Search Results (21,910)

Pancreatic ductal adenocarcinoma is highly malignant with poor prognosis. Its dense tumor microenvironment severely limits the efficacy of conventional chemotherapy and causes severe side-effects. Herein, we adopt the established Schiff-base crosslinked thermoresponsive injectable self-healing poly(2-(2-methoxyethoxy)ethyl methacrylate-co-oligo(ethylene glycol) methyl ether methacrylate-co-aldehyde 2-hydroxyethyl methacrylate)/carboxymethyl chitosan (APMOH/CMCS) hydrogel as the delivery scaffold. By regulating monomer composition, the volume phase transition temperature (T_VPT) of the hydrogel was tuned to around 43 °C to match the therapeutic temperature requirement. Subsequently, copper–metal organic framework (Cu-MOF) nanoparticles co-loaded with 2,2′-azobis(2-methylimidazoline) dihydrochloride (AIPH) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) cationic radicals (ABTS·⁺) (denoted as AB@Cu-MOF) were uniformly incorporated into the hydrogel network. Under near-infrared (NIR) irradiation, ABTS·⁺ acts as a photothermal agent to generate hyperthermia for tumor ablation; the elevated temperature further activates AIPH to produce alkyl radicals, which can oxidize inactivated ABTS back to ABTS·⁺ and construct a sustainable photothermal therapy–thermodynamic therapy (PTT-TDT) circulation. Meanwhile, Cu-MOF can consume intracellular glutathione (GSH) to protect active components from deactivation and initiate chemodynamic therapy (CDT) via Fenton-like reactions to produce toxic reactive oxygen species. Benefiting from the thermoresponsive characteristic, the hydrogel undergoes volume shrinkage upon heating, achieving NIR-triggered on-demand drug release with a cumulative release rate of 81.1%. In vitro and in vivo experiments verified that this integrated platform realizes remarkable triple synergistic efficacy of PTT, TDT, and CDT. The tumor volume of the treatment group was merely 13.3% of the control group, and the system also exhibited excellent biocompatibility. Collectively, it offers a feasible and promising intelligent platform for precise local treatment of pancreatic cancer. Full article

Background: Hyperuricemia is an adverse effect frequently observed during favipiravir treatment. The time course, from uric acid elevation to recovery, and quantitative relationship between drug exposure and changes in serum uric acid levels remain insufficiently characterized. We investigated the pharmacodynamic mechanism of uric acid elevation and described its time course by population pharmacokinetic and pharmacodynamic modelling. Methods: Patients who received favipiravir for coronavirus disease 2019 or severe fever with thrombocytopenia syndrome were retrospectively evaluated. The pharmacokinetics of favipiravir were described by a one-compartment model with first-order absorption and elimination. Metabolite concentrations were predicted based on previously reported values. Changes in serum uric acid levels were described by a turnover model with zero-order production and first-order elimination. The drug effect was implemented as inhibition of the uric acid elimination process. Simulations based on the final model were performed for 10 consecutive days after the clinical regimen, with a 21-day follow-up. Results: The final model supported the inhibition of uric acid elimination by favipiravir and its metabolite. Regarding simulations, serum uric acid levels reached a median peak of 6.93 mg/dL at 6.7 days after treatment initiation and returned to pre-treatment levels within 4.0 days after treatment discontinuation. Conclusions: This combined population pharmacokinetic and pharmacodynamic turnover model quantified favipiravir-associated increases in serum uric acid levels and showed a transient profile with rapid recovery after drug discontinuation. These findings underscore the need for monitoring serum uric acid levels during favipiravir treatment, particularly in patients at a higher risk of gout Full article

Background: MGMT-methylated glioblastomas respond well to temozolomide-based standard of care (Stupp protocol), demonstrate longer survival as compared to unmethylated tumors, and carry an increased risk of pseudo-progression. Establishing time to first true progression can serve as a non-invasive clinical reference point to distinguish true from pseudo-progression. Objective: To define the time to first true progression in patients with MGMT-methylated glioblastoma who were treated with the standard of care/Stupp protocol. Methods: We conducted a retrospective analysis from our institutional database of MGMT-methylated glioblastoma patients from 2018–2024. Time to first progression was measured from initial surgery to first true progression, as determined by a multidisciplinary team based on radiographic imaging review and/or pathology. Results: Fifteen patients met eligibility criteria. Median time to first progression of MGMT-methylated glioblastoma patients who received standard of care was twenty-one months. 40% of patients remained progression-free beyond thirty-six months after their initial surgery. Conclusions: Most patients with MGMT-methylated glioblastomas do not develop true progression within the first year and a half post-operatively. Therefore, MRI changes on surveillance scans should be carefully interpreted within this time frame. Expected timeline for true progression, alongside advanced radiographic imaging techniques and knowledge of treatment-specific pseudo-progression risk, may improve diagnostic accuracy. Full article

This study investigates the feasibility of utilizing locally sourced Nicotiana tabacum biomass from Adıyaman, Türkiye, as a cost-effective biosorbent for the removal of copper and chemical oxygen demand (COD) from industrial wastewater originating from the Adıyaman Organized Industrial Zone. Batch adsorption experiments were conducted to systematically investigate the influence of solution pH, contact time, and initial metal concentration on adsorption performance. The untreated wastewater exhibited elevated pollution levels, with mean chemical oxygen demand and copper concentrations of 925 ± 391 mg/L and 2.54 ± 0.97 mg/L, respectively. Four tobacco-derived biosorbents (Çelikhan, Ova, Bulam, and Çağlan) were evaluated under optimized experimental conditions (pH ≈ 8.3, 60 min contact time, and a biosorbent dosage of 2.2 g/L). The Çelikhan biosorbent exhibited the highest copper removal efficiency (approximately 83%), whereas chemical oxygen demand removal ranged between 28% and 34%. The adsorption kinetics were well described by the pseudo-second-order model, with coefficients of determination ranging from 0.987 to 1.000. Isotherm analysis further indicated favorable adsorption behavior, with a maximum Langmuir adsorption capacity of 1.867 mg/g. Fourier transform infrared (FT-IR) spectroscopy confirmed the involvement of hydroxyl, carbonyl, and ester functional groups in metal binding. These findings highlight tobacco biomass as a sustainable and cost-effective biosorbent for industrial wastewater treatment. This study presents the first comprehensive evaluation of locally sourced Adıyaman tobacco biomass as a biosorbent for the removal of copper and organic pollutants from real industrial wastewater, integrating kinetic, isotherm, and FT-IR analyses to elucidate the underlying adsorption mechanisms. Full article

Background: Glioblastoma (used to be called glioblastoma multiforme—GBM) is the most common and aggressive brain tumor, having the lowest overall survival rate. Initial focal neurological deficits are primarily attributable to surrounding edema; however, as tumor invasion progresses, these deficits become more pronounced and permanent. The standard treatment for newly diagnosed glioblastoma is represented by cytoreductive neurosurgery followed by the Stupp Protocol. Postoperative recovery of the patient with glioblastoma is a long-term process that should include, for overall more acceptable outcomes, neurorehabilitation. This review aims to bring together evidence from neuro-oncology, neurosurgery, and neurorehabilitation in order to better understand the factors associated with recovery, functional status, and quality of life (QoL) after glioblastoma surgery. Our work also aimed to update the related knowledge base and to attempt to optimize the related protocols in patients with operated cerebral glioblastoma. Methods: For these purposes, we conducted a systematic literature review to assess the current state of research referring to the above-mentioned topic. We have used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA—widely recognized internationally) methodology. We used, in this respect, specific keyword combinations/“syntaxes” for searching literature in the domain, in four international databases. Results: Following PRISMA screening, 14 studies met the predefined eligibility criteria. Additional manual reference screening and complementary searches identified further relevant publications, resulting in a total of 22 included articles. Together, the reviewed work addressed a diverse range of topics relevant to postoperative glioblastoma management, including the potential role of multidisciplinary rehabilitation, cognitive interventions, neuromodulation approaches, and functional assessment strategies in improving postoperative outcomes and QoL in glioblastoma patients, while emphasizing that this interdisciplinary domain warrants more extended approaches. Discussion and Conclusions: Despite the relatively limited and largely exploratory available information, neurorehabilitation may contribute to improved functional outcomes and QoL in patients with glioblastoma. Full article

Carbonation treatment can effectively address defects in recycled aggregates (RA) while achieving CO₂ sequestration, thereby improving properties of recycled aggregate concrete (RAC). However, the compressive strength of carbonated recycled aggregate concrete (CRAC) is governed by complex interactions among multiple parameters, and existing machine learning (ML) studies often rely on heterogeneous literature data with limited parameter coverage, resulting in constrained predictive accuracy. To address this issue, this study established a robust ML framework for precise strength prediction. By integrating published literature with original experimental results, a dataset of 226 groups was constructed, incorporating 12 key parameters across RA properties, carbonation processes, mix proportions, and concrete age to systematically compare three ML models (GPR, SVM, EDT). To enhance model transparency, global sensitivity analysis used the SHapley Additive exPlanations (SHAP) method, while X-ray diffraction (XRD), scanning electron microscopy (SEM), and microhardness tests were employed to reveal reinforcement mechanisms at the phase, microstructural, and micromechanical levels, supporting the connection between intelligent prediction and mechanistic explanation. Results show that the GPR model exhibited the highest predictive performance and generalization capability (R² = 0.98 for training, R² = 0.94 for testing; RMSE = 1.08 MPa), outperforming comparative models in handling high-dimensional nonlinear relationships. SHAP analysis identified concrete age, water–cement (W/C) ratio, and the initial crush index of the RA as the primary factors, while carbonation process parameters, particularly relative humidity, carbonation pressure, and carbonation time, exerted significant regulatory effects on strength. XRD results qualitatively confirmed the formation of CaCO₃ after carbonation, while SEM and microhardness analyses indicated that carbonation products contributed to pore filling and interfacial transition zone (ITZ) strengthening, providing a physical basis for both macroscopic performance improvement and model reliability. This study provides a scientific, data-driven solution for the mix design optimization and performance prediction of CRAC, delivering substantial environmental and economic benefits. Full article

Background: The 75 g oral glucose tolerance test (OGTT) is the gold standard for diagnosing gestational diabetes mellitus (GDM) and, according to current guidelines, is recommended for postpartum testing. German guidelines recommend a two-step screening approach, which can delay treatment initiation. In order to prevent complications for mother and child, treatment of GDM should be started as early as possible. To expedite clinical decisions, point-of-care testing (POCT) is often used alongside venous laboratory analysis. For historical reasons, capillary blood was used for POCT at our competence center. This analysis evaluates the diagnostic accuracy of capillary POCT compared to the venous reference standard analyzed in our department of clinical chemistry. Methods: We retrospectively analyzed 401 OGTTs (260 during pregnancy, 141 postpartum) with simultaneous capillary POCT and venous laboratory glucose measurements and investigated the agreement between the two methods. Optimal capillary cut-offs were determined using ROC analysis. Results: In pregnant women (n = 260), capillary POCT showed 80.8% sensitivity and 73.4% specificity. Regarding the diagnostic classification, the initial agreement with the reference standard at fasting was 71.9% (8.9% false positives, 19.2% false negatives). Optimized capillary cut-offs—fasting ≥95 mg/dL (5.3 mmol/L), 1-h ≥203 mg/dL (11.3 mmol/L), and 2-h ≥174 mg/dL (9.7 mmol/L)—increased the proportion of correctly classified cases to 85.5% (fasting), 97.0% (1-h), and 94.4% (2-h), respectively, and effectively eliminated false negatives. Conclusions: While capillary POCT offers >80% sensitivity, its false-positive rate of more than 20% must be managed. Utilizing optimized cut-off values can mitigate this uncertainty. If at least one of these cut-offs is exceeded, capillary POCT via StatStrip^® (Nova Biomedical Corporation, Waltham, MA, USA) provides a sufficient basis for treatment initiation. Full article

Background/Objectives: In recent years, efforts to understand obesity’s pathophysiology have focused on satiety signals in the hypothalamus and hormonal signalling in orexigenic and anorexigenic neurons. These signals, linked to hunger, satiety, and energy expenditure, are influenced by peptides that activate or suppress specific pathways. However, different phenotypes related to body composition result from mutations (allelic variants) in genes that encode these proteins, particularly peptide receptors. Specifically, the hormone receptor ghrelin (GHSR), located on the surface of orexigenic neurons, has been linked to the regulation of hunger. Additionally, the production and secretion of ghrelin, a peptide hormone produced by the stomach, may exhibit varying sensitivity in its receptor based on an individual’s nutritional status. Moreover, allelic variants of the GHSR gene may potentially lead to significant alterations in signalling provided by the GHSR receptor, resulting in modified hormone-binding phenotypes. In this context, the search for allelic variants that can account for diverse phenotypes, whether thinness or overweight/obesity, can aid in comprehending the pathway and defining new strategies for early laboratory diagnosis or target peptides for treatment. Methods: Initial mining produced 373 non-random SNPs located in missense regions. A total of 373 missense variants were initially identified in the GHSR gene. After applying a global minor allele frequency (MAF) filter of <1%, 20 rare missense variants remained. Results: These variants were subsequently analyzed using nine in silico pathogenicity prediction tools, resulting in the prioritization of eight variants predicted as deleterious by at least four algorithms. These variants were further analysed using the HOPE project web server and the SwissModel database. Conclusions: Through these analyses and future investigations into these mutations, we may gain a more comprehensive understanding of the implications of these mutations and their potential correlation with the pathophysiology of obesity. Full article

Repeated heat–moisture treatment (RHMT) is an efficient approach for modifying starch. However, the role of treatment temperature, a critical parameter, remains poorly understood. Therefore, this study investigated the effects of RHMT temperatures (80, 100, 120 °C) and cycles (1, 3, 5, 7) on the multi-scale structure and in vitro digestibility of hard proso millet starch, using native starch as a control. Compared with the severe 120 °C treatment, processing at 100 °C better preserved double-helical organization (supported by moderately retained enthalpy, ΔH) and short-range order, while maintaining granule integrity. These structural retentions restricted swelling, improved pasting stability, and reinforced the macroscopic gel network. Furthermore, multivariate analysis suggested that the rigidified internal granular architecture delayed initial enzymatic hydrolysis, maximizing slowly digestible starch (SDS) formation (47.44% in 100-RHMT-5). Conversely, 120 °C caused severe granular collapse and a drastic drop in ΔH, diminishing gel elasticity and triggering a surge in rapidly digestible starch (RDS, 59%). Overall, 100 °C RHMT yields an SDS-enriched starch, which may be a promising ingredient for the development of starch-based foods with slower in vitro digestibility. Full article

CoCrFeMnNi high-entropy alloy (HEA) coatings were fabricated on an S41500 stainless steel substrate by laser cladding and subsequently strengthened using machine hammer peening (MHP) at three hammering energies of 1.7 J, 3.5 J, and 5.0 J. The effects of MHP treatment on the phase structure, surface morphology, microhardness, and tribological properties of the coatings were systematically investigated. The results showed that all coatings retained a single-phase face-centered cubic (FCC) structure after MHP treatment, indicating excellent microstructural stability during impact-induced strengthening. With increasing hammering energy, the surface morphology gradually evolved from discrete hammering indentations to a more continuous orange-peel-like texture, while the surface roughness initially increased and then decreased. MHP significantly enhanced the surface hardness of the coatings. In particular, the MHP3.5 sample exhibited the highest surface hardness of approximately 420 HV, representing an increase of about 120% compared with the untreated coating. Under dry sliding conditions at a load of 30 N, the MHP3.5 sample exhibited the lowest and most stable friction coefficient, maintaining a steady-state value of approximately 0.40–0.45. Its specific wear rate decreased by nearly 45% compared with that of the untreated coating. The improved wear resistance was mainly attributed to the combined effects of strain hardening, grain refinement, and dislocation strengthening induced by machine hammer peening. Considering the hardness, friction coefficient, and specific wear rate results together, a hammering energy of 3.5 J was identified as the most suitable MHP parameter under the low-load wear conditions investigated in this study. Full article

This study investigated carbonaceous materials prepared from Paulownia tomentosa leaves by hydrothermal carbonization, slow pyrolysis, and HCl post-treatment for the adsorption of metribuzin and tebuconazole from water. Hydrochars were prepared at 180–220 °C, pyrochars at 400–600 °C, and the pyrochar produced at 600 °C was further treated with HCl. The materials were characterized by yield, ash content, active and exchangeable pH, oxidizable organic carbon content, FTIR, SEM, and CO₂-derived surface and pore properties. Increasing processing temperature reduced the yield in both conversion routes. Hydrochars retained more oxygen-containing and oxidizable organic structures, whereas pyrochars showed stronger carbonization, higher ash content, and higher CO₂-derived surface area. HCl treatment decreased the ash residue, thereby resulting in improved CO₂-accessible surface and pore properties and more fragmented morphology. Metribuzin adsorption was better described by the pseudo-second-order kinetic model across all sorbents, with the highest fitted equilibrium adsorbed amount observed following HCl treatment. Tebuconazole showed higher initial uptake toward most untreated materials, but its kinetic profiles were non-monotonic, with a decrease in the adsorbed amount at longer contact times. Consequently, the conventional PFO and PSO models did not adequately describe its complete kinetic behavior. Nonlinear isotherm modeling showed predominantly Freundlich-type fitting for metribuzin, suggesting heterogeneous adsorption sites, whereas tebuconazole was formally better described by Langmuir-type fitting, although with poorer fit quality for several materials. The results show that Paulownia tomentosa leaves are a suitable precursor for carbonaceous sorbents and that HCl-treated pyrochar is the most promising material for metribuzin adsorption. Full article

ANCA-associated vasculitis (AAV) with kidney involvement represents small-vessel vasculitis, characterized by rapidly progressive glomerulonephritis and a high risk of end-stage kidney disease (ESKD) and increased mortality. AAV typically presents with multisystem involvement, with renal manifestations occurring more frequently in microscopic polyangiitis (MPA) (90–100%) and granulomatosis with polyangiitis (GPA) (50–80%). The classic clinical presentation includes acute kidney injury with hematuria and proteinuria, accompanied by ANCA positivity (MPO-ANCA or PR3-ANCA). Histologically, the predominant pattern is segmental necrotizing glomerulonephritis with crescent formation. Treatment consists of two phases: (a) induction of remission with a lower cumulative dose of glucocorticoids (according to the reduced-dose PEXIVAS regimen) in combination with rituximab or cyclophosphamide and (b) maintenance of remission with rituximab for 2–4 years. The C5a receptor inhibitor avacopan can be used as a steroid-sparing agent in patients with severe kidney involvement or at high risk of corticosteroid-related complications. Beyond the traditional markers of disease activity (hematuria, proteinuria, eGFR), novel biomarkers such as urinary soluble CD163, MCP-1, complement activation products (C5a, sC5b-9), and urinary Treg/Th17 profiles have demonstrated prognostic value. Early diagnosis and prompt initiation of immunosuppressive therapy significantly improve both kidney and overall survival, while prevention of relapses and long-term complications plays a key role in improving the long-term prognosis of patients with AAV. Full article

Background: Fixed-ratio combinations of basal insulin and glucagon-like peptide-1 receptor agonists have emerged as an effective strategy for treatment intensification in type 2 diabetes mellitus (T2DM). However, long-term real-world data on their metabolic, β-cell, and renal effects remain limited. This study aimed to evaluate the 12-month real-world outcomes of insulin glargine/lixisenatide (iGlarLixi) therapy. Methods: This retrospective observational study included 78 patients with T2DM who were initiated on iGlarLixi and followed for 12 months. Clinical and laboratory parameters were assessed at baseline, 3 months, and 12 months. Changes in anthropometric, glycemic, biochemical, and renal parameters were analyzed. Early (3-month) changes were evaluated as predictors of long-term outcomes using correlation and receiver operating characteristic (ROC) analyses. Results: Median HbA1c decreased from 9.0% to 8.2% at 12 months (p = 0.015), with clinically meaningful improvement (≥1% reduction) observed in 21 (26.9%) patients. Body weight decreased significantly from 93.0 kg to 89.5 kg (p < 0.001). C-peptide levels increased from 2.46 to 3.00 ng/mL (p = 0.016). Median albumin-to-creatinine ratio (ACR) showed statistically significant paired changes; however, group-level median values remained similar over time. A reduction in albuminuria was observed in 34 (54.8%) of patients with available paired data. Exploratory ROC analyses suggested that early changes in body weight (AUC: 0.82), HbA1c (AUC: 0.74), and C-peptide (AUC: 0.76) may be associated with long-term outcomes. A combined model incorporating early weight and C-peptide changes showed improved exploratory predictive performance (AUC: 0.88). Conclusions: In a real-world setting, iGlarLixi therapy was associated with significant improvements in glycemic control and body weight, along with increased C-peptide levels that may reflect improved endogenous insulin secretion. While group-level renal changes were modest, individual-level improvements in albuminuria were observed in a substantial proportion of patients. Early treatment responses may serve as practical predictors of long-term outcomes, supporting a personalized approach to diabetes management. These findings should be interpreted in the context of concomitant therapies and comorbidities that may have influenced metabolic and renal outcomes in routine clinical practice. Full article

Background and Objectives: Robotics training improves gait after stroke, but no prior studies have investigated whether emerging long-term gait biomechanics improvements occur after training. We assessed the temporal profile of pre-post gait biomechanics changes after 9 weeks of dorsiflexion specific adaptive control ankle robot (AMBLE™) training, and at 9 weeks post-training and 17 months later in three persons with chronic stroke to probe for ongoing locomotor plasticity versus post-training disuse decay. Materials and Methods: Three densely hemiparetic subjects (mean ± SD), age 62 ± 7 years., stroke latency 8 ± 4 years, available for repeat testing from an original N = 24 robotics training cohort study, underwent three-dimensional gait analyses pre-post 9 weeks of AMBLE training, and then 9 weeks and 17 months after all robotics training ended. Results: We found that only 47% of total improvements in heel-first strikes and 31% increased paretic step length occurred pre-post training. Unexpectedly, all other biomechanical improvements manifested progressively 17 months after training ended, including ankle peak swing angle (∆ = 7°), dorsiflexion angular velocity (∆ = 23°/s), peak knee flexion (∆ = 11.1°) and hip flexion (∆ = 6°). Robotics prescription progressions in level of assistance and dorsiflexion target angle strongly correlated to gait biomechanical outcomes at 17 months, including improved heel-first strikes and peak dorsiflexion swing angle in this small sample. Conclusions: These findings show that initial improvements in foot–ankle function across training are followed by emergent biomechanical improvements in ankle, knee and hip kinematics across 17 months post-training, with delayed outcomes related to robotics prescription progression. The temporal profile of biomechanical adaptations might suggest delayed, progressive reduction in pathological multi-joint synergies of the hemiparetic leg. However, findings are exploratory and cannot establish causality, treatment efficacy or broad generalizability. Future research is needed to determine whether ankle robotics training can catalyze improvements in long-term gait biomechanical safety and efficiency in the chronic disease management of stroke. Full article

To develop a rapid, scalable, and eco-friendly hydrogel for wastewater decontamination, an industrial internal mixer was employed to fabricate a green hydrogel adsorbent based on starch and humic acid. Starch-grafted polyacrylamide hydrogels incorporated with humic acid were rapidly synthesized within 5 min using an internal mixer as the reactor. Starch was gelatinized in situ, followed by graft polymerization with acrylamide via free-radical polymerization and cross-linking with N,N′-methylenebisacrylamide in the same reactor. Humic acid was introduced as a natural modifier to boost the dye adsorption performance of the starch-based hydrogel. The adsorption capacity for methylene blue was evaluated under different humic acid dosages, and the maximum adsorption capacity occurred at a humic acid dosage of 20 g. Additional batch experiments revealed that the adsorption capacity increased with increasing the solution pH (from 22.6 to 54.0 mg g⁻¹ over pH 4–12) and the initial dye concentration (from 14.6 to 34.1 mg g⁻¹ over 40–200 mg L⁻¹), while it decreased with increasing the adsorbent dosage (from 35.9 to 10.6 mg g⁻¹ over 0.1–0.9 g). Distinguished from conventional laboratory stirred reactors that require 2–3 h for hydrogel synthesis, the internal mixer achieves a one-pot synthesis within 5 min, showing outstanding potential for industrial large-scale production. This work provides a time-efficient, industrially compatible strategy to prepare eco-friendly starch–humic acid hydrogels, which show promising potential as sustainable adsorbents for dye-contaminated wastewater treatment. Full article