Search Results (56)

The purpose of this study was to estimate the peak stresses in a laser powder bed fusion (LPBF) additive-manufactured (AM) osteosynthesis plate during physiological loading and establish if the mechanical properties of LPBF titanium alloy were suitable for this use case. Finite element models of subject-specific osteosynthesis plates for a cohort of 28 patients were created and used to calculate the peak maximum principal stresses during physiological loading, which was estimated to be 166 MPa twelve weeks post-operatively. All specimens were LPBF additively manufactured in Ti-6Al-4V alloy. ISO compliant tests were performed for tensile and fatigue, respectively. Fatigue testing was performed for specimens that had been heat-treated only and those that had been heat-treated and polished. The Upper Yield Stress was 1012.5 ± 19.2 MPa. The fatigue limit was 227 MPa for heat-treated only specimens and increased to 286 MPa for heat-treated and polished specimens. The finite element predicted stresses were below the experimentally established limits of yield and fatigue. The tensile and fatigue properties of heat-treated LPBF Ti-6Al-4V are therefore sufficient to meet the mechanical requirements of osteosynthesis plates. Polishing is recommended to improve fatigue resistance. Full article

Introduction: Early-onset colorectal cancer (EOCRC) is rising rapidly, particularly among the Hispanic/Latino (H/L) populations, who face disproportionately poor outcomes. The transforming growth factor-beta (TGF-β) signaling pathway plays a critical role in colorectal cancer (CRC) progression by mediating epithelial-to-mesenchymal transition (EMT), immune evasion, and metastasis. However, integrative analyses linking TGF-β alterations to clinical features remain limited—particularly for diverse populations—hindering translational research and the development of precision therapies. To address this gap, we developed AI-HOPE-TGFbeta (Artificial Intelligence agent for High-Optimization and Precision Medicine focused on TGF-β), the first conversational artificial intelligence (AI) agent designed to explore TGF-β dysregulation in CRC by integrating harmonized clinical and genomic data via natural language queries. Methods: AI-HOPE-TGFbeta utilizes a large language model (LLM), Large Language Model Meta AI 3 (LLaMA 3), a natural language-to-code interpreter, and a bioinformatics backend to automate statistical workflows. Tailored for TGF-β pathway analysis, the platform enables real-time cohort stratification and hypothesis testing using harmonized datasets from the cBio Cancer Genomics Portal (cBioPortal). It supports mutation frequency comparisons, odds ratio testing, Kaplan–Meier survival analysis, and subgroup evaluations across race/ethnicity, microsatellite instability (MSI) status, tumor stage, treatment exposure, and age. The platform was validated by replicating findings on the SMAD4, TGFBR2, and BMPR1A mutations in EOCRC. Exploratory queries were conducted to examine novel associations with clinical outcomes in H/L populations. Results: AI-HOPE-TGFbeta successfully recapitulated established associations, including worse survival in SMAD4-mutant EOCRC patients treated with FOLFOX (fluorouracil, leucovorin and oxaliplatin) (p = 0.0001) and better outcomes in early-stage TGFBR2-mutated CRC patients (p = 0.00001). It revealed potential population-specific enrichment of BMPR1A mutations in H/L patients (OR = 2.63; p = 0.052) and uncovered MSI-specific survival benefits among SMAD4-mutated patients (p = 0.00001). Exploratory analysis showed better outcomes in SMAD2-mutant primary tumors vs. metastatic cases (p = 0.0010) and confirmed the feasibility of disaggregated ethnicity-based queries for TGFBR1 mutations, despite small sample sizes. These findings underscore the platform’s capacity to detect both known and emerging clinical–genomic patterns in CRC. Conclusions: AI-HOPE-TGFbeta introduces a new paradigm in cancer bioinformatics by enabling natural language-driven, real-time integration of genomic and clinical data specific to TGF-β pathway alterations in CRC. The platform democratizes complex analyses, supports disparity-focused investigation, and reveals clinically actionable insights in underserved populations, such as H/L EOCRC patients. As a first-of-its-kind system studying TGF-β, AI-HOPE-TGFbeta holds strong promise for advancing equitable precision oncology and accelerating translational discovery in the CRC TGF-β pathway. Full article

The growing burden of degenerative, cardiovascular, neurodegenerative, and cancerous diseases necessitates innovative approaches to improve our pathophysiological understanding and ability to modulate biological processes. Organic bioelectronics has emerged as a powerful tool in this pursuit, offering a unique ability to interact with biology due to the mixed ionic–electronic conduction and tissue-mimetic mechanical properties of conducting polymers (CPs). These materials enable seamless integration with biological systems across different levels of complexity, from monolayers to complex 3D models, microfluidic chips, and even clinical applications. CPs can be processed into diverse formats, including thin films, hydrogels, 3D scaffolds, and electrospun fibers, allowing the fabrication of advanced bioelectronic devices such as multi-electrode arrays, transistors (EGOFETs, OECTs), ion pumps, and photoactuators. This review examines the integration of CP-based bioelectronics in vivo and in in vitro microphysiological systems, focusing on their ability to monitor key biological events, including electrical activity, metabolic changes, and biomarker concentrations, as well as their potential for electrical, mechanical, and chemical stimulation. We highlight the versatility and biocompatibility of CPs and their role in advancing personalized medicine and regenerative therapies and discuss future directions for organic bioelectronics to bridge the gap between biological systems and electronic technologies. Full article

This study addresses the dual challenges of water pollution and waste management by exploring the valorization of chicken bone biomass in native (NBio) and calcined (CBio) forms as biosorbents for dye removal. Basic fuchsine (BF) and methylene blue (MB) were selected as model pollutants, and adsorption was assessed under varying operational conditions. Characterization using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD) showed that calcination improved crystallinity, eliminated organic impurities, and increased surface area (247 m²/g for NBio vs. 370 m²/g for CBio). Adsorption tests revealed higher performance for CBio, with maximum adsorption capacities of 100 mg/g (BF) and 142.85 mg/g (MB) based on the Langmuir isotherm, while NBio with maximum adsorption capacities of 111 mg/g (BF) and 111.11 mg/g (MB) followed the Freundlich model. Adsorption kinetics indicated pseudo-second-order behavior, suggesting chemisorption. The possible interactions between dyes and the biosorbent are hydrogen bonding, electrostatic interactions, and Lewis acid–base interactions. Thermodynamic analysis highlighted exothermic behavior for NBio and endothermic, entropy-driven adsorption for CBio, with both processes being spontaneous. A decision tree with Least Squares Boosting (DT_LSBOOST) provided accurate predictions (R² = 0.9999, RMSE < 0.003) by integrating key parameters. These findings promote chicken bone biomass as a cost-effective, sustainable biosorbent, offering promising potential in wastewater treatment and environmental remediation. Full article

Challenges in investment decisions for new fuels remain due to uncertain scenarios regarding profitability. There is also a challenge to improve production efficiency and waste utilization, either for biomass or by-products. This study evaluates the economic potential of biomethane production within sugarcane biorefineries through the principles of the circular economy and economic feasibility. To obtain price data for CBios, Brent crude oil, and natural gas, stochastic models based on GBM and Monte Carlo simulations were applied to project prices and assess revenue potential over a 10-year horizon. Price data were incorporated to assess market correlations and revenue scenarios. Key findings reveal that biomethane’s price stability, driven by its strong correlation with oil markets, supports its viability as a renewable energy source, while CBio presents a weak correlation and limited price predictability with present challenges for long-term planning. Economic modeling indicates high investment returns, with IRR values surpassing 35% in conservative scenarios and payback periods from 2 to 6 years. These results highlight biomethane’s potential for energy efficiency, carbon emission reduction, and the creation of new revenue through waste use. We conclude that targeted investments in biomethane infrastructure, coupled with policy and market support, are essential for achieving global sustainability goals. Full article

At present, lead halide PVSKSCs are promising photovoltaic cells but have some limitations, including their low stability in ambient conditions and the toxicity of lead. Thus, it will be of great significance to explore lead-free perovskite materials as an alternative absorber layer. In recent years, the numerical simulation of perovskite solar cells (PVSKSCs) via the solar cell capacitance simulation (SCAPS) method has attracted the attention of the scientific community. In this work, we adopted SCAPS for the theoretical study of lead (Pb)-free PVSKSCs. A cesium bismuth iodide (CsBi₃I₁₀; CBI) perovskite-like material was used as an absorber layer. The thickness of the CBI layer was optimized. In addition, different electron transport layers (ETLs), such as titanium dioxide (TiO₂), tin oxide (SnO₂), zinc oxide (ZnO), and zinc selenide (ZnSe), and different hole transport layers, such as spiro-OMeTAD (2,2,7,7-tetrakis(N,N-di(4-methoxyphenylamine)-9,9′-spirobifluorene), poly(3-hexylthiophene-2,5-diyl) (P₃HT), poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine (PTAA), and copper oxide (Cu₂O), were explored for the simulation of CBI-based PVSKSCs. A device structure of FTO/ETL/CBI/HTL/Au was adopted for simulation studies. The simulation studies showed the improved photovoltaic performance of CBI-based PVSKSCs using spiro-OMeTAD and TiO₂ as the HTL and ETL, respectively. An acceptable PCE of 11.98% with a photocurrent density (J_sc) of 17.360258 mA/cm², a fill factor (FF) of 67.10%, and an open-circuit voltage (V_oc) of 1.0282 V were achieved under the optimized conditions. It is expected that the present study will be beneficial for researchers working towards the development of CBI-based PVSKSCs. Full article

Dual- or multi-template molecularly imprinted polymers have been an attractive research field for many years as they allow simultaneous detection of more than one target with high selectivity and sensitivity by creating template-specific recognition sites for multiple targets on the same functional monomer. Dual/multi-template molecular imprinting techniques have been applied to identify, extract, and detect many targets, from heavy metal ions to viruses, by different methods, such as high-performance liquid chromatography (HPLC), liquid chromatography–mass spectrometry (LC-MS), and piezoelectric, optical, and electrochemical methods. This article focuses on electrochemical sensors based on dual/multi-template molecularly imprinted polymers detecting a wide range of targets by electrochemical methods. Furthermore, this work highlights the use of these sensors for point-of-care applications, their commercialization and their integration with microfluidic systems. Full article

Mycorrhizal inoculants can contribute to the development of corn crops by improving crop productivity. In this sense, the objective of this study was to evaluate the effects of a mycorrhizal inoculant on the dynamics of root system growth, gas exchange, corn crop productivity, and microbial activity in the rhizospheric soil in a no-till area with different levels of available soil phosphorus. The experiment was conducted during the 2019/2020 and 2020/2021 growing seasons. At 75 days after plant emergence, root morphological parameters (total root length (cm), average root diameter (mm), root surface area (cm²), and root volume), shoot biomass production, P content in the plant shoots, gas exchange, and microbiological attributes of the rhizospheric soil of corn were evaluated. At the end of the cycle, corn grain yield was determined. A beneficial effect of AMF inoculation was observed on the root and shoot parameters regardless of soil P level. Under conditions of evenly distributed rainfall during the experiment (2019/2020 season), AMF inoculation contributed to a 90% increase in acid phosphatase activity and a 76% increase in microbial biomass carbon (C-BIO), independent of soil P level. In contrast, under water deficit conditions (2020/2021 season), AMF inoculation provided a 29% increase in grain yield. We concluded that introducing a commercial mycorrhizal inoculant in corn benefits root system morphological parameters and physiological traits, and favors the activity of enzymes related to increased P availability, contributing to increased crop productivity in a no-till system. Full article

Cancer cells typically divide with weaker synchronisation with the circadian clock than normal cells, with the degree of decoupling increasing with tumour maturity. Chronotherapy exploits this loss of synchronisation, using drugs with circadian-clock-dependent activity and timed infusion to balance the competing demands of reducing toxicity toward normal cells that display physiological circadian rhythms and of efficacy against the tumour. We analysed optimal chronotherapy for one-compartment nonlinear tumour growth models that were no longer synchronised with the circadian clock, minimising a cost function with a periodically driven running cost accounting for the circadian drug tolerability of normal cells. Using Pontryagin’s Minimum Principle (PMP), we show, for drugs that either increase the cell death rate or kill dividing cells, that optimal solutions are aperiodic bang–bang solutions with two switches per day, with the duration of the daily drug administration increasing as treatment progresses; for large tumours, optimal therapy can in fact switch mid treatment from aperiodic to continuous treatment. We illustrate this with tumours grown under logistic and Gompertz dynamics conditions; for logistic growth, we categorise the different types of solutions. Singular solutions can be applicable for some nonlinear tumour growth models if the per capita growth rate is convex. Direct comparison of the optimal aperiodic solution with the optimal periodic solution shows the former presents reduced toxicity whilst retaining similar efficacy against the tumour. We only found periodic solutions with a daily period in one-compartment exponential growth models, whilst models incorporating nonlinear growth had generic aperiodic solutions, and linear multi-compartments appeared to have long-period (weeks) periodic solutions. Our results suggest that chronotherapy-based optimal solutions under a harmonic running cost are not typically periodic infusion schedules with a 24 h period. Full article

Biomass from willow and poplar harvested for feed during the growing season may be preserved by ensiling; however, little research has focused on ensiling of these biomasses. This study focuses on the use of ensiling additives to reduce the pH to around 4.0 to secure stable storage. Lab-scale ensiling experiments were conducted with different willow and poplar clones, shoot ages, and harvest times (June or September). Ensiling without additives often resulted in limited pH reduction. The pH could be reduced in the biomass of both species by adding formic acid, and the required dose to reduce the pH to 4.0 (buffering capacity, BC) ranged significantly between biomass types but was in the range of 2–5 kg formic acid (78%) per ton fresh weight. BC decreased with increasing dry matter (DM) content and decreasing crude protein content. The pH could also be reduced during ensiling by applying molasses and/or lactic acid bacteria, although not sufficiently in poplar. Willow biomass was ensiled effectively at the pilot scale with less than 7% DM loss by adding formic acid or by mixing with grass biomass. Comparable pH results were obtained at the lab scale and pilot scale. The study demonstrates how willow and poplar can be ensiled; however, more research is needed on quality changes during ensiling. Full article

Early-stage knee osteoarthritis is often suitable for treatment with high tibial osteotomy (HTO). This is an effective joint-preserving treatment, resulting in good postoperative outcomes. To overcome the limitations of traditional HTO, the surgical technique and correction accuracy can be enhanced by personalised procedures using three-dimensional digital planning and metal additive manufacturing, The purpose of this clinical trial study was to evaluate the three-dimensional accuracy of a new personalised HTO procedure, using modern imaging techniques, 3D modelling, and distance map analysis (DMA). Twenty-five patients were treated with the personalised HTO procedure. Before surgery and after 6 months, they underwent clinical evaluation scoring, radiographic imaging, and computed-tomography scanning to generate morphological models. Specifically, preoperative tibia models were used to plan the tibia correction and the design and position of the fixation plate. Preoperative, planned, and postoperative models were imported in computer-aided and designing software (Geomagic ControlTM 2014, 3D Systems, Rock Hill, SC, USA) for DMA implementation to assess geometrical differences between model surfaces. A very good reproduction of the planned tibia morphology was achieved postoperatively (average differences between −0.9 mm and 1.4 mm). DMA values associated with fixation-plate deformation were less than 1 mm, similar to those for plate-to-tibia surface-contour matching. Overall, personalised digitally planned HTO utilising three-dimensional printed surgical guides and plates enables accurate planned correction and plate placement. Full article

The microfluidic measurement of capillary flow can be used to evaluate the response of biological samples to stimulation, where distance and velocity are altered. Melt-extruded multi-bored microfluidic capillaries allow for high-throughput testing with low device cost, but simple devices may limit control over sample flow when compared to the more complex “lab-on-a-chip” devices produced using advanced microfluidic fabrication methods. Previously, we measured the dynamics of global haemostasis stimulated by thrombin by dipping straight vertical microcapillaries into blood, but only the most rapid response could be monitored, as flow slowed significantly within 30 s. Here, we show an innovative method to extend both the stimulation process and flow measurement time without increasing the cost of the device by adding simple loops to the flexible extruded device. The loops enable longer time-scale measurements by increasing resistance to flow, thereby reducing the dependence on high stimulus concentrations for rapid reactions. The instantaneous velocity and equilibrium heights of straight and looped vertical microcapillary films were assessed with water, plasma and whole blood, showing that the loops create additional frictional resistances, reduce flow velocity and prolong residence times for increased time scales of the stimulation process. A modified pressure balance model was used to capture flow dynamics with the added loop. Looped devices loaded with thrombin and collagen showed an improved detection of blood stimulation responses even with lower stimulus concentrations, compared to straight vertical capillaries. Thrombin-activated blood samples in straight capillaries provided a maximum measurement zone of only 4 mm, while the looped design significantly increased this to 11 mm for much longer time scale measurements. Our results suggest that extending stimulation times can be achieved without complex microfluidic fabrication methods, potentially improving concentration–response blood stimulation assays, and may enhance the accuracy and reliability. We conclude adding a loop to low-cost extruded microfluidic devices may bring microfluidic devices closer to delivering on their promise of widespread, decentralized low-cost evaluation of blood response to stimulation in both research and clinical settings. Full article

Bruton’s tyrosine kinase (BTK) is pivotal in B-cell signaling and a target for potential anti-cancer and immunological disorder therapies. Improved selective reversible BTK inhibitors are in demand due to the absence of direct BTK engagement measurement tools. Promisingly, PET imaging can non-invasively evaluate BTK expression. In this study, radiolabeled BIO-2008846 ([¹¹C]BIO-2008846-A), a BTK inhibitor, was used for PET imaging in NHPs to track brain biodistribution. Radiolabeling BIO-2008846 with carbon-11, alongside four PET scans on two NHPs each, showed a homogeneous distribution of [¹¹C]BIO-2008846-A in NHP brains. Brain uptake ranged from 1.8% ID at baseline to a maximum of 3.2% post-pretreatment. The study found no significant decrease in regional VT values post-dose, implying minimal specific binding of [¹¹C]BIO-2008846-A compared to free and non-specific components in the brain. Radiometabolite analysis revealed polar metabolites with 10% unchanged radioligand after 30 min. The research highlighted strong brain uptake despite minor distribution variability, confirming passive diffusion kinetics dominated by free and non-specific binding. Full article

Implantable and wearable bioelectronic systems can enable tailored therapies for the effective management of long-term diseases, thus minimising the risk of associated complications. In this context, glucose fuel cells hold great promise as in- or on-body energy harvesters for ultra-low-power bioelectronics and as self-powered glucose sensors. We report here the generation of gold nanostructures through a gold electrodeposition method in a soft template for the abiotic electrocatalysis of glucose in glucose fuel cells. Two different types of soft template were used: a lipid cubic phase-based soft template composed of Phytantriol and Brij^®-56, and an emulsion-based soft template composed of hexane and sodium dodecyl sulphate (SDS). The resulting gold structures were first characterised by SAXS, SEM and TEM to elucidate their structure, and then their electrocatalytic activity towards glucose was compared in both a three-electrode set-up and in a fuel cell set-up. The Phytantriol/Brij^®-56 template led to a nanofeather-like Au structure, while the hexane/SDS template led to a nanocoral-like Au structure. These templated electrodes exhibited similar electrochemical active surface areas (0.446 cm² with a roughness factor (RF) of 14.2 for Phytantriol/Brij^®-56 templated nanostructures and 0.421 cm² with an RF of 13.4 for hexane/SDS templated nanostructures), and a sensitivity towards glucose of over 7 μA mM⁻¹ cm⁻². When tested as the anode of an abiotic glucose fuel cell (in a phosphate-buffered solution with a glucose concentration of 6 mM), a maximum power density of 7 μW cm⁻² was reached; however the current density in the case of the fuel cell with the Phytantriol/Brij^®-56 templated anode was approximately two times higher, reaching the value of 70 μA cm⁻². Overall, this study demonstrates two simple, cost-effective and efficient strategies to manipulate the morphology of gold nanostructures, and thus their catalytic property, paving the way for the successful manufacturing of functional abiotic glucose fuel cells. Full article

Plants’ response to single environmental changes can be highly distinct from the response to multiple changes. The effects of a single environmental factor on wheat growth have been well documented. However, the interactive influences of multiple factors on different wheat genotypes need further investigation. Here, treatments of three important growth factors, namely water regime, temperature, and CO₂ concentration ([CO₂]), were applied to compare the response of two wheat genotypes with different heat sensitivities. The temperature response curves showed that both genotypes showed more variations at elevated [CO₂] (e[CO₂]) than ambient [CO₂] (a[CO₂]) when the plants were treated under different water regimes and temperatures. This corresponded to the results of water use efficiency at the leaf level. At e[CO₂], heat-tolerant ‘Gladius’ showed a higher net photosynthetic rate (P_n), while heat-susceptible ‘Paragon’ had a lower P_n at reduced water, as compared with full water availability. The temperature optimum for photosynthesis in wheat was increased when the growth temperature was high, while the leaf carbon/nitrogen was increased via a reduced water regime. Generally, water regime, temperature and [CO₂] have significant interactive effects on both wheat genotypes. Two wheat genotypes showed different physiological responses to different combinations of environmental factors. Our investigation concerning the interactions of multi-environmental factors on wheat will benefit the future wheat climate-response study. Full article