Journal of Advanced Research

Abstract Background: Glycosylated RNAs (GlycoRNAs) participate in immune recognition and intercellular communication, but their relationship with brain cell-type transcriptional signatures in major depressive disorder (MDD) remains unclear. We examined GlycoRNA-related transcriptional coupling with microglial and other cellular signatures in the dorsolateral prefrontal cortex (DLPFC). Method: Postmortem DLPFC transcriptomic data from 22 controls and 26 MDD patients (GSE102556) were analyzed. GlycoRNA-related pathway enrichment was quantified using gene set variation analysis (GSVA), whereas microglial, neuronal, astrocytic, and oligodendrocytic signatures were derived using single-sample gene set enrichment analysis (ssGSEA). Pearson correlations, linear regression, and generalized estimating equations (GEE) evaluated cell-type-specific associations and diagnostic interactions. Exploratory GEE results underwent false discovery rate (FDR) correction. Results: No differentially expressed genes survived FDR correction, and GlycoRNA-related and cell-type signatures did not differ significantly between groups. In controls, GlycoRNA enrichment was positively associated with the microglial signature (beta = 0.447, FDR-adjusted P = 0.006), with significantly weaker associations for neurons, astrocytes, and oligodendrocytes (all FDR-adjusted P < 0.05). The two-way GlycoRNA x is_microglia interaction was nominally significant (beta = 0.210, P = 0.048), confirming that GlycoRNA transcriptional coupling is substantially stronger for microglia than for the other three cell types combined. The microglial association was numerically attenuated in MDD (beta difference = -0.273, P = 0.167), but diagnostic interactions were nonsignificant. Conclusions: GlycoRNA pathway transcriptional enrichment exhibits preferential microglial association in control DLPFC. Its possible attenuation in MDD remains to be validated. keyword: Major depressive disorder; GlycoRNA; microglia; dorsolateral prefrontal cortex; generalized estimating equation; ssGSEA; bioinformatics

Introduction: Neuroinflammation is a known pathophysiologic mechanism in multiple sclerosis and a proposed mechanism in fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Positron Emission Tomography (PET) imaging of the translocator protein (TSPO) has been widely used to measure neuroinflammation, though second-generation ligands are highly sensitive to a single nucleotide polymorphism, rs6971, resulting in high, mixed, and low affinity binders. It is unknown whether this polymorphism is associated with neuroinflammatory disorders. Materials and Methods: Eighty-six total participant genotypes for TSPO binding affinity were identified through Sanger sequencing (30 fibromyalgia, 21 ME/CFS, 11 multiple sclerosis, and 24 healthy controls). Associations between patient group and genotype were assessed with Fishers Exact test. Associations between genotype and symptom severity from self-report questionnaires were assessed with Kruskal-Wallis tests. Results: In the present study individuals with fibromyalgia, (ME/CFS), or multiple sclerosis were more likely to have a mixed- or low-affinity genotypes compared to healthy controls. Presence of the low or mixed genotypes were also associated with greater self-reported fatigue severity and depressive symptoms. Discussion: These findings should be confirmed in larger samples but suggest functional consequences of rs6971 polymorphism that may be related to the pathophysiology of pain and fatigue illnesses.

Objective: Current guidelines recommend different adjuvant treatment strategies for women with endometrioid early stage endometrial cancer exhibiting a p53 abnormal pattern. We aimed to evaluate recurrence patterns and explore the clinical implications for adjuvant therapy in this population. Materials and methods: This multicenter retrospective study included 86 patients with endometrioid, p53 abnormal, FIGO stage I, II endometrial cancer treated between 2013 and 2023 at six hospitals in the Republic of Korea. Clinicopathologic data were collected through medical record review. Progression free survival (PFS) was estimated using the Kaplan Meier method, and prognostic factors were analyzed using Cox proportional hazards regression models. Results: The 12, 24, and 36 month PFS rates were 91%, 78%, and 76%, respectively. Among the 16 patients who experienced recurrence, 12 (75%) had distant metastases. Adjuvant chemotherapy showed a trend toward improved PFS compared with adjuvant radiation therapy with or without chemotherapy (p=0.10). In multivariable analysis, the p53 overexpression pattern was independently associated with worse PFS compared with the p53 null pattern (HR 8.59, 95% CI 1.61 to 45.79, p=0.01). Conclusion: Given the poor PFS, the predominance of distant recurrence and the observed trend toward improved PFS with chemotherapy, adjuvant chemotherapy may be considered in women with endometrioid early stage endometrial cancer exhibiting a p53 abnormal pattern. Further studies are warranted to clarify the prognostic impact of p53 abnormality subtypes.

Chemobrain, characterized by cognitive dysfunction, has emerged as a significant health concern following cancer treatment. Doxorubicin, an FDA-approved chemotherapeutic agent, is widely used to treat various cancers. However, its adverse effects raise concerns regarding toxicity in non-cancerous cell types. Microglia, the resident immune cells of the brain, play a central role in maintaining neural homeostasis. Despite this, the mechanisms by which microglia become dysfunctional following doxorubicin exposure remain poorly understood. Understanding the transcriptomic alterations induced by doxorubicin in microglia could provide critical insights into mechanisms underlying its neurotoxic effects. In this study, the transcriptomic response of human microglia to doxorubicin using mRNA sequencing combined with bioinformatic analysis was investigated. Exposure to doxorubicin significantly altered microglial morphology, promoting a shift toward a process-bearing phenotype in human HMC3 cells. This phenotypic change was accompanied by elevated levels of DNA damage and was associated with the induction of cellular senescence. At the gene regulation level, the Illumina-based transcriptomic analysis provided 25,834 gene expression profiling in which 5,669 were differentially expressed. The future analyses revealed that 3,431 (upregulated) and 2,238 (downregulated) were differentially expressed under the treatment of doxorubicin. Genes associated with the p53 signaling pathway and inflammatory responses were upregulated, whereas genes involved in translation, DNA replication, and cell-cycle progression were downregulated. This transcriptional dysregulation was accompanied by differential expression of key transcription factors. This study provides transcriptomic evidence elucidating the genotoxic response to doxorubicin in microglial cells, offering mechanistic insights into chemobrain and highlighting key molecular pathways as potential targets for therapeutic intervention.

Background: Pre-operative triage of adnexal masses with serum CA-125, HE4, and ultrasound (O-RADS) has limited accuracy, contributing to unnecessary surgery. We develop and validate a first of its kind, biomarker panel-free plasma proteomic classifier that distinguishes malignant from benign adnexal masses from a single blood draw, operating directly on discovery-mode mass spectrometry. Methods: In this multicenter prospective observational study, plasma from women with adnexal masses and from healthy controls at a large urban academic center (discovery and four validation cohorts) and an external academic center from another Urban-suburban area (external validation) was analyzed by data-independent-acquisition mass spectrometry (Orbitrap Astral), quantifying >1,000 proteins per sample. Cancerous (malignant, borderline adnexal mass, or metastasis to ovary) versus benign adnexal masses were classified with ADAPT-MS (Adaptive Diagnostic Architecture for Personalized Testing by Mass Spectrometry), which retrains an ElasticNet model for each sample based on the proteins measured. The primary outcome was discrimination (area under the receiver operating characteristic curve [AUC]). Pre-operative O-RADS scores and serum CA-125 were compared and combined with proteomics on matched subsets. Findings: Using a discovery cohort (n=1062), an ADAPT-MS classifier, validated across five independent cohorts (n=623), achieved a summary AUC of 0.835 (cohort range 0.779-0.904). Among patients with pre-operative O-RADS (n=231), proteomics (AUC 0.852) was comparable to O-RADS alone (0.863) and combining them raised discrimination to 0.922. Proteomics outperformed serum CA-125 (0.915 versus 0.777; n=125) and proteome-derived ROMA-like and two-marker surrogates. Biologically, the classification-relevant proteins are enriched for host response proteins rather than tumor cell associated protein changes, comprising ECM remodeling, complement and innate immune response pathways. This explains good detection of tumor with heterogenous pathology and also metastasis to ovary. Interpretation: A single plasma proteomic measurement interpreted using adaptive machine learning discriminates malignant from benign adnexal masses with good internal and external validation, and is complementary to ultrasound, warranting prospective evaluation as a panel-free diagnostic adjunct to imaging.

Introduction: Tumors are known to develop genomic heterogeneity over time, particularly in metastatic disease, raising concerns that a single-site biopsy may be insufficient to accurately predict response to medications. Methods: We used our 3D microtumor functional profiling platform that preserves key features of the native tumor microenvironment. We tested (i) six split samples from primary tumors and (ii) seven samples from primary tumors (ovarian, colon, and breast cancer) matched with their locoregional or distant metastases. Fresh tissue specimens were processed within 24 hours after surgery and treated with NCCN guideline-recommended chemo or targeted therapies at concentrations over four orders of magnitude. Cytotoxicity was evaluated after three days to generate dose response curves. The response correlations between the split sample or between the two matched sites were quantified using the concordance correlation coefficient ({rho}c) for the drug efficacy metrics. Results: We compared a total of 275 drug responses. The six split samples resulted in a strong correlation between the two tumor areas ({rho}c=0.95, p<0.001), supporting high assay reproducibility across distinct regions of the same tumor. Locoregional metastases were highly correlated with their primaries (ovarian to omentum {rho}c=0.97, p<0.001; ovarian to liver capsule {rho}c=0.93, p<0.001; colon to peritoneum {rho}c=0.91, p<0.001). A lesser correlation was observed with lymphogenic metastases (breast to axilla {rho}c=0.87, p<0.001), and the correlations of hematogenic metastases were even lower (colon to lung {rho}c=0.69 p<0.001; ovarian to soft tissue/colon {rho}c=0.58, p<0.001). No correlation was observed among specimens that were resistant to all tested medications. Conclusion: Tumor drug responses were highly preserved in locoregional metastases, whereas somewhat greater divergence was observed in lymphogenic or hematogenic metastases. Single-site functional profiling may remain informative for identifying treatment resistance and might reduce the risk of ineffective therapy selection in metastatic disease.

Humans often communicate meaningfully during existential transition, yet the structure of final communications before death remains poorly understood. Suicide notes provide rare behavioral records, but two questions remain unresolved: whether note-leavers represent the broader population of suicide decedents, and whether notes follow systematic narrative structures. We analyzed a nationwide police-investigated registry of 102,922 suicide deaths in South Korea from 2013 to 2020, including 38,044 notes. Note-leavers differed systematically from non-leavers across demographic, situational and behavioral characteristics, indicating that note production reflects a selective communicative act within the suicidal process. Modeling notes as sequential narratives, we identified consistent patterns across opening, middle and closing sections, organized around apology and shame, love and gratitude, and practical directives concerning post-mortem affairs. Emotional trajectories also varied by age and gender. These findings provide population-scale evidence that suicide notes are structured final communications shaped by social relationships and demographic context under extreme circumstances.

The cornea is the outermost layer of the eye, most vulnerable to injury including from chemical exposure, either environmental, industrial or chemical weapons. For example, exposure of the eye to sulfur mustard (SM) can cause mustard gas keratopathy, resulting in devastating consequences for vision. Available treatments for corneal mustard keratopathy are either ineffective, or if used for a prolonged time, have deleterious side effects. Here, we aimed to harness the anti-inflammatory and anti-angiogenic peptide angiotensin-(1-7), known as Ang-(1-7), that is derived from the renin-angiotensin system (RAS). We designed and developed a protein-like polymer (PLP) displaying a brush of norleucine modified Ang (1-7) peptides (NLE Ang (1-7) PLP), which is a more potent derivative of Ang-(1-7), for administration as an eye drop. In a mouse model of nitrogen mustard (NM)-induced corneal injury, topical treatment and intraperitoneal (i.p.) injection of NLE Ang (1-7) PLP persistently minimized: (i) corneal haze; (ii) edema; (iii), expression of pro-inflammatory and pro-angiogenic genes; and (iv) neovascularization and conjunctivalization as evidenced after a prolonged treatment and recovery period. Collectively, our observations have demonstrated the efficacy of this novel polymer proteomimetic based eye drop treatment in reducing chemical agent-induced corneal injury as well as indicating its potential application in other ocular surface diseases associated with inflammation and angiogenesis.

During pregnancy, mother and fetus co-exist albeit as two physiologically distinct individuals, connected through the placenta and the umbilical cord. This connection allows for the exchange of vital substances, while individual blood homeostasis remains intact. We hypothesized that comparing maternal and cord plasma (N-glyco)proteomes would provide insights into the biological communication and unique physiological state of each individual. As comparing only matched maternal and umbilical cord blood plasma misses a crucial identifier in determining whether observed changes are related to infancy, pregnancy or both, we designed a triad study by adding a non-pregnant women control group. This allowed us to distinguish pregnancy-specific proteins and their potentially altered N-glycosylation from those in infancy. We found that the fetus and mother have distinct proteomes, N-glycoproteoforms and alternative complement regulation. Moreover, we observed that pregnancy in women led to specific N-glycosylation changes on a select set of primarily HDL-associated and acute-phase proteins. Lastly, our data provide evidence for an early fetal development of the humoral immune system as especially fetal IgM displayed distinctive N-glycosylation signatures.

Influenza A virus (IAV) defective interfering particles (DIPs) are regarded as promising broad-spectrum antivirals due to their high efficacy demonstrated in animal trials. Previously, an OP7 chimera DIP was generated that showed markedly enhanced antiviral efficacy compared to conventional IAV DIPs. In addition, a high-yield cell culture-based production process for OP7 chimera DIPs was established in perfusion mode. However, due to the technical complexity of this technology, we aimed to combine the advantages of perfusion in terms of yield with that of a simple and less complex batch process. In the present work, we established a fed-batch production process for OP7 chimera DIPs that allows a more straightforward implementation into existing production facilities. Using a feeding regime that was able to overcome the cell density effect, we achieved productive virus infection in stirred tank reactors until a cell density of 10E+6 cells/mL. Furthermore, we obtained a high virus titer of 3.8 log10(HAU/100 uL), corresponding to a 3.4-fold increase compared to a reference batch production. Moreover, the produced material demonstrated a significantly increased interfering bioactivity shown by an in vitro potency assay. Interestingly, this efficacy was similarly high as compared to OP7 chimera DIP material previously produced in perfusion mode, despite twofold lower virus titers. Finally, we demonstrate robustness of OP7 chimera DIP seed virus trains, which is significant step towards later pharmaceutical production. Further, corresponding GMP MDCK-PB2(sus) cell and OP7 chimera virus banks are now available for later biomanufacturing further use. In conclusion, the established fed-batch process offers a valid n additional option for pharmaceutical grade OP7 chimera DIP GMP manufacturing production under GMP conditions required for subsequent clinical testing and for later large-scale manufacturing.

BACKGROUND Twin pregnancies have a two- to three-fold higher risk of preeclampsia (PE), but early prediction remains poor because current biomarkers and prediction models are largely derived from singleton pregnancies. Defining the biological changes that precede PE in twins may facilitate the development of more effective risk assessment approaches. OBJECTIVE We aimed to characterize maternal plasma protein changes preceding PE in twin pregnancies and to explore whether early circulating proteins could serve as improved risk stratification for twin PE. STUDY DESIGN We performed a nested case-control study within a prospective twin pregnancy cohort at Peking University Third Hospital. A total of 84 women with twin pregnancies were included, comprising 40 pregnancies complicated by PE and 44 normotensive controls. Longitudinal maternal plasma samples were collected in the first, second, and third trimesters. In the discovery cohort, maternal plasma proteins were profiled by mass spectrometry to identify trimester-specific protein changes associated with PE. Candidate proteins were then validated in an independent validation set. We further assessed the functional relevance of selected proteins in trophoblast and endothelial cell models and constructed prediction models integrating biomarkers with maternal clinical characteristics. RESULTS Twin pregnancies complicated by PE showed distinct trimester-dependent protein alterations, with first- and second-trimester changes mainly involving immune regulation and glycolipid metabolism, and later changes enriched in cardiovascular-related pathways. Several proteins demonstrated early discriminatory patterns, including increased annexin A3, chitotriosidase-1, and ferritin light chain (FTL), together with decreased annexin A2 in the first trimester, whereas the conventional singleton markers (sFlt-1 and PAPP-A) did not differ. ELISA validation of these candidate biomarkers yielded an AUC of 0.93 for twin preeclampsia prediction; integration with standard maternal clinical factors further improved discriminatory performance to an AUC of 0.97. Accordingly, a multivariable model combining annexin A2, annexin A3, chitotriosidase-1, FTL, and maternal clinical factors achieved strong internal performance for early discrimination of PE in twin pregnancies (AUC, 0.97; 95% CI, 0.93-1.00). Moreover, annexin A2 knockdown impaired trophoblast migration and invasion and reduced inflammatory cytokine secretion in endothelial cells, supporting a role in placental development and maternal vascular adaptation. CONCLUSION Twin pregnancies that later develop PE exhibit early and progressive maternal plasma protein alterations that can be detected before clinical disease onset. These findings identify candidate biomarkers and biologically relevant pathways that may help explain why PE in twins differs from singleton disease and may support future twin-specific risk stratification strategies. These results require external validation before clinical application.

BACKGROUND: Because of the high mortality rate associated with fulminant myocarditis (FM), there is limited evidence regarding the prognostic efficacy of endomyocardial biopsy (EMB). In this study, we aimed to evaluate the influence of EMB in the early phase after admission on treatment and prognosis in FM using a large-scale nationwide registry in Japan. METHODS: Patients with FM who required catecholamine or mechanical circulatory support between 2012 and 2017 from 235 hospitals across Japan were included. The primary outcome of death or heart transplantation within 90 days according to performance of early EMB were determined using Kaplan-Meier and Cox regression analyses. Factors associated with performance of early EMB, and subsequent medical treatment were analyzed. RESULTS: The median age of 736 patients with clinical FM was 56 years, and 407 patients (55%) received EMB. Most EMB (89%) were performed during the early phase (within 5 days of admission) and 63% were performed on the first day of admission. The prognosis of FM patients who underwent EMB was more favorable than that of those who did not based on the landmark analysis (log-rank test, P=0.04). Factor analysis demonstrated that FM patients who underwent EMB had a lower left ventricular ejection fraction, higher incidence of cardiogenic shock on admission, and higher rate of early mechanical circulatory support, as well as early initiation of corticosteroids and guideline-directed medical therapy (GDMT) for heart failure. Absence of any GDMT was associated with a less favorable prognosis on multivariate analysis (hazard ratio, 4.34 [95% CI, 3.14?6.01]; P<0.0001). CONCLUSIONS: Although performing EMB in the early phase after admission depends on disease severity in FM patients, it is associated with early initiation of advanced medical treatment and may contribute to improving the prognosis.

The goat research community benefits from one of the most comprehensive livestock genome assemblies, ARS1. However, the rich diversity of goat breeds suggests that a single individual genome is not enough to represent the species full genomic content. Third-generation sequencing technologies have recently made it possible to generate very high quality assemblies that should enable to elucidate unique and/or complex phenotype determinisms depending on genetic structural variations. In the SeqOccin project, nine goat breeds were selected to represent French goat genetic diversity: Alpine, Boer, Creole, Fosses, Poitevine, Provencale, Pyreneenne, Rove and Saanen. High-molecular-weight DNA was extracted from blood samples and subjected to long read whole-genome sequencing. There reads were used to generate de novo assemblies and were aligned onto the public reference to call structural variants. PacBio HiFi and parental Illumina reads were used to assemble phased haplotypes of the Alpine breed. For the other breeds, PacBio raw (CLR) or ONT reads were generated. Our work demonstrates the feasibility of assembling genomes with a reasonable amount of data and appropriate software packages, delivering one high-quality assembly and 8 standard goat assemblies that pave the way for pangenome construction and structural variant functional studies.

HIV infection significantly elevated the odds of cardiovascular diseases, including myocardial fibrosis. We aimed to determine the difference of late gadolinium enhancement (LGE), extracellular volume (ECV), T1, and T2 using cardiac magnetic resonance imaging (CMR) in patients living with HIV (PLWH) and healthy controls. The databases Scopus, Web of Science, Embase, and PubMed were searched systematically using relevant keywords. STATA version 17 was used for meta-analysis using random effect and fixed effect models for heterogeneous and non-heterogeneous analyses. An overall number of 13 studies were included in the current analysis involving 1425 PLWH and 766 healthy controls. PLWH showed significantly higher LGE (OR: 5.47, 95% CI: 1.90-15.64, p<0.001) and ECV (mean difference: 1.46, 95% CI: 0.21-2.71, p=0.02) compared to controls. However, differences in Left Ventricular Ejection Fraction (LVEF) were not significant (mean difference: -1.41, 95% CI: -2.81- -0.01, p=0.05). There were no meaningful disparities in pro B-type natriuretic peptide (BNP) values (mean difference: 8.67, 95% CI: 0.04-17.29, p=0.05) or T2 values (mean difference: 0.91 ms, 95% CI: -1.04-2.86, p=0.36), but T1 values were significantly higher in PLWH (mean difference: 13.78 ms, 95% CI: 9.16-18.40, p<0.001). In meta regression, LGE was correlated with nadir CD4 (z=-3.41, p-value<0.001). In addition, ECV was correlated with white race (Z=-3.97, p-value<0.001), Hepatitis C (Z=-2.08, p-value=0.037), and smoking (Z=2.05, p-value=0.041). HIV is related to a significantly elevated rate of myocardial fibrosis, and factors such as lower nadir CD4, white race, hepatitis C, and smoking were correlated with hepatitis C. Keywords: Myocardial fibrosis, HIV, AIDS, Cardiovascular diseases, Heart failure

Background: Huntington's disease (HD) is an inherited neurodegenerative disorder primarily associated with motor and psychiatric manifestations. No disease-modifying treatment currently exists, with vesicular monoamine transporter type-2 inhibitors (VMAT2i's) being the only FDA-approved therapy for motor features in HD. Previous studies evaluated the antichorea effects of VMAT2i's but did not address its effects on non-choreiform features. Objectives: This study aimed to characterize the effect of VMAT2i's on hyperkinetic, hypokinetic and total hypokinetic subscores of the UHDRS motor assessment in patients with motor-manifest HD from the Enroll-HD research platform. Methods: Data from 622 participants were analyzed. Linear mixed effects models were constructed to compare the rates of change of choreiform and non-choreiform motor scores before and after the initiation of a VMAT2i. We calculated and plotted the direction, magnitude and significance of VMAT2i administration on the rates of change of motor subscores. A similar analysis was performed investigating the effect of antipsychotic medications on motor subscales in HD. Results: VMAT2i's reversed progression of hyperkinesis but significantly increased the rates of change in the hypokinetic and total hypokinetic subscores. Antipsychotics also displayed efficacy in reversing progression of chorea but did not significantly influence progression of hypokinesis. Conclusions: The initiation of VMAT2i's was associated with an improvement in hyperkinesis but was associated with worsening of other motor features of HD. Hypokinesis increases progressively in HD and is correlated with functional impairment and global decline. Therefore, the use of VMAT2i's to treat motor features in HD should be a nuanced decision, considering its multipronged impact.

Minor introns are rare but evolutionarily conserved introns in the human genome. Defects in minor spliceosome components have been reported to cause several human diseases. Mutations in ZRSR2 are frequently observed in myelodysplastic syndrome (MDS) patients. However, the precise molecular mechanism by which these mutations cause a loss of ZRSR2 function in minor intron splicing remain elusive. In this study, we characterized the impact of MDS-causing missense mutations in ZRSR2. Most of the mutant ZRSR2 proteins we tested showed different subnuclear localization pattern from that of wild-type ZRSR2 protein. Co-immunoprecipitation (co-IP) analysis revealed that UHM missense mutations disrupted the interaction between ZRSR2 and SF3B complex. We also demonstrated that ZRSR2 preferentially immunoprecipitated minor spliceosome components over major spliceosome components and it directly interacts with SF3B1. Furthermore, co-IP analysis utilizing a variety of ZRSR2 mutants revealed that mutations in the UHM and Zn2 domains significantly attenuated the interaction with SF3B complex. Finally, UHM and Zn2 mutations markedly disrupted the supporting activity of ZRSR2 for minor intron splicing. Our results indicate that disruption of the physical interaction with SF3B complex is one of the hallmarks of MDS-causing mutations of ZRSR2, which results in aberrant splicing of minor introns.

Dementia is a major global health challenge; however, current diagnostic approaches often rely on invasive or costly procedures. Non-invasive molecular approaches using Raman spectroscopy and sweat-derived extracellular vesicles (EVs) may provide an accessible strategy for characterizing dementia-associated molecular changes. To determine whether Raman spectral profiling of sweat EVs can discriminate individuals with dementia from cognitively healthy controls (HC) and distinguish between Alzheimer disease (AD) and frontotemporal dementia (FTD) including the assessment of a sex-specific spectral signatures. This proof-of-concept cross-sectional study included 88 participants: 26 HC, 37 patients with AD, and 25 patients FTD, comprising female and male participants. Sweat EVs were isolated from sweat patches and characterized using Raman spectroscopy. Differences in Raman spectral signatures between groups and diagnostic performance assessed by receiver operating characteristic analysis. Distinct Raman spectral fingerprints were identified in sweat EVs from dementia patients compared with HC. Participant-level Raman classification discriminated dementia patients from HC with an AUC of 0.76 in the full cohort and 0.83 in a balanced sensitivity analysis. Distinct spectral differences were also observed between AD and FTD, achieving modest classification performance of 0.73 AUC. Sex-stratified analyses further revealed Raman spectral heterogeneity between diagnostic groups, highlighting additional molecular differences that were not observed in the overall cohort. These findings provide proof-of-concept evidence that Raman spectroscopy of sweat EVs can identify dementia-associated molecular signatures potentially related to differences in protein, lipid, and metabolic composition. Furthermore, Raman profiling showed modest ability to differentiate AD from FTD. As a non-invasive approach, our strategy may represent a promising platform for molecular characterization of dementia, warranting validation in larger longitudinal cohorts.

Importance: Phosphorylated tau at threonine 217 (p-tau217) and brain-derived tau (BD-tau) are increasingly used as blood biomarkers of Alzheimer's disease (AD) and related neurological disorders. However, the distributions and biological correlates of elevated plasma p-tau217 and BD-tau in plasma from individuals eligible for blood donation remain unclear. Objective: To estimate the proportions of plasma p-tau217 and BD-tau exceeding exploratory study-specific thresholds, and examine associated inflammatory and transcriptomic features. Design: Cross-sectional study. Setting: Hospital blood bank. Participants: 257 de-identified donor samples were obtained between September 2025 and June 2026. Plasma samples from 30 population reference participants and 20 AD patients were used to derive study-specific thresholds. Complementary transcriptomic analyses were performed in 29 fresh whole blood samples. Main Outcomes and Measures: The primary outcome was the proportion of donor samples exceeding the study-specific ROC-derived Youden threshold. The proportion exceeding the prespecified published p-tau217 threshold was the secondary outcome. Other measures included plasma concentrations of BD-tau, tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6); correlations among plasma p-tau217, BD-tau and inflammatory cytokines; and associated transcriptomic alterations. Results: Plasma p-tau217 concentrations exceeded the study-specific ROC-derived Youden threshold in 53 of 256 donor samples (21%; 95% CI, 16%-26%) and the published threshold, used for a secondary comparison, in 99 of 256 samples (39%; 95% CI, 33%-45%). Plasma BD-tau concentrations exceeded the study-specific threshold in 89 of 257 samples (35%; 95% CI, 29%-41%). Plasma p-tau217 concentrations were positively associated with plasma TNF-alpha (Kendall's tau = 0.339; P < .001) and IL-6 (Kendall's tau = 0.310; P < .001) concentrations. Exploratory transcriptomic analyses identified gene expression patterns associated with p-tau217 concentrations. Measurement using a second p-tau217 antibody showed the similar findings. Conclusions and Relevance: Plasma p-tau217 and BD-tau concentrations exceeded exploratory study-specific thresholds in a subset of blood-donor samples, and higher p-tau217 concentrations were associated with inflammatory biomarkers and exploratory transcriptomic differences. These findings raise the possibility of elevated circulating tau species in some blood donors, but their clinical significance requires confirmation. Whether elevated circulating p-tau217 in donated blood has biological consequences for transfusion recipients is unknown, but deserves investigation.

Perovskite quantum dots (PQDs) are exceptionally promising next-generation optical materials for bioimaging applications. This paper presents an optical PQDs nanocomposite method to identify bacterial species associated with breast cancer, employing a LSTM deep learning model. The results indicate that the developed PQD-based nano-sensor offers impressive sensitivity, selectivity, and practical application. The four bacterial species identified in the study, Pseudomonas aeruginosa, Vibrio parvula, Acinetobacter baumannii, and Streptococcus vestibularis, were considered the most relevant indicators of breast cancer. With rapid detection, an intuitive design, and improved reliability, the PQD sensor could be an excellent breast cancer diagnostic tool for a point-of-care application. Furthermore, it has the potential to be integrated into healthcare systems, specifically in resource-limited settings, thereby improving the accessibility and efficiency of early breast cancer detection.

Objective: Mindfulness is a robust predictor of mental health, yet the psychometric properties of the short-form Five Facet Mindfulness Questionnaire (FFMQ-15) have not been examined in Iranian populations. This study evaluated the psychometric properties, factor structure, and diagnostic utility of the FFMQ-15 among medical sciences students. Participants: A total of 348 students (178 females, 170 males) from Kermanshah University of Medical Sciences participated. Methods: Participants completed the FFMQ-15, Penn State Worry Questionnaire (PSWQ), Difficulties in Emotion Regulation Scale (DERS), and Emotion Regulation Questionnaire (ERQ). Data were analyzed using exploratory and confirmatory factor analyses, composite reliability, and ROC curve analysis. Results: Both EFA and CFA supported the five-factor model, revealing a culturally unique item loading pattern. The FFMQ-15 demonstrated strong convergent and discriminant validity. ROC analysis indicated acceptable diagnostic accuracy for distinguishing high- and low-worry groups (AUC = 0.72, 95% CI: 0.66-0.78). Conclusions: The FFMQ-15 demonstrated acceptable psychometric properties in Iranian medical students. The non-reactivity facet exhibited cultural variability, suggesting that cross-cultural adaptation is essential. The instrument shows promise for screening in high-stress educational settings.