Search Results (515)

Background: Precision medicine refers to the formulation of personalized drug regimens according to the individual characteristics of patients to achieve optimal efficacy and minimize adverse reactions. Additive manufacturing (AM), also known as three-dimensional (3D) printing, has emerged as an optimal solution for precision drug delivery, enabling customizable and the fabrication of multifunctional structures with precise control over morphology and release behavior in pharmaceutics. However, the influence of 3D printing parameters on the printed tablets, especially regarding in vitro and in vivo performance, remains poorly understood, limiting the optimization of manufacturing processes for controlled-release profiles. Objective: To establish the fabrication process of 3D-printed controlled-release tablets via comprehensively understanding the printing parameters using fused deposition modeling (FDM) combined with hot-melt extrusion (HME) technologies. HPMC-AS/HPC-EF was used as the drug delivery matrix and carbamazepine (CBZ) was used as a model drug to investigate the in vitro drug delivery performance of the printed tablets. Methodology: Thermogravimetric analysis (TGA) was employed to assess the thermal compatibility of CBZ with HPMC-AS/HPC-EF excipients up to 230 °C, surpassing typical processing temperatures (160–200 °C). The formation of stable amorphous solid dispersions (ASDs) was validated using differential scanning calorimetry (DSC), hot-stage polarized light microscopy (PLM), and powder X-ray diffraction (PXRD). A 15-group full factorial design was then used to evaluate the effects of the fan speed (20–100%), platform temperature (40–80 °C), and printing speed (20–100 mm/s) on the tablet properties. Response surface modeling (RSM) with inverse square-root transformation was applied to analyze the dissolution kinetics, specifically t_50% (time for 50% drug release) and Q_4h (drug released at 4 h). Results: TGA confirmed the thermal compatibility of CBZ with HPMC-AS/HPC-EF, enabling stable ASD formation validated by DSC, PLM, and PXRD. The full factorial design revealed that printing speed was the dominant parameter governing dissolution behavior, with high speeds accelerating release and low speeds prolonging release through porosity-modulated diffusion control. RSM quadratic models showed optimal fits for t_50% (R² = 0.9936) and Q_4h (R² = 0.9019), highlighting the predictability of release kinetics via process parameter tuning. This work demonstrates the adaptability of polymer composite AM for tailoring drug release profiles, balancing mechanical integrity, release kinetics, and manufacturing scalability to advance multifunctional 3D-printed drug delivery devices in pharmaceutics. Full article

Typhoon Yagi (2024) was a rapidly moving storm that lasted for eight days and made landfall in three locations, producing heavy rainfall over Hainan and Vietnam. This study aims to investigate the dynamical processes contributing to the heavy rainfall, concentrating on enthalpy flux (EF) and moisture flux (MF). The results indicate that both EF and MF increased significantly during the typhoon’s intensification stage and were high at the time of landfall. Before landfalling at Hainan, latent heat flux (LHF) reached 600 W/m², while sensible heat flux (SHF) was recorded as 80 W/m². Landfall at Hainan resulted in a decrease in LHF and SHF. LHF and SHF subsequently increased to 700 W/m² and 100 W/m², respectively, as noted prior to the landfall in Vietnam. The increased LHF led to higher evaporation, which subsequently elevated moisture flux (MF) following the landfall in Vietnam, while the region’s topography further intensified the rainfall. The mean daily rainfall observed over Philippines is 75 mm on 2 September (landfall and passing through), 100 mm over Hainan (landfall and passing through) on 6 September, and 95 mm at over Vietnam on 7 September (landfall and after), respectively. Heavy rainfall was observed over the land while the typhoon was passing and during the landfall. This research reveals that Typhoon Yagi’s intensity was maintained by a well-organized and extensive circulation system, supported by favorable weather conditions, including high sea surface temperatures (SST) exceeding 30.5 °C, substantial low-level moisture convergence, and elevated EF during the landfall in Vietnam. Full article

Low-temperature stress severely limits plant growth and reduces agricultural productivity. Calmodulin-like (CML) proteins are crucial calcium sensors in plant cold responses. Transcriptome analysis of cold-stressed Saussurea involucrata identified seven differentially expressed CML genes. qRT-PCR confirmed that SiCML6 was strongly induced at 4 °C and −2 °C. Bioinformatics analysis showed that SiCML6 encodes a transmembrane protein containing an EF-hand domain. This protein carries a signal peptide and shows the closest phylogenetic relationship to Helianthus annuus CML3. Its promoter contains ABA, methyl jasmonate (MeJA), and cold-response elements. Arabidopsis plants overexpressing SiCML6 showed significantly higher survival rates at −2 °C than wild-type plants. Under freezing stress, SiCML6-overexpressing lines exhibited reduced malondialdehyde content, relative electrolyte leakage, and ROS accumulation (H₂O₂ and O₂⁻), along with increased proline, soluble sugars, soluble proteins, and total antioxidant capacity (T-AOC). SiCML6 elevated the expression of cold-responsive genes CBF3 and COR15a under normal conditions and further upregulated CBF1/2/3 and COR15a at 4 °C. Thus, low temperatures induced SiCML6 expression, which was potentially regulated by ABA/MeJA. SiCML6 enhances freezing tolerance by mitigating oxidative damage through boosted T-AOC and osmoprotectant accumulation while activating the CBF-COR signaling pathway. This gene is a novel target for improving crop cold resistance. Full article

Chiral molecules are crucial in the field of optical devices, molecular recognition, and other novel functional materials due to their unique spatially asymmetric configuration and optical activity. In this study, a chiral molecule, Cholest-3-yl (E)-3-(4-carbamoylphenyl)acrylate (CCA), was combined with dyes containing large conjugated structures, tetramethylporphyrin tetrasulfonic acid (TPPS), and Nickel(II) phthalocyanine-tetrasulfonic acid tetrasodium salt (TsNiPc), and composite LB films of CCA/TPPS and CCA/TsNiPc were successfully prepared by using Langmuir-Blodgett (LB) technology. The circular dichroism (CD) test proved that the CCA/TPPS composite film had a strong CD signal at 300–400 nm, and the composite film showed chirality. This significant optical activity provides a new idea and option for the application of LB films in chiral sensors. In the Surface Enhanced Raman Spectroscopy (SERS) test, the CCA/TPPS composite film was sensitive to signal sensing, in which the enhancement factor EF = 2.28 × 10⁵, indicating that a large number of effective signal response regions were formed on the surface of the film, and the relative standard deviation (RSD) = 12.08%, which demonstrated that the film had excellent uniformity and reproducibility. The high sensitivity and low signal fluctuation make the CCA/TPPS composite LB film a promising SERS substrate material. Full article

Background/Objectives. Previous research with extremely and very preterm children indicates that these children obtain significantly lower results in executive functions (EFs) and in reading skills than full-term (FT) children. The comparison results do not seem to be so clear when other PT children in lower-risk conditions are studied. Many studies with typically developing and preterm (PT) children indicate that reading ability is determined, in part, by EFs. Therefore, the study of EFs and reading and their relationships in low-risk PT children is pertinent. Methods. In the present study, 111 PT children, classified into three groups with different ranges of gestational age (GA), and one group of 34 FT children participated in a longitudinal study, carried out from 4 to 9 years of age. The results obtained from the four groups in different EFs measured at 4, 5, and 8 years of age, and in reading skills at 9 years of age were compared. The possible effects of EFs on reading skills were studied through multiple linear regression analyses. Results. The results obtained indicate that no significant difference was found between FT children and any of the GA groups of PT children, either in EFs or reading skills. The effect of EFs on reading skills was low to moderate. Verbal and non-verbal working memory had a positive significant effect on decoding skills (letter names, same–different, and word reading), but not on reading comprehension processes. Higher-order EFs (cognitive flexibility and planning), as well as inhibitory control, showed positive effects on reading comprehension skills. The effects of the different EFs varied depending on the reading process. Conclusions. In conclusion, low-risk PT children do not differ from FT children in their competence in EFs or reading skills. There are long-lasting effects of EFs, measured several years before, on reading skills measured at 9 years of age. Full article

Background/Objectives: This study aimed to evaluate myocardial scar burden and distribution, as well as other nuclear imaging parameters, in predicting cardiac resynchronization therapy (CRT) responses and long-term outcomes in patients selected for CRT with ischemic HF etiology. Methods: Seventy-one patients were prospectively included. They all had NYHA class II/III despite optimal medical therapy, LVEF ≤ 35%, wide QRS complexes, and ischemic HF etiology. All were indicated for de novo CRT implantation and underwent a SPECT MPI viability test prior to CRT implantation. Two-dimensional echocardiography was performed one day before CRT implantation and 6 months after the intervention. The follow-up examination was conducted six months after the CRT implantation and, after 5 years, patients underwent a telephone follow-up to assess survival. Results: Most patients (85%) were male, with an average age of 66.26 ± 9.25 yrs. SPECT MPI revealed large myocardial scars (44.53 ± 20.94%) with high summed rest scores (SRSs) of 25.02 ± 11.29 and low EFs of 26.67 ± 7.71%. At the 6-month follow-up, after the CRT implantation, the NYHA class significantly changed and 35% of the patients were classified as CRT responders. The only difference between responders and non-responders was in the SRS and myocardial scar size (p < 0.001). A scar size of 19.5% was an optimal cutoff for the prediction of CRT response (AUC 0.853, Sn 85% and 1-sp 94%). Conclusions: SPECT MPI parameters are valuable in predicting responses and long-term survival in patients with CRT. Patients with myocardial scars of less than 19.5% may be suited to CRT and experience better cardiovascular survival. Full article

Background: CCAAT/enhancer-binding protein alpha–basic leucine zipper in-frame (CEBPA^bZIP-inf) mutations are associated with favorable outcomes in acute myeloid leukemia (AML). So far, there are limited data on integrating clinical and genomic features impacting the outcomes. Methods: Clinical and genomic data from consecutive patients with CEBPA^bZIP-inf were reviewed. A Cox proportional hazards regression was used to identify the variables associated with event-free survival (EFS), relapse-free survival (RFS) and survival. Results: 224 CEBPA^bZIP-inf patients were included in this study. In the 201 patients, except for the 19 receiving the transplant in the first complete remission with no events (the transplant cohort), multivariate analyses showed that IKZF1 mutations/deletions were significantly associated with poor EFS (p = 0.001) and RFS (p < 0.001); FLT3-ITD mutations, poor RFS (p = 0.048). In addition, increasing WBC count, lower hemoglobin concentration, non-intensive induction, and MRD positivity after first consolidation predicted poor outcomes. On the basis of the number of adverse prognostic covariates for RFS, the 201 patients were classified into low-, intermediate- or high-risk subgroups, and there were significant differences in the 3-year EFS, RFS and survival rates (all p < 0.001); however, except for survival in the low-risk group, these metrics were lower than those in the transplant cohort. Conclusions: We identified a potential high-risk population with adverse prognostic factors in CEBPA^bZIP-inf AML patients for which transplantation should be considered. Full article

Background/Objectives: Fibromyalgia syndrome (FMS) is a chronic pain condition in which executive function (EF) alterations have been reported, though strikingly, relationships between simple executive functions (EFs) (updating, inhibition, and mental flexibility) and high-order ones, such as planning and problem-solving, have not been addressed yet in this population. This research aimed to firstly explore how low-level EFs play a role in planning and problem-solving performances. Methods: Thirty FMS patients and thirty healthy participants completed a series of neuropsychological tests evaluating low- and high-order EFs. Clinical and emotional symptoms were assessed with self-report questionnaires, while pain and fatigue levels were measured with numerical scales. Importantly, specific drug restrictions were accounted for. Results: Patients scored lower in most neurocognitive tests, with statistical significance noted only for visuospatial working memory (WM) and two planning and problem-solving tests. Pain, fatigue, and sleep disturbances showed important effects on most of the cognitive outcomes. Multiple regression analyses reflected that planning and problem-solving were successfully and partially predicted by updating, inhibition, and mental flexibility (though differences emerged between tasks). Conclusions: Our study confirms the presence of cognitive impairments in FMS, especially in high-order EFs, supporting patients’ complaints. Clinical symptoms play a role in FMS dyscognition but do not explain it completely. For the first time, as far as the authors know, simple EF influences on planning and problem-solving tests have been described for FMS patients. These results might help in unraveling the dysexecutive profile in FMS to design more adjusted treatment options. Full article

Background: We investigated the role of a high-sensitive cardiac troponin T (hsTnT) increase below the upper limit of normal (ULN) in patients with breast cancer (BC). hsTnT assays accurately quantify very low plasma troponin concentrations and enable the early detection of cardiomyocyte injury before a drop in the left ventricular ejection fraction (LVEF). The increase in hsTnT below the ULN in response to chemotherapy has not previously been studied. Method: This was an open-label pilot study. Female patients with newly diagnosed BC scheduled to receive systemic cancer treatment were recruited. Blood sampling and echocardiography were performed at baseline, at 3 and 6 months of cancer treatment. hsTnT concentrations were measured using the Elecsys TnT hs assay (Roche Diagnostics). The limit of blank and 99th percentile cutoff values for the hsTnT assay were 3 and 14 ng/L. We calculated the rise in hsTnT (ΔhsTnT) by the difference (%) between its baseline level and during follow-up (FU) in each patient. Results: Among eligible subjects, we excluded 4 patients before the start of treatment and 17 patients during the follow-up with values for the hsTnT >14 ng/L. Finally, 60 women with a median age of 48.6 ± 1.3 years were included in the study. The median baseline hsTnT concentration was 5.5 ± 1.4 ng/L. During 6 months of cancer treatment, hsTnT increased in all patients by up to 10–305% from baseline, with an average of 94.2%. LV EF was normal at baseline and decreased significantly compared to the value before cancer treatment (61.9 ± 3.3% vs. 56.3 ± 7.0%; p < 0.045). We correlated the hsTnT rise with a drop in LV EF ≥ 10% from its baseline level. Logistic regression analysis showed that Δ hsTnT has a good predictive value for LV dysfunction, 0.78 (p = 0.05), 95% CI (0.67–0.90). The increase in hsTnT > 81% was determined as the optimal threshold value for detecting early biochemical cardiotoxicity. Conclusion: It was investigated that hsTnT rise within the cutoff < 14 ng/L can be used as a marker of early biochemical cardiotoxicity and is valuable for predicting LV drop in 6 months of FU. We conclude that BC patients with increased hsTnT plasma concentration > 81% from the baseline value should be considered as high-risk patients for cardiotoxicity and need more precise cardiac monitoring and early preventive medical intervention strategies. Full article

Women’s greater vulnerability to intrusive memories following trauma may be partially explained by the influence of ovarian hormones on memory consolidation processes. Contributing to accumulating research examining the influence of ovarian hormones on the development of intrusive memories, we hypothesized that cyclical fluctuations in estradiol and progesterone, not merely absolute levels, contribute to this risk. We further hypothesized that hormonal contraceptives, which effectively eliminate fluctuations and keep ovarian hormones at chronic low levels, can convey protective effects against memory intrusions following analogue trauma exposure. We examined the development of memory intrusions following trauma film stressor exposure among men (n = 27), hormonal contraceptive (HC) users (n = 41), and naturally cycling (NC) women in the early follicular (EF; n = 24), late follicular (n = 20), ovulatory window (n = 14), and luteal phases (n = 21) for 5 days to assess whether low ovarian hormone levels convey a protective effect for women. Contrary to hypotheses, this study found no support for this prospect; rather, exposure to stressors during the window around ovulation increased the risk for more frequent intrusive memories. Enhanced stress responsivity may have particular effects on ovulation, promoting evolutionary fitness. Full article

Sulfamethazine (SMT) is an antibiotic with good antimicrobial effect and is widely used to treat human and livestock diseases. Though the degradation of SMT by the conventional Fenton and electro-Fenton (EF) processes is efficient, it is limited by a narrow pH and iron sludge generation. Herein, we constructed a cost-effective EF system with the synergistic effect of zero-valent iron (Fe⁰) and sulfite (Fe⁰-EF/Sulfite), and key parameters such as applied current, catalyst dosing, sulfite dosage, and initial pH were optimized. Under the optimal conditions (Fe⁰ dosing of 50 mg/L, sulfite dosage of 1.5 mM, current of 40 mA, and pH of 3), the removal efficiency of 10 mg/L SMT reached 100% within 30 min, and the degradation rate constant reached 0.194 min⁻¹. Electron paramagnetic resonance (EPR) analysis and quenching experiments confirmed the generation of various reactive oxygen species (ROS), such as ^•OH, SO₄⁻, O₂⁻, and ¹O₂, which significantly improved the pollutant removal efficiency. Sulfite accelerated iron cycling and inhibited the formation of iron sludge, thus broadening the pH range of the reaction from three to eight and overcoming the limitations of the conventional EF process. The Fe⁰-EF/Sulfite system performs cost-effectively at a wide pH range, providing an efficient and low-carbon solution for environmental pollution remediation with broad application prospects. Full article

High-density lipoprotein (HDL) and small dense low-density lipoprotein (sdLDL) represent two critical yet contrasting components in lipid metabolism and cardiovascular risk modulation. While HDL has traditionally been viewed as cardioprotective due to its role in reverse cholesterol transport and anti-inflammatory effects, emerging evidence emphasizes that HDL functionality—rather than concentration alone—is pivotal in atheroprotection. Conversely, sdLDL particles are increasingly recognized as highly atherogenic due to their enhanced arterial penetration, oxidative susceptibility, and prolonged plasma residence time. This review critically examined the physiological roles, pathological implications, and therapeutic interventions targeting HDL function and sdLDL burden. Lifestyle modifications, pharmacologic agents including statins, fibrates, PCSK9 inhibitors, and novel therapies such as icosapent ethyl were discussed in the context of their effects on HDL quality and sdLDL reduction. Additionally, current clinical guidelines were analyzed, highlighting a paradigm shift away from targeting HDL-C levels toward apoB-driven risk reduction. Although HDL-targeted therapies remain under investigation, the consensus supports focusing on lowering apoB-containing lipoproteins while leveraging lifestyle strategies to improve HDL functionality. In the setting of heart failure, particularly with preserved ejection fraction (HFpEF), alterations in HDL composition and elevated sdLDL levels have been linked to endothelial dysfunction and systemic inflammation, further underscoring their relevance beyond atherosclerosis. A comprehensive understanding of HDL and sdLDL dynamics is essential for optimizing cardiovascular prevention strategies. Full article

The present study investigates the extent and spatial distribution of metal concentration in stream sediments that flow into Keban Dam Lake, Turkey. Sediment samples were analysed for trace and potentially toxic elements (PTEs), including V, Cr, Co, Ni, Cu, Zn, Pb, Tl, Th, and U. Enrichment Factor (EF), Contamination Factor (CF), Geo-accumulation Index (Igeo), and Pollution Load Index (PLI) were employed to assess contamination levels. Results reveal that Cr exhibited very high enrichment (EF = 15.95) in downstream urban samples, while Cu and Zn showed high enrichment in samples collected from the middle to lower reaches of the stream, probably indicating anthropogenic contributions. Most other elements, such as Pb, Tl, Th, and U, were within natural background levels. Sediment Quality Guidelines (SQGs) indicate that Cr, Ni, and Cu may pose potential ecological risks, especially in samples from urban-influenced and downstream areas where concentrations exceed the Probable Effect Levels (PEL; Cr: 160 mg/kg, Ni: 42.8 mg/kg, Cu: 108 mg/kg). Multivariate statistical analyses, including Pearson correlation and hierarchical clustering, reveal three distinct geochemical groupings. Among these, the most contaminated cluster—corresponding to midstream and downstream regions—is characterized by elevated Cu and Zn concentrations. Strong correlations among Cu–Zn, Ni–Cu, and Th–U suggest there is a combination of anthropogenic and lithogenic sources for most metals. While most sites showed low to moderate pollution, urban downstream locations exhibited significant metal accumulation, necessitating the region’s continued environmental monitoring and management strategies. Full article

Classification of BIM objects is critical for enhancing information interoperability and standardization within construction projects; however, research on automated BIM object classification based on standardized classification systems remains limited. Therefore, this study proposes an automated method to classify BIM objects using IFC data under the Uniclass system, aiming to enhance standardization, semantic clarity, and practical applicability. The proposed method first assigns Uniclass codes to 8715 BIM objects, then extracts 13 types of IFC-derived feature variables—including semantic, spatial, and dimensional information, and uses 2 categories of Uniclass coding information (EF and Ss tables) as classification labels, each comprising 11 and 17 classes, respectively. A Random Forest model with 100 decision trees and 10-fold cross-validation is then employed to perform automatic classification. Experimental results demonstrate that the proposed method achieves classification accuracies of 1.00 and 0.99 for BIM objects under the Elements/Functions and Systems classification tasks. This study demonstrates that accurate and fine-grained classification of BIM objects can be achieved using only low-LOD IFC data, thereby contributing to standardized information structuring and facilitating intelligent model management during the early design phase. Full article

Transition metal borides have garnered significant research interest due to their versatile properties, including superconductivity and exceptional hardness. This study examines the stable crystal structures of Rhodium-Boron (Rh-B) compounds under high pressure using first-principles structural searching. Beyond the previously known Rh₂B, RhB₂, and RhB₄ phases, three new boron-rich phases—C2/m-RhB₆, Amm2-RhB₆, and Cmca-RhB₈—are identified, each characterized by three-dimensional covalent bonding networks. Their mechanical and thermodynamic stability is validated through elastic property assessments and phonon dispersion calculations. Surprisingly, these phases exhibit low bulk and shear moduli, ruling them out as candidates for hard materials. The metallic character of these borides is evident from their electronic density of states, which exhibits a sharp peak at the E_F-a signature often associated with superconducting systems. Indeed, our calculations predict T_c values of 8.93 K and 9.36 K for Amm2-RhB₆ and Cmca-RhB₈, respectively, at 100 GPa. Full article