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Objectives: Classical Hirschsprung disease (HD) is defined by the absence of ganglion cells in the rectosigmoid colon. The diagnosis is made from rectal biopsy, which reveals the aganglionosis and the presence of cholinergic hyperinnervation. However, depending on the method of rectal biopsy, the quality of the specimens and the related diagnostic accuracy varies substantially. To facilitate and objectify the diagnosis of HD, we investigated whether software-based identification of cholinergic hyperinnervation in digitalized histopathology slides is suitable for distinguishing healthy individuals from affected individuals., Methods: N = 190 samples of 112 patients who underwent open surgical rectal biopsy at our pediatric surgery center between 2009 and 2019 were included in this study. Acetylcholinesterase (AChE) stained slides of these samples were collected and digitalized via slide scanning and analyzed using two digital imaging software programs (HALO, QuPath). The AChE-positive staining area in the mucosal layers of the intestinal wall was determined. In the next step machine learning was employed to identify patterns of cholinergic hyperinnervation., Results: The area of AChE-positive staining was greater in HD patients compared to healthy individuals (p < 0.0001). Artificial intelligence-based assessment of parasympathetic hyperinnervation identified HD with a high precision (area under the curve [AUC] 0.96). The accuracy of the prediction model increased when nonrectal samples were excluded (AUC 0.993)., Conclusions: Software-assisted machine-learning analysis of AChE staining is suitable to improve the diagnostic accuracy of HD., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Making sense of the social world is an intricate process heavily influenced by cultural elements. Gambling is a prevalent leisure-time activity characterized by risk-taking conduct. While some individuals who engage in it do so without experiencing any harm, others will develop gambling problems. Judaism tends to perceive gambling negatively since it contradicts fundamental Jewish principles. The current study focuses on the Jewish Ultra-Orthodox community in Israel which is characterized as a cultural enclave with minimal interaction with the secular world. Hence, it provides a unique and novel socio-cultural context to inquire how individuals with gambling disorder (GD) from this community make sense of gambling. Following constructivist grounded theory guidelines, 22 Ultra-Orthodox men with GD were interviewed using a purposeful sampling design. Sixteen Rabbis were also interviewed, illuminating the socio-cultural context of Halachic regulations and norms regarding gambling in this community. An abductive analysis of the data, interwoven with Bourdieu's concept of habitus , yielded an overarching theme that we dub as "sense for gambling," encompassing matrices of Ultra-Orthodox external (e.g., a conservative cultural structure with numerous prohibitions and life marked by poverty) and internal (e.g., feelings of loneliness, dissatisfaction, and deviance) dispositions imprinted onto the body, creating diverse embodied reactions (emotional and sensory) to gambling, and leading to developing GD. We recommend placing the body, as the locus of internalized dispositions, at the core of examination when researching pathways to GD. We propose that this intricate interplay between external and internal dispositions shapes the decision-making regarding gambling, thus mitigating individual responsibility for GD., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: A developing theoretical framework for the investigation of tight cultures' reaction toward members who violate communal norms is societal conditional regard (SCR)., Methods: Using a qualitative interpretive approach, in the current study we investigated the way the Ultraorthodox Jewish community uses SCR to cope with substance use disorders (SUDs), which considered to be a norms violation in closed religious communities. We did so by drawing on in-depth interviews with 14 young men from the Ultraorthodox community in Israel who were diagnosed as having an SUD and were in recovery., Results: (a) The community's socialization process, educating its members to lead a life that is the only right one; (b) The community's use of God as the one whose love and regard are conditional; (c) The SCR emotional and behavioral practices used by the community toward individuals who violate norms, and (d) How, paradoxically, the use of SCR may eventuate in the initiation of drug use, and within the community itself., Discussion: Findings are discussed in the context of self-determination theory and SCR, and shed light on how tight cultures cope with the threat of deviation of communal norms. Implications for intervention and policy are outlined., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Itzhaki-Braun and Gavriel-Fried.)

Background: Acute graft-versus-host disease (aGvHD) is a major cause of death for patients following allogeneic hematopoietic stem cell transplantation (HSCT). Effective management of moderate to severe aGvHD remains challenging despite recent advances in HSCT, emphasizing the importance of prophylaxis and risk factor identification., Methods: In this study, we analyzed data from 1479 adults who underwent HSCT between 2005 and 2017 to investigate the effects of aGvHD prophylaxis and time-dependent risk factors on the development of grades II-IV aGvHD within 100 days post-HSCT., Results: Using a dynamic longitudinal time-to-event model, we observed a non-monotonic baseline hazard overtime with a low hazard during the first few days and a maximum hazard at day 17, described by Bateman function with a mean transit time of approximately 11 days. Multivariable analysis revealed significant time-dependent effects of white blood cell counts and cyclosporine A exposure as well as static effects of female donors for male recipients, patients with matched related donors, conditioning regimen consisting of fludarabine plus total body irradiation, and patient age in recipients of grafts from related donors on the risk to develop grades II-IV aGvHD. Additionally, we found that higher cumulative hazard on day 7 after allo-HSCT are associated with an increased incidence of grades II-IV aGvHD within 100 days indicating that an individual assessment of the cumulative hazard on day 7 could potentially serve as valuable predictor for later grades II-IV aGvHD development. Using the final model, stochastic simulations were performed to explore covariate effects on the cumulative incidence over time and to estimate risk ratios., Conclusion: Overall, the presented model showed good descriptive and predictive performance and provides valuable insights into the interplay of multiple static and time-dependent risk factors for the prediction of aGvHD., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)