ABSTRACT Bioaugmentation, the process of soil restoration by introducing microorganisms capable of degrading pollutants, is a promising and cost-effective strategy for environmental remediation. Aromatic hydrocarbons, such as benzene, toluene, ethylbenzene, and p-xylene (BTEX), are highly toxic environmental contaminants that could be transformed to less harmful products through the inoculation of certain organisms capable of BTEX degradation. However, a barrier to successful bioaugmentation is the inoculant’s failure to establish within the resident microbial community. In an effort to improve inoculant proliferation, we have investigated phosphite as a phosphorus source for selective nutrient supply. Phosphite is an inaccessible form of phosphorus to organisms that lack the capacity for phosphite oxidation to phosphate. We introduced a phosphite dehydrogenase-coding gene (ptxD) into the genome of the toluene-degrading bacterium Pseudomonas veronii 1YdBTEX2 to couple phosphite metabolism and aromatic hydrocarbon clearance. When inoculated in either soil matrix or liquid soil extract, P. veronii proliferates in a phosphite- and toluene-dependent manner in both growing and stable synthetic soil microbial communities, although the selective effects of phosphite and toluene were not additive in a carbon-limited context. Once toluene is metabolized, P. veronii abundance decays, and the microbial community recovers diversity and abundance resembling the uninoculated controls. Additional members of the microbial community were also enriched in the presence of phosphite, and genomic analysis suggests that these microorganisms utilize an alkaline phosphatase, phoV, for phosphite assimilation. IMPORTANCE Bioaugmentation is a promising solution to soil contamination, but its practical application is limited due to poor inoculant establishment in the native soil community. This can often be attributed to low nutrient availability and resource competition with native microorganisms. We proposed the use of phosphite as a selective nutrient source to support the growth of a toluene-degrading bacterium, Pseudomonas veronii, in a model soil system. We engineered a strain of this organism that was capable of using phosphite as a phosphorus source and saw that phosphite application enhanced the abundance of the inoculant sixfold within a synthetic soil community. In this study, we present the first investigation of a phosphite selection system in the soil microbiome and characterize the environmental conditions in which it is effective. By demonstrating the potential of formulated nutritional niches in soil microbiome interventions, we provide significant insights into the field of microbiome engineering. Bioaugmentation is a promising solution to soil contamination, but its practical application is limited due to poor inoculant establishment in the native soil community. This can often be attributed to low nutrient availability and resource competition with native microorganisms. We proposed the use of phosphite as a selective nutrient source to support the growth of a toluene-degrading bacterium, Pseudomonas veronii, in a model soil system. We engineered a strain of this organism that was capable of using phosphite as a phosphorus source and saw that phosphite application enhanced the abundance of the inoculant sixfold within a synthetic soil community. In this study, we present the first investigation of a phosphite selection system in the soil microbiome and characterize the environmental conditions in which it is effective. By demonstrating the potential of formulated nutritional niches in soil microbiome interventions, we provide significant insights into the field of microbiome engineering.

Conformers have shown great results in speech processing due to their ability to capture both local and global interactions. In this work, we utilize a self-supervised contrastive learning framework to train conformer-based encoders that are capable of generating unique embeddings for small segments of audio, generalizing well to previously unseen data. We achieve state-of-the-art results for audio retrieval tasks while using only 3 seconds of audio to generate embeddings. Our models are almost completely immune to temporal misalignments and achieve state-of-the-art results in cases of other audio distortions such as noise, reverb or extreme temporal stretching. Code and models are made publicly available and the results are easy to reproduce as we train and test using popular and freely available datasets of different sizes.

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Background The concept of flipped classrooms (FCs) is gaining attention in medical education as it aligns with the digital age’s demand for more interactive and accessible learning experiences. By shifting the delivery of instructional content outside of the classroom, an FC allows students to engage with materials at their own pace, thereby maximizing in-class time for discussions, problem-solving, and other active learning activities. Objective This study aimed to conduct a comprehensive meta-analysis to appraise the comparative effectiveness of FC instruction in contrast to traditional pedagogical modalities, with a particular focus on postepidemic analyses within specific subfields of medical education. Methods The PubMed, Web of Science, and Scopus databases were systematically searched for studies comparing academic outcomes between the FC and traditional learning approaches in medical education. The primary outcome measures were knowledge assessment and students’ satisfaction. The standardized mean difference (SMD) was used as a measure of the overall effect, and subgroup analysis was performed according to the study design (randomized controlled trial [RCT] vs observational). The Cochran Q test and Baujat plots were used to estimate heterogeneity, coupled with I2. Highly influential studies were identified; sensitivity analyses and metaregression were performed. Results In total, 141 studies were included in the systematic review; 127 (90.1%) studies with 21,171 participants were included in the meta-analysis of students’ knowledge assessment, of which 37 (29.1%) were RCTs. FCs had significantly better outcomes than the traditional method in knowledge test scores in both observational studies and RCTs (SMD 0.90, 95% CI 0.59-1.20, P<.001 and SMD 0.93, 95% CI 0.65-1.22, P<.001, respectively). There was substantial heterogeneity among included studies (I2=95.2%, τ2=1.614; P<.001). The funnel plot showed high asymmetry with significant small study effects (P<.001). However, the effect estimate remained robust to the exclusion of highly influential studies in the sensitivity analysis. In total, 27 (21.3%) studies with a total of 5842 participants reported students’ satisfaction. Higher student satisfaction scores for FCs were demonstrated in contrast to control groups (SMD 0.82, 95% CI 0.45-1.19; P<.001). There was substantial heterogeneity among the included studies (I2=97.8%, τ2=0.913; P<.001) but no evidence for publication bias, and no studies were found to be influential. Conclusions The FC method is associated with better knowledge achievement and greater student satisfaction than the traditional approach in medical education, paving the way for its broader integration into medical school curricula. However, it is essential to consider various factors, such as the availability of resources, faculty readiness, and student preferences when implementing any new educational approach. This study holds promise for advancing medical education by exploring innovative teaching methodologies that leverage technology to enhance learning outcomes.

Internet of Things (IoT) devices are increasingly being deployed in critical applications, such as eHealth systems, enabled by advancements in 5G technology, which offer more than 100 Mbps of throughput, less than 5 ms of latency, and $99,999 \%$ of reliability. However, to overcome computing limitations and security measures, IoT devices rely on cloudbased solutions to outsource data processing. This dependency introduces significant security concerns, as sensitive data must be transmitted over the network and processed in external environments, increasing the risk of interception, unauthorized access, and data breaches. To mitigate these security risks, within the scope of the MOZAIK project, we deploy Network Slicing to ensure end-to-end inter-slice and intra-slice isolation across all network domains i.e., 5G Core (5GC), Transport Network (TN), and Radio Access Network (RAN). We deploy a synergy across the entire network infrastructure i.e., $5 \mathrm{GC}, \mathrm{TN}$, and RAN, to isolate the IoT data flows from the moment the data is generated until it reaches the cloud, safeguarding sensitive data during transmission. The results of our real-life experiments demonstrate that our proof of concept provides robust isolation between slices, effectively addressing the security concerns of IoT devices and enhancing the reliability and security of IoT applications. Additionally, we also include aspects of secure data storage and secure data processing, covered in the MOZAIK project.

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.