Stimulated Raman Histology Interpretation by Artificial Intelligence Provides Near-Real-Time Pathologic Feedback for Unprocessed Prostate Biopsies.

PURPOSE: Stimulated Raman histology is an innovative technology that generates real-time, high-resolution microscopic images of unprocessed tissue, significantly reducing prostate biopsy interpretation time. This study aims to evaluate the ability for an artificial intelligence convolutional neural network to interpretate prostate biopsy histologic images created with stimulated Raman histology. MATERIALS AND METHODS: Unprocessed, unlabeled prostate biopsies were prospectively imaged using a stimulated Raman histology microscope. Following stimulated Raman histology creation, the cores underwent standard pathological processing and interpretation by at least 2 genitourinary pathologists to establish a ground truth assessment. A network, trained on 303 prostate biopsies from 100 participants, was used to measure the accuracy, sensitivity, and specificity of detecting prostate cancer on stimulated Raman histology relative to conventional pathology. The performance of the artificial intelligence was evaluated on an independent 113-biopsy test set. RESULTS: Prostate biopsy images obtained through stimulated Raman histology can be generated within a time frame of 2 to 2.75 minutes. The artificial intelligence system achieved a rapid classification of prostate biopsies with cancer, with a potential identification time of approximately 1 minute. The artificial intelligence demonstrated an impressive accuracy of 96.5% in detecting prostate cancer. Moreover, the artificial intelligence exhibited a sensitivity of 96.3% and a specificity of 96.6%. CONCLUSIONS: Stimulated Raman histology generates microscopic images capable of accurately identifying prostate cancer in real time, without the need for sectioning or tissue processing. These images can be interpreted by artificial intelligence, providing physicians with near-real-time pathological feedback during the diagnosis or treatment of prostate cancer.

Search for a Sub-eV Sterile Neutrino Using Daya Bay's Full Dataset.

This Letter presents results of a search for the mixing of a sub-eV sterile neutrino with three active neutrinos based on the full data sample of the Daya Bay Reactor Neutrino Experiment, collected during 3158 days of detector operation, which contains 5.55×10^{6} reactor ν[over ¯]_{e} candidates identified as inverse beta-decay interactions followed by neutron capture on gadolinium. The analysis benefits from a doubling of the statistics of our previous result and from improvements of several important systematic uncertainties. No significant oscillation due to mixing of a sub-eV sterile neutrino with active neutrinos was found. Exclusion limits are set by both Feldman-Cousins and CLs methods. Light sterile neutrino mixing with sin^{2}2θ_{14}≳0.01 can be excluded at 95% confidence level in the region of 0.01 eV^{2}≲|Δm_{41}^{2}|≲0.1 eV^{2}. This result represents the world-leading constraints in the region of 2×10^{-4} eV^{2}≲|Δm_{41}^{2}|≲0.2 eV^{2}.

Precision Measurement of Reactor Antineutrino Oscillation at Kilometer-Scale Baselines by Daya Bay.

We present a new determination of the smallest neutrino mixing angle θ_{13} and the mass-squared difference Δm_{32}^{2} using a final sample of 5.55×10^{6} inverse beta-decay (IBD) candidates with the final-state neutron captured on gadolinium. This sample is selected from the complete dataset obtained by the Daya Bay reactor neutrino experiment in 3158 days of operation. Compared to the previous Daya Bay results, selection of IBD candidates has been optimized, energy calibration refined, and treatment of backgrounds further improved. The resulting oscillation parameters are sin^{2}2θ_{13}=0.0851±0.0024, Δm_{32}^{2}=(2.466±0.060)×10^{-3} eV^{2} for the normal mass ordering or Δm_{32}^{2}=-(2.571±0.060)×10^{-3} eV^{2} for the inverted mass ordering.

Improved Measurement of the Evolution of the Reactor Antineutrino Flux and Spectrum at Daya Bay.

Reactor neutrino experiments play a crucial role in advancing our knowledge of neutrinos. In this Letter, the evolution of the flux and spectrum as a function of the reactor isotopic content is reported in terms of the inverse-beta-decay yield at Daya Bay with 1958 days of data and improved systematic uncertainties. These measurements are compared with two signature model predictions: the Huber-Mueller model based on the conversion method and the SM2018 model based on the summation method. The measured average flux and spectrum, as well as the flux evolution with the ^{239}Pu isotopic fraction, are inconsistent with the predictions of the Huber-Mueller model. In contrast, the SM2018 model is shown to agree with the average flux and its evolution but fails to describe the energy spectrum. Altering the predicted inverse-beta-decay spectrum from ^{239}Pu fission does not improve the agreement with the measurement for either model. The models can be brought into better agreement with the measurements if either the predicted spectrum due to ^{235}U fission is changed or the predicted ^{235}U, ^{238}U, ^{239}Pu, and ^{241}Pu spectra are changed in equal measure.

[Associations between indoor volatile organic compounds and nocturnal heart rate variability of young female adults: A panel study].

OBJECTIVE: To investigate the association between short-term exposure to indoor total volatile organic compounds (TVOC) and nocturnal heart rate variability (HRV) among young female adults. METHODS: This panel study recruited 50 young females from one university in Beijing, China from December 2021 to April 2022. All the participants underwent two sequential visits. During each visit, real time indoor TVOC concentration was monitored using an indoor air quality detector. The real time levels of indoor temperature, relative humidity, noise, carbon dioxide and fine particulate matter were monitored using a temperature and humidity meter, a noise meter, a carbon dioxide meter and a particulate counter, respectively. HRV parameters were measured using a 12-lead Holter. Mixed-effects models were used to evaluate the association between the TVOC and HRV parameters and establish the exposure-response relationships, and two-pollutant models were applied to examine the robustness of the results. RESULTS: The mean age of the 50 female subjects was (22.5±2.3) years, and the mean body mass index was (20.4±1.9) kg/m2. During this study, the median (interquartile range) of indoor TVOC concentrations was 0.069 (0.046) mg/m3, the median (interquartile range) of indoor temperature, relative humidity, carbon dioxide concentration, noise level and fine particulate matter concentration were 24.3 (2.7) ℃, 38.5% (15.0%), 0.1% (0.1%), 52.7 (5.8) dB(A) and 10.3 (21.5) µg/m3, respectively. Short-term exposure to indoor TVOC was associated with significant changes in time-domain and frequency-domain HRV parameters, and the exposure metric for most HRV parameters with the most significant changes was 1 h-moving average. Along with a 0.01 mg/m3 increment in 1 h-moving average concentration of indoor TVOC, this study observed decreases of 1.89% (95%CI: -2.28%, -1.50%) in standard deviation of all normal to normal intervals (SDNN), 1.92% (95%CI: -2.32%, -1.51%) in standard deviation of average normal to normal intervals (SDANN), 0.64% (95%CI: -1.13%, -0.14%) in percentage of adjacent NN intervals differing by more than 50 ms (pNN50), 3.52% (95%CI: -4.30%, -2.74%) in total power (TP), 5.01% (95%CI: -6.21%, -3.79%) in very low frequency (VLF) power, and 4.36% (95%CI: -5.16%, -3.55%) in low frequency (LF) power. The exposure-response curves showed that indoor TVOC was negatively correlated with SDNN, SDANN, TP, and VLF when the concentration exceeded 0.1 mg/m3. The two-pollutant models indicated that the results were generally robust after controlling indoor noise and fine particulate matter. CONCLUSION: Short-term exposure to indoor TVOC was associated with significant negative changes in nocturnal HRV of young women. This study provides an important scientific basis for relevant prevention and control measures.

[Epidemiological analysis of influenza during COVID-19 epidemic in Jiangsu Province from 2020 to 2022].

By analyzing the epidemic characteristics of influenza during the COVID-19 epidemic in Jiangsu Province from 2020 to 2022, it found that 90 721 influenza-like case samples were collected in Jiangsu Province from 2020 to 2022, of which 6 732 were nucleic acid-positive samples, with an average positive detection rate of 7.4% in three years. The annual positive detection rate presented a U-shaped distribution, with positive detection rates of 4.4%, 3.2% and 14.7%, respectively, with statistically significant differences (χ2=12 126.00, P<0.001). During the seasonal peak period of influenza from 2020 to 2022, there was a significant decrease in the intensity of the two influenza activity peaks that occurred before the virus became fully prevalent in the population. The first peak occurred from January to February 2020, and the positive detection rate of influenza nucleic acid decreased from 54.4% (317/583) in the third week to 2.1% (12/584) in the eighth week, with a statistically significant difference (χ2=394.49, P<0.001). The second occurred in December 2022, and the positive detection rate of influenza nucleic acid decreased from 14.9% (90/605) at the 49th week to 1.9% (11/572) at the 52nd week, with a statistically significant difference (χ2=62.88, P<0.001). The influenza epidemic in Jiangsu Province from 2020 to 2022 had obvious seasonal characteristics, and the distribution differences of influenza virus-positive cases in each month were statistically significant (χ2=858.00, P<0.001), with two epidemic peaks each year: winter, spring (December to March of the following year), and summer, and autumn (July to November). The epidemic strains were the B-V strain and seasonal H3 strain, respectively. There was a statistically significant difference in the positive detection rate of influenza cases detected in different age groups (χ2=60.00, P<0.001). The age group between 5 and 14 years old had the highest influenza-positive detection rate (10.4%), while the age group≥60 years old had a relatively low influenza-positive detection rate (5.1%). The positive detection rate decreased with the increase in the age group (Ztrend=12.82, P<0.001).

[Developmental effects of TCIPP and TnBP on zebrafish (Danio rerio) embryos].

Objective: To investigate the toxicity of tris (2-chloropropyl) phosphate (TCIPP) and tributyl phosphate (TnBP) on the growth and development of zebrafish embryos, as well as to explore the underlying mechanisms at the transcriptional level. Methods: With zebrafish as a model, two hpf zebrafish embryos were exposed to TCIPP and TnBP (0.1, 1, 10, 100, 500, and 1 000 µmol/L) using the semi-static method, and their rates of lethality and hatchability were determined. The transcriptome changes of 120 hpf juvenile zebrafish exposed to environmentally relevant concentrations of 0.1 and 1 µmol/L were measured. Results: The 50% lethal concentrations (LC50) of TCIPP and TnBP for zebrafish embryos were 155.30 and 27.62 µmol/L (96 hpf), 156.5 and 26.05 µmol/L (120 hpf), respectively. The 72 hpf hatching rates of TCIPP (100 µmol/L) and TnBP (10 µmol/L) were (23.33±7.72)% and (91.67±2.97)%, which were significantly decreased compared with the control group (P<0.05). Transcriptome analysis showed that TnBP had more differential genes (DEGs) than TCIPP, with a dose-response relationship. These DEGs were enriched in 32 pathways in total, including those involved in oxidative stress, energy metabolism, lipid metabolism, and nuclear receptor-related pathways, using the IPA pathway analysis. Among them, three enriched pathways overlapped between TCIPP and TnBP, including TR/RXR activation and CAR/RXR activation. Additionally, DEGs were also mapped onto pathways of LXR/RXR activation and oxidative stress for TnBP exposure only. Conclusion: Both TCIPP and TnBP have growth and developmental toxicities in zebrafish embryos, with distinct biomolecular mechanisms, and TnBP has a stronger effect than TCIPP.

[A panel study on the effect of atmospheric PM2.5 exposure on the gut microbiome in healthy elderly people aged 60-69 years old].

Objective: To analyze the short-term effect of individual atmospheric PM2.5 exposure on the diversity, enterotype, and community structure of gut microbiome in healthy elderly people in Jinan, Shandong province. Methods: The present panel study recruited 76 healthy elderly people aged 60-69 years old in Dianliu Street, Lixia District, Jinan, Shandong Province, and followed them up five times from September 2018 to January 2019. The relevant information was collected by questionnaire, physical examination, precise monitoring of individual PM2.5 exposure, fecal sample collection and gut microbiome 16S rDNA sequencing. The Dirichlet multinomial mixtures (DMM) model was used to analyze the enterotype. Linear mixed effect model and generalized linear mixed effect model were used to analyze the effect of PM2.5 exposure on gut microbiome α diversity indices (Shannon, Simpson, Chao1, and ACE indices), enterotype and abundance of core species. Results: Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 352 person-visits. The age of 76 subjects was (65.0±2.8) years old with BMI (25.0±2.4) kg/m2. There were 38 males accounting for 50% of the subjects. People with an educational level of primary school or below accounted for 10.5% of the 76 subjects, and those with secondary school and junior college or above accounting for 71.1% and 18.4%. The individual PM2.5 exposure concentration of 76 subjects during the study period was (58.7±53.7) µg/m3. DMM model showed that the subjects could be divided into four enterotypes, which were mainly driven by Bacteroides, Faecalibacterium, Lachnospiraceae, Prevotellaceae, and Ruminococcaceae. Linear mixed effects model showed that different lag periods of PM2.5 exposure were significantly associated with a lower gut α diversity index (FDR<0.05 after correction). Further analysis showed that PM2.5 exposure was significantly associated with changes in the abundances of Firmicutes (Megamonas, Blautia, Streptococcus, etc.) and Bacteroidetes (Alistipes) (FDR<0.05 after correction). Conclusion: Short-term PM2.5 exposure is significantly associated with a decrease in gut microbiome diversity and changes in the abundance of several species of Firmicutes and Bacteroidetes in the elderly. It is necessary to further explore the underlying mechanisms between PM2.5 exposure and the gut microbiome, so as to provide a scientific basis for promoting the intestinal health of the elderly.

[Analysis of distribution characteristics and influencing factors of chord µ in young myopia].

Objective: To explore and analyze the distribution characteristics of chord µ related parameters, as well as the pupil center's relative position to the coaxial corneal light reflex on the corneal surface, and the influencing factors in young myopia. Methods: This was a cross-sectional study. A total of 761 myopic patients (761 eyes) were collected from March 2021 to December 2021 in the Refractive Surgery Center of Tianjin Eye Hospital, including 388 males and 373 females, with an average age of (24±6) years. The relationship between age, sex, diopter, anterior and posterior corneal surface parameters, and chord µ related parameters was analyzed, including the x and y absolute values of the pupil center, chord µ length, and angle. The normality of the data was tested using the Kolmogorov-Smirnov test, and the influencing factors of chord µ were analyzed through Pearson and Spearman correlation analysis. Results: The equivalent spherical degree and chord µ length were (-5.47±1.66) D and (0.178±0.095) mm, respectively. The chord µ length followed an approximately normal distribution. The chord µ length of 266 eyes (35%) was distributed in the range of 0.120 to 0.200 mm, while the chord µ length of 479 eyes (63%) was<0.200 mm, and the chord µ length of 620 eyes (81%) was<0.260 mm. The chord µ angle distribution accounted for the largest proportion in the superior nasal quadrant (45.6%), followed by the superior temporal quadrant (34.3%), the inferior temporal quadrant (10.1%), and the inferior nasal quadrant (10.0%). High myopia (r=0.11, P=0.002) and high astigmatism (r=0.08, P=0.023) were associated with an increase in chord µ length. The higher the degree of myopia, the smaller the chord µ angle (r=-0.09, P=0.019). The larger the ISV (r=0.09, P=0.017), IVA (r=0.08, P=0.025), and IHD (r=0.08, P=0.039) on the anterior surface of the cornea, the longer the chord µ length. The higher the astigmatism of the posterior corneal surface, the greater the absolute value of the Y coordinate of the pupil center (r=0.07, P=0.044), and the longer the chord µ length (r=0.08, P=0.035), and the smaller the chord µ angle (r=-0.08, P=0.032). Conclusions: The chord µ length of young myopic individuals in China followed an approximately normal distribution, with the majority located in the superior nasal and superior temporal quadrants. High myopia, high astigmatism, and irregular corneal shape are the main factors related to an increase in chord µ length.

First Measurement of High-Energy Reactor Antineutrinos at Daya Bay.

This Letter reports the first measurement of high-energy reactor antineutrinos at Daya Bay, with nearly 9000 inverse beta decay candidates in the prompt energy region of 8-12 MeV observed over 1958 days of data collection. A multivariate analysis is used to separate 2500 signal events from background statistically. The hypothesis of no reactor antineutrinos with neutrino energy above 10 MeV is rejected with a significance of 6.2 standard deviations. A 29% antineutrino flux deficit in the prompt energy region of 8-11 MeV is observed compared to a recent model prediction. We provide the unfolded antineutrino spectrum above 7 MeV as a data-based reference for other experiments. This result provides the first direct observation of the production of antineutrinos from several high-Q_{ß} isotopes in commercial reactors.

Joint Determination of Reactor Antineutrino Spectra from

A joint determination of the reactor antineutrino spectra resulting from the fission of ^{235}U and ^{239}Pu has been carried out by the Daya Bay and PROSPECT Collaborations. This Letter reports the level of consistency of ^{235}U spectrum measurements from the two experiments and presents new results from a joint analysis of both data sets. The measurements are found to be consistent. The combined analysis reduces the degeneracy between the dominant ^{235}U and ^{239}Pu isotopes and improves the uncertainty of the ^{235}U spectral shape to about 3%. The ^{235}U and ^{239}Pu antineutrino energy spectra are unfolded from the jointly deconvolved reactor spectra using the Wiener-SVD unfolding method, providing a data-based reference for other reactor antineutrino experiments and other applications. This is the first measurement of the ^{235}U and ^{239}Pu spectra based on the combination of experiments at low- and highly enriched uranium reactors.

[Association of ambient fine particulate air pollution with hospitalization costs and stays for depression in China: a multicity analysis].

Objective: To explore the effect of fine particulate matter (PM2.5) pollution on depression hospitalization cost and length of stay in 57 cities of China. Methods: A total of 84 207 patients with depression in 57 cities of China from January 2013 to December 2017 were selected as the subjects. The demographic characteristics and hospitalization status of the patients were obtained from the database of basic medical insurance for urban workers and urban residents in China. The environmental exposure data of the same period were obtained from the national air quality real-time release platform of China Environmental Monitoring Station. A generalized additive model based on quasi-Poisson distribution was used to analyze PM2.5 exposure effect in each city, and the nonlinear mixing of moving average temperature, relative humidity and date was controlled by natural smooth spline function. Results: Among the included cities, southern cities accounted for 50.88% (29), and the number of female inpatients, hospitalization costs and hospitalization days accounted for 62.65%, 63.50% and 60.85% (42 735 cases, 567.78 million yuan and 1.14 million days, respectively). The proportion of hospitalized cases, hospitalization cost and length of stay in the age group of 40 to 64 years old were 59.15% (40 346 cases), 53.92% (482.15 million yuan) and 52.07% (0.98 million days), respectively. PM2.5 level was positively correlated with the number of hospitalized cases with depression, hospitalization cost and length of stay. When the 3-day moving average of PM2.5 exposure level increased by 10 µg/m3, the number of hospitalization cases increased by 0.64%. The attributed percentage (95%CI) of hospitalized cases, hospitalization costs and length of stay were 3.35% (0.57%-6.04%), 3.04% (0.52%-5.48%) and 3.07% (0.49%-5.56%), respectively. Subgroup analysis showed that the attributed percentage of hospitalization cases, hospitalization cost and length of stay to PM2.5 exposure ranged from 3.97% to 4.68%, 4.04% to 4.33% and 4.13% to 4.30% in northern China, male and cold season, respectively. Conclusion: PM2.5 exposure is associated with the increase of hospitalization cost and length of stay among Chinese urban population with depression.

[Prokaryotic expression and purification of nucleoprotein of Guertu virus and its establishment of ELISA detection method].

Objective: To obtain purified protein antigen of guertu virus (GTV) nucleoprotein (NP) and establish a rapid and accurate enzyme-linked immunosorbent assay (ELISA) method for detection of GTV antibody. Methods: Codon optimized GTV NP encoding genes were synthesized, cloned into the pet32a (+) vector, and recombinant expression plasmids were constructed and transformed into BL21 (DE3). Recombinant protein (rNP) obtained from the optimized expression were purified over a Ni column and identified by SDS-PAGE and Western blot. The purified protein was used as the antigen to optimize the reaction conditions, and an indirect ELISA assay for GTV IgG antibody was developed and optimized, which was evaluated and initially applied. Results: The prokaryotic expression plasmid pet32a-NP was successfully constructed, the recombinant protein was highly expressed in E. coli in the form of inclusion bodies, the size was about 44 kD, and the results of Western blot indicated that the recombinant protein had good antigenicity with GTV positive serum. The optimized ELISA (GTV-rNP-iELISA) established in this study showed strong specificity, high sensitivity, and the coefficient of variation within and between batches is less than 10%, and has good repeatability; the detection results are consistent with the IFA detection results. Using the established ELISA method to detect 162 sheep sera from some regions of Xinjiang in 2017-2019, the total positive rate of antibodies was 39.8%. Conclusions: The GTV NP antibody detection ELISA method has good sensitivity, reproducibility, and specificity and has the potential to be a powerful tool for the diagnosis and serological investigation of GTV infection.

[Comparative analysis of metagenomic and 16S rDNA sequencing in gut microbiota of healthy elderly].

Objective: To explore the differences in subsequent analysis between metagenomic and 16Sr DNA sequencing in compositionally characterizing gut microbiota of healthy elderly. Methods: By using a panel study design, five monthly repeated measurements were performed among 76 healthy older people in Jinan City, Shandong Province. Their fecal samples were collected, and genomic DNA was extracted and analyzed through metagenomic and 16Sr DNA sequencing to compare the composition and diversity of gut microbiota. The correlation between species abundance and α diversity was analyzed by Pearson correlation analysis, and the correlation between species abundance and ß diversity was determined by Procrustes analysis. Results: The age of 76 participants was (65.07±2.75), and the body mass index was (25.03±2.40) kg/m2. There were 38 males and 38 females. A total of 345 fecal samples were obtained from five monthly repeated measurements. Compared with 16S rDNA sequencing, metagenomic sequencing showed more annotated species at each level. The difference in the number of two sequencing species increased with the decrease of the level. Although there were significant differences in species richness between the two sequencing methods. Their species richness was highly correlated at both phylum (r=0.88, P<0.001) and genus (r=0.77, P<0.001) levels. Bacteroidetes and Firmicutes were the common dominant species. Gut microbiota diversity analysis further showed that there was a significantly positive correlation between α diversity (r=0.70, P<0.001) and ß diversities (M2=0.84, P<0.05) in the two groups. Conclusion: The annotation efficiency of metagenomic sequencing is much higher than that of 16S rDNA sequencing. The two sequencing methods are consistent in phylum abundance as well as α diversity.

[Associations between personal fine particulate matter and blood lipid profiles: A panel study in Chinese people aged 60-69 years].

Objective: To explore the association between short-term exposures to fine particulate matter (PM2.5) on blood lipids in the elderly. Methods: In this panel study, five repeated measurements were performed on 76 people aged 60-69 in Jinan city. Each participant had a PM2.5 monitor for 72 hours before each health examination, including a questionnaire survey, physical examination, and biological sample collection. Serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were examined, and non-HDL-C concentrations were calculated by subtracting HDL-C from TC. The generalized linear mixed-effects model was used to quantify the association of personal PM2.5 exposure at different lag with blood lipids and dyslipidemia. Results: The age of 70 participants was (65.0±2.8) years, of which 48.6% (34/70) were males. The BMI of participants was (25.0±2.5) kg/m2. Their TC, TG, LDL-C, HDL-C, and non-HDL-C concentrations were (5.75±1.32), (1.55±0.53), (3.27±0.94), (1.78±0.52), and (3.97±1.06) mmol/L, respectively. Generalized linear mixed-effects model showed that after adjusting for confounding factors, at lag 72 hours, each 10 µg/m3 increase in PM2.5 was associated with the percentage change in TC, LDL-C, HDL-C and non-HDL-C about 1.77% (95%CI: 1.22%-2.32%), 1.90% (95%CI: 1.18%-2.63%), 1.99% (95%CI: 1.37%-2.60%) and 1.74% (95%CI: 1.11%-2.37%), and the OR values (95%CI) of hypercholesterolemia, hypertriglyceridemia and hyperbetalipoproteinemia were 1.11 (1.01-1.22), 1.33 (1.03-1.71) and 1.15 (1.01-1.31), respectively. Conclusion: There is a significant association of short-term PM2.5 exposure with the concentration of blood lipids and the risk of dyslipidemia in the elderly.

Improved Constraints on Sterile Neutrino Mixing from Disappearance Searches in the MINOS, MINOS+, Daya Bay, and Bugey-3 Experiments.

Searches for electron antineutrino, muon neutrino, and muon antineutrino disappearance driven by sterile neutrino mixing have been carried out by the Daya Bay and MINOS+ collaborations. This Letter presents the combined results of these searches, along with exclusion results from the Bugey-3 reactor experiment, framed in a minimally extended four-neutrino scenario. Significantly improved constraints on the θ_{µe} mixing angle are derived that constitute the most constraining limits to date over five orders of magnitude in the mass-squared splitting Δm_{41}^{2}, excluding the 90% C.L. sterile-neutrino parameter space allowed by the LSND and MiniBooNE observations at 90% CL_{s} for Δm_{41}^{2}<13 eV^{2}. Furthermore, the LSND and MiniBooNE 99% C.L. allowed regions are excluded at 99% CL_{s} for Δm_{41}^{2}<1.6 eV^{2}.

[Monitoring metrics for short-term exposure to ambient ozone and pulmonary function and airway inflammation in healthy young adults].

OBJECTIVE: To assess the associations of different monitoring metrics for short-term exposure to ambient ozone (O3) with pulmonary function and airway inflammation in healthy young adults. METHODS: A total of 97 healthy young college students were recruited and followed in a panel study conducted from December 2017 to June 2018. Each participant underwent 3 follow-up visits, and lung function and fractional exhaled nitric oxide (FeNO) were measured at each visit. Ambient air pollutant concentrations were obtained from the environment monitoring station of Beijing closest to the participant residences, and meteorological data were collected from China Meteorological Data Service Center. Linear mixed-effect models were applied to assess the associations between different monitoring metrics for ambient O3 short-term exposure with pulmonary function or airway inflammation in the healthy young adults. RESULTS: During the study period, the P50 (P25, P75) values for ambient O3 concentration expressed as daily 1-hour maximum (O3-1 h max), daily maximum 8-hour average (O3-8 h max) and 24-hour average (O3-24 h avg) were 102.5 (76.8, 163.0) µg/m3, 91.1 (68.3, 154.3) µg/m3 and 61.6 (36.9, 81.7) µg/m3, respectively. The different monitoring metrics for short-term exposure to ambient O3 were significantly associated with reduced forced expiratory volume in the first second (FEV1) and increased FeNO. An interquartile range (IQR) increase in 6-d moving average of O3-1 h max (IQR=71.5 µg/m3) was associated with a 6.2% (95%CI: －11.8%, －0.5%) decrease in FEV1 and a 63.3% (95%CI: 13.8%, 134.3%) increase in FeNO. An IQR increase in 7-d moving average of O3-8 h max (IQR=62.0 µg/m3) was associated with a 6.2% (95%CI: －11.6%, －0.7%) decrease in FEV1and a 75.5% (95%CI: 19.3%, 158.0%) increase in FeNO. An IQR increase in 5-d moving average of O3-24 h avg (IQR=32.9 µg/m3) was associated with a 3.7% (95%CI: －7.1%, －0.2%) decrease in FEV1and a 25.3% (95%CI: 3.6%, 51.6%) increase in FeNO. There was no significant association between the three monitoring metrics for O3 exposure and peak expiratory flow (PEF). CONCLUSION: Short-term exposure to ambient O3 was associated with decreased lung function and increased airway inflammation among the healthy young adults, and daily 1-hour maximum was more sensitively to the respiratory effects of O3.

[Adverse maternal and infant health effects caused by thallium exposure during pregnancy].

Thallium is a highly toxic heavy metal. The adverse maternal and infant health effects caused by thallium exposure during pregnancy have also attracted more and more scholars' attention. This study focused on the sources of thallium exposure and its influencing factors, the association between thallium exposure during pregnancy and pregnancy complications and adverse birth outcomes in newborns, the effects of thallium exposure during pregnancy on children's growth and development after birth. In terms of potential mechanisms, the related research progress was reviewed in this study, which could provide a new basis for further research on the harm, prevention and control of thallium exposure during pregnancy.

[Research advances in the adverse effects of azo dyes].

China is the world's largest producer and user of dyes. The mass production and widespread use of disperse azo dyes led to environmental pollutions and potential human health risks. Azo dyes in environmental media (i.e., water, soil, air, and dust), food and clothing can enter the human body through multiple exposure routes, and some of them can be metabolized to produce more toxic metabolites, which can trigger toxic effects such as allergic reactions, tumor formation, and endocrine disruptions. This study systematically reviewed the production and use of azo dyes, environmental concentrations, human exposures, toxic effects and their underlying mechanisms, and regulations and standards. Meanwhile, the research trends of azo dyes were also discussed.

Extraction of the

This Letter reports the first extraction of individual antineutrino spectra from ^{235}U and ^{239}Pu fission and an improved measurement of the prompt energy spectrum of reactor antineutrinos at Daya Bay. The analysis uses 3.5×10^{6} inverse beta-decay candidates in four near antineutrino detectors in 1958 days. The individual antineutrino spectra of the two dominant isotopes, ^{235}U and ^{239}Pu, are extracted using the evolution of the prompt spectrum as a function of the isotope fission fractions. In the energy window of 4-6 MeV, a 7% (9%) excess of events is observed for the ^{235}U (^{239}Pu) spectrum compared with the normalized Huber-Mueller model prediction. The significance of discrepancy is 4.0σ for ^{235}U spectral shape compared with the Huber-Mueller model prediction. The shape of the measured inverse beta-decay prompt energy spectrum disagrees with the prediction of the Huber-Mueller model at 5.3σ. In the energy range of 4-6 MeV, a maximal local discrepancy of 6.3σ is observed.