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Ensuring optimal iodine nutrition in pregnant women is a global public health concern. However, there is no direct data on safe tolerable upper intake levels (ULs) for pregnant women. A cross-sectional study was performed to determine the ULs of pregnant women. A total of 744 pregnant women were enrolled in this study. The median (IQR) urinary iodine concentration (UIC) in pregnant women was 150.2 (87.6, 268.0) μg/L, and the urinary iodine excretion (UIE) over 24 h was 204.2 (116.0, 387.0) μg/day. Compared with those with a UIE figure of between 150–250 μg/day, the reference group, the prevalence of thyroid dysfunction was 5.7 times higher (95%CI: 1.7, 19.2) in pregnant women with a UIE figure of between 450–550 μg/day, and 3.9 times higher (95%CI: 1.5, 10.3) in pregnant women with a UIE figure of ≥550 μg/day. Compared with an estimated iodine intake (EII) of between 100–200 μg/day, the reference group, the prevalence of thyroid dysfunction was 4.3 times higher (95%CI: 1.3, 14.4) in pregnant women with a UIE figure of between 500–600 μg/day, and 3.6 times higher (95%CI: 1.5, 8.9) in pregnant women with UIE of ≥600 μg/day. In general, our cross-sectional study found that excessive iodine intake during pregnancy appears to directly increase the risk of thyroid dysfunction. Avoiding chronic iodine intakes of 500 μg/day or higher or having a UIE figure of ≥450 μg/day is recommended for pregnant women in China.

The relationship between serum iodine and thyroid dysfunctions in male and female adults is poorly understood. This study aimed to explore the relationship between serum and urine iodine and thyroid dysfunction in male and female adults. A total of 1320 participants were included in the final analysis. We collected basic demographic information, as well as blood and spot urine samples, to determine serological indices and iodine nutritional status of subjects. The median (IQR) of UIC, UIC/UCr, SIC were 155.8 (94.5, 211.1) µg/L, 138.1 (91.1, 207.6) µg/g and 70.6 (59.8, 83.9) µg/L, respectively. SIC was positively correlated with UIC and UIC/UCr (P P P = 0.02, P = 0.002). In male subjects, subjects with SIC༞97.1 µg/L had a higher risk of hyperthyroidism (OR = 2.91, 95% CI: 1.38, 6.19) and overt hypothyroidism (OR = 5.59, 95% CI: 1.88, 6.42). In female subjects, subjects with SIC

Background The relationship between low serum iodine and thyroid dysfunctions in adults is not well understood. This study aimed to explore the relationship between serum and urinary iodine and thyroid dysfunctions in the adult population. Methods: A total of 1320 participants were included in the final analysis. We collected basic demographic information, as well as blood and spot urine samples, to determine serological indices and iodine nutritional status of subjects. Results: The median (IQR) serum iodine (SI) level was 70.5µg/L (59.6–83.6µg/L). Compared to those with 59.6µg/L ≤ SI P = 0.02) was significantly higher than that of sUIC/UCr (0.446, P = 0.005). Conclusions: Serum iodine is more sensitive than urine iodine in the diagnosis of thyroid dysfunctions. Low serum iodine concentration is associated with an increased risk of thyroid dysfunctions, especially hypothyroidism.

Objectives: The reference values for thyroid volume (Tvol) determined by ultrasound require supportive data of normal Tvol from local iodine-sufficient populations. This study aimed to explore new reference values for Tvol in Chinese adults and comprehensively evaluate the factors associated with enlarged Tvol. Methods: A cross-sectional study was conducted in Tianjin, China. Tvol was measured by ultrasound in adults with long-term iodine sufficiency. Blood and urine samples were collected to evaluate biochemical indexes, thyroid function, and iodine status. Results: A total of 1,991 adults from the urban and suburban areas were analysed. The trend of Tvol increasing with age was observed in men under age 40 years and in women under age 52 years. In the quantile regression analyses, we found that body surface area (BSA) (β = 7.22, 95% CI: 5.33, 9.12), thyroid-stimulating hormone (TSH) (β = −1.48, 95% CI: −2.39, −0.57), thyroid nodules (TNs) (β = 6.70, 95% CI: 2.19, 11.22), and metabolic syndrome (MetS) (β = 1.40, 95% CI: 0.63, 2.17) had a strong effect on Tvol at higher percentiles in males. The dominant factors influencing Tvol were BSA (β = 9.64, 95% CI: 2.66, 16.61), TSH (β = −0.78, 95% CI: −1.16, −0.39), and TNs (β = 1.11, 95% CI: 0.43, 1.79) in females. The largest reference values for Tvol based on BSA were 20.18 (17.79, 24.32) mL in males and 15.31 (14.05, 16.70) mL in females. Conclusions: Quantile regression analyses showed that a high BSA index, a decreased TSH level, and the prevalence of TNs were essential factors associated with the enlargement of the thyroid gland. Our findings reported the new reference values for Tvol determined by ultrasound based on gender and BSA in Chinese adults.

This paper develops a new biased estimator—generalized ridge and principal correlation (GRPC) estimator of the regression coefficient in the growth curve model. The properties of the proposed estimator are shown to be superior to those of least squares (LS) estimator, principal correlation estimator, principal component estimator, and generalized ridge and principal component estimator in terms of both the mean squared error (MSE) and Pitman closeness (PMC). Moreover, a numerical study on synthetic data has been performed to demonstrate the optimality of the proposed estimator.

We aimed to explore the genotypic and phenotypic characteristics of neonatal-onset inflammatory bowel disease (IBD) with combined immunodeficiency due to

Iodine intake and excretion vary widely; however, these variations remain a large source of geometric uncertainty. The present study aims to analyse variations in iodine intake and excretion and provide implications for sampling in studies of individuals or populations. Twenty-four healthy women volunteers were recruited for a 12-d sampling period during the 4-week experiment. The duplicate-portion technique was used to measure iodine intake, while 24-h urine was collected to estimate iodine excretion. The mean intra-individual variations in iodine intake, 24-h UIE (24-h urinary iodine excretion) and 24-h UIC (24-h urinary iodine concentration) were 63, 48 and 55 %, respectively, while the inter-individual variations for these parameters were 14, 24 and 32 %, respectively. For 95 % confidence, approximately 500 diet samples or 24-h urine samples should be taken from an individual to estimate their iodine intake or iodine status at a precision range of ±5%. Obtaining a precision range of ±5% in a population would require twenty-five diet samples or 150 24-h urine samples. The intra-individual variations in iodine intake and excretion were higher than the inter-individual variations, which indicates the need for more samples in a study on individual participants.

This research aimed to investigate the compensation mechanism of iodine deficiency and excess in the mammary gland during lactation. Female rats were divided into the low iodine group (LI), the normal iodine group (NI), the 10-fold high iodine group (10HI) and the 50-fold high iodine group (50HI). We measured the iodine levels in the urine, blood, milk, and mammary gland. The protein expression of sodium/iodide symporter (NIS), DPAGT1, and valosin-containing protein (VCP) in the mammary gland was also studied. The 24-hour urinary iodine concentration, serum total iodine concentration, serum non-protein-bound iodine concentration, breast milk iodine concentration, and mammary gland iodine content in the 50HI group were significantly higher than those in the NI group (p < 0.05). Compared with the NI group, NIS expression in the 50HI group significantly decreased (p < 0.05). DAPGT1 expression was significantly higher in the LI group than in the NI group (p < 0.05). The expression level of VCP was significantly increased in the 10HI and 50HI groups. In conclusion, milk iodine concentration is positively correlated with iodine intake, and the lactating mammary gland regulates the glycosylation and degradation of NIS by regulating DPAGT1 and VCP, thus regulating milk iodine level. However, the mammary gland has a limited role in compensating for iodine deficiency and excess.

In this work, we incorporate matrix projections into the reduced rank regression method, and then develop reduced rank regression estimators based on random projection and orthogonal projection in high-dimensional multivariate linear regression model. We propose a consistent estimator of the rank of the coefficient matrix and achieve prediction performance bounds for the proposed estimators based on mean squared errors. Finally, some simulation studies and a real data analysis are carried out to demonstrate that the proposed methods possess good stability, prediction performance and rank consistency compared to some other existing methods.

With widening deployments of natural language processing (NLP) in daily life, inherited social biases from NLP models have become more severe and problematic. Previous studies have shown that word embeddings trained on human-generated corpora have strong gender biases that can produce discriminative results in downstream tasks. Previous debiasing methods focus mainly on modeling bias and only implicitly consider semantic information while completely overlooking the complex underlying causal structure among bias and semantic components. To address these issues, we propose a novel methodology that leverages a causal inference framework to effectively remove gender bias. The proposed method allows us to construct and analyze the complex causal mechanisms facilitating gender information flow while retaining oracle semantic information within word embeddings. Our comprehensive experiments show that the proposed method achieves state-of-the-art results in gender-debiasing tasks. In addition, our methods yield better performance in word similarity evaluation and various extrinsic downstream NLP tasks., Comment: Accepted by AAAI 2022

Context The effectiveness of saliva iodine concentration (SIC) in evaluating iodine status in children is not clear. Objective We aimed to explore associations between SIC and assessed indicators of iodine status and thyroid function. Design Cross-sectional study. Setting Primary schools in Shandong, China. Participants Local children aged 8 to 13 years with no known thyroid disease were recruited to this study. Main outcome measures Blood, saliva, and urine samples were collected to evaluate thyroid function and iodine status. Results SIC positively correlated with spot urinary iodine concentration (r = 0.29, P < 0.0001), 24-hour urinary iodine concentration (r = 0.35, P < 0.0001), and 24-hour urinary iodine excretion (r = 0.40, P < 0.0001). The prevalence of thyroid nodules (TN) and goiter showed an upward trend with SIC quantiles (P for trend < 0.05). Children with SIC 273 μg/L were associated with greater risks of TN (OR = 2.70; 95% CI, 1.38-5.26) and excessive iodine status (OR = 18.56; 95% CI, 5.66-60.91) than those with lower SIC values. Conclusions There is a good correlation between SIC and urinary iodine concentrations. It is of significant reference value for the diagnosis of iodine deficiency with SIC of less than 105 μg/L and for the diagnosis of iodine excess and TN with SIC of more than 273 μg/L. Given the sanitary nature and convenience of saliva iodine collection, SIC is highly recommended as a good biomarker of recent iodine status in school-aged children.

Structure-based optimization was conducted to improve the potency, selectivity, and cell-based activities of β-catenin/B-cell lymphoma 9 (BCL9) inhibitors based on the 4′-fluoro-N-phenyl-[1,1′-biphenyl]-3-carboxamide scaffold, which was designed to mimic the side chains of the hydrophobic α-helical hot spots at positions i, i + 3, and i + 7. Compound 29 was found to disrupt the β-catenin/BCL9 protein–protein interaction (PPI) with a K(i) of 0.47 μM and >1900-fold selectivity for β-catenin/BCL9 over β-catenin/E-cadherin PPIs. The proposed binding mode of new inhibitors was consistent with the results of site-directed mutagenesis and structure–activity relationship studies. Cell-based studies indicated that 29 disrupted the β-catenin/BCL9 interaction without affecting the β-catenin/E-cadherin interaction, selectively suppressed transactivation of Wnt/β-catenin signaling, downregulated expression of Wnt target genes, and inhibited viability of Wnt/β-catenin-dependent cancer cells in dose-dependent manners. A comparison of the biochemical and cell-based assay results offered the directions for future inhibitor optimization.

For a given general linear model ℳ = { y , X β , Σ } , we investigate relationships between the best linear unbiased estimations (BLUEs) under its two transformed models ℳ 1 = { A y , A X β , A Σ A ′ } and ℳ 2 = { B y , B X β , B Σ B ′ } . We first establish some expansion formulas for calculating the ranks and inertias of the covariance matrices of BLUEs and their operations under ℳ 1 and ℳ 2 . We then derive from the rank and inertia formulas necessary and sufficient conditions for equalities and inequalities of BLUEs’ covariance matrices to hold. We also give applications of the rank and inertia formulas to two sub-sample models of ℳ .

Protein–protein interactions (PPIs) are important targets for the development of chemical probes and therapeutic agents. From the initial discovery of the existence of hot spots at PPI interfaces, it has been proposed that hot spots might provide the key for developing small-molecule PPI inhibitors. However, there has been no review on the ways in which the knowledge of hot spots can be used to achieve inhibitor design, nor critical examination of successful examples. This Digest discusses the characteristics of hot spots and the identification of druggable hot spot pockets. An analysis of four examples of hot spot-based design reveals the importance of this strategy in discovering potent and selective PPI inhibitors. A general procedure for hot spot-based design of PPI inhibitors is outlined.

The cross-coupling of alkyl cyanamides with a number of aryl, heteroaryl, and vinyl halide and pseudohalide coupling partners has been developed via a modification of Pd-catalyzed amidation methods. The reactions proceed selectively under mild conditions with reasonable reaction times in moderate to excellent yields.