Eye movements represent an objective, quantitative indicator of the integrity of cognitive and perceptual processes. Since the beginning of the 20th century, research has shown that individuals with schizophrenia demonstrate characteristic deviations in smooth pursuit, -egulation, and visual exploration behaviour. These oculomotor alterations are linked to dysfunctions in attention, executive control, and perceptual organization, and have been discussed as potential biomarkers of impaired neural network regulation. More recent work further implicates disturbances in visual attention and integration, as well as reduced executive control over oculomotor activity, which may manifest in altered gaze behaviour.Building on this literature, the present study examined whether free-viewing eye-movement patterns capture markers of restricted exploration and altered scanpath organization under ecologically valid conditions. We recorded eye movements during passive viewing of landscape and abstract images in three groups: patients with schizophrenia (n = 30), healthy controls (n = 30), and close relatives (n = 21). Visual exploration was quantified using integrative indices of fixation number and duration (mean/median/total), scanpath length, coverage fraction, spatial dispersion (mean/median; dispersion_x and dispersion_y), center bias, fixations per second, gaze entropy (bits), and saccade metrics. Group and image type were tested in 2 × 2 mixed ANOVA models with FDR correction across metrics.In the patient-control analysis (N = 60), a significant main effect of group was observed across multiple exploration and oculomotor parameters after FDR correction (partial ηp² ≈ .12–.21; pFDR ≤ .032), with no main effect of image type and no group × image type interaction surviving correction, supporting a stimulus-nonspecific alteration of visual exploration in schizophrenia. In the relatives-controls analysis (N = 51), uncorrected trends suggested a more compact scan pattern (reduced dispersion and saccade amplitude). However, no effects remained significant after FDR correction. Overall, free-viewing eye-movement metrics showed medium-to-large, stimulus-nonspecific group differences in schizophrenia, consistent with a restricted and altered exploration mode, whereas potential vulnerability-related signals in first-degree relatives were weaker and did not survive correction, indicating the need for larger samples and/or targeted paradigms with predefined core metrics in familial-risk designs.
BACKGROUND:Geographic disparities in access to molecular diagnostics and targeted therapies affect the implementation of precision oncology in metastatic colorectal cancer (mCRC), particularly in Eastern Europe. This prospective study aimed to characterize the molecular landscape of advanced CRC in Bulgarian patients and evaluate associations between genomic alterations, mismatch repair (MMR) status, and stromal immune features. METHODS:Formalin-fixed paraffin-embedded tumor samples from 198 Bulgarian patients with advanced CRC were analyzed using targeted next-generation sequencing (TruSight Tumor 15, Illumina®). MMR status was assessed via immunohistochemistry using the VENTANA MMR RxDx Panel. Stromal immune reactions were histologically graded and evaluated for associations with MMR status. Statistical analyses included Chi-square tests and logistic regression. RESULTS:The most frequently mutated genes were TP53 (60.6%), KRAS (37.3%), and BRAFV600E (21.2%). Other alterations included PIK3CA (11.1%), NRAS (4.0%), and AKT1 (2.0%). No mutations were detected in EGFR, ERBB2, NTRK, or RET. Deficient MMR was observed in ∼9% of cases. Stromal reactions were significantly associated with MMR status (χ²(2) = 8.43, p = 0.015), with fibroblast-rich stroma more commonly seen in proficient MMR tumors. Logistic regression supported the results. CONCLUSIONS:This study provides a regional molecular profile of advanced CRC in Bulgaria, highlighting a high prevalence of KRAS mutations and dMMR status, while underrepresentation of rare targetable alterations, likely due to limited use of broad molecular profiling. The association between stromal features and MMR status supports their potential role as surrogate markers in settings with constrained testing resources. Findings underscore the urgent need for equitable access to molecular diagnostics and targeted therapies to close the survival gap between Eastern and Western Europe.
Transitional cell carcinoma (TCC) of the endometrium is an extremely rare histologic subtype of endometrial carcinoma. While TCC is more frequently observed in the ovary, only a few cases have been documented in the cervix, fallopian tubes, adnexa, and endometrium. We describe the clinical presentation, diagnostic work-up, treatment, and histopathological features of a patient with pure high-grade endometrial TCC, followed by a focused review of previously published cases. A 70-year-old woman presented with an enlarging endometrial mass detected incidentally on imaging, despite two prior benign curettages. A total laparoscopic hysterectomy with bilateral salpingo-oophorectomy was performed. Histopathology revealed a pure high-grade TCC confined to the endometrium, without lymphovascular invasion or myometrial infiltration. The immunophenotype was CK7+, Vimentin+, CK HMW+, p16+, and CK20-, with a very high Ki-67 index (> 90%). Molecular classification (The Cancer Genome Atlas/ProMisE) could not be established due to unavailable p53 and mismatch repair testing. One-month follow-up showed no evidence of recurrence. Pure endometrial TCC is extremely rare. Although its morphology is high grade, early-stage disease without invasion may demonstrate favourable short-term outcomes. This case contributes a unique value because it shows a completely pure TCC pattern, absence of invasion, and early detection. Primary high-grade TCC of the endometrium represents a diagnostic and therapeutic challenge due to its rarity, aggressive histologic features, and lack of standardized treatment protocols. This unusual case underscores the importance of integrating histopathological and immunohistochemical findings for accurate diagnosis and guiding optimal patient management.
Background and Clinical Significance: Lues remains a global health concern despite the well-known nature of its symptoms, the availability of diagnostic methods, and the existence of effective therapy. The recent increase in maternal syphilis has been accompanied by a rise in congenital infections, which are associated with stillbirth, prematurity, neonatal mortality, and severe multisystemic disorder. In newborns, it may present with highly variable clinical manifestations, making timely diagnosis and treatment essential. We report a case of severe early congenital syphilis in a premature newborn with extensive multiorgan involvement; Case Presentation: We present a case of a male infant born at 31 + 6 weeks of gestation to a 26-year-old mother with inadequate antenatal care and no documented screening or treatment for syphilis during pregnancy. Prenatal ultrasound revealed fetal ascites. At birth, the infant presented with severe respiratory failure requiring immediate resuscitation, endotracheal intubation, and intensive care support. Clinical findings included hepatosplenomegaly, generalized edema, ascites, petechial rash, palmoplantar desquamation, severe thrombocytopenia, anemia, coagulopathy, liver dysfunction, and hemorrhagic syndrome. Maternal and neonatal serologic testing confirmed syphilis infection. The clinical course was complicated by pneumonia with prolonged mechanical ventilation, cardiovascular involvement impairing cardiac function, and heart failure. Treatment consisted of intravenous penicillin G, broad-spectrum antimicrobial therapy, antifungal medication, respiratory support, transfusion therapy, cardiovascular management, and intensive multidisciplinary care; Conclusions: This report presents consequences of untreated maternal syphilis and underscores the importance of timely diagnosis, early initiation of penicillin therapy, and close multidisciplinary follow-up to optimize outcomes in neonates.
Background and Clinical Significance: Brenner tumors are rare epithelial tumors that can occur in both males and females. They consist of ovarian transition cells surrounded by dense fibrous tissue and can be classified as benign, borderline, or malignant. While most commonly found in the ovary, extraovarian Brenner tumors (EOBTs) have been reported in the uterus, vagina, broad ligament, and omentum. Case Presentation: A 71-year-old postmenopausal woman presented with a polypous formation on the upper third of the posterior vaginal wall, which was found at a routine health check. Macroscopically, the lesion appeared as a solid, polypoid mass with a yellowish-gray cut surface, measuring approximately 25 × 20 mm. Histological examination revealed a polypoid formation covered by stratified squamous epithelium, with a dense fibrous stroma (Van Gieson [VG]+) and tubular structures lined by clear epithelial cells. Parenchymal cells showed low proliferative activity, with Ki-67 expression in less than 5% of cells, also Cytokeratin (CK) 7/+/p63:/+/ CK AE1/AE3: /+/ Estrogen Receptor (ER): /+/ and Progesterone Receptor (PR)/−/; CK20/-/; p53/−/, Wilms’ Tumor (WT)-1/−/; Prostate-Specific Acid Phosphatase (PSAP)/−/. The final diagnosis was an extraovarian Brenner tumor. The patient was monitored for two months post-excision, with no signs of recurrence. Conclusions: EOBTs are extremely rarely seen and vaginal involvement is far less common. Due to their rarity, these tumors may be confused with other benign or malignant vaginal lesions. In order to differentiate EOBTs from other neoplasms, histological analysis is crucial due to their characteristic transitional-type epithelium and large fibrous stroma. Further studies are required to understand the origin and clinical behavior of EOBTs. Long-term monitoring should be performed to look for any recurrence or malignant change, even though benign Brenner tumors usually have a good prognosis. Awareness of EOBTs and their possible locations is essential for accurate diagnosis and appropriate management.
