bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective Study of Pain Outcomes Associated With Breast Surgery in Women With Nonhereditary Breast Cancer
Authors: Smith-Graziani Demetria J. , Parker Patricia A. , Peterson Susan K. , Bedrosian Isabelle , Shen Y , Black Dalliah M. , DeSnyder Sarah M. , Hunt Kelly K. , Dong Wenli , Brewster Abenaa M.
Published: May 2021

Objective:

To assess pain severity and interference with life in women after different types of breast cancer surgery and the demographic, treatment-related, and psychosocial variables associated with these pain outcomes.

Summary of Background Data:

Data are conflicting regarding pain outcomes and quality of life (QOL) among women who undergo different types of breast surgery.

Methods:

Women with nonhereditary breast cancer completed the brief pain inventory before surgery and at 1, 6, 12, and 18 months postsurgery. We assessed associations between pain outcomes and CPM status and mastectomy status using multivariable repeated measures models. We assessed associations between pain outcome and QOL and decision satisfaction.

Results:

Of 288 women (mean age 56 years, 58% non-Hispanic White), 50 had CPM, 75 had unilateral mastectomy, and 163 had BCS. Mean pain severity scores were higher at one (2.78 vs 1.9, P = 0.016) and 6 months (2.79 vs 1.96, P = 0.031) postsurgery in women who had CPM versus those who did not, but there was no difference at 12 and 18 months. Comparing mastectomy versus BCS, pain severity was higher at 1 and 12 months. There was a significant interaction between pain severity and time point for CPM (P = 0.006), but not mastectomy status (P = 0.069). Regardless of surgery type, Black women had higher pain severity (P = 0.004) than White women. Higher pain interference was associated with lower QOL (P < 0.001) and lower decision satisfaction (P = 0.034).

Conclusions:

Providers should counsel women considering mastectomy about the potential for greater acute pain and its impact on overall well-being. Racial/ethnic disparities in pain exist and influence pain management in breast surgical patients.
Challenging the Contraindications of Minimally Invasive Inguinal Lymph Node Dissection: Report of 2 Cases
Authors: Abdel Mageed Hisham Hassan , Saad Ihab , Lasithiotakis Konstantinos
Published: May 2021

Background:

Endoscopic inguinal dissection is an emerging procedure utilizing minimally invasive technology to perform inguinal dissections aiming to avoid skin complications. Despite numerous reports there seems to be no consensus on inclusion and exclusion criteria, raising the question of when and when not to choose the minimally invasive technique. We compare the inclusion and exclusion criteria in published literature, and present our experience with 2 challenging cases; 1 with skin infiltration and the other with a previous lymphadenectomy scar.

Materials and Methods:

We present 2 cases where this procedure was performed, despite limited nodal skin infiltration in the first case, and presence of a fresh scar of a previous biopsy and recent history of chemotherapy treatment in the second case.

Results:

Despite skin infiltration by inguinal nodes, endoscopic inguinal dissection was performed and the attached skin was excised and delivered with the lymph nodes through the incision in the first case. Presence of a fresh scar and history of chemotherapy did not affect the outcomes in the second case, albeit fibrosis and adhesions.

Conclusions:

Skin infiltration, previous lymphadenectomy, and previous groin therapy might not represent absolute contraindications in selected cases and in the hands of experienced surgeons.
Deaths from cardiovascular disease involving anticoagulants: a systematic synthesis of coroners’ case reports
Authors: Anis Ali , Heneghan Carl , Aronson Jeffrey K. , DeVito Nicholas J. , Richards Georgia C.
Published: May 2021

Background

The global burden of cardiovascular disease (CVD) is forecast to increase, and anticoagulants will remain important medicines for its management. Coroners’ Prevention of Future Death reports (PFDs) provide valuable insights that may enable safer and more effective use of these agents.

Aim

To identify CVD-related PFDs involving anticoagulants.

Design and Setting

Retrospective observational study of coronial case reports in England and Wales between 2013 and 2019.

Method

We screened 3037 PFDs for eligibility and included PFDs where CVD and an anticoagulant caused or contributed to the death. We descriptively analysed included cases and used content analysis to assess concerns raised by coroners and who responded to them.

Results

We identified 113 cardiovascular disease-related PFDs involving anticoagulants. Warfarin (36%), enoxaparin (11%), and rivaroxaban (11%) were the most common anticoagulants reported. Concerns most frequently raised by coroners included poor systems (31%), poor communication (25%), and failures to keep accurate medical records (25%). These concerns were most often directed to NHS trusts (29%), hospitals (10%), and general practices (8%). Nearly two-thirds (60%) of PFDs had not received responses from such organisations, which are mandatory under regulation 28 of the Coroners’ (Investigations) Regulations 2013. We created a publicly available tool,https://preventabledeathstracker.net/, which displays coroners’ reports in England and Wales to streamline access and identify important lessons to prevent future deaths.

Conclusion

National organisations, healthcare professionals, and prescribers should take actions to address the concerns of coroners’ in PFDs to improve the safe use of anticoagulants in patients with cardiovascular disease.

How this fits in

A previous assessment of 500 PFDs identified anticoagulants as the class of drugs most often involved in fatal medication errors. This study uses innovative methods to automatically collect all available PFDs between 2013 and 2019 to identify deaths from cardiovascular disease when the use of or lack of anticoagulants caused or contributed to the death. Coroners’ raised hundreds of coroners in their reports, including issues with communication, following protocols, education and training, access to resources, and safety. Despite repeat concerns with national relevance being identified, most CVD-anticoagulant PFDs were sent locally to NHS Trusts, hospitals, and general practices, limiting their ability to reduce harms and prevent premature deaths.
COVID-19 Vaccine Acceptance Among Healthcare Workers in a United States Medical Center
Authors: Moniz Michelle H. , Townsel Courtney , Wagner Abram L. , Zikmund-Fisher Brian J. , Hawley Sarah , Jiang Charley , Stout Molly J.
Published: May 2021

Background

The Centers for Disease Control and Prevention prioritized healthcare personnel for the first phase of COVID-19 vaccination in the United States to keep critical healthcare infrastructure open and functioning, but vaccine hesitancy may limit vaccine uptake.

Objective

To evaluate vaccine intentions among healthcare workers eligible for COVID-19 vaccination and explore differences by sociodemographic and occupational characteristics.

Design

From February 1-15, 2021, we conducted a cross-sectional, opt-in online survey at a Midwest U.S. academic healthcare center that began vaccinating employees in December 2020.

Participants

The entire employee workforce of the study site was eligible.

Main Measures

COVID-19 vaccination intention, categorized as Received/Scheduled/ASAP, Not Now, and Not Ever. Logistic regression models to assess the relationship between demographic and occupational characteristics and intention to receive COVID-19 vaccination.

Key Results

Most participants (n=11,387, of 39,259 individual and group email accounts invited) had received or were scheduled to receive the COVID-19 vaccine (n=9081, 79.8%) or planned to receive it as soon as possible (n=546, 4.8%), while fewer were hesitant (Not Now, n=954, 8.4%; Not Ever, n=369, 3.2%). In multivariable logistic regression models predicting vaccine intention, physicians (aOR 22.2, 9.1-54.3), trainees (aOR 5.9, 3.0-11.4), and nurse practitioners/nurse midwives/physician assistants (aOR 1.9, 1.2-3.0) were significantly more likely to demonstrate vaccine acceptance, compared to nurses, whereas other clinical staff were significantly less likely (aOR 0.8, 0.6-0.9). Prior infection with COVID-19, gender, race/ethnicity, and age were all significantly associated with vaccine intention. Overall, 29.6% reported at least one concern about COVID-19 vaccination.

Conclusions

In a large, diverse sample of healthcare workers, over 11% delayed COVID-19 vaccination when it was available to them, with notable variation in vaccine hesitancy across professional roles and demographic groups. Our findings suggest immediate opportunities to empathetically engage those with COVID-19 vaccine concerns and optimize vaccine coverage across our healthcare system.
Hypercoagulation detected by Rotational Thromboelastometry predicts mortality in COVID-19: A risk model based on a prospective observational study
Authors: Almskog Lou M. , Wikman Agneta , Svensson Jonas , Bottai Matteo , Kotormán Mariann , Wahlgren Carl-Magnus , Wanecek Michael , van der Linden Jan , Ågren Anna
Published: May 2021

Background

Severe disease due to COVID-19 has been shown to be associated with hypercoagulation. Early identification of prothrombotic patients may help guiding anticoagulant treatment and improve survival. The aim of this study was to assess Rotational Thromboelastmetry (ROTEM®) as a marker of coagulopathy in hospitalized COVID-19 patients.

Methods

This was a prospective, observational study. Patients hospitalized due to a COVID-19 infection were eligible for inclusion. Conventional coagulation tests and ROTEM were taken after hospital admission, and patients were followed for 30 days. Patient characteristics and outcome variables were collected, and a prediction model including variables age, respiratory frequency and ROTEM EXTEM-MCF, was developed using logistic regression to evaluate the probability of death.

Results

Out of the 141 patients included, 18 (13%) died within 30 days. D-dimer (p=0.01) and Activated Partial Thromboplastin Time (APTT) (p=0.002) were increased, and ROTEM EXTEM-/INTEM-CT (p<0.001) were prolonged in non-survivors. In the final prediction model, the risk of death within 30 days for a patient hospitalized due to COVID-19 was increased with increased age, respiratory frequency and EXTEM-MCF. Longitudinal ROTEM data in the severely ill subpopulation showed enhanced hypercoagulation. In our in vitro analysis, no heparin effect on EXTEM-CT was observed, supporting a SARS-CoV-2 effect on initiation of coagulation.

Conclusions

Here we show that hypercoagulation measured with ROTEM predicts 30-day mortality in COVID-19. Longitudinal ROTEM data strengthen the hypothesis of hypercoagulation as a driver of severe disease in COVID-19. Thus, ROTEM may be a useful tool to assess disease severity in COVID-19, and could potentially guide anticoagulation therapy.
Metabologenomic approach reveals intestinal environmental features associated with barley-induced glucose tolerance improvements in Japanese cohort: a randomized controlled trial
Authors: Goto Yuka , Nishimoto Yuichiro , Murakami Shinnosuke , Nomaguchi Tatsuhiro , Mori Yuka , Ito Masaki , Nakaguro Ryohei , Kudo Toru , Matsuoka Tsubasa , Yamada Takuji , Kobayashi Toshiki , Fukuda Shinji
Published: May 2021

Consumption of barley has been known to exert beneficial effects on metabolic disorders; however, it has also been reported that there are inter-individual differences in these responses. Recent evidence has suggested that these individual differences are mediated by the gut microbiota. Therefore, in the present study, we aimed to understand the relationship between the intestinal environment, including gut microbiota, and metabolic disorders. A randomized controlled trial in Japanese subjects with 4-week consumption of barley or control food was conducted. In this study, we analyzed the intestinal environment, including microbiota and their metabolites, and blood parameters were assessed collectively. We found that microbial genera Blautia and Agathobacter belonging to Lachnospiraceae, and fecal metabolites such as azelate were increased 1.31-fold, 1.84-fold, and 1.48-fold after barley consumption, respectively. Furthermore, the subjects whose glucose tolerance were slightly impaired showed improvement in their glucose tolerance index following the barley consumption. Additionally, the analysis showed that the increase in the abundance of the Anaerostipes was correlated with the improvement in the glucose tolerance index. Our findings indicate that the effects of barley consumption for glucose tolerance are partly defined by the intestinal environment of consumers, providing a quantitative measurement of the dietary effect based on the intestinal environment.
Preterm birth is associated with immune dysregulation which persists in infants exposed to histologic chorioamnionitis: a descriptive study
Authors: Sullivan Gemma , Galdi Paola , Borbye-Lorenzen Nis , Stoye David Q. , Lamb Gillian J. , Evans Margaret J. , Skogstrand Kristin , Chandran Siddharthan , Boardman James P.
Published: May 2021

Objective

To characterise the umbilical cord blood immune profile in preterm infants compared to term-born controls and the postnatal immune response following exposure to histologic chorioamnionitis (HCA) in preterm infants.

Design

Descriptive, observational cohort study.

Setting

Edinburgh, UK.

Population

118 preterm infants (mean gestational age 29+0 weeks, range 23+2 to 32+0) and 59 term-born controls.

Methods

Placental histopathology was used to identify reaction patterns indicative of HCA, and a customised immunoassay of 24 inflammatory markers and trophic proteins selected to reflect the perinatal immune response was performed on umbilical cord blood in term and preterm participants and postnatal day 5 blood in the preterm group.

Results

The umbilical cord blood immune profile classified gestational age category with 86% accuracy (95% CI 0.78-0.92), p-value=1.242×10−14. Pro-inflammatory proteins IL-6, MCP-1 and CRP were elevated in the cord blood of preterm infants whilst BDNF, C3, C9, IL-18, MMP-9 and RANTES were decreased, compared to infants born at term. In preterm infants, exposure to HCA was associated with elevations in 5 immune proteins on postnatal day 5 (BDNF, C3, IL-8, MIP-1β and MMP-9) when compared to preterm infants who were not exposed.

Conclusion

Preterm birth is associated with a distinct immune profile in umbilical cord blood and infants exposed to HCA experience specific alterations in immune function that persist to day 5 of postnatal life.
Transcriptional Pathology Evolves Over Time in Rat Hippocampus Following Lateral Fluid Percussion Traumatic Brain Injury
Authors: Catta-Preta Rinaldo , Zdillar Iva , Jenner Bradley , Doisy Emily T. , Tercovich Kayleen , Nord Alex S. , Gurkoff Gene G.
Published: May 2021

Traumatic brain injury (TBI) causes acute and lasting impacts on the brain, driving pathology along anatomical, cellular, and behavioral dimensions. Rodent models offer the opportunity to study TBI in a controlled setting, and enable analysis of the temporal progression that occurs from injury to recovery. We applied transcriptomic and epigenomic analysis, characterize gene expression and in ipsilateral hippocampus at 1 and 14 days following moderate lateral fluid percussion (LFP) injury. This approach enabled us to identify differential gene expression (DEG) modules with distinct expression trajectories across the two time points. The major DEG modules represented genes that were up- or downregulated acutely, but largely recovered by 14 days. As expected, DEG modules with acute upregulation were associated with cell death and astrocytosis. Interestingly, acutely downregulated DEGs related to neurotransmission mostly recovered by two weeks. Upregulated DEG modules related to inflammation were not necessarily elevated acutely, but were strongly upregulated after two weeks. We identified a smaller DEG module with delayed downregulation at 14 days including genes related to cholesterol metabolism and amyloid beta clearance. Finally, differential expression was paralleled by changes in H3K4me3 at the promoters of differentially expressed genes at one day following TBI. Following TBI, changes in cell viability, function and ultimately behavior are dynamic processes. Our results show how transcriptomics in the preclinical setting has the potential to identify biomarkers for injury severity and/or recovery, to identify potential therapeutic targets, and, in the future, to evaluate efficacy of an intervention beyond measures of cell death or spatial learning.
An automated approach to improve the speed and accuracy of pericyte and microglia quantification in whole mouse brain sections
Authors: Courtney Jo-Maree , Morris Gary P , Cleary Elise M , Howells David W , Sutherland Brad A
Published: May 2021

Whole slide scanning technology has enabled the generation of high-resolution images of complete tissue sections. However, commonly used analysis software is often unable to handle the large data files produced. Here we present a method using the open-source software QuPath to detect, classify and quantify fluorescently-labelled cells (microglia and pericytes) in whole coronal brain tissue sections. Whole brain sections from both male and female NG2DsRed x CX3CR1+/GFP mice were analysed. Small regions of interest were selected and manual counts were compared to counts generated from an automated approach, across a range of detection parameters. The optimal parameters for detecting cells and classifying them as microglia or pericytes in each brain region were determined and applied to annotations corresponding to the entire cortex, hippocampus, thalamus and hypothalamus in each section. 3.71% of all detected cells were classified as pericytes, however this proportion was significantly higher in the thalamus (6.39%) than in other regions. In contrast, microglia (4.45% of total cells) were more abundant in the cortex (5.54%). No differences were detected between male and female mice. In conclusion, QuPath offers a user-friendly, rapid and accurate solution to whole-slide image analysis which could lead to important new discoveries in both health and disease.

Significance Statement

Rapid and accurate quantification of cell numbers and distributions from whole tissue sections represents a difficult challenge in biomedical research. Slide scanning microscopes generate high-resolution images of complete tissue sections but most common image analysis software packages struggle to cope with the large data files they produce. We provide a method for rapidly and accurately quantifying pericyte and microglia cell numbers in whole brain tissue sections using QuPath, a new open-source software designed specifically to overcome this challenging roadblock.
Allosteric Cross-Talk Among SARS-CoV-2 Spike’s Receptor-Binding Domain Mutations Triggers an Effective Hijacking of Human Cell Receptor
Authors: Spinello Angelo , Saltalamacchia Andrea , Borišek Jure , Magistrato Alessandra
Published: May 2021

The rapid and relentless emergence of novel highly transmissible SARS-CoV-2 variants, possibly decreasing vaccine efficacy, currently represents a formidable medical and societal challenge. These variants frequently hold mutations on the Spike protein’s Receptor-Binding Domain (RBD), which, binding to the Angiotensin-Converting Enzyme 2 (ACE2) receptor, mediates viral entry into the host cells.

Here, all-atom Molecular Dynamics simulations and Dynamical Network Theory of the wild-type and mutant RBD/ACE2 adducts disclose that while the N501Y mutation (UK variant) enhances the Spike’s binding affinity towards ACE2, the N501Y, E484K and K417N mutations (South African variant) aptly adapt to increase SARS-CoV-2 propagation via a two-pronged strategy: (i) effectively grasping ACE2 through an allosteric signaling between pivotal RBD structural elements; and (ii) impairing the binding of antibodies elicited by infected/vaccinated patients. This information, unlocking the molecular terms and evolutionary strategies underlying the increased virulence of emerging SARS-CoV-2 variants, set the basis for developing the next-generation anti-COVID-19 therapeutics.

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Tracing cortical circuits in humans and non-human primates from high resolution connectomic, transcriptomic, and temporal dimensions
Authors: Charvet Christine J. , Ofori Kwadwo , Baucum Christine , Sun Jianli , Modrell Melinda S. , Hekmatyar Khan , Edlow Brian L. , van der Kouwe Andre J.
Published: May 2021

The neural circuits that support human cognition are a topic of enduring interest. Yet, the lack of tools available to map human brain circuits has precluded our ability to trace the human and non-human primate connectome. We harnessed high-resolution connectomic, anatomic, and transcriptomic data to investigate the evolution and development of frontal cortex circuitry. We applied machine learning to RNA sequencing data to find corresponding ages between humans and macaques and to compare the development of circuits across species. We transcriptionally defined neural circuits by testing for associations between gene expression and white matter maturation. We then considered transcriptional and structural growth to test whether frontal cortex circuit maturation is unusually extended in humans relative to other species. We also considered gene expression and high-resolution diffusion MR tractography of adult brains to test for cross-species variation in frontal cortex circuits. We found that frontal cortex circuitry development is extended in primates, and concomitant with an expansion in cortico-cortical pathways compared with mice in adulthood. Importantly, we found that these parameters varied relatively little across humans and studied primates. These data identify a surprising collection of conserved features in frontal cortex circuits across humans and Old World monkeys. Our work demonstrates that integrating transcriptional and connectomic data across temporal dimensions is a robust approach to trace the evolution of brain connectomics in primates.

Significance Statement

We lack appropriate tools to visualize the human brain connectome. We develop new approaches to study connections in the human and non-human primate brains. The integration of transcription with structure offers an unprecedented opportunity to study circuitry evolution. Our integrative approach finds corresponding ages across species and transcriptionally defines neural circuits. We used this information to test for variation in circuit maturation across species and found a surprising constellation of similar features in frontal cortex neural circuits across humans and primates. Integrating across scales of biological organization expands the repertoire of tools available to study connections in primates, which opens new avenues to study connections in health and diseases of the human brain.
A non-coding A-to-T Kozak site change related to the transmissibility of Alpha, Delta and Omicron VOCs
Authors: Yang Jianing , Zhang Guoqing , Yu Dalang , Cao Ruifang , Wu Xiaoxian , Ling Yunchao , Pan Yi-Hsuan , Yi Chunyan , Sun Xiaoyu , Sun Bing , Zhang Yu , Zhao Guo-Ping , Li Yixue , Li Haipeng
Published: May 2021

Three prevalent SARS-CoV-2 Variants of Concern (VOCs) were emerged and caused epidemic waves. It is essential to uncover the key genetic changes that cause the high transmissibility of VOCs. However, different viral mutations are generally tightly linked so traditional population genetic methods may not reliably detect beneficial mutation. In this study, we proposed a new pandemic-scale phylogenomic approach to detect mutations crucial to transmissibility. We analyzed 3,646,973 high-quality SARS-CoV-2 genomic sequences and the epidemiology metadata. Based on the sequential occurrence order of mutations and the instantaneously accelerated furcation rate, the analysis revealed that two non-coding mutations at the position of 28271 (g.a28271-/t) might be crucial for the high transmissibility of Alpha, Delta and Omicron VOCs. Both two mutations cause an A-to-T change at the core Kozak site of theNgene. The analysis also revealed that the non-coding mutations (g.a28271-/t) alone are unlikely to cause high viral transmissibility, indicating epistasis or multilocus interaction in viral transmissibility. A convergent evolutionary analysis revealed that g.a28271-/t, S:P681H/R and N:R203K/M occur independently in the three-VOC lineages, suggesting a potential interaction among these mutations. Therefore, this study unveils that non-synonymous and non-coding mutations could affect the transmissibility synergistically.
The Split-Belt Rimless Wheel
Authors: Butterfield Julia K. , Simha Surabhi N. , Donelan J. Maxwell , Collins Steven H.
Published: May 2021

Split-belt treadmill training, common in stroke rehabilitation and motor learning experiments, reveals a mechanism through which energy can be extracted from the environment. People can extract net positive work from a split-belt treadmill by lengthening their step onto the fast belt. To understand how leg angles and belt speed differences affect energy transfer between the treadmill and the person during split-belt walking, we simulated a split-belt rimless wheel that alternates rotating on fast and slow treadmill belts. We found that the split-belt rimless wheel can passively walk steadily forward under a range of conditions, extracting enough energy from the treadmill to overcome losses during collisions. The simulated wheel can tolerate both speed disturbances and ground height variability, and it can even capture enough energy to walk uphill. We also built a physical split-belt rimless wheel robot, demonstrating the feasibility of energy extraction during split-belt treadmill walking. In comparing the wheel solutions to human split-belt gait, we found that humans do not maximize positive work performed by the treadmill; costs associated with balance and free vertical moments likely limit adaptation. This study characterizes the mechanics and energetics of split-belt walking, demonstrating that energy capture through intermittent contacts with the two belts is possible when the belt speed difference is paired with an asymmetry in leg angles at step-to-step transitions. This study demonstrates a novel way of harnessing energy through individual rotations rather than continuous contact and offers a simple model framework for understanding human choices during split-belt walking.
The chromatin insulator CTCF regulates HPV18 transcript splicing and differentiation-dependent late gene expression
Authors: Ferguson Jack , Leon Karen Campos , Pentland Ieisha , Stockton Joanne , Günther Thomas , Beggs Andrew , Roberts Sally , Noyvert Boris , Parish Joanna L.
Published: May 2021

The ubiquitous host protein, CCCTC-binding factor (CTCF), is an essential regulator of cellular transcription and functions to maintain epigenetic boundaries, stabilise chromatin loops and regulate splicing of alternative exons. We have previously demonstrated that CTCF binds to the E2 open reading frame (ORF) of human papillomavirus (HPV) 18 and functions to repress viral oncogene expression in undifferentiated keratinocytes by co-ordinating an epigenetically repressed chromatin loop within HPV episomes. Cellular differentiation, which is necessary for HPV life cycle completion disrupts CTCF-dependent chromatin looping of HPV18 episomes inducing enhanced activity of the HPV18 early promoter P105and increased viral oncogene expression.

To further characterise CTCF function in HPV transcription control we utilised direct, long-read Nanopore RNA-sequencing which provides information on the structure and abundance of full-length transcripts. Nanopore analysis of primary human keratinocytes containing HPV18 episomes before and after synchronous differentiation allowed quantification of viral transcript species in these cultures, including the identification of low abundance novel transcripts. Comparison of transcripts produced in wild type HPV18 genome-containing cells to those identified in CTCF-binding deficient genome-containing cells (HPV18-ΔCTCF) identifies CTCF as a key regulator of differentiation-dependent late promoter activation, required for efficient E1^E4 and L1 protein expression. Furthermore, our data show that CTCF binding at the E2 ORF of HPV18 promotes usage of the downstream weak splice donor (SD) sites SD3165 and SD3284, to the dominant E4 splice acceptor site at nucleotide 3434. These findings demonstrate importance of CTCF-dependent transcription regulation at multiple stages of the HPV life cycle.

IMPORTANCE

Oncogenic human papillomavirus (HPV) infection is the cause of a subset of epithelial cancers of the uterine cervix, other anogenital areas and the oropharynx. HPV infection is established in the basal cells of epithelia where a restricted programme of viral gene expression is required for replication and maintenance of the viral episome. Completion of the HPV life cycle is dependent on the maturation (differentiation) of infected cells which induces enhanced viral gene expression and induction of capsid production. We previously reported that the host cell transcriptional regulator, CTCF, is hijacked by HPV to control viral gene expression. In this study, we use long-read mRNA sequencing to quantitatively map the variety and abundance of HPV transcripts produced in early and late stages of the HPV life cycle and to dissect the function of CTCF in controlling HPV gene expression and transcript processing.
mir124-dependent tagging of glutamatergic synapses by synaptopodin controls non-uniform and input-specific homeostatic synaptic plasticity
Authors: Dubes Sandra , Soula Anaïs , Benquet Sébastien , Tessier Béatrice , Poujol Christel , Favereaux Alexandre , Thoumine Olivier , Letellier Mathieu
Published: May 2021

Homeostatic synaptic plasticity (HSP) is a process by which neurons adjust synaptic strengths to compensate for various perturbations and which allows to stabilize neuronal activity. Yet, whether the highly diverse synapses harboring a neuron respond uniformly to a same perturbation is unclear and the underlying molecular determinants remain to be identified. Here, using patch-clamp recordings, immunolabeling and imaging approaches, we report that the ability of individual synapses to undergo HSP in response to activity-deprivation paradigms depends on the local expression of the spine apparatus related protein synaptopodin (SP) acting as a synaptic tag to promote AMPA receptor synaptic accumulation and spine growth. Gain and loss-of-function experiments indicate that this process relies on the local de-repression of SP translation by miR124 which supports both non-uniform and synapse-autonomous HSP induced by global or inputspecific activity deprivation, respectively. Our findings uncover an unexpected synaptic-tagging mechanism for HSP, whose molecular actors are intriguingly shared with Hebbian plasticity and linked to multiple neurological diseases.
Phylodynamic signatures in the emergence of community-associated MRSA
Authors: Steinig Eike , Aglua Izzard , Duchêne Sebastián , Meehan Michael T. , Yoannes Mition , Firth Cadhla , Jaworski Jan , Drekore Jimmy , Urakoko Bohu , Poka Harry , Wurr Clive , Ebos Eri , Nangen David , Müller Elke , Mulvey Peter , Jackson Charlene , Blomfeldt Anita , Aamot Hege Vangstein , Laman Moses , Manning Laurens , Earls Megan , Coleman David C. , Greenhill Andrew , Ford Rebecca , Stegger Marc , Syed Muhammed Ali , Jamil Bushra , Monecke Stefan , Ehricht Ralf , Smith Simon , Pomat William , Horwood Paul , Tong Steven Y.C. , McBryde Emma
Published: May 2021

Community-associated, methicillin-resistantStaphylococcus aureus(MRSA) lineages have emerged in many geographically distinct regions around the world during the past 30 years. Here, we apply consistent phylodynamic methods across multiple community-associated MRSA lineages to describe and contrast their patterns of emergence and dissemination. We generated whole genome sequencing data for the Australian sequence type (ST) 93-MRSA-IV from remote communities in Far North Queensland and Papua New Guinea, and the Bengal Bay ST772-MRSA-V clone from metropolitan communities in Pakistan. Increases in the effective reproduction number (Re) and sustained transmission (Re> 1) coincided with spread of progenitor methicillin-susceptibleS. aureus(MSSA) in remote northern Australia, dissemination of the ST93-MRSA-IV geno-type into population centers on the Australian East Coast, and sub-sequent importation into the highlands of Papua New Guinea and Far North Queensland. Analysis of a ST772-MRSA-V cluster in Pakistan suggests that sustained transmission in the community following importation of resistant genotypes may be more common than previously thought. Applying the same phylodynamic methods to existing lineage datasets, we identified common signatures of epidemic growth in the emergence and epidemiological trajectory of community-associatedS. aureuslineages from America, Asia, Australasia and Europe. Surges in Rewere observed at the divergence of antibiotic resistant strains, coinciding with their establishment in regional population centers. Epidemic growth was also observed amongst drug-resistant MSSA clades in Africa and northern Australia. Our data suggest that the emergence of community-associated MRSA and MSSA lineages in the late 20th century was driven by a combination of antibiotic resistant genotypes and host epidemiology, leading to abrupt changes in lineage-wide transmission dynamics and sustained transmission in regional population centers.
Green project management from employees' perspective in Hong Kong's engineering and construction sectors
Authors: To Wai Ming , Lam K.H.
Published: May 2021

Purpose

The study investigates employees’ perceptions of green project management in Hong Kong's engineering and construction sectors.

Design/methodology/approach

Green project management attributes were identified and categorized in terms of organization and process aspects based on a literature review. A questionnaire was developed to collect responses from employees working in Hong Kong's engineering and construction sectors.

Findings

Respondents perceived “using Design for Environment approach,” “training employees about green project management” and “recycling the used or excessive materials/components” as the most important attributes. Generally, females gave higher importance ratings than males to most attributes. Respondents who had higher education qualifications or held senior positions perceived green project management attributes as more important than their counterparts with lower education qualifications or in lower positions. Green project management was found to have four distinct factors: “Management Commitment,” “Green Technologies and Processes,” “Green Partnerships” and “External Communication.”

Originality/value

The study is one of the first empirical works on green project management in Hong Kong's engineering and construction sectors. It demonstrates that green project management should be characterized as a multidimensional concept.
A retrospective overview ofJournal of Enterprise Information Managementusing bibliometric analysis
Authors: Donthu Naveen , Kumar Badhotiya Gaurav , Kumar Satish , Soni Gunjan , Pandey Nitesh
Published: May 2021

Purpose

Journal of Enterprise Information Management(JEIM) is a leading journal that publishes studies on applied information management relevant to industry personals, academicians and researchers. This study uses bibliometric tools to present a retrospective analysis of the journal's outcomes.

Design/methodology/approach

The authors applied bibliometric tools for analysing the impact, topic coverage, renowned authors with affiliation, citation, methodology and analysis of theJEIMcorpus. Additionally, they used bibliographic coupling to develop a graphical visualisation and analyse the journal's thematic evolution.

Findings

With 16 yearly articles,JEIMcontributed 656 research articles on various themes. The major themes that have come to define theJEIMover this time include information and systems, supply chain management, manufacturing resource planning, communication technologies and small- to medium-sized enterprises. Empirical methodology, quantitative techniques with descriptive analysis and regression methods are the most preferred. The article's primary research purpose shows the majority of theory-verifying articles. Co-authorship analysis reveals that the single-author trend is decreasing and the journal now has articles with international collaborations.

Originality/value

This study is the retrospective analysis of theJEIM, which is useful for aspiring contributors and the journal's editors.
The dichotomisation fallacy of public and private corruption and the quantification dilemma
Authors: Ekwueme Ejike
Published: May 2021

Purpose

This paper aims to examine the concept of corruption and dirty money. Corruption is amorphous and lacks a congruent definition. It is mainly divided into public and private corruption. This divide, is unnecessary, given the fact that both cause incalculable damage to the markets and lager society. Globalisation has necessitated liberalisation and resulted in amalgamating both public and private ventures. This, as a result, has made it more difficult to stick to this. Pronouncements from International Chamber of Commerce (ICC) and the Law Commission’s attitude not to segregate between private and public bribery prior to the legislation of United Kingdom Bribery Act 2010, has added greater impetus to the debate. Attempts to quantify the amount of corruption and money laundering, has equally, hit a dead end. The figures being bandied about are all estimates or “guesstimates” that cannot stand the empirical test. As a result, the conjectures have strong potentials to continue for a longer time. The purpose of this paper is to bring to the fore the need to jettison the long-held perception that public and private corruption should be seen in different lights.

Design/methodology/approach

This paper relies substantially on both primary and secondary sources in the analysis.

Findings

Indicatively, the facts tilt towards the conclusion that it is impossible to actually ascertain the quantifiable amount of money that is involved in corruption and the money laundering process. It is an illusion.

Originality/value

The paper provides the platform that the time is ripe for both public and private corruption to be seen as the same thing, as they both unleash catastrophic consequences on society. The issues of globalisation and liberalisation make this inevitable.
Aircraft routing problem model for fractional fleets using fault prognostics
Authors: Pereira Barreto Eduardo Afonso , Abrahão Fernando Teixeira Mendes Teixeira Mendes , Olivares Loesch Vianna Wlamir
Published: May 2021

Purpose

The objective of this work is to provide a novel aircraft allocation model for fractional business aviation. This model may provide decision-makers with alternative routing solutions that take into consideration preventive maintenance and failure prognostics information. The expected results are more efficient routing solutions when compared to conventional planning models, to help decision-makers improve operations and maintenance planning.

Design/methodology/approach

The model is a mixed integer linear problem formulation addressing and considering preventive maintenance and failure prognostics for optimal operations. Numerical experiments were performed using both field and synthetic data to validate the proposed method. All instances are solved using branch, price and cut algorithms from open-source software.

Findings

The results obtained in this study show that the use of failure prognostics information in aircraft routing can provide improvements in overall planning. By choosing slightly longer flight legs, the flight cost will increase, but putting an aircraft with a higher risk of failure on a leg inbound to a maintenance base can reduce maintenance and overall operating cost.

Originality/value

The model and method provide decision-makers with routing solutions that consider new aspects of planning, not used in previous works, such as failure. Most of the literature focuses on solving routing problems for large commercial airlines. Considering that, few solutions are found in literature for fractional business operators, which have their own operational particularities, such as a company managing a fleet of aircraft belonging to multiple shareowners. In such operation, clients may not always fly in the aircraft that they are shareowners, but an aircraft from the fractional fleet of the same category. Here, the company managing the aircraft guarantees that an aircraft will be ready to attend client demands in minimum time. One of the major differences from other models of operation is the dynamic nature of its flight demands, thus requiring flexible and agile planning limiting the available time to find a routing solution.
Entrepreneurs' emotional intelligence as a factor explaining entrepreneurial psychological ownership and high-tech start-up growth
Authors: Yitshaki Ronit
Published: May 2021

Purpose

The purpose of this study is to examine the role of emotional intelligence (EI) in explaining high-tech entrepreneurs' psychological ownership (PO) and, in turn, how their PO influences venture growth.

Design/methodology/approach

This study is based on data collected from 106 high-tech Israeli entrepreneurs.

Findings

The findings indicate that using emotions for problem-solving is positively associated with PO sense of efficacy, and that appraisal of emotions of others is negatively associated with PO sense of territoriality. Moreover, PO sense of efficacy is positively associated with growth, whereas sense of territoriality is negatively associated with growth. Finally, sense of territoriality has a curvilinear effect on venture growth.

Research limitations/implications

Understanding of the antecedents of entrepreneurs' PO and its influence on firms' growth is scant. The findings contribute to the psychology of entrepreneurship and PO literature by showing the influence of affective-based processes on high-tech start-up growth.

Practical implications

The findings of this study suggest the entrepreneurs' EI indirectly affects other affective behaviors such as PO, which in turn influence venture growth. It highlights the need of entrepreneur to regulate their emotions and manage the emotional- and cognitive-based processes for the sake of firms' growth.

Originality/value

The findings expand the knowledge pertaining to the psychology of entrepreneurship by showing how EI as an affective dimension is interrelated with affective-based process and entrepreneurial firms' growth.
Entrepreneurial competencies, entrepreneurial orientation, entrepreneurial network, government business support and SMEs performance. The moderating role of the external environment
Authors: Pulka Buba Musa , Ramli Azahari , Mohamad Armanurah
Published: May 2021

Purpose

The purpose of this study is to examine the moderating influence of the external environment on the relationship between entrepreneurial competencies, entrepreneurial orientation, entrepreneurial network, government business support and SMEs performance. The objectives of the study are achieved using the resource-based view and dynamic capability theory.

Design/methodology/approach

The survey method of research was used by personally administering questionnaires to the respondents. Multistage sampling techniques are used in selecting 470 SMEs owners/managers that participated in the survey. SPSS 24 and PLS-SEM 3.0 were used in the analysis of the data.

Findings

In the Nigerian context, the findings indicated that EC, EO and GBS directly influence the SMEs performance. Surprisingly, SMEs performance is not influenced by EN. Similarly, EE significantly moderated the relationship between EC, GBS and SMEs performance. On the contrary, EE does not have any moderating influence on the relationship between EO, EN and SMEs performance.

Research limitations/implications

The study is limited to northeastern Nigeria. The study is limited to the EC, EO, EN GBS EE and SMEs performance and the use of cross-sectional data. The findings imply that SMEs owners/managers need a high level of entrepreneurial competencies and government business support to achieve a better performance especially in an external environment that is characterised by dynamism, diversity, complexity and hostility. Hence, providing support for both RBV and DCT.

Practical implications

Thus, the study offers additional empirical evidence from Nigeria and also expands knowledge and understanding in this field. The findings offer owners/managers, government agencies, financial institutions and other stakeholders of SMEs strategies EC, EO, GBS and EE to achieve a better SMEs performance.

Originality/value

The conceptual framework of the study is unique, and the study was conducted in northeastern Nigeria which is grossly underrepresented in the literature. It also provided understanding on the moderating influence of EE on the framework.
Knowledge and attitudes toward genetically modified (GM) food among health sciences university students in Karachi, Pakistan
Authors: Amin Rafat , Khan Sadaf , Zeb Tehseen Fatima , Ali Shaukat , Baqai Neha , Baqai Maham , Shuja Shajiha
Published: May 2021

Purpose

Genetically modified (GM) foods have global importance as they can significantly improve food security challenges. However, risks associated with the consumption of GM foods have affected consumers’ acceptance. This study aims to assess the student’s awareness regarding GM foods.

Design/methodology/approach

A cross-sectional survey-based study was conducted to explore the knowledge and attitude of health sciences university students toward GM foods. Students (n = 400) from different academic disciplines were participated in the study.

Findings

The majority of the university students heard about GM organisms and GM food (67.5% and 60.8%, respectively) and have correctly defined GM foods (48.2%). The mean percentage score of knowledge and attitude toward GM foods among university students was 36.0 ± 29.4% and 29.8 ± 23.1%, respectively. No significant difference was observed in knowledge and attitude between undergraduate and postgraduate students. A significant difference was found toward the acceptability of GM food in students from different health sciences disciplines (p = 0.006).

Originality/value

The findings indicate that educational programs are needed to improve the knowledge of students about GM food and food safety challenges.
Empirical examination of an integrative model for asset pricing – evidence from US market
Authors: Bhaskaran Rajesh Kumar , Kovilathumpaday Sukumaran Sujit
Published: May 2021

Purpose

The current study proposes an integrative framework for examination of determinants of stock returns in US market based on the five-factor Fama and French (FF) model, macroeconomic variables and investor sentimental factors. The study is based on both value weighted and equally weighted monthly portfolio returns of all CRSP firms which are incorporated in the United States and listed on the NYSE, AMEX or NASDAQ.

Design/methodology/approach

The study applies PLS-SEM methodology to examine the major determinants of portfolio return.

Findings

The study suggests that investor sentiments are the major driving forces which positively influence the portfolio stock returns. The macroeconomic factors, the FF Factors and Momentum factor have negative influences on portfolio stock returns.

Originality/value

The study is the first of its kind which aim to determine the determinants of portfolio returns using the PLS-SEM methodology.