Purpose In pancreatic ductal adenocarcinoma (PDAC), immune checkpoint inhibitors have shown limited efficacy, and the role of the TIGIT axis remains underexplored. This study aimed to characterize TIGIT axis components on protein level and their relationship to PD-1/PD-L1 expression in matched blood and tumor samples from PDAC patients to identify immunosuppressive mechanisms and fuel future strategies for immune checkpoint co-targeting in PDAC patients. Experimental design Fresh tumor and peripheral blood samples were collected from PDAC patients undergoing surgical resection. Flow cytometry was performed on tumor-infiltrating lymphocytes and PBMCs to assess expression of TIGIT, DNAM-1, TACTILE, and PD-1. Ligands CD111, CD112, CD113, and CD155 were analyzed using immunohistochemistry. Additional RNA expression analysis (TCGA/GTEx) was used to evaluate ligand distribution and gene expression profiles. Results TIGIT was highly upregulated on intratumoral CD8⁺ T cells and regulatory T cells, frequently co-expressed with PD-1. DNAM-1 expression was significantly reduced in tumors. However, contrasting pattern emerges with Tregs, which uniquely upregulate DNAM-1 in the PDAC TME. In addition, CD112 and CD155 were broadly expressed, including novel stromal CD112 localization. NK cells were nearly absent intratumorally, correlating with DNAM-1 downregulation. Conclusions Our findings identify TIGIT as a promising immunotherapeutic target in PDAC and suggest that dual checkpoint blockade (TIGIT/PD-1), alongside restoration of DNAM-1 signaling, may overcome immune suppression. These results provide mechanistic rationale to inform future clinical trials in PDAC. Supplementary Information The online version contains supplementary material available at 10.1007/s00262-026-04343-w.

Pristranost u citiranju literature ponajprije se odnosi na tendenciju citiranja pozitivnih i jasnih empirijskih rezultata i tvrdnji naspram onih negativnih i nejasnih. Iako je taj tip pristranosti opisan za različite literature, postoje pokazatelji koji ukazuju i na razlike u stupnju pristranosti među raznim disciplinama. Stoga je važno analizirati pristranosti u citiranju u specifičnim istraživačkim područjima. Cilj je ovoga rada bio istražiti pristranost u citiranju u komparativnoj psihologiji u području koje se bavi ispitivanjem fizičke kognicije životinja. Testirana je pristranost u citiranju radova objavljenih između 1994. i 2019. godine (ukupno 57 radova), uzimajući u obzir kategoriju kojoj je glavna tvrdnja iz izvornoga članka bila dodijeljena („pozitivna”, „negativna”, „nejasna”) i čimbenik odjeka časopisa u kojemu je članak objavljen. Ukupno je pronađen 2991 citirajući rad. Rezultati ukazuju na to da ne postoji jasan učinak kategorizacije glavne tvrdnje na stopu citiranosti, kao ni jasna uloga čimbenika odjeka časopisa kao medijatora. Ti rezultati upućuju na to da za to područje istraživanja u komparativnoj psihologiji ne postoji jasna pristranost u citiranosti radova koja se temelji na prirodi rezultata i tvrdnji.

Extant literature captures the benefits and risks concerning young adults’ use of digital technologies and platforms, but it does not unilaterally recognize the drivers of problematic digital behavior. Those drivers might differ across dimensions of young adults’ digital lives, their socioeconomic backgrounds, and other demographic determinants. In this study, we analyze the determinants of addictive digital behavior of economics and business students from a Southeast European (SEE) sample of 372 participants. We measure digital addictive behavior regarding Internet use, with a focus on mobile phones, using established psychological scales. Our results show that age is generally associated with lower problematic digital behavior (significant in the full sample), while female students report higher PRIUSS-3 scores than male students. Higher ICT proficiency is associated with lower PRIUSS-3 and MPPUS-10 scores. Daily screen time is associated with higher MPPUS-10 scores, but it does not significantly predict PRIUSS-3 in the multivariable model. The empirical results can be used to frame the higher education policies and targeted interventions in the SEE region.

In the present study, two types of graphene quantum dots (GQDs) were investigated: green-emitting (G-GQDs) and blue-emitting (B-GQDs). Physicochemical characterisation was performed using transmission electron microscopy (TEM), zeta potential, and hydrodynamic radius measurements to evaluate the morphology, particle size, aggregation behaviour, and colloidal stability of the GQDs in both water and cell culture medium. G-GQDs exhibited superior colloidal stability and more uniform dispersion than B-GQDs, whereas both types showed reduced aggregation and surface charge in cell culture medium due to protein corona formation. Toxicological characterisation was performed using an in vitro human hepatocellular carcinoma (HepG2) 3D spheroid model, with GQDs exposures up to 250 µg/mL (100 µg/cm2). Cytotoxicity was measured using the CellTiter-Glo luminometric assay, while genotoxicity was evaluated by the comet assay and flow cytometric analysis of γH2AX and phosphorylated histone H3 (p-H3) after 24 h of exposure. Both GQDs induced dose-dependent cytotoxic effects in HepG2 spheroids. At non-cytotoxic concentrations, a dose-dependent increase in DNA damage was observed, as determined by the comet assay. However, no evidence of DNA double-strand breaks (γH2AX) or elevated p-H3 levels was detected, suggesting the absence of clastogenic and aneugenic activity. The observed DNA single-strand breaks may be partly attributed to reactive oxygen species induction. These results indicate that, although GQDs induced cytotoxicity and single-strand DNA damage, no clear evidence of more severe genotoxic effects was observed under the tested conditions. Further studies are warranted to elucidate underlying mechanisms and comprehensively assess the safety profile of GQDs for biomedical applications.

Introduction: Type 2 diabetes mellitus (T2DM) is associated with a high burden of complications, most of which first present to primary care.Objective: To assess the prevalence and predictors of diabetes-related complications among patients seeking primary health care.Methods: This retrospective study analysed records of 1000 patients with T2DM in primary care. Demographic, clinical, and therapeutic variables were examined, and multivariate logistic regression was used to identify independent predictors of complications.Results: Majority of the patients (58.3%) had at least one complication. Neuropathy (41.8%), retinopathy (32.3%), and chronic coronary syndrome (CCS)(22.3%) were most frequent. Independent predictors for complications included older age, longer disease duration and higher HbA1c (p<0.001 for all). Neuropathy was significantly associated with female sex (p=0.016), while myocardial infarction and CCS showed significant association with male sex (p=0.027 and p=0.002 respectively). All complications were strongly associated with hospitalisations (all p<0.001), except for retinopathy. Family history independently predicted retinopathy (p=0.039) and CCS (p=0.014).Conclusion: Diabetes-related complications remain highly prevalent and are strongly linked to glycaemic control, disease duration, and age. Sex, and family history also shape complication patterns, while treatment modality reflects disease severity. These findings highlight the need for early, individualised management and implementation of guideline-based strategies to reduce complication burden and improve outcomes in frontline care.

ABSTRACT This study investigates the historical context and the creation process of the painting Tito and Our Revolution by Vojo Dimitrijevic, housed at the Historical Museum of Bosnia and Herzegovina, through the application of various instrumental examination techniques. The artwork represents an intriguing fusion of socialist themes with contemporary European artistic movements of the era. Additionally, conservation efforts were undertaken to preserve the damaged painting and reintroduce it to public attention. The materials used in the painting were analyzed through a combination of non-invasive (radiography, X-ray fluorescence spectroscopy) and invasive (Fourier- transform infrared spectroscopy, thin-layer chromatography, polarized light microscopy, scanning electron microscopy / energy dispersive spectroscopy) techniques. The analyses revealed an earlier, concealed composition beneath the visible painting, characterized by significantly different color choices and structural arrangement. Furthermore, the study sheds light on the true motivations behind the artwork and clarifies the conflicting narratives surrounding it. Radiography, stratigraphic, and elemental analyses confirmed not only the precise material characterization but allowed to better understand the materials and also the artist’s technical awareness and decision-making during his creative work. The findings were used to guide the conservation strategy, but also contributed to the re-evaluation of the painting as a work that transcends propaganda and embodies the personal expression of the artist.

Teaching quality is crucial for positive student outcomes, yet it can be limited by challenges in the classroom. In this study, we examine how teacher-reported limitations to teaching (e.g., student absenteeism, disruptive behavior, lack of engagement, language barriers) relate to student-reported teaching quality. We also explore whether teacher job satisfaction mediates this relationship. Using data from the Norwegian extension of the TIMSS 2019 Grade 9 student questionnaire, we assess three dimensions of teaching quality based on the three basic dimensions (TBD) framework. Results show that more frequent limitations to teaching are linked to lower student-reported quality. We find that more satisfied teachers deliver clearer instruction and achieve better classroom management. However, we find no evidence that limitations to teaching are associated with lower job satisfaction, nor that job satisfaction mediates the relationship between limitations and teaching quality. We discuss implications for teacher education and educational policymaking.

There are increasing calls for greater availability of plant genetic resources (PGR) for use in plant breeding to help counter the adverse impacts of a changing climate and threats from pests and diseases, particularly in a context of reduced agricultural inputs, and the needs of the increasing human population. Managing and promoting ex situ and in situ conservation of PGR requires an effective data and informatics foundation. However, in situ data management is particularly undeveloped, especially when compared to ex situ documentation. The work presented here is a consolidated descriptor list to support in situ conservation of PGR. The consolidated PGR descriptor list is based on numerous partial lists collated from historic PGR activities, biodiversity conservation and protected area networking activities. New descriptors for in situ conservation activities were developed where gaps were identified. The draft consolidated PGR descriptor list was reviewed and revised through a process of consultation with experts in PGR documentation and in situ conservation. In total, 171 descriptors were identified, of which seven are defined as mandatory, 47 are defined as core descriptors and 29 are newly developed descriptors for in situ conservation of PGR. The descriptors cover all aspects of in situ conservation, from gathering passport data (for which there are already well-established descriptors), to monitoring and managing crop wild relative and landrace populations. Recommendations are made for the most effective use and future development of descriptors and how they could be used to further develop and support in situ PGR conservation implementation.

There are increasing calls for greater availability of plant genetic resources (PGR) for use in plant breeding to help counter the adverse impacts of a changing climate and threats from pests and diseases, particularly in a context of reduced agricultural inputs, and the needs of the increasing human population. Managing and promoting ex situ and in situ conservation of PGR requires an effective data and informatics foundation. However, in situ data management is particularly undeveloped, especially when compared to ex situ documentation. The work presented here is a consolidated descriptor list to support in situ conservation of PGR. The consolidated PGR descriptor list is based on numerous partial lists collated from historic PGR activities, biodiversity conservation and protected area networking activities. New descriptors for in situ conservation activities were developed where gaps were identified. The draft consolidated PGR descriptor list was reviewed and revised through a process of consultation with experts in PGR documentation and in situ conservation. In total, 171 descriptors were identified, of which seven are defined as mandatory, 47 are defined as core descriptors and 29 are newly developed descriptors for in situ conservation of PGR. The descriptors cover all aspects of in situ conservation, from gathering passport data (for which there are already well-established descriptors), to monitoring and managing crop wild relative and landrace populations. Recommendations are made for the most effective use and future development of descriptors and how they could be used to further develop and support in situ PGR conservation implementation.

Caffeine (1,3,7-trimethylxanthine) is an alkaloid that acts as a stimulant on the central nervous system. Caffeine consumption brings a momentary increase in awareness and alertness in humans, as well as in experimental animals. The refluxing method and the regular coffee preparation method were used to extract caffeine from several coffee varieties that were sold in Bosnia. TLC and melting point analysis were performed before and after purification using vacuum sublimation. Chemical characterization of samples by FTIR (Fourier Transform Infrared Spectroscopy) analysis was performed by comparing with caffeine standard spectra. The percentage of extracted impure caffeine was higher in coffee samples obtained by the ordinary brewing method compared to reflux. After purification of crude extracts, all refluxed samples yielded more caffeine than those prepared by conventional brewing. In developed TLC chromatograms, Rf values of samples and standard match the literary Rf values of caffeine. Unprocessed caffeine samples showed a melting point from 185 to 216°C, corresponding to the range of 180 to 220°C, the melting point of crude caffeine. After vacuum sublimation, the melting point of all samples was between 235 and 237 °C, which corresponds to the literary values (235-239 °C for the “Merck” caffeine standard). Comparing the FTIR spectra of samples and standard, characteristic caffeine signals were observed confirming successful caffeine isolation. The caffeine content in the analyzed coffee samples from the Bosnia and Herzegovina market complies with FDA (Food and Drug Administration) regulations on the daily amount of caffeine intake per cup of coffee.