Background/Objectives: Totally endoscopic mitral valve repair reduces surgical trauma and accelerates recovery but can be technically challenging, particularly for precise annuloplasty suturing. The VirtuoSEW® (LSI Solutions, Victor, NY 14564m, USA) automated annular suturing system was developed to standardize and simplify suture placement. This study was an early evaluation of this technology’s safety, efficacy, and feasibility in totally endoscopic microInvasive mitral valve repair (µMVr). Methods: We conducted a retrospective observational study of 20 patients with severe mitral valve disease of various etiologies. All patients underwent mitral valve repair using the VirtuoSEW® system for automated placement of annuloplasty sutures, combined with leaflet resection or chordal management as appropriate. Postoperative outcomes were assessed at one month using echocardiography and clinical evaluation. Perioperative and postoperative complications and early mortality were systematically recorded. Results: VirtuoSEW®-assisted mitral valve repair was safe and effective, achieving complete elimination of severe mitral regurgitation in all patients (N = 20, 100%). Annuloplasty rings included Physio-ring (N = 12, 60%), Memo 3D (N = 4, 20%), and Memo 4D (N = 4, 20%), combined with leaflet repair techniques: leaflet plication (N = 5, 25%), neochordae implantation (N = 7, 35%), sliding plasty (N = 2, 10%), commissural repair (N = 1, 5%), and hemibutterfly repair (N = 1, 5%). Concomitant procedures included: tricuspid valve repair (N = 1, 5%) and atrial septal defect closure (N = 1, 5%). Mitral annulus diameter decreased from 42.0 ± 5.3 mm to 34.2 ± 2.2 mm (p = 0.001). Mean total surgery, cardiopulmonary bypass, and aortic cross-clamp times were 170.3 ± 21.3, 143.4 ± 21.5, and 80.4 ± 7.9 min, respectively. ICU stay was 1.0 ± 0.2 days, with a hospital stay of 8.0 ± 1.9 days. No perioperative complications—including bleeding (N = 0, 0%), stroke (N = 0, 0%), infections (N = 0, 0%), or 30-day mortality (N = 0, 0%)—occurred. Conclusions: µMVR invasive mitral valve repair using the VirtuoSEW® system is safe, effective, and reproducible, as well as compatible with almost all repair techniques, providing complete restoration of valve competence with no early device-related complications. To our knowledge, this is the first clinical study reporting outcomes with this device, supporting its potential to streamline mitral repair and improve procedural efficiency.

The Tortonese’s stingray (Dasyatis tortonesei Capapé, 1975) is a poorly understood species, likely endemic to the Mediterranean Sea, where its distribution remains inadequately delineated due to historical taxonomic uncertainty and misidentification with its closely related congeners. The present study reports the first well-documented records of D. tortonesei in the Adriatic Sea, based on six specimens collected during systematic field surveys off Vlorë, Albania. All specimens were identified through a comprehensive assessment of diagnostic morphological features, and detailed biometric data are provided. Notably, one individual exhibited a fully healed traumatic loss of both the tail and stinging apparatus, suggesting a degree of resilience to sub-lethal injury. The present findings extend the range of D. tortonesei and establish a valuable baseline for future biodiversity assessments. In addition, this paper underscores the urgent need for integrative taxonomic approaches and regional capacity-building to improve species-level identification and inform effective conservation of Mediterranean elasmobranchs (sharks and rays).

Precision surgical interventions rely on accurate integration of preoperative and intraoperative imaging to guide clinical decision-making and improve patient outcomes. Traditionally, most 3D imaging modalities capture the entirety of the target object, allowing for the segmentation of its entire volume. However, some medical imaging devices trade full field-of-view for other considerations, such as size and ability to access the target organ in unique ways. This is particularly true of ultrasound, where imaging deeper organs from outside the body is not viable due to attenuation, thus motivating the need for alternative imaging strategies. In scenarios such as image-guided intervention, it is often necessary to put this partial view of the object in its full anatomical context, such as alignment to a pre-operative MRI. We propose a method for jointly segmenting the portion of the object visible in the acquired image and estimating its full shape. We do this by combining a pre-trained shape prior with a patient-specific expectation of organ shape acquired via pre-operative imaging. In a simulated dataset for prostate MRI/US fusion, we show the ability to accurately estimate the prostate shape from ultrasound images capturing only a fraction of its total volume.

Noise-induced hearing loss (NIHL) occurs as a result of long term exposure to workplace noise. The aim of the study was to identify job positions with an increased risk of hearing impairment due to occupational noise exposure, by analyzing changes in audiometric findings over a six-month period of work under conditions with elevated noise levels. The study included participants exposed to workplace noise and participants working in a quiet environment, employed in the same companies but in different job positions. Audiometric examinations were conducted at baseline and after six months of follow-up. Paired and independent-samples t-tests were applied. A statistically significant difference in hearing loss was found among participants exposed to occupational noise during the six-month period (t = 4.84, df = 35, p < 0.001), while no significant difference was observed among participants working in a quiet environment (t = 1.64, df = 35, p = 0.109). A significant difference was also identified between the noise-exposed group and the control group in mean hearing threshold values at baseline and at the final assessment after six months (t = 4.13, df = 71, p < 0.001). Occupations with an increased risk of the development and progression of hearing impairment were identified. The results confirmed the need for continuous monitoring and implementation of preventive hearing protection measures in high-risk workplaces, including oil refineries, textile and metal industries, the wood-processing sector, and selected service industries.

This study aimed to describe and compare background factors and symptoms at diagnosis of patients with non-advanced or advanced stage lung cancer and patients without cancer, and to develop predictive models identifying key variables that contribute to the detection of early and late-stage lung cancer. Univariate logistic regression and three machine learning algorithms were used. Compared to patients without cancer, six background factors and two symptoms differed in non-advanced lung cancer, while 11 background factors and 19 symptoms differed in advanced cases. The machine learning models showed moderate performance in classifying patients with lung cancer from those without cancer. Notably, top predictors extended beyond classic respiratory symptoms. Demographic and lifestyle factors, particularly age, smoking status, and living situation, remained essential alongside symptoms such as pain, appetite loss, weight reduction, and respiratory problems. These findings support integrating clinical, demographic, and patient-reported symptoms to improve lung cancer risk models and refine referral decisions in screening pathways. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-026-46710-8.

The fruit of Rosa canina (rosehip) has long been used in traditional medicine, and recent studies confirm its health benefits due to its content of flavonoids, carotenoids, fatty acids, and high vitamin C levels. This study examined three preparations: infusion, ultrasound-assisted extract, and traditional jam. Total phenols were measured using the Folin-Ciocalteu method, and antioxidant activity by the DPPH method. The highest total phenolic content was observed in the infusion of dried fruit (163.477 mg GAE/l), followed by the fruit extract (44.932 mg GAE/l), with the jam extract showing the lowest content (23.477 mg GAE/l). Antioxidant activity was assessed via DPPH inhibition percentage and IC50 values to identify the most effective form of compounds. The findings suggest that infusion of dried rosehip fruit provides the highest antioxidative capacity, highlighting its potential as a functional food ingredient.

Strict minimum message length (SMML) is an information-theoretic coding principle that represents a continuous statistical model by a finite set of assertions and a partition of the sample space. We show that the SMML objective decomposes into assertion entropy and conditional cross-entropy, balancing the cost of identifying an assertion against the cost of encoding data under the assigned model. For any fixed partition, the optimal codepoint for each cell is the model distribution that minimises Kullback–Leibler (KL) divergence from the data distribution restricted to that cell. Using the local Fisher–Rao geometry of regular parametric models, we show that, under a high-resolution LAN-scale regime, SMML partitions are asymptotically the pullback, through the maximum-likelihood estimator, of weighted Fisher–Rao Voronoi tessellations in parameter space, with assertion probabilities appearing as additive weights. For regular canonical exponential families, SMML codepoints satisfy a moment-matching condition and admit an interpretation as KL/Bregman centroids, while exact SMML cells are pullbacks of convex polyhedra in sufficient-statistic space. Together, these results show that SMML induces a natural information-geometric quantisation linking entropy-based coding, KL projection, and divergence-based Voronoi geometry.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, driven by profound molecular heterogeneity and resistance to current therapy. To support systematic target identification, we established a proteomics-anchored knowledge discovery framework integrating cross-model proteomics harmonization, network topology, high-confidence structural modeling, and large-scale in silico docking. From 1,975 proteins consistently detected across murine and human PDAC models, 32 immunohistochemically confirmed candidates were prioritized for structure-based screening against 7,509 clinically characterized compounds. Blind docking, refined pose sampling, ligand-efficiency scoring, and ADME filtering identified EIF2A, STAM, ANXA2, and AHNAK2 as robustly druggable targets. These proteins exhibited high-affinity interactions with zavegepant (a clinically approved CGRP receptor antagonist), omilancor, bemcentinib, conivaptan, and APTO-253. Docking validation (RMSD 1.98 to 2.56 Å) confirmed methodological reliability, and network analyses placed the 4 proteins within modules linked to endosomal/membrane trafficking and invasive phenotypes. Survival analyses in 176 PDAC patients further supported their clinical relevance. Thus, we suggest a systems-level platform for nominating ligandable PDAC targets and clinically actionable compounds. The framework highlights opportunities for rational drug repurposing and motivates future mechanistic studies at the intersection of proteomics and structure-based screening for targets to PDAC.

Urbanization of cities demands efficient spatial management. The construction of utility lines significantly alters the spatial landscape. The subsurface space is often neglected, resulting in outdated or absent records of underground utility infrastructure. This clearly underscores the need and importance of maintaining accurate utility records. Modern non-destructive techniques for underground utility detection, such as ground penetrating radar (GPR), can enhance the documentation and mapping of subsurface infrastructure. The subject of this paper is the optimization of GPR survey and processing workflows to improve the accuracy of underground utility detection when using the Leica DS2000. The research comprises both theoretical and experimental analyses, including the application of various GPR data collection methods on test sites. The experimental component of the research was conducted using the Leica DS2000 GPR system. The geospatial data were processed using several software applications, including uNext Advanced, IQMaps, and Geolitix. Based on the multicriteria analysis of these results and an assessment of detection accuracy, an optimal workflow (decision diagram) was defined for the detection of underground utility infrastructure using Leica DS2000 under favorable soil conditions. This study explored the feasibility of efficiently updating the cadastral database of public utility infrastructure through non-invasive technologies, thereby contributing to the improvement of subsurface utility infrastructure management.

In this study, we analyze a discrete two-dimensional host–parasitoid model in which the host population follows logistic growth and is additionally subject to a strong Allee effect on the proportion of hosts that avoid parasitism. The parasitoid population dynamics are driven by host availability, attack success rate, and the number of parasitoids produced per successful attack. We classify the equilibrium points and explore the system’s local and global dynamics. Our analysis shows that, in certain parameter regions, an extinction equilibrium can be globally stable. For the boundary equilibrium, we prove the existence of transcritical and period-doubling bifurcations. Regarding interior equilibria, when multiple equilibria exist, their stabilities alternate. We prove the occurrence of codimension-1 period-doubling and Neimark–Sacker bifurcations, indicating the emergence of complex dynamics, including quasi-periodic and even chaotic behavior. Despite the possibility of complex dynamics, we prove that the system can exhibit uniform persistence and permanence under specific conditions, thereby ensuring the long-term coexistence of the host and parasitoid populations.

This text is a review of the book: Nidžara Ahmetašević, Media as a Tool of International Intervention: House of Cards, Routledge, London and New York, 2024

The phenomenon of digital obituaries and posthumous identities is increasingly shaping the way contemporary society perceives death, remembrance, and the grieving process. Death no longer signifies the complete end of social presence, as digital profiles of the deceased remain active on social media platforms even after physical death, enabling a continuity of symbolic connection with them. This paper explores the emotional, psychological, social, ethical, and legal dimensions of digital memorialization, focusing on the impact of virtual spaces and algorithmic reminders on the grieving process and emotional resolution. A qualitative approach was employed in analyzing secondary sources, grounded in contemporary theories of identity, grief, and digital legacy. The paradoxes of digital mourning are analyzed, wherein memorial profiles and digital obituaries may offer a sense of presence and support, yet simultaneously prolong emotional attachment and hinder acceptance of loss. The paper also examines how the algorithmic functioning of digital platforms generates memories and reminders without sensitivity to the emotional state of users, potentially burdening the grieving process further. It raises critical ethical and legal questions surrounding the management of digital identities after death, including unclear ownership, control, and rights to content removal. The complexity of survivors’ emotional responses and the growing significance of digital legacy further reinforce the need for clear regulations aligned with the psychological dimensions of grief and ethical principles of dignity. In this context, digital memorialization emerges not only as a form of remembrance, but also as a challenge requiring thoughtful consideration within the frameworks of mental health, social practice, and legal accountability.

Intra-tumor heterogeneity (ITH) of somatic mutations is a hallmark of sporadic clear cell renal cell carcinoma (ccRCC). In contrast, the extent and nature of ITH in hereditary (VHL-associated) ccRCC remain poorly characterised, primarily due to the rarity of these tumors. This study aims to comprehensively characterise this heterogeneity and elucidate its evolutionary dynamics and biological relevance. To investigate intra- and inter-tumor heterogeneity in VHL-associated ccRCC, we performed multi-region whole-genome sequencing (WGS) of 23 primary tumor biopsies obtained from four spatially distinct regions of six small (≤3 cm) renal tumors across two patients carrying pathogenic germline VHL mutations. Somatic single-nucleotide variants (SNVs) and copy number alterations (CNAs) were analysed to reconstruct the genomic histories of these tumors. We found that all tumors were clonally independent, each harboring distinct sets of somatic variants and chromosomal copy number alterations, including the characteristic chromosome 3p loss. Within individual tumors, copy number profiles were homogeneous across regions, suggesting early acquisition of these events. Subclonal diversification of somatic SNVs was detected in all tumors. Notably, in one patient, two of the three analysed tumors displayed pronounced ITH, with most mutations being unique to a single region. Moreover, markedly distinct patient-specific molecular profiles emerged, characterised by divergent driver events and copy number landscapes that correlated with differences in their clinical grades. Although preliminary, these findings provide new insights into the genomic heterogeneity of VHL-associated ccRCC, advancing our understanding of how inherited kidney cancers develop and diversify, and potentially informing improved clinical management of patients with VHL disease. Francesca Corea, Husayn A. Pallikonda, Scott T. Shepherd, Isaline Rowe, Alessandro Larcher, Andrea Salonia, Samra Turajlic, Thomas J. Mitchell, Rosa Bernardi, Umberto Capitanio. Genomic evolution and heterogeneity of von Hippel-Lindau (VHL)-associated clear cell renal cell carcinoma revealed by multi-region whole-genome sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7507.

Clear Cell Renal Cell Carcinoma (ccRCC) is the most common and aggressive type of kidney cancer. ccRCC originates from proximal tubule (PT) epithelial cells in the nephron. Its initiation is characterised by a linear evolution from the loss of one copy of chromosome 3p to the inactivation of the second VHL allele on the remaining copy of 3p. Computational studies established that 3p loss occurs several decades before diagnosis. This offers an unprecedented window of opportunity for early detection, cancer prevention and for broader pan-cancer learning. However, the biological mechanisms driving the pre-cancerous expansion of PT cells harboring these events remain elusive. One of the major unmet needs in ccRCC initiation is the identification of molecular biomarkers for the initially quiescent tumor-initiating cell. Previous studies established that the putative ccRCC cell of origin (COO) is a subtype of PT cells characterized by VCAM1 expression, a marker of tubular injury in human kidneys. Therefore, we hypothesized that VCAM1 can be used as a marker to enrich for cells that have lost a copy of chromosome 3p. Preliminary single-cell whole genome sequencing (WGS) of VCAM1+ PT cells revealed a high incidence of aneuploidies, including chromosome 3-related aneuploidies, indicating that these cells represent a chromosomally unstable epithelial subpopulation within morphologically normal kidney tissue. Therefore, this data supports VCAM1 as a candidate marker for the study of ccRCC initiation in human kidneys.Despite its quasi-ubiquitous role in ccRCC initiation, several studies show that VHL inactivation is insufficient for tumorigenesis in mammalian kidneys. To study this, we used histological analysis of VHL patient-derived normal kidney tissues, where 3p loss occurs on the background of a germline VHL mutation. We demonstrated that VHL inactivation (marked by CAIX expression) occurs in all major cortical epithelial cell types. Surprisingly, only the proportion of CAIX+ distal tubule (DT) cells showed a significant correlation with the age of the patient at the time of tissue collection. In addition, there is a significantly higher proportion of multicellular DT CAIX+ foci compared to CAIX+ PT foci, suggesting clonal expansion after VHL inactivation is favored in DT cells. Only a minority of CAIX+ PT foci were multicellular, indicating that unknown cell-intrinsic or extrinsic factors are necessary for clonal expansion. Results from our cohort show a positive association between the density of VCAM1+ PT cells and CAIX+ PT in VHL patient-derived normal kidney tissues, indicating that tissue stress levels may potentiate the selection and expansion of VHL inactivation in the human kidney. Our data offers novel insight in the putative COO of ccRCC and the mechanisms driving the earliest stages of ccRCC. Moving forward, we plan to expand our cohort and molecularly profile VCAM1+ and CAIX+ cells using multi-omic approaches. Omar Bouricha, Daqi Deng, Anne-Laure Cattin, Matous Elphick, Scott Shepherd, Cathy D. Vocke, W. Marston Linehan, Samra Turajlic. Spatial and molecular profiling of tumor initiation in ccRCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3330.

Neoantigens from somatic tumor mutations are essential for effective anti-tumor immune responses. Frameshift insertions and deletions (fs-indels) represent a rare but highly immunogenic mutation subtype, as they create novel open reading frames (neoORFs) that generate peptides that are significantly distinct from self-antigens. Nevertheless, fs-indels often introduce premature termination codons, leading to transcript degradation via the nonsense-mediated mRNA decay (NMD) pathway, leading to loss of immunogenic neoantigen. For the first time, we pharmacologically inhibited SMG1, a core component of the NMD pathway, across a range of preclinical models, including human and mouse cancer cell lines, patient-derived tumor organoids (PDTOs), patient-derived tumor fragments (PDTFs), and syngeneic mouse xenografts. We analyzed the changes in transcriptome, proteome, and immunopeptidome following SMG1 inhibition (SMG1i) and peptide reactivity in in vitro priming experiments. We then combined tumor-T cell co-cultures and PDTFs to assess the anti-tumor immunogenicity induced by SMG1i. Ex vivo and in vivo immunological responses were assessed by high-dimensional flow cytometry, cytometric bead array, and single-cell RNA- and TCR-sequencing. Using multi-omic and checkpoint inhibitor (CPI) response data from over 1,000 patients, we show that decreased expression of the key NMD mediator, SMG1, correlates with improved CPI response. Inhibiting SMG1 ex vivo and in vivo activates and expands tumor-reactive T cells and sensitizes CPI efficacy. Mechanistically, SMG1 inhibition stabilizes frameshift-derived transcripts, increasing the abundance and surface presentation of immunogenic neoantigens. This results in an increase in neoepitope burden in tumors, similar to that seen in tumors with high tumor mutational burden (TMB), without inducing DNA damage. Co-culturing tumor cells and PDTOs with CD8+ T cells after SMG1i results in strong MHC class I antigen-dependent T cell activation and tumor cell killing. Our findings highlight SMG1 inhibition as a promising strategy to exploit an untapped source of highly immunogenic peptides. It enhances anti-tumor immunogenicity without introducing DNA mutations, regardless of tumor type or TMB status, providing translational evidence for sensitizing ICB responses. Hongchang Fu, Roberto Vendramin, Shanila Fernandez Patel, Yue Zhao, Danwen Qian, Lorena Ligammari, Osnat Bartok, Polina Greenberg, Ronen Levy, Andrea Castro, Krupa Thakkar, Jun Murai, Wei-ting Lu, Christopher C. Sng, Chen Weller, Gordon Beattie, Amandeep Bhamra, Roc Farriol-Duran, Despoina Karagianni, Marcellus Augustine, Krijn Djikstra, Christopher L. Pinder, Benjamin S. Simpson, Gordon Weng-Kit Cheung, TRACERx Consortium, Felipe Galvez Cancino, Petra Vlckova, Silvia Surinova, Manuel Rodriguez-Justo, Mansi Shah, Nicholas McGranahan, Jeremy G. Carlton, Eva Camilla Gronroos, Sergio Quezada, James Luke Reading, Samra Turajlic, Yardena Samuels, Charles Swanton, Kevin Litchfield. Nonsense-mediated mRNA decay inhibition augments in vitro, in vivo, and ex vivo anti-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6742.