Major depression and suicide are critical public health concerns, particularly in underrepresented populations with unique genetic and sociocultural contexts. The Maya-mestizo population presents the highest suicide rates in the country but remains understudied in psychiatric genetics. This study evaluated the association between three genetic variants, rs7305115 (TPH2), rs6265 (BDNF), and rs2428707 (HTR2C), and the presence of major depression, melancholic subtype, and suicide risk in Maya-mestizo adults. A total of 598 participants were recruited from urban and rural areas. Psychiatric evaluations were performed using the MINI 5.0 (DSM-IV), and functional status was assessed with the Karnofsky scale. Genotyping was performed with TaqMan assays, and ancestry was confirmed with ancestry-informative markers. Analyses included Hardy-Weinberg equilibrium testing and logistic regression models adjusted for sex and included age, body mass index, Karnofsky performance scale score, and sociodemographic variables as covariates. The prevalence of major depression was 38.9%, while suicide risk reached 24.7%. The rs2428707 variant of HTR2C was significantly associated with major depression (OR 2.31, 95% CI 1.03-5.18, p = 0.041). Variants in TPH2 and BDNF were associated with the melancholic subtype. No statistically significant associations were found with suicide risk, though overlap with depressive phenotypes suggests shared vulnerability. This first report of psychiatric genetics in the Maya-mestizo population highlights the need for culturally and genetically tailored interventions.
Most lake-carbonate-isotope records from the Maya Lowlands are based on picking fossil carbonate ostracods and gastropods, often using the species Pyrgophorus coronatus, and then combining individual specimens from a single core layer to provide a composite sample. What has been left relatively unexplored is the variability between individual shells and the impact this might have on the values obtained from such composite samples. Here, the stable carbon and oxygen isotope signatures of modern P. coronatus, a littoral and detritivore species, and other Hydrobiidae taxa (Aroapyrgus sp. and Tryonia sp.) found in Lake Esmeralda and its much larger sister lake Chichancanab, in the Northern Maya Lowlands (also called Mayab or Yucatan Peninsula), were analysed to explore some of the environmental variables that might affect isotope composition. In addition, the carbon and oxygen isotope values derived from individual downcore gastropod shells were compared with those from bulk fine-fraction carbonate sediment from a core from Lake Esmeralda covering the last c. 6600 years. The results show that the median oxygen isotope value of a set of shells collected for a single stratigraphic layer tends to be about the same as the bulk sediment, even though their individual values can present a bimodal distribution, which might represent changes between dry and rainy seasons across the sample's period. In addition, no significant difference in the oxygen isotope values was found in using a particular Hydrobiidae taxon over another, indicating a lack of significant vital effects. The carbon isotopic signature of modern shells varies with location within the lake, and shows relatively little variability down core, suggesting non-climatic factors may be more dominant in controlling shell carbonate δ13C values in these systems. The online version contains supplementary material available at 10.1007/s10933-026-00385-3.
A cross-sectional study was carried out from November 2023 to May 2024 on lactating dairy cows in Maya city, in the eastern part of Ethiopia, with the aim of estimating mastitis prevalence, isolate Klebsiella pneumoniea and determine antibiotic resistance profiles of the isolates. A total of 281 animals were selected for screening of mastitis. The city was selected purposively, while kebeles, households/dairy farms, and dairy cows were chosen by the simple random sampling method. The California mastitis test (CMT) was used to screen for subclinical mastitis. Milk samples from CMT-positive and clinical mastitis cases were aseptically collected and used to isolate and identify K. pneumoniea, a common cause of mastitis. The isolates were tested for antimicrobial susceptibility using the disk diffusion method against 7 selected drugs. The overall mastitis prevalence at the cow and quarter levels was 48.4% and 28.11%, respectively, while the isolation rate of K. pneumoniea was 11.7% and 12.6%, respectively. Potential risk factors like parity, house floor, and previous history of mastitis were associated with prevalence of mastitis. Additionally, parity, management system, and teat lesion risk factor were statistically associated with isolates of K. pneumoniea. The K. pneumoniea isolates showed 100% susceptibility to ciprofloxacin, 60% to chloramphenicol, and 29% to cephalothin. In contrast, the highest (100%) resistance was observed for amoxicillin, ampicillin, and ceftriaxone, followed by 60% for vancomycin. In conclusion, the study indicated an increase in prevalence of mastitis, with K.pneumonia isolates showing high resistance to the commonly used antibiotics. Routine mastitis control measures combined with antimicrobial therapy guided by culture and susceptibility testing are recommended to reduce mastitis prevalence and limit antimicrobial resistance.
Both typicality and novelty shape aesthetic preference-typicality as conformity to a product's prototype, and novelty as perceived difference and originality. While prior research has highlighted the tension and balance between these two factors, few studies have examined how product category structure moderates their effects. This study aims to investigate the roles of typicality and novelty in shaping consumer preferences, as well as whether product type (poor vs. rich categories) influences the relative impact of these factors. To achieve this, we conducted a within-subjects experiment using 20 ceramic product stimuli: 10 ceramic vases(poor categories) and 10 ceramic lighting items (rich categories). A total of 200 Chinese participants evaluated the typicality, novelty, and liking of each product using 7-point Likert scales. Data were analyzed using repeated-measures ANOVA, partial correlation, generalized estimating equations (GEE), and hierarchical regression. Findings revealed that typicality was more predictive in poor categories, while novelty played a greater role in rich categories. Moreover, product category structure significantly moderated these effects, confirming and refining the boundary conditions of the MAYA (Most Advanced Yet Acceptable) principle. Furthermore, regression analyses revealed that typicality and novelty together explained 21.8% of the variance in aesthetic preference for ceramic vases and 20.3% for ceramic lighting items. This research deepens theoretical understanding of aesthetic judgment by highlighting the contextual role of category structure. It also provides practical design guidance, emphasizing typical features in poor categories and prioritizing novelty in rich categories to optimize consumer appeal.
Microsatellite-stable (MSS) colorectal cancers (CRC) are largely unresponsive to immune checkpoint inhibition (ICI). The MAYA trial used temozolomide (TMZ) in MGMT-silenced MSS mCRC, hypothesizing that TMZ-induced hypermutation could sensitize tumors to ICI; the primary endpoint was met, showing durable responses with TMZ plus ipilimumab and nivolumab. We perform integrated spatial, transcriptomic, and immune profiling of longitudinal tumor and blood samples from patients treated on the MAYA trial. Post-TMZ increases in tumor mutational burden associate with improved progression-free survival. Spatial profiling demonstrates that clinical benefit is greatest in permissive tumor microenvironments. Responders exhibit enrichment of cytotoxic T cells across tumor and stromal compartments, whereas non-responders display heterogeneous cellular neighborhoods, with fibroblasts in close spatial proximity to T cells, consistent with barriers to immune-mediated clearance. Longitudinal peripheral immune profiling shows that early upregulation of TIGIT and PD-1 following TMZ exposure predicts resistance. Together, these findings indicate that both mutational evolution and spatial immune architecture contribute to immune sensitization in MGMT-silenced MSS CRC. Clinical Trial Identification: NCT03832621.
Introduction Vector-borne diseases (VBDs) remain endemic in Guatemala, including in Indigenous communities where access to preventive and healthcare resources may be limited. This cross-sectional study aimed to estimate the prevalence of household-level VBD prevention practices, transmission knowledge, healthcare access barriers, and self-reported syndromic illness among Indigenous Maya households in Alta Verapaz, Guatemala. Methods A cross-sectional household survey was conducted over five days in July 2025 across four mobile outreach clinic sites in Alta Verapaz. One adult representative per household (N = 111) completed a structured questionnaire assessing VBD prevention behaviors, transmission knowledge, healthcare access barriers, housing characteristics, and recent household febrile illness. Descriptive analyses were performed using R statistical software (R Foundation for Statistical Computing, Vienna, Austria). Results Preventive practices varied across clinic sites. A total of 91 (82.0%) households reported covering water containers, and mosquito net use ranged from eight (22.2%) to 19 (54.3%) households, depending on the clinic site. Additionally, 64 (57.7%) households reported taking no preventive action. Knowledge related to VBD transmission was generally low and varied across clinic sites. The most frequently reported barriers to healthcare access were distance to care for 56 (50.5%), lack of money for 41 (36.9%), and transportation barriers for 20 (18.0%) households. Recent household febrile illness with rash and joint pain was reported by 43 (38.7%) households; however, these findings were not laboratory confirmed. Conclusions This descriptive assessment identified variation in prevention practices and healthcare access barriers among Indigenous Maya households in Alta Verapaz. Rapid household surveys integrated into mobile outreach clinics may provide locally relevant information to support context-specific prevention planning.
Lameness is often associated with degenerative joint disease (DJD). Current therapies focus on minimizing pain or treating specific lesions but generally do not address the pathomechanical forces that are the root cause of degeneration. Treatments based on specific, whole-body therapies are becoming common in humans with DJD, but are still not routinely applied in equine cases. Designing targeted therapies for horses requires recognizing habitual postures and movements that are pathological. An important but often missing component for understanding movement postures is accurate and manipulatable anatomical models. In this case study, a three-dimensional model of a horse based on CT data is manipulated using advanced imaging and animation software Autodesk® Maya® to demonstrate the habitual working posture of a horse with DJD of the fetlock joints before, during, and after the application of a whole-body exercise regime focused on rebalancing the forces negatively impacting the hindlimbs. The horse's movement postures throughout the targeted therapy are compared by assessing qualitative and quantitative changes in spinal curvature and fetlock joint angles. This case study serves as proof of concept for the feasibility of modeling working postures before and after rehabilitative therapy for the purpose of demonstrating the effects of physical therapy or training programs. It also provides an example of how data obtained from advanced imaging techniques like computed tomography can be used for veterinary medical breakthroughs that are based on rethinking: (1) the relationship between equine posture/movement and pathological conditions of the musculoskeletal system and (2) related training and rehabilitative strategies.
The gut microbiota of insects plays a crucial role in host health and is thought to have co-evolved with each species. In stingless bees, a general understanding of these associations has begun to emerge; however, several important knowledge gaps remain. In this study, we employed amplicon sequencing to compare the gut microbiota of individual specimens from two closely related and sympatric Neotropical stingless bee species from the Maya region, Melipona beecheii and Melipona yucatanica. Our results revealed that (i) most amplicon sequence variants (ASVs) in both species were transient; (ii) the core microbiota of these species was almost entirely distinct, sharing only one ASV out of a total of 31; and (iii) despite this divergence, all core ASVs identified in both species belonged to only four bacterial orders. This pattern suggests that, while their microbiota have differentiated at finer taxonomic scales, it likely originated from a shared ancestral community. We contextualize these findings within the current understanding of stingless bee microbiotas and highlight future directions for exploring their evolution and diversity. The online version contains supplementary material available at 10.1007/s42770-026-01905-z.
In this essay, I read Seth Holmes and Maya Ponte's work on "en-casement" alongside Immanuel Kant's Critique of Pure Reason to argue that faculties of biomedical apperception cultivated through clinical training are symptomatic of an orientation to sensational experience developed within Enlightenment philosophy. Characterized by the negation of subjectivity, en-casement is an expression of the anti-Black tendency to dehumanize and dominate the other in ways that render the biomedical paradigm of healing impotent with regard to the redress of Black suffering. I problematize narrative medicine as an intervention to resist en-casement by drawing on Afropessimism to elaborate limits and failures derivative from its assumptive logic of a free, agentive, autonomous, and sovereign subject capable of dramatizing suffering. Insofar as paradigmatic social death renders Blackness as a site of absolute dereliction on the level of the Symbolic, Black suffering is aporetic to narrative in ways that make even the humanist intervention no less impotent as a mode of redress. Given that the totalizing violence of anti-Blackness forecloses the redress of Black suffering within humanist paradigms of healing writ large, from the biomedical to the narrative, I consider the unmet demand for ante-anti-Black forms of care from the framework of abolition medicine.
Drawing on ethnographic fieldwork among Belizean Maya and Garifuna communities, this paper forefronts the therapeutics of sensory experience in traditional healing practice. Exploring the sensory aspects of daily ecological interactions and asking which ways community heritage practices become constitutive of healing practices, it engages the embodied ecological heritage (EEH) framework to ask how these practices respond to ongoing forces of imperial projects. This paper brings together research around Indigenous land rights and identity-making in times of change with the author's personal experience of grief and collective healing toward a sensory ecology of therapeutics as a responsive, anti-colonial, community healing practice.
During arthroscopic labral repair, anchors are inserted into the acetabular rim between 10- and 4-o'clock via multiple portals. This study evaluates in situ bone quality along each trajectory and precisely defines the spatial relationships between the drill path and adjacent neurovascular, capsular, and chondral structures, thereby establishing an evidence-based safety envelope for acetabular anchor placement. In stage one, 11 patients (22 hips) underwent skin marking of surface portals followed by 0.625 mm CT acquisition; Mimics reconstructed the bony model, and Autodesk Maya simulated anchor trajectories to define a preliminary safety zone. In stage two, six formalin-fixed specimens (12 hips) were equipped with 3-D-printed, patient-specific guides after portal marking, dissected, and instrumented at 10-4 o'clock positions. Anchors inserted via anterior, anterolateral, and DALA portals validated the virtual safety map, after which the refined data were applied prospectively in clinical application. Virtual anchoring revealed marked, position-dependent differences: the DALA portal at 12-o'clock achieved only 50.0% success, significantly below the anterolateral (86.4%) and anterior (90.9%) portals (P = 0.004); the anterior portal at 1-o'clock reached 95.5%, exceeding both anterolateral (46.7%) and DALA (27.3%) (P < 0.001); DALA at 3-o'clock yielded 77.3%, surpassing anterolateral (27.3%) and anterior (13.6%) (P < 0.001); and anterolateral at 4-o'clock fell to 18.2%, well below DALA (86.4%) and anterior (72.7%) (P < 0.001). Success rates at 10-, 11-, and 2-o'clock did not differ among portals. Cadaveric validation closely mirrored these trends: no significant inter-portal differences were observed at 10-, 11-, 12-, 1-, 2-, or 3-o'clock, whereas 4-o'clock showed a significant disparity (χ² = 8.222, P = 0.016), with the anterior portal (75.0%) outperforming the anterolateral (16.7%); DALA (50.0%) did not differ significantly from either. Adherence to these validated trajectories enhances procedural safety and anchor reliability. For arthroscopic labral repair, anchor placement should follow these portal-specific safe corridors: anterior portal-10, 11, 12, 1, 2, and 4 o'clock; anterolateral portal-10, 11, 12, and 2 o'clock; DALA portal-10, 11, 2, 3, and 4 o'clock.
暂无摘要（点击查看详情）
Primary hyperparathyroidism is a prevalent endocrine disorder marked by excessive parathyroid hormone secretion. Beyond its classical biochemical features, accumulating evidence suggests that primary hyperparathyroidism may adversely affect cardiovascular homeostasis. In this context, we aimed to evaluate whether patients with primary hyperparathyroidism exhibit impaired vascular function and heightened systemic inflammation compared with matched healthy controls. This cross-sectional study initially recruited 39 patients with primary hyperparathyroidism. After predefined exclusion criteria were applied, 30 patients with primary hyperparathyroidism were included and compared with 45 age-, sex-, and body mass index-matched healthy controls. Endothelium dependent and independent vasodilation were assessed using venous occlusion plethysmography. High-sensitivity C-reactive protein levels were measured. Endothelium-independent vasodilation was reduced in primary hyperparathyroidism compared to controls (-15.5%; p=0.01), indicating vascular smooth muscle dysfunction. High-sensitivity C-reactive protein levels were significantly higher in primary hyperparathyroidism (905.7%; p<0.001). The mean arterial pressure was elevated (~12.2%; p<0.001), with a higher prevalence of hypertension (60% vs. 35.6%; p=0.03). These findings suggest that primary hyperparathyroidism is associated with impaired vascular function and systemic inflammation, even in patients without overt cardiovascular disease. This highlights a possible subclinical cardiovascular risk in primary hyperparathyroidism and supports the need for further longitudinal studies to confirm these associations and their clinical relevance.
The general public in the Himalayan region is exposed to considerable radiation from indoor radon, thoron, and their decay products. The estimation of natural radiation, source apportionment, and concentrations of its decay products is vital for population health risk assessment. In this study, the inhalation dose and seasonal variability of indoor radon, thoron, and their progeny were investigated in the sub-mountainous Dhauladhar region of the north-west (NW) Himalaya, India. A total of 51 dwellings from 17 villages, such as cemented (H1), slate + mud (H2), and cemented + tin roofs (H3), were randomly selected for indoor radon, thoron, and their progeny measurements. The annual indoor average radon and thoron concentrations measured in H1 houses were 74.8-53.0 Bq/m3, respectively. Whereas, in H2 and H3, it showed an average of 90.6, 67.8, 69.8 and 48.4 Bq/m3, respectively. The correlation between indoor radon and thoron was found to be 0.77. The inhalation dose in the H1 was found to be 0.69-0.35 mSv/y, respectively. Similarly, for the H2 and H3, the values found to be 0.80, 0.43,0.65 and 0.32 mSv/y, respectively. The result suggests that the high indoor radon, thoron, and their progeny were recorded during winter seasons and radon and thoron levels in H2 houses was found slightly higher compared to the H1 and H2 houses, mainly depending on the type of dwelling, ventilation rate and cold environmental conditions.
Organic formulations are emerging as sustainable and eco-friendly solutions for enhancing crop production and promoting long-term agro-ecosystem resilience. The present investigation was carried out on kiwifruit cv. ‘Allison’ under mid-hill conditions of Himachal Pradesh. The study aimed to assess the influence of integrated nutrient management modules comprising organic manures, biofertilizers (UHF-Jeevanu Khad) and Jeevamrit-based formulations on plant physiological traits, soil physico-chemical and chemical properties, and microbial activity. A field experiment, laid out in a randomized block design (RBD) with seven treatments and three replications, revealed significant improvements in physiological parameters, specifically, chlorophyll content, photosynthetic rate, stomatal conductance and transpiration rate, which collectively enhanced overall plant metabolic efficiency. Among the treatments, the combination of 75% recommended dose of fertilizers (RDF) and 25% UHF-Jeevanu Khad significantly enhanced soil macronutrients, namely N, P and K by 17.75, 20.58 and 19.78%, respectively, over their sole application, along with notable improvements in micronutrients (Fe, Zn, Mn, Cu), indicating improved nutrient dynamics. Microbial populations, including bacteria, fungi and actinomycetes, increased substantially under organic inputs, indicating enhanced microbial activity in the rhizosphere, which may improve root-microbe interactions and nutrient cycling. Multivariate statistical analyses including principal component analysis (PCA) and heatmap cluster revealed strong associations among microbial, nutrient and physiological traits, with the treatment comprising 75% RDF combined with 25% UHF-Jeevanu Khad, and the treatment involving RDF at 800:600:800 g N:P:K per vine forming distinct, high-loading clusters. Correlation analysis showed significant positive relationships between available nitrogen and photosynthetic rate (r = 0.983), stomatal conductance (r = 0.964) and chlorophyll content (r = 0.958), indicating close linkage between nutrient availability and plant physiological performance. Additionally, multiple regression analysis (R2 = 0.9938) identified available nitrogen and photosynthetic traits as dominant predictors of yield. The integration of organic manures, biofertilizers and Jeevamrit-based formulations with recommended fertilizers enhanced soil fertility, microbial activity and plant physiological performance, thus supporting sustainable kiwifruit production in mid-hill regions. These findings underline the importance of combining organic and microbial inputs with conventional practice to improve nutrient cycling, plant health and productivity. The online version contains supplementary material available at 10.1186/s12870-026-08259-6.
Avian infectious bronchitis virus (IBV) is a highly contagious coronavirus that causes severe respiratory, renal, and reproductive disease in chickens, resulting in significant economic losses in the poultry industry worldwide. The high mutation and recombination rates of IBV, especially in structural proteins like the spike glycoprotein, limit the effectiveness of current live attenuated and inactivated vaccines. This study aimed to design and computationally evaluate a novel multi-epitope vaccine (MEV) targeting the highly conserved RNA-dependent RNA polymerase (RdRp) of IBV in order to provide broad and lasting immune protection. The RdRp protein (NCBI: NP_740629.1) was chosen as the vaccine target due to its high sequence conservation and crucial role in viral replication. B-cell lymphocyte, cytotoxic T-lymphocyte, and helper T-lymphocyte epitopes were predicted using various immunoinformatics tools, followed by strict screening for antigenicity, non-allergenicity, non-toxicity, interferon-γ induction potential, and lack of homology with Gallus gallus proteins. The selected epitopes were assembled into a single construct with suitable linkers, incorporating avian β-defensin 8 as an N-terminal adjuvant. The vaccine candidate was analyzed in silico for physicochemical properties, structural stability, solubility, molecular docking with chicken Toll-like receptor 7 (TLR7), molecular dynamics, and immune response simulation. The final multi-epitope construct showed favorable physicochemical properties, including high stability (instability index: 25.74), hydrophilicity, and predicted solubility (Protein-Sol score: 0.504). Structural modeling and validation confirmed a reliable tertiary structure. Molecular docking demonstrated strong, stable binding to TLR7, supported by multiple hydrogen bonds and salt bridges, while molecular dynamics analysis indicated sufficient flexibility for immune recognition. Immune simulations forecasted robust humoral and cellular immune responses, characterized by increased IgG levels, expansion of memory B and T cells, and a Th1-biased cytokine profile with significant interferon-γ production. This immunoinformatics-designed RdRp-based MEV is a promising candidate for broad-spectrum protection against IBV. By targeting a conserved non-structural protein, it may address limitations linked to strain-specific vaccines. In vitro and in vivo testing is needed to confirm its safety, immunogenicity, and protective efficacy in poultry.
Sacral dural tears are an underrecognized cause of spontaneous intracranial hypotension, and their clinical behavior and response to treatment remain incompletely defined. We hypothesized that outcomes following epidural patching in sacral dural tears are driven primarily by disease chronicity and baseline imaging features, mirroring patterns observed in other SIH leak subtypes, and are less dependent on procedural variables. We performed a multicenter retrospective cohort study of patients with SIH attributed to sacral dural tears who underwent epidural patching and had clinical and/or imaging follow-up. Of 61 identified patients, 54 met inclusion criteria. Clinical outcomes, brain and spine imaging findings, and procedural variables were analyzed. Univariate and multivariable logistic regression models were used to identify predictors of clinical and imaging outcomes. Myelographic techniques were compared for rates of precise leak localization. The mean age was 37.8 years, and 85% of patients were women. Complete clinical improvement following patching occurred in 28 of 50 patients (56%), and complete resolution of sacral extradural CSF on follow-up spine MRI occurred in 17 of 37 patients (46%). Greater improvement in Bern score was independently associated with complete clinical improvement (OR 0.73, 95% CI 0.54-0.99, p = 0.04) and showed a pattern toward imaging resolution. Unorganized baseline extradural CSF morphology predicted better clinical (p = 0.03) and imaging (p = 0.03) outcomes. Procedural variables, including injectate type, volume, and needle approach were not associated with outcome. Dynamic CT myelography precisely localized the leak more frequently than digital subtraction myelography (75% vs 31%, p = 0.02). Eight patients underwent surgery, with mixed clinical and imaging outcomes. Epidural patching outcomes in sacral dural tears causing SIH are driven primarily by baseline imaging phenotype, disease stage, and intracranial imaging response rather than procedural technique. These findings support a morphology- and chronicity-aware approach to diagnosis and treatment and suggest that sacral dural tears represent a distinct SIH subtype with outcome patterns similar to other leak mechanisms.
Alzheimer disease (AD) risk differs across ancestral populations, yet most genetic studies have focused on non-Hispanic White (NHW) cohorts. We conducted a multi-population transcriptome-wide association study (TWAS) using whole-blood RNA sequencing (RNA-seq) and genotype data from NHW (n = 235), African American (AA; n = 224), and Hispanic (HISP; n = 292) Multi-Ancestry Genomics, Epigenomics, and Transcriptomics of Alzheimer's (MAGENTA) participants. Using sum of shared single effects (SuShiE) for multi-population cis-eQTL fine-mapping, we identified credible sets for 8,748 genes, improving fine-mapping precision relative to analyses using fewer populations. cis-eQTL effects were largely shared across populations, with a subset showing population-specific regulation. We performed population-stratified TWAS of AD and inverse-variance-weighted meta-analysis, followed by gene-level TWAS fine-mapping (MA-FOCUS), prioritizing nine genes (false discovery rate [FDR] <0.05, posterior inclusion probability [PIP] >0.8), including established AD loci (BIN1, PTK2B, DMPK) with broadly consistent effects across populations. At BIN1, fine-mapped cis-eQTL variants used in the TWAS prediction model highlighted rs11682128, which is only modestly correlated with the genome-wide association study (GWAS) index SNP rs6733839 (r2 ≈ 0.34), demonstrating how integrating eQTL fine-mapping with TWAS can refine signals beyond sentinel GWAS variants. We also identified an association between COG4 expression and AD in NHW, implicating Golgi-related pathways. Using independent SuShiE-derived models from TOPMed MESA (PBMC), several signals replicated directionally across ancestries, with the strongest statistical support in NHW. Overall, multi-population eQTL fine-mapping improves model interpretability and helps resolve shared and population-specific regulatory mechanisms relevant to AD.
Current diagnostic approaches for Alzheimer's disease (AD), including neuroimaging and cerebrospinal fluid (CSF) analysis, are limited by their invasiveness, high cost, and restricted accessibility. In contrast, ultrasensitive blood-based assays overcome these limitations while offering higher patient compliance, making them increasingly attractive. In recent years, substantial progress has been made in identifying blood biomarkers of AD, yet systematic overviews linking these biomarkers to ultrasensitive detection strategies remain limited. To address this gap, this review first discusses the relevance of blood tests to AD pathophysiology and the underlying disease mechanisms, and summarizes blood biomarkers within the established A/T/N framework. We then comprehensively discuss emerging ultrasensitive detection platforms, including single-molecule immunoassay (SiMoA), mass spectrometry, electrochemical biosensors, nucleic acid amplification techniques, surface plasmon resonance (SPR), and optical spectroscopy, focusing on their capabilities to enhance sensitivity and specificity in blood-based AD detection. Notably, we discuss ultrasensitive AD detection strategies from the standpoint of materials engineering and device innovation, revealing how nanomaterials and functional interfaces improve assay performance, thereby addressing a gap not covered by prior clinical or conventional biochemical studies.
Late-onset Alzheimer's disease (LOAD) is highly heritable; however, its estimated incidence across populations remains unclear. We computed family-based heritability leveraging Alzheimer's Disease Sequencing Project pedigrees from non-Hispanic White (404 pedigrees), non-Hispanic Black (13 pedigrees), Dominican (100 pedigrees), and Dutch isolate (10 pedigrees), with four models incorporating age, sex, apolipoproten E epsilon4 (APOE ε4), and contributing study using two methods. Heritability estimates varied by method, model, and study populations. Statistical Analysis for Genetic Epidemiology (S.A.G.E.) estimates were highest for Dutch isolate (78.3%), followed by non-Hispanic Blacks (39.1%), Dominicans (31.7%), and non-Hispanic Whites (29.1%), adjusted for age and sex. APOE adjustment reduced estimates (4.9% on average), while study adjustment primarily affected groups that included multiple studies. Sequential Oligogenic Linkage Analysis Routines (SOLAR-Eclipse) estimates were higher (45.2% to 80.2%) than S.A.G.E. (20.4% to 80.9%) but behaved in parallel, except for the Dutch isolate. LOAD heritability estimates are dependent on study population and may reflect or indicate differences in LOAD risk by population.