bluuebunny/crossref_metadata_2025 huggingface dataset:
Proportionality and Strict Proportionality in the Case-law of the Court of Justice of the European Union on Data Retention
Authors: Nardi Daniele
Published: February 2025

Chapter 5 analyses the foundation of the case-law of the Court of Justice of the European Union that led to the ban of general and indiscriminate retention of communications’ metadata in the light of the classical three limbs of ‘appropriateness’, ‘necessity’, and ‘strict proportionality’ of the proportionality test that every measure imposing limitations on fundamental rights must pass. It will discuss the notions of ‘strict necessity’, and the initial reticence of the Court to perform the balancing exercise inherent in the last limb of the test, strict proportionality. It will thus question whether the Court actually performed a ‘strict proportionality’ assessment, that is, a balancing exercise between costs and benefits of the measures at stake. Chapter 5 concludes that the fact that proportionality of an interference with fundamental rights may require to be adjudicated by resorting to a strict proportionality assessment is in line with the constitutional role of the Court, and a more explicit recourse to it, when necessary, would enhance legal certainty.
Data Retention in the Proposed ePrivacy Regulation Caught between the Well-established Case Law of the Court of Justice and the Deep Disagreements of the EU Legislature
Authors: Tracol Xavier
Published: February 2025

In 2017, the European Commission made a Proposal for an ePrivacy Regulation which includes a provision on data retention. The Commission and the EDPS both emphasised the need for this provision to comply with all the requirements set out in the applicable case law of the Court of Justice. Whilst the Parliament generally supported the Proposal, including the provision on data retention, Member States have been divided on the matter and the Council has consequently not managed to reach any common position. In 2020, the Court of Justice rendered the two La Quadrature du Net ‘I’ and Privacy International judgments on data retention. These judgments are both legally based inter alia on Article 4(2) of the Treaty of the EU and relevant provisions of the Charter which are part of EU primary law. The Council reacted to these two judicial decisions with amendments to the ePrivacy Regulation, which do not comply with the case law of the Court of Justice on data retention. As a result, the Parliament and the Council disagree on the provision about data retention and the draft ePrivacy Regulation has consequently been stuck since 2021. Since EU secondary law must comply with EU primary law, the ePrivacy Regulation which is EU secondary law must comply with the applicable case law of the Court of Justice which is based inter alia on EU primary law. As a consequence, the EU legislature should simply codify such case law in the provision on data retention of the ePrivacy Regulation.
Data Retention in Germany
Authors: Bäcker Matthias
Published: February 2025

For a long time, the dispute over data retention in Germany seemed like a never-ending story. The legislator twice enacted legal provisions on data retention, both of which were overturned in court proceedings after a short time. The focus of the legal dispute, however, shifted between these proceedings. The Federal Constitutional Court (Bundesverfassungsgericht—BVerfG) nullified the first set of provisions on data retention on the grounds that they infringed German fundamental rights, although they were mandated by the Data Retention Directive. In contrast, the successful proceedings against the second data retention, which is based on a regulatory decision by the German legislator, primarily invoked European Union law. Data retention thus forms a benchmark case for the Europeanisation of the protection of fundamental rights in Germany. The legal policy discussion on data retention seems to have focused on a few individual issues recently. There is currently an opportunity to pacify the debate on data retention in Germany, although the effects of the recent La Quadrature du Net ‘II’ judgment of the CJEU remain to be seen.
Consequences of the Collapse of a Directive
Authors: Markou Christiana
Published: February 2025

Chapter 9 examines the effects of the annulment of the Data Retention Directive on the Cypriot legal order regarding data retention. Case law had been heading towards a direction that was not in line with the relevant CJEU case law up until 2021, when the Cyprus Supreme Court ruled that the Cyprus legislation on data retention was ineffective as it contravened EU law. The particular decision was expected to lead to the ‘collapse’ of the court orders issued on the basis of said legislation authorizing police access to retained data. Surprisingly, the Supreme Court judgment was not unanimous. Moreover, it did not have the expected results either, something which, though may appear surprising at first, can perhaps be justified by reference to more recent CJEU case law and a different approach adopted more recently by a Cyprus court.
To Retain or (not) to Retain Data? The Danish Case
Authors: Næsborg-Andersen Ayo
Published: February 2025

Denmark had implemented laws on data retention prior to the Digital Rights Ireland judgment of 2014, collecting more data than allowed by that judgment. Various governments and parliaments have, however, since then seemingly been unwilling to abide by the judgments of the Court. Thus, the Danish legislation on data retention was unchanged until very recently, where the data retention act was finally amended, only to be halted by a new judgment from the Court of Justice of the European Union (CJEU) very shortly thereafter. Chapter 15 presents the content of the old and new Danish retention rules and examines whether aspects of the current law are in accordance with EU law, looking at legislative preparatory works and debates in the Danish Parliament, finding several issues potentially in violation of fundamental rights.
The Swedish Data Retention Saga
Authors: Bergström Maria
Published: February 2025

Chapter 17 provides a contextual and historical analysis of the Swedish data retention saga evolving around the Swedish support to introduce data retention legislation at EU level, the penalty payments for non-implementation, the annulment of the EU Directive, and the requests for preliminary references in order to clarify the required safeguards for data retention to be lawful, with particular focus on reviewed and revised national legislation in the absence of an EU legal framework. The Swedish data retention saga provides a rich example of the interrelation between national and European law and politics and the legal processes that led to legal changes both on national and European levels, including an analysis of data retention, but with focus more on lawmaking and judicial processes rather than data retention as such and in detail. This chapter thereby analyses the interplay between Swedish and European law and politics against the necessary balance between effective and efficient criminal investigation, legal certainty, and fundamental rights protection in data retention regulation.
Introduction: the hypothesis and the project
Authors: Pettit Philip
Published: February 2025

Homo sapiens is distinguished by being able, publicly and privately, to make judgments and reason to conclusions, to make value commitments, and to ascribe responsibility. A possible explanation for those and related capacities is that this animal is also homo loquens: a great ape that is capable of speech and converse. But how to defend that hypothesis? This book does so by trying to show that certain counterparts—the humanoids—would be robustly likely to develop relevant capacities in the presence of speech, whatever the origin of language among them; the capacities would emerge as skills in the conversive practices that speech would enable. Such a genealogy might serve to explicate the nature and function of the capacities in the human case, even if it did not reflect the actual history of their appearance among humans. But it ought not to obscure the fact that human capacities have been responsible for ill as well as for good.
Preliminaries to the argument
Authors: Pettit Philip
Published: February 2025

We human beings are characterized by an ability to judge and reason and probe perception, and a capacity to form value commitments, to ascribe responsibility, and to assume the status of persons. One promising way of explaining those capacities is to see how they would spontaneously evolve in the wake of a simple language among humanoid counterparts: this would give rise to a corresponding range of social practices and the capacities would be constituted by skills in their social and mentally interiorized exercise. If the humanoids envisaged are credited with linguistically independent forms of human competence that are recognized in science and common sense, there is no mystery—not even a rule-following mystery—about how signaling and speech might appear among them.
Normativity and value
Authors: Pettit Philip
Published: February 2025

The humanoids will each have a reputational and prudential motive to treat others well, generating collectively beneficial regularities, and to regulate others as well as themselves for conformity, thereby treating the regularities as social norms. Moreover, they will each manifestly want others to conform to such beneficial norms and so each may aspire without fear of contradiction to speak for all in regulating another, whether in educating them, in enjoining conformity, or in correcting offenders. This will give the demands of their social norms a categorical, if still overrideable status. With those norms manifest—and their acceptance by everyone also manifest—they will each be disposed to commit to conforming and upholding those norms: to bet on themselves to do so, at risk of not being able to excuse a failure by invoking a misleading mind or a changed mind. Indeed, they will be committed to this line just by acquiescing in the expectations of others. Among the attitudes to which they will commit in this active or virtual way is the intention to obey and uphold relevant norms: in effect, to value universal conformity in a decisive way. In that case, they will treat the desiderata that explain the commitment as impartial values. And as they may recognize and commit to such values, so they may do so with more personal or sectional values as well.
Responsibility and free will
Authors: Pettit Philip
Published: February 2025

Imposing a norm-based, expectational discipline on one another, the humanoids will be motivated by the fear of anyone’s defection to manifest their expectations to that individual, exhorting them to conform. They will say, ‘You should and can conform’, ascribing but also reinforcing that capacity. Let the person fail, however, and in the absence of a (full) excuse—a failure of rationality, knowledge, or voluntariness—they will reaffirm ex post the ability ascribed ex ante in exhortation: ‘You should and could have conformed’. And viewing the breach of the norm in that way—as one that occurred in the presence of a capacity to conform—they will intuitively blame or censure the offender. They will be positioned to do this, moreover, by identifying with the ex-ante exhortation of someone else or even with the self-exhortation of the agent. Perhaps that agent’s active self-exhortation—‘I can conform’—or perhaps a standby variant: this will materialize when the individual manifestly commits to the norm and is positioned so that any temptation to defect will raise a red flag, alerting them exhortatively to its appeal. In the emerging sense of blame, they will be able to interiorize the exercise and blame themselves as well. To the extent that someone is self-exhortatively effective in holding themselves to shared norms and values—or more personal counterparts—they will be possessed of free will in an intuitively recognizable sense: in a sense in which it is constituted by willpower.
Conclusion: toward ethics and politics
Authors: Pettit Philip
Published: February 2025

If the story of humanoid practices and capacities is sound, then that is likely to tell us something about human nature, as stressed throughout the book. But a striking feature of the genealogy is that, in its ideal form, it presupposes relationships of equality between the humanoids, valorizes relationships of respect, and holds out the prospect that they would value freedom in a distinctive sense: freedom as non-domination. The conclusion explores the significance of the genealogy in providing normative support for a relational conception of equality, for a conversive ideal of respect, and for a republican view of freedom.
Korngold and the Hollywood Studio System
Authors: Winters Ben
Published: February 2025

Chapter 1 outlines the nature of Korngold’s working relationship with the Hollywood studio system at Warner Bros., setting out the various stages at which his involvement with a film was required, his fluctuating working relationships with studio executives such as Hal B. Wallis, and his interactions with fellow music-department colleagues including orchestrators. The picture that emerges from the archival evidence is of an individual who garnered considerable respect; however, that respect did not always necessarily result in the kinds of creative freedom we may sometimes imagine (perhaps idealistically) should be enjoyed by a composer with an existing “high-art” pedigree working within a commercial sphere.
Emerging Adults’ Financial Well-Being: Conceptualization and Measurement
Authors: Sorgente Angela , Lanz Margherita
Published: February 2025

Financial well-being is a positive financial condition that has both an objective and a subjective side. Objective financial well-being refers to material resources such as income, savings, and assets, while subjective financial well-being corresponds to an individual’s emotional and cognitive evaluation of their own financial condition. The current chapter aims to properly define this construct, clarify how the conceptualization of financial well-being has changed over the last decades, and emphasize important considerations related to financial well-being among emerging adults. In particular, we stress adjustments this construct should receive in terms of conceptualization and measurement. Furthermore, we highlight that the meaning emerging adults attribute to financial well-being is shaped by the culture they belong to and the socioeconomic conditions of the country they live in. The chapter ends with three suggestions to help emerging adults flourish financially.
Emerging Adults’ Financial Stress and Financial Anxiety
Authors: Kim Jinhee , Chatterjee Swarn , Chan Alexander
Published: February 2025

This chapter explores literature related to the impact of financial stress and financial anxiety on the mental health and well-being of emerging adults. It discusses the antecedents and outcomes of various financial stress and financial anxiety of emerging adults. The factors that exacerbated financial stress and anxiety among emerging adults during the COVID-19 pandemic and potential strategies for building more financially resilient emerging adults are also discussed. This chapter distinguishes financial stress and financial anxiety constructs and explores their association with the financial attitudes, behaviors, and well-being of emerging adults. Furthermore, it identifies previously established linkages between unhealthy financial behaviors and adverse mental health outcomes that can perpetuate cycles of persistent financial stress and anxiety that can affect the overall well-being of emerging adults. The chapter also provides research and policy recommendations for improving the financial capability of emerging adults and helping reduce financial stress and anxiety.
College and Student Loans in Emerging Adulthood
Authors: Lee Yoon G , Hales Emily
Published: February 2025

This chapter reviews literature related to college and student loans in emerging adulthood. Specifically, the topics include college education and human capital investments, the student loan crisis in the United States, student loan repayment and default in the United States, student loans across generations, financial literacy and student loan decisions, sociodemographic differences in student loan decisions, and student loans and financial well-being. Student loan debt is a seemingly never-ending topic of conversation among financial professionals, policymakers, and even emerging adults considering attending college. Student loans might be necessary to achieve higher education, and it seems like the “best” option or solution for many emerging adults. Nonetheless, it is crucial for financial professionals to share alternative financial opportunities and resources for emerging adults who may be planning for college in the future.
Finances and Romantic Relationships in Emerging Adulthood
Authors: Li Xiaomin
Published: February 2025

This chapter reviews studies on finances and romantic relationships in emerging adulthood. Finances refer to the ownership and management of money by either partner or both. Romantic relationships refer to the formation and quality of the partnership. The primary foci in this chapter are the reciprocal and circular associations between finances and romantic relationships. Realizing that money—in addition to satisfying material needs—carries many psychological meanings (e.g., symbols of self-worth, security, and privilege), this chapter also reviews studies on how attachment orientations and power may relate to finances and romantic relationships. Collectively, this chapter provides an overview of how emerging adults navigate their finances in the context of romantic relationships. Suggestions for researchers, practitioners, and emerging adults are provided.
Financial Socialization and Emerging Adults’ Financial Outcomes
Authors: Saxey Matthew T , LeBaron-Black Ashley B , Kelley Heather
Published: February 2025

This chapter reviews peer-reviewed research on the financial socialization of emerging adults. Because parents have repeatedly been found to be the most impactful financial socialization agent, this chapter primarily focuses on parent financial socialization. Informed by theoretical advances from recent qualitative scholarship, we review quantitative scholarship related to how emerging adults’ parents taught them about finances through parent–child financial discussion, parent financial modeling, and experiential learning of finances. That is, we review specific financial outcomes in emerging adulthood that these three methods of parent financial socialization are associated with. Afterward, we review research about other impactful financial socialization agents and associated financial outcomes in emerging adulthood. Diversity, equity, and inclusion-related findings in financial socialization scholarship are also reviewed. Specific implications for researchers, practitioners, and emerging adults are provided in call-out boxes.
Introduction
Authors: Talbott Siobhan
Published: February 2025

There are a number of core themes that run through this book. I argue that print did not supersede manuscript and oral methods of information exchange in early modern business networks; that merchants were individuals whose actions were determined more by their individual circumstances, motivations, experiences, and personal relationships than by political contexts or societal expectations; that the specificities of ‘business information’ set it apart from news and information as a broader genre; and that we should consider a much more extensive range of manuscript material as ‘didactic’. These themes are introduced in this Introduction, and the book is situated in relation to scholarship surrounding the ‘print revolution’ and the ‘Atlantic world’. I illuminate my temporal and geographic approach, explore my source base, and explain the book’s structure.
Conclusion
Authors: Talbott Siobhan
Published: February 2025

When information was lacking, delays were caused and financial damage was threatened. To be successful in early modern business, merchants needed knowledge of commodities, shipping, exchange rates, and local markets; they required education in business etiquette; and they relied on personal information such as recommendations and character testimonies. All of this information, gleaned from a variety of sources, shaped merchants’ decision-making processes. The short concluding chapter to this book underscores my central themes: arguing for the specificity of business information and critiquing the role of the ‘print revolution’ in business.
Introduction
Authors: Miller Peter
Published: February 2025

The book’s introduction makes the historical and theoretical case for understanding prosody as a form of media theory. It opens with an anecdote from George Saintsbury’s History of English Prosody (1910) and then considers three scientific attempts to write sound in order to introduce what it calls the “matter” of prosody: the physical materials used to record poetic sound but also the customs, discourses, and tools used to parse that sound. After surveying recent work in literary sound studies, historical poetics, and new formalism, the introduction lays out the book’s three guiding principles: to examine poetry’s language alongside the media that embody it, to take seriously instances of creative remediation and performance, and to understand traditional prosodic concepts (e.g. iambs, blank verse) as one class of sound media among others. The introduction concludes with a close reading of a poem by Edmund Spenser and a song lyric by Beyoncé, a statement of the book’s argument, and a chapter summary.
Egyptian Students and Politics beyond Protest
Authors: Ramzy Farah
Published: February 2025

The legacy of the student movements in Egypt in the twentieth century makes some forms of political activity among Egyptian students, namely protests for national or regional causes, familiar and even expected. However, the significant neoliberal turn in the Egyptian economy in the late 1990s changed the structure of higher education and with it the status and behaviour of students. The usual analytical lens used to examine Egyptian students’ political activity by looking at protests, does not capture the realities of contemporary higher education nor the complexities of the impact of the major critical events of 2011 and 2013. This book uncovers politics and politicization processes in diverse locations where students act and organize such as student unions, partisan student organizations, student clubs and associations including simulation models, in addition to activist groups, by drawing on interviews conducted in Egypt between 2013 and 2015 with members of these groups and ethnographic observation of their activities. Proposing a dynamic theoretical framework to make sense of student politicization in authoritarian neoliberal contexts marked by sociopolitical change, this book argues that students collectively and individually negotiated the scope of their political activities as well as the meanings they attributed to these activities. The resulting student politics were, not only diverse and unexpected, but reflected the intertwinement of the historical representation of students as leaders of the nation, the neoliberal imperative to prepare for a competitive job market, and the impact of the revolution of 2011 and of the post-2013 context.
AT-rich interaction domain 5A facilitates axon regeneration through docking protein 6 in the peripheral nervous system
Authors: Ren Zhixian , Huang Weixiao , Gu Xiaosong , Zhao Lili
Published: February 2025

Background

Peripheral nerves are easily damaged in accidental trauma due to their shallow location. Compared to the limited regeneration of the central nerve, the peripheral nerve has a certain regenerative ability after injury. However, this ability is not sufficient to achieve functional recovery. To increase the rate of regeneration after nerve injury, increasing regeneration-associated genes (RAGs) expression by transcription factors in neurons is necessary.

Methods

Sciatic nerve crush (SNC) animal models were generated in Sprague–Dawley (SD) rats. Bioinformatics analysis and real-time polymerase chain reaction (qPCR) were applied to detect genes expression; immunofluorescence staining and western blotting were applied to detect protein expression. The neurites outgrowth of cultured DRG neurons was performed to evaluate axon regeneration in vitro. Intrathecal injection of adeno-associated virus (AAV) was applied to suppress or overexpress the target in vivo. Following transfection, immunofluorescence staining of newborn axons’ marker (SCG10) in sciatic nerve after crush was used to evaluate the function of AT-rich interaction domain 5A (Arid5a) or docking protein 6 (Dok6) on axon regeneration. The binding between TF and the promoter of target genes was verified by chromatin immunoprecipitation (ChIP).

Result

has high activity in specific regenerating clusters and it accumulates specifically in the nucleus of DRG neurons after sciatic nerve injury. Upon Arid5a inhibition by siRNA, the outgrowth of neurites in vitro and the regeneration of axons in vivo were inhibited. In contrast, after Arid5a overexpression in rats, axon regeneration was significantly accelerated. In addition, Arid5a promotes the expression of Dok6 by binding to its promoter in DRG neurons. Suppression of Dok6 represses the neurites outgrowth of cultured DRG neurons, while its overexpression enhances axon regeneration in vivo. Furthermore, overexpression of Dok6 restored the impaired effect of Arid5a suppression on axon regeneration.

Conclusions

These findings indicate that axonal injury induced nucleus accumulation of Arid5a in neurons. Through Dok6, Arid5a accelerates axon regeneration of DRG neurons both in vitro and in vivo. This study enriched our understanding the function of Arid5a in the peripheral nervous system and the transcriptional regulatory network involved in neural regeneration.
Bile acids as germinants for Clostridioides difficile spores, evidence of adaptation to the gut?
Authors: Vinay Gianni , Seppen Jurgen , Setlow Peter , Brul Stanley
Published: February 2025

Bacterial spores formed upon metabolic stress have minimal metabolic activity and can remain dormant for years. Nevertheless, they can sense the environment and germinate quickly upon exposure to various germinants. Germinated spores can then outgrow into vegetative cells. Germination of spores of some anaerobes, especially Clostridioides difficile, is triggered by cholic acid and taurocholic acid. Elevated levels of these bile acids are thought to correlate with a perturbed gut microbiome, which cannot efficiently convert primary bile acids into secondary bile acids. That bile acids are germination-triggers suggests these bacteria have a life cycle taking place partially in the mammalian digestive tract where bile acids are plentiful; notably bile acids can be made by all vertebrates. Thus, spores survive in the environment until taken up by a host where they encounter an environment suitable for germination and then proliferate in the largely anaerobic large intestine; some ultimately sporulate there, regenerating environmentally resistant spores in the C. difficile life cycle. This review summarizes current literature on effects of bile acids and their metabolites on spore germination in the gut and evidence that adaptation to bile acids as germinants is a consequence of a life cycle both inside and outside the digestive tract.
Segmentectomy versus lobectomy in younger patients with early-stage non-small cell lung cancer
Authors: Kamigaichi Atsushi , Mimae Takahiro , Tsubokawa Norifumi , Miyata Yoshihiro , Kudo Yujin , Nagashima Takuya , Ito Hiroyuki , Ikeda Norihiko , Okada Morihito
Published: February 2025

OBJECTIVES

Despite clinical trials supporting the efficacy of segmentectomy for early-stage non-small cell lung cancer (NSCLC), a previous report indicated its limited efficacy in younger patients, raising concerns about its indication.

METHODS

Patients aged <70 years with radiologically solid-dominant clinical stage IA NSCLC ≤2 cm who underwent lobectomy or segmentectomy at three institutions between 2010 and 2017 were enrolled. Propensity scores were estimated to adjust for confounding variables (age, sex, smoking history, tumour location, size, ground-glass opacity, maximum standardized uptake value, and histological type). To elucidate the prognostic impact of surgical indications in the late postoperative phase, restricted mean survival time (RMST) from 0 to 5 and 8 years was also determined.

RESULTS

Overall, 388 patients with a median age of 63 years were enrolled. Overall survival (OS) (hazard ratio [HR], 0.447; 95% confidence interval [CI], 0.152–1.316) and recurrence-free survival (RFS) (HR, 0.638; 95% CI, 0.335–1.216) did not differ significantly between the segmentectomy (n = 114) and lobectomy groups (n = 274). In the propensity score matching of 100 pairs, OS (HR, 0.577; 95% CI, 0.162–2.056) and RFS (HR, 0.945; 95% CI, 0.408–2.191) were comparable between the segmentectomy and lobectomy groups. Regarding OS in the segmentectomy and lobectomy groups, the 5- and 8-year RMST were 4.95 y versus 4.92 y (difference: 0.02 y; 95% CI, -0.09–0.13; P=0.699) and 7.82 y versus 7.69 y (difference: 0.12 y; 95% CI, -0.17–0.42; P=0.420), respectively.

CONCLUSIONS

Segmentectomy is a viable option for younger patients with early-stage NSCLC, suggesting that indications for segmentectomy need not vary by age.
Ambulatory children with spastic cerebral palsy have smaller bone area and deficits in trabecular microarchitecture
Authors: Zimmermann Elizabeth A , Veilleux Louis-Nicolas , Gagnon Marianne , Audet Dominique , Yap Rita , Julien Catherine , Hosseinitabatabaei Seyedmahdi , Trottier Eliane Rioux , Willie Bettina M , Carriero Alessandra , Farmer Jean-Pierre
Published: February 2025

Cerebral palsy (CP) is a non-progressive neurological syndrome resulting in abnormal muscle tone, movement, and posture. It is unclear whether ambulatory children with CP have deficits in bone quantity or quality. Furthermore, the relationship between abnormal muscle tone, altered function, and bone health remains largely unexplored. This observational study investigated bone mineral density (BMD) and microarchitecture in ambulatory children with spastic CP and associations of BMD with function, muscle spasticity, and gait. Children with spasticity in both lower limbs (n = 12) aged 3-8 years were recruited. Areal BMD was measured with dual-energy x-ray absorptiometry (DXA) at the proximal femur and lateral distal femur and compared to normative data. High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed at the metaphyseal tibia and radius in a subset of participants (n = 5) and compared to healthy children (n = 7). Gait pathology and cardiopulmonary function were investigated with the Gait Deviation Index, Edinburgh Visual Gait Score, and energy expenditure index. DXA aBMD Z-scores at the lateral distal femur were within a normal range. Instead, the CP group’s median aBMD Z-score at the proximal femur was -1.8 (interquartile range: -2.2, -1.2, p=.03) indicating potential skeletal fragility. Strong correlations were found between gait pathology and DXA-based bone outcomes (correlation coefficient 0.62 (p=.04) to 0.73 (p=.01)) as well as energy expenditure index and DXA-based bone outcomes (correlation coefficient -0.63 (p=.03) to -0.98 (p = <0.001)). At the metaphyseal tibia, children with spastic CP had significant deficits in HR-pQCT-measured bone geometry and trabecular microarchitecture: 35% lower total area, 42% lower trabecular area, and 48% lower trabecular number than controls. HR-pQCT parameters were similar between groups at the metaphyseal radius. These differences in tibial metaphysis size and trabecular microarchitecture are similar to those observed in disuse and thus could be a result of abnormal biomechanics or low levels of physical activity.
A10 RESTORATION OF ARYL HYDROCARBON RECEPTOR SIGNALING IN CELIAC DISEASE BY ORAL TRYPTOPHAN SUPPLEMENTATION: AN EXPLORATORY STUDY
Authors: Kirtikar U , Rueda G H , Szeto J , Galipeau H , Constante M , Wang X , pinto-sanchez M , Bercik P , Armstrong D , Verdu E
Published: February 2025

Background

Celiac disease(CeD) is an autoimmune disease triggered by the ingestion of gluten in genetically predisposed individuals. The only treatment is a strict gluten-free diet(GFD), however up to 40% of remain symptomatic and have residual inflammation, highlighting the need for adjuvant therapies. We showed CeD patients exhibit impaired microbial metabolism of tryptophan, resulting in reduced activation of the aryl hydrocarbon receptor(AhR), which plays immunomodulatory roles. Increased AhR ligands and activation in the small intestine have been shown in healthy individuals after oral tryptophan, but it is unknown if this supplementation may affect treated symptomatic CeD patients.

Aims

To determine whether tryptophan supplementation improves CeD-specific symptoms, mood symptoms and quality of life in GFD non-responders.

Methods

This double-blinded, placebo-controlled trial aimed to recruit 50 CeD adults on >1 year of GFD with persistent symptoms from McMaster University’s Celiac Clinic. Participants were randomized to L-tryptophan(3g/day) or placebo to be taken daily for 3 weeks. Before and post-intervention, participants completed symptom questionnaires, provided biological samples and underwent endoscopy. The primary outcome was a ≥4-point reduction in Celiac Symptom Index(CSI) from baseline, with secondary outcomes of improvement in Gastrointestinal Symptom Rating Scale(GSRS), Hospital Anxiety and Depression Scale(HADS), and Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life(PAGI-QoL). An interim analysis of first 25 participants was performed to investigate early trends in symptom improvement, expressed as Odds Ratio(OR), 95% Confidence Intervals(CI).

Results

Post-intervention, CSI scores decreased in 67% of participants (8/12) in the tryptophan group compared to 30% (3/10) in the placebo group (OR=4.36; 95% CI:0.77-28.47). Similarly, GSRS improved in 75% of participants (9/12) in the tryptophan group vs 40% (4/10) in the placebo group (OR=4.5; 95% CI:0.73-27.74). HAD scores improved in 41% (5/12) of the tryptophan group vs 30% (3/10) in the placebo group (OR 1.6; 95% CI:0.28-9.82). The PAGI-QoL improved in 58.3% (7/12) of the tryptophan group vs 0% in the placebo group, p=0.0053.

Conclusions

A greater proportion of participants under the tryptophan intervention showed improvement in their gastrointestinal, mood symptoms and quality of life compared with the placebo group. We are not currently powered to establish statistical significance for these differences, however, if these results were replicated in the planned study sample size, the study could fulfil its primary outcome. These results encourage to complete recruitment, with further evaluation of the gut microbiota composition and AhR activity.

Funding Agencies:
A14 INVESTIGATING THE IMPACT OF PARKINSON’S DISEASE-ASSOCIATED GENE PINK1 ON INTESTINAL HOMEOSTASIS AND RESPONSE TO INFECTION
Authors: Pei J , Recinto S J , Kazanova A , Burns L , MacDonald A , Gavino C , Desjardins M , Stratton J A , Gruenheid S
Published: February 2025

Background

Intestinal epithelial cells (IECs) provide an essential physical barrier between luminal contents and host tissue. Dysregulation of IECs leads to barrier dysfunction, causing pathologies in both intestinal and extra-intestinal diseases. While Parkinson’s Disease (PD) is primarily a neurodegenerative disorder, increasing evidence links PD progression and gastrointestinal dysfunction. Our group developed a model to investigate the role of the gut in PD, demonstrating that mice with genetic ablation of the PD-associated gene Pink1 exhibited motor phenotypes only when previously infected with gram-negative Citrobacter rodentium intestinal bacteria. As Pink1 is expressed in IECs and the colonic lamina propria, we hypothesize that PD-associated gene mutations directly affect the epithelium and impact early PD pathophysiology.

Aims

1. To characterize the transcriptional profiles of Pink1 WT and KO IECs at baseline and following in vivo C. rodentium infection.

2. Use in vitro cell line and colonic organoid systems to study the effect of Pink1 on epithelial activity in an isolated system.

Methods

Single-cell RNA sequencing was performed on colonic IECs isolated from Pink1 WT and KO mice, at steady state and following in vivo C. rodentium infection. Mice were sacrificed at D6 post infection to elucidate transcriptional differences between IEC lineages of each genotype. To validate scRNAseq findings, we derived ex vivo colonoids from Pink1 WT and KO mouse crypts and used a Pink1 KO CMT-93 epithelial cell line with WT clone as control. The cultures were treated with lipopolysaccharide (LPS), or infected with gram-negative pathogens to determine how PINK1 loss-of-function affects the inflammatory response of the epithelium.

Results

At baseline, our data revealed upregulation of interferon (IFN)-signaling genes (ISGs) in Pink1 KO enterocytes (ECs) compared to WT; whereby more than 70% of upregulated differentially expressed genes were linked to type I or II IFN signaling. In vitro stimulation of Pink1 KO epithelial cell line with IFN resulted in stark upregulation of ISGs compared to WT. During infection, Pink1 KO ECs demonstrated significant alterations in actin-cytoskeleton-related GO term pathways compared to WT. Infection of Pink1 KO CMT-93 epithelial cells revealed morphological changes in F-actin structures.

Conclusions

Using in vivo and in vitro models encompassing PD-genetic susceptibility and environmental stimuli, we identified dysregulation in Pink1 KO epithelium, suggesting altered inflammatory responses at baseline and infection. By investigating PD-associated genes in IECs, we will contribute to better understanding the role of the intestine in PD initiation, progression, and pathogenesis.

Funding Agencies

CAG, CIHR
A16 ROLE OF HIPPO SIGNALING EFFECTORS YAP&TAZ IN GASTRIC METAPLASIA AND TUMORIGENESIS
Authors: Ju Z , sung J , Farag M , Fiset P , Ferri L , Gregorieff A
Published: February 2025

NOT PUBLISHED AT AUTHOR’S REQUEST

Please acknowledge all funding agencies listed below

Funding Agencies: CIHRstudent is supported by CIHR CGS D and TRIANGLE Canada
A19 INTERLEUKIN-6 AND INTERLEUKIN-22 MEDIATE DISTICT REGULATION OF MITOCHONDRIAL DYNAMICS IN PATHOBIONT INFECTED GUT EPITHELIA
Authors: Navaneetha Krishnan S , Wang A , Shutt T E , McKay D
Published: February 2025

Background

The IBD-associated pathobiont attaching-invading Escherichia coli (AIEC) strain LF82 induces mitochondrial fragmentation and depolarization in epithelial cells, resulting in impaired ATP production and reduced barrier function. Interleukin (IL)-6 and IL-22 are omnipresent in the inflamed gut, can directly affect epithelial function and both mobilize STAT-3, the serine727 phosphorylated form of which can translocate to mitochondria. Thus, we posed the question, will IL-6 or IL-22 rescue or exaggerate the mitochondrial damage evoked by exposure to E. coli-LF82?

Aims

1. To determine if IL-6 and IL-22 modulate mitochondrial function during E. coli-LF82 infection

2. To assess the mechanisms by which IL-6 and IL-22 affect mitochondrial function in model gut epithelia

Methods

Human colon-derived T84 epithelial cells were infected with E. coli-LF82 (108 CFU/mL, 4h) ± a 18h pre-treatment and then co-treatment with IL-6 or IL-22 (both 10 ng/mL). Bacterial internalization was evaluated, and mitochondrial network morphology visualized with MitoTracker Red and confocal microscopy. Mitochondrial membrane potential was evaluated using TMRE staining and flow cytometry, and ATP measured by a luminescence assay. STAT3 phosphorylation (S727 and Y705) in whole-cell extracts was determined via western blot in response to IL-6 or IL-22 during E. coli-LF82 infection.

Results

IL-6 inhibited E. coli-LF82 evoked mitochondrial fragmentation, with significantly more cells showing a fused tubular pattern: mitochondrial membrane potential was restored by ~50% and ATP depletion was less severe (n=5). IL-6 elicited increased pS727-STAT3. In contrast, IL-22 failed to prevent any of the mitochondrial changes caused by E. coli-LF82, did not cause increased pS727-STAT3 but bioactivity was confirmed by increased pY705-STAT3. IL-6, but not IL-22, reduced the number of viable intracellular bacteria without affecting bacterial growth and increased markers of autophagy activation.

Conclusions

We have uncovered divergent effects of the STAT3 activators, IL-6 and IL-22, in the control of epithelial mitochondrial dynamics and function when challenged with a bacterial pathobiont. We speculate that IL-6 limits the effects of E. coli-LF82 via mitochondrially-directed pS727-STAT3 signaling and upregulation of autophagy. Understanding the precise role of STAT3- activating cytokines signaling in mitochondrial regulation could reveal new target to enhance epithelial barrier function.

Funding Agencies

CIHR
A22 USING AN AIR-LIQUID INTERFACE (ALI) COLONOID MODEL TO DEFINE INTESTINAL MICROBE-MUCUS INTERACTIONS: CITROBACTER RODENTIUM EMPLOYS ESPC TO PENETRATE MOUSE COLONIC MUCUS
Authors: Chen Y , Liang Q , Gilliland A , Yang H , Yu H , vallance B
Published: February 2025

NOT PUBLISHED AT THE AUTHOR’S REQUEST

Funding Agencies: None
A36 SERRATED POLYPOSIS SYNDROME OUTCOMES IN THE COLD SNARE RESECTION ERA
Authors: Zarrin A , Jiang S X , Taylor E , Tavakoli P , Bell S , Walia A , Pang S , Yu M , Motomura D , Enns R , Telford J , Xiong W , Shahidi N
Published: February 2025

Background

Surgery is indicated in patients with serrated polyposis syndrome [SPS] when the polyp burden is no longer manageable endoscopically. Evidence has emerged supporting the efficacy and safety of cold snare resection [CSR] for large sessile serrated lesions; however, the role of a primary cold snare resection algorithm [PCSRA] in patients with SPS is unknown

Aims

We aimed to evaluate the efficacy of a PCSRA in patients with SPS

Methods

Utilizing an established retrospective cohort (2013-2023), all patients with a diagnosis of SPS were evaluated, based on the 2019 World Health Organization [WHO] criteria. Patients were stratified by index colonoscopy into the pre-PCSRA (01/2013-12/2020) and the post-PCSRA (01/2021-08/2023). Outcomes included achieving clearance (complete removal of all serrated class lesions [SCL] at procedure completion), adverse events, and referral for surgery. Continuous and categorical variables were summarised using median (IQR) and frequencies respectively. Fisher Exact test was used to compare categorical variables.

Results

178 patients with SPS were included in the analysis (N=144, 80.9% pre-PCSRA; N=34, 19.1% post-PCSRA). Median age at first colonoscopy was 62 years (IQR 9 years) and 115 (64.6%) were female. In the post-PCSRA, 593 SCLs were identified: 326 diminutive (< 5mm), 147 small (5-9mm), 66 medium (10-19mm), and 54 large (≥ 20mm). Among both SCLs and adenomatous lesions, 93.4% (N=627) were removed by CSR. Endoscopic clearance was achieved in 30 (88.2%) patients and 1 patient (2.9%) underwent surgery, which preceded referral for endoscopic management. In comparing the pre-PCSRA vs. the post-PCSRA: 110 (76.4%) achieved clearance in the pre-PCSRA group (P=0.09). No delayed bleeding was observed in the post-PCSRA group as opposed to 3 (2.2%) in pre-UCSRA (p = 0.50). Intra-procedural perforation was reported in 1 patient in the post-PCSRA vs. 2 in the pre-PCSRA group (p=0.47). Only 1 delayed perforation was reported in the pre-PCSRA group (p=0.81). Twenty-one (13.9%) patients underwent surgery: 20 in the pre-PCSRA (94.7%; 9 due to polyp burden and 11 for colorectal cancer) and 1 in the post-PCSRA (colorectal cancer) (p=0.08).

Conclusions

Cold snare resection should be considered as the first-line resection modality for most lesions identified in patients with SPS.

Funding Agencies

None
A50 SUCCESSFUL HEMOSTASIS WITH THROUGH THE SCOPE CLIPS FOLLOWING OVER THE SCOPE CLIP FAILURE IN DIEULAFOY LESION
Authors: Hendis S , Tomaszewski M
Published: February 2025

Background

Dieulafoy lesions account for 1-2% of acute GI bleeding and can be difficult to treat endoscopically.

Aims

We present a case a 59-year-old male who presented with hematemesis, melena, and hemodynamic instability.

Methods

Initial esophago-gastro-duodenoscopies (EGD) did not detect a source of active bleeding. Abdominal CT angiography revealed vascular structure in the stomach’s greater curvature, indicating a Dieulafoy lesion. Embolization via interventional radiology was unsuccessful. A third EGD finally showed the bleeding as a focal ooze localized in the proximal part of the greater curvature of the stomach. We used a padlock over-the-scope clip (OTSC). Despite successful deployment and placement of the OTSC, the bleeding persisted.

Results

Ultimately, hemostasis was achieved using five through-the-scope clips in a zipper fashion to the mound of tissue that had been raised by the over the scope clip. We hypothesize that although the OTSC grasped the Dieulafoy lesion, the feeding vessels were not significantly compressed to achieve hemostasis. This case demonstrates the failure of an OTSC to control bleeding from a Dieulafoy lesion, which was ultimately managed with through-the-scope clips.

Conclusions

This underscores the importance of combining traditional and novel endoscopic techniques to achieve hemostasis.

Funding Agencies

None