Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are effective in treating NSCLC with EGFR mutations, the development of resistance limits their long-term efficacy. Autophagy has been implicated as a potential mechanism behind this acquired resistance. This study aims to investigate the role of Stanniocalcin 2 (STC2) in mediating autophagy and its contribution to EGFR TKI resistance.

STC2 expression was manipulated to examine its effects on autophagy and EGFR TKI resistance both in vitro and in vivo. Autophagic activity was assessed by measuring LC3B-II expression levels, the number of LC3 puncta, and the accumulation of autophagic vacuoles. Pharmacological inhibitors and small interfering RNA (siRNA) were used to assess whether the regulatory relationship between STC2 and Beclin 1 was involved in STC2-mediated autophagy and EGFR TKI resistance.

Here, we found that STC2 was associated with increased autophagic activity, as evidenced by elevated LC3B-II levels, enhanced LC3 puncta formation, and increased accumulation of autophagic vacuoles. Conversely, STC2 knockdown resulted in reduced autophagic activity. We identified that STC2 is associated with ERK1/2 activation and Beclin 1-related autophagic activity. Importantly, inhibiting autophagy reversed the resistance to EGFR TKIs induced by STC2, as demonstrated in vitro and in vivo xenograft mouse models.

These findings suggest that STC2 appears to promote cytoprotective autophagy, and targeting the STC2-associated ERK/Beclin 1 signaling axis may offer a promising strategy to overcome resistance to EGFR TKIs.

Rasamsonia species are thermophilic fungi that primarily cause infection in immunocompromised patients. R.argillacea species complex is frequently misidentified as a pathogen due to its morphological similarity to the genera Penicillium and Paecilomyces and its incidence remains undetermined. This situation further complicates the process of timely diagnosis and treatment. Rasamsonia species can be identified using internal transcribed spacer (ITS) sequence analysis, which is considered the primary fungal barcode. Accurate species identification is imperative for the administration of appropriate antifungal treatment. In this report, a case of acute myeloid leukaemia (AML) with R.argillacea growth was presented. A 69-year-old female patient diagnosed with AML who was undergoing chemotherapy was admitted to the hospital due to febrile neutropenia. Despite the administration of appropriate antibiotic therapy, the patient's fever did not respond and her respiratory distress worsened. A subsequent chest computerized tomography scan revealed the presence of bilateral nodular lesions and halo findings in some nodules. The empirical liposomal amphotericin B was initiated at a dosage of 3 mg/kg/day. Following a 17-day course of empirical amphotericin B therapy, the patient exhibited an escalation in respiratory distress and an increase in her blood galactomannan (GM) level (Platelia™ Aspergillus Ag; Bio-Rad, France). Consequently, intravenous (IV) voriconazole was administered at a loading dose of 2x6 mg/kg followed by a maintenance dose of 2x4 mg/kg. Notwithstanding the administration of voriconazole therapy, the patient's blood GM levels persisted at elevated levels on three separate occasions. Consequently, a bronchoalveolar lavage (BAL) sample was obtained for further analysis. However, no growth was detected in the bronchoalveolar lavage (BAL) culture. The BAL GM level was found to be elevated (optic indices: 4.38). The patient developed increasing respiratory distress and confusion and was intubated. A deep tracheal aspirate (DTA) sample was collected. The patient died shortly thereafter. Velvety, beige-colored colonies were observed in the culture media to which the DTA sample inoculated. Microscopic examination of the culture using a lactophenol cotton blue stain revealed cylindrical conidia, rough-walled conidiophores and long, pointed phialides. The isolate was identified as R.argillacea using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (Bruker, Bremen, Germany). This isolate could not be identified based on colony morphology and microscopic appearance; however, it was identified as R. argillacea using the ribosomal DNA ITS region. Its antifungal susceptibility was then assessed using the microdilution method according to the Clinical and Laboratory Standards Institute M38-A2 guidelines. The minimum inhibitory concentrations (MICs) for the antifungal drugs were as follows: fluconazole >64 μg/mL, itraconazole 0.5 μg/mL, voriconazole >16 μg/mL, posaconazole 0.5 μg/ mL, anidulafungin ≤0.015 μg/mL, micafungin 0.03 μg/mL and amphotericin B 1 μg/mL. In this case, the patient died without the causative agent being identified. Although it cannot be definitively stated that R. argillacea was the cause of the patient's mortality due to the lack of an autopsy, this case was presented because it is the first suspected case of R. argillacea isolated and confirmed by molecular methods in Türkiye and to highlight the importance of not neglecting Rasamsonia species which are rare mold fungi.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder frequently associated with ovarian teratomas in young women. Although infectious triggers have been proposed to contribute to immune activation, direct evidence linking viral presence within tumor tissue to disease pathogenesis remains limited.

An 18-year-old woman presented with acute neuropsychiatric symptoms, fever, gastrointestinal prodrome, and rapidly progressive behavioral disturbance progressing to encephalopathy. Cerebrospinal fluid and blood test results, together with clinical features, supported the diagnosis of anti-NMDAR encephalitis. Imaging identified an ovarian mass, and surgical resection was performed. Histopathology confirmed a mature teratoma containing neuroglial elements. Molecular analysis detected parvovirus B19 DNA within the resected teratomatous tissue. No systemic viremia or active central nervous system viral infection was identified. The patient received immunotherapy combined with tumor removal, with subsequent clinical improvement.

Ovarian teratomas remain a critical etiologic factor in anti-NMDAR encephalitis and mandate prompt surgical management. Detection of B19 viral DNA within teratomatous neuroglial tissue raises the hypothesis that viral persistence could enhance local immune activation and autoantibody generation. However, in this case polymerase chain reaction positivity does not indicate active infection, and the biological significance of this finding remains uncertain.

This case documents rare detection of B19V DNA within an ovarian teratomatous tissue in anti-NMDAR encephalitis. The observation is hypothesis-generating rather than causal; established management priorities remain immunotherapy and tumor resection, and viral nucleic acid detection should be interpreted within the broader clinical context.

Malignant gliomas remain highly treatment-resistant brain tumors despite surgery and adjuvant therapies. Targeted toxin therapies represent a unique strategy that exploits receptor-mediated cellular internalization to deliver cytotoxic components that result in the irreversible inhibition of protein synthesis independent of DNA damage or cell-cycle status. Advances in molecular profiling, toxin engineering, and delivery development have refined components targeting IL4Rα, IL13Rα2, EGFR/EGFRvIII, uPAR, and the transferrin receptor. Early clinical studies demonstrated biological activity, acceptable safety, and durable responses in subsets of patients, validating the fundamental mechanism of this approach. However, late-phase trials failed to demonstrate a population-level survival benefit, largely due to variability in delivery, receptor heterogeneity, and limitations in trial design rather than insufficient cytotoxic potency. Recent progress has focused on multiple receptor-targeting and delivery systems capable of achieving reliable intratumoral distribution. MRI-guided convection-enhanced delivery, vector-mediated toxin expression, and blood-brain barrier penetrant nanocarriers now enable more precise tumor targeting. Emerging evidence also reveals that toxin-mediated cytotoxicity can enhance antitumor immune responses, supporting their integration with immunotherapy. These advances position targeted toxins as precision cytotoxic compounds whose success depends on coordinated molecular targeting, delivery optimization, and biologically stratified patient selection, establishing a translational pathway for future glioma therapy.

Cancer cells face continual stressors, which they must overcome to proliferate and survive in the body. Under these conditions, essential biochemical pathways are disrupted, contributing to various stress responses that either promote adaptation and survival or eventual cell death. The evolutionarily conserved integrated stress response (ISR) is a key adaptive mechanism that transiently rewires the transcriptome and translatome in response to various stressors. While the ISR is activated in healthy cells under moderate stress, cancers especially rely on this pathway to overcome harsh conditions experienced during tumor growth and metastasis. We explore the pro-tumorigenic role of the ISR, along with the upstream stress-sensing kinases that activate it. These include protein kinase R-like endoplasmic reticulum kinase, general control non-derepressible 2, double-stranded RNA-dependent protein kinase, and heme-regulated eukaryotic translation initiation factor 2α kinase (HRI), which initiate an ISR in response to diverse stressors by phosphorylating their shared substrate, eukaryotic initiation factor-2α. An in-depth understanding of the pro-survival functions of the ISR and the contexts in which it is pro-tumorigenic is necessary to leverage the ISR as a therapeutic strategy.

The Magnetic Resonance Imaging (MRI)-based tumor segmentation remains a challenging problem in medical imaging due to tumor heterogeneity, unpredictable morphological features, and the high complexity of calculations needed to implement it in clinical practice, putting it out of the scope of real-time applications. Although neural networks have significantly improved segmentation performance, they still struggle to capture morphological tumor features while maintaining computational efficiency. This work introduces Hybrid Adaptive Attention U-Net (HAAU-Net) framework, combining context-aware morphologically stable features and spatial channel attention to achieve high-quality tumor segmentation with less computational cost.

The proposed HAAU-Net framework integrates multi-scale Adaptive Attention Blocks (AAB), Context-Aware Morphological Feature Module (CAMFM) and Spatial-Channel Hybrid Attention Mechanism (SCHAM). CAMFM is used to maintain the stability of morphological features by hierarchical aggregation and dynamic normalization of features. SCHAM enhances feature representation by modelling channels and spatial regions where the strongest feature are determined to use in segmentation. On the BRaTS 2022/2023 data, the proposed HAAU-Net is evaluated using four modalities including T1, T1GD, T2 and T2-FLAIR sequences.

The proposed model able to obtain 96.8% segmentation accuracy with a Dice coefficient of 0.89 on the entire tumor region, outperforming the alternative U-Net (0.83) and conventional CNN methods of segmentation (0.81). The proposed HAAU-Net architecture cuts the computational complexity of the standard deep learning models by 43% and still achieve real-time inference (28 FPS on a regular GPU). The hybrid model used to predict survival has a C-Index of 0.91 which is higher than the traditional SVM-based methods (0.72).

Spatial-channel attention, combined with morphologically stable features, can be combined to allow clinically significant interpretability in attention maps. The proposed framework significantly improves segmentation performance while maintaining computational effeciency. This broad system has a serious potential of AI-enabled clinical decision support system and early prognostic diagnosis in neuro-oncology with practical deployment capability.

Background/Objectives: Human papillomavirus (HPV) infection is a major concern in public health, given its role as a persistent sexually transmitted infection and a causative agent of non-cancerous and cancerous lesions (neoplasms). The increasing infection rates observed in recent years underscore the need for effective public health measures to address this issue. The objective of this study is to describe the challenges and the results of conducting vaccination campaigns within a university setting and its impact on the HPV vaccination rate. Methods: A multifaceted approach was adopted, entailing the implementation of two distinct interventions. Following the promotional and educational online campaign (described elsewhere), vaccination delivery took place from November 2024 to July 2025 in the university campus and in three university hospitals in Milan. Overall and covariate-specific drop-out rate is calculated; significance is tested through a chi-square test of homogeneity between the population that completed less than three doses vs. those who completed the full cycle. Overall and vaccine-specific vaccination proportion is reported. Results: The vaccination rate for first doses reached 92% of available appointments, with a slight female majority (50.9%) and the 23-26 age as the most represented group (47%). The most represented nationality was Italian (58.4%), followed by Iranian (26.5%). Regarding the vaccination sites, the university venue recorded the highest rates in terms of both vaccines booked (56.4%) and vaccines administered (64.7%). With a net loss in follow up, consistent with WHO data, the three-dose HPV vaccination campaign was completed by 82.5% of participants. A chi-squared test of homogeneity revealed significant differences in age distribution between vaccination groups, χ² (3) = 347.78, p < 0.001, Cramér's V = 0.457. Participants who received only one dose were predominantly younger (17-22 years: 71.1% vs. 19.0%, difference = 52.1 percentage points, 95% CI [46.6, 57.7]). Meanwhile, a catch-up strategy raised interest on other crucial vaccinations. Conclusions: The findings pertaining to the vaccination rate underscore the heightened awareness among young adults concerning the HPV vaccine. They further substantiate the efficacy of the integrated strategy encompassing advisory and educational site-based campaigns as an initial measure to attain the WHO-endorsed vaccination rates.

Background: This study employed artificial intelligence (AI) to analyze quantitative nuclear morphological features obtained from digital pathology images to predict postoperative recurrence in patients with lung squamous cell carcinoma (LSQCC). We aimed to develop a prediction model that contributes to the realization of 'personalized postoperative management' tailored to individual tumor biology by integrating AI-extracted morphological features with clinical information. Methods: A total of 185 of the 253 surgically resected LSQCC cases were included; 136 were randomly assigned to the training set and 49 to the test set. Nuclear features from manually selected regions of interest were extracted and used to build AI-based prediction models. Three recurrence models were developed: recurrence within 2 years, within 5 years, and a three-category model (≤2 years, 3-5 years, >5 years or no recurrence). Support vector machine (SVM) and random forest (RF) algorithms were applied to each, yielding six predictive models. An ensemble approach was used to calculate AI-based risk scores, and a "total risk score" was developed by integrating these with the pathologic stage. Results: All six AI models demonstrated stable predictive performance, with AUC values ranging from 0.76 to 0.91. Kaplan-Meier analysis showed that the total risk score provided the most precise risk stratification (p < 0.005), with clearer separation between risk groups than the AI-based risk score alone. Conclusions: The integration of AI-based nuclear morphology analysis and clinical data provides an objective and practical tool for personalized postoperative management in LSQCC. This approach enables tailored clinical decision-making by identifying patients at high risk for early recurrence and customizing postoperative treatment plans to meet the specific needs of each individual.

Antibody-drug conjugates (ADCs) are reshaping the therapeutic approach to advanced gastrointestinal cancers by integrating tumor-specific monoclonal antibodies with potent cytotoxic payloads to improve targeted tumor cell destruction while minimizing systemic exposure. Compared to traditional chemotherapy, trastuzumab deruxtecan has significantly improved objective response rates and overall survival in HER2-positive gastric and gastroesophageal junction tumors after trastuzumab-based therapy. This supports its role as an important second-line or later treatment option. The ongoing advancement of ADCs targeting CLDN18.2, TROP2, and CEACAM5 indicates that this therapeutic category will continue to expand across gastrointestinal neoplasms. Nonetheless, these advancements are accompanied by a specific and clinically significant toxicity profile. Hematologic suppression, gastrointestinal side effects, hepatotoxicity, and notably interstitial lung disease (ILD) are essential consequences that may need inpatient assessment and care. Interstitial lung disease (ILD), although uncommon, may be severe or lethal if not identified immediately and treated swiftly with medication cessation and corticosteroids. In hospitalized patients, distinguishing ADC-related toxicity from infection or disease progression is often difficult owing to overlapping clinical manifestations, requiring meticulous evaluation and interdisciplinary cooperation. As ADCs are integrated into earlier treatment lines and across a broader patient population, hospital systems must evolve to ensure prompt identification, consistent management protocols, and efficient collaboration between oncology and inpatient teams. This study analyzes the mechanisms, clinical effectiveness, and safety profile of ADCs in gastrointestinal oncology, pointing out the importance of institutional preparedness to safely incorporate these medicines into standard clinical practice. These features also align ADC therapy with personalized medicine by emphasizing biomarker-guided patient selection and individualized toxicity monitoring.

Background: High recurrence rates for non-muscle-invasive bladder cancer (NMIBC) remain a clinical challenge. Recommended post-operative treatments are underutilized, highlighting the need for alternative strategies. Given the variability in bladder cancer prognosis, personalized treatment approaches are highly relevant. In this study, we evaluated post-operative two-hour continuous sterile water bladder irrigation (CSWBI) regarding recurrence and safety, as a potential addition to the treatment arsenal for bladder cancer. Method: In 2018, two-hour CSWBI was implemented as routine treatment after all transurethral resection procedures of the bladder (TURB), at the urology department of Sundsvall Hospital. All patients who underwent TURBs four years prior (control group) and four years after the implementation of CSWBI (intervention group) were analyzed. Primary NMIBC were included, MIBC and CIS were excluded. Data were collected retrospectively from patient records, including baseline characteristics, adverse events, and recurrence rates within 12 months follow-up. Statistical analyses included Chi-squared test, Wilcoxon rank-sum test, univariate and multivariate logistic regression analyses, Kaplan-Meier curves and log-rank test. Results: A total of 168 patients were included (control group n = 90, irrigation group n = 78). Median age was 73 years, 23% were female, 77% were male, and 74% were active or previous smokers. The recurrence rate within twelve months for the intervention group vs. the control group was: 27% vs. 21% (p = 0.4) respectively. CSWBI had no statistically significant impact on recurrence (OR 1.25, 95% CI 0.58-2.68, p = 0.6). Adverse effects were limited and equal between groups. Conclusions: Post-operative two-hour CSWBI did not significantly reduce NMIBC recurrence within twelve months in this cohort.