bluuebunny/crossref_metadata_2025 huggingface dataset:
Intestinal Epithelial Cell-specific Deletion of Cytokine-inducible SH2-containing Protein Alleviates Experimental Colitis in Ageing Mice
Authors: Hu Xiaoming , Jiao Fuxin , Deng Jiali , Zhou Ziheng , Chen Shanghai , Liu Changqin , Liu Zhanju , Guo Feifan
Published: March 2023

Background and Aims

The incidence of inflammatory bowel disease [IBD] in the elderly has increased in recent years. However, the mechanisms underlying the ageing-related IBD susceptibility remain elusive. Cytokine-inducible SH2-containing protein [CISH] is involved in regulating metabolism, the expansion of intestinal tuft cells and type-2 innate lymphoid cells, and ageing-related airway inflammation. Here, we investigated the role of CISH in ageing-related colitis susceptibility.

Methods

CISH and phosphorylated signal transducer and activator of transcription-3 [p-STAT3] levels were evaluated in the colons of ageing mice and older ulcerative colitis [UC] patients. Mice with intestinal epithelial cell-specific knockout of Cish [CishΔIEC] and Cish-floxed mice were administered dextran sodium sulphate [DSS] or trinitrobenzene sulphonic acid [TNBS] to induce colitis. Colonic tissues were analysed in quantitative real-time polymerase chain reaction, immunoblotting, immunohistochemical, and histological staining experiments. Differentially expressed genes from colonic epithelia were analysed by RNA sequencing.

Results

Ageing increased the severity of DSS-induced colitis and the expression of colonic epithelial CISH in mice. CishΔIEC prevented DSS- or TNBS-induced colitis in middle-aged mice but not in young mice. RNA-sequencing analysis revealed that CishΔIEC significantly suppressed DSS-induced oxidative stress and proinflammatory responses. During ageing in the CCD841 cell model, knockdown of CISH decreased ageing-induced oxidative stress and proinflammatory responses, whereas these effects were compromised by knocking down or inhibiting STAT3. The increase in CISH expression was higher in the colonic mucosa of older patients with UC than in that of healthy controls.

Conclusions

CISH might be a proinflammatory regulator in ageing; therefore, targeted therapy against CISH may provide a novel strategy for treating ageing-related IBD.
Alerting trends in epidemiology for calcific aortic valve disease, 1990–2019: An age–period–cohort analysis for the Global Burden of Disease Study 2019
Authors: Shu Songren , Yang Yicheng , Sun Bo , Su Zhanhao , Fu Mengxia , Xiong Changming , Zhang Xueyi , Hu Shengshou , Song Jiangping
Published: March 2023

Aims

To assess the trends in calcific aortic valve disease (CAVD) epidemiology, with an emphasis on CAVD mortality, leading risk factors, and their associations with age, period, and birth cohort.

Methods and results

Prevalence, disability-adjusted life years, and mortality were derived from the Global Burden of Disease Study 2019. The age–period–cohort model was employed to study the detailed trends of CAVD mortality and its leading risk factors. Globally, CAVD showed unsatisfactory results from 1990 to 2019, with the CAVD deaths of 127 000 in 2019. CAVD mortality was substantially reduced in high socio-demographic index (SDI) countries [−1.45%, 95% confidence interval (CI) (−1.61 to −1.30)], mildly increased in high-middle SDI countries [0.22%, 95% CI (0.06–0.37)], and unchanged in other SDI quintiles. There was a noticeable transition in CAVD deaths from younger to older populations globally. The CAVD mortality increased exponentially with age, and the male had higher mortality than the female before 80 years old. Favourable period [0.69, 95% CI (0.66–0.72)] and birth effects [0.30, 95% CI (0.22–0.43)] were mainly observed in high SDI countries, while unfavourable effects were mostly noticed in high-middle SDI countries. High systolic blood pressure was the leading risk factor of CAVD deaths globally, and it showed favourable trends in high SDI regions.

Conclusion

Although CAVD mortality reduction was observed globally, unfavourable period, and cohort effects were found in many countries. Increase of mortality rate among the population ≥85 years was the common challenge across all SDI quintiles, stressing the necessity to further improve health care for CAVD patients worldwide.
STereotactic Arrhythmia Radioablation (STAR): the Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary consortium (STOPSTORM.eu) and review of current patterns of STAR practice in Europe
Authors: Grehn Melanie , Mandija Stefano , Miszczyk Marcin , Krug David , Tomasik Bartłomiej , Stickney Kristine E , Alcantara Pino , Alongi Filippo , Anselmino Matteo , Aranda Ricardo Salgado , Balgobind Brian V , Boda-Heggemann Judit , Boldt Leif-Hendrik , Bottoni Nicola , Cvek Jakub , Elicin Olgun , De Ferrari Gaetano Maria , Hassink Rutger J , Hazelaar Colien , Hindricks Gerhard , Hurkmans Coen , Iotti Cinzia , Jadczyk Tomasz , Jiravsky Otakar , Jumeau Raphaël , Kristiansen Steen Buus , Levis Mario , López Manuel Algara , Martí-Almor Julio , Mehrhof Felix , Møller Ditte Sloth , Molon Giulio , Ouss Alexandre , Peichl Petr , Plasek Jiri , Postema Pieter G , Quesada Aurelio , Reichlin Tobias , Rordorf Roberto , Rudic Boris , Saguner Ardan M , ter Bekke Rachel M A , Torrecilla José López , Troost Esther G C , Vitolo Viviana , Andratschke Nicolaus , Zeppenfeld Katja , Blamek Slawomir , Fast Martin , de Panfilis Ludovica , Blanck Oliver , Pruvot Etienne , Verhoeff Joost J C
Published: March 2023

The EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a pooled treatment database to evaluate patterns of practice and outcomes of STAR and finally to harmonize STAR within Europe. The consortium comprises 31 clinical and research institutions. The project is divided into nine work packages (WPs): (i) observational cohort; (ii) standardization and harmonization of target delineation; (iii) harmonized prospective cohort; (iv) quality assurance (QA); (v) analysis and evaluation; (vi, ix) ethics and regulations; and (vii, viii) project coordination and dissemination. To provide a review of current clinical STAR practice in Europe, a comprehensive questionnaire was performed at project start. The STOPSTORM Institutions’ experience in VT catheter ablation (83% ≥ 20 ann.) and stereotactic body radiotherapy (59% > 200 ann.) was adequate, and 84 STAR treatments were performed until project launch, while 8/22 centres already recruited VT patients in national clinical trials. The majority currently base their target definition on mapping during VT (96%) and/or pace mapping (75%), reduced voltage areas (63%), or late ventricular potentials (75%) during sinus rhythm. The majority currently apply a single-fraction dose of 25 Gy while planning techniques and dose prescription methods vary greatly. The current clinical STAR practice in the STOPSTORM consortium highlights potential areas of optimization and harmonization for substrate mapping, target delineation, motion management, dosimetry, and QA, which will be addressed in the various WPs.
Evaluating metabolic and genomic data for predicting grain traits under high night temperature stress in rice
Authors: Bi Ye , Yassue Rafael Massahiro , Paul Puneet , Dhatt Balpreet Kaur , Sandhu Jaspreet , Do Phuc Thi , Walia Harkamal , Obata Toshihiro , Morota Gota
Published: March 2023

The asymmetric increase in average nighttime temperatures relative to increase in average daytime temperatures due to climate change is decreasing grain yield and quality in rice. Therefore, a better genome-level understanding of the impact of higher night temperature stress on the weight of individual grains is essential for future development of more resilient rice. We investigated the utility of metabolites obtained from grains to classify high night temperature (HNT) conditions of genotypes, and metabolites and single-nucleotide polymorphisms (SNPs) to predict grain length, width, and perimeter phenotypes using a rice diversity panel. We found that the metabolic profiles of rice genotypes alone could be used to classify control and HNT conditions with high accuracy using random forest or extreme gradient boosting. Best linear unbiased prediction and BayesC showed greater metabolic prediction performance than machine learning models for grain-size phenotypes. Metabolic prediction was most effective for grain width, resulting in the highest prediction performance. Genomic prediction performed better than metabolic prediction. Integrating metabolites and genomics simultaneously in a prediction model slightly improved prediction performance. We did not observe a difference in prediction between the control and HNT conditions. Several metabolites were identified as auxiliary phenotypes that could be used to enhance the multi-trait genomic prediction of grain-size phenotypes. Our results showed that, in addition to SNPs, metabolites collected from grains offer rich information to perform predictive analyses, including classification modeling of HNT responses and regression modeling of grain-size-related phenotypes in rice.
Tapping Culture Collections for Fungal Endophytes: First Genome Assemblies for Three Genera and Five Species in theAscomycota
Authors: Hill Rowena , Levicky Quentin , Pitsillides Frances , Junnonen Amy , Arrigoni Elena , Bonnin J Miguel , Kermode Anthony , Mian Sahr , Leitch Ilia J , Buddie Alan G , Buggs Richard J A , Gaya Ester
Published: March 2023

The Ascomycota form the largest phylum in the fungal kingdom and show a wide diversity of lifestyles, some involving associations with plants. Genomic data are available for many ascomycetes that are pathogenic to plants, but endophytes, which are asymptomatic inhabitants of plants, are relatively understudied. Here, using short- and long-read technologies, we have sequenced and assembled genomes for 15 endophytic ascomycete strains from CABI’s culture collections. We used phylogenetic analysis to refine the classification of taxa, which revealed that 7 of our 15 genome assemblies are the first for the genus and/or species. We also demonstrated that cytometric genome size estimates can act as a valuable metric for assessing assembly “completeness”, which can easily be overestimated when using BUSCOs alone and has broader implications for genome assembly initiatives. In producing these new genome resources, we emphasise the value of mining existing culture collections to produce data that can help to address major research questions relating to plant–fungal interactions.
Significant Acceleration of Regional Brain Aging and Atrophy After Mild Traumatic Brain Injury
Authors: Shida Alexander F , Massett Roy J , Imms Phoebe , Vegesna Ramanand V , Amgalan Anar , Irimia Andrei
Published: March 2023

Brain regions’ rates of age-related volumetric change after traumatic brain injury (TBI) are unknown. Here, we quantify these rates cross-sectionally in 113 persons with recent mild TBI (mTBI), whom we compare against 3 418 healthy controls (HCs). Regional gray matter (GM) volumes were extracted from magnetic resonance images. Linear regression yielded regional brain ages and the annualized average rates of regional GM volume loss. These results were compared across groups after accounting for sex and intracranial volume. In HCs, the steepest rates of volume loss were recorded in the nucleus accumbens, amygdala, and lateral orbital sulcus. In mTBI, approximately 80% of GM structures had significantly steeper rates of annual volume loss than in HCs. The largest group differences involved the short gyri of the insula and both the long gyrus and central sulcus of the insula. No significant sex differences were found in the mTBI group, regional brain ages being the oldest in prefrontal and temporal structures. Thus, mTBI involves significantly steeper regional GM loss rates than in HCs, reflecting older-than-expected regional brain ages.
Lower Myelin Content Is Associated With Lower Gait Speed in Cognitively Unimpaired Adults
Authors: Faulkner Mary E , Laporte John P , Gong Zhaoyuan , Akhonda Mohammad A B S , Triebswetter Curtis , Kiely Matthew , Palchamy Elango , Spencer Richard G , Bouhrara Mustapha
Published: March 2023

Mounting evidence indicates that abnormal gait speed predicts the progression of neurodegenerative diseases, including Alzheimer’s disease. Understanding the relationship between white matter integrity, especially myelination, and motor function is crucial to the diagnosis and treatment of neurodegenerative diseases. We recruited 118 cognitively unimpaired adults across an extended age range of 22–94 years to examine associations between rapid or usual gait speeds and cerebral myelin content. Using our advanced multicomponent magnetic resonance relaxometry method, we measured myelin water fraction (MWF), a direct measure of myelin content, as well as longitudinal and transverse relaxation rates (R1 and R2), sensitive but nonspecific magnetic resonance imaging measures of myelin content. After adjusting for covariates and excluding 22 data sets due to cognitive impairments or artifacts, our results indicate that participants with higher rapid gait speed exhibited higher MWF, R1, and R2 values, that is, higher myelin content. These associations were statistically significant within several white matter brain regions, particularly the frontal and parietal lobes, splenium, anterior corona radiata, and superior fronto-occipital and longitudinal fasciculus. In contrast, we did not find any significant associations between usual gait speed and MWF, R1, or R2, which suggests that rapid gait speed may be a more sensitive marker of demyelination than usual gait speed. These findings advance our understanding on the implication of myelination in gait impairment among cognitively unimpaired adults, providing further evidence of the interconnection between white matter integrity and motor function.
“The Dynamic Nature of Being a Person”: An Ethnographic Study of People Living With Dementia in Their Communities
Authors: Birt Linda , Charlesworth Georgina , Moniz-Cook Esme , Leung Phuong , Higgs Paul , Orrell Martin , Poland Fiona
Published: March 2023

Background and Objectives

A dementia diagnosis can affect social interactions. This study aims to understand how people living with dementia act as social beings within everyday interactions in their local communities.

Research Design and Methods

Focused ethnography informed by Spradley’s approach to data collection and analysis. Observations in community spaces.

Results

Twenty-nine observations were undertaken in everyday social settings with 11 people with dementia who were part of a longitudinal interview study. Data consisted of 40 hr of observation, and researcher field notes. The overarching theme “the dynamic nature of being a person” encapsulates participants’ exhibited experiences in negotiating to attain and sustain an acknowledged place in their communities. Two subthemes characterized contexts and actions: (1) “Being me—not dementia”: Participants constructed narratives to assert their ontological presence in social settings. They and others used strategies to mediate cognitive changes evidencing dementia. (2) “Resisting or acquiescing to ‘being absent in place’”: Participants were often able to resist being absent to the gaze from others, but some social structures and behaviors led to a person being “in place,” yet not having their presence confirmed.

Discussion and Implications

People living with dementia can actively draw on personal attributes, familiar rituals, objects, and social roles to continue to present themselves as social beings. Identifying how postdiagnosis people may self-manage cognitive changes to retain their presence as a person can help health and social care practitioners and families collaborate with the person living with dementia enabling them to have a continued social presence.
Cell-free expression and characterization of multivalent rhamnose-binding lectins using bio-layer interferometry
Authors: Warfel Katherine F , Laigre Eugénie , Sobol Sarah E , Gillon Emilie , Varrot Annabelle , Renaudet Olivier , Dejeu Jerome , Jewett Michael C , Imberty Anne
Published: March 2023

Lectins are important biological tools for binding glycans, but recombinant protein expression poses challenges for some lectin classes, limiting the pace of discovery and characterization. To discover and engineer lectins with new functions, workflows amenable to rapid expression and subsequent characterization are needed. Here, we present bacterial cell-free expression as a means for efficient, small-scale expression of multivalent, disulfide bond-rich, rhamnose-binding lectins. Furthermore, we demonstrate that the cell-free expressed lectins can be directly coupled with bio-layer interferometry analysis, either in solution or immobilized on the sensor, to measure interaction with carbohydrate ligands without purification. This workflow enables the determination of lectin substrate specificity and estimation of binding affinity. Overall, we believe that this method will enable high-throughput expression, screening, and characterization of new and engineered multivalent lectins for applications in synthetic glycobiology.
Correlates of motivation to quit waterpipe tobacco smoking among US young adults: implications for cessation interventions
Authors: Alalwan Mahmood A , Keller-Hamilton Brittney , Long Lauren , Lipkus Isaac , Wagener Theodore L , Mays Darren
Published: March 2023

Waterpipe tobacco smoking is a public health concern that poses many of the same health risks as cigarette smoking, especially among young adults—a subpopulation characterized by the highest prevalence of waterpipe tobacco smoking. Nevertheless, it remains understudied relative to other forms of tobacco use. We examined sociodemographic, behavioral and cognitive factors associated with young adults’ motivation to quit waterpipe smoking using a theory-informed approach. We completed a secondary analysis of baseline data on waterpipe tobacco smoking beliefs and behavior collected from 349 US young adults aged 18–30 years. We analyzed sociodemographics, tobacco use and cessation behaviors and perceptions, and theory-related constructs associated with motivation to quit waterpipe tobacco smoking using linear regression. Overall, participants reported low motivation (mean = 2.68, SD = 1.56, scale range 1–7) and high self-efficacy (mean = 5.12, SD = 1.79) to quit waterpipe tobacco smoking. In multivariable analysis, prior quit attempts (β = 1.10, P < 0.01), greater perceived risks of waterpipe tobacco smoking (β = 0.42, P < 0.01) and increasingly negative attitudes toward waterpipe tobacco smoking (β = 0.29, P < 0.01) were associated with higher motivation to quit. These findings highlight the importance of those factors as potential cessation determinants. These findings can help guide the development and refinement of interventions targeting young adult waterpipe tobacco smoking.
Gender and early career status: variables of participation at an international marine science conference
Authors: Johannesen E , Barz F , Dankel D J , Kraak S B M
Published: March 2023

Conference participation is an important part of academic practice and contributes to building scientific careers. Investigating demographic differences in conference participation may reveal factors contributing to the continued under-representation of women in marine and ocean science. To explore the gender and career stage dimensions of participation in an international marine science conference, preferences of presentation type (oral/poster) as well as acceptance and rejection decisions were investigated using 5-years of data (2015–2019) from an International Marine Science Conference. It was found that early career scientists were more likely to be women, while established scientists were more likely to be men. Although overall, gender did not show a significant effect on the decisions to “downgrade” requests for oral presentations to poster presentations, early career scientists were significantly more likely to be downgraded than established scientists. Given that more women were often early career scientists, more women than men had their presentations downgraded. Other indicators and evidence from conference prize-giving and recognition awards point to a gender gap remaining at senior levels, highlighting the need for further actions as well as monitoring and researching conference participation from a gender perspective.
Chasing inter-species communication: what marine mammals are telling us about our oceans
Authors: Moore Sue E
Published: March 2023

I describe my path through a series of opportunities that provided stepping stones from childhood years in the landlocked US Midwest to a 45-year-long career focused on cetacean behaviour and ecology. My early interest in the ocean and dolphins led me to switch from majoring in journalism to biology during my undergraduate years. While pursuing a master’s degree focused on bioacoustics, I was employed as a contract scientist with the US Navy’s marine mammal laboratory. During 20 years there, my work ranged from dolphin calling behaviour to marine mammal distribution in Alaskan waters, culminating in a Ph.D. dissertation on cetacean habitats in the Alaskan Arctic. Subsequently, I enjoyed a 20-year career with the US NOAA National Marine Fisheries Service. There, I developed and advanced the idea that marine mammals can act as sentinels of ocean variability. To interpret the messages that marine mammals convey about the ocean, we must broaden science discourse to include Indigenous Knowledge and lessons from the experiences of people whose livelihoods depend on the sea. My advice to students and young professionals is to follow your passion while seeking the perspectives of colleagues from a variety of disciplines and people from all cultures and backgrounds. Coupled with a healthy dose of luck, this approach worked for me.
Total and Subgenomic RNA Viral Load in Patients Infected With SARS-CoV-2 Alpha, Delta, and Omicron Variants
Authors: Dimcheff Derek E , Blair Christopher N , Zhu Yuwei , Chappell James D , Gaglani Manjusha , McNeal Tresa , Ghamande Shekhar , Steingrub Jay S , Shapiro Nathan I , Duggal Abhijit , Busse Laurence W , Frosch Anne E P , Peltan Ithan D , Hager David N , Gong Michelle N , Exline Matthew C , Khan Akram , Wilson Jennifer G , Qadir Nida , Ginde Adit A , Douin David J , Mohr Nicholas M , Mallow Christopher , Martin Emily T , Johnson Nicholas J , Casey Jonathan D , Stubblefield William B , Gibbs Kevin W , Kwon Jennie H , Talbot H Keipp , Halasa Natasha , Grijalva Carlos G , Baughman Adrienne , Womack Kelsey N , Hart Kimberly W , Swan Sydney A , Surie Diya , Thornburg Natalie J , McMorrow Meredith L , Self Wesley H , Lauring Adam S ,   for the Investigating Respiratory Viruses in the Acutely Ill (IVY) Network
Published: March 2023

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic and subgenomic RNA levels are frequently used as a correlate of infectiousness. The impact of host factors and SARS-CoV-2 lineage on RNA viral load is unclear.

Methods

Total nucleocapsid (N) and subgenomic N (sgN) RNA levels were measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in specimens from 3204 individuals hospitalized with coronavirus disease 2019 (COVID-19) at 21 hospitals. RT-qPCR cycle threshold (Ct) values were used to estimate RNA viral load. The impact of time of sampling, SARS-CoV-2 variant, age, comorbidities, vaccination, and immune status on N and sgN Ct values were evaluated using multiple linear regression.

Results

Mean Ct values at presentation for N were 24.14 (SD 4.53) for non-variants of concern, 25.15 (SD 4.33) for Alpha, 25.31 (SD 4.50) for Delta, and 26.26 (SD 4.42) for Omicron. N and sgN RNA levels varied with time since symptom onset and infecting variant but not with age, comorbidity, immune status, or vaccination. When normalized to total N RNA, sgN levels were similar across all variants.

Conclusions

RNA viral loads were similar among hospitalized adults, irrespective of infecting variant and known risk factors for severe COVID-19. Total N and subgenomic RNA N viral loads were highly correlated, suggesting that subgenomic RNA measurements add little information for the purposes of estimating infectivity.
Factors associated with COVID-19 vaccine hesitancy among healthcare workers in Cameroon and Nigeria: a web-based cross-sectional study
Authors: Aseneh Jerry Brown , Agbor Valirie Ndip , Kadia Benjamin Momo , Okolie Elvis Anyaehiechukwu , Ofomata Chinelo Janefrances , Etombi Christie Linonge , Ekaney Domin Sone M , Joko Fru Yvonne Walburga
Published: March 2023

Background

This study investigated the determinants of coronavirus disease 2019 (COVID-19) vaccine hesitancy among healthcare workers (HCWs) in Cameroon and Nigeria.

Methods

This analytic cross-sectional study was conducted from May to June 2021, including consenting HCWs aged ≥18 y identified using snowball sampling. Vaccine hesitancy was defined as indecisiveness or unwillingness to receive the COVID-19 vaccine. Multilevel logistic regression yielded adjusted ORs (aORs) for vaccine hesitancy.

Results

We included a total of 598 (about 60% women) participants. Little or no trust in the approved COVID-19 vaccines (aOR=2.28, 95% CI 1.24 to 4.20), lower perception of the importance of the vaccine on their personal health (5.26, 2.38 to 11.6), greater concerns about vaccine-related adverse effects (3.45, 1.83 to 6.47) and uncertainty about colleagues’ acceptability of the vaccine (2.98, 1.62 to 5.48) were associated with higher odds of vaccine hesitancy. In addition, participants with chronic disease (aOR=0.34, 95% CI 0.12 to 0.97) and higher levels of concerns about getting COVID-19 (0.40, 0.18 to 0.87) were less likely to be hesitant to receive the COVID-19 vaccine.

Conclusions

COVID-19 vaccine hesitancy among HCWs in this study was high and broadly determined by the perceived risk of COVID-19 and COVID-19 vaccines on personal health, mistrust in COVID-19 vaccines and uncertainty about colleagues’ vaccine acceptability.
Evaluating Visual Analytics for Relevant Information Retrieval in Document Collections
Authors: da Silva Sherlon Almeida , Milios Evangelos E , de Oliveira Maria Cristina F
Published: March 2023

Retrieving information from document collections is necessary in many contexts, e.g. researchers search for papers on a topic, physicians search for records of patients with a certain condition and police investigators seek relationships between different criminal reports. Finding relevant textual content in a corpus can be challenging in scenarios where the users expect a retrieval process with high recall. Visual Analytics (VA) systems that integrate interactive visualizations and machine learning algorithms are often advocated to support retrieval tasks in such complex scenarios. However, few studies report an end-user perspective on the utility of such systems. We present results from observational studies on VA-supported information retrieval conducted with graduate students and researchers using a system to explore collections of scientific papers. While users have, in general, positive views of the system’s potential to facilitate their retrieval tasks, some faced practical difficulties in using it effectively, and we found considerable variation in their assessment of specific functionalities. Our findings reinforce the potential of VA systems and also the importance of carefully informing users of the underlying conceptual models in such systems and their limitations.
Evaluation of a rapid combination disc test (RCDT) for direct phenotypic detection of extended-spectrum β-lactamase production inE. colifrom positive blood culture bottles
Authors: Berinson Benjamin , Degel-Brossmann Nicole , Olearo Flaminia , Roggenkamp Hannes G , Both Anna , Aepfelbacher Martin , Christner Martin , Rohde Holger
Published: March 2023

Background

The spread of multi-resistant bacteria endangers the effectiveness of empirical antimicrobial treatment, particularly in Gram-negative bloodstream infections. Thus, rapid and reliable susceptibility testing has become a key challenge of modern microbiology. Here, we evaluated a combination disc test for rapid detection of ESBL production in Escherichia coli (rapid combination disc test, RCDT) directly from blood cultures.

Methods

RCDT with discs containing cefotaxime and ceftazidime alone or in combination with clavulanic acid was validated using a cryo-collection of 96 third-generation cephalosporin-resistant (3GCR), whole-genome sequenced E. coli isolates spiked into blood culture bottles. All isolates were subjected to RCDT and rapid antibiotic susceptibility testing (RAST). Zone diameters were assessed after 4, 6 and 8 h of incubation. All isolates also underwent conventional combination disc testing. The real-life performance of RCDT was assessed by analysis of 306 blood cultures growing E. coli.

Results

Eighty of 90 (88.9%) ESBL-positive E. coli validation isolates were correctly identified by RCDT after 4 h of incubation. The detection rate increased to 100% after 6 and 8 h. RCDT was negative in six 3GCR E. coli isolates expressing class B or C β-lactamases. RCDT from routine blood cultures correctly classified all 56 ESBL producers and 245/250 ESBL-negative isolates after 4 h, resulting in 100% sensitivity and 98.8% specificity.

Conclusions

RCDT is a reliable method for rapid ESBL detection in E. coli directly from positive blood cultures. RCDT might complement RAST to support antibiotic stewardship interventions and treatment decisions.
Health outcomes of penicillin allergy testing in children: a systematic review
Authors: Kwok Mo , Heard Katie L , May Anthony , Pilgrim Rachel , Sandoe Jonathan , Tansley Sarah , Scott Jennifer
Published: March 2023

Background

Penicillin allergy labels are commonly acquired in childhood and lead to avoidance of first-line penicillin antibiotics. Understanding the health outcomes of penicillin allergy testing (PAT) can strengthen its place in antimicrobial stewardship efforts.

Objectives

To identify and summarize the health outcomes of PAT in children.

Methods

Embase, MEDLINE, Web of Science, Cochrane Library, SCOPUS and CINAHL were searched from inception to 11 Oct 2021 (Embase and MEDLINE updated April 2022). Studies that utilized in vivo PAT in children (≤18 years old) and reported outcomes relevant to the study objectives were included.

Results

Thirty-seven studies were included in the review, with a total of 8411 participants. The most commonly reported outcomes were delabelling, subsequent penicillin courses, and tolerability to penicillin courses. Ten studies had patient-reported tolerability to subsequent penicillin use, with a median 93.6% (IQR 90.3%–97.8%) of children tolerating a subsequent course of penicillins. In eight studies, a median 97.3% (IQR 96.4%–99.0%) of children were reported as ‘delabelled’ after a negative PAT without further definition. Three separate studies verified delabelling by checking electronic or primary care medical records, where 48.0%–68.3% children were delabelled. No studies reported on outcomes relating to disease burden such as antibiotic resistance, mortality, infection rates or cure rates.

Conclusions

Safety and efficacy of PAT and subsequent penicillin use was the focus of existing literature. Further research is required to determine the long-term impact of delabelling penicillin allergies on disease burden.
A3 CROHN’S DISEASE PROTEOLYTIC MICROBIOTA ENHANCES INFLAMMATION THROUGH PAR2 PATHWAY IN GNOTOBIOTIC MICE
Authors: Hann A , Santiago Badenas A , Galipeau H J , Constante M , Libertucci J , Rahmani S , Jackson K , Rueda G , Rossi L , Ramachandran R , Ruf W , Caminero A , Bercik P , Verdu E F
Published: March 2023

Background

An imbalance in host proteases has been implicated in inflammatory bowel disease (IBD). Recent evidence implicates microbial proteolytic activity (PA) in ulcerative colitis but whether it also plays a role in Crohn’s disease (CD) remains unclear.

Purpose

We therefore investigated the colitogenic potential and underlying pathways of proteolytic CD microbiota.

Method

Adult germ-free (GF) C57BL/6 mice were colonized with CD microbiota selected based on high (CD-HPA) or low fecal proteolytic activity (CD-LPA), and from healthy controls with LPA (HC-LPA), after which total fecal proteolytic, elastolytic and mucolytic activity were analyzed in the mice. Microbial community was assessed by 16S rRNA gene sequencing. Immune function and colonic injury were investigated by inflammatory gene expression (NanoString) and histology. Colitis severity and underlying pathways were investigated in C57BL/6, Nucleotide-binding Oligomerization Domain-2 knock-out (Nod2-/-), and Protease-Activated Receptor 2 (PAR2) cleavage resistant mice (R38E-PAR2) subjected to 2% dextran sodium sulfate in drinking water for 5 days followed by 2 days on water.

Result(s)

Colonization with HC-LPA or CD-LPA lowered baseline fecal proteolytic activity compared with GF mice, which was paralleled by lower acute inflammatory cell infiltrate. CD-HPA further increased proteolytic activity compared with GF mice. Fecal supernatants from CD-LPA or HC-LPA colonized mice had lower in vitro PAR2 cleavage compared to supernatants from GF and CD-HPA colonized mice. Several genes, such as Map kinases, Rhoa, Myd88, and Tollip, were increased in GF mice compared to colonized mice. 18 genes related to inflammation and barrier function (e.g., Mapk2k6, Tnf, Claudin1) were differentially expressed between CD-LPA and CD-HPA. CD-HPA mice had lower alpha diversity, distinct microbial profiles, and higher fecal proteolytic activity compared with CD-LPA. Abundance of several beneficial species (e.g., Akkermansia muciniphilia) was decreased while other taxa were increased (e.g., Hungattella hathewayi) in CD-HPA compared to CD-LPA. H. hathewayi as well as the serine protease K04772 were transcriptionally increased in fecal samples from CD-HPA colonized mice. C57BL/6 and Nod2-/- mice, but not R38E-PAR2 mice, colonized with CD-HPA developed earlier and more severe colitis compared with mice colonized with CD-LPA.

Conclusion(s)

CD proteolytic microbiota is proinflammatory through a PAR2 pathway. H. hathewayi correlates with the proinflammatory phenotype through the serine protease K04772 in this model. The results support a role of microbial PA in CD, which could constitute a biomarker for identifying patients who would benefit from anti-proteolytic therapies.

Disclosure of Interest

None Declared
A17 EVIDENCE OF PROTEASE-MEDIATED PRO-NOCICEPTIVE EFFECTS OF FECAL SUPERNATANTS FROM CROHN'S DISEASE PATIENTS
Authors: Wood H , Alward T , Abu Omar A , Guzman-Rodriguez M , Vanner S , Reed D , Lomax A
Published: March 2023

Background

Abdominal pain is a debilitating symptom of Crohn’s disease (CD). Despite the current treatment options for this disease, abdominal pain is an unresolved problem that commonly persists in the absence of active inflammation. This suggests that something other than inflammation is driving the pain during the quiescent phase. We have previously reported that microbial proteases can directly modulate the excitability of dorsal root ganglia (DRG) neurons, many of which are pain-sensing. We hypothesize that luminal proteases of CD patients are contributing to their abdominal pain.

Purpose

Determine whether luminal mediators in CD fecal samples induce changes in pain signalling.

Method

The effects of patient (active CD [n = 3] and healthy volunteer (HV) [n = 3]) fecal supernatant (FS) samples on pain-sensing neurons were assessed using ex-vivo single unit afferent nerve recordings from mouse colons. Each sample was tested in colonic preparations from a least 5 mice. To further examine cellular mechanisms, DRG neurons were isolated and incubated overnight in media containing CD FS or HV FS media. Changes in neuronal excitability were recorded by determining the rheobase (lower rheobase=increased excitability) using patch clamp recordings (n ≥ 9 DRG neurons/group). Protease inhibitors were applied in both bioassays to determine whether these inhibited the excitatory effect of FS. Lastly, total proteolytic activity in the CD and HV fecal samples was calculated using a casein colorimetric protease detection assay.

Result(s)

FS from HV had no effect on afferent nerve excitability (p = 0.8920). FS from active CD patients increased action potential discharge from colonic afferent nerves by 85% (p<0.0001) and selectively increased the activation of high-threshold units, which are putative nociceptors, by 44% (p=0.0074). A protease inhibitor cocktail (1:1000) and protease-activated receptor (PAR)-2 antagonist GB83 (10µM) both blocked the excitatory effects of CD FS (p<0.05). Overnight incubation with CD FS also had an excitatory effect on DRG neurons compared to HV FS (rheobase decreased by 46%, p<0.05). The effect of CD FS was blocked by GB83 (10µM) (p<0.001) and a serine protease inhibitor (FUT175; 100µM) (p<0.05) independently, but the activity was not blocked by E64 (30nM) a cysteine protease inhibitor. A 200-fold increase (p<0.0001) in total proteolytic activity was found in CD FS compared to HV FS.

Conclusion(s)

Luminal serine proteases, but not cysteine proteases, appear to be driving nociceptive signalling in CD patients. This provides insight into the generation of pain in CD patients and may be a potential target to mitigate this action. Further research is required to elucidate whether these pro-nociceptive proteases are of bacterial or host origin and their effects in the quiescent phase.

Disclosure of Interest

None Declared
A23 INTESTINAL STEM CELL REGULATION BY THE BACTERIAL METABOLITE ADP-HEPTOSE VIA ACTIVATION OF THE ALPK1-TIFA SIGNALLING PATHWAY
Authors: Goyal S , Gray-Owen S , Girardin S
Published: March 2023

NOT PUBLISHED AT AUTHOR’S REQUEST

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CCC, CIHR

Disclosure of Interest

None Declared
A43 SEX DIFFERENCES IN THE ASSOCIATION OF HIV WITH METABOLIC DYSFUNCTION-ASSOCIATED FATTY LIVER DISEASE (MAFLD)
Authors: Kablawi D , Tadjo T F , Milic J , Elgretli W , Gioè C , Lebouché B , Cascio A , Guraldo G , Mazzola G , Sebastiani G
Published: March 2023

Background

People with HIV (PWH) are at high risk for metabolic dysfunction-associated fatty liver disease (MAFLD). In the general population, sex differences seem to exist in frequency and severity of MAFLD, with higher prevalence of MAFLD in men, but higher incidence of liver fibrosis in women. Less is known about sex differences in MAFLD and liver fibrosis in the setting of HIV infection.

Purpose

The aim of this study is to investigate the sex differences in the prevalence of MAFLD in PWH and the severity of liver fibrosis among this population.

Method

This was a multicenter cohort study including consecutive PWH who underwent screening for MAFLD and liver fibrosis by liver stiffness measurement (LSM) with associated controlled attenuation parameter (CAP). MAFLD was defined as the presence of hepatic steatosis, diagnosed as CAP>270 dB/m, plus any among type 2 diabetes, overweight (BMI>25 Kg/m2) or two other metabolic abnormalities. Significant liver fibrosis was diagnosed as LSM>8 kPa. Incidence of MAFLD and significant liver fibrosis was assessed through survival analysis.

Result(s)

1359 PWH (25% females, 30% HCV coinfected) were included. Prevalence of MAFLD at baseline was lower in women than in men with HIV (17.7% vs. 24.3%, p=0.013). Conversely, there was no difference in prevalence of liver fibrosis (10.7% vs. 13.4%). Women with MAFLD were more frequently of black ethnicity (48% vs. 14%, p<0.001), had lower ALT (26.4+20.4 vs. 33.4+22.5; p=0.035), higher HDL cholesterol (1.46+0.57 vs. 1.11+0.33; p<0.001), lower triglycerides (1.69+0.96 vs. 2.47+2.63; p=0.035) compared to men with MAFLD. 485 of these PWH were followed for a median of 3.5 years. Incidence of MAFLD was similar between women and men with HIV. However, incidence of liver fibrosis was higher in women compared to men with HIV (7.0 per 100 person-years [PY] vs. 5.9 per 100 PY; p=0.035) (Figure 1). The higher incidence of significant liver fibrosis occurred particularly after the age of 50 years. On multivariable Cox regression analysis and after adjusting for age, presence of MAFLD (adjusted hazard ratio [aHR] 3.3, 95% CI 2.0-5.6) and female sex (aHR 2.2, 95% CI 1.3-3.5) were independent predictors of developing significant liver fibrosis while CD4 cell count was protective (aHR 0.99, 95% CI 0.99-0.99).

Image

Conclusion(s)

MAFLD seems a sexual dimorphic disease in PWH. Despite having lower rates of MAFLD, women with HIV have higher incidence of significant liver fibrosis compared to men, especially after 50 years of age. Future studies should target adequate consideration of sex differences in clinical investigation of MAFLD to fill current gaps and implement precision medicine for PWH.

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None

Disclosure of Interest

None Declared
A127 TIMING OF CHOLECYSTECTOMY AFTER ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY IN A TERTIARY CENTRE: EVALUATION OF OUTCOMES
Authors: Liu C S , Kao D , Mohamed M , Bigam D , Zepeda-Gomez S
Published: March 2023

Background

Endoscopic retrograde cholangiopancreatography (ERCP) is the treatment of choice for patients with choledocholithiasis. Early cholecystectomy (within 24 to 72 hours) is recommended after the initial ERCP to reduce the risk of subsequent biliary events.

Purpose

To investigate the timing of cholecystectomy after ERCP in patients with choledocholithiasis and its associated outcomes in a single tertiary care centre.

Method

This is a retrospective analysis of adult patients who underwent cholecystectomy after ERCP from August 2021 to April 2022 at the University of Alberta Hospital. Outcomes data were stratified according to the length of time between ERCP and cholecystectomy, within 72 hours (early) or after 72 hours (delayed).

Result(s)

During the study period, 55 subjects were examined. Indications for ERCP included gallstone pancreatitis (24/55, 44%), choledocholithiasis (19/55, 34%), and acute cholangitis (12/55, 21%).

In total, 30 (55%) subjects received cholecystectomy within 72 hours, while 25 (45%) subjects received cholecystectomy after 72 hours. The two groups were comparable in age, sex ratios, and comorbidities. Out of the patients who received cholecystectomy after 72 hours, 8 (32%) subjects received their cholecystectomy on a subsequent admission. Of these, 2 subjects developed recurrent biliary events before their cholecystectomy, and 1 subject required a conversion to open cholecystectomy. There were no recurrent biliary events amongst the individuals with early cholecystectomy.

Subjects who received early cholecystectomy had a shorter total hospital stay compared to those with delayed cholecystectomy (4.5 days vs 7.3 days, p=0.0002). There was no significant difference between early and late cholecystectomy in conversion rate (3% vs 8%, p=0.58), average operating time (86min vs 83min, p=0.79), intraoperative complications including adhesions (13% vs 12%, p>0.05) and empyema (27% vs 28%, p>0.05), as well as histological rate of chronic cholecystitis (88% vs 92%, p=0.68).

Reasons associated with significantly delayed (>7 days) cholecystectomy after ERCP (n=12) include requiring coordination/consultation with other services prior to operation (3 subjects), prolonged course of gallstone pancreatitis (3 subjects), poor candidate for operation due to comorbidities (2 subjects), surgical cancellation/delays (2 subjects), post-ERCP pancreatitis (1 subject), and patient preference (1 subject).

Image

Conclusion(s)

Early cholecystectomy is associated with a shorter length of hospital stay and absence of recurrent biliary events. Other post-cholecystectomy outcomes were comparable. Early laparoscopic cholecystectomy should continue to be encouraged through an interdisciplinary approach.

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None

Disclosure of Interest

None Declared
A177 RISK OF VENOUS THROMBOEMBOLISM IN COVID-19 PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A POPULATION-BASED MATCHED COHORT STUDY
Authors: Khan R , Kuenzig E , Tang A , Im J , Widdifield J , McCurdy J , Kaplan G , Benchimol E
Published: March 2023

Background

Venous thromboembolism (VTE), is associated with significant morbidity and mortality. Inflammation increases the risk of VTE, and it is a well-recognised complication of both inflammatory bowel disease (IBD) and COVID-19.

Purpose

To compare the risk of VTE among individuals with and without IBD following a positive COVID-19 test.

Method

Using health administrative data from Ontario, Canada we conducted a retrospective matched cohort study.All Ontario residents with a positive SARS-CoV-2 PCR test between January 1,2020 and December 30,2021 who had been diagnosed with IBD prior to their COVID-19 infection (identified using a validated algorithm) were matched to 5 individuals without IBD based on year of birth, sex, mean neighbourhood income quintile, date of positive COVID-19 test, and rural/urban residence. Individuals with a cancer diagnosis in the 5 years prior to their first COVID-19 positive test were excluded. Individuals were followed from positive COVID-19 PCR test until VTE event, death, migration out of Ontario or March 31, 2022.VTEs were identified from emergency department or hospitalization data using ICD-10 codes. Incidence rate of VTEs among individuals with IBD were assessed at 1, 6 and 12 months. Proportional cause-specific hazards models compared the risk of VTEs in people with and without IBD, treating death as a competing risk and controlling for vaccination status (2nd dose ≥14 days prior to positive COVID-19 test) and a history of VTE (VTE in the 5 years prior to infection).

Result(s)

There were 4293 people with IBD (44% Crohn’s disease, mean age ±SD 46.1±17.2 y) matched to 20,207 with out IBD (mean age 45.3±16.8 y) with a positive SARS-CoV-2 PCR test. Within 1 month of a positive COVID-19 test, the crude incidence rate of VTE in individuals with IBD was 4.77(95%CI, 4.75-4.80) per 100,000 person-days compared to 8.25(95%CI, 8.20-8.30) per 100,000 among people without IBD.Within 6 months, these rates were 1.86(95%CI, 1.86-1.87) and 2.12(95%CI, 2.11-2.12) per 100,000 person-days among people with and without IBD, respectivley. Within 12 months, these rates were 1.59(95% CI, 1.58-1.59) and 1.42(95% CI, 1.42-1.42) per 100,000 person-days among people with and without IBD, respectively.After adjusting for vaccination status and history of VTE there was no difference in the risk of VTE for people with and without IBD (HR 1.08, 95%CI, 0.64 to 1.83).

Conclusion(s)

IBD patients with COVID-19 were not more likely to experience a VTE infection compared with the general popluation. The risk of VTE was highest soon after COVID-19 and declined thereafter.

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None

Disclosure of Interest

None Declared