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Prominin-1 (Prom1) is a five-transmembrane-pass integral membrane protein that associates with curved regions of the plasma membrane. Prom1 interacts with membrane cholesterol and actively remodels the plasma membrane. Membrane bending activity is particularly evident in photoreceptors, where Prom1 loss-of-function mutations cause failure of outer segment homeostasis, leading to cone-rod retinal dystrophy (CRRD). The Tweety Homology (Ttyh) protein family has been proposed to be homologous to Prominin, but it is not known whether Ttyh proteins have an analogous membrane-bending function. Here, we characterize the membrane-bending activity of human Prom1 and Ttyh1 in native bilayer membranes. We find that Prom1 and Ttyh1 both induce formation of extracellular vesicles (EVs) in cultured mammalian cells and that the EVs produced are physically similar. Ttyh1 is more abundant in EV membranes than Prom1 and produces EVs with membranes that are more tubulated than Prom1 EVs. We further show that Prom1 interacts more stably with membrane cholesterol than Ttyh1 and that this may contribute to membrane bending inhibition in Prom1 EVs. Intriguingly, a loss-of-function mutation in Prom1 associated with CRRD induces particularly stable cholesterol binding. These experiments provide mechanistic insight into Prominin function in CRRD and suggest that Prom and Ttyh belong to a single family of functionally related membrane-bending, EV-generating proteins.
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Metabolic syndrome has been associated with reduced brain white matter integrity in older individuals. However, less is known about how metabolic syndrome might impact white matter integrity in younger populations. This study examined metabolic syndrome-related global and regional white matter integrity differences in a sample of 537 post-9/11 Veterans. Metabolic syndrome was defined as ≥3 factors of: increased waist circumference, hypertriglyceridemia, low high-density lipoprotein cholesterol, hypertension, and high fasting glucose. T1 and diffusion weighted 3 T MRI scans were processed using the FreeSurfer image analysis suite and FSL Diffusion Toolbox. Atlas-based regions of interest were determined from a combination of the Johns Hopkins University atlas and a Tract-Based Spatial Statistics-based FreeSurfer WMPARC white matter skeleton atlas. Analyses revealed individuals with metabolic syndrome (n = 132) had significantly lower global fractional anisotropy than those without metabolic syndrome (n = 405), and lower high-density lipoprotein cholesterol levels was the only metabolic syndrome factor significantly related to lower global fractional anisotropy levels. Lobe-specific analyses revealed individuals with metabolic syndrome had decreased fractional anisotropy in frontal white matter regions compared with those without metabolic syndrome. These findings indicate metabolic syndrome is prevalent in this sample of younger Veterans and is related to reduced frontal white matter integrity. Early intervention for metabolic syndrome may help alleviate adverse metabolic syndrome-related brain and cognitive effects with age.
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Síndrome Metabólico , Veteranos , Sustancia Blanca , Humanos , Síndrome Metabólico/patología , Síndrome Metabólico/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Adulto Joven , Imagen por Resonancia Magnética , Anisotropía , Imagen de Difusión Tensora/métodos , Ataques Terroristas del 11 de SeptiembreRESUMEN
Rates of microbial growth are fundamental to understanding environmental geochemistry and ecology. However, measuring the heterogeneity of microbial activity at the single-cell level, especially within complex populations and environmental matrices, remains a forefront challenge. Stable Isotope Probing (SIP) is a method for assessing microbial growth and involves measuring the incorporation of an isotopic label into microbial biomass. Here, we assess Raman microspectroscopy as a SIP technique, specifically focusing on the measurement of deuterium (2H), a tracer of microbial biomass production. We correlatively measured cells grown in varying concentrations of deuterated water with both Raman spectroscopy and nanoscale secondary ion mass spectrometry (nanoSIMS), generating isotopic calibrations of microbial 2H. Relative to Raman, we find that nanoSIMS measurements of 2H are subject to substantial dilution due to rapid exchange of H during sample washing. We apply our Raman-derived calibration to a numerical model of microbial growth, explicitly parameterizing the factors controlling growth rate quantification and demonstrating that Raman-SIP can sensitively measure the growth of microorganisms with doubling times ranging from hours to years. The measurement of single-cell growth with Raman spectroscopy, a rapid, non-destructive technique, represents an important step towards application of single-cell analysis into complex sample matrices or cellular assemblages.
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Introduction: Fluctuations of chronic pain levels are determined by a complex interplay of cognitive, emotional and perceptual variables. We introduce a pain tracking platform composed of wearable neurotechnology and a smartphone application to measure and predict chronic pain levels and its interplay with other dimensions of experience. Methods: Our method measures, dynamically and at home, pain strength, phenomenal and neural time series collected with an online tool and low-density EEG. Here we used data from a single participant who performed an attention task at home for a period of 20 days to investigate the role of attention to different bodily systems in chronic pain. Results: We show a relationship between emotions and pain strength while allocating attention to the heartbeat, the breathing, the affected or the unaffected limb. We found that pain was maximal when attending to the affected limb and decreased when the participant focused on his breathing or his heartbeat. These results provide interesting insights regarding the role of attention to interoceptive signals in chronic pain. We found power changes in the delta, theta, alpha and beta (but not in the gamma) band between the four attention conditions. However, there was no reliable association of these changes to pain intensity ratings. Theta power was higher when attention was directed to the unaffected limb compared to the others. Further, the pain ratings, when attending to unaffected limb, were associated with alpha and theta power band changes. Conclusion: Overall, we demonstrate that our neurophysiology and experience tracking platform can capture how body attention allocation alters the dynamics of subjective measures and its neural correlates. This research approach is proof of concept for the development of personalized clinical assessment tools and a testbed for behavioural, subjective and biomarkers characterization.
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Encéfalo , Humanos , Encéfalo/crecimiento & desarrollo , Encéfalo/fisiología , Relaciones Interpersonales , Ambiente , AnimalesRESUMEN
Hydrogen sulfide (H2S) is an endogenously produced gasotransmitter involved in many physiological processes that are integral to proper cellular functioning. Due to its profound anti-inflammatory and antioxidant properties, H2S plays important roles in preventing inflammatory skin disorders and improving wound healing. Transdermal H2S delivery is a therapeutically viable option for the management of such disorders. However, current small-molecule H2S donors are not optimally suited for transdermal delivery and typically generate electrophilic byproducts that may lead to undesired toxicity. Here, we demonstrate that H2S release from metal-organic frameworks (MOFs) bearing coordinatively unsaturated metal centers is a promising alternative for controlled transdermal delivery of H2S. Gas sorption measurements and powder X-ray diffraction (PXRD) studies of 11 MOFs support that the Mg-based framework Mg2(dobdc) (dobdc4- = 2,5-dioxidobenzene-1,4-dicarboxylate) is uniquely well-suited for transdermal H2S delivery due to its strong yet reversible binding of H2S, high capacity (14.7 mmol/g at 1 bar and 25 °C), and lack of toxicity. In addition, Rietveld refinement of synchrotron PXRD data from H2S-dosed Mg2(dobdc) supports that the high H2S capacity of this framework arises due to the presence of three distinct binding sites. Last, we demonstrate that transdermal delivery of H2S from Mg2(dobdc) is sustained over a 24 h period through porcine skin. Not only is this significantly longer than sodium sulfide but this represents the first example of controlled transdermal delivery of pure H2S gas. Overall, H2S-loaded Mg2(dobdc) is an easily accessible, solid-state source of H2S, enabling safe storage and transdermal delivery of this therapeutically relevant gas.
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Administración Cutánea , Sulfuro de Hidrógeno , Estructuras Metalorgánicas , Sulfuro de Hidrógeno/química , Sulfuro de Hidrógeno/administración & dosificación , Estructuras Metalorgánicas/química , Animales , Porcinos , Piel/metabolismoRESUMEN
The features of the physical environment set the stage upon which sexual selection operates, and consequently can have a significant impact on variation in realized individual fitness, and influence a population's evolutionary trajectory. This phenomenon has been explored empirically in several studies using fruit flies (Drosophila melanogaster) which have found that changing the spatial complexity of the mating environment influenced male-female interaction dynamics, (re)mating rates and realized female fecundities. However, these studies did not explore mating patterns, which can dramatically alter the genetic composition of the next generation, and frequently only compared a single, small "simple" environment to a single larger "complex" environment. While these studies have shown that broadly changing the characteristics of the environment can have big effects on reproductive dynamics, the plasticity of this outcome to more subtle changes has not been extensively explored. Our study set out to compare patterns of mating and courtship between large- and small-bodied males and females, and female fecundities in both a simple environment and two distinctly different spatially-complex environments. We found that realized offspring production patterns differed dramatically between all three environments, indicating that the effects of increasing spatial complexity on mating outcomes are sensitive to the specific type of environmental complexity. Furthermore, we observed female fecundities were higher for flies in both complex environments compared those in the simple environment, supporting its role as a mediator of sexual conflict. Together, these results show that the union of gametes within a population can be greatly influenced by the specific spatial features of the environment and that while some outcomes of increased environmental complexity are likely generalizable, other phenomena like mating patterns and courtship rates may vary from one complex environment to another.
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Identifying the neuronal markers of consciousness is key to supporting the different scientific theories of consciousness. Neuronal markers of consciousness can be defined to reflect either the brain signatures underlying specific conscious content or those supporting different states of consciousness, two aspects traditionally studied separately. In this paper, we introduce a framework to characterize markers according to their dynamics in both the "state" and "content" dimensions. The 2D space is defined by the marker's capacity to distinguish the conscious states from non-conscious states (on the x-axis) and the content (e.g. perceived versus unperceived or different levels of cognitive processing on the y-axis). According to the sign of the x- and y-axis, markers are separated into four quadrants in terms of how they distinguish the state and content dimensions. We implement the framework using three types of electroencephalography markers: markers of connectivity, markers of complexity, and spectral summaries. The neuronal markers of state are represented by the level of consciousness in (i) healthy participants during a nap and (ii) patients with disorders of consciousness. On the other hand, the neuronal markers of content are represented by (i) the conscious content in healthy participants' perception task using a visual awareness paradigm and (ii) conscious processing of hierarchical regularities using an auditory local-global paradigm. In both cases, we see separate clusters of markers with correlated and anticorrelated dynamics, shedding light on the complex relationship between the state and content of consciousness and emphasizing the importance of considering them simultaneously. This work presents an innovative framework for studying consciousness by examining neuronal markers in a 2D space, providing a valuable resource for future research, with potential applications using diverse experimental paradigms, neural recording techniques, and modeling investigations.
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Extracellular vesicles (EVs) are considered a vital component of cell-to-cell communication and represent a new frontier in diagnostics and a means to identify pathways for therapeutic intervention. Recently, studies have revealed the importance of tissue-derived EVs (Ti-EVs), which are EVs present in the interstitial spaces between cells, as they better represent the underlying physiology of complex, multicellular tissue microenvironments in biology and disease. EVs are native, lipid bilayer membraned nano-sized particles produced by all cells that are packaged with varied functional biomolecules including proteins, lipids, and nucleic acids. They are implicated in short- and long-range cellular communication and may elicit functional responses in recipient cells. To date, studies have often utilized cultured cells or biological fluids as a source for EVs that do not capture local molecular signatures of the tissue microenvironment. Recent work utilizing Ti-EVs has elucidated novel biomarkers for disease and provided insights into disease mechanisms that may lead to the development of novel therapeutic agents. Still, there are considerable challenges facing current studies. This review explores the vast potential and unique challenges for Ti-EV research and provides considerations for future studies that seek to advance this exciting field.
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Throughout the day, humans show natural fluctuations in arousal that impact cognitive function. To study the behavioural dynamics of cognitive control during high and low arousal states, healthy participants performed an auditory conflict task during high-intensity physical exercise (N = 39) or drowsiness (N = 33). In line with the pre-registered hypotheses, conflict and conflict adaptation effects were preserved during both altered arousal states. Overall task performance was markedly poorer during low arousal, but not for high arousal. Modelling behavioural dynamics with drift diffusion analysis revealed evidence accumulation and non-decision time decelerated, and decisional boundaries became wider during low arousal, whereas high arousal was unexpectedly associated with a decrease in the interference of task-irrelevant information processing. These findings show how arousal differentially modulates cognitive control at both sides of normal alertness, and further validate drowsiness and physical exercise as key experimental models to disentangle the interaction between physiological fluctuations on cognitive dynamics.
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Emerging and re-emerging pathogens often stem from zoonotic origins, cycling between humans and animals, and are frequently vectored and maintained by hematophagous arthropod vectors. The efficiency by which these disease agents are successfully transmitted between vertebrate hosts is influenced by many factors, including the host on which a vector feeds. The Lyme disease bacterium Borrelia burgdorferi sensu lato has adapted to survive in complex host environments, vectored by Ixodes ticks, and maintained in multiple vertebrate hosts. The versatility of Lyme borreliae in disparate host milieus is a compelling platform to investigate mechanisms dictating pathogen transmission through complex networks of vertebrates and ticks. Squamata, one of the most diverse clade of extant reptiles, is comprised primarily of lizards, many of which are readily fed upon by Ixodes ticks. Yet, lizards are one of the least studied taxa at risk of contributing to the transmission and life cycle maintenance of Lyme borreliae. In this review, we summarize the current evidence, spanning from field surveillance to laboratory infection studies, supporting their contributions to Lyme borreliae circulation. We also summarize the current understanding of divergent lizard immune responses that may explain the underlying molecular mechanisms to confer Lyme spirochete survival in vertebrate hosts. This review offers a critical perspective on potential enzootic cycles existing between lizard-tick-Borrelia interactions and highlights the importance of an eco-immunology lens for zoonotic pathogen transmission studies.
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Ixodes , Lagartos , Enfermedad de Lyme , Animales , Lagartos/microbiología , Enfermedad de Lyme/microbiología , Enfermedad de Lyme/transmisión , Ixodes/microbiología , Humanos , Grupo Borrelia Burgdorferi/fisiología , Grupo Borrelia Burgdorferi/genética , Borrelia burgdorferi/genética , Borrelia burgdorferi/fisiologíaRESUMEN
In eukaryotes, the essential process of cellular respiration takes place in the cristae of mitochondria. The protein Mic60 is known to stabilize crista junctions; however, how the C-terminal Mitofilin domain of Mic60 mediates cristae-supported respiration remains elusive. Here, we used ancestral sequence reconstruction to generate Mitofilin ancestors up to and including the last opisthokont common ancestor (LOCA). We found that yeast-lineage derived Mitofilin ancestors as far back as the LOCA rescue respiration. By comparing Mitofilin ancestors with different respiratory phenotypes, we identify four residues that explain the difference between respiration functional yeast- and non-functional animal-derived common Mitofilin ancestors. Our results imply that Mitofilin-supported respiration in yeast stems from a conserved mechanism, and provide a foundation for investigating the divergence of candidate crista junction interactions present during the emergence of eukaryotes.
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Mental health issues are markedly increased in individuals with autism, making it the number one research priority by stakeholders. There is a crucial need to use personalized approaches to understand the underpinnings of mental illness in autism and consequently, to address individual needs. Based on the risk factors identified in typical mental research, we propose the following themes central to mental health issues in autism: sleep difficulties and stress. Indeed, the prevalence of manifold circadian disruptions and sleep difficulties in autism, alongside stress related to sensory overload, forms an integral part of autistic symptomatology. This proof-of-concept study protocol outlines an innovative, individualised approach towards investigating the interrelationships between stress indices, sleep and circadian activation patterns, and sensory sensitivity in autism. Embracing an individualized methodology, we aim to collect 14 days of data per participant from 20 individuals with autism diagnoses and 20 without. Participants' sleep will be monitored using wearable EEG headbands and a sleep diary. Diurnal tracking of heart rate and electrodermal activity through wearables will serve as proxies of stress. Those objective data will be synchronized with subjective experience traces collected throughout the day using the Temporal Experience Tracing (TET) method. TET facilitates the quantification of relevant aspects of individual experience states, such as stress or sensory sensitivities, by providing a continuous multidimensional description of subjective experiences. Capturing the dynamics of subjective experiences phase-locked to neural and physiological proxies both between and within individuals, this approach has the potential to contribute to our understanding of critical issues in autism, including sleep problems, sensory reactivity and stress. The planned strives to provide a pathway towards developing a more nuanced and individualized approach to addressing mental health in autism.
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Trastorno Autístico , Ritmo Circadiano , Estrés Psicológico , Humanos , Trastorno Autístico/fisiopatología , Trastorno Autístico/psicología , Ritmo Circadiano/fisiología , Estrés Psicológico/fisiopatología , Calidad del Sueño , Masculino , Femenino , Adulto , Adolescente , Sueño/fisiología , Frecuencia Cardíaca/fisiología , Adulto Joven , ElectroencefalografíaRESUMEN
Important efforts have been made to describe the neural and cognitive features of healthy and clinical populations. However, the neural and cognitive features of socially vulnerable individuals remain largely unexplored, despite their proneness to developing neurocognitive disorders. Socially vulnerable individuals can be characterised as socially deprived, having a low socioeconomic status, suffering from chronic social stress, and exhibiting poor social adaptation. While it is known that such individuals are likely to perform worse than their peers on executive function tasks, studies on healthy but socially vulnerable groups are lacking. In the current study, we explore whether neural power and connectivity signatures can characterise executive function performance in healthy but socially vulnerable individuals, shedding light on the impairing effects that chronic stress and social disadvantages have on cognition. We measured resting-state electroencephalography and executive functioning in 38 socially vulnerable participants and 38 matched control participants. Our findings indicate that while neural power was uninformative, lower delta and theta phase synchrony are associated with worse executive function performance in all participants, whereas delta phase synchrony is higher in the socially vulnerable group compared to the control group. Finally, we found that delta phase synchrony and years of schooling are the best predictors for belonging to the socially vulnerable group. Overall, these findings suggest that exposure to chronic stress due to socioeconomic factors and a lack of education are associated with changes in slow-wave neural connectivity and executive functioning.
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Encéfalo , Función Ejecutiva , Humanos , Electroencefalografía , CogniciónRESUMEN
Introduction: Social adaptation is a multifaceted process that encompasses cognitive, social, and affective factors. Previous research often focused on isolated variables, overlooking their interactions, especially in challenging environments. Our study addresses this by investigating how cognitive (working memory, verbal intelligence, self-regulation), social (affective empathy, family networks, loneliness), and psychological (locus of control, self-esteem, perceived stress) factors interact to influence social adaptation. Methods: We analyzed data from 254 adults (55% female) aged 18 to 46 in economically vulnerable households in Santiago, Chile. We used Latent profile analysis (LPA) and machine learning to uncover distinct patters of socioadaptive features and identify the most discriminating features. Results: LPA showed two distinct psychosocial adaptation profiles: one characterized by effective psychosocial adaptation and another by poor psychosocial adaptation. The adaptive profile featured individuals with strong emotional, cognitive, and behavioral self-regulation, an internal locus of control, high self-esteem, lower stress levels, reduced affective empathy, robust family support, and decreased loneliness. Conversely, the poorly adapted profile exhibited the opposite traits. Machine learning pinpointed six key differentiating factors in various adaptation pathways within the same vulnerable context: high self-esteem, cognitive and behavioral self-regulation, low stress levels, higher education, and increased social support. Discussion: This research carries significant policy implications, highlighting the need to reinforce protective factors and psychological resources, such as self-esteem, self-regulation, and education, to foster effective adaptation in adversity. Additionally, we identified critical risk factors impacting social adaptation in vulnerable populations, advancing our understanding of this intricate phenomenon.
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Sleep is crucial for many vital functions and has been extensively studied. By contrast, the sleep-onset period (SOP), often portrayed as a mere prelude to sleep, has been largely overlooked and remains poorly characterized. Recent findings, however, have reignited interest in this transitional period and have shed light on its neural mechanisms, cognitive dynamics, and clinical implications. This review synthesizes the existing knowledge about the SOP in humans. We first examine the current definition of the SOP and its limits, and consider the dynamic and complex electrophysiological changes that accompany the descent to sleep. We then describe the interplay between internal and external processing during the wake-to-sleep transition. Finally, we discuss the putative cognitive benefits of the SOP and identify novel directions to better diagnose sleep-onset disorders.
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Electroencefalografía , Vigilia , Humanos , Vigilia/fisiología , Sueño/fisiologíaRESUMEN
The process of embryonic development involves remarkable cellular plasticity, which governs the coordination between cells necessary to build an organism. One role of this plasticity is to ensure that when aberrant cells are eliminated, growth adjustment occurs so that the size of the tissue is maintained. An important regulator of cellular plasticity that ensures cellular cooperation is a fitness-sensing mechanism termed cell competition. During cell competition, cells with defects that lower fitness but do not affect viability, such as those that cause impaired signal transduction, slower cellular growth, mitochondrial dysregulation or impaired protein homeostasis, are killed when surrounded by fitter cells. This is accompanied by the compensatory proliferation of the surviving cells. The underlying factors and mechanisms that demarcate certain cells as less fit than their neighbouring cells and losers of cell competition are still relatively unknown. Recent evidence has pointed to mitochondrial defects and proteotoxic stress as important hallmarks of these loser cells. Here, we review recent advances in this area, focussing on the role of mitochondrial activity and protein homeostasis as major mechanisms determining competitive cell fitness during development and the importance of cell proteostasis in determining cell fitness.
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Competencia Celular , Proteostasis , Transducción de Señal/fisiología , Proliferación Celular , MitocondriasRESUMEN
Introduction: Liquid biopsy is recommended to diagnose molecular resistance to targeted therapy in patients with lung cancer. Nevertheless, not all jurisdictions provide funding and patient access. We report patients' perceived value of liquid biopsy in targeted therapy resistance. Methods: Canadian patients participating in a national EGFR T790M liquid biopsy validation study completed structured interviews measuring perceived value and willingness-to-pay for plasma circulating tumor DNA testing as an alternative to tumor biopsy using open-ended and iterative bidding approaches. Results: A total of 60 patients with advanced lung cancer participated with a median age of 64 years (range: 31-87 y); 69% were Asian and 45% female. All had received prior EGFR tyrosine kinase inhibitor; 17% also received chemotherapy. All patients preferred to have plasma testing over repeat tumor biopsy. In the context of the Canadian publicly funded system, patients estimated that a median of 300 (interquartile range: 150-800) Canadian dollars was a reasonable price to pay for liquid biopsy. Patients were personally willing to pay a median 100 (interquartile range: 33-350) Canadian dollars. Conclusions: In a system that covers the cost of standard diagnostic tests, patients with lung cancer indicated high willingness-to-pay out-of-pocket for liquid biopsy in the setting of acquired targeted therapy resistance. Patients have high perceived value of plasma genotyping and prefer it to repeat tumor biopsy.
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OBJECTIVES: COVID-19 has been at the forefront of global concern since its emergence in December of 2019. Determining the social factors that drive case incidence is paramount to mitigating disease spread. We gathered data from the Social Vulnerability Index (SVI) along with Democratic voting percentage to attempt to understand which county-level sociodemographic metrics had a significant correlation with case rate for COVID-19. METHODS: We used elastic net regression due to issues with variable collinearity and model overfitting. Our modelling framework included using the ten Health and Human Services regions as submodels for the two time periods 22 March 2020 to 15 June 2021 (prior to the Delta time period) and 15 June 2021 to 1 November 2021 (the Delta time period). RESULTS: Statistically, elastic net improved prediction when compared to multiple regression, as almost every HHS model consistently had a lower root mean square error (RMSE) and satisfactory R2 coefficients. These analyses show that the percentage of minorities, disabled individuals, individuals living in group quarters, and individuals who voted Democratic correlated significantly with COVID-19 attack rate as determined by Variable Importance Plots (VIPs). CONCLUSIONS: The percentage of minorities per county correlated positively with cases in the earlier time period and negatively in the later time period, which complements previous research. In contrast, higher percentages of disabled individuals per county correlated negatively in the earlier time period. Counties with an above average percentage of group quarters experienced a high attack rate early which then diminished in significance after the primary vaccine rollout. Higher Democratic voting consistently correlated negatively with cases, coinciding with previous findings regarding a partisan divide in COVID-19 cases at the county level. Our findings can assist regional policymakers in distributing resources to more vulnerable counties in future pandemics based on SVI.
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COVID-19 , Humanos , Estados Unidos , COVID-19/epidemiología , Incidencia , Votación , Pandemias/prevención & control , Factores de RiesgoRESUMEN
Background: Cholangiocarcinoma is an epithelial malignancy of the intrahepatic or extrahepatic biliary tree, primarily driven by chronic inflammation and fibrosis. Fibrosis has been shown to correlate with malignancy, and the aminotransferase-platelet ratio index (APRI) score, a marker for hepatic fibrosis, has proved useful in prognosticating hepatocellular carcinoma. This study aimed to assess the utility of APRI score in predicting post-surgical outcomes in cholangiocarcinoma patients. Methods: Clinical data from a total of 152 cholangiocarcinoma patients who underwent surgical resection at the Mayo Clinic were collected. The data were subsequently analyzed to determine if there was a relationship between APRI score and the demographic, laboratory, pathologic and outcome data, including overall survival. To determine the relationship between quantitative and qualitative data and the APRI score, a P-value <0.05 was considered as statistically significant. Results: No relationship between APRI score and demographic factors was identified. There were correlations between APRI score and alanine transaminase, albumin and bilirubin, but the remaining laboratory parameters showed no correlation. APRI score did not prove to be useful as a prognostic tool, as it did not correlate with tumor pathology features (tumor grade t-test P=0.86, N stage ANOVA P=0.94, vascular invasion t-test P=0.59, and perineural invasion t-test P=0.14), or with post-surgical recurrence (t-test P=0.22) and mortality (t-test P=0.39). Conclusion: APRI score is not a prognostic tool for post-surgical outcomes in patients with cholangiocarcinoma.