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21.
The prognostic and predictive value of human gastrointestinal microbiome and exosomal mRNA expression of PD-L1 and IFNγ for immune checkpoint inhibitors response in metastatic melanoma patients : protocol trial
Ana Erman, Marija Ignjatović, Katja Leskovšek, Simona Miceska, Urša Lampreht Tratar, Maša Omerzel, Veronika Kloboves-Prevodnik, Maja Čemažar, Lidija Kandolf Sekulović, Gorazd Avguštin, Janja Ocvirk, Tanja Mesti, 2023, original scientific article

Abstract: Background: Immunotherapy has been successful in treating advanced melanoma, but a large proportion of patients do not respond to the treatment with immune checkpoint inhibitors (ICIs). Preclinical and small cohort studies suggest gastrointestinal microbiome composition and exosomal mRNA expression of PD-L1 and IFNγ from the primary tumor, stool and body fluids as potential biomarkers for response. Methods: Patients treated with immune checkpoint inhibitors as a first line treatment for metastatic melanoma are recruted to this prospective study. Stool samples are submitted before the start of treatment, at the 12th (+/−2) week and 28th (+/−2) week, and at the occurrence of event (suspected disease progression/hyperprogression, immune-related adverse event (irAE), deterioration). Peripheral venous blood samples are taken additionally at the same time points for cytologic and molecular tests. Histological material from the tumor tissue is obtained before the start of immunotherapy treatment. Primary objectives are to determine whether the human gastrointestinal microbiome (bacterial and viral) and the exosomal mRNA expression of PD-L1 and IFNγ and its dynamics predicts the response to treatment with PD-1 and CTLA-4 inhibitors and its association with the occurrence of irAE. The response is evaluated radiologically with imaging methods in accordance with the irRECIST criteria. Conclusions: This is the first study to combine and investigate multiple potential predictive and prognostic biomarkers and their dynamics in first line ICI in metastatic melanoma patients.
Keywords: gastrointestinal microbiome, mRNA expression of PD-L1 and IFNγ, immune checkpoint inhibitors, metastatic melanoma
Published in DiRROS: 21.03.2024; Views: 91; Downloads: 45
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Trilinear embedding for divergence-form operators with complex coefficients
Andrea Carbonaro, Oliver Dragičević, Vjekoslav Kovač, Kristina Ana Škreb, 2023, original scientific article

Abstract: We prove a dimension-free $L^p(\Omega)\times L^q(\Omega)\times L^r(\Omega)\rightarrow L^1(\Omega\times (0,\infty))$ embedding for triples of elliptic operators in divergence form with complex coefficients and subject to mixed boundary conditions on $\Omega$, and for triples of exponents $p,q,r \in (1,\infty)$ mutually related by the identity $1/p+1/q+1/r=1$. Here $\Omega$ is allowed to be an arbitrary open subset of $\mathbb{R}^d$. Our assumptions involving the exponents and coefficient matrices are expressed in terms of a condition known as $p$-ellipticity. The proof utilizes the method of Bellman functions and heat flows. As a corollary, we give applications to (i) paraproducts and (ii) square functions associated with the corresponding operator semigroups, moreover, we prove (iii) inequalities of Kato-Ponce type for elliptic operators with complex coefficients. All the above results are the first of their kind for elliptic divergence-form operators with complex coefficients on arbitrary open sets. Furthermore, the approach to (ii),(iii) through trilinear embeddings seems to be new.
Keywords: elliptic differential operator, p-ellipticity, operator semigroup, multilinear estimate
Published in DiRROS: 15.03.2024; Views: 88; Downloads: 51
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Reviewing the modeling aspects and practices of shallow geothermal energy systems
Paul Christodoulides, Ana Vieira, Stanislav Lenart, João Maranha, Gregor Vidmar, Rumen Popov, Aleksandar Georgiev, Lazaros Aresti, Georgios Florides, 2020, review article

Abstract: Shallow geothermal energy systems (SGES) may take different forms and have recently taken considerable attention due to energy geo-structures (EGS) resulting from the integration of heat exchange elements in geotechnical structures. Still, there is a lack of systematic design guidelines of SGES. Hence, in order to contribute towards that direction, the current study aims at reviewing the available SGES modeling options along with their various aspects and practices. This is done by first presenting the main analytical and numerical models and methods related to the thermal behavior of SGES. Then, the most important supplementary factors affecting such modeling are discussed. These include: (i) the boundary conditions, in the form of temperature variation or heat flow, that majorly affect the predicted thermal behavior of SGES; (ii) the spatial dimensions that may be crucial when relaxing the infinite length assumption for short heat exchangers such as energy piles (EP); (iii) the determination of SGES parameters that may need employing specific techniques to overcome practical difficulties; (iv) a short-term vs. long-term analysis depending on the thermal storage characteristics of GHE of different sizes; (v) the influence of groundwater that can have a moderating effect on fluid temperatures in both heating and cooling modes. Subsequently, thermo-mechanical interactions modeling issues are addressed that may be crucial in EGS that exhibit a dual functioning of heat exchangers and structural elements. Finally, a quite lengthy overview of the main software tools related to thermal and thermo-hydro-mechanical analysis of SGES that may be useful for practical applications is given. A unified software package incorporating all related features of all SGES may be a future aim.
Keywords: shalow geothermal energy systems, energy geo-structures, thermal analysis, thermo-hydro-mechanical, modelling, software tools
Published in DiRROS: 05.03.2024; Views: 126; Downloads: 57
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Incidenca raka v prvem letu epidemije covida-19
Vesna Zadnik, Tina Žagar, Nika Bric, Mojca Birk, Amela Duratović Konjević, Ana Mihor, Katarina Lokar, Sonja Tomšič, 2023, professional article

Abstract: Uvod: Število novih diagnoz raka (incidenca) se v Sloveniji v zadnjem desetletju povečuje za povprečno 1,6 % na leto. V letu 2020, prvem letu omejitvenih ukrepov zaradi epidemije covida19, smo s platformo OnKOvid predvideli 3–8-odstotni padec novih diagnoz raka. Namen je predstaviti uradno incidenco raka za Slovenijo za leto 2020 in ugotoviti, kolikšen je bil dejansko manko novih diagnoz raka. Metode: V Registru raka Republike Slovenije smo v skladu z mednarodnimi pravili registrirali vse nove primere raka pri prebivalcih s stalnim prebivališčem v Sloveniji. Primerjali smo jih z registrirano incidenco za 2019, modelno incidenco za 2020, preliminarnimi rezultati OnKovida in dostopnimi rezultati incidence iz registrov raka iz drugih držav. Rezultati: V letu 2020 je za rakom zbolelo 15.096 oseb v Sloveniji (7.034 žensk, 8.002 moška). Glede na modelno oceno incidence za leto 2020 gre za manko 1.854 oseb (10,9 %; 11,6 % žensk, 10,4 % moških). Pri tem je za 10,5 % manj ugotovljenih rakov v omejenem stadiju, najbolj izrazito v starosti 50–69 let (za 13,2 %). Upad je primerljiv s poročili iz Anglije, ZDA in Kanade ter deloma večji kot na Škotskem in Švedskem. Najbolj izrazit upad novih diagnoz raka ugotavljamo pri nemelanomskem kožnem raku (23 %, najbolj po 50. letu), raku prostate (15,9 %, najbolj v omejenem stadiju), pljučnem raku (8,9 %, 60–64 let, v razširjenem stadiju), raku dojk (8,3 %, 45–64 let), ne-Hodgkinovem limfomu (9 %) in levkemijah (11,6 %). Pri kožnem melanomu, raku debelega črevesa in danke ni bilo primanjkljaja. Zaključek: Upad incidence raka v letu 2020 gre verjetno na račun omejitvenih ukrepov, reorganizacije zdravstva in z zdravjem povezanega vedenja med epidemijo covida-19, beležijo jo v več državah. Med epidemijami je potrebno nemoteno izvajanje onkologije.
Keywords: rak, incidenca, register raka, epidemija, covid-19
Published in DiRROS: 26.02.2024; Views: 161; Downloads: 36
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The role of p38 MAP kinase in cancer cell apoptosis
Metka Lenassi, Ana Plemenitaš, 2006, review article

Abstract: Background. Cellular behaviour in response to many extracellular stimuli is mediated through MAP kinase signalling pathways. p38 MAP kinase that is represented in mammals by four isoforms (p38alfa, p38beta, p38gama and p38delta) is one of the four main subgroups of MAP kinases. Recent studies show that p38 activation is necessary for cancer cell death initiated by variety of anti-cancer agents. This finding connected cancer therapies previously considered to be mechanistically unrelated and raised the possibility of developing anti-cancer agents that lack the side effects causedby events upstream of p38 MAPK Many of the details of p38 induced apoptosis still need to be elucidated. Since most of the past studies rely only on the cell culture models, all the results have to be verified using in vivo models. Also very little is known about the role of p38 mediated apoptosis on non-neoplastic cells in response to anti-cancer agents. Conclusion. Although p38 activation of cancer cell apoptosis is a very complexprocess, recent studies indicate a good starting point for new strategies that would increase the efficiency and decrease the toxicity of proven therapies.
Published in DiRROS: 15.02.2024; Views: 136; Downloads: 27
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