Alterations in sperm DNA methylation may as a mediator of paternal air pollution exposure and offspring birth outcomes: Insight from a birth cohort study.

Paternal exposure to environmental risk factors influences the offspring health. This study aimed to evaluate the association between paternal air pollution exposure mediated by sperm DNA methylation and adverse birth outcomes in offspring. We recruited 1607 fertile men and their partners from 2014 to 2016 and collected semen samples to detect sperm DNA methylation. Multivariate linear regression and weighted quantile sum regression models were used to assess the associations between paternal air pollution exposure and offspring birth outcomes. A critical exposure window was identified. Reduced representation bisulfite sequencing was used to detect sperm DNA methylation. The results demonstrated that high paternal exposure to PM2.5 (ß = -211.31, 95% CI: (-386.37, -36.24)), PM10 (ß = -178.20, 95% CI: (-277.13, -79.27)), and NO2 (ß = -84.22, 95% CI: (-165.86, -2.57)) was negatively associated with offspring's birthweight, especially in boys. Additionally, an early exposure window of 15-69 days before fertilization was recognized to be the key exposure window, which increased the risk of low birth weight and small for gestational age. Furthermore, paternal co-exposure to six air pollutants contributed to lower birthweight (ß = -51.91, 95% CI: (-92.72, -11.10)) and shorter gestational age (ß = -1.72, 95% CI: (-3.26, -0.17)) and PM2.5 was the most weighted pollutant. Paternal air pollution exposure resulted in 10,328 differentially methylated regions and the IGF2R gene was the key gene involved in the epigenetic process. These differentially methylated genes were predominantly associated with protein binding, transcriptional regulation, and DNA templating. These findings indicate that spermatogenesis is a susceptible window during which paternal exposure to air pollution affects sperm DNA methylation and the birth outcomes of offspring.

Antibacterial Effect of Euryale ferox Seed Shell Polyphenol Extract on Salmonella Typhimurium.

This study aimed to evaluate the effects of Euryale ferox Seed Shell Polyphenol Extract (EFSSPE) on a foodborne pathogenic bacterium. EFSSPE showed antimicrobial activity toward Salmonella Typhimurium CICC 22956; the minimum inhibitory concentration of EFSSPE was 1.25 mg/mL, the inhibition curve also reflected the inhibitory effect of EFSSPE on the growth of S. Typhimurium. Detection of alkaline phosphatase outside the cell revealed that EFSSPE treatment damaged the cell wall integrity of S. Typhimurium. EFSSPE also altered the membrane integrity, thereby causing leaching of 260-nm-absorbing material (bacterial proteins and DNA). Moreover, the activities of succinate dehydrogenase and malate dehydrogenase were inhibited by EFSSPE. The hydrophobicity and clustering ability of cells were affected by EFSSPE. Scanning electron microscopy showed that EFSSPE treatment damaged the morphology of the tested bacteria. These results indicate that EFSSPE can destroy the cell wall integrity and alter the permeability of the cell membrane of S. Typhimurium.

Observation of the "invisible" pulsation of soliton molecules in a bidirectional ultrafast fiber laser.

A novel optical soliton dynamics phenomenon, called "invisible" pulsation, has gradually attracted extensive interest in recent years, which can only be identified effectively with the help of real-time spectroscopy technique, i.e., dispersive Fourier transformation (DFT). In this paper, based on a new bidirectional passively mode-locked fiber laser (MLFL), the "invisible" pulsation dynamics of soliton molecules (SMs) is systematically studied. It is indicated that the spectral center intensity, pulse peak power and relative phase of SMs are periodically changed during the "invisible" pulsation, while the temporal separation inside the SMs is constant. The degree of spectral distortion is positively correlated with the pulse peak power, which verifies that self-phase modulation (SPM) is the inducement of spectral distortion. Finally, the universality of the SMs "invisible" pulsation is further experimentally verified. We believe our work is not only conducive to the development of compact and reliable bidirectional ultrafast light sources, but also of great significance to enrich the study of nonlinear dynamics.

"Invisible" pulsation and period-doubling bifurcation of harmonic mode locking in a bidirectional fiber laser.

The harmonic mode-locking (HML) "invisible" pulsation (IP) is reported, here, in a bidirectional passively mode-locked fiber laser (BPMLFL). With the help of dispersive Fourier transform (DFT) technology, it is found that due to the alike nonlinear effects experienced by two pulse trains in HML, their evolution is consistent during the IP. Further, as the increase of pump power, period-doubling bifurcations (PDBs) can be observed based on the IP phenomenon in the HML regime, the PDB path experienced by the HML from steady to chaotic is statistically obtained. Finally, the IP and PDB in the bidirectional laser are reproduced and studied through numerical simulations. The effect of IP on the coherence of solitons is further analyzed. We believe our research results will provide new insights into the study of soliton dynamics in fiber lasers.

Association of Endocrine-Disrupting Chemicals with All-Cause and Cause-Specific Mortality in the U.S.: A Prospective Cohort Study.

Wide exposure to endocrine-disrupting chemicals (EDCs) poses a great risk on human health. However, few large-scale cohort studies have comprehensively estimated the association between EDCs exposure and mortality risk. This study aimed to investigate the association of urinary EDCs exposure with mortality risk and quantify attributable mortality and economic loss. Multivariable Cox proportional hazards regression models were performed to investigate the association of 38 representative EDCs exposure with mortality risk in the National Health and Nutrition Examination Survey (NHANES). During a median follow-up of 7.7 years, 47,279 individuals were enrolled. All-cause mortality was positively associated with 1-hydroxynaphthalene, 2-hydroxynaphthalene, cadmium, antimony, cobalt, and monobenzyl phthalate. Cancer mortality was positively associated with cadmium. Cardiovascular disease (CVD) mortality was positively associated with 1-hydroxynaphthalene, 2-hydroxynaphthalene, and 2-hydroxyfluorene. Nonlinear U-shaped relationships were found between all-cause mortality and cadmium and cobalt, which was also identified between 2-hydroxyfluorene and CVD mortality. J-shaped association of cadmium exposure with cancer mortality was also determined. EDCs exposure may cause 56.52% of total deaths (1,528,500 deaths) and around 1,897 billion USD in economic costs. Exposure to certain phthalates, polycyclic aromatic hydrocarbons, phytoestrogens, or toxic metals, even at substantially low levels, is significantly associated with mortality and induces high economic costs.

Maternal BPAF exposure impaired synaptic development and caused behavior abnormality in offspring.

Bisphenol A (BPA) has been widely restricted, leading to a significant increase in the production of bisphenol AF (BPAF), one of the most common bisphenol analogs use as a substitute for BPA. However, there is limit evidence on the neurotoxicity of BPAF, especially the potential effects of maternal exposed to BPAF on offspring. A maternal BPAF exposure model was used to evaluate its effects on long-term neurobehaviors in offspring. We found that maternal BPAF exposure resulted in immune disorders, characterized by abnormal CD4+T cell subsets, and their offspring exhibited anxiety- and depression-like behaviors, as well as impairments in learning-memory, sociability and social novelty. Further, brain bulk RNA-sequencing (RNA-seq) and hippocampus single-nucleus RNA-sequencing (snRNA-seq) of offspring showed that differentially expressed genes (DEGs) were enriched in pathways related to synaptic and neurodevelopment. Synaptic ultra-structure of offspring was damaged after maternal BPAF exposure. In conclusion, maternal BPAF exposure induced behavior abnormality in adult offspring, together with synaptic and neurodevelopment defects, which might be related to maternal immune dysfunction. Our results provide a comprehensive insight into the neurotoxicity mechanism of maternal BPAF exposure during gestation. Given the increasing and ubiquitous exposure to BPAF, especially during sensitive periods of growth and development, the safety of BPAF requires urgent attention.

Human X chromosome exome sequencing identifies BCORL1 as contributor to spermatogenesis.

BACKGROUND: Infertility affects approximately 15% of couples worldwide with male infertility being responsible for approximately 50% of cases. Although accumulating evidence demonstrates the critical role of the X chromosome in spermatogenesis during the last few decades, the expression patterns and potential impact of the X chromosome, together with X linked genes, on male infertility are less well understood. METHODS: We performed X chromosome exome sequencing followed by a two-stage independent population validation in 1333 non-obstructive azoospermia cases and 1141 healthy controls to identify variant classes with high likelihood of pathogenicity. To explore the functions of these candidate genes in spermatogenesis, we first knocked down these candidate genes individually in mouse spermatogonial stem cells (SSCs) using short interfering RNA oligonucleotides and then generated candidate genes knockout mice by CRISPR-Cas9 system. RESULTS: Four low-frequency variants were identified in four genes (BCORL1, MAP7D3, ARMCX4 and H2BFWT) associated with male infertility. Functional studies of the mouse SSCs revealed that knocking down Bcorl1 or Mtap7d3 could inhibit SSCs self-renewal and knocking down Armcx4 could repress SSCs differentiation in vitro. Using CRISPR-Cas9 system, Bcorl1 and Mtap7d3 knockout mice were generated. Excitingly, Bcorl1 knockout mice were infertile with impaired spermatogenesis. Moreover, Bcorl1 knockout mice exhibited impaired sperm motility and sperm cells displayed abnormal mitochondrial structure. CONCLUSION: Our data indicate that the X-linked genes are associated with male infertility and involved in regulating SSCs, which provides a new insight into the role of X-linked genes in spermatogenesis.

Association between maternal diabetes mellitus and allergic diseases in children - A systematic review and meta-analysis.

BACKGROUND: Existing knowledge suggests that gestational diabetes mellitus was inconsistently associated with offspring allergic diseases. The aim of this study was to identify the association between maternal diabetes mellitus and the risk of offspring allergic diseases by systematic review. METHODS: We searched and retrieved three databases (PubMed, Web of Science, and Cochrane Library) for articles on the association between maternal diabetes mellitus and offspring allergic diseases published before December 31, 2019. Stata software version 16.0 was used for statistical analysis. RESULTS: Eight published studies were included in this meta-analysis. The pooled effect estimates showed the association between maternal diabetes mellitus and allergic outcomes, including asthma (OR: 1.13, 95% CI: 1.01-1.27), wheezing (OR: 1.13, 95% CI: 1.07-1.21), and atopic dermatitis (OR: 1.43, 95% CI: 1.22-1.57). Maternal diabetes mellitus was not associated with the risk of allergic sensitization, with a pooled effect estimate of 1.07 (95% CI: 0.45, 2.58). CONCLUSION: Maternal diabetes mellitus may increase the risk of allergic diseases in their children. However, this finding should be validated with future large-sample epidemiological studies covering a wider spectrum of allergic diseases.

Sufentanil EC50 for endotracheal intubation with aerosol inhalation of carbonated lidocaine by ultrasonic atomizer.

BACKGROUND: Nebulized lidocaine reduced stress response for endotracheal intubation. However, the impact of novel lidocaine aerosol inhalation for intubation by ultrasonic atomizer was unclear. Hence, we designed aerosol inhalation of lidocaine by ultrasonic atomizer, to seek whether the dosage of sufentanil for intubation could be less or not. METHODS: Intravenous injection of sufentanil started at 0.5 µg/kg, and sufentanil dosage was increased/decreased (step-size 0.05 µg/kg for sufentanil) using Dixon's up and down method. The observation was terminated after 8 reflexes. RESULTS: The EC50 and EC95 of sufentanil with lidocaine by ultrasonic atomizer for intubation were found to be 0.232 µg/kg (95% CI: 0.187-0.270 µg/kg) and 0.447 µg/kg (95% CI: 0.364-0.703 µg/kg). 55.88% out of 34 patients showed hemodynamic index change < 20% of baseline during intubation. CONCLUSION: Aerosol inhalation of lidocaine by ultrasonic atomizer reduced the dosage of sufentanil for endotracheal intubation. Lidocaine inhalation by ultrasonic atomizer for airway anesthesia with minimal dosage of sufentanil could be recommended, particularly in patients who need more stable hemodynamic changes or spontaneous respiration. TRIAL REGISTRATION: Chinese Registry of Central Trial, ChiCTR-IOR-17014198 . Registered 28 December 2017.

Urinary polycyclic aromatic hydrocarbons and sex hormones in children and adolescents: Evidence from NHANES.

BACKGROUND: Evidences showed that polycyclic aromatic hydrocarbons (PAHs) do harm to human body. However, the association between PAHs and sex hormones in children and adolescents remains unclear. OBJECTIVES: The study aims to investigate the associations between PAHs and sex hormones in the general children and adolescent population. METHODS: 967 participants aged 6-19 with complete data of PAHs exposure biomarkers, covariates and sex hormones [total testosterone (TT), estradiol (E2) and sex hormone binding globulin (SHBG)] were recruited from National Health and Nutrition Examination Survey (NHANES), 2013-2016. Free androgen index (FAI) was calculated with TT/SHBG. Multivariate linear regression models were performed in six subgroups (male children, male adolescents, male late adolescents, female children, female adolescents and female late adolescents) to estimate the associations between sex hormone alterations and PAHs exposure. RESULTS: In male puberty adolescents, weighted multivariate linear regression indicated that negative trends for 2-Hydroxynaphthalene, 1-Hydroxyphenanthrene, 2&3-Hydroxyphenanthrene and E2 (2-Hydroxynaphthalene: ß: -0.104, 95%CI: -0.180, -0.029, P < 0.01; 1-Hydroxyphenanthrene: ß: -0.112, 95%CI: -0.206, -0.018, P = 0.019; 2&3-Hydroxyphenanthrene: ß: -0.125, 95%CI: -0.232, -0.018, P = 0.022), while exposure to 2-Hydroxynaphthalene was related to TT reduction (ß: -0.099, 95%CI: -0.177, -0.020, P = 0.014). Same pattern between 2&3-Hydroxyphenanthrene and E2 alteration (2&3-Hydroxyphenanthrene: ß: -0.139, 95%CI: -0.236, -0.041, P < 0.01) was also observed in male late adolescents. In male children, we determined that 1-Hydroxyphenanthrene was negatively associated with SHBG (ß: -0.121, 95%CI: -0.205, -0.037, P < 0.01), while the same patterns were observed in male puberty children. We did not observe any significant result in female subgroups. All these results above were determined to have q value < 0.05. CONCLUSION: PAHs exposure was associated with the alterations of sex hormones in male adolescents and children. Considering the cross-sectional study design, further large-scale epidemiological study is necessary.

Hypomethylation of PRDM1 is associated with recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) rates have continued to rise during the last few decades, yet the underlying mechanisms remain poorly understood. An emerging area of interest is the mediation of gene expression by DNA methylation during early pregnancy. Here, genome-wide DNA methylation from placental villi was profiled in both RPL patients and controls. Subsequently, differentially expressed genes were analysed for changes in gene expression. Many significant differentially methylated regions (DMRs) were identified near genes dysregulated in RPL including PRDM1. Differentially expressed genes were enriched in immune response pathways indicating that abnormal immune regulation contributes to RPL. Integrated analysis of DNA methylome and transcriptome demonstrated that the expression level of PRDM1 is fine-tuned by DNA methylation. Specifically, hypomethylation near the transcription start site of PRDM1 can recruit other transcription factors, like FOXA1 and GATA2, leading to up-regulation of gene expression and resulting in changes to trophoblast cell apoptosis and migration. These phenotypic differences may be involved in RPL. Overall, our study provides new insights into PRDM1-dependent regulatory effects during RPL and suggests both a mechanistic link between changes in PRDM1 expression, as well as a role for PRDM1 methylation as a potential biomarker for RPL diagnosis.

Sensation of TRPV1 via 5-hydroxytryptamine signaling modulates pain hypersensitivity in a 6-hydroxydopamine induced mice model of Parkinson's disease.

Parkinson's disease (PD) related pain can be assigned to either nociceptive pain or neuropathic pain, in which Transient receptor potential vanilloid 1 (TRPV1) has been demonstrated to play a pivotal role. Yet little research has examined possible involvement of TRPV1 in pain in PD. Here, we show that TRPV1 is highly expressed in PD and blocking TRPV1 can alleviate pain in PD. The level of TRPV1 in 6-OHDA induced semi mice model of PD was evaluated. The effect of TRPV1 and involved serotonin (5-HT) was also examined in the model. Unilateral injection of 6-OHDA in striatum significantly decreased thermal pain threshold and induced mechanical allodynia without changes in conditioned place preference. Immunostaining revealed that great increased expression in TRPV1 in the Vc of 6-OHDA lesioned mice compared with sham mice. TRPV1 sensitization was maintained by 5-HT/5-HT3A. In 6-OHDA-lesioned mice model of PD, TRPV1 sensitization might be implicated in the maintenance of behavioral hypersensitivity by enhanced descending 5-HT pain facilitation and dorsal horn 5-HT3AR mechanism.

Epoxyeicosatrienoic acids: Emerging therapeutic agents for central post-stroke pain.

Central post-stroke pain (CPSP) is chronic neuropathic pain due to a lesion or dysfunction of the central nervous system following cerebrovascular insult. This syndrome is characterized by chronic somatosensory abnormalities including spontaneous pain, hyperalgesia and allodynia, which localize to body areas corresponding to the injured brain region. However, despite its potential to impair activities of daily life and cause mood disorders after stroke, it is probably the least recognized complication of stroke. All currently approved treatments for CPSP have limited efficacy but troublesome side effects. The detailed mechanism underlying CPSP is still under investigation; however, its diverse clinical features indicate excessive central neuronal excitability, which is attributed to loss of inhibition and excessive neuroinflammation. Recently, exogenous epoxyeicosatrienoic acids (EETs) have been used to attenuate the mechanical allodynia in CPSP rats and proven to provide a quicker onset and superior pain relief compared to the current first line drug gabapentin. This anti-nociceptive effect is mediated by reserving the normal thalamic inhibition state through neurosteroid-GABA signaling. Moreover, mounting evidence has revealed that EETs exert anti-inflammatory effects by inhibiting the expression of vascular adhesion molecules, activating NFκB, inflammatory cytokines secretion and COX-2 gene induction. The present review focuses on the extensive evidence supporting the potential of EETs to be a multi-functional therapeutic approach for CPSP. Additionally, the role of EETs in the crosstalk between anti-CPSP and the comorbid mood disorder is reviewed herein.

The Major Factors Causing the Microspore Abortion of Genic Male Sterile Mutant NWMS1 in Wheat (Triticum aestivum L.).

Male sterility is a valuable trait for genetic research and production application of wheat (Triticum aestivum L.). NWMS1, a novel typical genic male sterility mutant, was obtained from Shengnong 1, mutagenized with ethyl methane sulfonate (EMS). Microstructure and ultrastructure observations of the anthers and microspores indicated that the pollen abortion of NWMS1 started at the early uninucleate microspore stage. Pollen grain collapse, plasmolysis, and absent starch grains were the three typical characteristics of the abnormal microspores. The anther transcriptomes of NWMS1 and its wild type Shengnong 1 were compared at the early anther development stage, pollen mother cell meiotic stage, and binucleate microspore stage. Several biological pathways clearly involved in abnormal anther development were identified, including protein processing in endoplasmic reticulum, starch and sucrose metabolism, lipid metabolism, and plant hormone signal transduction. There were 20 key genes involved in the abnormal anther development, screened out by weighted gene co-expression network analysis (WGCNA), including SKP1B, BIP5, KCS11, ADH3, BGLU6, and TIFY10B. The results indicated that the defect in starch and sucrose metabolism was the most important factor causing male sterility in NWMS1. Based on the experimental data, a primary molecular regulation model of abnormal anther and pollen developments in mutant NWMS1 was established. These results laid a solid foundation for further research on the molecular mechanism of wheat male sterility.

Identification and Pathogenicity of Fungal Pathogens Causing Black Point in Wheat on the North China Plain.

Fungi associated with black point were isolated from three highly susceptible wheat genotypes in the North China Plain. The 21 isolates represented 11 fungal genera. The most prevalent genera were Alternaria (isolation frequency of 56.7%), Bipolaris (16.1%), and Fusarium (6.0%). The other eight genera were Curvularia, Aspergillus, Cladosporium, Exserohilum, Epicoccum, Nigrospora, Penicillium, and Ulocladium; their isolation frequencies ranged from 0.8 to 4.8%. The pathogenicity of the isolates was individually assessed in the greenhouse by inoculating wheat plants with spore suspensions. Ten of the 21 isolates caused significantly higher incidences of black point than that the controls. These isolates belonged to eight fungal species (A. alternata, B. sorokiniana, B. crotonis, B. cynodontis, C. spicifera, F. equiseti, E. rostratum, and E. sorghinum) based on morphological traits and phylogenetic analysis. The average incidences of black point in the eight fungal species were 32.4, 54.3, 43.0, 41.9, 37.2, 38.8, 50.1, and 34.1%, respectively. B. sorokiniana and A. alternata were determined to be the most important pathogens in the North China Plain based on fungal prevalence and symptom severity. This study is the first to identify E. rostratum as a major pathogen causing black point in wheat.

Prognostic significance of preoperative nutritional status for postoperative acute kidney injury in older patients undergoing major abdominal surgery: a retrospective cohort study.

BACKGROUND: The association between malnutrition and postoperative acute kidney injury (AKI) has not been well studied. In this study, the authors examined the association between preoperative nutritional status and postoperative AKI in older patients who underwent major abdominal surgery, as well as the predictive value of malnutrition for AKI. MATERIALS AND METHODS: The authors retrospectively included patients aged 65 or older who underwent major elective abdominal surgery. The nutritional status of the patient was evaluated using three objective nutritional indices, such as the geriatric nutritional risk index (GNRI), the prognostic nutritional index (PNI), and the controlling nutritional status (CONUT). AKI was determined using the KDIGO criteria. The authors performed logistic regression analysis to investigate the association between preoperative nutritional status and postoperative AKI, as well as the predictive value of nutritional scores for postoperative AKI. RESULTS: A total of 2775 patients were included in the study, of which 707 (25.5%), 291 (10.5%), and 517 (18.6%) had moderate to severe malnutrition according to GNRI, PNI, and CONUT calculations. After surgery, 144 (5.2%) patients developed AKI, 86.1% at stage 1, 11.1% at stage 2, and 2.8% at stage 3 as determined by KDIGO criteria. After adjustment for traditional risk factors, worse nutritional scores were associated with a higher AKI risk. In addition to traditional risk factors, these nutritional indices improved the predictive ability of AKI prediction models, as demonstrated by significant improvements in integrated discrimination and net reclassification. CONCLUSIONS: Poor preoperative nutritional status, as assessed by GNRI, PNI, and CONUT scores, was associated with an increased risk of postoperative AKI. Incorporating these scores into AKI prediction models improved their performance. These findings emphasize the need for screening surgical patients for malnutrition risk. Further research is needed to determine whether preoperative malnutrition assessment and intervention can reduce postoperative AKI incidence.

Effect of prenatal exposure to phthalates on birth weight of offspring: A meta-analysis.

Prenatal exposure to phthalates is common. However, its effect on birth weight has always been met with conflicting conclusions. To explore the effects of prenatal phthalate exposure on neonatal weight, we searched PubMed, Web of Science (WOS), Cochrane Library, and Embase databases for articles published up to October 24, 2023. Observational studies with 95% confidence intervals (CI) were included. Our findings indicate no significant association between either mixed exposure effects or single phthalate metabolites and offspring birth weight when monitoring maternal urine phthalate metabolites. When stratified by sex, ΣHMWPs and MMP significantly reduced the birth weight of female offspring (ΣHMWPs: Pooled ß = -62.08, 95%CI: -123.11 to -1.05, P = 0.046; MMP: Pooled ß = -10.77, 95%CI: -18.74 to -2.80, P = 0.008). The results of subgroup analysis showed that ΣPAEs and ΣDEHP significantly decreased birth weight in the specific gravity correction group (ΣPAEs: Pooled estimates = -29.31, 95%CI: -58.52 to -0.10, P = 0.049; ΣDEHP: Pooled estimates = -18.25, 95%CI: -33.03 to -3.47, P = 0.016), and MECPP showed a positive correlation in the creatinine correction group (MECPP: Pooled estimates = 18.45, 95%CI: 0.13 to 36.77, P = 0.048). MEP and MBzP were negatively associated with birth weight in the no adjustment for gestational age group (MEP: Pooled estimates = -7.70, 95%CI: -14.19 to -1.21, P = 0.020; MBzP: Pooled estimates = -9.55, 95%CI: -16.08 to -3.03, P = 0.004). To make the results more convincing, more high-quality studies with large samples are urgently required.

Development of interpretable machine learning models for prediction of acute kidney injury after noncardiac surgery: a retrospective cohort study.

BACKGROUND: Early identification of patients at high-risk of postoperative acute kidney injury (AKI) can facilitate the development of preventive approaches. This study aimed to develop prediction models for postoperative AKI in noncardiac surgery using machine learning algorithms. The authors also evaluated the predictive performance of models that included only preoperative variables or only important predictors. MATERIALS AND METHODS: Adult patients undergoing noncardiac surgery were retrospectively included in the study (76 457 patients in the discovery cohort and 11 910 patients in the validation cohort). AKI was determined using the KDIGO criteria. The prediction model was developed using 87 variables (56 preoperative variables and 31 intraoperative variables). A variety of machine learning algorithms were employed to develop the model, including logistic regression, random forest, extreme gradient boosting, and gradient boosting decision trees. The performance of different models was compared using the area under the receiver operating characteristic curve (AUROC). Shapley Additive Explanations (SHAP) analysis was employed for model interpretation. RESULTS: The patients in the discovery cohort had a median age of 52 years (IQR: 42-61 years), and 1179 patients (1.5%) developed AKI after surgery. The gradient boosting decision trees algorithm showed the best predictive performance using all available variables, or only preoperative variables. The AUROCs were 0.849 (95% CI: 0.835-0.863) and 0.828 (95% CI: 0.813-0.843), respectively. The SHAP analysis showed that age, surgical duration, preoperative serum creatinine, and gamma-glutamyltransferase, as well as American Society of Anesthesiologists physical status III were the most important five features. When gradually reducing the features, the AUROCs decreased from 0.852 (including the top 40 features) to 0.839 (including the top 10 features). In the validation cohort, the authors observed a similar pattern regarding the models' predictive performance. CONCLUSIONS: The machine learning models the authors developed had satisfactory predictive performance for identifying high-risk postoperative AKI patients. Furthermore, the authors found that model performance was only slightly affected when only preoperative variables or only the most important predictive features were included.

Estimating lead-attributable mortality burden by socioeconomic status in the USA.

BACKGROUND: This study aimed to estimate population-level and state-level lead-attributable mortality burdens stratified by socioeconomic status (SES) class in the USA. METHODS: Based on the National Health and Nutrition Examination Survey (NHANES), we constructed individual-level SES scores from income, employment, education and insurance data. We assessed the association between the blood lead levels (BLL) and all-cause mortality by Cox regression in the NHANES cohort (n = 31 311, 4467 deaths). With estimated hazard ratios (HR) and prevalences of medium (2-5 µg/dL) and high (≥ 5 µg/dL) BLL, we computed SES-stratified population-attributable fractions (PAFs) of all-cause mortality from lead exposure across 1999-2019. We additionally conducted a systematic review to estimate the lead-attributable mortality burden at state-level. RESULTS: The HR for every 2-fold increase in the BLL decreased from 1.23 (1.10-1.38) for the lowest SES class to 1.05 (0.90-1.23) for the highest SES class. Across all SES quintiles, medium BLL exhibited a greater mortality burden. Individuals with lower SES had higher lead-attributable burdens, and such disparities haver persisted over the past two decades. In 2017-19, annually 67 000 (32 000-112 000) deaths in the USA were attributable to lead exposure, with 18 000 (2000-41 000) of these deaths occurring in the lowest SES class. Substantial disparities in the state-level mortality burden attributable to lead exposure were also highlighted. CONCLUSIONS: These findings suggested that disparities in lead-attributable mortality burden persisted within US adults, due to heterogeneities in the effect sizes of lead exposure as well as in the BLL among different SES classes.