221. Gene therapy of rare diseases as a milestone in medicine : overview of the field and report on initial experiences in SloveniaUrh Grošelj, Marko Kavčič, Ana Drole Torkar, Jan Kafol, Duško Lainšček, Roman Jerala, Matjaž Sever, Samo Zver, Gregor Serša, Maja Čemažar, Primož Strojan, Aleš Grošelj, Mojca Žerjav-Tanšek, Špela Miroševič, Simona Ivančan, Tomaž Prelog, David Gosar, Jasna Oražem, Matej Mlinarič, Sara Bertok, Jernej Kovač, Jana Kodrič, Saba Battelino, Marko Pokorn, Alojz Ihan, Janez Jazbec, Tadej Battelino, Damjan Osredkar, 2025, review article Abstract: Gene therapy has transitioned from a long-awaited promise to a clinical reality, offering transformative treatments for rare congenital diseases and certain cancers, which have a significant impact on patients’ lives. Current approaches focus on gene replacement therapy, either in vivo or ex vivo, mostly utilizing viral vectors to deliver therapeutic genes into target cells. However, refining these techniques is essential to overcome challenges and complications associated with gene therapy to ensure long-term safety and efficacy. Slovenia has witnessed significant advancements in this field since 2018, marked by successful gene therapy trials and treatments for various rare diseases. Significant strides have been made in the field of gene therapy in Slovenia, treating patients with spinal muscular atrophy and rare metabolic disorders, including the pioneering work on CTNNB1 syndrome. Additionally, immune gene therapy, exemplified by IL-12 adjuvant therapy for cancer, has been a focus of research in Slovenia. Through patient-centred initiatives and international collaborations, researchers in Slovenia are advancing preclinical research and clinical trials, paving the way for accessible gene therapies. Establishing clinical infrastructure and genomic diagnostics for rare diseases is crucial for gene therapy implementation. Efforts in this regard in Slovenia, including the establishment of a Centre for Rare Diseases, Centre for the Technologies of Gene and Cell Therapy, and rapid genomic diagnostics, demonstrate a commitment to comprehensive patient care. Despite the promises of gene therapy, challenges remain, including cost, distribution, efficacy, and long-term safety. Collaborative efforts are essential to address these challenges and ensure equitable access to innovative therapies for patients with rare diseases.
Keywords: gene therapy, rare genetic diseases, Slovenia, CAR-T cells, cancer, immune gene therapy
Published in DiRROS: 04.12.2025; Views: 140; Downloads: 117
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222. Functional determinants for false vacuum decayPietro Baratella, Miha Nemevšek, Katarina Trailović, Yutaro Shoji, Lorenzo Ubaldi, 2025, original scientific article Abstract: We derive simple expressions to regularise functional determinants from fluctuations of fields with spin 0, 1/2, and 1. These are important for the precise dimensionful determination of false vacuum decay rates. We work in D = 4 Euclidean dimensions and use familiar Feynman diagrammatic techniques with a double expansion in interactions and masses, together with dimensional regularisation in momentum space. We Fourier transform to coordinate space and end up with a simple regularisation prescription in terms of single integrals over the Euclidean radius of field-dependent masses and their derivatives. Our results apply to models with an arbitrary scalar potential and with any number of scalars, fermions, gauge bosons and associated ghosts. We exemplify this approach on the Standard Model with a streamlined calculation of the renormalisation and isolation of divergences in fluctuation determinants.
Keywords: false vacuum, decay rates, Higgs properties, multi-Higgs models, functional determinants
Published in DiRROS: 04.12.2025; Views: 114; Downloads: 61
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223. Revising the full one-loop gauge prefactor in electroweak vacuum stabilityPietro Baratella, Miha Nemevšek, Yutaro Shoji, Katarina Trailović, Lorenzo Ubaldi, 2025, original scientific article Abstract: We revisit the decay rate of the electroweak vacuum in the standard model with the full one-loop prefactor. We focus on the gauge degrees of freedom and derive the degeneracy factors appearing in the functional determinant using group theoretical arguments. Our treatment shows that the transverse modes were previously overcounted, so we revise the calculation of that part of the prefactor. The new result modifies the gauge fields’ contribution by 6% and slightly decreases the previously predicted lifetime of the electroweak vacuum, which remains much longer than the age of the Universe. Our discussion of the transverse mode degeneracy applies to any calculation of functional determinants involving gauge fields in four dimensions.
Published in DiRROS: 04.12.2025; Views: 132; Downloads: 43
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224. False vacuum decay rate from thin to thick wallsMarco Matteini, Miha Nemevšek, Yutaro Shoji, Lorenzo Ubaldi, 2025, original scientific article Abstract: We consider a single real scalar field in flat spacetime with a polynomial potential up to ϕ4, that has a local minimum, the false vacuum, and a deeper global minimum, the true vacuum. When the vacua are almost degenerate we are in the thin wall regime, while as their difference in potential energy increases, we approach the thick wall regime. We give explicit simple formulae for the decay rate of the false vacuum in 3 and 4 spacetime dimensions. Our results include a careful treatment both of the bounce action, which enters at the exponent of the decay rate, and of the functional determinant at one loop, which determines the prefactor. The bounce action is computed analytically as an expansion in the thin wall parameter in generic D dimensions. We find that truncating such an expansion at second order we obtain a remarkably accurate bounce action also deep into thick wall regimes. We calculate the functional determinant numerically in 3 and 4 dimensions and fit the results with simple polynomials of the same thin wall parameter. This allows us to write the complete one-loop decay rate as a compact expression, which works accurately from thin to thick wall regimes.
Keywords: metastable states, false vacuum, decay rates, thermal field theory, early Universe
Published in DiRROS: 04.12.2025; Views: 135; Downloads: 95
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225. Super heavy dark matter from inflationary Schwinger productionMar Bastero-Gil, Paulo B. Ferraz, Lorenzo Ubaldi, Roberto Vega-Morales, 2024, original scientific article Abstract: We consider a simple setup with a dark sector containing dark electrons charged under an Abelian �(1)� gauge symmetry. We show that, if the massless dark photon associated to the �(1)� is produced during inflation in such a way as to form a classical dark electric field, then dark electron-positron pairs are also produced close to the end of inflation via the Schwinger effect even if they are very massive. For large enough dark electric force, dark electrons with masses larger than the Hubble scale can be produced which are nonrelativistic at production and throughout their cosmic evolution. They can account for the dark matter abundance today for masses in the range ∼100 GeV to 1017 GeV and up to 6 orders of magnitude larger than the Hubble scale at the end of inflation where purely gravitational production is exponentially suppressed. We examine the regime where the dark electrons do not thermalize with the dark photons throughout their cosmic history and assume negligible kinetic mixing with the visible �(1) so they remain decoupled from the Standard Model thermal bath as well. Thus, the final dark matter relic abundance is determined only by the initial inflationary Schwinger production and redshifting after reheating.
Published in DiRROS: 04.12.2025; Views: 116; Downloads: 51
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230. Bisphenol A in the urine : association with urinary creatinine, impaired kidney function, use of plastic food and beverage storage products but not with serum anti-müllerian hormone in ovarian malignanciesMateja Sladič, Špela Smrkolj, Gorazd Kavšek, Senka Imamović-Kumalić, Ivan Verdenik, Irma Virant-Klun, 2025, original scientific article Abstract: Bisphenol A (BPA) is a high-production-volume industrial chemical and component of commonly used plastic products. However, it is also an endocrine-disrupting chemical that can negatively affect human health. It is not yet known whether it is associated with the development of epithelial ovarian cancer (EOC), a severe and highly fatal human disease. Therefore, the purpose of this study was to determine the concentrations of BPA in the urine of women with EOC or epithelial borderline ovarian tumors (EBOTs) using gas chromatography tandem mass spectrometry (GC-MS/MS) and find their possible associations with kidney function at the molecular level, urine and blood biochemical parameters related to metabolism, anti-Müllerian hormone (AMH) (a marker of ovarian reserve/fertility), and lifestyle habits determined via a questionnaire in comparison to healthy controls. The results suggest that the unadjusted or urine-specific-gravity-adjusted BPA levels were significantly increased in women with EOC/EBOT. The unadjusted BPA was significantly positively associated with urinary creatinine (p = 0.007) in all women with EOC/EBOT after adjustment for age, body mass index, and pregnancy using multiple linear regression analysis. This may be related to kidney injury. However, no association was found between urinary BPA and serum AMH levels in women. Women with ovarian malignancies were more exposed to plastic products for storing foods and drinks. Some lifestyle habits, including refilling plastic bottles, correlate with higher urinary BPA levels across the entire cohort of women. When considering EOC or EBOT, it is necessary to consider the potential higher exposure of women to BPA, as reflected in their urine and lifestyle habits.
Keywords: anti-Müllerian hormone, kidney function, lifestyle habits, ovarian cancer, thrombocytes, urine, female exposure
Published in DiRROS: 03.12.2025; Views: 156; Downloads: 60
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