bluuebunny/crossref_metadata_2025 huggingface dataset:
A single dose of replication-competent VSV-vectored vaccine expressing SARS-CoV-2 S1 protects against virus replication in a hamster model of severe COVID-19
Authors: Malherbe Delphine C. , Kurup Drishya , Wirblich Christoph , Ronk Adam J. , Mire Chad , Kuzmina Natalia , Shaik Noor , Periasamy Sivakumar , Hyde Matthew A. , Williams Julie M. , Shi Pei-Yong , Schnell Matthias J. , Bukreyev Alexander
Published: January 2021

The development of effective countermeasures against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the agent responsible for the COVID-19 pandemic, is a priority. We designed and produced ConVac, a replication-competent vesicular stomatitis virus (VSV) vaccine vector that expresses the S1 subunit of SARS-CoV-2 spike protein. We used golden Syrian hamsters as animal model of severe COVID-19 to test the efficacy of the ConVac vaccine. A single vaccine dose elicited high levels of SARS-CoV-2 specific binding and neutralizing antibodies; following intranasal challenge with SARS-CoV-2, animals were protected from weight loss and viral replication in the lungs. No enhanced pathology was observed in vaccinated animals upon challenge, but some inflammation was still detected. The data indicate rapid control of SARS-CoV-2 replication by the S1-based VSV-vectored SARS-CoV-2 ConVac vaccine.
Transcutaneous penetration of a single-chain variable fragment (scFv) compared to a full-size antibody: potential tool for Atopic Dermatitis (AD) treatment
Authors: Baylet Audrey , Vyumvuhore Raoul , Laclaverie Marine , Marchand Laëtitia , Mainzer Carine , Bordes Sylvie , Closs-Gonthier Brigitte , Delpy Laurent
Published: January 2021

Background

Currently, several biologics are used for the treatment of cutaneous pathologies such as atopic dermatitis (AD), psoriasis (PSO) or skin cancers. The main administration routes are subcutaneous and intravenous injections. However, little is known about antibody penetration through the skin.

Objectives

The aim was to study the transcutaneous penetration of a reduced-size antibody as a single-chain variable fragment (scFv) compared to a whole antibody (Ab) and to determine its capacity to neutralize an inflammatory cytokine involved in AD such as human interleukin-4 (hIL-4).

Methods

Transcutaneous penetration was evaluated byex vivostudies on tape-stripped pig ear skin. Antibody visualization through the skin was measured by Raman microspectroscopy. In addition, hIL-4 neutralization was studied using two 2D models. First, embryonic alkaline phosphatase (SEAP) secretion by HEK-Blue™ IL-4/IL-13 cells, proportional to hIL-4 cells stimulation, was quantified by OD 620 nm measurement in presence or absence of an anti-hIL4 scFv or Ab. Then, normal human keratinocytes (NHKs) were stimulated with polyinosinic-polycytidylic acid (poly I:C) +/− hIL-4 and treated with anti-hIL4 scFv. Human Interleukin-8 (hIL-8) concentrations were determined in culture supernatants by ELISA.

Results

After 24h of application, analysis by Raman microspectroscopy showed that scFv penetrated into the upper dermis while Ab remained on thestratum corneum. In addition, the anti-hIL4 scFv showed better efficiency compared to Ab, with a neutralization percentage at 200 nM of 68% and 47%, respectively, in the HEK-Blue™ IL-4/IL-13 model. hIL-8 dosage in stimulated NHKs supernatants revealed that addition of scFv induced a dose-dependent hIL-4 neutralization.

Conclusions

scFv penetrates through to the upper papillary dermis while Ab remains on the surface. The anti-hIL4 scFv neutralizes its target effectively in two 2D models suggesting its potential use as topical therapy for AD.
STARCH SYNTHASE 4 is required for normal starch granule initiation in amyloplasts of wheat endosperm
Authors: Hawkins Erica , Chen Jiawen , Watson-Lazowski Alexander , Ahn-Jarvis Jennifer , Barclay J. Elaine , Fahy Brendan , Hartley Matthew , Warren Frederick J. , Seung David
Published: January 2021

Starch granule initiation is poorly understood at the molecular level. The glucosyltransferase, STARCH SYNTHASE 4 (SS4), plays a central role in granule initiation in Arabidopsis leaves, but its function in cereal endosperms is unknown. We investigated the role of SS4 in wheat, which has a distinct spatiotemporal pattern of granule initiation during grain development.

We generated TILLING mutants in tetraploid wheat (Triticum turgidum) that are defective in both SS4 homoeologs. The morphology of endosperm starch was examined in developing and mature grains.

SS4 deficiency led to severe alterations in endosperm starch granule morphology. During early grain development, while the wild type initiated single ‘A-type’ granules per amyloplast, most amyloplasts in the mutant formed compound granules due to multiple initiations. This phenotype was similar to mutants deficient in B-GRANULE CONTENT 1 (BGC1). SS4 deficiency also reduced starch content in leaves and pollen grains.

We propose that SS4 and BGC1 are required for the proper control of granule initiation during early grain development that leads to a single A-type granule per amyloplast. The absence of either protein results in a variable number of initiations per amyloplast and compound granule formation.
MicroRNA775 and targetGalactosyltransferase(GALT9) module regulates recovery from submergence induced senescence by modulatingSAGsinArabidopsis thaliana
Authors: Mishra Vishnu , Singh Archita , Gandhi Nidhi , Sarkar Das Shabari , Yadav Sandeep , Kumar Ashutosh , Sarkar Ananda K.
Published: January 2021

Submergence induced hypoxic condition is one of the abiotic stresses which negatively affects the plant growth and development, and causes early onset of senescence. Hypoxic conditions ateres the expression of a number of non-coding microRNAs (miRNAs), besides protein-coding genes. However, the molecular function of stress-induced miRNA in submergence induced physiological or developmental changes and recovery remains to be understood. The expression of miR775 is highly induced under hypoxic stress conditions. Here, we show that miR775 is a potential post-transcriptional regulator number of targets, includingGalactosyltransferase(GALT9). The expression of miR775 and targetGALT9was significantly induced and reduced respectively at 24 hours of submergence. The overexpression of miR775 (miR775-Oe) confers enhanced recovery from submergence stress and reduced accumulation of ROS, in contrast to wild type and endogenous target mimic of miR775 (MIM775) Arabidopsisplants. We observed a similar recovery phenotype in case of targetgalt9mutant plants, indicating the role of miR775-GALT9module in recovery from submergence. Further, we showed that the expression ofSENESCENCE ASSOCIATED GENES(SAGs), such asSAG12, SAG29, andORE1. was increased inMIM775and reduced in miR775-Oe andgalt9plants. Thus, our results suggest that miR775-GALT9module plays a crucial role in the recovery from submergence by modulating the expression ofSAGsthrough differential accumulation of ROS.
Comprehensive molecular features of polycystic ovary syndrome revealed by transcriptome analysis of oocytes and cumulus cells
Authors: Li Jie , Chen Haixia , Gou Mo , Tian Chenglei , Wang Huasong , Song Xueru , Keefe David. L. , Bai Xiaohong , Liu Lin
Published: January 2021

PCOS is typically characterized by polycystic ovarian morphology, hyperandrogenism, ovulatory dysfunction and infertility. Furthermore, PCOS patients undergoing ovarian stimulation have more oocytes, however, poor quality of oocytes lead to lower fertilization and implantation rates, decreased pregnancy and increased miscarriage rates. Our study suggests that global gene expression and cell to cell interactions of oocytes and CCs are significantly altered in women with PCOS. Noticeably, genes related to microtubules such as TUBB8 and TUBA1C are abnormally highly expressed in PCOS oocytes, reducing oocyte quality. The pattern of transposable element expression distinguishes PCOS from Control oocytes, implying the role of transposable elements in the occurrence of PCOS.
Multiscale mechanics and temporal evolution of vimentin intermediate filament networks
Authors: Schepers Anna V. , Lorenz Charlotta , Nietmann Peter , Janshoff Andreas , Klumpp Stefan , Köster Sarah
Published: January 2021

The cytoskeleton, an intricate network of protein filaments, motor proteins, and crosslinkers, largely determines the mechanical properties of cells. Among the three filamentous components, F-actin, microtubules, and intermediate filaments (IFs), the IF network is by far the most extensible and resilient to stress. We present a multiscale approach to disentangle the three main contributions to vimentin IF network mechanics – single filament mechanics, filament length, and interactions between filaments – including their temporal evolution. Combining particle tracking, quadruple optical trapping and computational modeling, we derive quantitative information on the strength and kinetics of filament interactions. Specifically, we find that hydrophobic contributions to network mechanics enter mostly via filament elongation kinetics, whereas electrostatics have a direct influence on filament–filament interactions. These results indicate that cells might need to explicitly suppress attractive interactions to re-organize the extremely stable cellular vimentin network.
Fidelity varies in the symbiosis between a gutless marine worm and its microbial consortium
Authors: Sato Yui , Wippler Juliane , Wentrup Cecilia , Ansorge Rebecca , Sadowski Miriam , Gruber-Vodicka Harald , Dubilier Nicole , Kleiner Manuel
Published: January 2021

In obligate symbioses, partner fidelity plays a central role in maintaining the association over evolutionary time. Fidelity has been well studied in hosts with only a few symbionts, but little is known about how fidelity is maintained in obligate associations with multiple co-occurring symbionts. Here, we show that partner fidelity varies from strict to absent in a gutless marine annelid and its consortium of co-occurring symbionts that provide it with nutrition. We sequenced the metagenomes of 80Olavius algarvensisindividuals from the Mediterranean, and compared host mitochondrial and symbiont phylogenies based on single nucleotide polymorphisms across genomes, using a low-coverage sequencing approach that has not yet been applied to microbial community analyses. Fidelity was strongest for the two chemoautotrophic, sulphur-oxidizing symbionts that dominated the microbial consortium in all host individuals. In contrast, fidelity was only intermediate to absent in the sulphate-reducing and spirochaetal symbionts, which occurred in lower abundance and were not always present in all host individuals. We propose that variable degrees of fidelity are advantageous for these hosts by allowing the faithful transmission of their nutritionally most important symbionts and flexibility in the acquisition of other symbionts that promote ecological plasticity in the acquisition of environmental resources.
Development of a yeast-based vaccine forTheileria parvainfection in cattle
Authors: Goh Shan , Kolakowski Jeannine , Holder Angela , Pfuhl Mark , Ngugi Daniel , Ballingall Keith , Tombacz Kata , Werling Dirk
Published: January 2021

East Coast Fever (ECF), caused by the tick-borne apicomplexan parasiteTheileria parva,remains one of the most important livestock diseases in sub-Saharan Africa with more than 1 million cattle dying from infection every year. Disease prevention relies on the so-called “Infection and Treatment Method” (ITM), which is costly, complex, laborious, difficult to standardise on a commercial scale and results in a parasite strain specific, MHC class I restricted cytotoxic T cell response. We therefore attempted to develop a safe, affordable, stable, orally applicable and potent subunit vaccine for ECF using five differentT. parvaschizont antigens (Tp1, Tp2, Tp9, Tp10 and N36) andSaccharomyces cerevisiaeas an expression platform. Full-length native Tp2 and Tp9 as well as fragments of native Tp1 were successfully expressed on the surface ofS. cerevisiae.In vitroanalyses highlighted that recombinant yeast expressing Tp2 can elicit IFNy responses using PBMCs from ITM-animals, while Tp2 and Tp9 induced IFNy responses from enriched bovine CD8+T cells. A subsequentin vivostudy showed that oral administration of heat-inactivated, freeze-dried yeast stably expressing Tp2 increased total murine serum IgG over time, but more importantly, induce Tp2 specific serum IgG antibodies in individual mice compared to the control group. While these results will require subsequent experiments to verify induction of protection in neonatal calves, our data indicates that oral application of yeast expressing Theileria antigens could provide an affordable and easy vaccination platform for sub-Saharan Africa. Evaluation of antigen specific cellular immune responses, especially cytotoxic CD8+T cell immunity in cows will further contribute to the development of a yeast-based vaccine for ECF.
Lrrcc1 and Ccdc61 are conserved effectors of multiciliated cell function
Authors: Nommick Aude , Boutin Camille , Rosnet Olivier , Bazellières Elsa , Thomé Virginie , Loiseau Etienne , Viallat Annie , Kodjabachian Laurent
Published: January 2021

Ciliated epithelia perform a variety of essential functions across animal evolution, ranging from locomotion of marine organisms to mucociliary clearance of airways in mammals. These epithelia are composed of multiciliated cells (MCCs) harbouring myriads of motile cilia, which rest on modified centrioles called basal bodies (BBs), and beat coordinately to generate directed fluid flows. Thus, BB biogenesis and organization is central to MCC function. In basal eukaryotes, the coiled-coil domain proteins Lrrcc1 and Ccdc61 were shown to be required for proper BB construction and function. Here, we used theXenopusembryonic ciliated epidermis to characterize Lrrcc1 and Ccdc61 in vertebrate MCCs. We found that they both encode BB components, with a prominent association to striated rootlets. Knocking down either gene caused defects in BB docking, spacing, and polarization. Moreover, their depletion impaired the apical cytoskeleton, and altered ciliary beating. Consequently, cilia-powered fluid flow was greatly reduced in morphant tadpoles, which displayed enhanced mortality when exposed to pathogenic bacteria. This work illustrates how integration across organizational scales make elementary BB components essential for the emergence of the physiological function of ciliated epithelia.
ENDORSE: a prognostic model for endocrine therapy response in advanced estrogen-receptor positive breast cancers
Authors: Nath Aritro , Cohen Adam L. , Bild Andrea H.
Published: February 2021

Endocrine therapy remains the primary treatment for advanced and metastatic estrogen receptor-positive (ER+) breast cancers. Patients who progress on endocrine therapy may benefit from add-on treatment targeting the PI3K/MTOR signaling pathways or by switching to chemotherapy. However, these options are only available after progression on first-line treatment with endocrine therapy. In the absence of reliable prognostic tests for advanced ER+ breast cancers, it is currently not possible to stratify patients into pertinent treatment arms at the baseline. To address this, we have developed a low-dimensional endocrine response signature (ENDORSE) model for advanced ER+ breast cancers. The ENDORSE model was developed using the baseline tumor transcriptomes and long-term survival outcomes of >800 invasive ER+ breast cancers and predicts the risk of death on endocrine therapy. ENDORSE was validated in multiple clinical trial datasets for endocrine therapy response in metastatic ER+ breast cancers and demonstrated superior predictive performance over clinical factors and published gene signatures. Our results show that ENDORSE is a reproducible and accurate prognostic model for endocrine therapy response in advanced and metastatic ER+ breast cancers.
A typology of conspicuous donation on Facebook
Authors: Wallace Elaine , Buil Isabel
Published: February 2021

Purpose

This study aims to present a typology of Facebook followers of charities, drawing on theories of value co-creation, impression management and conspicuous donation behavior.

Design/methodology/approach

Data from 234 students based in an Irish University and 296 adults in the USA were subjected to cluster analysis.

Findings

Four segments were identified, common to both samples. Quiet donors are less likely to engage with a charity on Facebook, yet they may donate to the charity. They follow a charity if it offers intrinsic meaning, and they quietly donate money. Facebook expressives mention charities on Facebook to impress others, but have low intention to donate. Following the charity on Facebook is a means to virtue signal, but it helps to spread word of mouth. Friendly donors are active on social media and engage with charities on Facebook when there is personal meaning, and they will donate. Following the charity offers them intrinsic value, and their Facebook mentions promote the charity online. Finally, dirty altruists are motivated by a desire to help, but also to impress others. They will donate, but they will ensure to highlight their good deed on Facebook, to virtue signal.

Originality/value

The study contributes to the literature investigating individuals’ motivations to connect with charities through social media and suggests value co-created by types of charity followers on Facebook.
Regulation of pro‐σK activation: a key checkpoint in Bacillus subtilis sporulation
Authors: Sun Gaohui , Yang Moua , Jiang Longguang , Huang Mingdong
Published: February 2021

The Gram‐positive bacterium Bacillus subtilis initiates the sporulation process under conditions of nutrient limitation. Here, we review related work in this field, focusing on the protein processing of the pro‐σK activation. The purpose of this review is to illustrate the mechanism of pro‐σK activation and provide structural insights into the regulation of spore production. Sporulation is not only important in basic science but also provides mechanistic insight for bacterial control in applications in, e.g., food industry.
Covid‐19 and Football: Crisis Creates Opportunity
Authors: Maguire Kieran
Published: February 2021

This article looks at the financial performance and position of English professional football before Covid‐19 and the impact that the pandemic has had on the industry. It analyses revenue streams in different divisions, the dependency that clubs have on them and how they have changed as a result of the pandemic. The article also reviews key costs for football clubs, the extent to which they can be reduced, different business models that operate, and possible funding sources for the sport from third parties and within the industry.
Food preferences, food neophobia and chemosensation among adolescents with ADHD
Authors: Stankovic Jelena , Hove Thomsen Per , Ovesen Therese
Published: February 2021

Aim

It has been suggested that adolescents diagnosed with ADHD have an unhealthier diet compared to their peers without ADHD. The association between chemosensation (smell and taste) and dietary patterns remains unknown. The aim is to investigate unhealthy food preferences and food neophobic behaviour among adolescents diagnosed with ADHD. Additionally, it is to investigate the relationship between dietary patterns and chemosensory function.

Methods

We enrolled 36 adolescents with and without ADHD to complete a food item and a food neophobia questionnaire and to undergo chemosensory testing.

Results

Adolescents with ADHD performed significantly worse on both chemosensory tests compared to the non‐ADHD group. No difference in food preferences nor food neophobia was found between the two groups.

Conclusion

Adolescents with ADHD have a lower score on chemosensory tests compared to their peers, suggesting impaired chemosensory function. No differences in dietary preferences nor food neophobia were seen between the two groups.
Paediatric ischaemic stroke is a valid diagnosis in the Swedish National Patient Register
Authors: Walås Anna , Svensson Katarina , Gyris Maria , Bang Peter , Sundelin Heléne E. K.
Published: February 2021

Aim

The Swedish National Patient Register offers unique opportunities for epidemiological research of paediatric ischaemic stroke. We aimed to validate the diagnosis of paediatric ischaemic stroke in the National Patient Register to ensure the quality of future research.

Methods

The PedStroke cohort consists of 1606 individuals aged <18 years with a diagnosis of paediatric ischaemic stroke (ICD‐10: I63, I64; ICD‐8 and 9: 433, 434, 436) in Swedish national health registers between 1969 and 2016. We selected 292 cases for validation by reviewing medical charts.

Results

In all, 277 of the 292 medical charts were received, of which 273 had enough information to qualify for review. The diagnosis was correct in 242/273 cases, yielding a positive predictive value (PPV) of 89% (95% confidence interval (CI): 0.85–0.92) for paediatric ischaemic stroke in the National Patient Register. After validation, seven cases of 222 with childhood stroke were re‐categorised to perinatal stroke, resulting in a total of 56 perinatal stroke cases. In the Medical Birth Register, 38 stroke cases were identified of which 37 had correct diagnosis, generating a PPV of 97% (95% CI: 0.92–1.0). Incorrect diagnoses decreased over time and the number of diagnoses confirmed by radiology increased correspondingly.

Conclusion

The National Patient Register is reliable for epidemiological research of paediatric ischaemic stroke because of its high PPV for this diagnosis.
Examining the role of technology‐related policy and constructivist teaching belief on English teachers’ technology acceptance: A study in Chinese universities
Authors: Huang Fang , Teo Timothy
Published: February 2021

This large scale study investigated the influences that technology‐related policies and teachers’ constructivist teaching beliefs have on their intention to use technology in Chinese universities. Data were collected from 696 English teachers working in 59 Chinese universities. Five variables (subjective norm, constructivist teaching belief, perceived importance of policy, computer self‐efficacy and voluntariness) were examined in this study. Results indicated that perceived importance of policy, constructivist teaching beliefs and subjective norm were significant antecedents of perceived usefulness. The relationship between subjective norm and teachers’ intentions to use technology was moderated by voluntariness. Besides perceived usefulness, perceived ease of use also had significantly influenced English teachers’ behavioural intention. Overall, the research model explained 69% of variance of teachers’ intentions to use technology. This study has the potential to enrich our understanding of technology acceptance in teaching by contextualising the study in the rarely researched English teaching context in Chinese universities. The findings from this study also provide suggestions for policy makers and teacher educators.
Redirecting drug repositioning to discover innovative cosmeceuticals
Authors: Sotiropoulou Georgia , Zingkou Eleni , Pampalakis Georgios
Published: February 2021

Skin appearance is essential for self‐esteem and quality of life; consequently, skin care products represent a huge market. In particular, cosmeceuticals constitute a hybrid category of skin care formulations, at the interphase of cosmetics and pharmaceuticals, rationally designed to target (patho) physiological mechanisms aiming to enhance skin health and appearance. Cosmeceuticals are marketed as anti‐ageing, anti‐wrinkle, hair regrowth, skin whitening and wound healing agents with special emphasis on scar‐free healing. An overview on recent cutting‐edge advances concerning the discovery and development of enhanced performance cosmeceuticals by drug repositioning approaches is presented here. In this context, we propose “target repositioning,” a new term, to highlight that druggable protein targets implicated in multiple diseases (hubs in the diseasome) can be exploited to accelerate the discovery of molecularly targeted cosmeceuticals that can promote skin health as an added benefit, which is a novel concept not described before. In this direction, emphasis is placed on the role of mouse models, for often untreatable skin diseases, as well as recent breakthroughs on monogenic rare skin syndromes, in promoting compound repositioning to innovative cosmeceuticals.
Experience with oral tofacitinib in severe alopecia areata with different clinical responses
Authors: Dincer Rota Didem , Emeksiz Mehmet Ali Can , Erdogan Fatma Gulru , Yildirim Dilsun
Published: February 2021

Background

Alopecia areata (AA) and generalized form, universalis (AU) are common causes of noncicatricial alopecia, targeting anagen hair follicles. A dominant interferon‐gamma transcriptional signaling and cytotoxic T lymphocytes were accused as the main drivers of disease pathogenesis. Tofacitinib is a Janus kinase inhibitor that has been proven to interfere with the positive feedback loop between the follicular cell and the cytotoxic T lymphocytes in AA. There is an increasing number of studies reporting success with tofacitinib in AA.

Aims

We aimed to assess oral tofacitinib's safety and efficacy in 13 recalcitrant AA and AU patients.

Methods

This is a retrospective pilot study performed between 2017 and 2020. The demographic features and the treatment responses were evaluated with Severity of Alopecia Tool score changes.

Results

Thirteen recalcitrant alopecia areata patients (3 AA, 10 AU), aged between 17 and 49, were included in the study. The treatment duration was 3‐15 months. All three AA patients responded well; however, the therapy was unsuccessful in five of ten AU patients. Relapse was observed in one of the AA and three of the AU responders. Acneiform lesions and elevation of transaminases were the major side effects.

Conclusion

Tofacitinib seems to be more promising and thriving in the treatment of AA than AU. Starting the therapy earlier can bring more successful results. Unfortunately, even in the cases that fully respond to treatment, relapse can be observed after discontinuation of the treatment. It is essential to inform patients about this situation in reducing the frustrations that may occur later.
Determinants of caregiving burden among informal caregivers of adult care recipients with chronic illness
Authors: Rodríguez‐González Ana‐María , Rodríguez‐Míguez Eva , Claveria Ana
Published: February 2021

Aims and Objectives

This study examined the predictors of caregiver burden based on patient and caregiver characteristics in a sample of Spanish caregivers looking after adult patients with chronic disease. The effect of task type and patient–caregiver interaction is also analysed.

Background

Specific predictors of caregiver burden have been widely examined in the literature. Few studies, however, jointly analyse a wide range of factors, including the effect of task type and patient–caregiver interaction.

Design

Correlational study.

Methods

One hundred and thirty five informal caregivers for 148 care recipients were recruited from primary health care centres. The caregivers responded to the short version of the Zarit Burden Interview (ZBI), the DEPendency index‐6 Dimensions (DEP‐6D), and reported how long they spent on caregiving on a daily basis. Sociodemographic and health characteristics were also recorded. Linear and logistic regression models were used to evaluate factors associated with ZBI scores and the likelihood of being severely burdened, respectively. This research complies with STROBE guidelines for observational studies.

Results

Severe burden was present in 62% of the caregivers. Regression analysis shows that burden severity increases significantly with the level of dependence when the latter is measured either by DEP‐6D or by time spent on basic activities. Care related to incontinence and mobility has the greatest effect on burden, which is aggravated when the patient has behavioural problems. Poor caregiver health or not being retired also contributes to burden levels.

Conclusions

These results establish that caregiver burden is related to characteristics of both the caregiver and the care recipient as well as to their interaction.

Relevance to clinical practice

The findings indicate that the socio‐sanitary attention focused on reducing caregiver burden must address the caregiver and patient as a dyad. Identifying the dependence level and the patient's aggressive behaviour can be a good predictor of caregiver burden.
Mortality is not increased in SARS‐CoV‐2 infected persons with hepatitis C virus infection
Authors: Butt Adeel A. , Yan Peng , Chotani Rashid A. , Shaikh Obaid S.
Published: February 2021

Background

Impact of SARS‐CoV‐2 infection upon hospitalization, intensive care unit (ICU) admissions and mortality in persons with hepatitis C virus (HCV) infection is unknown.

Methods

We used the Electronically Retrieved Cohort of HCV infected Veterans (ERCHIVES) database to determine the impact of HCV infection upon the rates of acute care hospitalization, ICU admission and all‐cause mortality. We identified Veterans with chronic HCV infection and propensity score matched controls without HCV in ERCHIVES. We excluded those with HIV or hepatitis B virus coinfection.

Results

We identified 975 HCV+ and 975 propensity score matched HCV− persons with SARS‐CoV‐2 infection. Mean FIB‐4 score (±SD) was higher in those with HCV (1.9 ± 2.1 vs 1.2 ± 0.9; P < .0001) and a larger proportion of those with HCV had cirrhosis (8.1% vs 1.4%; P < .0001). A larger proportion of HCV+ were hospitalized compared to HCV‐ (24.0% vs 18.3%; P = .002); however, those requiring ICU care and mortality were also similar in both groups (6.6% vs 6.5%; P = .9). Among those with FIB‐4 score of 1.45‐3.25, hospitalization rate/1000‐person‐years was 41.4 among HCV+ and 20.2 among HCV−, while among those with a FIB‐4 > 3.25, the rate‐ was 9.4 and 0.6 (P < .0001). There was no difference in all‐cause mortality by age, gender, FIB‐4 score, number of comorbidities or treatment with remdesivir and/or systemic corticosteroids.

Conclusions

HCV+ persons with SARS‐CoV‐2 infection are more likely to be admitted to a hospital. The hospitalization rate also increased with higher FIB‐4 score. However, admission to an ICU and mortality are not different between those with and without HCV infection.
Is Investment in Data Analytics Always Profitable? The Case of Third‐Party‐Online‐Promotion Marketplace
Authors: Zhang Zhe (James) , Shivendu Shivendu , Wang Peng
Published: February 2021

Studies show that merchants are heterogeneous in profitability from offering promotions on third‐party‐online‐promotion marketplaces who often charge a single commission rate. Using a data analytics system, a marketplace can classify merchants according to their heterogeneous characteristics and offer merchant‐type specific commission rates. In this study, we construct a game‐theoretic model consisting a marketplace with two types of merchants who have heterogeneous proportion of consumers who are informed about their offering. The types are merchants’ private information, but the marketplace can invest in data analytics capability to classify merchants as per their types with a probability. We study a signal‐based strategy, where the marketplace invests in data analytics capability and offers a specific commission rate to individual merchant based on the merchant‐type classification and compare it with a single‐rate strategy of offering one commission rate to all merchants. We show that the relative strength and weakness of the signal‐based strategy depend on the merchant type distribution and the investment cost of improving the classification accuracy rate. Interestingly, the marketplace can be better off with the single‐rate strategy when a merchant type dominates the market. Moreover, we show that the signal‐based strategy, can lead to an increase in profit for merchants and an increase in consumer surplus. This is so because the marketplace’s signal‐based strategy has a cascade effect on consumers through the merchant’s optimal discount rate strategy. We conclude by identifying the conditions for a win–win–win situation wherein investment in data analytics capabilities by the marketplace also benefits merchants and consumers.
Optimal control of COVID-19
Authors: Moussouni Nacima , Aliane Mohamed
Published: January 2021

Coronavirus disease of 2019 or COVID-19 (acronym for coronavirus disease 2019) is an emerging infectious disease caused by a strain of coronavirus called SARS-CoV-22, contagious with human-to-human transmission via respiratory droplets or by touching contaminated surfaces then touching them face. Faced with what the world lives, to define this problem, we have modeled it as an optimal control problem based on the models of William Ogilvy Kermack et Anderson Gray McKendrick, called SEIR model, modified by adding compartments suitable for our study. Our objective in this work is to maximize the number of recovered people while minimizing the number of infected. We solved the problem theoretically using the Pontryagin maximum principle, numerically we used and compared results of two methods namely the indirect method (shooting method) and the Euler discretization method, implemented in MATLAB.
Effects of Thickness and Winding Angle of Reinforcement Laminates on Burst Pressure Capacity of Thermoplastic Composite Pipes
Authors: Xia H. , Shi C. , Wang J. , Bao X. , Li H. , Fu G.
Published: February 2021

The cross section of thermoplastic composite pipes (TCPs) consists of three layers: an inner liner, reinforcement laminates, and an outer jacket; the three layers are fully bonded together to form a solid-walled structure. In this study, the mechanical behaviors of TCPs under internal pressures were investigated using analytical and finite element analysis (FEA) methods. The analytical method that is based on the three-dimensional (3D) anisotropy elastic theory takes into account the nonuniform distribution of stresses and strains through the wall thickness of the pipe. FEA models were setup using the software abaqus to predict the stress distribution of a TCP. The 3D Tsai-Wu failure criterion was used to predict the maximum burst pressure of TCPs. Effects of winding angles and the number of reinforcement plies on the burst pressure of TCPs were studied. Results derived from the analytical method and the FEA method verified each other, which show that the burst pressure of a TCP increases asymptotically as the number of reinforcement plies increases. The optimal winding angle associated with the maximum burst pressure is not a constant value, instead, it varies as the thickness of the laminate layer increases. This study provides useful tools and guidance for the design and analysis of TCPs, while further validation experiments are still needed.
Basophils getting on your nerves? Itching for clarity on flares in atopic dermatitis
Authors: Henrickson Sarah E.
Published: February 2021

Flares of acute itch in the setting of atopic dermatitis may engage a novel neuroimmune axis that includes basophils, LTC4, and sensory neurons.
Intramuscular myxoma of the longus colli mistaken for a cervical rootlet schwannoma
Authors: Mijalis Eleni Marie , Manzi Brian , Cuellar Hugo , Nathan Cherie Ann O
Published: February 2021

An 86-year-old woman was referred to the otolaryngology clinic for a 1-year history of a painless, slow-growing neck mass. Physical examination showed a fixed, immobile right level II neck mass with normal vocal cord movement. MRI demonstrated a lobulated mass laterally displacing the carotid vessels, consistent with a schwannoma. Despite the pathognomonic radiographic findings for schwannoma, core needle biopsy of the mass was consistent with intramuscular myxoma (IM), which rarely presents in the head and neck region. After multiple years of slow growth with bulging into the pharynx, the patient ultimately underwent surgery to reduce the risk of airway compromise. The location of this IM together with its unusual imaging appearance is a unique finding in the head and neck and adds to the differential diagnoses for neck masses displacing the carotid sheath.
Allogeneic simple limbal epithelial transplantation: an appropriate treatment for bilateral stem cell deficiency
Authors: Kaur Amanjot , Jamil Zeeshan , Priyadarshini Smruti Rekha
Published: February 2021

A 39-year-old man presented with both eyes limbal stem cell deficiency status post chemical injury. He was managed initially with topical medications to subside the ocular surface inflammation. Over the course of subsequent visits, the fibrovascular pannus over the cornea gradually progressed, leading to further diminution of vision in left eye more than right eye. Since, the ocular surface was wet, the patient committed for lifelong immunosuppression and his brother consented to donate healthy limbal tissue; he underwent living-related allogeneic simple limbal epithelial transplantation in the left eye.
Concomitant nephrotic syndrome and tubulointerstitial nephritis in a child with Epstein-Barr virus mononucleosis
Authors: Acharya Ratna , Zeng Xu , Upadhyay Kiran
Published: February 2021

Acute kidney injury (AKI) and nephrotic syndrome (NS) are uncommon manifestations of Epstein-Barr virus (EBV) mononucleosis. We report a 4-year-old boy with Infectious mononucleosis (IM) who presented with dialysis-requiring AKI and NS. Renal biopsy showed severe acute tubular necrosis, mild chronic interstitial nephritis and focal podocyte foot processes effacement. EBV early RNA was not detected in the renal tissue. However, immunophenotyping of peripheral lymphocytes showed increased cytotoxic T cell activity and increased memory B cells. Treatment with steroid led to rapid resolution of NS within 3 weeks. Renal function stabilised. EBV viral capsid antigen (VCA) IgM remained elevated until 4 months before starting to decline when VCA IgG and nuclear antigen started appearing. B lymphocytes are the predominant target cells in EBV infection and additionally may also act as antigen presenting cells to T lymphocytes, thereby eliciting the strong immune response and leading to podocyte and tubulointerstitial injury.
A rare emergence of resistance to ceftolozane/tazobactam inKlebsiella pneumoniaecausing urinary tract infection
Authors: Arumairaj Antony , Agarwal Sanket , Popli Tarun , Lopez Eliana
Published: February 2021

The management of infections caused by carbapenem-resistant organisms has been a challenge. We report a rare emergence of resistance to the novel beta-lactam/ beta-lactamase combination ceftolozane/tazobactam byKlebsiella pneumoniae, causing urinary tract infection. TheK. pneumoniae, in this case, was reported to be sensitive to the other novel beta-lactam/ beta-lactamase combination of ceftazidime/avibactam. The timely administration of ceftazidime/avibactam resulted in prompt clinical resolution of the urinary tract infection caused by an extensively drug-resistantK. pneumoniae.
Late diagnosis of metastatic pheochromocytoma in multiple endocrine neoplasia 2B with rapid clinical decline
Authors: Jester Grant , Hassanein Hatem , El-Far Ahmad
Published: February 2021

Multiple endocrine neoplasia type 2B (MEN2B) is the rarest and most aggressive of the MEN syndromes. It is characterised by medullary thyroid cancer (MTC), pheochromocytoma, marfanoid body habitus, mucosal neuromas and colonic dysfunction. Patients typically present with chronic constipation and MTC in early childhood. We discuss an atypical late presentation of MEN2B in a 19-year-old man with chronic constipation since childhood admitted with acute spinal cord compression. He underwent emergent neurosurgical intervention followed by postoperative radiotherapy. Bone biopsy revealed metastatic pheochromocytoma. Thyroid nodule biopsy showed MTC. MIBG scan confirmed pheochromocytoma as the dominant malignancy. Germline testing revealed a RET mutation (p.M918T). He received one cycle of cyclophosphamide, vincristine and dacarbazine and subsequently developed a pathological right femur fracture requiring repair. Postoperative course was complicated by hypoxic respiratory failure requiring intubation. Imaging showed lymphangitic spread of disease in the lungs. He unfortunately did not respond to a short trial of sunitinib and transitioned to comfort care.
Congenital syphilis in a 4-month-old infant with limb weakness
Authors: Morrisroe Elizabeth , Farzana Syeda Farah , McKinnon James
Published: February 2021

We describe a rare case of a 4-month-old girl presenting with a several month history of reduced movement to the left arm accompanied by a maculopapular rash to the limbs. X-ray findings included inflammatory periosteal changes to the radius and ulna.Treponema pallidumIgM was detected in both baby and mother, and a diagnosis of congenital syphilis was made. This case is an interesting clinical picture with a variety of important differential diagnoses, including non-accidental injury, malignancy, autoimmune disease and other congenital infections. With an increasing rate of congenital syphilis infection in the developed world, it is vital that clinicians are able to recognise symptoms to ensure prompt diagnosis and treatment. In this respect, we can attempt to avoid the chronic and potentially life-threatening complications of untreated infection.
Recommendations for improving follow-up care for patients with mesothelioma: a qualitative study comprising documentary analysis, interviews and consultation meetings
Authors: Henshall Catherine , Davey Zoe , Walthall Helen , Ball Hannah , Shahidi Mitra , Park John , Rahman Najib
Published: January 2021

Objectives

The study aim was to explore experiences of patients with pleural mesothelioma of follow-up care in three National Health Service (NHS) Trusts to develop recommendations for practice.

Design

The study design was qualitative and comprised three interlinked phases: a documentary analysis, interviews and consultation meetings. Altheide and Johnson’s Analytic Realism theoretical framework guided the thematic data analysis process.

Setting

The study was conducted in three NHS Trusts in South England. Two were secondary care settings and the third was a tertiary centre.

Participants

The secondary care trusts saw 15–20 patients with new mesothelioma per year and the tertiary centre 30–40. The tertiary centre had a designated mesothelioma team. Twenty-one patients met the inclusion criteria: >18 years, mesothelioma diagnosis and in follow-up care. Non-English speaking participants, those unable to provide written informed consent or those whom the clinical team felt would find participation too distressing were excluded. All participants were white, 71% were 70–79 years old and 71% were men. Three consultation meetings were conducted with key stakeholders including mesothelioma nurse specialists, patients with mesothelioma, carers and local clinical commissioning group members.

Main outcome measures

Specific outcomes were to gain a detailed understanding of mesothelioma follow-up care pathways and processes and to develop coproduced recommendations for practice.

Results

Mesothelioma pathways were not always distinct from lung cancer care pathways. All trusts provided follow-up information and resources but there was varied information on how to access local support groups, research or clinical trial participation. Five themes were developed relating to people; processes; places; purpose and perception of care. Coproduced recommendations for improving mesothelioma follow-up pathways were developed following the consultation meetings.

Conclusions

This study has developed recommendations which identify the need for patients with pleural mesothelioma to access consistent, specialist, streamlined mesothelioma care, centred around specialist mesothelioma nurses and respiratory consultants, with input from the wider multidisciplinary team.
Scoping review protocol: bladder cancer in Nigeria: what are the gaps in clinical care and research?
Authors: Kibaru Joyce , Kotecha Pinky , Iya Abdulkarim Muhammad , Russell Beth , Abdullahi Muzzammil , Alhassan Sani Usman , Mustapha Muhammad Inuwa , Bryan Richard T , Van Hemelrijck Mieke
Published: January 2021

Introduction

Bladder cancer (BC) is the 10th common cancer worldwide and ranks seventh in Nigeria. This scoping review aims to identify the gaps in clinical care and research of BC in Nigeria as part of the development of a larger national research programme aiming to improve outcomes and care of BC.

Methods and analysis

This review will be conducted according to Arksey and O’Malley scoping review methodology framework. The following electronic databases will be searched: Medline (using the PubMed interface), Ovid Gateway (Embase and Ovid), Cochrane library and Open Grey literature. Two independent reviewers will screen titles and abstracts and subsequently screen full-text studies for inclusion, any lack of consensus will be discussed with a third reviewer. Any study providing insight into the epidemiology or treatment pathway of BC (RCTs, observations, case series, policy paper) will be included. A data chart will be used to extract relevant data from the included studies. Results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. A consultation process will be carried out with a multidisciplinary team of Nigerian healthcare professionals, patients and scientists.

Ethics and dissemination

The results will be disseminated through peer-reviewed publications. By highlighting the key gaps in the literature, this review can provide direction for future research and clinical guidelines in Nigeria (and other low-income and middle-income countries), where BC is more prevalent due to local risk factors and healthcare settings.
Sex differences in vectorcardiogram of African-Americans with and without cardiovascular disease: a cross-sectional study in the Jackson Heart Study cohort
Authors: Pollard James D , Haq Kazi T , Lutz Katherine J , Rogovoy Nichole M , Paternostro Kevin A , Soliman Elsayed Z , Maher Joseph , Lima Joao AC , Musani Solomon , Tereshchenko Larisa G
Published: January 2021

Objectives

We hypothesised that (1) the prevalent cardiovascular disease (CVD) is associated with global electrical heterogeneity (GEH) after adjustment for demographic, anthropometric, socioeconomic and traditional cardiovascular risk factors, (2) there are sex differences in GEH and (3) sex modifies an association of prevalent CVD with GEH.

Design

Cross-sectional, cohort study.

Setting

Prospective African-American The Jackson Heart Study (JHS) with a nested family cohort in 2000–2004 enrolled residents of the Jackson, Mississippi metropolitan area.

Participants

Participants from the JHS with analysable ECGs recorded in 2009–2013 (n=3679; 62±12 y; 36% men; 863 family units). QRS, T and spatial ventricular gradient (SVG) vectors’ magnitude and direction, spatial QRS-T angle and sum absolute QRST integral (SAI QRST) were measured.

Outcome

Prevalent CVD was defined as the history of (1) coronary heart disease defined as diagnosed/silent myocardial infarction, or (2) revascularisation procedure defined as prior coronary/peripheral arterial revascularisation, or (3) carotid angioplasty/carotid endarterectomy, or (4) stroke.

Results

In adjusted mixed linear models, women had a smaller spatial QRS-T angle (−12.2 (95% CI −19.4 to -5.1)°; p=0.001) and SAI QRST (−29.8 (−39.3 to −20.3) mV*ms; p<0.0001) than men, but larger SVG azimuth (+16.2(10.5–21.9)°; p<0.0001), with a significant random effect between families (+20.8 (8.2–33.5)°; p=0.001). SAI QRST was larger in women with CVD as compared with CVD-free women or men (+15.1 (3.8–26.4) mV*ms; p=0.009). Men with CVD had a smaller T area (by 5.1 (95% CI 1.2 to 9.0) mV*ms) and T peak magnitude (by 44 (95%CI 16 to 71) µV) than CVD-free men. T vectors pointed more posteriorly in women as compared with men (peak T azimuth + 17.2(8.9–25.6)°; p<0.0001), with larger sex differences in T azimuth in some families by +26.3(7.4–45.3)°; p=0.006.

Conclusions

There are sex differences in the electrical signature of CVD in African-American men and women. There is a significant effect of unmeasured genetic and environmental factors on cardiac repolarisation.