Disease Research Research Articles

Protocol and research program of the European registry and biobank for interstitial lung diseases (eurILDreg)

Abstract Background and Aims Interstitial lung diseases (ILDs), encompassing both pediatric and adult cases, present a diverse spectrum of chronic conditions with variable prognosis. Despite limited therapeutic options beyond antifibrotic drugs and immunosuppressants, accurate diagnosis is challenging, often necessitating invasive procedures that may not be feasible for certain patients. Drawn against this background, experts across pediatric and adult ILD fields have joined forces in the RARE-ILD initiative to pioneer novel non-invasive diagnostic algorithms and biomarkers. Collaborating with the RARE-ILD consortium, the eurILDreg aims to comprehensively describe different ILDs, analyze genetically defined forms across age groups, create innovative diagnostic and therapeutic biomarkers, and employ artificial intelligence for data analysis. Methods The foundation of eurILDreg is built on a comprehensive parameter list developed and adopted by clinical experts, encompassing over 1,800 distinct parameters related to patient history, clinical examinations, diagnosis, lung function and biospecimen collection. This robust dataset is further enriched with daily assessments captured through the patientMpower app, including handheld spirometry and exercise tests, conducted on approximately 350 patients over the course of a year. This approach involves app-based daily assessments of quality of life, symptom tracking, handheld spirometry, saturation measurement, and the 1-min sit-to-stand test (1-STST). Additionally, pediatric data from the ChILD-EU registry will be integrated into the RARE-ILD Data Warehouse, with the ultimate goal of including a total of 4.000 ILD patients and over 100.000 biospecimen. Discussion The collaborative efforts within the consortium are poised to streamline research endeavors significantly, promising to advance patient-centered care, foster innovation, and shape the future landscape of interstitial lung disease research and healthcare practices. Trial Registration EurILDreg is registered in the German Clinical Trials Register (DRKS 00028968, 26.07.2022), and eurIPFreg is registered in ClinicalTrials.gov (NCT02951416).

Exploring the Perspectives of Older Adults on a Digital Brain Health Platform Using Natural Language Processing: Cohort Study

Background Although digital technology represents a growing field aiming to revolutionize early Alzheimer disease risk prediction and monitoring, the perspectives of older adults on an integrated digital brain health platform have not been investigated. Objective This study aims to understand the perspectives of older adults on a digital brain health platform by conducting semistructured interviews and analyzing their transcriptions by natural language processing. Methods The study included 28 participants from the Boston University Alzheimer’s Disease Research Center, all of whom engaged with a digital brain health platform over an initial assessment period of 14 days. Semistructured interviews were conducted to collect data on participants’ experiences with the digital brain health platform. The transcripts generated from these interviews were analyzed using natural language processing techniques. The frequency of positive and negative terms was evaluated through word count analysis. A sentiment analysis was used to measure the emotional tone and subjective perceptions of the participants toward the digital platform. Results Word count analysis revealed a generally positive sentiment toward the digital platform, with “like,” “well,” and “good” being the most frequently mentioned positive terms. However, terms such as “problem” and “hard” indicated certain challenges faced by participants. Sentiment analysis showed a slightly positive attitude with a median polarity score of 0.13 (IQR 0.08-0.15), ranging from –1 (completely negative) to 1 (completely positive), and a median subjectivity score of 0.51 (IQR 0.47-0.53), ranging from 0 (completely objective) to 1 (completely subjective). These results suggested an overall positive attitude among the study cohort. Conclusions The study highlights the importance of understanding older adults’ attitudes toward digital health platforms amid the comprehensive evolution of the digitalization era. Future research should focus on refining digital solutions to meet the specific needs of older adults, fostering a more personalized approach to brain health.

Are oligodendrocytes the missing link in Alzheimer's disease and related dementia research?

Are oligodendrocytes the missing link in Alzheimer's disease and related dementia research?

Uncovering disease-related multicellular pathway modules on large-scale single-cell transcriptomes with scPAFA.

Pathway analysis is a crucial analytical phase in disease research on single-cell RNA sequencing (scRNA-seq) data, offering biological interpretations based on prior knowledge. However, currently available tools for generating cell-level pathway activity scores (PAS) exhibit computational inefficacy in large-scale scRNA-seq datasets. Additionally, disease-related pathways are often identified through cross-condition comparisons within specific cell types, overlooking potential patterns that involve multiple cell types. Here, we present single-cell pathway activity factor analysis (scPAFA), a Python library designed for large-scale single-cell datasets allowing rapid PAS computation and uncovering biologically interpretable disease-related multicellular pathway modules, which are low-dimensional representations of disease-related PAS alterations in multiple cell types. Application on colorectal cancer (CRC) datasets and large-scale lupus atlas over 1.2 million cells demonstrated that scPAFA can achieve over 40-fold reductions in the runtime of PAS computation and further identified reliable and interpretable multicellular pathway modules that capture the heterogeneity of CRC and transcriptional abnormalities in lupus patients, respectively. Overall, scPAFA presents a valuable addition to existing research tools in disease research, with the potential to reveal complex disease mechanisms and support biomarker discovery at the pathway level.

The potential of lactoferrin as antiviral and immune-modulating agent in viral infectious diseases

Emerging infectious diseases are caused by unpredictable viruses with the dangerous potential to trigger global pandemics. These viruses typically initiate infection by utilizing the anionic structures of host cell surface receptors to gain entry. Lactoferrin (Lf) is a multifunctional glycoprotein with multiple properties such as antiviral, anti-inflammatory and antioxidant activities. Due to its cationic structure, Lf naturally interacts with certain host cell receptors, such as heparan sulfate proteoglycans, as well as viral particles and other receptors that are targeted by viruses. Therefore, Lf may interfere with virus-host cell interactions by acting as a receptor competitor for viruses. Herein we summarize studies in which this competition was investigated with SARS-CoV-2, Zika, Dengue, Hepatitis and Influenza viruses in vitro. These studies have demonstrated not only Lf’s competitive properties, but also its potential intracellular impact on host cells, such as enhancing cell survival and reducing infection efficiency by inhibiting certain viral enzymes. In addition, the immunomodulatory effect of Lf is highlighted, as it can influence the activity of specific immune cells and regulate cytokine release, thereby enhancing the host’s response to viral infections. Collectively, these properties promote the potential of Lf as a promising candidate for research in viral infectious diseases.

Viral hepatitis A in children: a false prosperity?

The article presents current data on the state of the issue of Hepatitis A (HA) in children in the Russian Federation and describes clinical and epidemiologic features of rare cases of severe course of the disease, as well as pathogenetic mechanisms of liver damage mediated by cell immune response. Objective. To identify clinical and epidemiologic features of the modern course of HA and its outcomes in children of Saint Petersburg within the period of 2018— 2023. Materials and methods. The study included 89 children diagnosed with HA, undergoing treatment at the Children's Research and Clinical Center for Infectious Diseases from 2018 to 2023. The analysis of disease progression in this group of patients was presented using clinical-anamnestic, epidemiologic, biochemical, virologic and instrumental data. Results. The analysis of infection sources showed a high frequency of HA infection within the family (44.9 ± 0.8%) and significantly less in childcare facilities and schools (7.9 ± 1.0%). The frequency of children with unidentified sources of infection remained high (47.2 ± 0.7%). One-third of all disease cases were imported from southern regions. Most hospitalized children had icteric HA (64.0 ± 0.6%) of moderate severity (79.8 ± 0.5%). Severe HA was observed in 6 patients (6.7 ± 1.0%). During the study, 17 patients (19.1 ± 0.9%) had a prolonged, complicated course of the disease, including ascites and aplastic anemia (12.6 ± 2.2%). Ascites was found in 4 patients with severe severity and in 5 patients with moderate severity of HA. Conclusions. Currently, there is an upward trend in the incidence of HA in the Russian Federation and Saint Petersburg, especially among schoolchildren (56.2%). A rather high frequency of severe (6.7%) and complicated forms (19.1%) of the disease is observed, and the growth of ascites and aplastic anemia cases in HA draws particular attention.

Pure LATE-NC: Frequency, clinical impact, and the importance of considering APOE genotype when assessing this and other subtypes of non-Alzheimer's pathologies.

Pure limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (pure LATE-NC) is a term used to describe brains with LATE-NC but lacking intermediate or severe levels of Alzheimer's disease neuropathologic changes (ADNC). Focusing on pure LATE-NC, we analyzed data from the National Alzheimer's Coordinating Center (NACC) Neuropathology Data Set, comprising clinical and pathological information aggregated from 32 NIH-funded Alzheimer's Disease Research Centers (ADRCs). After excluding subjects dying with unusual conditions, n = 1,926 autopsied subjects were included in the analyses. For > 90% of these participants, apolipoprotein E (APOE) allele status was known; 46.5% had at least one APOE 4 allele. In most human populations, only 15-25% of people are APOE ε4 carriers. ADRCs with higher documented AD risk allele (APOE or BIN1) rates had fewer participants lacking ADNC, and correspondingly low rates of pure LATE-NC. Among APOE ε4 non-carries, 5.3% had pure LATE-NC, 37.0% had pure ADNC, and 3.6% had pure neocortical Lewy body pathology. In terms of clinical impact, participants with pure LATE-NC tended to die after having received a diagnosis of dementia: 56% died with dementia among APOE ε4 non-carrier participants, comparable to 61% with pure ADNC. LATE-NC was associated with increased Clinical Dementia Rating Sum of Boxes (CDR-SOB) scores, i.e. worsened global cognitive impairments, in participants with no/low ADNC and no neocortical Lewy body pathology (p = 0.0023). Among pure LATE-NC cases, there was a trend for higher LATE-NC stages to be associated with worse CDR-SOB scores (p = 0.026 for linear trend of LATE-NC stages). Pure LATE-NC was not associated with clinical features of disinhibition or primary progressive aphasia. In summary, LATE-NC with no or low levels of ADNC was less frequent than pure ADNC but was not rare, particularly among individuals who lacked the APOE 4 allele, and in study cohorts with APOE 4 frequencies similar to those in most human populations.

Animal models for exploring Chagas disease pathogenesis and supporting drug discovery.

SUMMARYInfections with the parasitic protozoan Trypanosoma cruzi cause Chagas disease, which results in serious cardiac and/or digestive pathology in 30%-40% of individuals. However, symptomatic disease can take decades to become apparent, and there is a broad spectrum of possible outcomes. The complex and long-term nature of this infection places a major constraint on the scope for experimental studies in humans. Accordingly, predictive animal models have been a mainstay of Chagas disease research. The resulting data have made major contributions to our understanding of parasite biology, immune responses, and disease pathogenesis and have provided a platform that informs and facilitates the global drug discovery effort. Here, we provide an overview of available animal models and illustrate how they have had a key impact across the field.

Candidate genetic loci modifying the colorectal cancer risk caused by lifestyle risk factors

Objective: 65-70% of colorectal cancer (CRC) cases are considered sporadic; they arise under the influence of environmental factors in individuals lacking a family history of CRC. Low-risk genetic variants are believed to contribute to CRC risk, in tandem with lifestyle factors. Design: 616 non-familial Swedish CRC cases with at least 1 of the following five risk factors: smoking, excessive alcohol consumption, physical inactivity, adherence to an unhealthy diet, and excess body weight were included in this study. A control group consisting of 1642 healthy individuals was used. Cases and controls were genotyped from blood samples at the Centre for Inherited Disease Research at Johns Hopkins University within the Colorectal Transdisciplinary Study (CORECT) research collaboration, using the Illumina Infinium® OncoArray-500 K BeadChip. Five separate genome-wide haplotype association analyses were performed, one for each risk factor. Logistic regression models were employed to estimate associations between haplotypes (exposure) and CRC (outcome) in cases with lifestyle risk factors versus controls. Haplotypes with an odds ratio (OR) >1 were considered candidate risk markers, denoting an area of interest in the genome. A significance threshold of p < 5×10-8 was used. Results: We found 17 haplotype regions significantly associated with CRC in cases vs controls. Several regions included genes linked to inflammation and tumor promotion. Conclusion: We concluded that having certain genetic variants was associated with an increased risk of CRC compared to healthy controls among cases with known lifestyle risk factors. The interplay of lifestyle and genetic risk factors calls for further elucidation.

Sex disparities in myocardial infarction related cardiogenic shock.

Women are underrepresented In cardiovascular disease research, constituting only 30 % of the cardiogenic shock (CS) population. Consequently, guidelines are mainly based on male patients. This study aims to comprehensively examine the sex-specific aspects of acute myocardial infarction (AMI)-related CS, encompassing presentation, treatment and outcomes. Patients with CS undergoing percutaneous coronary intervention (PCI) between 2017 and 2021 were identified using the national Netherlands Heart Registration. Mortality was assessed using the Kaplan Meier method, and logistic regression was performed to investigate differences in clinical management between sexes. Furthermore, a sensitivity analysis excluding patients with out-of-hospital cardiac arrest (OHCA) was conducted. Among 2274 patients, 614 (27 %) were female. Women were older (70 vs. 66 years, p < 0.001) and presented with longer symptom duration (> 3 h: 52 % vs. 37 %, p < 0.001). Men more often presented with multivessel disease (62 % vs. 56 %, p < 0.001), a prior myocardial infarction (23 % vs. 15 %, p < 0.001) and after an OHCA (46 % vs. 29 %, p < 0.001). A trend towards more usage of mechanical circulatory support in men was observed (adjusted OR 0.86, 95 % CI 0.67-1.09). Mortality, both adjusted and unadjusted, was not statistically different for men and women. Women with CS present with distinct clinical characteristics, including longer symptom duration, underscoring the importance of symptom recognition. Furthermore, men present at younger age and with more OHCA. Mortality in men and women was similar despite differences in presentation and clinical management.

Genetic study of intrahepatic cholestasis of pregnancy in Chinese women unveils East Asian etiology linked to historic HBV epidemic.

Intrahepatic cholestasis of pregnancy (ICP) is the most common and high-risk liver disorder during pregnancy, with varying prevalence across populations. Our understanding of the mechanisms underlying ICP and its population difference remains limited. This study delves into the genetic etiology of ICP in East Asians, drawing comparisons with Europeans to comprehend ICP etiology in the context of genetic background and evolution. We conducted the hitherto largest-scale genome-wide association studies (GWAS) on fasting total serum bile acids (TBA) and ICP in 98,269 Chinese pregnancies. The findings were replicated in three cohorts and compared with European populations. Additionally, phenome-wide association and spatio-temporal evolution analyses were employed to investigate the function and evolutionary patterns of ICP-associated loci. We identified eight loci for fasting TBA and four for ICP, including ten novel loci. Notably, we discovered an East-Asian-specific locus within a 0.4Mbp region at 14q24.1, which increases fasting TBA by 6.12 μmol/L and ICP risk by 16.56-fold per risk allele (95% CI: 16.43 to 16.69, P = 7.06×10-381). Phenome-wide association and spatial-temporal evolution analyses revealed that this 14q24.1 ICP risk locus confers resistance to hepatitis B and has become prevalent in East and Southeast Asia within the last 3,000 years. We uncovered a distinct genetic etiology of ICP in East Asians, likely linked to a historic HBV epidemic in East and Southeast Asia within the last 3,000 years. These findings enhance our understanding of ICP pathophysiology and offer potential for more precise detection, assessment, and treatment of the disorder. This study provides novel insights into the genetic basis of intrahepatic cholestasis of pregnancy (ICP) in East Asian populations, where little was previously known. The identification of the East-Asian-specific 14q24.1 locus, associated with both fasting TBA and ICP, and its connection to a historical hepatitis B epidemic emphasize the importance of incorporating population-specific history into disease research. These findings are crucial for researchers studying pregnancy-related liver disorders and clinicians providing care to pregnant women, enabling more accurate screening, risk assessment, and targeted interventions for ICP.

The ADNI Administrative Core: Ensuring ADNI's success and informing future AD clinical trials.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) Administrative Core oversees and coordinates all ADNI activities, to ensure the success and maximize the impact of ADNI in advancing Alzheimer's disease (AD) research and clinical trials. It manages finances and develops policies for data sharing, publications using ADNI data, and access to ADNI biospecimens. The Core develops and executes pilot projects to guide future ADNI activities and identifies key innovative methods for inclusion in ADNI. For ADNI4, the Administrative Core collaborates with the Engagement, Clinical, and Biomarker Cores to develop and evaluate novel, digital methods and infrastructure for participant recruitment, screening, and assessment of participants. The goal of these efforts is to enroll 500 participants, including>50% from underrepresented populations, 40% with mild cognitive impairment, and 80% with elevated AD biomarkers. This new approach also provides a unique opportunity to validate novel methods. HIGHLIGHTS: The Alzheimer's Disease Neuroimaging Initiative (ADNI) Administrative Core oversees and coordinates all ADNI activities. The overall goal is to ensure ADNI's success and help design future Alzheimer's disease (AD) clinical trials. A key innovation is data sharing without embargo to maximize scientific impact. For ADNI4, novel, digital methods for recruitment and assessment were developed. New methods are designed to improve the participation of underrepresented populations.

Fostering the international interoperability of clinical research networks to tackle undiagnosed and under-researched rare diseases

Clinical research is an essential component to advance diagnosis and therapeutic development. In 2022, the International Rare Diseases Research Consortium (IRDiRC) and the European Joint Programme on Rare Diseases (EJP RD) brought together key stakeholders from across the globe to discuss common themes in clinical research networks (CRNs) for rare diseases. Various topics were raised during discussions including current state of CRNs, the need for new CRNs, multi-stakeholder perspectives on value of CRNs, and ways to collaborate on a global scale. Communication and coordination between various groups, taking advantage of existing experiences, can expedite establishment and execution of complex collaborations that will be necessary for CRNs. In this perspective, we discuss opportunities and highlight key considerations for developing successful collaborative CRNs across the globe.

Machine learning for precision diagnostics of autoimmunity.

Early and accurate diagnosis is crucial to prevent disease development and define therapeutic strategies. Due to predominantly unspecific symptoms, diagnosis of autoimmune diseases (AID) is notoriously challenging. Clinical decision support systems (CDSS) are a promising method with the potential to enhance and expedite precise diagnostics by physicians. However, due to the difficulties of integrating and encoding multi-omics data with clinical values, as well as a lack of standardization, such systems are often limited to certain data types. Accordingly, even sophisticated data models fall short when making accurate disease diagnoses and presenting data analyses in a user-friendly form. Therefore, the integration of various data types is not only an opportunity but also a competitive advantage for research and industry. We have developed an integration pipeline to enable the use of machine learning for patient classification based on multi-omics data in combination with clinical values and laboratory results. The application of our framework resulted in up to 96% prediction accuracy of autoimmune diseases with machine learning models. Our results deliver insights into autoimmune disease research and have the potential to be adapted for applications across disease conditions.

TraceEyeDisease: a web-based database for investigating trace elements and their imbalances in eye diseases.

Eye diseases remain a significant global health concern, with trace elements crucial in maintaining ocular health and preventing ocular disorders. In ocular health, trace elements have been recognized as critical factors influencing the development and progression of multiple eye diseases. In this study, we conducted a thorough literature search through PubMed to acquire data concerning different eye diseases associated with trace elements. These diseases are essential in trace element imbalances or deficiencies in their progression. Our approach included a meticulous compilation of information from various databases, systematically integrated into a carefully curated database. In total, we identified 178 distinct genes that encode proteins linked to fourteen trace elements in this comprehensive list. A web-based database designed to formulate evidence-based hypotheses regarding the impact of trace element deficiency and imbalance on eye diseases was presented using Shiny R. This study underscores the vital role of trace elements in preserving ocular health. The Shiny R application facilitates subsequent investigations, fostering enhanced insights into public health, clinical practices, and eye disease research. The URL of TraceEyeDiseas is https://tredis.shinyapps.io/TraceEyeDisease/ .

Structural diversity of Alzheimer-related protein aggregations revealed using photothermal ratio-metric micro-spectroscopy

The crucial link between pathological protein aggregations and lipids in Alzheimer’s disease pathogenesis is increasingly recognized, yet its spatial dynamics remain challenging for labeling-based microscopy. Here, we demonstrate photothermal ratio-metric infrared spectro-microscopy (PRISM) to investigate the in situ structural and molecular compositions of pathological features in brain tissues at submicron resolution. By identifying the vibrational spectroscopic signatures of protein secondary structures and lipids, PRISM tracks the structural dynamics of pathological proteins, including amyloid and hyperphosphorylated Tau (pTau). Amyloid-associated lipid features in major brain regions were observed, notably the enrichment of lipid-dissociated plaques in the hippocampus. Spectroscopic profiling of pTau revealed significant heterogeneity in phosphorylation levels and a distinct lipid-pTau relationship that contrasts with the anticipated lipid-plaque correlation. Beyond in vitro studies, our findings provide direct visualization evidence of aggregate-lipid interactions across the brain, offering new insights into mechanistic and therapeutic research of neurodegenerative diseases.

EPID-24. OPTIMIZING PATIENT RECRUITMENT FOR BRAIN TUMOR STUDIES: LEVERAGING THE POWER OF GOOGLE ADS TO CONNECT WITH AFFECTED FAMILIES

Abstract OBJECTIVE We assessed the effectiveness of using Google Ads to recruit individuals with familial glioma into a genetic research study. METHODS We conducted a comparative analysis between two periods: March 1 to June 30, 2023 (with Google Ads) and March 1 to June 30, 2021 (without Google Ads). We targeted individuals searching for brain tumor information using Google Ads, directing them to a study landing page. We analyzed metrics such as advertisement clicks, impressions, click-through rate, and cost per click. Our eligibility criteria included families with at least two members having glioma, with one currently living with the condition, aged 18 or older, and residing in the United States. RESULTS The 2023 Google Ads campaign generated 7,228 clicks, 82,242 impressions, an 8.79% click-through rate, and a cost per click of $0.62. The number of interested individuals increased from 13 in 2021 (without Google Ads) to 35 in 2023 (with Google Ads), with 20 indicating they found the study through Google Ads. However, the increase lacked statistical significance (x2=1.48, p=0.22). CONCLUSION Google Ads enhanced our participant outreach and recruitment for the glioma study, although the results were not statistically significant. This approach shows promise for recruiting participants for rare disease research. We recommend that future studies consider longer durations and larger sample sizes to better assess its impact. Additionally, due to the prevalence of misinformation about familial glioma, we submitted and conducted a survey to the Society of NeuroOncology to evaluate the attitudes and beliefs of physicians and other healthcare professionals towards familial glioma. This survey aims to address misconceptions and improve understanding within the healthcare community.

Noninvasive Monitoring of Steatotic Liver Disease in Western Diet-Fed Obese Mice Using Automated Ultrasound and Shear Wave Elastography.

Ultrasound imaging and shear wave elastography (SWE) can be used to noninvasively stage hepatopathologies and are widespread in clinical practice. These techniques have recently been adapted for small animal use in a novel 3D invivo imaging system capable of high-throughput automated scanning. Our goal was to evaluate the feasibility of using this imaging tool in the murine Western diet (WD) model, a highly translatable preclinical model of obesity, metabolic disease and liver fibrosis. Female C57BL/6 mice (N = 48) were placed on WD or chow diet and imaged longitudinally for a period of 48 weeks. Imaging consisted of 3D B-mode and targeted SWE captures. Liver volume, liver echogenicity and liver stiffness were quantified from invivo imaging data. A subset of mice was sacrificed at various timepoints (0, 12, 24 and 48 weeks) for histological workup. Correlation analysis was performed between invivo imaging and histological measurements to determine level of agreement. Noninvasive imaging showed statistically significant increases in liver volume and echogenicity, but non-significant increase in liver stiffness in the WD-fed cohort, suggesting development of hepatomegaly and steatosis, but negligible fibrosis. Exvivo analysis confirmed significant increases in liver weight, liver triglycerides and ALT, but limited increases in fibrosis corroborating noninvasive imaging results. Correlation analysis between imaging and histology demonstrated good agreement between liver volume/liver weight (R2 = 0.85) and echogenicity/triglycerides (R2 = 0.76). This study demonstrated that noninvasive ultrasound liver assessments are feasible in the WD mouse model and closely reflect the underlying pathological state of the animal. Automated ultrasound can serve as a high-throughput noninvasive screening method for preclinical liver disease research and drug development.

Observational Analyses of Ex Vivo Native American Platelet Responses

Platelet activation plays an essential role in clot formation to prevent blood loss following vascular damage. In pathologic conditions, platelet activation can lead to obstructive clots, disrupting blood flow and resulting in thrombosis. Native Americans suffer disproportionately from arterial disease and previous research has shown that Blacks are enriched in genetic polymorphisms that correlate with higher platelet reactivity contributing to an increased risk for thrombosis. Therefore, the current study sought to determine phenotypic variations in Native American platelet responses following stimulation with agonists, simulating vascular damage. Several donors from a small cohort of Native Americans showed atypical robust platelet aggregation when stimulated with submaximal concentrations of agonists. Further, when comparing α-granule secretion, a specific marker of platelet activation, Native Americans were more likely to have elevated responses to multiple agonist conditions of stimulation compared to Whites. Interestingly, there were no noticeable differences in integrin activation between Native Americans and Whites. Our study is the first to observe elevated Native American platelet responses compared to Whites, supporting further mechanistic studies and investigation of treatment approaches for the prevention of thrombosis.

Genome-wide transcriptome analysis of Aβ deposition on PET in a Korean cohort.

Despite the recognized importance of including ethnic diversity in Alzheimer's disease (AD) research, substantial knowledge gaps remain, particularly in Asian populations. RNA sequencing was performed on blood samples from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) to perform differential gene expression (DGE), gene co-expression network, gene-set enrichment, and machine learning analyses for amyloid beta (Aβ) deposition on positron emission tomography. DGE analysis identified 265 dysregulated genes associated with Aβ deposition and replicated three AD-associated genes in an independent Korean cohort. Network analysis identified two modules related to pathways including a natural killer (NK) cell-mediated immunity. Machine learning analysis showed the classification of Aβ positivity improved with the inclusion of gene expression data. Our results in a Korean population suggest Aβ deposition-associated genes are enriched in NK cell-mediated immunity, providing a better understanding of AD molecular mechanisms and yielding potential diagnostic and therapeutic strategies. Dysregulated genes were associated with amyloid beta (Aβ) deposition on positron emission tomography in a Korean cohort. Dysregulated genes in Alzheimer's disease were replicated in an independent Korean cohort. Gene network moduleswere associated with Aβ deposition. Natural killer (NK) cell proportion in blood was associated with Aβdeposition. Dysregulated genes were related to a NK cell-mediated immunity.