bluuebunny/crossref_metadata_2025 huggingface dataset:
BadgerFilm: A new thin film analysis programme (with other useful applications for EPMA)
Authors: Moy A , Fournelle J H
Published: February 2025

Characterisation of thin films upon substrates, i.e., thickness and composition determination, can be performed using the non-destructive technique of electron probe microanalysis (EPMA). This technique, first introduced in the 1960’s and refined in the 1990’s, is based on the accurate description of the electron ionisation depth distribution, the so-called ϕ(ρz)-distribution. Using these models, several thin film analysis computer programmes have been developed and distributed. However, these programmes have some limitations: (1) older programmes may not be compatible with modern computer systems; (2) the majority of the programmes are “black boxes” making it difficult to assess the reliability of the quantification results; and (3) commercial programmes can be expensive and this might prevent a lab from acquiring one of them especially when demands for thin film quantification are occasional. And experience has shown that where an EPMA lab is searching for funds and new users/customers, the ability to do thin film characterisation can be valuable. In this article, we present the thin film analysis programme BADGERFILM. The programme is free, open-source and implements documented ϕ(ρz)-models and algorithms. The programme is versatile and can be used to characterise multilayer samples but also bulk samples. BADGERFILM demonstrated excellent quantification results for the films and for the substrates when compared to other EPMA thin film analysis programmes and to other techniques. BADGERFILM can also be employed to calculate mass absorption coefficients from multi-voltage EPMA measurements and can calculate absolute X-ray intensities directly comparable to Monte Carlo simulations.
The Long Way to the Compliance of Data Retention with European Union Law
Authors: Montuori Luigi , Tondi Veronica
Published: February 2025

In Chapter 8 the authors examine the evolution of Italian rules on retention and access to traffic data. After some introductory remarks on the guarantees ensured by Article 15 of the Italian Constitution, protecting the freedom and secrecy of communications, special attention is paid to the evolution of the case law, considering the issues which appear most sensitive, in light of the pronouncements of the Court of Justice. The analysis therefore focuses on the principles of legality and proportionality, the control by an impartial authority and the usability of data acquired in violation of European Union law. The chapter then proceeds to examine the role and decisions of the Italian Supervisory Authority, and, finally, deals with the latest intervention of the Italian legislator on the matter, which raises some doubts on the real consistency with European requirements.
Data Retention and Law Enforcement Access to Personal Data in India
Authors: Degalahal Shweta Reddy
Published: February 2025

In 2017, while affirming the status of the right to privacy as a fundamental right under the Indian Constitution, the Supreme Court set forth a threefold test (ie legality, necessity, and proportionality) that must be satisfied to impose any restrictions on the espoused right in the now famously known Puttaswamy judgment. The Court specifically stated the importance of enacting data protection legislation to protect the privacy of the individuals against the legitimate interest of the State. Despite the absence of enactment of such a legislation, there have been fragmented regulations that can be considered as a restriction on the privacy of the individuals such as the ones regarding the data retention and law enforcement access to retained personal data. Chapter 18 identifies the relevant requirements across the fragmented landscape and argues that none of them pass all the three steps of the test laid out in the Puttaswamy judgment.
Agency with judgment
Authors: Pettit Philip
Published: February 2025

When human beings make judgments, they often act intentionally in seeking and scrutinizing evidence and in deciding whether to go along with it. This intentional activity typically leads them to form corresponding beliefs and related attitudes: on–off beliefs most obviously, and by implication scalar beliefs as well. How might the humanoids come to do this, as the genealogy suggests, in the wake of language? They would naturally come to make assertions in that language—on peril of disesteem, careful and truthful assertions—sharing information with one another. Every truthful assertion would constitute a public judgment and presuppose a private or mental counterpart. Recognizing this, the humanoids would learn to make judgments for themselves alone. And as they would often be able gain new information by seeking to answer the questions of others, they would learn to look for such information by asking questions of themselves and seeking to generate answers on their own. In short, they would learn to think in an active, reflective manner.
Rationality with reasoning
Authors: Pettit Philip
Published: February 2025

Reasoning requires the subject to move from believing certain propositions to believing propositions they allegedly support because, at least in part, of believing in a supportive, premise–conclusion connection between those propositions. It presupposes a sophisticated ability to conceptualize propositions as objects to make judgments and form beliefs about, but the humanoids would learn to do this by using corresponding sentences in quotation marks as names: ‘p’ supports ‘q’. It also presupposes a conception of the normative connection of support. The humanoids would form such a connection by learning to explain and reinforce an assertion by naming the presumptively persuasive evidence or proposition that prompted it; by recognizing that this would reinforce it only for others who are not subject to distorting effects that block them from being prompted in the normal manner; and by presenting the explanation therefore as one that will work only for those whose functioning is not disrupted in that way. In effect, they will see and present it as one that any functional agent ought to endorse: as one that supports the conclusion for normally functioning agents. With that concept of support in mind they can profitably explore a range of questions together and, after interiorization, on their own. They can master reasoning and come to be able to think, in a particularly rich sense of that term.
Knowledge, Information, and Business Education in the British Atlantic World, 1620–1760
Authors: Talbott Siobhan
Published: February 2025

Accurate information is essential to successful business activity. The early modern period saw an increase in printed commercial information, including newspapers, printed exchange rates, and educational texts—part of the ‘print revolution’ that permeated all aspects of the early modern world. Yet, as this book shows, the circulation of information in manuscript and oral form remained central to business activity. Rather than relying on externally produced printed works, commercial agents retained agency in creating and sharing their own business and educational information, which was prioritized and valued over printed material. The spaces in which these agents exchanged information and the increased distances over which knowledge travelled in an expanding commercial world impacted and shaped this information exchange. An increase in volume of information presented challenges as well as benefits, producing conflicting data, giving rise to issues of trust, and increasing the need to identify and deal with misinformation. Prioritizing a wide range of manuscript material held in disparate collections, including merchants’ correspondence, letter-books, notebooks, family papers, exercise books, and ships’ logs, this book explores the ways that knowledge, information, and business education was created, circulated, and used in the early modern British Atlantic world. It offers an alternative way of looking at the exchange of business information in a period dominated by discussions of print, prioritizing manuscript and oral forms of exchange. In doing so, it presents a more holistic account of the ways that networks of knowledge operated in early modern business, centralizing the creation, circulation, and use of business information specifically by those individuals most involved in—and most affected by—its production.
Commercial Education
Authors: Talbott Siobhan
Published: February 2025

Commerce in the early modern period was a highly skilled profession. We know much about the increase in formal commercial education, the role of apprenticeships, and the publication of printed didactic texts such as advice books, but we know less about the limitations of these sources of commercial education, and much less about the other ways in which merchants trained for business. Formal learning, which was neither accessible to all nor a prerequisite for commercial success, was augmented by informal knowledge exchange and practical experience. Using manuscript notebooks, exercise books, ships’ logs, and correspondence, this chapter constructs a more holistic picture of how merchants became educated in business. Skills considered include abilities in foreign languages, knowledge of commercial jargon, understanding of weather and climate, and education in mathematics and navigation. This chapter consolidates the argument in Chapter 1 that the ‘print revolution’ did not foster a fundamental shift from manuscript and oral learning to text-based learning. It shows that merchants were not a homogeneous group, but individuals who learned in different ways and through different methods, seeking specific training that benefited their distinct business interests.
Knowledge and Use of Legal Processes
Authors: Talbott Siobhan
Published: February 2025

Commercial agents operated in peculiarly complex legal landscapes in the early modern British Atlantic world. As commercial worlds expanded, this complexity increased. This chapter explores how merchants educated themselves about legal processes and considers the information that influenced decisions about whether or not to pursue legal cases. It shows that merchants’ knowledge of ‘the law’ was not embedded in formal legal education, but in practical understandings of the ways in which justice operated in their commercial networks. While some merchants saw law courts as a last resort, others were prolifically litigious, and the context within which business took place was a highly influential factor on whether legal action was pursued. This chapter considers the role of arbitration, the rise in formal marine insurance as a legal mechanism, and the increasing use of legal instruments such as bills of exchange.
The Truth Shall Set You Free
Authors: Kovras Iosif
Published: February 2025

The chapter seeks to explain variations in the success of commissions of inquiry into economic crises, drawing on the comparative experience of the US (1930s), and Iceland (post-2008), considering them the two ‘most different’ cases. They had completely different background conditions, including the historical period (1930s vs 2010s), how the crisis unfolded (slow crisis vs rapid meltdown), the significance of the crisis for the global economy, the institutional setting of the commission (independent vs congressional), and the status of the country in the global financial system (powerful state vs small peripheral state). Yet both reached equally successful conclusions. In 1932, the US Senate mandated the Pecora Commission to identify the causes of the 1929 Wall Street Crash. In addition to analyzing the causes of the crisis, Pecora recommended innovative institutional reforms, resulting in the Glass-Steagall Act; this led to the separation of commercial and investment banking, ultimately protecting markets from a financial crisis for several decades. Iceland set up a similarly successful truth commission after the 2008 crash; its final report revealed the causes of the collapse, its recommendations were embedded in a national legal/regulatory framework, and the report itself became an instant bestseller. Drawing on extensive fieldwork, in-depth interviews with national stakeholders, and archival research, the chapter argues that having politicians with an embedded institutional learning approach is a prerequisite for a successful truth commission that can convert past policy failures into institutional lessons for the future.
Unexpected Politics
Authors: Ramzy Farah
Published: February 2025

This introductory chapter starts by asking what was the impact of the neoliberal shift in higher education in the late 1990s, and the two critical political events that Egypt witnessed, the 2011 revolution and the 2013 coup d’état, on student politics. Detailing the study of various student organizations such as clubs, associations, unions, party sections, and activist groups, through interviews and ethnographic observation, it argues for the necessity of accounting for contemporary student politics beyond its historically familiar and expected forms such as protests for national or regional causes. This chapter builds a theoretical framework to make sense of how being a student in a context of political change produces specific dynamics of politicization, by looking at the way students collectively and individually negotiate the scope of possible political action and the meanings attributed to that action.
Students and the ‘New Republic’
Authors: Ramzy Farah
Published: February 2025

This chapter shifts the perspective away from students to look at the post-2013 regime and examine the evolution of the actors and practices of repression and co-optation in universities. The post-2013 instruments of political control reflect a concomitant depoliticization of repression and politicization of co-optation, a combination rendered possible due to ambivalence within the neoliberal policies and discourses. In universities, the introduction of a private security company in a stark break with historically familiar tools and practices of repression reflects the authoritarian reconfiguration where both old and new practices are part of a new game. Furthermore, a new multidimensional youth policy, fully embracing the neoliberal imperative of the professionalization of youth, amplifies existing intersections between the regime and student organizations, systematizes a counter-revolutionary discourse, and sketches the outlines of a new illusionary authoritarian polity where youth are expected to play the role of juvenile neoliberal subjects.
Semisynthetic simulation for microbiome data analysis
Authors: Sankaran Kris , Kodikara Saritha , Li Jingyi Jessica , Cao Kim-Anh Lê
Published: February 2025

High-throughput sequencing data lie at the heart of modern microbiome research. Effective analysis of these data requires careful preprocessing, modeling, and interpretation to detect subtle signals and avoid spurious associations. In this review, we discuss how simulation can serve as a sandbox to test candidate approaches, creating a setting that mimics real data while providing ground truth. This is particularly valuable for power analysis, methods benchmarking, and reliability analysis. We explain the probability, multivariate analysis, and regression concepts behind modern simulators and how different implementations make trade-offs between generality, faithfulness, and controllability. Recognizing that all simulators only approximate reality, we review methods to evaluate how accurately they reflect key properties. We also present case studies demonstrating the value of simulation in differential abundance testing, dimensionality reduction, network analysis, and data integration. Code for these examples is available in an online tutorial (https://go.wisc.edu/8994yz) that can be easily adapted to new problem settings.
The role of Obinutuzumab in rituximab-refractory membranous nephropathy and minimal change disease
Authors: Chen Zewei , Xu Dechao , Wu Shuangcheng , Liu Wenyu , Wu Jianxiang , Yu Shengqiang , Dai Bing , Mao Zhiguo , Gao Xiang
Published: February 2025

Background

Obinutuzumab, a new-generation anti-CD20 monoclonal antibody, was originally emerged to overcome resistance to rituximab in B-cell malignancies. There is limited research regarding the use of Obinutuzumab in patients with rituximab-refractory membranous nephropathy (MN) and minimal change disease (MCD).

Methods

A retrospective analysis was performed at Changzheng Hospital from September 2022 to September 2024, and screened patients with rituximab-refractory MN or MCD. Participants were treated because of refractory to rituximab and consented to receive infusions of Obinutuzumab. Primary outcomes were defined as complete remission (CR, proteinuria < 0.3 g/d) or partial remission (PR, proteinuria < 3.5 g/d with a ≥ 50% reduction). Secondary outcome was immunological remission in patients with PLA2R-related MN.

Results

Seven patients with MN and five with MCD were included in the cohort. Among patients with MN, 6 of 7 (86%) achieved at least PR, of whom two patients reached CR with a median time to first remission (either PR or CR) of 8.0 months. Among patients with positive serum anti-phospholipase A2 receptor (PLA2R) antibodies at baseline, all achieved an immunological response. No patients experienced a relapse during the follow-up period. Among patients with MCD, all patients achieved a CR with the median time of 1.0 months. Patients with steroid-dependent or immunosuppressant-dependent were able to taper their medications in the short term without experiencing relapse. No treatment-related severe adverse events were reported.

Conclusions

Our study demonstrated that Obinutuzumab represents a promising alternative therapeutic option for the management of rituximab-refractory MN and MCD.
Comparative Public Attitudes about Drone Strikes: Survey Experiments in Italy, Poland, and Germany
Authors: Alparone Diletta , Kantorowicz Jaroslaw , Klein Graig R
Published: February 2025

Research on public attitudes about the use and efficacy of drone strikes primarily focuses on the United States. While there is a burgeoning second generation of public opinion research on drone strikes and drone warfare, in general, our understanding of cross-national public attitudes remains limited, particularly if non-US respondents behave and/or think differently. To address this, we extend Krep’s (2014) and Walsh and Schulzke’s (2018) research and conduct four surveys in three countries (Italy, Poland, and Germany) with 5,485 respondents to investigate how individuals outside the United States interpret ethical, moral, and casualty aversion framing in relation to support for drone strikes. Our results show that in all three countries, like the United States, respondents prefer drone strikes to traditional military operations but that support for drone strikes decreases when prompted with ethical and moral framing. Additional information about casualty aversion and reducing the physical risk to servicemembers’ lives does not significantly influence support for drone strikes compared to traditional military operations.
Differing Realties among Assisted Living Residents with Dementia: Understanding Care Partner Responses
Authors: Kemp Candace L , Anglin Emerald , Morgan Jennifer Craft , Perkins Molly M , Burgess Elisabeth O
Published: February 2025

Background and Objectives

Persons living with dementia can experience confusion in terms of orientation to time, place, and scenario. The ways care partners respond are apt to shape quality of life and care experiences. With a focus on assisted living (AL) residents with dementia, we seek to: 1) examine differing realities and care partner responses and 2) identify influential resident and care partner factors, other contributing contextual conditions, and response outcomes.

Research Design and Methods

We present analysis of qualitative data gathered from a grounded theory (GT) study involving eight diverse AL communities each studied for a one-year period between 2019 and 2023. Researchers followed 73 residents with dementia and 103 care partners (family, friends, AL staff, external workers, volunteers), conducting interviews (n=236) and participant observation (980 visits and 2,676 hours), and reviewing resident participants’ AL records. Guided by principles of GT, analysis was iterative, involved initial, axial, and selective coding, and led to the identification of the core category, “reality management.”

Results

Most residents experienced dementia-related confusion. In response, care partners engaged in a process of “reality management,” which involved strategies that invalidated or validated realities and emotions; these included: ignoring, dismissing, correcting, redirecting, and joining. The nature, types and expression of confusion, and resident and care partner characteristics and capacities, influenced responses and outcomes.

Discussion and Implications

Findings reinforce the value of person- and situation-specific responses and have implications for practice and underscore the need for additional research.
Killing It Softly: The ILC’S Articles on State Responsibility
Authors: Douglas Zachary
Published: February 2025

By preferring tautologies supplied by the theory of objective responsibility over general principles of liability derived from comparative law, the ILC’s Articles on State Responsibility cannot assist in operationalising the general and opentextured treaty standards for State conduct that are commonplace in many fields of international law, particularly in environmental law. Moreover, the one-size-fits-all approach to defining the secondary consequences of a wrongful act in the ILC’s Articles rests upon a conception of outright prohibition of the conduct in question and a community interest in securing the cessation of that conduct, whereas many primary obligations, if transgressed, should be properly seen as generating a duty of compensation only without the other secondary consequences that automatically follow in the ILC’s scheme of responsibility.
A1 BACTERIAL LYSOPHOSPHATIDYLCHOLINE (LPC) AND LYSOPHOSPHATIDIC ACID (LPA) INDUCE VISCERAL HYPERSENSITIVITY THROUGH TRANSIENT RECEPTOR POTENTIAL CANONICAL 5 (TRPC5) AND LYSOPHOSPHATIDIC ACID RECEPTOR 1 (LPAR1) AND 3 (LPAR3) DEPENDENT-MECHANISMS
Authors: Pujo J , De Palma G , Lu J , Rueda G H , Vicentini F A , Hall-Bruce M , Nardelli A , Verdu E , Reed D E , Vanner S J , Collins S , Bercik P
Published: February 2025

Background

Abdominal pain is the key symptom in Irritable Bowel Syndrome (IBS). Its pathophysiology is not fully understood, but low-grade inflammation and gut microbiota-diet interactions have been implicated. LPC and LPA are phospholipids generated by inflammatory processes in mammals, which are known to induce neurogenic pain through multiple channels and G-protein-coupled receptors. It is unknown whether bacteria can produce LPC/LPA and through which pathways they signal to the host.

Aims

To investigate whether bacterial LPC and LPA induce visceral hypersensitivity and identify the underlying mechanisms.

Methods

Germ-free NIH Swiss and Swiss Webster mice (n=117) were colonized for 5 weeks with fecal microbiota from IBS patients with either low or high fecal LPC/LPA levels, or microbiota from healthy controls. The mice were fed either regular chow or a diet enriched with phosphatidylcholine (PC) (2g/kg) a precursor of LPC and LPA. Visceral sensitivity was assessed by visceromotor responses (VMRs) to colorectal distension. Dorsal root ganglion (DRG) neurons from C57BL/6 mice were pretreated with a TRPC5 inhibitor (AC1903; 30 μM), an LPAR1 antagonist (AM095; 10 μM), or an LPAR1 and LPAR3 antagonist (Ki16425; 10 μM) or their vehicle (0.1% DMSO), and then treated with LPC (10 μM) or LPA (10 μM), respectively. Calcium mobilization was measured by a Cytation C10 imaging reader using a fluorescent probe Fluo-4 (1 mM). C57BL/6 mice received intracolonic infusion with a vehicle or a mix of LPC (600 μM) /LPA (25 μM), one group of mice was pretreated with AC1903 (30 μM) and Ki16425 (10 μM) prior to LPC/LPA administration, CRD was performed 90 minutes later.

Results

Mice with fecal microbiota from IBS patients with high fecal LPC/LPA displayed visceral hypersensitivity compared to mice with microbiota from healthy controls or from patients with low fecal LPC/LPA. These increased responses were seen only in mice fed PC-enriched diet, but not with regular chow. Both LPC and LPA administration increased the percentage of responding DRG neurons compared to the vehicle. The pretreatment with AC1903, AM095 or Ki16425 decreased the percentage of responding neurons when treated with LPC or LPA, respectively, compared to the vehicle. Intracolonic administration of LPC and LPA induced a significant increase in visceral sensitivity compared to the vehicle-treated mice. This increase was prevented in mice pretreated with an intracolonic injection of AC1903 and Ki16425.

Conclusions

Bacterial LPC and LPA induce neuronal activation and visceral hypersensitivity through TRPC5 and LPAR1/LPAR3-dependent mechanisms, respectively.

Funding Agencies

CIHRWeston Family Foundation
A3 CELIAC DISEASE AUTOIMMUNITY INCREASING AMONG VARIOUS PEDIATRIC SUBGROUPS IN ALBERTA, CANADA
Authors: King J A , Coward S , Godley J , Metcalfe A , Ronksley P , Kaplan G G , Williamson T
Published: February 2025

Background

Celiac disease (CeD) autoimmunity, defined as elevated tissue transglutaminase (TTG) levels with or without biopsy confirmation, is rising among children in Canada; however, further investigation is needed to understand if this varies across pediatric subpopulations.

Aims

To evaluate incidence and trends in CeD autoimmunity among different pediatric subgroups.

Methods

Using population-based administrative data, we identified individuals under 15 years old during their first positive TTG test in Alberta from April 2015 to March 2024. Based on the year of test, we determined socioeconomic status by matching patient postal code to census level dissemination area (which translate to material and social deprivation quintiles) and geographic residence. Incidence per 100,000 person-years (PY) and 95% confidence intervals (CIs) were calculated for subgroups (sex, age, rurality, material and social deprivation) within time periods (pre-pandemic [2015–2019], pandemic [2020–2022], and post-pandemic [2023–2024]). Incidence rate ratios (IRRs) were estimated to compare pre-pandemic and post-pandemic rates.

Results

A total of 5,141 children with incident CeD autoimmunity were identified. The highest incidence was observed post-pandemic (92 per 100,000 PY), particularly among those aged 5–9 years (135 per 100,000 PY), those living in the least materially deprived areas (117 per 100,000 PY), and females (113 per 100,000 PY). All subgroups saw significantly higher rates in the post-pandemic period relative to the pre-pandemic period, except for those most materially deprived (IRR = 1.1 [95% CI: 0.9, 1.4]). A larger increase in rates was seen in those most materially privileged (IRR = 1.7 [95% CI: 1.5, 2.0]). A change in incidence was also more pronounced among children in rural (IRR = 1.7 [95% CI: 1.5, 1.9]) compared to those in urban areas (IRR = 1.3 [95% CI: 1.2, 1.4]).

Conclusions

Although rates of CeD autoimmunity vary between pediatric subpopulations, most groups are experiencing significant increases over time. This includes populations historically experiencing lower rates (e.g., those in rural areas), indicating a mounting burden of CeD for the future.

Incidence rates for CeD autoimmunity across subgroups and time

*comparing post-pandemic to pre-pandemic

Funding Agencies

CIHRTRIANGLE (Training a new generation of researchers in gastroenterology and liver)
A7 THERAPEUTIC DIETARY INTERVENTION IN ADULT CROHN’S DISEASE PATIENTS: EFFECTS ON REMISSION MARKERS, QUALITY OF LIFE, AND PHYSICAL ACTIVITY
Authors: Toews B R , Lu C , Raman M , Reimer R
Published: February 2025

Background

Current evidence recognizes diet and physical activity as important factors in influencing the natural history of Crohn’s disease (CD); however, the relationship between dietary components and disease relapse remains unclear. Patients with active CD have a lower quality of life (QoL) compared to healthy controls.

Aims

The aims of this study were threefold: 1) to explore the effect of a CD specific therapeutic dietary intervention (CD-TDI) upon clinical and biochemical remission in adults with active, mild luminal CD, 2) to investigate outcomes related to patient-reported health QoL, and 3) to investigate the relationship between IBD parameters and physical activity. We hypothesized that a CD-TDI would be more effective when compared to conventional management (CM) to induce clinical and biochemical remission and improve patient-reported QoL in symptomatic and asymptomatic patients with active, mild luminal CD.

Methods

This was a randomized controlled trial whereby 51 participants were randomly allocated in a 2:1 ratio to the intervention group (CD-TDI) or CM for 13 weeks. Patients receiving the CD-TDI, an anti-inflammatory diet developed specifically for CD with foundational principles rooted in the Mediterranean diet, were offered patient-centered counseling by a Registered Dietitian for 12 weeks. QoL was measured using the 12-item short form health survey (SF-12). Physical activity was measured using ActivPAL® inclinometers (PAL Technologies, Glasgow). The Harvey Bradshaw Index (HBI) and fecal calprotectin (mcg/g) were used to assess clinical and biochemical remission.

Results

The CD-TDI group experienced both significant decreases in HBI from baseline to week 13 (Wk0: 3.0, IQR:1.0-5.3; Wk13: 2.0, IQR:0-3.0; p=0.05) and FCP from 130 ug/g (IQR: 38-411) at baseline to 72 ug/g (IQR:3-153) at week 13 (p= 0.01). The CM group saw no change in HBI and there was an increase in FCP by 337 ug/g or 55% from baseline to week 13. The SF-12 yielded two summary scores, the mental component score (MCS-12) and physical component score (PCS-12). The CD-TDI group experienced an increase in both the PCS-12 from 46.9 (SEM: 2.0) to 50.0 (SEM: 1.6) (p=0.10) and the MCS-12 from 49.2 (SEM: 1.8) to 50.9 (SEM: 1.8) (p=0.17), moving both scores to the mean healthy population score of 50, but the changes were not significant. Linear modelling revealed that both FCP (F(1, 58), p<0.001) and CRP (F(1, 62), p<0.001) act as significant predictors of the MCS-12 change score from baseline to week 13. There was no significant change in step count (p=0.41) within the CD-TDI group from baseline to week 13.

Conclusions

It can be concluded that the CD-TDI group experienced a significant decrease in gut inflammation and improved symptoms. Deeper analysis is underway to examine the influence of physical activity parameters on QoL.

Funding Agencies

CIHRNSERC CREATE, University of Calgary
A15 THERAPEUTIC POTENTIAL OF THE GLYCOCAGE TARGETED DELIVERY SYSTEM FOR IMPROVING INFLAMMATORY BOWEL DISEASE TREATMENT
Authors: Ma W , Menzies S , Wang C , Kothandapani J , Brumer H , Sly L M
Published: February 2025

Background

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is marked by chronic inflammation along the gastrointestinal tract (GIT). IBD cases are rising globally, with Canada having one of the highest prevalance rates. Thus, there is a critical need for more effective treatments. Current IBD therapy includes orally administered small molecule anti-inflammatory drugs, such as corticosteroids and JAK inhibitors. However, their use is limited by the high doses required due to systemic uptake, and consequently, negative off-target effects. To improve delivery of these drugs to the inflamed tissue in the lower GIT for better efficacy, our GlycoCaged prodrug technology links the drug to a plant carbohydrate for targeted release by gut bacterial glycosidases at the disease site. To demonstrate proof-of-principle, we used dexamethasone (DEX), a potent corticosteroid that is not used in IBD treatment due to inherent side effects. We showed that “GlycoCaging’‘ Dex improves its efficacy (10-X lower doses required) and reduces systemic side effects as compared to free DEX in the SHIP-/- model of CD-like ileitis.

We hypothesize that Glycocaging IBD drugs will increase drug efficacy and reduce off-target effects by delivering drugs to the site of intestinal inflammation.

Aims

1) Investigate the location of prodrug decaging in the GIT using SHIP-/- mouse model. 2) Evaluate GlycoCaged dexamethasone in the T cell transfer model of colitis.

Methods

To delineate the location of decaging activity in vivo, SHIP+/+ and SHIP-/- mice were orally gavaged with 3 mg/kg of DEX or the molar equivalent of GlycoCaged DEX and collected sections of intestinal tissues for LC-MS/MS analysis at multiple timepoints post oral gavage. To assess the GlycoCage system in another mouse model of IBD, T cell transfer model of colitis is established by injecting (i.p) CD4+CD25-CD45RBhigh T cells (isolated from CD45.1 mice by FACS) into age- and sex-matched Rag-/- mice. A dose titration was performed from 3mg/kg/d for 5 weeks of DEX or the molar equivalent of caged DEX to determine and compare their minimal effective doses. Treatment effects were assessed with histology, flow cytometry and multiplexed cytokine assay.

Results

Free DEX is absorbed early in the proximal GIT, while the GlycoCage prodrug system protects the DEX to be released starting in the distal small intestine and cecum, closer to the inflamed sites. Caged DEX ameliorated colonic inflammation in the T cell transfer model of colitis at lower doses than free DEX.

Conclusions

Our results highlight a novel microbiome-cleavable glycoconjugate drug delivery platform that has the potential to improve the therapeutic indices of diverse drugs for treating IBD. In the future, we will evaluate the efficacy of other GlycoCaged drugs.

Funding Agencies

CAG, CIHRTRIANGLE
A34 EVALUATION OF GASTRIC ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) EFFICACY IN A SINGLE CANADIAN CENTER
Authors: Maniere T , Kaufman D
Published: February 2025

Background

Endoscopic Submucosal Dissection (ESD), developed in Japan, is a minimally invasive method for resecting large superficial gastric lesions. It allows high en-bloc resection rates, reducing local recurrence and enabling complete histological assessment, overcoming the limitations of Endoscopic Mucosal Resection (EMR). Although well-studied in Asia, ESD’s evaluation in North America remains limited due to lower gastric cancer incidence.

Aims

The aim of our study is to evaluate gastric ESD’s effectiveness and assess peri-procedural complications

Methods

This retrospective cohort study included 75 patients who underwent ESD for gastric adenocarcinoma, neuroendocrine tumors, high-grade and low-grade dysplasia at Charles Le Moyne Hospital between 2017 and 2024. Data collected included patient demographics, procedural details, and pathology outcomes. Primary outcomes were en-bloc and R0 resection rates, while secondary outcomes included complications like perforation and hemorrhage. Five patients were excluded from the R0 and curative resection analysis due to non-evaluable pathology:piece meal resection (1), unconclusive margins (2), failure of resection(2).

Results

A total of 75 patients were included, with a mean age of 73 years (), and 64% were men. Polyp characteristics based on Paris classification were: 0-IIa+c (21%), 0-IIa (20%), 0-Is (17%), 0-IIB (9%), 0-Ip (4%), 0-Is+IIa (4%), 0-IIc (4%), 0-Isp (3%), 0-IIa+b (3%), and 0-IIb+c (1%). Lesions were located in antrum (32), body (25) GE junction (14), angulus (5) and gastro-jejunum anastomosis (1). One patient had two polyps resected concurrently (0-Ip + 0-Is). Paris class identification was missing in 13% of cases. The mean maximum endoscopic size visual estimation was 24 mm (5-90), while the mean maximum pathology specimen size was 40 mm (8-75). Pathology results showed: 25% invasive adenocarcinoma, 18% intra-mucosal adenocarcinoma, 18% high-grade dysplasia, 20% low-grade dysplasia, 11% hyperplastic polyps, 3% neuroendocrine tumors (grades 1-2), and 2% had no pathology due to complications. The mean procedural time was 117 minutes (40-412). Perforations occurred in 17% (13/76) of patients, with successful endoscopic closure in 92% (12/13) of cases. One patient required surgical repair. En-bloc and R0 resection rates were 80% and 73%, respectively, with curative resections in 67% of cases.

Conclusions

ESD demonstrated high en-bloc and R0 resection rates, confirming its effectiveness for managing gastric lesions. These results are consistent with North American studies. Though complications like perforation occurred, most were managed endoscopically. This provides preliminary evidence for ESD as a safe and effective option for gastric lesion resection in Canada.

Funding Agencies

None
A37 OPTIMIZING ENDOSCOPIC SCHEDULING USING THE SMSA SCORE FOR ENDOSCOPIC MUCOSAL RESECTION.
Authors: Maillet D , Chapelle N , Martel M , Menard C
Published: February 2025

Background

Colonoscopies prevent colorectal cancer (CRC) by detecting and removing neoplastic polyps. Complex polyps (CP) pose many challenges. While endoscopic mucosal resection (EMR) is the standard treatment, its procedure time is unpredictable, leading to scheduling inefficiencies. The SMSA (Size, Morphology, Site, Access) score helps classify CP and predict clinical risks but has never been used as a predictor of procedural time. A tool to predict EMR duration is needed to improve efficiency in resource-limited settings.

Aims

We aim to assess if the SMSA and SMSA+ scores can predict procedural time and to determine whether the specific domains of the score, as well as additional pre-procedure factors, are associated with increased procedural duration.

Methods

We conducted a retrospective cohort study at a tertiary-care center in Sherbrooke, Canada, involving consecutive adult patients who underwent EMR for CP between November 2020 and August 2024. The primary outcome is to evaluate if the SMSA and SMSA+ scores can estimate procedure duration. Secondary outcomes include identifying variables associated with procedure time. Data on demographics, polyp characteristics, procedure details, and adverse events were collected and analyzed using descriptive statistics and regression models.

Results

A total of 100 patients were included (mean age: 67.9 ± 9.3, 53% female, Charlson score: 3.62 ± 1.98), The distribution of SMSA scores was as follows: Score 1: 0%; Score 2: 10.0% (mean time: 48.1 ± 15.3 mins); Score 3: 37.0% (mean time: 54.1 ± 15.7), and Score 4: 53.0% (mean time: 74.2 ± 30.5). The SMSA+ was distributed as score 0: 16.3% (mean time: 56.3 ± 16.4) and score 1: 83.7% (mean time: 66.3 ± 28.6). A mean of 2.3 ± 2.3 additional cold snare polypectomies were performed during the procedure with a similar distribution across all scores. Regression model indicated that both the SMSA score (P=13.3, t=3.0, p<0.01) and intra-procedural complications (P=29.9, t=3.9, p<0.01) were significant predictors of procedure time. Age, sex, Charlson score, fibrosis, fragmented specimen, and EMR technique did not significantly contribute to procedural time. Further analysis revealed that only the size domain of the SMSA score was associated with procedural duration (P=4.45, t=3.3, p<0.01). The SMSA+ score was not predictive of procedural time.

Conclusions

The SMSA score, especially the size domain, is a useful predictor of EMR procedural time, while the SMSA+ score does not predict duration. These findings suggest that incorporating the SMSA score into clinical practice could enhance scheduling efficiency. However, further studies using multicenter data is needed to explore additional factors.

Funding Agencies

None
A40 INITIAL OUTCOMES FOLLOWING THE LAUNCH OF A PERORAL ENDOSCOPIC MYOTOMY (POEM) PROGRAM FOR ACHALASIA: A SINGLE-CENTRE EXPERIENCE IN CANADA
Authors: Tsai C H , Woo M , Gupta M , Schieman C , Belletrutti P J
Published: February 2025

Background

Peroral endoscopic myotomy (POEM) has gained prominence as a minimally invasive therapeutic option for achalasia. Despite its growing adoption worldwide, the establishment of POEM programs in Canada is relatively recent, and local data on clinical outcomes remain limited.

Aims

This study aims to assess the short-term outcomes of patients undergoing POEM for achalasia including symptom improvement, complication rates, and detailing the endoscopic and hospital resources necessary to sustain a POEM program.

Methods

A retrospective chart review was conducted to collect procedural and clinical outcome data for patients who underwent POEM and completed follow-up assessments from the inception of the program in October 2023 to September 2024 at the Foothills Medical Centre in Calgary, Alberta. The Eckardt symptom score was used to objectively evaluate symptoms pre-operatively and one-month post-POEM.

Results

A total of 20 patients, with a mean age of 59.2 (± 13.4) years, completed a one-month postoperative assessment after POEM. Each procedure was performed jointly by a gastroenterologist and a thoracic surgeon in the operating room. Most patients (16/20) were classified as ASA category II. The median Charlson Comorbidity Index was 2. 65.0% of patients had prior endoscopic interventions for achalasia, including pneumatic dilation or botulinum toxin injection. The pre-procedural mean integrated relaxation pressure at the lower esophageal sphincter was 25.8 ± 11.4 mmHg. The mean POEM procedural time was 110.5 (± 33.6) minutes, with an average of 6.5 endoscopic clips used per case for tunnel closure. The esophageal myotomy lengths were 4.79 (± 0.38) cm for type I and type II achalasia, and 9.0 (± 0.89) cm for type III achalasia. The postoperative length of stay was a median of 1 day. Postoperative complications occurred in 2 patients, both of which were managed conservatively, with no procedure-related deaths. The mean pre-POEM Eckardt score was 7.00 (± 1.79), which decreased to a mean of 1.00 (± 0.89) at one-month post-POEM (p < 0.001) [Figure 1].

Conclusions

POEM is a safe and effective treatment option for patients with symptomatic achalasia. We demonstrate marked initial symptom improvement and a low complication rate. However, POEM is resource- and time-intensive. Further studies are warranted to evaluate long-term outcomes and complications such as gastroesophageal reflux disease (GERD) and Barrett’s esophagus.

Figure 1: Total Eckardt symptom score before and after POEM. Each line represents data from an individual patient.

Funding Agencies:
A45 EXPLORING COST AND VALIDITY OF NOVEL COMMERCIAL AND NON-COMMERCIAL (SELF-ASSEMBLED) SIMULATORS IN GASTROINTESTINAL ENDOSCOPY TRAINING: A SCOPING REVIEW
Authors: Zhao A Y , Gimpaya N , Lisondra J , Wiggin A , Almneni A , Tran W , Grover S
Published: February 2025

Background

Simulation-based training improves trainee learning curves and minimizes patient risk. However, not all endoscopic procedures have commercially available simulation models. Further, costs and location may limit trainee access to commercial simulators. This has driven the design and development of non-commercial, self-assembled simulators by educators, training programs, and learners.

Aims

To perform a scoping review to explore reporting of validity, assembly time and cost of novel simulators developed in the last 5 years.

Methods

A search on MEDLINE, PubMed, and ProQuest from January 2019 to September 2024 identified articles that developed or used simulators for gastrointestinal (GI) endoscopy procedures and techniques. A five-year date limit was implemented to account for advancement in simulation technology over this time frame. Two independent reviewers screened the articles. Included articles were designated as non-commercial simulators if they are open-access, not for purchase, and intended for self-assembly; or commercial simulators if they did not meet these points. Data on cost, assembly time, and method of validity testing were recorded. Costs were converted to USD using a consumer price index calculator (2024). The primary outcome was the type of validity testing as reported in the articles. Other outcomes are the differences between cost and assembly time.

Results

28 articles were included. Figure 1 summarizes each study, the characteristics and the specific skills simulated for each simulator, and the methods used for validity testing. 19 articles were on non-commercial simulators (18 mechanical, 1 Virtual Reality (VR)) and 9 were on commercial simulators (7 mechanical and 2 VR). Validity testing was conducted in 12 of the 19 non-commercial simulator studies (9 instances of face validity, 10 content, and 11 construct), and in 8 of the 9 commercial simulator articles (3 instances of face validity, 2 content, and 2 construct). The single study on a non-commercial VR simulator did not report cost. Costs ranged from $28-$1035, for non-commercial mechanical simulators, $247-$12,995 for commercial mechanical simulators, and $62,087-$136,591 for commercial VR simulators. Only four articles on mechanical simulators reported assembly time, which ranged from 1-8 hours, with additional set-up ranges of 10-20 minutes.

Conclusions

This scoping review explored the validity testing, cost, preparation time and types of validity used in newly-developed commercial and non-commercial simulators. Future iterations of this study will expand the search strategy, assess the quality of studies, evaluate and compare the validity testing performed between commercial and non-commercial simulators.

Included articles.

Funding Agencies

None