搜索结果：Processes

Breast cancer exhibits profound molecular and clinical heterogeneity, manifested through diverse subtypes, metastatic patterns, and therapeutic responses. Emerging evidence underscores that this complexity stems not merely from genetic and epigenetic aberrations but also from post-transcriptional regulatory mechanisms, particularly alternative splicing (AS), which amplifies proteomic diversity and functional versatility. AS generates multiple mRNA isoforms from a single gene, directly influencing oncogenic processes including cell migration, metabolic reprogramming, immune evasion, and therapy resistance. Recent advances in high-throughput sequencing and bioinformatics have enabled systematic mapping of AS landscapes in breast cancer. This review delineates the mechanistic underpinnings of AS regulation and synthesizes cutting-edge discoveries in AS-driven oncogenic pathways. We further evaluate the translational potential of AS signatures in clinical applications, such as molecular subtyping, prognostic biomarkers, and splice-switching therapeutics. Finally, we address persisting challenges, including tumor heterogeneity and the lack of splicing specificity, that must be overcome to harness AS modulation as a precision oncology strategy.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem illness marked by fatigue, cognitive impairment, and post-exertional malaise. Gastrointestinal (GI) symptoms are frequently reported, yet their relationship to central features of the illness and biological correlates remains poorly understood. We aimed to characterize GI symptom burden in ME/CFS and evaluate its associations with core clinical features and specific immune and inflammatory markers, with attention to potential gut-related contributions to disease expression. GI symptoms and 49 additional symptoms across nine domains were assessed in 116 ME/CFS patients and 80 matched controls. Plasma C-reactive protein (CRP) and antibodies against dietary and microbial antigens were measured as indicators of systemic inflammation and putative gut-derived antigen exposure. ME/CFS patients reported significantly elevated GI symptom frequency and severity compared with controls, with 53% of ME/CFS patients versus 8% of controls reporting a prior diagnosis of irritable bowel syndrome. GI symptom burden correlated with fatigue, cognitive difficulties, flu-like symptoms, pain, sleep disturbances, neurological complaints, and sensory sensitivities, independent of illness duration. CRP levels were higher in patients with greater GI symptoms and correlated with GI, fatigue, musculoskeletal pain, and flu-like symptom burden. Patients with greater flu-like symptom expression exhibited higher IgM responses to dietary gliadin and bacterial lipopolysaccharide. These associations were not detected in controls. GI symptoms are a prominent, clinically relevant dimension of ME/CFS, associated with broader symptom burden and inflammatory heterogeneity. These findings highlight the relevance of gut-related and immune processes in ME/CFS and underscore the value of incorporating GI symptom assessment in translational studies to help refine mechanistic understanding and improve therapeutic stratification.

Primary care forms the basis for valued outcomes in health systems, including population health, high quality care, and reduced health expenditures. However, the primary care system in the United States (US) faces many difficulties, including financial pressures and clinician burnout that accelerated following the Covid-19 pandemic. This study examines the ability of primary care practices to adapt to post-pandemic challenges using a lean management system for quality and process improvement. We used data from the National Survey of Healthcare Organizations and Systems II, a nationally representative sample of 1,245 physician practices located across the US. We first described the status of lean implementation among these primary care practices. We then conducted bivariate analyses followed by multivariate logistic regressions to examine relationships between lean implementation and outcomes of interest, including pandemic response activities, financial performance after the pandemic, and impacts of workforce shortages on patient care. Practices that adopted lean management were significantly larger in size (p&#x2009;<&#x2009;0.05), affiliated with a health system or federally qualified health center (p&#x2009;<&#x2009;0.0001), had a higher percentage of revenue from Medicaid (p&#x2009;<&#x2009;0.0001) but lower percentage from Medicare insurance (p&#x2009;<&#x2009;0.05), participated in more capitated payment arrangements and Accountable Care Organization contract types (p&#x2009;<&#x2009;0.01), and were more evenly distributed across geographic regions of the country (p&#x2009;<&#x2009;0.001). Controlling for these contextual features, we found that lean practices were more likely to participate in an incident command system for pandemic response (OR&#x2009;=&#x2009;2.45, 95% CI: 1.24-4.82), engage in efforts to address clinician burnout (OR&#x2009;=&#x2009;1.29, 95% CI: 1.03-1.60), and report stronger financial performance after the pandemic (OR&#x2009;=&#x2009;2.57, 95% CI: 1.40-4.73). Additionally, after adjusting for all other lean processes, practice use of rapid improvement events (OR&#x2009;=&#x2009;0.20, 95% CI: 0.06-0.70) and real-time data analysis tools (OR&#x2009;=&#x2009;0.31, 95% CI: 0.11-0.90) was associated with lower reported impacts of workforce shortages on patient care. Health systems continue to face challenges, making them vulnerable to major disruptions as experienced with the recent pandemic. Lean management may enhance organizational resilience and theability of primary care practices to respond to rapidly evolving environments.

The limestone monuments of the Rectangular Tower in the Xiaoling Tomb of the Ming Dynasty, created in the mid-fourteenth century, are biodeteriorating from environmental exposure, resulting in the formation of black biocrusts. However, the microbiomes that shape biocrust formation and the biodeterioration processes involved remain unclear, significantly challenging the conservation of stone monuments at this archaeological site. Here, we systematically investigated the physicochemical properties and microbial communities of biocrusts to identify keystone taxa that shape their formation and biodeterioration. Physicochemical analysis indicated that biological crusts are associated with calcium mobilization and redistribution of the limestone monuments. Microscopy and spectroscopy indicated that microbial interactions with limestone promote the formation of biological crusts. Importantly, we observed the significant predominance of Cyanobacteria and/or Chloroflexi in biocrusts, suggesting that photosynthesis may be a crucial process in biocrust formation. Fungal communities in biocrusts were dominated by Ascomycota, Basidiomycota, and Chytridiomycota, while archaeal communities were dominated solely by Nitrososphaerota. Microbial co-occurrence network and correlation analyses identified 12 keystone taxa across 11 genera that shape biocrust formation. Importantly, Scytonema spp. could provide organic carbon and nitrogen for Spirosomaceae spp., and members of the classes Cyanobacteriia and Agaricomycetes, as well as the genera Setophaeosphaeria and Plectosphaerella, are likely the keystone taxa responsible for both biocrust formation and the associated biodeterioration. Additionally, two predominant ammonia-oxidizing archaeal families (i.e., Nitrososphaeraceae and Candidatus Nitrocosmicus) could support chemolithoautotrophic growth in the microbiome by oxidizing ammonia and fixing carbon dioxide. Together, these findings underscore the need for targeted conservation strategies to mitigate microbial biodeterioration of stone monuments during biocrust formation.

Academic medicine (AM) careers combine research, teaching, and patient care, yet their attractiveness has declined in recent years, particularly among women, who remain underrepresented in this field. Previous research highlights the central role of interest in research, but the cognitive and contextual processes underlying academic career intentions during residency remain insufficiently understood. Social Cognitive Career Theory (SCCT) provides a relevant framework for examining how individual cognitions and learning experiences jointly shape career intentions. This cross-sectional study included 1,570 French medical residents who completed an online questionnaire. Guided by the SCCT framework, we examined the relationships between learning experiences (academic satisfaction and perceived stress), self-efficacy, outcome expectations (operationalized through work centrality), professional interest in research, and intention to pursue a career in academic medicine. Hierarchical ordinal regression models were used to predict AM career intention, and structural equation modeling was conducted to investigate the formation of professional interest in research. Gender and prior research experiences (master's or PhD) were examined as moderating factors. Overall, residents reported low intention to pursue a career in academic medicine, with women expressing significantly lower intentions than men. Professional interest in research emerged as the strongest predictor of AM career intention, followed by research experiences and mentorship. Outcome expectations, measured through work centrality, also contributed significantly to career intentions. Structural equation modeling supported key assumptions of SCCT: perceived stress was negatively associated with self-efficacy, academic satisfaction was positively associated with outcome expectations, and work centrality played a central role in shaping professional interest in research. Gender differences in career intentions were largely explained by disparities in learning experiences and research opportunities rather than by differences in outcome expectations. Moderation analyses suggested gender-specific patterns at advanced levels of research involvement. These findings support the relevance of SCCT for understanding academic medicine career intentions and highlight the central role of professional interest in research and contextual learning experiences. Promoting positive learning environments, providing early and structured research exposure, and ensuring access to mentorship may represent key levers for fostering academic career engagement and addressing gender disparities in academic medicine.

Solar salterns are environmentally stable yet biologically extreme ecosystems that serve as vital models for understanding and managing hypersaline environments, including industrial saline effluents. Despite their ecological and biotechnological significance, Indian solar salterns remain functionally underexplored. In this study, we integrated culture-dependent isolation with whole-metagenome sequencing to investigate microbial community assembly, functional specialization, and eco-technological potential across four geographically distinct Indian salterns.Physicochemical analyses revealed pronounced spatial variation in salinity, pH, and electrical conductivity, which together strongly structured microbial communities. Metagenomic sequencing generated between 4.84 and 8.68 Gb of raw data across individual site, yielding between 429,420 and 669,991 predicted genes in high-salinity locations. Taxonomic reconstruction demonstrated archaeal dominance at extreme salinity, particularly among Euryarchaeota, whereas comparatively moderate salinity sites supported more balanced bacterial-archaeal assemblages. Alpha diversity patterns indicated higher richness in Tamil Nadu and Rajasthan, while Gujarat exhibited reduced evenness consistent with environmental filtering.Culture-dependent approaches recovered 42 halophilic and polyextremophilic isolates, primarily affiliated with Halobacteriaceae and Bacillaceae, complementing the broad taxonomic detection of these lineages inferred from metagenomic data. Functional annotation revealed extensive enrichment of genes involved in ion transport, energy production, osmoprotectant biosynthesis, and DNA repair, reflecting an adaptive mechanism critical for survival in high-salinity industrial processes. Amino acid metabolism genes exceeded 25,000 hits in selected sites, and replication and repair genes reached 32,554 in Gujarat, indicating heightened stress-response activity. Secondary metabolite biosynthetic gene clusters, including pathways for novel antimicrobial peptides, terpene, ribosomally synthesized and post-translationally modified peptide-like, and type III polyketide synthase pathways, were widely distributed, offering new biological control mechanisms for environments impaired by stress. Antimicrobial resistance signatures were limited and unevenly distributed across sites.These findings demonstrate that salinity acts as a dominant ecological filter driving both taxonomic composition and functional specialization in Indian solar salterns. By linking environmental gradients to adaptive genomic traits, this study establishes a functional baseline for hypersaline ecosystems.

Growing research highlights interpretation inflexibility as a key transdiagnostic mechanism across psychopathologies. Yet, few studies have examined its role in everyday socio-emotional processing. This review bridges that gap by exploring how interpretation inflexibility contributes to psychopathology-particularly depression and psychosis-in social contexts. Evidence suggests disrupted interpersonal processes, including rigid interpretations of social scenarios and impressions of others, are central to understanding depressive and psychotic symptoms. Depression is marked by valence-specific, context-dependent inflexibility, with difficulty disengaging from negative biases. In contrast, psychosis shows a broader inflexibility across emotional valences. The review also outlines evolving measures of interpretation inflexibility, emphasizing the need to account for social context in interpretation revision. Current findings highlight the value of examining inflexibility within social frameworks to better understand its role in adaptive functioning and psychopathology. Future research on interpretation inflexibility in social contexts could inform novel interventions and improve clinical outcomes.

Neonatal exposure to sevoflurane has been implicated in long-term neurodevelopmental abnormalities, yet the underlying mechanisms remain unresolved. This study sought to determine whether cGAS-STING-mediated microglial activation and aberrant synaptic pruning underlie sevoflurane-induced cognitive deficits and to assess how environmental conditions modulate these processes. Neonatal mice underwent sevoflurane exposure followed by rearing in enriched (EE) or impoverished (IE) environments. Cognitive function, synaptic structure, microglial activity, mitochondrial status, and cGAS-STING signaling were evaluated using behavioral tests, immunostaining, biochemical assays, and pharmacological inhibition. Sevoflurane exposure induced cognitive impairment, microglial overactivation, mitochondrial dysfunction, and excessive synaptic pruning resulting from microglial overactivation. EE mitigated these abnormalities by preserving mitochondrial integrity and reducing mtDNA-driven cGAS-STING activation, thereby preventing the microglia-mediated imbalance in synaptic pruning and improving cognitive outcomes. In contrast, IE exacerbated mitochondrial injury, aggravated synaptic loss, and further worsened cognitive impairment. Sevoflurane disrupts neurodevelopment through a mitochondria-cGAS-microglia-synapse pathway. Environmental enrichment offers significant neuroprotection, highlighting both cGAS-STING signaling and early-life environmental modulation as promising targets for preventing anesthesia-related neurodevelopmental injury.

Osteoarthritis is a leading cause of pain and disability, yet the biological processes linking peripheral joint pathology with central pain mechanisms and wider symptom burden remain poorly defined. We performed an integrated metabolomic and inflammatory analysis of cerebrospinal fluid and serum obtained from patients with osteoarthritis (n&#x2009;=&#x2009;81) and healthy pain-free controls (n&#x2009;=&#x2009;70). Proton nuclear magnetic resonance spectroscopy was used for metabolomic profiling, alongside targeted protein assays for inflammatory mediators. Orthogonal partial least squares discriminant analysis was applied to assess separation between groups and to determine diagnostic accuracy. Associations between metabolites and clinical outcomes, including pain intensity, disability and sleep disturbance, were examined, with adjustment for age and BMI. Clear separation between osteoarthritis and healthy pain-free control participants was observed in both biofluids, with classification accuracies of 87% for serum and 89% for cerebrospinal fluid. Reduced serum histidine, glutamine, albumin (lysyl) and lysine distinguished osteoarthritis from healthy controls. In cerebrospinal fluid, osteoarthritis was characterised by higher lactate and glutamate and lower glucose and glutamine compared to controls. Combining metabolomic data with inflammatory proteins increased diagnostic accuracy to 90% and remained significant after matching for age and BMI. Reductions in serum histidine and glutamine were consistent across subgroups, including stratification by pain severity. These metabolites correlated inversely with pain intensity, disability, sleep disturbance and overall symptom impact, and were more markedly altered in women, who also reported greater symptom burden. Osteoarthritis is associated with a distinct pattern of peripheral and central metabolic disturbance. Histidine and glutamine emerge as promising biomarkers related to pain and clinical severity, highlighting metabolic pathways as potential targets for improved stratification and intervention in osteoarthritis pain.

Aging results from the gradual accumulation of molecular and cellular damage, and it is a risk factor for neurodegenerative disease. The aryl hydrocarbon receptor (AhR) is increasingly recognized as a key in the regulatory molecular mechanisms that drive aging. AhR is a cytoplasmic receptor activated by diverse endogenous and exogenous ligands. It modulates cell proliferation and differentiation in development and the adult brain. Besides, AhR participates in multiple physiological mechanisms that become dysregulated with age, including neuroinflammation, gut dysbiosis, stem cell maintenance, genomic stability, lipid metabolism, and mitochondrial function, contributing to the onset of neurodegeneration. These interconnected physiological processes lead to cumulative damage that ultimately impairs physical and cognitive function in older individuals. Activation of AhR by selective ligands has been shown to dampen neuroinflammatory responses and support cognitive integrity, underscoring its regulatory role in central nervous system (CNS) homeostasis. This review plumbs current evidence on how AhR influences the molecular mechanisms of aging and explores its potential as a therapeutic target to preserve brain health and mitigate age-related neurological decline.

Spinal cord injury (SCI) causes massive release of myelin&#x2011;derived lipids, driving macrophage&#x2011;to&#x2011;foam&#x2011;cell transformation that sustains inflammation and impedes repair. Although reverse cholesterol transport (RCT) mediates lipid efflux, its functional dynamics within the SCI microenvironment remain unclear. Using a mouse T10 contusion model, we examined key RCT components (ABCA1, ABCG1, and APOE) by qRT&#x2011;PCR, Western blot, and immunofluorescence. We also evaluated the LXR agonist AZ876 for its capacity to modulate RCT and promote functional recovery. We observed a pronounced imbalance in RCT after SCI. ABCA1 and APOE were persistently upregulated, but ABCA1 localized predominantly to astrocytes rather than macrophages. Notably, ABCG1 protein levels declined progressively despite increased mRNA expression, indicating a post&#x2011;transcriptional bottleneck that favors foam&#x2011;cell accumulation. AZ876 activated the LXR/RXR axis and induced long&#x2011;term transcriptomic remodeling of lipid metabolism. Early AZ876 treatment increased ABCA1 and partially restored ABCG1 protein expression, markedly reducing Oil Red O-positive foam&#x2011;cell accumulation at the lesion site. These microenvironmental improvements were associated with decreased TNF&#x2011;&#x3b1; levels and enhanced locomotor recovery, as evidenced by improved BMS scores and open&#x2011;field performance. The lipid-rich environment after spinal cord injury rapidly activates the initial steps of RCT, but a pronounced post-transcriptional suppression of ABCG1 impedes downstream RCT processes. Although the LXR agonist AZ876 partially overcomes this bottleneck and improves neurological outcomes, it fails to fully restore ABCG1 protein levels, indicating that transcriptional activation alone is insufficient. Future strategies should target the mechanisms of ABCG1 protein instability to fully correct lipid metabolic dysregulation.

Loneliness in youth (15-24 years old) is increasing. The impacts over the life course are more fully recognised and require co-designed responses. A participatory designed project, a/part of the crowd, has led to a web-delivered, preventive response to loneliness with young adults 18-25 years old. As a part of this, an integrated Lived Experience Advisory Group with co-researcher roles was established to centre youth perspectives and to grow research capabilities. The co-designed response was developed from 128 short stories, poetry, artworks (hand-drawn, digital and collage), and music submitted by 18 to 25-year-olds in Australia. Ethics approval was granted for the larger project. A 12-member Lived Experience Advisory Group provided advice on design, recruiting, and promoting. They shared impressions on data and supported elements of the co-designed web space and steps for further translation. Five members of the LEAG were also appointed as co-researchers. In this paper, we outline the Lived Experience Advisory Group establishment and role, and share co-reflections on the contributions made and how to embed lived experience in the research process and practice. Five co-researchers worked alongside the interdisciplinary research team. Reflections identified the importance of a project coordinator to maintain communication and connection, and that collaborative research meetings supported working alongside as a team sharing interpretations and discussing research. The Lived Experience Advisory Group role has included advising on design elements for the co-designed response, and user testing, which was recently made publicly available. The advisory group and co-research roles created a mechanism to increase participation in decision processes and share roles in research activities. Co-researchers have been trained to analyse content, and frequent reflective meetings have fostered understanding of current lived realities for 18- to 25-year-olds, and grown new collaborations and activities. This has developed the capabilities of co-researchers and the wider research team in youth-centred approaches to loneliness research. Members of the LEAG and co-researchers have now adopted additional roles in other activities supporting an element of implementation into mental health research translation. This led to an example of an integrated lived-experience approach to adopt within research studies in the future. Loneliness is becoming more common for young adults and has large personal and societal impacts. Young adulthood is a time of big life changes, and these can lead to feelings of loneliness. To understand and address this, we must work with people who have lived experience of loneliness. We also need to work together to develop effective supports and solutions. a/part of the crowd seeks to understand how young adult experience loneliness through the lens of big life changes. The broader project has used a participatory approach to gather 128 stories from adults aged 18&#x2013;25 about their experience of loneliness using creative methods (these findings are reported separately). This has supported a deeper understanding of loneliness than a biomedical approach would have provided. The project involved people with lived experience of loneliness working as advisors and as co-researchers to support activities, which we outline in this paper. This includes reflections from a 12-person Lived Experience Advisory Group as part of writing and during collaborative research meeting discussions. We also outline how safe opportunities to discuss loneliness were created. a/part of the crowd has enabled us to learn together with creative tension and build skills across the team. This model has required intentional work and resourcing from the university-based project leads. This is essential to ensure young adult with a lived experience of loneliness are well supported. Finally, we prioritised young adult most affected by loneliness. They guided this work and co-designed its outcomes.

Adoptive T-cell transfer therapy (ACT) has significantly propelled the advancement of tumor immunotherapy. Among various strategies targeting solid tumors, the T-cell receptor (TCR)-engineered T-cell (TCR-T cell) therapy has emerged as a highly promising approach, exhibiting an expanded therapeutic window across diverse patient populations and superior tumoricidal activity in certain solid malignancies compared with chimeric antigen receptor T cell (CAR-T) and tumor-infiltrating T cells/lymphocyte (TIL) therapies. However, its clinical efficacy remains constrained. In this paper, we introduce the limitations and challenges faced by TCR-T cells in solid tumor treatment, and summarize recent efforts overcoming these limitations and translating TCR-T cell therapies into clinical application. Furthermore, their current status and effectiveness in clinical solid tumor patients were analyzed. We expect that the precision therapies of TCR-T cells, with the support of high-affinity TCRs and a diverse array of target antigens, multimodal synergistic therapy strategies and efficient in vitro production processes, will benefit a wider patient population, thus revealing new clinical application potential.

Population aging has received considerable attention across economies presenting significant social, economic, and health challenges. While research has focused on demographics and health, limited attention has been given to the context, processes and outcomes of active aging in Ghanaian society. An exploration into this is essential to understanding the underlying dynamics between social stability, socioeconomic growth, health promotion and quality of life of older adults in Ghana. We conducted a systematic review to compile and report on existing empirical evidence on population trends, age-related health issues, available support systems, and needs of older adults in Ghana to inform age-friendly services and policies. In accordance with PRISMA guidelines, we screened peer-reviewed articles published between 2015 and 2025 using search terms related to aging in Ghana. Through thematic synthesis, four themes were identified - health utilization, health status, social support, and policy implications. Older adults who had better emotional, relational, and instrumental support from family and the community demonstrated higher levels of wellbeing, greater use of healthcare services, and reduced feelings of social isolation. Individuals reported unmet needs in food insecurity, financial hardship, lack of assistance with daily activities, and limited access to healthcare. Furthermore, older adults who reported multiple chronic conditions reported high levels of functional disabilities and physical difficulties. This review underscores an immediate, coordinated policy intervention and research action to prepare Ghana for its next demographic phase. Priority action should focus on enhancing healthcare access, fostering social inclusion and promoting community engagement among older adults in Ghana to improve their quality of life.

Mitochondrial proteases are essential for mitochondrial protein import and constitute the core of the organelle's intrinsic protein quality control system. However, their physiological functions across tissues, as well as their influence on cytosolic proteostasis, remain incompletely understood. We generated loss- and gain-of-function alleles for 15 conserved mitochondrial proteases in Drosophila melanogaster to systematically dissect their in vivo functions. Disruption of specific proteases caused male sterility or organismal lethality, whereas tissue-specific knockouts in the eye, muscle, or fat body led to mitochondrial protein aggregates, structural defects, and age-dependent degeneration. Loss of UQCR-C1 or Afg3l2 robustly increased mitophagy, while overexpression of several proteases severely impaired muscle integrity. Loss of UQCR-C1, Mppa, or CG11771 promoted HTT72Q aggregation, and reducing UQCR-C1 or Afg3l2 markedly elevated cytosolic HTT72Q levels. Conversely, overexpressing Mppa-but with reduced efficacy in its disease-associated variants-suppressed HTT96Q aggregation and neuronal toxicity. Mppa forms a complex with UQCR-C1 to regulate mitochondrial pre-protein processing and import, indicating that enhancing mitochondrial protein import is sufficient to alleviate cytosolic proteotoxic stress caused by HTT polyglutamine (polyQ) proteins. This work establishes a comprehensive in vivo resource for mitochondrial protease functions and their roles in shaping cytosolic proteostasis.

The mut-L homologue 1 gene (MLH1) is a DNA repair gene. Loss of biallelic expression of MLH1 in humans leads to increased predisposition to several cancer types. In the koala (Phascolarctos cinereus) and brushtail possum (Trichosurus vulpecula), MLH1 is imprinted, resulting in monoallelic parent-of-origin specific gene expression. Allele-specific methylation and expression analysis of MLH1 in tammar wallaby (Notamacropus (Macropus) eugenii) pouch young indicated MLH1 was maternally methylated and paternally expressed. A second site of MLH1 was identified, lacking introns. This site was a retrocopy, formed through the MLH1 mRNA incorporating into the tammar genome. An orthologous MLH1 retrocopy was identified in two macropodid marsupials and an additional two non-orthologous MLH1 retrocopies were identified in the bilby (Macrotis lagotis) and marsupial mole (Notoryctes typhlops). The tammar, bilby and marsupial mole MLH1 retrocopies had intact open reading frames and the tammar and bilby retrocopies were expressed. Protein structure alignment indicated the conformation of the 'parental' and retrocopy MLH1 protein may be conserved and therefore may have a comparable function to the parental MLH1 protein. This second site of MLH1 expression may have introduced redundancy to MLH1 expression and compensate for silencing of the maternal MLH1 allele in marsupials.

Standardized Nursing Terminologies are used to describe diagnoses, interventions, and care outcomes. This study explores the use of Standardized Nursing Terminologies among Primary Care nurses, particularly in the context of frailty syndrome, and identifies barriers to and facilitators of their integration into clinical practice. Descriptive-interpretive qualitative study with a phenomenological approach. Purposive and snowball sampling techniques were used to select 33 Primary Care nurses involved in healthcare, teaching, management, and research in Spain. Three focus groups and fourteen semi-structured interviews were conducted in 2024. The qualitative data were transcribed, aggregated, analysed, and interpreted using reflexive thematic analysis. Three 3 main themes related to the use of Standardized Nursing Terminologies were identified: (1) The value of a common language: professional autonomy; (2) From standardization to action: integration into clinical practice; and (3) Skills-building: towards Nursology. Participants described language standardization as a driving force for professional development and the use of real-world data in research. The NANDA-I, NIC, and NOC terminologies were the most widely used; however, they generated certain ambivalence due to their complexity, cost, and need for regular updates, and were seldom used in clinical practice. Study participants identified several facilitators of their use, such as their usefulness in structuring clinical reasoning, improving continuity of care, planning resources, and addressing complex care. They also identified barriers, primarily insufficient training, poor usability, scant enforcement, bureaucratic approach, and the absence of a clearly defined organizational strategy. In the context of frailty syndrome, Standardized Nursing Terminologies were reported to promote comprehensive care, although their use was limited, training scarce, and evidence of their impact lacking. Participants also referred to the role of Nursology in fostering research in person-centred, outcome-oriented care, and highlighted leadership as key to strengthening a professional identity based on a reflective and thoughtful-critical approach to nursing. Standardized Nursing Terminologies hold significant potential to transform nursing care; however, their integration into Primary Care remains limited. Frailty syndrome illustrates the gap between this potential and its practical implementation. Bridging this gap requires targeted training strategies, strong institutional support, and leadership committed to fostering person-centred, evidence-based practice.

Medical Assistance in Dying (MAiD) and related services are legally available in a number of countries under specific conditions and continue to be the subject of ongoing international debate. In Canada, MAiD has been legally available since 2016, with eligibility expanded in 2021 to include individuals whose natural death is not reasonably foreseeable (Track 2), in addition to those whose death is reasonably foreseeable (Track 1). MAiD is federally regulated, but services are organized and delivered at the provincial and territorial levels, resulting in substantial variation in staffing, funding, oversight, and training. To date, most research has focused on the experiences of individual professional groups, such as physicians, or on single jurisdictions. Less is known about how the service delivery process functions as a whole and how its organizational and operational features shape the experiences of the healthcare professionals (HCPs), administrators, and policymakers involved. This study examines the barriers to and facilitators of MAiD service delivery from the perspectives of professionals across the service delivery process throughout Canada and identifies key system-level and operational factors that may inform MAiD policy and program planning both domestically and internationally. Participants were recruited through professional networks, provincial and territorial MAiD working groups, and MAiD-related non-profit organizations. Participants included healthcare professionals (HCPs), program administrators, and policymakers involved in MAiD service delivery. Interviews were held virtually and were recorded and transcribed. Data was analyzed using a qualitative descriptive design with a structured, five-phase inductive thematic analysis approach and constant comparison to identify barriers to and facilitators of MAiD service delivery. A total of 46 semi-structured interviews were conducted between July 2024 and January 2025 with participants from seven provinces and one territory. Ten themes and 25 sub-themes were identified. Barriers included high workloads, limited collaboration with other health services, limited coordination, and inadequate training and financial support. Emerging issues included misinformation about MAiD eligibility criteria, limited bereavement support services for patients' families, and acquiring and transporting MAiD-related medications. Facilitators included centralized coordination systems, standardized documentation and reporting, interprofessional collaboration, and supportive leadership. These findings offer a process-level view of how MAiD services have been operationalized in Canada a decade after its legalization. They highlight persistent and emerging challenges in MAiD service delivery as well as promising innovations used to address them. As Canada prepares for the March 2027 expansion of MAiD to persons whose sole underlying medical condition is a mental illness, and as other jurisdictions continue to develop assisted dying legislation, these findings map the system-, operational-, and support-level factors needed to sustain and strengthen MAiD service delivery.

Xenosurveillance, which uses blood-feeding insects as biological samplers, is an emerging non-invasive approach for monitoring pathogens circulating among humans, livestock, and wildlife. However, its application to livestock-associated bacterial pathogens at human-animal-wildlife interfaces remains underexplored. We investigated whether mosquito blood meals could be used to detect tick-borne bacterial pathogens circulating in livestock in Kenya. We collected 4673 mosquitoes, belonging to Culex, Anopheles, Aedes, Mansonia, and Coquillettidia genera around livestock enclosures in Kajiado and Naivasha counties, Kenya, using CO&#x2082;-baited CDC miniature light traps. Traps were selected to maximise species diversity, and as light traps capture fewer engorged mosquitoes than resting traps, only 56 blood-fed individuals (1.2%) were collected and processed as whole-specimen homogenates and analysed for vertebrate blood-meal sources using cytochrome b sequencing. In total, 303 mosquito pools, including blood-fed individuals processed as single-mosquito pools, were screened for Anaplasma, Ehrlichia, Rickettsia, Theileria, and Babesia using PCR-high-resolution melting analysis and confirmatory sequencing. All pathogen-positive detections were exclusively from blood-fed individuals. We detected Anaplasma marginale in Culex pipiens (1/150; 0.7%) and Aedes hirsutus (2/11; 18.2%), Anaplasma sp. in Cx. pipiens (2/150; 1.4%) and Ae. hirsutus (1/11; 9.1%), and Candidatus Neoehrlichia mikurensis in Mansonia africana (2/50; 4%). Pathogen detections showed strong host concordance, where A. marginale was associated with cattle-derived blood meals and Anaplasma sp. with goat-derived blood meals, while Candidatus Neoehrlichia mikurensis was detected in Mn. africana that had fed on cattle and on a host that could not be determined. Our results provide preliminary evidence that mosquito-based xenosurveillance can detect tick-borne bacterial pathogens circulating in livestock at human-wildlife interfaces in Kenya. The strong concordance between pathogen identity and vertebrate host in blood-fed mosquitoes supports the biological plausibility of this approach. Notably, detection of Ca. Neoehrlichia mikurensis represents the first report of this zoonotic pathogen in mosquitoes in Africa, highlighting the One Health relevance of xenosurveillance in identifying settings, where pathogen circulation and cross-interface feeding coincide. Mosquito-derived sampling has potential to complement existing surveillance tools in agro-pastoral systems, where direct host sampling is difficult or costly.