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Epigenetic mechanisms might play a role in modulating susceptibility to bipolar disorder (BD) and response to lithium, the mainstay treatment for BD. Additionally, individuals with BD experience accelerated biological aging.
Methods
We compared blood DNA methylation profiles measured with EPIC v.2.0 arrays between patients with BD (33 lithium responders and 31 nonresponders) and nonpsychiatric controls (n = 32), as well as based on long-term lithium response. In addition, we compared cellular aging between these groups using epigenetic age, pace of aging, and, for the first time, transcriptional age acceleration based on bulk RNA sequencing in 93 patients and 56 controls.
Results
We identified 191 differentially methylated positions (DMPs) and 8 differentially methylated regions between patients with BD and controls, located in genes enriched for “Postsynaptic Density” (odds ratio = 6.81, p = 0.001). No DMP was significantly associated with lithium response after multiple testing correction. Patients showed a significantly higher biological age acceleration than controls based on two epigenetic clocks (GrimAge, Mann–Whitney U = 551, p = 0.0009; GrimAge2: U = 477, p = 9.0E-05) and pace of aging (DunedinPACE, t = 3.01, p = 0.003), but not on transcriptional age. While we observed no significant difference in epigenetic aging based on lithium response, lithium responders showed lower epigenetic acceleration using all clocks, with a trend observed using the PhenoAge clock (t = 1.97, p = 0.053).
Conclusions
Our findings point to methylation patterns characterizing BD and support the hypothesis of accelerated cellular aging in BD.
This study aimed to compare the outcome of the standard trans-cervical approach and modified trans-cervical approach regarding cosmesis and complications outcomes in a tertiary hospital in Nigeria.
Methods
In this study, 25 patients with submandibular salivary gland lesions adjudged not to be malignant neoplasia were included. They were randomised into the two groups by balloting method.
Results
Twelve (48 per cent) patients had the traditional transcervical approach while 13 (52per cent) had the modified approach. There was no statistically significant difference between the groups in terms of general complication, transient paresthesia and wound infection (p > 0.05). The presence of a non-visible scar was reported in almost 85 per cent of patients in the modified trans-cervical approach group compared to 50 per cent in the standard trans-cervical approach group.
Conclusions
Though by observation the modified trans-cervical approach was superior to the standard trans-cervical approach, the differences were statistically insignificant.
This article explores the potential of large language models (LLMs), particularly through the use of contextualized word embeddings, to trace the evolution of scientific concepts. It thus aims to extend the potential of LLMs, currently transforming much of humanities research, to the specialized field of history and philosophy of science. Using the concept of the virtual particle – a fundamental idea in understanding elementary particle interactions – as a case study, we domain-adapted a pretrained Bidirectional Encoder Representations from Transformers model on nearly a century of Physical Review publications. By employing semantic change detection techniques, we examined shifts in the meaning and usage of the term “virtual.” Our analysis reveals that the dominant meaning of “virtual” stabilized after the 1950s, aligning with the formalization of the virtual particle concept, while the polysemy of “virtual” continued to grow. Augmenting these findings with dependency parsing and qualitative analysis, we identify pivotal historical transitions in the term’s usage. In a broader methodological discussion, we address challenges such as the complex relationship between words and concepts, the influence of historical and linguistic biases in datasets, and the exclusion of mathematical formulas from text-based approaches.
This article examines how post-Soviet Azerbaijani literature redefined creative and narrative forms, challenging Soviet literary norms through experimentation and new modes of characterization. Following independence in 1991, Azerbaijani literature moved from the transitional, trauma-marked works of the 1990s to the pluralism and experimentation of the 2000s and, after 2020, toward a discourse of triumph. Writers such as Aziza Jafarzadeh, Huseyn Ibrahimov, Elchin Afandiyev, Anar, and Afag Masud employ non-linear structures, allegory, symbolism, and introspection to transform inherited Soviet forms into vehicles of cultural resistance. Drawing on postcolonial theory (Bakhtin, Bhabha, Spivak, and Annus) and close textual readings, this article situates Azerbaijani literature within broader Eurasian and postcolonial frameworks, demonstrating how creative characterization fosters new expressions of identity, memory, and cultural reimagining.
The Shast-Sheshi festival is held annually in the village of Siān, beginning on the sixty-sixth day after Nowruz. This timing matches the ancient Khordadgan festival, celebrated on the sixth day of the month of Khordad, dedicated to the Zoroastrian goddess Khordad. The central rite of Shast-Sheshi was immersion in the now-dry Shāh Chashme spring. Other rites include visits to nearby sacred sites linked to Khordad, the female guardian of water. The festival, drawing thousands from nearby settlements, lasts ten days and features a seasonal fair. Although centered at a Shia shrine complex, it remains a largely secular event. Jarquyeh uniquely preserves this ancient Iranian tradition and shows how forgotten myth can resurface in an unexpected place and time.
Anthracological studies of preserved wooden building materials can help reveal ancient networks of resource mobilisation. Here, the authors report on the analysis of 657 charred timbers from four ancillary pits at the UNESCO World Heritage Site of the Mausoleum of the First Qin Emperor. The frequent use of dark coniferous wood (fir, spruce and hemlock) indicates sophisticated logistical planning and labour organisation—matching historic records of Qin administrative ascendency—because these species required sourcing from across many kilometres of rugged terrain. Identification of a temporal shift towards the use of higher-elevation species points to the ecological impact of large-scale timber harvesting.
The goal of this chapter is to explain the normative force of personal projects and the project-dependent reasons they generate. Scheffler argues that it is not wrong to ignore project-dependent reasons. I point to three considerations that aim to show, pace Scheffler, that it is wrong to simply ignore the project-dependent reasons we once acknowledged. First, it is a condition for valuing a particular project that we have reasons to continue to respond to project-dependent reasons, even in cases where the project has been completed, where circumstances have forced us to abandon it, or where we have become less prone to value the project positively. Second, it is the fact of having once attained meaning in our lives by valuing a particular project that explains why we face additional reasons to sustain the project and to continue to respond to the project-dependent reasons we once acknowledged. Third, to the extent that a particular project accounts, in part at least, for our normative identity, and provided that it is valuable to thereby have conditions for having reasons at all, we have a further explanation of why project-dependent reasons carry a particular normative force for us to continue to value that project.
In 1770, the Rohilla chief Ḥāfiz̤ Raḥmat Ḵẖān wrote a text called Ḵẖulāṣat ul-Ansāb, focusing on the genealogical and ancestral history of the Rohilla Afghans. This article analyses the text as a glimpse into the emotions he went through—such as anxiety, uncertainty, confidence, determination, and strength—as the ruler of a small principality founded by a new political group in the competitive political milieu of eighteenth-century South Asia. It studies the textual expression of these emotions he experienced during a period that brought both challenges and opportunities for the Rohilla Afghans. It firstly shows how the text served as a means of creating unity among the Rohilla Afghans by elaborating an origin story, adapting them to new circumstances, and legitimising the emerging Rohilla state. Secondly, it discusses how Ḥāfiz̤ Raḥmat aimed to rectify the negative portrayals of the Afghans by Mughal chroniclers and enhance Afghan prestige in northern India by creating a haloed genealogy. Finally, it explains how the text claimed religious legitimacy for the Rohilla Afghans by linking them to the prophets, Muslim invaders of the past, and local religious figures. Overall, this textual analysis contributes to the historiography of eighteenth-century South Asia by studying the political anxieties associated with Rohilla Afghan state formation.
This article explores young children’s relations with soil, drawing on research that positioned soil as animate, lively and interconnected. The paper investigates how animist approaches offered a mode of encounter for children and their teachers, encouraging them to see themselves as part of a larger ecological community. The research began with a “soil biome immersion” experience where teachers engaged with soil through sensory and arts-based experiences. These initial encounters led to further exploration of child-soil relations through experiential learning and storytelling. Children, as active meaning-makers, co-constructed the inquiry through imaginative and sensory engagements. Findings suggest animism cultivates soil relations, challenging traditional notions of soil as inert and promoting a dynamic understanding of soil ecosystems. Through practices such as storying, drawing and listening, educators supported children’s animist perspectives, deepening their attunement to the more-than-human world. This article contributes to environmental education by demonstrating how animism can enrich children’s ecological awareness and their sense of connectedness to the world.
In the cultural context of China, it holds profound significance for nursing students to engage in discussions about hospice and palliative care with their families. This study aimed to explore nursing students’ willingness to discuss hospice and palliative care with their families and the factors associated with it.
Methods
Nursing students from three schools in three Chinese provinces (n = 1,234) completed questionnaires on general information, hospice and palliative care awareness, attitude toward death, and willingness to discuss hospice and palliative care with their families. This cross-sectional analysis utilized logistic regression to investigate the predictors of participants’ willingness to discuss hospice and palliative care with their families.
Results
The mean hospice and palliative care knowledge score was 6.68, and 19.1% were willing to discuss the topic with their families. Factors associated with nursing students’ willingness to discuss hospice and palliative care with their families included region, whether their family members considered talking about death a taboo, whether a family member was severely ill and at risk of death, their knowledge of World Hospice and Palliative Care Day, hospice and palliative care knowledge score, and death avoidance attitude. Participants with higher hospice and palliative care knowledge scores were more willing to discuss the topic with their families, while a higher death avoidance score was associated with unwillingness.
Significance of results
Nursing students significantly lack hospice and palliative care awareness, and their willingness to discuss the topic with their families needs improvement. Nursing schools should provide systematic and standardized hospice and palliative care education and communication skills training.
This Element tackles the question of how – in what way, and in virtue of what – facts about the legal properties and relations of particulars (such as their rights, duties, powers, etc.) are metaphysically explained. This question is divided into two separate issues. First, the Element focuses on the nature of the explanatory relation connecting legal facts to their metaphysical determinants. Second, it looks into the kinds of entities that figure in the explanation of legal facts. In doing so, special attention is paid to the role that laws, or legal norms, play in such explanations. As it turns out, there are different ways in which legal facts might be explained, all of which have something to be said in their favor, and none of which is immune from problems. This title is also available as Open Access on Cambridge Core.
This Element develops a stock-flow consistent agent-based macroeconomic model with Schumpeterian and Keynesian characteristics. On the Schumpeterian side, technological change is modelled as productivity growth as a result of research and development (R&D). The R&D strategies of firms are determined by an evolutionary selection process. On the Keynesian side, demand is endogenous on current income and the stock of households' financial wealth. In the long run, an evolutionary stable R&D strategy of firms emerges, leading to endogenous productivity growth. Demand adjusts endogenously to match labour-saving productivity growth, so that the employment rate is stationary, although with business cycle fluctuations. The authors use Monte Carlo simulations to analyze the emergence of an evolutionary stable R&D strategy, as well as the long-run properties of the model and the nature of business cycles. This title is also available as Open Access on Cambridge Core.
Narratives like those portraying development workers as heroes and local populations as victims needing to be saved from their own unsustainable practices have led to problematic policies and interventions. Based on fieldwork across four continents, this Element critically analyzes such metanarratives. First, it demonstrates the ways their simplifying, universalistic narrative plots fail to capture more complex lived realities. Second, it argues that such metanarratives on development are converging with influential metanarratives on climate change and sustainability, thereby strengthening hierarchical geopolitical mindsets. Third, it uncovers how the emergence of for-profit sustainability superhero metanarratives reinforces universalistic development logics by combining these logics with global business management logics. The Element concludes that a multiplicity of locally grounded stories and related forms of agency must be mobilized and recognized so that policy and practice are premised upon lived realities, not abstract and unrealistic global imaginaries. This title is also available as open access on Cambridge Core.
Corporations are legal bodies with duties and powers distinct from those of individual people. Kant discusses them in many places. He endorses universities and churches; he criticises feudal orders and some charitable foundations; he condemns early business corporations' overseas activities. This Element argues that Kant's practical philosophy offers a systematic basis for understanding these bodies. Corporations bridge the central distinctions of his practical philosophy: ethics versus right, public versus private right. Corporations can extend freedom, structure moral activity, and aid progress towards more rightful conditions. Kant's thought also highlights a fundamental threat. In every corporation, some people exercise the corporation's legal powers, without the same liabilities as private individuals. This threatens Kant's principle of innate equality: no citizen should have greater legal rights than any other. This Element explores the justifications and safeguards needed to deal with this threat. This title is also available as Open Access on Cambridge Core.
We gather evidence on a new local-global conjecture of Moretó and Rizo on values of irreducible characters of finite groups. For this we study subnormalisers and picky elements in finite groups of Lie type and determine them in many cases, for unipotent elements as well as for semisimple elements of prime power order. We also discuss subnormalisers of unipotent and semisimple elements in connected as well as in disconnected reductive linear algebraic groups.
This essay, by revisiting the capitalism and slavery debate, explores the material relations between the Industrial Revolution and the crisis of Black slavery in the British Empire from the perspectives of critical theory and global history. After suggesting that the debate has made capital invisible as a category of historical analysis, I argue that the Industrial Revolution unleashed a process of widening trade circuits around the Atlantic and the Indo-Pacific within which the abolition debate should be understood. These new global circuits of trade became a powerful material mediation between the crisis of slavery in the West Indies; the rise of slavery in the United States, Cuba, and Brazil; and the advancement of New Imperialism in the East.
Pulmonary atresia with ventricular septal defect (PA/VSD) is a complex cyanotic CHD that requires an early diagnosis for optimal management and outcomes. The purpose of this study is to evaluate the effectiveness of an inter-hospital management protocol utilising the prenatal CHD diagnosis for achieving favourable postnatal outcomes in PA/VSD patients in Vietnam.
Methods:
We described the protocol implemented between two tertiary medical settings in Vietnam for the prenatal diagnosis and postnatal management of PA/VSD infants. All PA/VSD patients with prenatal diagnosis between January 2016 and December 2022 were retrospectively reviewed. The primary outcome was postnatal survival, and the secondary outcome was the presence of major morbidities such as bleeding or the need for Extra Corporeal Membrane Oxygenation (ECMO) after total repair.
Results:
During the study period, 35 PA/VSD patients were identified including 29 infants who underwent surgical correction utilising a valved conduit and 6 infants who are still waiting for the next evaluation after the palliative surgery. No death prior to the surgery occurred. For 29 patients, one hospital death happened, two patients required ECMO initially in their postoperative course but both survived, one late mortality due to pneumonia, and three reoperations were due to conduit failure. In the mean follow-up time of 2.92 (0.51–7.92) years, all survivors had completed follow-up.
Conclusion:
Our protocol including a multidisciplinary management and a close follow-up has shown promising short-term results in achieving favourable postnatal outcomes for PA/VSD patients.