Search Results (2,396)

The diffusion of generative artificial intelligence has moved educational debate beyond access to new tools, placing teacher work, pedagogical mediation, assessment, and digital competence under renewed pressure. This article examines teachers’ perceptions, declared uses, and forms of engagement with generative AI in Gymnasien (academic-track secondary schools) and Gesamtschulen (comprehensive secondary schools) in North Rhine-Westphalia, Germany. The study is based on an anonymous and voluntary online questionnaire circulated through school leaderships. The operational database comprised 204 records, while the main analysis was based on 156 completed questionnaires. Closed-item responses were examined through descriptive statistics and interpreted through DigCompEdu and its AI-related supplement. The findings indicate an asymmetrical incorporation of generative AI across teachers’ work. Its presence is stronger in preparation, organisation, professional reflection, and risk awareness than in direct classroom mediation, process-oriented assessment, and institutionally supported student use. The strongest contrasts concern perceived student overreliance on AI-generated answers, the need to adapt assessment practices, limited school-level guidance, and weak use of AI-supported process monitoring. Rather than interpreting this imbalance as a simple delay in adoption, the article argues that teacher competence in relation to generative AI is produced through the interaction between professional judgement, pedagogical purposes, and institutional conditions. It therefore cannot be reduced to an individual technical attribute. Full article

As variable renewable generation grows, intermittent dispatch of run-of-river hydropower plants may transfer required environmental-flow releases from turbines to spillways, creating conditions that favor total dissolved gas (TDG) supersaturation and may constrain hydropower flexibility. This study presents a reproducible basin-scale screening assessment for 24 selected hydropower plants in the Brazilian Amazon and Tocantins–Araguaia basins. The analysis combines a plant inventory, spillway typology, standardized environmental-flow scenarios, and two configuration-specific linear relationships between unit discharge and the increase in TDG saturation (ΔTDG), derived from digitized Pubugou and Gongzui observations. Two release configurations were examined: flow distributed among all available bays and flow concentrated in a single bay as a theoretical hydraulic bounding case. The Pubugou-based relationship was applied only to broadly comparable ski-jump configurations within 9.1 ≤ UD ≤ 72.3 m³ m⁻¹ s⁻¹, whereas the Gongzui-based relationship was provisionally assigned, as an inventory-level first-order analog, to controlled spillways discharging into stilling basins within 34.6 ≤ UD ≤ 234.6 m³ m⁻¹ s⁻¹. Hydraulically dissimilar cases were classified as NE-H, and cases outside the applicable empirical domain as NE-UD. Digitization sensitivity, regression uncertainty, and model-form selection were explicitly evaluated and documented. None of the distributed-flow scenarios produced a numerical estimate: cases assigned to the Pubugou- or Gongzui-based relationships were classified as NE-UD, whereas hydraulically dissimilar free-surface cases were classified as NE-H. Four single-bay scenarios produced configuration-specific $\Delta \mathrm{T}\mathrm{D}\mathrm{G}$ increments: 22.5–33.4 percentage points for three Gongzui-based cases and 13.6 percentage points for one Pubugou-based case. Upstream TDG was not added, and no plant-specific final concentration or universal ranking was reported. Sinop and Colíder observations were retained as qualitative contextual evidence of limited transferability and the importance of site-specific hydraulics. The outputs support conditional monitoring prioritization under standardized assumptions, not compliance prediction, ecological-risk assessment, or gate-operation recommendations. Synchronized monitoring and plant-specific rating curves are required before TDG-related variables can be incorporated into operational planning. Full article

Proteases are widely studied hydrolases as “green technologies” for degrading structures within complex matrices, although combining different classes poses challenges for catalytic stability. To the best of our knowledge, this is the first study to specifically evaluate the biochemical control of Cryptosporidium spp. oocysts using plant- and microbial-derived proteases. This study evaluated the compatibility and sanitizing potential of the microbial serine protease subtilisin Carlsberg (HPF-1SCA) and the plant cysteine protease papain (1PPP), both individually and in a 15% (w/v) combination, hypothesizing a synergistic effect due to their distinct catalytic specificities, as a potential biochemical approach to reduce contamination by these zoonotic protozoa of global importance, which are highly resilient to conventional disinfectants. The experimental design comprised five distinct treatment groups: a negative control (distilled water), a positive chemical control (0.04% v/v NaClO), treatment with isolated papain (15% w/v), treatment with isolated microbial HPF formulation (15% w/v), and a combined treatment using both enzymes simultaneously (15% w/v each). Concurrently, an in silico molecular docking investigation was conducted to elucidate the predicted binding scores, structural compatibility, and preferential binding mechanisms of these enzymes toward the Cryptosporidium Oocyst Wall Protein (COWP). In vitro compatibility assays revealed an immediate antagonistic effect due to mutual proteolysis, reducing overall proteolytic activity by 45% after 72 h. Despite this antagonism, the enzyme mixture (G5) and the isolated microbial protease (G4) achieved a 93% reduction in oocysts, equivalent to the conventional 0.04% NaClO treatment (G2), while papain (G3) achieved 65%. All these results represented statistically significant efficacy (p < 0.01) compared to the negative control (G1). In silico molecular docking studies provided a structural predictive basis for the experimental data, suggesting that subtilisin Carlsberg (HPF-1SCA) exhibits more favorable predicted binding scores and structurally compatible interfaces, compared to papain, particularly toward the major oocyst structural proteins COWP8 (estimated ΔG = −15.2 kcal·mol⁻¹) and COWP6 (estimated ΔG = −13.3 kcal·mol⁻¹). This provides robust evidence for initial target recognition and molecular anchoring, although these static models do not definitively confirm catalytically productive cleavage conformations. In summary, this in vitro proof-of-concept demonstrates that microbial proteases show promise for the biochemical destabilization of oocysts without generating toxic chlorinated byproducts. While these baseline findings align with the One Health concept, future field-scale validations assessing enzyme stability under variable environmental conditions and in vivo infectivity assays are required before practical application in sanitation protocols. Full article

Rhipicephalus microplus is a cattle ectoparasite responsible for economic losses in livestock systems. The present study aimed to evaluate the essential oil (EO) of Piper hemmendorffii and its major constituent, limonene, for their activity against R. microplus larvae. The EO of P. hemmendorffii and its major compound, limonene, were evaluated against pyrethroid-resistant R. microplus larvae using larval immersion bioassays, biochemical analyses of detoxification enzymes and acetylcholinesterase, and scanning electron microscopy (SEM). The EO showed higher larvicidal potency (LC₅₀ = 10.46 mg/mL; 95% CI: 9.86–11.09) compared to limonene (LC₅₀ = 31.62 mg/mL; 95% CI: 30.86–32.40). Piper hemmendorffii EO affected the following classes of enzymes investigated: α-Esterase (α-EST) activity increased at LC₂₅ and LC₅₀, reaching its highest level at LC₅₀, whereas β-esterase (β-EST) activity increased only at LC₂₅. Cytochrome P450 (CYP450)-associated heme content activity showed a significant increase exclusively at LC₅₀, suggesting a response of the surviving larvae to EO exposure, although this increase does not by itself demonstrate the activation of detoxification pathways. In contrast, limonene did not significantly affect the activity of the three evaluated enzymes. The inhibition of AChE by the EO suggests a possible effect on the cholinergic system, which may be associated with neurotoxic activity, whereas limonene had no significant effect. The absence of detectable ultrastructural changes by SEM suggests that treatment with either EO or limonene did not induce evident external morphological damage to the larval cuticle under the evaluated conditions. EO toxicity seems to be associated with changes in detoxification enzyme and AChE activities, suggesting the involvement of these biochemical pathways in larval response. Full article

This article proposes the Collective Delivery Demand Matrix (CDD Matrix), which repositions the New Agile as a correspondence property between collective delivery demands and teams’ operating regimes, aiming to form teams that are simultaneously agile, high-performing, and endowed with dynamic capabilities. It addresses a gap in the agility literature: the Agile Manifesto principles have been extended to many contexts, yet no theory explains when they should be maintained, adapted, or replaced. Developed as a theoretical-conceptual essay, the work synthesizes studies on naturalistic decision-making, team learning, neurostrategy, sociotechnical systems, and decision support. It proposes a taxonomy of seven demand typologies along five classificatory axes, and a correspondence matrix that articulates demand types, operating regimes, shared heuristics, sociotechnical configurations, and managerial errors. The matrix clarifies that agility generates value when it first favors effectiveness, delivering the right objective in the right regime at the appropriate risk level, and only then efficiency. The New Manifesto reformulates the Agile Manifesto as conditional correspondence rules sensitive to demand typology, and six testable propositions guide future empirical research. The main finding is that a team becomes simultaneously agile, high-performing, and dynamically capable only when its operating regime corresponds to the demand typology it faces, matching effectiveness before efficiency, calibrating risk, and building a renewable repertoire of shared heuristics. For managers, teams, and organizations, this implies diagnosing the delivery demand before selecting a method, composing and leading teams according to the demand’s dominant axes, and protecting the psychological safety that turns reversible error into collective learning. The contribution integrates the Agile Manifesto, decision theory, the sociotechnical tradition, and neurostrategy into a single theory of Agile, High-Performance, and Dynamic Teams (EAD²), oriented toward verifiable objectives, goals, and results. Full article

Targeted therapies have substantially advanced cancer treatment; however, therapeutic resistance remains a major challenge, particularly in lung cancer. Polo-like kinase 1 (PLK-1), a key regulator of mitosis, is frequently overexpressed in lung tumors and has emerged as an attractive anticancer target. Although PLK-1 inhibition induces robust antitumor effects in preclinical models, its translation into clinical benefit has been limited, particularly when used as monotherapy. Previous in vitro work from our group demonstrated that combining PLK-1 inhibition with the pro-apoptotic agent Navitoclax markedly enhanced cancer cell death by reducing mitotic slippage and promoting post-mitotic apoptosis. Here, we investigated whether this combinatorial strategy translates into therapeutic benefit in vivo. Using Lewis lung carcinoma (LLC1) cells, we evaluated the effects of BI2536 (a PLK-1 inhibitor) and Navitoclax, alone or in combination, in vitro and in male C57BL/6J mice using three lung cancer models: subcutaneous, intranasal, and intrapulmonary. The in vitro results corroborated the findings of our previous work, demonstrating synergistic effects. In the murine models, tumor progression, body weight, survival, and histopathological features were assessed to evaluate therapeutic efficacy and systemic toxicity. In the subcutaneous model, BI2536 monotherapy significantly reduced tumor volume compared with vehicle-treated controls, while Navitoclax alone and the combination therapy also produced tumor growth inhibition. In contrast, in the intranasal model, no significant differences were observed in body weight or survival among groups. Nonetheless, treatment with BI2536 alone or in combination with Navitoclax significantly reduced tumor cell proliferative activity. In the aggressive intrapulmonary (orthotopic) model, rapid disease progression and high mortality were observed across all groups. Notably, BI2536 treatment was associated with improved survival compared with Navitoclax monotherapy, whereas the combination therapy did not confer additional survival benefit. Histological analyses revealed highly proliferative tumors with pronounced cellular and nuclear atypia. Moreover, the BI2536 monotherapy group exhibited significantly greater necrosis/apoptosis than the other treatment groups, while diffuse and focal hepatic steatosis was observed exclusively in the combination group. Together, these findings indicate that while PLK-1 inhibition exerts antitumor effects in certain in vivo contexts, the therapeutic synergy observed in vitro with Navitoclax does not consistently translate to in vivo lung cancer models. This study highlights the challenges of translating combinatorial mitotic and apoptotic targeting strategies into effective in vivo therapies and underscores the importance of model selection and tumor microenvironment in preclinical drug evaluation. Full article

Plant diseases impose major constraints on global crop productivity and pose a major threat to food security. Here, we review transcription factors (TFs) as central orchestrators of plant defense, consolidating recent advances in how these regulators connect pathogen perception to immune signaling, transcriptional reprogramming, and durable defense responses. Initially, we combined a literature-based synthesis with a natural language processing (NLP) analysis of 1647 PubMed abstracts published between 2021 and 2026 to map dominant and underexplored TF families associated with plant immunity. WRKY, MYB, AP2/ERF, bHLH/MYC, and NAC dominated the recent literature, whereas families such as NF-Y, Trihelix, PLATZ, TCP, and GRAS represent emerging regulatory actors. Across these and other families, TFs integrate pattern- and effector-triggered immunity, hormone crosstalk, chromatin dynamics, non-coding RNA regulation, post-translational modifications, and metabolic remodeling, in addition to cell-type-specific expression. Further evidence indicates that pathogens frequently manipulate TFs to weaken host defense, underscoring their central position in plant molecular physiology and plant-pathogen coevolution. The data emphasize that TF function is context-dependent and influenced by multilayered regulation, cell type, pathogen lifestyle, and host genetic background. This review provides a framework for understanding TFs in plant immune control and highlights TF-centered strategies for engineering durable crop resistance, along with future challenges. Full article

Background: Bacteria of the genus Providencia are emerging pathogens associated with a wide range of infections, particularly in healthcare settings. In veterinary medicine, infections caused by these organisms are uncommon, and, to date, there have been no reports of carbapenem-resistant Providencia spp. causing infection in companion animals. Methods and Results: This study describes a comprehensive investigation of bacterial endocarditis caused by carbapenem-resistant Providencia rettgeri in a cat, including clinical, imaging, pathological, microbiological, and genomic findings. A 1.5-year-old mixed-breed female cat was admitted to a referral veterinary hospital with an extensive pelvic limb wound and a recent history of laparotomy. During hospitalization, a heart murmur was detected, and echocardiographic examination revealed vegetation-like lesion on the mitral valve. Despite intensive treatment, the patient’s clinical condition progressively deteriorated over a 15-day period, ultimately leading to euthanasia. Necropsy confirmed bacterial endocarditis with evidence of systemic septic embolization. P. rettgeri was isolated from blood collected from both heart ventricles and from an endocardial swab and its identity was confirmed by MALDI-ToF mass spectrometry. Antimicrobial susceptibility testing demonstrated resistance to meropenem. Whole-genome sequencing confirmed the species identification and revealed a Col3M plasmid carrying multiple antimicrobial resistance genes, including the carbapenemase gene bla_NDM-1. Discussion: To the best of our knowledge, this is the first report of carbapenem-resistant Providencia spp. causing infection in a companion animal. This case highlights the emergence of Providencia spp. as potential veterinary pathogens capable of causing severe, invasive and fatal infections. Full article

Agrochemicals are used worldwide in food production, but their use varies between countries due to the damage observed to nature and human health. Allelopathy is the primary pathway of chemical communication in plants, interfering with biome development through stimulation and/or inhibition mechanisms. Therefore, this study aimed to assess the biological activities of the ethanol extract (EE) and fractions of S. fluminensis leaves on monocotyledonous and eudicotyledonous models. The EE was obtained by percolation with ethanol, and the hexane (HEXF), dichloromethane (DCMF), ethyl acetate (EAF), and hydroethanol (HEF) fractions were obtained by liquid–liquid partition. The phytochemical characterization was performed by ¹H nuclear magnetic resonance (NMR). The allelopathic activity was evaluated on Allium cepa (onion) and Lactuca sativa (lettuce) seeds. The cytotoxic, genotoxic, and antigenotoxic effects on A. cepa meristematic cells were analyzed in vitro. Aliphatic compounds, saponins, and flavonoids derived from quercetin and kaempferol were characterized in the samples. All samples decreased the vigor, germination rate, and germination speed index (GSI) of A. cepa seeds. In contrast, they did not alter the vigor and viability of L. sativa seeds, but decreased the GSI, except for HEF. The samples inhibited the epicotyl and root growth of A. cepa and L. sativa, except HEXF, which stimulated the growth of epicotyls (750 µg/mL) and roots (750 and 1000 µg/mL). The cytotoxic assays showed that the EE and HEXF had cytotoxic action at low concentrations, and no sample showed a genotoxic effect. The following samples exhibited an antigenotoxic effect after pretreatment with atrazine (ATZ): EE (125 and 750 µg/mL), HEXF (750 and 1000 µg/mL), DCMF (125, 250, and 1000 µg/mL), EAF (at all tested concentrations), and HEF (125, 250, and 750 µg/mL). Furthermore, the EAF at 125 and 500 µg/mL and HEF at 125 µg/mL demonstrated the potential to reverse genetic damage induced by glyphosate (GLY). Full article

Acute deep vein thrombosis (DVT) continues to represent a significant global contributor to morbidity and mortality. Although multiple international societies have published evidence-based clinical practice guidelines, important differences persist. This structured narrative review compares contemporary international guidance to identify areas of consensus, methodological divergence, evidence gaps, and priorities for future research. Recommendations were compared across diagnostic evaluation, anticoagulant selection, treatment duration, outpatient management, compression therapy, endovascular intervention, and special populations. Broad agreement was identified regarding clinical pretest probability assessment, D-dimer testing, compression ultrasonography, and direct oral anticoagulants as first-line therapy for most eligible patients with acute DVT. Clinically important differences remain, however, in the management of isolated distal DVT, anticoagulation duration, catheter-directed interventions, compression therapy, and selected high-risk populations. These discrepancies primarily reflect differences in publication timing, methodological frameworks, interpretation of emerging evidence, and healthcare-system context rather than fundamentally conflicting evidence. Contemporary international guidance therefore demonstrates substantial convergence on the core principles of acute DVT management while continuing to differ in areas supported by limited or evolving evidence. Future harmonization will require high-quality randomized trials, broader international collaboration, and the integration of precision medicine, validated risk-prediction models, biomarkers, and emerging anticoagulant strategies into guideline development. Full article

(1) Background: Snake bite envenomation is a neglected disease that affects impoverished and rural areas, causing deaths and physical sequelae. (2) Objective: A novel series of eight 1,2,3-triazole compounds, AM50, AM51, AM52, AM53, AM54, AM55, AM56, and AM57, were synthesized and assessed as inhibitors of toxic activities of B. jararacussu venom. Methods: B. jararacussu venom was pre-incubated with each of the compounds and after the coagulant, proteolytic, hemorrhagic, edematogenic, and lethal activities were assessed. The structure of compounds was analyzed by NMR and FT-IR spectroscopy techniques, and toxicity was predicted through OSIRIS and SwissADME. (3) Results: AM56 and AM57 inhibited the plasma coagulant and prevented hemorrhagic activity of the venom. Proteolysis and hemorrhage were inhibited by AM52, AM54, AM55, and AM56 (20–30%), as well as AM50, AM51, and AM57 (30–60%). AM57 fully protected the mice from death caused by venom, and AM50, AM53–AM57 inhibited edema of venom by 10–20%; AM51 and AM52 did not inhibit edema. In silico analysis of compounds revealed satisfactory parameters for drug discovery. (4) Conclusions: 1,2,3–triazole compounds inhibited the major toxic activities of B. jararacussu venom and should be considered as a lead for further investigation as adjunct of antivenom therapeutics. Full article

The mantle of bivalves plays a fundamental role in shell formation and maintenance through biomineralization. Experiments performed on mantle–shell preparations using different experimental techniques revealed the presence of phosphorus (P)-containing compounds in the shell as the first mineral phase formed at the growing edge of the periostracum in the freshwater bivalve Limnoperna fortunei. The low P concentration in the shells suggests that phosphate is restricted to the growth regions and occurs at concentrations too low to be detected by techniques such as X-ray diffraction (XRD). Nevertheless, a crystal morphology closely resembling that of hydroxyapatite (HAp) was identified at the shell growth front, and a Ca/P ratio of 1.67, consistent with HAp, was determined in two of these regions. Fourier transform infrared (FTIR) spectroscopy also revealed the principal and most intense absorption band of the phosphate group (PO₄³⁻) at 1024 cm⁻¹. Enzymes such as carbonic anhydrase (CA), or proteins with equivalent functions, are likely involved in phosphate dissolution and the subsequent precipitation of calcium carbonate. In addition, the occurrence of calcium phosphate was confirmed in the shells of the marine bivalve Perna perna. Phosphate dissolution and carbonate precipitation during biomineralization suggest two important evolutionary advantages: first, the release and availability of phosphate, an essential nutrient for energy production and other metabolic functions; and second, the formation of a calcium carbonate shell, a structure indispensable for the protection, mechanical support, and survival of mollusks. Full article

Orofacial pain is a multifactorial condition that severely impacts basic functions and overall quality of life in patients, underscoring the need for non-opioid therapeutic strategies. Targeting the Transient Receptor Potential Vanilloid 1 (TRPV1) pathway has emerged as a biologically plausible approach, given its central role in nociceptive transduction and peripheral sensitization. Capsaicin, a selective TRPV1 agonist, induces receptor desensitization and has shown potential in chronic pain modulation; however, its efficacy in orofacial conditions remains unclear. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of capsaicin in managing orofacial pain, compared to placebo or other pharmacological interventions. Following PRISMA guidelines, a comprehensive search of five databases (PubMed, Scopus, Web of Science, CDSR, and LILACS) was conducted without language or date restrictions. Studies involving human participants with orofacial pain treated with capsaicin were included. The protocol was registered in PROSPERO (CRD420251004538). Risk of bias was assessed using the RoB2, RoB2 crossover trial and ROBINS-I checklist, and meta-analyses were performed using random-effects models. Nine studies enrolling a total of 164 participants met the eligibility criteria and encompassed temporomandibular disorders, burning mouth syndrome, oral mucositis, trigeminal neuralgia, and neuropathic facial pain. Although placebo-controlled comparisons showed a trend toward pain reduction that did not reach statistical significance (MD = –1.87; [95% CI: –3.94, 0.19]; p = 0.08; I² = 86%), and no significant difference was found between capsaicin concentrations (MD = 0.46; [95% CI: –2.67, 3.60]; p = 0.77, I² = 66%), pre–post analyses of uncontrolled (single-arm) studies demonstrated a significant and clinically meaningful reduction in pain following capsaicin treatment (MD = –6.39; [95% CI: –7.40, –5.38; p < 0.001, I² = 0%). Capsaicin also showed an acceptable safety profile: although adverse events were significantly more frequent than with control (OR = 19.84; [95% CI: 4.32–91.21]; p < 0.001, I² = 0%), these were mild, localized, and self-limited. Capsaicin may provide clinically meaningful pain relief in selected orofacial conditions, particularly burning mouth syndrome, where uncontrolled evidence was most consistent (I² = 0%); evidence for temporomandibular disorders was more heterogeneous and did not reach significance in pooled placebo-controlled analyses. Full article

High-resolution wind resource maps are essential for wind farm siting and renewable-energy planning, but national-scale assessment is often limited by sparse meteorological stations and the coarse resolution of reanalysis products. This study introduces a self-supervised Physics-Constrained Super-Resolution CNN (PC-SRCNN) that enhances ERA5 wind fields from 0.25° to 0.025°, for settings lacking a high-resolution, hourly-resolved reference wind field, by embedding kinematic and vertical-profile consistency as soft regularization penalties, without solving the full Navier-Stokes momentum balance. The framework was evaluated against 190 independent INMET stations, alongside interpolation, data-driven, and climatological baselines, using a station-wise bootstrap and the Diebold-Mariano test. The full model reduced the bootstrap MAE from 1.22 to 1.04 m/s relative to native ERA5, a 14.85% improvement confirmed by both tests, and achieved a vertical-profile $R^2$ of 0.90 against baselines below 0.70. Ablation shows physical regularization is not automatically beneficial: a variant constrained only by horizontal kinematics performed significantly worse than ERA5, with gains obtained only when vertical logarithmic-profile consistency was included. All other baselines evaluated were statistically indistinguishable from native ERA5 against station observations. These results indicate that sharper spatial detail alone is insufficient to improve wind-resource estimates unless supported by physically meaningful, vertically consistent constraints. Full article

Background/Objectives: Cervical integument aging is a complex, multifactorial process characterized by thinning dermis, loss of elasticity, and platysmal band prominence. Multimodal treatments targeting these distinct anatomical layers simultaneously remain limited. This study aimed to evaluate the clinical efficacy, safety, and rejuvenation potential of the STIIM UP Protocol, a single-session treatment combining calcium hydroxyapatite (CaHA), hyaluronic acid (HA), and botulinum toxin type A (BoNT-A) for neck rejuvenation. Methods: This prospective, open-label, exploratory clinical study enrolled 13 healthy women (n = 13) presenting with cervical laxity. The STIIM UP suspension was delivered bilaterally into the subdermal plane of the anterior neck region using a retro-injection fanning technique with a 22G cannula at Day 0 (D0). Evaluated outcomes included the IBSA Neck Grading Scale, Global Aesthetic Improvement Scale (GAIS), FACE-Q module scores, and high-frequency ultrasound (USG) tissue thickness measurements at baseline and Day 120 (D120). Safety was monitored throughout. Results: The median consensus IBSA scores decreased significantly from 4.0 at baseline to 2.0 at both D30 and D120 (p-value < 0.01), indicating a rapid and sustained reduction in laxity. At D120, the GAIS responder rate reached 100% according to independent evaluators and 90.9% based on patient self-assessments. Quantitative USG confirmed statistically significant bilateral tissue thickening across the epidermis, dermis, and subcutaneous strata (p-value < 0.05). Progressive, clinically meaningful improvements were captured via the FACE-Q scales. No local or systemic adverse events were observed. Conclusions: The STIIM UP Protocol is a safe and effective multilayer intervention that successfully achieves comprehensive neck rejuvenation, bridging immediate clinical enhancement with sustained, tissue-proven structural remodeling. Full article