Developmental Trajectories Research Articles

Fiscal legibility and state development: Theory and evidence from colonial Mexico

AbstractWe examine how fiscal legibility, the ability of central authorities to observe local conditions for the purposes of taxation, shapes political centralization and state development. When rulers lack information about the periphery, they may benefit from ceding autonomy to tax‐collecting intermediaries to encourage fiscal performance. As information quality improves, rulers become better able to monitor and sanction local officials, allowing them to tighten control over taxation and establish more direct state presence. Centralization, in turn, encourages investment in improving fiscal legibility, leading to long‐term divergence in state development. We study the consequences of a technological innovation that dramatically improved the Spanish Crown's fiscal legibility in colonial Mexico: the discovery of the patio process to refine silver. We show that political centralization differentially accelerated in affected districts and that these areas subsequently saw disproportionate state investment in informational capacity, altering the trajectory of state development.

Family Communication With Children and Adolescents Post Parental Loss in Road Traffic Accidents: A Qualitative Study

Background: Traumatic parental loss during childhood and adolescence can have long-lasting effects on the developmental trajectory of youngsters. While there is some literature on the advantages of positive family communication fostering better adjustment in bereaved children and adolescents, patterns of family communication post parental loss have not received much attention. An understanding of these patterns can pave the way for more holistic interventions in this vulnerable group. Aim: The aim of the study was to explore parental loss-related communication in families of children and adolescents who have lost a parent to a road traffic accident. Method: The study was carried out in a tertiary hospital setting in Bengaluru. The sample comprised of 24 children and 17 surviving parents. The study employed a qualitative research design. Semi-structured in-depth interviews were conducted with surviving parents/caregivers and the children/adolescents. The interviews were analysed by using inductive thematic analysis. Results: The themes generated from the semi-structured interviews highlighted patterns of communication in parentally bereaved families. Four major themes emerged from the semi-structured interviews – mode of getting to know about the death, disclosure regarding the death, discussion regarding the death and individual needs related to communication. Conclusions: Communication regarding parental loss as a result of road traffic accidents in the family context seems to be desirable and may enable healthy grieving in youngsters. Short-term interventions aimed at enhancing family communication patterns following traumatic parental loss need to be developed in the Indian context.

Democratic Socialism of BP and its Imperatives in Nepal's Politics and Development: A Critical Outlook

This paper explores Bishweshwar Prasad Koirala’s interpretation of democratic socialism and its influence on Nepal’s political and developmental trajectory. Adopting a review-based methodology within a critical framework, the research delves into BP’s principles of democratic socialism, which aim to blend democratic governance with social fairness and economic equity. The study evaluates how these principles were reflected in development policies during the Nepali Congress leadership, noting both positive outcomes and limitations. Additionally, it addresses the substantial obstacles encountered in applying democratic socialism in Nepal, such as political instability, leadership crisis, economic constraints, and societal challenges. In conclusion, the paper assesses the ongoing significance and future prospects of democratic socialism in Nepal, advocating for its effective theorization and application through development strategies centered on the people, improved governance practices, and reinforced institutional structures to promote political morality and sustainable development.

Embryonic Leucine Promotes Early Postnatal Growth via mTOR Signalling in Japanese Quails.

Nutritional cues during embryonic development can alter developmental trajectories and affect postnatal growth. However, the specific mechanisms by which nutrients influence avian growth remain largely unknown. Amino acids can directly interact with the nutrient-sensing pathways, such as the insulin-like growth factor 1 (IGF-1)/mechanistic target of rapamycin (mTOR) pathways, which are known to regulate growth. We examined the effects of embryonic leucine on gene expression and phenotypic growth in Japanese quails by injecting 2.5 mg leucine or saline (control) into Japanese quail eggs on the tenth day of incubation and incubating them under standard conditions. The treatment groups had similar hatching success and size at hatching. However, between 3 and 7 days post-hatching, quails treated with embryonic leucine showed increased growth in body mass and wing, tarsus, head, and intestinal lengths, lasting up to 21 days. The hepatic expression of IGF1, IGF1R, mTOR, and RPS6K1 was upregulated in leucine-treated quails, while the expression of FOXO1 remained unaffected. In conclusion, a subtle increase in embryonic leucine may induce developmental programming effects in Japanese quail by interacting with the IGF-1/mTOR nutrient-sensing pathway to promote growth. This study highlights the role of embryonic amino acids as crucial nutrients for enhancing growth. It provides valuable insight into nutrient intervention strategies during embryonic development to potentially improve poultry growth performance.

Single-cell RNA sequencing explored potential therapeutic targets by revealing the tumor microenvironment of neuroblastoma and its expression in cell death

BackgroundNeuroblastoma (NB) is the most common extracranial solid tumor in childhood and is closely related to the early development and differentiation of neuroendocrine (NE) cells. The disease is mainly represented by high-risk NB, which has the characteristics of high mortality and difficult treatment. The survival rate of high-risk NB patients is not ideal. In this article, we not only conducted a comprehensive study of NB through single-cell RNA sequencing (scRNA-seq) but also further analyzed cuproptosis, a new cell death pathway, in order to find clinical treatment targets from a new perspective.Materials and MethodsThe Seurat software was employed to process the scRNA-seq data. This was followed by the utilization of GO enrichment analysis and GSEA to unveil pertinent enriched pathways. The inferCNV software package was harnessed to investigate chromosomal copy number variations. pseudotime analyses involved the use of Monocle 2, CytoTRACE, and Slingshot software. CellChat was employed to analyze the intercellular communication network for NB. Furthermore, PySCENIC was deployed to review the profile of transcription factors.ResultUsing scRNA-seq, we studied cells from patients with NB. NE cells exhibited superior specificity in contrast to other cell types. Among NE cells, C1 PCLAF + NE cells showed a close correlation with the genesis and advancement of NB. The key marker genes, cognate receptor pairing, developmental trajectories, metabolic pathways, transcription factors, and enrichment pathways in C1 PCLAF + NE cells, as well as the expression of cuproptosis in C1 PCLAF + NE cells, provided new ideas for exploring new therapeutic targets for NB.ConclusionThe results revealed the specificity of malignant NE cells in NB, especially the key subset of C1 PCLAF + NE cells, which enhanced our understanding of the key role of the tumor microenvironment in the complexity of cancer progression. Of course, cell death played an important role in the progression of NB, which also promoted our research on new targets. The scrutiny of these findings proved advantageous in uncovering innovative therapeutic targets, thereby bolstering clinical interventions.

The Brain Imaging for Global Health (BRIGHT) Project: Longitudinal cohort study protocol.

There is a scarcity of prospective longitudinal research targeted at early postnatal life which maps developmental pathways of early-stage processing and brain specialisation in the context of early adversity. Follow up from infancy into the one-five year age range is key, as it constitutes a critical gap between infant and early childhood studies. Availability of portable neuroimaging (functional near infrared spectroscopy (fNIRS) and electroencephalography (EEG)) has enabled access to rural settings increasing the diversity of our sampling and broadening developmental research to include previously underrepresented ethnic-racial and geographical groups in low- and middle- income countries (LMICs). The primary objective of the Brain Imaging for Global Health (BRIGHT) project was to establish brain function - using longitudinal data from mother - for-age reference curves infant dyads living in the UK and rural Gambia and investigate the association between context-associated moderators and developmental trajectories across the first two years of life in The Gambia. In total, 265 participating families were seen during pregnancy, at 7-14 days, 1-, 5-, 8-, 12-, 18- and 24-months post-partum. An additional visit is now underway at 3-5 years to assess pre-school outcomes. The majority of our Gambian cohort live in poverty, but while resource-poor in many factors they commonly experience a rich and beneficial family and caregiving context with multigenerational care and a close-knit supportive community. Understanding the impact of different factors at play in such an environment ( i.e., detrimental undernutrition versus beneficial multigenerational family support) will (i) improve the representativeness of models of general cognitive developmental pathways from birth, (ii) identify causal pathways of altered trajectories associated with early adversity at both individual and group level, and (iii) identify the context-associated moderators ( i.e. social context) that protect development despite the presence of poverty-associated challenges. This will in turn contribute to the development of targeted interventions.

When inclusive growth is not enough: advances and limitations of development policies in Uruguay 2005–2019

ABSTRACT Along most of the 2005–2019 period, Uruguay experienced an impressive economic growth. The country extended its public policies across industrial, technological, and social domains. However, there was a dearth of significant structural changes, constraining Uruguay’s ability to embark on a sustained developmental trajectory. Our findings reveal that the majority of implemented policies were designed to enhance competitiveness and build capabilities horizontally, rather than promoting structural changes. This allows us to discuss the dynamic nature of developmental processes marked by increasing policy challenges. In doing so, we stress the relevance of policy support and coordination to sustain inclusive growth processes.

Single-cell transcriptional atlas of tumor-associated macrophages in breast cancer

BackgroundThe internal heterogeneity of breast cancer, notably the tumor microenvironment (TME) consisting of malignant and non-malignant cells, has been extensively explored in recent years. The cells in this complex cellular ecosystem activate or suppress tumor immunity through phenotypic changes, secretion of metabolites and cell-cell communication networks. Macrophages, as the most abundant immune cells within the TME, are recruited by malignant cells and undergo phenotypic remodeling. Tumor-associated macrophages (TAMs) exhibit a variety of subtypes and functions, playing significant roles in impacting tumor immunity. However, their precise subtype delineation and specific function remain inadequately defined.MethodsThe publicly available single-cell transcriptomes of 49,141 cells from eight breast cancer patients with different molecular subtypes and stages were incorporated into our study. Unsupervised clustering and manual cell annotation were employed to accurately classify TAM subtypes. We then conducted functional analysis and constructed a developmental trajectory for TAM subtypes. Subsequently, the roles of TAM subtypes in cell-cell communication networks within the TME were explored using endothelial cells (ECs) and T cells as key nodes. Finally, analyses were repeated in another independent publish scRNA datasets to validate our findings for TAM characterization.ResultsTAMs are accurately classified into 7 subtypes, displaying anti-tumor or pro-tumor roles. For the first time, we identified a new TAM subtype capable of proliferation and expansion in breast cancer-TUBA1B+ TAMs playing a crucial role in TAMs diversity and tumor progression. The developmental trajectory illustrates how TAMs are remodeled within the TME and undergo phenotypic and functional changes, with TUBA1B+ TAMs at the initial point. Notably, the predominant TAM subtypes varied across different molecular subtypes and stages of breast cancer. Additionally, our research on cell-cell communication networks shows that TAMs exert effects by directly modulating intrinsic immunity, indirectly regulating adaptive immunity through T cells, as well as influencing tumor angiogenesis and lymphangiogenesis through ECs.ConclusionsOur study establishes a precise single-cell atlas of breast cancer TAMs, shedding light on their multifaceted roles in tumor biology and providing resources for targeting TAMs in breast cancer immunotherapy.

Clinical characteristics of 217 Chinese cases with depersonalization/derealization disorder

Depersonalization/derealization disorder (DPD) is a prevalent yet inadequately understood clinical condition characterized by a recurrent or persistent sense of unreality. This study aims to provide insight into DPD through descriptive and comparative analyses involving a large group of Chinese participants. The socio-demographic details (age, gender proportion, education, occupational status, marital status), depersonalized and dissociative symptom characteristics (symptomatic factors or subscales of the Cambridge Depersonalization Scale and the Dissociative Experiences Scale), development trajectory (age of onset, potential precipitating factors, course characteristics), treatment history (duration of delayed healthcare attendance, duration of delayed diagnosis, previous diagnoses), and adverse childhood experiences of the DPD patients are presented. Comparisons of anxiety and depressive symptoms, alongside psychosocial functioning, between DPD participants and those diagnosed with generalized anxiety disorder, bipolar disorders, and major depressive disorder were conducted. The analysis highlights a higher male preponderance and early onset of DPD, symptomatology marked by derealization, notable impairment in psychosocial functioning, and prolonged periods of delayed healthcare attendance and diagnosis associated with symptom severity. Furthermore, noteworthy relationships between adverse childhood experiences and symptom levels were identified. The findings substantiate the view that DPD is a serious but neglected mental disorder, urging initiatives to improve the current condition of DPD patients.

Similar patterns of brain activity for holistic representation of working memory: a study in children and adults.

Working memory is the fundamental function of the various cognitive processes and abilities in the overall trajectory of development. Significant advances in multivariate analysis of human functional magnetic resonance imaging data have converged functional segregation models toward integrated representation-based models. However, due to the inherent limitations of the multi-voxel pattern analysis method, we are unable to determine whether the underlying neural representations are spatially similar in the brain. Our study attempts to answer this question by examining the spatial similarity of brain activity during the working memory task in children and adults. Our results reveal similar patterns of activity between the regions involved in working memory. This functional network of similar spatial patterns was observed in both normally developing children and adults. However, the between-region similarity was more pronounced in adults than in children and associated with better performance. We propose an exchange of similar information flows through the brain at an integrated level of working memory processes, underpinning the holistic nature of working memory representation.

Developmental trajectories of loneliness in Chinese children: Environmental and personality predictors

BackgroundThis study aimed to identify the developmental trajectories of loneliness in Chinese children and examine the predictive roles of domain-specific environmental factors (i.e., family dysfunction and satisfaction of relatedness needs at school), personality factors (i.e., neuroticism and extraversion), and their interactions in these developmental trajectories. MethodsA total of 702 Chinese children (Mage = 8.95, SD = 0.76; 54.1 % boys) participated in assessments at six time points over three years at six-month intervals. Growth mixture modeling (GMM) was used to estimate trajectory classes for loneliness, followed by multivariate logistic regression analyses exploring associations between these classes and predictors. ResultsGMM analyses identified three distinct trajectories of loneliness: “low-stable” (81.5 %), “moderate-increasing” (9.4 %), and “high-decreasing” (9.1 %). Multivariate logistic regression analyses revealed that family dysfunction and neuroticism served as risk factors for adverse loneliness trajectories, while satisfaction of relatedness needs at school and extraversion acted as protective factors. Furthermore, the interaction between family dysfunction and extraversion indicated that extraversion did not mitigate the adverse effects of high family dysfunction on children's loneliness, emphasizing the vital need to support positive family functioning among all children. LimitationsThis study did not incorporate biological variables (e.g., genetics), which are crucial in the evolutionary theory of loneliness. ConclusionsThe identification of three distinct trajectory groups of children's loneliness, along with key environmental and personality predictors, suggests that interventions should be tailored to each group's unique characteristics.

Investigating ‘Land-Use Trajectories’ in Mediterranean Rural Areas with Official Statistics and a Multiway Factor Analysis

While displaying diversified economic values, agro-ecosystems remain a relevant component of rural landscapes in Southern Europe. Coupled with the expansion of ecologically fragile areas because of climate warming, intensification and simplification of rural landscapes—e.g., in lowland—represent frequent trajectories of rural land-use change (RLUC) in the Mediterranean region and demonstrated to harm ecosystem functionality and ecological quality, especially in a context of socioeconomic transformations of landscapes. Additionally, an incipient ‘extensivation’ of geographically remote and economically marginal agricultural systems was also observed, likely following depopulation and land abandonment. The present study elaborated in this direction, providing an integrated RLUC evaluation scheme based on a multivariate analysis of land-use indicators derived from official statistics. This approach was applied to a continuous, long-term RLUC monitoring of a rural landscape in an ecologically complex Mediterranean region (Latium, Central Italy) experiencing multiple trends (e.g., lowland urbanization, crop intensification in gently sloping areas, and land abandonment/depopulation in steep zones) with diversified environmental implications. Based on administrative inventories, such evaluation was carried out over fifty years (1970–2020) in the study area, considering trends over time in selected crop surfaces at the municipal scale as inputs of a multiway factor analysis (MFA). This analysis quantifies stability in the main rural land-use types and possible changes in the dominant farming systems. Simplified indicators of land configuration (namely a crop intensity index and a rural woodland index reflecting ‘intensification’ or ‘extensivation’ of local farming systems) made available at the same spatial and temporal scales completed the informative picture corroborating MFA results. Taken together, our findings delineate multiple changes in rural landscapes, discriminating land-use trajectories in coastal and inland districts. These development trajectories were basically dependent on processes of (i) land abandonment in relict and remote areas, (ii) crop intensification in dynamic rural districts, and (iii) fringe urbanization along the coastal strip.

Imagining an Alternative Future: Children’s Bodies in Wonder Boy (1988), Magic Watch (1990), and Mad Rabbit (1997)

Abstract Since China launched its reform and opening-up campaign, the country experienced significant economic growth and infrastructure expansion, which helped spur the release of numerous science fiction works. Among these works, Zhang Zhilu’s three children’s sf films presented an alternative future for Chinese children and teenagers. This essay contends that while these films portray children as integral to infrastructure and the construction of a market economy network, they opt for natural and playful growth driven by a longing for freedom and emotional connection, and by doing so they circumvent the predetermined and goal-oriented trajectory of social development.

Developmental Trajectories of Transactional Sex and Age-Disparate Relationships During Adolescence: An HPTN 068 Analysis.

Transactional sex and sexual relationships with older partners increase HIV risk in adolescent girls and young women (AGYW), yet little is known about how these behaviors co-evolve over time. We characterize temporal patterns of transactional sex and age-disparate relationships among AGYW in South Africa. Longitudinal data are from a randomized controlled trial (HPTN 068) of school-aged, HIV-negative, AGYW who attended ≥ 3 study visits. We used group-based trajectory modeling to identify trajectories of transactional sex and age-disparate relationships (partner ≥ 5 years older) in the last year and assessed the interrelationship (conditional probability) between both trajectories. At baseline, median age was 14 years, 14.5% of girls were sexually active, and transactional sex (2.1%) and age-disparate relationships were uncommon (2.7%). We identified two trajectories for transactional sex ("low" [81.9%] and "increasing" [18.1%]) and two for age-disparate relationships ("low" [91.7%] and "increasing" [8.3%]). In a separate joint trajectory analysis, nearly a third (28%) had increasing trajectories for both transactional sex and age-disparate relationships, but most (53%) had a low trajectory of both outcomes. Baseline reporting of early sexual debut, depression, and inequitable gender norms were highest in the increasing transactional sex group. Prior pregnancy, early sexual debut, and IPV were highest among those with increasing age-disparate relationships. AGYW who engage in transactional sex or age-disparate partnerships in early adolescence are more likely to experience sustained engagement in both behaviors as they transition to adulthood, increasing HIV risk. Engaging girls early may maximize effectiveness of behavioral and biomedical HIV prevention efforts.

Professional development is the key to securing a future rheumatology workforce. Long term evaluation of a summer school for medical students-a national scientific society's educational initiative.

A cumulative imbalance between rheumatologic need and an inadequate number of young colleagues entering the field leads to a dearth of rheumatologists in the near future. The Austrian Society for Rheumatology and Rehabilitation (ÖGR) has been organizing an annual Rheumatology Summer School (RSS) for medical students since 2017. The aim of this study was to analyze the annual RSS evaluations, the RSS' overall effects on attracting new talent into the field and the lasting promotion of rheumatology. A questionnaire was distributed immediately after each RSS meeting. Additionally, we conducted an electronic survey among RSS participants (2017-2022) to assess their career development trajectories. From 2017-2023, a total of 220 students attended the RSS. They all completed the annual evaluation. Accordingly, students' expectations were met in 80% (2017) to 97% (2023) of cases. The electronic survey was completed by 64/133 (48%) students; 49 (77%) indicated that the RSS had markedly increased their desire to specialize in rheumatology. Among the 36 graduates, 10 (28%) had already been working in the field of rheumatology and 6 (17%) were considering this specialty but had not decided yet. RSS attendees in their 6th study year were influenced to a greater extent by the RSS to choose rheumatology as their primary specialty than 4th or 5th year students. The participants indicated that they benefited most from the RSS in terms of knowledge gain, personal awareness of rheumatology, networking among fellow students as well as gaining access to RSS faculty. The RSS enhanced students' intention to choose rheumatology, particularly in those close to graduation, and led to increased awareness and deeper knowledge about rheumatology.

Development Strategy Management Model for Tennis Club in Guangzhou City, the People’s Republic of China

Background and Aim: More tennis players in Guangzhou offer a larger platform for the sport's growth. The Guangzhou Tennis Club has grown quickly in the last few years. However, as the tennis club has grown, several issues have emerged, including management, staffing, and club operations. Materials and Methods: This study used a questionnaire to look into 286 club members, 143 club coaches, and 53 club administrators from 50 tennis clubs in Guangzhou. The data is analyzed using the descriptive statistics method, and the resultant conclusion serves as a foundation for guidance for the Guangzhou Tennis Club's strategic management model. The instrument; (1) Survey data questionnaire for research purposes. (2) Evaluation form for focus groups. (3) Expert interview guide. (4) Questionnaire for expert assessment. Analyzing Data: (1) The average and percentage must be used in the questionnaire. (2) Content analysis will be used to analyze the data from focus groups and interviews. Results: (1) Able to fully mobilize resources to support development; good at forging cooperative relationships with pertinent institutions. (2) There are organizations to support the growth of the tennis club, and the staff management structure is well-defined. (3) There are standards and design requirements for both members and staff to meet to enter the club. Issues and challenges: (1) Absence of strategies to encourage tennis club growth in conjunction with pertinent institutional or national policies. (2) Professional staff is absent from tennis club management and instruction, and the clubs' development trajectory is unidirectional. (3) Absence of a system for tracking tennis club performance and lack of authority over the maximum number of members. And (4) abusing the tennis club welfare allowance, pressuring staff members. Conclusion: (1) Guangzhou Tennis Club should be taken into consideration when creating the phased development plan, and national and government policies should be used to promote development. The organizing section's management development strategy can be summed up as follows: using the organization's current resources to support the club's quick development. The leading development strategy should be summed up in the leadership section as follows: suitable systems should be developed to standardize each employee's daily work and have requirements for employees. The following succinctly describes the controlling development strategy in the control section: planning employee development and effectively ensuring employee welfare, as well as collaboratively advancing the growth of Guangzhou Tennis Club. (2) Fifteen experts have given the Guangzhou Tennis Club's development strategy management mode, which was created for this study, high marks. The Guangzhou Tennis Club's development strategic management mode received an average score of 4.65 from 15 participants, indicating that the experts are satisfied with the mode's practical application and overall impact.

The potential synergy between air pollution control and employment growth

Public service sectors play crucial roles in maintaining societal functioning through the provision of essential services. However, amidst the backdrop of air pollution, their developmental trajectories may veer off course from their intended goals. Quantifying the impact of air pollution on public service sectors, particularly from an employment perspective, offers valuable insights for policymakers aiming to foster the sustainable growth of these sectors and expand the analysis framework on air pollution externalities. Drawing on monthly data spanning from January 2015 to December 2019 across 269 prefecture cities, this paper therefore explores the impact of air pollution on public service sector employment using a cross-lagged panel model with fixed effects. I find that air pollution negatively affects the employment scales in public service sectors. This negative employment shock is also unevenly distributed across areas and sub-sectors and intensifies over time. Cities belong to key areas for air pollution prevention and control, small and medium-sized cities, and secondary-industry dominated cities, suffer disproportionately negative employment shocks in their public service sectors. These findings offer actionable insights for policymakers to implement targeted measures supporting the continued growth of public service sectors and deepen understanding of the economic ramifications of air pollution.

Examining trajectories of nonsuicidal self-injury across the first year of university

BackgroundNonsuicidal self-injury (NSSI) is prevalent among emerging adults in post-secondary school, but little is known about change and stability in NSSI during the transition to university. Moreover, there has been limited person-centered work focusing on heterogeneity in NSSI engagement among students over time. The present study aimed to investigate the development and maintenance of NSSI across the first year of university and explore predictors of potential variability in trajectories of NSSI. MethodsThe present sample consisted of 1125 first-year university students at a large post-secondary institution (Mage = 17.96, 71 % female, 28 % male, 1 % gender diverse) who participated in a larger longitudinal study. Participants completed an online survey three times over their first year of university. Latent growth curve modeling (LGCM) in Mplus was utilized to explore different NSSI group trajectories across first year university. ResultsNSSI was prevalent among first year students (35 %). LGCM revealed one developmental trajectory; NSSI engagement decreased across the first year of university. Students who engaged in NSSI had increased difficulties with emotion regulation, lower self-compassion, and lower levels of social support compared to students who did not engage in NSSI. LimitationsThe present study may be subject to recall errors and future studies should include more gender diverse samples to increase generalization of findings. ConclusionsFindings highlight the transition to university as a peak period of vulnerability for NSSI engagement and emphasize the need for proactive university intervention efforts to mitigate risk and improve student well-being.

Investigating the shared genetic architecture between depression and subcortical volumes

Depression, a widespread and highly heritable mental health condition, profoundly affects millions of individuals worldwide. Neuroimaging studies have consistently revealed volumetric abnormalities in subcortical structures associated with depression. However, the genetic underpinnings shared between depression and subcortical volumes remain inadequately understood. Here, we investigate the extent of polygenic overlap using the bivariate causal mixture model (MiXeR), leveraging summary statistics from the largest genome-wide association studies for depression (N = 674,452) and 14 subcortical volumetric phenotypes (N = 33,224). Additionally, we identify shared genomic loci through conditional/conjunctional FDR analyses. MiXeR shows that subcortical volumetric traits share a substantial proportion of genetic variants with depression, with 44 distinct shared loci identified by subsequent conjunctional FDR analysis. These shared loci are predominantly located in intronic regions (58.7%) and non-coding RNA intronic regions (25.4%). The 269 protein-coding genes mapped by these shared loci exhibit specific developmental trajectories, with the expression level of 55 genes linked to both depression and subcortical volumes, and 30 genes linked to cognitive abilities and behavioral symptoms. These findings highlight a shared genetic architecture between depression and subcortical volumetric phenotypes, enriching our understanding of the neurobiological underpinnings of depression.

Single-cell and spatial sequencing identifies senescent and germinal tumor cells in adamantinomatous craniopharyngiomas

Adamantinomatous craniopharyngioma (ACP) is a clinically aggressive tumor without effective treatment method. Previous studies proposed a paracrine tumorigenesis model, in which oncogenic β-catenin induces senescence in pituitary stem cells and the senescent cells lead the formation of paracrine tumors through secretion of pro-tumorigenic factors. However, there lacks characterization on senescent cells in ACPs. Here, we profiled 12 ACPs with single-cell RNA and TCR-sequencing to elucidate the cellular atlas in ACPs and 3 of them were also subject to spatial sequencing to localize different subpopulations of the tumor cells. In total, we obtained the transcriptome profiles of 70,682 cells. Tumor cells, which were unambiguously identified through the cellular mutation status of the driver CTNNB1 mutations, were clustered into 6 subsets. The whorl-like cluster (WC) cells show distinct molecular features from the other tumor cells and the palisading epithelium (PE) cells consists of a proliferating subset. Other than typical PE and WC, we identified two novel subpopulations of the tumor cells. In one subpopulation, the cells express a high level of cytokines, e.g., FDCSP and S100A8/A9, and are enriched with the senescence-associated secretory phenotype (SASP) factors. Hematoxylin and eosin staining reveals that these SASP cells lack an ordered structures and their nuclei are elongated. In the other subpopulation, the cell sizes are small and they are tightly packed together with an unusual high density expressing a high level of mitochondrial genes (median 10.9%). These cells are the origin of the tumor developmental trajectories revealed by RNA velocity and pseudo-time analysis. Single-cell RNA and TCR analysis reveals that some ACPs are infiltrated with clonally expanded cytotoxic T cells. We propose a hypothesis that WC and PE are formed via different negative regulation mechanisms of the overactivated WNT/β-catenin signaling which provides a new understanding on the tumorigenesis of ACPs. The study lays a foundation for future studies on targeting senescent cells in ACPs with senolytic compounds or other therapeutic agents.