bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategic Uses of International Law in Peace Negotiations in Colombia
Authors: Alviar García Helena , Betancur-Restrepo Laura
Published: January 2025

This chapter explores the clashes and contradictions between the aims of achieving peace and the demands imposed by international institutions and treaties. Helena Alviar García and Laura Betancur-Restrepo explore that tension by discussing the negotiations and peace agreement between the Colombian government and the FARC guerrillas. The case offers an interesting example of the tense, complex, and far-reaching interaction between international law and domestic goals of ending civil conflict. Both national and external actors presented international law as univocal, universal, and neutral in relation to local political discussions. Building upon this insight, the text analyzes how different actors use international law strategically according to their political preferences or economic goals. The Colombian example is relevant to other jurisdictions as previous experiences in different parts of the world nourished the negotiations. It is the first peace agreement achieved since the International Criminal Court entered into force.
The Promise of Environmental Cooperation in Latin America
Authors: Garcia Beatriz
Published: January 2025

In this chapter, Beatriz Garcia explores the current forms of environmental cooperation in Latin America. The chapter examines whether new pathways could be open, especially regarding forest conservation, given new regulatory trends focused on global supply chains targeting commodities associated with forest destruction. Agricultural and forestry products represent a large share of Latin American domestic markets, while commodity exports, particularly to China and the United States, are likely to grow. This leads to whether international norms targeting global supply chains could be instrumental in reshaping Latin American forest conservation efforts. The argument is that these regulations open an opportunity to refocus Latin American cooperation into more tangible actions toward forest and biodiversity conservation.
Can the Inter-American Court Tip Us toward Climate Justice?
Authors: Huneeus Alexandra
Published: January 2025

In this chapter, Alexandra Huneeus argues that the Inter-American Court is poised to play a distinct role in the complex new realm of global climate emergency litigation. Increasingly, international courts are being called on to issue judgments on questions of state responsibilities in the face of climate change, including the International Court of Justice, the European Court of Human Rights, and the International Tribunal for the Law of the Sea. But the Inter-American Court is uniquely suited to the task given its rich jurisprudence on socioeconomic rights and differential harm doctrines, which can inform questions about climate justice for frontline communities and other vulnerable groups. Huneeus uses the emerging international climate docket as a site to reflect on the Court’s contributions to the development of structural approaches to human rights protection. Drawing on its legacy, the Court will have a unique voice in the new climactic regime.
Health Law and Pandemics in Latin America
Authors: Villarreal Pedro A
Published: January 2025

In this chapter, Pedro Villarreal discusses regional challenges in the field of international health law, with an emphasis on communicable disease pandemics. While COVID-19 represents the most acute disease-related problem in an entire century, the chapter shows how the regional dimension not only plays a role but may actually be a determining factor in the pandemic’s short- and longer-term impact. The chapter looks at the legal landscape, including the role of the Inter-American Human Rights System, and identifies the structural ailments that distinguish the region. It concludes by underscoring how the legal challenges posed by the COVID-19 pandemic in the region can be understood as a manifestation of economic inequality and the resulting social exclusion of marginalized groups.
Latin America and the Regulation of Internet and Digital Trade
Authors: Polanco Rodrigo
Published: January 2025

In this chapter, Rodrigo Polanco argues that Latin American contributions to the internet have not been sufficiently acknowledged. He describes how the countries of the region have played an active role in regulating the web, with particular emphasis on one of its more essential uses—digital trade. Latin American countries have made a distinct contribution to internet regulations, advancing principles like open access and net neutrality. In addition, they have pioneered the inclusion of e-commerce and data flow provisions in preferential trade agreements (PTAs). The chapter closes by highlighting potential conflicts between these countries’ domestic regulations and international commitments concerning the internet and digital trade.
Introduction
Authors: Savigliano Marta E , Schwadron Hannah
Published: January 2025

Bodies and movement are intrinsic to dance, but bodies in their diversity and plethora of moves are ready-made for funniness. Bodies become funny by refusing to look, act, or move as they “should,” though intentionality is often not knowable. Dancing only heightens the risk of being laughed at. Signature moves of the most renowned dance forms may seem funny to viewers not taught to appreciate them as serious art. Meanwhile, the constant risk of being found funny helps explain why many professional or aspiring dancers tend to look so humorless, egging on masterful mockeries of formality. Dance disciplines “out” the funny, working hard to keep it at bay. As the introduction insists through “politicking” theories of humor as they relate to dance, funny is the Other to Dance: intrinsic to it and yet too often overlooked. Dance humor is always already there, a potency always waiting in the wings.
The Argument against Conscientious Objection
Authors: Giubilini Alberto , Schuklenk Udo , Minerva Francesca , Savulescu Julian
Published: January 2025

This chapter defines and defends ‘professionalism’ as the main principle against a right to conscientious objection in health care. It outlines the principle’s history and its modern conceptualization on the basis of a contractualist view of professional duties. The chapter provides three plausible criteria for professional obligations: the Legal model, the Professional Codes model, and the Medical Ethics model. While each of these has its own problems and they can be in tension with one another, none of these is compatible with a right to conscientious objection in health care. The chapter endorses a version of the so-called incompatibilist thesis, whereby a commitment to professionalism is incompatible with a right to conscientious objection accommodation in health care. It illustrates through cases how conscientious objection can fall short of professional standards.
Conclusions
Authors: Giubilini Alberto , Schuklenk Udo , Minerva Francesca , Savulescu Julian
Published: January 2025

The last chapter summarizes and synthetizes the main points of the book into an overarching point against a right to conscientious objection in health care. It suggests that there should be vigorous ethical debate within the profession and in society at large about what medicine and health care should provide to patients as technology and social values evolve. Individual doctors should be able to contribute to that debate by making their personal values matter in public discussion. However, medicine and health care as professions must be fundamentally guided by standards of professionalism and not by the personal values of professionals. There is a pressing need to avoid turning the authority that health care professionals have over medical and scientific matters into a moral authority and, indeed, into medical and moral authoritarianism.
Minding the Metaphors of Weight and Weighing
Authors: Tucker Chris
Published: January 2025

Ethical theory is steeped in two related metaphors: reasons have weight and reasons are weighed on a balance scale to determine an act’s deontic status (e.g., whether the act is permissible or required). Are these metaphors good ones? Or are they distorting ethicists’ understanding of how considerations systematically interact to determine what is permissible and required? This chapter argues that these metaphors are instructive: they allow one to better understand the functional structure of morality and practical rationality. In particular, they tell us that reasons have at least two weight values (justifying weight and requiring weight) and that it takes two scales to model how considerations interact to determine whether an action is required, at least in cases with only two options.
The Representational Limits of Single Scale
Authors: Tucker Chris
Published: January 2025

The fundamental model of weighing reasons determines what it is to weigh reasons correctly. It can represent every normative theory—even every false theory—that weighs reasons correctly. This chapter argues that the most natural model, Single Scale, is not the fundamental model. Roughly, Single Scale holds that φ is permissible when the reasons for φ are at least as weighty as the reasons for ~φ, and φ is required when the reasons in its favor are weightier. While Single Scale can represent justifying and requiring weight, it cannot represent the possibility that these weight values vary independently of one another. Alas, many normative theories hold that they do vary independently of one another. If one of these theories is true, then Single Scale is false. But even if all these theories are false, they still weigh reasons correctly. Hence, Single Scale is not the fundamental model of weighing reasons.
Against Weight Monism
Authors: Tucker Chris
Published: January 2025

Weight Monism is the view that there is only a single weight of reasons, which makes it even more restrictive than Single Scale. The simplest versions hold that there are exactly three weight comparatives (weightier than, less weighty than, and equally weighty as). These simple versions cannot resolve the normative significance of small improvements or the justification intransitivity paradox. Building on work from Ruth Chang, the chapter develops a version of Weight Monism that adds parity, or on a par, as a fourth weight comparative. This view can explain the normative significance of small improvements but not permissible partiality, supererogation, or the justification intransitivity paradox. This chapter treats Parity Weight Monism as the most promising version of Monism, and it briefly explains why other accounts of monism (e.g., those that appeal to vagueness) are unlikely to do better.
The All or Nothing Ranking Reversal and the Unity of Morality
Authors: Tucker Chris
Published: January 2025

Supererogatory acts are (morally) better than their non-supererogatory alternatives. But what is it for one option A to be better than an alternative B? This chapter argues for three main conclusions. First, relative rankings are a type of all-in action guidance. If A is better than B, then morality recommends that you A rather than B. Such all-in guidance is useful when acts have the same deontic status. Second, Right > Wrong: permissible acts are always better than their impermissible alternatives. If Right > Wrong were false, then morality’s deontic verdicts would sometimes conflict with its relative rankings. Such conflict would undermine the thought that morality is a coherent, authoritative guide to action. Third, the All or Nothing Problem is not a counterexample to Right > Wrong. Instead, it involves a ranking reversal: whether A > B can depend on whether a certain alternative is added as a third option.
Modeling Requirement for Any Number of Options
Authors: Tucker Chris
Published: January 2025

This is the last and least chapter, but it completes the narrative of the book by identifying the fundamental model (Dynamic Scale), explaining why Dual Scale is not the fundamental model (it has difficulty detecting exotic kinds of dilemmas), and why it should be used anyway (it has the best balance of reliability and ease of use). At the heart of this chapter is the attempt to minimize the computational complexity of calculating which, if any, option is required when there are more than just a few options. Along the way, it also further defends contrastivism and explains how it is different from holism.
The Cold War and Our Own Times
Authors: Westad Odd Arne
Published: January 2025

This chapter looks at differences and similarities between the Cold War international system and the pattern of international affairs that seems to come together in the 2020s. In conclusion, it discusses whether there are significant lessons from the Cold War that leaders ought to draw on today. Before it moves to comparisons and lessons, the chapter considers the debate about historical recurrences and its near relative, path dependency, in history and the social sciences. The chapter is first and foremost an argument for taking comparisons more seriously, by considering differences and similarities between the past and the present. The thinking about comparing the Cold War era and today’s world should be understood within these frameworks of thought. Even though it stresses skepticism of the idea of repetitions, the chapter argues that they play a significant role in how people reflect on the past and the present.
Technological Competition and the US-China Rivalry
Authors: Fravel M Taylor
Published: January 2025

This chapter examines the role of competition over technology in the US-China rivalry, whose onset coincides with the Fourth Industrial Revolution. The United States and China are competing not only for relative power position but also to remain at the frontier of new technological developments that are likely to serve as new sources of national wealth and new instruments of military power that can further bolster a state’s relative power position. This chapter shows that technology has become an increasingly central object of competition between the United States and China, shaping mutual perceptions of intentions and threats. The technological competition has also elevated the role of US allies and other closely aligned states, many of whom, as technological powers, are key actors in efforts to limit China’s access to specific technologies, such as by enforcing export controls.
Technological Change and the Intensifying US-China Security Dilemma
Authors: Hiim Henrik Stålhane
Published: January 2025

Security dilemma dynamics is a crucial driver of the intensifying superpower rivalry between the United States and China. This chapter demonstrates that technological shifts are exacerbating the new superpower security dilemma. It outlines two main pathways. First, the advent of advanced precision-strike capabilities—coupled with the maturation of missile defense technology—is undermining nuclear stability and contributing to China’s nuclear expansion. Second, both states are developing capabilities that generate significant first-strike incentives, such as counterspace weapons. Because of its complexity, the new superpower security dilemma will be very hard to mitigate, and the military competition between China and the United States is likely to remain severe.
Can NATO Survive the Geostrategic Pivot to Asia?
Authors: Heisbourg François
Published: January 2025

The North Atlantic Treaty Organization (NATO) has a proven track record of surviving deep geopolitical shifts in its seventy-five years of existence. Several templates are examined with which NATO may cope with the pivot to Asia. One, “equidistance” by the European members of NATO vis-à-vis the United States and China, poses more problems than it resolves. A second, an explicit “division of labour,” with Asia being the Americans’ strategic responsibility while the Europeans deal with Europe, is not particularly attractive as war rages in Ukraine. “Risk sharing,” which involves putting more European “skin” in the Indo-Pacific theatre than is currently the case, is of limited utility. However, “Euro-Atlantic integration,” along lines emerging during the full-scale invasion of Ukraine, carries substantial potential. Conversely, a “global NATO” risks creating greater strategic unity between member countries. As ever, imponderables will be significant, but there is no basic reason to assume that NATO can’t manage it.
Dynamic color change in the grouper Variola louti during interspecific interactions and swimming
Authors: Marom Sagi , Kiflawi Moshe , Akkaynak Derya , Holzman Roi
Published: January 2025

Animals can change their body color for various ecological functions. In fish, rapid dynamic color change is primarily known in contexts of intraspecific communication and camouflage, while examples in interspecific contexts are rare. We studied dynamic color changes and their associated behaviors in the grouper Variola louti in its native coral reef environment in the Red Sea. Using underwater videos to record natural behaviors and color-calibrated still images to measure body colors, we quantified color displays as the brightness of the body and the contrast of three distinct patterns: body patches, head stripe, and side bars. V. louti exhibited a diverse range of pattern displays, which rapidly transformed according to its behavioral shifts. A high-contrast head stripe pattern was observed when V. louti engaged in agonistic interspecific interactions, but was interestingly absent when hunting alone or in cooperation with moray eels. The brightness of V. louti’s body color and the contrasts of the body patches and side bars were associated with its swimming behavior. Darker body colors and high contrast body patches and side bars were expressed when the fish rested on the bottom, whereas bright and uniform body colors were displayed when swimming higher above the reef. Our results suggest that V. louti utilizes dynamic color displays for camouflage and interspecific communication in agonistic and competitive interspecific interactions. These findings highlight the importance of dynamic color changes for communication and provide valuable insights into the behavioral ecology of animals.
A comprehensive graph neural network method for predicting triplet motifs in disease–drug–gene interactions
Authors: Kang Chuanze , Liu Zonghuan , Zhang Han
Published: January 2025

Motivation

The drug–disease, gene–disease, and drug–gene relationships, as high-frequency edge types, describe complex biological processes within the biomedical knowledge graph. The structural patterns formed by these three edges are the graph motifs of (disease, drug, gene) triplets. Among them, the triangle is a steady and important motif structure in the network, and other various motifs different from the triangle also indicate rich semantic relationships. However, existing methods only focus on the triangle representation learning for classification, and fail to further discriminate various motifs of triplets. A comprehensive method is needed to predict the various motifs within triplets, which will uncover new pharmacological mechanisms and improve our understanding of disease–gene–drug interactions. Identifying complex motif structures within triplets can also help us to study the structural properties of triangles.

Results

We consider the seven typical motifs within the triplets and propose a novel graph contrastive learning-based method for triplet motif prediction (TriMoGCL). TriMoGCL utilizes a graph convolutional encoder to extract node features from the global network topology. Next, node pooling and edge pooling extract context information as the triplet features from global and local views. To avoid the redundant context information and motif imbalance problem caused by dense edges, we use node and class-prototype contrastive learning to denoise triplet features and enhance discrimination between motifs. The experiments on two different-scale knowledge graphs demonstrate the effectiveness and reliability of TriMoGCL in identifying various motif types. In addition, our model reveals new pharmacological mechanisms, providing a comprehensive analysis of triplet motifs.

Availability and implementation

Codes and datasets are available at https://github.com/zhanglabNKU/TriMoGCL and https://doi.org/10.5281/zenodo.14633572.
A deep learning tissue classifier based on differential co-expression genes predicts the pregnancy outcomes of cattle
Authors: Huo Chenxi , Zhang Chuanqiang , Lu Jing , Su Xiaofeng , Qi Xiaoxia , Guo Yaqiang , Bao Yanchun , Jia Hongxia , Cao Guifang , Na Risu , Zhang Wenguang , Li Xihe
Published: January 2025

Economic losses in cattle farms are frequently associated with failed pregnancies. Some studies found that the transcriptomic profiles of blood and endometrial tissues in cattle with varying pregnancy outcomes display discrepancies even before artificial insemination (AI) or embryo transfer (ET). In the study, 330 samples from seven distinct sources and two tissue types were integrated and divided into two groups based on the ability to establish and maintain pregnancy after AI or ET: P (pregnant) and NP (nonpregnant). By analyzing gene co-variation and employing machine learning algorithms, the objective was to identify genes that could predict pregnancy outcomes in cattle. Initially, within each tissue type, the top 100 differentially co-expressed genes (DCEGs) were identified based on the analysis of changes in correlation coefficients and network topological structure. Subsequently, these genes were used in models trained by seven different machine learning algorithms. Overall, models trained on DCEGs exhibited superior predictive accuracy compared to those trained on an equivalent number of differential expression genes. Among them, the deep learning models based on differential co-expression genes in blood and endometrial tissue achieved prediction accuracies of 91.7% and 82.6%, respectively. Finally, the importance of DCEGs was ranked using SHapley Additive exPlanations (SHAP) and enrichment analysis, identifying key signaling pathways that influence pregnancy. In summary, this study identified a set of genes potentially affecting pregnancy by analyzing the overall co-variation of gene connections between multiple sources. These key genes facilitated the development of interpretable machine learning models that accurately predict pregnancy outcomes in cattle.
Pseudo-observations for bivariate survival data
Authors: Travis-Lumer Yael , Mandel Micha , Betensky Rebecca A
Published: January 2025

The pseudo-observations approach has been gaining popularity as a method to estimate covariate effects on censored survival data. It is used regularly to estimate covariate effects on quantities such as survival probabilities, restricted mean life, cumulative incidence, and others. In this work, we propose to generalize the pseudo-observations approach to situations where a bivariate failure-time variable is observed, subject to right censoring. The idea is to first estimate the joint survival function of both failure times and then use it to define the relevant pseudo-observations. Once the pseudo-observations are calculated, they are used as the response in a generalized linear model. We consider 2 common nonparametric estimators of the joint survival function: the estimator of Lin and Ying (1993) and the Dabrowska estimator (Dabrowska, 1988). For both estimators, we show that our bivariate pseudo-observations approach produces regression estimates that are consistent and asymptotically normal. Our proposed method enables estimation of covariate effects on quantities such as the joint survival probability at a fixed bivariate time point or simultaneously at several time points and, consequentially, can estimate covariate-adjusted conditional survival probabilities. We demonstrate the method using simulations and an analysis of 2 real-world datasets.
Solar-powered hydrogen: exploring production, storage, and energy integration strategies
Authors: Chen Ge , Sun Renhui , Wang Baodong
Published: January 2025

This review explores the advancements in solar technologies, encompassing production methods, storage systems, and their integration with renewable energy solutions. It examines the primary hydrogen production approaches, including thermochemical, photochemical, and biological methods. Thermochemical methods, though highly efficient, require advanced materials and complex reactor designs, while photochemical methods offer a simpler alternative but suffer from low conversion efficiencies. Biological hydrogen production presents a low-cost option but faces limitations in scalability and production rates. The review also highlights innovative hydrogen storage technologies, such as metal hydrides, metal-organic frameworks, and liquid organic hydrogen carriers, which address the intermittency of solar energy and offer scalable storage solutions. Additionally, the potential of hybrid energy systems that integrate solar hydrogen with photovoltaics, thermal energy systems, battery storage, and smart grids is emphasized. Despite technical and economic barriers, ongoing advancements in catalyst development, material optimization, and artificial intelligence-driven energy management systems are accelerating the adoption of solar hydrogen technologies. These innovations position solar hydrogen as a pivotal solution for achieving a sustainable and low-carbon energy future.
The symbolic power of sustainability: Gulf megaprojects and the case of Expo City Dubai
Authors: Koch Natalie
Published: January 2025

Sustainability has a unique symbolic power in the contemporary political landscape, as ordinary people, governments and institutions grapple with the effects of the climate crisis. Proponents of megaprojects have tapped into the symbolic power by framing their initiatives as “green,” however resource-intensive they might really be. This article illustrates how this works in the UAE through a case study of Expo City Dubai, the greenfield site developed for the World’s Fair, Expo 2020, and then used to host the UN’s COP28 climate negotiations in late 2023. At both events, sustainability’s symbolic power was used to advertise the UAE’s supposedly pro-environment credentials on a world stage, as well as to recruit investments in the Expo site’s redevelopment as a new green technopole in Dubai—and in so doing legitimate Emirati leaders’ ongoing commitment to megaprojects that are ultimately designed to continue and intensify the country’s resource-intensive political economy.
Variation in faecal testosterone levels in male gray whales on a foraging ground relative to maturity and timing
Authors: Fernandez Ajó A , Buck C L , Hunt K E , Pirotta E , New L , Dillon D , Bierlich K C , Hildebrand L , Bird C N , Torres L G
Published: January 2025

Understanding wildlife reproductive seasonality is crucial for effective management and long-term monitoring of species. This study investigates the seasonal variability of testosterone in male Pacific Coast Feeding Group (PCFG) gray whales, using an eight-year dataset (2016–2023) of individual sightings, drone-based photogrammetry and endocrine analysis of faecal samples. We analyzed the relationship between faecal testosterone levels and total body length (TL), body condition (body area index, BAI), sexual maturity and day of the year using generalized additive mixed models. Our findings reveal a significant increase in faecal testosterone levels in mature males (MM) towards the end of the foraging season. This increase was not observed in JM, highlighting age-dependent development of sexual characteristics. No significant relationship was found between testosterone levels and TL. Additionally, BAI was not significantly associated with testosterone levels. Our results suggest that the increasing testosterone levels in MM gray whales may indicate preparation for mating before the southbound migration. These findings provide valuable insights into the reproductive biology of PCFG gray whales and underscore the importance of non-invasive faecal sampling for studying reproductive seasonality in large whales. Our approach not only provides further insights into the seasonality of male reproduction for the PCFG gray whales but also offers tools to enhance the understanding of male reproduction in baleen whales broadly with non-invasive approaches.
Green Insurance for Pesticide Reduction: Acceptability and Impact for French Viticulture
Authors: Lefebvre Marianne , Raineau Yann , Aubert Cécile , Möhring Niklas , Pedehour Pauline , Raynal Marc
Published: January 2025

Green insurance can help producers manage the risks of transitioning to more environmentally friendly practices. We investigate the uptake determinant and potential pesticide reduction in the viticulture sector, a major pesticide user, using a choice experiment with 412 French growers. Correcting for sampling bias, we find that between 48 per cent and 60 per cent (depending on contract features) are likely to take up green insurance. The insurance offers compensation for yield losses caused by the failure to contain diseases of a Decision Support System targeting pesticide reduction. We find an average 45 per cent reduction in fungicide use for adopters and conclude that green insurance can be a cost-effective tool for achieving the EU’s ambitious pesticide objectives.
Phylogenetic signal in primate tooth enamel proteins and its relevance for paleoproteomics
Authors: Fong-Zazueta Ricardo , Krueger Johanna , Alba David M , Aymerich Xènia , Beck Robin M D , Cappellini Enrico , Carrillo-Martin Guillermo , Cirilli Omar , Clark Nathan , Cornejo Omar E , Farh Kyle Kai-How , Ferrández-Peral Luis , Juan David , Kelley Joanna L , Kuderna Lukas F K , Little Jordan , Orkin Joseph D , Paterson Ryan S , Pawar Harvinder , Marques-Bonet Tomas , Lizano Esther
Published: January 2025

Ancient tooth enamel, and to some extent dentin and bone, contain characteristic peptides that persist for long periods of time. In particular, peptides from the enamel proteome (enamelome) have been used to reconstruct the phylogenetic relationships of fossil taxa. However, the enamelome is based on only about 10 genes, whose protein products undergo fragmentation in vivo and post mortem. This raises the question as to whether the enamelome alone provides enough information for reliable phylogenetic inference. We address these considerations on a selection of enamel-associated proteins that has been computationally predicted from genomic data from 232 primate species. We created multiple sequence alignments for each protein and estimated the evolutionary rate for each site. We examined which sites overlap with the parts of the protein sequences that are typically isolated from fossils. Based on this, we simulated ancient data with different degrees of sequence fragmentation, followed by phylogenetic analysis. We compared these trees to a reference species tree. Up to a degree of fragmentation that is similar to that of fossil samples from 1-2 million years ago, the phylogenetic placements of most nodes at family level are consistent with the reference species tree. We tested phylogenetic analysis on combinations of different enamel proteins and found that the composition of the proteome can influence deep splits in the phylogeny. With our methods, we provide guidance for researchers on how to evaluate the potential of paleoproteomics for phylogenetic studies before sampling valuable ancient specimens.
Mitochondrial Dysfunction: Unraveling the Elusive Biology Behind Anti-TNF Response During Ulcerative Colitis
Authors: Kioroglou Dimitrios , Peña-Cearra Ainize , Corraliza Ana M , Seoane Iratxe , Castelo Janire , Panés Julian , Gómez-Irwin Laura , Rodríguez-Lago Iago , Ortiz de Zarate Jone , Fuertes Miguel , Martín-Ruiz Itziar , Gonzalez Monika , Aransay Ana M , Salas Azucena , Rodríguez Héctor , Anguita Juan , Abecia Leticia , Marigorta Urko M
Published: January 2025

Background

Recent studies hint at mitochondrial genes influencing UC patient response to anti-TNF treatment. We evaluated this hypothesis by following a targeted strategy to identify gene expression that captures the relationship between mitochondrial dysregulation and response to treatment. Our objective was to initially examine this relationship in colon samples and subsequently assess whether the resulting signal persists in the bloodstream.

Methods

We analyzed the transcriptome of colon samples from an anti-TNF-treated murine model characterized by impaired mitochondrial activity and treatment resistance. We then transferred the findings that linked mitochondrial dysfunction and compromised treatment response to an anti-TNF-treated UC human cohort. We next matched differential expression in the blood using monocytes from the peripheral blood of controls and IBD patients, and we evaluated a classification process at baseline with whole blood samples from UC patients.

Results

In human colon samples, the derived gene set from the murine model showed differential expression, primarily enriched metabolic pathways, and exhibited similar classification capacity as genes enriching inflammatory pathways. Moreover, the evaluation of the classification signal using blood samples from UC patients at baseline highlighted the involvement of mitochondrial homeostasis in treatment response.

Conclusions

Our results highlight the involvement of metabolic pathways and mitochondrial homeostasis in determining treatment response and their ability to provide promising classification signals with detection levels in both the colon and the bloodstream.
Texts without authors: ascribing literary meaning in the case of AI
Authors: Vlaad Sofie
Published: January 2025

With the increasing popularity of large language models, there has been an increase in the number of AI-generated literary works. In the absence of clear authors, and assuming such works have meaning, there lies a puzzle in determining who or what fixes the meaning of such texts. I give an overview of six leading theories for ascribing meaning to literary works. These are Extreme Actual Intentionalism, Modest Actual Intentionalism (1 and 2), Conventionalism, Actual Author Hypothetical Intentionalism, and Postulated Author Hypothetical Intentionalism. I argue that only Conventionalism and Postulated Author Hypothetical Intentionalism show any promise of adjudicating how we ought to ascribe meaning in the case of AI-generated texts, and further that Postulated Author Hypothetical Intentionalism is the stronger of the two views.
Incorporating area-level social drivers of health in predictive algorithms using electronic health record data
Authors: Foryciarz Agata , Gladish Nicole , Rehkopf David H , Rose Sherri
Published: January 2025

Objectives

The inclusion of social drivers of health (SDOH) into predictive algorithms of health outcomes has potential for improving algorithm interpretation, performance, generalizability, and transportability. However, there are limitations in the availability, understanding, and quality of SDOH variables, as well as a lack of guidance on how to incorporate them into algorithms when appropriate to do so. As such, few published algorithms include SDOH, and there is substantial methodological variability among those that do. We argue that practitioners should consider the use of social indices and factors—a class of area-level measurements—given their accessibility, transparency, and quality.

Results

We illustrate the process of using such indices in predictive algorithms, which includes the selection of appropriate indices for the outcome, measurement time, and geographic level, in a demonstrative example with the Kidney Failure Risk Equation.

Discussion

Identifying settings where incorporating SDOH may be beneficial and incorporating them rigorously can help validate algorithms and assess generalizability.
Responses of biological characteristics and detoxification enzymes in the fall armyworm to methoxyfenozide stress
Authors: Yang Shuqi , Yuan Yue , Zhang Xiongwei , Zou Yaqin , Yao Pan , Ye Danni , Ye Liutong , Zhang Xiaolei , Li Junkai
Published: January 2025

Methoxyfenozide is an insecticide with a unique mode of action on the insect ecdysone receptor and has been registered for the control of insect pests all over the world. In the present work, Spodoptera frugiperda was exposed to sublethal and lethal concentrations of methoxyfenozide to determine its impact on specific biological traits, metabolic enzyme activity, and the expression of detoxification enzymes. The result showed that 72-h posttreatment with LC50 and LC70 of methoxyfenozide significantly reduced the fecundity (eggs/female) of the F0 generation compared to those of the control group. However, the duration of the prepupal period was significantly increased. The exposure to LC10, LC30, LC50, and LC70 concentrations of methoxyfenozide significantly extended the developmental duration of larvae in F1 individuals. The fecundity of the F1 generation was significantly decreased, and the population life table parameters of F1 were also significantly affected. The activity of carboxylesterases showed little significant change, whereas the activity of glutathione S-transferases (GSTs) and cytochrome P450 monooxygenases (P450s) was significantly altered after exposure to LC10, LC30, LC50, and LC70 of methoxyfenozide. In total, 24-, 48-, and 96-h posttreatment with LC10, LC30, LC50, and LC70 of methoxyfenozide could cause upregulation of P450 genes such as CYP6AE44, CYP6B39, CYP9A26, CYP9A58, CYP9A59, and CYP9A60, as well as GST genes including GSTe3, GSTe9, GSTe10, GSTe15, GSTo2, GSTs1, GSTs5, GSTm2, and GSTm3. These findings could be instrumental in elucidating the molecular mechanisms underlying the sublethal and lethal effects of methoxyfenozide to S. frugiperda.
The ICJ and the protection of foreign property under customary international law: quid novi?
Authors: Ouellet André-Philippe
Published: January 2025

The protection of foreign property has been a key feature of CIL for at least the last century. The central protection under this regime is the MST. Still, the more specific investment protection regime reached its apex around 2010 with thousands of BITs in force. This article focuses on customary property protection, the scope of which exceeds that of BITs because it protects not only investors, but also any foreigner. To identify the relevant CIL rules, this article assesses the International Court of Justice Certain Iranian Assets case against the backdrop of previous cases. To this end, it first analyses elements characterized as CIL by the Court, eg police powers. Secondly, it deals with elements whose CIL character must be found between the lines of this case, such as the obligation to compensate indirect takings. Finally, it discusses legal questions the Court peremptorily set aside, for example whether assets’ blocking constitutes indirect expropriation.
Preservation of sexual function with Optilume—a novel treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia
Authors: Copelan Olivia , Moss Jared , Freedman Sheldon , Coutinho Karl , Elterman Dean , Marotte Jeffrey , Padron Osvaldo , Shore Neal , Spier Jeffrey , Kaminetsky Jed , Mazzarella Brian , Te Alexis , Kaplan Steven A , McVary Kevin T
Published: January 2025

Background

The Optilume benign prostatic hyperplasia (BPH) catheter system is a novel minimally invasive paclitaxel-coated dilation system that has demonstrated substantial and durable results in urinary flow and symptoms.

Aim

We now assess the impact of Optilume BPH procedure on sexual function.

Methods

Prior published results have described the methods of data collection during the PINNACLE study, which demonstrated durable improvement in urinary symptoms. Follow-up assessments for the current study included IIEF-EF and Male Sexual Health Questionnaire for Ejaculatory Dysfunction (MSHQ-EjD). Semen quality was also examined.

Outcomes

IIEF-EF and MSHQ-EjD scores in the Optilume BPH group were not different from the sham group at 3 months, 6 months, or 12 months.

Results

A total of 148 men were randomized to receive the procedure (100) or a sham surgical procedure (48). Subjects in both groups had similar rates of erectile dysfunction (ED) previously diagnosed at baseline (56% vs 54.2%, P = .83) and those men who were sexually active. IIEF-EF and MSHQ-EjD scores in the Optilume BPH group were not different from the sham group at 3, 6, or 12 months. Change in IIEF-EF scores remained consistent across all levels of baseline ED severity after Optilume BPH procedure. No clear trend was seen after treatment with Optilume BPH for semen volume, sperm motility, progressive motility, or sperm morphology.

Clinical Implications

The Optilume BPH catheter system provides patients with a durable improvement in lower urinary tract symptoms while preserving sexual function.

Strengths and limitations

This study uses validated questionnaires to assess patients’ sexual function at baseline and regularly for 1 year after the procedure. Given exclusion criteria regarding patient age and prostate size, the results may not be applicable to all BPH phenotypes.

Conclusion

Optilume appears to provide clinical benefit with a high degree of patient satisfaction and minimal impact on sexual function.
The fifty shades of black: about black box AI and explainability in healthcare
Authors: Raposo Vera Lúcia
Published: January 2025

Artificial Intelligence (AI) is revolutionizing healthcare by enhancing patient care, diagnostics, workflows, and treatment personalization. The integration of AI in healthcare promises significant advancements and better patient outcomes. However, the lack of explainability in many AI models, known as ‘black-box AI’, raises concerns for patients, doctors, and developers. This issue, termed ‘black box medicine’, challenges the adoption of AI in healthcare. The demand for explainable AI has grown as AI systems become more complex. The absence of explanations in AI decisions, especially in critical situations like healthcare, has sparked debates and even suggestions to exclude black-box AI from healthcare provision. This article examines the impact and causes of unexplainable AI in healthcare, critically evaluates its performance, and proposes strategies to address this challenge.
The clinical and molecular landscape of diffuse hemispheric glioma, H3 G34-mutant
Authors: Le Rhun Emilie , Bink Andrea , Felsberg Joerg , Gramatzki Dorothee , Brandner Sebastian , Benhamida Jamal K , Wick Antje , Tonn Joerg C , Mohme Malte , Tabatabai Ghazaleh , Capper David , Snuderl Matija , Razis Evangelia , Ronellenfitsch Michael W , Neidert Nicolas , Ng Ho-Keung , Pohl Ute , Bale Tejus , Quach Stefanie , Rieger David , Schüller Ulrich , Onken Julia , Drüschler Katharina , Maurage Claude-Alain , Regli Luca , Healy Estelle , Graham Maya , Hortobagyi Tibor , Paine Simon , Bridges Leslie , Lausova Tereza , Medici Valentina , Sievers Philipp , Schrimpf David , Wick Wolfgang , Sahm Felix , Reifenberger Guido , von Deimling Andreas , Weller Michael ,   H3 G34 DHG Study Group
Published: January 2025

Background

Diffuse hemispheric glioma, histone 3 (H3) G34-mutant, has been newly defined in the 2021 WHO classification of central nervous system tumors. Here we sought to define the prognostic roles of clinical, neuroimaging, pathological, and molecular features of these tumors.

Methods

We retrospectively assembled a cohort of 114 patients (median age 22 years) with diffuse hemispheric glioma, H3 G34-mutant, CNS WHO grade 4 and profiled the imaging, histological and molecular landscape of their tumors.

Results

Compared with glioblastoma, H3 G34-mutant diffuse hemispheric gliomas exhibited less avid contrast enhancement, necrosis and edema on MRI. Comprehensive analyses of mutational and DNA copy number profiles revealed recurrent mutations in TP53 and ATRX, homozygous deletions of CDKN2A/B, and amplifications of PDGFRA, EGFR, CCND2, and MYCN. MGMT promoter methylation was detected in 79 tumors (75%); 11 tumors (13%) showed DNA copy number profiles suggestive of circumscribed deletions on 10q26.3 involving the MGMT locus. Median survival was 21.5 months. Female sex, gross total resection, and MGMT promoter methylation were positive prognostic factors on univariate analysis. Among radiological, pathological and molecular features, absence of pial invasion, and presence of microvascular proliferation and CDK6 amplification were positive prognostic factors on univariate analyses.

Conclusions

This study refines the clinical and molecular landscape of H3 G34-mutant diffuse hemispheric gliomas. Dedicated trials for this novel tumor type are urgently needed.
Auxin fluctuation and PIN polarization in moss leaf cell reprogramming
Authors: Tang Han , Chen Li-Hang , Friml Jiří
Published: January 2025

Auxin and its PIN-FORMED (PIN) exporters are essential for tissue repair and regeneration in flowering plants. To gain insight into the evolution of this mechanism, we investigated their roles in leaves excised from Physcomitrium patens, a bryophyte known for its remarkable cell reprogramming capacity. We used various approaches to manipulate auxin levels, including exogenous application, pharmacological manipulations, and auxin biosynthesis mutants. We observed no significant effect on the rate of cell reprogramming. Rather, our analysis of auxin dynamics revealed a decrease in auxin levels upon excision, which was followed by a local increase before the reprogramming process began. Mutant analysis revealed that PpPINs are required for effective cell reprogramming, and endogenously expressed PpPINA-GFP accumulates polarly at sites that will develop into future filamentous stem cells. In addition, hyperpolarized PpPINA variants carrying mutated phosphorylation sites showed a marked delay in reprogramming, whereas endogenous or non-polar versions do not have this effect. These results underscore that both, the levels and the polarity of PpPINA are important for efficient cell reprogramming. Overall, these findings highlight the pivotal role of PIN polarity in plant regeneration. Furthermore, they suggest that understanding polarity mechanisms could have broader implications for improving regenerative processes across various plant species.
Assessing the readability of dermatological patient information leaflets generated by ChatGPT-4 and its associated plugins
Authors: Todorov Dominik , Park Jae Yong , Hing Cheung James Andrew Ng , Avramidou Eleni , Gnanappiragasam Dushyanth
Published: January 2025

Background

In the UK, 43% of adults struggle to understand health information presented in standard formats. As a result, Health Education England recommends that patient information leaflets (PILs) be written at a readability level appropriate for an 11-year-old.

Objectives

To evaluate the ability of ChatGPT-4 and its three dermatology-specific plugins to generate PILs that meet readability recommendations and compare their readability with existing British Association of Dermatologists (BAD) PILs.

Methods

ChatGPT-4 and its three plugins were used to generate PILs for 10 preselected dermatological conditions. The readability of these PILs was assessed using three readability formulas Simple Measure of Gobbledygook (SMOG), Flesch Reading Ease Test (FRET) and Flesch–Kincaid Grade Level Test (FKGLT) and compared against the readability of BAD PILs. A one-way ANOVA was conducted to identify any significant differences.

Results

The readability scores of PILs generated by ChatGPT-4 and its plugins did not meet the recommended target range. However, some of these PILs demonstrated more favourable mean readability scores compared with those from the BAD, with certain plugins, such as Chat with a Dermatologist, showing significant differences in mean SMOG (P = 0.0005) and mean FKGLT (P = 0.002) scores. Nevertheless, the PILs generated by ChatGPT-4 were found to lack some of the content typically included in BAD PILs.

Conclusions

ChatGPT-4 can produce dermatological PILs free from misleading information, occasionally surpassing BAD PILs in terms of readability. However, these PILs still fall short of being easily understood by the general public, and the content requires rigorous verification by healthcare professionals to ensure reliability and quality.