Ephrin B2 (EFNB2) potentially protects against intervertebral disc degeneration through inhibiting nucleus pulposus cell apoptosis.

Nucleus pulposus (NP) cell apoptosis is a significant indication of accelerated intervertebral disc degeneration; however, the precise mechanism is unelucidated as of yet. Ephrin B2 (EFNB2), the only gene down-regulated in the three degraded intervertebral disc tissue microarray groups (GSE70362, GSE147383 and GSE56081), was screened for examination in this study. Subsequently, EFNB2 was verified to be down-regulated in degraded NP tissue samples. Interleukin-1 (IL-1ß) treatment of NP cells to simulate the IDD environment indicated that IL-1ß treatment decreased EFNB2 expression. In degenerative NP cells stimulated by IL-1ß, EFNB2 knockdown significantly increased the rate of apoptosis as well as the apoptosis-related molecules cleaved-caspase-3 and the Bax to Bcl-2 ratio. EFNB2 was found to promote AKT, PI3K, and mTOR phosphorylation; the PI3K/AKT signaling role was investigated using the PI3K inhibitor LY294002. EFNB2 overexpression significantly increased PI3K/AKT pathway activity in IL-1ß-stimulated NP cells than the normal control. Moreover, EFNB2 partially alleviated NP cell apoptosis induced by IL-1ß, reduced the cleaved-cas3 level, and decreased the Bax/Bcl-2 ratio after the addition of the inhibitor LY294002. Additionally, EFNB2 overexpression inhibited the ERK1/2 phosphorylation; the effects of EFNB2 overexpression on ERK1/2 phosphorylation, degenerative NP cell viability, and cell apoptosis were partially reversed by ERK signaling activator Ceramide C6. EFNB2 comprehensively inhibited the apoptosis of NP cells by activating the PI3K/AKT signaling and inhibiting the ERK signaling, obviating the exacerbation of IDD. EFNB2 could be a potential target to protect against degenerative disc changes.

The Pharmacogenetic Variability Associated With the Pharmacokinetics and Pharmacodynamics of Rivaroxaban in Healthy Chinese Subjects: A National Multicenter Exploratory Study.

PURPOSE: This study aimed to explore the pharmacogenetic variability associated with the pharmacokinetics (PK) and pharmacodynamics (PD) of rivaroxaban in healthy Chinese subjects. METHODS: This was a multicenter study that included 304 healthy adults aged 18 to 45 years with unknown genotypes. All participants were administered a single dose of rivaroxaban at 10 mg, 15 mg, or 20 mg. PK and PD parameters were measured, and exome-wide association analysis was conducted. FINDINGS: Sixteen SNPs located on 11 genes influenced the AUC0-t. Among these, the 3 most influential genes were MiR516A2, PARP14, and MIR618. Thirty-six SNPs from 28 genes were associated with the PD of rivaroxaban. The 3 most influential genes were PKNOX2, BRD3, and APOL4 for anti-Xa activity, and GRIP2, PLCE1, and MLX for diluted prothrombin time (dPT). Among them, BRD3 played an important role in both the PK and PD of rivaroxaban. Anti-Xa activity (ng/mL) differed significantly among subjects with BRD3 rs467387: 145.1 ± 55.5 versus 139.9 ± 65.1 versus 164.0 ± 68.6 for GG, GA, and AA carriers, respectively (P = 0.0002). IMPLICATIONS: This study found that that the regulation of the BRD3 gene might affect the PK and PD of rivaroxaban, suggesting that it should be studied as a new pharmacologic target. The correlation between this gene locus and clinical outcomes has yet to be verified in patients undergoing clinical treatment.

Associations between cord blood acetaminophen biomarkers and childhood asthma with and without allergic comorbidities.

BACKGROUND: Previous studies have linked prenatal acetaminophen use to increased asthma risk in children. However, none have explored this association while differentiating between asthma cases with and without other allergic conditions or by employing objective biomarkers to assess acetaminophen exposure. OBJECTIVE: To evaluate whether the detection of acetaminophen biomarkers in cord blood is associated with the subgroups of asthma both with and without allergic comorbidities in children. METHODS: Acetaminophen biomarkers, including unchanged acetaminophen and acetaminophen glucuronide, were measured in neonatal cord blood samples from the Boston Birth Cohort. Asthma subgroups were defined on the basis of physician diagnoses of asthma and other allergic conditions (atopic dermatitis and allergic rhinitis). Multinomial regressions were used to evaluate the associations between acetaminophen biomarkers and asthma subgroups, adjusting for multiple confounders, including potential indications for maternal acetaminophen use such as maternal fever. RESULTS: The study included 142 children with asthma and at least 1 other allergic condition, 55 children with asthma but no other allergic condition, and 613 children free of asthma. Detection of acetaminophen in cord blood, reflecting maternal exposure to acetaminophen shortly before delivery, was associated with 3.73 times the odds of developing asthma without allergic comorbidities (95% CI: 1.79-7.80, P = .0004). In contrast, the detection of acetaminophen in cord blood was not associated with an elevated risk of asthma with allergic comorbidities. Analysis of acetaminophen glucuronide yielded consistent results. CONCLUSION: In a prospective birth cohort, cord blood acetaminophen biomarkers were associated with an increased risk of childhood asthma without allergic comorbidities, but were not associated with childhood asthma with allergic comorbidities.

Optimal folic acid dosage in lowering homocysteine: Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy).

BACKGROUND: While folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes. METHODS: This multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment. RESULTS: The intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0-1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2-1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering. CONCLUSIONS: This randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg. GOV IDENTIFIER: NCT03472508 (Registration Date: March 21, 2018).

Evaluation of plasma vitamin E and development of proteinuria in hypertensive patients.

Background: The prospective relationship between plasma vitamin E levels and proteinuria remains uncertain. We aimed to evaluate the association between baseline plasma vitamin E levels and the development of proteinuria and examine any possible effect modifiers in patients with hypertension. Methods: This was a post hoc analysis of the renal sub-study of the China Stroke Primary Prevention Trial (CSPPT). In total, 780 participants with vitamin E measurements and without proteinuria at baseline were included in the current study. The study outcome was the development of proteinuria, defined as a urine dipstick reading of a trace or ≥ 1+ at the exit visit. Results: During a median follow-up duration of 4.4 years, the development of proteinuria occurred in 93 (11.9%) participants. Overall, there was an inverse relationship between plasma vitamin E and the development of proteinuria (per standard deviation [SD] increment; odds ratio [OR]: 0.73, 95% confidence interval [CI]: 0.55-0.96). Consistently, when plasma vitamin E was assessed as quartiles, lower risk of proteinuria development was found in participants in quartiles 2-4 (≥ 7.3 µg/mL; OR: 0.57, 95% CI: 0.34-0.96) compared to those in quartile 1. None of the variables, including sex, age, and body mass index, significantly modified the association between vitamin E and proteinuria development. Conclusion: There was a significant inverse association between plasma vitamin E levels and the development of proteinuria in patients with hypertension. The results were consistent among participants with different baseline characteristics.

MUC20 regulated by extrachromosomal circular DNA attenuates proteasome inhibitor resistance of multiple myeloma by modulating cuproptosis.

BACKGROUND: Proteasome inhibitors (PIs) are one of the most important classes of drugs for the treatment of multiple myeloma (MM). However, almost all patients with MM develop PI resistance, resulting in therapeutic failure. Therefore, the mechanisms underlying PI resistance in MM require further investigation. METHODS: We used several MM cell lines to establish PI-resistant MM cell lines. We performed RNA microarray and EccDNA-seq in MM cell lines and collected human primary MM samples to explore gene profiles. We evaluated the effect of MUC20 on cuproptosis of PI-resistant MM cells using Co-immunoprecipitation (Co-IP), Seahorse bioenergetic profiling and in vivo assay. RESULTS: This study revealed that the downregulation of Mucin 20 (MUC20) could predict PI sensitivity and outcomes in MM patients. Besides, MUC20 attenuated PI resistance in MM cells by inducing cuproptosis via the inhibition of cyclin-dependent kinase inhibitor 2 A expression (CDKN2A), which was achieved by hindering MET proto-oncogene, receptor tyrosine kinase (MET) activation. Moreover, MUC20 suppressed MET activation by repressing insulin-like growth factor receptor-1 (IGF-1R) lactylation in PI-resistant MM cells. This study is the first to perform extrachromosomal circular DNA (eccDNA) sequencing for MM, and it revealed that eccDNA induced PI resistance by amplifying kinesin family member 3 C (KIF3C) to reduce MUC20 expression in MM. CONCLUSION: Our findings indicated that MUC20 regulated by eccDNA alleviates PI resistance of MM by modulating cuproptosis, which would provide novel strategies for the treatment of PI-resistant MM.

MBA-DNet: A mask block attention-based foreign matter detection network for tobacco packages.

Foreign matter, such as varia and mildew in the cutaway view of tobacco packages, can be detected using machine vision detection technology. However, mainstream object detection algorithms have poor detection ability for small targets when applied to foreign matter detection in the cutaway view of tobacco packages. To solve this problem, this study proposes Mask Block Attention (MBA) and introduces it into the feature extraction network to improve the global modeling ability of the object detection network, further enhancing its ability to detect foreign matter in the cutaway view of tobacco packages. Meanwhile, this study establishes a K-fold packet slicing defect dataset called K-PSDDS (K-fold packet slicing defect dataset) for foreign matter in the cutaway view of tobacco packages and conducts numerous experiments on K-PSDDS. The experimental results indicate that the AP50 and APbbox of DINO (DETR with an improved denoising anchor box for end-to-end target detection) + MBA reached 94.9% and 47.7%, respectively, showing an improvement of 0.3% and 0.9% over the baseline network DINO. Meanwhile, it achieves better performance and detection capabilities than fast region-based convolutional neural networks and other detection algorithms.

Uterine Fibroids and Hypertensive Disorders in Pregnancy: A Systematic Review and Meta-Analysis.

Capsule: In this study the presence of uterine fibroids was significantly associated with an increased risk of development of hypertensive disorders of pregnancy even when accounting for age and BMI in meta-regression. This finding has potential implications for risk stratification and monitoring for hypertension during pregnancy in this population. Objective: To examine the association between uterine fibroids and the development of hypertensive disorders in pregnancy. Data sources: Cochrane, Embase, PubMed, MEDLINE, Scopus, and Web of Science databases were searched from inception through April 2023. Study Selection and Synthesis: Cohort, case-control, or case series studies including uterine fibroid status and hypertensive disorders of pregnancy status were included. The comparison group was pregnant women without uterine fibroids. Inverse-variance weighted random effects models were used to pool RR and OR estimates separately. Age and BMI were explored as potential sources of heterogeneity using inverse-variance weighted meta-regression. Main Outcomes: Hypertensive disorders of pregnancy (HDP) defined as gestational hypertension, pre-eclampsia, eclampsia, superimposed preeclampsia, or hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Results: A total of 17 studies were included (Total N=1,374,395 participants, N=64,968 with uterine fibroids). Thirteen studies were retrospective cohorts and four were case-control studies. Women with uterine fibroids had a significantly higher risk of hypertensive disorders in pregnancy compared to women without uterine fibroids with RR 1.74 (95% CI 1.33-2.27, p<0.01), and OR 2.87 (95% CI 1.38-5.97, p<0.01), in cohort studies and case-control studies, respectively. In meta-regression analyses, age did not significantly change the positive association between uterine fibroids and hypertensive disorders in pregnancy. Conclusion: Uterine fibroids were associated with an increased risk of hypertensive disorders of pregnancy when all available literature was synthesized, including when shared risk factors are examined in meta-regression analyses. Relevance: If confirmed in future studies, investigations into the mechanisms of this association are needed as this finding potentially has implications for risk stratification and monitoring for hypertensive disorders of pregnancy in this population. Trial Registration: PROSPERO, ID # 331528.

Metabolomic profiles during early childhood and risk of food allergies and asthma in multiethnic children from a prospective birth cohort.

BACKGROUND: There are increasing numbers of metabolomic studies in food allergy (FA) and asthma, which, however, are predominantly limited by cross-sectional designs, small sample size, and being conducted in European populations. OBJECTIVE: We sought to identify metabolites unique to and shared by children with FA and/or asthma in a racially diverse prospective birth cohort, the Boston Birth Cohort. METHODS: Mass spectrometry-based untargeted metabolomic profiling was performed using venous plasma collected in early childhood (n = 811). FA was diagnosed according to clinical symptoms consistent with an acute hypersensitivity reaction at food ingestion and food specific-IgE > 0.35 kU/L. Asthma was defined on the basis of physician diagnosis. Generalized estimating equations were applied to analyze metabolomic associations with FA and asthma, adjusting for potential confounders. RESULTS: During a mean ± standard deviation follow-up of 11.8 ± 5.2 years from birth, 78 children developed FA and 171 developed asthma. Androgenic and pregnenolone steroids were significantly associated with a lower risk of FA, especially for egg allergy. N,N,N-trimethyl-5-aminovalerate (odds ratio [OR] = 0.65, 95% confidence interval [CI] = 0.48-0.87), and 1-oleoyl-2-arachidonoyl-sn-glycero-3-phosphoinositol (OR = 0.77; 95% CI = 0.66-0.90) were inversely associated with FA risk. Orotidine (OR = 4.73; 95% CI = 2.2-10.2) and 4-cholesten-3-one (OR = 0.52; 95% CI = 0.35-0.77) were the top 2 metabolites associated with risk of asthma, although they had no association with FA. In comparison, children with both FA and asthma exhibited an altered metabolomic profile that aligned with that of FA, including altered levels of lipids and steroids. CONCLUSION: In this US multiethnic prospective birth cohort, unique and shared alterations in plasma metabolites during early childhood were associated with risk of developing FA and/or asthma. These findings await further validation.

Hybrid energy storage configuration method for wind power microgrid based on EMD decomposition and two-stage robust approach.

Data centers are usually characterized by high energy loads, which raises increasing sustainability concerns in both academic and daily usage. To mitigate the uncertainty and high volatility of distributed wind energy generation, this paper proposes a hybrid energy storage allocation strategy by means of the Empirical Mode Decomposition (EMD) technique and the two-stage robust method. First, this paper conducts the evolution analyses for the over- and under-evaluated uncertainty of wind power fluctuation under different time scales. Second, we employ the EMD technique to configure a high-frequency flywheel energy storage device, realizing the wind power transformation from large fluctuations to small fluctuations and the convergence of the wind power fluctuation curves in minute- and hour levels. Finally, based on the hour-level wind energy stable power curves, we carry out two-stage robust planning for the equipment capacity of low-frequency cold storage tanks and lithium bromide chillers. The case study on a data center microgrid in northeastern China confirms the effectiveness of our proposed strategy.

Isobavachalcone exhibits antifungal and antibiofilm effects against C. albicans by disrupting cell wall/membrane integrity and inducing apoptosis and autophagy.

Isobavachalcone (IBC) is a natural flavonoid with multiple pharmacological properties. This study aimed to evaluate the efficacy of IBC against planktonic growth and biofilms of Candida albicans (C. albicans) and the mechanisms underlying its antifungal action. The cell membrane integrity, cell metabolic viability, and cell morphology of C. albicans treated with IBC were evaluated using CLSM and FESEM analyses. Crystal violet staining, CLSM, and FESEM were used to assess the inhibition of biofilm formation, as well as dispersal and killing effects of IBC on mature biofilms. RNA-seq combined with apoptosis and autophagy assays was used to examine the mechanisms underlying the antifungal action of IBC. IBC exhibited excellent antifungal activity with 8 µg/mL of MIC for C. albicans. IBC disrupted the cell membrane integrity, and inhibited biofilm formation. IBC dispersed mature biofilms and damaged biofilm cells of C. albicans at 32 µg/mL. Moreover, IBC induced apoptosis and autophagy-associated cell death of C. albicans. The RNA-seq analysis revealed upregulation or downregulation of key genes involved in cell wall synthesis (Wsc1 and Fks1), ergosterol biosynthesis (Erg3, and Erg11), apoptisis (Hsp90 and Aif1), as well as autophagy pathways (Atg8, Atg13, and Atg17), and so forth, in response to IBC, as evidenced by the experiment-based phenotypic analysis. These results suggest that IBC inhibits C. albicans growth by disrupting the cell wall/membrane, caused by the altered expression of genes associated with ß-1,3-glucan and ergosterol biosynthesis. IBC induces apoptosis and autophagy-associated cell death by upregulating the expression of Hsp90, and altering autophagy-related genes involved in the formation of the Atg1 complex and the pre-autophagosomal structure. Together, our findings provide important insights into the potential multifunctional mechanism of action of IBC.

Purine degradation pathway metabolites at birth and the risk of lower respiratory tract infections in infancy.

Background: Lower respiratory tract infections (LRTIs) are the leading cause of infant morbidity and mortality worldwide, and altered metabolite production is recognised as a critical factor in LRTI pathogenesis. Methods: This study aimed to identify prenatal metabolic changes associated with LRTI risk in infancy, using liquid chromatography-mass spectrometry unbiased metabolomics analysis on cord blood from 810 full-term newborns. Results: We identified 22 compounds linked to LRTIs in infancy, enriched for purine degradation pathway (PDP) metabolites. High cord blood PDP metabolites, including xanthine, hypoxanthine, xanthosine and inosine, were linked to reduced LRTI risk during infancy. Notably, a low xanthine to uric acid ratio at birth predicted a four-fold increased LRTI risk. Conclusion: This study is the first to reveal that high cord blood PDP metabolites identify newborns at lower LRTI risk, stratifying disease risk at birth. Moreover, our results prompt further study on PDP enzymes as pharmacological targets to decrease LRTI morbidity and mortality for at-risk newborns.

Integrative analysis of noncoding mutations identifies the druggable genome in preterm birth.

Preterm birth affects ~10% of pregnancies in the US. Despite familial associations, identifying at-risk genetic loci has been challenging. We built deep learning and graphical models to score mutational effects at base resolution via integrating the pregnant myometrial epigenome and large-scale patient genomes with spontaneous preterm birth (sPTB) from European and African American cohorts. We uncovered previously unidentified sPTB genes that are involved in myometrial muscle relaxation and inflammatory responses and that are regulated by the progesterone receptor near labor onset. We studied genomic variants in these genes in our recruited pregnant women administered progestin prophylaxis. We observed that mutation burden in these genes was predictive of responses to progestin treatment for preterm birth. To advance therapeutic development, we screened ~4000 compounds, identified candidate molecules that affect our identified genes, and experimentally validated their therapeutic effects on regulating labor. Together, our integrative approach revealed the druggable genome in preterm birth and provided a generalizable framework for studying complex diseases.

High-dimensional quantile mediation analysis with application to a birth cohort study of mother-newborn pairs.

MOTIVATION: There has been substantial recent interest in developing methodology for high-dimensional mediation analysis. Yet, the majority of mediation statistical methods lean heavily on mean regression, which limits their ability to fully capture the complex mediating effects across the outcome distribution. To bridge this gap, we propose a novel approach for selecting and testing mediators throughout the full range of the outcome distribution spectrum. RESULTS: The proposed high-dimensional quantile mediation model provides a comprehensive insight into how potential mediators impact outcomes via their mediation pathways. This method's efficacy is demonstrated through extensive simulations. The study presents a real-world data application examining the mediating effects of DNA methylation on the relationship between maternal smoking and offspring birthweight. AVAILABILITY AND IMPLEMENTATION: Our method offers a publicly available and user-friendly function qHIMA(), which can be accessed through the R package HIMA at https://CRAN.R-project.org/package=HIMA.

Tumor markers for lipid metabolism-related genes: Based on small cell lung cancer and bronchial asthma dual analysis.

Numerous studies have elucidated the intricate relationship between bronchial asthma and small cell lung cancer (SCLC), as well as the role lipid metabolism genes play in transitioning from bronchial asthma to SCLC. Despite this, the predictive power of single gene biomarkers remains insufficient and necessitates the development of more accurate prognostic models. In our study, we downloaded and preprocessed scRNA-seq of SCLC from the GEO database GSE164404 and severe asthma scRNA-seq from GSE145013 using the Seurat package. Using the MSigDB database and geneCard database, we selected lipid metabolism-related genes and performed scRNA-seq data analysis from the gene expression GEO database, aiming to uncover potential links between immune signaling pathways in bronchial asthma and SCLC. Our investigations yielded differentially expressed genes based on the scRNA-seq dataset related to lipid metabolism. We executed differential gene analysis, gene ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. In-depth GSEA pathway activation analysis, crucial target gene predictions via protein-protein interactions, and key cluster gene evaluations for differential and diagnostic ROC values correlation analysis confirmed that key cluster genes are significant predictors for the progression of bronchial asthma to SCLC. To validate our findings, we performed wet laboratory experiments using real-time quantitative PCR to assess the expression of these relevant genes in SCLC cell lines. In conclusion, this research proposes a novel lipid metabolism-related gene marker that can offer comprehensive insights into the pathogenesis of bronchial asthma leading to SCLC. Although this study does not directly focus on senescence-associated molecular alterations, our findings in the lipid metabolism genes associated with inflammation and cancer progression offer valuable insights for further research targeting senescence-related changes in treating inflammatory diseases.

The U.S. PFAS exposure burden calculator for 2017-2018: Application to the HOME Study, with comparison of epidemiological findings from NHANES.

BACKGROUND: The 2017-2018 U.S. PFAS exposure burden calculator was designed to provide a summary exposure score for per- and polyfluoroalkyl substances (PFAS) mixtures using targeted PFAS analyte data. Its aim was to place PFAS burden score estimates onto a common scale based on nationally representative U.S. reference ranges from 2017 to 2018, enabling comparisons of overall PFAS burden scores across studies even if they did not measure the same set of PFAS analytes. OBJECTIVE: To use the U.S. PFAS exposure burden calculator for comparing the same mixture of PFAS compounds in similarly aged adolescents and their associations with cardiometabolic outcomes in the HOME Study and NHANES between 2015 and 2018. METHODS: We applied the PFAS burden calculator to 8 PFAS analytes measured in the serum of adolescents from the HOME Study (Cincinnati, Ohio; age range 11-14 years; years: 2016-2019; n = 207) and NHANES (US; age range 12-14 years; years 2015-2018; n = 245). We used the non-parametric Mann-Whitney U test and chi-squared test to compare the two study samples. In both studies, we examined associations of PFAS burden scores with the same cardiometabolic outcomes, adjusted for the same core set of covariates using regression analyses. We conducted sensitivity analyses to verify robustness of exposure-outcome associations, by accounting for measurement error of PFAS burden scores. RESULTS: PFAS burden scores were significantly different (p = 0.004) between the HOME Study (median: 0.00, interquartile range - 0.37, 0.34) and the NHANES samples (median: 0.04, IQR -0.11, 0.54), while no significant difference was found for PFAS summed concentrations (p = 0.661). In the HOME Study, an interquartile (IQR) increase in PFAS burden score was associated with higher total cholesterol [7.0 mg/dL, 95% CI: 0.6, 13.4]; HDL [2.8 mg/dL, 95% CI: 0.4, 5.2]; LDL [5.9 mg/dL, 95% CI: 0.5, 11.3], insulin [0.1 log(mIU/L), 95% CI: 0.01, 0.2], and HOMA-IR [0.1, 95% CI: 0.01, 0.2]. In NHANES, an IQR increase in PFAS burden score was associated with higher diastolic blood pressure [2.4 mmHg, 95% CI: 0.4, 4.4] but not with other outcomes. Sensitivity analyses in the HOME Study and NHANES were consistent with the main findings. CONCLUSIONS: Performance of the U.S. PFAS exposure burden calculator was similar in a local versus national sample of adolescents, and may be a useful tool for the assessment of PFAS mixtures across studies.

Spinal infection after vertebral augmentation: a covert complication with serious havoc.

INTRODUCTION: Vertebral augmentation, including percutaneous vertebroplasty (PVP) or kyphoplasty (PKP), is the current least invasive surgical option and has been widely used to treat the painful osteoporotic vertebral compression fractures (OVCF). However, the postoperative infections could be life-threatening, even though they rarely occur. Our studies aim to clarify the causation and outcomes of spinal infections following augmentation and meanwhile to identify the risk factors. METHODS: A retrospective study was conducted on patients with OVCF who underwent PVP or PKP, and were subsequently admitted to our institution with postoperative spinal infection between January 2010 and December 2022. A total of 33 patients were finally included. RESULTS: The rate of spinal infection after augmentation in our single institute was 0.05% (2/3893). In addition to these 2 patients, the remaining 31 were referred from other hospitals. All 33 patients exhibited elevated inflammatory parameters, 14 patients presented with fever, and 9 patients experienced neurological deficits. Additionally, 29 patients had comorbidity and risk factors. Pathogens were identified in 26 patients, while only 7 patients were examined as culture negative. 27 patients underwent revision surgery and 6 patients only received conservative therapy. Anterior surgery was performed in 2 patients, while posterior surgery was performed in 20 patients. A combined anterior-posterior surgery was performed in 5 patients. At the final follow-up, 18 patients had unrestricted mobility, 10 patients required assistance from crutches or a walker for ambulation, 4 patients needed a wheelchair, and 1 patients died after revision surgery. CONCLUSIONS: Spinal infection after vertebral augmentation is rare, but it cannot be ignored. Surgeons should make every effort to detect the potential preoperative spondylitis or discitis. Once postoperative spinal infection is confirmed, a prompt intravenous antibiotic therapy is warranted. If medication therapy fails, revision surgery involving debridement and spinal reconstruction should be considered.

Maternal Mediterranean-Style Diet Adherence during Pregnancy and Metabolomic Signature in Postpartum Plasma: Findings from the Boston Birth Cohort.

BACKGROUND: The health benefits of a Mediterranean-style diet (MSD) are well observed, but the underlying mechanisms are unclear. Metabolomic profiling offers a systematic approach for identifying which metabolic biomarkers and pathways might be affected by an MSD. OBJECTIVES: This study aimed to identify postpartum plasma metabolites that are associated with MSD adherence during pregnancy and to further test whether these identified metabolites may vary by maternal characteristics. METHODS: We analyzed data from 1410 mothers enrolled in the Boston Birth Cohort (BBC). A maternal food frequency questionnaire (FFQ) was administered and epidemiologic information was obtained via an in-person standard questionnaire interview within 24-72 h postpartum. Maternal clinical information was extracted from electronic medical records. A Mediterranean-style diet score (MSDS) was calculated using responses to the FFQ. Metabolomic profiling in postpartum plasma was conducted by liquid chromatography-MS. Linear regression models were used to assess the associations of each metabolite with an MSDS, adjusting for covariates. RESULTS: Among the 380 postpartum plasma metabolites analyzed, 24 were associated with MSDS during pregnancy (false discovery rate < 0.05). Of 24 MSDS-associated metabolites, 19 were lipids [for example, triacylglycerols, phosphatidylcholines (PCs), PC plasmalogen, phosphatidylserine, and phosphatidylethanolamine]; others were amino acids (methionine sulfoxide and threonine), tropane (nor-psi-tropine), vitamin (vitamin A), and nucleotide (adenosine). The association of adenosine and methionine sulfoxide with MSDS differed by race (P-interaction = 0.033) and maternal overweight or obesity status (P-interaction = 0.021), respectively. CONCLUSIONS: In the BBC, we identified 24 postpartum plasma metabolites associated with MSDS during pregnancy. The associations of the 2 metabolites varied by maternal race and BMI. This study provides a new insight into dietary effects on health under the skin. More studies are needed to better understand the metabolic pathways underlying the short- and long-term health benefits of an MSD during pregnancy.

Severe disseminated Nocardia brasiliensis pneumonia with normal immune function: A case report.

RATIONALE: Members of the genus Nocardia brasiliensis are Gram-positive, aerobic bacteria and exist ubiquitously in most environments. In recent years, the incidence of Nocardia brasiliensis has increased significantly and become a global concern. It may be predominantly caused pulmonary infections in immunocompromised hosts. Interestingly, however, we found that it can be present not only on immunocompromised hosts, but also to infect patients with a normal immune system. PATIENT CONCERNS: We report a very rare case of a 49-year-old immunocompetent man with disseminated Nocardia brasensis pneumonia. He had a fever for 14 days (maximum temperature about 38°C) and a history of mass rupture. DIAGNOSES: Severe Disseminated Nocardia brasiliensis pneumonia with normal immune function. INTERVENTIONS: No. OUTCOMES: The patient was finally diagnosed with Severe Disseminated Nocardia brasiliensis pneumonia and received compound sulfamethoxazole treatment for 4 months. LESSONS SUBSECTIONS: Our report highlights when cold pus appears in soft tissues such as the lower limbs, neck, nose, scalp, etc, should prompt timely evaluation and biopsy for definitive diagnosis. Be alert to a normally immunocompetent, disseminated Nocardia brasiliensis infection. Early recognition and effective treatment are necessary conditions for successful results. This would allow for better disease prognostication while enabling physicians to develop more effective treatment strategies.

Comparison of feature selection and data fusion of Fourier transform infrared and Raman spectroscopy for identifying watercolor ink.

The identification of different kinds of watercolor inks is an important work in the field of forensic science. Four different kinds of watercolor ink Spectroscopy data fusion strategies (Fourier Transform Infrared spectroscopy and Raman spectroscopy) combined with a non-linear classification model (Extreme Learning Machine) were used to identify the brand of watercolor inks. The study chose Competitive Adaptive Reweighted Sampling (CARS), Random Frog (RF), Variable Combination Population Analysis-Genetic Algorithm (VCPA-GA), and Variable Combination Population Analysis-Iteratively Retains Informative Variables (VCPA-IRIV) to extract characteristic variables for mid-level data fusion. The Cuckoo Search (CS) algorithm is used to optimize the extreme learning machine classification model. The results showed that the classification capacity of the mid-level fusion spectra model was more satisfactory than that of single Infrared spectroscopy or Raman spectroscopy. The CS-ELM models based on infrared spectroscopy used to recognize the watercolor ink according to brands (ZHENCAI, DELI, CHENGUANG, and STAEDTLER) obtained an accuracy of 66.67% in the test set using all spectral datasets. The accuracy of CS-ELM models based on Raman spectroscopy was 67.39%. The characteristic wavelength selection algorithms effectively improved the accuracy of the CS-ELM models. The classification accuracy of the mid-level spectroscopy fusion model combined with the VCPA-IRIV algorithm was 100%. The data fusion method increased effectively spectral information. The method could satisfactorily identify different brands of watercolor inks and support the preservation of artifacts, paintings, and forensic document examination.