STEM enables mapping of single-cell and spatial transcriptomics data with transfer learning.

Profiling spatial variations of cellular composition and transcriptomic characteristics is important for understanding the physiology and pathology of tissues. Spatial transcriptomics (ST) data depict spatial gene expression but the currently dominating high-throughput technology is yet not at single-cell resolution. Single-cell RNA-sequencing (SC) data provide high-throughput transcriptomic information at the single-cell level but lack spatial information. Integrating these two types of data would be ideal for revealing transcriptomic landscapes at single-cell resolution. We develop the method STEM (SpaTially aware EMbedding) for this purpose. It uses deep transfer learning to encode both ST and SC data into a unified spatially aware embedding space, and then uses the embeddings to infer SC-ST mapping and predict pseudo-spatial adjacency between cells in SC data. Semi-simulation and real data experiments verify that the embeddings preserved spatial information and eliminated technical biases between SC and ST data. We apply STEM to human squamous cell carcinoma and hepatic lobule datasets to uncover the localization of rare cell types and reveal cell-type-specific gene expression variation along a spatial axis. STEM is powerful for mapping SC and ST data to build single-cell level spatial transcriptomic landscapes, and can provide mechanistic insights into the spatial heterogeneity and microenvironments of tissues.

Detection and subtyping of hepatic echinococcosis from plain CT images with deep learning: a retrospective, multicentre study.

BACKGROUND: Hepatic echinococcosis is a severe endemic disease in some underdeveloped rural areas worldwide. Qualified physicians are in short supply in such areas, resulting in low rates of accurate diagnosis of this condition. In this study, we aimed to develop and evaluate an artificial intelligence (AI) system for automated detection and subtyping of hepatic echinococcosis using plain CT images with the goal of providing interpretable assistance to radiologists and clinicians. METHODS: We developed EDAM, an echinococcosis diagnostic AI system, to provide accurate and generalisable CT analysis for distinguishing hepatic echinococcosis from hepatic cysts and normal controls (no liver lesions), as well as subtyping hepatic echinococcosis as alveolar or cystic echinococcosis. EDAM includes a slice-level prediction model for lesion classification and segmentation and a patient-level diagnostic model for patient classification. We collected a plain CT database (n=700: 395 cystic echinococcosis, 122 alveolar echinococcosis, 130 hepatic cysts, and 53 normal controls) for developing EDAM, and two additional independent cohorts (n=156) for external validation of its performance and generalisation ability. We compared the performance of EDAM with 52 experienced radiologists in diagnosing and subtyping hepatic echinococcosis. FINDINGS: EDAM showed reliable performance in patient-level diagnosis on both the internal testing data (overall area under the receiver operating characteristic curve [AUC]: 0·974 [95% CI 0·936-0·994]; accuracy: 0·952 [0·939-0·965] for cystic echinococcosis, 0·981 [0·973-0·989] for alveolar echinococcosis; sensitivity: 0·966 [0·951-0·979] for cystic echinococcosis, 0·944 [0·908-0·970] for alveolar echinococcosis) and the external testing set (overall AUC: 0·953 [95% CI 0·840-0·973]; accuracy: 0·929 [0·915-0·947] for cystic echinococcosis, 0·936 [0·919-0·950] for alveolar echinococcosis; sensitivity: 0·913 [0·879-0·944] for cystic echinococcosis, 0·868 [0·841-0·897] for alveolar echinococcosis). The sensitivity of EDAM was robust across images from different CT manufacturers. EDAM outperformed most of the enrolled radiologists in detecting both alveolar echinococcosis and cystic echinococcosis. INTERPRETATION: EDAM is a clinically applicable AI system that can provide patient-level diagnoses with interpretable results. The accuracy and generalisation ability of EDAM demonstrates its potential for clinical use, especially in underdeveloped areas. FUNDING: Project of Qinghai Provincial Department of Science and Technology of China, National Natural Science Foundation of China, and Tsinghua-Fuzhou Institute of Data Technology Project. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

hECA: The cell-centric assembly of a cell atlas.

The accumulation of massive single-cell omics data provides growing resources for building biomolecular atlases of all cells of human organs or the whole body. The true assembly of a cell atlas should be cell-centric rather than file-centric. We developed a unified informatics framework for seamless cell-centric data assembly and built the human Ensemble Cell Atlas (hECA) from scattered data. hECA v1.0 assembled 1,093,299 labeled human cells from 116 published datasets, covering 38 organs and 11 systems. We invented three new methods of atlas applications based on the cell-centric assembly: "in data" cell sorting for targeted data retrieval with customizable logic expressions, "quantitative portraiture" for multi-view representations of biological entities, and customizable reference creation for generating references for automatic annotations. Case studies on agile construction of user-defined sub-atlases and "in data" investigation of CAR-T off-targets in multiple organs showed the great potential enabled by the cell-centric ensemble atlas.

Male waist circumference in relation to semen quality and partner infertility treatment outcomes among couples undergoing infertility treatment with assisted reproductive technologies.

BACKGROUND: Male obesity has been related to poor semen quality and may also have a negative effect on assisted reproductive technologies (ART) outcomes. Whether male waist circumference (WC), as a measure of central obesity, impacts a couple's fertility independently of BMI is unclear. OBJECTIVES: To examine the associations of male WC with semen quality and couples' outcomes of infertility treatment with ART. METHODS: Couples presenting to the Massachusetts General Hospital Fertility Center were invited to participate in the study. Between 2009 and 2019, 269 males provided 671 semen samples and 176 couples underwent 317 ART cycles. Height, weight, and WC were measured on site. We analyzed the association of male WC with semen quality and pregnancy outcomes using cluster-weighted regression models to account for repeated observations while adjusting for potential confounders. Models were also stratified by male BMI (<25 kg/m2 compared with ≥25 kg/m2). RESULTS: The median male age, WC, and BMI were 36.1 years, 96.0 cm, and 26.8 kg/m2, respectively. A 5-cm increase in WC was associated with a 6.3% (95% CI, 2.1-10.5%) lower sperm concentration after adjustment for potential confounders, including BMI. Male WC was also inversely related to the probability of achieving a live birth. For each 5-cm increase in male WC, the odds of a live birth per initiated cycle decreased by 9.0% (95% CI, 1.1%-16.4%) after accounting for several anthropometric and demographic characteristics of both partners. These associations were stronger among males in the normal BMI category (<25 kg/m2) than among overweight or obese males. CONCLUSIONS: A higher male WC may be an additional risk factor for poor outcomes of infertility treatment, even after accounting for male and female partner BMIs, particularly in couples where the male partner has a normal BMI.

Association of the inflammatory potential of diet and lower urinary tract symptoms among men in the United States.

BACKGROUND: Inflammation is crucial in the pathogenesis of lower urinary tract symptoms (LUTS) in men. Diet modulates inflammation. Therefore, diet could be a modifiable factor in male LUTS prevention and treatment. We aimed to investigate the association between dietary inflammatory potential and male LUTS. METHODS: We used two cycles of National Health and Nutrition Examination Survey (NHANES) with self-report LUTS data. We calculated the dietary inflammatory index (DII) based on a 24 h diet recall and evaluated male LUTS. Clinical LUTS was defined as two or more coexisting symptoms. We used univariate and multivariate logistic regression models, the smooth curve fitting to analyze the relationship between clinical LUTS and the DII score. Subgroup analyses were conducted. RESULTS: We observed a positive non-linear relationship between clinical LUTS and DII. We found that when DII was higher than the inflection point 2.39, a 1-unit increase in DII was associated with 26.1% higher adjusted odds of clinical LUTS. Subgroup analyses showed that the DII score was only positively correlated with clinical LUTS risk in non-drinkers, smokers, and non-obese people (DII >2.39). CONCLUSIONS: Inflammation might be the key mechanism bridging dietary consumption to male LUTS. Excessive pro-inflammatory food intake (DII >2.39) warrants special vigilance, especially for non-drinkers, smokers, and non-obese men.

The Association between Dietary Inflammatory Index and Sex Hormones among Men in the United States.

PURPOSE: This study investigated the association between Dietary Inflammatory Index and sex hormones in a large, nationally representative adult male sample. MATERIALS AND METHODS: We utilized data from the 2013-2014 and 2015-2016 National Health and Nutrition Examination Survey. Males aged ≥20 years who provided a 24-hour dietary intake history and underwent serum sex hormone testing were included in analysis. Weighted proportions and multivariable analysis controlling for age, race, energy, smoking status, education level, body mass index and time of venipuncture were used to evaluate the associations between Dietary Inflammatory Index and sex hormones. RESULTS: For 4,151 participants, Dietary Inflammatory Index ranged from -5.05 to 5.48. Mean±SD total testosterone was 419.30±176.27 ng/dl. Mean±SD total testosterone was lower among men in the highest tertile compared with men in the lowest tertile group (410.42±171.97 vs 422.71±175.69, p <0.001). A per unit increase in Dietary Inflammatory Index was related to 4.0% (95% CI 0.5-7.6) higher odds of testosterone deficiency. In the fully adjusted multivariable model, males in Dietary Inflammatory Index tertile 3 (the most pro-inflammatory) had 29.6% (3.1-63.0) higher odds of testosterone deficiency than those in tertile 1 (p trend=0.025). Interaction tests revealed no significant effect of body mass index on the association of Dietary Inflammatory Index with testosterone deficiency and all sex hormone parameters. CONCLUSIONS: Men adhering to a more pro-inflammatory diet appear to have a higher risk of testosterone deficiency, indicating the important role of diet in male reproductive health.

Associations between the dietary inflammatory index and urinary incontinence among women younger than 65 years.

The purpose of this study was to evaluate the association between dietary inflammatory index (DII) and urinary incontinence (UI) among a representative sample of the US women. We performed a cross-sectional analysis of women younger than 65 years using the 1999 to 2016 NHANES (National Health and Nutrition Examination Survey) populations. DII were calculated based on baseline dietary intake using 24-h dietary recalls. UI was determined and categorized by self-reported questions. Multivariable logistic regression models were used to assess the association between DII and UI. Stratified linear regression models were applied to test for interaction in prespecified subgroup of interest. A total of 13,441 women age between 20 and 65 years were included in the final analysis. Of these participants 3230 (24.03%) complained of urgency UI, 5276 (39.25%) complained of stress UI and 2028 (15.09%) complained of mixed UI. On multivariate analysis, analysis with DII categorized as quartiles revealed significantly increase odds of urgency UI in the most pro-inflammatory quartile compared to the most anti-inflammatory quartile (OR 1.24, 95% CI 1.07-1.44, P = 0.004 for trend) in full adjustment model. Similar results were observed in SUI (OR 1.14, 95% CI 1.00-1.30, P = 0.021 for trend) and MUI (OR 1.20, 95% CI 1.02-1.43, P = 0.022 for trend). More pro-inflammatory diets, as presented by higher DII scores are associated with an increased likelihood of UI in American women younger than 65 years. Further studies are needed to explore the possible physiological mechanism and evaluate the potential therapeutic implications.

Low lean mass and cognitive performance: data from the National Health and Nutrition Examination Surveys.

BACKGROUND: Low lean mass and cognitive impairment are both age-related diseases. In addition, these conditions share many risk factors. However, the association between them has been controversial in recent years. OBJECTIVE: To investigate the association between low lean mass and cognitive performance in U.S. adults using NHANES data from 1999 to 2002. METHODS: A total of 2550 participants were identified in the National Health and Nutrition Examination Survey Database (1999-2002). The independent variable was low lean mass, and the dependent variable was cognitive performance. Men and women were classified as having low lean mass if appendicular lean mass (ALM) adjusted for BMI (ALMBMI) was < 0.789 and < 0.512, respectively. Cognitive performance was assessed using the Digit Symbol Substitution Test (DSST). Higher scores on the DSST indicated better cognitive performance. The covariates included sex, age, race, poverty income ratio, comorbidity index, educational level, physical activity and smoking status. RESULTS: For the primary outcome, our multivariate linear regression analysis indicated that participants without low lean mass were associated with better cognitive performance (ß = 1.50; 95% CI [0.12-2.89]). Subgroup analysis results indicated that the association was similar in sex, age, race, poverty income ratio, comorbidity index, educational level, physical activity and smoking status. CONCLUSIONS: Participants without low lean mass were associated with better cognitive performance. We might be able to improve cognitive performance by treating low lean mass, thus providing an opportunity for intervention at a younger age.

Association between Dietary Inflammatory Index and kidney stones in US adults: data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016.

OBJECTIVE: We evaluate the association between the Dietary Inflammatory Index (DII) and kidney stones. DESIGN: We performed a cross-sectional analysis using data from National Health and Nutrition Examination Survey (NHANES). Dietary intake information was assessed using first 24-h dietary recall interviews, and the Kidney Conditions were presented by a questionnaire. The primary outcome was to investigate the association between DII and incidence of kidney stones, and the secondary outcome was to assess the association between DII and nephrolithiasis recurrence. SETTING: The NHANES, 2007-2016. PARTICIPANTS: The study included 25 984 NHANES participants, whose data on DII and kidney stones were available, of whom 2439 reported a history of kidney stones. RESULTS: For the primary outcome, after fully multivariate adjustment, DII score is positively associated with the risk of kidney stones (OR = 1·07; 95 % CI 1·04, 1·10). Then, compared Q4 with Q1, a significant 38 % increased likelihood of nephrolithiasis was observed. (OR = 1·38; 95 % CI 1·19, 1·60). For the secondary outcome, the multivariate regression analysis showed that DII score is positively correlated with nephrolithiasis recurrence (OR = 1·07; 95 % CI 1·00, 1·15). The results noted that higher DII scores (Q3 and Q4) are positively associated with a significant 48 % and 61 % increased risk of nephrolithiasis recurrence compared with the reference after fully multivariate adjustment (OR = 1·48; 95 % CI 1·07, 2·05; OR = 1·61; 95 % CI 1·12, 2·31). CONCLUSIONS: Our findings revealed that increased intake of pro-inflammatory diet, as a higher DII score, is correlated with increased odds of kidney stones incidence and recurrence.

Demographic variations and temporal trends in prenatal use of multiple micronutrient supplements in Beijing, 2013-2017.

OBJECTIVE: To provide updated information about demographic variations and temporal trends in the prenatal use of multiple micronutrient (MMN) supplements in the metropolitan areas of China. DESIGN: Descriptive analysis of routine prenatal healthcare data between 2013 and 2017. SETTING: Chaoyang District, Beijing, China. PARTICIPANTS: A total of 197 346 pregnant women who attended their first prenatal care visit and provided information about MMN supplementation during the periconceptional period. RESULTS: Of these pregnant women, 60·6 % reported consuming prenatal MMN supplements. In multivariate-adjusted models, there were significant gradients of age, education and parity in prenatal MMN supplementation, with the highest likelihood of MMN use among the oldest, the most highly educated and nulliparous women (Pfor trend < 0·001). Compared with that among unemployed women, prenatal MMN supplementation was more common among the employed, especially those engaged in business (adjusted relative risks (95 % CI): 1·08 (1·06, 1·10)) and management (1·10 (1·08, 1·12)). The proportion of prenatal MMN supplementation was 57·0 % in 2013, which increased to 63·5 % in 2017 (Pfor trend < 0·001). The trends varied by age, education and parity (Pfor heterogeneity < 0·001), whereas no significant difference was observed in trends across subgroups of ethnicity or occupation. The greatest magnitude increase in MMN supplement use occurred in women of age < 25 years (annual percent change: 5·7 %), less than high school education (9·6 %), parity ≥ 2 (6·8 %) or unemployment (6·1 %). CONCLUSION: Approximately two-thirds of women consumed prenatal MMN supplements during the periconceptional period in the central area of Beijing and the proportion increased over time, indicating a need to evaluate the effectiveness and safety and to develop a guideline for relatively well-nourished women.

Dietary inflammatory potential and risk of sarcopenia: data from national health and nutrition examination surveys.

This study used National Health and Nutrition Examination Surveys data from 1999 to 2006 to investigate the association between dietary inflammatory potential, represented by dietary inflammatory index (DII) scores, and the risk of sarcopenia in U.S. adults. A total of 25,781 participants were included in the study. The DII scores were calculated based on dietary information collected from 24-hour recalls. Men and women were classified as sarcopenic if appendicular lean mass (ALM) adjusted for BMI (ALMBMI) was <0.789 or <0.512, respectively. The covariates included comorbidities, dietary data, demographic data, and physical examination data. In a full-adjusted model, each unit of increase in DII score was associated with a 12% increase in risk of sarcopenia. When categorizing sarcopenia into tertiles, the adjusted effect size (relative to Tertile1) was 1.26 (95% CI, 1.07, 1.47) for Tertile 2 and 1.55 (95% CI, 1.31, 1.83) for Tertile 3. The trend test showed that the risk of sarcopenia increased with increasing DII tertiles, (P <0.0001). These findings demonstrate that dietary inflammatory potential correlates positively with the risk of sarcopenia and suggest that making ones diet inflammatory may reduce the incidence of sarcopenia and its associated negative health outcomes.

Effects of the blood urea nitrogen to creatinine ratio on haemorrhagic transformation in AIS patients with diabetes mellitus.

BACKGROUND: The effect of the blood urea nitrogen (BUN) to creatinine (Cr) ratio (henceforth BUN/Cr) on haemorrhagic transformation (HT) of acute ischaemic stroke (AIS) patients is unclear. METHODS: AIS patients in the West China Hospital, Sichuan University, Chengdu, China, admitted within seven days from stroke onset (2012-2016) were included in the study. Baseline data, including BUN and Cr levels, were collected. The outcome was defined as HT during hospitalization. RESULTS: In this study, 1738 participants with an average age of 62.7 ± 14.0 years were included. After adjusting potential confounders (age, blood platelet, albumin, stroke severity, triglycerides and low-density lipoprotein [LDL]), multivariate logistic regression analyses indicated that BUN/Cr is independently associated with HT. The nonlinear relation between BUN/Cr and HT was explored in a dose-dependent manner, with an apparent inflection point of 30.71. On the left and right sides of the inflection point, the odds ratio (OR) and 95% confidence interval (CI) were 1.05 (1.02-1.08) and 0.96 (0.88-1.05), respectively. Interaction between BUN/Cr and diabetes mellitus (DM) and HT (P for interaction = 0.0395) was noted. BUN/Cr showed positive correlation with HT in DM patients (OR = 1.07; 95% CI: [1.02, 1.12]) but no significant relationship with HT in patients without DM. CONCLUSION: BUN/Cr is significantly associated with HT in AIS patients in a linear fashion, with an apparent cut point demarcating the HT difference. When the patients have DM, BUN/Cr is positively correlated with HT. These results support a revision in how we anticipate the prognosis for AIS patients.

Association between Blood Urea Nitrogen-to-creatinine Ratio and Three-Month Outcome in Patients with Acute Ischemic Stroke.

BACKGROUND: Hydration status significantly affects the clinical outcome of acute ischemic stroke (AIS) patients. Blood urea nitrogen-to-creatinine ratio (BUN/Cr) is a biomarker of hydration status. However, it is not known whether there is a relationship between BUN/Cr and three-month outcome as assessed by the modified Rankin Scale (mRS) score in AIS patients. METHODS: AIS patients admitted to West China Hospital from 2012 to 2016 were prospectively and consecutively enrolled and baseline data were collected. Poor clinical outcome was defined as three-month mRS > 2. Univariate and multivariate logistic regression analyses were performed to determine the relationship between BUN/Cr and three-month outcome. Confounding factors were identified by univariate analysis. Stratified logistic regression analysis was performed to identify effect modifiers. RESULTS: A total of 1738 patients were included in the study. BUN/Cr showed a positive correlation with the three-month outcome (OR 1.02, 95% CI 1.00-1.03, p=0.04). However, after adjusting for potential confounders, the correlation was no longer significant (p=0.95). An interaction between BUN/Cr and high-density lipoprotein (HDL) was discovered (p=0.03), with a significant correlation between BUN/Cr and three-month outcome in patients with higher HDL (OR 1.03, 95% CI 1.00-1.07, p=0.04). CONCLUSION: Elevated BUN/Cr is associated with poor three-month outcome in AIS patients with high HDL levels.

Serum Albumin Is Negatively Associated with Hemorrhagic Transformation in Acute Ischemic Stroke Patients.

BACKGROUND AND OBJECTIVE: Hemorrhagic transformation (HT) is a major complication of acute ischemic stroke (AIS). Serum albumin is known for its neuroprotective effects and is a marker of improved AIS patient outcomes. However, it is not known whether there is a relationship between serum albumin and HT. METHODS: AIS patients admitted to the Department of Neurology of West China Hospital from 2012 to 2016 were prospectively and consecutively enrolled. Baseline characteristics were collected. HT during hospitalization was diagnosed by brain imaging. Multivariate logistic regression analysis was performed to determine the relationship between serum albumin and HT. Confounding factors were identified by univariate analysis. Stratified logistic regression analysis was performed to identify effect modifiers. RESULTS: A total of 1996 AIS patients were recruited, of whom 135 (6.8%) developed HT. Serum albumin negatively correlated with HT. Patients in the upper serum albumin tertile (42.6-54.1 g/L) had a 46% lower risk of HT than patients in the lower tertile (19.3-39.1 g/L) after adjustment for potential confounders (OR 0.54, 95% CI 0.29-0.99, p = 0.04). Risk of HT decreased stepwise with higher serum albumin tertile (p for trend = 0.04). There was a significant interaction between serum albumin and age (p = 0.02), with no significant correlation between serum albumin and HT in patients over 60 years of age. CONCLUSIONS: Higher serum albumin is associated with lower HT risk in a dose-dependent manner in AIS patients younger than 60 years.