bluuebunny/crossref_metadata_2025 huggingface dataset:
State-of-the-Art Carbon-Nanotubes-Reinforced Copper-Based Composites: The Interface Design of CNTs and Cu Matrix
Authors: Ren Xiaona , Chang Yue , Ge Changchun
Published: December 2024

Carbon nanotubes (CNTs)-reinforced copper-based composites (CNT/Cu) have been extensively investigated due to their exceptional theoretical electrical, thermal, and mechanical properties. However, the actual performance of these composites has consistently fallen short of theoretical expectations. This discrepancy primarily arises from the inability to achieve direct chemical bonding between copper and carbon nanotubes or to alloy them effectively. Consequently, this leads to interference in electron and phonon transmission at the interface between the two materials, adversely affecting their electrical and thermal conductivity as well as other properties. In recent years, research has increasingly focused on optimizing and regulating the interfacial interactions between carbon nanotubes and the copper matrix to enhance overall performance while also exploring potential applications. This article reviews recent advancements from an interface regulation perspective, summarizing typical interfacial characteristics such as physical interfaces, chemical bonding, and metallurgical bonding along with their respective preparation methods and effects on performance enhancement. Furthermore, a novel microstructural design of CNT/Cu is put forward, where amorphous CNTs (aCNTs) were utilized as the reinforcing phase to form a nanoscale networked composite interface. This not only enables Cu to adhere to the aCNTs’ sidewall but also fills the sidewall within them, with the aim of significantly strengthening the interfacial bonding strength of CNT/Cu and achieving comprehensive improvement of the composite material properties.
Indicators of Obesity and Cardiorespiratory Fitness in Croatian Children
Authors: Badrić Marko , Roca Leona , Pelemiš Vladan , Branković Dragan , Živanović Vladimir
Published: December 2024

Background/Objectives: The aim of this study is to investigate the relationship between CRF (cardiorespiratory fitness) and body composition, specifically obesity indicators, in a sample of schoolchildren from the continental and Adriatic regions of the Republic of Croatia. Given that Croatia ranks among the leading countries in Europe in terms of obesity, it is believed that there is a need to combat this condition starting from school age. The usefulness of cardiorespiratory fitness (CRF) lies in the fact that it is one of the indicators of children’s overall health and is considered a measure of general health status. The findings will emphasize the need to determine CRF and BMI as important factors that should be addressed from early school years in order to prevent future cardiovascular diseases. Methods: The total sample consisted of 423 students, including 212 girls and 211 boys, from the continental and Adriatic regions of the Republic of Croatia, with an average age of 10.32 years. Body height was measured using a portable stadiometer, while body weight, body mass index (BMI), and body fat percentage were measured using a dual-frequency body composition analyzer (TANITA DC-360P) based on the principles of bioelectrical impedance. The WHR index was calculated as the ratio of waist to hips, while the WHtR index was calculated as the ratio of waist circumference to height. Cardiorespiratory fitness was assessed using the 20-meter multistage shuttle run test. Results: The results show that 25% of the participants were overweight, and 9% were obese. The ANOVA results indicate that the boys had significantly higher values for BMI, WC, HC, WHtR, and WHR, while the girls had a significantly higher body fat percentage (BF%). Additionally, the boys had better CRF, as they ran more meters in the 20-meter shuttle run test. The variance analysis revealed that the participants with normal body weight had significantly higher cardiorespiratory capacity values compared to overweight or obese students. Regression analysis showed statistical significance for the set of predictor variables, which were BMI indicators, on the criterion variable predicting cardiorespiratory fitness (CRF) in both genders. The coefficient of determination (R2) explained almost 22% of the shared variability in boys and 19% in girls. Statistically significant beta coefficients were found for body fat percentage (−0.60) in boys and (−0.98) in girls. Conclusions: Body fat percentage (BF%) was shown to be a significant and useful predictor of cardiorespiratory fitness in school-aged boys and girls. Maintaining an optimal body weight along with high levels of CRF should be an important goal in promoting health among children and adolescents.
Cleft Palate and Presurgical Orthopedics: A Systematic Review and Meta-Analysis of Intra-Arch Dimensions During the First Year of Life
Authors: Rabal-Soláns Ana , Mediero-Pérez Carmen , Yáñez-Vico Rosa M.
Published: December 2024

Background: This systematic review and meta-analysis aimed to investigate the effects of presurgical orthopedics (PSO) on maxillary arch dimensions in infants with cleft lip and palate during the first year of life. Methods: The review was conducted following PRISMA guidelines. A comprehensive electronic search was performed in MEDLINE, Embase, Cochrane, Scopus, and Google Scholar databases, supplemented by manual searching. Two reviewers independently conducted study selection, data extraction, quality assessment, and risk of bias evaluation. Results: Five studies were included in the meta-analysis. Quantitative analysis was performed based on the primary outcomes. The estimate was calculated using a random-effects model and z distribution (95% confidence interval (CI)). The results showed similar alveolar cleft widths (mean difference, −3.06; 95% CI, −8.03 to 2.70, p = 0.30, I2 = 99%) with clinical differences in favor of PSO, and comparable posterior cleft widths (mean difference, −0.88; 95% CI, −2.06 to 0.30, p = 0.14, I2 = 89%) with and without PSO in CLP babies. Conclusions: This meta-analysis found no statistically significant effects of presurgical orthopedic treatment on maxillary arch dimensions in infants with cleft lip and palate during the first year of life. Further high-quality randomized controlled trials are needed to definitively establish the efficacy of PSO.
Structure-Activity Relationship Study of Majusculamide D: Overcoming Metabolic Instability and Severe Toxicity with a Fluoro Analogue
Authors: Zhao Xiuhe , Xi Xiaonan , Zhang Mingxiao , Lv Mengxue , Zhang Xiang , Lu Yaxin , Wang Liang , Chen Yue
Published: December 2024

Majusculamide D, isolated from the marine cyanobacterium Moorea producens, is an anticancer lipopentapeptide consisting of fatty acid, tripeptide, and pyrrolyl proline moieties. In this work, by utilizing a convergent synthetic approach, late-stage modification, and bioisostere strategy, 26 majusculamide D analogues were synthesized, and two (1i and 1j) demonstrated IC50 values < 1 nM against PANC-1 cancer cells. The results summarized a preliminary structure-activity relationship mainly at the C23, C4, C34, and C10 sites. A series of in vitro assays, including wound healing, transwell, clone formation, EdU, and western blot, confirmed that majusculamide D inhibited the migration, invasion, and proliferation of pancreatic cancer cells. The optimized fluorinated analogue 1n demonstrated a notable enhancement in stability during the mouse plasma assay (>50% left after 24 h), exhibited tumor-suppressive effects (51.5% at a dosage of 5 mg/kg), and successfully mitigated the severe toxicity (no mouse dead) observed in the group treated with majusculamide D (3 mice dead) in a xenografted mouse model.
Establishing an Extracorporeal Cardiopulmonary Resuscitation Program
Authors: Bertini Pietro , Sangalli Fabio , Meani Paolo , Marabotti Alberto , Rubino Antonio , Scolletta Sabino , Ajello Valentina , Aloisio Tommaso , Baiocchi Massimo , Monaco Fabrizio , Ranucci Marco , Santonocito Cristina , Silvetti Simona , Sanfilippo Filippo , Paternoster Gianluca
Published: December 2024

Extracorporeal cardiopulmonary resuscitation (ECPR) is a complex, life-saving procedure that uses mechanical support for patients with refractory cardiac arrest, representing the pinnacle of extracorporeal membrane oxygenation (ECMO) applications. Effective ECPR requires precise patient selection, rapid mobilization of a multidisciplinary team, and skilled cannulation techniques. Establishing a program necessitates a cohesive ECMO system that promotes interdisciplinary collaboration, which is essential for managing acute cardiogenic shock and severe pulmonary failure. ECPR is suited for selected patients, emphasizing the need to optimize every step of cardiac arrest management—from public education to advanced post-resuscitation care. The flexibility of ECMO teams allows them to manage various emergencies such as cardiogenic shock, massive pulmonary embolism, and severe asthma, showcasing the program’s adaptability. Launching an ECPR program involves addressing logistical, financial, and organizational challenges. This includes gaining administrative approval, assembling a diverse team, and crafting detailed protocols and training regimens. The development process entails organizing teams, refining protocols, and training extensively to ensure operational readiness. A systematic approach to building an ECPR program involves establishing a team, defining patient selection criteria, and evaluating caseloads. Critical elements like patient transport protocols and anticoagulation management are vital for the program’s success. In conclusion, initiating an ECPR program demands thorough planning, collaborative effort across specialties, and ongoing evaluation to improve outcomes in critical cardiac emergencies. This guide offers practical insights to support institutions in navigating the complexities of ECPR program development and maintenance.
Assessment of Quadriceps Muscle in Advanced Knee Osteoarthritis and Correlation with Lower Limb Alignment
Authors: Bae Ki-Cheor , Son Eun-Seok , Yon Chang-Jin , Park Jubin , Kim Du-Han
Published: December 2024

Background and Objectives: Despite extensive studies of the role of quadriceps and quadriceps/hamstring balance in knee osteoarthritis (OA), the roles of the vastus intermedius, medialis, and lateralis in OA remain unclear. The purpose of this study was to investigate the relationship of lower limb alignment and the ratio of the quadriceps femoris muscle to the knee extensor muscle. Materials and Methods: This study included 50 patients with advanced knee OA (Kellgren/Lawrence grade of 3 or 4) and 25 healthy control persons between June 2021 and May 2022. The osteoarthritis grade and anatomical tibiofemoral angle were measured based on plain radiography and scanography. All participants were divided into normal (0~5°), mild varus (5°~10°), and severe varus (>10°) groups. Using MRI, muscle size was determined by calculating the cross-sectional area (CSA) of the total quadriceps (rectus femoris, vastus intermedius, vastus medialis, and vastus lateralis) and its components. Results: The CSA ratio of the vastus lateralis was significantly smaller in the severe varus group than in the normal or mild varus groups. There was a significant positive correlation between the mechanical tibiofemoral angle and vastus lateralis CSA (ρ = 0.282, p = 0.014) and between the anatomical tibiofemoral angle and vastus lateralis CSA (ρ = 0.294, p = 0.011). There was a significant negative correlation between the mechanical tibiofemoral angle and vastus intermedius CSA (ρ = −0.263, p = 0.023) and between the anatomical tibiofemoral angle and vastus intermedius CSA (ρ = −0.243, p = 0.036). Conclusions: Patients with severe varus alignment exhibited vastus lateralis atrophy. This study highlights vastus lateralis atrophy in severe varus alignment, though causality between atrophy and varus knee OA remains uncertain. We think that patients with severe varus may require strengthening exercises focused on the vastus lateralis before and after surgery for alignment correction.
Diagnosis of Pain Deception Using Minnesota Multiphasic Personality Inventory-2 Based on XGBoost Machine Learning Algorithm: A Single-Blinded Randomized Controlled Trial
Authors: Chung Hyewon , Nam Kihwan , Lee Subin , Woo Ami , Kim Joongbaek , Park Eunhye , Moon Hosik
Published: December 2024

Background and Objectives: Assessing pain deception is challenging due to its subjective nature. The main goal of this study was to evaluate the diagnostic value of pain deception using machine learning (ML) analysis with the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) scales, considering accuracy, precision, recall, and f1-score as diagnostic parameters. Materials and Methods: This study was a single-blinded, randomized controlled trial. Subjects were randomly allocated into a non-deception (ND) group and a deception (D) group. Pain deception, as a form of psychological intervention, was taught to subjects in the D group to deceive the physician. MMPI-2, Waddell’s sign, and salivary alpha-amylase (SAA) were also measured. For analyzing the MMPI-2, the XGBoost ML algorithm was applied. Results: Of a total of 96 participants, 50 and 46 were assigned to the ND group and the D group, respectively. In the logistic regression analysis, pain and MMPI-2 did not show diagnostic value. However, in the ML analysis, values of the selected MMPI-2 (sMMPI-2) scales related to pain deception showed an accuracy of 0.724, a precision of 0.692, a recall of 0.692, and an f1-score of 0.692. Conclusions: Using MMPI-2 test results, ML can diagnose pain deception better than the conventional logistic regression analysis method by considering different scales and patterns together.
Bilateral Rectus Sheath Block with Continuous Bupivacaine Infusions After Elective Open Gastrectomy: A Randomized Controlled Trial
Authors: Opincans Janis , Ivanovs Igors , Miscuks Aleksejs , Pavulans Janis , Martinsone Katrina Deja , Rudzats Agris , Kecbaja Zurabs , Gutnikovs Olegs , Kaminskis Aleksejs
Published: December 2024

Background and Objectives: Multimodal analgesia has been shown to be effective in facilitating early postoperative gastrointestinal function and rehabilitation in patients undergoing open gastrectomy. We conducted a clinical trial to investigate the effectiveness of bilateral rectus sheath block (RSB) with continuous bupivacaine infusion in comparison with placebo following elective open gastrectomy. Materials and Methods: Patients indicated for elective open gastrectomy were screened, enrolled, and randomised between October 2021 and September 2023. The patients were randomised to either Group A (intervention—continuous bupivacaine) or Group B (control—NaCl saline). The primary outcome measures were the quantity of an opioid analgesic administered during the initial 72 h post-surgery and the level of postoperative pain as indicated by the visual analogue scale (VAS). Mann–Whitney U test was used for quantitative analysis while Pearson Chi-square was used for categorical variables. Results: A total of 60 patients completed the trial, with 30 patients in each of the two groups. Patients in Group A reported lower median VAS pain scores at all observed time points following surgery (p < 0.001). No patient in Group A required rescue opioid analgesia, although non-steroidal anti-inflammatory drugs were necessary during the initial 12 h postoperatively. Clinically, Group A patients had a significantly shorter time to first gas (p = 0.001), a shorter time to first bowel movement (p < 0.001), a shorter time to first out-of-bed activity (p < 0.001), and a shorter overall hospitalisation duration (p < 0.001) compared to Group B patients. Conclusions: Bilateral RSB with continuous bupivacaine infusion is effective in managing pain and can reduce the use of opioid analgesics in the postoperative period. Furthermore, it promotes early recovery, and a shorter hospital stay.
Pediatric Nephrolithiasis: A Changing Landscape Through Time and Space
Authors: Pecoraro Luca , Zuccato Arianna , Vitella Rebecca , Pietrobelli Angelo , Piacentini Giorgio , Brugnara Milena
Published: December 2024

Pediatric nephrolithiasis is an ancient and complex disorder that has seen a significant rise in recent decades and the underlying causes contributing to stone formation in children may also be shifting. Historically, kidney stones have been linked to factors such as metabolic disorders, congenital abnormalities, and family history. However, the recent increase in incidence appears to be associated with new risk factors, including changes in lifestyle and diet, the growing prevalence of obesity, metabolic syndrome, diabetes, and even climate change. Given this evolving landscape, performing a comprehensive metabolic evaluation during the diagnostic process is essential. A complete metabolic evaluation should thus be performed during the diagnostic assessment to identify any modifiable risk factors predisposing to stone recurrence and reduce the need for surgical management, extrarenal comorbidity, and the increased burden of care.
Evaluation of the Psychometric Properties of the Musculoskeletal Health Questionnaire (MSK-HQ) in a Population of Kitesurfers: A Cross-Sectional Study
Authors: Tonti Marco Alessandro , Carlizza Alessandra , Galeoto Giovanni
Published: December 2024

Background and Objectives: Musculoskeletal disorders affect a large portion of the population worldwide. The Musculoskeletal Health Questionnaire (MSK-HQ) is a helpful tool for assessing the health state of patients with these disorders. The primary goal of this study is to evaluate the psychometric properties of the MSK-HQ-IT in a population of kitesurfers. Materials and Methods: The study was conducted from September 2023 to July 2024. The questionnaire was completed using an online or paper form. Data were collected by submitting both the Italian and English versions of the MSK-HQ to a global sample of kitesurfers from various countries. Results: A total of 102 participants were recruited, consisting of 40 professionals and 62 non-professional kitesurfers. Cervical spine discomfort was significantly more prevalent among professionals (42.5%) compared to non-professionals (24%), as well as right shoulder pain (37.5% vs. 22.5%) and right wrist pain (12.5% vs. 3.2%). Non-professionals exhibited a significantly higher prevalence of functional limitations in the lumbar spine (25.8% vs. 5%) and reported more thoracic pain (21% vs. 17.5%). These findings indicate differing biomechanical stress patterns between the two groups, with professionals showing higher upper limb strain and non-professionals experiencing more lower back issues due to harness reliance. Conclusions: The MSK-HQ proved to be a reliable and valid tool for assessing musculoskeletal health in kitesurfers. The study highlights distinct injury patterns between professionals and non-professionals, with professionals being more prone to upper limb injuries and non-professionals showing a higher prevalence of lumbar and thoracic spine issues. These findings emphasize the need for targeted injury prevention strategies. Further research should focus on expanding the sample size and investigating long-term impacts of repetitive high-impact landings on musculoskeletal health in kitesurfers.
Application of Solution-Processed High-Entropy Metal Oxide Dielectric Layers with High Dielectric Constant and Wide Bandgap in Thin-Film Transistors
Authors: Liu Jun , Xiong Xin , Li Han , Huang Xiangchen , Wang Yajun , Sheng Yifa , Liang Zhihao , Yao Rihui , Ning Honglong , Wei Xiaoqin
Published: December 2024

High-k metal oxides are gradually replacing the traditional SiO2 dielectric layer in the new generation of electronic devices. In this paper, we report the production of five-element high entropy metal oxides (HEMOs) dielectric films by solution method and analyzed the role of each metal oxide in the system by characterizing the film properties. On this basis, we found optimal combination of (AlGaTiYZr)Ox with the best dielectric properties, exhibiting a low leakage current of 1.2 × 10−8 A/cm2 @1 MV/cm and a high dielectric constant, while the film’s visible transmittance is more than 90%. Based on the results of factor analysis, we increased the dielectric constant up to 52.74 by increasing the proportion of TiO2 in the HEMOs and maintained a large optical bandgap (>5 eV). We prepared thin film transistors (TFTs) based on an (AlGaTiYZr)Ox dielectric layer and an InGaZnOx (IGZO) active layer, and the devices exhibit a mobility of 18.2 cm2/Vs, a threshold voltage (Vth) of −0.203 V, and an subthreshold swing (SS) of 0.288 V/dec, along with a minimal hysteresis, which suggests a good prospect of applying HEMOs to TFTs. It can be seen that the HEMOs dielectric films prepared based on the solution method can combine the advantages of various high-k dielectrics to obtain better film properties. Moreover, HEMOs dielectric films have the advantages of simple processing, low-temperature preparation, and low cost, which are expected to be widely used as dielectric layers in new flexible, transparent, and high-performance electronic devices in the future.
Coupled Effects of Time and Temperature on the Rheological and Pipe Flow Properties of Cemented Paste Backfill
Authors: Liu Bo , Zhang Yaoping , Zou Xionggang , Zhang Chaomei , Chang Yingjie
Published: December 2024

As mineral resources at shallow depths become increasingly depleted, the development of these resources is progressively shifting to greater depths. This transition presents challenges for the pipeline transport of cement paste backfill (CPB), particularly in terms of long-distance transport and elevated temperatures. To investigate this phenomenon, we conducted rheological tests, developed a resistance model that accounts for both time and temperature, and performed numerical simulations. The results show that the rheological parameters of CPB exhibit a gradual decline as the flow progresses. Specifically, at 20 °C, the plastic viscosity of CPB decreases by 1.6 Pa·s, and the yield stress decreases by 48.15 Pa; at 30 °C, the plastic viscosity decreases by 1.3 Pa·s, and the yield stress decreases by 18.69 Pa; at 40 °C, the plastic viscosity decreases by 0.84 Pa·s, and the yield stress decreases by 12.55 Pa; and at 50 °C, the plastic viscosity decreases by 0.58 Pa·s, with the yield stress decreasing by 12.53 Pa. Furthermore, the influence of shear time on the rheological properties of CPB diminishes as temperature increases within the range of 20 °C to 50 °C. These results offer significant insights for optimizing the pipeline transport of CPB in mining operations. These findings provide valuable guidance for pipeline transport of CPB in mining operations.
Ceria-Catalysed Production of Dimethyl Carbonate from Methanol and CO2: Effect of Using a Dehydrating Agent Combined with a Solid Cocatalyst
Authors: Shi Dichao , Heyte Svetlana , Capron Mickaël , Paul Sébastien
Published: December 2024

The direct synthesis of dimethyl carbonate (DMC) from CO2 and methanol over ceria-based catalysts, in the presence of a dehydrating agent shifting the thermodynamical equilibrium of the reaction, has received significant interest recently. In this work, several dehydrating agents, such as molecular sieves, 2,2-dimethoxypropane (DMP), dimethoxymethane (DMM) and 1,1,1-trimethoxymethane (TMM), are combined with commercial ceria to compare their influence on the DMC yield obtained under the same set of operating conditions. TMM is found to be the most efficient; however, its conversion is not complete even after 48 h of reaction. Therefore, it is proposed for the very first time, to the best of our knowledge, to add a second solid cocatalyst in the reaction medium to accelerate the TMM hydration reaction without degrading the DMC already formed. Basic oxides and acidic zeolites with different Si/Al ratios are employed to accelerate the hydration of TMM, so as to improve the DMC yield. 13X was identified as the best option to play this role. Finally, three different commercial cerias are tested in the presence of TMM and molecular sieve 13X as the second catalyst. The most efficient combination of ceria, TMM, and molecular sieve 13X is ultimately tested in a 250 mL autoclave to start to scale up the process. A very high DMC production of 199.5 mmol DMC/gcat. is obtained.
Addressing Inflammaging and Disease-Related Malnutrition: Adequacy of Oral Nutritional Supplements in Clinical Care
Authors: Madini Nagaia , Vincenti Alessandra , Beretta Alice , Santero Sara , Viroli Giulia , Cena Hellas
Published: December 2024

Background: Disease-related malnutrition, with or without inflammation, in older adults is currently emerging as a public health priority. The use of Foods for Special Medical Purposes, including Oral Nutritional Supplements, and supplements is crucial to support patients in achieving their nutritional needs. Therefore, this article aims to comprehensively provide an analysis of the adequacy of FSMPs in meeting the nutritional requirements of different age-related diseases and takes into account the emerging role of inflammation. Moreover, it provides an identikit of the ideal products, following the pathology-specific guidelines. Methods: Data on 132 products were gathered through face-to-face meetings with companies’ consultants. Specifically, information on energy, macronutrient, and micronutrient contents were collected, as well as on texture and flavors, osmolarity, cost, and packaging. Results: Most FSMPs met the daily recommendations for energy and protein intake. Nonetheless, few products contained β-hydroxy-β-methylbutyrate, optimal Branched-Chain Amino Acids ratios, arginine, glutamine, and omega-3 fatty acids. Furthermore, a marked predominance of FSMPs with a high osmolarity (85.7%), sweet taste (72%), and only animal protein content (79.5%) was observed. Cost analysis of FSMPs revealed a mean cost of EUR 5.35/portion. Products were mostly adequate for cancer, neurodegenerative diseases, diabetes, inflammatory bowel disease, end-stage kidney disease, dysphagiam and chronic obstructive pulmonary disease. However, gaps have been found for sarcopenia and abdominal surgery. Conclusion: In light of the current market landscape, there is a need for a comprehensive regulation that indicates the optimal composition of FSMPs and the production of such products to tackle disease-related malnutrition.
A Novel Supplement Consisting of Rice, Silkworm Pupae and a Mixture of Ginger and Holy Basil Improves Post-Stroke Cognitive Impairment
Authors: Thongwong Putthiwat , Wattanathorn Jintanaporn , Thukham-mee Wipawee
Published: December 2024

Backgrounds/Objectives: Despite the increasing importance of the condition of post-stroke cognitive impairment (PSCI), the current therapy efficacy is limited. Since oxidative stress and inflammation are targeted in anti-stroke therapy, we aimed to assess the protective effect against PSI of an orodispersible film loaded with silkworm pupae hydrolysate and a combined extract of holy basil and ginger (JP1), which show antioxidant, and anti-inflammation effects. Methods: Male Wistar rats (200–250 g) were administered JP1 at doses of 1, 10, and 100 mg/kg BW 45 min before a 6 h immobilization stress exposure for 14 days. Then, the right middle cerebral artery was permanently occluded (MCAO) and JP1 was continually administered for 21 days after MCAO. Spatial and non-spatial memory and the possible underlying mechanisms were also explored. Results: JP1 improved oxidative stress, inflammation, apoptosis, Erk signaling pathway, cholinergic function, and the growth of Lactobacillus and Bifidobacterium spp. in feces. These results suggest that JP1 improves PSCI, possibly involving the above mechanisms. Furthermore, serum corticosterone also decreased. Conclusions: Our results suggest that JP1 is a potential candidate for combating PSCI following exposure to stroke plus stress. However, a clear understanding of the precise active ingredient and the detailed mechanisms require further investigation.
Biosynthesis and Characterization of Silver Nanoparticles and Simvastatin Association in Titanium Biofilms
Authors: Roque Sindy Magri , Furian Ana Carolina , Takemoto Marcela Kim , Duarte Marta Cristina Teixeira , Parolina Rafaela Durrer , Roque Adriano Luís , Duran Nelson , Sardi Janaína de Cássia Orlandi , Duarte Renata Maria Teixeira , Muller Karina Cogo
Published: December 2024

Introduction: Simvastatin is an antilipidemic drug that has already demonstrated antibacterial activities on oral and non-oral microorganisms. Silver nanoparticles also exhibit antimicrobial properties, particularly for coating implant surfaces. In this study, we evaluated the effects of combining simvastatin with silver nanoparticles on the formation and viability of biofilms consolidated on titanium discs. Methods: Silver nanoparticles were first biosynthesized using the fungus Fusarium oxysporum and then characterized using Dynamic Light Scattering, X-ray Diffraction, Transmission Electron Microscopy, and energy dispersive spectroscopy. Species of Streptococcus oralis, Streptococcus mutans, Porphyromonas gingivalis, Methicillin-sensitive Staphylococcus aureus, and Methicillin-resistant Staphylococcus aureus were used and tested using Minimum Inhibitory Concentration assays with concentrations of silver nanoparticles and simvastatin alone and in combination. Biofilm inhibition and viability tests were performed on titanium surfaces. Toxicity tests were also performed on Galleria mellonella moth larvae. Results: The silver nanoparticles had a spherical shape without the formation of aggregates as confirmed by Transmission Electron Microscopy. Dynamic Light Scattering revealed nanoparticles with an average diameter of 53.8 nm (±1.23 nm), a polydispersity index of 0.23 and a zeta potential of −25 mV (±2.19 mV). The silver nanoparticles inhibited the growth of the strains tested in the range of 0.001592 and 63.75, while simvastatin alone inhibited the growth of the same strains in the range of 3.125–62.5 µg/mL. The antibacterial activity test of the combination of the two substances showed a reduction in the Minimum Inhibitory Concentration of about two to eight times, showing synergistic effects on Staphylococcus aureus and additive effects on Streptococcus oralis and Porphyromonas gingivalis. As for biofilm, sub-inhibitory concentrations of the combination of substances showed better antibacterial activity in inhibiting the formation of Streptococcus oralis biofilm, and this combination also proved effective in eradicating already established biofilms compared to the substances alone. The combination of silver nanoparticles and simvastatin showed low toxicity to Galleria mellonella moth larvae. Conclusions: The results presented indicate that the combination of the two substances could be an alternative for the prevention and reduction of biofilms on implants. These findings open up new possibilities in the search for alternatives for the treatment of peri-implant infections, as well as the possibility of using lower doses compared to single drugs, achieving the same results and reducing potential toxic effects.
Evaluating the Binding Potential and Stability of Drug-like Compounds with the Monkeypox Virus VP39 Protein Using Molecular Dynamics Simulations and Free Energy Analysis
Authors: Hassan Ahmed M. , Gattan Hattan S. , Faizo Arwa A. , Alruhaili Mohammed H. , Alharbi Azzah S. , Bajrai Leena H. , AL-Zahrani Ibrahim A. , Dwivedi Vivek Dhar , Azhar Esam I.
Published: December 2024

Background/Objectives: Monkeypox is a re-emerging viral disease with features of infectiously transmitted zoonoses. It is now considered a public health priority because of its rising incidence and transmission from person to person. Monkeypox virus (MPXV) VP39 protein is identified as an essential protein for replication of the virus, and therefore, it is a potential target for antiviral drugs. Methods: This work analyzes the binding affinities and the differential conformational stability of three target compounds and one control compound with the VP39 protein through multiple computational methods. Results: The re-docking analysis revealed that the compounds had high binding affinities towards the target protein; among these compounds, compounds 1 and 2 showed the highest binding energies in the virtual screening, and thus, these were considered as the most active inhibitor candidates. Intermolecular interaction analysis revealed distinct binding mechanisms. While compound 1 had very strong hydrogen bonds and hydrophobic interactions, compound 2 had numerous water-mediated interactions, and compound 3 had only ionic and hydrophobic contacts. In molecular dynamic simulations, compounds 1 and 2 showed that the protein–ligand complexes had a stable conformation, with protein RMSD values around 2 Å for both compounds. In contrast, compound 3 was slightly flexible, and the control compound was more flexible. MM/GBSA analysis again supported these results, which gave the binding free energies that were also supportive for these compounds. Conclusions: Notably, all the selected compounds, especially compounds 1 and 2, demonstrate high binding affinity. Therefore, these compounds can be further tested as antiviral agents against monkeypox treatment.
Quantification of Amlodipine Maleate Content in Amorphous Solid Dispersions Produced by Fluidized Bed Granulation Using Process Analytical Technology Tools
Authors: Svetič Sandi , Medved Laura , Korasa Klemen , Vrečer Franc
Published: December 2024

Background: Active pharmaceutical ingredient (API) content is a critical quality attribute (CQA) of amorphous solid dispersions (ASDs) prepared by spraying a solution of APIs and polymers onto the excipients in fluid bed granulator. This study presents four methods for quantifying API content during ASD preparation. Methods: Raman and three near-infrared (NIR) process analysers were utilized to develop methods for API quantification. Four partial least squares (PLS) models were developed using measurements from three granulation batches, with an additional batch used to evaluate model predictability. Models performance was assessed using metrics such as root mean square error of prediction (RMSEP), root mean square error of cross-validation (RMSECV), residual prediction deviation (RPD), and others. Results: Off-line and at-line NIR models were identified as suitable for process control applications. Additionally, at-line Raman measurements effectively predicted the endpoint of the spraying phase. Conclusions: To the best of authors’ knowledge, this is the first study focused on monitoring API content during fluidized bed granulation (FBG) used for ASD preparation. The findings provide novel insights into the application of Raman and NIR process analysers with PLS modelling for monitoring and controlling ASD preparation processes.
Antimicrobial Peptides: A Promising Solution to the Rising Threat of Antibiotic Resistance
Authors: Islam Tarequl , Tamanna Noshin Tabassum , Sagor Md Shahjalal , Zaki Randa Mohammed , Rabbee Muhammad Fazle , Lackner Maximilian
Published: December 2024

The demand for developing novel antimicrobial drugs has increased due to the rapid appearance and global spread of antibiotic resistance. Antimicrobial peptides (AMPs) offer distinct advantages over traditional antibiotics, such as broad-range efficacy, a delayed evolution of resistance, and the capacity to enhance human immunity. AMPs are being developed as potential medicines, and current computational and experimental tools aim to facilitate their preclinical and clinical development. Structural and functional constraints as well as a more stringent regulatory framework have impeded clinical translation of AMPs as possible therapeutic agents. Although around four thousand AMPs have been identified so far, there are some limitations of using these AMPs in clinical trials due to their safety in the host and sometimes limitations in the biosynthesis or chemical synthesis of some AMPs. Overcoming these obstacles may help to open a new era of AMPs to combat superbugs without using synthetic antibiotics. This review describes the classification, mechanisms of action and immune modulation, advantages, difficulties, and opportunities of using AMPs against multidrug-resistant pathogens and highlights the need and priorities for creating targeted development strategies that take into account the most cutting-edge tools currently available. It also describes the barriers to using these AMPs in clinical trials.
Cyclodextrin Inclusion Complexes with Hydrocortisone-Type Corticosteroids
Authors: Kowalska Aleksandra , Szeleszczuk Łukasz
Published: December 2024

The hydrocortisone-type corticosteroid (HTC) group includes valuable active pharmaceutical ingredients (APIs) such as hydrocortisone, hydrocortisone acetate, cortisone acetate, tixocortol pivalate, prednisolone, methylprednisolone, and prednisone. Unfortunately, those APIs are characterized by low solubility, which hampers their application and reduces their therapeutic efficacy. The low polarity of HTC molecules allows them to form inclusion complexes with various cyclodextrins (CDs); however, as shown in this review, the type of applied CDs has a major impact on the final properties of the formed complex. HTC–CD complexes have been routinely used for over 40 years to achieve various aims. Most frequently, CDs have been utilized as HTC solubilizers and absorption enhancers in pharmaceutical formulations, as well as for separation and analysis by chromatographic and electrophoretic methods. This article reviews the studies describing the synthesis as well as the biological, physiochemical, and structural properties of the inclusion complexes formed between HTC and various cyclodextrins.
Experimental Investigation of Spray Drying Breakup Regimes of a PVP-VA 64 Solution Using High-Speed Imaging
Authors: Welch Cooper , Khawar Mobaris , Böhm Benjamin , Gryczke Andreas , Ries Florian
Published: December 2024

Background: Atomization plays a key role in spray drying, a process widely used in the pharmaceutical, chemical, biological, and food and beverage industries. In the pharmaceutical industry, spray drying is particularly important in the preparation of amorphous solid dispersions, which enhance the bioavailability of active pharmaceutical ingredients when mixed with a polymer. Methods: In this study, a 3D-printed adaptation of a commercial spray dryer nozzle (PHARMA-SD® PSD-1, GEA Group AG) was used to investigate the atomization of PVP-VA 64 polymer solutions under varying flow conditions using high-speed diffuse back-illumination. Results: Unlike pure water, the atomization process of the polymer solution was governed by viscous effects rather than surface tension, as indicated by stringing effects in the liquid core and the formation of larger droplets. In addition, the classical Ohnesorge diagram accurately predicted the atomization regime with increasing Reynolds numbers and could be modified to reasonably predict the breakup regime by considering the transitions between regime boundaries. Conclusions: The use of such a modified diagram facilitates the efficient selection of viscous fluid solutions and process parameters to achieve complete spray formation.
Synthesis and Characterization of Polyimide with High Blackness and Low Thermal Expansion by Introducing 3,6-bis(thiophen-2-yl)diketopyrrolopyrrole-Based Chromophores
Authors: Liu Yiwu , Liu Xueyuan , Tan Jinghua , Huang Jie , Yuan Jiazhen , Li Huipeng , Guo Jieping , Yu Penghao , Chen Yue
Published: December 2024

The market demand for black polyimide (BPI) has grown hugely in the field of flexible copper-clad laminates (FCCLs) as a replacement for transparent yellow polyimide. The 3,6-bis(thiophen-2-yl)diketopyrrolopyrroles (TDPP) derivative is recognized for its high molar extinction coefficient. In this research, we have synthesized a diamine monomer named 3,6-bis[5-(4-amino-3-fluorophenyl)thiophen-2-yl]-2,5-bis(2-ethylhexyl)pyrrolo[4,3-c]pyrrole-1,4-dione (DPPTENFPDA), featuring a TDPP unit attached by fluorinated benzene rings. The subsequent reaction of DPPTENFPDA with pyromellitic dianhydride (PMDA) yielded an inherent BPI (DPPTENFPPI). By introducing chromophores derived from TDPP, the light absorption spectrum of DPPTENFPPI was broadened and red-shifted, thereby achieving full absorption within the visible spectrum and producing a highly black color that has a cut-off wavelength (λcut) of 717 nm and a CIE-Lab coordinate L* of 0.86. Additionally, DPPTENFPPI exhibited a low coefficient of thermal expansion (CTE) and remarkable thermal and electrical performance. Density functional theory calculations were conducted to explore the electronic nature of DPPTENFPPI. The outcomes revealed that the excellent light absorption of DPPTENFPPI predominantly originates from the transition from HOMO to LUMO + 1 within the chromophore moiety. The FCCL made from DPPTENFPPI films has high solder heat resistance and peel strength. This research contributes valuable insights into the structure and design of high-performance intrinsically black PIs for microelectronics applications.
Influence of Kazakhstan’s Shungites on the Physical–Mechanical Properties of Nitrile Butadiene Rubber Composites
Authors: Beknazarov Kanat , Tokpayev Rustam , Nakyp Abdirakym , Karaseva Yulia , Cherezova Elena , El Fray Miroslawa , Volfson Svetoslav , Nauryzbayev Mikhail
Published: December 2024

This study presents data on the use of shungite ore (the Bakyrchik deposit, Kazakhstan) and its concentrate as fillers in elastomer composites based on nitrile butadiene rubber. In addition to carbon, these shungite materials contain oxides of Si, Fe, K, Ca, Ti, Mn, and Al. The shungite concentrate was obtained through a flotation process involving five stages. The chemical composition analysis of these natural fillers revealed that during flotation, the carbon content increased 3.5 times (from 11.0 wt% to 39.0 wt%), while the silicon oxide content decreased threefold (from 49.4 wt% to 13.6 wt%). The contents of oxides of K, Ca, Ti, Mn, and Al decreased by less than 1%, and iron oxide content increased by 40% (from 6.7 wt% to 9.4 wt%). The study explored the impact of partial or full replacement of carbon black (CB) of P 324 grade with the shungite ore (ShO) and the shungite concentrate (ShC) on the vulcanization process and the physical–mechanical properties of the rubber. It was found that replacing CB with ShO and ShC reduces Mooney viscosity ML (1 + 4) 100 °C of the rubber compounds by up to 29% compared to the standard CB-filled sample. The use of the shungite fillers also increased scorch time (ts) by up to 36% and cure time (t90) by up to 35%. The carbon content in the shungite fillers had little influence on these parameters. Furthermore, it was demonstrated that replacing 5–10 wt% of CB with ShO or ShC improves the tensile strength of the rubber. The results of the flotation enrichment process enable the assessment of how these shungite fillers affect the properties of the composites for producing rubbers with specific characteristics. It was also found that substituting CB with ShO or ShC does not significantly affect the rubber’s resistance to standard oil-based media. The findings indicate that Kazakhstan’s shungite materials can be used as fillers in rubber to partially replace CB.
A Novel Polymer Film to Develop Heart Valve Prostheses
Authors: Zhuravleva Irina Yu. , Dokuchaeva Anna A. , Vaver Andrey A. , Kreiker Ludmila V. , Mochalova Alexandra B. , Chepeleva Elena V. , Surovtseva Maria A. , Kolodin Aleksei N. , Kuznetsova Elena V. , Grek Rostislav I.
Published: December 2024

Polymer heart valves are a promising alternative to bioprostheses, the use of which is limited by the risks of calcific deterioration of devitalized preserved animal tissues. This is especially relevant in connection with the increasingly widespread use of transcatheter valves. Advances in modern organic chemistry provide a wide range of polymers that can replace biological material in the production of valve prostheses. In this work, the main properties of REPEREN® polymer film, synthesized from methacrylic oligomers reinforced with ultra-thin (50 µm) polyamide fibers, are studied. The film structure was studied using scanning electron microscopy (SEM) and atomic force microscopy (AFM). The hydrophilicity and cytocompatibility with EA.hy926 endothelial cells were assessed, and a hemocompatibility evaluation was carried out by studying the platelet aggregation and adhesion upon contact of the REPEREN® with blood. The mechanical behavior and biocompatibility (subcutaneous implantation in rats for up to 90 days, followed by a histological examination) were studied in comparison with a bovine pericardium (BP) cross-linked with an ethylene glycol diglycidyl ether (DE). The results showed that REPEREN® films have two surfaces with a different relief, smooth and rough. The rough surface is more hydrophilic, hemo- and cytocompatible. Compared with the DE-BP, REPEREN® has a higher ultimate tensile stress and better biocompatibility when implanted subcutaneously in rats. The key properties of REPEREN® showed its potential for the development of a polymeric heart valve. Further studies should be devoted to assessing the durability of REPEREN® valves and evaluating their function during orthotopic implantation in large animals.
A Taguchi Approach for Optimization of Antimicrobial Effect of Whey Protein Based Edible Film Fermented by Bacillus clausii
Authors: Khan Ali Raza , Sezer Elif , Aslan Özge , Çağrı-Mehmetoglu Arzu
Published: December 2024

Bacillus clausii, an antagonistic bacterium, was utilized to develop antimicrobial edible films based on whey protein concentrate. This study employed a Taguchi test (3 × 3) to evaluate the impact of temperature, pH, and protein concentration on film properties. Optimal growth of B. clausii occurred at 6% (w/v) protein and pH 9.5. The resulting film solutions demonstrated antimicrobial activity, exhibiting inhibition zones against Aspergillus niger, Penicillium expansum, Staphylococcus aureus, and Escherichia coli, with inhibition zone diameters of 13.68 mm, 16.88 mm, 11.38 mm, and 17.15 mm, respectively. The optimum antimicrobial property of the films was observed when the incubation condition of pH 8.5, 35 °C and 6% (w/v) protein. Survival rates of B. clausii in the dry film were 86% at 4 °C and 87% at 25 °C over 14 days. Additionally, the highest tensile strength (TS) and percent elongation at break (%E) for the films were recorded at 3.14 MPa (pH = 9.5, 37 °C, 8% protein) and 27.63% (pH = 9.0, 35 °C, 10% protein), respectively. These findings demonstrate the potential for developing effective antimicrobial films through 24-h fermentation of B. clausii in the film solution. This antimicrobial film shows potential for use in wound dressings or food packaging applications.