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.

Background:Irritable Bowel Syndrome (IBS), a disorder of gut-brain interaction, is diagnosed using symptom-based Rome criteria. These criteria classify IBS patients into four subtypes in accordance to their stool patterns. However, whether this subtyping approach is based on true differences in the underlying biology of IBS patients, is unclear. Volatile organic compounds (VOCs) in the faecal headspace reflect both the gut microbial and host intestinal intraluminal processes and thereby may be used to study pathophysiological differences between IBS and its subtypes. Methods:We profiled faecal headspace VOCs in a cohort of 164 patients with IBS and 143 healthy controls using gas chromatography-mass spectrometry (GC-MS). Random forest models were employed to impute missing values and identify discriminatory VOCs to differentiate IBS patients from healthy controls. We corrected for faecal water content using Partial Least Squares Regression. Multivariate associations between the obtained volatile profiles and Rome III IBS subtypes were evaluated using regularized MANOVA. Results:A total of 39 VOCs, including short-chain fatty acid esters, neurotransmitter-related metabolites, alcohols, and sulphides, were selected as significantly altered in patients with IBS. Our classification model achieved an area under the curve (AUC) of 0.82 on both training and independent test sets, demonstrating robust separation between IBS patients and healthy individuals. However, VOC profiles did not associate to Rome III -based IBS subtypes. Conclusion:This study highlights the potential of faecal VOC profiling as a non-invasive tool for studying and characterising IBS, yet they also reveal a disconnect between metabolic signatures and current stool-based subtypes. While the Rome criteria remain the clinical standard for diagnosis and subtyping of IBS, they offer limited insight into underlying disease mechanisms. Future research should focus on integrating VOC analysis with other omics approaches to refine IBS sub-classification into biologically relevant clusters, which may aid to improve personalised therapeutic strategies.

Cultural and event tourism plays a key role in the global tourism industry, contributing significantly to national, regional, and cross-border development strategies. It attracts visitors interested in cultural heritage, artistic events, and local traditions, supporting the preservation and promotion of local identity. Assessing cultural tourist flows become essential to understand their economic and social impact, and this article proposes an integrated methodology, combining quantitative and qualitative approaches, including data collection on cultural events, participant estimation, economic analysis, satisfaction assessment, data visualization, reporting, and continuous monitoring. The proposed model ensures a comprehensive evaluation of cultural tourist flows and supports the sustainable development of cultural tourism. Its relevance is both theoretical and applied: it offers a conceptual and analytical framework for studying this complex phenomenon, but also, it provides useful insights for decision-makers and stakeholders involved in tourism development, helping to design effective policies and strategies for promoting and managing cultural tourism. The novelty of the research lies in the proposal of a detailed and integrated methodology tailored to the specific challenges of evaluating cultural tourism, aiming to improve data accuracy, strategic planning, and long-term sustainability.

Background: Peritoneal lymphangiomatosis is a rare benign lymphatic disorder with diagnostic and therapeutic challenges. It may mimic peritoneal carcinomatosis or mesothelioma, often requiring histological confirmation. Management options are limited, and long-term data on targeted therapies, including sirolimus, remain scarce. Case Presentation: We present the case of a 45-year-old woman with a history of surgically corrected atrial septal defect, who developed progressive abdominal distension and dysuria in May 2014. Abdominal ultrasound (US) and contrast-enhanced abdominal computed tomography (CT) revealed diffuse ascites, peritoneal thickening, and cystic changes. Diagnostic uncertainty led to an exploratory laparotomy in May 2015, where histopathology confirmed peritoneal lymphangiomatosis. After failed conservative management including dietary modification, diuretic therapy, and repeated paracenteses, she was started on sirolimus 2 mg/day in August 2016. Her serum trough levels were maintained between 5–15 ng/mL. She achieved a Karnofsky Performance Score of 100% (indicating full functional capacity) within two months and has remained in complete clinical and radiologic remission for over 8 years. Diabetes mellitus type 2 was diagnosed during follow-up and is well controlled with insulin therapy. Conclusion: This case underscores the difficulty of diagnosing peritoneal lymphangiomatosis and highlights the transformative potential of sirolimus therapy. To our knowledge, this is one of the longest documented remissions of peritoneal lymphangiomatosis under mechanistic target of rapamycin (mTOR) inhibition. Keywords: peritoneal lymphangiomatosis, sirolimus, mTOR inhibitor, rare disease, ascites, lymphatic malformation, case report, remission, Karnofsky score, targeted therapy.

The primary objective of external fixation is to stabilize bone fractures, with the mechanical characteristics of the fixation system playing a critical role in shaping the biomechanical environment of the fracture and, consequently, the healing process. This study presents an experimental investigation of the stability of eight unilateral external fixation configurations applied to an open tibial fracture. The stiffness of each configuration was evaluated under axial compression, anterior–posterior (AP) bending, medial–lateral (ML) bending, and torsional loading. In addition, the effects of structural parameters—such as the number of half-pins, planarity of the configuration, and interfragmentary distance—on fixator stiffness and generated stresses were examined. The results revealed a linear relationship between applied load and both bone segment displacement and principal stresses. Biomechanical tests demonstrated that biplanar configurations provide sufficient stability for open tibial fractures, while simultaneously offering an optimal structural design for the fixation system. Moreover, the number of half-pins was identified as a statistically significant factor influencing configuration stiffness under axial loading and torsion, with biplanar configurations proving particularly effective in torsional scenarios. However, in AP and ML bending tests, neither configuration type nor any individual parameter produced statistically significant differences in bending stiffness. Interestingly, interfragmentary distance did not exert a statistically significant effect on configuration stiffness under any loading condition. Furthermore, neither configuration type nor the analyzed parameters had a notable influence on the principal stresses measured at the control points.

In this research, the impact of applications on improving urban logistics was examined using the example of the company EX, with an emphasis on the sustainability of its business. To conduct this research, expert decision-making was used. The model used ten criteria and eight applications. To incorporate uncertainty into this research, an intuitionistic fuzzy approach was used. Based on the obtained CC values, the criteria weights were determined using the SiWeC (Simple Weight Calculation) method, while the WASPAS (Weighted Aggregated Sum Product Assessment) method ranked the applications. The results showed that “Security and data protection” and “System reliability and stability” were the most important criteria, while Application 1 achieved the best results. These results were confirmed by the consistency analysis of the WASPAS method and the sensitivity analysis, which considered 30 scenarios.

OBJECTIVE To report two additional cases of glycogen-rich clear cell carcinoma (GRCC) of the breast - detailing their clinicopathologic features, immunophenotypes, and follow-up - and to provide an updated literature review since 2020. CASE REPORTS Two patients (66 and 52 years old) had GRCC confirmed morphologically and histochemically. Case 1 was ER-positive/HER2- positive (luminal B/HER2-positive) and was managed with surgery, followed by adjuvant chemotherapy, endocrine therapy, and anti-HER2 therapy (trastuzumab). Case 2 was triple-negative and received neoadjuvant chemoimmunotherapy (pembrolizumab- based) with marked pathologic tumor regression at resection. Both patients were disease-free at one and 12 months, respectively. CONCLUSIONS GRCC is heterogeneous and should not be regarded as a single clinicopathologic entity within invasive breast carcinoma of no special type or assumed to have a uniform prognosis. Management should be biomarker-guided, as illustrated by these cases. The role of targeted and immune therapies in GRCC warrants multi-institutional studies.