1. Ovrednotenje vpliva mobilnega učenja z resno igro in igrifikacijo v procesu usvajanja temeljnih postopkov oživljanja odraslih osebNino Fijačko, 2025, doctoral dissertation Abstract: Zunajbolnišnični srčni zastoj vsako leto na svetovni ravni prizadene 3,7 milijona ljudi, v Evropi približno 300.000 ljudi in v Sloveniji približno 1.700 ljudi. Raziskave kažejo, da pravilno izvajanje temeljnih postopkov oživljanja odrasle osebe s strani laikov poveča možnosti za preživetje, vendar je stopnja izvajanja nizka, predvsem zaradi pomanjkanja znanja. Posledično Evropski reanimacijski svet predlaga uporabo naprednejših tehnologij, na primer mobilno učenje, in sicer kot podporo pri izobraževanju temeljnih postopkov oživljanja odrasle osebe za laike. V doktorski disertaciji smo z uporabo mešanih metod ovrednotili vpliv uporabe mobilnega učenja z resno igro MOBICPR na usvajanje kognitivnih, vedenjskih in motivacijskih učnih izidov ter na raven stresa pri posredovanju vsebin s področja temeljnih postopkov oživljanja odrasle osebe v domačem okolju. Na vzorcu 43 študentov zdravstvene nege smo z randomizirano raziskavo s kontrolno skupino deležne odložene obravnave potrdili, da dvotedensko mobilno učenje z resno igro MOBICPR v domačem okolju vpliva na usvajanje kognitivnih učnih izidov (t(41) = 1,717, p = 0,047), ne vpliva pa na usvajanje vedenjskih (t(41) = 1,313, p = 0,448) in motivacijskih (t(41) = 1,816, p = 0,394) učnih izidov. Slednje smo z uporabo vsebinske analize podatkov dodatno potrdili. Prav tako dvotedensko mobilno učenje z resno igro MOBICPR v domačem okolju ne vpliva na stopnjo stresa pred izvajanjem in po izvajanju temeljnih postopkov oživljanja odrasle osebe (U = 227,5; p = 0,465). Mobilno učenje predstavlja izobraževalno orodje, ki bi se lahko v prihodnje vključilo v tečaje temeljnih postopkov oživljanja odrasle osebe, po opravljenih tečajih pa bi se lahko uporabljalo v domačem okolju za vzdrževanje in osvežitev znanja temeljnih postopkov oživljanja odrasle osebe.
Keywords: temeljni postopki oživljanja odrasle osebe, mobilno učenje, resna igra, učni izidi, laiki
Published in DKUM: 27.01.2025; Views: 0; Downloads: 31
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2. Single-cell transcriptomic and targeted genomic profiling adjusted for inflammation and therapy bias reveal CRTAM and PLCB1 as novel hub genes for anti-tumor necrosis factor alpha therapy response in Crohn’s diseaseMario Gorenjak, Boris Gole, Larisa Goričan, Gregor Jezernik, Uršula Prosenc Zmrzljak, Cvetka Pernat Drobež, Pavel Skok, Uroš Potočnik, 2024, original scientific article Abstract: The lack of reliable biomarkers in response to anti-TNFα biologicals hinders
personalized therapy for Crohn’s disease (CD) patients. The motivation behind our study is to shift
the paradigm of anti-TNFα biomarker discovery toward specific immune cell sub-populations using
single-cell RNA sequencing and an innovative approach designed to uncover PBMCs gene expression
signals, which may be masked due to the treatment or ongoing inflammation; Methods: The singlecell
RNA sequencing was performed on PBMC samples from CD patients either naïve to biological
therapy, in remission while on adalimumab, or while on ustekinumab but previously non-responsive
to adalimumab. Sieves for stringent downstream gene selection consisted of gene ontology and
independent cohort genomic profiling. Replication and meta-analyses were performed using publicly
available raw RNA sequencing files of sorted immune cells and an association analysis summary.
Machine learning, Mendelian randomization, and oligogenic risk score methods were deployed to
validate DEGs highly relevant to anti-TNFα therapy response; Results: This study found PLCB1 in
CD4+ T cells and CRTAM in double-negative T cells, which met the stringent statistical thresholds
throughout the analyses. An additional assessment proved causal inference of both genes in response
to anti-TNFα therapy; Conclusions: This study, jointly with an innovative design, uncovered
novel candidate genes in the anti-TNFα response landscape of CD, potentially obscured by therapy
or inflammation.
Keywords: inflammatory bowel diseases, Crohn’s disease, tumor necrosis factor alpha, adalimumab, single-cell gene expression analysis
Published in DKUM: 10.12.2024; Views: 0; Downloads: 7
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3. Discovery of novel biomarkers with extended non-coding RNA interactor networks from genetic and protein biomarkersGregor Jezernik, Damjan Glavač, Pavel Skok, Martina Krušič, Uroš Potočnik, Mario Gorenjak, 2024, original scientific article Abstract: Curated online interaction databases and gene ontology tools have streamlined the analysis of highly complex gene/protein networks. However, understanding of disease pathogenesis has gradually shifted from a protein-based core to complex interactive networks where non-coding RNA (ncRNA) is thought to play an essential role. As current gene ontology is based predominantly on protein-level information, there is a growing need to analyze networks with ncRNA. In this study, we propose a gene ontology workflow integrating ncRNA using the NPInter V5.0 database. To validate the proposed workflow, we analyzed our previously published curated biomarker datasets for hidden disease susceptibility processes and pharmacogenomics. Our results show a novel involvement of melanogenesis in psoriasis response to biological drugs in general. Hyperpigmentation has been previously observed in psoriasis following treatment with currently indicated biological drugs, thus calling attention to melanogenesis research as a response biomarker in psoriasis. Moreover, our proposed workflow highlights the need to critically evaluate computed ncRNA interactions within databases and a demand for gene ontology analysis of large miRNA blocks.
Keywords: gene ontology, non-coding RNA, disease pathogenesis
Published in DKUM: 06.12.2024; Views: 0; Downloads: 7
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4. Identification of novel loci involved in adalimumab response in Crohn’s disease patients using integration of genome profiling and isoform-level immune-cell deconvoluted transcriptome profiling of colon tissueMario Gorenjak, Gregor Jezernik, Martina Krušič, Pavel Skok, Uroš Potočnik, 2022, original scientific article Abstract: Crohn’s disease is a consequence of dysregulated inflammatory response to the host’s microbiota. Although anti-TNF treatment improves the quality of the patient’s life, a large proportion of patients lose response to the treatment. The past decade of research has led to a continuum of studies showcasing the heterogeneity of anti-TNF response; thus, the aim of the present study was to dissect transcriptome-wide findings to transcript isoform specific levels and combine the analyses with refined information of immune cell landscapes in colon tissue, and subsequently select promising candidates using gene ontology and genomic integration. We enrolled Slovenian Crohn’s disease patients who were naïve with respect to adalimumab treatment. We performed colon tissue RNA sequencing and peripheral blood mononuclear cell DNA genotyping with a subsequent contemporary integrative approach to combine immune cell deconvoluted isoform transcript specific transcriptome analysis, gene ontology layering and genomic data. We identified nine genes (MACF1, CTSE, HDLBP, HSPA9, HLA-DMB, TAP2, LGMN, ANAPC11, ACP5) with 15 transcripts and 16 variants involved in the adalimumab response. Our study identified loci, some of which were previously shown to contribute to inflammatory bowel disease susceptibility, as novel loci involved in adalimumab response in Crohn’s disease patients.
Keywords: Crohn’s disease, adalimumab, transcriptome, isoforms, deconvolution
Published in DKUM: 05.12.2024; Views: 0; Downloads: 4
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5. Effects of a serious smartphone game on nursing students` theoretical knowledge and practical skills in adult basic life support : randomized wait list-controlled trialNino Fijačko, Ruth Masterson Creber, Špela Metličar, Matej Strnad, Robert Greif, Gregor Štiglic, Pavel Skok, 2024, original scientific article Abstract: Background: Retention of adult basic life support (BLS) knowledge and skills after professional training declines over time.To combat this, the European Resuscitation Council and the American Heart Association recommend shorter, more frequent BLS sessions. Emphasizing technology-enhanced learning, such as mobile learning, aims to increase out-of-hospital cardiac arrest (OHCA) survival and is becoming more integral in nursing education.
Objective: The aim of this study was to investigate whether playing a serious smartphone game called MOBICPR at home can improve and retain nursing students’ theoretical knowledge of and practical skills in adult BLS.
Methods: This study used a randomized wait list–controlled design. Nursing students were randomly assigned in a 1:1 ratio to either a MOBICPR intervention group (MOBICPR-IG) or a wait-list control group (WL-CG), where the latter received the MOBICPR game 2 weeks after the MOBICPR-IG. The aim of the MOBICPR game is to engage participants in using smartphone
gestures (eg, tapping) and actions (eg, talking) to perform evidence-based adult BLS on a virtual patient with OHCA. The participants’ theoretical knowledge of adult BLS was assessed using a questionnaire, while their practical skills were evaluated on cardiopulmonary resuscitation quality parameters using a manikin and a checklist.
Results: In total, 43 nursing students participated in the study, 22 (51%) in MOBICPR-IG and 21 (49%) in WL-CG. There were differences between the MOBICPR-IG and the WL-CG in theoretical knowledge (P=.04) but not in practical skills (P=.45) after MOBICPR game playing at home. No difference was noted in the retention of participants’ theoretical knowledge and practical
skills of adult BLS after a 2-week break from playing the MOBICPR game (P=.13). Key observations included challenges in response checks with a face-down manikin and a general neglect of safety protocols when using an automated external defibrillator.
Conclusions: Playing the MOBICPR game at home has the greatest impact on improving the theoretical knowledge of adult BLS in nursing students but not their practical skills. Our findings underscore the importance of integrating diverse scenarios into adult BLS training.
Keywords: serious smartphone game, adult basic life support, teaching, games, gaming, education, nurses, nursing, educational, mHealth, mobile health, applications, smartphones, randomized controlled trial, technology-enhanced learning, life support, knowledge retention, practical
Published in DKUM: 27.11.2024; Views: 0; Downloads: 3
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6. Pomen nujne endoskopije zgornjih prebavil pri odstranjevanju tujkov - rezultati obdobja 1994-2008Pavel Skok, Andreja Ocepek, 2008, original scientific article Abstract: Purpose: Foreign bodies in the upper gastrointestinal tract (GIT) rarely cause urgent problems in gastroenterology. The purpose of the study was to assess the percentage of patients in whom urgent endoscopic investigation revealed true foreign bodies in the upper GIT and to evaluate the success of emergency endoscopic procedures. Methods: The study includes patients in whom urgent endoscopic investigations of the upper GIT were performed in the period 1 January 1994 to 1 May 2008. Results: 8552 patients were investigated,average age 60,6 years (SD +/- 17,1 years, range 1 - 106 years), with 3276 (38 %) females and 5276 males (62 %). In 69 patients (0,8 %), "true" foreign bodies were detected in the esophagus or stomach. In these patients a total of 90 endoscopic investigations were performed: in 65/69 patients (94,2 %) the foreign bodies were removed endoscopically; in 4 (5,8 %) cases the endoscopic procedures were unsuccessful. Among the foreign bodiesremoved were a variety metal or plastic objects, such as coins, keys, screws, hooks, batteries, razor blades, needles, lighters, buttons and parts of kitchen, toilet or writting utensils. In patients with successful endoscopic removal of the objects, no significant complications were noted. In 4 patients (4/69, 5,8 %) mild hemorrhages from the region of the esophagogastric junction were observed. Conclusion: Endoscopic technologies allow successful removal of a variety of types of foreign bodies from the upper GIT.
Keywords: tujki, zgornja prebavna cev, endoskopija, odstranitev, zapleti
Published in DKUM: 19.04.2024; Views: 156; Downloads: 3
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8. Biološki procesi in napovedovanje neodzivnosti na zaviralce dejavnika tumorske nekroze pri Crohnovi bolezni z integracijo genomskih podatkovGregor Jezernik, 2020, doctoral dissertation Abstract: Razvoj bioloških zdravil je pomembno prispeval k možnostim zdravljenja raka in imunsko pogojenih bolezni. Med najpogosteje uporabljenimi biološkimi zdravili so zaviralci dejavnika tumorske nekroze (TNF). Crohnova bolezen je pogosta imunsko pogojena bolezen prebavil, ki se zdravi z zaviralci TNF. Kljub tarčnemu delovanju zaviralcev TNF del bolnikov s Crohnovo boleznijo žal ne doseže dobrega odziva na zaviralce TNF že ob uvedbi terapije ali pa sprva dober odziv na zaviralce TNF s časom izzveni. Neodzivnost na zaviralce TNF predstavlja pomeni izgubo nadzora nad pogosto hudim bolezenskim stanjem bolnika s Crohnovo boleznijo, ki je po nepotrebnem izpostavljen potencialno hudim neželenim stranskim učinkom bioloških zdravil, in tudi precejšnje finančno breme za zdravstveno blagajno. Ti razlogi utemeljujejo potrebo po napovedovanju odziva na biološka zdravila, po možnosti še pred uvedbo zdravljenja.
V doktorski disertaciji smo celostno raziskali biološke označevalce odziva na zaviralce dejavnika tumorske nekroze na ravni DNA in RNA ter maščobnih kislin v vzorcih periferne venske krvi skupine slovenskih bolnikov s Crohnovo boleznijo, ki se je zdravila z adalimumabom. Rezultate teh analiz smo uporabili za oblikovanje novih napovednih modelov s pristopi strojnega učenja, t.i. metode podpornih vektorjev. Za namene iskanja vzročnih bioloških procesov, ki pogojujejo neodzivnost na zaviralce dejavnika tumorske nekroze, smo sistematsko preučili gensko ontologijo že objavljenih bioloških označevalcev odziva na zaviralce dejavnika tumorske nekroze v kronični vnetni črevesni bolezni. Za primerjalno analizo genske ontologije smo zbrali tudi biološke označevalce odziva v revmatoidnem artritisu. Ker je neodzivnost pogostejša med pediatričnimi bolniki, smo analizo genske ontologije razširili še na vzročne gene pediatričnih dednih oblik kronične vnetne črevesne bolezni in sindrome s klinično sliko, skladno s kronično vnetno črevesno boleznijo. Dodatno smo tudi poskusili ponoviti že objavljen napovedni model odziva na infliksimab, ki temelji na izražanju petih genov v črevesni sluznici.
Rezultati genske ontologije že objavljenih označevalcev kažejo na povezavo med krvnimi lipoproteini in odzivom na zaviralce dejavnika tumorske nekroze pri kronični vnetni črevesni bolezni, kot tudi pri revmatoidnem artritisu. Na osnovi rezultatov genske ontologije pediatričnih dednih oblik kronične vnetne črevesne bolezni lahko sklepamo, da so zelo zgodnje pediatrične oblike z nastopom bolezni pred šestim letom starosti ločena genetska entiteta in je neodzivnost pogojena z drugimi procesi, npr. s primarno imunsko pomanjkljivostjo.
Analiza bioloških podatkov na ravni DNA in RNA ter maščobnih kislin ni pokazala biološkega označevalca, ki bi dosegel statistično značilnost, kar odraža tudi analiza napovedne moči s pristopi strojnega učenja. Profili maščobnih kislin nimajo napovedne moči za določevanje odziva na zaviralce dejavnika tumorske nekroze, genomski in transkripromski podatki pa imajo le nizko napovedno moč. Napovedni model na osnovi že objavljenega modela izražanja genov v črevesni sluznici smo uspešno ponovili in prenesli na drugo učinkovino (adalimumab). Na osnovi izražanja štirih genov v vneti in nevneti črevesni sluznici je možno napovedati odziv na zaviralce dejavnika tumorske nekroze s natančnostjo do 100 %. Nato smo še analizirali diagnostično napovedno moč bioloških podatkov s vključitvijo bioloških podatkov zdravih prostovoljcev, ki so že bili na voljo. Napovedni model na osnovi dednega zapisa in profilov maščobnih kislin je z natančnostjo do 100 % ločil med zdravimi prostovoljci in bolniki s Crohnovo boleznijo.
Keywords: Crohnova bolezen, genomika, transkriptomika, adalimumab, izid zdravljenja, genska ontologija
Published in DKUM: 20.01.2021; Views: 1462; Downloads: 156
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9. Vloga endoskopskega ultrazvoka in protivnetnih citokinov pri pojasnitvi etiologije in potekaakutnega pankreatittisaDavorin Ćeranić, 2019, doctoral dissertation Abstract: Izhodišča in namen raziskave
Akutni pankreatitis (AP) je akutno vnetje tkiva trebušne slinavke. Prizadene tako bližnje kot oddaljene organe, lahko poteka kot blago vnetje ali kot hudo, z zapleti, ko je potrebno intenzivno zdravljenje. Namen raziskave je bil opredeliti etiologijo obolenja s slikovnimi metodami, vključno z endosonografijo, napovedati potek bolezni z vnetnimi pokazatelji, določitvijo interlevkinov (IL) IL-6, IL-8, IL-10 ter uporabo napovednih točkovnih sistemov.
Bolniki in metode
V raziskavo smo vključili bolnike, ki smo jih zdravili zaradi akutnega vnetja trebušne slinavke v obdobju od maja 2012 do januarja 2015 in so izpolnjevali vključitvene kriterije: značilno klinično sliko, trikratni porast aktivnosti serumske amilaze/lipaze in/ali potrditev s slikovnimi preiskavami. Raziskavo je odobrila Komisija Republike Slovenije za medicinsko etiko (št. 36/11/09). Bolnikom smo v prvih 24-tih urah po sprejemu in nato čez 48 ur odvzeli dodatne krvne vzorce za določitev interlevkinov ter razširjene laboratorijske preiskave. Zdravljenje je potekalo v skladu s smernicami in priporočili slovenskega gastroenterološkega združenja ter mednarodnih zdravniških združenj (ESGE, AGA). Opravljena je bila statistična analiza in inteligentna analiza podatkov s tvorjenjem napovednega modela.
Rezultati
V končno analizo smo uvrstili 117 bolnikov, prevladovali so moški, v 59 % (69/117), žensk pa je bilo 41 % (48/117). Povprečna starost bolnikov je bila 62,5 let, v razponu 22-91 let, SD 15,4 let. Žolčni kamni so bili najpogostejši vzrok za akutni pankreatitis, v 56 %; alkohol v 33 % in v 14 % ostali vzroki. Po Ransonovem točkovanju in BISAP lestvici je večina bolnikov (81 %) sodila v skupino z blagim potekom vnetja, pri ostalih (19 %) pa je bil potek težji. Le trije bolniki, 2,5 % (3/117) so umrli zaradi večorganske odpovedi. Razvoj psevdociste smo potrdili pri 11 % bolnikov. Pred ERCP smo vsem bolnikom endosonografsko potrdili holedoholitiazo. V analizi smo ugotavljali največjo napovedno vrednost IL-6 ob sprejemu AUC 0.782, pri mejni vrednosti IL-6=70.05 je občutljivost 0.80 in specifičnost 0.701, ob kontroli je AUC 0.835, pri mejni vrednosti IL-6=35.1 je občutljivost 0.867 in specifičnost 0.75. Ob primerjavi količnika IL-6/IL-10 ob sprejemu, in količnika IL-6/IL-10 ob kontroli, ima višjo napovedno vrednost količnik ob kontroli, AUC=0.789. Pri mejni vrednosti količnika 7.2, je občutljivost 0.667 in specifičnost 0.663.
Zaključek
Kljub sodobnim postopkom zdravljenja, imajo bolniki s hudo potekajočim AP, še vedno pomembno število zapletov. Žolčni kamni in alkohol sta najpogostejši vzroka AP v skupini naših bolnikov. V naši raziskavi smo potrdili vrednost določanja IL-6, IL-8 in IL-10 ob sprejemu in kontroli za napoved poteka bolezni, endosonografija pa je učinkovita slikovna metoda za pojasnitev etiologije. Z napovednimi modeli lažje napovemo potek AP, še posebej ob podpori s sodobnimi laboratorijskimi metodami in endoskopsko-radiološkimi slikovnimi preiskavami.
Keywords: akutni pankreatitis, vnetni pokazatelji, prognoza z napovednim modelom, provnetni in protivnetni interlevkini, endosonografija
Published in DKUM: 14.01.2020; Views: 1463; Downloads: 194
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