This study explored the perspectives of adults in substance use recovery about obtaining and strategically building recovery capital on social media. In this qualitative interview study, we used a combined inductive and deductive content analysis approach to derive themes informed by the Recovery Capital Model. Participants (N = 49) in virtual interviews were recruited via substance use treatment centers in the northeast and southeast US. Most identified as female (59.2%) and White (57.1%), with an average age of 39.09 years (SD = 10.06). Most (77.6%) reported receiving treatment for alcohol use, and almost half had received treatment for cannabis (49.0%). We used semi-structured interviews focused on the perspectives of adults in recovery about their motivations and the positive and negative impacts of their social media use. Participants' descriptions of recovery capital built on social media were organized in four thematic categories based on the type of capital: Human Recovery Capital (e.g., Online information/content), Physical Recovery Capital (e.g., Instrumental support), Social Recovery Capital (e.g., Emotional support), and Cultural/Community Recovery Capital (e.g., Online peer recovery communities). We also coded instances of Negative Recovery Capital (e.g., Negative/deceptive content) across domains and characterized a variety of Strategies to Gain Recovery Capital (e.g., Disclosing their recovery journey at specific times online). Social media can provide access to recovery capital, especially human and social capital, with little effort expenditure, and online contexts may allow more strategic disclosure of concealable stigmatized identities, such as being in recovery. However, adults must also navigate online content and connections perceived as harmful to their recovery journey.
The emerging literature about parenthood indicates specific differences in autistic individuals' experiences compared with non-autistic ones. We conducted a systematic search of the literature across PubMed, Embase, Web of Science, and CINAHL Complete to identify articles related to pregnancy, childbirth, and parenthood in autistic individuals. The search was completed on March 5, 2024, and identified 35,581 records. Inclusion criteria included the use of semistructured interviews or focus groups for data collection and interpretative phenomenological analysis or thematic analysis for data analysis as the best methods for exploring our subject. After applying inclusion and exclusion criteria, six articles were included in the systematic review and underwent thematic synthesis. Each study comprised between 7 and 24 autistic participants (all females except three). Their methodological quality was assessed with the Critical Appraisal Skills Programme tool for qualitative studies. We identified three key themes as follows: 1. Parental Challenges and Adaptations; 2. Social Relations and Support; and 3. Identity and Personal Growth. Our analysis identified that autistic individuals face diverse challenges in becoming parents and parenting, including primarily sensory and communication difficulties, which impact their ability to interact with professionals and to manage daily tasks, requiring the implementation of diverse strategies and adaptations to cope. Autistic adults reported a strong emotional connection they build with their children, the need to advocate for them when they are also neurodivergent, and the difficulty in finding formal and informal support fulfilling their specific needs. The educational approach of autistic parents seems influenced by their autism, bringing both strengths and challenges to create, ultimately, a supportive parenting environment. The experience of becoming a parent and raising a child is described as a key step in their personal development. These findings will help autistic parents by promoting a better understanding of their experiences, challenges, and strengths by health care professionals and social workers. Why is this an important issue?: Many people are diagnosed autistic as adults, and some autistic children want to become parents when they grow up. However, there are few specific supports for autistic parents. Research shows that their experience of parenthood has unique aspects, which can be both strengths and challenges.What was the purpose of this study?: We conducted a comprehensive review of the literature on pregnancy, childbirth, and parenthood in autistic adults. Our goal was to identify, synthesize, and analyze qualitative studies to pinpoint the strengths, challenges, and specific needs of autistic adults in this area and to propose supportive interventions.What did the researchers do?: We performed a thorough search across four scientific databases to find relevant articles. We selected the applicable studies and analyzed their data by coding the results line by line. We reused codes from previous studies and created new ones as necessary. We then organized these codes into related areas to develop descriptive themes and combined them into analytical themes.What were the results of the study?: We identified three key themes as follows: 1. Parental Challenges and Adaptations; 2. Social Relations and Support; and 3. Identity and Personal Growth. We found that autistic individuals encounter several challenges in becoming parents and raising children, mainly due to sensory and communication difficulties. These issues affect their interactions with professionals and their management of daily tasks. Despite this, autistic adults report deep emotional connections with their children, a strong need to advocate for them, and difficulties in finding adequate support. Their parenting style, shaped by their autistic traits, presents both strengths and challenges. They view parenthood as a major milestone in their personal growth.What do these findings add to what was already known?: Our work identifies and describes the unique strengths, challenges, and needs of autistic adults in their parenting journey. It allows us to propose interventions to support autistic parents and highlights areas for future research.What are the potential weaknesses in the study?: As a qualitative literature review, our study did not include data from quantitative or mixed-method studies. By focusing on studies using the most adequate methodology, we may have missed some other qualitative studies offering new insights. Some participants were included based on self-reported diagnoses rather than confirmed by a mental health professional. In addition, the studies included very few men and no autistic parents with intellectual disability or borderline intellectual ability, which limits the generalizability of our findings to these populations.What do the authors recommend for future research on this topic?: Study the parenting experiences of autistic men, focusing on how sensory challenges affect their involvement with their children. Assess the importance of support from relatives and strategies to mobilize it. Describe the parenting style of autistic parents to enhance professional understanding and reduce bias. Identify obstacles to parenthood for autistic adults to develop suitable support. Examine the prevalence of autism in the children of autistic adults, which appears significant but remains unexplored.How will these findings help autistic adults now or in the future?: These findings highlight the challenges autistic adults face in parenting and suggest interventions to support them. They also help counteract biases among health care professionals and society, fostering better understanding and support for autistic parents.
Autistic individuals report high levels of interest in pursuing and maintaining romantic relationships but indicate fewer and less satisfying relationships when compared with non-autistic populations. In this mixed-methods study, we investigated the self-identified factors that contribute to successful romantic relationships for autistic adults with the additional goal of understanding if and how their partners' neurotypes may influence relationship satisfaction. We compared levels of relationship satisfaction among 106 autistic individuals by categorizing each participant into one of three groups based on the specific neurotype of their partner: (1) autistic/autistic (A/A) dyads; (2) autistic/neurotypical (A/NT) dyads; and (3) autistic/non-autistic but neurodivergent (A/ND) dyads. All participants completed a series of online surveys to gather information about their autistic traits, overall relationship satisfaction, reciprocal communication and support, and perceived impact of autism on relationships. Across the three dyads, participants reported similar levels of relationship satisfaction, and we found no statistically significant differences when comparing the mean satisfaction of each sample group. Participants indicated a wide variety of positive and negative relational aspects, with a few themes changing in frequency based on partner neurotype. Participants with autistic partners tended to focus on an inherent and deep sense of understanding when discussing the positive aspects of their relationships, while those with non-autistic partners were more likely to discuss the presence of mutual support and accommodation. In addition to some differences in reported themes, participants tended to report that their autistic traits positively impacted satisfaction in A/A dyads, while those in A/NT and A/ND dyads tended to report that their autistic traits posed challenges in their relationships. The results of this study indicate that the neurotype of an autistic individual's partner may influence some of the reported positive and challenging aspects of their relationships. However, survey results indicate that autistic populations generally find comparable levels of satisfaction in romantic relationships irrespective of neurotype, which suggests that while partner neurotype may shape the enabling and barring factors for relationship success, it does not directly affect the overall health of a relationship. Finally, how an autistic individual perceives the impact of autism on their relationship may be affected by the neurotype of their partner. Why is this an important issue?: Many autistic folks seek out and thrive in romantic relationships, but studies report that autistic people experience lower relationship satisfaction than non-autistic people. Despite this, the autism research field has made little progress toward understanding (a) why this is the case and (b) how we can better support autistic individuals who are navigating romantic relationships. To best understand what autistic people seek in relationships, we created a space where autistic participants could share their experiences without comparison with those of non-autistic people.What was the purpose of this study?: We contributed to the current body of literature by learning more about what autistic people seek in relationships. We also wanted to see what they may struggle with and if these factors are influenced by whether their partner is neurotypical (referring to someone whose brain works in a way that is socially "typical"), neurodivergent (broadly referring to someone whose brain works differently from what is considered "typical"), and/or autistic. In doing this, we hope to help develop more effective ways of supporting autistic individuals who seek romantic connections.What did the researchers do?: The lead researcher, J.K., developed the project based on her experiences navigating romantic relationships as an autistic person. She recruited 106 autistic participants to complete a series of surveys regarding relationship satisfaction. Then, participants completed free-response questions about the most positive and negative parts of those relationships. She asked how they felt autism affected their relationships and gathered these components to identify what increased and decreased relationship satisfaction.What were the results of the study?: We found that autistic people are similarly satisfied in their relationships regardless of whether their partners are autistic or not. Despite this, participants consistently identified different positive and challenging factors within their relationships that tended to align with the neurotype of their partners. We found an interesting link between how autistic people view positive and negative factors in successful romantic relationships and their partners' neurotypes.What do these findings add to what was already known?: We added to a broad body of knowledge about relationship satisfaction by including a greater, more detailed consideration of autistic adults. Instead of comparing survey responses between autistic and non-autistic participants, we compared how autistic people viewed relationship satisfaction based on if their partners were autistic, non-autistic but still neurodivergent, or neurotypical.What are potential weaknesses in the study?: Potential limitations include the following: (1) we recruited a low number of male-identified participants, (2) we did not collect co-occurring diagnoses and conditions from the autistic participants, and (3) we did not verify partner neurotype.How will these findings help autistic adults now or in the future?: Through this project, we were able to highlight positive communication and interpersonal skills among autistic adults. We hope that the results of this study will help autistic people and their partners find some peace and community by reading about others with similar relationship experiences. We also hope to help them further understand what factors might serve as potential strengths and weaknesses in their relationships.
Entry of HIV into latency is likely determined by a combination of factors, including stochastic fluctuations in the viral Tat protein during infection, as well as the transcriptomic phenotype of the host cell. Determining the impact of the proviral integration site on viral expression and latency has been challenging, in part due to difficulty in measuring the integration site and viral expression from the same cell. To investigate the influence of the HIV integration site on HIV expression, we analyzed a combined scRNA-seq/scATAC-seq data set from 117,610 HIV-infected primary CD4 T cells. We used the scATAC-seq data to recover HIV integration site information from 1,530 cells and correlated this information with viral RNA reads in the scRNA-seq data. We observed that, overall, HIV expression did not differ, depending on the genomic features of viral integration, such as genic vs non-genic, intron vs exon, and forward vs reverse orientation. Furthermore, we found that there was no significant difference in HIV expression across 15 distinct chromatin compartments. Additionally, single-cell expression analysis of HIV integration target genes revealed frequent (~5% of infections) insertional activation of host cell gene expression by HIV. This insertional activation occurred almost exclusively when HIV was integrated in the same orientation as the host cell gene and occurred as a result of integration within diverse positions across a gene body. These findings suggest that, overall, HIV expression is relatively robust to the genomic context of the HIV integration site and that HIV frequently upregulates expression of integration site genes during infection. HIV integrates into the host genome during viral replication. In this study, we examine the impact of the integration site on HIV expression. We find that HIV expression is largely robust to variation in the genomic location of integration. We also find that HIV integration can often dramatically upregulate expression of host genes that HIV integrates into. Insertional activation of host cell genes could have important implications for HIV persistence during therapy and for pathogenesis. These findings provide new insight into how the virus HIV and the host cell interact and affect each other during viral replication.
The microtubule-associated protein tau is implicated in neurodegenerative diseases, but its physiological roles remain poorly understood. Here, we find that panneuronal expression of human tau (HsTau) in Drosophila coupled with injury triggers elevated aggression in male flies, which was not observed in flies expressing nonphosphorylatable tau. These behavioral manifestations result from activation of dopaminergic circuits without neurodegeneration. Using in vitro reconstitution assays, we find that phosphorylated HsTau maintains microtubule binding but loses its ability to suppress catastrophes, thereby promoting microtubule dynamicity. In contrast, unphosphorylated HsTau as well as fly tau (DmTau) stabilize microtubules by reducing catastrophe frequency. Our findings challenge the canonical view of tau as a simple microtubule stabilizer and instead position it as a dynamic regulator of microtubule function and neuronal excitability. These results reveal how acute tau phosphorylation can alter neural circuit function and behavior prior to neurodegeneration, providing insights into tau's physiological and pathological roles.
Cancer screening is central to early detection and healthy ageing, yet evidence on how major life transitions shape screening uptake remains limited. Using four waves of the Household, Income and Labour Dynamics in Australia (HILDA) Survey covering 2009, 2013, 2017, and 2021, with 18,875 person-wave observations from 8343 individuals aged 50-75, we estimate the causal effect of retirement on cancer screening using an instrumental-variable design that exploits discontinuities in Age Pension eligibility. Retirement significantly increases participation in organised cancer screening, with the clearest effects appearing in low-friction, invitation-based programmes. The strongest and most robust increases are observed for bowel cancer screening, and among women we also find positive effects for breast screening. By contrast, we find little evidence of comparable changes in broader health care use or in tests that rely more heavily on patient or provider initiative. This pattern points to the importance of programme architecture: retirement matters most where screening is actively prompted, easy to access, and simple to complete. These findings identify retirement as an important phase for engagement with organised screening and underscore the role of institutional design in translating additional time into preventive action in ageing societies.
No studies on abdominal aortic aneurysm (AAA) screening in elderly male patients with coronary artery disease (CAD) in China have been conducted. This study aims to determine AAA prevalence, identify risk factors, and assess transthoracic echocardiography (TTE) as a screening modality to optimize screening strategies and enhance early diagnosis. This observational study prospectively enrolled male CAD patients aged ≥65 who had coronary angiography at Liaocheng People's Hospital from January to June 2024. All underwent routine TTE with abdominal aortic diameter measurements for AAA screening. AAA prevalence was calculated, and clinical characteristics were compared using appropriate tests. Univariate and multivariate logistic regression analyses were done to find independent risk factors. 384 elderly male CAD patients were included, all completing AAA screening via TTE in 2.1±1.7 minutes on average. AAA was detected in 23 patients (6.0%), and 361 had no evidence. 4 AAA cases (17.4%) with aneurysms ≥50 mm were referred to vascular surgery. Multivariate analysis identified age, smoking history, hypertension, and multivessel coronary disease as independent risk factors. The overall AAA prevalence was 6.0% (23/384), and it was 16.8% (16/95) in patients with concurrent multivessel disease, hypertension, and smoking history. This study shows a relatively high AAA prevalence among elderly male CAD patients in China and identifies multivessel disease as a potential independent risk factor for the first time, although this finding should be interpreted cautiously. TTE, a non - invasive and easily implementable tool, is effective in AAA detection and suitable for routine cardiac evaluations of CAD patients. These findings provide a basis for AAA screening in this high - risk population, potentially improving early detection, reducing rupture risk, and enhancing patient outcomes.
PurposeOnline directories play an important apomediary role in shaping how older adults find and compare potential providers. However, little is known about how this type of health information represents older adult needs and aging-related mental health expertise. This study examines how mental health professionals represent older adults and age-related care in their Psychology Today profiles.MethodsWe conducted a mixed-methods content analysis of 281 Psychology Today provider profiles across 8 U.S. cities. We used frequency counts and descriptive statistics to characterize provider attributes and areas of expertise. Using thematic analysis, we examined how providers describe their approach to serving older adults and aging-related mental health care. Quantitative findings informed and contextualized the qualitative analysis.ResultsWe identified one overarching theme "Older Adults at the Limits of Apomediated Visibility" and four subthemes: "Absent Narratives of Aging," "Token Mentions of Older Adults", "Misaligned Descriptions of Expertise", and "Generalist Framings Obscure Age-Specific Care". These results suggest that apomediary signals of relevance may not consistently match substantive descriptions of provider expertise in older adult mental health care.ConclusionsFindings reveal gaps between platform filters and profile narratives that may undermine the directory's apomediary role, making "older adult" care appear searchable while obscuring the age-relevant information older adults need to make informed health decisions. Better alignment between structured search criteria and narrative self-representation would strengthen informed decision-making and advance equitable access to age-responsive mental health services.
While eye movements have been shown to track the speech envelope, it is unknown whether this reflects a hard-wired mechanism or one shaped by (lifetime) audiovisual experience. Further, questions remain about whether ocular tracking is modulated by speech intelligibility and which brain regions drive these synchronized eye movements. Here, we investigate ocular speech tracking in 47 (20 male), blindfolded early blind, late blind, and sighted individuals using magnetoencephalography (MEG) and source-reconstructed oculomotor signals while participants listened to narrative speech of varying intelligibility. We find that oculomotor activity tracks acoustic speech features; however, while neural speech tracking is modulated by intelligibility, ocular tracking patterns remain ambiguous. Interestingly, we find effects reflected in two frequency-specific components: a low-frequency (∼1 Hz) effect present across all groups, indicating that visual experience is not required, and a high-frequency (∼6 Hz) effect reduced in early- and late-blind individuals. Moreover, this finding is not driven by cerebro-ocular connectivity, as late-blind individuals exhibit stronger connectivity between the eyes and the left temporal cortices without a corresponding increase in ocular tracking. In conclusion, ocular speech tracking seems to respond selectively to acoustic features of speech, and does not require visual experience to develop. It may thus represent a hard-wired oculomotor mechanism within the oculo-cerebral network involved in speech processing.Significance Statement Eye movements provide a unique window into the interaction between auditory and visual systems. By studying early blind, late blind, and sighted individuals, we demonstrate that speech related eye movements arise from at least two distinct mechanisms: a low-frequency component that occurs independently of (lifetime) visual experience and is linked to processing of acoustic speech features, and a high-frequency component shaped by prior visual exposure. Importantly, while neural measures were clearly modulated by speech intelligibility, the corresponding ocular responses yielded statistically ambiguous patterns. This potential dissociation suggests that eye movements may reflect mechanisms of spoken language processing that operate independently of intelligibility, revealing novel pathways of auditory-motor coupling that warrant further causal investigation.
The transport properties of single-molecule junctions are fundamentally governed by the energy alignment of molecular frontier orbitals relative to the electrode Fermi level. Although charging-induced reorganization is known to significantly shift this alignment, precisely how these shifts give rise to distinct transport behaviors remains elusive. Here, we use combined scanning tunneling microscopy (STM) and non-contact atomic force microscopy (AFM) at 5.5 K to investigate individual copper phthalocyanine (CuPc) molecules on a bilayer NaCl film supported by Cu(100) substrate. We identified three distinct transport phenotypes on the same substrate-characterized by behaviors ranging from elastic tunneling and dynamic charging to stable charge trapping. These phenotypes depend mainly on the reorganized orbital energy of the singly occupied molecular orbital (SOMO) relative to the substrate Fermi energy. We find that when the SOMO lies close to the substrate Fermi level, the molecule enters a sensitive charge-trapping regime in which an energy shift of only ~100 meV can change the charged-state lifetime by several orders of magnitude. This result is well captured by a theoretical model. Furthermore, we demonstrate that a pentacene molecule-functionalized tip can switch the transport behaviors. Our findings reveal how atomic-scale dielectric disorder within the moiré superlattice amplifies subtle electronic inhomogeneities into discrete transport regimes, underscoring the extreme sensitivity of molecular conductance to orbital-level alignment near the charge trapping regime and to local environmental engineering.
Precise regulation of progenitor identity is essential for the formation of functional auditory circuits. Cochlear nuclei arise from two major progenitor populations: Atoh1-expressing progenitors generate excitatory glutamatergic neurons, while Ptf1a-expressing progenitors generate inhibitory GABAergic and glycinergic neurons. Lmx1a and Lmx1b, expressed in the hindbrain roof plate, must maintain Atoh1 expression in lower rhombic lip progenitors that give rise to excitatory neurons of the cochlear nuclei. Detailed analysis using dye tracing of cochlear and vestibular central projections revealed an overall reduction of input in both Lmx1a knockout mice and Lmx1a knockout mice with added loss of one copy of Lmx1b, although projections to the dorsal cochlear nucleus (DCN) remain relatively preserved. Dye insertion at the crossing of the acoustic stria proved a progressive loss of the ventral acoustic stria (VAS) and its altered trajectory between the trigeminal and restiform body in Lmx1a-/- and Lmx1a-/-; Lmx1b+/- mice. Together, these data show that the anteroventral cochlear nucleus (AVCN) is most severely affected at both embryonic and postnatal stages, showing loss and reduction of central projections. Ultimately, these findings find Lmx1-dependent regulatory activity as a critical checkpoint for the proper development and connectivity of auditory pathways.
Extremes of maternal age are associated with an increased risk of adverse pregnancy outcomes (APOs). Less is known about the independent effects of extremes of paternal age on reproductive risk. We conducted a secondary analysis using data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) using restricted cubic spline logistic regression to examine the non-linear association between paternal age and APOs and adverse fetal/neonatal outcomes. After adjusting for maternal health and sociodemographic and paternal sociodemographic confounders, we found no evidence of overall association (χ2 = 3.88, p = 0.143) or non-linearity (χ2 = 1.72, p = 0.189) between paternal age and composite APOs and adverse fetal/neonatal outcomes (Table 1). Additionally, after adjustment we did not find any statistical significance when examining separate composite APO outcomes (overall: χ2 = 3.02, p = 0.221; non-linearity: χ2 = 2.68, p = 0.101) or composite adverse fetal/neonatal outcomes (overall: χ2 = 1.73, p = 0.421; non-linearity: χ2 = 0.14, p = 0.706). Among adjusted individual outcomes, only gestational hypertension showed statistical significance for both overall association (χ2 = 6.72, p = 0.035) and evidence of non-linearity (χ2 = 4.12, p = 0.042). While our findings do not support a strong independent association between paternal age and composite APOs and adverse fetal/neonatal outcomes, the non-linear association with gestational hypertension may warrant further study with sufficient paternal age representation and paternal health factors.
Polyploidization is a key evolutionary force in plants, but the reasons behind its prevalence remain unclear. While the potential ecological benefits of established polyploids are well studied, little is known about the short-term genomic and epigenetic responses immediately after polyploidization, which are crucial for successful speciation. In this study, we assemble the genomes of the two progenitors of Arabidopsis kamchatica (A. halleri and A. lyrata) and examine the epigenome of synthetic and natural tetraploids of A. kamchatica to investigate the combined effect of allopolyploidization and environment on DNA methylation changes. We find the most significant methylation changes at allopolyploidization, followed by smaller changes in subsequent generations. Offspring grown under different conditions show divergent patterns, suggesting environmental effects, while their methylation patterns converge toward those of natural tetraploids over generations. Our findings highlight two key epigenetic changes post-polyploidization: convergence toward established polyploids and divergence driven by environmental factors.
Targeting replication-associated DNA repair mechanisms, including the control of ADP-ribosylation by PARP1/2 and PARG, is a powerful therapeutic approach for cancer. However, the mechanisms by which PARG inhibition impacts DNA replication remain unclear. Here, we combine isolation of proteins on nascent DNA (iPOND) with quantitative proteomics and functional assays to investigate replication fork dynamics upon acute PARG inhibition. We find that FET family proteins (FUS, EWS, and TAF15) are recruited to replication forks in a PAR-dependent manner, forming condensates that slow fork progression and promote fork reversal. FET proteins control fork dynamics in response to some, but not all, replication stresses. FUS inactivation leads to unrestrained fork progression via RECQ1 and PRIMPOL, increased single-stranded DNA gaps, genome instability, and synthetic lethality with BRCA1 deficiency. These findings reveal that FET protein assemblies modulate replication stress responses, influencing genome stability and the cellular response to cancer therapeutics targeting PARylation pathways.
The origin of superconductivity in oxide interfaces and its relation to ferroelectricity remains an open question. At LaAlO3/SrTiO3 interfaces, quantum confinement and inversion symmetry breaking create a two-dimensional electron gas near a ferroelectric quantum critical point, yet direct evidence linking phonon dynamics to electron pairing has been lacking. Here we directly probe lattice vibrations and atomic structure at LaAlO3/SrTiO3 interfaces across the superconducting phase diagram using vibrational spectroscopy with momentum selectivity in a scanning transmission electron microscope. We find that superconductivity across the doping series correlates with inversion symmetry breaking and the appearance of high-frequency localized phonons. These tunable, polar vibrations-confined near the interface-exhibit strong electron-phonon coupling and evolve systematically with carrier density. Our findings establish a link between lattice instability, superconductivity and strong electron-phonon coupling mediated by tunable localized phonons, providing new insights into possible microscopic pairing pathways in quantum paraelectric systems.
Cancer cells adapt to treatment, leading to the emergence of clones that are more aggressive and resistant to anti-cancer therapies. We have a limited understanding of resistance mechanisms as we lack technologies to map cancer evolution under the selective pressure of treatment. To address this, we present a hierarchical, dynamic lineage-tracing method, FLARE (Following Lineage Adaptation and Resistance Evolution). We use FLARE to track the progression of acute myeloid leukemia (AML) cell lines treated with Cytarabine (AraC), a front-line treatment in AML, both in vitro and in vivo. We map distinct cellular lineages in both murine and human AML cell lines that are predisposed to AraC resistance. Using FLARE, we identify treatment-naïve populations responsible for seeding resistance that are characterized by upregulation of stemness markers and a cell adhesion-associated AraC-resistant lineage signature. We find that expression of this signature in pediatric AML is associated with the expansion of HSC-like malignant cells at relapse and significantly shorter overall survival. These findings underscore the role of pre-existing lineage states in driving relapse and establish FLARE as a platform for uncovering the evolving, heritable transcriptional programs that underlie tumor evolution.
Suicide is a leading cause of death amongst children and young people (CYP), and numbers of CYP presenting with suicidality continue to rise. CYP seeking help for suicidal thoughts and behaviours are generally referred to Child and Adolescent Mental Health Services (CAMHS) for assessment and treatment. However, CAMHS across the UK are unable to meet the demand for their services. Little is known about what happens to these children after they have been referred to CAMHS. Grounded in critical realism, and informed by a children's rights approach and feminist perspectives, this qualitative study sought to explore how children and young people presenting with suicidality experience the CAMHS referral process and care journey thereafter. In-depth interviews of between 60-90 minutes duration, were conducted with ten CYP aged between 13-17yrs, living in two different health board areas in Scotland, and having been referred to two different CAMHS (sites A and B). Using Charmaz constructing grounded theory approach, analysis revealed three main themes which are presented: Nothing got resolved: the care experience; "If you had more choice…" about how, when and where they worked with you; The person not the profession who helped, each built upon layers of overlapping subthemes. Further interrogation of the data, and synthesis supported the development of a substantive theory, that conceptualises children and young people presenting with suicidality as "Seen but not Heard". It is argued that CAMHS do not meet these CYP needs even when they are seen. This finding has implications for policy makers and service providers as the CYP in this study express that the support they need and find most helpful is not congruent with CAMHS. Further research is urgently required to develop and design a new service model that better meets the needs of children and young people and prioritises their views.
Carboranes find use in a wide variety of applications ranging from specialty catalysts to medicinal uses. Certain functionalized carboranes are described as explosive materials, although their nonfunctionalized precursors are regarded as inherently stable and not explosive. Herein, we report new findings on the sensitization of nonfunctionalized 12-vertex ortho-, meta-, and para-carboranes as well as dodecaborate in physical mixtures with several common inorganic salts. These mixtures were evaluated for explosive properties with drop hammer impact tests, friction tests, and differential scanning calorimetry thermal gravimetric analysis (DSC-TGA). Results indicate explosive sensitization to mechanical stimuli for the nonfunctionalized carboranes tested with a wide variety of inorganic salts, especially oxidizers. Sensitization of these compounds has not previously been reported, and raising awareness to the broader scientific community on this matter is warranted, especially as several of the mixtures evaluated are more sensitive to mechanical stimuli than primary explosives such as lead azide or pentaerythritol tetranitrate.
The factors influencing the oral microbiome during childhood and adolescence remain under-explored at the population level. Furthermore, details on how the oral microbiome differs with age, varies between individuals of different ethnicities, or is associated with socioeconomic factors and diet in children and adolescents are almost entirely unknown. Saliva samples and detailed demographic, health, diet and socioeconomic data were collected from children and adolescents that attended the Ontario Science Centre (Toronto, Canada) and were enrolled in the Spit for Science cohort. We characterised the bacterial microbiota of 4812 samples using 16S rRNA gene sequencing to make this the largest population cohort of the paediatric oral microbiome to date. Exploration of limited participant genotyping information and more than 50 variables encompassing the demographics, health, diet, socioeconomic status and living environment of participants revealed that almost all of the investigated variables were associated with overall community structure and/or the abundance of specific bacterial genera. However, most of these associations were modest (R2 < 0.01) and the correlation between genetic relatedness and salivary bacteriome similarity was weak (R2 = -0.014), while the strongest determinants of oral bacteriome composition were shared family/household environment (R2 = 0.61 in the subset of participants from multi-child households), age (R2 = 0.014) and ethnicity (R2 = 0.01). We show that older children and adolescents have higher richness but lower evenness than younger children, suggesting that their oral bacteriome changes as they are exposed to more influences outside the home, and that the oral bacteriome is more consistent with more core taxa among children and adolescents than adults. We also find that diet variables related to the frequency of sugar consumption have the largest impact on the oral bacteriome of children and adolescents, and that microbial differences attributed to ethnicity and diet are likely intertwined. This study provides an atlas of the demographic, health and lifestyle factors that are associated with the salivary bacteriome of children and adolescents. These findings highlight the complex interplay between social, environmental, and biological factors in shaping the developing oral microbiome and underscore the importance of inclusive, demographically diverse cohorts in microbiome research. This presents a reference for the variables that are important to account for in paediatric oral microbiome studies. Video Abstract.
Topological defects determine the collective properties of anisotropic materials. Nonetheless, it is not fully understood how their configurations are controlled, especially in three dimensions. In living matter, contributions of two-dimensional topological defects to biological functions have been demonstrated, but whether three-dimensional polar defects have any biological relevance is unclear. Here we report a charge-preserving transition between three-dimensional defect configurations driven by boundary geometry and independent of material parameters. Moreover, we find that three-dimensional polar defects in the mouse embryo are the sites where fluid-filled lumina form, essential structures for subsequent development. We validate these findings by experimentally perturbing embryo shape beyond the transition point, which results in the creation of additional lumen initiation sites near predicted defect locations. Overall, our results reveal how boundary geometry controls polar defects, and how embryos use this mechanism for shape-dependent lumen formation. We expect this defect-control principle to apply broadly to systems with orientational order.