Genomic imprinting is an epigenetic phenomenon in which gene expression depends on the parental origin of an allele. Since its discovery in the 1980s, genomic imprinting has fundamentally changed our understanding of mammalian development and human diseases. Unlike classical Mendelian inheritance, imprinted genes are monoallelically expressed in a parent-of-origin-specific manner, making them particularly vulnerable to genetic and epigenetic disturbances. The concept of genomic imprinting was first established via nuclear transfer experiments in mice, which demonstrated that maternal and paternal genomes are functionally non-equivalent. Subsequent clinical observations in humans, including hydatidiform mole and uniparental disomy, provided compelling evidence that genomic imprinting also plays a crucial role in human development. Disruption of imprinting regulation leads to various congenital disorders, such as Prader–Willi and Angelman syndromes, which are characterized by growth abnormalities, neurodevelopmental defects, and metabolic dysregulation. At the molecular level, genomic imprinting is regulated primarily by epigenetic mechanisms, including DNA methylation at imprinting control regions, histone modifications, and long noncoding RNAs. Genome-wide studies have revealed both conserved and species-specific imprinted genes in mice and humans, highlighting imprinting as an evolutionarily dynamic process. Recent findings indicate that lineage-specific long terminal repeat retrotransposons contribute to the emergence of novel imprinted loci by acting as alternative promoters during oogenesis or embryogenesis. This review summarizes the historical discovery of genomic imprinting, its clinical relevance in humans, and recent insights into its molecular and evolutionary mechanisms.

Viral entry into host cells is a fundamental determinant of infection efficiency, host range, tissue tropism, and pathogenicity, yet the mechanistic diversity of this process remains incompletely understood. Clathrin-mediated endocytosis (CME) coupled with dynamin-dependent membrane scission has long served as the canonical model; however, accumulating evidence reveals that many viruses—spanning large enveloped viruses (Ebola virus, vaccinia virus), medium-sized enveloped viruses (chikungunya virus, SARS-CoV-2, dengue virus), non-enveloped RNA viruses (echovirus, reovirus), and DNA viruses (adenovirus, SV40, human papillomavirus) —exploit routes partially or entirely independent of dynamin. A central thesis of this review is that dynamin involvement in viral entry is not a binary property but a variable parameter along a mechanistic continuum, modulated by virus particle geometry, receptor expression, membrane composition, cytoskeletal state, and cell type. This perspective reframes apparently conflicting reports—wherein dynamin inhibition partially rather than completely suppresses infectivity, or where the same virus uses distinct entry routes in different cellular contexts—as reflections of condition-dependent pathway selection rather than categorically distinct mechanisms. This review further examines methodological limitations of pharmacological and genetic approaches and surveys the molecular diversity of co-existing dynamin-independent pathways, including macropinocytosis, the CLIC/GEEC route, the Arf6-regulated pathway, and fast endophilin-mediated endocytosis. Conceptualizing viral entry as a plastic process governed by the relative engagement of multiple endocytic pathways deepens our understanding of virus–host interactions and suggests that targeting convergent downstream steps, rather than single entry routes, may yield more effective antiviral strategies.

Chimeric antigen receptor (CAR)-T cell therapy has emerged as a highly effective treatment for relapsed or refractory hematologic malignancies, offering the potential for durable remission and even cure. However, its clinical success relies heavily on the appropriate recognition and management of characteristic toxicities after CAR-T cell infusion. This review outlines the treatment flow of CAR-T cell therapy and summarizes recent advances in the management of its adverse events. The adverse events associated with CAR-T cell therapy can be categorized into early and late toxicities, and early toxicities include cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and immune effector cell-associated hematotoxicity. CRS and ICANS remain the most clinically significant acute complications, and their management has evolved toward earlier intervention strategies using tocilizumab and corticosteroids without compromising therapeutic efficacy, although vigilance for infectious complications and appropriate management remain essential. Late toxicities, including prolonged cytopenia, infections, hypogammaglobulinemia, cardiac events, and secondary malignancies, are gaining attention as patient short-term survival improves. Preventive strategies such as immunoglobulin replacement and vaccination play a critical role in long-term management. Despite improvements in safety, optimal management strategies for several complications remain to be fully established. Overall, advances in toxicity management have improved the safety profile of CAR-T cell therapy. Continued accumulation of real-world data and refinement of standardized management approaches are essential to further optimize patient outcomes.

Pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas, are characterized by abnormal growth in the pituitary gland. These tumors may occur with or without excess hormone secretion, leading to various clinical complications. Management often involves a multimodal approach, utilizing surgical resection, chemotherapy, radiotherapy, and molecularly targeted therapy to minimize the risks of resistance, recurrence, and side effects. In this review, we summarize existing standard therapeutic approaches, novel pharmacological treatments, and ongoing research for PitNETs. While the latter requires further clinical investigation, these emerging therapeutic strategies are expected to maintain or improve the quality of life for patients with PitNETs.

The present study aimed to evaluate the diagnostic process and clinical decision-making for jaw lesions presenting as cystic-appearing radiolucencies. A retrospective analysis was conducted on 262 patients treated at our institution between April 2014 and March 2023 who exhibited intraosseous radiolucent lesions ≥ 10 mm in diameter. Lesions clinically diagnosed as obvious radicular cysts < 20 mm were excluded. Clinical and radiological findings, timing of biopsy, and final pathological diagnoses based on the 2022 WHO classification were analyzed. Comparisons were performed using the chi-square test.

The initial clinical diagnoses included 58 radicular cysts, 143 dentigerous cysts, 20 odontogenic keratocysts (OKCs), and 40 ameloblastomas. Concordance rates between clinical and final pathological diagnoses were high for radicular cysts (94.8%) and dentigerous cysts (95.1%), but lower for OKCs (50.0%) and ameloblastomas (52.5%).

Several radiological findings, including root resorption, tooth displacement, cortical bone expansion, multilocular radiolucency, and lesion size, showed significant differences among disease entities (all P < 0.001). In addition, when lesions were classified into cystic and neoplastic groups, these radiological features and larger lesion size were significantly associated with neoplastic lesions.

These findings suggest that, although clinical findings alone are insufficient, radiological assessment and lesion size may be useful indicators for distinguishing neoplastic lesions from cystic lesions and for guiding clinical decision-making in daily practice.

Introduction: Some infants who are diagnosed with both atopic dermatitis (AD) and food allergy (FA) have very early sensitization to inhalant allergens. However, few studies have examined the time course of specific IgE (sIgE) to inhalant allergens in infants diagnosed with AD and/or FA. Therefore, we conducted a prospective longitudinal study of sIgE in infants diagnosed with AD and/or FA.

Methods: The subjects were infants diagnosed with AD and/or FA at nine hospitals and clinics. Baseline characteristics were collected for sex, family history, exposure to pets, and second-hand smoking. sIgE was examined by chemiluminescent enzyme immunoassay every 6 months up to age 3 years from the day of registration, and the subjects were categorized into food, mite, pollen, and pet allergen groups. Cumulative sensitization rates in each allergen group were compared for subjects that were or were not exposed to pets; and in AD and/or FA cases.

Results: The sensitization rate was significantly higher in the group of children who kept pets than in the group who did not (p < 0.001). In an analysis of AD + FA (n = 45), AD (n = 23), and FA (n = 24) cases, the sensitization rates were significantly higher in AD + FA cases compared to FA cases in the mite (p = 0.020) and pollen (p = 0.047) allergen groups.

Conclusion: Infants with coexisting AD and FA are likely to become sensitized to pollen and mite allergens earlier than infants with FA alone, and that exposure to pets during infancy diagnosed AD and/or FA accelerates pet allergen sensitization.

Alcoholic ketoacidosis (AKA) is a potentially life-threatening metabolic disorder that is often underrecognized because of its nonspecific gastrointestinal manifestations and frequently normal or mildly elevated blood glucose levels. Diagnostic difficulty is further increased in patients with preexisting diagnoses associated with recurrent symptoms. We report the case of a woman in her 40s with a long-standing diagnosis of abdominal migraine who presented to the emergency department with severe nausea, vomiting, and abdominal pain. Although her presentation initially suggested a recurrence of her usual episodic attacks or an acute abdominal condition, the unusually intense and prolonged nature of her nausea prompted diagnostic reassessment. Targeted history-taking revealed recent escalation of alcohol intake combined with poor oral intake. Laboratory evaluation demonstrated high–anion gap metabolic acidosis with markedly elevated β-hydroxybutyrate levels, leading to the diagnosis of AKA. Treatment with intravenous saline and thiamine, followed by early resumption of oral intake, resulted in rapid clinical and biochemical improvement. This case illustrates how diagnostic anchoring and premature closure may delay recognition of metabolic conditions such as AKA in patients with recurrent gastrointestinal symptoms and highlights the importance of recognizing deviations from established symptom patterns and performing diagnostic time-outs to mitigate cognitive bias.

Collision tumors of the skin, where two distinct neoplasms occur within the same anatomical location, present unique diagnostic and biological challenges. While the association of basal cell carcinoma (BCC) with common melanocytic nevi or seborrheic keratosis is well-documented, the simultaneous occurrence of BCC and blue nevus is exceptionally rare. We report the case of a 75-year-old Japanese woman who presented with a rapidly growing black nodule on a pre-existing blue macule on the nose. Histopathological examination confirmed a nodular BCC colliding with a common blue nevus. Notably, immunohistochemical analysis revealed that dendritic melanocytes from the blue nevus colonized the BCC nests specifically in areas adjacent to the nevus. This spatial correlation suggests potential paracrine interactions or a "migration" phenomenon between the two neoplasms. This report, constituting only the third documented case of this specific collision, provides a detailed discussion on pathogenic mechanisms and the diagnostic importance of recognizing such lesions to avoid clinical misdiagnosis of malignant melanoma.

Copper deficiency is a recognized but often overlooked complication of long-term zinc supplementation. Although most reported cases involve adults, pediatric cases remain rare, particularly among children with severe motor and intellectual disabilities who often require prolonged nutritional and dermatologic management. We report a 9-year-old boy with severe motor and intellectual disabilities who developed copper deficiency following prolonged, unmonitored oral zinc acetate therapy for perianal mucocutaneous lesions. He presented with hematochezia and was found to have macrocytic anemia and leukopenia. Laboratory evaluation revealed markedly decreased serum copper and ceruloplasmin levels, despite normal serum zinc levels, with an elevated zinc-to-copper ratio (22:1). Discontinuation of zinc acetate and initiation of copper supplementation with pure cocoa powder led to gradual hematologic improvement. Subsequent maintenance with a commercial enteral formula providing balanced zinc and copper intake normalized hematologic and trace element parameters, with no recurrence during follow-up. This case highlights the risk of copper deficiency during prolonged zinc supplementation, even when serum zinc levels are within the normal range, and highlights the importance of regular monitoring of trace elements and maintaining an appropriate balance between zinc and copper intake, particularly in children with severe motor and intellectual disabilities.

Introduction: Double-orifice mitral valve (DOMV) is a rare congenital anomaly. We describe a case of isolated DOMV with severe MR that was successfully treated with minimally invasive cardiac surgery (MICS).

Case presentation: A 69-year-old man presented with exertional dyspnoea and leg edema. Transthoracic echocardiography revealed severe MR caused by P3 chordae tendineae rupture. Intraoperative transoesophageal echocardiography identified a central bridge-type DOMV. The patient underwent mitral valve repair via a right mini-thoracotomy MICS approach. The central fibrous bridge was preserved to maintain leaflet symmetry and subvalvular geometry, and repair was achieved with P3 leaflet plication and a 32-mm Colvin-Galloway Future™ Annuloplasty Band. Postoperative echocardiography demonstrated no residual MR, a mean transmitral gradient of 2.3 mmHg, and a mitral valve area of 3.2 cm².

Discussion: Preserving the bridge allowed the maintenance of native valvular morphology and function, provided that the orifice area was sufficient and no bridge-related pathology was present. Our case suggests that minimally invasive mitral valve repair with central bridge preservation may be considered in selected patients with isolated central bridge type DOMV.

Conclusion: MICS mitral valve repair with preservation of the central fibrous bridge may be a feasible surgical option in patients with isolated central-bridge type DOMV.