bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceiving Others
Authors: Doyon Maxime
Published: May 2024

If empathy is a sui generis form of perceptual intentionality, one may wonder whether empathic acts are governed by norms and have a sui generis character as well. This chapter answers this question positively and identifies the norms that are at play in our empathic understanding of others. Since empathy involves embodied, affective, and cognitive processes that yield different forms of understanding of others, the chapter distinguishes between basic empathy and various higher-level forms of social understanding. Drawing in the work of Husserl, Stein, and Merleau-Ponty, it suggests that different sets of norms come into play in every such form of experience. While considering arguments recently put forward by critical phenomenology, the chapter then argues that the norms identified by classical phenomenologists, which constitutively belong to the perceptual processes of empathy, should not be confused with the impact that social, historical, and cultural norms have on our experience of others.
Propagandists of the Book
Authors: Feitoza Pedro
Published: May 2024

This book examines the intricacies of the early history of Brazilian Protestantism through an in-depth analysis of the production and circulation of evangelical texts. It looks at a wide array of periodicals, tracts, books, and Bibles and contextualizes their ideas, trajectories, the agents who circulated them, and the practices that emerged in their wake. Foreign missionaries, itinerant booksellers, and evangelists devoted energy and resources to set texts in motion. This monograph considers their aspirations, experiences, and ordeals, and their role in bringing this new religious universe into being. Through the pages of such texts, evangelical ministers and writers projected themselves and their religious communities into the public debates of their era. The book takes the intellectual dynamic of this history into account. Its chapters examine how foreign missionaries and the local religious experts navigated between multiple conceptual and ideological landscapes and translated Protestant ideas and theology to the Brazilian public, while simultaneously channeling them into religious and sociopolitical arguments. Some texts, such as missionary correspondence, conversion narratives, and autobiographies shed light on the social and religious configurations of the earliest evangelical communities. Through a detailed exploration of these texts, the book reconstructs the religious imagination of the first generations of Brazilian Protestants and the cultural transformations involved in conversion experiences. The book has an overarching narrative that starts with the formation of the first Protestant communities in the mid-nineteenth century and closes with an examination of the rise of a Brazilian evangelical intelligentsia in the twentieth century.
Bibles and Tracts in Motion
Authors: Feitoza Pedro
Published: May 2024

This chapter is a case study of the operations of two London-based evangelical publishers in Brazil between 1870 and 1900: the British and Foreign Bible Society (BFBS) and the Religious Tract Society (RTS). The chapter concentrates on the experiences of itinerant booksellers called colporteurs. They circulated an impressive number of Bibles and evangelical tracts throughout the country that far outnumbered the sales of Brazil’s best-selling authors. The chapter explores the interactions of colporteurs with customers, their encounters with Catholic priests and believers, and the reading practices that emerged out of the circulation of Christian texts. It also examines the rise of a Lusophone evangelical public sphere by tracing the flow of texts, people, and ideas throughout the transatlantic conduits of the BFBS and the RTS in Brazil, Portugal, Madeira, and Britain.
Conclusion
Authors: Feitoza Pedro
Published: May 2024

This conclusion recovers some of the central discussions of the previous chapters and relates them to studies of the worldwide diffusion of evangelical Christianity and to the religious transformations of modern Brazil. It begins by examining how interactions and conflict between Protestants and Catholics in the country energized both sides of the religious divide and generated new forms of religious mobilization. It also depicts converts, ministers, and missionaries as innovators in the religious and cultural life of Brazil, looking at the religious communities they engineered and the effects of the Protestant cultivation of literacy. Finally, the conclusion considers how the first generations of Brazilian evangelicals domesticated the symbols and practices of Protestantism and located the new religion into Brazilian culture and history.
The Moon Agreement—A Swan Song
Authors: Hanlon Michelle LD
Published: May 2024

We will soon be able to extract and use resources found beyond national jurisdiction—and beyond the bounds of our Earth. Multiple States and private companies are considering the use of the natural resources on the Moon and other celestial bodies in situ, to support space activities and even an entire space-based economy. Further in the future, some even consider bringing these resources back to Earth to supplement our waning terrestrial resources. Yet no formal agreement has been achieved regarding the characterization of those resources or how extraction and use thereof should or might be regulated. The Moon Agreement was negotiated over a decade, from 1969 to 1979, and while an agreement was concluded by consensus and unanimously approved by the United Nations, it has to date garnered only 18 ratifications. A review and analysis of the Moon Agreement, including its historical context and its current profile, offer both a cautionary tale and valuable guidance to inform a governance framework for space resource utilization activities. Ultimately, the question of how to characterize space resources remains unanswered because, as we shall see, the Moon Agreement proved that the answer cannot be imposed but must be permitted to evolve. Nevertheless, a review of the Agreement is important both as a cautionary tale and an interpretive tool.
Moon Agreement: Key Provisions
Authors: Tronchetti Fabio
Published: May 2024

The Moon Agreement is the least successful international space treaty with only 17 States being Party to it, not including any of the space-faring ones. Despite its limited number of ratifications, the Moon Agreement maintains its legal relevance, especially in consideration of the present interest towards setting up principles governing space resource utilization activities. There are at least three elements that render the Moon Agreement relevant in this context. First, it is the only international treaty that contains rules dedicated to the conduct of human activities on a celestial body, including the utilization of resources for scientific and non-scientific purposes. Secondly, it is worth assessing how the multilateral approach endorsed by the Agreement may (or may not) coexist with the numerous domestic and regional legal initiatives that States have taken in the area of space resource utilization. Thirdly, one has to investigate the role that the States Parties to the Agreement are playing (and will play) in the process of formation of a potential framework governing lunar and other celestial bodies’ activities within the United Nations Committee on the Peaceful Uses of Outer Space, particularly by assessing whether these countries are effectively promoting the Agreement’s provisions or are taking a more cautious approach.
Soft Laws Relating to Space Activities
Authors: Zhao Yun
Published: May 2024

In light of the difficulties in reaching binding legal documents with increasingly diversified space interests, soft laws have been taking up more and more important roles in the regulation of space activities in recent years. The United Nations General Assembly (UNGA) resolutions are a major type of soft law instrument. With the ongoing space commercialization and privatization, UNGA resolutions have filled in the legal vacuum by providing important guidance on legal issues related to specific space activities. The United Nations Committee on the Peaceful Uses of Outer Space (UNCOPUOS) has also played a vital role by issuing guidelines regarding such issues as space debris mitigation and space sustainability. Outside the United Nations (UN) forum, various entities have also been active in the field. The increasing use of soft laws for various existing and emerging space activities is an important way to build consensus on relevant legal issues.
Role of the International Telecommunication Union in Regulating Space Activities
Authors: Brobst Jennifer A
Published: May 2024

This chapter addresses the legal framework and role of the International Telecommunication Union (ITU), with respect to governmental and commercial activities in space. The ITU is a large, specialised agency of the United Nations with 193 member states and hundreds of other private sector members and associates. ITU regulation involves a licensing and planning scheme for allocation of radio wave frequencies and satellite launch, but also intersects with key legal concerns that do not inherently involve orbital or outer space, such as national security export controls and equitable access to telecommunications for developing nations. As the number of satellites in orbit increases and the commercial satellite industry takes hold, legal challenges arise in how to address satellite congestion and debris hazards, rational competition for launch of new satellites, licensure of higher spectrum levels, the militarisation of space, and ongoing questions of sovereignty relating to resource exploitation and common heritage rights.
International Secured Transactions Law in Outer Space
Authors: Hameed Hamza
Published: May 2024

This chapter will examine the application of international private law-related instruments to the space sector, with a focus on international commercial law and secured transactions law. The chapter will pay special attention to the Space Protocol of the Cape Town Convention, which is an international secured transactions law treaty for the space sector, adopted at a Diplomatic Conference in 2012 under the auspices of the International Institute for the Unification of Private Law (UNIDROIT). As private investment in the space sector grows, alongside the development of innovative technologies such as on-orbit servicing, in-space manufacturing, and software-deployed satellites, the importance of security rights in space assets increases and more deals are concluded with traditional creditor-debtor-type arrangements. This chapter will highlight how these types of arrangements would operate in outer space and the remedies available to creditors in cases of insolvency of a debtor. In examining the Space Protocol, the chapter will also highlight its potential benefits for NewSpace, as well as the safeguards included in the Treaty, keeping in mind the nature of the space industry. The chapter will conclude with an assessment of where the space financing industry presently stands in terms of the financing models being used, the areas it is likely to expand into, and how secured transactions law could become an important part of this.
International Norms on the Settlement of Space Disputes
Authors: Sundahl Mark J
Published: May 2024

Due to the rapid expansion of the space economy, a surge in the number of space-related disputes is inevitable. These disputes will take a variety of forms arising from, for example, the violation of international treaties, the breach of contracts, satellite collisions, operational interference, or injury to space tourists. In each case, the appropriate method for resolving the dispute must be carefully selected to accommodate the special nature of the dispute. In some cases, litigation before the International Court of Justice will be the appropriate venue, while informal negotiation or arbitration may be best suited for other disputes. The factors that affect this choice will include, among other things, the identity of the parties, whether the matter is international in nature, and whether the parties have a contractual relationship. This chapter explains the dispute resolution options available to the space industry and provides guidance when practitioners must choose among them.
Women as Signs
Authors: Marchesi Ilaria
Published: May 2024

The chapter provides several examples of normative treatments of what women are or are supposed to be, extracted from Martial’s poetry and chronologically neighboring cultural contexts. A compact front emerges, in which woman is treated as signifier of male identity. The role is, however, highly problematic: since a woman’s social task is the representation of the father and reproduction of the husband, she is at once valued for her stability and for her mutability. Pliny’s letter about the virtues of his wife Calpurnia is juxtaposed with an epigram Martial dedicates to his patron Regulus about the signs of brilliancy displayed by his young son. Deep strategic oppositions mark these texts, but both appear similarly engaged in constructing a paradigm of motherhood as semantic neutrality, while simultaneously haunted by the ambiguities and tensions associated with the maternal imprint.
A Typology of Martial’s Women
Authors: Marchesi Ilaria
Published: May 2024

The chapter consists of a systematic set of contrasting comparisons between Martial’s positive and negative portrayals of women. Martial presents a select few women as models of behavior: Argentaria Polla, Lucan’s widow; the poetess Sulpicia; and Claudia Rufina, the wife of a prominent Roman citizen. As portraits of stable, subservient, and docile signifiers, the poems in which these women appear illuminate the varied phenomenology of negative characters paraded in the Epigrams: women who oppose their social and cultural definition, impose identity on their male counterparts, and strategically pose as something they are not—the resisting Bassa, who claims for herself the lexically masculine term fututor; the dominating Naevia, whose name has taken over her lover’s mind, language, and writing; and the shifting Laevina, who leaves for Baiae a model of chastity, a Penelope, only to come back a champion of debauchery, a Helen.
A Way Forward
Authors: Marchesi Ilaria
Published: May 2024

The Epilogue introduces possible avenues for future inquiry into Martial’s corpus of epigrammatic poetry. It points, in particular to patronage, in its unstable relation with the assumption of symbolic reciprocity; the mechanisms of inheritance and captatio, its looming negative counterpart; Saturnalian freedom, a potential challenge to the semiotic boundaries of the Roman enslavement system; the highly formalized protocols of dining, an activity which invests food with meaning at a most basic level; the socially appropriate care for clothing style, scent, and teeth—all movable and mutable signs of one’s own public identity. These are material and symbolic phenomena which Martial treats in the Epigrams and that may be subjected to semiotic readings of the kind proposed in the book.
No Peace Without Punishment? Reintegrating Islamic State “Collaborators” in Iraq
Authors: Revkin Mara R , Kao Kristen
Published: May 2024

How does variation in the severity of punishment affect public opinion toward the reintegration of former enemy “collaborators” after war? We study this question in the context of Iraq where the Islamic State, an armed rebel group, captured and governed a population of more than five million Iraqi citizens between 2014 and 2017. Building upon extensive fieldwork and interviews in Iraq, we designed a survey experiment that randomly varied the severity of sentences in hypothetical scenarios of civilians who supported the Islamic State in non-violent roles (e.g., cleaners, cooks, and wives of fighters). The experiment allows us to estimate the causal effects of punishment on attitudes toward reintegration. We find that a long prison sentence (fifteen years) does not increase the likelihood of participants’ willingness to allow the reintegration of former collaborators; instead, a noncarceral punishment (community service) has a small but statistically significant positive effect. Our most striking findings show that noncarceral and community-based justice mechanisms can significantly increase the likelihood of successful reintegration after punishment. Fifteen percent of respondents who were initially opposed to the return of former collaborators into their communities said that they would be willing to change their judgment and support reintegration if they were asked to do so by a tribal or religious leader, or if the offender completes a noncarceral rehabilitation program. These findings suggest that noncarceral, restorative, and community-based justice mechanisms may be equally or potentially more effective than long-term incarceration for achieving the objectives of rehabilitation and eventual reintegration of former nonviolent offenders. This Article advances the field of comparative empirical legal scholarship by providing an innovative experimental research design that can be replicated by scholars studying other contexts to help answer important questions about the causal effects of criminal justice policies.
Domestic sexual abuse in early Christianity: conflations of violence and desire in the Acts of John
Authors: Crabbe Kylie
Published: May 2024

‘Either I’ll have you as a wife, as I had you before, or you must die!’ So Andronicus yells at Drusiana, having locked her in a tomb for refusing to have sex with him, in the second-century Acts of John. Drusiana’s domestic setting houses a nested story of violence. Her husband’s abuse parallels that of a rival assailant, Callimachus, who in turn also involves Andronicus’ steward in his violent planning. After a brief overview of the passage, and consideration of its genre alongside other Greek novels and its use of comedy, this paper analyzes the domestic setting’s violence through the portraits of these three male characters and Drusiana. The article suggests that intersectional dynamics support the text’s rehabilitation of the elite male characters and denunciation of the ‘unchangeable’ steward, with implications also for understanding broader attitudes about marriage and sexual abuse in antiquity. In keeping with other portraits of sexual desire and violence elsewhere in the Acts of John, it argues that the text conflates violence and desire in the interest of championing celibacy, which is idealized in a mixed message about the one named female character in this passage, Drusiana.
P23 The influence of maternal inflammatory status on the risk of atopic eczema in offspring during infancy
Authors: El-Heis Sarah , Crozier Sarah , Tham Elizabeth , Inskip Hazel , Harvey Nick , Godfrey Keith
Published: May 2024

Introduction and aims

Maternal influences on infantile atopic eczema are complex, with emerging evidence for a protective role for maternal T helper (Th)1 inflammation during pregnancy. Substantial literature on characterization of a proinflammatory dietary pattern, led us to hypothesize that analyses of maternal diet and markers of inflammation might help identify mechanisms influencing the risk of infantile atopic eczema. The aim of this study was to examine the associations between energy-adjusted dietary inflammatory index (eDII) scores indicative of a proinflammatory diet pattern, maternal serum neopterin levels (a biomarker elevated in Th1 immune activation which counteracts Th2 inflammation seen in atopic eczema), and infantile risk of atopic eczema.

Methods

Within the UK Southampton Women’s Survey, scores for the eDII were derived from mothers’ diets (questionnaires at preconception, early and late pregnancy). Atopic eczema was ascertained at age 6 and 12 months using the UK Working Party Diagnostic Criteria (n = 262 and 270, respectively). Late pregnancy maternal serum neopterin levels were measured in a subsample (n = 497). Directed acyclic graphs were used to determine covariates to be included in linear regression analyses.

Results

A higher eDII score in late pregnancy was associated with a reduced risk of atopic eczema at age 6 months [odd ratios (OR) 0.89, 95% CI confidence interval (CI) 0.81–0.98; P = 0.02], with a similar trend at age 12 months (OR 0.91, 95% CI 0.83–1.00; P = 0.06). Consistent with this, and adjusting for maternal body mass index, education, smoking during pregnancy, and recent eczema, and infant filaggrin single-nucleotide polymorphism rs7512552, breastfeeding duration and sex, higher maternal serum concentrations of neopterin were associated with lower risks of infant eczema at age 6 months (OR 0.72, 95% CI 0.51–1.01; P = 0.05) and 12 months (OR 0.71, 95% CI 0.53–0.96; P = 0.03).

Conclusions

These findings suggest that a proinflammatory maternal diet that promotes a Th1 predominant environment protects the developing infant from Th2 inflammation and reduces the risk of atopic eczema.
P39 Using single-cell transcriptomics to investigate the potential role of the human hair follicle dermal papilla in controlling hair fibre pigmentation
Authors: Redmond Leah C , Limbu Summik , Jiménez Francisco , D’Souza Chris , Williams Greg , Higgins Claire
Published: May 2024

Introduction and aims

The human dermal papilla (DP) is a population of cells located at the base of the hair follicle, which signals to surrounding matrix cells facilitating their incorporation into the layers of the hair fibre and the hair follicle. The DP controls the process of hair follicle induction, reflecting its critical role in orchestrating processes integral in hair growth. We hypothesize that distinct functional subgroups exist within the structure, which would mean that there are different types of DP cells within each follicle.

Methods

To begin testing this, we reanalysed the single-cell RNA sequencing (RNA-Seq) dataset of the human anagen hair follicle used in the 2022 study by Shim et al. To expand on this, we are now generating single-cell RNA-Seq datasets of patient-matched pigmented and nonpigmented hair follicles (n = 4 patients). These datasets will be used to explore heterogeneity in the human DP, and to investigate which subpopulations are potentially changed in the case of pigmentation loss. This will allow us to explore a potentially undiscovered role of the DP in controlling hair fibre pigmentation.

Results

We found four distinct subpopulations in the DP with statistically significant marker genes in the Shim dataset. This confirms transcriptional heterogeneity in the human DP, hinting at clusters of DP cells with specialized functions within each hair follicle. One subcluster, which expressed S100B, endothelin-3 and bone morphogenetic protein (BMP)4, was of particular interest and gene ontology analysis of the genes in this cluster revealed terms associated with skeletal development and BMP signalling. We hypothesize that this DP cluster regulates melanin transfer from bulbar melanocytes to neighbouring keratinocytes, owing to the known involvement of the mentioned genes in both melanogenesis and melanin transfer.

Conclusions

The human DP is a heterogeneic structure, with a potentially unexplored role in controlling hair fibre pigmentation.
National epidemiology of digital papillary adenocarcinoma in England 2013–2020: a population-based registry study
Authors: Andrew Kashini , van Bodegraven Birgitta , Vernon Sally , Balogun Mariam , Craig Paul , Rajan Neil , Venables Zoe C , Tso Simon
Published: May 2024

Background

Digital papillary adenocarcinoma (DPA), formerly known as aggressive DPA, is a rare adnexal cancer of sweat gland differentiation with metastatic potential. DPA epidemiology and patient outcome data are prerequisites for developing diagnostic and therapeutic guidance, which are lacking for this rare cancer.

Objectives

To report the incidence, patient demographics and treatment of patients with DPA in England from 1 January 2013 to 31 December 2020 using national cancer registry data.

Methods

DPA diagnoses in England during 2013–2020 were identified from the National Cancer Registration and Analysis Service dataset using morphology and behaviour codes. These were registered from routinely collected pathology reports, along with cancer outcomes and services datasets. The 2013 European age-standardized incidence rates (EASRs) were calculated.

Results

In total, 36 cases of DPA (7 in women and 29 in men) were diagnosed. The median age at diagnosis for the cohort was 54 years (interquartile range 46–64). The most frequently affected sites were the upper limbs (81%). All patients in the cohort received surgical excisions. The EASR was 0.10 (95% confidence interval 0.07–0.14) per 1 000 000 person-years.

Conclusions

This study reports the incidence and variation of DPA in England between 2013 and 2020. DPA was more common in older men and predominantly affected the upper limbs. This finding supports the need to develop a national policy for the reporting and management of DPA as well as development of a clinical guideline.
Association Between Infectious Diseases Consultation and Mortality in Hospitalized Patients With Gram-negative Bloodstream Infection: A Retrospective Population-wide Cohort Study
Authors: Ong Sean W X , Luo Jin , Fridman Daniel J , Lee Samantha M , Johnstone Jennie , Schwartz Kevin L , Diong Christina , Patel Samir N , MacFadden Derek R , Langford Bradley J , Tong Steven Y C , Brown Kevin A , Daneman Nick
Published: May 2024

Objectives

Data supporting routine infectious diseases (ID) consultation in gram-negative bloodstream infection (GN-BSI) are limited. We evaluated the association between ID consultation and mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario using linked health administrative databases.

Methods

Hospitalized adult patients with GN-BSI between April 2017 and December 2021 were included. The primary outcome was time to all-cause mortality censored at 30 days, analyzed using a mixed effects Cox proportional hazards model with hospital as a random effect. ID consultation 1–10 days after the first positive blood culture was treated as a time-varying exposure.

Results

Of 30 159 patients with GN-BSI across 53 hospitals, 11 013 (36.5%) received ID consultation. Median prevalence of ID consultation for patients with GN-BSI across hospitals was 35.0% with wide variability (range 2.7%–76.1%, interquartile range 19.6%–41.1%). In total, 1041 (9.5%) patients who received ID consultation died within 30 days, compared to 1797 (9.4%) patients without ID consultation. In the fully adjusted multivariable model, ID consultation was associated with mortality benefit (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] .77–.88, P < .0001; translating to absolute risk reduction of −3.8% or number needed to treat [NNT] of 27). Exploratory subgroup analyses of the primary outcome showed that ID consultation could have greater benefit in patients with high-risk features (nosocomial infection, polymicrobial or non-Enterobacterales infection, antimicrobial resistance, or non-urinary tract source).

Conclusions

Early ID consultation was associated with reduced mortality in patients with GN-BSI. If resources permit, routine ID consultation for this patient population should be considered to improve patient outcomes.
Using artificial intelligence to predict mortality in AKI patients: a systematic review/meta-analysis
Authors: Raina Rupesh , Shah Raghav , Nemer Paul , Fehlmen Jared , Nemer Lena , Murra Ali , Tibrewal Abhishek , Sethi Sidharth Kumar , Neyra Javier A , Koyner Jay
Published: May 2024

Background

Acute kidney injury (AKI) is associated with increased morbidity/mortality. With artificial intelligence (AI), more dynamic models for mortality prediction in AKI patients have been developed using machine learning (ML) algorithms. The performance of various ML models was reviewed in terms of their ability to predict in-hospital mortality for AKI patients.

Methods

A literature search was conducted through PubMed, Embase and Web of Science databases. Included studies contained variables regarding the efficacy of the AI model [the AUC, accuracy, sensitivity, specificity, negative predictive value and positive predictive value]. Only original studies that consisted of cross-sectional studies, prospective and retrospective studies were included, while reviews and self-reported outcomes were excluded. There was no restriction on time and geographic location.

Results

Eight studies with 37 032 AKI patients were included, with a mean age of 65.1 years. The in-hospital mortality was observed to be 19.8%. The pooled [95% confidence interval (CI)] AUC was observed to be highest for the broad learning system (BLS) model [0.852 (0.820–0.883)] and elastic net final (ENF) model [0.852 (0.813–0.891)], and lowest for proposed clinical model (PCM) [0.765 (0.716–0.814)]. The pooled (95% CI) AUC of BLS and ENF did not differ significantly from other models except PCM [Delong's test P = 0.013]. PCM exhibited the highest negative predictive value, which supports this model's use as a possible rule-out tool.

Conclusion

Our results show that BLS and ENF models are equally effective as other ML models in predicting in-hospital mortality, with variability across all models. Additional studies are needed.
Impact of Direct Measurement of Small Dense Low-Density Lipoprotein Cholesterol for Long-Term Secondary Prevention in Patients with Stable Coronary Artery Disease
Authors: Koba Shinji , Satoh Noriyuki , Ito Yasuki , Yokota Yuya , Tsunoda Fumiyoshi , Sakai Koshiro , Nakamura Yuya , Shoji Makoto , Hirano Tsutomu , Shinke Toshiro
Published: May 2024

Background

This study investigated whether directly measured small dense low-density lipoprotein cholesterol (D-sdLDL-C) can predict long-term coronary artery disease (CAD) events compared with low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apoB), and estimated small dense low-density lipoprotein cholesterol (E-sdLDL-C) determined by the Sampson equation in patients with stable CAD.

Methods

D-sdLDL-C measured at Showa University between 2010 and 2022, and E-sdLDL-C were evaluated in 790 male and 244 female patients with stable CAD. CAD events, defined as sudden cardiac death, onset of acute coronary syndrome, and/or need for coronary revascularization, were monitored for 12 years. Cutoff lipid levels were determined by receiver operating characteristic curves.

Results

CAD events were observed in 238 male and 67 female patients. The Kaplan–Meier event-free survival curves showed that patients with D-sdLDL-C ≥32.1 mg/dL (0.83 mmol/L) had an increased risk for CAD events (P = 0.007), whereas risk in patients with E-sdLDL-C ≥36.2 mg/dL (0.94 mmol/L) was not increased. In the group with high D-sdLDL-C, the multivariable-adjusted hazard ratio (HR) was 1.47 (95% CI, 1.15–1.89), and it remained significant after adjustment for LDL-C, non-HDL-C, or apoB and in patients treated with statins. HRs for high LDL-C, non-HDL-C, or apoB were not statistically significant after adjustment for high D-sdLDL-C. Higher D-sdLDL-C was associated with enhanced risk of high LDL-C, non-HDL-C, and apoB (HR 1.73; 95% CI, 1.27–2.37).

Conclusions

Higher D-sdLDL-C can predict long-term recurrence of CAD in stable CAD patients independently of apoB and non-HDL-C. D-sdLDL-C is an independent risk enhancer for secondary CAD prevention, whereas E-sdLDL-C is not.

UMIN-CTR Clinical Trial Number: UMIN000027504
Cyclophosphamide-free Mobilisation Increases Safety While Preserving the Efficacy of Autologous Haematopoietic Stem Cell Transplantation in Refractory Crohn’s Disease Patients
Authors: Giordano Antonio , Rovira Montserrat , Veny Marisol , Barastegui Rebeca , Marín Pedro , Martínez Carmen , Fernández-Avilés Francesc , Suárez-Lledó María , Domènech Ariadna , Serrahima Anna , Lozano Miquel , Cid Joan , Ordás Ingrid , Fernández-Clotet Agnés , Caballol Berta , Gallego Marta , Vara Alejandro , Masamunt Maria Carme , Giner Àngel , Teubel Iris , Esteller Miriam , Corraliza Anna María , Panés Julian , Salas Azucena , Ricart Elena
Published: May 2024

Background and Aim

Autologous haematopoietic stem cell transplantation [AHSCT] is a therapeutic option for refractory Crohn’s disease [CD]. However, high adverse event rates related to chemotherapy toxicity and immunosuppression limit its applicability. This study aims to evaluate AHSCT’s safety and efficacy using a cyclophosphamide [Cy]-free mobilisation regimen.

Methods

A prospective, observational study included 14 refractory CD patients undergoing AHSCT between June 2017 and October 2022. The protocol involved outpatient mobilisation with G-CSF 12–16 μg/kg/daily for 5 days, and optional Plerixafor 240 μg/d [1–2 doses] if the CD34 + cell count target was unmet. Standard conditioning with Cy and anti-thymocyte globulin was administered. Clinical, endoscopic, and radiological assessments were conducted at baseline and during follow-up.

Results

All patients achieved successful outpatient mobilisation [seven patients needed Plerixafor] and underwent transplantation. Median follow-up was 106 weeks (interquartile range [IQR] 52–348). No mobilisation-related serious adverse events [SAEs] or CD worsening occurred. Clinical and endoscopic remission rates were 71% and 41.7% at 26 weeks, 64% and 25% at 52 weeks, and 71% and 16.7% at the last follow-up, respectively. The percentage of patients who restarted CD therapy for clinical relapse and/or endoscopic/radiological activity was 14% at 26 weeks, 57% at 52 weeks, and 86% at the last follow-up, respectively. Peripheral blood cell populations and antibody levels post-AHSCT were comparable to Cy-based mobilisation.

Conclusions

Cy-free mobilisation is safe and feasible in refractory CD patients undergoing AHSCT. Although relapse occurs in a significant proportion of patients, clinical and endoscopic responses are achieved upon CD-specific therapy reintroduction.
Serum Extracellular Matrix Molecules and Their Fragments as Biomarkers of Inflammation and Fibrosis in Inflammatory Bowel Diseases: A Systematic Review
Authors: Poulsen Anja , Ovesen Pernille Dige , Lu Cathy , Bettenworth Dominik , Jairath Vipul , Feagan Brian G , Seidelin Jakob Benedict , Rieder Florian
Published: May 2024

Background and Aim

Contemporary techniques to assess disease activity or bowel damage in patients with inflammatory bowel disease [IBD], such as endoscopy and imaging, are either invasive or lack accuracy. Non-invasive biomarkers for this purpose remain an unmet medical need. Herein, we provide a comprehensive systematic review of studies evaluating blood extracellular matrix [ECM] biomarkers and their relevance in IBD.

Methods

We conducted a systematic review of PubMed, EMBASE, Web of Science, and Scopus to identify citations pertaining to ECM biomarkers of IBD up to March 1, 2024. Studies were categorized based on marker subtype and clinical use.

Results

Thirty-one ECM markers were identified, 28 of which demonstrated the ability to differentiate IBD disease activity. Collagen III emerged as the most extensively investigated [1212 IBD patients], with the degradation marker C3M and deposition marker PRO-C3 being associated with IBD and subtypes. Collagen V markers C5M and PRO-C5 emerged as the most accurate single markers for diagnosis of IBD, with an area under the curve of 0.91 and 0.93, respectively. Overall, studies were characterized by variable endpoints. None of the studies included histological grading of intestinal damage, repair, or fibrosis formation as the primary outcome in relation to the ECM blood markers.

Conclusions

Multiple ECM markers are linked with IBD and its phenotypes. However, more rigorous study designs and clearly defined endpoints are needed to ensure reproducibility and develop reliable and accurate biomarkers. ECM markers hold promise as they provide a ‘window’ into transmural tissue remodelling and fibrosis burden, warranting further investigation.
Tractable Bayesian estimation of smooth transition vector autoregressive models
Authors: Bruns Martin , Piffer Michele
Published: May 2024

We develop a tractable way of estimating the parameters ruling the nonlinearity in the popular smooth transition VAR model, and identify structural shocks using external instruments. This jointly offers an alternative to the option of identifying shocks recursively and calibrating key parameters. In an illustration, we show that monetary policy shocks generate larger effects on economic activity during economic expansions compared to economic recessions. We then document that calibrating rather than estimating the parameters ruling the nonlinearity of the model can lead to values for which the key results are lost. This suggests caution in the calibration of these parameters.
Incident heart failure in chronic kidney disease: proteomics informs biology and risk stratification
Authors: Dubin Ruth F , Deo Rajat , Ren Yue , Wang Jianqiao , Pico Alexander R , Mychaleckyj Josyf C , Kozlitina Julia , Arthur Victoria , Lee Hongzhe , Shah Amil , Feldman Harold , Bansal Nisha , Zelnick Leila , Rao Panduranga , Sukul Nidhi , Raj Dominic S , Mehta Rupal , Rosas Sylvia E , Bhat Zeenat , Weir Matthew R , He Jiang , Chen Jing , Kansal Mayank , Kimmel Paul L , Ramachandran Vasan S , Waikar Sushrut S , Segal Mark R , Ganz Peter ,   CRIC Study Investigators, Appel Lawrence J , Cohen Debbie L , Lash James P , Nelson Robert G , Shah Vallabh O , Unruh Mark L
Published: May 2024

Background and Aims

Incident heart failure (HF) among individuals with chronic kidney disease (CKD) incurs hospitalizations that burden patients and health care systems. There are few preventative therapies, and the Pooled Cohort equations to Prevent Heart Failure (PCP-HF) perform poorly in the setting of CKD. New drug targets and better risk stratification are urgently needed.

Methods

In this analysis of incident HF, SomaScan V4.0 (4638 proteins) was analysed in 2906 participants of the Chronic Renal Insufficiency Cohort (CRIC) with validation in the Atherosclerosis Risk in Communities (ARIC) study. The primary outcome was 14-year incident HF (390 events); secondary outcomes included 4-year HF (183 events), HF with reduced ejection fraction (137 events), and HF with preserved ejection fraction (165 events). Mendelian randomization and Gene Ontology were applied to examine causality and pathways. The performance of novel multi-protein risk models was compared to the PCP-HF risk score.

Results

Over 200 proteins were associated with incident HF after adjustment for estimated glomerular filtration rate at P < 1 × 10−5. After adjustment for covariates including N-terminal pro-B-type natriuretic peptide, 17 proteins remained associated at P < 1 × 10−5. Mendelian randomization associations were found for six proteins, of which four are druggable targets: FCG2B, IGFBP3, CAH6, and ASGR1. For the primary outcome, the C-statistic (95% confidence interval [CI]) for the 48-protein model in CRIC was 0.790 (0.735, 0.844) vs. 0.703 (0.644, 0.762) for the PCP-HF model (P = .001). C-statistic (95% CI) for the protein model in ARIC was 0.747 (0.707, 0.787).

Conclusions

Large-scale proteomics reveal novel circulating protein biomarkers and potential mediators of HF in CKD. Proteomic risk models improve upon the PCP-HF risk score in this population.
Catheter ablation for persistent atrial fibrillation: patterns of recurrence and impact on quality of life and health care utilization
Authors: Crowley Rose , Chieng David , Sugumar Hariharan , Ling Liang-Han , Segan Louise , William Jeremy , Prabhu Sandeep , Voskoboinik Aleksandr , Wong Geoffrey , Morton Joseph B , Lee Geoffrey , McLellan Alex J , Wong Michael , Pathak Rajeev K , Sterns Laurence , Ginks Matthew , Sanders Prashanthan , Kalman Jonathan M , Kistler Peter M
Published: May 2024

Background and Aims

Patterns of atrial fibrillation (AF) recurrence post-catheter ablation for persistent AF (PsAF) are not well described. This study aimed to describe the pattern of AF recurrence seen following catheter ablation for PsAF and the implications for healthcare utilization and quality of life (QoL).

Methods

This was a post-hoc analysis of the CAPLA study, an international, multicentre study that randomized patients with symptomatic PsAF to pulmonary vein isolation plus posterior wall isolation or pulmonary vein isolation alone. Patients underwent twice daily single lead ECG, implantable device monitoring or three monthly Holter monitoring.

Results

154 of 333 (46.2%) patients (median age 67.3 years, 28% female) experienced AF recurrence at 12-month follow-up. Recurrence was paroxysmal in 97 (63%) patients and persistent in 57 (37%). Recurrence type did not differ between randomization groups (P = .508). Median AF burden was 27.4% in PsAF recurrence and .9% in paroxysmal AF (PAF) recurrence (P < .001). Patients with PsAF recurrence had lower baseline left ventricular ejection fraction (PsAF 50% vs. PAF 60%, P < .001) and larger left atrial volume (PsAF 54.2 ± 19.3 mL/m² vs. PAF 44.8 ± 11.6 mL/m², P = .008). Healthcare utilization was significantly higher in PsAF (45 patients [78.9%]) vs. PAF recurrence (45 patients [46.4%], P < .001) and lowest in those without recurrence (17 patients [9.5%], P < .001). Patients without AF recurrence had greater improvements in QoL as assessed by the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire (Δ33.3 ± 25.2 points) compared to those with PAF (Δ24.0 ± 25.0 points, P = .012) or PsAF (Δ13.4 ± 22.9 points, P < .001) recurrence.

Conclusions

AF recurrence is more often paroxysmal after catheter ablation for PsAF irrespective of ablation strategy. Recurrent PsAF was associated with higher AF burden, increased healthcare utilization and antiarrhythmic drug use. The type of AF recurrence and AF burden may be considered important endpoints in clinical trials investigating ablation of PsAF.
Phenotypically plastic responses to environmental variation are more complex than life history theory predicts
Authors: Hayes Abigail M , Worthington Amy M , Lavine Mark , Lavine Laura
Published: May 2024

For insects that exhibit wing polyphenic development, abiotic and biotic signals dictate the adult wing morphology of the insect in an adaptive manner such that in stressful environments the formation of a flight-capable morph is favored and in low-stress environments, a flightless morph is favored. While there is a relatively large amount known about the environmental cues that dictate morph formation in wing polyphenic hemipterans like planthoppers and aphids, whether those cues dictate the same morphs in non-hemipteran (i.e., cricket) wing polyphenic species has not been explicitly investigated. To experimentally test the generality of environmental cue determination of wing polyphenism across taxa with diverse life histories, in this study, we tested the importance of food quantity, parasitic infection, and tactile cues on wing morph determination in the wing polyphenic sand field cricket, Gryllus firmus. Our results also show that certain stress cues, such as severe diet quantity limitation and parasitic infection, actually led to an increase in the production of flightless morph. Based on these findings, our results suggest that physiological and genetic constraints are important to an organism’s ability to respond to environmental variation in an adaptive manner beyond simple life history trade-offs.
Moss abundance increased along a gradient of postfire interventions from high to low intensity after a forest fire in Brandenburg, Germany
Authors: Fröhlich Katrin , Schmidtlein Sebastian , Saha Somidh
Published: May 2024

The intensity and frequency of forest fires are increasing in the cultural landscape of central Europe as the climate is becoming warmer and drier. This requires an understanding of natural regeneration processes in forests and the effects of traditional and new approaches to restoring fire-damaged forests; however, it warrants more research in Germany, where large-scale stand-replacing fire is a new phenomenon in recent times. Specifically, early successional plant pioneer communities, such as mosses, influence the regenerating forest system, by providing viable conditions and habitats for subsequent plant species. The present work focuses on the processes that take place in the moss communities undergoing management interventions of a gradient of intervention intensities after fire disturbance. In a plot-based field inventory, we investigated early successional moss communities three years after a forest fire in Brandenburg, Germany. The study area was subjected to various postfire interventions: high intensity site preparation and dense row planting, natural regeneration (no intervention), and a moderate site preparation in combination with low-density group planting approach. Utilizing Bray–Curtis-based nonmetric multidimensional scaling to assess similarities among postfire moss communities, a simplification of moss communities under high-intensity postfire intervention was observed. We found that the diversity and abundance of mosses decreased with the application of high-intensity postfire intervention but increased with the application of moderate postfire interventions. Furthermore, we found a higher share of light-demanding pioneer mosses in areas under high intensity postfire intervention. In areas under moderate or no postfire intervention, more shade-tolerant species were present. We conclude that moderate interventions with low-intensity site preparation and group planting resulted in reduced losses of moss species and coverage in the successional moss community.
A Coordinated Data Analysis of Four Studies Exploring Age Differences in Social Interactions and Loneliness During a Global Pandemic
Authors: Neupert Shevaun D , Graham Eileen K , Ogle Destiny , Ali Sumbleen , Zavala Daisy V , Kincaid Reilly , Hughes MacKenzie L , Hu Rita X , Antonucci Toni , Suitor J Jill , Gilligan Megan , Ajrouch Kristine J , Scott Stacey B
Published: May 2024

Objectives

Examining loneliness and social isolation during population-wide historical events may shed light on important theoretical questions about age differences, including whether these differences hold across different regions and the time course of the unfolding event. We used a systematic, preregistered approach of coordinated data analysis (CDA) of 4 studies (total N = 1,307; total observations = 18,492) that varied in design (intensive repeated-measures and cross-sectional), region, timing, and timescale during the first year of the coronavirus disease 2019 pandemic.

Methods

We harmonized our data sets to a common period within 2020–2021 and created a common set of variables. We used a combination of ordinary least squares regression and multilevel modeling to address the extent to which there was within- and between-person variation in the associations between social isolation and loneliness, and whether these associations varied as a function of age.

Results

Within- and between-person effects of social interactions were negatively associated with loneliness in 1 study; in follow-up sensitivity analyses, these patterns held across early and later pandemic periods. Across all data sets, there was no evidence of age differences in the within-person or between-person associations of social interactions and loneliness.

Discussion

Applying the CDA methodological framework allowed us to detect common and divergent patterns of social interactions and loneliness across samples, ages, regions, periods, and study designs.