Purpose: Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, with approximately 30% of patients eventually developing brain metastases (BM), which result in poor outcomes. An understanding of the tumor microenvironment (TME) at both primary and metastatic sites offers insights into the mechanisms underlying BM and potential therapeutic targets. Materials and Methods: Spatial RNA sequencing (spRNA-seq) was performed on primary TNBC and paired BM tissues from three patients, one of whom had previously received immune checkpoint inhibitors before BM diagnosis. Specimen regions were categorized into tumor, proximal, and distal TME based on their spatial locations. Gene expression differences across these zones were analyzed, and immune cell infiltration was estimated using TIMER. A gene module analysis was conducted to identify key gene clusters associated with BM. Results: Distinct gene expression profiles were noted in the proximal and distal TMEs. In BM, the proximal TME exhibited neuronal gene expression, suggesting neuron-tumor interactions compared to tumor, and upregulation of epithelial genes compared to the distal TME. Immune cell analysis revealed dynamic changes in CD8+ T cells and macrophages across the tumor and TME zones. Gene module analysis identified five key modules, including one related to glycolysis, which correlated with patient survival. Drug repurposing analysis identified potential therapeutic targets, including VEGFA, RAC1, EGLN3, and CAMK1D. Conclusion This study provides novel insights into the transcriptional landscapes in TNBC BM using spRNA-seq, emphasizing the role of neuron-tumor interactions and immune dynamics. These findings suggest new therapeutic strategies and underscore the importance of further research.

Background: and Purpose: Plasma biomarkers, including phosphorylated tau (ptau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL), are promising tools for detecting Alzheimer’s disease (AD) pathology. However, cross-laboratory reproducibility remains a challenge, even when using identical analytical platforms such as single-molecule array (Simoa). This study aimed to compare plasma biomarker measurements (ptau217, GFAP, and NfL) between 2 laboratories, the University of Gothenburg (UGOT) and DNAlink, and evaluate their associations with amyloid positron emission tomography (PET) imaging. Methods: Plasma biomarkers were measured using Simoa platforms at both laboratories:the UGOT and DNAlink Incorporation. Diagnostic performance for predicting amyloid PET positivity, cross-laboratory agreement, and the impact of normalization techniques were assessed. Bland-Altman plots and correlation analyses were employed to evaluate agreement and variability. Results: Plasma ptau217 concentrations exhibited strong correlations with amyloid PET global centiloid values, with comparable diagnostic performance between laboratories (area under the curve=0.94 for UGOT and 0.95 for DNAlink). Cross-laboratory agreement for ptau217 was excellent (r=0.96), improving further after natural log transformation. GFAP and NfL also demonstrated moderate to strong correlations (r=0.86 for GFAP and r=0.99 for NfL), with normalization reducing variability. Conclusions Plasma biomarker measurements were consistent across laboratories using identical Simoa platforms, with strong diagnostic performance and improved agreement after normalization. These findings support the scalability of plasma biomarkers for multicenter studies and underscore their potential for standardized applications in AD research and clinical practice.

Background: and Purpose: Plasma biomarkers, including phosphorylated tau (ptau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL), are promising tools for detecting Alzheimer’s disease (AD) pathology. However, cross-laboratory reproducibility remains a challenge, even when using identical analytical platforms such as single-molecule array (Simoa). This study aimed to compare plasma biomarker measurements (ptau217, GFAP, and NfL) between 2 laboratories, the University of Gothenburg (UGOT) and DNAlink, and evaluate their associations with amyloid positron emission tomography (PET) imaging. Methods: Plasma biomarkers were measured using Simoa platforms at both laboratories:the UGOT and DNAlink Incorporation. Diagnostic performance for predicting amyloid PET positivity, cross-laboratory agreement, and the impact of normalization techniques were assessed. Bland-Altman plots and correlation analyses were employed to evaluate agreement and variability. Results: Plasma ptau217 concentrations exhibited strong correlations with amyloid PET global centiloid values, with comparable diagnostic performance between laboratories (area under the curve=0.94 for UGOT and 0.95 for DNAlink). Cross-laboratory agreement for ptau217 was excellent (r=0.96), improving further after natural log transformation. GFAP and NfL also demonstrated moderate to strong correlations (r=0.86 for GFAP and r=0.99 for NfL), with normalization reducing variability. Conclusions Plasma biomarker measurements were consistent across laboratories using identical Simoa platforms, with strong diagnostic performance and improved agreement after normalization. These findings support the scalability of plasma biomarkers for multicenter studies and underscore their potential for standardized applications in AD research and clinical practice.

Background: and Purpose: Plasma biomarkers, including phosphorylated tau (ptau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL), are promising tools for detecting Alzheimer’s disease (AD) pathology. However, cross-laboratory reproducibility remains a challenge, even when using identical analytical platforms such as single-molecule array (Simoa). This study aimed to compare plasma biomarker measurements (ptau217, GFAP, and NfL) between 2 laboratories, the University of Gothenburg (UGOT) and DNAlink, and evaluate their associations with amyloid positron emission tomography (PET) imaging. Methods: Plasma biomarkers were measured using Simoa platforms at both laboratories:the UGOT and DNAlink Incorporation. Diagnostic performance for predicting amyloid PET positivity, cross-laboratory agreement, and the impact of normalization techniques were assessed. Bland-Altman plots and correlation analyses were employed to evaluate agreement and variability. Results: Plasma ptau217 concentrations exhibited strong correlations with amyloid PET global centiloid values, with comparable diagnostic performance between laboratories (area under the curve=0.94 for UGOT and 0.95 for DNAlink). Cross-laboratory agreement for ptau217 was excellent (r=0.96), improving further after natural log transformation. GFAP and NfL also demonstrated moderate to strong correlations (r=0.86 for GFAP and r=0.99 for NfL), with normalization reducing variability. Conclusions Plasma biomarker measurements were consistent across laboratories using identical Simoa platforms, with strong diagnostic performance and improved agreement after normalization. These findings support the scalability of plasma biomarkers for multicenter studies and underscore their potential for standardized applications in AD research and clinical practice.

Background: and Purpose: Plasma biomarkers, including phosphorylated tau (ptau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL), are promising tools for detecting Alzheimer’s disease (AD) pathology. However, cross-laboratory reproducibility remains a challenge, even when using identical analytical platforms such as single-molecule array (Simoa). This study aimed to compare plasma biomarker measurements (ptau217, GFAP, and NfL) between 2 laboratories, the University of Gothenburg (UGOT) and DNAlink, and evaluate their associations with amyloid positron emission tomography (PET) imaging. Methods: Plasma biomarkers were measured using Simoa platforms at both laboratories:the UGOT and DNAlink Incorporation. Diagnostic performance for predicting amyloid PET positivity, cross-laboratory agreement, and the impact of normalization techniques were assessed. Bland-Altman plots and correlation analyses were employed to evaluate agreement and variability. Results: Plasma ptau217 concentrations exhibited strong correlations with amyloid PET global centiloid values, with comparable diagnostic performance between laboratories (area under the curve=0.94 for UGOT and 0.95 for DNAlink). Cross-laboratory agreement for ptau217 was excellent (r=0.96), improving further after natural log transformation. GFAP and NfL also demonstrated moderate to strong correlations (r=0.86 for GFAP and r=0.99 for NfL), with normalization reducing variability. Conclusions Plasma biomarker measurements were consistent across laboratories using identical Simoa platforms, with strong diagnostic performance and improved agreement after normalization. These findings support the scalability of plasma biomarkers for multicenter studies and underscore their potential for standardized applications in AD research and clinical practice.

Background: The life expectancy of people living with human immunodeficiency virus (PLWH) has significantly improved with advancements in antiretroviral therapy (ART). However, aging PLWH face a growing burden of noncommunicable diseases (NCDs), polypharmacy, and drug-drug interactions (DDIs), which pose challenges in their management. This study investigates the prevalence of NCDs, polypharmacy, and DDIs among PLWH aged ≥50 years in Korea and their impact on quality of life (QOL). Materials and Methods: A cross-sectional study was conducted among 243 PLWH aged ≥50 years receiving ART for at least three months at three university hospitals in Korea between January and July 2022. Data were collected through electronic medical records and personal interviews, assessing demographics, comorbidities, polypharmacy, ART adherence, and QOL using the Korean version of WHOQOL-HIV BREF scale. Potential DDIs were analyzed using the University of Liverpool HIV Drug Interaction Database, and potentially inappropriate medications (PIMs) were identified using the 2023 American Geriatrics Society Beers Criteria. We classified participants into three age groups:50–<65 years, 65–<75 years, and ≥75 years. Results: The prevalence of comorbidities was 71.6%, with older participants (≥75 years) showing a significantly higher burden, including bone diseases, osteoarthritis, and dementia (P<0.001). Polypharmacy was observed in 28.4% of participants and increased with age, with 53.3% of those aged ≥75 years taking ≥10 pills daily.Polypharmacy was associated with poorer QOL (71.6 vs. 76.6, P=0.010). Amber-flag DDIs were found in 81 participants (33.3%), most commonly involving metformin and divalent cations. No red-flag DDIs were identified.PIMs were observed in 6.6% of participants aged ≥65 years. Conclusion Aging PLWH in Korea face significant challenges from comorbidities, polypharmacy, and DDIs, which negatively impact QOL. Integrated, age-specific, and multidisciplinary care strategies are urgently needed to improve outcomes and ensure the well-being of older PLWH.

Background: The life expectancy of people living with human immunodeficiency virus (PLWH) has significantly improved with advancements in antiretroviral therapy (ART). However, aging PLWH face a growing burden of noncommunicable diseases (NCDs), polypharmacy, and drug-drug interactions (DDIs), which pose challenges in their management. This study investigates the prevalence of NCDs, polypharmacy, and DDIs among PLWH aged ≥50 years in Korea and their impact on quality of life (QOL). Materials and Methods: A cross-sectional study was conducted among 243 PLWH aged ≥50 years receiving ART for at least three months at three university hospitals in Korea between January and July 2022. Data were collected through electronic medical records and personal interviews, assessing demographics, comorbidities, polypharmacy, ART adherence, and QOL using the Korean version of WHOQOL-HIV BREF scale. Potential DDIs were analyzed using the University of Liverpool HIV Drug Interaction Database, and potentially inappropriate medications (PIMs) were identified using the 2023 American Geriatrics Society Beers Criteria. We classified participants into three age groups:50–<65 years, 65–<75 years, and ≥75 years. Results: The prevalence of comorbidities was 71.6%, with older participants (≥75 years) showing a significantly higher burden, including bone diseases, osteoarthritis, and dementia (P<0.001). Polypharmacy was observed in 28.4% of participants and increased with age, with 53.3% of those aged ≥75 years taking ≥10 pills daily.Polypharmacy was associated with poorer QOL (71.6 vs. 76.6, P=0.010). Amber-flag DDIs were found in 81 participants (33.3%), most commonly involving metformin and divalent cations. No red-flag DDIs were identified.PIMs were observed in 6.6% of participants aged ≥65 years. Conclusion Aging PLWH in Korea face significant challenges from comorbidities, polypharmacy, and DDIs, which negatively impact QOL. Integrated, age-specific, and multidisciplinary care strategies are urgently needed to improve outcomes and ensure the well-being of older PLWH.