Time Of Sample Collection Research Articles

Metabolomic profiling of preterm birth in pregnant women living with HIV

BackgroundPreterm birth is a leading cause of death in children under the age of five. The risk of preterm birth is increased by maternal HIV infection as well as by certain antiretroviral regimens, leading to a disproportionate burden on low- and medium-income settings where HIV is most prevalent. Despite decades of research, the mechanisms underlying spontaneous preterm birth, particularly in resource limited areas with high HIV infection rates, are still poorly understood and accurate prediction and therapeutic intervention remain elusive.ObjectivesMetabolomics was utilized to identify profiles of preterm birth among pregnant women living with HIV on two different antiretroviral therapy (ART) regimens.MethodsThis pilot study comprised 100 mother-infant dyads prior to antiretroviral initiation, on zidovudine monotherapy or on protease inhibitor-based antiretroviral therapy. Pregnancies that resulted in preterm births were matched 1:1 with controls by gestational age at time of sample collection. Maternal plasma and blood spots at 23–35 weeks gestation and infant dried blood spots at birth, were assayed using an untargeted metabolomics method. Linear regression and random forests classification models were used to identify shared and treatment-specific markers of preterm birth.ResultsClassification models for preterm birth achieved accuracies of 95.5%, 95.7%, and 80.7% in the untreated, zidovudine monotherapy, and protease inhibitor-based treatment groups, respectively. Urate, methionine sulfone, cortisone, and 17α-hydroxypregnanolone glucuronide were identified as shared markers of preterm birth. Other compounds including hippurate and N-acetyl-1-methylhistidine were found to be significantly altered in a treatment-specific context.ConclusionThis study identified previously known as well as novel metabolomic features of preterm birth in pregnant women living with HIV. Validation of these models in a larger, independent cohort is necessary to ascertain whether they can be utilized to predict preterm birth during a stage of gestation that allows for therapeutic intervention or more effective resource allocation.

Systemic cytokine and viral antigen-specific responses in hepatitis D virus RNA positive versus HDV RNA negative patients.

Hepatitis B virus (HBV)/Hepatitis D Virus (HDV) co-infection increases the risk of severe liver disease compared to HBV mono-infection. Adaptive immune responses to HDV are weakly detectable, and the involvement of innate immunity in the progression of HDV-related liver fibrosis is suggested. We hypothesize that an overall innate immune activation in HBV/HDV co-infection plays a role in liver disease progression and also impacts virus specific T cell response. Sixteen HBV/HDV-co-infected-patients (median age 42y/7F/6 Asian/4 White/6 Black/15 HBeAg-) and 8 HBV monoinfected-patients (median age 39y/4F/4 Asian/3 Black/1 White/HBeAg-) with median follow-up of 5 years were enrolled. Liver fibrosis was assessed by liver stiffness measurement (LSM, FibroScan®). Proliferation of CD3 + CD4+ T cells in response to viral antigens using CFSE assays and cytokine secreting monocytes was analyzed by flow cytometry. Of 16 HBV/HDV, 11 were HDV-RNA+ (HBV-DNA 0-1,040 IU/mL), 5/11 Interferon (IFN) + Nucleos/tide Analog (NA), 3/11 NA monotherapy, median ALT 77 U/L at the time of sample collection, median LSM of 9.8. In 5 HDV RNA-, median HBV DNA 65 IU/mL, 4/5 prior IFN and/or NA, ALT 31 U/L, and median LSM 8.5 kPa. In 8 HBV controls, median HBV-DNA, ALT, LSM was 69 IU/mL, 33 U/L,5 kPa, respectively. PBMC stimulation with HBV core antigen (HBcAg) and HDV antigen (HDAg) showed weaker CD3 + CD4 + T-cell proliferation in HDV-RNA+ vs. HDV RNA- and HBV-mono-infected patients (p < 0.05). In HDV-RNA+ patients, a correlation between ALT and TNF-α (r = 0.76, p = 0.008), higher IL-10 levels and increased proportion of CD14 + TNF-α+ cells were found. In summary, during HBV/HDV coinfection, HDV RNA+ patients had weaker HBV and HDV specific responses, associated with increased TNF-α + monocytes irrespective of IFN treatment.

THU174 Model-Based Analysis Of IGF-I Response, Dosing, And Monitoring For Once-Weekly Somapacitan In Children With GH Deficiency

Abstract Disclosure: R.J. Kildemoes: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. Y. Kamal Lyauk: Employee; Self; Novo Nordisk. J.C. Blair: Speaker; Self; Novo Nordisk, Pfizer, Inc., Ipsen. Other; Self; Novo Nordisk. B.S. Miller: Consulting Fee; Self; Novo Nordisk, Abbvie, Endo Pharmaceuticals, Ascendis Pharma, Bristol-Myers Squibb, Pfizer, Inc., EMD Serono, BioMarin Pharmaceutical, Tolmar. Research Investigator; Self; Alexion Pharmaceuticals, Inc., Abbvie, Aeterna Zentaris, Amicus, Lumos Pharma, Novo Nordisk, Lysogene, OPKO Health, Pfizer, Inc., Prevail Therapeutics, Sangamo Therapeutics. J. Mori: None. M. Højby Rasmussen: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. P.F. Backeljauw: Consulting Fee; Self; Novo Nordisk, Novartis Pharmaceuticals, Ascendis Pharma, BioMarin Pharmaceutical, Tolmar Pharmaceuticals, Cavalry Biosciences, Ipsen. Research Investigator; Self; Novo Nordisk, Novartis Pharmaceuticals, Ipsen. Growth hormone (GH) replacement therapy improves overall health and adult height in children with GH deficiency (GHD). GH stimulates insulin-like growth factor-I (IGF-I) release, the biomarker commonly used for guiding GH dose adjustments to ensure optimal long-term safety and efficacy. This study aims to provide model-based insights into the dose-IGF-I responses of once-weekly somapacitan, a novel long-acting GH, compared to daily GH in pediatric patients with GHD. Pharmacokinetic/pharmacodynamic (PK/PD) modeling was used to characterize somapacitan dose-IGF-I response and to predict the response to change of dosing day and missed dosing of somapacitan. Analyses included dosing information and 1473 PK samples from 210 GHD patients treated with somapacitan across three trials: phase 1 (NCT01973244), phase 2 (NCT02616562; REAL3), and phase 3 (NCT03811535; REAL4), as well as 1381 IGF-I samples from 186 GHD patients treated with somapacitan from REAL3 and REAL4. A clear dose-response relationship was observed with increasing somapacitan exposure and increasing change from baseline IGF-I SDS. A linear model permitted the development of a tool to calculate the estimated average weekly IGF-I exposure from a single IGF-I sample obtained at any time within the somapacitan dosing interval at steady state. In practice, the use of this tool will require knowledge of the timing of the somapacitan injection relative to the timing of the IGF-I sample collection. IGF-I SDS simulations support flexible dosing day changes while maintaining a minimum of 4 days between doses. In this study, we present a practical guide that may inform clinicians about the expected weekly average IGF-I concentration in somapacitan-treated pediatric patients with GHD from a single sample taken on any chosen day during the weekly dosing interval. The ability to determine weekly average IGF-I enhances our understanding of somapacitan dosing and should support physicians in monitoring long-term safety and efficacy of this therapy. Furthermore, we provide insights on flexibility to change of dosing day and missed dosing of somapacitan. Presentation: Thursday, June 15, 2023

Is a real-time quantifiable liquid biopsy achievable using a microfluidic lab-on-chip ?

Abstract An increasingly relevant functional measurement is a liquid biopsy to assist in the diagnosis of cancers. The existing approach for liquid biopsy is to utilize microfluidic chips for the isolation of circulating tumor cells (CTCs) or exosomes or extracellular vesicles (EV) from patient samples, and then for the analysis of the cargo contained inside the CTCs, exosomes or EVs. However, such an analysis does not provide a real-time liquid biopsy, since there is a long delay between the time of sample collection and the results from the analysis. Microfluidic chip-formats also provide the capability to mimic tissue functions from the analysis of small numbers of cells cultured in the chip. Analysis of the secreted molecules from such cells could provide a measurement of the secretome, which could be analogous to a liquid biopsy. A 3D structural organization of cells in microfluidic chips is usually in the form of organoids or spheroids. The analysis of organoids or spheroids is well-adapted for immunohistochemistry or ELISA-type identification of surface markers, but not for real-time analysis of secreted molecules since the fluid and molecules in the interior volume of the organoid or spheroid is not accessible in real-time. We have recently proposed an alternative novel design for a microfluidic chip format comprising 3D micro-niches that provide a real-time analysis of secretions produced directly from small numbers of cells. The microfluidic chip with 3D micro-niches then analyses the secretions from these monolayers in real-time (“secretome”). The microfluidic chip includes electronic biosensors that provide real-time measurement of secreted molecules. This short review concludes with a proposition for the means to utilize this novel microfluidic chip to function as a real-time and quantifiable diagnostic screening device to differentiate cancerous cells from healthy cells.

Influence of time-dependent sampling on the plasma metabolome and exposome of fish collected from an effluent-dependent pond

Metabolomics is increasingly recognized as a useful approach to characterize environmental pollution gradients. While the performance of analytical procedures must be validated and documented, many studies only briefly describe sampling and sample storage. Here we advance our recent study on the influences of sampling delay and holding media on contaminants of emerging concern in fish plasma by targeted analysis. We specifically examined the metabolome and exposome of common carp under three conditions: plasma sampled immediately after field collection (t = 0 h) and then after 3 h (t = 3 h) or 20 h (t = 20 h) of holding fish in lab water. Plasma samples were analyzed using reversed-phase and HILIC chromatography with mass spectrometric detection. 6143 of the 12,904 compounds (after clustering features) varied among the groups. We observed different metabolite variation patterns depending on the sample collection time. We also identified several xenobiotics (2-Ethylhexyl sulfate, 6-Chloro-5-methyl-1H-benzotriazole) at concentrations generally found at the highest levels in plasma sampled immediately after field collection (t = 0 h). Both the metabolome and the exposome changed rapidly in fish plasma with a time lag, which indicates that obtaining relevant results is complicated by fish-holding conditions. We further identified that non-lethal, relatively low-volume blood sample collection was sufficient with this species, which presents ethical and practical advantages.

Genetic risk score in multiple sclerosis is associated with unique gut microbiome

Multiple sclerosis (MS) is a complex autoimmune disease in which both the roles of genetic susceptibility and environmental/microbial factors have been investigated. More than 200 genetic susceptibility variants have been identified along with the dysbiosis of gut microbiota, both independently have been shown to be associated with MS. We hypothesize that MS patients harboring genetic susceptibility variants along with gut microbiome dysbiosis are at a greater risk of exhibiting the disease. We investigated the genetic risk score for MS in conjunction with gut microbiota in the same cohort of 117 relapsing remitting MS (RRMS) and 26 healthy controls. DNA samples were genotyped using Illumina’s Infinium Immuno array-24 v2 chip followed by calculating genetic risk score and the microbiota was determined by sequencing the V4 hypervariable region of the 16S rRNA gene. We identified two clusters of MS patients, Cluster A and B, both having a higher genetic risk score than the control group. However, the MS cases in cluster B not only had a higher genetic risk score but also showed a distinct gut microbiome than that of cluster A. Interestingly, cluster A which included both healthy control and MS cases had similar gut microbiome composition. This could be due to (i) the non-active state of the disease in that group of MS patients at the time of fecal sample collection and/or (ii) the restoration of the gut microbiome post disease modifying therapy to treat the MS. Our study showed that there seems to be an association between genetic risk score and gut microbiome dysbiosis in triggering the disease in a small cohort of MS patients. The MS Cluster A who have a higher genetic risk score but microbiome profile similar to that of healthy controls could be due to the remitting phase of the disease or due to the effect of disease modifying therapies.

DETERMINE PRE-ANALYTICAL ERRORS ' PERCENTAGE IN CLINICAL BIOCHEMISTRY LABS AND DEVELOP REMEDIAL PROCEDURES FOR THEIR PREVENTION

Diagnostic inaccuracies pose a formidable issue in Laboratory Medicine, necessitating immediate initiatives to expand understanding and minimize these discrepancies. Our study delves into the nuances of errors associated with laboratory testing processes, from the test request to result interpretation, underlining the imperative for reducing such errors. Our investigation seeks to identify the incidence of errors in a round-the-clock lab setting over four months, covering pre-analytical, analytical, and post-analytical phases.Over a span period from Jan 2021 to Jan 2022, a broad spectrum of errors within pre-analytical, analytical, and post-analytical phases was methodically logged using a bespoke proforma. The collected data was systematically analyzed utilizing SPSS version 22.All venous and arterial blood samples were processed in the 24-hour lab throughout this period. From the 185,012 samples received, 2,450 were deemed unsuitable for testing, accounting for a 1.32% rejection rate. These samples were disqualified due to an array of pre-analytical errors, including misidentification (0.07%), incorrect tube usage (0.11%), missing samples (0.07%), drawing from an intravenous site (0.10%), inadequate sample volume (0.51%), improper timing of sample collection (0.10%), hemolysed samples (0.31%), and lipemic samples (0.11%).Utilizing an agreed list of evidence-based Quality Indicators, compliant with the current International Standard (ISO 15189:2012), for incorporation into accreditation programs of clinical laboratories stands as a potent approach to augment quality, mitigate error risks, and bolster patient safety.

The Diagnostic Performance of Various Clinical Specimens for the Detection of COVID-19: A Meta-Analysis of RT-PCR Studies.

The diagnostic performance of numerous clinical specimens to diagnose COVID-19 through RT-PCR techniques is very important, and the test result outcome is still unclear. This review aimed to analyze the diagnostic performance of clinical samples for COVID-19 detection by RT-PCR through a systematic literature review process. A compressive literature search was performed in PubMed/Medline, Scopus, Embase, and Cochrane Library from inception to November 2022. A snowball search on Google, Google Scholar, Research Gate, and MedRxiv, as well as bibliographic research, was performed to identify any other relevant articles. Observational studies that assessed the clinical usefulness of the RT-PCR technique in different human samples for the detection or screening of COVID-19 among patients or patient samples were considered for this review. The primary outcomes considered were sensitivity and specificity, while parameters such as positive predictive value (PPV), negative predictive value (NPV), and kappa coefficient were considered secondary outcomes. A total of 85 studies out of 10,213 non-duplicate records were included for the systematic review, of which 69 articles were considered for the meta-analysis. The meta-analysis indicated better pooled sensitivity with the nasopharyngeal swab (NPS) than saliva (91.06% vs. 76.70%) and was comparable with the combined NPS/oropharyngeal swab (OPS; 92%). Nevertheless, specificity was observed to be better with saliva (98.27%) than the combined NPS/OPS (98.08%) and NPS (95.57%). The other parameters were comparable among different samples. The respiratory samples and throat samples showed a promising result relative to other specimens. The sensitivity and specificity of samples such as nasopharyngeal swabs, saliva, combined nasopharyngeal/oropharyngeal, respiratory, sputum, broncho aspirate, throat swab, gargle, serum, and the mixed sample were found to be 91.06%, 76.70%, 92.00%, 99.44%, 86%, 96%, 94.4%, 95.3%, 73.63%, and above 98; and 95.57%, 98.27%, 98.08%, 100%, 37%, 100%, 100%, 97.6%, and above 97, respectively. NPS was observed to have relatively better sensitivity, but not specificity when compared with other clinical specimens. Head-to-head comparisons between the different samples and the time of sample collection are warranted to strengthen this evidence.

FOXO3 and PTEN expression in the ovary of girls with extra-gonadal cancer with or without chemotherapy treatment prior to cryopreservation

BackgroundFOXO3/pFOXO3 and PTEN expression is known to regulate the dormancy/activation of ovarian primordial follicles. How chemotherapy could influence the expression of FOXO3 and PTEN in pre- and post-menarcheal girls with extra-gonadal cancer remains unexplored.MethodsOvarian samples were collected from 27 girls suffering from extra-gonadal cancer. Of these, 8 patients had received chemotherapy before the time of sample collection. Ovarian tissue collected at the time of surgery was fixed in 10% formaldehyde for FOXO3/pFOXO3 and PTEN immunohistochemistry or immunofluorescence, or stored at -80 °C for Western blot, or preserved in RNA later for RT-PCR.ResultsPTEN was detected in a limited number of primordial follicle-enclosed oocytes in approximately fifty percent of the patients, regardless of whether they had received anti-cancer treatment or not. However, there was a significant decrease in PTEN detection in patients who underwent chemotherapy treatment prior to the retrieval of the sample. Both primordial follicle-enclosed oocytes that expressed FOXO3 and those that did not were identified in patients who were treated with chemotherapy and those who were not. FOXO3-positive primordial follicles exhibited either nuclear FOXO3 localization or cytoplasmic pFOXO3 localization. Furthermore, transitional primordial follicles that expressed nuclear FOXO3 and cytoplasmic pFOXO3 were also observed. Primary follicle-enclosed oocytes displayed cytoplasmic pFOXO3 localization, whereas in more advanced stages of folliculogenesis, the expression moved to the somatic stratum. No significant statistical differences were identified in the detection of FOXO3 and pFOXO3 in patients who had or had not received chemotherapy prior to sample collection.ConclusionPrimordial follicles expressing and not expressing FOXO3 were equally present in both the ovaries of patients who underwent chemotherapy and those who did not. The expression of FOXO3 remained unaltered in response to chemotherapy treatment. Notably, the detection of PTEN was significantly reduced in the treated patients, thereby warranting in-depth investigation, given the limited sample size examined in the present study.

Large-scale analysis of sheep rumen metagenome profiles captured by reduced representation sequencing reveals individual profiles are influenced by the environment and genetics of the host

BackgroundProducing animal protein while reducing the animal’s impact on the environment, e.g., through improved feed efficiency and lowered methane emissions, has gained interest in recent years. Genetic selection is one possible path to reduce the environmental impact of livestock production, but these traits are difficult and expensive to measure on many animals. The rumen microbiome may serve as a proxy for these traits due to its role in feed digestion. Restriction enzyme-reduced representation sequencing (RE-RRS) is a high-throughput and cost-effective approach to rumen metagenome profiling, but the systematic (e.g., sequencing) and biological factors influencing the resulting reference based (RB) and reference free (RF) profiles need to be explored before widespread industry adoption is possible.ResultsMetagenome profiles were generated by RE-RRS of 4,479 rumen samples collected from 1,708 sheep, and assigned to eight groups based on diet, age, time off feed, and country (New Zealand or Australia) at the time of sample collection. Systematic effects were found to have minimal influence on metagenome profiles. Diet was a major driver of differences between samples, followed by time off feed, then age of the sheep. The RF approach resulted in more reads being assigned per sample and afforded greater resolution when distinguishing between groups than the RB approach. Normalizing relative abundances within the sampling Cohort abolished structures related to age, diet, and time off feed, allowing a clear signal based on methane emissions to be elucidated. Genus-level abundances of rumen microbes showed low-to-moderate heritability and repeatability and were consistent between diets.ConclusionsVariation in rumen metagenomic profiles was influenced by diet, age, time off feed and genetics. Not accounting for environmental factors may limit the ability to associate the profile with traits of interest. However, these differences can be accounted for by adjusting for Cohort effects, revealing robust biological signals. The abundances of some genera were consistently heritable and repeatable across different environments, suggesting that metagenomic profiles could be used to predict an individual’s future performance, or performance of its offspring, in a range of environments. These results highlight the potential of using rumen metagenomic profiles for selection purposes in a practical, agricultural setting.

Neuroprognostication value of serum neurofilament light chain for out-of-hospital cardiac arrest: A systematic review and meta-analysis.

Neurofilament light chain (NfL) is a novel biomarker for the assessment of neurological function after cardiac arrest (CA). Although meta-analysis has confirmed its predictive value, it has not conducted a more detailed analysis of its research. We conducted a meta-analysis to evaluate the relationship between serum NfL level and neurological prognosis in patients with spontaneous circulation recovery after CA, and subgroup analysis was conducted according to sample collection time, time to assess neurological function, study design, whether TTM was received, the method of specimen determination, and the presence of neurological disease in patients. To analyze the influence of these factors on the predictive value of serum NfL. Published Cochrane reviews and an updated, extended search of MEDLINE, Cochrane Library, Embase, Scopus, ClinicalKey, CINAHL, and Web of Science for relevant studies until March 2022 were assessed through inclusion and exclusion criteria. The standard mean difference and 95% confidence interval were calculated using the random-effects model or fixed-effects model to assess the association between one variable factor NfL level and the outcome of CA patients. Subgroup analysis according to sample collection time was performed. The prognosis analysis and publication bias were also assessed using Egger's and Begg's tests. Among 1209 related articles for screening, 6 studies (1360 patients) met the inclusion criteria and were selected for meta-analysis. The level of serum NfL in the good prognosis group (CPC1-2, CPC: cerebral performance category score) was significantly lower than that in the poor prognosis group (CPC3-5)SMD(standardized mean difference) = 0.553, 95%CI(confidence interval) = 0.418-0.687, I2 = 65.5% P<0.05). And this relationship also exists at each sampling time point (NfL specimens were collected on admission: SMD:0.48,95%CI:0.24-0.73; Samples were collected 24 hours after CA: SMD:0.60,95%CI:0.32-0.88;Specimens were obtained 48 hours after CA: SMD:0.51, 95%CI:0.18-0.85;Specimens were obtained 72 hours after CA: SMD:0.59, 95%CI:0.38-0.81). NfL may play a potential neuroprognostication role in postcardiac arrest patients with spontaneous circulation, regardless of when the sample was collected after CA.

Model-Based Analysis of IGF-I Response, Dosing, and Monitoring for Once-Weekly Somapacitan in Children With GH Deficiency.

Growth hormone (GH) replacement therapy improves longitudinal growth and adult height in children with GH deficiency (GHD). GH stimulates insulin-like growth factor (IGF)-I release, the biomarker used for monitoring GH activity during treatment. This study aims to provide model-based insights into the dose-IGF-I responses of once-weekly somapacitan, a novel long-acting GH, compared with daily GH in children with GHD. Analyses included dosing information and 1473 pharmacokinetic samples from 210 somapacitan-treated pediatric patients with GHD across 3 trials, including phase 1 (NCT01973244), phase 2 (NCT02616562; REAL 3), and phase 3 (NCT03811535; REAL 4), as well as 1381 IGF-I samples from 186 patients with GHD treated with somapacitan in REAL 3 and REAL 4. Pharmacokinetic/pharmacodynamic modeling to characterize somapacitan dose-IGF-I response and predict the response to dosing day changes. Relationships were established between somapacitan dose, exposure, change from baseline IGF-I SD score (SDS), and height velocity (HV). A linear model permitted the development of a tool to calculate estimated average weekly IGF-I exposure from a single IGF-I sample obtained at any time within the somapacitan dosing interval at steady state. In practice, the use of this tool requires knowledge of somapacitan injection timing relative to IGF-I sample collection timing. IGF-I SDS simulations support flexible dosing day changes while maintaining at least 4 days between doses. We characterized the dose-IGF-I response of somapacitan in children with GHD. To support physicians in IGF-I monitoring, we present a practical guide about expected weekly average IGF-I concentrations in these patients and provide insights on dosing day flexibility.

Accelerated epigenetic clock aging in maternal peripheral blood and preterm birth

Epigenetic clocks use CpG DNA methylation to estimate biological age. Acceleration is associated with cancer, heart disease, and shorter life span. Few studies evaluate DNA methylation age and pregnancy outcomes. AgeAccelGrim is a novel epigenetic clock that combines 7 DNA methylation components. This study aimed to determine whether maternal biological aging (via AgeAccelGrim) is associated with early preterm birth. A prospective cohort of patients with singleton pregnancies and at high risk of spontaneous preterm birth delivering at a tertiary university hospital were included in this study. Genome-wide CpG methylation was measured using the Illumina EPIC BeadChip (Illumina, Inc, San Diego, CA) from maternal blood samples obtained at <28 weeks of gestation. AgeAccelGrim and its 7 DNA methylation components were estimated by the Horvath DNA methylation age online tool. Positive values are associated with accelerated biological aging, whereas negative values are associated with slower biological aging relative to each subject's age. The primary outcome was preterm birth at <34 weeks of gestation (any indication). The secondary outcomes were preterm birth at <37 and <28 weeks of gestation. AgeAccelGrim was analyzed as a continuous variable and in quartiles. Exploratory analyses evaluated each of the 7 DNA methylation components included in the composite AgeAccelGrim. Data were analyzed by chi-square test, t test, rank-sum test, logistic regression (controlling a priori for maternal age, cell counts, low socioeconomic status, and gestational age at the time of sample collection), and Kaplan-Meier survival analyses. The log-rank test was used to test the equality of the survival functions. Overall, 163 patients met the inclusion criteria. Of the patients, 48%, 39%, and 21% delivered at <37, <34, and <28 weeks of gestation, respectively. The median AgeAccelGrim was-0.35 years (interquartile range,-2.24 to 1.31) for those delivering at term. Those delivering preterm had higher AgeAccelGrim values that were inversely proportional to delivery gestational age (preterm birth at <37 weeks of gestation:+0.40 years [interquartile range:-1.21 to+2.28]; preterm birth at <34 weeks of gestation:+0.51 years [interquartile range:-1.05 to+2.67]; preterm birth at <28 weeks of gestation:+1.05 years [interquartile range:-0.72 to+2.72]). Estimated DNA methylation of the 7 epigenetic clock component values was increased among those with preterm birth at <34 weeks of gestation, although the differences were only significant for DNA methylation of plasminogen activation inhibitor 1. In regression models, AgeAcccelGrim was associated with an elevated risk of preterm birth with increasing magnitude for increasing severity of preterm birth. For each 1-year increase in the AgeAccelGrim value (ie, each 1-year increase in biological age compared with chronologic age), the adjusted odds of preterm birth were 11% (adjusted odds ratio, 1.11; 95% confidence interval, 1.00-1.24), 13% (adjusted odds ratio, 1.13; 95% confidence interval, 1.01-1.26), and 18% (adjusted odds ratio, 1.18; 95% confidence interval, 1.04-1.35) higher for preterm birth at <37, <34, and <28 weeks of gestation, respectively. Similarly, individuals with accelerated biological aging (≥75th percentile AgeAccelGrim) had more than double the odds of preterm birth at <34 weeks of gestation (adjusted odds ratio, 2.36; 95% confidence interval, 1.10-5.08) and more than triple the odds of preterm birth at <28 weeks of gestation (adjusted odds ratio, 3.89; 95% confidence interval, 1.61-9.38). The adjusted odds ratio for preterm birth at <37 weeks of gestation was 1.73 but spanned the null (adjusted odds ratio, 1.73; 95% confidence interval, 0.81-3.69). In Kaplan-Meier survival analyses, those in the highest AgeAccelGrim quartile delivered the earliest (log-rank Pvalue of <.001). Accelerated biological aging was associated with preterm birth among high-risk patients. Future research confirming these findings and elucidating factors that slow biological aging may improve birth outcomes.

OS13.6.A SURVIVAL IS ASSOCIATED WITH CIRCULATING B-CELLS AND AGE AMONG OLIGODENDROGLIOMA PATIENTS

Abstract BACKGROUND Though patients with oligodendroglioma have improved outcomes versus astrocytomas, there remains marked variability in their survival experience that is unexplained by known prognostic factors. Immunomethylomics uses DNA methylation as a substitute for flow cytometry to characterize immune cells in whole blood. We applied immunomethylomics to archived samples from patients with oligodendroglioma enrolled in the UCSF Adult Glioma Study (AGS) to assess the impact of immune-related characteristics on prognosis. MATERIAL AND METHODS We used immunomethylomics to evaluate immune cell fractions in archived whole blood from the AGS. We identified 141 patients with oligodendroglioma (IDH and TERT mutant, and 1p19q co-deleted) and compared them to other adult diffuse glioma subtypes (N = 347) and controls (N = 454). RESULTS The median age at diagnosis of the 141 oligodendrogliomas was 44 years (range 19 - 83), 57% were male, and 75% white. A total of 60% of patients had received chemotherapy, with or without radiation, prior to blood draw and 25% were taking dexamethasone at the time of sample collection. Oligodendroglioma patients had lower proportions of B cell fractions (total, memory, naïve) than people without glioma. Still, there were higher proportions of B cell (total, memory) and lymphocyte fractions (total, CD4-total and memory), basophil, eosinophil, and NK cells in oligodendrogliomas compared to other glioma subtypes. Median overall survival for the oligodendrogliomas was 17.5 years (95% CI 16.9 - NA) with median follow-up time of 12 years (95% CI 11 - 14). Recursive partitioning analysis delineated two statistically significantly different survival groups for oligodendroglioma patients based on an interaction between age at diagnosis and B naïve cell proportions. The group with the best outcome had a median survival of 24.2 years (95% CI 20.4 - NR) comprised of patients &amp;lt;/= 42 years of age with a higher proportion of B naïve cells (&amp;gt;1.91%) (N = 37). The group with the worse outcome had a median survival of 16.9 years (14.8 - NR) and included patients &amp;lt;/= 42 years of age with a lower proportion of B naïve cells (&amp;lt;/= 1.91%) (N = 28) OR patients &amp;gt; 42 years of age (N = 76) (p = 0.00032). Additionally, proportions of lymphocyte fractions (CD4 and CD8 total, memory, and naïve) were significantly lower in the worse outcome group. Grade or prior treatment did not differ between the groups. CONCLUSION We identified an interaction between age and B naïve cell proportions that distinguished survival outcomes for patients with oligodendrogliomas. Immunomethylomics is a powerful tool for assessing immune status and these findings suggest that blood-immune characteristics may play a vital role in the prognosis of patients with gliomas.

Natural infection versus hybrid (natural and vaccination) humoral immune response to SARS-CoV-2: a comparative paired analysis.

There is substantial immunological evidence that vaccination following natural infection increases protection. We compare the humoral immune response developed in initially seropositive individuals (naturally infected) to humoral hybrid immune response (developed after infection and vaccination) in the same population group after one year. The study included 197 male individuals who were naturally infected with SARS-CoV-2 and then vaccinated with SARS-CoV-2 vaccine. Trimeric spike, nucleocapsid, and ACE2-RBD blocking antibodies for SARS-CoV-2 were measured. Nasal swabs were collected for SARS-CoV-2 PCR testing. Information on vaccination against SARS-CoV-2 and PCR verified infection was retrieved from official databases (Abu Dhabi Health Data Services- SP LLC. ("Malaffi"), including number of vaccine doses received, date of vaccination, and type of the received vaccine. All the study population were tested PCR-Negative at the time of sample collection. Our results showed that there was a significant rise in the mean (SD) and median (IQR) titers of trimeric spike, nucleocapsid and ACE2-RBD blocking antibodies in the post-vaccination stage. The mean (± SD) and median (IQR) concentration of the anti-S antibody rose by 3.3-fold (+230% ± 197% SD) and 2.8-fold (+185%, 220-390%, p<0.001), respectively. There was an observed positive dose-response relationship between number of the received vaccine doses and having higher proportion of study participants with higher than median concentration in the difference between the measured anti-S and ACE2-RBD blocking antibodies in the post-vaccination compared to pre-vaccination. Our study demonstrates that COVID-19 vaccination post natural infection elicits a robust immunological response with an impressive rise of SARS-CoV-2 antibodies, especially the ACE2-RBD blocking antibodies.

Cardiac Troponin Release after Exercise in Healthy Young Athletes: A Systematic Review.

Cardiac troponin (cTn) is a recognized marker used to assess damage to the heart muscle. Actual research has indicated that the levels of cTn increase after doing exercise in individuals who are in good health, and this is believed to be a result of a normal cellular process rather than a pathological one. The main goal of this study was to investigate the evidence of a postexercise release of cTn in child and adolescent athletes (6-17.9 years old) of different ages, sex, and sports disciplines. The Web of Science, MEDLINE, and Scopus databases were used to conduct the research up to March 2023. Three hundred and twenty-eight records were identified from the databases, however, only twenty-three studies were included in the review after being screened and quality-assessed by two independent authors. The gender, age of the participants, maturational status, and training level of the participants, the timing of sample collection, the exercise modality, and the number of participants with values above the cut-off reference were the data analyzed. Males, older young people, and individual sports seemed to have higher levels of serum cTn after practice exercise. Different methodologies, analyzers, and cut-off reference values make it difficult to compare the data among studies.

Design, construction and validation of a simple, low-cost phi meter

The best correlation between the yields of the major toxicants in fire smoke and the fire condition is obtained by expressing the ventilation in terms of the equivalence ratio, phi. Phi meters allow this fuel-air equivalence ratio to be determined during a large-scale fire test. The original design used a platinum catalyst, a large furnace, and required pure oxygen. This work aimed to make a simple, low-cost device which could monitor the equivalence ratio during a large-scale fire test. The current design produces the same quality of measurement with a much smaller footprint and throughput. Benefits include enhanced portability, reduction in sample gas cleaning and drying requirements and lower cost. The work showed that normal furnace components (alumina and silica) provide suitably catalytic surfaces at 900 °C eliminating the requirement for platinum catalysts and the use of pure oxygen. The ISO/TS 19700 steady state tube furnace (SSTF) was used to validate the phi meter measurements as it can both pre-set and independently quantify the equivalence ratio during a test. Long sample collection times were overcome with a larger sampling pump and effluent being split between the phi meter furnace and the exhaust. It is hoped that this simpler, optimized apparatus will encourage more widespread use and lead to better prediction of smoke toxicity.

Analytical factors for eight short-chain fatty acid analyses in mouse feces through headspace solid-phase microextraction-triple quadrupole gas chromatography tandem mass spectrometry.

This study developed a method for quantifying eight short-chain fatty acids (SCFAs) in mouse fecal samples using solid-phase microextraction (SPME) coupled with triple quadrupole gas chromatography tandem mass spectrometry. Furthermore, significant factors affecting SCFA analysis, including SPME fiber selection, pH, salting-out agent, and sample collection time, were investigated. Contrary to previous studies, we found that the CAR/PDMS fiber had the highest extraction efficiency for all SCFAs. The optimal extraction efficiency was observed at pH 2.0, particularly for low-molecular-weight SCFAs. NaH2PO4 showed a more effective extraction efficiency than NaCl, owing to its pH stability and less interference with the solvent matrix. Additionally, our results showed that the SCFA concentration increased over collection time. The composition ratio of the eight SCFAs was maintained for up to 24h; thus, we concluded that samples should be collected within four hours to obtain reliable results. Our findings may improve laboratory methods for SCFA extraction and mouse fecal sample analysis.

Cumulative and lagged effects of varying-sized particulate matter exposure associates with toddlers’ gut microbiota

Particulate matter (PM) is an important component of air pollutants and is associated with various health risks. However, the impact of PM on toddlers’ gut microbiota is rarely investigated. This study aimed to assess the cumulative and lagged effects of varying-sized PMs on toddlers’ gut microbiota. We collected demographic information, stool samples, and exposure to PM from 36 toddlers aged 2–3 years. The toddlers were divided into warm season group and cooler season group according to the collection time of stool samples. The gut microbiota was processed and analyzed using 16S rRNA V3–V4 gene regions. The concentration of PM was calculated using China High Air Pollutants (CHAP) database. To assess the mixed effects of varying-sized PM, multiple-PM models were utilized. There were significant differences between the community composition, α- and β-diversity between two groups. In multiple-PM models, there was a significant effect of weight quantile sum (PM1, PM2.5, and PM10) on α-diversity indices. In weight quantile sum models, after adjusting for a priori confounders, we found a negative effect of weight quantile sum on Enterococcus (β = -0.134, 95% CI -0.263 to -0.006), positive effects of weight quantile sum on unclassified_f__Ruminococcaceae (β = 0.247, 95% CI 0.102 to 0.393), Ruminococcus_1 (β = 0.444, 95% CI 0.238 to 0.650), unclassified_f__Lachnospiraceae (β = 0.278, 95% CI 0.099 to 0.458), and Family_XIII_AD_3011_group (β = 0.254, 95% CI 0.086 to 0.422) in WSG and CSG. In lagged weight quantile sum models, the correlation between lag time PM levels and the gut microbiota showed seasonal trends, and weights of PM changed with lag periods. This is the first study to highlight that cumulative and lagged effects of PMs synergistically affect the diversities (α- and β-diversity) and abundance of the gut microbiota in toddlers. Further research is needed to explore the mediating mechanism of varying-sized PMs exposure on the gut microbiota in toddlers.

The relevance of NMDA receptor antibody-specific index for diagnosis and prognosis in patients with anti-NMDA receptor encephalitis

The clinical implications of the presence of anti-N-methyl-D-aspartate receptor (NMDAR)-specific intrathecal immunoglobulin G synthesis and whether it determines the diagnosis of anti-NMDAR encephalitis have not been thoroughly investigated yet. Thus, the aim of this study was to investigate whether the detection of intrathecal anti-NMDAR-specific IgG synthesis contributes to the diagnostic confirmation of anti-NMDAR encephalitis, to disease severity, and to prognosis in patients with positive serum anti-NMDAR-IgG. In this study, patients with detectable anti-NMDAR IgG in serum and/or cerebrospinal fluid (CSF) were included and separated into two groups that either met the 2016 criteria by Graus et al. of definite anti-NMDAR encephalitis (n = 27) or did not (n = 15). In a total, of 80 paired CSF/serum samples, antibody titers were titrated manually and end-point titer levels were carefully determined in a blinded manner to the subgroup attribution. The disease course was assessed via the modified Rankin Scale (mRS) and prognosis was estimated by the anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score. With respect to whether the diagnostic Graus criteria for definite anti-NMDAR encephalitis were fulfilled, a significantly unequal distribution of intrathecal anti-NMDAR antibody-specific synthesis could be shown with a high negative predictive value in case of a negative anti-NMDAR antibody-specific index (NMDAR AI, p = .008. OR = 23.9, sensitivity = 1.0, specificity = 0.4, negative predictive value = 1). A weak correlation was found between the CSF antibody titer and mRS value at the time of sample collection (rs = .37, p = .008, 95% CI [.09, .59]). During the disease course a higher delta-mRS value formed of the mRS at initial presentation minus that at the last recorded presentation correlated with a higher NMDAR AI at first lumbar puncture (rs = − .56, p = .017, 95% CI [− .83, − .11]). No association with the prognostic NEOS score was found. In conclusion, a negative antibody-specific index for anti-NMDAR IgG antibodies has a highly negative predictive value for the diagnosis of anti-NMDAR encephalitis. Yet, a positive NMDAR AI alone does not allow the diagnosis of anti-NMDAR encephalitis.