bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital Image Correlation and Reliability-Based Methods for the Design of Structural Beams Made from Recycled Concrete Using Aggregates from Precast Rejects
Authors: López-Rebollo Jorge , Teijón-López-Zuazo Evelio , García-Martin Roberto , Sánchez-Aparicio Luis Javier , González-Aguilera Diego
Published: January 2025

The use of recycled aggregates in the manufacture of concrete is presented as a solution to reduce the consumption of resources and waste in the construction sector and contribute to a lower environmental impact. This work aims to explore the possibility of producing structural beams from recycled concrete using aggregates from precast concrete rejects and to improve their design using advanced characterisation techniques. To this end, the experimental data coming from mechanical test and the use of the digital image correlation approach are combined with a robust reliability-based method. The full-field data provided by the digital image correlation approach allow to determine the probabilistic density functions of the mechanical data. From these data, a predictive analysis of the maximum strength and deflection of flexural beams is carried out based on robust design techniques. This approach uses analytical theoretical models and a Monte Carlo-based simulation strategy that allows the prediction of the behaviour of the beams. This methodology was validated by manufacturing six beams with the previously analysed recycled concrete, HA-30, and testing them in the laboratory. All the beams showed behaviour within the predicted range: around 49.7 kN maximum load and just over 9.3 mm maximum deflection. These results demonstrate the robustness of the approach as well as the feasibility of using precast rejects for the manufacture of structural elements.
A Comparison of the Braking and Propulsion Phase Characteristics of Traditional and Accentuated Eccentric Loaded Back Squats in Resistance-Trained Women
Authors: Campbell Brookelyn A. , Cantwell Conor J. , Marshall-Ciochon Lauren K. , Schroeder Zachary S. , Sundh Adam E. , Chard Jack B. , Taber Christopher B. , Suchomel Timothy J.
Published: January 2025

The aim of this study was to compare the braking and propulsion force–time and barbell velocity characteristics between back squat sets performed using traditional (TRAD) or accentuated eccentric loading (AEL) in resistance-trained women. In total, 14 participants completed four separate testing sessions that included a one repetition maximum (1RM) back squat and three squat testing sessions that used either TRAD or AEL. During the squat testing sessions, participants performed sets of three back squat repetitions using TRAD loads with 50, 60, 70, and 80% 1RM or performed the same loads with the addition of weight releasers that equated the total load to 100% (AEL-MAX) or 110% (AEL-SUPRA) 1RM during the eccentric phase of the first repetition of each set. Braking and propulsion mean force, duration, and impulse as well as mean and peak barbell velocity were examined across each back squat set. Significantly greater braking impulses were produced during the AEL conditions across all loads (p < 0.02), while greater braking mean force during AEL-SUPRA was produced compared to TRAD during with 50 and 60% 1RM (p < 0.02). There were no other significant differences in braking, propulsion, or barbell velocity that existed between different conditions (p > 0.05). AEL-MAX and AEL-SUPRA provide a greater braking stimulus compared to TRAD squats, while the propulsion phase may not be significantly impacted. Rapid and maximal force production may be favored by larger and smaller load spreads, respectively.
The Influence of Vitamin D Levels and Supplementation on the Treatment of Patients Affected by MRONJ
Authors: Michalak Filip , Dominiak Marzena , Kiryk Jan , Popecki Paweł , Kubicki Dominik , Matys Jacek , Grzech-Leśniak Kinga
Published: January 2025

Background: Advancements in pharmacology have led to the introduction of novel antiresorptive and antiangiogenic drugs, which are associated with the side effect of medication-related osteonecrosis of the jaw (MRONJ). The aim of this study was to evaluate the impact of different blood levels of vitamin D on the course of treatment, as well as the role of vitamin D supplementation during the treatment of primary diseases involving bisphosphonates or denosumab. Methods: The clinical trial involved 64 patients diagnosed with medication-related osteonecrosis of the jaw (MRONJ) treated at the Department of Oral Surgery. Participants underwent baseline panoramic radiographs and Cone Beam Computed Tomography (CBCT) scans, with MRONJ severity categorized according to the AAOMS classification. This study included two groups: 37 patients (n = 37) in the experimental group received high-dose vitamin D supplementation (10,000 IU/day for 4 weeks, followed by a maintenance dose of 5000 IU/day), while 27 patients (n = 27) in the control group received no supplementation. Vitamin D levels were measured at baseline, 3 months, and 6 months, and the relationship between vitamin D supplementation and clinical outcomes, including MRONJ risk and healing, was evaluated. All participants received an antibiotic regimen pre- and post-surgery. Pain intensity was assessed at multiple time points using the Visual Analog Scale (VAS). Results: This study showed significant increases in serum vitamin D levels in the experimental group at 3 and 6 months (p < 0.05). In the prophylactic context, Vitamin D supplementation prior to or during tooth extraction reduced the risk of developing severe MJRON (OR = 68.57; p < 0.001). In the therapeutic context among patients with established MJRON, vitamin D supplementation did not significantly predict postoperative complications (p = 0.079) or complete healing (OR = 2.34; p = 0.051). However, overall healing rates were somewhat higher in the supplemented group, though they did not reach statistical significance. Antibiotic protection uses also reduced the need for further treatment (OR = 6.20; p < 0.001). Conclusions: Prophylactic high-dose vitamin D supplementation may help prevent severe MRONJ in at-risk patients undergoing tooth extraction. Once MRONJ is established, however, vitamin D alone may not significantly alter immediate postoperative outcomes, although further research is needed to clarify its potential adjunctive benefits.
Effects of Neural Load on Hamstring Stretching upon Flexibility, Maximum Isometric Strength, and Tibial Nerve Pressure Pain Threshold in Healthy Subjects: A Randomized Clinical Trial
Authors: Fernández-del Rivero Carlos , García-Gil Pablo , Mínguez-Cruz Juan , Pecos-Martín Daniel , Fernández-Carnero Samuel , Achalandabaso-Ochoa Alexander , Rodríguez-Almagro Daniel
Published: January 2025

(1) Background: Stretching has been shown to improve flexibility, muscle activation, and coordination, but its effects may depend on neural tension during the stretch. This study evaluated the short- and medium-term effects of hamstring stretching with and without neural load on flexibility, tibial nerve pressure pain threshold, and maximum isometric strength. (2) Methods: Seventy-eight healthy participants (mean age: 24.96 ± 6.11 years) were randomly assigned to stretching programs with (n = 39) or without neural load (n = 39). Flexibility, pressure pain threshold, and maximum isometric strength were assessed at baseline, after the first session, at the end of the intervention, and one month later. (3) Results: The group using neural load showed significant flexibility improvements after the first session (MD = −5.2; p < 0.001), which were maintained at two months (MD = −8.6; p < 0.001) and follow-up (MD = −6.4; p < 0.001). In the control group, flexibility gains diminished at follow-up (MD = −3.9; p = 0.052). Other variables showed no significant changes across time points. (4) Conclusions: Since neither treatment showed superior efficacy, no specific stretching type could be recommended.
FPGA-QNN: Quantized Neural Network Hardware Acceleration on FPGAs
Authors: Tasci Mustafa , Istanbullu Ayhan , Tumen Vedat , Kosunalp Selahattin
Published: January 2025

Recently, convolutional neural networks (CNNs) have received a massive amount of interest due to their ability to achieve high accuracy in various artificial intelligence tasks. With the development of complex CNN models, a significant drawback is their high computational burden and memory requirements. The performance of a typical CNN model can be enhanced by the improvement of hardware accelerators. Practical implementations on field-programmable gate arrays (FPGA) have the potential to reduce resource utilization while maintaining low power consumption. Nevertheless, when implementing complex CNN models on FPGAs, these may may require further computational and memory capacities, exceeding the available capacity provided by many current FPGAs. An effective solution to this issue is to use quantized neural network (QNN) models to remove the burden of full-precision weights and activations. This article proposes an accelerator design framework for FPGAs, called FPGA-QNN, with a particular value in reducing high computational burden and memory requirements when implementing CNNs. To approach this goal, FPGA-QNN exploits the basics of quantized neural network (QNN) models by converting the high burden of full-precision weights and activations into integer operations. The FPGA-QNN framework comes up with 12 accelerators based on multi-layer perceptron (MLP) and LeNet CNN models, each of which is associated with a specific combination of quantization and folding. The outputs from the performance evaluations on Xilinx PYNQ Z1 development board proved the superiority of FPGA-QNN in terms of resource utilization and energy efficiency in comparison to several recent approaches. The proposed MLP model classified the FashionMNIST dataset at a speed of 953 kFPS with 1019 GOPs while consuming 2.05 W.
Runoff Simulation and Waterlogging Analysis of Rainstorm Scenarios with Different Return Periods on Campus: A Case Study at China University of Geosciences
Authors: Zuo Changqun , Yin Baoguo , Tan Fei , Ma Zhen , Gong Shenglong , Qi Xin
Published: January 2025

Urban flooding disasters are increasingly prevalent because of global climate change and urbanization. University campuses, as independent functional zones, exhibit complex rainfall–runoff dynamics. This study focuses on the China University of Geosciences, using data from two extremely heavy rainfall events and on-site waterlogging investigations in Wuhan in 2020 and 2021. A stormwater management model was employed to simulate campus catchment runoff and pipe network performance under rainstorm scenarios of various return periods, illustrating the spatial and temporal evolution of waterlogging on the campus. The simulation results indicate that the discharge at the main outlets aligned with rainfall patterns but exhibited a delayed response. During an overload period exceeding one hour, the ratios of overflow nodes and overloaded conduits reached 72.22% and 57.94%, respectively. Ponding was concentrated mainly in the southwest region of the campus, with the maximum ponding depth reaching 0.5 m. Future flood mitigation measures, such as enhancing permeable surfaces, upgrading pipeline infrastructure, and promoting rainwater reuse, could support the development of a “sponge campus” layout to alleviate flood pressure and enhance campus sustainability and resilience.
Relationship of Meteorological Variables with the Concentration of Various Tree Pollen Types in Madrid (Spain)
Authors: Chico-Fernández Javier , Ayuga-Téllez Esperanza
Published: January 2025

This study analyzes the behavior of airborne pollen in relation to meteorological parameters. It may be helpful to understand the consequences of this interaction on the health of the population of Madrid in the form of respiratory allergic pathologies. To this end, a multivariate analysis was carried out using Spearman’s linear correlation coefficient between the concentrations in the Madrid atmosphere of six types of tree pollen (Cupressaceae, Olea, Platanus, Pinus, Ulmus and Populus) and each of the six meteorological variables: relative humidity, precipitation, temperature, wind, radiation and insolation. The meteorological parameters most correlated with pollen types, with monthly values, are temperature and insolation, followed by radiation and relative humidity. In addition, there are more significant correlations of meteorological variables with Cupressaceae, Olea, Pinus and Platanus pollen types. Radiation is the meteorological parameter with the highest ρ values, especially with Olea, with ρ > 0.8. Wind is the only variable with significant correlations, all of them positive, with pollen types. The number of statistically significant results obtained from daily values is lower compared to monthly values, and only with Populus, Cupressaceae and Olea. The inter-relationship of meteorological variables with pollen grains can lead to an increase in the number of cases of pollinosis, when there are significant positive correlations.
Production, Characterization, and In Vitro Antifungal Evaluation of Itraconazole-Loaded Fibrous Sheets Prepared by Electrospinning with a Factorial Design
Authors: Rédai Emőke-Margit , Péterfi Orsolya , Gergely Attila Levente , Barabás Enikő , Pintea Andrada , Antonoaea Paula , Vlad Robert-Alexandru , Todoran Nicoleta , Cotoi Cornelia-Titiana , Ciurba Adriana , Sipos Emese
Published: January 2025

Itraconazole (ITZ) is a broad-spectrum triazole antifungal agent suitable for the treatment of superficial and systemic mycoses. This study aimed to formulate, characterize, and evaluate the in vitro antifungal performance of single-jet electrospun itraconazole-loaded polyvinylpyrrolidone-based fibers. Fibrous mats were prepared under the following experimental conditions: 10, 12.5, and 15 cm needle–collector distance, 20 kV tension, and 1, 1.5, and 2 mL/hour flow rate. The fibers were characterized by SEM, DSC, FTIR, assays, disintegration tests, dissolution tests, and in vitro antifungal activity. Using a 22 factorial design, the effects of preparation variables on the characteristics of the fibrous sheets were described. The electrospinning process led to smooth-surfaced, randomly oriented, and bead-free fibers. The average fiber diameter ranged from 887 nm to 1175 nm. The scanning calorimetry of pure ITZ revealed a sharp endothermic melting point at a temperature of 170 °C, not present in the curves of the fibers. After 60 min, between 70 and 100% of ITZ was released. The antifungal assay revealed that the fibers inhibited the growth of Candida albicans and Candida parapyilosis. The obtained fiber mats prepared from the hydrophilic polymer presented almost instantaneous disintegration, with potential applications for rapid antifungal delivery in oral or topical pharmaceutical form.
Impact of Key DMD Parameters on Modal Analysis of High-Reynolds-Number Flow Around an Idealized Ground Vehicle
Authors: Ahani Hamed , Uddin Mesbah
Published: January 2025

This study provides a detailed analysis of the convergence criteria for dynamic mode decomposition (DMD) parameters, with a focus on sampling frequency and period in high-Reynolds-number flows. The analysis is based on flow over an idealized road vehicle, the Ahmed body (Re=7.7×105), using computational fluid dynamics (CFD) data from improved delayed detached eddy simulation (IDDES). The pressure and velocity spectrum analysis validated IDDES’s ability to capture system dynamics, consistent with existing studies. For a comprehensive understanding of the contributions of different components of the circle, the Ahmed body was divided into three regions: (a) front; (b) side, lower, and upper surfaces; and (c) rear fascia. Both pressure and skin-friction drag were analyzed in terms of frequency spectra and cumulative energy. Key findings show that a 90% contribution to the pressure drag comes from modes with a frequency of less than 26 Hz (St = 0.187), while the friction drag requires 84 Hz (St = 0.604) for similar energy capture. This study highlights the significance of accounting for intermittency and non-stationary behavior in turbulent flows for DMD convergence. A minimum of 3000 snapshots is necessary for the convergence of DMD eigenvalues, and sampling frequency ratios between 5 and 10 are needed to achieve a reconstruction error of less than 1%. The sampling period’s convergence showed that T*=250 (equivalent to 20 cycles of the slowest coherent structures) stabilizes coherent mode shapes and energy levels. Beyond this, DMD may become unstable. Additionally, mean subtraction was found to improve DMD stability. These results offer critical insights into the effective application of DMD in analyzing complex vehicle flow fields.
Sounds and Natures Do Often Agree: Prediction of Esports Players’ Performance in Fighting Games Based on the Operating Sounds of Game Controllers
Authors: Hiratsuka Yamato , Kuga Kazuki , Miura Takahiro , Tanaka Tetsuo , Ueda Mari
Published: January 2025

In research focusing on esports, studies have been conducted on designs that attract competitors, performance estimation, training methods, and motivational factors. However, quantitative and convenient methods for performance evaluation are still in the development stage among the numerous performance evaluation methods. In particular, few method has been developed to objectively measure an individual’s mental state utilizing limited equipment. It has been observed that when players’ performance deteriorates or they are under pressure, they occasionally operate the controller in accordance with their state, resulting in the sound of the controller increasing. Therefore, this study aimed to clarify the relationship between the sound of esports players’ controller operations and their objective as well as subjective metrics, including their emotional state and performance during the game. Initially, the controller sounds of players of various ranks in Super Smash Bros. Ultimate (SSBU) by Nintendo were explored, aiming to elucidate the connection between the operation sounds of adept and intermediate esports competitors and their day-to-day fluctuations in game performance and emotional well-being. The findings revealed a discernible pattern: the more proficient the player, the more resonant the sounds emanating from their controller during gameplay. Furthermore, the operational sounds of skilled players exhibited an escalation when their performance faltered.
Determination of the Antioxidant Capacity of Germinated and Yeast-Fermented Sweet and Bitter Lupin Seeds and Sprouts via Cyclic Voltammetry Compared to the Spectrophotometric and Photochemiluminescence Methods
Authors: Zielińska Danuta , Gulewicz Piotr , Kasprowicz-Potocka Małgorzata , Zieliński Henryk
Published: January 2025

This paper describes the total antioxidant capacity (TAC) of sweet lupin (Lupinus luteus cv. Lord—LLL) and narrow-leaved bitter lupin (Lupinus angustifolius cv. Mirela—LAM) sprouts fermented by yeast, determined by deploying the updated analytical strategy based on three assays. The procedures covered electrochemical, spectrophotometric, and photochemiluminescence methods. Cyclic voltammetry (CV), the scavenging of 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH⦁), and photochemiluminescence (PCL) assays against superoxide anion radicals were applied to hydrophilic (ACW) and lipophilic (ACL) fractions, and the data obtained were used to calculate the TAC after sequence extraction of the samples with 80% methanol followed by methanol/hexane (4:1; v/v). The total polyphenol content (TPC) in the hydrophilic fractions was measured using Folin–Ciocalteu reagent. The fermentation of the LLL and LAM seeds had no impact on the antioxidant capacity of their H fractions, whereas it increased the content of their L fractions up to 56%. The germinated lupin seeds of both cultivars showed slightly increased TAC than the fermented ones. The TPC in the yeast-fermented sprouts was slightly higher compared to the LLL sprouts, about twofold higher than in the fermented LLL seeds, and finally almost fivefold higher compared to the LLL seeds. A beneficial effect of fermentation was found with respect to LAM materials. The TAC of the fermented LLL and LAM sprouts measured via CV and PCL assays was almost twofold higher and eight and six times higher, respectively, compared to the seeds. These findings clearly suggest that the seeds of yellow sweet lupin (Lupinus luteus cv. Lord) are the most suitable for producing fermented sprouts with a high content of electroactive polar compounds able to scavenge multiple free radicals of biological and non-biological origin. The updated analytical strategy for the determination of the total antioxidant capacity proved to be a viable tool for screening processed lupin seeds.
Multi-Object Tracking with Predictive Information Fusion and Adaptive Measurement Noise
Authors: Cheng Xiaohui , Zhao Haoyi , Deng Yun , Shen Shuangqin
Published: January 2025

Multi-object tracking (MOT) aims to detect objects in video sequences and associate them across frames. Currently, the mainstream research direction regarding MOT is the tracking-by-detection (TBD) framework. Tracking results are highly sensitive to detection outputs, and challenges from object occlusion and complex motion present significant obstacles in the field of MOT. To reduce dependence on detection outputs, we propose a method that integrates predictive information to improve Non-Maximum Suppression (NMS). By applying secondary modulation to the suppression scores and dynamically adjusting the suppression threshold using tracking information, our method better retains candidate boxes for occluded objects. Furthermore, to track occluding and overlapping objects more effectively, we introduce an adaptive measurement noise method that adjusts the measurement noise to mitigate the impact of object occlusion or overlap on tracking accuracy. Additionally, we enhance the affinity matrix in the association algorithm by incorporating height information, thereby improving the stability of complex moving objects. Our method outperforms the baseline model ByteTrack on the DanceTrack dataset, increasing Higher Order Tracking Accuracy (HOTA), Multi-Object Tracking Accuracy (MOTA), and the ID F1 Score (IDF1) by 10.2%, 3.0%, and 4.8%, respectively.
Prospects for the Use of Quasi-Mersen Numbers in the Design of Parallel-Serial Processors
Authors: Kadyrzhan Aruzhan , Kadyrzhan Kaisarali , Bakirov Akhat , Suleimenov Ibragim
Published: January 2025

It is shown that a serial-parallel processor, comparable in bit capacity to a 16-bit binary processor, can be implemented based on an algorithm built on the residue number system, a distinctive feature of which is the use of the first four quasi-Mersenne numbers, i.e., prime numbers representable as pk=2k+1, k=1,2,3,4. Such a set of prime numbers satisfies the criterion 2p1p2p3p4+1=P, where P is also a prime number. Fulfillment of this criterion ensures the possibility of convenient use of the considered RNS for calculating partial convolutions developed for the convenience of using convolutional neural networks. It is shown that the processor of the proposed type can be based on the use of a set of adders modulo a quasi-Mersenne number, each of which operates independently. A circuit of a modulo 2k+1 adder is proposed, which can be called a trigger circuit, since its peculiarity is the existence (at certain values of the summed quantities) of two stable states. The advantage of such a circuit, compared to known analogs, is the simplicity of the design. Possibilities for further development of the proposed approach related to the use of the digital logarithm operation, which allows reducing the operations of multiplication modulo 2k+1 to addition operations, are discussed.
On the Work of Cartan and Münzner on Isoparametric Hypersurfaces
Authors: Cecil Thomas E. , Ryan Patrick J.
Published: January 2025

A hypersurface Mn in a real space form Rn+1, Sn+1, or Hn+1 is isoparametric if it has constant principal curvatures. This paper is a survey of the fundamental work of Cartan and Münzner on the theory of isoparametric hypersurfaces in real space forms, in particular, spheres. This work is contained in four papers of Cartan published during the period 1938–1940 and two papers of Münzner that were published in preprint form in the early 1970s and as journal articles in 1980–1981. These papers of Cartan and Münzner have been the foundation of the extensive field of isoparametric hypersurfaces, and they have all been recently translated into English by T. Cecil. The paper concludes with a brief survey of the recently completed classification of isoparametric hypersurfaces in spheres.
A State-of-Health Estimation Method of a Lithium-Ion Power Battery for Swapping Stations Based on a Transformer Framework
Authors: Shi Yu , Xie Haicheng , Wang Xinhong , Lu Xiaoming , Wang Jing , Xu Xin , Wang Dingheng , Chen Siyan
Published: January 2025

Against the backdrop of automobile electrification, an increasing number of battery-swapping stations for electric vehicles have been launched to address the issue of slow battery charging under cold temperature conditions. However, due to the separation of the discharging and charging processes for lithium-ion batteries (LIBs) at swapping stations, and the circulation of batteries across different vehicles and stations, the operating data become fragmented, making it difficult to accurately identify the battery state-of-health (SOH). This study proposes a BiLSTM-Transformer framework that extracts the Constant Voltage Time (CVT) feature using only charging data, enabling the precise estimation of battery capacity degradation. Validation experiments conducted on battery samples under different operating temperatures showed that the model achieved a normalized RMSE of less than 1.6%. In ideal conditions, the normalized RMSE of the estimation reached as low as 0.11%. This model enables SOH estimation without relying on discharge data, contributing to the efficient and safe operation of battery swapping stations.
Pond Water eDNA Reflects Broad Consistency with Surrounding Terrestrial Plant Ecosystems
Authors: Bozdogan Duygu , Takizawa Shogo , Furukori Norihiro , Homma Kosuke , Abe Harue , Sakio Hitoshi , Harada Naoki , Suzuki Kazuki
Published: January 2025

This study evaluates the potential of using pond water eDNA to reflect the surrounding terrestrial plant communities, aiming to develop a sustainable, large-scale, and long-term monitoring method for plant diversity in forest ecosystems. Water samples were collected four times from two ponds with different vegetation types during the late spring to autumn seasons in Japan. eDNA was extracted from dissolved particles fractionated by sequential filtration through pore sizes of 200 µm, 5 µm, and 0.45 µm, followed by high-throughput amplicon sequencing targeting the plant rbcL gene. By comparing field surveys with the eDNA data, we identified 79% and 63% of plant families and genera, respectively, suggesting that pond water eDNA may reflect the surrounding terrestrial plant ecosystem. Additionally, different trends were observed in the seasonal variation of plant taxa and their composition detected in eDNA, based on particle size. This study highlights the potential of pond water eDNA to provide valuable insights into forest plant richness and seasonal dynamics, offering a novel approach for ecological monitoring.
A New Antibody–Cytokine Construct Targeting Natural Killer Cells: An Immunotherapeutic Approach to Chronic Lymphocytic Leukemia
Authors: Flego Michela , Andreotti Mauro , Mauro Francesca Romana , Arasi Maria Beatrice , Zamboni Silvia , Michelini Zuleika , Pepe Sara , Galluzzo Clementina Maria , Amici Roberta , Moricoli Diego , Mazzei Chiara , Ascione Alessandro , Mallano Alessandra
Published: January 2025

In chronic lymphocytic leukemia (CLL), natural killer (NK) cells show a dysfunctional phenotype that correlates with disease progression. Our aim was to restore NK cell functionality in CLL through a specifically targeted IL15-stimulating activity; IL15 targeting could, in fact, potentiate the activity of NK cells and reduce off-target effects. We designed and developed a cis-acting immunocytokine composed of an anti-CD56 single-chain Fragment variable (scFv) and IL15, labeled scFvB1IL15. scFvB1IL15 was tested in vitro on peripheral blood mononuclear cells (PBMCs) obtained from both different healthy donors (HDs) and CLL patients in order to evaluate its ability to target NK cells and enhance their activation and NK-mediated directed cytotoxicity. scFvB1IL15 specifically induced strong degranulation and cytokine and chemokine production in NK cells in both HD- and CLL patient-derived PBMC samples. Furthermore, compared to IL15 alone, it was able to induce higher levels of NKG2D- and NKp30-activating receptors and restore NK-mediated direct killing in the CLL patient-derived samples. The preliminary data presented in this work suggest that IL15’s targeting of NK cells via scFvB1 potentiates the effects of IL15 and that scFvB1IL15 can be a useful agent for overcoming NK functional gaps and contribute to NK-cell-based immunotherapies.
Differentiating Liver Metastases from Primary Liver Cancer: A Retrospective Study of Imaging and Pathological Features in Patients with Histopathological Confirmation
Authors: Ghenciu Laura Andreea , Grigoras Mirela Loredana , Rosu Luminioara Maria , Bolintineanu Sorin Lucian , Sima Laurentiu , Cretu Octavian
Published: January 2025

Background and Objectives: This study aimed to identify and analyze imaging and pathological features that differentiate liver metastases from primary liver cancer in patients with histopathological confirmation, and to evaluate the diagnostic accuracy of imaging modalities. Materials and Methods: This retrospective study included 137 patients who underwent liver biopsy or resection between 2016 and 2024, comprising 126 patients with liver metastases and 11 patients with primary liver cancer (hepatocellular carcinoma). Imaging features on contrast-enhanced MRI were evaluated, including lesion number, size, margins, enhancement patterns, presence of capsule, T1/T2 signal characteristics, diffusion-weighted imaging (DWI) signal, and portal vein thrombosis. Laboratory data such as liver function tests and alpha-fetoprotein (AFP) levels were collected. Pathological features recorded included tumor differentiation, vascular invasion, necrosis, and fibrosis. Statistical analyses were performed using chi-squared tests, t-tests, and logistic regression, with a significance level of p < 0.05. The diagnostic accuracy of imaging features was assessed using receiver operating characteristic (ROC) curve analysis. Results: Liver metastases were more likely to present as multiple lesions (82.5% vs. 27.3%, p < 0.001), had irregular margins (78.6% vs. 36.4%, p = 0.002), rim enhancement (74.6% vs. 18.2%, p < 0.001), and were hypointense on T1-weighted images (85.7% vs. 45.5%, p = 0.004). Primary liver cancers were more likely to be solitary (72.7% vs. 17.5%, p < 0.001), have smooth margins (63.6% vs. 21.4%, p = 0.002), exhibit arterial phase hyperenhancement (81.8% vs. 23.8%, p < 0.001), and portal venous washout (72.7% vs. 19.0%, p < 0.001). Vascular invasion was more common in primary liver cancer (45.5% vs. 11.1%, p = 0.01). AFP levels > 400 ng/mL were significantly associated with primary liver cancer (63.6% vs. 4.8%, p < 0.001). ROC curve analysis showed that a combination of imaging features had an area under the curve (AUC) of 0.91 for differentiating the two entities. Conclusions: Imaging features such as lesion number, margin characteristics, enhancement patterns, T1/T2 signal characteristics, and portal venous washout, along with pathological features like vascular invasion and AFP levels, can effectively differentiate liver metastases from primary liver cancer. The diagnostic accuracy of imaging is high when multiple features are combined.
Neuroinflammation at the Dorsolateral Inferior Medulla: A Possible Central Nervous System Localization for POTS and Long COVID
Authors: Blitshteyn Svetlana
Published: January 2025

Both postural orthostatic tachycardia syndrome (POTS) and Long COVID are currently viewed as heterogeneous disorders with complex, multi-factorial and multi-systemic pathophysiology. POTS, one of the most common autonomic disorders, is a frequent sequela of SARS-CoV-2 infection. Both POTS and autonomic dysfunction, in general, are major pathophysiologic mechanisms of Long COVID. There is emerging evidence that neuroinflammation of the brainstem may be one of the mechanisms of POTS and Long COVID. This commentary argues that neuroinflammation at the dorsolateral inferior medulla is a possible central nervous system localization for POTS and Long COVID based on the limited scientific literature available to date and the neurologic manifestations of both disorders. Further studies involving advanced neuroimaging techniques and animal models with immunohistochemical brainstem tissue assessments are needed to understand how and why possible neuroinflammation at the dorsolateral inferior medulla may occur in patients with Long COVID, POTS and other disorders involving autonomic dysfunction.
The Importance of Dose Escalation in the Treatment of Pulmonary Arterial Hypertension with Treprostinil
Authors: Kędzierski Piotr , Banaszkiewicz Marta , Florczyk Michał , Piłka Michał , Mańczak Rafał , Wieteska-Miłek Maria , Szwed Piotr , Kasperowicz Krzysztof , Wrona Katarzyna , Darocha Szymon , Torbicki Adam , Kurzyna Marcin
Published: January 2025

Background: Treprostinil, which is administered via continuous subcutaneous or intravenous infusion, is a medication applied in the treatment of pulmonary arterial hypertension (PAH). The dose of treprostinil is adjusted on an individual basis for each patient. A number of factors determine how well patients respond to treatment. Objectives: The aim of this study was to identify factors that may influence the clinical response to the dose of treprostinil at 3 months after the start of therapy. Methods: The factors influencing treatment response were analyzed in consecutive PAH patients who started receiving treprostinil treatment. The treatment efficacy was assessed as improvement in 6 min walk distance (6MWD) and WHO functional class (WHO FC), a reduction in N-terminal prohormone of brain natriuretic peptide (NTproBNP), and the percentage of patients achieving low-risk status after 12 months of treatment. Results: A total of 83 patients were included in this analysis. Classification of patients according to the tertiles of treprostinil dose achieved at 3 months after drug inclusion shows that after 12 months of follow-up, the median WHO FC in the highest dose group was lower than that in the intermediate dose group (WHO FC II vs. WHO FC III, p = 0.005), the median NTproBNP was lower (922 pg/mL, vs. 1686 pg/mL, p = 0.036) and 6MWD was longer (300 m vs. 510 m, p = 0.015). The French Noninvasive Criteria (NIFC) scale score was higher (2 vs. 0, p = 0.008), and the Reveal scale score was lower (5.0 vs. 8.5, p = 0.034). In the group of patients who exceeded a dose of 19.8 ng/kg/min within 3 months, an improvement in 6MWD was observed significantly more often after one year of therapy, and they were more likely to show an increase in NIFC scale scores after one year of therapy than the group of patients who received the lower dose (65% vs. 30%, p = 0.02). In the group of patients younger than 50 years of age, a statistically significant correlation was observed between the dose of treprostinil achieved after three months of treatment and the parameters assessed after 12 months of treatment, including WHO FC, 6MWD, and NIFC prognostic scale scores (all p < 0.05). Conclusions: The clinical effect of treatment is critically dependent on the rapid escalation of the treprostinil dose during the first three months of treatment.
Investigating the Role of Osteopontin (OPN) in the Progression of Breast, Prostate, Renal and Skin Cancers
Authors: Kundu Gautam , Elangovan Selvakumar
Published: January 2025

Background/Objectives: Cancer is caused by disruptions in the homeostatic state of normal cells, which results in dysregulation of the cell cycle, and uncontrolled growth and proliferation in affected cells to form tumors. Successful development of tumorous cells proceeds through the activation of pathways promoting cell development and functionality, as well as the suppression of immune signaling pathways; thereby providing these cells with proliferative advantages, which subsequently metastasize into surrounding tissues. These effects are primarily caused by the upregulation of oncogenes, of which SPP1 (secreted phosphoprotein 1), a non-collagenous bone matrix protein, is one of the most well-known. Methods: In this study, we conducted a further examination of the transcriptomic expression profile of SPP1 (Osteopontin) during the progression of cancer in four human tissues, breast, prostate, renal and skin, in order to understand the circumstances conducive to its activation and dysregulation, the biological pathways and other mechanisms involved as well as differences in its splicing patterns influencing its expression and functionality. Results: A significant overexpression of SPP1, as well as a set of other highly correlated genes, was seen in most of these tissues, indicating their extensive implication in cancer. Increased expression was observed with higher tumor stages, especially in renal and skin cancer, while applying therapeutic modalities targeting these genes dampened this effect in breast, prostate and skin cancer. Pathway analyses showed gene signatures related to cell growth and development enriched in tumorigenic conditions and earlier cancer stages, while later stages of cancer showed pathways associated with weakened immune response, in all cancers studied. Moreover, the utilization of therapeutic methods showed the activation of immunogenic pathways in breast, prostate and skin cancer, thereby confirming their viability. Further analyses of differential transcript expression levels in these oncogenes showed their exonic regions to be selectively overexpressed similarly in tumorigenic samples in all cancers studied, while also displaying significant differences in exon selectivity between constituent transcripts, providing a basis for their high degree of multifunctionality in cancer. Conclusions: Overall, this study corroborates the entrenched role of SPP1 in the progression of these four types of cancer, as confirmed by its overexpression and activation of related oncogenes, their co-involvement in key cellular pathways, and predisposition to exhibit differential splicing between their transcripts, while the above effects were found to be highly inhibitable through treatment methods, thereby highlighting its promising role in therapeutic development.
The Effect of Prebiotics, Alone or as Part of Synbiotics, on Cardiometabolic Parameters in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Razmpoosh Elham , Sivanandy Mala S. , Ehrlich Alan M.
Published: January 2025

Background/Objectives: This systematic review and meta-analysis aimed to investigate the effect of prebiotics, alone or as part of synbiotics, on cardiometabolic parameters in polycystic ovary syndrome (PCOS) women. Methods: Databases, including PubMed, Scopus, ISI Web of Science, Embase, and the Cochrane Central Register of Controlled Trials, were searched for relevant randomized-controlled trials (RCTs) until 12 December 2024. Changes in mean ± standard deviations were extracted and combined using a random-effects model. Bias was assessed using Cochrane risk of bias and evidence quality with GRADE. Results: Twenty RCTs with 1271 participants were included. Results showed high-quality evidence supporting prebiotics’ effects, alone or as part of synbiotics, in reducing body-mass index [n = 853; weighted-mean difference (WMD): −0.510, 95%CI: −0.669, −0.351 kg/m2] and diastolic blood pressure (WMD: −2.218, 95%CI: −4.425, −0.010 mmHg), moderate-quality evidence for weight, waist-to-hip ratio, and triglycerides improvements, and low or very-low-quality evidence for waist circumference (WC), fat mass, fasting plasma glucose, fasting insulin, low-density lipoprotein (LDL), total cholesterol (TC), high sensitive-C reactive protein, total testosterone, follicle-stimulating hormone and free androgen index improvements. Subgroup analyses revealed possible reduction in LDL with prebiotics, as well as possible decreases in WC, TC, and total testosterone with synbiotics. Dietary approaches to stop hypertension diet improved insulin sensitivity. Conclusions: This study suggests that prebiotics may beneficially affect several cardiometabolic parameters in PCOS women. Approximately one-third of the results were based on moderate-to-high-quality evidence. This study highlights the need for future well-designed, larger RCTs with longer treatment duration to strengthen the evidence base and guide clinical decision-making.
Design of Novel Human Wrist Prostheses Based on Parallel Architectures: Dimensional Synthesis and Kinetostatics
Authors: Di Gregorio Raffaele
Published: January 2025

The human wrist affects the ability to efficiently perform many manipulation tasks. Despite this, most upper-limb prostheses are focused on the hand’s mobility, which makes users compensate for the lost wrist mobility with complex manipulation strategies relying on the mobility of other body parts. In this context, research on wrist prostheses is still open to new contributions, even though a number of such prostheses are already present in the literature and on the market. In particular, the potential uses of parallel mechanisms in wrist prosthesis design have not been fully explored yet. In this work, after recalling the mobility characteristics of human wrists and reviewing the literature both on wrist prostheses and parallel mechanisms, a number of parallel architectures employable in a wrist prosthesis are selected. Then, with reference to the design requirements of this prosthesis type, the dimensional synthesis and kinetostatic analysis of the selected architectures are addressed. The results of this work are new wrist prosthesis architectures together with the analysis of their kinetostatic performances. These findings complete the first step of a research project aimed at developing new concepts for mechatronic wrists.
Gibbs Free Energy and Enthalpy–Entropy Compensation in Protein Folding
Authors: Benítez María J. , Jiménez Juan S.
Published: January 2025

The thermodynamic study of protein folding shows the generation of a narrow range of ΔG° values, as a net result of large changes in the ΔH° and TΔS° values of the folding process. The obvious consequence of this narrow range of values is that a linear enthalpy–entropy relationship, showing apparent enthalpy–entropy compensation (EEC), is clearly observed to be associated with the study of protein folding. Herein, we show the ΔH°, TΔS°, and ΔG° values for a set of 583 data from protein folding processes, at various temperatures, as calculated by using the Gibbs–Helmholtz equations. This set of thermodynamic data was calculated from the melting temperature (Tm), the melting enthalpy (ΔHm), and the change in heat capacity (ΔCp°) values, all of them associated with the heat-induced protein unfolding processes and included in the ProTherm Data Base. The average values of enthalpy (ΔH°av), entropy (TΔS°av), and free energy (ΔG°av) for the folding process were calculated within the range of temperature from 0 °C to the average value of Tm. The values and temperature dependency of TΔS°av within this temperature range are practically equal to those corresponding to ΔH°av, while ΔG°av remains small and displaying a curve with a minimum at about 10 °C and a value of ΔG° = −30.9 kJ/mol at the particular temperature of 25 °C. The large negative value of TΔS°av, together with the also large and negative value of ΔCp°av, suggests large conformational changes and important EEC, thus causing the small average value of ΔG° for protein folding, which is enough to guarantee both protein stability and molecular flexibility to allow for adaptation to the chemical potentials of the environment. Our analysis suggests that EEC may be the quantum-mechanical evolutive mechanism to make functional proteins adaptative to environmental temperature and metabolite concentrations. The analysis of protein folding data, compared with those of protein–ligand interaction, allows us to suggest strategies to overcome EEC in the design of new drugs.
Pioneering Role of Nanopore Single-Molecule Sensing in Environmental and Food Surveillance
Authors: Tian Wenqiang , Wang Xu , Zhang Yan , Weng Ting , Chaker Tlili , Chen Xiaohan , Kong Qingke , Wang Deqiang
Published: January 2025

In recent years, environmental and food safety have garnered substantial focus due to their intimate connection with human health. Numerous biosensors have been developed for identifying deleterious compounds; however, these biosensors reveal certain limitations. Nanopore sensors, featuring nano-scaled pore size, have demonstrated outstanding performance in terms of rapidity, sensitivity, and selectivity as a single-molecule technique for environmental and food surveillance. In this review, we present a comprehensive overview of nanopore applications in these two fields. To elucidate the pioneering roles of nanopores, analytes are categorized into three distinct groups, including metal ions, synthetic contaminants, and biotoxins. Moreover, a variety of strategies are involved, such as the coalescence with ligand probes, the implementation of chemical reactions, the functionalization of nanopores, etc. These scientific studies showcase the versatility and diversity of the nanopore technique, paving the way for further developments of nanopore technology in environmental and food safety.
Phase II Study of Nanoliposomal Irinotecan (Nal-IRI) with 5-Fluorouracil and Leucovorin in Refractory Advanced High-Grade Neuroendocrine Cancer of Gastroenteropancreatic (GEP) or Unknown Origin
Authors: Mukherjee Sarbajit , Pattnaik Harsha , Sonti Sahithi , Ramesh Mrinalini , Jain Prantesh , Ramirez Robert A. , Fountzilas Christos , Vadehra Deepak , Attwood Kristopher , Iyer Renuka
Published: January 2025

Background: Neuroendocrine carcinomas (NECs) are treated with a frontline platinum–etoposide combination with no standard second-line therapies. We explored a novel combination of nanoliposomal irinotecan (Nal-IRI), 5-fluorouracil (5-FU), and leucovorin (LV) in advanced refractory NECs and investigated the impact of UGT1A1*28 polymorphism on treatment outcomes and toxicity. Methods: We conducted an open-label, single-arm, multi-center Phase 2 trial in advanced NEC patients of gastroenteropancreatic (GEP) or unknown origin with progression or intolerance to first-line therapy. Eligible patients received nal-IRI 70 mg/m2 and leucovorin 400 mg/m2, followed by 5-FU 2400 mg/m2 biweekly till disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Next-generation sequencing (NGS) was performed on blood/tissue samples at baseline and during treatment. Results: Eleven patients were enrolled, with nine evaluable for the primary endpoint. Seven were male, the median age was 66.7 years, and the median Ki-67 was 90%. We observed partial response in one patient, stable disease in six patients, and progressive disease in two patients. The median OS was 9.4 months (95% CI 2.9–29.3), and the median PFS was 4.4 months (95% CI 1.7–6.7). The most common adverse events were diarrhea (45%), nausea (45%), vomiting (45%), and fatigue (45%). The most common genetic mutations on NGS were TP53 (88.9%), CHEK2 (88.9%), and APC (33.3%). Patients with CHEK2 and APC mutation had longer PFS (p = 0.005 and p = 0.013, respectively). UGT1A1*28 polymorphism was not associated with OS, PFS, or toxicity. Conclusion: Nal-IRI with 5-FU/LV is a safe and effective treatment for refractory high-grade NECs of GEP or unknown origin. Future studies should explore novel combinations with Nal-IRI in high-grade NECs both in frontline and refractory settings.