Mucopolysaccharidosis type I is an inborn error of glycosaminoglycan catabolism with phenotypes ranging from severe (Hurler syndrome) to attenuated (Hurler–Scheie and Scheie syndromes). Cardiovascular involvement is common and contributes significantly to morbidity and mortality. We conducted a retrospective analysis of the prevalence and natural history of cardiac abnormalities in treatment-naïve individuals enrolled in the international Mucopolysaccharidosis Type I Registry. Interrogation of echocardiography data (presence of cardiac valve regurgitation and/or stenosis; measurements of left ventricular chamber dimensions in diastole and systole, diastolic left ventricular posterior wall and interventricular septal thicknesses and ventricular systolic function (shortening fraction)) showed that mitral regurgitation was the most common and earliest finding for individuals with both severe (58.3%, median age 1.2 years) and attenuated (74.2%, median age 8.0 years) disease. Left-sided valve stenosis was also common in individuals with attenuated disease (mitral 30.3%; aortic 25%). Abnormal ventricular wall and septal thickness (Z-scores ≥2) were observed early in both phenotypes. Z-scores for diastolic left ventricular posterior wall and interventricular septal thicknesses increased with age in the severe phenotype (annualised slopes of 0.2777 [p = 0.037] and 0.3831 [p = 0.001], respectively); a similar correlation was not observed in the attenuated phenotype (annualised slopes of −0.0401 [p = 0.069] and −0.0029 [p = 0.875], respectively). Decreased cardiac ventricular systolic function (defined as shortening fraction <28%) was uncommon but, when noted, was more frequent in infants with the severe phenotype. While cardiac abnormalities occur early in both severe and attenuated mucopolysaccharidosis type I, the pattern of valve dysfunction and progression of ventricular abnormalities vary by phenotype.

A multi-agent deep reinforcement learning (DRL)-based model is presented in this study to reconstruct flow fields from noisy data. A combination of reinforcement learning with pixel-wise rewards, physical constraints represented by the momentum equation and the pressure Poisson equation, and the known boundary conditions is used to build a physics-constrained deep reinforcement learning (PCDRL) model that can be trained without the target training data. In the PCDRL model, each agent corresponds to a point in the flow field and learns an optimal strategy for choosing pre-defined actions. The proposed model is efficient considering the visualisation of the action map and the interpretation of the model operation. The performance of the model is tested by using direct numerical simulation-based synthetic noisy data and experimental data obtained by particle image velocimetry. Qualitative and quantitative results show that the model can reconstruct the flow fields and reproduce the statistics and the spectral content with commendable accuracy. Furthermore, the dominant coherent structures of the flow fields can be recovered by the flow fields obtained from the model when they are analysed using proper orthogonal decomposition and dynamic mode decomposition. This study demonstrates that the combination of DRL-based models and the known physics of the flow fields can potentially help solve complex flow reconstruction problems, which can result in a remarkable reduction in the experimental and computational costs.

Iodine is a vital trace element in the human body and is associated with several important coronary artery disease (CAD) risk factors. We aimed to explore the correlation between urinary iodine concentration (UIC) and CAD. Data from 15 793 US adults in the National Health and Nutrition Examination Survey (2003–2018) were analysed. We conducted multivariable logistic regression models and fitted smoothing curves to study the correlation between UIC and CAD. Furthermore, we performed subgroup analysis to investigate possible effect modifiers between them. We found a J-shaped association between UIC and CAD, with an inflection point at Lg UIC = 2·65 μg/l. This result indicated a neutral association (OR 0·89; 95 % CI 0·68, 1·16) between UIC and CAD as Lg UIC < 2·65 μg/l, but the per natural Lg [UIC] increment was OR 2·29; 95 % CI 1·53, 3·43 as Lg UIC ≥ 2·65 μg/l. An interaction between diabetes and UIC might exist. The increase in UIC results in an increase in CAD prevalence (OR 1·84, 95 % CI 1·32, 2·58) in diabetes but results in little to no difference in non-diabetes (OR 0·98, 95 % CI 0·77, 1·25). The J-shaped correlation between UIC and CAD and the interaction between diabetes and UIC should be confirmed in a prospective study with a series of UIC measurements. If excessive iodine precedes CAD, then this new finding could guide clinical practice and prevent iodine deficiency from being overcorrected.

Coastal eutrophication and hypoxia remain a persistent environmental crisis despite the great efforts to reduce nutrient loading and mitigate associated environmental damages. Symptoms of this crisis have appeared to spread rapidly, reaching developing countries in Asia with emergences in Southern America and Africa. The pace of changes and the underlying drivers remain not so clear. To address the gap, we review the up-to-date status and mechanisms of eutrophication and hypoxia in global coastal oceans, upon which we examine the trajectories of changes over the 40 years or longer in six model coastal systems with varying socio-economic development statuses and different levels and histories of eutrophication. Although these coastal systems share common features of eutrophication, site-specific characteristics are also substantial, depending on the regional environmental setting and level of social-economic development along with policy implementation and management. Nevertheless, ecosystem recovery generally needs greater reduction in pressures compared to that initiated degradation and becomes less feasible to achieve past norms with a longer time anthropogenic pressures on the ecosystems. While the qualitative causality between drivers and consequences is well established, quantitative attribution of these drivers to eutrophication and hypoxia remains difficult especially when we consider the social economic drivers because the changes in coastal ecosystems are subject to multiple influences and the cause–effect relationship is often non-linear. Such relationships are further complicated by climate changes that have been accelerating over the past few decades. The knowledge gaps that limit our quantitative and mechanistic understanding of the human-coastal ocean nexus are identified, which is essential for science-based policy making. Recognizing lessons from past management practices, we advocate for a better, more efficient indexing system of coastal eutrophication and an advanced regional earth system modeling framework with optimal modules of human dimensions to facilitate the development and evaluation of effective policy and restoration actions.

We propose the helicity-conserved Navier–Stokes (HCNS) equation by modifying the non-ideal force term in the Navier–Stokes (NS) equation. The corresponding HCNS flow has strict helicity conservation, and retains major NS dynamics with finite dissipation. Using the helical wave decomposition, we show that the pentadic interaction of Fourier helical modes in the HCNS dynamics is more complex than the triadic interaction in the NS dynamics, and enhanced variations for left- and right-handed helicity components cancel each other in the HCNS flow to keep the invariant helicity. A comparative study of HCNS and NS flow evolutions with direct numerical simulation elucidates the influence of the helicity conservation on flow structures and statistics in the vortex reconnection and isotropic turbulence. First, the HCNS flow evolves towards a Beltrami state with a $-4$ scaling law of the energy spectrum at high wavenumbers at long times. Second, large-scale flow structures are almost identical during the viscous reconnection of vortex tubes in the two flows, whereas many more small-scale helical structures are generated via the pentadic mode interaction in the HCNS flow than in the NS flow. Moreover, we demonstrate that parity breaking at small scales can trigger a notable helicity variation in the NS flow. These findings hint that the helicity may not be conserved in the inviscid limit of the NS flow.

Telocyte (TC)—a new type of interstitial cell with long telopodes, can form cellular junctions with various tissues or cells to participate in the regulation of multitudes of physiological activities and diseases. This study aimed to characterize the morphology, molecular features, and potential functions of hormone regulation in Chinese soft-shelled turtle (Pelodiscus sinensis) testis TCs at different reproductive stages by histological evaluation, immunohistochemistry (IHC), immunofluorescence (IF), and transmission electron microscopy. During hibernation, TCs were widely distributed in the interstitial tissue. In contrast, during reproductive activity, TCs were noted to be in close proximity with peritubular myoid cells surrounding the seminiferous tubule. Moreover, formed cell–cell junctions were observed between TCs and PTMs. The results of IHC and IF showed that the immunophenotype of testicular TCs in hibernating Chinese soft-shelled turtles is CD34+Vimentin−, while the reproductive telopodes (Tps) show low expression of vimentin. The androgen receptor is expressed in Tps of TCs of testis during hibernation. Our results showed also that TCs in seasonal breeding animals regulate the activity of neighboring cells by releasing extracellular microvesicles (EXMVs), thus influencing the activity of spermatogenesis and steroidogenesis. Consideration of our novel and interesting results indicate that the whole area warrants further research.

The association between dietary Cu intake and mortality risk remains uncertain. We aimed to investigate the relationship of dietary Cu intake with all-cause mortality among Chinese adults. A total of 17 310 participants from the China Health and Nutrition Survey, a national ongoing open cohort of Chinese participants, were included in the analysis. Dietary intake was measured by three consecutive 24-h dietary recalls in combination with a weighing inventory over the same 3 d. The average intakes of the 3-d dietary macronutrients and micronutrients were calculated. The study outcome was all-cause mortality. During a median follow-up of 9·0 years, 1324 (7·6 %) participants died. After adjusting for sex, age, BMI, ever alcohol drinking, ever smoking, education levels, occupations, urban or rural residents, systolic blood pressure, diastolic blood pressure and the intakes of fat, protein and carbohydrate, the association between dietary Cu intake and all-cause mortality followed a J-shape (P for nonlinearity = 0·047). When dietary Cu intake was assessed as quartiles, compared with those in the first quartile (<1·60 mg/d), the adjusted hazard ratios for all-cause mortality were 0·87 (95 % CI (0·71, 1·07)), 0·98 (95 % CI (0·79, 1·21)) and 1·49 (95 % CI (1·19, 1·86)), respectively, in participants in the second (1·60–<1·83 mg/d), third (1·83–<2·09 mg/d) and fourth (≥2·09 mg/d) quartiles. A series of subgroup analyses and sensitivity analyses showed similar results. Overall, our findings emphasised the importance of maintaining optimal dietary Cu intake levels for prevention of premature death.

Maternal gestational weight gain (GWG) is an important determinant of infant birth weight, and having adequate total GWG has been widely recommended. However, the association of timing of GWG with birth weight remains controversial. We aimed to evaluate this association, especially among women with adequate total GWG. In a prospective cohort study, pregnant women’s weight was routinely measured during pregnancy, and their GWG was calculated for the ten intervals: the first 13, 14–18, 19–23, 24–28, 29–30, 31–32, 33–34, 35–36, 37–38 and 39–40 weeks. Birth weight was measured, and small-for-gestational-age (SGA) and large-for-gestational-age were assessed. Generalized linear and Poisson models were used to evaluate the associations of GWG with birth weight and its outcomes after multivariate adjustment, respectively. Of the 5049 women, increased GWG in the first 30 weeks was associated with increased birth weight for male infants, and increased GWG in the first 28 weeks was associated with increased birth weight for females. Among 1713 women with adequate total GWG, increased GWG percent between 14 and 23 weeks was associated with increased birth weight. Moreover, inadequate GWG between 14 and 23 weeks, compared with the adequate GWG, was associated with an increased risk of SGA (43 (13·7 %) v. 42 (7·2 %); relative risk 1·83, 95 % CI 1·21, 2·76). Timing of GWG may influence infant birth weight differentially, and women with inadequate GWG between 14 and 23 weeks may be at higher risk of delivering SGA infants, despite having adequate total GWG.

Background: Outpatient parenteral antimicrobial therapy (OPAT) is used in the outpatient setting to treat infectious conditions that require a prolonged course of antimicrobials. OPAT has been shown to decrease length of hospital stay and healthcare costs without compromising patient care and has become a widely accepted practice nationally. Due to this trend, the study of OPAT is of vital importance and will continue to be relevant moving forward. Currently, few studies have explored risk factors associated with OPAT complications, and most are limited in their analysis by indication. Further work should be performed to expand upon what is currently known. We characterized factors associated with increased OPAT complication risk. Methods: We conducted a retrospective cohort study at 4 sites across NYU Langone Health in patients admitted from 2017 to 2020. We applied the following inclusion criteria: aged ≥18 years and discharged with OPAT. Complications were defined as follows: vascular-access-related (line occlusion, thrombosis, dislodgement, central-line associated bloodstream infection or CLABSI) and antimicrobial-related (laboratory derangement, drug reaction, Clostridioides difficile infection), all-cause 30-day readmission, and OPAT-related readmission. Data were obtained from electronic medical records and the OPAT database. This study was granted a waiver from informed consent by the NYU Institutional Review Board. Multivariate logistic regression was performed, adjusting for confounding variables (sex, age, hospital of admission, history of chronic medical conditions, line type, and line duration). Results: Overall, 1,846 patient encounters of 5,951 reviewed met inclusion criteria. The median age was 66 (IQR, 26), 42.2% were female. Moreover, 810 (44%) received a peripherally inserted central catheter (PICC) and 1,036 (56%) received a midline cathether. Also, 563 (30.5%) were discharged to subacute rehabilitation (SAR). The most frequent complications were line dislodgement (4.2% of all patients), laboratory derangement (3.0%), and drug reaction (2.4%). Furthermore, 27 patients (1.5%) developed CLABSI. Patients discharged to SAR were more likely to develop CLABSI (OR, 4.1l; P = .005), and they had higher rates of OPAT-related 30-day readmissions (OR, 2.675; P = .004) compared to those who were discharged home, after adjusting for key confounders. Conclusions: Discharge to SAR is strongly associated with increased risk of readmission for OPAT-related complications and CLABSI, after adjusting for key confounders. CLABSI prevention during SAR admission is a critically needed public health intervention.

Funding: None

Disclosures: None

Considering the influence of body’s growth and development on thyroid volume (TVOL), whether five existed corrected methods could be applied to correct TVOL remains unclear, in terms of Chinese children’s increased growth and development trends. This study aimed to compare the applicability of five correction methods: Body Surface Area corrected Volume (BSAV), Body Mass Indicator corrected Volume (BMIV), Weight and Height corrected Volume Indicator (WHVI), Height corrected Volume Indicator 1 (HVI1) and Height corrected Volume Indicator 2 (HVI2) and to establish the reference values for correction methods. The data of Iodine Nutrition and Thyroid Function Survey were used to analyse the differences in TVOL between normal and abnormal thyroid function children. Data of National Iodine Deficiency Disorders Survey were used to compare five correction methods and to establish their reference values. The median urinary iodine concentrations of children surveyed were 256·1 μg/l in 2009 and 192·6 μg/l in 2019. No significant difference was found in TVOL and thyroid goitre rate between children with normal and abnormal thyroid function. In the determination of goitre, HVI1, HVI2, BSAV and BMIV all showed high agreement with TVOL, while the area under the receiver operating characteristic curve (AUC) of WHVI was relatively low for children aged 8 (AUC = 0·8993) and 9 (AUC = 0·8866) years. Most differences of TVOL between light and heavy weight, short and tall height children can be eliminated by BSAV. BSAV was the best corrected method in this research. Reference values were established for corrected TVOL in Chinese children aged 8–10 years by sex.

Metabolically healthy obesity (MHO) might be an alternative valuable target in obesity treatment. We aimed to assess whether alternative Mediterranean (aMED) diet and Dietary Approaches to Stop Hypertension (DASH) diet were favourably associated with obesity and MHO phenotype in a Chinese multi-ethnic population. We conducted this cross-sectional analysis using the baseline data of the China Multi-Ethnic Cohort study that enrolled 99 556 participants from seven diverse ethnic groups. Participants with self-reported cardiometabolic diseases were excluded to eliminate possible reverse causality. Marginal structural logistic models were used to estimate the associations, with confounders determined by directed acyclic graph (DAG). Among 65 699 included participants, 11·2 % were with obesity. MHO phenotype was present in 5·7 % of total population and 52·7 % of population with obesity. Compared with the lowest quintile, the highest quintile of DASH diet score had 23 % decreased odds of obesity (OR = 0·77, 95 % CI 0·71, 0·83, P trend < 0·001) and 27 % increased odds of MHO (OR = 1·27, 95 % CI 1·10, 1·48, P trend = 0·001) in population with obesity. However, aMED diet showed no obvious favourable associations. Further adjusting for BMI did not change the associations between diet scores and MHO. Results were robust to various sensitivity analyses. In conclusion, DASH diet rather than aMED diet is associated with reduced risk of obesity and presents BMI-independent metabolic benefits in this large population-based study. Recommendation for adhering to DASH diet may benefit the prevention of obesity and related metabolic disorders in Chinese population.

Excessive iodine can lead to goiters. However, the relationship between the water iodine concentration (WIC) and goiter rate (GR) is unclear. This study aims to explore the factors that influence children’s GR in areas with high WIC and analyse the threshold value of the GR increase associated with the WIC. According to the monitoring of the areas with high WIC in China in 2018–2020, a total of 54 050 children in eight high water iodine provinces were chosen. Drinking water, urine and edible salt samples of children were collected. The thyroid volume (Tvol) was measured. A generalised additive model (GAM) was used to analyse the relationship between the WIC and GR in children. Among the 54 050 children in areas with high WIC, the overall GR was 3·34 %, the median of water iodine concentration was 127·0 µg/l, the median of urinary iodine concentration was 318 µg/l and the non-iodised salt coverage rate (NISCR) was 63·51 %. According to the GAM analysis results, water iodine and urinary iodine are factors that influence the Tvol and GR, while the NISCR affects only the GR. When the WIC was more than 420 µg/l or the urinary iodine concentration was more than 800 µg/l, the GR increased rapidly. When the NISCR reached more than 85 %, the GR was the lowest. Thus, in areas with high WIC, WIC more than 420 µg/l may increase the risk of goiter, and the NISCR should be increased to over 85 % to avoid goiters in children.

The article aims to estimate and forecast the transmissibility of shigellosis and explore the association of meteorological factors with shigellosis. The mathematical model named Susceptible–Exposed–Symptomatic/Asymptomatic–Recovered–Water/Food (SEIARW) was used to explore the feature of shigellosis transmission based on the data of Wuhan City, China, from 2005 to 2017. The study applied effective reproduction number (Reff) to estimate the transmissibility. Daily meteorological data from 2008 to 2017 were used to determine Spearman's correlation with reported new cases and Reff. The SEIARW model fit the data well (χ2 = 0.00046, p > 0.999). The simulation results showed that the reservoir-to-person transmission of the shigellosis route has been interrupted. The Reff would be reduced to a transmission threshold of 1.00 (95% confidence interval (CI) 0.82–1.19) in 2035. Reducing the infectious period to 11.25 days would also decrease the value of Reff to 0.99. There was a significant correlation between new cases of shigellosis and atmospheric pressure, temperature, wind speed and sun hours per day. The correlation coefficients, although statistically significant, were very low (<0.3). In Wuhan, China, the main transmission pattern of shigellosis is person-to-person. Meteorological factors, especially daily atmospheric pressure and temperature, may influence the epidemic of shigellosis.

Chronic inflammation exerts pleiotropic effects in the aetiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40–69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HR) as well as 95 % CI for the risk of incident COPD. During a median follow-up of 8·96 years (interquartile range 8·29–9·53 years), 9016 new-onset events of COPD were documented. We found that the regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0·80 (95 % CI, 0·75, 0·85; P < 0·001). When subgroup analyses were performed by smoking status, the adjusted HR for the association of regular glucosamine use with incident COPD were 0·84 (0·73, 0·96), 0·84 (0·77, 0·92) and 0·71 (0·62, 0·80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (P for interaction = 0·078). Incident COPD could be reduced by 14 % to 84 % through a combination of regular glucosamine use and smoking cessation.