AIM The aim of this study was to evaluate the impact of hospital antibiotic consumption on the rate of antimicrobial resistance (AMR) of gram-negative bacteria, specifically the Enterobacteriaceae family and the genus Acinetobacter, in the University Clinical Center (UCC) Tuzla, Bosnia and Herzegovina. METHODS A five-year retrospective, observational, pharmacoepidemiological study was conducted (2014 to 2018). Antibiotic consumption was calculated using the WHO Anatomical Therapeutic Chemical/defined daily dose (ATC/DDD) methodology and expressed as DDD per 100 bed-days (BD). Microbiological data were obtained for Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, and Acinetobacter species. The temporal associations between consumption and resistance were analyzed using linear regression and autoregressive integrated moving average (ARIMA) models. RESULTS The total antibiotic consumption at UCC Tuzla significantly increased from 61.35 to 73.51 DDD/100 BD (p=0.003). Consumption in intensive care units (ICUs) was significantly higher than the hospital-wide average (p<0.001), reaching up to 178.53 DDD/100 BD. ARIMA modeling confirmed significant positive correlations between the use of fluoroquinolones (J01MA) and resistance in Acinetobacter baumannii (beta = 7.678, p=0.006) and K. pneumoniae (beta = 18.368, p<0.001)9. A similar correlation was found for carbapenems (J01DD) and E. coli resistance (beta = 14.066, p=0.004). CONCLUSION The study demonstrates a significant temporal association between the volume of broad-spectrum antibiotic consumption and the escalation of AMR. The high selective pressure in ICUs identifies these units as primary reservoirs for multidrug-resistant pathogens. These findings highlight the importance of multidisciplinary antimicrobial stewardship programs and restricted use of reserve antibiotics to preserve therapeutic efficacy.

Objectives The COVID-19-associated hyperinflammatory syndrome (cHIS) score has been proposed as a tool for identifying patients at risk of clinical deterioration. This study evaluated the predictive accuracy of the admission cHIS score for invasive mechanical ventilation and ICU mortality in critically ill COVID-19 patients. Methods We conducted a single-center retrospective observational study including 85 adults with laboratory-confirmed COVID-19 who were admitted to the ICU. The cHIS score was calculated on admission, and patients were stratified into two groups (<3 and ≥3). Associations with mechanical ventilation and ICU mortality were examined using ROC curve analysis and multivariable logistic regression, adjusted for age and comorbidity burden. Results An admission cHIS score ≥3 demonstrated moderate discrimination for ICU mortality (AUROC = 0.70; sensitivity = 0.76; specificity = 0.66) and mechanical ventilation (AUROC = 0.71; sensitivity = 0.73; specificity = 0.65). Higher cHIS scores were significantly associated with both outcomes in unadjusted analyses. After adjustment, the associations were attenuated and became borderline for mortality and mechanical ventilation, suggesting potential confounding by age and underlying comorbidities. Key inflammatory markers within the cHIS score—CRP, LDH, and D-dimer—showed the strongest individual associations with adverse outcomes. Kaplan–Meier analysis demonstrated significantly reduced survival probabilities in patients with cHIS ≥3. Conclusion The admission cHIS score reflects the degree of systemic hyperinflammation and is associated with greater illness severity, ICU mortality, and the need for mechanical ventilation. Although its predictive value diminishes after adjusting for age and comorbidities, the score remains a useful adjunct for early risk stratification in critically ill COVID-19 patients. Larger multicenter studies are needed to determine its independent prognostic utility.

BACKGROUND One Class Modelling (CM) is popular among chemometricians, but not well known among omics scientists in general. One issue is that typical CM approaches, including SIMCA, often result in unsatisfactory results due to e.g. large variation, centring and scaling issues, sparsity, outliers, and non-linearities in typical omics data. These effects can cause an inflated decision boundary (of the target class), thereby returning many false positives (of non-target cases). Tree-based techniques are by nature resistant to these challenges. In this study we explore tree-Based SIMCA variants in omics scenarios and compare to existing strategies. RESULTS We present a non-linear form of SIMCA by making use of sample proximities obtained through Unsupervised Random Forest and Isolation Forest (termed URF-SIMCA and IF-SIMCA). We compare accuracy of the algorithms with (traditional) SIMCA, one-class support vector machines, and isolation forest. This comparison was based on five (previously published) clinical omics datasets and the wine-dataset. URF-SIMCA showed superior behaviour. Using the pseudo-sampling principles, an interpretation could be made on the important features for the separation between the target and non-target classes. Using the wine-dataset, we empirically show that these directly relate to information obtained through two-class algorithms. Moreover, feature trajectories in the score- and orthogonal distance spaces further enable interpretability of the model. SIGNIFICANCE URF-SIMCA offers an easy to use extension of SIMCA, which deflates the variance of the target class, allowing for better separation. The increased modelling performance comes at the cost of feature interpretation, but this can be tackled using the pseudo-sampling principle.

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disorder that typically affects young adults and is primarily characterized by demyelinating lesions in the central nervous system (CNS). According to the Revised McDonald Criteria, the clinical diagnosis of MS can be established based on a combination of clinical observations, the presence of focal lesions in at least two distinct CNS areas on magnetic resonance imaging (MRI) and the detection of specific oligoclonal bands in the cerebrospinal fluid. Conventional MRI remains a cornerstone of MS diagnosis and disease monitoring, providing high-resolution assessments of lesion burden and brain atrophy. In addition, advanced MRI methods are increasingly applied in research settings to probe myelin integrity, iron deposition, and biochemical changes, with the potential to complement established diagnostic workflows in the future. Despite remarkable advances in the management of MS over the past two decades, complex differential diagnoses and the lack of effective imaging tools for therapy monitoring remain major obstacles, thus channeling the development of innovative molecular imaging probes that can be harnessed in clinical practice. Indeed, positron emission tomography (PET) has a significant potential to advance the contemporary diagnosis and management of MS. Given the solid body of evidence implicating myelin dysfunction in the pathophysiology of MS, myelin-targeted imaging probes have been developed, and are currently under clinical evaluation for MS diagnosis and therapy monitoring. In parallel, ligands for the 18 kDa translocator protein (TSPO) and the cannabinoid receptor type 2 (CB2R) have been employed to capture neuroinflammatory processes by visualizing microglial activation, while other tracers allow the assessment of synaptic integrity across various disease stages of MS. Further, PET probes have been employed to delineate the role of activated microglia and facilitate the assessment of synaptic dysfunction across all disease stages of MS. This review discusses the challenges and opportunities of translational molecular imaging by highlighting key molecular concepts that are currently leveraged for diagnostic imaging, patient stratification, therapy monitoring and drug development in MS. Moreover, we shed light on potential future developments that hold promise to advance our understanding of MS pathophysiology, with the ultimate goal to provide the best possible patient care for every individual MS patient.

Type 1 conventional dendritic cells (cDC1s) acquire and cross-present tumor antigens to prime CD8⁺ T cells. Whether this selects for specific neoantigens is unclear. DNGR-1 (CLEC9A), a cDC1 receptor for F-actin exposed on dead cells, promotes cross-presentation of cell-associated antigens. Here we show that DNGR-1-deficient mice develop chemically induced tumors more rapidly and at higher incidence, and these are more frequently rejected on transplantation into wild-type recipients. Whole-exome sequencing reveals enrichment of predicted neoantigens derived from mutated F-actin-binding proteins. Consistent with this observation, tethering model antigens to F-actin enhances DNGR-1-dependent cross-presentation. These results suggest that DNGR-1-mediated recognition of F-actin exposed by dead cancer cells favors priming of CD8⁺ T cells specific for cytoskeletal neoantigens, which can then drive immune escape of cancer cells lacking or reverting those mutations. Thus, neoantigen cross-presentation by cDC1 can determine the immune visibility of the tumor mutational landscape and sculpt cancer evolution by immunoediting. Here the authors show DNGR-1 expressed by cDC1s promotes CD8⁺ T cell priming to cytoskeletal neoantigens from dying tumor cells, thereby shaping cancer immune visibility and tumor evolution through immunoediting.

Introduction/Objective. Urinary tract infections (UTIs) in children represent a significant public health problem due to their high prevalence and the need for timely diagnosis and adequate treatment. Automated methods using fluorescent flow cytometry are increasingly being used in laboratories for the screening of UTIs. The aim of this study was to determine the cut-off values for leukocyturia and bacteriuria using fluorescent flow cytometry for the screening of urinary tract infections in the pediatric population. Methods. A total of 821 urine samples were cultured, of which 366 samples met the criteria for fluorescent flow cytometry on the automated Sysmex UF-4,000 analyzer. The number of leukocytes and bacteria was compared with the culture results. Results. Of the total urine cultures tested, 209 (25.5%) were positive, and 599 (73%) were negative. There was a statistically significant difference in the prevalence of uropathogens according to the age of the children (p < 0.001). The area under the curve (AUC) for leukocyte count was 0.77 (95% CI: 0.71-0.84), while the AUC for bacterial count was 0.85 (95% CI: 0.81-0.89). A low negative likelihood ratio (0) was observed at the cut-off for bacteria of 40.1, and the negative predictive value was high (between 91% and 99%). Conclusion. Determination of leukocyte and bacterial counts in urine in children using fluorescent flow cytometry can serve as an initial test when deciding on urine culture in microbiological laboratories. These results may indicate the necessity of reducing unnecessary urine cultures while providing faster confirmation of negative test results.

In this paper, the physical layer secrecy performance of the classical Wyner wiretap channel with gamma-shadowed two-wave with diffuse power (GS-TWDP) composite fading is investigated. A closed-form expression for the average secrecy capacity (ASC) is derived, assuming that the transmitter dynamically adapts its transmission rate based on the available channel state information (CSI) of both the legitimate receiver and the eavesdropper. The derived expression is validated through Monte Carlo simulations and used to conduct a detailed analysis of the impact of shadowing and multipath severity on ASC. To further enhance secrecy performance in GS-TWDP fading environments, an optimal power allocation strategy is also designed and integrated with rate adaptation. The resulting secrecy performance is compared to that achieved using only rate adaptation, providing insight into the effectiveness of the joint power/rate adaptation strategy under varying composite fading conditions.

Background: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, and abrupt discontinuation can lead to severe neuropsychiatric destabilization, including withdrawal catatonia. High-potency dopamine D2 receptor antagonists may further precipitate neuroleptic malignant syndrome (NMS), a condition with substantial clinical overlap with malignant catatonia. Objective: This report follows CARE guidelines to provide a structured and transparent description of a complex case involving abrupt clozapine withdrawal and rapid antipsychotic transition. Case presentation: This report describes a male patient with schizophrenia who developed malignant catatonia with overlapping NMS features following abrupt clozapine withdrawal and initiation of fluphenazine. Conclusion: The case underscores the importance of cautious antipsychotic transitions and early recognition of catatonia and NMS.

Background/Aim: Selecting appropriately sized maxillary anterior teeth is of great importance for achieving satisfactory outcomes in complete denture therapy. When pre-extraction records are unavailable, clinicians use recommended anatomical landmarks for this purpose. Predictive value of these parameters in previous studies was inconsistent. The aim of this study was to assess sex-specific associations between selected hard palate measurements and the mesiodistal width of maxillary anterior teeth (ATW) in an adult Bosnian-Herzegovinian population. Materials and Methods: This retrospective cross-sectional study used 180 maxillary casts (114 women, 66 men). Recorded palatal dimensions included hamular distance, hard palate length, and distances from the incisive papilla to the right and left hamular notches. The mesiodistal width of the six maxillary anterior teeth was summed to obtain ATW. Sex differences were assessed using independent-samples and paired-samples t-tests. Associations between palatal measurements and ATW were evaluated using simple and multiple linear regression (α=0.05). Results: Men had higher mean values for almost all palatal and dental variables, with no significant difference observed for the left lateral incisor (p=0.155). ATW was significantly greater in men compared with women (t=3.96, p<0.001). Papilla-hamular notch distances (p=0.002) were significantly associated with ATW in men, while all palatal measurements showed significant simple correlations (p≤0.002) with ATW in women. In multiple regression, no palatal dimension remained independently predictive in men (R²=0.173, p=0.019), while hamular distance was the only significant predictor in women (β=0.219, p=0.020; R²=0.169, p<0.001). Conclusions: Hard palate measurements show sex-specific relationships with the width of maxillary anterior teeth. Although several dimensions have significant associations with ATW, their predictive value is modest. Therefore, these parameters may serve only as supportive guides when selecting artificial teeth.

Background: Chronic periodontitis is a biofilm-induced inflammatory disease leading to progressive destruction of periodontal supporting tissues. Mechanical debridement by scaling and root planing (SRP) remains the gold standard of therapy; however, complete elimination of pathogenic microorganisms from deep periodontal pockets is challenging. Adjunctive laser therapy has been proposed to enhance clinical outcomes. Objective: To compare the clinical effectiveness of two diode laser wavelengths (980 nm and 445 nm) as adjuncts to subgingival curettage/SRP in the treatment of periodontal pockets, and to evaluate their outcomes relative to SRP alone. Materials and Methods: Comparative analysis of two independent prospective studies with identical methodology were analyzed. The first study included 24 subjects (1,164 periodontal pockets) treated with SRP + 980 nm diode laser (SmilePro 980, Biolitec, Germany). The second study included a same number of subjects and a comparable number of periodontal pockets were treated (862 periodontal pockets) with SRP + 445 nm diode laser (SiroLaser Blue, Dentsply Sirona, Germany). Control groups received SRP alone. Clinical parameters included Plaque Index (PI), Gingival Index (GI), Bleeding on Probing (BOP), Probing Pocket Depth (PPD), and Clinical Attachment Level (CAL), assessed at baseline and 1 month post-therapy. Results: Both laser groups demonstrated statistically significant reductions in PI, GI, BOP, and PPD compared with baseline (p < 0.05). When compared to SRP alone, both adjunctive laser therapies showed significantly greater improvement in PPD reduction and CAL gain (p < 0.05). No statistically significant difference was observed between the 980 nm and 445 nm laser groups in overall clinical outcomes (p > 0.05). Conclusion: Both diode laser wavelengths (980 nm and 445 nm) significantly enhance short-term clinical outcomes when used adjunctively with SRP compared to SRP alone. No clear superiority of one wavelength over the other was demonstrated under the applied clinical conditions.

Objective: Ergonomics in dental practice plays a crucial role in maintaining professional health, as prolonged static postures and repetitive movements significantly increase the risk of work-related musculoskeletal disorders among dental professionals. Understanding ergonomic risk factors and their impact on musculoskeletal health is essential for identifying vulnerable groups and developing effective preventive strategies in dental practice. Aim: The aim of this study was to assess the occurrence of musculoskeletal pain as a manifestation of work-related musculoskeletal disorders among dentists and to analyze its association with demographic characteristics, work habits, and dental specialization. Materials and Methods: This cross-sectional study included 130 dentists from various dental specialties. Data were collected using a structured questionnaire addressing demographic variables, work habits, ergonomic conditions, and the presence of musculoskeletal pain. Descriptive statistical methods were applied, and chi-square tests were used to analyze associations between categorical variables, with statistical significance set at p < 0.05. Results: The results indicated that the majority of participants experienced work-related musculoskeletal disorders, with prevalence increasing with age and length of professional experience. Occupational factors such as prolonged sitting or standing, improper working posture, lack of ergonomic chairs, and insufficient physical activity were significantly associated with the occurrence of work-related musculoskeletal disorders (p < 0.05). A statistically significant association was also observed between dental specialty and the presence of work-related musculoskeletal disorders (χ²(9) = 25.83; p < 0.01). The highest prevalence was reported among specialists in prosthodontics, pediatric dentistry, orthodontics, and endodontics, while lower prevalence was observed among oral surgeons, general dental practitioners, and periodontists. Conclusion: These findings emphasize the importance of implementing ergonomic interventions, regular physical activity, and preventive strategies in dental practice to reduce the occupational risk of work-related musculoskeletal disorders.

Background: Lyme borreliosis/European borreliosis (LB/EB) is a multisystemic infection caused by the bacterium Borrelia burgdorferi, which is transmitted to humans by the bite of ticks and other hematophagous insects. Transmitted borrelia can occupy any organ where it causes a silent inflammation, which in sensitive persons is intermittently repeated chronically. Objective: The aim of this paper was to determine how much Borrelia burgdorferii participates in the occurrence of chronic urticaria in children and adults. Methods: In the 13-year period from January 1, 2013 to December 31, 2025, a study of all manifestations of Lyme borreliosis was conducted on a sample of 1,059 patients, treated and monitored in the Private practice of an infectious disease specialist. The research was retrospective-prospective, descriptive, clinical and analytical. It was carried out in three phases: the first retrospective phase and the second two prospective phases. The diagnosis of LB was established on the basis of anamnestic-epidemiological data, clinical picture, clinical findings of new borreliosis markers and performed examinations. Serological confirmation of borreliosis was done using ELISA, WB and Immunoblot methods, as well as the ex-yuvantibus method, and in the last six months of 2025, additionally, the finding of bacteria Borreliosis in a dark field with a light microscope. Results: The results showed that 92.1% of the patients in the study group had intermittent migratory redness with itching. In the majority of patients, redness was without exudation or with little or no exudation. In 4.8% of patients, typical urticarial changes were found that occurred occasionally or daily. In all subjects, we serologically confirmed the presence of Borrelia burgdorferi. All patients had intermittent itching of the skin, which lasted for years. Conclusion: Based on the results, it can be concluded that Borrelia burgdorfrii is one of the most important factors in the development of chronic urticaria in monitored patients with 96.9%. Due to its persistence in the macroorganism, it causes reduced tolerance to food. Only 3.1% of cases of urticaria are caused by some other factors. In all cases of chronic urticaria, new clinical markers should be sought on the patients’ skin. Serologically look for antibodies to Borrelia protein sequences in an immunoblot. In the active phase, look for Borrelia with a light microscope in the dark field. Administer antibiotic therapy together with antihistamines. Exclude food to which the intolerance test confirmed hypersensitivity greater than „2“.

The effectiveness of red light therapy (RLT) on cellular activity is important in determining if its usage is suitable for the treatment of various health conditions. In order to better understand the molecular and metabolic mechanisms related to RLT, our preliminary study of the effect of LED light sources 660 nm and 850 nm on the proliferation of human lymphocyte cells was further extended to analyze its effect on the synthesis of cellular enzymes. Using the Bradford method, the total concentration of proteins in lymphocytes was monitored for different time parameters and conditions of exposure and in relation to the untreated (non-irradiated) control cells. Our results show a higher protein concentration for all irradiated samples when compared to the unirradiated samples and it was especially increased for multiple exposures to red/infrared light. Since the used method cannot answer whether the increased protein concentration has positive or negative connotations, it is important to continue the research and include additional methods that test oxidative stress and the structure of chromosomes on a larger number of samples in order to gain additional understanding of the beneficial impact of RLT on lymphocyte cells.