bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Opportunities for Pharmacogenetic-Based Therapeutic Exploitation of Xanthine Dehydrogenase in Cardiovascular Disease
Authors: Massimo Gianmichele , Dyson Nicki , Olotu Fisayo , Khambata Rayomand S. , Ahluwalia Amrita
Published: November 2024

The majority of naturally occurring mutations of the human gene XDH, are associated with reduced or completely absent xanthine oxidoreductase (XOR) activity, leading to a disease known as classical xanthinuria, which is due to the accumulation and excretion of xanthine in urine. Three types of classical xanthinuria have been identified: type I, characterised by XOR deficiency, type II, caused by XOR and aldehyde oxidase (AO) deficiency, and type III due to XOR, AO, and sulphite oxidase (SO) deficiency. Type I and II are considered rare autosomal recessive disorders, a condition where two copies of the mutated gene must be present to develop the disease or trait. In most cases, xanthinuria type I and II result to be asymptomatic, and only occasionally lead to renal failure due to urolithiasis caused by xanthine deposition. However, in the last 10–15 years, new observations have been made about the link between naturally occurring mutations and pathological phenotypes particularly pertinent to cardiovascular diseases (CVD). These links have been attributed to a genetically driven increase of XOR expression and activity that is responsible for what is thought to be damaging uric acid (UA) and reactive oxygen species (ROS) accumulation, nitric oxide (·NO) depletion and endothelial dysfunction. In this review, we discuss the importance of genetics for interindividual variability of XOR expression and activity while focusing mainly on those variants thought to be relevant for CVD. In addition, we discuss the potential exploitation of the genetically driven increase of XOR activity to deliver more beneficial bioavailable ·NO. Finally, we examine the effect that non-synonymous mutations have on the tertiary structure of the protein and consequently on its capacity to interact with glycosaminoglycans (GAGs) localised on the outer surface of endothelial cells.
Neuroinflammation in Age-Related Neurodegenerative Diseases: Role of Mitochondrial Oxidative Stress
Authors: Abadin Xenia , de Dios Cristina , Zubillaga Marlene , Ivars Elia , Puigròs Margalida , Marí Montserrat , Morales Albert , Vizuete Marisa , Vitorica Javier , Trullas Ramon , Colell Anna , Roca-Agujetas Vicente
Published: November 2024

A shared hallmark of age-related neurodegenerative diseases is the chronic activation of innate immune cells, which actively contributes to the neurodegenerative process. In Alzheimer’s disease, this inflammatory milieu exacerbates both amyloid and tau pathology. A similar abnormal inflammatory response has been reported in Parkinson’s disease, with elevated levels of cytokines and other inflammatory intermediates derived from activated glial cells, which promote the progressive loss of nigral dopaminergic neurons. Understanding the causes that support this aberrant inflammatory response has become a topic of growing interest and research in neurodegeneration, with high translational potential. It has been postulated that the phenotypic shift of immune cells towards a proinflammatory state combined with the presence of immunogenic cell death fuels a vicious cycle in which mitochondrial dysfunction plays a central role. Mitochondria and mitochondria-generated reactive oxygen species are downstream effectors of different inflammatory signaling pathways, including inflammasomes. Dysfunctional mitochondria are also recognized as important producers of damage-associated molecular patterns, which can amplify the immune response. Here, we review the major findings highlighting the role of mitochondria as a checkpoint of neuroinflammation and immunogenic cell deaths in neurodegenerative diseases. The knowledge of these processes may help to find new druggable targets to modulate the inflammatory response.
Some Approaches for Light and Color on the Surface of Mars
Authors: Melgosa Manuel , Hernández-Andrés Javier , Sánchez-Marañón Manuel , Cuadros Javier , Vicente-Retortillo Álvaro
Published: November 2024

We analyzed the main colorimetric characteristics of lights on Mars’ surface from 3139 total spectral irradiances provided by the COMIMART model (J. Space Weather Space Clim. 5, A33, 2015), modifying the parameters of ‘solar zenith angle’ and ‘opacity’, related to the time of day and the amount of dust in the atmosphere of Mars, respectively. Lights on Mars’ surface have chromaticities that are mainly located below the Planckian locus, correlated color temperature in the range of 2333 K–5868 K, and CIE 2017 color fidelity indices above 93. For the 24 samples in the X-Rite ColorChecker® and an extreme dust opacity change from 0.1 to 8.1 in the atmosphere, the average color inconstancy generated by the change in Mars’ light using the chromatic adaptation transform CIECAT16 was about 5 and 8 CIELAB units for solar zenith angles of 0° and 72°, respectively. We propose a method to compute total spectral irradiances on the surface of Mars from a selected value of correlated color temperature in the range of 2333 K–5868 K. This method is analogous to the one currently adopted by the International Commission on Illumination to compute daylight illuminants on the surface of Earth (CIE 015:2018, clause 4.1.2). The average accuracy of 3139 reconstructed total spectral irradiances using the proposed method was 0.9999558 using GFC (J. Opt. Soc. Am. A 14, 1007–1014, 1997) and 0.0009 ΔEu′v′ units, a value just below noticeable chromaticity differences perceptible by human observers at 50% probability. Total spectral irradiances proposed by Barnes for five correlated temperatures agreed with those obtained from the current proposed method: on the average, GFC = 0.9979521 and 0.0023 ΔE′v′ units.
Quantitative Representation of Dynamic Mechanical Properties and Internal Damage in Deep-Seated Damaged Granite
Authors: Chen Luyang , Chu Huaibao , Wang Donghui , Sun Bo , Wen Zilong , Wei Haixia
Published: November 2024

Understanding the dynamics of damaged rock masses and the evolution of internal fractures is beneficial to the construction of deep engineering projects. Dynamic tests on damaged granite were carried out using a split Hopkinson device which can apply a confining pressure. A group of damaged granites was CT-scanned and three-dimensional reconstructed using Avizo 2020.1 software. The results indicate that with increasing damage, the peak stress and peak modulus of the damaged granite decrease, while the peak strain increases. When the initial damage is consistent, all three parameters increase with the increasing confining pressure. Confining pressure alters the number and development direction of internal fissures in granite. Higher confining pressure results in fewer fissures, with their development direction shifting more towards the center of the sample and becoming straighter. The total volume of fissures within the rock samples, the volume of through fissures, and the maximum length of the fissures are decreasing with the increase in the confining pressure. In addition, the three-dimensional fractal dimension and the internal damage also decreased continuously with the increase in the confining pressure. This research provides valuable theoretical guidance for supporting and constructing surrounding rock in deep engineering projects.
Processes Turning Saline Settling Basins into Freshwater Bodies (Selected Examples from the Upper Silesian Coal Basin)
Authors: Molenda Tadeusz , Woźniak Gabriela , Dyczko Artur , Bacler-Żbikowska Barbara , Kidawa Joanna
Published: November 2024

There are numerous deep coal mines in the Upper Silesian Coal Basin. Ensuring their proper exploitation requires constant drainage of the rock mass and the transfer of mine waters to rivers. Several technical solutions are used to prevent the adverse effects of saltwater discharge on the river ecosystem. One such solution is adapting the post-mining reservoirs into mine water settling basins. This article characterises two such facilities—the “Gliniok” and “Hubertus I” reservoirs. The physicochemical properties of their waters were analysed both when they served as settling basins and after their decommissioning. During their exploitation, the waters of the settling basins showed high salinity (>10 g/L). It was revealed that these basins turned into freshwater reservoirs very quickly after decommissioning. A sudden decrease in the electrolytic conductivity and the concentration of main cations and anions in the water was observed. The mixing processes also changed. The reservoirs were transformed from meromictic to polymictic. The processes that led to them turning into freshwater basins differed in the studied settling basins. The transformation of the Gliniok settling basin into a freshwater reservoir was a unique process, draining brines into the rock mass through cracks and crevices. The formation of cracks and crevices was a consequence of high-energy mining tremors. It is the first known case of this type in the world.
Assessment of Soil Loss Due to Wind Erosion and Dust Deposition: Implications for Sustainable Management in Arid Regions
Authors: Alzahrani Abdulhakim J. , Alghamdi Abdulaziz G. , Ibrahim Hesham M.
Published: November 2024

Soil loss due to wind erosion and dust deposition has become a growing concern, particularly in arid regions like Al-Baha, Saudi Arabia. The aim of this study was to quantitatively assess soil loss and dust deposition using three different dust collection methods across 20 sites during the summer of 2022. The methods include Big Spring Number Eight (BSNE), which measures airborne dust particles using passive samplers; Surface Dust Collector (SDC), designed to collect dust settling on the ground surface; and Marble Dust Collector (MDCO), which utilizes marble-coated surfaces to trap and measure dust deposition. These methods collectively provide a comprehensive evaluation of dust dynamics in the study area. The objective was to evaluate the effects of wind erosion and dust deposition on soil properties, offering insights into the mechanisms of soil loss in arid environments. The study revealed significant variations in soil characteristics, including low organic matter content (<1%), high calcite (up to 19.62%), and increased salinity levels, with notable quantities of Cl− (211.58 meq kg⁻1) and Na⁺ (165.98 meq kg⁻1). July showed the highest dust deposition (0.0133 ton ha−1), particularly at site S11, while soil loss was lowest at site S5. This research offers novel insights into the nonlinear relationship between soil loss and time, contributing to sustainable soil management strategies. By aligning with Saudi Arabia’s Vision 2030 and the Sustainable Development Goals (SDGs), the findings underscore the need to mitigate soil loss to enhance environmental sustainability, prevent desertification, and promote long-term resilience in arid regions.
Design and Analysis of Additional Tendon Path for Determining Bending Shape in Hyper-Redundant Manipulator with Rolling Joints
Authors: Kim Hansoul
Published: November 2024

Flexible surgical robots are emerging as advanced tools for minimally invasive surgeries, offering greater versatility compared to traditional rigid robots. Unlike commercial endoscopes, the overtube should remain fixed to maintain stability, ensure a clear field of view, and allow surgical tools to perform tasks efficiently. While constant curvature bending of the overtube is sufficient for some lesions, certain lesions require the overtube to bend into specific shapes to achieve appropriate positioning. Various methods for creating different bending shapes have been proposed in previous research, typically involving connecting multiple segments. However, this approach complicates control and reduces both space and cost efficiency. This study proposed a conceptual method for adding a shaping tendon to control the bending shape and mathematically analyzed the effect of this shaping tendon, inserted along an arbitrary path in addition to the main driving tendons for constant curvature bending, on the bending shape of the hyper-redundant manipulator with rolling joints. The overall system was modeled and analyzed from an energy perspective, and the validity of the proposed mathematical modeling was verified through comparison with results obtained from physical experiments. In addition, it was identified that the design parameter determining the tendon path is a significant element in defining the bending shape of the overtube.
Study on Optimization of Rice-Drying Process Parameters and Directional Regulation of Nutrient Quality
Authors: Li Jinquan , Chang Kezhen , Yin Jun , Jin Yi , Yi Xiaokang , Zhang Zhongjie , He Yichuan , Yang Qiaonan , Tang Zhihui , Liu Xiaoyu , Wu Wenfu
Published: November 2024

The physicochemical components of rice such as starch, protein, fat and water have significant influence on its nutritional value, and the drying process can easily cause changes in these components. In this paper, the effect of technical parameters on the nutritional quality of rice during hot-air drying was studied, and a control method of the rice-drying process based on effective accumulated temperature was proposed to ensure the drying quality and improve the drying efficiency. Through thin-layer drying experiments, hot-air temperature (T), humidity (RH), initial moisture content (MC), wind speed (V) and tempering ratio (TR) were selected as control factors, and the central composite design was adopted to optimize the experimental scheme. The relationship between each factor and nutrient quality was revealed through response surface analysis, and the regression model and process optimization parameters were established. The results show that the optimization parameters are as follows: hot-air temperature, 48.87 °C; humidity, 30.12%; initial moisture content, 21.31%; wind speed, 0.62 m/s; tempering ratio, 2.87; the optimized total drying time is 4.23 h; the effective accumulated temperature is 214.44 °C·h. The contents of protein, fat, amylose and amylopectin were 8.47 g/100 g, 1.97 g/100 g, 15.33 g/100 g and 60.50 g/100 g, respectively. The relative error of the verification test was 4.17%. The optimized process can effectively maintain the nutritional quality of rice and improve drying efficiency. This paper provides a new way to deeply explore the mechanism of rice quality change, and the established process reference chart provides a scientific basis for actual drying operations and the development of an intelligent control system.
Triple Validation of Calibrated Building Energy Models with Different Air Infiltration Values
Authors: Bastos Porsani Gabriela , Echeverría Trueba Juan Bautista , Fernández Bandera Carlos
Published: November 2024

Model calibration refines design-stage inputs to align with real-world building performance. Accurate parameter selection, especially for highly sensitive variables like air leakage, is crucial. This study compared two building energy model calibration methods. The “classic” method adjusted indoor air capacitance, internal mass, and air infiltration, while a novel method focused on capacitance and internal mass, using empirical data for infiltration. The infiltration values were calculated using the decay equation and the EnergyPlus equations with site-specific coefficients. A triple validation assessed model performance in terms of temperature (CIBSE TM63), energy consumption (minimization), and indoor air quality (represented by CO2 levels in accordance with the ASTM D5157 Standard). Results demonstrated the novel method’s superiority across all three performance metrics. All calibrated models met the CIBSE TM63 criteria even during the validation period, which was five times longer than the training period. Compared to the classic method, models incorporating dynamic empirical infiltration showed a 29% and 26% improvement in MAE and RMSE, respectively, in temperature prediction. In energy consumption results, the novel method models presented a 31% reduction, and for CO2 level agreement, these models achieved a 130% higher R2 value than the classic model. In addition, the classic method’s infiltration values failed to meet ASTM D5157 requirements, suggesting reliance on unrealistic parameter values for accurate temperature representation. The incorporation of calculated air leakage data into the BEM allowed a more realistic estimation of capacitance and internal mass values, emphasizing the importance of accurate air infiltration modeling for overall model reliability.
Fusing Machine Learning and AI to Create a Framework for Employee Well-Being in the Era of Industry 5.0
Authors: Rosca Cosmina-Mihaela , Stancu Adrian
Published: November 2024

Employees are the most valuable resources in any company, and their well-being directly influences work productivity. This research investigates integrating health parameters and sentiment analysis expressed in sent messages to enhance employee well-being within organizations in the context of Industry 5.0. Our primary aim is to develop a Well-Being Index (WBI) that quantifies employee health through various physiological and psychological parameters. A new methodology combining data collection from wearable devices from 1 January 2023 to 18 October 2024 and advanced text analytics was employed to achieve the WBI. This study uses the LbfgsMaximumEntropy ML classification algorithm to construct the Well-Being Model (WBM) and Azure Text Analytics for sentiment evaluation to assess negative messages among employees. The findings reveal a correlation between physiological metrics and self-reported well-being, highlighting the utility of the WBI in identifying areas of concern within employee behavior. We propose that the employee global indicator (EGI) is calculated based on the WBI and the dissatisfaction score component (DSC) to measure the overall state of mind of employees. The WBM exhibited a MacroAccuracy of 91.81% and a MicroAccuracy of 95.95% after 384 configurations were analyzed. Azure Text Analytics evaluated 2000 text messages, resulting in a Precision of 99.59% and an Accuracy of 99.7%. In this case, the Recall was 99.89% and F1-score was 99.73%. In the Industry 5.0 environment, which focuses on the employee, a new protocol, the Employee KPI Algorithm (EKA), is integrated to prevent and identify employee stress. This study underscores the synergy between quantitative health metrics and qualitative sentiment analysis, offering organizations a framework to address employee needs proactively.
The Impact of Outdoor Environmental Factors on Indoor Air Quality in Education Settings: A Systematic Review
Authors: Rožanec Jan , Galičič An , Kukec Andreja
Published: November 2024

Poor indoor air quality (IAQ) in schools is associated with pupils’ health and their learning performance. This study aims to provide an overview of the outdoor factors that affect the IAQ in educational settings in order to develop public health measures. We conducted a systematic literature review to investigate the outdoor factors that affect IAQ in educational settings. The selection of articles included 17,082 search string hits from the ScienceDirect database published between 2010 and 2023, with 92 relevant studies selected based on the inclusion and exclusion criteria. Based on a systematic review of the literature, we identified the following outdoor factors: proximity to busy roads, commercial and industrial establishments, meteorological conditions, compounds from the natural environment, emissions from heating buildings, atmospheric reactions and secondary pollutants, unpaved school playgrounds, and smoking. This study provides key information on the mentioned outdoor factors and gives recommendations on measures to reduce classroom pollutant concentrations while highlighting educational settings that require special attention. Our study shows that classroom IAQ is affected by many outdoor pollutant sources, the prevalence of which depends on the educational setting’s micro location. Therefore, it is essential to develop an appropriate classroom ventilation strategy for each educational setting.
Impact of Air Pollution on the Long-Term Decline of Non-Idiopathic Pulmonary Fibrosis Interstitial Lung Disease
Authors: Mariscal-Aguilar Pablo , Gómez-Carrera Luis , Bonilla Gema , Carpio Carlos , Zamarrón Ester , Fernández-Velilla María , Díaz-Almirón Mariana , Gayá Francisco , Villamañán Elena , Prados Concepción , Álvarez-Sala Rodolfo
Published: November 2024

Objective: This study examines the association between major urban pollutants and the long-term decline of non-idiopathic pulmonary fibrosis interstitial lung disease [non-IPF ILD]. Materials and methods: A total of 41 patients with non-IPF ILD were analyzed from 2011 to 2020, correlating disease long-term decline with concentrations of key pollutants [SO2, CO, NO2, O3, PM2.5, and PM10] in Madrid. The likelihood of meeting severity criteria was assessed using a generalized linear model, considering the average pollutant levels during severe episodes. Results: At diagnosis, the average age of patients was 62.95 ± 13.13 years, with 47.6% women. The study found no significant association between pollution levels and the probability of meeting severity criteria for non-IPF ILD. The odds ratios were as follows: OR SO2 = 0.92 [0.82–1.03], p = 0.16; OR CO = 0.99 [0.97–1.05], p = 0.70; OR NO2 = 0.97 [0.92–1.03], p = 0.38; OR PM2.5 = 0.79 [0.54–1.17], p = 0.24; OR PM10 = 1.1 [0.94–1.28], p = 0.21; OR O3 = 0.97 [0.92–1.01], p = 0.20. Conclusions: Our study suggests that, within the cohort of 41 patients with non-IPF ILD enrolled in this study, urban air pollutants in Madrid are not significantly linked to increased long-term decline of non-IPF ILD. This is one of the first studies to explore the impact of various urban pollutants on a diverse cohort of non-IPF ILD patients, including rare conditions like LAM and histiocytosis X. Further research with larger sample sizes and comprehensive exposure assessments is recommended.
Approximating Fixed Points via Hybrid Enriched Contractions in Convex Metric Space with an Application
Authors: Rani Bhumika , Kaur Jatinderdeep , Bhatia Satvinder Singh
Published: November 2024

In the present study, we define hybrid enriched contractions of the Hardy–Rogers type and of the Ćirić–Reich–Rus type in the framework of convex metric space. We demonstrate the presence and the approximation of fixed points for contraction mappings by using Krasnoselskij iteration. The main conclusions of this study are shown to be corollaries or implications of multiple important fixed point theory findings. Some examples have also been provided to show the validity of our results. Towards the end of this paper, we study the solution of the nonlinear equations as an application of our main results.
Prevalence and Predictors of Diabetic Retinopathy in Saudi Arabia: Insights from a Systematic Review and Meta-Analysis
Authors: Alshahrani Ali Mohammed , Alshahrani Alaa Mohammed , Al-Boqami Beshayer Abdullah H. , Alqahtani Alwaleed Abdulhadi , Alzahrani Bassam , Bassi Yousef , Almohaimeed Mohammed Yousef , Alalmaai Abeer Mohammed , Saraiva Ariana , Alhumaidi Bandar Naffaa , Albaridi Najla A. , Lima Maria João , Carrascosa Conrado , Raposo António
Published: November 2024

Background: Diabetic retinopathy (DR) is one of the leading causes of blindness among diabetic patients, particularly in areas with an increase in diabetes epidemics, such as Saudi Arabia. Notwithstanding the significant public health implications, data on the prevalence and risk factors of DR in Saudi Arabia are few and scattered, limited to certain geographic areas. Our study objective is to conduct a systematic review of the literature and a meta-analysis of the prevalence and predictors for DR in Saudi Arabia, within both type 1 and type 2 diabetes. Methods: A systematic review and meta-analysis were constructed according to PRISMA guidelines. We searched PubMed, Embase, Web of Science, and Google Scholar electronic databases for studies published from 2000–2023. Any study related to the prevalence of diabetic retinopathy in T1DM or T2DM among adult patients aged ≥18 years that was conducted in Saudi Arabia was included. Pooling prevalence estimates were calculated using a random-effects model, and heterogeneity across the studies was tested by the I2 statistic and Cochran’s Q test. Results: A total of 11 studies published between 2006 and 2019 met the inclusion criteria, with sample sizes ranging from 99 to over 50,000 participants. The overall pooled prevalence of DR was estimated to be 31% (95% CI: 24–39%), with substantial heterogeneity observed across studies (I2 = 99%). Prevalence estimates ranged from 16.7% to 69.8% and were influenced by variables such as study design, duration of diabetes, and glycemic control. Among individuals with type 2 diabetes, the pooled prevalence was 24% (95% CI: 20–28%). Poor glycemic control and longer diabetes duration were consistently identified as significant predictors of DR, while other factors, such as obesity and hypertension, were also associated with an increased risk of DR. Conclusions: The high prevalence of DR in Saudi Arabia highlights the critical need for focused public health initiatives, especially among those with type 2 diabetes. To minimize the effects of DR, early intervention, routine DR screening programs, and optimal diabetes control are essential. The increasing prevalence of DR in Saudi Arabia requires careful consideration of healthcare policy and resource allocation, which is made possible by our results.
Murine vs. Human Osteoblast Responses to Coagulation and Inflammatory Factors: Reconsidering the Use of Animal Models in Hemophilia A Research
Authors: Bernar Aline , Bauer Monika , Schirmer Michael , Streif Werner , Gebetsberger Jennifer
Published: November 2024

Background/Objectives: Hemophilia A is associated with frequent bleeding episodes, joint damage, and reduced bone mineral density (BMD). The role of coagulation factors and inflammatory cytokines on bone metabolism, particularly on osteoblast function, is of increasing interest. However, significant inter-species differences in bone remodeling raise concerns about the translatability of findings from murine models to human systems. This study aims to investigate the effects of human coagulation factors and cytokines on bone formation, focusing on inter-species differences in the cell viability and mineralization of murine and human osteoblasts. Methods: Murine MC3T3-E1 and human SaOs-2 osteoblasts were cultured in osteoblast differentiation medium supplemented with various coagulation factors (FVIII, vWF, vWF-FVIII, FIX, FX, thrombin, and FVIII-thrombin) or cytokines (IL-6, TNF-α). Cell viability was assessed at both two-week and three-week time points using the CCK-8 assay, and mineralization was evaluated via Alizarin red S staining. Results: Coagulation factors significantly enhanced cell viability in human osteoblasts but had no effects on the murine counterpart. FX inhibited mineralization in human cells, while murine cells showed no significant changes. TNF-α stimulated mineralization in murine osteoblasts but inhibited it in human cells, highlighting species-specific responses to inflammatory cytokines. Similar trends in response patterns were observed at two and three weeks, with greater consistency at the later time point. Conclusions: These findings reveal critical inter-species differences in osteoblast responses to coagulation factors and cytokines, raising questions about the validity of using murine models to study human bone metabolism. Future research must account for these differences to ensure that preclinical models accurately reflect human pathophysiology, particularly in the context of hemophilia A.
Optical Flow Sensor with Fluorescent-Conjugated Hyperelastic Pillar: A Biomimetic Approach
Authors: Seo Dongmin , Yoon Seungmin , Park Jaemin , Lee Sangwon , Han Seungoh , Byun Sung-Hoon , Oh Sangwoo
Published: November 2024

Although the Doppler velocity log is widely applied to measure underwater fluid flow, it requires high power and is inappropriate for measuring low flow velocity. This study proposes a fluid flow sensor that utilizes optical flow sensing. The proposed sensor mimics the neuromast of a fish by attaching a phosphor to two pillar structures (A and B) produced using ethylene propylene diene monomer rubber. The optical signal emitted by the phosphor is measured using a camera. An experiment was conducted to apply an external force to the reactive part using a push–pull force gauge sensor to confirm the performance of the proposed sensor. The optical signal emitted by the phosphor was obtained using an image sensor, and a quantitative value was calculated using image analysis. A simulation environment was constructed to analyze the flow field and derive the relationship between the flow rate and velocity. The physical properties of the pillar were derived from hysteresis measurement results, and the error was minimized when pillar types A and B were utilized within the ranges of 0–0.1 N and 0–2 N, respectively. A difference in the elastic recovery characteristics was observed; this difference was linear based on the shape of the pillar, and improvement rates of 99.585% and 99.825% were achieved for types A and B, respectively. The proposed sensor can help obtain important information, such as precise flow velocity measurements in the near field, to precisely navigate underwater unmanned undersea vehicles and precisely control underwater robots after applying the technology to the surface of various underwater systems.
Biomimetic Proteoglycans for Intervertebral Disc (IVD) Regeneration
Authors: Chopra Neha , Melrose James , Gu Zi , Diwan Ashish D.
Published: November 2024

Intervertebral disc degeneration, which leads to low back pain, is the most prevalent musculoskeletal condition worldwide, significantly impairing quality of life and imposing substantial socioeconomic burdens on affected individuals. A major impediment to the development of any prospective cell-driven recovery of functional properties in degenerate IVDs is the diminishing IVD cell numbers and viability with ageing which cannot sustain such a recovery process. However, if IVD proteoglycan levels, a major functional component, can be replenished through an orthobiological process which does not rely on cellular or nutritional input, then this may be an effective strategy for the re-attainment of IVD mechanical properties. Furthermore, biomimetic proteoglycans (PGs) represent an established polymer that strengthens osteoarthritis cartilage and improves its biomechanical properties, actively promoting biological repair processes. Biomimetic PGs have superior water imbibing properties compared to native aggrecan and are more resistant to proteolytic degradation, increasing their biological half-life in cartilaginous tissues. Methods have also now been developed to chemically edit the structure of biomimetic proteoglycans, allowing for the incorporation of bioactive peptide modules and equipping biomimetic proteoglycans as delivery vehicles for drugs and growth factors, further improving their biotherapeutic credentials. This article aims to provide a comprehensive overview of prospective orthobiological strategies that leverage engineered proteoglycans, paving the way for novel therapeutic interventions in IVD degeneration and ultimately enhancing patient outcomes.
Animals as Architects: Building the Future of Technology-Supported Rehabilitation with Biomimetic Principles
Authors: Bonnechère Bruno
Published: November 2024

Rehabilitation science has evolved significantly with the integration of technology-supported interventions, offering objective assessments, personalized programs, and real-time feedback for patients. Despite these advances, challenges remain in fully addressing the complexities of human recovery through the rehabilitation process. Over the last few years, there has been a growing interest in the application of biomimetics to inspire technological innovation. This review explores the application of biomimetic principles in rehabilitation technologies, focusing on the use of animal models to help the design of assistive devices such as robotic exoskeletons, prosthetics, and wearable sensors. Animal locomotion studies have, for example, inspired energy-efficient exoskeletons that mimic natural gait, while insights from neural plasticity research in species like zebrafish and axolotls are advancing regenerative medicine and rehabilitation techniques. Sensory systems in animals, such as the lateral line in fish, have also led to the development of wearable sensors that provide real-time feedback for motor learning. By integrating biomimetic approaches, rehabilitation technologies can better adapt to patient needs, ultimately improving functional outcomes. As the field advances, challenges related to translating animal research to human applications, ethical considerations, and technical barriers must be addressed to unlock the full potential of biomimetic rehabilitation.
Biomimetic Plant-Root-Inspired Robotic Sensor System
Authors: Alvira Margarita , Mondini Alessio , Puleo Gian Luigi , Tahirbegi Islam Bogachan , Beccai Lucia , Sadeghi Ali , Mazzolai Barbara , Mir Mònica , Samitier Josep
Published: November 2024

There are many examples in nature in which the ability to detect is combined with decision-making, such as the basic survival instinct of plants and animals to search for food. We can technically translate this innate function via the use of robotics with integrated sensors and artificial intelligence. However, the integration of sensing capabilities into robotics has traditionally been neglected due to the significant associated technical challenges. Inspired by plant-root chemotropism, we present a miniaturized electrochemical array integrated into a robotic tip, embedding a customized micro-potentiometer. The system contains solid-state sensors fitted to the tip of the robotic root to three-dimensionally monitor potassium and pH changes in a moist, soil-like environment, providing an integrated electronic readout. The sensors measure a range of parameters compatible with realistic soil conditions. The sensors’ response can trigger the movement of the robotic root with a control algorithm inspired by the behavior of the plant root that determines the optimal path toward root growth, simulating the decision-making process of a plant. This nature-inspired technology may lead, in the future, to the realization of robotic devices with the potential for monitoring and exploring the soil autonomously.
Obsessive–Compulsive Traits and Problematic Internet Use Are Increased Among Adults with Autism Spectrum Disorder: Is There a Role of Obsessive Doubts and Communication Impairment?
Authors: Carpita Barbara , Nardi Benedetta , Parri Francesca , Cerofolini Gianluca , Bonelli Chiara , Bocchino Cristina Gaia , Massimetti Gabriele , Cremone Ivan Mirko , Pini Stefano , Dell’Osso Liliana
Published: November 2024

Background: The link between autism spectrum disorder (ASD) and obsessive–compulsive disorder (OCD) and the complexity of their differential diagnosis has been vastly investigated. Growing attention has been paid to the presence of problematic Internet use (PIU) in autistic individuals. Studies assessing OCD traits in autistic individuals are scarce and even less take into account the role that this overlap may have on the development and maintenance of PIU. We aimed to investigate OCD features in ASD individuals and their association with autism severity and the prevalence of PIU, and the potential dimensions associated with a greater probability of PIU. Methods: a total of 46 participants with ASD and 53 controls were assessed with the Adult Autism Subthreshold Spectrum questionnaire and the Obsessive–Compulsive Spectrum—Short Version. Results: There were significantly higher OCD features in ASD participants along with important correlations between OCD and ASD dimensions and a higher prevalence of PIU in the ASD group. Participants with putative PIU reported greater scores on some ASD and OCD dimensions, the with Doubt and Non-verbal communication domains emerging as significant predictors of the presence of putative PIU. Conclusions: These results support the three-way link between ASD, OCD, and PIU, contributing to the hypothesis of a neurodevelopmental basis for those conditions.
Identifying Cyclical Patterns of Behavior Using a Moving-Average, Data-Smoothing Manipulation
Authors: Retzlaff Billie J. , Craig Andrew R. , Owen Todd M. , Greer Brian D. , O’Donnell Alex , Fisher Wayne W.
Published: November 2024

For some individuals, rates of destructive behavior change in a predictable manner, irrespective of the contingencies programmed. Identifying such cyclical patterns can lead to better prediction of destructive behavior and may allow for the identification of relevant biological processes. However, identifying cyclical patterns of behavior can be difficult when using traditional methods of visual analysis. We describe a data-manipulation method, called data smoothing, in which one averages the data across time points within a specified window (e.g., 3, 5, or 7 days). This approach minimizes variability in the data and can increase the saliency of cyclical behavior patterns. We describe two cases for which we identified cyclical patterns in daily occurrences of destructive behavior, and we demonstrate the importance of analyzing smoothed data across various windows when using this approach. We encourage clinicians to analyze behavioral data in this way when rates vary independently of programmed contingencies and other potentially controlling variables have been ruled out (e.g., behavior variability related to sleep behavior).
Adaptive Optimization of Wind Environment in Coastal Village Spatial Forms of Western Guangdong
Authors: Pang Yue , Liang Zhanxun , Xie Peisheng , Li Li
Published: November 2024

Naozhou Island is located in a subtropical marine monsoon climate, with frequent windy days throughout the year, which has a significant impact on the residents’ lives. The spatial form of local traditional villages has adapted to the local wind environment through long-term practical exploration. This study aims to quantitatively analyze this layout to explore the patterns of its climate adaptability, thereby providing guidance for modern village construction. The research method primarily involves using CFD software (2019) to analyze the spatial form parameters of the village, namely village scale, planar form, building density, and orientation, along with their effects on average wind speed, wind speed amplification factor, and wind field coefficient under normal and extreme wind conditions. The results show that an appropriate planar form can enhance the wind adaptability of the village, while village scale and building density significantly affect the wind environment. However, the orientation of the village does not have a significant impact on wind field changes due to the discontinuity of the street system. These patterns of wind adaptability can assist in the planning and design of future coastal villages to enhance the wind environment regulation and disaster resilience of island villages.
Clinical-Demographic Profile, Prognostic Factors and Outcomes in Classic Follicular Lymphoma Stratified by Staging and Tumor Burden: Real-World Evidence from a Large Latin American Cohort
Authors: Nogueira Daniel Silva , Lage Luís Alberto de Pádua Covas , Reichert Cadiele Oliana , Culler Hebert Fabrício , de Freitas Fábio Alessandro , Mendes João Antônio Tavares , Gouveia Ana Carolina Maia , Costa Renata de Oliveira , Ferreira Cristiane Rúbia , Maximino Jéssica Ruivo , Bydlowski Sérgio Paulo , Murga Zamalloa Carlos Alejandro , Rocha Vanderson , Levy Débora , Pereira Juliana
Published: November 2024

Background: Clinical staging (CS) and tumor burden (TB) play a significant role in FL prognosis and direct its up-front therapy. The aim of this study is to report prognostic factors and clinical outcomes in newly-diagnosed FL patients stratified according to CS and TB in early-stage (ES) disease, advanced-stage with low tumor burden (AS-LTB) and advanced-stage with high tumor burden (AS-HTB). Methods: Two hundred fourteen patients with FL grades 1–3A had baseline clinical characteristics and outcomes assessed. Survival according to up-front immunochemotherapeutic (ICT) regimens was assessed in the AS-HTB subgroup. Independent predictors for OS, PFS, POD-24, and Histological Transformation (HT) were identified. Results: Seventy-five percent of cases were categorized as AS-HTB, 13.5% as AS-LTB and 11.5% as ES. With a median follow-up of 8.15 years, the estimated 5-year OS and PFS were 75.4% and 57.2%, respectively. OS, but not PFS was markedly decreased in AS-HTB FL patients compared to ES and AS-LTB cases. POD-24 rate was 21.7% and overall mortality rate was 38.7% during the entire follow-up. The annual cumulative rate of HT to high-grade B-cell lymphoma (HGBCL) was 0.5%, and higher in AS-HTB cases, in comparison to ES and AS-LTB. Considering patients with AS-HTB there were no differences in clinical outcomes among cases submitted to ICT based on R-CHOP, R-CVP and regimens containing purine analogs. Additionally, ECOG ≥ 2, hypoalbuminemia, B-symptoms and HT were independently associated with poor survival. High content of centro-blasts (grade 3A), involvement of ≥3 nodal sites by FL and rituximab omission in up-front therapy predicted POD-24. Conclusions: FL has marked clinical–prognostic heterogeneity, translated into diverse CS and TB subcategories. Here, we demonstrated that FL patients classified as AS-HTB demonstrated decreased survival and higher rates of HT to HGBCL compared to ES and AS-LTB cases. Prognostic factors identified in our analysis may help to identify FL patients with higher-risk of HT and early-progression (POD-24).
Artificial Intelligence-Assisted Stimulated Raman Histology: New Frontiers in Vibrational Tissue Imaging
Authors: Krishnan Nambudiri Manu Krishnan , Sujadevi V. G. , Poornachandran Prabaharan , Murali Krishna C. , Kanno Takahiro , Noothalapati Hemanth
Published: November 2024

Frozen section biopsy, introduced in the early 1900s, still remains the gold standard methodology for rapid histologic evaluations. Although a valuable tool, it is labor-, time-, and cost-intensive. Other challenges include visual and diagnostic variability, which may complicate interpretation and potentially compromise the quality of clinical decisions. Raman spectroscopy, with its high specificity and non-invasive nature, can be an effective tool for dependable and quick histopathology. The most promising modality in this context is stimulated Raman histology (SRH), a label-free, non-linear optical process which generates conventional H&E-like images in short time frames. SRH overcomes limitations of conventional Raman scattering by leveraging the qualities of stimulated Raman scattering (SRS), wherein the energy gets transferred from a high-power pump beam to a probe beam, resulting in high-energy, high-intensity scattering. SRH’s high resolution and non-requirement of preprocessing steps make it particularly suitable when it comes to intrasurgical histology. Combining SRH with artificial intelligence (AI) can lead to greater precision and less reliance on manual interpretation, potentially easing the burden of the overburdened global histopathology workforce. We review the recent applications and advances in SRH and how it is tapping into AI to evolve as a revolutionary tool for rapid histologic analysis.
Advances in Immunotherapy for Endometrial Cancer: Insights into MMR Status and Tumor Microenvironment
Authors: Albertí-Valls Manel , Olave Sara , Olomí Anna , Macià Anna , Eritja Núria
Published: November 2024

Endometrial cancer is one of the most common gynecological malignancies, and while early-stage cases are highly treatable, recurrent or advanced EC remains challenging to manage. Immunotherapy, particularly immune checkpoint inhibitors, has revolutionized treatment approaches in oncology, and its application in EC has shown promising results. Key to immunotherapy efficacy in EC is the tumor’s mismatch repair status, with MMR-deficient tumors demonstrating a higher tumor mutational burden and increased PD-L1 expression, making them more susceptible to immune checkpoint inhibitors (ICIs) such as pembrolizumab, durvalumab, and dostarlimab. However, not all mismatch repair-deficient (MMRd) tumors respond to ICIs, particularly those with a “cold” tumor microenvironment (TME) characterized by poor immune infiltration. In contrast, some MMR-proficient tumors with a “hot” TME respond well to ICIs, underscoring the complex interplay between MMR status, tumor mutational burden (TMB), and TME. To overcome resistance in cold tumors, novel therapies, including Chimeric Antigen Receptor (CAR) T cells and tumor-infiltrating lymphocytes are being explored, offering targeted immune-based strategies to enhance treatment efficacy. This review discusses the current understanding of immunotherapy in EC, emphasizing the prognostic and therapeutic implications of MMR status, TME composition, and emerging cell-based therapies.
Circulating Tumor DNA in Early and Metastatic Breast Cance—Current Role and What Is Coming Next
Authors: Tegeler Christian Martin , Hartkopf Andreas Daniel , Banys-Paluchowski Maggie , Krawczyk Natalia , Fehm Tanja , Jaeger Bernadette Anna Sophia
Published: November 2024

The progress that has been made in recent years in relation to liquid biopsies in general and circulating tumor DNA (ctDNA) in particular can be seen as groundbreaking for the future of breast cancer treatment, monitoring and early detection. Cell-free DNA (cfDNA) consists of circulating DNA fragments released by various cell types into the bloodstream. A portion of this cfDNA, known as ctDNA, originates from malignant cells and carries specific genetic mutations. Analysis of ctDNA provides a minimally invasive method for diagnosis, monitoring response to therapy, and detecting the emergence of resistance. Several methods are available for the analysis of ctDNA, each with distinct advantages and limitations. Quantitative polymerase chain reaction is a well-established technique widely used due to its high sensitivity and specificity, particularly for detecting known mutations. In addition to the detection of individual mutations, multigene analyses were developed that could detect several mutations at once, including rarer mutations. These methods are complementary and can be used strategically depending on the clinical question. In the context of metastatic breast cancer, ctDNA holds particular promise as it allows for the dynamic monitoring of tumor evolution. Through ctDNA analysis, mutations in the ESR1 or PIK3CA genes, which are associated with therapy resistance, can be identified. This enables the early adjustment of treatment and has the potential to significantly enhance clinical outcome. The application of ctDNA in early breast cancer is an ongoing investigation. In (neo)adjuvant settings, there is preliminary data indicating that ctDNA can be used for therapy monitoring and risk stratification to decide on post-neoadjuvant strategies. In the monitoring of aftercare, the detection of ctDNA appears to be several months ahead of routine imaging. However, the feasibility of implementing this approach in a clinical setting remains to be seen. While the use of ctDNA as a screening method for the asymptomatic population would be highly advantageous due to its minimally invasive nature, the available data on its clinical benefit are still insufficient. Nevertheless, ctDNA represents the most promising avenue for fulfilling this potential future need.