Donated Blood Samples Research Articles

Protection of Omicron Bivalent Vaccine, Previous Infection, and Their Induced Neutralizing Antibodies Against Symptomatic Infection With Omicron XBB.1.16 and EG.5.1.

Data are limited on the protective role of the Omicron BA bivalent vaccine, previous infection, and their induced neutralizing antibodies against Omicron XBB.1.16 and EG.5.1 infection. We conducted a nested case-control analysis among tertiary hospital staff in Tokyo who had received ≥3 doses of COVID-19 vaccines and donated blood samples in June 2023 (1 month before the Omicron XBB.1.16 and EG.5.1 wave). We identified 206 symptomatic cases between June and September 2023 and selected their controls with 1:1 propensity score matching. We examined the association of vaccination, previous infection, and preinfection live virus neutralizing antibody titers against Omicron XBB.1.16 and EG.5.1 with the risk of COVID-19 infection. Previous infection during the Omicron BA- or XBB-dominant phase was associated with a significantly lower infection risk during the XBB.1.16 and EG.5.1-dominant phase than infection-naive status, with 70% and 100% protection, respectively, whereas Omicron BA bivalent vaccination showed no association. Preinfection neutralizing titers against XBB.1.16 and EG.5.1 were 39% (95% CI, 8%-60%) and 28% (95% CI, 8%-44%) lower in cases than matched controls. Neutralizing activity against XBB.1.16 and EG.5.1 was somewhat detectable in the sera of individuals with previous infection but barely detectable in those who were infection naive and received the Omicron bivalent vaccine. In the era when the Omicron XBB vaccine was unavailable, the Omicron BA bivalent vaccine did not confer the neutralizing activity and protection against Omicron XBB.1.16 and EG.5.1 symptomatic infection. The previous infection afforded neutralizing titers and protection against symptomatic infection with these variants.

Correlates of Nucleocapsid Antibodies and a Combination of Spike and Nucleocapsid Antibodies Against Protection of SARS-CoV-2 Infection During the Omicron XBB.1.16/EG.5-Predominant Wave.

We aimed to examine the association among nucleocapsid (N) antibodies, a combination of N and spike (S) antibodies, and protection against SARS-CoV-2 reinfection. We conducted a prospective cohort study among staff at a national medical research center in Tokyo and followed them for the incidence of SARS-CoV-2 infection between June and September 2023 (Omicron XBB.1.16/EG.5 wave). At baseline, participants donated blood samples to measure N- and S-specific antibodies. Cox regression was used to estimate the hazard ratio and protection ([1 - hazard ratio] × 100) against subsequent SARS-CoV-2 infection across these antibody levels. Among participants with previous infection, higher pre-reinfection N antibodies were associated with a lower risk of reinfection, even after adjusting S antibody levels (P < .01 for trend). Estimation of the protection matrix for N and S antibodies revealed that high levels in N and S antibodies conferred robust protection (>90%) against subsequent infection. In addition, a pattern of low pre-reinfection N antibodies but high vaccine-enhanced S antibodies showed high protection (>80%). Pre-reinfection N antibody levels correlated with protection against reinfection, independent of S antibodies. If the N antibodies were low, vaccine-boosted S antibodies might enhance the reinfection protection.

Psychological responses to blood donated by men who have sex with men.

Restrictions previously limiting the ability of men who have sex with men to donate blood are being eased in a number of nations worldwide. In the context of these changes, it is important to determine public perceptions of receiving a transfusion of blood donated by men who have sex with men. In online surveys, 510 (Study 1) and 1,062 (Study 2) heterosexual participants reported attitudes, anxiety, disgust, and gratitude towards potentially receiving a transfusion of blood donated by a homosexual male donor and a heterosexual male donor. In Study 2, half of the participants were reminded of the safety testing carried out on donated blood samples. Negative attitudes, anxiety, disgust, and gratitude were compared between the two donors using t-tests and within-participants indirect effects analysis. Stronger negative attitudes, higher anxiety and disgust, and lower gratitude were reported in relation to a potential transfusion of blood donated by the homosexual male donor relative to the heterosexual male donor (|d|=0.26-0.46). This was the case even when participants were reminded of the safety testing completed on donated blood samples in Study 2. In both studies, the effect of donor sexual orientation on attitudes was explained via heightened anxiety and disgust and attenuated gratitude (b=0.05-0.30). Considering receiving a transfusion of blood donated by a homosexual male donor elicits more negative attitudes, anxiety and disgust, and less positive emotion, relative to blood donated by a heterosexual male donor. These attitudes and emotional reactions are not shifted by a reminder of the safety testing carried out on donated blood samples. In the context of changing restrictions on blood donation by men who have sex with men, these findings highlight a challenge to shift public perception to embrace this cohort of donors.

Vitamin D deficiency during the coronavirus disease 2019 (COVID-19) pandemic among healthcare workers

Vitamin D deficiency is a common nutritional problem worldwide that may have worsened during the coronavirus disease 2019 (COVID-19) pandemic. The present study sought to examine the prevalence and correlates of vitamin D deficiency among healthcare workers three years after the start of the COVID-19 pandemic. Participants comprised 2543 staff members from a medical research institute, who completed a questionnaire and donated blood samples in June 2023. 25-hydroxyvitamin D (25[OH]D) levels were measured using an electrochemiluminescence immunoassay. Logistic regression was used to calculate the odds ratio and its 95% confidence interval while adjusting for covariates. The proportions of participants with vitamin D insufficiency (25[OH]D 20-29ng/mL) and deficiency (25[OH]D<20ng/mL) were 44.9% and 45.9%, respectively. In a multivariable-adjusted model, factors associated with a higher prevalence of vitamin D deficiency included younger age, female sex, fewer hours of daytime outdoor physical activity during leisure time (without regular use of sunscreen), lower intake of fatty fish, no use of vitamin D supplements, smoking, and no alcohol consumption. Occupational factors, including shift work, were not independently associated with vitamin D deficiency. Our results suggest that vitamin D insufficiency and deficiency are highly prevalent among healthcare workers. Health education regarding lifestyle modifications for this occupational group are warranted to improve their vitamin D status in the COVID-19 era.

Alteration of serum bile acids in amyotrophic lateral sclerosis.

Hydrophilic endogenous bile acids ursodeoxycholic acid (UDCA), tauroursodeoxycholic acid (TUDCA), and glucourosodeoxycholic acid (GUDCA) have suggested neuroprotective effects. We performed a case-control study to examine the association between ALS diagnosis and serum levels of bile acids. Sporadic and familial ALS patients, age- and sex-matched healthy controls, and presymptomatic gene carriers who donated blood samples were included. Non-fasted serum samples stored at -80°C were used for the analysis. Serum bile acid levels were measured by liquid chromatography-mass spectrometry (LC-MS). Concentrations of 15 bile acids were obtained, 5 non-conjugated and 10 conjugated, and compared between ALS versus control groups (presymptomatic gene carriers + healthy controls) using the Wilcoxon-Rank-Sum test. In total, 80 participants were included: 31 ALS (17 sporadic and 14 familial ALS); 49 controls (22 gene carriers, 27 healthy controls). The mean age was 50 years old and 50% were male. In the ALS group, 45% had familial disease with a pathogenic variant in C9orf72 (29%), TARDBP (10%), FUS (3%), and CHCHD10 (3%) genes. In the control group, 43% carried pathogenic variants: C9orf72 (27%), SOD1 (10%), and FUS (6%). The serum levels of UDCA, TUDCA, and GUDCA trended higher in the ALS group compared to controls (median 27 vs. 7 nM, 4 vs. 3 nM, 110 vs. 47 nM, p-values 0.04, 0.06, 0.04, respectively). No significant group differences were found in other bile acids serum levels. In conclusion, the serum level of UDCA, TUDCA, GUDCA trended higher in ALS patients compared to controls, and no evidence of deficiencies was found.

Abstract A112: Liquid biopsy shows distinctive proteome of long-term recurrence free survivors after PDAC resection

Abstract Pancreatic ductal adenocarcinoma (PDAC)patients have a 5-year survival rate of less than 10%, partly due to 80% developing recurrence within 2 years after curative intent surgery. As surgical resectability criteria expand and techniques progress, better understanding of tumor biology regarding post-resection prognosis is needed to improve patient outcomes. Our study therefore investigated usefulness of liquid biopsy and proteomics analysis for stratification of post-resection risk groups. Patients undergoing standardized follow-up after resection of PDAC at the European Pancreas Center (Heidelberg, Germany) donated blood samples and clinical data after giving informed consent. Outcomes were extracted from the institutional database or Electronic Health Records and documented retrospectively. From all included patients (n=101) 7mL serum was drawn at different follow-up time points. Overall, 139 samples were collected. Protein expression values of 2953 proteins were determined via antibody microarrays. For analysis and statistics, GenePix 6.0, R and GraphPad Prism were used. First, a principal component analysis was performed on the complete data set. Then the data set was split in a training and test set and A subgroup of 43 patients experienced recurrence of PDAC within 24 months post resection (median: 11.39 months), classified as “early recurrence” (ER). Furthermore, 23 patients experienced recurrence between 26 and 144 months and were termed “late recurrence” (LR). 32 patients had a follow up &amp;gt; 26 months after resection and 6 months after sampling and remained recurrence-free; those were termed “long-term recurrence free survivors” (LT-RFS). Principal component analysis of protein microarray data revealed distinct clustering of LT-RFS together along the primary axis. Contrarily, all of the samples taken at time of recurrence were exclusively found in other quadrants, as were all samples but one of the ER subgroup preceeding diagnosis of recurrence. Samples of the LR subgroup appeared to shift from clustering with LT-RFS samples towards samples from ER and post-recurrence. Lasso regression yielded a panel of 10 proteins, with a specificity of 98.0%/90.9% and a sensitivity of 89.4%/65.0% (training/test set), for identification of samples from LT-RFS. The findings of our protein microarray analysis on PDAC recurrence monitoring suggest a distinct proteome of patients with RFS of &amp;gt;2a post resection. Furthermore, we found hints that the post-resection proteome undergoes a dynamic shift from recurrence-free phenotype towards a phenotype of recurrence. These data need validation in prospective cohorts to determine clinical relevance, however, they point towards opportunities offered by liquid biopsy for sophisticated disease monitoring post resection and for novel insights into mechanisms of disease in PDAC. A protein panel predictive of long-term RFS might enable personalized follow-up pathways and have a positive impact on frequency and invasiveness of post-resection diagnostic testing for PDAC patients. Citation Format: Teresa Colbatzky, Fawaz N. Al-Shaheri, Andrea S. Bauer, Nathalia Giese, Jörg D. Hoheisel, Ulrike Heger. Liquid biopsy shows distinctive proteome of long-term recurrence free survivors after PDAC resection [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A112.

Whole exome germline sequencing in early-onset prostate cancer patients: Genomic findings and clinical outcomes.

Whole exome sequencing (WES) furthered our understanding of various tumors. We assessed the occurrence of germline likely pathogenic/pathogenic (LP/P) variants, disease features, and clinical outcomes in early-onset prostate cancer. This retrospective study (N = 134) included consecutive prostate cancer patients who donated blood samples for research purposes to the Kahn-Sagol-Maccabi biobank. Patients diagnosed at >65 years were excluded. Clinical characteristics were extracted from the medical records. Germline WES was performed with analysis reporting on oncogenetic, two immunogenic, and a secondary minimum list panels (121, 468, 76, and 59 genes, respectively). Median age at diagnosis was 61 (range 46-65) years; 131 (98%) were diagnosed with local disease. The median follow-up time from diagnosis was 14 (range <1-25) years. Of the patients with local disease, 32 (24%) and 10 (8%) had biochemical and distant recurrences, respectively. Twenty-five patients (19%) had ≥1 additional cancer (excluding non-melanoma skin cancer), most frequently bladder (6), colorectal (5), and lymphoma (5). Seven (5%) deaths were reported, with only one related to prostate cancer. LP/P variants were identified in 8 patients (6%), all in genes from the oncogenetic panel: ATM, BRCA1 (in two patients), BRCA2 (in two patients), HOXB13, MUTYH, and MYH7. Of these eight patients, with a median follow-up of 7 years (range <1-15), two (25%) had biochemical recurrences, one had (12.5%) distant recurrence, and no deaths were reported. In this cohort of 134 early-onset prostate cancer patients, we identified germline LP/P variants in an oncogenetic panel in 6% of participants, with no unique clinical outcome.

Association of high intra-patient variability in tacrolimus exposure with calcineurin inhibitor nephrotoxicity in kidney transplantation

Tacrolimus intra-patient variability (IPV) is a novel predictive marker for long-term kidney transplantation outcomes. We examined the association between IPV and calcineurin inhibitor (CNI) nephrotoxicity and the impact of pharmacogenes on CNI nephrotoxicity and IPV. Among kidney transplant recipients at our hospital between January 2013 and December 2015, the records of 80 patients who underwent 1-year protocol renal allograft biopsy and agreed to donate blood samples for genetic analysis were retrospectively reviewed. The cohort was divided into the low and high IPV groups based on a coefficient variability cutoff value (26.5%). In multivariate analysis, the IPV group was involved in determining CNI nephrotoxicity (HR 4.55; 95% CI 0.05–0.95; p = 0.043). The 5-year graft survival was superior in the low IPV group than in the high IPV group (100% vs 92.4% respectively, p = 0.044). Analysis of the time above therapeutic range (TATR) showed higher CNI nephrotoxicity in the high IPV with high TATR group than in the low IPV with low TATR group (35.7% versus 6.7%, p = 0.003). Genetic analysis discovered that CYP3A4 polymorphism (rs2837159) was associated with CNI nephrotoxicity (HR 28.23; 95% CI 2.2–355.9; p = 0.01). In conclusion, high IPV and CYP3A4 polymorphisms (rs2837159) are associated with CNI nephrotoxicity.

Preinfection Neutralizing Antibodies, Omicron BA.5 Breakthrough Infection, and Long COVID: A Propensity Score-Matched Analysis.

Data are limited on the role of preinfection humoral immunity protection against Omicron BA.5 infection and long coronavirus disease (COVID) development. We conducted nested case-control analysis among tertiary hospital staff in Tokyo who donated blood samples in June 2022 (1 month before Omicron BA.5 wave), approximately 6 months after receiving a third dose of COVID-19 mRNA vaccine. We measured live virus-neutralizing antibody titers against wild type and Omicron BA.5, and anti-receptor-binding domain (RBD) antibody titers at preinfection, and compared them between cases and propensity-matched controls. Among the breakthrough cases, we examined association between preinfection antibody titers and incidence of long COVID. Preinfection anti-RBD and neutralizing antibody titers were lower in cases than controls. Neutralizing titers against wild type and Omicron BA.5 were 64% (95% confidence interval [CI], 42%-77%) and 72% (95% CI, 53%-83%) lower, respectively, in cases than controls. Individuals with previous Omicron BA.1/BA.2 infections were more frequent among controls than cases (10.3% vs 0.8%), and their Omicron BA.5 neutralizing titers were 12.8-fold higher than infection-naive individuals. Among cases, preinfection antibody titers were not associated with incidence of long COVID. Preinfection immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may play a role in protecting against the Omicron BA.5 infection but not preventing long COVID.

Estimation of Seroprevalence of Anti-Herpes Simplex Virus Type-1 IgG Among Healthy Blood Donors in Sakaka City, Aljouf, Saudi Arabia

Background: Herpes simplex virus type-1 (HSV-1) is a highly infectious neurotropic virus. The data on HSV-1 infection in Saudi Arabia, including the seroprevalence of HSV-1 antibodies, are scarce. Objectives: This is the first study to evaluate the prevalence of anti-HSV-1 immunoglobulin G (IgG) in donated blood in Sakaka, Aljouf, Saudi Arabia. Methods: A total of 300 donated blood samples were collected from the Blood Bank of Prince Mutaib Bin Abdulaziz Hospital in Sakaka. Sensitive and specific enzyme-linked immunosorbent assay (ELISA) was used to detect anti-HSV-1 IgG. A comparison of the age, gender, education, occupation, income, hand hygiene, travel history, and cupping practice of blood donors stratified for the extent of anti-HSV-1 IgG was made. Results: There was a low prevalence of anti-HSV-1 IgG (20%; n = 60/300). Moreover, 50.0% of IgG-positive participants were in the age group of 41 - 45 years, and 81.7% of the participants had a household income of &lt; 10000 SAR (statistically highly significant; P &lt; 0.001*). All the participants performed hand washing with soap before handling food and after using the toilet. Furthermore, IgG-positive participants had a bachelor’s degree (50.0%), were governmental employees (60.0%), were international travelers (50.0%), and practiced cupping (50.0%) with statistically significant associations (P &lt; 0.05*). Conclusions: The current study’s findings support previous reports about the key importance of improving socioeconomic conditions and hygiene measures in reducing the spread of HSV-1. The present study provides an alarm regarding reaching the age of sexual debut without acquiring protective anti-HSV-1 immunoglobulins, consequently becoming more susceptible to acquiring HSV-1 infection through the genital route. These data support the urgent need to develop an effective anti-HSV-1 vaccine.

Humoral SARS-CoV-2 Vaccine Responses in Patients With Giant Cell Arteritis and Polymyalgia Rheumatica: Decay After Primary Vaccination and Effects of the Booster.

Vaccination remains essential in preventing morbidity of SARS-CoV-2 infections. We previously showed that >10 mg/day of prednisolone and methotrexate was associated with reduced antibody concentrations after primary vaccination in patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). This follow-up study was undertaken to measure the decay of antibody concentrations and the immunogenicity of SARS-CoV-2 booster vaccination. Patients with GCA/PMR included in the primary vaccination (BNT162b2 [Pfizer-BioNTech] or ChAdOx1 [Oxford/AstraZeneca]) study were asked again to donate blood samples 6 months after primary vaccination (n=24) and 1 month after booster vaccination (n=46, BNT162b2 or mRNA1273). Data were compared to those of age-, sex-, and vaccine-matched controls (n=58 and n=42, respectively). Multiple linear regression was performed with post-booster antibody concentrations as dependent variable and post-primary vaccination antibodies, prednisolone >10mg/day, and methotrexate use as predicting variables. Antibody concentrations decreased faster over time in GCA/PMR patients than in controls, which was associated with prednisolone treatment during primary vaccination. Post-booster antibody concentrations were comparable between patients and controls. Antibody concentrations post primary vaccination, but not treatment during booster vaccination, were predictive for antibody concentrations post booster vaccination. These results indicate that the decay of humoral immunity after primary vaccination is associated with prednisolone treatment, whereas the subsequent increase after booster vaccination, was not. Patients with low antibody concentrations following primary vaccination remained at an immunogenic disadvantage after a single booster vaccination. This longitudinal study in GCA/PMR patients stresses the importance of repeated booster vaccination for patients with poor responses to primary vaccination.

Lung cancer risk discrimination of prediagnostic proteomics measurements compared with existing prediction tools.

We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test. We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models' sensitivity. All tests were 2-sided. The area under the curve for the protein-based risk model in the validation sample was 0.75 (95% confidence interval [CI] = 0.70 to 0.81) compared with 0.64 (95% CI = 0.57 to 0.70) for the PLCOm2012 model (Pdifference = .001). The EarlyCDT-Lung had a sensitivity of 14% (95% CI = 8.2% to 19%) and a specificity of 86% (95% CI = 81% to 92%) for incident lung cancer. At the same specificity of 86%, the sensitivity for the protein-based risk model was estimated at 49% (95% CI = 41% to 57%) and 30% (95% CI = 23% to 37%) for the PLCOm2012 model. Circulating proteins showed promise in predicting incident lung cancer and outperformed a standard risk prediction model and the commercialized EarlyCDT-Lung.

Serological Profile of SARS-CoV-2 in Unvaccinated Blood Donors: A Nationwide Study During the Fifth Wave of the Pandemic in Iran

Background: Serological studies can demonstrate pathogen circulation in regional populations and reflect public health measures' effectiveness during different pandemic phases. By late November 2021, coinciding with the third pandemic wave, the seroprevalence of SARS-CoV-2 spike IgG antibodies among the Iranian population was 32.63%. Objectives: This study aimed to assess the Iranian population's seroprevalence during the fifth pandemic wave by analyzing donated blood samples. Methods: This population-based cross-sectional study was conducted on Iranian blood donors referred to all 31 main provincial capitals between August 2021 and September 2021. The participants selected through quota sampling were asked to complete a questionnaire on socio-demographics and coronavirus disease 2019 (COVID-19)-related information. Also, SARS-CoV-2 spike IgG antibodies were measured in serum samples using SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) kits. The seroprevalence was weighted based on the gender and age groups of the population and then adjusted for test performance. Results: Totally 3,339 blood donors participated in this study. The overall population-weighted seroprevalence adjusted for test performance was 52.67% (95% confidence interval (CI): 50.14 - 55.21). Seroprevalence was higher among participants with a high school diploma (55.45%, 95% CI 50.61 - 60.29), a positive history of close contact with COVID-19 patients (65.23%, 95% CI 60.83 - 69.63), and previous positive COVID-19 PCR tests (86.51%, 95% CI 82.32 - 90.7). Conclusions: More than half of the study population was exposed to SARS-CoV-2, indicating a 1.7-fold increase in the seroprevalence between late November 2020 and mid-September 2021. Our finding illuminated the pattern of Iran's fifth wave of the pandemic.

Abstract 3022: Prospective study of circulating metabolomic signatures and breast cancer incidence among predominantly premenopausal women

Abstract Background: Metabolomics has become a powerful tool to systematically examine metabolic pathways involved in carcinogenesis. Although several epidemiological studies examined the association between metabolites and breast cancer risk, metabolomic biomarkers of breast cancer measured in premenopausal women are still understudied. Herein, we prospectively investigated the associations between pre-diagnostic metabolomic signatures and subsequent risk of developing breast cancer among predominantly premenopausal women at blood collection. Methods: In the Nurses’ Health Study II, 29,611 healthy women (80% premenopausal) donated blood samples in 1996-1999. Between blood collection and 2011, 1,055 women were diagnosed with breast cancer, and each was matched with healthy control. Lipids, carbohydrates, and organic acid-related metabolites were profiled with liquid chromatography-tandem mass spectrometry. Multivariable (including adiposity) adjusted conditional logistic regression was used to estimate odds ratios (ORs) of breast cancer and 95% confidence intervals (CIs). Associations of metabolite groups with breast cancer were evaluated using metabolite set enrichment analysis and network analysis. All analyses were corrected for multiple comparisons. Results: Although no individual metabolites were statistically significantly associated with breast cancer risk after multiple comparisons correction, several individual metabolites were identified as nominally significant: taurodeoxycholate (OR=1.15; 95%CI=1.04-1.28), C16:1 cholesteryl ester (OR=0.88; 95%CI=0.79-0.97), C32:1 phosphatidylcholine (PC) (OR=0.88; 95%CI=0.79-0.98), C34:1 PC (OR=0.87; 95%CI=0.78-0.98), and C34:3 PC (OR=0.88; 95%CI=0.79-0.98). In analyses of grouped metabolites, triglycerides (TAGs) with &amp;lt;3 double bonds (DBs) (normalized enrichment score (NES)= -2.54; Padj&amp;lt;0.00001) and PCs (NES= -2.13; Padj=0.02) were significantly inversely associated with risk of overall breast cancer, with no obvious differences observed by menopausal or BMI status. Significant inverse associations of TAGs with ≥3 DBs were only observed among premenopausal women or among those with high BMI. Opposite enrichments of phospholipids, amino acids, and carbohydrate-related metabolites were observed by estrogen receptor (ER) status. Conclusions: In this prospective study of predominately premenopausal women, we found that the association between TAGs and breast cancer risk was dependent on the number of DBs. Notably, TAGs with &amp;lt;3 DBs, which have been associated with higher risk of type 2 diabetes, were strongly inversely associated with risk of developing breast cancer. Variations of associations with other metabolites were observed by menopausal, obesity, and ER status. Further validation of our findings in independent cohorts of premenopausal women is warranted. Citation Format: Tengteng Wang, Oana Zeleznik, Emma E. McGee, Kristen D. Brantley, Raji Balasubramanian, Bernard A. Rosner, Walter C. Willett, Clary B. Clish, A. Heather Eliassen. Prospective study of circulating metabolomic signatures and breast cancer incidence among predominantly premenopausal women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3022.

The association between dietary patterns, plasma lipid profiles, and inflammatory potential in a vascular dementia cohort.

Inflammation and altered lipid dyshomeostasis have been implicated in the pathogenesis of Alzheimer's disease and vascular dementia. To determine if there are any associations between dietary patterns, plasma lipid profiles, and inflammatory potential in a vascular dementia cohort. One hundred fifty participants (36 subjects with Vascular Dementia and 114 healthy controls) from two Australian teaching hospitals completed a cross-sectional survey examining their dietary and lifestyle patterns. Each participant's diet was further evaluated using the Empirical Dietary Inflammatory Index. Some participants also donated blood samples for lipidomic analysis. After adjusting for age, education, and socioeconomic status, participants with vascular dementia tend to have higher lipid profiles, do less exercise, and engage less frequently in social interaction, educational, or reading activities. They also tend to consume more deep-fried food and full-fat dairy compared to control subjects. However, there was no difference in Empirical Dietary Inflammatory Index between the two groups after adjusting for age, education, and socioeconomic status. Our findings suggest a graded inverse association between healthy lifestyle factors and vascular dementia.

Epidemiological serosurvey of chikungunya fever post outbreak at Tanjung Sepat, Malaysia.

Chikungunya fever is a mosquito-borne viral disease that usually presents with prominent arthralgia. An outbreak of chikungunya fever was reported in Tanjung Sepat, Malaysia in 2019. The outbreak was limited in size with a low number of cases being reported. The present study sought to determine the possible variables that could have affected the transmission of the infection. A cross-sectional study involving 149 healthy adult volunteers from Tanjung Sepat was performed soon after the outbreak had subsided. All the participants donated blood samples and completed the questionnaires. Laboratory detection of anti-CHIKV IgM and IgG antibodies was performed using enzyme-linked immunoassays (ELISA). Risk factors associated with chikungunya seropositivity were determined using logistic regression. The majority (72.5%, n = 108) of the study participants tested positive for CHIKV antibodies. Only 8.3% (n = 9) of the participants out of all the seropositive volunteers had an asymptomatic infection. Participants who resided with a febrile (p < 0.05, Exp(B) = 2.2, confidence interval [CI] 1.3-3.6) or a CHIKV-diagnosed person (p < 0.05, Exp(B) = 2.1, CI 1.2-3.6) in the same household were found likely to be tested positive for CHIKV antibodies. Findings from the study support that asymptomatic CHIKV infections and indoor transmission occurred during the outbreak. Hence, widespread community testing and indoor use of mosquito repellent are among the possible measures that can be implemented to reduce CHIKV transmission during an outbreak.

A chemiluminescence based approach to nucleic acid testing to detect HBV, HCV, and HIV-1 in blood screening

Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) are life-threatening blood-borne infections that can be unintentionally transmitted in transfused blood products. Here, we optimized a method for detecting HBV, HCV, and HIV-1 in blood screening using magnetic nanoparticles (MNPs) and polymerase chain reaction (PCR)-chemiluminescence. Viral genomes were extracted from donated blood samples using MNPs. The isolated viral DNA and RNA were amplified in a one-step parallel reverse transcription-PCR (RT-PCR). HBV, HCV, and HIV-1 were detected using complementary nucleic acid probes and quantified using a chemiluminescent substrate. 10 422 donated blood samples were tested both with the above method and Roche Cobas TaqScreen MPX Test. The lengths of the amplified PCR products for HBV, HCV, and HIV-1 were 119 bp, 220 bp, and 174 bp, respectively, indicating that the extraction methods successfully separated high-quality viral genomes from the serum samples. The probes and reaction conditions used for the chemiluminescent detection of HBV, HCV, and HIV-1 genomes in unknown samples were empirically optimized. Of the 10 422 blood samples screened, 12 were HBV positive and 2 were HCV positive. These results were consistent with those of a parallel-controlled study using Roche Cobas TaqScreen MPX Test. The assay described here is fast, accurate, and sensitive for detecting HBV, HCV, and HIV, which runs in parallel and has broad implications for blood screening and epidemiological studies.

Blood Donation Screening of Transfusion-Transmissible Viral Infection Using Two Different Nucleic Acid Testing (NAT) Platforms: A Single Tertiary Care Oncology Centre Experience.

Nucleic acid testing (NAT) is used to screen transfusiontransmittable infections (TTIs) in donated blood samples and provide an additional layer of blood safety. In this study, we describe our experience in screening viral TTIs using two formats of NAT: cobas® MPX2 polymerase chain reaction- based minipool NAT (PCR MP-NAT) and Procleix Utrio Plus transcription-mediated amplificationbased individual donor-NAT (TMA ID-NAT). Data routinely collected as a part of blood bank operations were retrospectively analysed over a period of 70months for TTIs. Blood samples were initially screened for HIV, HBV, HCV, syphillis by chemiluminescence and malaria by Rapid card test. In addition to serological testing, all samples were further screened by TMA-based ID-NAT (ProcleixUltrio Plus Assay) during Jan 2015-Dec 2016, and by PCR-based MP-NAT (Cobas® TaqScreen MPX2) during Jan 2017-Oct 2020. RESULTS: A total of 48,151 donations were processed over 70months, of which 16,212 donations were screened by ProcleixUtrio Plus TMA ID-NAT and 31,939 donations by cobas® MPX2 PCR MP-NAT. Replacement donors and male donors outnumbered voluntary donors and female donors respectively. The overall NAT yield rate of MP-NAT was 1:2281 compared to 1:3242 with ID-NAT, during the respective time period. ID-NAT detected 5 HBV infections missed by serology, whereas MP-NAT detected 13 HBV infections and 1 HCV infection missed by serology. The proportion of donations that were both seroreactive and NAT reactive was higher with MP-NAT (59.8%) compared to ID-NAT (34.6%). Cobas® MPX2MP-NAT had higher overall NAT yield rate compared to ProcleixUtrio Plus ID-NAT and confirmed a higher proportion of seroreactive donations. Due to the ease of operation, simple algorithm, cobas® MPX2 PCR based MP-NAT can be an effective solution for blood screening in India.

The Correlation between Risk Factors and Epstein-Barr Virus Serum Antibody with Histopathological Typing of Nasopharyngeal Carcinoma

BACKGROUND: The risk-combination of genetic or familial history, environmental risk factors, and EBV infection might cause nasopharyngeal carcinogenesis. The serum antibody for EBV IgA, namely, EBNA1+VCA-p18 has a good sensitivity as an early diagnostic test for nasopharyngeal carcinoma (NPC). AIM: This study aims to determine the correlation between risk factors and histopathological typing of NPC and also the correlation between the IgA [EBNA-1 + VCA p-18] ELISA and histologic type. METHODS: A cross-sectional method was used on 108 NPC patients which filled a questionnaire through an in-depth interview on the family condition to cancer, habit/lifestyle, and environmental risks. A total of 47 subjects were willing to donate blood samples for IgA [EBNA1 + VCA p-18] ELISA. Furthermore, Kendall’s tau-b (τ) correlation test was performed on NPC keratin type (WHO-1) and non-keratin (WHO-2 and 3). RESULTS: The results showed that the family history of non-keratinized NPC was associated with NPC WHO-3 as demonstrated by τ = 0.473, as well as salt-eating with τ = 0.334, smoked/grilled fish/meat eating τ = 0.205, instant noodle-eating τ = 0.356, consuming canned/packaged canned foods τ = 0.240, and flavored food eating habits τ = 0.364, along with passive smoking τ = 0.377, and chronic nasopharyngeal infection τ = 0.530. The IgA titers, namely, [EBNA1 + VCA p-18] ELISA for non-keratin type NPC was greater than the keratin type; however, it was not related to WHO-3 NPC as indicated by τ = 0.376, and p = 0.011 put this underlying before however. CONCLUSIONS: The positivity of IgA [EBNA-1 + VCA p-18] ELISA does not correlate with the non-keratin type histologic NPC, family history, as well as salt-eating, instant noodle, and flavored food eating habits, along with passive smoking and nasopharyngeal infection.

Soluble urokinase-type plasminogen activator receptor (suPAR) is elevated in caregivers of patients with parkinsonism

Caregivers are integral to the care of those with neurological disorders such as Parkinson's Disease (PD), but are often burdened by stress, anxiety, and depression. Previous research has suggested that the foundation of such stress is low-grade systemic inflammation, as evidenced by increased interleukin 6 (IL-6) and C-reactive protein (CRP) levels. Soluble urokinase-type plasminogen activator receptor (suPAR) is a kidney disease risk factor and marker of chronic inflammation that integrates psycho-social stress and organ dysfunction. Caregivers of PD experience an extraordinary amount of stress and suPAR's role as prognostic marker has not yet been assessed in caregivers of PD. The aim of this study was to determine the relationship between suPAR levels and PD caregiver burden. Healthy volunteers who accompanied patients with parkinsonism (n = 35) donated blood samples, and complete blood counts (CBC), CRP, and suPAR levels were measured. Participants were then interviewed by telephone and stratified into primary and non-primary caregiver groups. Their caregiver burden was quantified through the Zarit Caregiver Burden Short Form (ZBI-12). The resultant data demonstrated higher plasma levels of suPAR and ZBI-12 scores for the primary caregiver group relative to the non-primary caregiver group (suPAR level: 3.73 vs. 2.72 ng/mL, p = 0.01; ZBI-12: 18.57 vs. 5.4, p < 0.0001; Table). The data also revealed a moderate positive correlation between suPAR and ZBI-12 scores. These findings not only demonstrate a correlation between elevated suPAR and caregiving burden in PD, but also further support and raise awareness for the overall psychosocial burden and stress experienced by those caregivers.