Introduction: Rumination syndrome involves recurrent regurgitation of food and is believed to be underdiagnosed with patients experiencing long delays in diagnosis. It can be associated with significant social consequences, high rates of school absenteeism, and medical complications such as weight loss. The primary aims of the current review are to assess the literature regarding prevalence, pathophysiology, and treatment outcomes with a focus on neurotypical children and adolescents.Results: Population studies in children/adolescents, 5 years of age or older, range from 0 to 5.1%. There are fewer studies in clinical settings, but the prevalence appears to be higher in patients with other gastrointestinal symptoms, particularly chronic vomiting. While physiologic changes that occur during a rumination episode are well-described, the underlying cause is less well-defined. In general, rumination appears to have similarities to other functional gastrointestinal disorders including dysmotility, possibly inflammation, and an interaction with psychologic function. While diaphragmatic breathing is considered the mainstay of treatment, pediatric data demonstrating efficacy is lacking, especially as an isolated treatment.Conclusion: Pediatric rumination syndrome remains greatly understudied, particularly regarding treatment. There is a need to better define prevalence in both the primary care and subspecialty clinical settings, especially in patients presenting with vomiting or apparent gastroesophageal reflux. There is a need to determine whether treatment of co-morbid conditions results in improvement of rumination. Diaphragmatic breathing needs to be studied and compared to other competing responses.

Although many cancer prognoses have improved in the past 50 years due to advancements in treatments, there has been little improvement in therapies for small-cell lung cancer (SCLC). One promising avenue to improve treatment for SCLC is to understand its underlying genetic alterations that drive its formation, growth, and cellular heterogeneity. RB1 loss is one key driver of SCLC, and RB1 loss has been associated with an increase in pluripotency factors such as SOX2. SOX2 is highly expressed and amplified in SCLC and has been associated with SCLC growth. Using a genetically engineered mouse model, we have shown that Sox2 is required for efficient SCLC formation. Furthermore, genome-scale binding assays have indicated that SOX2 can regulate key SCLC pathways such as NEUROD1 and MYC. These data suggest that SOX2 can be associated with the switch of SCLC from an ASCL1 subtype to a NEUROD1 subtype. Understanding this genetic switch is key to understanding such processes as SCLC progression, cellular heterogeneity, and treatment resistance. Implications: Understanding the molecular mechanisms of SCLC initiation and development are key to opening new potential therapeutic options for this devastating disease.

Background Rumination syndrome has been associated with increased duodenal eosinophils and intraepithelial lymphocytes in adults. The aims of the current study were to assess densities of antroduodenal eosinophils and mast cells and duodenal intraepithelial lymphocytes in youth with rumination syndrome and to compare cell densities in those with and without abdominal pain or early satiety. Methods Twenty‐eight youth fulfilling Rome IV criteria for rumination syndrome who had undergone endoscopy were identified and compared to 10 controls. Antral and duodenal biopsies were assessed to determine densities of eosinophils, mast cells, and intraepithelial lymphocytes. Cell densities were also compared between rumination patients with and without abdominal pain and those with and without early satiety. Key results Antral mast cell (peak 18.5±6.5 vs. 12.5±2.7) and eosinophil (peak 9.6±5.2 vs. 4.9±2.1) densities were significantly greater in patients with rumination syndrome as compared to controls. Duodenal intraepithelial lymphocyte densities were also increased in rumination syndrome (18.9 ± 5.1 vs. 11.7 ± 1.5; p<.001). Associations were independent of the presence of abdominal pain or early satiety. Conclusions and Inferences In conclusion, we found an increase in eosinophil and mast cell densities in the gastric antrum and an increase in intraepithelial lymphocytes in the duodenum in youth with rumination syndrome which was independent of the presence of abdominal pain or early satiety. These findings suggest a potential role for inflammation in the pathophysiology of rumination syndrome. Future studies should address whether treatment directed at these cells are beneficial in treating rumination syndrome.

<p>WGCNA network identification</p>

<p>SOX2 CUT & RUN peak files</p>