Can novel biomarkers augment traditional surveillance paradigms in early-stage testicular germ cell tumors? A case study in pre-clinical relapse detection using a combination micro-RNA-371a-3p and 372-3p assay.

Attention-Guided Deep Learning of Chemical Exchange Saturation Transfer Magnetic Resonance Imaging to Differentiate Between Tumor Progression and Radiation Necrosis in Brain Metastasis.

Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions have emerged as important oncogenic drivers across a wide range of malignancies, including soft tissue sarcomas. Early detection of these fusions facilitates precision treatment with TRK inhibitors, significantly improving clinical outcomes. However, diagnosing NTRK-rearranged spindle cell neoplasms (NTRK-RSCNs) remains challenging due to their histological heterogeneity and overlap with other soft tissue tumors. We present the case of an 8-year-old boy with a history of infantile fibromatosis, who developed progressive right ankle dorsiflexion weakness and right foot drop. Magnetic resonance imaging revealed a large, homogeneously enhancing soft tissue mass with extensive perineural involvement and spinal cord compression spread from T8 to L3 levels. The patient underwent T10-L1 laminectomy and partial tumor resection under intraoperative neurophysiological monitoring. Histopathological analysis identified a low-grade spindle cell neoplasm with focal positivity for S100 and CD34, and patchy pan-tropomyosin receptor kinase (TRK) expression. Molecular studies using fluorescence in situ hybridization and RNA-based next-generation sequencing confirmed a TPM3-NTRK1 fusion, establishing the diagnosis of NTRK-rearranged low-grade spindle cell sarcoma. Postoperatively, targeted therapy with a TRK inhibitor Larotrectinib (100mg/m2/dose twice daily) was initiated. Over a 2-year follow-up period, the patient demonstrated significant neurological improvement and stable disease without evidence of progression on serial imaging studies. This case underscores the importance of integrating molecular diagnostics into the evaluation of atypical spindle cell tumors, particularly those presenting with aggressive clinical features despite low-grade histology. Early identification of NTRK fusions enables timely initiation of TRK inhibitor therapy, offering durable disease control and functional recovery. Broader awareness and implementation of molecular testing can greatly enhance the management of rare pediatric sarcomas.

Objective: To evaluate the role of computed tomography (CT) with maximum-intensity-projection (MIP) reconstruction at different slab thicknesses in detecting solid pulmonary nodules smaller than 5 mm. Materials and methods: Chest CT data from 39 patients with solid pulmonary nodules less than 5 mm in diameter were retrospectively analyzed. Each dataset was reconstructed into four image series: standard CT images (MIP0) and MIP images with slab thicknesses of 5, 10, and 15 mm. Two experienced radiologists independently reviewed all image series with at least a two-week interval between readings to minimize recall bias. The number, size, margin, and location of detected nodules were recorded. Interobserver agreement and differences in detection performance among MIP levels were statistically analyzed. Results: Most nodules had smooth margins and were located peripherally. Interobserver agreement for nodule detection was excellent across all MIP levels (p > 0.05; R² = 0.866). The detection rate of solid nodules smaller than 5 mm was highest on 10-mm MIP images compared with other reconstruction series. Conclusion: Computed tomography with 10-mm maximum-intensity-projection reconstruction is extremely effective for detecting solid pulmonary nodules smaller than 5 mm. Keywords: pulmonary nodule, maximum-intensity-projection.

Skeletal surveys are a series of X-ray images used to identify bone injuries in suspected cases of non-accidental injury (NAI). This study evaluates effective radiation doses and associated risks of radiation exposure from skeletal surveys that were performed on children under 5 years of age at a tertiary paediatric hospital in Australia. Radiographic exposure records were retrospectively analysed for 362 initial and follow-up skeletal surveys conducted between 2018 and 2023 for suspected physical abuse. Effective doses and organ absorbed doses were calculated using PCXMC software against background equivalent radiation times (BERT) in Australia. Nominal risks of radiation-induced cancer induction and fatality were estimated using Biologic Effects of Ionising Radiation (BEIR) VII risk coefficients. The mean effective dose was 0.24 mSv for initial examinations and 0.18 mSv for follow-up examinations, equivalent to 52 and 38 days of background radiation exposure, respectively. The averaged nominal risks associated with an initial skeletal survey are 9.3 in 10,000 for cancer induction, and 3.1 in 10,000 for fatal cancer. Variability of radiation effective dose is demonstrated, with an interquartile range of 0.17-0.30 mSv and an overall range of 0.04-0.76 mSv for initial skeletal surveys. Radiation doses for initial and follow-up skeletal surveys performed for suspected NAI were determined from a large set of examinations. Several radiation risk metrics have been presented to assist healthcare professionals and caregivers in understanding the associated risks of radiation exposure.

Abstract While the genetic paradigm of cancer etiology has proven powerful, it remains incomplete as evidenced by the widening spectrum of non-cancer cell-autonomous “hallmarks” of cancer. Studies have demonstrated the commonplace presence of high oncogenic mutational burdens in homeostatically-stable epithelia. Hence, the presence of driver mutations alone does not result in cancer. Here, we reveal additional forces governing the eco-evolutionary dynamics of carcinogenesis. Using a UV-driven mouse model of cutaneous squamous cell carcinoma, we tested our central hypothesis that cancer initiation occurs in three phases: 1) tissue disruption and the emergence of unusually large “goliath” clades (ecological driver), 2) clonal selection within a subset of these goliaths as evidenced by the presence of areas of unusually high local densities of cells (termed “micro-lumps”) with higher mutational burdens (evolutionary driver), and 3) emergence of macroscopic lesions (doi.org/10.1101/2024.12.28.623235). We tracked these tissue level ecological and evolutionary drivers of cancer initiation via in-vivo serial imaging and 3-D reconstruction of fluorescently labeled keratinocyte clades, yielding 25,085 clade measurements from 14 mice over 3 months, and 14,525 clades from 4 of these mice over 6 months. While median and mean clade sizes differed little between UV and non-UV exposure (cc. 65,000 µm3), our ecological survey revealed the emergence of large goliath clades (> cc. 4.2×106 µm3), almost exclusively within UV-exposed skin. Goliath clades emerged by month 2, increased dramatically in number by months 3-4, and plateaued between months 5-6. Goliath clades arose as serpentine structures, intercalating between adjacent keratinocytes. Unexpectedly, targeted DNA sequencing revealed mutations with very low variant allele frequencies within clades, but substantial differences among clades, suggesting that positive selection for these mutations is superfluous to the development of goliaths early in carcinogenesis. scRNAseq analysis of both bulk skin and sorted clades revealed epidermal de-differentiation and immune suppression as early events. By month 7, mutational burdens were significantly larger in goliath clades, particularly for those with micro-lumps. Finally, lesions began to emerge between months 6 and 7, only in UV-exposed skin. To confirm that goliath clades are orders of magnitude more likely to spawn lesions, we randomly selected 21 goliath clades at months 6-7, prior to the time of the emergence of detectable lesions, and followed them over time. Remarkably, 2 of these developed into macroscopic lesions. Our adaptation of the Drake equation estimated the probability of this to be <10-6. We thus document cancer initiation in its entirety and 1) show how the earliest step presages the acquisition of driver mutations, 2) identify the tiny subset of post-UV exposure clades (<1%) prone to acquire more mutations and spawn lesions, and 3) provide an explanation for why cancers are rare in relation to the degree of somatic mosaicism present. Citation Format: Stanislav Avdieiev, Leticia Tordesillas, Karol Prieto, Omar Chavez Chiang, Zhihua Chen, Nihir Patel, Sofia Cordero, Luiza Simoes, Y. Ann. Chen, Noemi Andor, Robert A. Gatenby, Elsa R. Flores, Christopher J. Whelan, Joel S. Brown, Kenneth Y. Tsai. Goliath clades and in vivo tracking of clonal dynamics show three phases of UV-induced skin carcinogenesis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Cancer Evolution: The Dynamics of Progression and Persistence; 2025 Dec 4-6; Albuquerque, NM. Philadelphia (PA): AACR; Cancer Res 2025;85(23_Suppl):Abstract nr B005.

A playful and speculative drafting of a reflection on a walking as a practice by two practitioners who work with walking as a part of a trans disciplinary set of tactics and methods. Myer Taub is a theatre maker engaged in questions of digital theatre making, ecological research and performance outside the theatre, such as an ongoing treasure hunt series, that metaphorphoses according to site and situation, as does all of Taub's performance, staged in local bars to parking lots to the woolworths grocery store. Bettina Malcomess is a writer and an artist whose work looks for new archival vocabularies to rethink the densities of historical material, carrying out a series of gestures in their films and sound works that attempt to embody counterpoint voices. For both artists, the multiplicity of their practice methodologies is an attempt to respond to a present marked by urgent ecological and political questions, a time of crisis. During the Covid 19 pandemic, the artists began to take a series of intentional walks along Johannesburg's urban / natural edges, a continuation of walks Malcomess undertook in the co-authored book Not No Place: Johannesburg, Fragments of Spaces and Times (2013) and Taub's everyday practice of walking as a choice and as an excercise in embodied motion through the city. These walks led to an understanding of the city through it's hidden waterways and green belts, hidden within what Malcomess calls the city's 'uitvalgrond' (surplus ground). To encounter this hidden city meant getting dirty, and so the walks coalesced into the curated walking project, Dirty Walks. These curated walks involved setting up a client who expressed a wish to Malcomess, who curated the walks from a studio in Grant Avenue, Norwood, essentially a suburban high street. Taub would then meet the client, with Malcomess playing fixer or broker for the 'price' of the walk. This model of exchange, desire, dirt was complemented by an archiving of the walk in a drawer in the studio. Thus the project presented here is the repository of the dirty walks, including various walks done over the years between the artists and between the artists and their clients. The repository is organised as a series of images as evidence, a series of links to cogent research and most importantly a conversation between Taub and Malcomess that was staged for a video piece inside a theatre. The sound of this conversation is presented here without the mis-en-scene of the stage, where documentation of a dirty walk was projected while the authors continually repositioned themselved and changed seats, and lighting. The original video is available as a vimeo link held on the Dirty Walks Dischord Server, where evidence of former and new walks continues to multiply. This multiple staging of liveness and the digital on several platforms is an intentional mirroring of the multiplicty of pathways necessary for a walking methodology. The invitation to the reader to move between this site and the Dirty Walks dischord server reflects the complexity of an attempt to walk a city in crisis into being, an ecology of ruptures and fragmentation of the enmeshment of the natural borders and the human-made world, of failing infrastructure as metaphor and fact. This multi-scalar and multi-modal journal entry attempts to embody this fragmentation and invite thinking within the movement and crisis.

Quantitative analysis of brain imaging after stroke provides a window into disease course and severity, critical factors for pathophysiology and outcome studies. While millions of patients experience a stroke each year, there are barriers to systematically analyzing the high volume of imaging studies across centers. This study demonstrates the capabilities of a cloud-based imaging repository and computational platform for extracting multi-dimensional imaging biomarkers from CT scans of ischemic and hemorrhagic stroke patients. The Stroke NeuroImaging Phenotype Repository (SNIPR) is built on the XNAT platform and has archived serial imaging data from several large stroke cohorts. The platform supports Docker-containerized analysis for the evaluation of lesion and edema volumes. This study outlines the deployment of these comprehensive image analysis pipelines, encompassing steps from brain scan classification to the segmentation of ischemic and hemorrhage regions and subsequent quantification of edema biomarkers, including net water uptake (NWU) and the ratio of hemispheric CSF volumes. Analysis pipelines were executed on 8029 CT sessions across ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage cohorts, yielding successful biomarker extraction in 91% of cases, demonstrating the platform's efficiency. Biomarker profiles extracted from these large cohorts illustrated the plausibility of big data analyses in stroke using SNIPR. The incorporation of containerized analysis pipelines into a stroke imaging platform significantly enhances the capacity for multi-centric collaborative stroke research, enabling the processing of thousands of brain CT images for biomarker extraction.

Morphological changes observed on serial magnetic resonance imaging of repaired medial meniscal horizontal cleavage tears.

Pancreatic imaging with ultra-high-resolution photon-counting computed tomography: Preliminary assessment of image quality.

Urban flooding is a major challenge to sustainable development in rapidly urbanizing cities. This study applies an integrated approach that combines Sentinel-1 SAR data, geomorphological analysis, and the DPSIR (Drivers–Pressures–State–Impacts–Responses) framework to assess the relationship between urbanization and flooding in Hanoi during the 2010–2024 period (with Sentinel-1 time-series data for 2015–2024). A time series of Sentinel-1 images (2015–2024) was processed on Google Earth Engine to detect inundation and construct a flood frequency map, which was validated against 148 field survey points (overall accuracy = 87%, Kappa = 0.79). The results show that approximately 80% of newly urbanized areas are situated on geomorphologically sensitive units, including inside- and outside-dike floodplains, fluvio-marine plains, paleochannels, and karst terrains, characterized by low elevation and high flood susceptibility. Meanwhile, about 73% of the total inundated area occurs within newly developed urban zones, primarily in western and southwestern Hanoi, where rapid expansion on flood-prone terrain has intensified hazards. The DPSIR analysis highlights rapid population growth, land use change, and inadequate drainage infrastructure as the main pressures driving both the frequency and extent of flooding. To our knowledge, this is the first study integrating geomorphology, Sentinel-1, and DPSIR for Hanoi, thereby providing robust evidence to support sustainable urban planning and climate-resilient development.

Fillnet: A cryogenic electron tomography restoration framework integrating FFT_Unet architecture and weight optimization strategy.

Birt-Hogg-Dubé Syndrome.

The Woodchuck Hepatitis Virus Model of Hepatocellular Carcinoma for Interventional Radiology Research.

Posterior fossa (PF) fractures are often associated with cerebral venous sinus thrombosis (CVST) yet rarely require treatment beyond anticoagulation. When observed with synchronous, atypical extradural haematoma (EDH) over the transverse sinuses, the management is more equivocal. We present a rare paediatric case of traumatic PF EDH with CVST incidentally unveiling an inherited bleeding disorder (IBD). A 3-year-old boy presented following an unwitnessed head injury. Serial imaging confirmed marginal growth of the EDH with stable CVST and an undisplaced occipital skull fracture. A clotting profile sent via PICU admission bloods informed a new diagnosis of haemophilia A. Conservative management monitored EDH evolution against operative risks over the sinus with a clotting disorder. Haematological treatment navigated the quandary of FVIII replacement to prevent bleeding against the need for CVST anticoagulation. The latter was not initiated. A full recovery was made without neurological deficit. A unifying diagnosis for these incongruent radiological features presented distinct diagnostic and therapeutic challenges. Haematological screening can be misleading in paediatric patients with unclear implications as a diagnostic measure. Excluding coagulopathies is more significant if neurosurgical intervention is indicated, evaluated against individual clinical correlates and symptomatology. In the absence of standardised guidelines for the management of traumatic paediatric EDH with intercurrent CVST and IBDs, the case presented an invitation to thought.

Rationale:Well-differentiated papillary mesothelial tumor (WDPMT) is an uncommon, slow-growing neoplasm that is often an incidental finding in the peritoneum of women of reproductive age. It can be misdiagnosed as malignant mesothelioma on routine histology, potentially leading to unnecessary aggressive therapy. The role of modern molecular techniques in resolving this diagnostic dilemma and guiding conservative management warrants emphasis.Patient concerns:A 32-year-old woman presented with vague abdominal discomfort. Imaging revealed bilateral ovarian cysts and significant pelvic free fluid.Diagnoses:Laparoscopy identified multiple small peritoneal nodules. Initial frozen-section histology suggested malignant mesothelioma. Definitive diagnosis of WDPMT was established through comprehensive immunohistochemistry (retained BAP1 expression) and next-generation sequencing, which revealed a low tumor mutational burden and a pathogenic GPR124 mutation. This genetic profile distinct from malignant mesothelioma.Interventions:After definitive diagnosis and thorough counseling, the patient opted against cytoreductive surgery or systemic therapy. A strategy of active surveillance with serial imaging and tumor marker assessment was implemented.Outcomes:The patient remained asymptomatic with no evidence of disease recurrence or progression 24 months after diagnosis.Lessons:This case highlights that a definitive distinction between WDPMT and malignant mesothelioma is paramount, as it dictates a radically different management strategy. Integration of immunohistochemistry (particularly BAP1) and molecular profiling is essential for accurate diagnosis and can prevent overtreatment. For appropriately selected patients with WDPMT, conservative management with active surveillance represents a safe and effective approach, underscoring the value of precision medicine in guiding patient-centric care.

Background:End-stage renal disease patients on maintenance hemodialysis are at high risk of severe infections. The co-occurrence of methicillin-sensitive Staphylococcus aureus septicemia and penetrating aortic ulcer in this population is rare, posing notable therapeutic challenges.Methods:A case of a 73-year-old male end-stage renal disease hemodialysis patient was analyzed. The patient presented with left flank pain, nausea, and anorexia. Diagnoses and treatment adjustments were based on laboratory tests, computed tomography angiography, and serial monitoring of biomarkers and imaging.Results:Laboratory tests showed severe inflammation (white blood cell: 23.95 × 10⁹/L; C-reactive protein: 196.06 mg/L; procalcitonin: 21.15 ng/mL) and methicillin-sensitive S. aureus bacteremia. computed tomography angiography revealed abdominal aortic ulcer with bilateral renal artery stenosis. Initial meropenem/linezolid was switched to vancomycin post-culture; further adjustment to piperacillin-tazobactam/moxifloxacin followed ulcer progression. The patient refused surgery, received conservative treatment, and had Candida albicans superinfection on hospital day 20 (treated with fluconazole). He was discharged with reduced inflammatory markers and resolved symptoms, but follow-up showed ulcer expansion with hematoma (high rupture risk).Conclusion:Aortic infections in dialysis patients are therapeutically challenging. Serial biomarker monitoring and imaging are crucial for detecting disease progression, even with improved clinical symptoms.

A 42-year-old female presented for routine examination. Fundus photography, Fluorescein Angiography (FA), and Optical Coherence Tomography (OCT) were performed to characterize a highly pigmented optic disc lesion. The patient was placed on an active annual surveillance protocol utilizing clinical examination and serial multimodal imaging. A jet-black, dome-shaped lesion on the left optic disc with feathered margins and preserved retinal vessels was documented (Fig. A, B). FA showed typical early hypofluorescence with late-phase filling (Fig. C). OCT confirmed the elevated structure with dense posterior shadowing (Fig. D). Over a two-year follow-up period, the lesion remained absolutely stable in size and morphology (Fig. E), confirming the benign diagnosis of ODM. Optic Disc Melanocytoma is a rare, typically stable tumor that poses a significant diagnostic challenge with choroidal malignant melanoma. While benign, the risk of rare malignant transformation and local vision-threatening complications mandates continuous vigilance. This case underscores the crucial role of active, long-term annual surveillance, particularly utilizing serial OCT and fundus photography, as the definitive and conservative management approach for clinically quiescent ODM.

Abstract Climbing a boulder for the first time often means entering a previously inaccessible ecosystem, many of which are inhabited by rare species. Little is known about the impacts of first ascents on cliff vegetation, especially with respect to different rock types. Our study builds on this knowledge gap and investigates how climbing activities affect undisturbed rock ecosystems. We experimentally climbed three previously unclimbed boulders (sandstone, limestone and granite) 500 times. Although limited to a single boulder per rock type, our experiment provides preliminary insight into how vegetation cover responds to climbing activities in different lithologies. The loss of vegetation was analysed using a time series of images of hand and footholds. For one site, vegetation recovery was quantified 3 years after climbing treatment. In addition, Raman spectroscopy was used to analyse possible microplastic abrasion of climbing shoes. The vegetation cover on climbing holds decreased by 0%–15%, with the first ascents being particularly decisive. Vegetation loss varies between rock types, with soft sandstone showing the highest loss due to abrasion of the rock surface. A partial recovery of the cover of the microbial community was observed over 3 years after climbing treatment on the sandstone boulder. Raman spectroscopy identified black particles found on climbing footholds as microplastic abrasion from climbing shoes. The mechanical stress caused by boulderers damages rock vegetation locally on climbing holds and is one of the impacts induced by climbing. Even moderate frequency and no prior cleaning of routes can lead to longer lasting damage to cliff vegetation. In sensitive areas, appropriate management actions should be developed by climbing associations, experts and nature conservation organizations. The strong effect on vegetation caused by first ascents suggests that climbing management should favour closing entire rocks while leaving others open (zonation concepts), promoting spatial concentration of impacts. Further studies on microplastics caused by climbing are recommended. Read the free Plain Language Summary for this article on the Journal blog.

Claudin 18.2 (CLDN18.2) is a tight-junction protein overexpressed and differently exposed in solid tumors such as gastric cancer (GCa), gastroesophageal junction adenocarcinoma, and pancreatic ductal adenocarcinoma (PDAC). We sought to explore the potential of CLDN18.2 as a biomarker for molecular imaging and targeted radiopharmaceutical therapy in GCa and PDAC models. Methods: Bulk and single-cell RNA sequencing for CLDN18.2 from 31 patients with PDAC were performed. Subcutaneous xenografts of GCa with the GSU cell line and PDAC with HUPT-4 and PATU8988S cell lines were developed in nude mice. Serial PET imaging with 89Zr-labeled zolbetuximab, an anti-CLDN18.2 monoclonal antibody ([89Zr]Zr-DFO-zolbetuximab), and human IgG ([89Zr]Zr-DFO-IgG) as control (5.5-7.4 MBq) was performed 1, 3, and 6 d after injection, followed by ex vivo analysis of biodistribution. Tumor-bearing mice received a single intravenous injection of [177Lu]Lu-DOTA-zolbetuximab (7.4 or 14.8 MBq), nonradiolabeled zolbetuximab, [177Lu]Lu-DOTA-IgG, [177Lu]Lu-DOTA, or saline as the control. Toxicity of [177Lu]Lu-DOTA-zolbetuximab was evaluated by laboratory and histologic analyses over 90 d. Results: RNA sequencing confirmed significantly higher expression of CLDN18.2 in human PDAC compared with noncancerous pancreas tissue, with no significant difference between treated and untreated tumors. Serial PET imaging demonstrated a high tumor uptake of [89Zr]Zr-DFO-zolbetuximab at all 3 time points (mean uptake on day 6: 24.4 ± 7.8 %ID/g in GSU; 36.6 ± 10.1 %ID/g in PATU8988S; 16.48 ± 4.7 %ID/g in HUPT-4), and significantly higher than the uptake seen in mice imaged with [89Zr]Zr-DFO-IgG (day 6: 4.8 ± 1.9 %ID/g in GSU; P = 0.0029). The highest tumor-to-background uptake ratio was achieved on day 6 (GSU tumor-to-muscle ratio, 14.85 ± 7.8). Biodistribution analyses were consistent with the PET imaging results. High-dose [177Lu]Lu-DOTA-zolbetuximab (14.8 MBq) resulted in reduced tumor growth in GSU and PATU8988S over 4 and 8 wk, respectively, with complete regression of most HUPT-4 tumors and improved 90-d survival compared with the mice treated with control conditions. The 90-day treatment toxicity assay indicated a favorable safety profile. Conclusion: CLDN18.2 could serve as a promising biomarker for precise quantitative imaging and effective treatment of GCa and PDAC. This proof-of-concept study encourages the clinical translation of CLDN18.2 as a radiotheranostic in patients with CLDN18.2-expressing tumors.