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Development and validation of a Malay version questionnaire for assessing risk perception of type 2 diabetes (RPDM)

Background The burden of type 2 diabetes is increasing globally. Risk perception of type 2 diabetes plays an important role in motivating adoption of healthy lifestyle and preventive health interventions. To address the increasing burden of type 2 diabetes in Malaysia, a better understanding on its risk perception is needed as a guide for preventive interventions. This study was aimed at developing and validating a Malay-language questionnaire to assess the risk perception of type 2 diabetes (RPDM) among Malaysians. Methods The questionnaire (RPDM) was developed based on the Health Belief Model and previous literature. A 59-item question pool was initially developed, reviewed by experts for content validity and pretested on five respondents. Different samples were used for pilot study (n = 100) and subsequent validation study (n = 158). Exploratory factor analysis (EFA) and Confirmatory factor analysis (CFA) were used to evaluate construct validity and construct reliability of the questionnaire. Results The EFA yielded five-factors model, including 48 items with good factor loadings of > 0.40. CFA was carried out using item parceling. The final model shows acceptable model fit and had sufficient convergent and discriminant validity. The value of construct reliability ranged between 0.76 and 0.90. Conclusion This newly developed and validated Malay-language RPDM questionnaire is valid and reliable for measuring the five constructs (perceived self-efficacy, perceived severity, perceived benefit, perceived susceptibility and perceived barrier) of risk perception of type 2 diabetes among Malaysians. This Malay-language questionnaire may contribute to a better understanding of risk perception of type 2 diabetes among Malaysians, as well as enhancement of diabetes prevention communication between healthcare providers and their clients.

Higher-order transient structures and the principle of dynamic connectivity in membrane signaling

We examine the role of higher-order transient structures (HOTS) in M2R regulation of GIRK channels. Electron microscopic membrane protein location maps show that both proteins form HOTS that exhibit a statistical bias to be near each other. Theoretical calculations and electrophysiological measurements suggest that channel activity is isolated near larger M2R HOTS. By invoking weak interactions that permit transient binding of M2R to M2R and GIRK to GIRK ( i-i interactions) and M2R to GIRK ( i-j interactions), the distribution patterns and electrophysiological properties of HL-1 cells are replicated in a reaction-diffusion simulation. We propose the principle of dynamic connectivity to explain communication between protein components of a membrane signaling pathway. Dynamic connectivity is mediated by weak, transient interactions between proteins. HOTS created by weak i-i interactions, and statistical biases created by weak i-j interactions promoted by the multivalence of HOTS, are the key elements of dynamic connectivity.

Research on boundary control of vehicle-mounted flexible manipulator based on partial differential equations

Vehicle-mounted flexible robotic arms (VFRAs) are crucial in enhancing operational capabilities in sectors where human intervention is limited due to accessibility or safety concerns, such as hazardous environments or precision surgery. This paper introduces the latest generation of VFRAs that utilize advanced soft materials and are designed with elongated structures to provide greater flexibility and control. We present a novel mathematical model, derived using Hamilton’s principle, which simplifies the analysis of the arm’s dynamic behaviors by employing partial differential equations (PDEs). This model allows us to understand how these arms behave over time and space, classifying them as distributed parameter systems. Furthermore, we enhance the practical utility of these robotic arms by implementing a proportional-derivative (PD) based boundary control law to achieve precise control of movement and suppression of vibrations, which are critical for operations requiring high accuracy. Our approach’s effectiveness and practical utility are evidenced by numerical simulations, which verify that our advanced control strategy greatly enhances the performance and dependability of VFRAs in actual applications. These advancements not only pave the way for more sophisticated robotic implementations but also have broad implications for the future of automated systems in various industries.

Conservation of symbiotic signaling since the most recent common ancestor of land plants

Plants have colonized lands 450 million years ago. This terrestrialization was facilitated by developmental and functional innovations. Recent evo-devo approaches have demonstrated that one of these innovations was the mutualistic arbuscular mycorrhizal symbiosis (AMS). The genetic pathways that have been involved in the establishment and functioning of AMS since its evolution remain poorly described. Here, we found that intracellular colonization by AM fungi induces a transcriptional reporter of the common symbiosis pathway, well-described in angiosperms, in the liverwort Marchantia paleacea . Mutants of either of the three main genes of this pathway, SYMRK , CCaMK, and CYCLOPS, disrupt the ability of M. paleacea to associate with AM fungi. Finally, overexpressing gain-of-function CCaMK or CYCLOPS leads to convergent transcriptomic signatures that partially overlap with AMS. Altogether, our data indicate that plants have maintained three genes of the common symbiotic pathway to support symbiotic interactions since their most recent common ancestor.

Using the Behaviour Change Wheel to develop an intervention to improve conversations about recovery on the stroke unit

Background Understanding recovery is important for patients with stroke and their families, including how much recovery is expected and how long it might take. These conversations can however be uncomfortable for stroke unit staff, particularly when they involve breaking bad news. This study aimed to begin development of a novel complex intervention to improve conversations about recovery on stroke units. Methods Informed by previously collected qualitative data, we used the Behaviour Change Wheel (BCW) approach to identify possible 1. barriers to communication about recovery on stroke units; 2. Intervention Functions; 3. Behaviour Change Techniques (BCTs) to incorporate in an intervention. We subsequently sought stroke professionals’ perspectives through an online survey. Respondents rated the importance of barriers for intervention inclusion and evaluated the usefulness and feasibility of the suggested BCTs. Results Our behavioural diagnosis identified a target behaviour of provision of information about recovery by stroke unit professionals to patients and carers. Twelve possible barriers to this behaviour were identified, with six potential Intervention Functions to address them, and 29 BCTs. Forty-eight multidisciplinary professionals responded to the survey. The six barriers rated as most important to address were: lack of confidence; perceptions of insufficient communication skills; lack of knowledge of the benefits; difficulties in deciding when and in what format to provide information; absence of private spaces for discussions; and lack of generic written information to support conversations. The developed intervention strategy comprised twelve clinically feasible and useful BCTs, encompassing the Intervention Functions of Training, Enablement, Persuasion, and Environmental restructuring. Conclusions The BCW approach was successfully used to begin development of an intervention to improve conversations about recovery on the stroke unit; our survey enabled incorporation of stakeholder perspectives. Further development work is required to design intervention materials and test whether the strategies are effective in improving staff and patient outcomes.

The carnivorous plant <i>Genlisea</i> harnesses active particle dynamics to prey on microfauna

Carnivory in plants is an unusual trait that has arisen multiple times, independently, throughout evolutionary history. Plants in the genus Genlisea are carnivorous and feed on microorganisms that live in soil using modified subterranean leaf structures (rhizophylls). A surprisingly broad array of microfauna has been observed in the plants’ digestive chambers, including ciliates, amoebae, and soil mites. Here, we show, through experiments and simulations, that Genlisea exploit active matter physics to “rectify” bacterial swimming and establish a local flux of bacteria through the structured environment of the rhizophyll toward the plant’s digestion vesicle. In contrast, macromolecular digestion products are free to diffuse away from the digestion vesicle and establish a concentration gradient of carbon sources to draw larger microorganisms further inside the plant. Our experiments and simulations show that this mechanism is likely to be a localized one and that no large-scale efflux of digested matter is present.

Parental effects provide an opportunity for coral resilience following major bleaching events

Identifying processes that promote coral reef recovery and resilience is crucial as ocean warming becomes more frequent and severe. Sexual reproduction is essential for the replenishment of coral populations and maintenance of genetic diversity; however, the ability for corals to reproduce may be impaired by marine heatwaves that cause coral bleaching. In 2014 and 2015, the Hawaiian Islands experienced coral bleaching with differential bleaching susceptibility in the species Montipora capitata, a dominant reef-building coral in the region. We tested the hypothesis that coral bleaching resistance enhances reproductive capacity and offspring performance by examining the reproductive biology of colonies that bleached and recovered (B) and colonies that did not bleach (NB) in 2015 in the subsequent spawning seasons. The proportion of colonies that spawned was higher in 2016 than in 2017. Regardless of parental bleaching history, we found eggs with higher abnormality and bundles with fewer eggs in 2016 than 2017. While reproductive output was similar between B and NB colonies in 2016, survivorship of offspring that year were significantly influenced by the parental bleaching history (egg donor × sperm donor: B × B, B × NB, NB × B, and NB × NB). Offspring produced by NB egg donors had the highest survivorship, while offspring from previously bleached colonies had the lowest survivorship, highlighting the negative effects of bleaching on parental investment and offspring performance. While sexual reproduction continues in M. capitata post-bleaching, gametes are differentially impacted by recovery time following a bleaching event and by parental bleaching resistance. Our results demonstrate the importance of identifying bleaching resistant individuals during and after heating events. This study further highlights the significance of maternal effects through potential egg provisioning for offspring survivorship and provides a baseline for human-assisted intervention (i.e., selective breeding) to mitigate the effects of climate change on coral reefs.

Evolution takes multiple paths to evolvability when facing environmental change

Life at all scales is surprisingly effective at exploiting new opportunities, as demonstrated by the rapid emergence of antimicrobial resistance and novel pathogens. How populations acquire this level of evolvability and the various ways it aids survival are major open questions with direct implications for human health. Here, we use digital evolution to show that changing environments facilitate the simultaneous evolution of high mutation rates and a distribution of mutational effects skewed toward beneficial phenotypes. The evolved mutational neighborhoods allow rapid adaptation to previously encountered environments, whereas higher mutation rates aid adaptation to completely new environmental conditions. By precisely tracking evolving lineages and the phenotypes of their mutants, we show that evolving populations localize on phenotypic boundaries between distinct regions of genotype space. Our results demonstrate how evolution shapes multiple determinants of evolvability concurrently, fine-tuning a population’s adaptive responses to unpredictable or recurrent environmental shifts.

Negligible contribution of body density to in-water vertical jump performance in elite male water polo players

The aim of this study was to investigate the associations among in-water vertical jump and various dry-land physical measures by taking the law of Archimedes into consideration, and by normalizing the dry-land measures both to body density and body mass. Seventeen elite water polo players from Hungarian first league were tested for dry-land counter movement and squat jump mechanical impulse, isometric squat force, and in-water vertical jump height. Body density was estimated by anthropometric measurements. Body density alone did not influence in-water vertical jump height. Both the impulse of counter movement jump normalized to body mass (9.42±0.86 N·s/kg) and impulse of counter movement jump normalized to body density (773.92±109.68 N·s/kg/g/cm3) correlated with the in water vertical jump height (69.37±6.12 cm) (p≤0.05), but the magnitudes of the correlation coefficients 0.49 vs. 0.50 were not statistically different (p = 0.480, z = 0.04). Neither the impulse of squat jump normalized to body mass (7.07±0.59 N·s/kg) nor impulse of squat jump normalized to body density (577.87±89.16 N·s/kg/g/cm3) correlated with the in water vertical jump height (both p&gt;0.05). The correlation between the force of the maximum voluntary isometric contraction normalized to body density (1052.13±244.65 N/kg/g/cm3) and the in water vertical jump height only approached the level of significance (p = 0.077). We concluded that dry-land reactive strength determines the ability to jump out of water, but players’ body density does not seem to contribute to jump height.

Dual-action kinase inhibitors influence p38α MAP kinase dephosphorylation

Reversible protein phosphorylation directs essential cellular processes including cell division, cell growth, cell death, inflammation, and differentiation. Because protein phosphorylation drives diverse diseases, kinases and phosphatases have been targets for drug discovery, with some achieving remarkable clinical success. Most protein kinases are activated by phosphorylation of their activation loops, which shifts the conformational equilibrium of the kinase toward the active state. To turn off the kinase, protein phosphatases dephosphorylate these sites, but how the conformation of the dynamic activation loop contributes to dephosphorylation was not known. To answer this, we modulated the activation loop conformational equilibrium of human p38α ΜΑP kinase with existing kinase inhibitors that bind and stabilize specific inactive activation loop conformations. From this, we identified three inhibitors that increase the rate of dephosphorylation of the activation loop phospho-threonine by the PPM serine/threonine phosphatase WIP1. Hence, these compounds are “dual-action” inhibitors that simultaneously block the active site and promote p38α dephosphorylation. Our X-ray crystal structures of phosphorylated p38α bound to the dual-action inhibitors reveal a shared flipped conformation of the activation loop with a fully accessible phospho-threonine. In contrast, our X-ray crystal structure of phosphorylated apo human p38α reveals a different activation loop conformation with an inaccessible phospho-threonine, thereby explaining the increased rate of dephosphorylation upon inhibitor binding. These findings reveal a conformational preference of phosphatases for their targets and suggest a unique approach to achieving improved potency and specificity for therapeutic kinase inhibitors.

Length of stay in the pediatrics emergency department and associated factors among pediatrics patients in Eastern Ethiopia public hospital, Ethiopia 2022

Introduction Patient length of stay is a crucial measure of the emergency department, and it is a vital indicator of health services to evaluate its efficacy, patient care, organizational management, and health care system. Despite this, there are a few studies conducted on pediatric emergency length of stay in developing countries. Therefore, this study serves as input for evidence of pediatric emergency length of stay and associated factors in public hospitals. Methods An institution-based cross-sectional study was conducted among children who attended in pediatric emergency department of Eastern Ethiopia public hospital from May 01 to Jun 31, 2022. A total of 761 children were selected by systematic sampling technique and interview using structured questionnaires. After data is collected and cleaned, entered using Epi data version 4.6 and then exported to Stata version 14.1 for analysis. Finally, an AOR with a 95% CI was computed, and variables with a P-value &lt; 0.05 in the multivariable analysis were taken as significant factors for prolonged length of stay. Result The prevalence of prolonged length of stay in the emergency ward was 214 (72%). Living in a rural residence ([AOR = 1.65, 95% CI (1.10–2.48)], having a duration of pain &gt; = 12 ([AOR = 1.92, 95% CI (1.13–3.25)], waiting time &gt; = 5 minute ([AOR = 2.24, 95% CI (1.1–4.248541)], having comorbid illness ([AOR = 1.92, 95%CI, 1.13–3.25)], and higher acuity level and absence of medication in the hospital were ([AOR = 2.26, 95%CI (1.02–2.46]) were significantly associated factors for prolonged length of stay. Conclusion and recommendation This study revealed that more than two-thirds of children admitted to pediatric emergency had prolonged lengths of stay. This result indicated that higher proportion of the length of stay in pediatric emergency in Eastern Ethiopian public hospitals compare to national. Hence, it is better to give priority to strengthening the focused evaluation of important variables and manage accordingly.

Structural and functional dynamics of human cone cGMP-phosphodiesterase important for photopic vision

Cone cGMP-phosphodiesterase (PDE6) is the key effector enzyme for daylight vision, and its properties are critical for shaping distinct physiology of cone photoreceptors. We determined the structures of human cone PDE6C in various liganded states by single-particle cryo-EM that reveal essential functional dynamics and adaptations of the enzyme. Our analysis exposed the dynamic nature of PDE6C association with its regulatory γ-subunit (Pγ) which allows openings of the catalytic pocket in the absence of phototransduction signaling, thereby controlling photoreceptor noise and sensitivity. We demonstrate evolutionarily recent adaptations of PDE6C stemming from residue substitutions in the Pγ subunit and the noncatalytic cGMP binding site and influencing the Pγ dynamics in holoPDE6C. Thus, our structural analysis sheds light on the previously unrecognized molecular evolution of the effector enzyme in cones that advances adaptation for photopic vision.

Association of varicose veins with the risk of heart failure: A nationwide cohort study

Background Research investigating the association between varicose veins (VV) and heart failure has been limited. Here, we examine this association within a nationwide longitudinal cohort, hypothesizing an increased risk of heart failure associated with the presence of VV. Methods Our study included 390,436 participants based on health screening results conducted from 2005 to 2010 in the South Korean health screening cohort database. Presence of VV was defined as having at least two claims based on International Classification of Diseases, Tenth Revision (ICD-10) codes I830-832, I839, or I868. Propensity score matching (PSM) at a ratio of 1:5 was employed to categorize the participants into two groups based on the presence of VV. The primary outcome, heart failure incidence, was defined as two or more claims with ICD-10 code I50 during follow-up. Results Among the participants, presence of VV was noted in 5,008 (1.28%) individuals. Over a median follow-up period of 13.33 years (interquartile range 10.4–16.26), 55,023 cases of heart failure (14.0%) occurred. In the multivariable analysis, the group with VV consistently showed an increased incidence risk of heart failure compared to the group without VV, both before (hazard ratios [HR], 1.174; 95% confidence interval [CI], 1.089–1.265) and after PSM (HR, 1.171; 95% CI, 1.070–1.283). Landmark analysis also found a consistent relationship between the presence of VV and the incidence risk of heart failure before (HR, 1.190; 95% CI, 1.103–1.285) and after PSM (HR, 1.144; 95% CI, 1.044–1.254). Conclusions This study revealed a significant increase in the risk of heart failure among patients with VV in the general population of South Korea. Given that the presence of VV is likely associated with an increased risk of heart failure in the general population, the potential for future heart failure should be taken into consideration when VV are present.

Reply to Caruso Bavisotto et al.: Toward exploring the potential of muscle-secreting exosomes in the muscle–brain axis

Geology and climate drive alpine plant compositional variation among peaks in the Cascade Range of Washington

Alpine areas are host to diverse plant communities that support ecosystems through structural and floral resources and persist through specialized adaptations to harsh high-elevation conditions. An ongoing question in these plant communities is whether composition is shaped by stochastic processes (e.g., dispersal limitations) or by deterministic processes (e.g., climate, geology), and if those processes select for common phylogenetic clades across space. This study evaluates the drivers of dissimilarity in alpine vascular plant communities across 32 peaks in the Cascade Mountain Range of Washington State and examines the effects of incorporating phylogenetic relatedness to these conclusions. We documented an average of 54 species per peak and used our overall inventory of 307 taxa to construct a phylogenetic tree for the entire mountain range plant community sampled. We used multivariate techniques to quantify the phylogenetic and taxonomic differences between alpine plant communities and to relate those differences to each peak’s climate, geology, and topography. Our models indicate that the age of each peak’s parent material formation, precipitation, latitude, and temperature had the largest role in shaping alpine plant communities relative to the baseline effects of distance between peaks and time of sampling. A unique result was a distinct plant community in peaks with ultramafic geologic parent material formed in the Paleozoic Era, which has an extreme geochemistry that we found to form evolutionarily distinct lineages compared to all other peaks. With changing climate conditions and disturbance regimes, understanding facets of alpine plant communities like species turnover, geologic endemism, and responses to precipitation changes are vital to conserving these ecosystems.

Structure-guided design and synthesis of C22- and C32-modified FK520 analogs with enhanced activity against human pathogenic fungi

Invasive fungal infections are a leading cause of death worldwide. Translating molecular insights into clinical benefits is challenging because fungal pathogens and their hosts share similar eukaryotic physiology. Consequently, current antifungal treatments have limited efficacy, may be poorly fungicidal in the host, can exhibit toxicity, and are increasingly compromised by emerging resistance. We have established that the phosphatase calcineurin (CaN) is required for invasive fungal disease and an attractive target for antifungal drug development. CaN is a druggable target, and there is vast clinical experience with the CaN inhibitors FK506 and cyclosporin A (CsA). However, while FK506 and its natural analog FK520 exhibit antifungal activity, they are also immunosuppressive in the host and thus not fungal-selective. We leverage our pathogenic fungal CaN-FK506-FKBP12 complex X-ray structures and biophysical data to support structure-based ligand design as well as structure–activity relationship analyses of broad-spectrum FK506/FK520 derivatives with potent antifungal activity and reduced immunosuppressive activity. Here, we apply molecular docking studies to develop antifungal C22- or C32-modified FK520 derivatives with improved therapeutic index scores. Among them, the C32-modified FK520 derivative JH-FK-44 ( 7 ) demonstrates a significantly improved therapeutic index compared to JH-FK-08, our lead compound to date. NMR binding studies with C32-derivatives are consistent with our hypothesis that C32 modifications disrupt the hydrogen bonding network in the human complex while introducing favorable electrostatic and cation–π interactions with the fungal FKBP12 R86 residue. These findings further reinforce calcineurin inhibition as a promising strategy for antifungal therapy.

Link prediction of heterogeneous complex networks based on an improved embedding learning algorithm

Link prediction in heterogeneous networks is an active research topic in the field of complex network science. Recognizing the limitations of existing methods, which often overlook the varying contributions of different local structures within these networks, this study introduces a novel algorithm named SW-Metapath2vec. This algorithm enhances the embedding learning process by assigning weights to meta-path traces generated through random walks and translates the potential connections between nodes into the cosine similarity of embedded vectors. The study was conducted using multiple real-world and synthetic datasets to validate the proposed algorithm’s performance. The results indicate that SW-Metapath2vec significantly outperforms benchmark algorithms. Notably, the algorithm maintains high predictive performance even when a substantial proportion of network nodes are removed, demonstrating its resilience and potential for practical application in analyzing large-scale heterogeneous networks. These findings contribute to the advancement of link prediction techniques and offer valuable insights and tools for related research areas.

An animal model recapitulates human hepatic diseases associated with <i>GATA6</i> mutations

Heterozygotic GATA6 mutations are responsible for various congenital diseases in the heart, pancreas, liver, and other organs in humans. However, there is lack of an animal that can comprehensively model these diseases since GATA6 is essential for early embryogenesis. Here, we report the establishment of a gata6 knockout zebrafish which recapitulates most of the symptoms in patients with GATA6 mutations, including cardiac outflow tract defects, pancreatic hypoplasia/agenesis, gallbladder agenesis, and various liver diseases. Particularly in the liver, the zebrafish gata6 model exhibits the paucity of intrahepatic bile ducts, disrupted bile canaliculi, cholestasis, resembling the liver diseases associated with GATA6 mutations. Moreover, an unreported phenotype, hepatic cysts, has been also revealed in the model. Mechanistically, Gata6 interacts with Hhex and binds lrh-1 promoter to synergistically activate its expression, thereby enhancing the Lrh-1-mediated β-catenin signaling which is essential for liver development. This transcriptional activation of lrh-1 is tightly controlled by the negative feedback, in which Lrh1 interacts with Gata6 to weaken its transactivation ability. Moreover, Gata6 level is regulated by Hhex-mediated proteasomal degradation. The orchestration by these three transcription factors precisely modulates Gata6 activity, ensuring β-catenin signaling output and proper liver development in zebrafish. Importantly, the molecular mechanism identified in zebrafish is conserved in human cells. GATA6 mutant variants associated with hepatobiliary malformations in humans interact aberrantly with HHEX, resulting in subsequent impairments of LRH-1 activation. Conclusively, the disease model established here provides both phenotypic and mechanism insights into the human hepatic diseases associated with GATA6 mutations.

Screening of serum biomarkers in patients with PCOS through lipid omics and ensemble machine learning

Polycystic ovary syndrome (PCOS) is a primary endocrine disorder affecting premenopausal women involving metabolic dysregulation. We aimed to screen serum biomarkers in PCOS patients using untargeted lipidomics and ensemble machine learning. Serum from PCOS patients and non-PCOS subjects were collected for untargeted lipidomics analysis. Through analyzing the classification of differential lipid metabolites and the association between differential lipid metabolites and clinical indexes, ensemble machine learning, data preprocessing, statistical test pre-screening, ensemble learning method secondary screening, biomarkers verification and evaluation, and diagnostic panel model construction and verification were performed on the data of untargeted lipidomics. Results indicated that different lipid metabolites not only differ between groups but also have close effects on different corresponding clinical indexes. PI (18:0/20:3)-H and PE (18:1p/22:6)-H were identified as candidate biomarkers. Three machine learning models, logistic regression, random forest, and support vector machine, showed that screened biomarkers had better classification ability and effect. In addition, the correlation of candidate biomarkers was low, indicating that the overlap between the selected biomarkers was low, and the combination of panels was more optimized. When the AUC value of the test set of the constructed diagnostic panel model was 0.815, the model’s accuracy in the test set was 0.74, specificity was 0.88, and sensitivity was 0.7. This study demonstrated the applicability and robustness of machine learning algorithms to analyze lipid metabolism data for efficient and reliable biomarker screening. PI (18:0/20:3)-H and PE (18:1p/22:6)-H showed great potential in diagnosing PCOS.

Reconciling heterogeneous dengue virus infection risk estimates from different study designs

Uncovering rates at which susceptible individuals become infected with a pathogen, i.e., the force of infection (FOI), is essential for assessing transmission risk and reconstructing distribution of immunity in a population. For dengue, reconstructing exposure and susceptibility statuses from the measured FOI is of particular significance as prior exposure is a strong risk factor for severe disease. FOI can be measured via many study designs. Longitudinal serology is considered gold standard measurements, as they directly track the transition of seronegative individuals to seropositive due to incident infections (seroincidence). Cross-sectional serology can provide estimates of FOI by contrasting seroprevalence across ages. Age of reported cases can also be used to infer FOI. Agreement of these measurements, however, has not been assessed. Using 26 y of data from cohort studies and hospital-attended cases from Kamphaeng Phet province, Thailand, we found FOI estimates from the three sources to be highly inconsistent. Annual FOI estimates from seroincidence were 1.75 to 4.05 times higher than case-derived FOI. Seroprevalence-derived was moderately correlated with case-derived FOI (correlation coefficient = 0.47) with slightly lower estimates. Through extensive simulations and theoretical analysis, we show that incongruences between methods can result from failing to account for dengue antibody kinetics, assay noise, and heterogeneity in FOI across ages. Extending standard inference models to include these processes reconciled the FOI and susceptibility estimates. Our results highlight the importance of comparing inferences across multiple data types to uncover additional insights not attainable through a single data type/analysis.