Search Results (63)

Introduction: Graphene, a two-dimensional arrangement of carbon atoms, has drawn significant interest in medical research due to its unique properties. In the context of bone regeneration, graphene has shown several promising applications. Its robust structure, electrical conductivity, and biocompatibility make it an ideal candidate for enhancing bone tissue regeneration and repair processes. Studies have revealed that the presence of graphene can stimulate the proliferation and differentiation of bone cells, thereby promoting the formation of new bone tissue. Additionally, its ability to act as an effective carrier for growth factors and drugs allows controlled release, facilitating the engineering of specific tissues for bone regeneration. Aim: To assess the efficacy of graphene in enhancing bone regeneration through in vitro studies, identify key safety concerns, and propose directions for future research to optimize its clinical applicability. Materials and methods: The present systematic review was carried out using the PRISMA 2020 guideline. A first search was carried out on 20 November 2023 and was later updated on 14 February and 15 April 2024 in the databases of PubMed, Scopus, and Web of Science. Those in vitro studies published in English that evaluated the potential for bone regeneration with graphene in dentistry and also those which met the search terms were selected. Furthermore, the quality of the studies was assessed following the modified CONSORT checklist of in vitro studies on dental materials. Results: A total of 17 in vitro studies met the inclusion criteria. Among these, 12 showed increased osteoblast adhesion, proliferation, and differentiation, along with notable enhancements in mineralized matrix formation. Additionally, they exhibited a significant upregulation of osteogenic markers such as RUNX and COL1 (p < 0.05). However, the variability in methodologies and a lack of long-term assessments were noted as critical gaps. Conclusions: The evaluation of the efficacy and safety of graphene in bone regeneration in dentistry revealed significant potential. However, it is recognized that clinical implementation should be approached with caution, considering identified areas of improvement and suggestions for future research. Future studies should focus on standardized experimental designs, including in vivo studies to evaluate long-term safety, immune responses, and vascularization processes in realistic biological environments. Full article

Ultra-low-voltage design brings considerable outcomes in power reduction and energy efficiency improvement at the cost of performance degradation and uncertainty. Conventional standard cell design methodology cannot guarantee optimal performance for subthreshold operations due to the lack of consideration of process variation. In this paper, an effective subthreshold cell sizing method is proposed to minimize the worst-case propagation delay by deriving the optimal pMOS-to-nMOS width ratio (β) analytically, which reveals the relation between the minimal worst-case delay and the process parameters and provides distinct guidance for standard cell library design. The proposed method demonstrated good agreement with the Monte Carlo SPICE simulation results and was validated at the cell level and the circuit level. At the cell level, the logic cells designed with the proposed method show at least 8.6% and 7.4% improvement, on average, for worst-case delay and energy-delay product (EDP), respectively, with an additional 3.2% energy overhead compared to the prior approaches. At the circuit level, the proposed method improves the worst-case performance and worst-case EDP of the ring oscillator by at least 15.5% and 15.0%, respectively, with a 0.9% energy penalty. Moreover, the ISCAS’89 and OpenCores circuits synthesized with the optimized cells achieve at least 6.6% worst-case performance enhancement, 6.9% power reduction, and 9.4% area saving. Full article

Gastric cancer (GC) presents a significant health challenge and ranks as the fifth most common cancer in the world. Unfortunately, most patients with GC exhaust standard care treatment options due to late diagnosis and tumour heterogeneity that leads to drug resistance, resulting in poor survival outcomes. Potentially, this situation can be improved by personalising treatment choice. Organoids are an emerging cell model system that recapitulates tumour heterogeneity and drug responses. Coupled with genomic analysis, organoid culture can be used to guide personalised medicine. The GC organoid field, however, lacks standardised methodologies for assessing organoid drug sensitivities. Comparing results across different GC organoid studies and correlating organoid drug responses with patient outcomes is challenging. Hence, we aim to summarise the methodologies used in GC organoid drug testing and correlation with clinical outcomes and discuss design considerations and limitations to enhance the robustness of such studies in the future. Full article

The slowdown of Moore’s Law necessitates an exploration of novel computing methodologies, new materials, and advantages in chip design. Thus, carbon-based materials have promise for more energy-efficient computing systems in the future. Moreover, sustainability emerges as a new concern for the semiconductor industry. The production and recycling processes associated with current chips present huge environmental challenges. Electronic waste is a major problem, and sustainable solutions in computing must be found. In this review, we examine an alternative chip design based on nanocellulose, which also features semiconductor properties and transistors. Our review highlights that nanocellulose (NC) is a versatile material and a high-potential composite, as it can be fabricated to gain suitable electronic and semiconducting properties. NC provides ideal support for ink-printed transistors and electronics, including green paper electronics. Here, we summarise various processing procedures for nanocellulose and describe the structure of exclusively nanocellulose-based transistors. Furthermore, we survey the recent scientific efforts in organic chip design and show how fully automated production of such a full NC chip could be achieved, including a Process Design Kit (PDK), expected variation models, and a standard cell library at the logic-gate level, where multiple transistors are connected to perform basic logic operations—for instance, the NOT-AND (NAND) gate. Taking all these attractive nanocellulose features into account, we envision how chips based on nanocellulose can be fabricated using Electronic Design Automation (EDA) tool chains. Full article

Background: Stress urinary incontinence (SUI) is a common condition with a significant impact on the quality of life of female patients. The limitations of current treatment strategies have prompted the exploration of new effective and minimally invasive alternative approaches, including cell therapy. Methods: A literature search was conducted to update the current clinical status of stem cell therapy in the management of female stress urinary incontinence. Results: Over thirty clinical studies have been designed to assess the feasibility, safety and efficacy of cell therapy for female SUI. Despite differences in cell types and protocols, the overall treatment procedures were similar. Standard subjective and objective assessment tools, and follow-up periods ranged from 6 weeks to 6 years have been used. Cell injection has shown to be a safe therapy in the treatment of female SUI. However, the results from more recent randomized trials have shown less promising results than expected in restoring continence. Heterogeneous research methodologies using different cell types and doses make it difficult to draw conclusions about effectiveness. Several key points remain that need to be further explored in future clinical trials. Conclusion: To advance in the development of cell therapy, it is essential to know the mechanisms involved to be able to direct it properly, its efficacy and the durability of the injected cells. Rigorous and homogenized preclinical and clinical studies that demonstrate its scope and improve its application are necessary for validation in the treatment of female SUI. Full article

(1) Background: Renal-cell carcinoma (RCC) incidence has been steadily rising, with obesity identified as a potential risk factor. However, the relationship between obesity and RCC prognosis remains unclear. This systematic review aims to investigate the impact of different adipose tissue measurements on RCC behavior and prognosis. (2) Methods: A search of MEDLINE databases identified 20 eligible studies focusing on various fat measurements, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), perirenal adipose tissue (PRAT), and the Mayo adhesive probability (MAP) score. (3) Results: The review revealed conflicting findings regarding the association between adipose tissue measurements and RCC outcomes. While some studies suggested a protective role of certain fat deposits, particularly VAT, against disease progression and mortality, others reported contradictory results across different adipose metrics and RCC subtypes. (4) Conclusions: Methodological variations and limitations, such as retrospective designs and sample size constraints, pose challenges to standardization and generalizability. Further research is needed to understand these associations better and establish standardized approaches for adiposity assessment in RCC patients, which could inform clinical practice and therapeutic decision-making. Full article

Three-dimensional porous scaffolds are substitutes for traditional bone grafts in bone tissue engineering (BTE) applications to restore and treat bone injuries and defects. The use of computational modelling is gaining momentum to predict the parameters involved in tissue healing and cell seeding procedures in perfusion bioreactors to reach the final goal of optimal bone tissue growth. Computational modelling based on finite element method (FEM) and computational fluid dynamics (CFD) are two standard methodologies utilised to investigate the equivalent mechanical properties of tissue scaffolds, as well as the flow characteristics inside the scaffolds, respectively. The success of a computational modelling simulation hinges on the selection of a relevant mathematical model with proper initial and boundary conditions. This review paper aims to provide insights to researchers regarding the selection of appropriate finite element (FE) models for different materials and CFD models for different flow regimes inside perfusion bioreactors. Thus, these FEM/CFD computational models may help to create efficient designs of scaffolds by predicting their structural properties and their haemodynamic responses prior to in vitro and in vivo tissue engineering (TE) applications. Full article

This study presents a decision-support methodology to design and optimize modular Boost converters in the context of fuel-cell electric vehicles. It involves the utilization of interleaved techniques to reduce fuel-cell current ripple, enhance system efficiency, tackle issues related to weight and size concerns, and offer better flexibility and modularity within the converter. The methodology incorporates emerging technologies by wide-bandgap semiconductors, providing better efficiency and higher temperature tolerance. It employs a multiphysical approach, considering electrical, thermal, and efficiency constraints to achieve an optimal power architecture for FCHEVs. Results demonstrate the advantages of wide-bandgap semiconductor utilization in terms of volume reduction and efficiency enhancements for different power levels. Results from one of the considered power levels highlight the feasibility of certain architectures through the utilization of WBG devices. These architectures reveal improvements in both efficiency and volume reduction as a result of incorporating WBG devices. Additionally, the analysis presents a comparison of manufacturing cost between standard and wide-bandgap semiconductors to demonstrate the market penetration potential. Full article

Proteomic analysis of extracellular vesicles presents several challenges due to the unique nature of these small membrane-bound structures. Alternative analyses could reveal outcomes hidden from standard statistics to explore and develop potential new biological hypotheses that may have been overlooked during the initial evaluation of the data. An analysis sequence focusing on deviating protein expressions from donors’ primary cells was performed, leveraging machine-learning techniques to analyze small datasets, and it has been applied to evaluate extracellular vesicles’ protein content gathered from mesenchymal stem cells cultured on bioactive glass discs doped or not with metal ions. The goal was to provide additional opportunities for detecting details between experimental conditions that are not entirely revealed with classic statistical inference, offering further insights regarding the experimental design and assisting the researchers in interpreting the outcomes. The methodology extracted a set of EV-related proteins whose differences between conditions could be partially explainable with statistics, suggesting the presence of other factors involved in the bioactive glasses’ interactions with tissues. Outlier identification of extracellular vesicles’ protein expression levels related to biomaterial preparation was instrumental in improving the interpretation of the experimental outcomes. Full article

For early and long-term patient and graft survival, drug therapy in solid organ and hematopoietic stem cell transplantation inevitably involves polypharmacy in patients with widely varying and even abruptly changing conditions. In this second part, relevant medication briefing is provided, in addition to the scores defined in the previously published first part on the design of the Individual Pharmacotherapy Management (IPM). The focus is on the growing spectrum of contemporary polypharmacy in transplant patients, including early and long-term follow-up medications. 1. Unlike the available drug–drug interaction (DDI) tables, for the first time, this methodological all-in-one device refers to the entire risks, including contraindications, special warnings, adverse drug reactions (ADRs), and DDIs. The selection of 65 common critical drugs results from 10 years of daily IPM with real-world evidence from more than 60,800 IPM inpatient and outpatient medication analyses. It includes immunosuppressants and typical critical antimicrobials, analgesics, antihypertensives, oral anticoagulants, antiarrhythmics, antilipids, antidepressants, antipsychotics, antipropulsives, antiemetics, propulsives, proton pump inhibitors (PPIs), sedatives, antineoplastics, and protein kinase inhibitors. As a guide for the attending physician, the drug-related risks are presented in an alphabetical overview based on the Summaries of Product Characteristics (SmPCs) and the literature. 2. Further briefing refers to own proven clinical measures to manage unavoidable drug-related high-risk situations. Drug-induced injuries to the vulnerable graft and the immunosuppressed comorbid patient require such standardized, intensive IPM and the comprehensive preventive briefing toolset to optimize the outcomes in the polypharmacy setting. Full article

This study sought to optimize the ultrasonic-assisted extraction of polyphenolic compounds from unmature Ajwa date seeds (UMS), conduct untargeted metabolite identification and assess antioxidant and depigmenting activities. Response surface methodology (RSM) utilizing the Box–Behnken design (BBD) and artificial neural network (ANN) modeling was applied to optimize extraction conditions, including the ethanol concentration, extraction temperature and time. The determined optimal conditions comprised the ethanol concentration (62.00%), extraction time (29.00 min), and extraction temperature (50 °C). Under these conditions, UMS exhibited total phenolic content (TPC) and total flavonoid content (TFC) values of 77.52 ± 1.55 mgGAE/g and 58.85 ± 1.12 mgCE/g, respectively, with low relative standard deviation (RSD%) and relative standard error (RSE%). High-resolution mass spectrometry analysis unveiled the presence of 104 secondary metabolites in UMS, encompassing phenols, flavonoids, sesquiterpenoids, lignans and fatty acids. Furthermore, UMS demonstrated robust antioxidant activities in various cell-free antioxidant assays, implicating engagement in both hydrogen atom transfer and single electron transfer mechanisms. Additionally, UMS effectively mitigated tert-butyl hydroperoxide (t-BHP)-induced cellular reactive oxygen species (ROS) generation in a concentration-dependent manner. Crucially, UMS showcased the ability to activate mitogen-activated protein kinases (MAPKs) and suppress key proteins including tyrosinase (Tyr), tyrosinase-related protein-1 and -2 (Trp-1 and -2) and microphthalmia-associated transcription factor (MITF), which associated melanin production in MNT-1 cell. In summary, this study not only optimized the extraction process for polyphenolic compounds from UMS but also elucidated its diverse secondary metabolite profile. The observed antioxidant and depigmenting activities underscore the promising applications of UMS in skincare formulations and pharmaceutical developments. Full article

The toolbox of modern antibody engineering allows the design of versatile novel functionalities exceeding nature’s repertoire. Many bispecific antibodies comprise heterodimeric Fc portions recently validated through the approval of several bispecific biotherapeutics. While heterodimerization methodologies have been established for low-throughput large-scale production, few approaches exist to overcome the bottleneck of large combinatorial screening efforts that are essential for the identification of the best possible bispecific antibody. This report presents a novel, robust and miniaturized heterodimerization process based on controlled Fab-arm exchange (cFAE), which is applicable to a variety of heterodimeric formats and compatible with automated high-throughput screens. Proof of applicability was shown for two therapeutic molecule classes and two relevant functional screening read-outs. First, the miniaturized production of biparatopic anti-c-MET antibody–drug conjugates served as a proof of concept for their applicability in cytotoxic screenings on tumor cells with different target expression levels. Second, the automated workflow enabled a large unbiased combinatorial screening of biparatopic antibodies and the identification of hits mediating potent c-MET degradation. The presented workflow utilizes standard equipment and may serve as a facile, efficient and robust method for the discovery of innovative therapeutic agents in many laboratories worldwide. Full article

Flavivirus infections, including dengue virus (DENV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV), present significant global public health challenges. For successful vaccine design, the assessment of neutralizing antibody activity requires reliable and robust methodologies for determining antibody titers. Although the plaque reduction neutralization test (PRNT) is commonly acknowledged as the gold standard, it has limitations in terms of time and cost, and its usage may be limited in resource-limited settings. To address these challenges, we introduced the micro-neutralization test (MNT) as a simplified alternative to the PRNT. The MNT employs a 96-well plate format, conducts microscale neutralization assays, and assesses cell viability by dissolving cells to create a uniform color solution, which is measured with a spectrometer. In this study, we evaluated the utility of the MNT by contrasting the end-point titers of the MNT and PRNT using 4 monoclonal antibodies, 15 non-human primate serum samples, and 2 therapeutic drug candidates across flaviviruses. The results demonstrated a strong correlation between the MNT and PRNT titers, affirming the robustness and reproducibility of the MNT for evaluating control measures against flaviviruses. This research contributes valuable insights toward the development of a cost-effective antibody titer testing approach that is particularly suitable for resource-limited settings. Full article

Methodologies for the synthesis and purification of metabolites, which have been developed following their discovery, analysis, and structural identification, have been involved in numerous life science milestones. The renewed focus on the small molecule domain of biological cells has also created an increasing awareness of the rising gap between the metabolites identified and the metabolites which have been prepared as pure compounds. The design and engineering of resource-efficient and straightforward synthetic methodologies for the production of the diverse and numerous metabolites and metabolite-like compounds have attracted much interest. The variety of metabolic pathways in biological cells provides a wonderful blueprint for designing simplified and resource-efficient synthetic routes to desired metabolites. Therefore, biocatalytic systems have become key enabling tools for the synthesis of an increasing number of metabolites, which can then be utilized as standards, enzyme substrates, inhibitors, or other products, or for the discovery of novel biological functions. Full article

The detection of circulating tumor DNA (ctDNA) in liquid biopsy samples as an oncological marker is being used in clinical trials at every step of clinical management. As ctDNA-based liquid biopsy kits are developed and used in clinics, companies work towards increased convenience, accuracy, and cost over solid biopsies and other oncological markers. The technology used to differentiate ctDNA and cell-free DNA (cfDNA) continues to improve with new tests and methodologies being able to detect down to mutant allele frequencies of 0.001% or 1/100,000 copies. Recognizing this development in technology, the FDA has recently given pre-market approval and breakthrough device designations to multiple companies. The purpose of this review is to look at the utility of measuring total cfDNA, techniques used to differentiate ctDNA from cfDNA, and the utility of different ctDNA-based liquid biopsy kits using relevant articles from PubMed, clinicaltrials.gov, FDA approvals, and company newsletters. Measuring total cfDNA could be a cost-effective, viable prognostic marker, but various factors do not favor it as a monitoring tool during chemotherapy. While there may be a place in the clinic for measuring total cfDNA in the future, the lack of standardization means that it is difficult to move forward with large-scale clinical validation studies currently. While the detection of ctDNA has promising standardized liquid biopsy kits from various companies with large clinical trials ongoing, their applications in screening and minimal residual disease can suffer from lower sensitivity. However, researchers are working towards solutions to these issues with innovations in technology, multi-omics, and sampling. With great promise, further research is needed before liquid biopsies can be recommended for everyday clinical management. Full article