Early life air pollution exposures and thyroid function in children: a prospective cohort study.

Studies on early life ambient air pollution exposures and childhood thyroid function are scarce. This study aimed to evaluate the relationships between early life fine particulate matter (≤ 2.5 µm; PM2.5) and nitrogen dioxide (NO2) exposures and thyroid function in children. We measured the levels of thyrotropin, triiodothyronine, and free thyroxine in children (n = 684) residing in a rural Korean area at age 2, 4, 6, or 8 years from 2012 to 2020 in the Environment and Development of Children cohort. The relationship between residential average exposure levels of PM2.5 and NO2 during pregnancy and 1-year average levels before visit and thyroid function during childhood were analyzed. Inverse association between increases of 10 µg/m3 in PM2.5 during the first trimester and thyrotropin levels at aged 4 (ß, -0.12; 95% CI: -0.22, -0.02) and 6 years (ß, -0.16; 95% CI: -0.26, -0.06) were observed. No association was found between PM2.5 exposure during the second and third trimester and childhood TSH levels. Childhood PM2.5 exposure was positively associated with thyrotropin rise at aged 4 (ß, 0.2; 95% CI: 0.06, 0.35) and 6 years (ß, 0.16; 95% CI: 0.02, 0.29) and inversely related with free thyroxine levels at aged 8 years (ß, -0.04; 95% CI: -0.07, -0.01). No relationship between NO2 exposure and thyroid function was found. In conclusion, association between PM2exposure and childhood thyrotropin levels varied depending on exposure timing. Early gestational exposure showed an inverse relationship, whereas childhood exposures were positively associated with childhood thyrotropin levels. The long-term effects of early life air pollution exposure and underlying mechanisms should be investigated in future studies.

Planned Immediate Chemotherapy and Cryopreservation of Oocytes or Embryos for Fertility Preservation in Women with Malignancies.

Purpose: Oocyte and embryo cryopreservation before gonadotoxic treatment are established methods to increase the likelihood of live births. Although several sociodemographic factors were found to be associated with undergoing fertility preservation (FP) treatment, clinical characteristics such as planned immediate chemotherapy were not fully investigated. We aimed to investigate whether the planned immediate chemotherapy is related to the decision to undergo oocyte/embryo cryopreservation for FP with adjustment for other clinical characteristics. Methods: This institutional cohort study included 491 premenopausal women aged 19 years or older who visited the FP clinic at a tertiary medical center between 2006 and 2019. The primary outcome was whether the participants underwent oocyte/embryo cryopreservation. We evaluated the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of undergoing oocyte/embryo cryopreservation according to whether immediate chemotherapy was planned using univariable and multivariable logistic regression. Results: Women scheduled for immediate chemotherapy were much less likely to undergo oocyte/embryo cryopreservation than women not scheduled for immediate chemotherapy (OR = 0.46, 95% CI 0.27-0.76) in univariable logistic regression analysis. After adjustment for covariates such as marital status, type of malignancies, and calendar year period, women scheduled for immediate chemotherapy were still less likely to undergo oocyte/embryo cryopreservation than women not scheduled for immediate chemotherapy (OR = 0.31, 95% CI: 0.17-0.56). The association was not different according to the type of malignancies (p for interaction = 0.13). Regarding breast cancer, the OR for undergoing oocyte/embryo cryopreservation in women scheduled for immediate chemotherapy was robust compared with those not planned for immediate chemotherapy (OR = 0.25, 95% CI: 0.12-0.53). Conclusion: The present study demonstrated that planned immediate chemotherapy was negatively associated with undergoing oocyte/embryo cryopreservation. This information can be helpful for FP counseling.

A "flexible" compulsory dental basic research course for undergraduate students: a three-year retrospective study.

INTRODUCTION: Since 2015, the Guanghua School of Stomatology has established an elective dental basic research course (EDBRC). To make all students benefit from the dental basic research course without causing excessive academic burden, the "flexible" compulsory dental basic research course (CDBRC) was settled in 2020. This study intends to introduce the "flexible" compulsory teaching module and assessment system of CDBRC, and analyze its effectiveness over 3 years. MATERIALS AND METHODS: The grade point average (GPA), course pressure, level of basic research knowledge and skills, and students' research achievements were collected and analyzed between EDBRC and CDBRC. The unpaired t test was used to analyze the difference. RESULTS: The "flexible" CDBRC has been successfully constructed with compulsory teaching module and hierarchical assessment system. The CDBRC has not caused significant course pressure to students compared with the EDBRC. Besides, the "flexible" CDBRC can improve the students' GPA, basic research knowledge, and research achievements. CONCLUSIONS: The "flexible" CDBRC can improve students' academic performance and basic research abilities without causing significant course pressure, which can be conducted in dental schools with similar backgrounds. TRIAL REGISTRATION: Not applicable.

The clinical impact of serum soluble CD25 levels in children with Langerhans cell histiocytosis.

OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm with inflammatory characteristics. This study aims to investigate the correlation between sCD25 levels and clinical characteristics, as well as prognosis, in pediatric LCH. METHODS: Serum sCD25 levels were measured in 370 LCH patients under 18 years old using ELISA assays. The patients were divided into two cohorts based on different treatment regimens. We further assessed the predictive value for the prognosis impact of sCD25 in a test cohort, which was validated in the independent validation cohort. RESULTS: The median serum sCD25 level at diagnosis was 3908 pg/ml (range: 231-44 000pg/ml). sCD25 level was significantly higher in multi-system and risk organ positive (MS RO+) LCH patients compared to single-system(SS) LCH patients (p < 0.001). Patients with elevated sCD25 were more likely to have involvement of risk organs, skin, lung, lymph nodes, or pituitary (all p < 0.05). sCD25 level could predict LCH progression and relapse, with an area under the ROC curve of 60.6 %. The optimal cutoff value was determined at 2921 pg/ml. Patients in the high-sCD25 group had significantly worse progression-free survival compared to those in the low-sCD25 group (p < 0.05). CONCLUSION: Elevated serum sCD25 level at initial diagnosis was associated with high-risk clinical features and worse prognosis. sCD25 level can predict the progression/recurrence of LCH following first-line chemotherapy.

Menopausal stage transitions and their associations with overall and individual sleep quality in middle-aged Korean women.

BACKGROUND: Understanding the association between the menopausal transition and declining sleep quality can guide optimal timing for preventive interventions in transitioning women. However, studies lack representation of Asian women and sufficient data on the progression of menopausal stages and sleep quality changes over time in this population. METHODS: This study included 3305 women in the pre-menopause stage at baseline. The sleep quality and its components were assessed using the Pittsburgh Sleep Quality Index (PSQI). Menopausal stages were classified as pre-menopause, early transition, late transition, and post-menopause according to the Stages of Reproductive Aging Workshop+10 (STRAW+10) criteria. We estimated the longitudinal association between menopausal stage changes over time and the PSQI score, and examined the effect of being overweight. RESULTS: The trends in the PSQI scores and its components according to the menopausal stage changes over time showed that with the exception of sleep duration and habitual sleep efficiency, an overall decline was noted in sleep health during late transition and post-menopause compared to pre-menopause. These associations were independent of time-variant annual chronological aging, which was not significantly associated with sleep deterioration. Additionally, although the associations between menopausal stages and sleep quality did not significantly differ by adiposity level, the overweight group exhibited worse PSQI scores and components than did the non-overweight group. LIMITATION: Sleep quality and menopausal stage were assessed using self-reported questionnaires without objective measures. CONCLUSION: Our study underscores the importance of screening for sleep quality deterioration and implementing appropriate measures for women experiencing menopausal transition.

Ginsenoside Rg1 ameliorates stress-exacerbated Parkinson's disease in mice by eliminating RTP801 and α-synuclein autophagic degradation obstacle.

Emerging evidence shows that psychological stress promotes the progression of Parkinson's disease (PD) and the onset of dyskinesia in non-PD individuals, highlighting a potential avenue for therapeutic intervention. We previously reported that chronic restraint-induced psychological stress precipitated the onset of parkinsonism in 10-month-old transgenic mice expressing mutant human α-synuclein (αSyn) (hαSyn A53T). We refer to these as chronic stress-genetic susceptibility (CSGS) PD model mice. In this study we investigated whether ginsenoside Rg1, a principal compound in ginseng notable for soothing the mind, could alleviate PD deterioration induced by psychological stress. Ten-month-old transgenic hαSyn A53T mice were subjected to 4 weeks' restraint stress to simulate chronic stress conditions that worsen PD, meanwhile the mice were treated with Rg1 (40 mg· kg-1 ·d-1, i.g.), and followed by functional magnetic resonance imaging (fMRI) and a variety of neurobehavioral tests. We showed that treatment with Rg1 significantly alleviated both motor and non-motor symptoms associated with PD. Functional MRI revealed that Rg1 treatment enhanced connectivity between brain regions implicated in PD, and in vivo multi-channel electrophysiological assay showed improvements in dyskinesia-related electrical activity. In addition, Rg1 treatment significantly attenuated the degeneration of dopaminergic neurons and reduced the pathological aggregation of αSyn in the striatum and SNc. We revealed that Rg1 treatment selectively reduced the level of the stress-sensitive protein RTP801 in SNc under chronic stress conditions, without impacting the acute stress response. HPLC-MS/MS analysis coupled with site-directed mutation showed that Rg1 promoted the ubiquitination and subsequent degradation of RTP801 at residues K188 and K218, a process mediated by the Parkin RING2 domain. Utilizing αSyn A53T+; RTP801-/- mice, we confirmed the critical role of RTP801 in stress-aggravated PD and its necessity for Rg1's protective effects. Moreover, Rg1 alleviated obstacles in αSyn autophagic degradation by ameliorating the RTP801-TXNIP-mediated deficiency of ATP13A2. Collectively, our results suggest that ginsenoside Rg1 holds promise as a therapeutic choice for treating PD-sensitive individuals who especially experience high levels of stress and self-imposed expectations.

Mitochondrial DNA copy number variation in asthma risk, severity, and exacerbations.

BACKGROUND: Asthma pathophysiology is associated with mitochondrial dysfunction. Mitochondrial DNA copy number (mtDNA-CN) has been used as a proxy of mitochondrial function, with lower levels indicating mitochondrial dysfunction in population studies of cardiovascular diseases and cancers. OBJECTIVES: We investigated whether lower levels of mtDNA-CN are associated with asthma diagnosis, severity, and exacerbations. METHODS: mtDNA-CN is evaluated in blood from 2 cohorts: UK Biobank (UKB) (asthma, n = 39,147; no asthma, n = 302,302) and Severe Asthma Research Program (SARP) (asthma, n = 1283; nonsevere asthma, n = 703). RESULTS: Individuals with asthma have lower mtDNA-CN compared to individuals without asthma in UKB (beta, -0.006 [95% confidence interval, -0.008 to -0.003], P = 6.23 × 10-6). Lower mtDNA-CN is associated with asthma prevalence, but not severity in UKB or SARP. mtDNA-CN declines with age but is lower in individuals with asthma than in individuals without asthma at all ages. In a 1-year longitudinal study in SARP, mtDNA-CN was associated with risk of exacerbation; those with highest mtDNA-CN had the lowest risk of exacerbation (odds ratio 0.333 [95% confidence interval, 0.173 to 0.542], P = .001). Biomarkers of inflammation and oxidative stress are higher in individuals with asthma than without asthma, but the lower mtDNA-CN in asthma is independent of general inflammation or oxidative stress. Mendelian randomization studies suggest a potential causal relationship between asthma-associated genetic variants and mtDNA-CN. CONCLUSION: mtDNA-CN is lower in asthma than in no asthma and is associated with exacerbations. Low mtDNA-CN in asthma is not mediated through inflammation but is associated with a genetic predisposition to asthma.

Prenatal and childhood exposure to endocrine-disrupting chemicals and early thelarche in 8-year-old girls: A prospective study using Bayesian kernel regression.

BACKGROUND: Studies on the combined effects of persistent and non-persistent endocrine-disrupting chemicals (EDCs) on puberty are insufficient. To date, no studies have analyzed breast development at age 8 years, a key criterion for determining precocious puberty. We investigated the relationship between prenatal or childhood exposure to EDC mixtures and early thelarche, defined as breast development before age 8 years in girls. METHODS: This prospective study included 211 girls with data on prenatal and 8-year-old exposure of cadmium (Cd), lead, mercury, bisphenol-A (BPA), 3-phenoxybenzoic acid, and three phthalate metabolites from the Environment and Development of Children cohort. Prenatal exposure was assessed through samples from pregnant women at 14-27th weeks of gestation. Tanner staging was assessed by a pediatric endocrinologist. The relationship between single and mixed chemical exposures and outcomes was assessed using logistic regression, generalized additive models (GAM), and Bayesian kernel machine regression (BKMR) models. RESULTS: Early thelarche was observed in 42 (19.9%) girls at age 8 years. In the logistic regression models, the risk of early thelarche increased with increased exposure to Cd in their mothers (adjusted odds ratio [aOR] per interquartile range [IQR] = 1.80, 95% confidence interval [CI] 1.23-2.65) but decreased with prenatal BPA exposure (aOR per IQR = 0.57, 95% CI 0.35-0.92). None of the 8-year-old chemical exposures was associated with early thelarche. In the GAM, early thelarche was positively correlated with prenatal Cd and inversely associated with prenatal BPA exposure (p = 0.004 for Cd and p = 0.036 for BPA). In the BKMR models, an increase in log-transformed prenatal Cd concentrations from the 25th to 75th percentile was associated with an increase in the estimated probability of early thelarche at age 8 years (risk difference: 0.46 [95% credible interval: 0.04-0.88]) when other chemicals were set at their median values. CONCLUSIONS: Considering the combined effects of persistent and non-persistent chemical mixtures, maternal Cd exposure during the second trimester may be associated with early thelarche in 8-year-old girls.

Predicting Lung Cancer in Korean Never-Smokers With Polygenic Risk Scores.

In the last few decades, genome-wide association studies (GWAS) with more than 10,000 subjects have identified several loci associated with lung cancer and these loci have been used to develop novel risk prediction tools for cancer. The present study aimed to establish a lung cancer prediction model for Korean never-smokers using polygenic risk scores (PRSs); PRSs were calculated using a pruning-thresholding-based approach based on 11 genome-wide significant single nucleotide polymorphisms (SNPs). Overall, the odds ratios tended to increase as PRSs were larger, with the odds ratio of the top 5% PRSs being 1.71 (95% confidence interval: 1.31-2.23) using the 40%-60% percentile group as the reference, and the area under the curve (AUC) of the prediction model being of 0.76 (95% confidence interval: 0.747-0.774). The receiver operating characteristic (ROC) curves of the prediction model with and without PRSs as covariates were compared using DeLong's test, and a significant difference was observed. Our results suggest that PRSs can be valuable tools for predicting the risk of lung cancer.

Retrospective analysis of efficacy and safety of recombinant human Rh-endostatinstatin combined with concurrent radiotherapy for cervical cancer.

Objective: Retrospective study and analysis of the safety and efficacy of Rh-Rh-endostatinstatin combined with simultaneous radiotherapy in the treatment of cervical cancer. Methods: A retrospective study was used to enroll cervical cancer patients who received Rh-endostatin combined with simultaneous radiotherapy (observation group) or radiotherapy alone (control group) from January 2019 to December 2022 in the Affiliated Hospital of Hebei University, and RECIST 1.1 criteria were used to evaluate the recent efficacy, and the WHO Adverse Reaction Scale for Anti-cancer Drugs to evaluate the toxic and side effects. Results: The difference between PR, SD, PD, ORR and DCR of the two groups was not statistically significant(P>0.05), and the CR of the observation group was significantly higher than that of the control group(P<0.05). The proportion of neutropenia, hypertension, arrhythmia, hemoglobin reduction in the observation group was significantly higher than that in the control group, and the proportion of nausea and vomiting was significantly lower than that in the control group(P<0.05), and there was no significant difference in other adverse reactions(P>0.05). After intervention, the CD3+, CD3-CD19+, CD16+CD56+, CEA, CY211 of both groups were significantly lower than before treatment(P<0.05). After treatment, CD3+, CD3-CD19+, CD16+CD56+ were significantly higher in the observation group than in the control group, and WBC and PLT were significantly lower than before treatment(P<0.05). The HPV conversion rate of the observation group was significantly higher than that of the control group(P<0.05). Conclusions: Our finding revealed that Rh-endostatinstatin combined with simultaneous radiotherapy showed better clinical outcomes and favorable toxic profile than that of radiotherapy alone in the treatment of cervical cancer.

CRISPR/Cas13a-based genome editing for establishing the detection method of H9N2 subtype avian influenza virus.

Avian influenza virus (AIV) subtype H9N2 has significantly threatened the poultry business in recent years by having become the predominant subtype in flocks of chickens, ducks, and pigeons. In addition, the public health aspects of H9N2 AIV pose a significant threat to humans. Early and rapid diagnosis of H9N2 AIV is therefore of great importance. In this study, a new method for the detection of H9N2 AIV based on fluorescence intensity was successfully established using CRISPR/Cas13a technology. The Cas13a protein was first expressed in a prokaryotic system and purified using nickel ion affinity chromatography, resulting in a high-purity Cas13a protein. The best RPA (recombinase polymerase amplification) primer pairs and crRNA were designed and screened, successfully constructing the detection of H9N2 AIV based on CRISPR/Cas13a technology. Optimal concentration of Cas13a and crRNA was determined to optimize the constructed assay. The sensitivity of the optimized detection system is excellent, with a minimum detection limit of 10° copies/µL and didn't react with other avian susceptible viruses, with excellent specificity. The detection method provides the basis for the field detection of the H9N2 AIV.

[Comprehensive intervention combined with cognitive psychological care based on quality chain for patients with benign prostatic hyperplasia].

OBJECTIVE: To investigate the application effect of comprehensive intervention combined with cognitive psychological care based on the quality chain in patients with BPH. METHODS: We prospectively selected 110 cases of BPH treated in our hospital from January 2022 to March 2023 and equally randomized them into groups A and B, the former given routine intervention, while the latter comprehensive intervention combined with cognitive psychological care based on the quality chain in addition. We analyzed the results of intervention, the patients' scores on Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS), improvement of clinical indicators, self-efficacy, disease awareness and treatment compliance, and compared the data obtained between the two groups of patients. RESULTS: The effectiveness of intervention was significantly better in group B than in A (96.36% vs 65.45%, χ2 = 17.009, P<0.05). Compared with the baseline, the SAS and SDS scores were remarkably improved in the two groups after intervention (P<0.05), even more significantly in group B than in A (P<0.05). Group B also showed a markedly shorter duration of bladder spasm, lower frequency of bladder spasm per day, shorter urethral catheterization time and postoperative hospital stay, better emotion control and health management, more regular schedule, higher disease knowledge awareness, and better treatment compliance than group A (all P<0.05). CONCLUSION: Comprehensive intervention combined with cognitive psychological care based on the quality chain is significantly effective in improving BPH patients' clinical indicators, disease awareness and treatment compliance, reducing their depression and anxiety, and enhancing their self-efficacy management.

Prenatal and early-life air pollutant exposure and epigenetic aging acceleration.

BACKGROUND: This study investigated the association of prenatal and early childhood exposure to air pollution with epigenetic age acceleration (EAA) at six years of age using the Environment and Development of Children Cohort (EDC Cohort) MATERIALS & METHODS: Air pollution, including particulate matter [< 2.5 µm (PM2.5) and < 10 µm (PM10) in an aerodynamic diameter], nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO), and sulfur dioxide (SO2) were estimated based on the residential address for two periods: 1) during the whole pregnancy, and 2) for one year before the follow-up in children at six years of age. The methylation levels in whole blood at six years of age were measured, and the methylation clocks, including Horvath's clock, Horvath's skin and blood clock, PedBE, and Wu's clock, were estimated. Multivariate linear regression models were constructed to analyze the association between EAA and air pollutants. RESULTS: A total of 76 children in EDC cohort were enrolled in this study. During the whole pregnancy, interquartile range (IQR) increases in exposure to PM2.5 (4.56 µg/m3) and CO (0.156 ppm) were associated with 0.406 years and 0.799 years of EAA (Horvath's clock), respectively. An IQR increase in PM2.5 (4.76 µg/m3) for one year before the child was six years of age was associated with 0.509 years of EAA (Horvath's clock) and 0.289 years of EAA (Wu's clock). PM10 (4.30 µg/m3) and O3 (0.003 ppm) exposure in the period were also associated with EAA in Horvath's clock (0.280 years) and EAA in Horvath's skin and blood clock (0.163 years), respectively. CONCLUSION: We found that prenatal and childhood exposure to ambient air pollutants is associated with EAA among children. The results suggest that air pollution could induce excess biological aging even in prenatal and early life.

In vitro Evaluation of DINCH-Plasticized Blood Bags for Red Blood Cell Storage with CPDA-1 Anticoagulant.

Introduction: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer commonly used in blood bags. Despite its protective effects on red blood cell (RBC) storage, concerns about its reproductive toxicity exist. This study investigated the in vitro quality of RBC concentrates stored in bags using di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) as an alternative plasticizer. Methods: Using a pool-and-split study design, we produced 20 matched homogenous quintets of RBC concentrates in two DINCH bags and three DEHP bags with citrate phosphate dextrose adenine (CPDA-1) anticoagulant. RBC storage quality was assessed weekly for 35 days. Results: On day 35, the median hemolysis levels in the DINCH bags (0.297-0.342%) were marginally higher (p < 0.05) than the DEHP bags (0.204-0.240%). All DINCH bags showed <0.8% hemolysis. RBCs in the DINCH bags showed increased mean corpuscular volume and decreased eosin 5' maleimide binding than in the DEHP bags. Higher pO2 and lower pCO2 levels in the DINCH bags indicated better gas permeability than in DEHP bags. Other metabolic parameters were comparable in both bags. Compared to DEHP, DINCH exhibited considerably lower levels of plasticizer leaching into blood bags. Conclusion: The quality of RBC concentrates stored for 35 days in DINCH-plasticized blood bags with CDPA-1 is generally comparable to those in DEHP bags. Hence, DINCH can be a viable alternative to DEHP in blood bags for nonleukoreduced RBC storage even without the use of next-generation additive solutions to improve RBC preservation quality.

A plasticizer is a chemical substance added to plastic to increase its flexibility. DEHP is a plasticizer that has been widely used in many products including plastic tubing and bags of medical devices. However, concerns about DEHP-related toxicity have been debated for many years. DEHP has been replaced with other plasticizers in many products, but it is still being used in blood bags due to its protective effect on RBC preservation. DINCH is an alternative plasticizer with a low toxicology profile. This study investigated the quality of RBC concentrates stored in blood bags using DINCH. Twenty sets of five RBC concentrates were produced using two DINCH bags and three DEHP bags with CPDA-1 anticoagulant, and the storage quality was assessed weekly for 35 days. On day 35, the median hemolysis levels in the DINCH bags (0.297­0.342%) were slightly increased than the DEHP bags (0.204­0.240%). However, all DINCH bags showed hemolysis lower than the regulatory limit of 0.8%. DINCH bags exhibited better gas permeability than DEHP bags. Compared to DEHP, DINCH exhibited considerably lower levels of plasticizer leaching into blood bags. Most of the other metabolic parameters were comparable in both bags. The quality of nonleukocyte-reduced RBC concentrates stored for 35 days in DINCH-plasticized blood bags with CDPA-1 is generally comparable to those in DEHP bags. Hence, DINCH can be a viable alternative to DEHP in blood bags for RBC storage, even without the use of next-generation additive solutions to improve RBC preservation quality.

Association between phthalate exposure and sleep quality in pregnant women: Results from the Korean Children's Environmental Health Study with repeated assessment of exposure.

Background: Evidence linking environmental toxicants to sleep quality is growing; however, these associations during pregnancy remain unclear. We examined the associations of repeated measures of urinary phthalates in early and late pregnancy with multiple markers of sleep quality among pregnant women. Methods: The study population included 2324 pregnant women from the Korean Children's Environmental Health Study. We analyzed spot urine samples collected at two time points during pregnancy for exposure biomarkers of eight phthalate metabolites. We investigated associations between four summary phthalates (all phthalates: ∑Phthalates; di-(2-ethylhexyl) phthalate: ∑DEHP; phthalates from plastic sources: ∑Plastic; and antiandrogenic phthalates: ∑AA) and eight individual phthalates and self-reported sleep measures using generalized ordinal logistic regression and generalized estimating equations models that accounted for repeated exposure measurements. The models were adjusted for age, body mass index, education, gestational age, income, physical activity, smoking, occupation, chronic diseases, depression, and urinary cotinine levels. Results: Multiple individual phthalates and summary measures of phthalate mixtures, including ∑Plastic, ∑DEHP, ∑AA, and ∑Phthalates, were associated with lower sleep efficiency. To illustrate, every 1-unit log increase in ∑AA was associated with a reduction of sleep efficiency by 1.37 % (95% confidence interval [CI] = -2.41, -0.32). ∑AA and ∑Phthalates were also associated with shorter sleep duration and longer sleep latency. Associations between summary phthalate measures and sleep efficiency differed by urinary cotinine levels (P for subgroup difference < 0.05). Conclusions: Findings suggest that higher phthalate exposure may be related to lower sleep efficiency, shorter sleep duration, and prolonged sleep latency during pregnancy.

A novel infrared spectroscopy marker for assessing the postoperative infection risk in patients with upper urinary tract calculus.

The aim of this study is to evaluate the ability of infrared wavenumber of calculus to predict postoperative infection in patients with upper urinary tract calculus (UUTC), and to establish a predictive model based on this. From March 2018 to March 2023, 480 UUTC patients from Fujian Provincial Hospital were included in this study. The infrared-wavenumbers related infection score (IR-infection score) was constructed by univariate analysis, multicollinearity screening, and Lasso analysis to predict postoperative infection. Continually, the Delong test was used to compare the predictive power between the IR-infection score and traditional indicators. Afterward, we performed urine metagene sequencing and stone culture to prove the correlation between calculus toxicity and IR-infection score. Finally, logistic regression was used to build a nomogram. IR-infection score composed of four independent wavenumbers could precisely predict postoperative infection (AUCvalidation cohort = 0.707) and sepsis (AUCvalidation cohort = 0.824). IR-infection score had better predictive ability than commonly used clinical indicators. Moreover, metagenomics sequencing and calculus culture confirmed the correlation between IR-infection score and calculus toxicity (all P < 0.05). The nomogram based on the IR-infection score had high predictive power (all AUCs > 0.803). Our study first developed a novel infrared spectroscopy marker and nomogram, which can help urologists better predict postoperative infection in UUTC patients.

Assessing the Impact of Defacing Algorithms on Brain Volumetry Accuracy in MRI Analyses.

Background and Purpose: To ensure data privacy, the development of defacing processes, which anonymize brain images by obscuring facial features, is crucial. However, the impact of these defacing methods on brain imaging analysis poses significant concern. This study aimed to evaluate the reliability of three different defacing methods in automated brain volumetry. Methods: Magnetic resonance imaging with three-dimensional T1 sequences was performed on ten patients diagnosed with subjective cognitive decline. Defacing was executed using mri_deface, BioImage Suite Web-based defacing, and Defacer. Brain volumes were measured employing the QBraVo program and FreeSurfer, assessing intraclass correlation coefficient (ICC) and the mean differences in brain volume measurements between the original and defaced images. Results: The mean age of the patients was 71.10±6.17 years, with 4 (40.0%) being male. The total intracranial volume, total brain volume, and ventricle volume exhibited high ICCs across the three defacing methods and 2 volumetry analyses. All regional brain volumes showed high ICCs with all three defacing methods. Despite variations among some brain regions, no significant mean differences in regional brain volume were observed between the original and defaced images across all regions. Conclusions: The three defacing algorithms evaluated did not significantly affect the results of image analysis for the entire brain or specific cerebral regions. These findings suggest that these algorithms can serve as robust methods for defacing in neuroimaging analysis, thereby supporting data anonymization without compromising the integrity of brain volume measurements.

EGFR Mutation and TKI Treatment Promote Secretion of Small Extracellular Vesicle PD-L1 and Contribute to Immunosuppression in NSCLC.

In Asian populations with non-small-cell lung cancer (NSCLC), EGFR mutations are highly prevalent, occurring in roughly half of these patients. Studies have revealed that individuals with EGFR mutation typically fare worse with immunotherapy. In patients who received EGFR tyrosine kinase inhibitor (TKI) treatment followed by anti-PD-1 therapy, poor results were observed. The underlying mechanism remains unclear. We used high-resolution flow cytometry and ELISA to detect the circulating level of small extracellular vesicle (sEV) PD-L1 in NSCLC individuals with EGFR mutations before and after receiving TKIs. The secretion amount of sEV PD-L1 of lung cancer cell lines with EGFR mutations under TKI treatment or not were detected using high-resolution flow cytometry and Western blotting. The results revealed that patients harboring EGFR mutations exhibit increased levels of sEV PD-L1 in circulation, which inversely correlated with the presence of CD8+ T cells in tumor tissues. Furthermore, tumor cells carrying EGFR mutations secrete a higher quantity of PD-L1-positive sEVs. TKI treatment appeared to amplify the levels of PD-L1-positive sEVs in the bloodstream. Mutation-induced and TKI-induced sEVs substantially impaired the functionality of CD8+ T cells. Importantly, our findings indicated that EGFR mutations and TKI therapies promote secretion of PD-L1-positive sEVs via distinct molecular mechanisms, namely the HRS and ALIX pathways, respectively. In conclusion, the increased secretion of PD-L1-positive sEVs, prompted by genetic alterations and TKI administration, may contribute to the limited efficacy of immunotherapy observed in EGFR-mutant patients and patients who have received TKI treatment.