Swab Testing to Optimize Pneumonia treatment with empiric Vancomycin (STOP-Vanc): study protocol for a randomized controlled trial.

Background: Vancomycin, an antibiotic with activity against Methicillin-resistant Staphylococcus aureus (MRSA), is frequently included in empiric treatment for community-acquired pneumonia (CAP) despite the fact that MRSA is rarely implicated in CAP. Conducting polymerase chain reaction (PCR) testing on nasal swabs to identify the presence of MRSA colonization has been proposed as an antimicrobial stewardship intervention to reduce the use of vancomycin. Observational studies have shown reductions in vancomycin use after implementation of MRSA colonization testing, and this approach has been adopted by CAP guidelines. However, the ability of this intervention to safely reduce vancomycin use has yet to be tested in a randomized controlled trial. Methods: STOP-Vanc is a pragmatic, prospective, single center, non-blinded randomized trial. Adult patients with suspicion for CAP who are receiving vancomycin and admitted to the Medical Intensive Care Unit at Vanderbilt University Medical Center will be screened for eligibility. Eligible patients will be enrolled and randomized in a 1:1 ratio to either receive MRSA nasal swab PCR testing in addition to usual care (intervention group), or usual care alone (control group). PCR testing results will be transmitted through the electronic health record to the treating clinicians. Primary providers of intervention group patients with negative swab results will also receive a page providing clinical guidance recommending discontinuation of vancomycin. The primary outcome will be vancomycin-free hours alive, defined as the number of hours alive and free of the use of vancomycin within the first seven days following trial enrollment estimated using a proportional odds ratio model. Secondary outcomes include 30-day all-cause mortality and time alive off vancomycin. Discussion: STOP-Vanc will provide the first randomized controlled trial data regarding the use of MRSA nasal swab PCR testing to guide antibiotic de-escalation. This study will provide important information regarding the effect of MRSA PCR testing and antimicrobial stewardship guidance on clinical outcomes in an intensive care unit setting. Trial registration: This trial was registered on ClinicalTrials.gov on February 22, 2024. (ClinicalTrials.gov identifier: NCT06272994).

Neuroimaging and fluid biomarkers in Parkinson's disease in an era of targeted interventions.

A major challenge in Parkinson's disease is the variability in symptoms and rates of progression, underpinned by heterogeneity of pathological processes. Biomarkers are urgently needed for accurate diagnosis, patient stratification, monitoring disease progression and precise treatment. These were previously lacking, but recently, novel imaging and fluid biomarkers have been developed. Here, we consider new imaging approaches showing sensitivity to brain tissue composition, and examine novel fluid biomarkers showing specificity for pathological processes, including seed amplification assays and extracellular vesicles. We reflect on these biomarkers in the context of new biological staging systems, and on emerging techniques currently in development.

Selective mural cell recruitment of pericytes to networks of assembling endothelial cell-lined tubes.

Mural cells are critically important for the development, maturation, and maintenance of the blood vasculature. Pericytes are predominantly observed in capillaries and venules, while vascular smooth muscle cells (VSMCs) are found in arterioles, arteries, and veins. In this study, we have investigated functional differences between human pericytes and human coronary artery smooth muscle cells (CASMCs) as a model VSMC type. We compared the ability of these two mural cells to invade three-dimensional (3D) collagen matrices, recruit to developing human endothelial cell (EC)-lined tubes in 3D matrices and induce vascular basement membrane matrix assembly around these tubes. Here, we show that pericytes selectively invade, recruit, and induce basement membrane deposition on EC tubes under defined conditions, while CASMCs fail to respond equivalently. Pericytes dramatically invade 3D collagen matrices in response to the EC-derived factors, platelet-derived growth factor (PDGF)-BB, PDGF-DD, and endothelin-1, while minimal invasion occurs with CASMCs. Furthermore, pericytes recruit to EC tube networks, and induce basement membrane deposition around assembling EC tubes (narrow and elongated tubes) when these cells are co-cultured. In contrast, CASMCs are markedly less able to perform these functions showing minimal recruitment, little to no basement membrane deposition, with wider and shorter tubes. Our new findings suggest that pericytes demonstrate much greater functional ability to invade 3D matrix environments, recruit to EC-lined tubes and induce vascular basement membrane matrix deposition in response to and in conjunction with ECs.

Impact of dosing schedules on performance of rotavirus vaccines in Ghana.

Background: Available live-oral rotavirus vaccines are associated with low to moderate performance in low- and middle-income settings. There is limited evidence relating to how the vaccine dosing schedule might be adjusted to improve vaccine performance in these settings. Methods: We used mathematical models fitted to rotavirus surveillance data for children <5 years of age from three different hospitals in Ghana (Korle-Bu Teaching Hospital in Accra, Komfo Anokye Teaching Hospital in Kumasi and War Memorial Hospital in Navrongo) to project the impact of rotavirus vaccination over a 10-year period (April 2012-March 2022). We quantified and compared the impact of the previous vaccination program in Ghana to the model-predicted impact for other vaccine dosing schedules across the three hospitals and the entire country, under different assumptions about vaccine protection. To project the rotavirus vaccine impact over Ghana, we sampled from the range of model parameters for Accra and Navrongo, assuming that these two settings represent the "extremes" of rotavirus epidemiology within Ghana. Results: For the previously implemented 6/10-week monovalent Rotarix vaccine (RV1) schedule, the model-estimated average annual incidence of moderate-to-severe rotavirus-associated gastroenteritis (RVGE) ranged between 1,151 and 3,002 per 100,000 people per year over the 10-year period for the three sites. Compared to no vaccination, the model-estimated median percentage reductions in RVGE ranged from 28-85% and 12-71% among children <1 year and <5 years of age respectively, with the highest and lowest percentage reductions predicted using model parameters estimated for Accra and Navrongo, respectively. The median predicted reductions in RVGE for the whole country ranged from 57-66% and 35-45% among children <1 year and <5 years of age, respectively. The 1/6/10- and 6/10/14-week schedules provided the best and comparable reductions in RVGE compared to the original 6/10-week schedule, whereas there was no improvement in impact for the 10/14-week schedule. Conclusions: We found that administering an additional dose of RV1 might be an effective strategy to improve rotavirus vaccine impact, particularly in settings with low vaccine effectiveness. The results could be extrapolated to other countries using a 2-dose vaccine schedule with low to moderate vaccine performance.

Structural variant landscapes reveal convergent signatures of evolution in sheep and goats.

BACKGROUND: Sheep and goats have undergone domestication and improvement to produce similar phenotypes, which have been greatly impacted by structural variants (SVs). Here, we report a high-quality chromosome-level reference genome of Asiatic mouflon, and implement a comprehensive analysis of SVs in 897 genomes of worldwide wild and domestic populations of sheep and goats to reveal genetic signatures underlying convergent evolution. RESULTS: We characterize the SV landscapes in terms of genetic diversity, chromosomal distribution and their links with genes, QTLs and transposable elements, and examine their impacts on regulatory elements. We identify several novel SVs and annotate corresponding genes (e.g., BMPR1B, BMPR2, RALYL, COL21A1, and LRP1B) associated with important production traits such as fertility, meat and milk production, and wool/hair fineness. We detect signatures of selection involving the parallel evolution of orthologous SV-associated genes during domestication, local environmental adaptation, and improvement. In particular, we find that fecundity traits experienced convergent selection targeting the gene BMPR1B, with the DEL00067921 deletion explaining ~10.4% of the phenotypic variation observed in goats. CONCLUSIONS: Our results provide new insights into the convergent evolution of SVs and serve as a rich resource for the future improvement of sheep, goats, and related livestock.

Potential association between PSCA rs2976395 functional variant and pancreatic cancer risk.

Correlated regions of systemic interindividual variation (CoRSIV) represent a small proportion of the human genome showing DNA methylation patterns that are the same in all human tissues, are different among individuals, and are partially regulated by genetic variants in cis. In this study we aimed at investigating single-nucleotide polymorphisms (SNPs) within CoRSIVs and their involvement with pancreatic ductal adenocarcinoma (PDAC) risk. We analyzed 29,099 CoRSIV-SNPs and 133,615 CoRSIV-mQTLs in 14,394 cases and 247,022 controls of European and Asian descent. We observed that the A allele of the rs2976395 SNP was associated with increased PDAC risk in Europeans (p = 2.81 × 10-5). This SNP lies in the prostate stem cell antigen gene and is in perfect linkage disequilibrium with a variant (rs2294008) that has been reported to be associated with risk of many other cancer types. The A allele is associated with the DNA methylation level of the gene according to the PanCan-meQTL database and with overexpression according to QTLbase. The expression of the gene has been observed to be deregulated in many tumors of the gastrointestinal tract including pancreatic cancer; however, functional studies are needed to elucidate the function relevance of the association.

Pregnancy risk in beef and dairy cows after supplementing semen with transforming growth factor beta-1 at the time of artificial insemination.

Our objective was to determine if the addition of a concentrated human recombinant transforming growth factor beta-1 (TGF) to bovine semen at the time of AI would result in increased risk of pregnancy in beef and dairy cows. Suckled beef cows (n = 1,132) in 11 herds across 2 states and lactating dairy cows (n = 2,208) in one organic-certified herd were enrolled. Beef cows received fixed-time AI (FTAI) following a 7 d CO-Synch + controlled internal drug release estrous synchronization protocol. Dairy cows were inseminated following observation of natural estrus expression. Cows received either no treatment as a control (CON) or 10 ng of TGF in 10 µl added through the cut-end of a thawed straw of semen immediately prior to AI. At the time of FTAI of beef cows, the mean ± SD age was 5.0 ± 2.4 yr, BCS was 5.3 ± 0.7, and days postpartum was 78.2 ± 15.5 d. The overall pregnancy risk in beef cows was 55.2% to AI and 90.5% season-long. Pregnancy risk in beef cows was not affected (P = 0.27) by addition of TGF (53.1% vs. 58.1%). Further, there was no difference (P = 0.88) for season-long pregnancy risk in beef cows that received TGF (91.2% vs. 91.5%). At the time of insemination of dairy cows, the mean ± SD lactation was 3.0 ± 1.3 lactations, BCS was 2.9 ± 0.3, days in milk was 115.6 ± 56.6 d, and cows had received 2.4 ± 1.5 inseminations per cow. The overall pregnancy risk to AI in dairy cows was 23.1%. Pregnancy risk to AI for dairy cows was not affected (P = 0.32) by addition of TGF (22.0% vs. 23.8%). In conclusion, pregnancy risk to AI was not affected by addition of TGF to thawed semen immediately prior to AI in beef or dairy cows.

Insufficient PD-1 expression during active autoimmune responses: a deep single-cell proteomics analysis in inflammatory arthritis.

Objectives: Programmed cell death protein-1 (PD-1) maintains peripheral immune tolerance by preventing T cell continuous activation. Aiming to understand the extent of PD-1 expression in inflammatory arthritis beyond its involvement with T cells, we assess its presence on various circulating single cells. Methods: Mass cytometry analysis of patients with active seropositive/seronegative rheumatoid (RA; n=9/8) and psoriatic (PsA; n=9) arthritis versus healthy controls (HC; n=13), re-evaluating patients after 3 months of anti-rheumatic treatment. Results: PD-1 was expressed in all leukocyte subpopulations, with the highest PD-1+ cell frequencies in eosinophils (59-73%) and T cells (50-60%), and the lowest in natural-killer cells (1-3%). PD-1+ cell frequencies and PD-1 median expression were comparable between patient subgroups and HC, in the majority of cell subsets. Exceptions included increases in certain T cell/B cell subsets of seropositive RA and specific monocyte subsets and dendritic cells of PsA; an expanded PD-1+CD4+CD45RA+CD27+CD28+ T subset, denoting exhausted T cells, was common across patient subgroups. Strikingly, significant inverse correlations between individual biomarkers of systemic inflammation (ESR and/or serum CRP) and PD-1+ cell frequencies and/or median expression were evident in several innate and adaptive immunity cell subsets of RA and PsA patients. Furthermore, all inverse correlations noted in individuals with active arthritis were no longer discernible in those who attained remission/low disease activity post-treatment. Conclusion: PD-1 expression may be insufficient, relative to the magnitude of the concomitant systemic inflammatory response on distinct leukocyte subsets, varying between RA and PsA. Our results point to the potential therapeutic benefits of pharmacological PD-1 activation, to rebalance the autoimmune response and reduce inflammation.

Unlocking Peer Review: Elevating Scholarly Writing and Research Competence in Urology Residency.

PURPOSE OF REVIEW: It is incumbent upon training programs to set the foundation for evidence-based practices and to create opportunities for trainees to develop into academic leaders. As dedicated resident research time and funding have declined in recent years, residency programs and the field at large will need to create new ways to incorporate scholarly activity into residency curricula. RECENT FINDINGS: Literature across specialties demonstrates barriers to resident involvement including lack of time, cost, and absent scholarly mentorship. Peer review stands as a ready-made solution that can be formalized into a collaborative relationship with journals. A formal relationship between professional societies, academic journals, and residencies can facilitate the use of peer review as a teaching tool for residency programs.

Transcriptomic profiling of gastrointestinal tracts in dairy cattle during lactation reveals molecular adaptations for milk synthesis.

During lactation, dairy cattle's digestive tract requires significant adaptations to meet the increased nutrient demands for milk production. As we attempt to improve milk-related traits through selective pressure, it is crucial to understand the biological functions of the epithelia of the rumen, small intestine, and colonic tissues in response to changes in physiological state driven by changes in nutrient demands for milk synthesis. In this study, we obtained a total of 108 transcriptome profiles from three tissues (epithelia of the colon, duodenum, and rumen) of five Holstein cows, spanning eight time points from the early, mid, late lactation periods to the dry period. On average 97.06% of reads were successfully mapped to the reference genome assembly ARS-UCD1.2. We analyzed 27,607 gene expression patterns at multiple periods, enabling direct comparisons within and among tissues during different lactation stages, including early and peak lactation. We identified 1645, 813, and 2187 stage-specific genes in the colon, duodenum, and rumen, respectively, which were enriched for common or specific biological functions among different tissues. Time series analysis categorized the expressed genes within each tissue into four clusters. Furthermore, when the three tissues were analyzed collectively, 36 clusters of similarly expressed genes were identified. By integrating other comprehensive approaches such as gene co-expression analyses, functional enrichment, and cell type deconvolution, we gained profound insights into cattle lactation, revealing tissue-specific characteristics of the gastrointestinal tract and shedding light on the intricate molecular adaptations involved in nutrient absorption, immune regulation, and cellular processes for milk synthesis during lactation.

Dynamin 1xA interacts with Endophilin A1 via its spliced long C-terminus for ultrafast endocytosis.

Dynamin 1 mediates fission of endocytic synaptic vesicles in the brain and has two major splice variants, Dyn1xA and Dyn1xB, which are nearly identical apart from the extended C-terminal region of Dyn1xA. Despite a similar set of binding partners, only Dyn1xA is enriched at endocytic zones and accelerates vesicle fission during ultrafast endocytosis. Here, we report that Dyn1xA achieves this localization by preferentially binding to Endophilin A1 through a newly defined binding site within its long C-terminal tail extension. Endophilin A1 binds this site at higher affinity than the previously reported site, and the affinity is determined by amino acids within the Dyn1xA tail but outside the binding site. This interaction is regulated by the phosphorylation state of two serine residues specific to the Dyn1xA variant. Dyn1xA and Endophilin A1 colocalize in patches near the active zone, and mutations disrupting Endophilin A binding to the long tail cause Dyn1xA mislocalization and stalled endocytic pits on the plasma membrane during ultrafast endocytosis. Together, these data suggest that the specificity for ultrafast endocytosis is defined by the phosphorylation-regulated interaction of Endophilin A1 with the C-terminal extension of Dyn1xA.

The Gut Microbiome and Symptom Burden After Kidney Transplantation: An Overview and Research Opportunities.

Many kidney transplant recipients continue to experience high symptom burden despite restoration of kidney function. High symptom burden is a significant driver of quality of life. In the post-transplant setting, high symptom burden has been linked to negative outcomes including medication non-adherence, allograft rejection, graft loss, and even mortality. Symbiotic bacteria (microbiota) in the human gastrointestinal tract critically interact with the immune, endocrine, and neurological systems to maintain homeostasis of the host. The gut microbiome has been proposed as an underlying mechanism mediating symptoms in several chronic medical conditions including irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, and psychoneurological disorders via the gut-brain-microbiota axis, a bidirectional signaling pathway between the enteric and central nervous system. Post-transplant exposure to antibiotics, antivirals, and immunosuppressant medications results in significant alterations in gut microbiota community composition and function, which in turn alter these commensal microorganisms' protective effects. This overview will discuss the current state of the science on the effects of the gut microbiome on symptom burden in kidney transplantation and future directions to guide this field of study.

Ceramic Implant Rehabilitation: Consensus Statements from Joint Congress for Ceramic Implantology.

The objectives of the study group focused on the following main topics related to the performance of one- and two-piece ceramic implants: defining bone-implant-contact percentages and its measurement methods, evaluating the pink esthetic score as an esthetic outcome parameter after immediate implantation, recognizing the different results of ceramic implant designs, as redefined by the German Association of Oral Implantology, incorporating the patient report outcome measure to include satisfaction and improvement in oral health-related quality of life, and conducting preclinical studies to address existing gaps in ceramic implants. During the Joint Congress for Ceramic Implantology (2022), the study group evaluated 17 clinical trials published between 2015 and 2021. After extensive discussions and multiple closed sessions, consensus statements and recommendations were developed, incorporating all approved modifications. A one-piece implant design features a coronal part that is fused to the implant body or interfaces with the post-abutment restoration platform, undergoing transmucosal healing. Long-term evaluations of this implant design have been supported by established favorable clinical evidence. Inaccuracies in the pink esthetic score and bone-implant-contact percentages were managed by establishing control groups for preclinical studies and randomizing clinical trials. The patient-reported outcome measures were adjusted to include an individual visual analog scale, collected from each clinical study, that quantified improved oral health and quality of life. Preclinical investigations should focus on examining the spread of ceramic debris and the impact of heat generation on tissue and cellular levels during drilling. Further technical advancements should prioritize wound management and developing safe drilling protocols.

Severity of effect considerations regarding the use of mutation as a toxicological endpoint for risk assessment: A report from the 8th International Workshop on Genotoxicity Testing (IWGT).

Exposure levels without appreciable human health risk may be determined by dividing a point of departure on a dose-response curve (e.g., benchmark dose) by a composite adjustment factor (AF). An "effect severity" AF (ESAF) is employed in some regulatory contexts. An ESAF of 10 may be incorporated in the derivation of a health-based guidance value (HBGV) when a "severe" toxicological endpoint, such as teratogenicity, irreversible reproductive effects, neurotoxicity, or cancer was observed in the reference study. Although mutation data have been used historically for hazard identification, this endpoint is suitable for quantitative dose-response modeling and risk assessment. As part of the 8th International Workshops on Genotoxicity Testing, a sub-group of the Quantitative Analysis Work Group (WG) explored how the concept of effect severity could be applied to mutation. To approach this question, the WG reviewed the prevailing regulatory guidance on how an ESAF is incorporated into risk assessments, evaluated current knowledge of associations between germline or somatic mutation and severe disease risk, and mined available data on the fraction of human germline mutations expected to cause severe disease. Based on this review and given that mutations are irreversible and some cause severe human disease, in regulatory settings where an ESAF is used, a majority of the WG recommends applying an ESAF value between 2 and 10 when deriving a HBGV from mutation data. This recommendation may need to be revisited in the future if direct measurement of disease-causing mutations by error-corrected next generation sequencing clarifies selection of ESAF values.

Application of intraoperative structured light scanning to enable post-operative evaluation of digital and 3D-printed penile models.

BACKGROUND: Penile phenotype in hypospadias is currently assessed visually or manually (e.g., ruler, goniometer) for clinical, education, and research applications. However, these methods lack precision and accuracy across raters and cannot be reevaluated retrospectively following a surgical repair. The project aim was to evaluate the precision and reliability of penile dimensions obtained from digital and three dimensional (3D) printed models created from intraoperative (OR) structured light scans (SLS) during primary pediatric penile procedures. METHODS: Boys ages 1 month to 6 years underwent first- or single-stage penile surgery at a single institution were enrolled in this prospective study (IRB #20-000143). For each patient, immediately following placement of a stay suture under consistent manual tension, intra-operative dimension measurements with a ruler were obtained. A digital 3D model was created prior to penile repositioning using an Artec Space Spider scanner and Artec Studio 13 software. Following the case, two different raters completed 10 digital measurements of each generated model in Autodesk Fusion 360. These digital models were subsequently 3D printed and two different raters completed 10 manual dimension measurements of each 3D printed model using a ruler. A one-way random effects intraclass correlation coefficient (ICC) evaluated measures of agreement between and within raters, respectively. Analyses were conducted in R version 4.2. RESULTS: Six scans were obtained (hypospadias: 4, circumcision: 2). Intra-rater assessments showed excellent precision across repeated digital measurements; manual measurements of 3D printed models had excellent reliability for glans width and penile length but poor to good reliability for glans height. Inter-rater reliability was good to excellent for glans width (0.77-0.95) and good for penile length (0.71-0.88). However, there was poor inter-rater reliability for glans height (0-0.14). Following training regarding glans height location, there was an improvement in precision and repeatability of manual and digital measurements. CONCLUSION: Digital measurement of OR-derived 3D models resulted in excellent repeatability for each rater and improved between-rater reliability over manual measurement of 3D printed models alone, ensuring that images can be compared by various surgeons both now and in the future. SLS is promising as a novel modality to digitally generate 3D models, thereby informing phenotypic analysis for research and education. Further development of digital measurement methods to ensure consistency between raters for quantitative assessment of additional parameters and assessment of the technology within the pre-operative environment for surgical planning is planned.

Synthesis of guidance available for assessing methodological quality and grading of evidence from qualitative research to inform clinical recommendations: a systematic literature review.

OBJECTIVE: To understand (1) what guidance exists to assess the methodological quality of qualitative research; (2) what methods exist to grade levels of evidence from qualitative research to inform recommendations within European Alliance of Associations for Rheumatology (EULAR). METHODS: A systematic literature review was performed in multiple databases including PubMed/Medline, EMBASE, Web of Science, COCHRANE and PsycINFO, from inception to 23 October 2020. Eligible studies included primary articles and guideline documents available in English, describing the: (1) development; (2) application of validated tools (eg, checklists); (3) guidance on assessing methodological quality of qualitative research and (4) guidance on grading levels of qualitative evidence. A narrative synthesis was conducted to identify key similarities between included studies. RESULTS: Of 9073 records retrieved, 51 went through to full-manuscript review, with 15 selected for inclusion. Six articles described methodological tools to assess the quality of qualitative research. The tools evaluated research design, recruitment, ethical rigour, data collection and analysis. Seven articles described one approach, focusing on four key components to determine how much confidence to place in findings from systematic reviews of qualitative research. Two articles focused on grading levels of clinical recommendations based on qualitative evidence; one described a qualitative evidence hierarchy, and another a research pyramid. CONCLUSION: There is a lack of consensus on the use of tools, checklists and approaches suitable for appraising the methodological quality of qualitative research and the grading of qualitative evidence to inform clinical practice. This work is expected to facilitate the inclusion of qualitative evidence in the process of developing recommendations at EULAR level.

Spatial N-glycomics of the normal breast microenvironment reveals fucosylated and high-mannose N-glycan signatures related to BI-RADS density and ancestry.

Higher breast cancer mortality rates continue to disproportionally affect black women (BW) compared to white women (WW). This disparity is largely due to differences in tumor aggressiveness that can be related to distinct ancestry-associated breast tumor microenvironments (TMEs). Yet, characterization of the normal microenvironment (NME) in breast tissue and how they associate with breast cancer risk factors remains unknown. N-glycans, a glucose metabolism-linked post-translational modification, has not been characterized in normal breast tissue. We hypothesized that normal female breast tissue with distinct Breast Imaging and Reporting Data Systems (BI-RADS) categories have unique microenvironments based on N-glycan signatures that varies with genetic ancestries. Profiles of N-glycans were characterized in normal breast tissue from BW (n = 20) and WW (n = 20) at risk for breast cancer using matrix assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI). A total of 176 N-glycans (32 core-fucosylated and 144 noncore-fucosylated) were identified in the NME. We found that certain core-fucosylated, outer-arm fucosylated and high-mannose N-glycan structures had specific intensity patterns and histological distributions in the breast NME dependent on BI-RADS densities and ancestry. Normal breast tissue from BW, and not WW, with heterogeneously dense breast densities followed high-mannose patterns as seen in invasive ductal and lobular carcinomas. Lastly, lifestyles factors (e.g. age, menopausal status, Gail score, BMI, BI-RADS) differentially associated with fucosylated and high-mannose N-glycans based on ancestry. This study aims to decipher the molecular signatures in the breast NME from distinct ancestries towards improving the overall disparities in breast cancer burden.