Photodynamic therapy (PDT) is a promising treatment for pleural malignancies, yet accurate dosimetry remains challenging due to complex cavity geometries and the need to protect surrounding critical structures. The reactive oxygen species ([ROS]rx) generated during treatment serve as a direct predictor of therapeutic efficacy. We developed a finite element model using COMSOL Multiphysics to simulate macroscopic photophysical kinetics, using clinical data inputs, including light fluence derived from a navigation system and patient-specific photosensitizer concentrations. Crucially, we integrated a deformable image registration framework to align intra-operative navigation data with pre-treatment CT scans, enabling the calculation of [ROS]rx dose accumulation in critical Organs at Risk (OARs), such as the lung, heart, and esophagus. The model successfully reconstructed 3D [ROS]rx distributions for multiple clinical cases. Point-to-point comparison at 32 detector locations across ten patients showed strong agreement between COMSOL-simulated and clinically calculated [ROS]rx (mean percentage difference 0.6 ± 5.8%), while volume-averaged values differed by -6.0%, reflecting the enhanced spatial coverage of the 3D model relative to discrete sampling. The two-stage deformable registration improved CT-to-navigation surface alignment from HD95 = 4.08 mm to 1.78 mm (56.4% reduction) and MSD = 1.77 mm to 0.68 mm (61.5% reduction), enabling the first patient-specific mapping of [ROS]rx onto OAR structures. This study demonstrates the feasibility of a comprehensive 3D dosimetry system for pleural PDT. By integrating kinetic modeling with deformable registration, we provide a robust platform for evaluating treatment efficacy and ensuring OAR safety, paving the way for eventual integration into treatment planning and real-time feedback.

Pulmonary brucellosis is a rare focal manifestation of human brucellosis with non-specific clinical features. Predominant imaging findings include pneumonia, pleural effusion, pulmonary nodules, abscesses, and interstitial changes. Multiple cavitary lesions are exceptionally rare. Herein, we report a case of bilateral multiple pulmonary cavities in a 76-year-old man with a 2-year history of intermittent cough, sputum production, and progressive dyspnea that acutely worsened 10 days prior to admission with intermittent fever, anorexia, and fatigue. Chest computed tomography (CT) revealed bilateral upper lobe irregular mass-like opacities and multiple nodules with heterogeneous density, punctate calcifications, and cavitation; multiple microcavitations in the right middle and lower lobes and the left lower lobe; and enlarged, calcified hilar and mediastinal lymph nodes. Metagenomic next-generation sequencing of bronchoalveolar lavage fluid identified Brucella species, which was confirmed by positive serology. After 3 days of doxycycline (0.1 g bid po) and rifampicin (0.6 g qd po), followed by 140 days of doxycycline (0.1 g bid po), rifapentine (0.6 g biw po), and levofloxacin (0.5 g qd po), along with silibinin meglumine tablets 0.1 g tid po for hepatoprotective therapy, the patient became afebrile with significant symptomatic improvement. Repeat chest CT demonstrated reduction in the right upper lobe consolidation/cavity and left upper lobe consolidation, resolution of the right lower lobe cavity, and complete resolution of the microcavitations. This case underscores that pulmonary brucellosis should be considered in the differential diagnosis of cavitary lung lesions in patients with livestock exposure and that prolonged combination antibiotic therapy can achieve favorable clinical and radiological outcomes.

Hereditary hemorrhagic telangiectasia (HHT) is a multiple-organ disease. Herein, we report a case of rupture of an undiagnosed pulmonary arteriovenous malformation (PAVM) during pregnancy in which good outcomes for both mother and children were achieved with transcatheter embolization. The patient was a pregnant 32-year-old Pashtun woman, G4P3, with a history of cesarean section. She had undergone pregnancy checkups at our hospital for a dichorionic diamniotic twin pregnancy. In gestational week 20, the patient experienced loss of consciousness at home and was transported by ambulance to our hospital. Her Glasgow Coma Scale score was 9 (E2V2M5) and her blood pressure was 57/27 mmHg. Blood test results showed severe anemia; right atelectasis and mediastinal shift were shown on chest radiography. Contrast-enhanced chest computed tomography revealed right hemothorax and a single pulmonary arteriovenous malformation measuring 35 mm in the middle lobe of the right lung. The patient was diagnosed with hemothorax due to rupture of the right PAVM. Emergency transcatheter embolization was performed, disappearance of the arteriovenous malformation was confirmed, and hemostasis was achieved. Recurrent epistaxis and telangiectasias on the tongue, buccal mucosa, and nasal cavity were noted, and the patient was diagnosed with HHT. An abdominal cesarean section was performed due to the low-lying placenta and right hydronephrosis. Two male neonates were delivered: one weighed 1988 g and the other 2166 g. Both mother and infants progressed well. This case illustrates how unrecognized HHT can lead to catastrophic PAVM rupture during pregnancy and emphasizes the lifesaving value of early diagnosis and prompt endovascular intervention. In addition, it highlights the critical importance of pre‑pregnancy screening for HHT to prevent life‑threatening complications.

The spotted seal (Phoca largha) is a flagship species and natural monument inhabiting Korean coastal waters. Due to its conservation importance and the rarity of carcass discoveries, determining the cause of death of each individual is critical. A juvenile female spotted seal carcass was discovered on the eastern coast of Korea in May 2025. External examination revealed multiple parallel lacerations consistent with propeller strike injuries. Post-mortem computed tomography (PMCT) was performed prior to necropsy to provide a comprehensive forensic analysis. CT imaging revealed the longest wound measured 10.49 cm in length and 1.58 cm in depth, suggesting a minimum propeller diameter of approximately 19 cm. Skeletal injuries included a coccygeal vertebral fracture and subluxation of the left astragalus and calcaneus. CT images of the respiratory tract showed frothy fluid in the nasal cavity and trachea, as well as ground-glass opacity and consolidation in the lung parenchyma. Necropsy findings confirmed severe pulmonary edema, congestion, and abundant frothy foam throughout the respiratory tract. Histological analysis revealed pulmonary edema with eosinophilic fluid and erythrocytes in alveolar spaces, markedly distended blood vessels, and intra-alveolar hemorrhage. This comprehensive approach demonstrated that the cause of death was drowning, secondary to propeller strike by a small vessel (<4.5 m). To the authors' knowledge, this is the first case report providing a detailed forensic analysis of a juvenile spotted seal found on the eastern coast of Korea. This case highlights the importance of integrating PMCT with conventional necropsy to improve cause-of-death determination in marine mammal conservation.

Limited understanding of the biological processes that govern metastatic dissemination hinders its prevention and treatment[1]. Here, using 501 longitudinally collected primary and metastatic tumour samples from 24 patients with non-small cell lung cancer (NSCLC) enrolled in the TRACERx lung study and PEACE autopsy programme, we infer tumour evolution from diagnosis to death. With DNA-sequencing data encompassing 70% of the metastases that were radiologically detected before death and paired multi-region sampled primary tumours, we show that the genomes of metastases diverge markedly from those of their ancestral primary tumour, with additional driver alterations and genome doubling events occurring after metastatic dissemination. In 62.5% of patients, multiple primary tumour subclones disseminated, each founding a distinct metastasis. These metastases served as sources of onward spread: more than half of the metastases sampled were seeded by other metastases. The duration that metastases existed in situ influenced their likelihood of seeding further metastases. Most metastatic migrations started and ended in the same anatomical cavity. The few subclones that exited the thorax to seed metastases disseminated widely and were enriched for somatic copy-number alterations, suggesting that chromosomal instability may facilitate extrathoracic spread. This spatial and temporal evolutionary analysis sheds light on the extent of metastatic diversity and seeding in advanced NSCLC-which tends to be underestimated in single metastasis biopsies-and identifies genomic and clinical mediators of metastatic progression.

The tumor suppressor p53 is the most frequently mutated protein in tumors and a target for drug development. More than 2000 cancer-associated p53 missense mutations have been reported, most of them located in the DNA-binding domain (DBD). Due to the low intrinsic thermostability of the latter, they often lead to unfolding at physiological temperature. Stabilizing the DBD with small molecules has been shown to be effective in reactivating the cavity-creating cancer mutant Y220C. Unfortunately, the majority of p53 mutants seem to lack druggable binding pockets for small molecules. Here we show that a designed ankyrin repeat protein (DARPin) that binds to the p53 DBD stabilizes temperature-sensitive (TS) p53 cancer mutants, thereby compensating for mutation-induced loss of stability. We determined high-resolution crystal structures of multiple DARPin-mutant p53 complexes, providing mechanistic insights into this mode of stabilization. Reporter gene assays across a comprehensive panel of cancer-associated mutants revealed reactivation of the majority of TS mutants, whereas DNA-contact mutants and those with local misfolding of the DNA-binding surface remained inactive, as expected. We demonstrate that this reactivation induces the transcription of canonical p53 target genes and elicits antiproliferative effects in cancer cell lines. A combination of this DARPin with an mRNA/lipid nanoparticle-based transfection approach may have the potential to reactivate most TS p53 mutants and resensitize cancer cells to chemotherapy.