The advent of immunotherapy in the treatment of cancer has opened a new dimension in the management of this complex multifaceted disease, bringing hope to many patients whose tumors have failed to respond to conventional therapies. The adoptive T cell therapy has since been extended to the treatment of several hematologic malignancies, initially in relapsed settings and more recently at the forefront of treatment due to high response rates. Despite exciting initial results, the preclinical antitumor effects of the first long-term studies show that CAR (Chimeric Antigen Receptor)-T cells have been slow to translate to the clinical setting, with early clinical trials showing suboptimal responses. The main reasons for the limited clinical performance seemed to be related to the low activation and short persistence of CAR-T cells. Thus, began a journey to improve the initial CAR structure, leading to the development of more complex constructs, which are grouped into five CAR generations. In this review, we describe the main challenges and potential solutions for the evaluation of CAR T-cell-based therapies in the preclinical setting.

BACKGROUND The strategy for controlling campylobacteriosis includes implementing a Hazard Analysis and Critical Control Point (HACCP) system and preventing cross-contamination of chicken meat in slaughterhouses and production facilities. For this reason, this study began with the assumption that mechanical cleaning of work surfaces in slaughterhouses can improve the effectiveness of even less effective disinfectants. Therefore, the aim of this study was to examine the effectiveness of applying the same sanitation procedure and measures to reduce Campylobacter spp., in facilities with and without HACCP for the purpose of testing the potential of 6% domestic vinegar, which is known to have mild antiseptic properties, is used in the household and is not harmful to the environment. RESULTS The study includes a total of 200 samples, 100 surface swabs and 100 hand swabs of workers from two slaughterhouses. Isolation of Campylobacter species was performed according to ISO 10272-2:2017 and identification (real-time polymerase chain reaction). The impact of sanitation on the reduction of Campylobacter jejuni and C. coli was analyzed (ISO 6887-2:2017). Campylobacter jejuni and C. coli were isolated from work surfaces. Sanitation measures reduced the number of Campylobacter species colonies on surfaces (facility B), before sanitation (average ~1741 ± 902 CFU cm-2), and after sanitation (average ~994 ± 535 CFU cm-2). After sanitation, the number of positive swabs did not decrease, but a decrease in the number of Campylobacter spp. colonies was found (average ~747 ± 965 CFU cm-2 or 42.9%). CONCLUSION After sanitizing all work surfaces using the same sanitizing procedure including acetic acid, there was a reduction in the number of Campylobacter spp., which indicates the effectiveness of the sanitizing procedure, but that sanitation must be done more frequently. © 2025 Society of Chemical Industry.

Human teaching effort is a significant bottleneck for the broader applicability of interactive imitation learning. To reduce the number of required queries, existing methods employ active learning to query the human teacher only in uncertain, risky, or novel situations. However, during these queries, the novice's planned actions are not utilized despite containing valuable information, such as the novice's capabilities, as well as corresponding uncertainty levels. To this end, we allow the novice to say:"I plan to do this, but I am uncertain."We introduce the Active Skill-level Data Aggregation (ASkDAgger) framework, which leverages teacher feedback on the novice plan in three key ways: (1) S-Aware Gating (SAG): Adjusts the gating threshold to track sensitivity, specificity, or a minimum success rate; (2) Foresight Interactive Experience Replay (FIER), which recasts valid and relabeled novice action plans into demonstrations; and (3) Prioritized Interactive Experience Replay (PIER), which prioritizes replay based on uncertainty, novice success, and demonstration age. Together, these components balance query frequency with failure incidence, reduce the number of required demonstration annotations, improve generalization, and speed up adaptation to changing domains. We validate the effectiveness of ASkDAgger through language-conditioned manipulation tasks in both simulation and real-world environments. Code, data, and videos are available at https://askdagger.github.io.

AIMS Differentiated or HPV-independent vulvar intraepithelial neoplasia (dVIN) can progress rapidly to invasive cancer and accurate pathological diagnosis is essential to facilitate appropriate interventions. Histological similarities of dVIN with non-neoplastic lesions, however, often make the diagnosis less reproducible. We investigated among a diverse group of pathologists whether the diagnostic agreement improves with the use of p53 immunohistochemistry (IHC) interpreted using the pattern-based schema. METHODS AND RESULTS Fifty haematoxylin-eosin (HE) stained archival slides (30 dVIN and 20 non-dysplastic vulvar lesions) were selected and p53-IHC was performed. Twenty-four board-certified pathologists from eight countries first assessed the HE slides alone, and after a washout period, re-evaluated them alongside the p53-IHC slides. During both rounds, slides were diagnosed as dVIN, favour dVIN, favour no-VIN or no-VIN. p53-IHC was scored as wild-type or mutant (diffuse, basal, cytoplasmic or null). Kappa (κ) statistics and McNemar's test were used for statistical analyses. Overall diagnostic agreement for dVIN saw a significant increase in the Kappa value (κ = 0.6 vs. κ = 0.4, P = 0.002) when HE and p53-IHC slides were assessed together compared with histology assessment alone, although the level of agreement remained moderate. For p53-IHC assessment, overall agreement was substantial (κ = 0.7). Diagnoses changing from no-VIN/favour no-VIN to dVIN correlated significantly with the identification of a p53-mutant pattern (P < 0.001). CONCLUSIONS Our findings indicate that p53-IHC is a robust ancillary tool that can be reproducibly interpreted by pathologists with varying experience levels and supports the routine use of p53-IHC in cases where dVIN is considered in the differential diagnosis.

<p><strong>Aim</strong> Any aesthetic procedure in the head and/or in the face might have an impact on psychological status of the treated participants. Aim of this study was<strong> </strong>to investigate whether Botulinum toxin treatment for aesthetic purpose in the face influences on the level of happiness, depression and anxiety.</p> <p><strong>Methods</strong> This prospective cohort observational study included 30 participants, who were treated by botulinum toxin (Botox) due to aesthetic corrections. The treatment included laugh lines, frown lines and horizontal forehead lines. Preprocedural, three and six months after the treatment the participants were assessed by The Oxford Happiness Questionnaire (OHQ), The Beck Depression Inventory (BDI) and The Beck Anxiety Inventory (BAI) to determine the level of happiness, anxiety and depression was used.</p> <p><strong>Results</strong> Three months after the treatment by Botox the level of happiness was significantly increased (5.26&plusmn;0.43 vs 4.3&plusmn;0.34; p&lt;0.0001). The levels of depression (7.6&plusmn;6.0 vs 14.2&plusmn;8.3; p&lt;0.0001) and anxiety (8.8&plusmn;6.3 vs 16.4&plusmn;8.8; p&lt;0.0001) were significantly decreased compared with preprocedural level. Significant increased level of happiness and decreased levels of depression and anxiety remained six months after the treatment, but attenuated. A dose of applied botulinum toxin was negatively correlated with the level of depression (r = -0.394; p=0.0421) and anxiety (r = -0.387; p=0.0302).</p> <p><strong>Conclusion </strong>Botulinum toxin treatment for aesthetic purpose in the face positively influences psychological status of the treated individual in the short-therm.</p>

Aim This study compared the extent of coronary artery calcification in patients with and without type 2 diabetes mellitus (T2DM) using Coronary Computed Tomography Angiography (CCTA). Methods This retrospective, observational cohort study included 107 patients who underwent CCTA at the Clinical Centre of the University of Sarajevo between July and December 2024. Patients were divided into two groups: those with T2DM (n=51) and those without T2DM (n=56). Laboratory parameters, demographic data, and calcium scores were analysed. The calcium score was categorised into six groups based on cardiovascular risk and the comparison was made using appropriate statistical analysis. Results Patients with T2DM had significantly higher calcium scores than non-diabetic patients (p=0.0001). In the T2DM group, 35.3% of patients had a calcium score >400, indicating high cardiovascular risk. Patients without diabetes were more frequently classified into lower-risk categories (p=0.0001). A significant correlation was found between calcium score and age (r=0.442, p=0.001) and gender (r=-0.218, p=0.024), with men having higher calcium scores. Additionally, total cholesterol, LDL, and uric acid levels were significantly higher in diabetic patients (p=0.005; p=0.025; p=0.03, respectively). Conclusion This study confirms a strong association between T2DM and increased coronary artery calcification. Age and male gender are significant predictors of higher calcium scores. Further research is needed to explore these relationships, particularly within the Bosnian population. Keywords Coronary angiography, coronary artery calcification, coronary disease, diabetes mellitus type 2.

Aim To investigate the relationship between postoperative serum thyroglobulin level ​​and outcome of therapy with I-131 of follicular thyroid cancer. Methods A total of 106 patients with follicular thyroid cancer who were being treated and monitored at the Clinic for Nuclear Medicine at Clinical Center of the University of Sarajevo were included. The inclusion criteria were: surgery of total thyroidectomy, histopathological diagnosis of follicular thyroid cancer, and applied therapy with radioactive iodine. Exclusion criteria were patients with incomplete data, who were not treated with radioidine treatment, or had a different histopathological diagnosis. Postoperative serum thyroglobulin levels were correlated with results of whole body scintigraphies after 12 months (first diagnostic scintigraphy) and whole body scintigraphies after 24 months (second diagnostic scintigraphy). Results The higher frequency of recurrent disease in patients with elevated level of thyroglobulin was found compared to patients with lower postoperative thyroglobulin level. Elevated level ​​of postoperative thyroglobulin correlated with positive scintigraphy findings, i.e., with the occurrence of recurrence and/or metastases in patients with follicular cancer. The cut-off level of postoperative thyroglobulin for recurrence and/or metastasis, i.e. for failure of ablative therapy with I-131, was >12.6 ng/mL. Conclusion  Our study showed that level of postoperative thyroglobulin is an important prognostic factor for the outcome of radiodine therapy of follicular thyroid cancer and should be taken into account in deciding on therapy in this type of cancer in everyday practice Keywords: prognosis, radioiodine, thyroid neoplasm, recurrence.

Spondylosis deformans (SD) is a common form of degenerative spinal disease in dogs, characterized byosseous bridging between vertebral bodies. This study focused on the lumbar and lumbosacral regions ofthe spine and analyzed radiographic records of 35 dogs of various breeds and age groups over a 12-monthperiod. Computed tomography (CT) was selectively employed in cases where radiographic interpretationwas inconclusive. The objective was to determine lesion localization and assess associations with breed, age,and gender. Findings showed that German Shepherds were most frequently diagnosed with SD, followedby Labrador Retrievers and mixed-breed dogs. Age distribution indicated that no cases were observed indogs aged 1-2 years, while the highest prevalence occurred in the 7-10-year age group. Lesion localizationdata revealed that the L4-L6 region was most commonly affected. These results highlight the age-relatedprogression of SD and its predilection for the lumbar spine, offering valuable insights for clinical assessmentand management in veterinary practice.

BACKGROUND It has long been hypothesized that increasing heritability with age of cognitive and educational performance is partly attributable to evocative gene-environment correlation. However, this hypothesis has not been widely tested. METHODS We addressed this gap by examining whether children's education polygenic scores (PGSedu) were associated with maternal self-reported positive and literacy-focused parenting when children were 5 years old, and if evoked parenting differences mediated genetic effects on children's educational outcomes (mother-reported at 6-8 years of age), while controlling for parental PGSedu. We also investigated whether maternal reports of children's language at 5 years old were associated with parenting and mediated genetic effects on educational performance. These questions were addressed in a sample of 83,627 parent-offspring trios from the Norwegian Mother, Father and Child Cohort Study, a longitudinal population-based pregnancy cohort. RESULTS Children's PGSedu were significantly associated with maternal literacy-focused (β = .03, 95% CI [0.01, 0.05], p = .021) but not positive parenting (β = 0.01, 95% CI [-0.02, 0.05], p = .410), and literacy-focused parenting significantly mediated the effects of children's PGSedu on their educational performance (β = 0.01, 95% CI [1 × 10-3, 0.01], p = .023). Children's language was associated with maternal parenting and mediated the effects of children's PGSedu on their educational performance (β = 0.01, 95% CI [3 × 10-3, 0.02], p = .002). CONCLUSIONS These findings support our hypotheses and suggest early language and parenting may be mechanisms implicated in the pathways from children's genetics to their educational outcomes.

This study focuses on evaluating the antioxidant activity of pomegranate (lat. Punica granatum L.) peel extracts obtained through various extraction methods, including ultrasound-assisted extraction (UAE), Soxhlet extraction, and maceration, using methanol and 96% ethanol as solvents. These techniques were chosen for their differing effects on the preservation of thermosensitive phytochemicals. Antioxidant potential was assessed using the DPPH radical scavenging assay, with absorbance measured at 517 nm using a UV-Vis spectrophotometer. The results demonstrated that the efficiency of antioxidant activity largely depended on the extraction method and solvent used. A lower IC50 value indicates higher antioxidant activity, as it reflects a greater efficiency in neutralizing free radicals at a lower concentration. Extracts obtained by ultrasound-assisted extraction exhibited the highest radical scavenging capacity with an IC50 value of 19.049 μg/mL, while those obtained by Soxhlet extraction with ethanol showed comparatively weaker activity with an IC50 value of 34.210 μg/mL, likely due to the thermal degradation of sensitive bioactive compounds. The maceration method, although mild and solvent-efficient, yielded moderate antioxidant activity, highlighting the balance between extraction intensity and preservation of functional constituents. The study emphasizes the importance of optimizing extraction conditions to maximize the recovery of bioactive compounds from plant materials. Given the phytochemical richness and biological potential of pomegranate peel, the findings support its application as a natural source of antioxidants in the development of dermocosmetic and pharmaceutical formulations aimed at combating oxidative stress and disorders related to hyperpigmentation and skin aging.

Plant species with strong antioxidant activity used in traditional medicine of B&H-Sambucus nigra, Filipendula vulgaris, Helichrysum italicum, Epilobium angustifolium, Crataegus rhipidophylla, Thymus serpyllum, Vaccinium myrtillus, Symphytum officinale, Corylus avellana, and Rubus fruticosus-were analysed for their phenolic profiles and cholinesterase inhibitory activity. The HPLC-DAD analysis revealed the highest concentration of phenolic acids in S. officinale extract. Catechin, rutin, and quercetin were identified in the majority of extracts. Rutin was most abundant, especially in S. nigra flowers (9.39 mg/g DW). AChE and BChE inhibition was determined spectrophotometrically. All extracts showed activity, with AChE IC50 ranging from 0.08 mg/mL (V. myrtillus) to 8.31 mg/mL (H. italicum), and BChE from 5.35 mg/mL (T. serpyllum) to 13.26 mg/mL (C. rhipidophylla). These findings highlight the neuroprotective potential of B&H medicinal plants, with molecular docking showing phenolics like rosmarinic acid and rutin inhibit cholinesterases. Merging traditional medicinal knowledge and molecular insights offers a novel path for discovery.