bluuebunny/crossref_metadata_2025 huggingface dataset:
Second-generation robotic angioplasty system use for the treatment of ST-elevation myocardial infarction: a first-in-man proof of concept case report
Authors: Hofmann Felix J , Dörr Oliver , Blachutzik Florian , Elsässer Albrecht , Möllmann Helge , Köhne Alessa-Janine , Nef Holger M
Published: March 2023

Background

Robotically assisted remote-controlled PCI (rPCI) was introduced in the past decade as one of the latest enhancements in this rapidly evolving field. The use of a second-generation rPCI system in ST-elevation myocardial infarction (STEMI) is an effort to couple immediate revascularization with the accuracy of newer robotic assistance and software support.

Case summary

Here we report on the safety and efficacy of rPCI applied to a 74-year-old female STEMI patient with persistent acute chest pain as well as regional wall motion abnormalities in the echocardiogram. The first medical contact-to-device time was 76 min, and door-to-balloon time was 33 min. The impatient course was uneventful, so the patient was discharged from hospital after 5 days. To the best of our knowledge, this is the first report of the successful application of second-generation rPCI in STEMI.

Discussion

In the case presented, rPCI was feasible and safe even in acute coronary syndrome based on a single-centre experience. rPCI is a revolutionary new technique that may be applied to various types of clinical presentations.
The 1832 Reform Act and the Place of Illuminations in Late Hanoverian Political Culture
Authors: Jenks Timothy
Published: March 2023

This article explores the place of illumination festivity in the struggle for the 1832 Reform Act. Illuminations, a form of revelry in which crowds took to the streets and threatened to break the windows of those householders who did not submit to the demand of an exhibition of lights, were a staple of Britain’s repertoire of popular contention throughout the long eighteenth century. But their role in the Reform Bill agitation, and their place in late Hanoverian political culture, has not been explored. The fifteen months of the Reform Bill struggle were a particularly intense period of illumination activity and witnessed a significant debate concerning the acceptability of the practice. This debate involved national political figures, local authorities, radicals and anti-reformers. An exploration of this episode not only helps to explain the process of change in a cultural practice, it also enhances our understanding of the debate over reform. Considerations of class are revealed to have been fundamental to the functioning of the illumination ritual, and those considerations were used by reformers for tactical purposes. Based on extensive research in contemporary newspapers, the article reframes our understanding of the changes occurring in Britain’s political culture as it entered a new phase of liberal democratic modernity.
Transiently achieved very low LDL-cholesterol levels by statin and alirocumab after acute coronary syndrome are associated with cardiovascular risk reduction: the ODYSSEY OUTCOMES trial
Authors: Schwartz Gregory G , Szarek Michael , Bhatt Deepak L , Bittner Vera A , Bujas-Bobanovic Maja , Diaz Rafael , Fazio Sergio , Fras Zlatko , Goodman Shaun G , Harrington Robert A , Jukema J Wouter , Manvelian Garen , Pordy Robert , Ray Kausik K , Scemama Michel , White Harvey D , Steg Ph Gabriel ,   for the ODYSSEY OUTCOMES Investigators
Published: March 2023

Aims

Long-term, placebo-controlled cholesterol-lowering trials have demonstrated legacy effects (clinical benefits that persist or emerge after trial end). It is unknown whether legacy effects follow a short period of very low low-density lipoprotein cholesterol (LDL-C) levels achieved with statin plus PCSK9 inhibitor.

Methods and results

In 18,924 patients post-acute coronary syndrome, the ODYSSEY OUTCOMES trial compared the PCSK9 inhibitor alirocumab with placebo, each added to high-intensity or maximum-tolerated statin therapy. Patients with two consecutive LDL-C levels <0.39 mmol/L (15 mg/dL) on alirocumab had blinded placebo substitution for the remainder of the trial with continued statin treatment. In post hoc analyses, major adverse cardiovascular events (MACE) in these patients were compared to MACE in propensity score-matched patients from the placebo group with similar baseline characteristics and study medication adherence. In the alirocumab group, 730 patients had blinded placebo substitution at a median 8.3 months from randomization, after a median 6.0 months with LDL-C < 0.39 mmol/L. They were matched to 1460 placebo patients. Both groups had lower baseline LDL-C and lipoprotein(a) and better study medication adherence than the overall cohort. Over a median follow-up of 2.8 years, MACE occurred in 47 (6.4%) alirocumab patients with limited-duration, very low achieved LDL-C versus 122 (8.4%) matched placebo patients (treatment hazard ratio 0.72; 95% confidence interval 0.51, 0.997; P = 0.047).

Conclusions

A short period of LDL-C levels <0.39 mmol/L achieved with statin and alirocumab, followed by statin monotherapy, was associated with lower risk of MACE than statin monotherapy throughout the observation period. Clinical benefit persisted for several years.

Trial registration

ClinicalTrials.gov NCT01663402
Non-coding RNA and arrhythmias: expression, function, and molecular mechanism
Authors: Zeng Yuhong , Wu Na , Zhang Zhihui , Zhong Li , Li Guowei , Li Yafei
Published: March 2023

Arrhythmias are a class of cardiac dysfunction characterized by heart rate disturbances and heart rhythm abnormalities, which are associated with substantial morbidity and mortality. Due to the limited understanding of pathological mechanism, current antiarrhythmic drugs and invasive therapies on arrhythmias lack sufficient efficacy and are always accompanied by potential adverse effects. Non-coding RNAs (including microRNAs, long non-coding RNAs, circular RNAs, and other small non-coding RNAs) have been demonstrated to be involved in the occurrence and development of various diseases including arrhythmias, which opens a new prospect for exploring the mechanism of arrhythmias and developing new therapeutic targets. Therefore, in this review, we aimed to provide an overview of the expression of ncRNAs in various arrhythmias, their roles in the arrhythmia’s development and pathophysiology, and the potential mechanism of ncRNAs in arrhythmias. As atrial fibrillation (AF) is the most common arrhythmia in clinical practice and current studies mainly focus on it, this review primarily discussed about AF. It was expected that this review may provide a basis for a better understanding of the mechanistic role of ncRNAs in arrhythmias and facilitate the development of mechanic-based therapeutic targets.
Outcomes of percutaneous left atrial appendage occlusion device implantation in atrial fibrillation patients based on underlying stroke risk
Authors: Messele Lydia Fekadu , Khan Muhammad Zia , Darden Douglas , Agarwal Siddharth , Krishan Satyam , Pasupula Deepak Kumar , Ul Abideen Asad Zain , Balla Sudarshan , Singh Gagan D , Srivatsa Uma N , Munir Muhammad Bilal
Published: March 2023

Aims

To determine outcomes in atrial fibrillation patients undergoing percutaneous left atrial appendage occlusion (LAAO) based on the underlying stroke risk (defined by the CHA2DS2-VASc score).

Methods and results

Data were extracted from the National Inpatient Sample for calendar years 2016–20. Left atrial appendage occlusion implantations were identified on the basis of the International Classification of Diseases, 10th Revision, Clinical Modification code of 02L73DK. The study sample was stratified on the basis of the CHA2DS2-VASc score into three groups (scores of 3, 4, and ≥5). The outcomes assessed in our study included complications and resource utilization. A total of 73 795 LAAO device implantations were studied. Approximately 63% of LAAO device implantations occurred in patients with CHA2DS2-VASc scores of 4 and ≥5. The crude prevalence of pericardial effusion requiring intervention was higher with increased CHA2DS2-VASc score (1.4% in patients with a score of ≥5 vs. 1.1% in patients with a score of 4 vs. 0.8% in patients with a score of 3, P < 0.01). In the multivariable model adjusted for potential confounders, CHA2DS2-VASc scores of 4 and ≥5 were found to be independently associated with overall complications [adjusted odds ratio (aOR) 1.26, 95% confidence interval (CI) 1.18–1.35, and aOR 1.88, 95% CI 1.73–2.04, respectively] and prolonged length of stay (aOR 1.18, 95% CI 1.11–1.25, and aOR 1.54, 95% CI 1.44–1.66, respectively).

Conclusion

A higher CHA2DS2-VASc score was associated with an increased risk of peri-procedural complications and resource utilization after LAAO. These findings highlight the importance of patient selection for the LAAO procedure and need validation in future studies.
Pruning revisited – effect of pruning season on wood discoloration and occlusion in four temperate broadleaved tree species
Authors: Lund Anna , Levinsson Anna , Östberg Johan , Wiström Björn
Published: March 2023

Pruning is a necessary part of tree management both in silvicultural systems and in urban forestry. For the wood industry’s production of high-quality timber, as well as for the urban forest’s risk reduction and ecosystem services enhancements, it is essential that the pruning is accurately implemented. This study aimed to determine the effect of pruning season on discoloration amount and occlusion rate in four broadleaved tree species. In 2014, 84 trees were pruned in January, May and September. Six years later, the 252 samples from the three pruning points per tree were collected and analysed. ‘Common oak (Quercus robur L.)’ and ‘small-leaved lime (Tilia cordata Mill.)’ showed least discoloration when pruned in January, ‘wild cherry (Prunus avium L.)’ showed least discoloration when pruned in September and ‘Norway maple (Acer platanoides L.)’ did not show any significant differences. All species occluded fastest when pruned in January, but at different rates. Common oak occluded 84 per cent of the samples, Norway maple 42 per cent, small-leaved lime 32 per cent and wild cherry 13 per cent. In summary, the pruning month affected discoloration amounts and occlusion rates of the tested tree species in varied ways. Our research suggests an important knowledge gap regarding optimal species-specific pruning times and underlying reasons for different reactions to pruning.
FAIR data station for lightweight metadata management and validation of omics studies
Authors: Nijsse Bart , Schaap Peter J , Koehorst Jasper J
Published: March 2023

Background

The life sciences are one of the biggest suppliers of scientific data. Reusing and connecting these data can uncover hidden insights and lead to new concepts. Efficient reuse of these datasets is strongly promoted when they are interlinked with a sufficient amount of machine-actionable metadata. While the FAIR (Findable, Accessible, Interoperable, Reusable) guiding principles have been accepted by all stakeholders, in practice, there are only a limited number of easy-to-adopt implementations available that fulfill the needs of data producers.

Findings

We developed the FAIR Data Station, a lightweight application written in Java, that aims to support researchers in managing research metadata according to the FAIR principles. It implements the ISA metadata framework and uses minimal information metadata standards to capture experiment metadata. The FAIR Data Station consists of 3 modules. Based on the minimal information model(s) selected by the user, the “form generation module” creates a metadata template Excel workbook with a header row of machine-actionable attribute names. The Excel workbook is subsequently used by the data producer(s) as a familiar environment for sample metadata registration. At any point during this process, the format of the recorded values can be checked using the “validation module.” Finally, the “resource module” can be used to convert the set of metadata recorded in the Excel workbook in RDF format, enabling (cross-project) (meta)data searches and, for publishing of sequence data, in an European Nucleotide Archive–compatible XML metadata file.

Conclusions

Turning FAIR into reality requires the availability of easy-to-adopt data FAIRification workflows that are also of direct use for data producers. As such, the FAIR Data Station provides, in addition to the means to correctly FAIRify (omics) data, the means to build searchable metadata databases of similar projects and can assist in ENA metadata submission of sequence data. The FAIR Data Station is available at https://fairbydesign.nl.
Estimation of location errors for local seismic network in an area with intense and weak seismicity
Authors: Kokowski Jakub , Rudziński Łukasz
Published: March 2023

We have modified a method for estimation of location errors distribution for local seismic networks in area with intense shallow seismicity. We have used the variance-covariance matrices in a regular grid of points. The traveltime residuals variance is calculated as a function of source–receiver distance, while the new idea is to estimate the detection range of seismic stations on the basis of the probability of detection plots. In consequence, the method enables the evaluation of the applied velocity models during the analysis of traveltime residuals, as well as evaluation of the usefulness of individual stations with the use of probability plots. Ultimately, it provides assessment of the station configuration by analysing the distribution of location errors. The data needed for the analysis are a seismic catalogue containing earthquakes locations together with traveltime residuals and the velocity model, as well as stations metadata. The method is tested on using the real data which come from the LUMINEOS local seismic network, the network used for induced seismicity monitoring in the Legnica–Głogow Copper District in Poland.
Novel method to specifically determine the structures of non-N297 glycans in IgGs
Authors: Bhide Gaurang P , Bohrer Natalie E , Song Danying , Cabel Jeanne , Lake Marc R , Harlan John E , Miesbauer Laura J
Published: March 2023

Monoclonal antibodies comprise a major class of biologic therapeutics and are also extensively studied in immunology. Given the importance of glycans on antibodies, fluorescent labeling of enzymatically released glycans and their LC/MS analysis is routinely used for in-depth characterization of antibody glycosylation. In this technical note, we propose a method for facile characterization of glycans in the variable region of antibodies using sequential enzymatic digests with Endoglycosidase-S2 and RapidTM Peptide-N-Glycosidase-F followed by labeling with a fluorescent dye carrying an NHS-carbamate moiety. The results and proposed mechanism also suggest that the choice of glycosidases along with the labeling chemistry is critical for accurate glycan analysis for a desired application.
Civilizational exceptionalism in international affairs: making sense of Indian and Turkish claims
Authors: Haug Sebastian , Roychoudhury Supriya
Published: March 2023

Claims to civilizational exceptionalism have long been part of how states manoeuvre international affairs. While scholarly attention has started to move beyond the civilizational claims of western powers by engaging with those of states beyond the West, few accounts provide in-depth examinations of specific cases or bring these into dialogue with one another. This article offers a comparative analysis of how and why India and Turkey are positioning themselves as civilizational forces in global forums and international cooperation initiatives. Under the Narendra Modi regime, civilizational framings in India have found expression in the seemingly benign discourse of Hindu internationalism. In Turkey, successive governments under Recep Tayyip Erdoğan have linked their engagement abroad to the legacies of the Ottoman Empire. While there are clear differences in their respective civilizational antecedents, both countries draw on a combination of moral superiority and responsibility—India as vishwaguru (the world's guru) and Turkey as dünyanın vicdanı (the world's conscience)—as the legitimizing base for their assumed (normative) exceptionalism on the international stage. Overall, we argue that Indian and Turkish claims to civilizational exceptionalism serve two distinct but interrelated political projects: attempts to overcome centuries-long international marginalization, and efforts to buttress competitive authoritarianism domestically.
Just decarbonization? Environmental inequality, air quality, and the clean energy transition
Authors: Diana Bridget , Ash Michael , Boyce James K
Published: March 2023

Environmental inequalities are often large and consequential, exacerbating vertical inequalities of income and class and horizontal inequalities along lines of race and ethnicity. Climate policies can widen these inequalities as well as mitigate them, depending on their design. Decarbonization of the US electricity sector illustrates these possibilities. A strategy narrowly focused on carbon reduction alone is likely in some regions to increase disparities in exposure to localized co-pollutants emitted by fossil fuel combustion and, in some cases, to increase exposure in absolute terms. Strategies that in addition explicitly mandate improvements in air quality, both overall and specifically for frontline communities, can couple decarbonization with remediation of environmental inequalities and broad-based gains in public health.
Influence of Chronic Electroconvulsive Seizures on Plasticity-Associated Gene Expression and Perineuronal Nets Within the Hippocampi of Young Adult and Middle-Aged Sprague-Dawley Rats
Authors: Jaggar Minal , Ghosh Shreya , Janakiraman Balaganesh , Chatterjee Ashmita , Maheshwari Megha , Dewan Vani , Hare Brendan , Deb Sukrita , Figueiredo Dwight , Duman Ronald S , Vaidya Vidita A
Published: March 2023

Background

Electroconvulsive seizure therapy is often used in both treatment-resistant and geriatric depression. However, preclinical studies identifying targets of chronic electroconvulsive seizure (ECS) are predominantly focused on animal models in young adulthood. Given that putative transcriptional, neurogenic, and neuroplastic mechanisms implicated in the behavioral effects of chronic ECS themselves exhibit age-dependent modulation, it remains unknown whether the molecular and cellular targets of chronic ECS vary with age.

Methods

We subjected young adult (2–3 months) and middle-aged (12–13 months), male Sprague Dawley rats to sham or chronic ECS and assessed for despair-like behavior, hippocampal gene expression, hippocampal neurogenesis, and neuroplastic changes in the extracellular matrix, reelin, and perineuronal net numbers.

Results

Chronic ECS reduced despair-like behavior at both ages, accompanied by overlapping and unique changes in activity-dependent and trophic factor gene expression. Although chronic ECS had a similar impact on quiescent neural progenitor numbers at both ages, the eventual increase in hippocampal progenitor proliferation was substantially higher in young adulthood. We noted a decline in reelin⁺ cell numbers following chronic ECS only in young adulthood. In contrast, an age-invariant, robust dissolution of perineuronal net numbers that encapsulate parvalbumin⁺ neurons in the hippocampus were observed following chronic ECS.

Conclusion

Our findings indicate that age is a key variable in determining the nature of chronic ECS-evoked molecular and cellular changes in the hippocampus. This raises the intriguing possibility that chronic ECS may recruit distinct, as well as overlapping, mechanisms to drive antidepressant-like behavioral changes in an age-dependent manner.
Effect of Immune-Modulatory Interventions on Asymptomatic Cytomegalovirus Shedding During Suppressive Antiretroviral Therapy
Authors: Hastie Elizabeth , Moser Carlee , Sun Xin , Lennox Jeffrey , Hsue Priscilla Y , Bosch Ronald J , Deeks Steven , Meneses Milenka V , Lederman Michael M , Hunt Peter , Henrich Timothy J , Marconi Vincent C , Gianella Sara
Published: March 2023

Long-term consequences of human immunodeficiency virus (HIV) are likely the result of persistent inflammation and immune dysfunction of which cytomegalovirus (CMV) is a known contributor. We leveraged 2 AIDS Clinical Trials Group clinical trials exploring the effects of immune modulators (ruxolitinib and sirolimus) on inflammation in people with HIV on antiretroviral therapy to determine whether these interventions affected CMV shedding at various mucosal sites. Analyzing 635 mucosal samples collected, we found no significant difference in CMV levels across study arms or time points. Men had more CMV shedding than women. We did confirm an association between higher CMV DNA and immune markers associated with HIV persistence and HIV-associated mortality rates.
The Art of Brexit
Authors: Tallis Benjamin
Published: March 2023

Brexit is widely acknowledged as an important event in recent international relations (IR) and emblematic of polarization in Western societies. This article challenges the conventional wisdom that the two sides of the Brexit debate (Leave and Remain) have little in common and that the division of British society into entrenched Euroskeptic/Europhile camps neatly corresponds to cleavages between liberal “cosmopolitans” and conservative “nationals.” Rather, I show that “Euroskeptic” positions are also found in “Europhile” culture. I focus on the British Broadcasting Corporation’s popular and prolific “Art of” collection of miniseries (nearly 40 hours of programming over a decade), which offers a significant but hitherto unexplored archive. I explore this novel empirical material by combining interpretive research with a “societal multiplicity” framework, which overcomes the methodological nationalism of some Brexit analyses, to demonstrate that this seemingly cosmopolitan, liberal programming also reproduces tropes of “Anglo-British” chauvinistic exceptionalism. I argue that this exceptionalism (across the divides) contributed to a mode of societal differentiation that helped drive Brexit and will continue to affect Britain's options and preferences for interaction and combination with other states and societies. This provides theoretically informed empirical analysis of IR “where we least expect it” and shows the policy value of cultural IR.
From Political Violence to Political Trust? How Transitional Justice Affects Citizen Views of Government
Authors: Kitagawa Risa
Published: March 2023

How does transitional justice affect trust in government? Political trust is central to peaceful conflict resolution, but less is known about the ability of different transitional justice efforts to build confidence in government after war. Using survey-experimental evidence from post-conflict Guatemala, I compare how three commonly deployed justice policies (trials, truth commissions, and reparations) and political rhetoric accompanying them affect citizen attitudes toward government. Exposure to information about a trial or reparations program, which convey costly signals, led to significantly higher levels of political trust and perceived political legitimacy, when compared to the truth commission treatment. Further, a moral rhetoric emphasizing the normative claims of war victims was significantly more effective than either an instrumental rhetoric emphasizing institutional benefits or the absence of justification, regardless of policy content. The micro-level evidence reveals how the trust-building functions of transitional justice are far from uniform, speaking to the pivotal role of political communication.
Exploitation of a novel adjuvant for polymyxin B against multidrug-resistantAcinetobacter baumannii
Authors: Kim Seon-Yeong , Seo Hwi Won , Park Min-Seon , Park Chul Min , Seo Jinho , Rho Jaerang , Myung Subeen , Ko Kwan Soo , Kim Jun-Seob , Ryu Choong-Min
Published: March 2023

Background

Although polymyxin has been used as a last-resort antibiotic against resistant bacteria, its use is restricted due to nephrotoxicity and neurotoxicity. While the present antibiotic resistance issue compels clinicians to reconsider polymyxin use in severe illness cases, polymyxin-resistant microorganisms exert an effect.

Objectives

To address the issue of antibiotic resistance, the cycle of developing new antibiotics to counteract emerging resistance must be discontinued. Here we tried to develop novel therapies that do not rely on direct antimicrobial activity and thus do not promote antibiotic resistance.

Methods

By a high-throughout screening system based on bacterial respiration, chemical compounds accelerating the antimicrobial effects of polymyxin B were screened. In vitro and in vivo tests were performed to validate adjuvanticity. In addition, membrane depolarization and total transcriptome analysis were used to determine molecular mechanisms.

Results

PA108, a newly discovered chemical compound, was used to eradicate polymyxin-resistant A. baumannii and three other species in the presence of polymyxin B at concentrations less than the MIC. Since this molecule lacks self-bactericidal action, we hypothesized that PA108 acts as an antibiotic adjuvant, enhancing the antimicrobial activity of polymyxin B against resistant bacteria. At working concentrations, no toxicity was observed in cell lines or mice, although co-treatment with PA108 and polymyxin B increased survival of infected mouse and decreased bacterial loads in organs.

Conclusions

Boosting antibiotic efficiency through the use of antibiotic adjuvants holds significant promise for tackling the rise in bacterial antibiotic resistance.
Development and preliminary validation of a modified EUCAST yeast broth microdilution MIC method with Tween 20-supplemented medium for rezafungin
Authors: Zuill Douglas E , Almaguer Amanda L , Donatelli Joanna , Arendrup Maiken Cavling , Locke Jeffrey B
Published: March 2023

Background

Rezafungin is a novel, once-weekly echinocandin. EUCAST rezafungin MIC testing has been associated with a good separation of WT and target gene mutant isolates in single-centre studies, but an unacceptable inter-laboratory MIC variation has prevented EUCAST breakpoint setting. This has been attributed to non-specific binding to surfaces across microtitre plates, pipettes, reservoirs, etc. used, as previously encountered for some antibiotics.

Objectives

To investigate use of a surfactant to mitigate non-specific binding of rezafungin in EUCAST E.Def 7.3 MIC testing.

Methods

Surfactants including Tween 20 (T20), Tween 80 (T80) and Triton X-100 (TX100) were evaluated for stand-alone or synergistic antifungal activity via checkerboard assays in combination with rezafungin. Subsequent T20 studies defined an optimized assay concentration, validated in up to four microtitre plate types for WT and fks mutant Candida strains (seven species total) and the six-strain EUCAST Candida quality control (QC) panel. Lastly, T20 inter-manufacturer variability, thermostability and best handling practices were investigated.

Results

T20 and T80 performed equivalently, with characteristics slightly preferable to TX100. Due to existing use in EUCAST mould susceptibility testing, T20 was pursued. An optimized concentration of 0.002% T20 normalized rezafungin MIC values across plate types for all Candida spp. evaluated, maintained differentiation of WT versus fks mutants and generated robust QC ranges. Additionally, T20 performance was consistent across manufacturers and temperatures. T20 can be reliably transferred utilizing a syringe, wide-orifice pipette tip and/or by mass.

Conclusions

Supplementation of RPMI (Roswell Park Memorial Institute) 1640 medium with 0.002% T20 generated a highly reproducible EUCAST yeast MIC methodology for rezafungin.
AACC Guidance Document on Cervical Cancer Detection: Screening, Surveillance, and Diagnosis
Authors: Zhu Yusheng , Feldman Sarah , Leung Shuk On Annie , Creer Michael H , Warrick Joshua , Williams Nicole , Mastorides Stephen
Published: March 2023

Background

Persistent genital infection with high-risk human papilloma virus (hrHPV) causes the vast majority of cases of cervical cancer. Early screening, ongoing surveillance, and accurate diagnosis are crucial for the elimination of cervical cancer. New screening guidelines for testing in asymptomatic healthy populations and management guidelines for managing abnormal results have been published by professional organizations.

Content

This guidance document addresses key questions related to cervical cancer screening and management including currently available cervical cancer screening tests and the testing strategies for cervical cancer screening. This guidance document introduces the most recently updated screening guidelines regarding age to start screening, age to stop screening, and frequencies of routine screening as well as risk-based management guidelines for screening and surveillance. This guidance document also summarizes the methodologies for the diagnosis of cervical cancer. Additionally, we propose a report template for human papilloma virus (HPV) and cervical cancer detection to facilitate interpretation of results and clinical decision-making.

Currently available cervical cancer screening tests include hrHPV testing and cervical cytology screening. The screening strategies can be primary HPV screening, co-testing with HPV testing and cervical cytology, and cervical cytology alone. The new American Society for Colposcopy and Cervical Pathology guidelines recommend variable frequencies of screening and surveillance based on risk. To implement these guidelines, an ideal laboratory report should include the indication for the test (screening, surveillance, or diagnostic workup of symptomatic patients); type of test (primary HPV screening, co-testing, or cytology alone); clinical history of the patient; and prior as well as current testing results.
Genetic associations between human-directed behavior and intraspecific social aggression in growing pigs
Authors: Desire Suzanne , Calderón Díaz Julia A , Lewis Craig R G , Roehe Rainer , Turner Simon P
Published: March 2023

This study estimated the genetic parameters for human-directed behavior and intraspecific social aggression traits in growing pigs, and explored the phenotypic correlations among them. Data on 2,413 growing pigs were available. Pigs were mixed into new social groups of 18 animals, at 69 ± 5.2 d of age and skin lesions (SL) were counted 24 h (SL24h) post-mixing. Individual behavioral responses to isolation in a weighing crate (CRATE) or when alone in an arena while a human directly approached them (IHAT) were assessed within 48 h post-mixing. Additionally, pigs were tested for behavioral responses to the presence of a single human observer walking in their home pen in a circular motion (WTP) within one (T1) and 4 wk post-mixing (T2) noting pigs that followed, nosed or bit the observer. Animal models were used to estimate genetic and phenotypic parameters for all studied traits. Heritabilities (h2) for SL, CRATE and IHAT responses were low to moderate (0.07 to 0.29), with the highest h2 estimated for speed of moving away from the approaching observer. Low but significant h2 were estimated for nosing (0.09) and biting (0.11) the observer at T2. Positive high genetic correlations (rg) were observed between CRATE and IHAT responses (0.52 to 0.93), and within SL traits (0.79 to 0.91) while positive low to high correlations between the estimated breeding values (rEBV) were estimated within the WTP test (0.24 to 0.59) traits. Positive moderate rg were observed between CRATE and central and posterior SL24h. The rEBV of CRATE and IHAT test responses and WTP test traits were low, mostly negative (−0.21 to 0.05) and not significant. Low positive rEBV (0.06 to 0.24) were observed between SL and the WTP test traits. Phenotypic correlations between CRATE and IHAT responses and SL or WTP test traits were mostly low and not significant. Under the conditions of this study, h2 estimates for all studied traits suggest they could be suitable as a method of phenotyping aggression and fear/boldness for genetic selection purposes. Additionally, genetic correlations between aggression and fear indicators were observed. These findings suggest selection to reduce the accumulation of lesions is likely to make pigs more relaxed in a crate environment, but to alter the engagement with humans in other contexts that depends on the location of the lesions under selection.
Attitudes of Practicing Radiologists Toward the Management of Palpable Circumscribed Breast Masses
Authors: Mahboubi-Fooladi Zahra , Sabahi Marjaan , Astani Seyed Amin , Khazaei Mehdi , Ghomi Zahra
Published: March 2023

Objective

To investigate the attitudes of radiologists toward palpable breast masses with benign features on US and to determine the factors influencing their decision.

Methods

A 20-question online questionnaire was sent to radiologists with membership of the Iranian Society of Radiology and included questions regarding demographics, practice experience, and management approach to palpable circumscribed breast masses based on patient age and risk factors. Radiologists’ management choice for masses in themselves or close relatives/friends was also queried.

Results

In total, 151 radiologists participated (response rate 16%). For palpable breast masses with benign imaging features in women at high risk, the majority of radiologists selected MRI (95/151, 62.9%) and core-needle biopsy (110/151, 72.8%). In average-risk patients, radiologists with >5 years of practice experience selected biopsy more frequently (33/79, 41.8%) than less experienced radiologists (17/79, 23.6%) for patients ≥40 years old (P < 0.001) and patients <40 years old (20/79, 25.3%; 11/72, 15.3%, respectively) (P = 0.014). Similarly, selecting biopsy was more common in radiologists who completed a breast imaging fellowship for patients ≥40 years old (23/45, 51.1% vs 27/106, 25.5%) (P = 0.04), as well as for patients <40 years old (18/45, 40% vs 13/106, 12.3%) (P = 0.02). Radiologists who were <40 years old selected biopsy more frequently if evaluating a mass in themselves (22/86, 25.6%) compared to patients (15/86, 17.4%) (P < 0.001).

Conclusion

Radiologist experience and educational background, as well as patient baseline breast cancer risk, can predispose radiologists to choose biopsy for palpable breast masses despite a benign appearance on imaging.
A30 EPITHELIAL FUNCTION OF THE CIRCADIAN CLOCK GENE, BMAL1, IS NECESSARY FOR COLONIC REGENERATION
Authors: Taleb Z , Haireek M , Stokes K , Wang H , Collins S , Khan W , Karpowicz P
Published: March 2023

Background

The circadian clock is a self-sustained molecular oscillator which drives 24-hour physiological rhythms. It consists of the genes Bmal1 and Clock that positively regulate Cry and Per, their negative regulators, resulting in a 24-hour transcription/translation feedback loop. Shift work, which causes disruptions to 24-hour physiological rhythms, has been shown to lead to an increased incidence of inflammatory bowel disease (IBD). We have previously established that mice lacking the non-redundant circadian regulator, Bmal1, exhibit more severe colitis compared to controls.

Purpose

This study aims to investigate the epithelial function of Bmal1 in colonic regeneration during colitis.

Method

In order to assess the cell-specific role of the clock, we tested the regenerative effects of Bmal1 in intestinal epithelial tissue using Vil+/+;Bmal1flox/flox (control) and VilCre/+;Bmal1flox/flox (conditional mutant) mice. Dextran Sulfate Sodium (DSS) was applied to induce acute colitis. Disease progression was evaluated during colitis and during recovery upon removal of DSS treatment. We hypothesized that the absence of a functional circadian clock disrupts effective proliferation and regeneration of intestinal epithelial cells during colitis remission.

Result(s)

Vil +/+ ;Bmal1 flox/flox control and VilCre/+;Bmal1flox/flox conditional mutant mice exhibit no significant differences in disease severity or tissue histopathology during colitis. However, after the removal of DSS, VilCre/+;Bmal1flox/flox conditional mutants show increased total lesions and overall inflammation, decreased crypt density as well as a higher propensity of hyperplastic crypts in the tissue. Regenerative ability of the colon is decreased in conditional mutants: phosphorylated-histone H3 and Ki67 show persistent increases in mitosis and overall proliferation near ulcerated lesions. This suggests that, while controls complete the regenerative response, conditional mutants fail to recover from colitis and show inefficient regeneration when Bmal1 is disrupted in intestinal epithelial cells.

Conclusion(s)

Our results support a critical role for Bmal1 in intestinal epithelial cells during post-colitis regeneration and recovery.

Please acknowledge all funding agencies by checking the applicable boxes below

CIHR, Other

Please indicate your source of funding;

OGS, Crohn's & Colitis Canada

Disclosure of Interest

None Declared
A36 INVESTIGATING TYPE 1 REGULATORY T CELLS AS A THERAPY FOR INFLAMMATORY BOWEL DISEASE USING A MOUSE MODEL OF ACUTE INTESTINAL EPITHELIAL DAMAGE
Authors: Poloni C , Sze A , Wang X , Lim S , Steiner T
Published: March 2023

Background

Inflammatory bowel disease (IBD) affects an estimated 270,000 people in Canada and is rapidly increasing in prevalence. All patients have relapsing disease, and a subset of individuals do not respond to current treatments. Further, there are no approved treatment options in Canada that reverse IBD-induced intestinal fibrosis. We have previously shown type 1 regulatory cells (Tr1s) are capable of suppressing inflammatory macrophages, promote barrier function of human intestinal epithelial cells, and induce differentiation of mucin-producing goblet cells. We hypothesize that Tr1 cells can prevent inflammatory damage and fibrosis in an mouse model of acute gut damage.

Purpose

We hypothesize that Tr1 cells can prevent inflammatory damage and fibrosis in an mouse model of gut damage. Here we evalute the therapeutic potential of Tr1 cells in an model of acute intestinal epithelial damage.

Method

Tr1 cells were isolated and expanded from CD4+ CD44high FOXP3- cells. Their phenotype was characterized by flow cytometry and cytokine secretion was measured via ELISA. WT B6 mice were given 2% DSS in H2O for 7 days, followed by H2O alone for 7 days. Prior to DSS treatment, mice were sub-lethally irradiated to facilitate engraftment, and given I.P. injections of PBS or 0.5 – 2 x 106 Tr1 cells. Mice weights and health scores were recorded daily. At the endpoint, blood, spleen, and mesenteric lymph nodes were analyzed for Tr1 cell engraftment (or lack thereof) for each mouse. Complete white blood counts were performed for each mouse. Additionally, proximal, medial, and distal portions of the ileum were processed for histologic scoring.

Result(s)

Tr1 cells isolated from CD4+ CD44high FOXP3- cells produce high levels of IL-10 following stimulation (>35,000 pg/ml/1 x 105 cells). Additionally, these cells express high levels of Tr1 markers CD49b and Lag-3. Optimization experiments indicated no significant differences between mice irradiated and given DSS and mice only given DSS (no irradiation). Our results suggest no significant differences in inflammatory cell infiltrate scores between control and Tr1 treated mice. However, gut architecture scores appeared to improve with increasing Tr1 doses. Further, weight change improved with Tr1 treatment, as compared to PBS controls. Interestingly, Tr1 treatment appeared to decrease total eosinophil and neutrophil counts from peripheral blood.

Conclusion(s)

Our initial findings indicate Tr1 adoptive transfer prior to acute damage via DSS improves gut damage and weight loss.

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CIHR

Disclosure of Interest

None Declared
A44 A 1000 PATIENT CANADIAN NETWORK FOR AUTOIMMUNE LIVER DISEASE EVALUATION OF CLINICAL AND DEMOGRAPHIC PATTERNS OF AUTOIMMUNE HEPATITIS
Authors: Plagiannakos C G , Montano-Loza A J , Lytvyak E , Pallotta J , Mason A L , Qumosani K M , Worobetz L , Flemming J A , Hercun J , Vincent C , Cheung A , Chen T , Grbic D , Swain M G , Gulamhusein A , Hansen B E , Hirschfield G M
Published: March 2023

Background

We sought to understand how the demographics of autoimmune hepatitis (AIH) have changed over time in Canada.

Purpose

Using a large multi-centre Canadian cohort of patients with AIH, we describe the trends in patient and disease characteristics at presentation across 30 years of clinical practice.

Method

Patients from the Canadian Network for Autoimmune Liver Disease with a confirmed diagnosis of AIH (simplified score ≥6) were included for analysis. Patients were grouped into five cohorts according to the year of diagnosis (i.e., <2000, 2000-2004, 2005-2009, 2010-2014, ≥2015). Patient demographics and baseline clinical and biochemistry features of disease activity were investigated using Chi-square tests and Kruskal-Wallis tests adjusted for multiple comparisons. Logistic and linear regression models with estimated means were utilized to further investigate relationships with time and to adjust for confounding.

Result(s)

1016 patients followed across 10 Canadian health centres with AIH were diagnosed between November 1965 and December 2021. Overall, 76.4% (n=776) of patients were female, and the median age at diagnosis was 46 years (IQR 28.2 - 58.3). Cirrhosis at presentation was seen in 20.6% of patients (n=209). The median age at diagnosis increased significantly from 31.8 years [IQR 17.9 - 46.8] pre-2000 to 54 years [IQR 9.0 - 95.2] after 2014 (p<0.001; Figure 1a). This effect of time persisted after adjusting for sex and cirrhosis status at diagnosis. Female sex and the presence of cirrhosis at diagnosis were factors independently associated with older age at presentation (p<0.0001).

The proportion of patients that presented with cirrhosis at diagnosis increased significantly over calendar time, from 13.7% (n=23) pre-2000 to 30.8% (n=69) after 2014 (p=0.003; Figure 1b). Male sex was independently associated with an increased odds of having cirrhosis at presentation (OR= 1.46, CI 1.02 - 2.07) and higher baseline ALT levels compared to females (p=0.036). The proportion of patients that identified as non-white ethnicity increased significantly from 15.2% (n= 24) pre-2000, to 32% (n= 86) after 2014 (p<0.001, Figure 1b). This effect of time on ethnicity was most pronounced after the year 2010 (OR= 2.32, CI 1.39 - 3.98) and persisted after adjusting for sex. There was no significant pattern of change in sex over calendar time.

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Conclusion(s)

In Canada, patients with AIH at presentation are now older, have more advanced disease, and are more ethnically diverse than when compared to 30 years ago.

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Other

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industry

Disclosure of Interest

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A65 VISCERAL FAT INDICES: DO THEY HELP DIFFERENTIATE CROHN’S DISEASE AND INTESTINAL TUBERCULOSIS IN CHILDREN?
Authors: Srivastava A , Seetharaman J , Yadav R R , Singh S , Mishra P , Sarma M S , Poddar U
Published: March 2023

Background

Crohn’s disease (CD) and Intestinal tuberculosis (ITB) mimic each other and are often difficult to differentiate. A correct and prompt diagnosis is essential for a good outcome. Mesenteric fat hypertrophy is a feature of CD and studies in adults have shown higher visceral fat in CD than ITB. There is no published data in children.

Purpose

This study evaluated the utility of visceral fat indices in differentiating CD and ITB in children.

Method

Symptomatic children diagnosed to have CD or ITB based on standard recommended criteria were enrolled. The clinical and laboratory details were noted. Abdominal fat was measured on Computed Tomography in supine position at the level of L4 vertebrae. Visceral fat (VF) and subcutaneous fat (SF) area was measured separately by an experienced radiologist, blinded to the diagnosis. Sum of VF and SF was taken as total fat (TF). VF/SF and VF/TF ratio was calculated.

Result(s)

34 children [14 boys, median age 14.0 (inter quartile range 10.8-17.0)] years were recruited, of which 12 (29%) had CD [7 boys, age 13.0 (IQR 9.25-16.5) years] and 22 (71%) had ITB [7 boys, age-14.5 (IQR 11-17) years]. Visceral fat area (VF) was significantly higher in CD compared to ITB (table 1). However, there was no significant difference in the SF (2199.5 (1537.6-3881.6) vs 2176.5 (671.0-6651.5) mm2; p=0.958) and TF (3096.1 (2108.2-5373.5) vs 4518.2 (2677.6-8456.3) mm2; p=0.245) in ITB and CD respectively. The ratio of VF/SF and VF/TF was significantly higher in CD as compared to ITB for all cases (table1). When comparing CD and ITB in boys and girls separately the same trend was observed but the difference was statistically significant only for boys. On ROC analysis, VF:SF ratio of 0.609 predicted CD with the sensitivity of 75% and specificity of 86.4% (area under curve [AUC]-0.795, 95% CI 0.636-0.955; p=0.005). VF:TF ratio of 0.379 had similar sensitivity of 75% and specificity of 86.4% (AUC-0.795, 95% CI 0.636-0.955; p=0.005). The VF area of 1485.26 mm2 had a sensitivity of 83.3% and specificity of 72.7% for CD (AUC-0.758, 95% CI 0.590-0.925; p=0.01).

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Conclusion(s)

The VF/SF ratio is a simple, non-invasive, objective parameter to differentiate CD and ITB in children with a good sensitivity and specificity.

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None

Disclosure of Interest

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A73 EFFECT OF FECAL IMMUNOCHEMICAL TEST CUT-OFF LEVELS ON ADENOMA DETECTION RATE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Zarandi-Nowroozi M , Taghiakbari M , Barkun A , Pohl H , Nauche B , Chagnon M , von Renteln D
Published: March 2023

Background

Adenoma detection rate (ADR) is higher after a positive fecal immunochemical test (FIT) compared to direct screening colonoscopy.

Purpose

This meta-analysis evaluated how ADR, the rates of advanced adenoma detection (AADR), colorectal cancer detection (CDR), and sessile serrated lesion detection (SSLDR) are affected by different FIT positivity thresholds.

Method

We searched MEDLINE, EMBASE, CINAHL, and EBM Reviews databases for studies reporting ADR, AADR, CDR, and SSLDR according to different FIT cut-off values in asymptomatic average-risk individuals aged 50 to 74 years old. Data were stratified according to sex, age, time to colonoscopy, publication year, continent, and FIT kit type. Study quality, heterogeneity, and publication bias were assessed.

Result(s)

Overall, 4280 articles were retrieved and fifty-seven studies were included (332,281 FIT-positive colonoscopies; mean cecal intubation 96.2%; mean age 60.7 years; male 52.1%). Mean ADR was 55.9% (95% CI 53.2% – 58.6%), while mean AADR, CDR, and SSLDR were 27.2% (95% CI 24.3% – 30.1%), 5.4% (95% CI 4.7% – 6.1%), and 3.0% (95% CI 1.7% – 4.6%), respectively. For each 20 μg Hb/g increase in FIT cut-off level, ADR increased by 2.87% (95% CI 1.70% – 4.05%, p < 0.01), AADR increased by 3.90% (95% CI 2.76% – 5.05%, p < 0.01) and CDR by 1.46% (95% CI 0.66% – 2.24%, p < 0.01). Many detection rates were greater amongst males and Europeans.

Conclusion(s)

ADRs in FIT-positive colonoscopies are influenced by the adopted FIT positivity threshold, and identified targets, importantly, proved to be higher than most current societal recommendations.

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None

Disclosure of Interest

None Declared