Shiga University of Medical Science

Busulfan, an alkylating agent used in hematopoietic stem cell transplantation conditioning, is associated with a high risk of ovarian toxicity. We established a time-resolved in vivo model of busulfan-induced ovarian injury and tested whether sapanisertib, an mTOR inhibitor, mitigates damage. Mice received busulfan (30 mg/kg, intraperitoneally) or saline; ovaries were assessed at 12, 24, and 72 h and 7 days by hematoxylin and eosin histology, follicle counting, TUNEL, and Ki-67 immunohistochemistry. A separate cohort received daily oral sapanisertib (0.3 mg/kg) from 7 days before busulfan through euthanasia; proliferation was assessed at 24 h, and follicle counts at 7 days. In the busulfan-only group, Ki-67 staining showed an early proliferative surge at 24 h in growing follicles, including primary follicles, whereas loss of primordial follicles and an increased primary-to-primordial follicle ratio were evident by 7 days. Primordial follicles showed no TUNEL-positive cells through 72 h, whereas growing follicles were frequently TUNEL-positive. Relative to busulfan alone, the mTOR inhibitor preserved primordial follicles, shifted the primary-to-primordial ratio toward control values, and reduced the proportion of primary follicles with extensive proliferation at 24 h. These findings are consistent with premature activation of primordial follicles as a proximate contributor to busulfan-induced loss of ovarian reserve and suggest that mTOR inhibition may mitigate this process. A two-time-point assay (24 h for proliferation, 7 days for morphology) provides a practical framework for future studies and translation.

Technical progress in noninvasive medical imaging continues to enhance diagnosis and intervention, with three-dimensional (3D) imaging emerging as a significant advancement over traditional methods. While 3D visualization is widely used to evaluate a living heart, precise measurement from such images remains challenging. This review describes a new technique named isosurface geometric measurement on volume-rendered images (IMVR), which facilitates accurate 3D measurement of complex cardiovascular anatomy.

Direct volume rendering provides clear visualization and tissue identification, but the lack of exact spatial boundaries inherently makes measurement of any anatomical feature difficult. However, by superimposing a surface-rendered polygonal mesh (representing isosurface geometry) onto a variably transparent volume image of the heart, IMVR enables significantly easier and more accurate 3D measurement. This technique demonstrates versatility across various cardiovascular, anatomical, and clinical applications, including preinterventional assessment and planning for structural heart diseases, notably expanding 3D imaging's utility toward precision medicine and personalized treatment.

This review article summarizes recent advances in cardiac imaging, highlighting an efficient IMVR technique, which combines volume-rendered images with superimposed surface-rendered image to facilitate accurate 3D measurements of cardiac anatomical features.

The incidence of Helicobacter pylori (Hp)-naïve gastric neoplasms (HpNGNs) is increasing due to a growing Hp-naïve population and improved recognition. Among these, HpNGNs that predominantly exhibit foveolar-cell differentiation include foveolar-type gastric adenomas (FGA) and fundic gland polyps with dysplasia (FGPD). Traditionally, FGAs have been considered large, whitish, flat lesions (flat-type FGA), primarily associated with syndromic conditions, such as familial adenomatous polyposis (FAP) and gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS), while sporadic cases are rare. This type exhibits a gastric immunophenotype with diverse differentiation, mainly toward foveolar cells, and harbors APC and KRAS mutations in all sporadic and most syndromic cases. A distinct subset of FGAs, termed foveolar-type gastric adenoma with a raspberry-like appearance (FGA-RA), has been identified. It presents as small, reddish polyps with unique macroscopic and microscopic features and only occurs sporadically. FGA-RA often mimics gastric hyperplastic polyps macroscopically and typically exhibits low-grade dysplasia, making biopsy-based diagnosis challenging and leading to its historical underrecognition. It shows pure foveolar differentiation and consistently harbors Krüppel-like factor 4 (KLF4) mutations. FGPD primarily develops sporadically in Hp-naïve individuals with long-term proton pump inhibitor use. A syndromic form, resembling flat-type FGAs, is also associated with FAP and GAPPS. Histologically, FGPD features dysplasia confined to the superficial foveolar epithelium and mucus neck cells overlying fundic gland polyps, with APC mutations detected in approximately 50% of cases. This review explores the clinicopathological and molecular characteristics of HpNGNs with predominant foveolar cell differentiation, emphasizing the need for an updated histological diagnostic framework.