bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacometric assessment of the in vivo antiviral activity of ivermectin in early symptomatic COVID-19
Authors: Schilling William HK , Jittamala Podjanee , Watson James A , Ekkapongpisit Maneerat , Siripoon Tanaya , Ngamprasertchai Thundon , Luvira Viravarn , Pongwilai Sasithon , Cruz Cintia , Callery James J , Boyd Simon , Kruabkontho Varaporn , Ngernseng Thatsanun , Tubprasert Jaruwan , Abdad Mohammad Yazid , Piaraksa Nattaporn , Suwannasin Kanokon , Hanboonkunupakarn Pongtorn , Hanboonkunupakarn Borimas , Sookprome Sakol , Poovorawan Kittiyod , Thaipadungpanit Janjira , Blacksell Stuart , Imwong Mallika , Tarning Joel , Taylor Walter RJ , Chotivanich Vasin , Sangketchon Chunlanee , Ruksakul Wiroj , Chotivanich Kesinee , Teixeira Mauro M , Pukrittayakamee Sasithon , Dondorp Arjen M , Day Nicholas PJ , Piyaphanee Watcharapong , Phumratanaprapin Weerapong , White Nicholas J
Published: July 2022

Background

There is no generally accepted methodology for in vivo assessment of antiviral activity in SARS-CoV-2 infection. Ivermectin has been recommended widely as a treatment of COVID-19, but whether it has significant antiviral activity in vivo is uncertain.

Methods

In a multicentre open label, randomized, controlled adaptive platform trial, adult patients with early symptomatic COVID-19 were randomized to one of six treatment arms including high dose ivermectin (600µg/kg daily for seven days), the monoclonal antibodies casirivimab and imdevimab (600mg/600mg), and no study drug. Viral clearance rates were derived from daily duplicate oropharyngeal quantitative PCR measurements. This ongoing trial is registered at ClinicalTrials.gov (NCT05041907).

Results

Randomization to the ivermectin arm was stopped after enrolling 205 patients into all arms, as the prespecified futility threshold was reached. Compared with the no study drug arm, the mean estimated SARS-CoV-2 viral clearance following ivermectin was 9.1% slower [95%CI -27.2% to +11.8%; n=45 versus n=41], whereas in a preliminary analysis of the casirivimab/imdevimab arm it was 52.3% faster [95%CI +7.0% to +115.1%; n=10 (Delta variant) versus n=41].

Conclusions

High dose ivermectin did not have measurable antiviral activity in early symptomatic COVID-19. Measured in this way viral clearance rate is a valuable pharmacodynamic measure in assessing antiviral COVID-19 therapeutics in vivo.

Funding

“Finding treatments for COVID-19: A phase 2 multi-centre adaptive platform trial to assess antiviral pharmacodynamics in early symptomatic COVID-19 (PLAT-COV)” is funded by the Wellcome Therapeutics Accelerator (223195/Z/21/Z).

Impact

Rate of viral clearance determined from daily duplicate oropharyngeal swabs over one week is an efficient measure of antiviral efficacy in early COVID-19 infection.

High dose ivermectin did not demonstrate measurable antiviral activity in early symptomatic COVID-19 infection.
Factors influencing adoption of oral health promotion by antenatal care providers in Moyo district, North-Western Uganda
Authors: Lulu Patrick Madrama , Nanyingi Miisa
Published: July 2022

Background

Oral health promotion(OHP) during pregnancy is an important global public health and basic human right issue related to quality of life. Several statements and guidelines have been published emphasizing the need for improved oral health care of pregnant mothers, prenatal care providers have missed this critical opportunity. In this study, we assessed factors influencing adoption of oral health promotion by Antenatal care providers.

Materials and Methods

A descriptive cross-sectional study design that employed both quantitative and qualitative data collection methods and analysis. 152 samples determined using Yamane’s 1967 and stratified sampling technique was used. Three FGDs and six KI interviews were held. Univariate, bivariate and multivariate analyses were done using SPSS (20.0) and ATLAS Ti for qualitative analysis.

Results

Adoption of OHP was low 28% (42). Factors influencing adoption were age of respondents(p=0.032*), level of care of health facility (p=0.004*), good understanding between dentists and ANC providers (aOR=0.283, 95%CI=0.084-0.958, p= 0.042*), availability of practice guideline for OHP in ANC (aOR=0.323, 95%CI=0.108-0.958, p= 0.043*), number of years at work (p=0.084), being knowledgeable (aOR=2.143, 95%CI=0.864-5.311, p= 0.100), having skills to advance OHP(aOR=0.734, 95%CI=0.272-1.984, p= 0.542), Management being good at influencing new practices (aOR=00.477.734, 95%CI=0.227-2.000, p= 0.477). More emphasis on national and local of oral health issues, continuous staff training on oral health, dissemination of National oral health policy (NOHP) were some of key issues that emerged from the qualitative results.

Conclusion

Adoption of OHP was low. This was attributed to age, number of years spent at work, level of health facility, having good understanding between dentists and ANC providers, availability of practice guidelines, dissemination of National oral health policy, continuous staff training. We recommend the current NOHP to be reviewed, develop prenatal OHC guidelines, enhance the capacity of ANC providers through training, collaboration with dentists and launch official adoption of OHP.
Impact of SARS-Cov-2 on Clinical Trial Unit Staff: The EPIC Observational Study
Authors: Phiri Peter , Yardley Lucy , Elliot Kathryn , Barnard-Kelly Katharine , Raymont Vanessa , Rathod Shanaya , Hu Jintong , Cavalini Heitor , Shi Jian Qing , Delanerolle Gayathri
Published: July 2022

Introduction

Clinical Trials Units (CTUs) are a key component of delivering non-commercial and commercial clinical research globally. Within the UK, CTUs are seen as a specialist and independent entity available to all researchers requiring support to setup, conduct and deliver clinical trials. Therefore, an involvement of a CTU is highly recommended by national regulators and positively accepted by funders, especially for drug and/or medical device and/or complex intervention trials.

Aim

This study aims to determine the challenges associated with the management of Covid-19 research managed via the CTU workforce, including the challenges associated with quality assurance, trial setup and data management. Additionally, this study will explore the by-stander effect on trial staff by way of evaluating the mental and physical health impact.

Methods/ Design

This is a mixed methods study. An online novel questionnaire survey study will be conducted among the UK CTU workforce. Quantitative data will be collected using the Qualtrics XM platform. We aim to recruit up to 1,500 CTU staff across the UK workforce. A subgroup sample will be randomly invited to take part in semi-structured interviews. Therefore, this survey will generate both quantitative and qualitative data inclusive of demographic data.

Results

The findings will inform current initiatives and identify key themes for prioritising in further research to develop robust approaches to support CTU staff, including the development of a start-re-start framework for CTUs for any future pandemics relevant to developing and delivering communicable diseases and non-communicable diseases-based research.

Strengths/Limitations

The validation of the EPIC impact questionnaire used qualitative and quantitative methods which is a strength of the study. However, the study has a single timepoint to obtain data with the secondary outcome measures to be completed at two timepoints as this is an exploratory study attempting to obtain a wider data pool.
Th1 cells alter the inflammatory signature of IL-6 by channeling STAT transcription factors toAlu-like retroelements
Authors: Millrine David , Figueras Ana Cardus , Fernandez Javier Uceda , Andrews Robert , Szomolay Barbara , Cossins Benjamin C , Rice Christopher M. , Li Jasmine , Tyrrell Victoria J , McLeod Louise , Holmans Peter , O’Donnell Valerie B , Taylor Philip R , Turner Stephen J. , Jenkins Brendan J. , Jones Gareth W , Topley Nicholas , Williams Nigel M , Jones Simon A
Published: July 2022

Cytokines that signal via STAT1 and STAT3 transcription factors instruct decisions affecting tissue homeostasis, anti-microbial host defense, and inflammation-induced tissue injury. To understand the coordination of these activities, we applied RNA-seq, ChIP-seq, and ATAC-seq to identify the transcriptional output of STAT1 and STAT3 in peritoneal tissues during acute resolving inflammation and inflammation primed to drive fibrosis. Bioinformatics focussed on the transcriptional signature of the immuno-modulatory cytokine IL-6 in both settings and examined how pro-fibrotic IFNγ-secreting CD4+T-cells altered the interpretation of STAT1 and STAT3 cytokine cues. In resolving inflammation, STAT1 and STAT3 cooperated to drive stromal gene expression affecting anti-microbial immunity and tissue homeostasis. The introduction of IFNγ-secreting CD4+T-cells altered this transcriptional program and channeled STAT1 and STAT3 to a previously latent GAS motif inAlu-like elements. STAT1 and STAT3 binding to this conserved sequence revealed evidence of reciprocal cross-regulation and gene signatures relevant to pathophysiology. Thus, we propose that effector T-cells re-tune the transcriptional output of IL-6 by shaping a regulatory interplay between STAT1 and STAT3 in inflammation.
Identification of a Papain-Like Protease Inhibitor with Potential for Repurposing in Combination with an Mpro Protease Inhibitor for Treatment of SARS-CoV-2
Authors: Campagna Jesus , Jagodzinska Barbara , Alvarez Pablo , Yeun Constance , Spilman Patricia , Enquist Kathryn M. , Cohn Whitaker , Fajtová Pavla , O’Donoghue Anthony J. , Arumugaswami Vaithilingaraja , Li Melody M.H. , Damoiseaux Robert , John Varghese
Published: July 2022

SARS-CoV-2 requires two cysteine proteases for viral polypeptide processing to allow maturation and replication: the 3C-like protease also known as the Main protease (Mpro) and the papain-like protease (PLpro). In addition to its critical role in viral replication, PLpro removes post-translational modifications like ubiquitin and interferon-stimulated gene product 15 (ISG15) from host proteins through its deubiquitinase domain, leading to host immunosuppression and increased ability of the virus to evade the host antiviral immune response. Through screening of a custom clinical compound library, we identified eltrombopag (DDL-701), a thrombopoietin receptor agonist, as having PLpro inhibitory activity that is sustained in the presence of the Mpro inhibitor nirmatrelvir. DDL-701 also suppressed both the deubiquitinase and ISG15 cleavage activities of PLpro. In addition, DDL-701 partially restored interferon-β induction – an element of the host immune response - in an in vitro model system. Further, modeling and docking studies suggest DDL-701 interacts with the active site region of the PLpro enzyme and pilot pharmacokinetic studies indicate it is brain permeable. DDL-701 is already approved for treatment of thrombocytopenia and has previously been shown to achieve human plasma levels after oral dosing that is above the IC50 needed for it to exert its PLpro inhibitory activity in vivo. In addition, it has also been reported to have antiviral efficacy against SARS-CoV-2. DDL-701 thus represents a drug that can immediately be repurposed and undergo clinical evaluation as a PLpro inhibitor that may be most effectively used in a protease inhibitor cocktail with an Mpro inhibitor such as nirmatrelvir (Paxlovid) for the treatment of COVID-19.
Replidec - Use naive Bayes classifier to identify virus lifecycle from metagenomics data
Authors: Peng Xue , Ru Jinlong , Mirzaei Mohammadali Khan , Deng Li
Published: July 2022

Motivation

Viruses are the most abundant biological entities on earth. The majority of these entities are bacterial viruses or phages which specifically infect bacteria. Phages can use different replication strategies to invade their hosts including lytic, lysogenic, chronic cycle and pseudolysogeny. While the determination of the replication strategy used by phages is important to explore the phage-bacteria relationships in different ecosystems there are not many tools that can predict this in metagenomic data. In addition, most of the tools available can only predict lytic and lysogenic cycles. To address this issue, we have developed a new software called Replidec to identify three most common phage replication cycles (virulent, temperate, chronic) in viral sequences.

Results

Replidec uses Naive Bayes classifier combined with alignment-based methods to improve the prediction accuracy in metagenomic data. We test Replidec on viral genomes with known replication cycle and simulated metagenomic sequences. Replidec perform relatively good both in isolated genomes (F1 score: 92.29% ± 0.81; mcc: 89.14% ± 1.22) and simulated metagenomic sequences(F1 score: 87.55% ± 2.12; mcc: 88.23% ± 2.55). Moreover, Replidec can also accurately predict the replication cycle in small viral fragments(∼3000bp). In conclusion, Replidec can achieve the best performance in simulated metagenomic data compared to most prediction softwares including BACPHLIP.
Dynamic acylome reveals metabolite driven modifications in Syntrophomonas wolfei
Authors: Fu Janine Y. , Muroski John M. , Arbing Mark A. , Salguero Jessica A. , Wofford Neil Q. , McInerney Michael J. , Gunsalus Robert P. , Loo Joseph A. , Loo Rachel R. Ogorzalek
Published: July 2022

Syntrophomonas wolfei is an anaerobic syntrophic microbe that degrades short-chain fatty acids to acetate, hydrogen, and/or formate. This thermodynamically unfavorable process proceeds through a series of reactive acyl-Coenzyme A species (RACS). In other prokaryotic and eukaryotic systems, the production of intrinsically reactive metabolites correlates with acyl-lysine modifications, which have been shown to play a significant role in metabolic processes. Analogous studies with syntrophic bacteria, however, are relatively unexplored and we hypothesize that highly abundant acylations could exist in S. wolfei proteins, corresponding to the RACS derived from degrading fatty acids. Here, by mass spectrometry-based proteomics (LC-MS/MS), we characterize and compare acylome profiles of two S. wolfei subspecies grown on different carbon substrates. Because modified S. wolfei proteins are sufficiently abundant for post-translational modification (PTM) analyses without antibody enrichment, we could identify types of acylations comprehensively, observing six types (acetyl-, butyryl-, 3-hydroxybutyryl-, crotonyl-, valeryl-, hexanyl-lysine), two of which have not been reported in any system previously. All of the acyl-PTMs identified correspond directly to RACS in fatty acid degradation pathways. A total of 369 sites of modification were identified on 237 proteins. Changing the carbon substrate altered the acylation profile. Moreover, structural studies and in vitro acylation assays of a heavily modified enzyme, acetyl-CoA transferase, provided insight on the possible impact of these acyl-protein modifications. Our findings link protein acylation by RACS to shifts in cellular metabolism.
A methodological framework to assess temporal trends and sub-national disparities in healthcare quality metrics using facility surveys, with applications to sick-child care in Kenya, Senegal, and Tanzania
Authors: Allorant Adrien , Fullman Nancy , Leslie Hannah H. , Sarr Moussa , Gueye Daouda Malick , Eliakimu Eliudi , Wakefield Jonathan , Dieleman Joseph L. , Pigott David , Puttkammer Nancy , Reiner Robert C.
Published: July 2022

Monitoring healthcare quality at a subnational resolution is key to identify and resolve geographic inequities and ensure that no sub-population is left behind. Yet, health facility surveys are typically not powered to report reliable estimates at a subnational scale.

In this study, we present a framework to fill this gap and jointly analyse publicly available facility survey data, allowing exploration of temporal trends and subnational disparities in healthcare quality metrics. Specifically, our Bayesian hierarchical model includes random effects to account for differences between survey instruments; space-time processes to leverage correlations in space and time; and covariates to incorporate auxiliary information. We apply this framework to Kenya, Senegal, and Tanzania - three countries with at least four rounds of standardized facility surveys each – and estimate the readiness and process quality of sick-child care over time and across subnational areas.

These estimates of readiness and process quality of care over time and at a fine spatial resolution show uneven progress in improving facility-based service provision in Kenya, Senegal, and Tanzania. For instance, while national gains in overall readiness of care improved in Tanzania, geographic inequities persisted; in contrast, Senegal, and Kenya experienced stagnation in overall readiness at the national level, but disparities grew across subnational areas. Overall, providers adhered to about one-third of the clinical guidelines for managing sick-child illnesses at the national level. Yet across subnational units, such adherence greatly varied (e.g., 25% to 85% between counties of Kenya in 2020).

Our new approach enables identifies precise estimation of changes in the spatial distribution of healthcare quality metrics over time, at a a programmatic spatial resolution, and with accompanying uncertainty estimates. Use of our framework will provide new insights at a policy-relevant spatial resolution for national and regional decision-makers, and international funders.
An iterative gene editing strategy broadens eIF4E1 genetic diversity in Solanum lycopersicum and generates resistance to several potyvirus isolates
Authors: Kuroiwa Kyoka , Danilo Benoit , Perrot Laura , Thenault Christina , Veillet Florian , Delacote Fabien , Duchateau Philippe , Nogué Fabien , Mazier Marianne , Gallois Jean-Luc
Published: July 2022

Resistance to potyviruses in plants have been largely provided by the selection of natural variant alleles of eukaryotic initiation factors (eIF) 4E in many crops. However, the sources of such variability for breeding can be limited for certain crop species, while new virus strains continue to emerge. Different methods of mutagenesis have been applied to inactivate the eIF4E genes to generate virus resistance, but with limited success due to the physiological importance of translation factors and their redundancy. Here, we employed genome editing approaches at the base level to induce non-synonymous mutations in the eIF4E1 gene and create genetic diversity in cherry tomato (Solanum lycopersicum var. cerasiforme). We sequentially edited the genomic sequences coding for two regions of eIF4E1 protein, located around the cap-binding pocket and known to be important for susceptibility to potyviruses. We show that the editing of only one of the two regions, by gene knock-in and base-editing, respectively, is not sufficient to provide resistance. However, combining amino acid mutations in both regions resulted in resistance to multiple potyviruses without affecting its functionality in translation initiation. Meanwhile, we report that extensive base editing in exonic region can alter RNA splicing pattern, resulting in gene knockout. Altogether our work demonstrates that precision editing allows to design plant factors based on the knowledge on evolutionarily selected alleles and enlarge the gene pool to potentially provide advantageous phenotypes such as pathogen resistance.
Experimental study of the boosters impact on the rocket aerodynamic characteristics
Authors: Krzysiak Andrzej , Cieśliński Dawid , Placek Robert , Kekus Pawel
Published: July 2022

Purpose

The purpose of this study is to determine the impact of two parallel boosters fixed to the ILR 33 AMBER 2 K core rocket stage on its aerodynamic characteristics in the subsonic and transonic regimes and for M = 2.3.

Design/methodology/approach

Wind tunnel tests of the rocket model were carried out in a trisonic wind tunnel using a six-component internal balance. Three rocket model configurations were investigated.

Findings

The results of the presented studies showed that the presence of boosters causes a significant increase in the total rocket drag, which depends on both the Mach number and the rocket flight phase. Experimental tests of the rocket model allowed to determine the difference in drag coefficient between active and passive flight versus Mach number. It was found that, in the case of a deviation from the rocket’s flight direction, the aerodynamic coefficients strongly depend on the location of the boosters in relation to the direction of the deviation.

Practical implications

Studies of the rocket model aerodynamic characteristics allow the assessment of the influence of parallel boosters on rocket performance, which is important when the decision of a rocket staging type is taken.

Originality/value

The presented wind tunnel test results of the rocket model equipped with the two parallel boosters are an original contribution to the rocket research results presented in the literature.
Does sustainable board governance drive corporate social responsibility? A structured literature review on European archival research
Authors: Velte Patrick
Published: July 2022

Purpose

This paper aims to analyze the impact that sustainable board governance has on corporate social responsibility (CSR) on the European capital market because of the current debate of future European regulations on the topic.

Design/methodology/approach

Based on a legitimacy and stakeholder theoretical framework, the author conducts a structured literature review and includes 86 quantitative peer-reviewed empirical (archival) studies on board gender diversity, sustainability board expertise and sustainability-related executive compensation and their impact on CSR variables.

Findings

Gender board diversity represents the most important variable in this literature review. The included categories of sustainable board governance positively influence both the total CSR and environmental outputs.

Research limitations/implications

A detailed analysis of sustainable board governance proxies is needed in future archival research to differentiate between symbolic and substantive use of CSR. In view of the current European reform initiatives on sustainable corporate governance in line with the EU Green Deal project, future research should also analyze the interactions between the included sustainable board governance variables and their contributions to CSR.

Practical implications

As both stakeholder demands’ on CSR outputs and CSR washing have increased since the financial crisis of 2008–2009, firms should be aware of a substantive integration of sustainability within their boards of directors (e.g. because of composition and compensation) to increase their CSR efforts and long-term firm reputation.

Originality/value

This analysis makes useful contributions to prior research by focusing on sustainable board governance as a key determinant of CSR outputs on the European capital market. The European Commission’s future evidence-based regulations [e.g. the corporate sustainability reporting directive (CSRD) and the corporate sustainability due diligence directive (CSDD)] should be promoted.
Do independent directors and big-4 audit firms limit classification shifting: evidence from Indian firms
Authors: Mulchandani Kalyani , Mulchandani Ketan
Published: July 2022

Purpose

This study investigates the moderating role of Big-4 audit firms on the association between board independence and classification shifting (CS) in Indian firms.

Design/methodology/approach

This study has employed a fixed-effect panel data regression model to analyze the sample data. Board independence is measured by taking the proportion of independent directors on a firm’s board. CS is measured from the core earnings expectation model (McVay, 2006). Principal Score Matching is applied to validate the results.

Findings

Based on 6,016 firm-year observations of Indian firms listed on the Bombay Stock Exchange, results show that firms with a higher proportion of independent directors on board are effective in limiting expense CS. Further, firms that Big-4 audit firms audit play a significant role in curbing expense CS. Overall, results also exhibit that Big-4 audit firms significantly influence the association between board independence and CS.

Originality/value

This study is one of its kind to examine the moderating role of Big-4 audit firms between board independence and CS.
Ruderals naturalize, competitors invade: Varying roles of plant adaptive strategies along the invasion continuum
Authors: Guo Kun , Pyšek Petr , Chytrý Milan , Divíšek Jan , Lososová Zdeňka , van Kleunen Mark , Pierce Simon , Guo Wen‐Yong
Published: July 2022

It is increasingly recognized that the factors facilitating plant invasions depend on the stage along the introduction–naturalization–invasion continuum. Adaptative strategies, that is, combinations of functional traits that represent overall fitness in the face of one or more selection pressures, have shown promise in explaining plant invasions. However, whether adaptive strategy patterns change with stages of plant invasion is not yet known.

Using the Pladias Database of the Czech Flora and Vegetation, we explored how Grime's adaptive strategies (competitors, stress‐tolerators, ruderals; CSR) and introduction pathways (deliberate vs. accidental) relate to plant invasion along the introduction–naturalization–invasion continuum.

Phylogenetically corrected ANOVAs showed that naturalized species (referring to non‐invasive naturalized species in this study) were mostly R‐selected, whereas invasive species tended to be C‐selected. The results of phylogenetic regression analysis further confirmed that across the deliberately and accidentally introduced species, R‐ and C‐selection were positively related to naturalization and invasion success respectively. We also found that deliberate introduction was negatively related to naturalization success and grid‐cell occupancy of naturalized species, likely due to the different CSR strategies of deliberately and accidentally introduced aliens.

Our study provides empirical evidence that different adaptive strategies are associated with species that have reached different invasion stages and confirms the usefulness of the CSR strategy framework for understanding plant invasion. This has implications for predicting and preventing potential high‐impact invaders. For example, our results show that naturalized C‐selected species have a higher probability of becoming invasive than naturalized R‐selected species. Therefore, management actions are essential to prevent further introductions and spread of competitors.

Read the free Plain Language Summary for this article on the Journal blog.
The lives of others: Class divisions, network segregation, and attachment to society in Chile
Authors: Otero Gabriel , Volker Beate , Rözer Jesper , Mollenhorst Gerald
Published: July 2022

In this paper, we examine whether social class and class divides in social networks contribute to individuals' attachment to society. We argue that network segregation restricts individuals' social worlds, thereby diminishing societal attachment. Our research site is Chile, a country with relatively low social cohesion and one of the world's highest levels of economic inequality. We use large‐scale representative survey data collected in 2016 for the Chilean urban population aged 18–75 years (n = 2983) and interrelate indicators of well‐established dimensions and sub‐dimensions of societal attachment. Results of our regression analyses show that members of the upper middle class are more attached to society than their fellow citizens from other social strata. In addition, having more social contacts within one's own social class reduces attachment to society. In particular, network homogeneity lessens societal attachment for lower‐ and upper‐class individuals, but not so strongly in the middle class. We conclude that social cohesion in Chilean society would be enhanced not only by more equal opportunities but also by changes to the social settings in which social class segregation is (re)produced.
Fecal calprotectin as a biomarker of microscopic bowel inflammation in patients with spondyloarthritis
Authors: Campos Júlia Faria , Resende Gustavo Gomes , Barbosa Alfredo José Afonso , de Carvalho Silas Castro , Lage Junia Aguiar , Cunha Pedro Ferrari Sales , de Souza Stela Cristina Silva , Ferrari Maria de Lourdes Abreu
Published: July 2022

Aim

Microscopic bowel inflammation is present in up to 60% of all patients with spondyloarthritis (SpA) and appears to be associated with more severe joint disease and a higher risk of developing inflammatory bowel disease (IBD). This study aimed to determine the utility of fecal calprotectin (fCAL) in evaluating endoscopic and histological bowel inflammation in SpA patients.

Methods

Ileocolonoscopies with biopsies and fCAL measurements were performed in 65 patients with SpA.

Results

In 47 (72.3%) patients, the fCAL levels were higher than 50 μg/g, whereas in 20 (30.7%), these levels were greater than 250 μg/g. A total of 38 (58.5%) patients presented with microscopic bowel inflammation, and 13 (20%) presented with signs of endoscopic inflammation. fCAL levels were significantly higher in patients with microscopic bowel inflammation than in those without inflammatory findings (P < .001); additionally, these levels were slightly higher in patients with endoscopic signs of bowel inflammation (P = .053). A fCAL cutoff value of 96 μg/g predicted histological bowel inflammation with 73% sensitivity and 67% specificity. No statistically significant difference was observed in the fCAL levels between patients who had been treated or not treated with nonsteroidal anti‐inflammatory drugs (NSAIDs).

Conclusion

Our findings confirm a high prevalence of microscopic bowel inflammation in SpA patients, regardless of the use of NSAIDs. The evaluation of fCAL levels proved to be useful in the identification of microscopic inflammation and could help in the more judicious indication of ileocolonoscopy. These results support the use of fCAL for the evaluation of microscopic bowel inflammation in SpA patients.
How to distinguish thoracic and cervical lymph nodes during minimally invasive esophagectomy
Authors: Zeng Taidui , Chen Maohui , Cai Bingqiang , Zheng Wei , Xu Chi , Xu Guobing , Chen Chun , Zheng Bin
Published: July 2022

Purpose

In this article, we aimed to reconstruct the cervical–thoracic junction plane (CTJP) using a three‐dimensional (3D) reconstruction system. Thus, the CTJP can be judged during surgery to better distinguish cervical–thoracic lymph nodes.

Methods

We included patients in Fujian Medical University Union Hospital from December 2019 to March 2020. All patients underwent a thin‐slice and enhanced computed tomography scan of the chest with 3D reconstruction using the IQQA system (EDDA technology) to reconstruct the CTJP, brachiocephalic trunk, right common carotid artery, and right subclavian artery. The distance from the intersection of the right subclavian artery and the CTJP to the origin of the right subclavian artery (ORSA) was measured, and the relationship between this distance and the patient's sex, BMI and height was analyzed.

Results

Seventy‐three patients were enrolled, of whom 12 had ORSA above the CTJP, while 61 had ORSA below the plane. There was a significant difference in age between the two groups (p = 0.04), compared with height, weight and BMI (p > 0.05). In 61 patients with the ORSA below the CTJP, the average distance was 24.7 ± 7.6 mm. The difference between the distance and BMI (p = 0.02) was statistically significant, and it was increased with increasing BMI.

Conclusions

The relationship between the ORSA and CTJP can be clarified through 3D reconstruction. The cervical‐thoracic recurrent laryngeal nerve lymph nodes can be distinguished clearly in minimally invasive esophagectomy, contributing to the accurate N staging of middle‐thoracic esophageal cancer.
The prevalence and significance of gestational cannabis use at an Australian tertiary hospital
Authors: Dunn Mikaela L. , Bradley Clare , Ayonrinde Oyedeji A. , Van Rooyen Derrick M. , Tait Robert J. , White Scott W. , Fisher Petrovia , Sunanda Gargeswari , Mehta Shailender , Ayonrinde Oyekoya T
Published: July 2022

Background

Cannabis is one of the most common non‐prescribed psychoactive substances used in pregnancy. The prevalence of gestational cannabis use is increasing.

Aim

The aim was to examine the prevalence of gestational cannabis use and associated pregnancy and neonate outcomes.

Materials and Methods

A retrospective observational study involving pregnant women delivering in 2019 was conducted at a tertiary hospital in Perth, Western Australia. Gestational cannabis and other substance use records were based on maternal self‐report. Pregnancy outcomes included neonatal gestational age, birthweight, birth length, head circumference, resuscitation measures, special care nursery admission, 5‐min Apgar score and initial neonatal feeding method.

Results

Among 3104 pregnant women (mean age: 31 years), gestational cannabis use was reported by 1.6% (n = 50). Cannabis users were younger, more likely to use other substances and experience mental illness or domestic violence compared with non‐users. Neonates born to cannabis users had a lower mean gestational age, birthweight and birth length compared to those born to non‐cannabis users. Gestational cannabis use (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.6–6.7) and tobacco smoking (OR 2.2, 95% CI 1.5–3.6) were associated with increased odds of a low‐birthweight neonate. Combined cannabis and tobacco use during pregnancy further increased the likelihood of low birthweight (LBW, adjusted OR 3.9, 95% CI 1.6–9.3). Multivariate logistic regression analysis adjusted for maternal sociodemographical characteristics, mental illness, alcohol, tobacco and other substance use demonstrated gestational cannabis use to be independently associated with LBW (OR 2.3, 95% CI 1.1–5.2).

Conclusion

Gestational cannabis use was independently associated with low birthweight, synergistically affected by tobacco smoking.
Optimising medical retrieval processes and outcomes in remote areas in high‐income countries: A scoping review
Authors: Mathew Supriya , Russell Deborah J. , Fitts Michelle S. , Wakerman John , Honan Bridget , Johnson Richard , Zhao Yuejen , Reeve David , Niclasen Petra
Published: July 2022

Objective

This scoping review explores the structure and process‐level strategies that are associated with medical retrieval outcomes. A secondary aim is to identify the range of medical retrieval outcomes used to assess the performance of remote retrieval services.

Design

A scoping review of peer‐reviewed literature from PubMed, CINAHL and the Web of Science was undertaken following guidelines set by the Johanna Briggs Institute manual for scoping reviews. All articles were assessed by two reviewers. Themes were derived inductively from the data extracted.

Setting

Medical retrievals in sparsely populated remote locations in high‐income countries.

Participants

Staff and clients of remote medical retrieval services.

Interventions

Structures and processes (e.g. resource availability, retrieval staff structures and governance protocols) that aimed to improve medical retrieval outcomes.

Outcomes

Patient health outcomes and service efficiency.

Results

Twenty‐four articles were included. Three broad themes, related to the nature of the interventions, were included: optimising prehospital management of retrievals, staffing and resourcing of retrieval services and retrieval model evaluation. Mortality was the most frequently used outcome indicator in these studies, but was not measured consistently across studies.

Conclusions

This review highlights significant gaps in the literature that describes the structure and processes of retrieval models operating in remote areas and a dearth of literature evaluating specific operational strategies implemented within medical retrieval models. The available literature does not meaningfully assist with identifying key outcome indicators for developing a consistent monitoring and evaluation framework for retrieval services in geographically, culturally and demographically diverse remote contexts.
Estimating sediment transport diffusion coefficients from reconstructed rifted margin architecture: measurements in the Ogooué and Zambezi deltas
Authors: Simon Brendan , Robin Cécile , Rouby Delphine , Braun Jean , Guillocheau François
Published: July 2022

Diffusion‐based stratigraphic models are widely used to simulate sedimentary systems and margin deltas. Diffusion‐based models assume that the topographic evolution primarily depends from its slope. Limited attention has however been given to the calibration of the transport coefficients. Here, we evaluate transport coefficient values from natural examples, the Ogooué and Zambezi rifted margin deltas over the last 5 to 12 Ma respectively. We developed a method to estimate transport coefficients based on high resolution seismic stratigraphy analysis of the stratigraphic architecture of these deltas. For each stratigraphic sequence, we calibrated the sand/shale ratios of the deposits, we restored their depositional slopes, we estimated their uncompacted accumulated volumes and we calculated the transport coefficient (Kd) from the sediment flux/slope ratio. Estimated values of Kd fall within one order of magnitude (×0.1 km2/ka), a much narrower range than previously published values (×0.0001 to ×100 km2/ka). We show that the diffusion approximation is optimal at 10–100 km scale and 0.5–1 Ma time resolution, independently of the stratigraphic context. We show that the diffusion assumption is appropriate for the formation of the clinoforms (mainly gravity driven). It is however not optimal for the shelf and distal domains where additional processes (e.g., wave, flood, hemipelagic, turbidites, oceanic current), not accounted for it the diffusion assumption, significantly impact sediment transport. We documented a significant increase of Kd values after 0.9 Ma, coeval of an increase in the amplitude of eustatic variations at this time indicating that the calibration of Kd from present day sedimentary systems might not be optimal for simulations of sedimentary systems before the last million years.
Elicitors and phenotypes of adult patients with proven IgE‐mediated food allergy and non‐immune‐mediated food hypersensitivity to food additives
Authors: Alexiou Aikaterina , Höfer Veronika , Dölle‐Bierke Sabine , Grünhagen Josefine , Zuberbier Torsten , Worm Margitta
Published: July 2022

Background

Food allergy is a growing health concern with a prevalence of 2%–3% in the adult population in Europe. Non‐immune‐mediated food hypersensitivities, which include reactions after ingestion of food additives, affect 1% of adults and may resemble IgE‐induced allergic reactions without identifiable immunologic sensitization. A double‐blind placebo‐controlled food challenge (DBPCFC) is the gold standard for the diagnosis of any food hypersensitivity.

Objective

We analysed a large group of adult patients with suspected food hypersensitivity, who had undergone DBPCFC, to better understand IgE‐mediated food allergy and non‐immune‐dependent food hypersensitivity to food additives in adults regarding elicitors, symptoms and positivity rates of oral challenges.

Methods

Data from 541 patients with suspected food hypersensitivity were analysed, who underwent an oral food challenge between 2010 and 2019.

Results

IgE‐dependent food allergy was confirmed in 114 of 329 adult patients (34.6%). The confirmation rate was lower in the group of patients with suspected non‐immune‐mediated reactions to food additives (65 of 286, 22.7%). Urticaria and angioedema appeared more frequently in patients with IgE‐mediated food allergies. By contrast, flush and diarrhoea were the most frequent symptoms after a challenge in the group with the non‐immune‐mediated reactions to food additives. Wheat and celery were the most frequently identified food allergens in adults, whereas colourings and preservatives were the most frequent elicitors of non‐immune‐mediated food hypersensitivity.

Conclusion

The importance of oral food challenges for the diagnosis of food hypersensitivity is confirmed. IgE‐dependent food allergy is more frequently proven, reaching a positivity rate of one‐third and only about 20% for non‐immune‐mediated hypersensitivity. Future studies should elaborate on the mechanisms of non‐immune‐mediated food hypersensitivity and the clinical impact of cofactors in this setting.
Measurement of ANP, BNP and endothelin‐1 concentrations in jumping horses with heart valvular regurgitation and their correlation with the dimensions of heart structures
Authors: Sadeghian Chaleshtori Sirous , Mokhber Dezfouli Mohammad Reza , Najizadeh Mohammad Hassan , Nikbakht Borujeni Golam Reza
Published: July 2022

Background

Natriuretic peptides and endothelin‐1 are used as biochemical biomarkers for the diagnosis and prognosis of heart diseases.

Objectives

This study aimed to investigate plasma ANP, BNP and endothelin‐1 in jumping horses with various manifestations of heart valve regurgitation and their association with echocardiographic variables.

Study design

Clinical evaluations including cardiac auscultation were performed in 198 jumping horses, and 30 horses were chosen.

Methods

Sixteen jumping horses with murmurs of grade 3/6 to 5/6 having various degrees of heart valve regurgitation with the severity of insignificant to moderate on colour Doppler echocardiography were considered as the valvular regurgitation group (average age 9.75 ± 3.28 years and weight 427.43 ± 82.22 kg, and consisting of 10 mares, three stallions and three castrated male horses with breeds of 12 Thoroughbred and four crossbred). Fourteen healthy horses were chosen as the healthy group (average age 8.64 ± 2.44 years and weight 462.14 ± 77.42 kg, and consisting of nine mares, three stallions and two castrated males with breeds of 12 Thoroughbreds, and two crossbred). Blood samples were collected from the jugular vein, and plasma concentration of ANP, BNP and endothelin‐1 was determined using Sandwich ELISA by a horse‐specific kit. Then, the plasma concentration of mentioned peptides and echocardiographic variables were compared between the two groups.

Results

B‐type natriuretic peptide was significantly increased in horses with valve regurgitation compared to healthy horses, but increases in ANP and endothelin‐1 were insignificant. Also, in the valvular regurgitation group, horses with a pulmonic valve disorder had a significantly higher concentration of BNP and endothelin‐1 than healthy horses. Assessment of the relation between ANP, BNP and endothelin‐1 with echocardiographic variables showed a significant correlation between ANP and right ventricle length (RVL) and left ventricle width (LVW) in systole and endothelin‐1 with right ventricle width (RVW) and left ventricle width in systole, but BNP had no significant correlation.

Conclusion and clinical importance

According to the study results, it can be assumed that the measurement of these cardiac biomarkers can be helpful in the diagnosis of the jumping horse with cardiac valvular disorders (especially pulmonic valve regurgitation) and changes in the dimensions of the heart ventricle.
Postural orthostatic tachycardia syndrome and migraine: A narrative review
Authors: Mueller Bridget R. , Robinson‐Papp Jessica
Published: July 2022

Objective

In this narrative review, we summarize experimental and clinical evidence demonstrating mechanistic connections between POTS and migraine.

Background

Migraine is the most common comorbidity in patients with POTS, a heterogenous disorder of the autonomic nervous system characterized by orthostatic intolerance and positional tachycardia. POTS is a debilitating illness with few effective treatments. We aim for this narrative review to increase awareness of the mechanistic connections between POTS and migraine providing foundational information that optimizes clinical care and advances the development of pathophysiologic‐based treatments.

Methods

We used the PubMed and Medline databases in November 2021 to perform a literature review and searched for the following keywords: “postural orthostatic tachycardia syndrome,” “POTS,” “autonomic nervous system,” AND “migraine,” “headache.”

Results

The high prevalence of migraine in patients with POTS may be explained by common pathologic mechanisms. There is evidence that dysregulation of the sympathetic nervous system, alterations in central and peripheral hemodynamics, and central sensitization increase vulnerability to both POTS and migraine. Non‐pharmacologic and pharmacologic treatments that target these shared mechanisms may provide significant benefit for the patient with POTS and migraine.

Conclusions

Identification of common affected pathways may provide important insight that advances our understanding and treatment of both migraine and POTS.
Diet restriction alone improves glucose tolerance and insulin sensitivity than its coadministration with krill or fish oil in a rabbit model of castration‐induced obesity
Authors: Grigorova Natalia , Ivanova Zhenya , Bjørndal Bodil , Berge Rolf Kristian , Vachkova Ekaterina , Milanova Aneliya , Penchev Georgi , Georgiev Ivan Penchev
Published: July 2022

This study investigated the effect of 50% diet restriction and its coadministration with krill oil (KO) or fish oil (FO) on glucose tolerance and insulin sensitivity in a rabbit model of obesity. Castrated male rabbits were 50% restricted fed and supplemented with KO or FO (600 mg omega‐3 polyunsaturated fatty acids/daily) for 2 months. Simultaneously, two control groups were used: castrated, full‐diet‐fed and castrated, 50% restricted fed rabbits without additives restricted group (RG). The energy‐restricted diet decreased final body weight in castrated male rabbits and improved most insulin sensitivity and β‐cell function indexes. Combining the same diet and KO or FO, further reduced fasting blood glucose levels. However, this feed regime significantly accelerated insulin secretion and reduced gene expression of insulin receptor substrate‐1, pyruvate kinase and 3‐hydroxy‐3‐methylglutaryl‐CoA synthase 2. This was manifested by reduced dynamic insulin sensitivity, assessment homoeostasis‐β‐cell function indices and increased glucose elimination rate to levels comparable to or above the obese animals. Aspartate and alanine aminotransferases enzyme activities were raised more than those in the obese group. Surprisingly, KO and FO administration downregulated acetyl‐coenzyme A oxidase and carnitine palmitoyltransferase 2 messenger RNA gene expression compared to the RG. In conclusion, we can assume that a better effect on insulin sensitivity and glucose tolerance was observed in the diet restriction alone than in the coadministration of KO or FO when animals are exposed to highly obesity predisposing factors. These effects could be at least in part ascribed to the modified gene expression levels of some critical enzymes and factors involved in liver glucose metabolism and β‐oxidation.