evident after food restriction, the molecular nature of these differences is as yet unknown. Expression monitoring of 6500 genes using oligonucleotide microarrays in wild-type, ob/ob, and transgenic mice expressing low levels of leptin revealed that differences in ambient leptin levels have dramatic effects on the phenotype of white adipose tissue. These data identified a large number of genes that are differentially expressed in ob/ob mice. To delineate the components of the transcriptional program specifically affected by leptin, the level of the same 6500 genes was monitored in wild-type and ob/ob mice at various times after leptin treatment or food restriction. A novel application ofk-means clustering identified 8 clusters of adipose tissue genes whose expression was different between leptin treatment and food restriction in ob/ob mice and 10 such clusters in wild-type experiments. One of the clusters was repressed specifically by leptin in both wild-type and ob/ob mice and included several genes known to be regulated by SREBP–1/ADD1. Further studies confirmed that leptin decreases the levels of SREBP–1/ADD1 RNA and transcriptionally active SREBP–1/ADD1 protein in white adipose tissue. Future studies of the molecular basis for the apparent coordinate regulation of the other clusters of leptin-regulated genes may reveal additional mechanisms by which leptin exerts its weight-reducing effects.
Induction of medulloblastomas inp53-null mutant mice by somatic inactivation ofRbin the external granular layer cells of the cerebellum
Authors: Marino Silvia , Vooijs Marc , van der Gulden Hanneke , Jonkers Jos , Berns Anton
Published: November 2021

Medulloblastomas are among the most common malignancies in childhood, and they are associated with substantial mortality and morbidity. The molecular pathogenesis as well as the ontogeny of these neoplasms is still poorly understood. We have generated a mouse model for medulloblastoma byCre–LoxP-mediated inactivation ofRbandp53tumor suppressor genes in the cerebellar external granular layer (EGL) cells.GFAP–Cre-mediated recombination was found both in astrocytes and in immature precursor cells of the EGL in the developing cerebellum.GFAP–Cre;RbLoxP/LoxP;p53−/−or LoxP/LoxPmice developed highly aggressive embryonal tumors of the cerebellum with typical features of medulloblastoma. These tumors were identified as early as 7 weeks of age on the outer surface of the molecular layer, corresponding to the location of the EGL cells during development. Our results demonstrate that loss of function of RB is essential for medulloblastoma development in the mouse and strongly support the hypothesis that medulloblastomas arise from multipotent precursor cells located in the EGL.
Effectiveness of customer social participation for academic purposes: a case of informal WhatsApp groups
Authors: Lakmali A.A.I. , Abeysekera Nalin , Silva D.A.C. Suranga
Published: November 2021

Purpose

Customer social participation (CSP) is a new phenomenon that has emerged with the evolution of social media. Current literature designates customer participation in social media as “CSP”. Although CSP has been investigated in the online brand community context in social media, it has been little investigated in the context of student customers using WhatsApp – a highly trending social media platform among learners. Thus, this study aims to investigate the effectiveness of CSP in informal WhatsApp groups for academic purposes among undergraduate students of management studies.

Design/methodology/approach

The study adopted a single cross-sectional survey design. A structured online questionnaire was employed. Using convenience sampling technique, data were collected from 170 undergraduates of the Bachelor of Management Studies programme at the Open University of Sri Lanka.

Findings

The results revealed significant positive effects of functional, social and hedonic benefits with CSP. Meanwhile, the relationship between psychological benefits and CSP was insignificant. Furthermore, there is no influence of age and level of study on CSP among the learners in informal WhatsApp groups. Moreover, at present, the level of CSP in WhatsApp for academic purposes among students is moderate.

Originality/value

The role of the student as the customer and student behaviour in informal WhatsApp groups established for academic purposes have been little investigated in the field of open and distance education services. In this context, this study empirically validated the model of participation benefits and CSP in WhatsApp groups informally established for academic purposes.
Cointegration test for the long-run economic relationships of East Africa community: evidence from a meta-analysis
Authors: Yussuf Yussuf Charles
Published: November 2021

Purpose

The purpose of the paper is to test and analyze the equilibrium economic relationships of the East Africa Community (EAC).

Design/methodology/approach

To attain the study's purpose the authors applied the Johansen cointegration test, including long-run structural modeling (LRSM), vector-error-correlation-model (VECM) and variance-decomposition (VDC).

Findings

At I(1), both Philips‐Peron (PP) and Kwiatkowski–Phillips–Schmidt–Shin (KPSS) tests show that the East Africa member states' economies are cointegrated. The result was further substantiated by the tests based on Johansen cointegration and VECM procedures, showing significant long-run and short-run economic relations. The result further reveals that despite some uncommon issues among member states such as Tanzania and Kenya, however, their economic relationships remain significant though it is negative. Moreover, the finding revealed positive and significant short-run economic relationships between Kenya, Burundi and Rwanda.

Originality/value

The paper applies the cointegration techniques in the context of EAC. The result is likely to be adding value to the policymaker and also to the existing literature on the subject. This may trigger policy implications and open new research direction within the region and out.
Willingness-to-pay for robot-delivered tourism and hospitality services – an exploratory study
Authors: Ivanov Stanislav , Webster Craig
Published: November 2021

Purpose

This paper aims to investigate potential consumers’ willingness to pay for robot-delivered services in travel, tourism and hospitality, and the factors that shape their willingness to pay.

Design/methodology/approach

An online survey yielded a sample of 1,573 respondents from 99 countries. Independent samplest-test, Analysis of variance (ANOVA), cluster, factor and regression analyses were used.

Findings

Respondents expected to pay less for robot-delivered services than human-delivered services. Two clusters were identified: one cluster willing to pay nearly the same price for robotic services as for human-delivered services, whilst the other expected deep discounts for robotic services. The willingness-to-pay was positively associated with the attitudes towards robots in tourism, robotic service experience expectations, men and household size. It was negatively associated to travel frequency, age and education.

Research limitations/implications

The paper’s main limitation is its exploratory nature and the use of a hypothetical scenario in measuring respondents’ willingness to pay. The data were gathered prior to the COVID-19 pandemic and do not reflect the potential changes in perceptions of robots due to the pandemic.

Practical implications

Practitioners need to focus on improving the attitudes towards robots in tourism because they are strongly and positively related to the willingness to pay. The marketing messages need to form positive expectations about robotic services.

Originality/value

This is one of the first papers to investigate consumers’ willingness to pay for robot-delivered services in travel, tourism and hospitality and factors that shape their willingness to pay.
MOEAGAC: an energy aware model with genetic algorithm for efficient scheduling in cloud computing
Authors: Marri Nageswara Prasadhu , Rajalakshmi N.R.
Published: November 2021

Purpose

Majority of the research work either concentrated on the optimization of scheduling length and execution cost or energy optimization mechanism. This research aims to propose the optimization of makespan, energy consumption and data transfer time (DTT) by considering the priority tasks. The research work is concentrated on the multi-objective approach based on the genetic algorithm (GA) and energy aware model to increase the efficiency of the task scheduling.

Design/methodology/approach

Cloud computing is the recent advancement of the distributed and cluster computing. Cloud computing offers different services to the clients based on their requirements, and it works on the environment of virtualization. Cloud environment contains the number of data centers which are distributed geographically. Major challenges faced by the cloud environment are energy consumption of the data centers. Proper scheduling mechanism is needed to allocate the tasks to the virtual machines which help in reducing the makespan. This paper concentrated on the minimizing the consumption of energy as well as makespan value by introducing the hybrid algorithm called as multi-objective energy aware genetic algorithm. This algorithm employs the scheduling mechanism by considering the energy consumption of the CPU in the virtual machines. The energy model is developed for picking the task based on the fitness function. The simulation results show the performance of the multi-objective model with respect to makespan, DTT and energy consumption.

Findings

The energy aware model computes the energy based on the voltage and frequency distribution to the CPUs in the virtual machine. The directed acyclic graph is used to represent the task dependencies. The proposed model recorded 5% less makespan compared against the MODPSO and 0.7% less compared against the HEFT algorithms. The proposed model recorded 125 joules energy consumption for 50 VMs when all are in active state.

Originality/value

This paper proposed the multi-objective model based on bio-inspired approach called as genetic algorithm. The GA is combined with the energy aware model for optimizing the consumption of the energy in cloud computing. The GA used priority model for selecting the initial population and used the roulette wheel selection method for parent selection. The energy model is used as fitness function to the GA for selecting the tasks to perform the scheduling.
An integrated approach to organizational resilience: a quality perspective
Authors: Madani Farshad , Parast Mahour Mellat
Published: November 2021

Purpose

The main components of resiliency, including resilience capacities, resilience activities and resilience measures, are identified, extracted and redefined by designing their ontologies. The integrated model is developed by adapting the PDCA (plan, do, check and act) model to resilience management and implementing the developed concepts in the model.

Design/methodology/approach

This study uses systems theory to define the main concepts discussed in the literature on resilience. This study then uses systems engineering theory and a resource-based view of the firm to develop an integrated framework to demonstrate how a resilient firm operates.

Findings

The revised terminologies and the integrated model address the current theoretical issues in the literature, and they also provide a reference model for practical implementation of resilience management at the firm level. Also, the integrated model addresses the role of innovation in resilience management.

Originality/value

The study examines the concept of resilience form a quality perspective and also examines how resilience and innovation are related.
The effect of ecotourism knowledge on residents' attitudes in Otavalo, Ecuador: the knowledge theory of attitude–behavior consistency
Authors: Yoon Sang-Eun (Amelia) , Lee Kyoung-Joo
Published: November 2021

Purpose

Residents' supportive attitudes are essential for the successful development of ecotourism. Although existing literature has heavily relied on social exchange theory to explain residents' attitudes, this study explores a new theoretical direction by focusing on the cognitive process of residents' attitude formation. This study adopts the knowledge theory of attitude–behavior consistency that emphasizes the amount, relevance and complexity of ecotourism knowledge in shaping residents' positive attitudes toward tourism development in the regional community.

Design/methodology/approach

Based on a survey of 394 residents of Otavalo, Ecuador, this study confirmed the reliability and validity of measurements, used PLS-SEM for statistical analysis, and evaluated the effect of ecotourism knowledge on residents' attitudes toward ecotourism.

Findings

Under the control of community attachment and fair distribution of economic benefits supported by existing literature, this study finds that ecotourism knowledge has a positive and significant effect on residents' supportive attitudes toward tourism development.

Research limitations/implications

By elucidating the cognitive process of residents' attitude formation and change, this paper shows the applicability of a knowledge-based theory to residents' attitudes toward tourism development, and offers practical implications for ecotourism policymakers and educational program developers.

Originality/value

This study adopts the knowledge theory of attitude–behavior consistency and shows the positive influence of ecotourism knowledge on residents' attitudes.
Entrepreneurship education in Brazil: Brazilian and Scottish approaches to policy and provision in vocational education
Authors: Stadler Adriano , Alberton Anete , Smith Anne M.J.
Published: November 2021

Purpose

This paper examines entrepreneurship education (EE) in Brazil and Scotland and unpacks convergent and divergent practices in vocational education (VE). The authors evaluate access to EE in VE and suggest and how it might be advanced in Brazil.

Design/methodology/approach

The authors conducted an interpretative phenomenological analysis (IPA); interpretative analysis of interviewee experiences with 12 educationalists, in management and academic roles, from two Brazilian and two Scottish VE institutions, contextual findings inform advances.

Findings

In Scotland, there is a well-defined entrepreneurial ecosystem where government policy and partners support and monitor provision of and accessibility to EE. In Brazil, government does not regulate policy provision of EE, and there is no defined entrepreneurial ecosystem of partners. IPA enabled the authors to examine divergent entrepreneurial education provision and evaluate accessibility to EE in Brazil.

Research limitations/implications

Implications include ways to advance educational inclusivity and accessibility for VE students in Brazil and a call to address availability through policy is underpinned by empirical data. Contextual characteristics of the study might be considered limiting but address a broad call to contribute to EE in VE settings.

Practical implications

The findings of this study equip educationalists with new knowledge about advancing EE provision and delivery in VE, which in turn supports inclusivity.

Originality/value

The authors contribute directly to an agenda that will create impact for young Brazilians through accessible EE models that place EE in VE at the forefront of social change in Brazil.
Comparative study on intelligent education research among countries based on bibliographic coupling analysis
Authors: Ma Chao , Xu Qiaoyun , Li Baiyang
Published: November 2021

Purpose

The continuous development of information technology leads to intelligent education research. In the context of internationalisation, the study aims to understand the relevant research status worldwide, research similarities and differences that need to be discovered, and research frontiers that need to be explored.

Design/methodology/approach

Web of Science (WoS) core collection was used as the data source, descriptive statistical analysis, geographic data visualisation and coupling analysis are used to reveal coupling relationships, present a cooperative situation and discover research frontiers.

Findings

Intelligent education research has been widely carried out in countries around the world, and there is extensive scientific research cooperation. According to coupling analysis results, the coupling strength of bibliographic between countries has been continuously improved, while the coupling strength of keywords has remained balanced, and there is standardisation and diversity of research.

Research limitations/implications

The weakness of the research lies in the limitations of the data sources. Important research achievements on a certain topic in many non-English speaking countries are usually published in native journals. In the future research direction, more coupling analysis objects can be carried out, such as focussing on authors and institutions.

Practical implications

Through the coupling analysis of country bibliographic and keywords, it reveals the consistency and divergence of intelligent education research between different countries at different time spans.

Originality/value

Design and implement country bibliographic coupling (CBC) and country keyword coupling (CKC) strength indicators to calculate the strength of coupling between countries.
Impact assessment indicators for the UK Web Archive
Authors: Fukuyama Julie , Tanner Simon
Published: November 2021

Purpose

The purpose of this paper is to present the results of a study to examine, determine and propose the optimal approach to develop impact assessment indicators for the UK Web Archive.

Design/methodology/approach

The paper analyses the existing literature on impact assessment frameworks for digital resources and the types of impact in related fields to set an approach to develop an impact assessment plan. Primarily drawing from the Balanced Value Impact Model, the approach consists of three stages: context setting, indicator development and indicator evaluation.

Findings

The development of a set of potential impact assessment indicators for the UK Web Archive shows not only an optimal approach for the development but also recommendations for web archiving organisations.

Research limitations/implications

The research did not carry out follow-up interviews regarding the feedback from UK Web Archive's staff. Adoption of the new set of indicators will further this development.

Practical implications

The staff's duties influence their prioritisation of the indicators, so discussions among partners will be helpful in recognising different perceptions, unnoticed strengths and potential values. A progressive accumulation of assessment and improvements from the current state and small regular evaluations will be also helpful to demonstrate the impact and value to the stakeholders in the future.

Originality/value

This paper proposes a set of 13 potential indicators for the UK Web Archive of which functionality was checked against set quality criteria and tested through semi-structured interviews and survey submissions with the UK Web Archive staff members.
The ethics of service work in a neoliberal healthcare context: doing embodied and “dirty” emotional labor
Authors: Whiley Lilith Arevshatian , Grandy Gina
Published: November 2021

Purpose

The authors explore how service workers negotiate emotional laboring with “dirty” emotions while trying to meet the demands of neoliberal healthcare. In doing so, the authors theorize emotional labor in the context of healthcare as a type of embodied and emotional “dirty” work.

Design/methodology/approach

The authors apply interpretative phenomenological analysis (IPA) to their data collected from National Health Service (NHS) workers in the United Kingdom (UK).

Findings

The authors’ data show that healthcare service workers absorb, contain and quarantine emotional “dirt”, thereby protecting their organization at a cost to their own well-being. Workers also perform embodied practices to try to absolve themselves of their “dirty” labor.

Originality/value

The authors extend research on emotional “dirty” work and theorize that emotional labor can also be conceptualized as “dirty” work. Further, the authors show that emotionally laboring with “dirty” emotions is an embodied phenomenon, which involves workers absorbing and containing patients' emotional “dirt” to protect the institution (at the expense of their well-being).
A fructose receptor gene influences development and feed intake in Helicoverpa armigera
Authors: Ai Dong , Dong Chenxi , Yang Bin , Yu Caihong , Wang Guirong
Published: November 2021

Gustatory receptors (GRs) are critical for multiple life activities of insects. Owing to the rapid development of genome and transcriptome sequencing, numerous insect GRs have been identified. However, the expression patterns and functions of these receptors are poorly understood. In this study, we analyzed the expression pattern of GRs in Helicoverpa armigera and found that the fructose receptor HarmGR9 was highly expressed in the foregut and abdomen. The function of HarmGR9 was identified using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9) system. Knockout of the HarmGR9 gene shortened the developmental period of the larval stages and increased food consumption in both larvae and adults. This study revealed the tissue distribution of sugar‐sense‐related receptors in H. armigera and thereby expanded the understanding of insect feeding regulation.