Background Enfortumab vedotin (EV) and Sacituzumab govitecan (SG) are antibody-drug conjugates (ADCs) with demonstrated activity in advanced bladder cancer. A subset of bladder tumors harbors a DNA repair deficiency in either the homologous recombination (HR) or nucleotide excision repair (NER) pathway that has the potential to impact sensitivity to specific classes of therapeutics. Objective Define the impact of HR or NER deficiency on sensitivity to ADC payloads alone or in combination with DNA repair targeted agents in bladder cancer. Methods Isogenic cell pairs with versus without HR or NER deficiency were profiled using DNA repair and drug sensitivity assays. Sensitivity to the ADC payloads monomethyl auristatin E (MMAE) and SN-38 alone or in combination with small molecule inhibitors of poly(ADP-ribose) polymerase (PARP), ATR, or USP1 were measured using cell viability assays. Results BRCA2 loss was sufficient to confer an HR deficient phenotype and increase sensitivity to cisplatin and PARP inhibition in bladder cancer cell lines. HR deficiency, but not NER deficiency, increased sensitivity to MMAE and SN-38 in bladder cancer cells. The combination of SN-38 and PARP inhibition displayed synergistic cell killing independent of HR or NER status. Conclusion HR and NER deficiency have distinct impacts on sensitivity to cisplatin and ADC payloads in bladder cancer preclinical models.

• Book : 11(1)
• Pub. Date : 2025
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Abstract Background Body fluids (BFs) are highly important in forensically relevant scenarios. Historically, conventional techniques have been used for their identification and detection purposes. However, there is no conventional technology available that can detect a mixture of body fluids in one go. Main body There is a need for an advanced confirmatory technique that can reliably detect all types of body fluids even in trace forms, whether in pure form or in mixture form. The discussed spectroscopic techniques include raman spectroscopy, fourier transform infrared (FTIR), mass spectroscopy (MS), and nuclear magnetic resonance spectroscopy (NMR). Conclusions These reviewed techniques have proven to be advanced, confirmatory, mostly non-destructive, sensitive, reliable, and reproducible techniques in body fluid identification when combined with advanced statistical analysis and available reference databases. 1H NMR spectroscopy can be an emerging versatile technique with wide-ranging forensic applications. The progressive research related to these advanced techniques can revolutionize the field of forensics.

• Book : 15(1)
• Pub. Date : 2025
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ABSTRACTSeparase is a well conserved endopeptidase that facilitates sister chromatid separation at the metaphase-anaphase transition by cleaving cohesins. Beyond its role in chromosome segregation, Separase also participates in various biological processes, including chromatin organization and replication, centrosome disengagement and duplication, cytokinesis, and telomere capping. Here, we report that the loss ofDrosophilaseparase (Sse) function induces significant changes in global protein expression and affects the protein levels of both A/C-type lamin C (LamC) and B-type lamin Dm0 (Dm0). We further demonstrate that SSE physically interacts with lamins and colocalizes with them at the nuclear envelope during interphase. Additionally, loss of SSE activity disrupts nuclear organization in larval muscles and impairs locomotion in adult flies. Notably, similar to SSE in flies, depletion of human separase (ESPL1) in SV40 fibroblasts leads to misshapen nuclei and increased levels of lamin A. Moreover, we show that ESPL1 interacts with lamin A in human fibroblasts, suggesting that the functional interaction between Separase and lamins is evolutionarily conserved across different organisms.

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• Pub. Date : 2025
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Crushed salt as backfill material in a repository for high-level nuclear waste is aimed to act as a long-term barrier. The sealing effect of crushed salt evolves with ongoing compaction and therefore reduction in porosity and permeability. For a reliable prognosis of the compaction behavior in the long-term, constitutive models are crucial that capture the experimentally observed processes and credibly extrapolate these processes outside the range they were calibrated in. Up to now there is still no constitutive model for crushed salt which is validated against all factors/processes influencing compaction and/or the whole porosity range (especially φ < 5%). The constitutive model for crushed salt compaction available in CODE_BRIGHT has been used in the field of repository research for several years. It has been applied in recent research projects on crushed salt compaction, where shortcomings in the modelling of compaction behaviour in dependence on mean stress and deviatoric stress variations are identified. Based on this discovered potential for improvement an approach for the modification of the constitutive model is proposed within this paper. It addresses the assumption of an idealized geometry and network of grains which is introduced by mathematically constraint functions dependent on void ratio. The proposed approach aims to give more flexibility in the handling of geometry dependence. The paper comprises an introduction into the use of crushed salt in the context of nuclear waste repository. The description of the constitutive model for crushed salt available in CODE_BRIGHT is given, as well as, the proposal for improvement and its application. It is finished with a sensitivity study for the new approach followed by a summary and outlook.

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• Pub. Date : 2025
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Background and importanceAtypical teratoid rhabdoid tumors (ATRTs) are typically aggressive pediatric tumors with a median survival of 11 months. Due to the paucity of cases in adults, the clinical behavior of these pathologies is not well understood. Here we present the case of a 41-year-old female patient with postoperative hyperprogression of a sellar ATRT and provide a detailed description of the molecular composition of this tumor, the protocol used to treat this patient, and the ultimate outcome of this patient.Clinical presentationThe patient is a 41-year-old woman who presented with headaches and double vision. MRI revealed a sellar/suprasellar mass with involvement of bilateral cavernous sinuses. Following the quick symptom progression, resection of the tumor with exploration of the bilateral cavernous sinuses was performed, with a final pathologic diagnosis of ATRT-MYC, a known subtype of ATRT. The tumor recurred within 1 month of surgery, attaining a size equivalent to its preoperative state. Postoperatively, the patient received craniospinal radiation and adjuvant chemotherapy with an excellent response but had a recurrence of the tumor in the brainstem 1 year after her diagnosis and died 13 months after presentation.DiscussionSellar ATRT in adults is an exceedingly rare entity. The detailed description of our case highlights the aggressiveness of these tumors and the utility of postoperative chemotherapy and radiation, but also the inevitable progression of these tumors along the craniospinal axis.ConclusionSellar ATRTs should be considered in the differential diagnosis of a sellar/suprasellar mass, especially in women in their 40s. Emphasis should be placed on accurate diagnosis and quick postoperative recovery with early initiation of adjuvant radiation and chemotherapy.

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• Pub. Date : 2025
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Introduction: While palliative radiotherapy (RT) is frequently used in the management of relapsed/refractory high-risk neuroblastoma (HR-NBL); outcomes after palliative hypofractionated RT (hypo-RT) remain poorly characterized. Methods: We conducted a multi-institutional retrospective study of 38 patients who were diagnosed with HR-NBL between 1997 and 2021 and received palliative RT. Conventional RT (conv-RT) and hypo-RT were defined as palliative treatment courses using dose ≤2 or >2 Gy per fraction, respectively. The primary outcome was cumulative incidence of in-field progression using Gray’s test. Univariate analyses were performed using the Cox proportional hazards model. Results: When analyzing by first course of palliative RT, 16 patients received conventionally fractionated RT (43%) and 21 received hypo-RT (57%). Clinical characteristics were similar between the two groups. With a median follow-up of 10.3 months (range: 0.3–104.0), the cumulative incidence of in-field progression was not statistically significantly different between hypo-RT and conv-RT (30% vs. 20% at 10 months; p = 0.80). Clinical response, defined as symptomatic improvement or decrease in the size of the lesion, was not statistically different between the two groups (92% conv-RT vs. 90% hypo-RT; p = 1.00). No grade ≥4 toxicities were observed. On univariate analysis, hypo-RT (HR 1.50; 95% CI 0.47–4.76; p = 0.493) was not statistically significantly associated with time to in-field progression, but MYCN amplification was associated with significantly longer time to in-field progression (HR: 0.20; 95% CI: 0.05–0.77; p = 0.020). Conclusions: We found no statistically significant difference in cumulative incidence of in-field progression and clinical outcomes between the conv-RT and hypo-RT groups. Palliative hypo-RT can be considered for relapsed/refractory HR-NBL, especially when shorter treatments may offer improved quality of life.

• Book : 32(3)
• Pub. Date : 2025
• Page : pp.124-124
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Abstract Background The global establishment of cancer registries has prompted a hunt for innovative medications that destroy cancer but not healthy cells. Researchers are currently searching marine environments for new anticancer drugs. Modern chemotherapy uses numerous compounds of aquatic origin. These substances exhibit cytotoxic characteristics through various methods, including DNA damage, apoptosis induction, and growth suppression of cancerous cells. The discovery and development of novel anticancer agents from abundant marine fish is generating increasing interest. The objective of this present study is to extract and assess the anti-proliferative effect of a crude muscle extract from marine pufferfish on human cancer cell lines. Methods The biochemical constituents, protein profile, and anticancer activities of the prepared crude muscle extract were analysed using standard methods on human cancer cell lines (HT-29, MDA-MB-231, A-549, and AGS). Results The biochemical contents, such as protein (7.19 ± 0.20 mg/mL), lipid (1.56 ± 0.14 mg/mL), and carbohydrate (1.19 ± 0.09 mg/mL), were quantitatively analysed. Native PAGE and SDS-PAGE qualitatively analysed the protein profiles, revealing distinct protein bands with molecular weights ranging from 220 to 14 kDa. The crude muscle extract was screened for its cytotoxicity (vero) and cell viability (HT-29, MDA-MB-231, A-549, and AGS) against human cancer cell lines by the MTT assay method. The nuclear morphological changes of the apoptotic cells were stained using propidium iodide, and the morphological changes associated with apoptosis were assessed using acridine orange/ethidium bromide (AO/EB) fluorescence staining. The intensity of the mitochondrial membrane potential of the treated cells was measured using the Rh-123 stain, and the results of the DNA fragmentation assay showed that the crude muscle extract-treated cells showed DNA damage, which is indicative of apoptosis. Conclusions This preliminary study supports that the crude muscle extract from milk spotted marine pufferfish, C. patoca has strong anticancer properties. This implies potential for the development of more effective anticancer drugs in future. Graphical abstract

• Book : 26(1)
• Pub. Date : 2025
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Nuclear fusion is a promising energy source. The International Thermonuclear Experimental Reactor aims to study the feasibility of tokamak-type reactors and test technologies and materials for commercial use. One major challenge is developing materials for the reactor’s divertor, which supports high thermal flux. Tungsten was chosen as the plasma-facing material, while a CuCrZr alloy will be used in the cooling pipes. However, the gradient between the working temperatures of these materials requires the use of a thermal barrier interlayer between them. To this end, refractory high-entropy (CrFeTiTa)70W30 and VFeTiTaW alloys were prepared by mechanical alloying and sintering, and their thermal and irradiation resistance was evaluated. Both alloys showed phase growth after annealing at 1100 °C for 8 days, being more pronounced for higher temperatures (1300 °C and 1500 °C). The VFeTiTaW alloy presented greater phase growth, suggesting lower microstructural stability, however, no new phases were formed. Both (as-sintered) alloys were irradiated with Ar+ (150 keV) with a fluence of 2.4 × 1020 at/m2, as well as He+ (10 keV) and D+ (5 keV) both with a fluence of 5 × 1021 at/m2. The morphology of the surface of both samples was analyzed before and after irradiation showing no severe morphologic changes, indicating high irradiation resistance. Additionally, the VFeTiTaW alloy presented a lower deuterium retention (8.58%) when compared to (CrFeTiTa)70W30 alloy (14.41%).

• Book : 18(5)
• Pub. Date : 2025
• Page : pp.1030-1030
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Hydroxylamine nitrate (HAN) and hydrazine nitrate (HN) are commonly found in radioactive waste solutions in nuclear fuel reprocessing, and their efficient removal is essential for waste treatment processes. In this study, six activated carbon carriers were selected to prepare Ru/AC catalysts for the simultaneous catalytic decomposition of HAN and HN, with the aim of exploring the effect of carrier properties on catalytic performance. The catalyst’s activity was evaluated in a batch reaction unit, and its structural properties were characterized using N2 physical adsorption, XRD, SEM, and TEM techniques. The results revealed that the catalyst’s activity was primarily determined by the carrier’s particle size and specific surface area. Additionally, corrosion-induced damage to the pore structure and Ru loss were identified as the main factors responsible for catalyst deactivation. This study highlights the importance of optimizing carrier structure to enhance the activity and stability of Ru/AC catalysts.

• Book : 13(3)
• Pub. Date : 2025
• Page : pp.641-641
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SummaryType 1 diabetes (T1D) is characterized by the autoimmune destruction of most insulin-producing β-cells, along with dysregulated glucagon secretion from pancreatic α-cells. We conducted an integrated analysis that combines electrophysiological and transcriptomic profiling, along with machine learning, of islet cells from T1D donors to investigate the mechanisms underlying their dysfunction. Surviving β-cells exhibit altered electrophysiological properties and transcriptomic signatures indicative of increased antigen presentation, metabolic reprogramming, and impaired protein translation. In α-cells, we observed hyper-responsiveness and increased exocytosis, which are associated with upregulated immune signaling, disrupted transcription factor localization and lysosome homeostasis, as well as dysregulation of mTORC1 complex signaling. Notably, key genetic risk signals for T1D were enriched in transcripts related to α-cell dysfunction, including MHC class I which were closely linked with α-cell dysfunction. Our data provide novel insights into the molecular underpinnings of islet cell dysfunction in T1D, highlighting pathways that may be leveraged to preserve residual β-cell function and modulate α-cell activity. These findings underscore the complex interplay between immune signaling, metabolic stress, and cellular identity in shaping islet cell phenotypes in T1D.HighlightsSurviving β-cells in T1D show disrupted electrical function linked to metabolic reprogramming and immune stress.Transcripts associated with α-cell dysfunction are enriched in genetic risk alleles for T1D.Upregulated MHC class I and impaired nuclear localization of key transcription factors associate with α-cell dysfunction in T1D.T1D α-cells exhibit increased hyper-activity, lysosomal imbalance and impaired mTORC1 signaling, which promotes dysregulated glucagon secretion.

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• Pub. Date : 2025
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