Background Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related disorders, but inappropriate or prolonged use carries potential health risks. Physicians, due to their access to medication and clinical knowledge, may be prone to self-medicating with PPIs without appropriate oversight. Objective To assess the prevalence and patterns of personal PPI use and self-medication among practicing physicians in Bosnia and Herzegovina, and to identify demographic and professional predictors of such behavior. Methods A cross-sectional, questionnaire-based survey was conducted among 448 physicians who responded to the study invitation, out of approximately 600 invited, from various healthcare levels in Bosnia and Herzegovina between January and May 2025. The survey collected data on PPI use history, consultation behavior, awareness of adverse effects, and adherence to treatment guidelines. Multivariable logistic regression was used to identify independent predictors of self-medication. Results A total of 65.4% of respondents reported past PPI use, during their medical practice, and 31.7% were current users. Over half (52.2%) admitted using PPIs without consulting another physician, and only 17.4% referred to clinical guidelines prior to use. Occasional use was the most common pattern (59.0%), while adverse effects were rarely reported (1.8%). No demographic or professional variable was significantly associated with self-medication with PPIs (defined as PPI use without consulting another physician) in the multivariable analysis. Conclusion Self-medication with PPIs is highly prevalent among physicians and frequently occurs without clinical consultation or adherence to guidelines. This behavior appears to be widespread across age groups, sexes, and care levels, highlighting the need for institutional interventions that promote rational prescribing and raise awareness about responsible self-care within the medical profession.

Severe hypoglycemia increases the risk of cardiovascular disease (CVD) in people with diabetes. Large cohort studies and scientific statements show that severe hypoglycemia is linked to higher rates of coronary heart disease, cardiovascular events, and mortality in both type 1 and type 2 diabetes. This risk is especially high in individuals with significant vascular risk, such as older adults and those with multiple cardiovascular risk factors. Hypoglycemia triggers several pathophysiological changes that increase cardiovascular risk. These include activation of the sympathoadrenal system, promotion of proinflammatory and prothrombotic states, arrhythmogenic changes, and increased hemodynamic stress. Experimental evidence shows that recurrent hypoglycemia worsens microvascular dysfunction and promotes adverse cardiac remodeling, especially in people with diabetes. While the link between hypoglycemia and cardiovascular events is well established, the causality remains debated. Hypoglycemia may directly contribute to cardiovascular disease or indicate underlying vulnerability, especially in patients with advanced disease or comorbidities. Minimizing hypoglycemic episodes is recommended for all patients with diabetes, particularly those with established cardiovascular disease, due to the clear association with adverse outcomes.

The automotive industry is undergoing a significant transformation towards electric vehicles (EVs) with the main goal of reducing greenhouse gas emissions and for a sustainable and green environment. Different types of EVs are introduced every day in the market where selecting an optimal vehicle for purchase constitutes a complex decision-making. Therefore, the purpose of this research was to evaluate EVs in Albania using multi-criteria decision-making methods (MCDM). A total of 12 vehicles were analyzed based on 4 main criteria and 12 sub-criteria. The fuzzy Logarithm Methodology of Additive Weights (LMAW) method was applied to find the weights of the main criteria while the fuzzy Logarithmic Percentage Change-driven Objective Weighting (LOPCOW) method was applied to find the weights of the sub-criteria. For the EV ranking, the fuzzy Ranking of Alternatives with Weights of Criterion (RAWEC) method was applied. The findings showed that the most important criteria are the technical criteria and the Auto 11 vehicle showed the best results. The combination of Fuzzy LMAW-Fuzzy LOPCOW-Fuzzy RAWEC methods also constitutes the novelty of this research, which has not been applied before in this field. The contribution of this research consists in providing a comprehensive set of selection criteria to choose the best alternative of the EV fleet in Albania. Furthermore, the contribution of this research was the application of a hybrid methodology in the evaluation and selection of an electric vehicle as an ongoing choice faced by vehicle buyers.

In sustainable portfolio management, categorizing assets as “brown“ or “green“ based solely on ESG ratings can be misleading. A positive ESG score does not inherently indicate environmental responsibility unless it is evaluated relative to a meaningful benchmark. We propose a rescaled ESG rating system that measures each asset’s environmental standing relative to a threshold set by policymakers, reflecting the urgency of the current climate crisis. In this system, assets are assigned positive scores if they exceed the threshold (green) and negative scores if they fall below it (brown), enhancing the interpretability of sustainability metrics in portfolio construction. However, a challenge arises when aggregating these scores into an overall portfolio rating. Under sustainable portfolio optimization developed in [11], short positions in brown assets, otherwise effectively betting against polluting companies, can paradoxically improve the portfolio’s sustainability score. This creates a misleading incentive structure. To address this, we introduce a constraint that prohibits short positions in brown assets, ensuring that such investments do not positively impact the portfolio’s sustainability rating. While this restriction better aligns with environmental objectives, it also introduces complexity into the optimization process. To resolve this, we present an intuitive algorithm inspired by the active set method, which we refer to as Green Portfolio Optimization, capable of handling these constraints efficiently even in high-dimensional settings.

In this paper, we study the dynamics and bifurcation of a two-dimensional discrete-time predator-prey model. The existence and local stability of the equilibrium points of the model are analyzed algebraically. It is shown that the model can undergo a transcritical bifurcation at equilibrium point on the $x$-axis and a Neimark-Sacker bifurcation in a small neighborhood of the unique positive equilibrium point. Some numerical simulations are presented to illustrate our theoretical results.  

In this paper, we investigate an open-access fishery model which is used to examine the dynamics of the resource and industry and to explain the current economic status of the anchovy fishery. We consider the local character of the interior and boundary equilibrium points. Also, we show that the considered system of difference equations exhibits Neimark-Sacker bifurcation under certain conditions. The existence of the repelling curve and invariant curve is demonstrated. We show that in a certain parameter region the corresponding map of the considered system is an area-preserving map, so the positive equilibrium point in that case is stable. Also, we produce numerical simulations to support our findings.

Steatosis extends beyond the liver to the pancreas, heart, and skeletal muscle, yet prevailing definitions remain narrowly organ-focused. This narrative review introduces the Metabolic Steatotic Axis (MSA) as a framework that captures the dynamic, bidirectional interactions among these organs, driving systemic metabolic dysfunction. We synthesize evidence linking lipotoxicity, inflammatory signaling, and endocrine cross-talk into a self-amplifying network accelerating insulin resistance, β-cell failure, and cardiometabolic risk. The MSA concept provides a rationale for axis-based staging systems and composite biomarker panels to quantify cumulative disease burden better and refine risk stratification. We highlight phenotypic heterogeneity within MSA stages, the possible hierarchy of organ vulnerability, and the implications for prognosis and therapy. Viewing pharmacological and lifestyle interventions through the MSA lens reframes them as systemic modulators rather than organ-specific treatments, underscoring the need for multi-organ endpoints in clinical trials. Finally, we outline priorities for longitudinal imaging, multi-omics integration, and global harmonization to translate the MSA from a conceptual construct to a clinically actionable paradigm. By unifying fragmented observations into a systemic model, the MSA has the potential to reshape disease classification, therapeutic strategies, and precision medicine in metabolic disorders.

Rapid detection of antibiotic-resistant bacteria is a crucial tool in the global fight against antimicrobial resistance, helping to limit the spread of resistance and guide treatment decisions. Here, we report the design, synthesis, and electrochemical evaluation of β-lactam-based redox-activatable probes for detecting β-lactamase activity. The probes incorporate a β-lactam core linked to redox reporters through cleavable linkages, enabling signal generation upon enzymatic hydrolysis. High-performance liquid chromatography and differential pulse voltammetry analyses were used to assess time-dependent activation and concentration-dependent responses against commercial β-lactamase blends and metallo-β-lactamases. Selected probes, bearing cephalosporin recognition motifs and maltol redox reporters, were further evaluated against clinical isolates, demonstrating selective activation in carbapenemase-producing strains. To extend the platform toward solid-state biosensing, an azide-functionalized analog was clicked on alkyne-modified glassy carbon electrodes. Stepwise surface functionalization and immobilization were validated electrochemically using model redox reporters, confirming their activity. The immobilized probe retained responsiveness, demonstrating the feasibility of integrating this sensing strategy into solid-state diagnostic devices. By integrating stable cephalosporin scaffolds with redox-reporter signaling, this work introduces a novel probe system that unites chemical probe design with surface-based electrochemical sensing, providing a strong foundation for the development of portable, point-of-care diagnostics for β-lactamase-mediated antibiotic resistance.

Perfluorohexyloctane (F6H8) is a semifluorinated alkane increasingly used in medical applications. Emerging evidence, however, indicates that this compound can persist in biological systems and influence cellular processes. These observations suggest that the exceptional stability of F6H8, while beneficial for medical performance, may also have implications for long-term biological and health outcomes.

Fibroblast growth factor receptor 2 (FGFR2) alterations have emerged as an important targetable oncogenic driver in a biologically distinct subset of biliary tract cancers (BTCs), particularly intrahepatic cholangiocarcinoma (iCCA), alongside other actionable genomic events such as IDH1 mutations, BRAF V600E, HER2 amplification and MSI-H. FGFR2 fusions and mutations define a distinct molecular subgroup whose prevalence varies across geographic regions and etiologic backgrounds such as liver fluke-associated disease. Clinical studies of both reversible and irreversible FGFR inhibitors have demonstrated meaningful activity in FGFR2-rearranged iCCA, while also highlighting a characteristic toxicity profile dominated by on-target hyperphosphataemia. Parallel translational work using cfDNA-based liquid biopsy has mapped a spectrum of secondary kinase-domain mutations that underlie acquired resistance, informing the development of next-generation FGFR2-selective inhibitors (eg, lirafugratinib) and combination strategies with EGFR/ERBB blockade. Collectively, these data underscore the need for comprehensive molecular profiling and innovative umbrella trial designs to optimise targeted therapy in this rare, biologically heterogeneous malignancy.

BACKGROUND Minimally invasive surgery is rapidly expanding globally, yet there is insufficient knowledge of how to scale this technology safely and equitably across diverse health systems. We aimed to identify health-system factors associated with safe implementation of minimally invasive surgery globally, using minimally invasive cholecystectomy as a tracer procedure. METHODS We conducted a multicentre, prospective cohort study of consecutive adults undergoing cholecystectomy between July 31 and Nov 19, 2023, in 1218 hospitals across 109 countries. Data were collected by more than 10 000 health-care workers using a core measurement set mapped to the WHO Health System Building Blocks and the Global Patient Safety Action Plan. The primary outcome was 30-day procedure-specific complications, with multilevel logistic regression used to examine associations between health-system features and patient outcomes. This study is registered on ClinicalTrials.gov (NCT06223061). FINDINGS Among 52 187 included patients, the adjusted procedure-specific complication rate varied 40-fold between hospitals, from 0·3% in the lowest risk quintile to 12·1% in the highest risk quintile. Despite large structural differences across income groups in access to minimally invasive surgery, diagnostics, and emergency services, country income level was not independently associated with complication rates (adjusted odds ratio [OR] 0·81 [95% CI 0·59-1·10] for upper-middle income vs high income and 0·99 [0·70-1·39] for lower-middle income or low income vs high income). Three modifiable hospital-level factors were strongly associated with safer outcomes: establishment of local simulation-based training facilities (adjusted OR 0·78 [0·71-0·86]; p<0·0001), adoption of intraoperative safety and communication strategies (0·87 [0·79-0·96]; p=0·0046), and on-site CT diagnostics (0·79 [0·65-0·97]; p=0·0220). Training facilities showed the greatest benefit in hospitals with limited infrastructure and an inexperienced workforce: the number needed to treat to prevent a procedure-specific complication was 21 (95% CI 14-35; p<0·0001). INTERPRETATION Safe implementation of minimally invasive surgery varies widely worldwide but is not defined by national income level; differences in outcomes reflect the ability of health systems to adopt and safely deploy new surgical techniques. We identified for the first time that the presence of local simulation-based training facilities is independently associated with improved patient outcomes. Simulation appears to be fundamental to the safe delivery of minimally invasive surgery, particularly in resource-constrained settings. Together with safety systems and diagnostic capacity, these findings offer actionable targets for health systems seeking to equitably scale up essential surgical technologies. FUNDING NIHR Global Health Research Unit and Wellcome Leap SAVE Programme.