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Prilagodljivo formativno vrednovanje temeljeno na poboljšanom modelu Bayesovog praćenja znanja
No full textThis doctoral thesis utilised enhanced Bayesian Knowledge Tracing (BKT) models to assess student knowledge adaptively and to extend the standard functionalities of widely used Learning Management Systems (LMS). It was hypothesised that incorporating time spent on task and the number of code evaluations in the introductory programming domain would enhance student performance’s predictive accuracy and knowledge mastery estimation within the vanilla BKT model. Empirical research employing in situ quasi-experimental design was conducted during an Introduction to Programming in Python course, involving a substantial sample of 174 undergraduate students. The weekly course topics were structured into granular Domain Knowledge Components (DKC) and Controlled Environment formative assessments (CE). The study examined 18 BKT models incorporating various combinations of Prior knowledge, Guess, Slip, Learn and Forgets parameter probabilities, implemented using the Python library for cognitive modelling, pyBKT. In general, the enhanced BKT models outperformed the baseline vanilla model in predicting student performance across multiple DKCs. Also, the enhanced BKT models outperformed the vanilla model in estimating students’knowledge mastery. Regarding the model convergence, the enhanced BKT models provided more effective and reliable paths to knowledge mastery than the vanilla model. The previous results supported the proposal of a framework for ranking BKT models based on their capacity to predict student performance, estimate knowledge mastery, and model efficient learning paths. This framework identified the most effective BKT models, offering a systematic approach to selecting models that outperformed the vanilla BKT model.Ne temelju prethodnih poboljšanja osnovnog Bayesovog modela za praćenje znanja učenika (eng. Bayesian Knowledge Tracing, BKT), u radu se istražuju BKT modeli za prilagodljivu procjenu znanja, proširujući pritom standardne funkcionalnosti sustava za e-učenje. Postavljena je hipoteza da uvođenje značajki vremena provedenog na pitanju i broja evaluacija koda u području početnog programiranja poboljšava prediktivnu točnost učenikovih odgovora te procjenu razine usvojenog znanja. Empirijsko istraživanje provedeno je korištenjem in situ kvazi-eksperimentalnog dizajna tijekom kolegija Uvod u programiranje u kojem je sudjelovalo 174 studenta prijediplomskog studija. Tjedni nastavni sadržaji strukturirani su u granularne komponente znanja (eng. Domain Knowledge Components, DKC) uz pripadajuća formativna vrednovanja (eng. Controlled Environment assessments, CE). Korištenjem pyBKT Python biblioteke za kognitivno modeliranje, istraženo je 18 BKT modela koji uključuju različite kombinacije parametara predznanja (eng. Prior), pogađanja (eng. Guess), slučajne pogreške (eng. Slip), učenja (eng. Learn) i zaboravljanja (eng. Forgets). Predloženi BKT modeli nadmašili su osnovni model u predviđanju uspjeha učenika u više DKC-ova. Također, nadmašili su osnovni model u procjeni razine usvojenog znanja. U kontekstu konvergencije modela, predloženi BKT modeli pružili su učinkovitije i pouzdanije modeliranje individualnih pristupa učenju. Rezultati istraživanja rezultirali su prijedlogom okvira za rangiranje BKT modela s obzirom na njihovu sposobnost predviđanja učenikovih odgovora, procjene razine usvojenog znanja i modeliranje individualnih pristupa učenju. Predloženi okvir identificirao je najučinkovitije BKT modele, nudeći sustavan pristup odabiru modela koji nadmašuju rezultate osnovnog BKT modela
Protective effect of pentadecapeptide BPC 157 on organ damage in abdominal compartment syndrome in a rat model
No full textNedavna istraživanja ukazuju da stabilni želučani pentadekapeptid BPC 157 djeluje protektivno na oštećenja tkiva i organa kod okluzivnih sindroma velikih krvnih žila – bilo da se radi o perifernoj ili centralnoj okluziji na način da aktivira kolateralnu cirkulaciju. U ovom istraživanju po prvi smo puta u svijetu ispitivali utjecaj stabilnog želučanog pentadekapeptida BPC 157 na oštećenje organa u abdominalnom kompartment sindromu na animalnom modelu. Inducirali smo abdominalni komapartment sindrom u štakora koji predstavlja model polikompartment multiokluzivnog sindroma. Istraživali smo oštećenje organa i protektivno djelovanje BPC 157 na modelu ishemije i modelu reperfuzije. Intraabdominalni tlak, kojim je induciran abdominalni kompartment sindrom, i vrijeme trajanja ishemije je za štakore koji su bili anestezirani tiopentalom iznosio je 25 mm Hg (60 min), 30 mm Hg (30 min), 40 mm Hg (30 min) i 50 mm Hg (15 min) te kod štakora koji su bili anestezirani sa esketaminom (25 mm Hg tijekom 120 min). Kod modela reperfuzije prije dekompresije (kalvariektomija, laparotomija) štakori su imali dugotrajnu tešku intraabdominalnu hipertenziju, stupanj III (25 mm Hg/60 min) i stupanj IV (30 mm Hg/30 min; 40 mm Hg/30 min) te tešku okluziju / sindrom sličan okluziji odnosno ishemiju. Daljnje pogoršanje oštećenja organa uzrokovano je reperfuzijom od 60 minuta ili 30 minuta nakon dekompresije. Ozbiljno vaskularno i multiorgansko zatajenje (lezije mozga, srca, jetre, bubrega i probavnog sustava), raširena tromboza (periferno i centralno), teške aritmije, intrakranijalna (gornji sagitalni sinus) hipertenzija, portalna i kavalna hipertenzija te aortalna hipotenzija su se javile umodelu ishemije, a dodatno su se pogoršale u modelu reperfuzije. Štakori s intraabdominalnom hipertenzijom u modelu ishemije (stupanj III, stupanj IV) primili su BPC 157 (10 μg ili 10 ng/kg sc) ili fiziološku otopinu (5 ml) nakon 10 minuta. Kod modela reperfuzije, terapija BPC 157 (10 μg/kg, 10 ng/kg sc) primijenjena je u reperfuzijskim vremenima od 3 minute po dekompresiji i induciranju reperfuzije. Primjena BPC 157 oporavila je venu azygos putem spasonosnog kolateralnog puta gornje i donje šuplje vene. Dodatno, smanjena je intrakranijska (gornji sagitalni sinus), portalna i kavalna hipertenzija te aortalna hipotenzija, kao i izrazita kongestija želuca i velike hemoragijske lezije, oticanje mozga, venska i arterijska tromboza, kongestija donje šuplje vene i gornje mezenterične vene te kolabirana vena azygos; stoga je inače neuspjeli kolateralni put potpuno oporavljen kod primjene BPC 157. Ozbiljni EKG poremećaji (tj. teška bradikardija i ST-elevacija do asistolije) također su bili poništeni. Mikroskopski, transmuralna hiperemija gastrointestinalnog trakta, redukcija resica crijevne sluznice, redukcija kripte s fokalnom denudacijom površinskog epitela i dilatacija debelog crijeva bili su inhibirani. U jetri je BPC 157 smanjio kongestiju i ozbiljno povećanje sinusoida. U plućima je primijećena normalna prezentacija, bez žarišnog zadebljanja alveolarne membrane i bez plućne kongestije ili edema, a izostalo je ozbiljno intraalveolarno krvarenje. Spriječena je teška srčana kongestija, subendokardijalni infarkt, bubrežno krvarenje, edem mozga, krvarenje i neuralna oštećenja. Terapija s BPC 157 u reperfuziji eliminirala je / smanjila je vensku hipertenziju (intrakranijalnu (gornji sagitalni sinus), portalnu i kavalnu) i aortnu hipotenziju i spriječila povećanje lezije organa i vrijednosti malondialdehida (krv ˃ srce, pluća, jetra, bubrezi ˃ mozak, gastrointestinalni trakt). Brzo je došlo do vaskularnog oporavka (tj. začepljene donja šuplja vena i gornja mezenterična vena preokrenute su u normalnu prezentaciju krvnih žila, kolabirana vena azigos preokrenuta je u potpuno funkcionalno stanje, šant donje šuplje vene vene–gornje šuplje vene je oporavljen i vraćena je izravna isporuka krvi). Terapija s BPC 157 gotovo je poništila trombozu i krvarenje (tj. intracerebralno krvarenje) kao dokaz suzbijanja općeg zastoja i okolnosti Virchow trijade i reorganiziranog krvotoka. Poboljšanjem funkcije venskog sustava s BPC 157 preokrenuli smo lanac štetnih događaja u ishemiji i reperfuziji. Terapija s BPC 157 i protektivni učinak na organe mogao bi biti prenesen na pacijente, poništavajući lezije uzrokovane povišenim intraabdominalnim tlakom, potičući tako potpuni oporavak oštećenih organa. U konačnici, terapijska primjena BPC 157 kod pacijenata s abdominalnim kompartment sindromom smanjila bi visoku stopu smrtnosti i potrebom za hitnom dekompresijskom laparotomijom.Recent research indicates that the stable gastric pentadecapeptide BPC 157 has a protective effect on tissue and organ damage in occlusive syndromes of large blood vessels, whether there is a case of peripheral or central occlusion, by activating collateral circulation. In this research, for the first time in the world, we examined the influence of stable gastric pentadecapeptide BPC 157 on organ damage in abdominal compartment syndrome in an animal model. We induced abdominal compartment syndrome in rats, which represents a model of polycompartment multiocclusive syndrome. We investigated organ damage and the protective effect of BPC 157 in ischemia and reperfusion models. The intra-abdominal pressure that induced abdominal compartment syndrome and the duration of ischemia for rats anesthetized with thiopental was 25 mm Hg (60 min), 30 mm Hg (30 min), 40 mm Hg (30 min), and 50 mm Hg (15 min). and in rats anesthetized with esketamine (25 mm Hg for 120 min). In the reperfusion model before decompression (calvariectomy, laparotomy), rats had long-term severe intra-abdominal hypertension, grade III (25 mm Hg/60 min) and grade IV (30 mm Hg/30 min; 40 mm Hg/30 min) and severe occlusion/like syndrome or ischemia. Further worsening of organ damage was caused by reperfusion for 60 minutes or 30 minutes after decompression. Severe vascular and multiorgan failure (lesions of the brain, heart, liver, kidneys, and digestive system), widespread thrombosis (peripheral and central), severe arrhythmias, intracranial (superior sagittal sinus) hypertension, portal and caval hypertension, and aortic hypotension occurred in the ischemia model and further worsened in the reperfusion model. Rats with intra-abdominal hypertension in the ischemia model (grade III, grade IV) received BPC 157 (10 μg or 10 ng/kg sc) or saline (5 ml) after 10 minutes. In the reperfusion model, BPC 157 therapy (10 μg/kg, 10 ng/kg sc) was administered at reperfusion times of 3 minutes after decompression and induction of reperfusion. Administration of BPC 157 recovered the azygos vein via the superior and inferior vena cava salvage collateral route. In addition, intracranial (upper sagittal sinus), portal and caval hypertension and aortic hypotension were reduced, as well as pronounced gastric congestion and large hemorrhagic lesions, brain swelling, venous and arterial thrombosis, congestion of the inferior vena cava and superior mesenteric veins and collapsed azygos vein; therefore, the otherwise failed collateral pathway was fully restored with BPC 157 administration. Severe ECG disturbances (ie, severe bradycardia and ST-elevation to asystole) were also reversed. Microscopically, transmural hyperemia of the gastrointestinal tract, villi reduction of the intestinal mucosa, crypt reduction with focal denudation of the surface epithelium, and colon dilatation were inhibited. In the liver, BPC 157 reduced congestion and severe sinusoidal enlargement. A normal presentation was observed in the lungs, without focal thickening of the alveolar membrane and without pulmonary congestion or edema, and severe intraalveolar hemorrhage was absent. Severe cardiac congestion, subendocardial infarction, renal hemorrhage, brain edema, hemorrhage, and neural damage were prevented. Therapy with BPC 157 in reperfusion eliminated/reduced venous hypertension (intracranial (upper sagittal sinus), portal and caval) and aortic hypotension and prevented an increase in organ lesions and malondialdehyde values (blood ˃ heart, lungs, liver, kidneys ˃ brain, gastrointestinal tract). Vascular recovery occurred rapidly (ie, the occluded inferior vena cava and superior mesenteric vein were reversed to a normal presentation of blood vessels, the collapsed azygos vein was reversed to a fully functional state, the inferior vena cava–superior vena cava shunt was repaired and returned direct delivery of blood). BPC 157 therapy almost reversed thrombosis and hemorrhage (ie, intracerebral hemorrhage) as evidenced by suppression of general stasis and circumstances of the Virchow triad and reorganized blood flow. By improving the function of the venous system with BPC 157, we reversed the chain of harmful events in ischemia and reperfusion. Therapy with BPC 157 and the protective effect on the organs could be transferred to the patients, reversing the lesions caused by increased intra-abdominal pressure and thus promoting the full recovery of the damaged organs. Ultimately, the therapeutic use of BPC 157 in patients with abdominal compartment syndrome would reduce the high mortality rate and the need for emergency decompressive laparotomy
The effects of teacher-student interaction quality on students' academic dishonesty – the multilevel approach
No full textAkademsko nepoštenje je relativno često zastupljeno u školskom okruženju. Dosadašnja istraživanja ukazuju da je akademsko nepoštenje rezultat djelovanja više individualnih i kontekstualnih odrednica. Međutim, istraživanja su najčešće provedena grupno, unutar razrednih odjeljenja u osnovnim i srednjim školama ili studijskim skupinama studenata. S obzirom da je svaka skupina pod djelovanjem specifičnih dijeljenih iskustava i kontekstualnih odrednica, za pretpostaviti je da članovi jedne skupine imaju sličnu percepciju svoje okoline. Stoga, cilj ovog istraživanja bio je ispitati višerazinsku strukturu i doprinose kontekstualnih i osobnih varijabli u objašnjenju izraženosti akademskog nepoštenja učenika, u okviru hijerarhijskog modela motivacije za postignućem. U predispitivanju konstruiran je instrument namijenjen mjerenju akademskog nepoštenja. Na srednjoškolskom uzorku od 168 učenika provjerena je faktorska struktura instrumenta koja je rezultirala dimenzijama aktivnog i pasivnog varanja te nedopuštene razmjene informacija. U glavnom dijelu ispitivanja sudjelovalo je 912 srednjoškolaca iz ukupno 78 razrednih odjeljenja. Među nastavničkim interpersonalnim karakteristikama davanje slobode učenicima pokazalo se kao glavni pozitivan prediktor aktivnog i pasivnog varanja. Razredne strukture ovladavanja te izvedbe uključivanjem su u negativnoj vezi s akademskim nepoštenjem dok je razredna struktura izvedbe izbjegavanjem pozitivan prediktor varanja. Djelomična medijacijska uloga osobnih ciljeva postignuća potvrđena je za ciljeve ovladavanja uključivanjem, izvedbe uključivanjem i izvedbe rada, dok ciljevi ovladavanja izbjegavanjem i izvedbe izbjegavanjem nemaju značajan doprinos u objašnjenju akademskog nepoštenja. Ciljevi ovladavanja uključivanjem i izvedbe uključivanjem su u negativnoj vezi s aktivnim te u pozitivnoj vezi s pasivnim oblikom varanja. Izbjegavanje rada, s druge strane, je pozitivan prediktor aktivnog varanja. Analiza na razini učenika u višerazinskom modelu pokazala je slične obrasce veza kontekstualnih varijabli s akademskim nepoštenjem. Na razini odjeljenja, jedina značajna veza utvrđena je između nastavničkog vodstva i nedopuštene razmjene informacija. Ovaj je oblik varanja na razini odjeljenja izraženiji u uvjetima razredne klime sniženog nastavničkog vodstva. Istraživanje doprinosi spoznajama o važnosti karakteristika okoline u objašnjenju izraženosti ciljeva postignuća i akademskog nepoštenja u školskom kontekstu.Introduction
Academic dishonesty refers to various forms of unethical behavior in school setting, including cheating, plagiarism, falsifiying data and unauthorized collaboration. The act of academic dishonesty leads to unfair advantage in student's achievement and to teacher's erroneous inferences about student's knowledge or performance (Cizek, 2003).
Several individual and situational factors contribute to academic dishonesty. On an individual level, students' personal traits, including low self-control, academic self-efficacy, and performance pressure, can make them more likely to engage in dishonest behavior (Anderman & Murdock, 2007). Motivation also plays a critical role, particularly when students adopt performance-oriented goals over mastery-oriented goals. Students with performance goals often focus on achieving high grades rather than learning, which can drive them to cheat to meet those expectations (Murdock & Anderman, 2006). Situational factors are equally important. These include academic workload, pressure from parents or peers, and the perceived severity of consequences for dishonesty. Furthermore, students who perceive that others are cheating or that their environment lacks strict enforcement of academic integrity policies are more likely to justify dishonest behavior (Rettinger & Kramer, 2009).
Contextual factors in school settings significantly influence academic dishonesty. Classroom dynamics and teacher behavior, can either promote integrity or unintentionally foster dishonesty. Research show that classrooms with rigid structures focused on performance-avoidance goals may encourage cheating as students aim to avoid failure rather than enhance learning (Anderman et al., 1998). Teachers' interpersonal behavior also plays a crucial role; a teacher perceived as controlling or unsupportive may drive students to opt for cheating, as students feel less connected to the learning process (Wubbels et al., 2006).
The hierarchical theory of achievement motivation (Elliot & Church, 1997) may offer a framweork for understanding how students choose to engage in academically dishonest acts. Classroom environments and teacher's interpersonal behaviors serve as possible antecedents of achievement goals and, indirectly, academic dishonesty.
The aim of this study was to examine the multilevel structure and contributions of contextual and personal variables in explaining the prevalence of academic dishonesty among high-school students, within the framework of the hierarchical model of achievement motivation.
Methodology
Prior to main research, a preliminary study was conducted to develop and validate a new measure of academic dishonesty. The factor structure of the instrument was examined on a sample of 168 high school students, resulting in dimensions of active and passive cheating as well as unauthorized information exchange.
The main part of the study involved 912 high school students (50.3% female) from a total of 78 classes. Each class had a different mathematics teacher. The participants answered questions from several questionnaires: Academic dishonesty scale, which was developed for this research's purposes; Questionnaire on Teacher Interaction (Wubbels et al., 1995); Achievement Goals Scale (Rovan, 2011); Perception of Classroom Goals Structures – Patterns for Adaptive Learning Scales (Midgley et al., 2000).
Using structural equation modelling with clustered error correction five separate mediation models were tested. Also, multilevel structural equation modelling was used to check for higher level contextual effects on academic dishonesty in the classes.
Results and discussion
The results of this study highlight the role of contextual conditions and personal achievement goals in the prevalence of academic dishonesty in mathematics classes. It was found that contextual variables have both direct and indirect effects on the incidence of cheating.
Academic dishonesty varies depending on contextual variables and personal achievement goals. Active cheating is reduced in conditions with pronounced mastery approach and performance approach goals, while it is increased when students are more inclined to work avoidance. Passive cheating follows somewhat different patterns – this form of cheating is more pronounced among students with prominent mastery approach and performance approach goals. Freedom, as an interpersonal teacher characteristic, and the performance avoidant structure positively predict both active and passive cheating, while performance approach structure has a negative contribution in explaining these two forms of academic dishonesty.
Considering the significance and direction of the effects of contextual variables, the research hypotheses about the direct and indirect effects of contextual variables on academic dishonesty were mostly not confirmed. The partial mediating role of achievement goals, as predicted by the hierarchical model of achievement motivation, was confirmed for personal goals with approach valence and, in the case of active cheating, for the goal of work avoidance.
Also, the multilevel structure and multilevel relationships among variables in predicting the prevalence of three dimensions of academic dishonesty (active cheating, passive cheating, unauthorized information exchange) were examined. It was found that the variances in the perception of interpersonal teacher behavior and academic dishonesty can partly be explained at the classroom level. At the classroom level, only the perception of leadership was found to be a significant predictor of unauthorized information exchange. This form of cheating is less pronounced in classrooms where there is a high level of teacher leadership. In other words, if a classroom is characterized by similarly high ratings of lesson structure, clear rules, and responses to rule violations, the likelihood of information exchange regarding tests from the specific mathematics teacher is lower.
Conclusion
The research contributes to the understanding of the importance of environmental characteristics in explaining the prevalence of achievement goals and academic dishonesty in the school context. It supports the notion that academic dishonesty can be considered a characteristic of the classroom and that teacher interpersonal behavior represents the classroom climate, which is similarly perceived among students within the same class compared to students from other classes
EVALUATION AND PROGNOSTIC VALUE OF CALCIFICATIONS IN ILIAC ATERIES AMONG PATIENTS WHO HAVE UNDERGONE KIDNEY TRANSPLANTATION
No full textCilj istraživanja: Cilj istraživanja bio je procijeniti učestalost kalcifikacija ilijačnih arterija kod bolesnika u kojih je učinjena transplantacija bubrega te procijeniti povezanost između kalcificiranosti arterija i ishoda transplantacije. Drugi cilj bio je procijeniti razinu biljega koštane pregradnje i njihovu moguću povezanost sa kalcificiranošću ilijačnih arterija. Materijali i metode: U prospektivno istraživanje uključeno je 79 primatelja bubrežnog presatka u Kliničkom bolničkom centru Rijeka. Procjena opsežnosti kalcifikacija ilijačnih arterija učinjena je na preoperativnom pregledu abdomena i zdjelice računalnom tomografijom (CT). Analizirane su obje zajedničke i vanjske ilijačne arterije, a kalcificiranost je procijenjena semikvantitativno te je za svakog pacijenta izračunat pelvični kalcifikacijski zbroj (PKZ). PKZ se kretao od 0 (bez kalcifikacija) do 44 (ekstenzivne kalcifikacije). Temeljem PKZ vrijednosti, bolesnici su dodatno podijeljeni u tri jednako velike skupine (PKZ skupina 1-3). Kliničke ishode kod bolesnika pratili smo kroz najmanje godinu dana, a oni su uključivali preživljenje bolesnika, preživljenje presatka, funkciju presatka nakon godinu dana (serumska vrijednost uree i kreatinina te scintigrafija bubrega) te pojavnost velikih srčanožilnih događaja (MACE). Rezultati: Srednja dob bolesnika iznosila je 59 godina, većina su bili muškog spola (63%). Kod 77,2% bolesnika kalcifikacije su bile prisutne na barem jednom arterijskom segmentu, njihova opsežnost je bila povezana s dobi bolesnika, a značajno je bila veća u zajedničkim ilijačnim arterijama u usporedbi s vanjskim ilijačnim arterijama (P < 0,001). Jednogodišnje preživljenje bolesnika bilo je 95%, a jednogodišnje preživljenje presatka 92,4%. Kod bolesnika iz PKZ skupine 3 zabilježeno je značajno kraće jednogodišnje preživljenje bolesnika i presatka u usporedbi s onima iz PKZ skupine 1 i PKZ skupine 2 (P = 0,006 i P = 0,008). Nije bilo značajne razlike u parametrima bubrežne funkcije i razini biljega koštane pregradnje ovisno o PKZ-u ili među različitim PKZ skupinama. MACE je zabilježen u 18,9% bolesnika, no unatoč većoj učestalosti u PKZ skupini 3 razlika između skupina nije dosegnula statističku značajnost. Zaključak: Većina primatelja bubrežnog transplantata imala je kalcifikacije na barem jednom arterijskom segmentu. Bolesnici s većom kalcificiranošću arterija (PKZ skupina 3) imali su kraće ukupno preživljenje kao i kraće preživljenje presatka. Kalcificiranost ilijačnih arterija određena s PKZ ima potencijalnu ulogu u predviđanju kliničkih ishoda nakon transplantacije bubrega uključujući preživljenje i bolesnika i presatka.Aim of the study: This study aimed to assess the incidence of iliac artery calcifications in kidney transplant (KT) patients and the relationship between arterial calcifications and renal transplant outcomes. Additionaly, we aimed to assess the level of bone remodeling biomarkers and their potential correlation with the severity of iliac artery calcifications. Materials and Methods: This prospective study involved 79 KT recipients at the Clinical Hospital Center Rijeka. All patients underwent pretransplant abdominopelvic computerized tomography (CT) scans. Quantification of iliac arteries calcifications was performed by evaluating common and external iliac arteries bilaterally, resulting in a pelvic calcifications score (PCS) for each patient as a semiquantitative measure of vascular calcifications. PCS ranged from 0 (no calcifications) to 44 (extensive calcifications). Based on PCS values, patients were divided into three equal-sized groups (PCS group 1-3). Post-transplant outcomes were monitored for a minimum of one yeer and included patient survival, graft survival, graft function (serum value of urea and creatinine, renal scintigraphy) and incidence of major cardiovascular events (MACE). Results: The median patient age was 59 years, with a majority being male (63%). 77.2% of the patients had calcifications in at least one arterial segment, the severity of calcifications correlated with patient age, with a significantly higher incidence in the common iliac arteries compared to the external iliac arteries. (P < 0.001). One-year patient survival was 95%, and one-year graft survival was 92.4%. Patients categorized in PCS group 3 had significantly lower one-year patient and graft survival compared to those in PCS group 2 and group 1 (P = 0.006 and P = 0.008, respectively). No significant differences were observed in renal function parameters or bone remodeling biomarker levels depending on PCS value or different PCS groups. MACE occurred in 18.9% of patients, and although the incidence was higher in PCS group 3, this difference did not reach statistical significance. Conclusions: Our study demonstrated that a significant majority of KT recipients exhibit calcifications in the iliac arteries. Patients with a higher burden of calcifications (PCS group 3) had lower overall and graft survival rates. The presence of iliac artery calcifications, as assessed by PCS, has potential predictive value for transplant outcomes, including both patient and graft survival
Association of Epstein-Barr virus expression and prognosis in patients with primary cutaneous T-cell lymphoma
No full textCilj ovog istraživanja bio je odrediti utjecaj Epstein-Barr virusa (EBV) na kliničku sliku i prognozu kod bolesnika s primarnim kožnim T-staničnim limfomom (CTCL) te prepoznati skupinu bolesnika koja bi eventualno razvila bržu progresiju bolesti i pojavnost drugog primarnog malignoma. U ovu retrospektivnu studiju bila su uključena 84 bolesnika kod kojih je postavljena dijagnoza CTCL-a u Kliničkom bolničkom centru Zagreb u razdoblju od siječnja 2003. godine do prosinca 2017. godine te su opservirani minimalno pet godina. Metodom in situ hibridizacije (ISH) nije dokazan EBV kod bolesnika s CTCL-om te je EBV isključen kao potencijalni etiopatogenetski čimbenik. Od 84 ispitanika, njih 16 (19%) imalo je drugu primarnu neoplazmu, a 50% neoplazmi bilo je hematološke etiologije. Niti jedan ispitanik nije imao melanom iako je 58,3% njih liječeno fotokemoterapijom (PUVA). U našem istraživanju do progresije bolesti došlo je u 22,6% ispitanika (n=19), a ispitanici su imali neki od posebnih oblika MF-a, kao što su FMF i velikostaničnu transformaciju (P<0,001). Nijedan laboratorijski parametar niti klinički pokazatelj nije bio statistički značajan među bolesnicima s i bez progresije bolesti. Ispitanici s posebnim oblikom MF-a ili SS-a imali su značajno kraće vrijeme do progresije bolesti te značajno lošije preživljenje. Ovim istraživanjem, EBV odbačen je kao potencijalni etiopatogenetski čimbenik razvitka CTCL-a, kao i eventualne progresije. Definirana je skupina bolesnika koji su brže razvili progresiju bolesti te imali viši mortalitet.The aim of this research was to determine the impact of Epstein-Barr virus (EBV) on the clinical findings and prognosis in patients with primary cutaneous Tcell lymphoma (CTCL) and to identify a group of patients who would develop a progression of the disease and the development of a second primary malignancy. This retrospective study included 84 patients who were diagnosed with CTCL in the Clinic for Dermatovenerology and the Clinic for Pathology and Cytology of the Zagreb Clinical Hospital Center in the period from January 2003 to December 2017. All patients were followed up at least 5 years. The method of in situ hybridization (ISH) did not prove EBV in patients with CTCL, and EBV was excluded as a potential pathogenetic factor. Of the 84 subjects, 16 (19%) had a second primary malignancy, and 50% of the neoplasms
were of hematological etiology. No patient had melanoma even though 58.3% of them were treated with PUVA photochemotherapy. In our study, disease progression occurred in 22.6% of subjects (n=19), and the subjects had some of
the special forms of MF, such as FMF and large cell transformation (P<0.001). None of the laboratory parameters or clinical indicators were statistically significant between patients with and without disease progression. Subjects with a special form of MF or SS had significantly shorter time to disease progression and significantly worse survival. This research rejected EBV as a potential pathogenetic factor in the development of CTCL itself, as well as disease progression. We defined a group of patients who developed disease progression and had higher mortality significantly more often
The world in the (self)constitution of the transcendental subject
No full textOvaj rad se prvenstveno bavi temom konstitucije unutar Husserlove fenomenologije i svim bitnim momentima koji pritom dolaze u obzir. Transcendentalna subjektivnost se, kroz istra~ivanja u polju iste svijesti, kroz intencionalne analize i transcendentalnu refleksiju, pokazala sredibnjom to kom konstitucije, koju treba shvatiti kao <događanje u transcendentalnoj subjektivnosti=. Ona je aktivni pol intencionalnog odnosa, svaki predmetni smisao konstituira se u njoj (ona je istovremeno i samokonstituiraju a). S druge strane, svijet kao intencionalni korelat transcendentalne subjektivnosti nema bitak po sebi, ve uvijek upu uje na nju kao na praizvor stvaranja. U radu je pokazano da konstitucija nije samo <pubtanje da se bivstvuju e vidi u svojoj predmetnosti=, ve da ona za Husserla ima i dublji smisao te je u svom bitnom dijelu inidbena, stvarala ka djelatnost transcendentalnog subjekta. Ti uvidi ne ostaju samo u strogo teoretskim okvirima, nego imaju dalekose~ne implikacije, kako na ostale filozfijske discipline tako i na sve druge slojeve ~ivotnoga svijeta.This paper primarily deals with the topic of constitution within Husserl's phenomenology and all the important moments that come into consideration. Transcendental subjectivity, through research in the field of pure consciousness, through intentional analyzes and transcendental reflection, proved to be the central point of the constitution, which should be understood as "an event in transcendental subjectivity". It is the active pole of the intentional relationship, every objective sense is constituted in it (it is also self-constitutive at the same time). On the other hand, the world as an intentional correlate of transcendental subjectivity does not have a being in itself, but always refers to it as the primordial source of creation. The paper shows that the constitution is not only "allowing the existing to be seen in its objectivity", but that for Husserl it also has a deeper meaning and is in its essential part the active, creative activity of the transcendental subject. These insights do not remain only in strictly theoretical frameworks, but have far-reaching implications, both for other philosophical disciplines and for all other layers of the life world
Choir stalls and Wooden Doors of the Split Cathedral : Design Techniques and Chronology
No full textMultidisciplinarno istraživanje djela romaničke drvene polikromirane plastike u Splitu autorica je počela u sklopu proučavanja povijesnoga razvoja glavnog oltara splitske katedrale, čiju je konzervaciju-restauraciju vodila od 2006. do 2012. godine. Buvinine vratnice istraživala je unutar konzervacije-restauracije između 2014. i 2018. godine, što je bilo potaknuto obilježavanjem 800 godina od njihova nastanka. Dovršetkom toga projekta, rezultati istraživanja višekratno su publicirani; cjelovito 2020. godine u recenziranom zborniku radova o vratnicama. Objavljena studija okosnica je drugoga poglavlja disertacije, dopunjena nizom novih zaključaka i komparacija s djelima iz toga vremena u Splitu i Dalmaciji, kao i sa srodnim primjerima u Europi. Obuhvaća se i stupanj istraživanja njihove ikonografije te predlažu dopune objašnjenju. Zaključci se kontekstualiziraju unutar dalmatinske romaničke umjetnosti te europskog naslijeđa malobrojnih primjera srednjovjekovnih drvenih vratnica s kristološkim ciklusom (ukupno pet primjera). Istraživanja korskih klupa započeta proučavanjem povijesnoga razvoja glavnog oltara i svetišta splitske katedrale intenzivirana su 2021. godine pokretanjem (još uvijek aktivnog) konzervatorsko-restauratorskog projekta koji autorica vodi unutar Hrvatskog restauratorskog zavoda. U sklopu njega istražena je konstrukcija korskih klupa, njihova polikromija i povijesne faze, odnosno kronologija, pa se istraživanja ovom prilikom zaokružuju, premda će projekt trajati do 2026. godine. Prijedlog povijesnoga razvoja drvenog kora s izvornom fazom korskih klupa unutar romaničke katedrale objavljen je u recenziranom radu o glavnom oltaru 2013. godine, a sad je ista hipoteza proširena te dopunjena skupinama novih povijesnih, povijesnoumjetničkih, arhitektonskih, arheoloških, tehničkih i drugih izvora i podataka. Zaključuje se cjeloviti prijedlog, odnosno teza o njihovim oblikovnim tehnikama i kronologiji, čime je omogućena informatička vizualizacija njihove izvorne pojavnosti u prostoru katedrale, uz argumentiranje njihove uloge u arhitekturi i liturgiji. Istražena je gradbena materija djela, njezina geneza i kontekst, analizama je utvrđena starost materijala, tehnike sječe i pripreme drvene građe, konstruiranja i spajanja, drvodjeljske i rezbarske tehnike i alati, materijali i tehnike oslikavanja, što je omogućilo izradu tehničke baze naše najstarije umjetnosti u drvu. Velik broj ciljano mapiranih i istraženih komponenti srednjovjekovne drvene plastike i slikarstva na dasci nastalih izravnim proučavanjem više spomenika (što je jedna od metoda istraživanja te se donosi kao nova skupina izvora) interpretiran je u poveznicama s ponajprije povijesnoumjetničkom literaturom te raznovrsnim povijesnim izvorima, za što je autorica kreirala specifičan metodološki alat. Obrađena je sva literatura o temi, poznati izvori dopunjeni su novima, istraženi su novi dosjei i dokumenti, fotografije i slike, izrađeni novi nacrti i kolorističke vizualizacije spomenika, a u pisanom radu je (u formi DVD-a) predstavljena informatička baza obrađenih djela drvene polikromirane plastike i slikarstva na dasci, koja se može pretraživati i uspoređivati prema ključnim riječima te pregledati originalna laboratorijska izvješća. Tehnička istraživanja obuhvatila su, naime, širi kontekst: povijest, drvenu građu, polikromiju i kronologiju drvene plastike i slika na dasci u Dalmaciji od 9. do 15. stoljeća, uključujući slikarsko vezivo, čime su detektirane najstarije kiparske i slikarske tehnike u Hrvatskoj. Uz iluminacije, prilažu se i podaci o polikromiji srednjovjekovnog liturgijskog kamenog namještaja, portala i zidnih slika od Dubrovnika do Zadra. U fokusu studije su dva poglavlja: o drvenim vratnicama i korskim klupama splitske katedrale. U uvodu se govori o samoj katedrali, u tri cjeline, koje opisuju izvornu antičku građevinu, njezinu konverziju u crkvu te nastanak i povijesni razvoj srednjovjekovne katedrale, njezina interijera, namještaja i inventara, zadržavajući se na njezinu sadržaju definiranom u 13. stoljeću. U drugom i trećem poglavlju obrađuje se povijest djela, ali i paleta gradbenih materijala i umjetničkih tehnologija iz 13. stoljeća u Splitu: procesi planiranja, konstruiranja i oblikovanja te materijali, recepti i tehnike prepariranja, oslikavanja i pozlaćivanja. Dokazuju se i u radu vizualiziraju monumentalni oslikani reljefi vratnica i naslona korskih klupa u jedinstvu slike i skulpturalne obradbe koja je bila svojstvena romaničkoj umjetnosti. Ta je slika, naime, gotovo nestala u nizu povijesnih restauratorskih postupaka koji su djela transformirali konstrukcijski i optički, fizički i kemijski, posebice Buvinine vratnice restauracijom 1908. godine. Nasloni korskih klupa pak, kako se dokazuje istraživanjem, ispod zatečenih slojeva otkrivaju jedno od najbolje očuvanih djela romaničke polikromirane plastike u Europi. Kronološki retrogradno od mjesta i zatečenih pojavnosti djela, autorica niže povijesne pisane i slikovne izvore koji dokazuju ritam i opseg njihova mijenjanja; datira, opisuje i valorizira ključne obnove te tako imaginarno 'ljušti' povijesne slojeve do izvorne konstrukcije i polikromije, smještaja i pojavnosti u prostoru nestale romaničke katedrale koju opisuje i rekonstruira, odnosno iznosi pretpostavku o njezinoj izvornoj prostornoj koncepciji i ikonografiji. Povijesnim fazama prilaže konzultiranu literaturu i izvore kao dokaze i alate za rad, kojih je prema 13. stoljeću sve manje, pa se kao glavnim argumentima i izvorima za prijedloge rekonstrukcije izvornih faza klupa i vratnica koristi rezultatima brojnih fizičkih i kemijskih analiza te pomnim dugogodišnjim opservacijama tehnika i tehnologija njihove izrade, dokazujući da su oba djela zaista izradili domaći umjetnici i da su odraz visokih umjetničkih i tehničkih razina ondašnje splitske komune koja je u 13. stoljeću živjela svoje zlatno doba. Rezultati istraživanja povijesti splitske katedrale, njezina interijera, namještaja i opreme s nizom rezultata analiza materijala i tehnika izrade, uz njihovu višeslojnu kontekstualizaciju, premrežavaju se u radu s ostalim razmatranjima, obuhvaćajući gotovo dvadeset godina autoričina profesionalnog rada u splitskoj katedrali te desetak godina istraživanja romaničkog slikarstva na dasci u Splitu i Dalmaciji. Slikarstvom se ona ovdje bavi u poveznicama s temom, zaobilazeći, shodno užoj temi rada, o tome napisati zasebno poglavlje, premda je istraženo svih šest djela iz 13. stoljeća u Splitu (najopsežnije ikona Gospa od Žnjana), a u različitom opsegu još i jedanaest slikarskih djela iz 13. stoljeća u Dalmaciji. Dokazivanje da su oba djela polikromirane drvene plastike oslikali sami rezbari, odnosno da su rezbari tih djela ujedno bili i njihovi slikari, dovela je do saznanja koja ne samo u hrvatskom nego i u europskom kontekstu unapređuju još uvijek slabo poznate umjetničke i tehničke procese izrade djela srednjovjekovne drvene polikromirane plastike. Razmatrajući studije i izvore koje pridonose razumijevanju kronologije vratnica i korskih klupa te interijera splitske katedrale i njezine opreme, radom se objedinjuje i interpretira građa o toj temi te se donose prve generacije povijesno-tehničkih podataka kao cjelovitoga priloga za sljedeću generaciju povijesnoumjetničkih istraživanja djela, kao i njegova objedinjavanja s poljem zaštite umjetničke baštine, budući da se donosi opservacija izazova njihova suvremenog očuvanja. Kao cjeloviti zaključak, predlaže se dokazani izvorni izgled drvenih vratnica i korskih klupa, njihova konstrukcija, polikromija i smještaj u interijeru katedrale iz 13. stoljeća.The author began multidisciplinary research into Romanesque polychrome wood sculpture in Split as part of her research into the historical development of the high altar of Split Cathedral, which she and her team restored in 2006-2012. She researched and restored the Buvina Door in 2014 2018, prompted by the celebration of its 800th birthday; the historical and technical research results were published on completion of the project. These make up the backbone of the first chapter of the study. Research into the choir stalls, which began at the same time as the work on the high altar, has continued until the present, and was intensified in 2021 when a conservation-restoration project was launched that included a series of technical examinations, presented here. The hypothesis on the original phase of the wood choir, submitted here, was drafted and published in 2013. The results of research into the history of Split Cathedral, the Buvina Door, the high altar and the choir stalls, as an integral part of the development of the altar, included analyses of materials and production techniques with contextualisation; they are interwoven in the study and cover more than twenty years of the author's professional work in Split Cathedral and about ten years of research into Romanesque panel painting in Split. Here she addresses painting through links, thus avoiding write a separate chapter about it although all the 13th-century works in Split have been researched, most extensively the icon of Our Lady of Žnjan, which was also one of the author's projects while this study was being written (2018-2020). Not only were all the six paintings in Split examined in a varied extent, but so were also seventeen 13th-century paintings in Dalmatia, in collaboration with colleagues. A large number of separate facts that resulted from direct research into the pieces, which forms the backbone of this study, was interpreted through links to professional literature primarily in the field of art history and diverse historical sources, for which the author created a specific methodological tool. All the literature on the subject was processed, and also files, documents, plans, photographs and images from many archives and galleries, laboratory reports on the materials she sampled from the monuments, as well as those that are kept in the databases of Croatian laboratories. The text of the thesis is accompanied by all the basic data referring to the results of technical research into the processed items of polychrome wood sculpture and panel painting, which have been collected in a computer database and can be searched and mutually compared. The study on the Buvina Door and choir stalls in Split Cathedral covers these two units and also includes a third, a reconstruction of the context and historical development of the space of Split Cathedral with a focus on its appearance as defined in the 13th century. The knowledge that both the above items of polychrome wood sculpture were painted by the carvers themselves, that is, that the carvers of these items were also their painters, significantly advanced insight, not only in the Croatian but also in the European context, into the as yet poorly known artistic and technical processes used to create medieval sculpture in wood. The study deals with the history of the works, but also with the range of building materials and art technologies used in the 13th century in Split: the processes of planning, constructing and sculpting, as well as materials, recipes and techniques of priming, painting and gilding. All this makes it possible to visualise, in the study, the monumental painted reliefs on the door and the backs of the wooden choir stalls and prove that they show the unity of painting and sculpture so characteristic of Romanesque art. The paintings almost disappeared in the succession of historical restoration procedures that transformed the pieces structurally and visually, physically and chemically, especially the Buvina Door in the restoration of 1908. However, the backs of the choir stalls have been surprisingly well preserved, which includes them among the best-preserved testimonies of medieval polychrome wood sculpture in Europe. Through detecting and analysing the structural materials of the pieces it is possible to visualise their original appearance in the cathedral space, and to argument their role in the architecture and liturgy. The author researches the structural material of the works, its genesis and context, its age, the techniques of cutting and preparing the wood, constructing and joining, carpentry and carving techniques and tools, painting materials and techniques, which made it possible to create the technical base of our oldest art in wood. She moves back through time from the current point and condition of the works and chronologically registers historical written and pictorial sources that show the rhythm and scope of changes; she dates, describes and evaluates the key renovations and thus fictitiously peels off historical layers to reach the original structural and visual effect, location and appearance in the space of the vanished Romanesque cathedral that she is reconstructing. She proposes the spatial conception, position, construction and appearance of the sanctuary elements and of the sanctuary as a whole. On this journey she attaches to the historical phases the literature and sources she consulted as evidence and working tools, which decrease in number as she approaches the 13th century. Because of this the main arguments and sources for her proposals of reconstructing the original phases of the stalls and door are based on many physical and chemical analyses and careful long-term observations of the techniques and technology of their production, which prove that both the pieces were indeed created by the hands of local artists and that they are a reflection of the high artistic and technical levels of the then Split commune, which was living its golden age. The study does not deal with the history of art in the narrower sense, its role is to provide unified material for a new generation of researchers
Innovative Designs of Ecological in silico Experiments Based on Artifcial Intelligence
No full textOvom doktorskom disertacijom primjenom tradicionalnih metoda modeliranja i metoda neuronskih mreža razvile su se in silico metode za rješavanje složenih ekoloških
izazova. Razvijenim metodama su kroz niz in silico pokusa istraživana važna ekološka
pitanja podijeljena u pet tematskih cjelina: (i) razumijevanje dinamike populacija gujavica, (ii) predvidanje populacije komaraca kao funkcije okolišnih uvjeta, (iii) predvi ¯ danje ¯
dinamike rasta ribe, (iv) utjecaji na prostorno-vremenske distribucije komaraca, te (v)
kartiranje morskih staništa.
Istraživanje dokazuje da integracija klasicnih pristupa s umjetnom intelignecijom una- ˇ
prjeduje ekološko modeliranje, nude ¯ ci brže i preciznije alate za razumijevanje ekosustava ´
i održivo upravljanje. Rezultati daju smjernice za adaptaciju na klimatske promjene, optimizaciju poljoprivrednih praksi i ocuvanje morskih resursa. Razvijene metode primje- ˇ
njive su i na brojne druge ekološke kontekste, pa se disertacijom dopridonosi i razumijevanju i rješavanju globalnih ekoloških izazova.This doctoral dissertation explores the application of artifcial intelligence (AI) and in
silico methods to address complex ecological challenges, such as population dynamics,
climate change, and natural resource management. Through fve thematic studies, innovative models were developed to simulate earthworm and mosquito populations, gilthead
seabream growth, and marine habitat mapping. The integration of mathematical models
(e.g., matrix population models, dynamic energy budget theory) with AI techniques (neural networks, optimization algorithms) enabled the prediction of temperature impacts,
pest control management, and the analysis of spatial ecosystem dynamics.
The research demonstrates that integrating classical approaches with AI enhances ecological modeling, providing faster and more precise tools for sustainable management.
The results emphasize the importance of adapting to climate change, optimizing agricultural practices, and preserving marine resources. These methodological frameworks
are applicable to diverse ecological contexts, contributing to scientifc understanding and
practical solutions for global ecological threats
Autophagy and the role of osteogenic macrophages in chronic Philadelphia-negative myeloproliferative neoplasm
No full textUvod: Cilj našeg rada je bio ispitati autofagiju i osteogene makrofage u koštanoj srži oboljelih od mijelofibroze.
Ispitanici i metode: Metodom RT-PCR smo analizirali ekspresiju biljega autofagije (Beclin-1 i LC3B-II), Onkostatina M i SPARC u stanicama koštane srži oboljelih od mijelofibroze (74 ispitanika) u odnosu na kontrolnu skupinu (11 ispitanika). Na uzorcima bioptata kosti od 81 ispitanika oboljelog od mijelofibroze smo imunohistokemijski istražili izražaj Beclin-1, LC3B-II, Onkostatina M i SPARC te udio osteogenih makrofaga fenotipa CD169, F4/80.
Rezultati: Na temelju rezultata RT-PCR-a nije bilo statistički značajne razlike u ekspresiji Beclin-1, LC3B-II, Onkostatina M i SPARC između oboljelih od mijelofibroze i kontrolnih ispitanika. Nakon stratifikacije ekspresije LC3B-II kod oboljelih od primarne mijelofibroze, viša ekspresija je bila statistički značajno povezana s nižim DIPSS-om. Viša ekspresija Beclin-1 bila je statistički značajno povezana s boljim preživljenjem bolesnika. Imunohistokemijskom analizom su biljezi autofagije bili dominantno izraženi u megakariocitima i granulocitima. Najveći dio oboljelih od mijelofibroze nije imunohistokemijski imao pozitivnu reakciju na biljeg osteogenih makrofaga CD169.
Zaključak: Rezultati našeg istraživanja govore u prilog da autofagija možda ima povoljan učinak na prognozu i preživljenje oboljenih od mijelofibroze.Introduction: The aim of our research was to investigate autophagy and osteogenic macrophages in the bone marrow of patients with myelofibrosis.
Subjects and methods: Using the RT-PCR method, we analyzed the expression of autophagy markers (Beclin-1 and LC3B-II), Oncostatin M and SPARC in bone marrow of patients with myelofibrosis (74 participants) compared to the control group (11 participants). We immunohistochemically investigated the expression of Beclin-1, LC3B-II, Oncostatin M, SPARC and the proportion of CD169, F4/80 phenotype osteogenic macrophages on bone biopsy samples from 81 patients suffering from myelofibrosis.
Results: Based on the results of RT-PCR, there was no statistically significant difference in the expression of Beclin-1, LC3B-II, Oncostatin M and SPARC between patients with myelofibrosis and control subjects. After stratification of LC3B-II expression in patients with primary myelofibrosis, higher expression was statistically significantly associated with lower DIPSS. Higher Beclin-1 expression was statistically significantly associated with better patient survival. By immunohistochemical analysis, autophagy markers were dominantly expressed in megakaryocytes and granulocytes. The majority of patients with myelofibrosis didn't have a positive reaction to marker CD169 of osteogenic macrophages.
Conclusion: The results of our research suggest that autophagy may have a beneficial effect on the prognosis and survival of patients with myelofibrosis
BIOLOGICAL CHARACTERIZATION OF CHIMERIC VIRUSES BASED ON MUMPS VIRUS WITH INSERTED GENES FOR SURFACE PROTEINS OF HEPATITIS C VIRUS
No full textRekombinantni virusi bazirani na atenuiranim sojevima virusa zaušnjaka jedna su od bioloških platformi
za vektorska cjepiva. Tijekom njihova razvoja nužno je istražiti gensku stabilnost proizvedenih kimernih
virusa jer mutacije i promjene u strukturi virusne kvazivrste mogu utjecati na atenuacijski i imunosni profil
cijepnog soja. U ovom istraživanju su dizajnirana i proizvedena dva kimerna virusa temeljena na konsenzus
sekvenciji soja L-Zagreb s ugrađenim genima za površinske proteine virusa hepatitisa C (HCV). Virusi su
dobiveni u visokom titru, no tijekom kultivacije na dvije vrste stanica za proizvodnju cjepiva uočene su
genske promjene koje su uzrokovale smanjenje ekspresije gena HCV-a. Za virus koji je imao veću gensku
stabilnost su ispitane imunogeničnost i neškodljivost u animalnim modelima. Rezultati su pokazali da virus
nije dovoljno neuroatenuiran i da ne inducira snažne imunosne odgovore na HCV. Istraživanje naglašava
potrebu za strogom kontrolom genske stabilnosti tijekom razvoja cjepiva.Recombinant viruses based on attenuated mumps strains are one of biological platforms for vector vaccines.
During their development, it is necessary to investigate the genetic stability of produced chimeric viruses
because mutations and changes in viral quasispecies structure can influence attenuation and immune profile
of vaccine strain. In this study, two chimeric viruses were designed and produced using consensus sequence
of L-Zagreb, with genes encoding hepatitis C virus (HCV) surface proteins inserted. Viruses were obtained
in high titers; however, genetic changes leading to reduced HCV gene expression were observed during
cultivation in two cell types suitable for vaccine production. The virus showing higher genetic stability was
evaluated for immunogenicity and safety in animal models. It was insufficiently neuroatenuated and failed
to induce strong immune responses to HCV. This study highlights the need for strict control of genetic
stability during vaccine development