Optimizing evaluation of endometrial receptivity in recurrent pregnancy loss: a preliminary investigation integrating radiomics from multimodal ultrasound via machine learning.

Background: Recurrent pregnancy loss (RPL) frequently links to a prolonged endometrial receptivity (ER) window, leading to the implantation of non-viable embryos. Existing ER assessment methods face challenges in reliability and invasiveness. Radiomics in medical imaging offers a non-invasive solution for ER analysis, but complex, non-linear radiomic-ER relationships in RPL require advanced analysis. Machine learning (ML) provides precision for interpreting these datasets, although research in integrating radiomics with ML for ER evaluation in RPL is limited. Objective: To develop and validate an ML model that employs radiomic features derived from multimodal transvaginal ultrasound images, focusing on improving ER evaluation in RPL. Methods: This retrospective, controlled study analyzed data from 346 unexplained RPL patients and 369 controls. The participants were divided into training and testing cohorts for model development and accuracy validation, respectively. Radiomic features derived from grayscale (GS) and shear wave elastography (SWE) images, obtained during the window of implantation, underwent a comprehensive five-step selection process. Five ML classifiers, each trained on either radiomic, clinical, or combined datasets, were trained for RPL risk stratification. The model demonstrating the highest performance in identifying RPL patients was selected for further validation using the testing cohort. The interpretability of this optimal model was augmented by applying Shapley additive explanations (SHAP) analysis. Results: Analysis of the training cohort (242 RPL, 258 controls) identified nine key radiomic features associated with RPL risk. The extreme gradient boosting (XGBoost) model, combining radiomic and clinical data, demonstrated superior discriminatory ability. This was evidenced by its area under the curve (AUC) score of 0.871, outperforming other ML classifiers. Validation in the testing cohort of 215 subjects (104 RPL, 111 controls) confirmed its accuracy (AUC: 0.844) and consistency. SHAP analysis identified four endometrial SWE features and two GS features, along with clinical variables like age, SAPI, and VI, as key determinants in RPL risk stratification. Conclusion: Integrating ML with radiomics from multimodal endometrial ultrasound during the WOI effectively identifies RPL patients. The XGBoost model, merging radiomic and clinical data, offers a non-invasive, accurate method for RPL management, significantly enhancing diagnosis and treatment.

The effects of dietary supplementation with hyodeoxycholic acid on the differentiation and function of enteroendocrine cells and the serum biochemical indices in weaned piglets1.

Bile acid, a cholesterol metabolite, promotes gastrointestinal tract digestion and absorption of cholesterol, lipids, and fat-soluble vitamins. It is a signaling regulatory molecule that influences a variety of endocrinal and metabolic activities. This study investigated the effects of hyodeoxycholic acid (HDCA) as a dietary supplement on endocrine cell differentiation and function and weaned piglet serum biochemical indices. Sixteen piglets [Duroc × (Landrace × Yorkshire)] were individually housed and weaned at 21 d of age (BW of 6.14 ± 0.22 kg). Uniform weight animals were randomly assigned to 1 of 2 treatments (8 replicate pens per treatment and 1 piglet per pen). The treatments were 1) base diet (control) and 2) base diet supplemented with 2 g/kg of HDCA. Control and HDCA piglet numbers of chromogranin A (CgA)-positive cells per crypt did not differ. HDCA CgA-positive cells numbers decreased (P < 0.05) in the jejunal villi showed a tendency to decrease (P < 0.10) in the ileal villi and showed tendency toward an increase (P < 0.10) in the duodenal villi compared with the controls. The HDCA diet led to a decline in glucagon-like peptide 2 (P < 0.01) concentrations, but did not affect plasma glucagon-like peptide 1. HDCA supplementation increased (P < 0.05) the mRNA expression of jejunal Insm1, Sst, PG, and Gast, but decreased (P < 0.05) duodenal expression of Insm1, jejunal Pdx1, and ileal NeuroD1. HDCA elevated globulin and immunoglobulin A (P < 0.05) serum concentrations and decreased the albumin/globulin ratio (P < 0.05). Total protein and immunoglobulin G serum levels tended to increase compared with the control group. These results indicate that dietary HDCA at 2 g/kg may regulate enteroendocrine cell differentiation and play a role in increasing weaned piglet humoral immunity.

The effects of dietary supplementation with hyodeoxycholic acid on the differentiation and function of enteroendocrine cells and the serum biochemical indices in weaned piglets.

Bile acid, a cholesterol metabolite, promotes gastrointestinal tract digestion and absorption of cholesterol, lipids, and fat-soluble vitamins. It is a signaling regulatory molecule that influences a variety of endocrinal and metabolic activities. This study investigated the effects hyodeoxycholic acid (HDCA) as a dietary supplement on endocrine cell differentiation and function and weaned piglet serum biochemical indices. Sixteen piglets (Duroc × [Landrace × Yorkshire]) were individually housed and weaned at 21 days of age (body weight of 6.14 ± 0.22 kg). Uniform weight animals were randomly assigned to one of two treatments (eight replicate pens per treatment and one piglet per pen). The treatments were 1) base diet (control); and 2) base diet supplemented with 2 g/kg of HDCA. Control and HDCA piglet numbers of CgA-positive cells per crypt did not differ. HDCA CgA-positive cells numbers decreased (P < 0.05) in the jejunal villi, showed a tendency to decrease (P < 0.10) in the ileal villi, and showed tendency toward an increase (P < 0.10) in the duodenal villi compared to the controls. The HDCA diet led to a decline in GLP-2 (P < 0.01) concentrations, but did not affect plasma GLP-1. HDCA supplementation increased (P < 0.05) the mRNA expression of jejunal Insm1, Sst, PG, and Gast, but decreased (P < 0.05) duodenal expression of Insm1, jejunal Pdx1, and ileal NeuroD1. HDCA elevated GLO and IgA (P < 0.05) serum concentrations and decreased the A/G ratio (P < 0.05). TP and IgG serum levels tended to increase compared to the control group. These results indicate that dietary HDCA at 2 g/kg may regulate enteroendocrine cell differentiation and play a role in increasing weaned piglet humoral immunity.

Rapid Communication: The relationship of enterocyte proliferation with intestinal morphology and nutrient digestibility in weaning piglets.

Understanding the regulatory mechanisms of intestinal morphology and function is essential for improving postweaning growth in pigs. The objective of this study was to identify the relationships of enterocyte proliferation with intestinal villus height, crypt depth, and nutrient digestibility in piglets. Sixty-four 21-d-old weaned piglets were used. Gastrointestinal cell proliferation was evaluated via Ki-67 immunohistochemistry. Villus height and crypt depth were measured using hematoxylin and eosin (H&E)-stained sections. The apparent total tract digestibility (ATTD) of CP and GE was determined by chemical analysis. The activities of lactase and sucrase were determined with commercial kits. Western blot was carried out to assess the expression of nutrient transporters. The number of Ki-67 positive cells was associated with villus height (r = 0.548, P < 0.001) and crypt depth (r = 0.759, P < 0.001) in the jejunum. The number of Ki-67 positive cells was also associated with the ATTD of CP (r = 0.715, P = 0.001). Furthermore, a positive relationship between Ki-67 positive cell populations and lactase activity (r = 0.559, P < 0.001) was observed. Additionally, the number of Ki-67 positive cells was associated with the protein expression levels of nutrient transporters PEPT1 (r = 0.511, P = 0.030) and SGLT1 (r = 0.601, P = 0.014). Weak relationships were found between Ki-67 positive cell numbers and the ATTD of GE (r = 0.401, P = 0.099) and the activity of sucrase (r = 0.313, P = 0.087). In conclusion, enterocyte proliferation was positively associated with intestinal villus height, crypt depth, and nutrient digestibility in weaning piglets. Our findings suggested that intestinal morphology and function can be improved by regulating epithelial cell proliferation in piglets.

Dietary sulfur amino acids affect jejunal cell proliferation and functions by affecting antioxidant capacity, Wnt/ß-catenin, and the mechanistic target of rapamycin signaling pathways in weaning piglets.

Intestinal epithelial cells undergo rapid renewal along the crypt-villus axis (CVA), which ensures intestinal functions. Weaning stress differentially effects intestinal epithelial cell metabolism and physiological states along the CVA. Sulfur amino acids (SAA) play a key role in intestinal epithelial cell functioning. This study evaluated the effects of SAA dietary supplementation on weaning pig jejunal epithelial cells along the CVA. Sixteen Duroc × Landrace × Yorkshire piglets (6.16 ± 0.22 kg BW) were weaned at 21 d of age and were blocked by BW and gender and the randomly assigned to 1 of 2 groups fed diets consisting of low (0.53%) or high (0.85%) levels of SAA for a 7-d period. All piglets were euthanized for tissue sampling on day 7 postweaning. Jejunal epithelial cells were isolated along the CVA to yield 3 "cell fractions" (upper villus, middle villus, and crypt cells). The number of proliferating cells per crypt of piglets fed the high SAA diet was lower (P < 0.05) than that for low SAA diet. High SAA diet piglets tended to have decreased (P = 0.059) sucrase activities compared low SAA diet piglets. A high SAA diet increased (P < 0.05) total antioxidant capacity, catalase, and superoxide dismutase activities compared with a low SAA diet. mRNA expression levels of claudin-1, Slc5a1, and Slc7a9 in high SAA diet piglets were lower (P < 0.05) than for low SAA diet piglets. There were no interactions between dietary SAA and cell sections along the CVA for enzyme activities and mRNA expression in any of the weaned piglets. Protein amounts and phosphorylation levels related to Wnt/ß-catenin and mechanistic targeting of rapamycin (mTOR) signaling pathways were affected by SAA in weaning piglets. These findings indicate that dietary SAA affects jejunal cell proliferation and functions in weaning piglets. There appears to be no interactions between dietary SAA and cell sections along the CVA. The effects of SAA may be partly through affecting antioxidant capacity, and Wnt/ß-catenin and mTOR signaling pathway.