Association of improved air quality with lower dementia risk in older women.

Late-life ambient air pollution is a risk factor for brain aging, but it remains unknown if improved air quality (AQ) lowers dementia risk. We studied a geographically diverse cohort of older women dementia free at baseline in 2008 to 2012 (n = 2,239, aged 74 to 92). Incident dementia was centrally adjudicated annually. Yearly mean concentrations of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were estimated using regionalized national universal kriging models and averaged over the 3-y period before baseline (recent exposure) and 10 y earlier (remote exposure). Reduction from remote to recent exposures was used as the indicator of improved AQ. Cox proportional hazard ratios (HRs) for dementia risk associated with AQ measures were estimated, adjusting for sociodemographic, lifestyle, and clinical characteristics. We identified 398 dementia cases during follow up (median = 6.1 y). PM2.5 and NO2 reduced significantly over the 10 y before baseline. Larger AQ improvement was associated with reduced dementia risks (HRPM2.5 0.80 per 1.78 µg/m3, 95% CI 0.71-0.91; HRNO2 0.80 per 3.91 parts per billion, 95% CI 0.71-0.90), equivalent to the lower risk observed in women 2.4 y younger at baseline. Higher PM2.5 at baseline was associated with higher dementia risk (HRPM2.5 1.16 per 2.90 µg/m3, 95% CI 0.98-1.38), but the lower dementia risk associated with improved AQ remained after further adjusting for recent exposure. The observed associations did not substantially differ by age, education, geographic region, Apolipoprotein E e4 genotypes, or cardiovascular risk factors. Long-term AQ improvement in late life was associated with lower dementia risk in older women.

CuFe Cooperativity at the Membrane-Electrode Interface Elicits a Tandem 2e-+2e- Mechanism for Exclusive O2-To-H2O Electroreduction.

High O2 reduction reaction (ORR) kinetics and exclusive 4e- pathway selectivity are keys to realizing a sustainable society. However, nonprecious electrocatalysts at present cannot enhance the ORR turnover frequency and H2O Faradaic efficiency (FE) concurrently. To address these two challenges, hybrid bilayer membrane (HBM) electrodes with earth-abundant metal centers are developed to control proton-coupled electron transfer (PCET) in ORR. Here, an oxidase-inspired CuFe active site is supported on a tris(2-pyridylmethyl)amine HBM and explored as a unique interface for efficient ORR. This bimetallic HBM displayed an ORR activity 1.4 times higher than the monometallic systems and exhibited the highest FE for H2O (∼94%) among Cu-, Fe-, Ni-, and Co-based HBMs. Contrary to previous studies where the ORR current decreases upon embedding the metal center in a hydrophobic lipid environment, here, the incorporation of a nitrile-terminated proton carrier at the HBM interface boosts the ORR current by 1.7 folds relative to the case where the catalytic site is directly exposed to protons in solution. This intriguing dual improvement is supported by density function theory calculations where an additional 2e-+2e- mechanism occurs in parallel to the direct 4e- pathway, highlighting the synergistic effect of the CuFe HBM for facilitating high-performance ORR. A Zn-air battery is constructed using this CuFe HBM for the first time, further demonstrating that the knowledge gained from this HBM technology holds practical values in real-life applications. These findings on interfacial PCET are envisioned to spark new design principles for future catalysts with optimal electrochemical properties for advanced energy conversion schemes.

Association between particulate air pollution and hypertensive disorders in pregnancy: A retrospective cohort study.

BACKGROUND: Epidemiological findings regarding the association of particulate matter ≤2.5 µm (PM2.5) exposure with hypertensive disorders in pregnancy (HDP) are inconsistent; evidence for HDP risk related to PM2.5 components, mixture effects, and windows of susceptibility is limited. We aimed to investigate the relationships between HDP and exposure to PM2.5 during pregnancy. METHODS AND FINDINGS: A large retrospective cohort study was conducted among mothers with singleton pregnancies in Kaiser Permanente Southern California from 2008 to 2017. HDP were defined by International Classification of Diseases-9/10 (ICD-9/10) diagnostic codes and were classified into 2 subcategories based on the severity of HDP: gestational hypertension (GH) and preeclampsia and eclampsia (PE-E). Monthly averages of PM2.5 total mass and its constituents (i.e., sulfate, nitrate, ammonium, organic matter, and black carbon) were estimated using outputs from a fine-resolution geoscience-derived model. Multilevel Cox proportional hazard models were used to fit single-pollutant models; quantile g-computation approach was applied to estimate the joint effect of PM2.5 constituents. The distributed lag model was applied to estimate the association between monthly PM2.5 exposure and HDP risk. This study included 386,361 participants (30.3 ± 6.1 years) with 4.8% (17,977/373,905) GH and 5.0% (19,381/386,361) PE-E cases, respectively. In single-pollutant models, we observed increased relative risks for PE-E associated with exposures to PM2.5 total mass [adjusted hazard ratio (HR) per interquartile range: 1.07, 95% confidence interval (CI) [1.04, 1.10] p < 0.001], black carbon [HR = 1.12 (95% CI [1.08, 1.16] p < 0.001)] and organic matter [HR = 1.06 (95% CI [1.03, 1.09] p < 0.001)], but not for GH. The population attributable fraction for PE-E corresponding to the standards of the US Environmental Protection Agency (9 µg/m3) was 6.37%. In multi-pollutant models, the PM2.5 mixture was associated with an increased relative risk of PE-E ([HR = 1.05 (95% CI [1.03, 1.07] p < 0.001)], simultaneous increase in PM2.5 constituents of interest by a quartile) and PM2.5 black carbon gave the greatest contribution of the overall mixture effects (71%) among all individual constituents. The susceptible window is the late first trimester and second trimester. Furthermore, the risks of PE-E associated with PM2.5 exposure were significantly higher among Hispanic and African American mothers and mothers who live in low- to middle-income neighborhoods (p < 0.05 for Cochran's Q test). Study limitations include potential exposure misclassification solely based on residential outdoor air pollution, misclassification of disease status defined by ICD codes, the date of diagnosis not reflecting the actual time of onset, and lack of information on potential covariates and unmeasured factors for HDP. CONCLUSIONS: Our findings add to the literature on associations between air pollution exposure and HDP. To our knowledge, this is the first study reporting that specific air pollution components, mixture effects, and susceptible windows of PM2.5 may affect GH and PE-E differently.

Twin-Field Quantum Key Distribution with Local Frequency Reference.

Twin-field quantum key distribution (TFQKD) overcomes the linear rate-loss limit, which promises a boost of secure key rate over long distance. However, the complexity of eliminating the frequency differences between the independent laser sources hinders its practical application. We analyzed and determined the frequency stability requirements for implementing TFQKD using frequency-stabilized lasers. Based on this analysis, we proposed and demonstrated a simple and practical approach that utilizes the saturated absorption spectroscopy of acetylene as an absolute reference, eliminating the need for fast frequency locking to achieve TFQKD. Adopting the 4-intensity sending-or-not-sending TFQKD protocol, we experimentally demonstrated the TFQKD over 502, 301, and 201 km ultralow-loss optical fiber, respectively. We expect this high-performance scheme will find widespread usage in future intercity and free-space quantum communication networks.

Non-alcoholic fatty liver disease is associated with brain function disruption in type 2 diabetes patients without cognitive impairment.

AIMS: To investigate the neural static and dynamic intrinsic activity of intra-/inter-network topology among patients with type 2 diabetes (T2D) with non-alcoholic fatty liver disease (NAFLD) and those without NAFLD (T2NAFLD group and T2noNAFLD group, respectively) and to assess the relationship with metabolism. METHODS: Fifty-six patients with T2NAFLD, 78 with T2noNAFLD, and 55 healthy controls (HCs) were recruited to the study. Participants had normal cognition and underwent functional magnetic resonance imaging scans, clinical measurements, and global cognition evaluation. Independent component analysis was used to identify frequency spectrum parameters, static functional network connectivity, and temporal properties of dynamic functional network connectivity (P < 0.05, false discovery rate-corrected). Statistical analysis involved one-way analysis of covariance with post hoc, partial correlation and canonical correlation analyses. RESULTS: Our findings showed that: (i) T2NAFLD patients had more disordered glucose and lipid metabolism, had more severe insulin resistance, and were more obese than T2noNAFLD patients; (ii) T2D patients exhibited disrupted brain function, as evidenced by alterations in intra-/inter-network topology, even without clinically measurable cognitive impairment; (iii) T2NAFLD patients had more significant reductions in the frequency spectrum parameters of cognitive executive and visual networks than those with T2noNAFLD; and (iv) altered brain function in T2D patients was correlated with postprandial glucose, high-density lipoprotein cholesterol, and waist-hip ratio. CONCLUSION: This study may provide novel insights into neuroimaging correlates for underlying pathophysiological processes inducing brain damage in T2NAFLD. Thus, controlling blood glucose levels, lipid levels and abdominal obesity may reduce brain damage risk in such patients.

Differential molecular responses of hemolymph and hepatopancreas of swimming crab, Portunus trituberculatus, infected with Ameson portunus (Microsporidia).

Ameson portunus (Microsporidia) has caused serious economic losses to the aquaculture industry of swimming crab, Portunus trituberculatus. The hemolymph and hepatopancreas are the main immune organs of P. trituberculatus, and the main sites of A. portunus infection. Elucidating the response characteristics of hemolymph and hepatopancreas to microsporidian infection facilitates the development of microsporidiosis prevention and control strategy. This study performed comparative transcriptomic analysis of hemolymph (PTX/PTXA) and hepatopancreas (PTG/PTGA) of P. trituberculatus uninfected and infected with A. portunus. The results showed that there were 223 and 1309 differentially expressed genes (DEGs) in PTX/PTXA and PTG/PTGA, respectively. The lysosome pathway was significantly enriched after the invasion of the hemolymph by A. portunus. Also, immune-related genes were all significantly up-regulated in the hemolymph and hepatopancreas, suggesting that the invasion by A. portunus may activate host immune responses. Unlike hemolymph, antioxidant and detoxification-related genes were also significantly up-regulated in the hepatopancreas. Moreover, metabolism-related genes were significantly down-regulated in the hepatopancreas, suggesting that energy synthesis, resistance to pathogens, and regulation of oxidative stress were suppressed in the hepatopancreas. Hemolymph and hepatopancreas have similarity and tissue specificity to microsporidian infection. The differential genes and pathways identified in this study can provide references for the prevention and control of microsporidiosis.

Prenatal Exposure to Source-Specific Fine Particulate Matter and Autism Spectrum Disorder.

In this study, associations between prenatal exposure to fine particulate matter (PM2.5) from 9 sources and development of autism spectrum disorder (ASD) were assessed in a population-based retrospective pregnancy cohort in southern California. The cohort included 318,750 mother-child singleton pairs. ASD cases (N = 4559) were identified by ICD codes. Source-specific PM2.5 concentrations were estimated from a chemical transport model with a 4 × 4 km2 resolution and assigned to maternal pregnancy residential addresses. Cox proportional hazard models were used to estimate the hazard ratios (HR) of ASD development for each individual source. We also adjusted for total PM2.5 mass and in a separate model for all other sources simultaneously. Increased ASD risk was observed with on-road gasoline (HR [CI]: 1.18 [1.13, 1.24]), off-road gasoline (1.15 [1.12, 1.19]), off-road diesel (1.08 [1.05, 1.10]), food cooking (1.05 [1.02, 1.08]), aircraft (1.04 [1.01, 1.06]), and natural gas combustion (1.09 [1.06, 1.11]), each scaled to standard deviation increases in concentration. On-road gasoline and off-road gasoline were robust for other pollutant groups. PM2.5 emitted from different sources may have different impacts on ASD. The results also identify PM source mixtures for toxicological investigations that may provide evidence for future public health policies.

Air pollution and age-dependent changes in emotional behavior across early adolescence in the U.S.

Recent studies have linked air pollution to increased risk for behavioral problems during development, albeit with inconsistent findings. Additional longitudinal studies are needed that consider how emotional behaviors may be affected when exposure coincides with the transition to adolescence - a vulnerable time for developing mental health difficulties. This study investigates if annual average PM2.5 and NO2 exposure at ages 9-10 years moderates age-related changes in internalizing and externalizing behaviors over a 2-year follow-up period in a large, nationwide U.S. sample of participants from the Adolescent Brain Cognitive Development (ABCD) Study®. Air pollution exposure was estimated based on the residential address of each participant using an ensemble-based modeling approach. Caregivers answered questions from the Child Behavior Checklist (CBCL) at the baseline, 1-year follow-up, and 2-year follow-up visits, for a total of 3 waves of data; from the CBCL we obtained scores on internalizing and externalizing problems plus 5 syndrome scales (anxious/depressed, withdrawn/depressed, rule-breaking behavior, aggressive behavior, and attention problems). Zero-inflated negative binomial models were used to examine both the main effect of age as well as the interaction of age with each pollutant on behavior while adjusting for various socioeconomic and demographic characteristics. Against our hypothesis, there was no evidence that greater air pollution exposure was related to more behavioral problems with age over time.

Repeatability assessment of anterior segment measurements in myopic patients using an anterior segment OCT with placido corneal topography and agreement with a swept-source OCT.

BACKGROUND: The precision of anterior segment biometric measurements in eyes has become increasingly important in refractive surgery. The purpose of this study is to assess the repeatability of the automatic measurements provided by a new spectral-domain optical coherence tomograph (SD-OCT)/Placido topographer (MS-39, CSO) and its agreement with a swept-source OCT (SS-OCT) biometer (CASIA SS-1000, Tomey) in patients with myopia. METHODS: The right eye of 235 subjects was scanned 3 times with both devices. The evaluated parameters included central corneal radius of the steep meridian, central corneal radius of the flat meridian, mean central corneal radius, thinnest corneal thickness, central corneal thickness, anterior chamber depth, corneal volume and diameter. The intraobserver repeatability of the MS-39 measurements was calculated using intraclass correlation coefficient (ICC), within subject standard deviation, coefficient of repeatability, coefficient of variation and repeated-measures analysis of variance of the 3 repeated measurements. The agreement between the two devices was evaluated by 95% limits of agreement (LoA). RESULTS: The majority of the parameters acquired from MS-39 showed high repeatability. The repeatability of corneal diameter was slightly lower than the other measurements, although the ICC remained high. Agreement with the CASIA SS-1000 was good, indicated by the Bland-Altman plots with narrow 95% LoA values for all parameters assessed. CONCLUSIONS: The high repeatability of automatic measurements by the new device supports its clinical application in eyes with myopia, and the good agreement between the two devices indicates they could be used interchangeably for the parameters evaluated.

Insights into the differential molecular response of non-germinated and germinated spores of Ameson portunus in vitro by comparative transcriptome analysis.

Ameson portunus, the recently discovered causative agent of "toothpaste disease" of pond-cultured swimming crabs in China has caused enormous economic losses in aquaculture. Understanding the process of spore germination is helpful to elucidate the molecular mechanism of its invasion of host cells. Here, we obtained mature and germinating spores by isolation and purification and in vitro stimulation, respectively. Then, non-germinated and germinated spores were subjected to the comparative transcriptomic analysis to disclose differential molecular responses of these two stages. The highest germination rate, i.e., 71.45 %, was achieved in 0.01 mol/L KOH germination solution. There were 9,609 significantly differentially expressed genes (DEGs), with 685 up-regulated and 8,924 down-regulated DEGs. The up-regulated genes were significantly enriched in ribosome pathway, and the down-regulated genes were significantly enriched in various metabolic pathways, including carbohydrate metabolism, amino acid metabolism and other metabolism. The results suggested that spores require various carbohydrates and amino acids as energy to support their life activities during germination and synthesize large amounts of ribosomal proteins to provide sites for DNA replication, transcription, translation and protein synthesis of the spores of A. portunus within the host cells. Functional genes related to spore germination, such as protein phosphatase CheZ and aquaporin, were also analyzed. The analysis of transcriptome data and identification of functional genes will help to understand the process of spore germination and invasion.

20-year depressive symptoms, dementia, and structural neuropathology in older women.

INTRODUCTION: The course of depressive symptoms and dementia risk is unclear, as are potential structural neuropathological common causes. METHODS: Utilizing joint latent class mixture models, we identified longitudinal trajectories of annually assessed depressive symptoms and dementia risk over 21 years in 957 older women (baseline age 72.7 years old) from the Women's Health Initiative Memory Study. In a subsample of 569 women who underwent structural magnetic resonance imaging, we examined whether estimates of cerebrovascular disease and Alzheimer's disease (AD)-related neurodegeneration were associated with identified trajectories. RESULTS: Five trajectories of depressive symptoms and dementia risk were identified. Compared to women with minimal symptoms, women who reported mild and stable and emerging depressive symptoms were at the highest risk of developing dementia and had more cerebrovascular disease and AD-related neurodegeneration. DISCUSSION: There are heterogeneous profiles of depressive symptoms and dementia risk. Common neuropathological factors may contribute to both depression and dementia. Highlights The progression of depressive symptoms and concurrent dementia risk is heterogeneous. Emerging depressive symptoms may be a prodromal symptom of dementia. Cerebrovascular disease and AD are potentially shared neuropathological factors.

Synergy between Cu and Co in a Layered Double Hydroxide Enables Close to 100% Nitrate-to-Ammonia Selectivity.

Nitrate electroreduction (NO3RR) holds promise as an energy-efficient strategy for the removal of toxic nitrate to restore the natural nitrogen cycle and mitigate the adverse impacts caused by overfertilization from suboptimal agricultural practices. However, existing catalysts suffer from limited electrocatalytic activity, poor selectivity, inadequate durability, and low scalability. To address this quadrilemma, in this study, we developed a cost-effective layered double hydroxide (LDH) electrocatalyst with a lamellar structure that presents trimetallic CuCoAl active sites on the nanomaterial surface. This codoping design enabled electrochemical upcycling of nitrate into ammonia exclusively and efficiently with an onset potential at 0 V vs RHE, where the electrocatalytic process is less energy intensive and has a lower carbon footprint than conventional practices. The synergistic interaction among Cu, Co, and Al further afforded a 99.5% Faradic efficiency (FE) and a yield rate of 0.22 mol h-1 g-1 for nitrate-to-ammonia electroreduction, surpassing the performance of state-of-the-art nonprecious metal NO3RR electrocatalysts over an extended operation period. To gain insights into the origin of the catalytic performance observed on LDH, control materials were employed to elucidate the roles of Cu and Co. Cu was found to improve the NO3RR onset potential despite displaying limited FE for ammonia synthesis, while Co was discovered to suppress the formation of nitrite byproduct though requiring large overpotential. Simulated wastewater containing phosphate and sulfate, which are typically present in industrial effluents, was used to further investigate the effect of electrolytes on NO3RR. Intriguingly, the use of phosphate buffer resulted in a superior yield rate and FE for ammonia production while simultaneously inhibiting nitrite byproduct formation compared with the sulfate case. These experimental findings were supported by density functional theory (DFT) calculations, which explored the adsorption strength of nitrate adducts adjacent to coadsorbed electrolytes on the LDH surface. Additionally, the relative free energies of NO3RR species were also computed to examine the proton-coupled electron transfer (PCET) mechanism on CuCoAl LDH, shedding light on the potential-dependent step (PDS) and the exclusive selectivity for nitrate-to-ammonia conversion. The CuCoAl LDH developed here offers scalability by eliminating the need for precious metals, rendering this earth-abundant catalyst particularly appealing for sustainable nitrate electrovalorization technology.

Genetic mechanisms of COVID-19 and its association with smoking and alcohol consumption.

We aimed to investigate the genetic mechanisms associated with coronavirus disease of 2019 (COVID-19) outcomes in the host and to evaluate the possible associations between smoking and drinking behavior and three COVID-19 outcomes: severe COVID-19, hospitalized COVID-19 and COVID-19 infection. We described the genomic loci and risk genes associated with the COVID-19 outcomes, followed by functional analyses of the risk genes. Then, a summary data-based Mendelian randomization (SMR) analysis, and a transcriptome-wide association study (TWAS) were performed for the severe COVID-19 dataset. A two-sample Mendelian randomization (MR) analysis was used to evaluate the causal associations between various measures of smoking and alcohol consumption and the COVID-19 outcomes. A total of 26 protein-coding genes, enriched in chemokine binding, cytokine binding and senescence-related functions, were associated with either severe COVID-19 or hospitalized COVID-19. The SMR and the TWAS analyses highlighted functional implications of some GWAS hits and identified seven novel genes for severe COVID-19, including CCR5, CCR5AS, IL10RB, TAC4, RMI1 and TNFSF15, some of which are targets of approved or experimental drugs. According to our studies, increasing consumption of cigarettes per day by 1 standard deviation is related to a 2.3-fold increase in susceptibility to severe COVID-19 and a 1.6-fold increase in COVID-19-induced hospitalization. Contrarily, no significant links were found between alcohol consumption or binary smoking status and COVID-19 outcomes. Our study revealed some novel COVID-19 related genes and suggested that genetic liability to smoking may quantitatively contribute to an increased risk for a severe course of COVID-19.

Experimental Twin-Field Quantum Key Distribution over 1000 km Fiber Distance.

Quantum key distribution (QKD) aims to generate secure private keys shared by two remote parties. With its security being protected by principles of quantum mechanics, some technology challenges remain towards practical application of QKD. The major one is the distance limit, which is caused by the fact that a quantum signal cannot be amplified while the channel loss is exponential with the distance for photon transmission in optical fiber. Here using the 3-intensity sending-or-not-sending protocol with the actively-odd-parity-pairing method, we demonstrate a fiber-based twin-field QKD over 1002 km. In our experiment, we developed a dual-band phase estimation and ultra-low noise superconducting nanowire single-photon detectors to suppress the system noise to around 0.02 Hz. The secure key rate is 9.53×10^{-12} per pulse through 1002 km fiber in the asymptotic regime, and 8.75×10^{-12} per pulse at 952 km considering the finite size effect. Our work constitutes a critical step towards the future large-scale quantum network.

Identification of the ataxin-1 interaction network and its impact on spinocerebellar ataxia type 1.

BACKGROUND: Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by a polyglutamine expansion in the ataxin-1 protein. The pathogenic mechanism resulting in SCA1 is still unclear. Protein-protein interactions affect the function and stability of ataxin-1. METHODS: Wild-type and mutant ataxin-1 were expressed in HEK-293T cells. The levels of expression were assessed using real-time polymerase chain reaction (PCR) and Western blots. Co-immunoprecipitation was done in HEK-293T cells expressing exogenous wild-type and mutant ataxin-1 using anti-Flag antibody following by tandem affinity purification in order to study protein-protein interactions. The candidate interacting proteins were validated by immunoprecipitation. Chromatin immunoprecipitation and high-throughput sequencing and RNA immunoprecipitation and high-throughput sequencing were performed using HEK-293T cells expressing wild-type or mutant ataxin-1. RESULTS: In this study using HEK-293T cells, we found that wild-type ataxin-1 interacted with MCM2, GNAS, and TMEM206, while mutant ataxin-1 lost its interaction with MCM2, GNAS, and TMEM206. Two ataxin-1 binding targets containing the core GGAG or AAAT were identified in HEK-293T cells using ChIP-seq. Gene Ontology analysis of the top ataxin-1 binding genes identified SLC6A15, NTF3, KCNC3, and DNAJC6 as functional genes in neurons in vitro. Ataxin-1 also was identified as an RNA-binding protein in HEK-293T cells using RIP-seq, but the polyglutamine expansion in the ataxin-1 had no direct effects on the RNA-binding activity of ataxin-1. CONCLUSIONS: An expanded polyglutamine tract in ataxin-1 might interfere with protein-protein or protein-DNA interactions but had little effect on protein-RNA interactions. This study suggested that the dysfunction of protein-protein or protein-DNA interactions is involved in the pathogenesis of SCA1.

Radiogenomics to characterize the immune-related prognostic signature associated with biological functions in glioblastoma.

OBJECTIVES: The tumor microenvironment and immune cell infiltration (ICI) associated with glioblastoma (GBM) play a vital role in cancer development, progression, and prognosis. This study aimed to establish an ICI-related prognostic biomarker and explore the associations between ICI signatures and radiomic features in patients with GBM. METHODS: The gene expression and survival data of patients with GBM were obtained from three databases. Based on the ICI pattern, an individualized ICI score for each GBM patient was developed in the discovery set (n = 400) and independently verified in the validation set (n = 374). A total of 5915 radiomic features were extracted from the intratumoral and peritumoral regions. Recursive feature elimination and support vector machine methods were performed to select the key features and generate a model predictive of low- or high- ICI scores. The prognostic value of the identified radio genomic model was examined in an independent dataset (n = 149) using imaging and survival data. RESULTS: We found that higher ICI scores often indicated worse patient prognosis (multivariable hazard ratio: 0.48 and 0.63 in discovery and validation set, respectively) and higher expression levels of immune checkpoint-related genes. A model that combined 11 radiomic features could well distinguish tumors with different ICI scores (AUC = 0.96, accuracy = 94%). This model was proven to be helpful for noninvasive prognostic stratification in an independent validation cohort. CONCLUSIONS: ICI scores may serve as an effective prognostic biomarker to characterize potential biological processes in patients with GBM. This ICI signature can be evaluated noninvasively through radiogenomic analysis. KEY POINTS: • Immune cell infiltration (ICI) scores can serve as an effective prognostic biomarker in patients with glioblastoma. • The ICI signature can be evaluated noninvasively through radiomic features derived from the intratumoral and peritumoral regions. • The prognostic value of the radiogenomic model can be verified by independent survival and MRI data.

Structural plasticity of the contralesional hippocampus and its subfields in patients with glioma.

OBJECTIVES: To characterize the structural plasticity of the contralesional hippocampus and its subfields in patients with unilateral glioma. METHODS: 3D T1-weighted MRI images were collected from 55 patients with tumors infiltrating the left (HipL, n = 27) or right (HipR, n = 28) hippocampus, along with 30 age- and sex-matched healthy controls (HC). Gray matter volume differences of the contralesional hippocampal regions and three control regions (superior frontal gyrus, caudate nucleus, and superior occipital gyrus) were evaluated using voxel-based morphometry (VBM) analyses. Volumetric differences in the hippocampus and its subregional volume were measured using the FreeSurfer software. RESULTS: Compared with HC, patients with unilateral hippocampal glioma exhibited significantly larger gray matter volume in the contralesional hippocampus and parahippocampal regions (cluster = 571 voxels for HipL; cluster 1 = 538 voxels and cluster 2 = 88 voxels for HipR; family-wise error corrected p < 0.05). No significant alterations were found in control regions. Volumetric analyses showed the same trend in the contralesional hippocampal subregions for both patient groups, including the CA1 head, CA3 head, hippocampus amygdala transition area (HATA), fimbria, and the granule cell molecular layer of the dentate gyrus head (GC-ML-DG head). Notably, the differences of the contralesional HATA (HipL: η2 = 0.418, corrected p = 0.002; HipR: η2 = 0.313, corrected p = 0.052) and fimbria (HipL: η2 = 0.450, corrected p < 0.001; HipR: η2 = 0.358, corrected p = 0.012) still held after the Bonferroni correction. CONCLUSIONS: Our findings provide evidence for macrostructural plasticity of the contralateral hippocampus in patients with unilateral hippocampal glioma. Specifically, HATA and fimbria exhibit great potential in this process. KEY POINTS: • Glioma infiltration of the hippocampal regions induces a significant increase in gray matter volume on the contralateral side. • Specifically, the HATA and fimbria regions exhibit favorable plastic potential in the process of lesion-induced structural remolding.

Associations of Autism Spectrum Disorder with PM2.5 Components: A Comparative Study Using Two Different Exposure Models.

This retrospective cohort study examined associations of autism spectrum disorder (ASD) with prenatal exposure to major fine particulate matter (PM2.5) components estimated using two independent exposure models. The cohort included 318 750 mother-child pairs with singleton deliveries in Kaiser Permanente Southern California hospitals from 2001 to 2014 and followed until age five. ASD cases during follow-up (N = 4559) were identified by ICD codes. Prenatal exposures to PM2.5, elemental (EC) and black carbon (BC), organic matter (OM), nitrate (NO3-), and sulfate (SO42-) were constructed using (i) a source-oriented chemical transport model and (ii) a hybrid model. Exposures were assigned to each maternal address during the entire pregnancy, first, second, and third trimester. In single-pollutant models, ASD was associated with pregnancy-average PM2.5, EC/BC, OM, and SO42- exposures from both exposure models, after adjustment for covariates. The direction of effect estimates was consistent for EC/BC and OM and least consistent for NO3-. EC/BC, OM, and SO42- were generally robust to adjustment for other components and for PM2.5. EC/BC and OM effect estimates were generally larger and more consistent in the first and second trimester and SO42- in the third trimester. Future PM2.5 composition health effect studies might consider using multiple exposure models and a weight of evidence approach when interpreting effect estimates.

The search for a maximum of the D-π-A paradigm for second order nonlinear optical molecular materials.

Push-pull π-conjugated molecules are one of the paradigms of second order nonlinear optical (NLO) materials and have been extensively explored. However, high-performance second order NLO materials with an optimum electron donor (D), π-bridge (π) and acceptor (A) under this paradigm are still the most sought-after. In the present work, D-π-A molecules with optimal D, π and A combination for strong second order NLO properties are proposed based on molecular orbital theories. The optimal D-π-A push-pull molecule achieves an unprecedentedly strong NLO response under the D-π-A paradigm, i.e., the static first hyperpolarizability reaches -453.92 × 10-30 esu per heavy atom using azulene as part of the π-bridge and acceptor to synergistically reinforce the strength of the acceptor. The protocols of D-π-A NLO molecule design through frontier molecular orbital matching of D, π and A with optimal combination of electron donating and accepting strengths shed light on future molecular NLO materials exploration. The simulated two-dimensional second order spectra provide useful information (e.g., sum frequency generation) on the applications of those D-π-A push-pull molecules in nonlinear optics.

Modeling spatially varying compliance effects of PM2.5 exposure reductions on gestational diabetes mellitus in southern California: Results from electronic health record data of a large pregnancy cohort.

Gestational diabetes mellitus (GDM) is a major pregnancy complication affecting approximately 14.0% of pregnancies around the world. Air pollution exposure, particularly exposure to PM2.5, has become a major environmental issue affecting health, especially for vulnerable pregnant women. Associations between PM2.5 exposure and adverse birth outcomes are generally assumed to be the same throughout a large geographical area. However, the effects of air pollution on health can very spatially in subpopulations. Such spatially varying effects are likely due to a wide range of contextual neighborhood and individual factors that are spatially correlated, including SES, demographics, exposure to housing characteristics and due to different composition of particulate matter from different emission sources. This combination of elevated environmental hazards in conjunction with socioeconomic-based disparities forms what has been described as a "double jeopardy" for marginalized sub-populations. In this manuscript our analysis combines both an examination of spatially varying effects of a) unit-changes in exposure and examines effects of b) changes from current exposure levels down to a fixed compliance level, where compliance levels correspond to the Air Quality Standards (AQS) set by the U.S. Environmental Protection Agency (EPA) and World Health Organization (WHO) air quality guideline values. Results suggest that exposure reduction policies should target certain "hotspot" areas where size and effects of potential reductions will reap the greatest rewards in terms of health benefits, such as areas of southeast Los Angeles County which experiences high levels of PM2.5 exposures and consist of individuals who may be particularly vulnerable to the effects of air pollution on the risk of GDM.