Simple Summary This study presents the Endoscopic One-Nostril Transseptal Transsphenoidal Approach (EONOTTA) as a minimally invasive surgical technique for selected cases of pituitary macroadenomas. Derived from the classic endoscopic endonasal approach, EONOTTA allows excellent exposure of the sellar region while preserving nasal mucosa and olfactory function. The technique offers comparable disease control to standard endoscopic endonasal approaches, with reduced sinonasal morbidity and postoperative discomfort. Despite limitations such as retrospective design and small sample size, findings support EONOTTA as a safe, efficient alternative for non-extended pituitary tumors requiring limited surgical exposure.

BACKGROUND Older women face disproportionate health challenges, exacerbated by multiple unprecedented challenges such as global aging, disease outbreaks, and geopolitical as well as technological upheavals. This study examines technology-based mental health interventions for this demographic, aiming to inform policy. METHODS A systematic review of randomized controlled trials (RCTs) targeting older women's mental health post-COVID-19 was conducted using databases like Web of Science and PubMed, adhering to PRISMA guidelines and registered with PROSPERO (CRD42020194003). RESULTS A total of 3463 articles were screened for eligibility, among which, 17 RCTs met the inclusion criteria. The review results show that 17 RCTs were conducted in middle-income and high-income countries. Fifteen RCTs generated statistically significant outcomes and reported specific aspects of their interventions to improve the mental health of older women. CONCLUSION Technology-based interventions show promise for improving older women's mental health. Policy recommendations include establishing comprehensive mental health centers, implementing universal healthcare, promoting digital literacy, and strengthening public awareness campaigns.

Abstract The toxicity of vanadium(IV) acetophenone–isoniazid hydrazone complexes (V1–V4) was evaluated in Artemia salina. Nauplii were exposed for 24–72 h at 1, 5, 10, and 50 mg/L. Responses were concentration dependent: reduced hatching, increased mortality, and morphological changes (appendage and carapace defects, intestinal accumulation). Toxicity ranked by substituent: V2 (F) most toxic (≈60% mortality at 72 h, 50 mg/L), V3 (Cl) intermediate, V1 (H) and V4 (Br) lower (near 30% under the same conditions). Findings were compared with data from streptozotocin-induced diabetic Wistar rats. V4, moderately toxic in Artemia, showed the strongest antihyperglycemic effect (ca. 72% glucose reduction to near-normoglycemia) and the lowest renal bioaccumulation. V2 aligned with unfavorable renal/hepatic markers. V1 was well tolerated in Artemia and produced moderate glucose lowering with lipid improvements. V3 gave intermediate efficacy but higher bioaccumulation and hematological deviations. A. salina is a suitable early toxicity screen that, combined with mammalian data, reveals structure–activity–toxicity relationships. Halogen substitution modulates both efficacy and toxicity: Br provides the most balanced profile, F the highest liability, and H the safest but least potent. V4 (Br) emerges as the leading candidate for further preclinical study. Graphical abstract

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 Fractional flow reserve (FFR)-negative coronary lesions are usually managed medically. Lesion-specific plaque characterization and FFR changes over time remain elusive. AIMS To assess disease progression in FFR-negative lesions over a two-year period using FFR derived from coronary CT angiography (CCTA) (FFRct) and to investigate whether FFR decline over a two-year period is associated with plaque characteristics. METHODS This single-center prospective study included patients undergoing coronary angiography with one or more invasive intermediate lesions (FFR 0.81-0.90) in non-stented, non-culprit coronary arteries. Two years after the index procedure, patients underwent CCTA with FFRct and quantitative plaque analysis. RESULTS We enrolled 131 patients (152 vessels). Two-year follow-up with FFRct and plaque analysis was available in 68 (52 ​%) patients (73 vessels). Compared to invasive FFR at baseline, FFRct at 2y follow-up was significantly lower (median difference -0.06) at vessel level analysis (p ​< ​0.001). FFR declined in 55 (75 ​%) lesions. The 35 study vessels with an FFRct≤0.80 ​at 2-year follow-up had higher total percent atheroma volume (PAV) (41 ​% vs. 23 ​%; p ​= ​0.002) and more high-risk plaque composition, including noncalcified PAV (30 ​% vs. 18 ​%; p ​= ​0.002), and low-attenuation PAV (1.1 ​% vs. 0.7 ​%; p ​= ​0.046) compared to vessels with an FFRct>0.80 (n ​= ​38). Rates of study vessel revascularization in the 131 patients were 6.9 ​% at 2 years and 15.1 ​% after 4.9 years of follow-up after index procedure. CONCLUSIONS Rates of coronary revascularization are substantial in patients with medically managed intermediate lesions. In this selected cohort, an FFRct ≤0.80 ​at two-year follow-up was associated with higher plaque burden and presence of high-risk plaque composition.

Background/Objectives: COVID-19 severity is influenced by a complex interplay between host, viral, and environmental factors. Emerging evidence suggests that Neanderthal-derived genetic variants may influence the progression and severity of SARS-CoV-2 infection. This study aimed to evaluate the association between selected Neanderthal-derived variants and COVID-19 severity in the population of the Republic of Srpska, considering relevant clinical, sociodemographic, and lifestyle factors. Methods: This multicentric cross-sectional study included 402 participants, classified as healthy or SARS-CoV-2-positive individuals. A total of 378 COVID-19-positive participants were further stratified according to disease severity and hospitalization status. All individuals were genotyped for the Neanderthal-derived OAS3 rs1156361 (C/T) and LZTFL1 rs35044562 (A/G) variants. Detailed sociodemographic, clinical, and lifestyle data were also collected. Results: A higher frequency of the LZTFL1 rs35044562 AG genotype was observed among hospitalized patients compared with non-hospitalized individuals (36.8% vs. 20.9%; p = 0.005), while the AA genotype was more prevalent among non-hospitalized patients (77.3% vs. 63.2%, p = 0.015). Multivariable logistic analysis showed that carriers of the LZTFL1 AG genotype had a higher chance of hospitalization compared to AA carriers (adjusted OR = 1.372, 95% CI = 0.763–6.383, and p = 0.021). Hospitalized patients more frequently carried the combined CT (OAS3) and AG (LZTFL1) genotypes, supporting a potential synergistic effect. Several sociodemographic factors, including age, sex, education, employment, and urban residence, were also associated with COVID-19 severity, while no significant associations were observed in allele-based analyses. Conclusions: LZTFL1 gene polymorphisms may influence COVID-19 severity, with heterozygote-specific and combined risk effects observed. These preliminary findings are exploratory and require validation in larger cohorts, but may guide future studies and targeted interventions in high-risk groups.

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.