bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine Perfusion Enables 24-h Preservation of Vascularized Composite Allografts in a Swine Model of Allotransplantation
Authors: Goutard Marion , Tawa Pierre , Berkane Yanis , Andrews Alec R. , Pendexter Casie A. , de Vries Reinier J. , Pozzo Victor , Romano Golda , Lancia Hyshem H. , Filz von Reiterdank Irina , Bertheuil Nicolas , Rosales Ivy A. , How Ira Doressa Anne L. , Randolph Mark A. , Lellouch Alexandre G. , Cetrulo Curtis L. , Uygun Korkut
Published: May 2024

The current gold standard for preserving vascularized composite allografts (VCA) is 4°C static cold storage (SCS), albeit muscle vulnerability to ischemia can be described as early as after 2 h of SCS. Alternatively, machine perfusion (MP) is growing in the world of organ preservation. Herein, we investigated the outcomes of oxygenated acellular subnormothermic machine perfusion (SNMP) for 24-h VCA preservation before allotransplantation in a swine model. Six partial hindlimbs were procured on adult pigs and preserved ex vivo for 24 h with either SNMP (n = 3) or SCS (n = 3) before heterotopic allotransplantation. Recipient animals received immunosuppression and were followed up for 14 days. Clinical monitoring was carried out twice daily, and graft biopsies and blood samples were regularly collected. Two blinded pathologists assessed skin and muscle samples. Overall survival was higher in the SNMP group. Early euthanasia of 2 animals in the SCS group was linked to significant graft degeneration. Analyses of the grafts showed massive muscle degeneration in the SCS group and a normal aspect in the SNMP group 2 weeks after allotransplantation. Therefore, this 24-h SNMP protocol using a modified Steen solution generated better clinical and histological outcomes in allotransplantation when compared to time-matched SCS.
EPSOM-Hyb: A General Purpose Estimator of Log-Marginal Likelihoods with Applications in Probabilistic Graphical Models
Authors: Chuu Eric , Niu Yabo , Bhattacharya Anirban , Pati Debdeep
Published: May 2024

We consider the estimation of the marginal likelihood in Bayesian statistics, with primary emphasis on Gaussian graphical models, where the intractability of the marginal likelihood in high dimensions is a frequently researched problem. We propose a general algorithm that can be widely applied to a variety of problem settings and excels particularly when dealing with near log-concave posteriors. Our method builds upon a previously posited algorithm that uses MCMC samples to partition the parameter space and forms piecewise constant approximations over these partition sets as a means of estimating the normalizing constant. In this paper, we refine the aforementioned local approximations by taking advantage of the shape of the target distribution and leveraging an expectation propagation algorithm to approximate Gaussian integrals over rectangular polytopes. Our numerical experiments show the versatility and accuracy of the proposed estimator, even as the parameter space increases in dimension and becomes more complicated.
Improving 2–5 Qubit Quantum Phase Estimation Circuits Using Machine Learning
Authors: Woodrum Charles , Wagner Torrey , Weeks David
Published: May 2024

Quantum computing has the potential to solve problems that are currently intractable to classical computers with algorithms like Quantum Phase Estimation (QPE); however, noise significantly hinders the performance of today’s quantum computers. Machine learning has the potential to improve the performance of QPE algorithms, especially in the presence of noise. In this work, QPE circuits were simulated with varying levels of depolarizing noise to generate datasets of QPE output. In each case, the phase being estimated was generated with a phase gate, and each circuit modeled was defined by a randomly selected phase. The model accuracy, prediction speed, overfitting level and variation in accuracy with noise level was determined for 5 machine learning algorithms. These attributes were compared to the traditional method of post-processing and a 6x–36 improvement in model performance was noted, depending on the dataset. No algorithm was a clear winner when considering these 4 criteria, as the lowest-error model (neural network) was also the slowest predictor; the algorithm with the lowest overfitting and fastest prediction time (linear regression) had the highest error level and a high degree of variation of error with noise. The XGBoost ensemble algorithm was judged to be the best tradeoff between these criteria due to its error level, prediction time and low variation of error with noise. For the first time, a machine learning model was validated using a 2-qubit datapoint obtained from an IBMQ quantum computer. The best 2-qubit model predicted within 2% of the actual phase, while the traditional method possessed a 25% error.
Motion Correction for Brain MRI Using Deep Learning and a Novel Hybrid Loss Function
Authors: Zhang Lei , Wang Xiaoke , Rawson Michael , Balan Radu , Herskovits Edward H. , Melhem Elias R. , Chang Linda , Wang Ze , Ernst Thomas
Published: May 2024

Purpose: Motion-induced magnetic resonance imaging (MRI) artifacts can deteriorate image quality and reduce diagnostic accuracy, but motion by human subjects is inevitable and can even be caused by involuntary physiological movements. Deep-learning-based motion correction methods might provide a solution. However, most studies have been based on directly applying existing models, and the trained models are rarely accessible. Therefore, we aim to develop and evaluate a deep-learning-based method (Motion Correction-Net, or MC-Net) for suppressing motion artifacts in brain MRI scans. Methods: A total of 57 subjects, providing 20,889 slices in four datasets, were used. Furthermore, 3T 3D sagittal magnetization-prepared rapid gradient-echo (MP-RAGE) and 2D axial fluid-attenuated inversion-recovery (FLAIR) sequences were acquired. The MC-Net was derived from a UNet combined with a two-stage multi-loss function. T1-weighted axial brain images contaminated with synthetic motions were used to train the network to remove motion artifacts. Evaluation used simulated T1- and T2-weighted axial, coronal, and sagittal images unseen during training, as well as T1-weighted images with motion artifacts from real scans. The performance indices included the peak-signal-to-noise ratio (PSNR), the structural similarity index measure (SSIM), and visual reading scores from three blinded clinical readers. A one-sided Wilcoxon signed-rank test was used to compare reader scores, with p < 0.05 considered significant. Intraclass correlation coefficients (ICCs) were calculated for inter-rater evaluations. Results: The MC-Net outperformed other methods in terms of PSNR and SSIM for the T1 axial test set. The MC-Net significantly improved the quality of all T1-weighted images for all directions (i.e., the mean SSIM of axial, sagittal, and coronal slices improved from 0.77, 0.64, and 0.71 to 0.92, 0.75, and 0.84; the mean PSNR improved from 26.35, 24.03, and 24.55 to 29.72, 24.40, and 25.37, respectively) and for simulated as well as real motion artifacts, both using quantitative measures and visual scores. However, MC-Net performed poorly for images with untrained T2-weighted contrast because the T2 contrast was unseen during training and is different from T1 contrast. Conclusion: The proposed two-stage multi-loss MC-Net can effectively suppress motion artifacts in brain MRI without compromising image quality. Given the efficiency of MC-Net (with a single-image processing time of ~40 ms), it can potentially be used in clinical settings.
Beyond Static Obstacles: Integrating Kalman Filter with Reinforcement Learning for Drone Navigation
Authors: Marino Francesco , Guglieri Giorgio
Published: May 2024

Autonomous drones offer immense potential in dynamic environments, but their navigation systems often struggle with moving obstacles. This paper presents a novel approach for drone trajectory planning in such scenarios, combining the Interactive Multiple Model (IMM) Kalman filter with Proximal Policy Optimization (PPO) reinforcement learning (RL). The IMM Kalman filter addresses state estimation challenges by modeling the potential motion patterns of moving objects. This enables accurate prediction of future object positions, even in uncertain environments. The PPO reinforcement learning algorithm then leverages these predictions to optimize the drone’s real-time trajectory. Additionally, the capability of PPO to work with continuous action spaces makes it ideal for the smooth control adjustments required for safe navigation. Our simulation results demonstrate the effectiveness of this combined approach. The drone successfully navigates complex dynamic environments, achieving collision avoidance and goal-oriented behavior. This work highlights the potential of integrating advanced state estimation and reinforcement learning techniques to enhance autonomous drone capabilities in unpredictable settings.
Investigation of High-Speed Rubbing Behavior of GH4169 Superalloy with SiC/SiC Composites
Authors: Mi Zhaoguo , Jiang Kanghe , Yang Yicheng , Cheng Zhenhua , Yang Weihua , Sun Zhigang
Published: May 2024

The silicon carbide fiber-reinforced silicon carbide matrix (SiC/SiC), ceramic matrix composite (CMC) and nickel-based superalloy GH4169 can be utilized in high-temperature applications due to their high-temperature performance. The SiC/SiC composites are commonly used in turbine outer rings, where they encounter friction and wear against the turbine blades. This high-speed rubbing occurs frequently in aircraft engines and steam turbines. To investigate the tribological behavior of these materials, rubbing experiments were conducted between the SiC/SiC and the GH4169 superalloy. The experiments involved varying the blade tip speeds ranging from 100 m/s to 350 m/s and incursion rates from 5 μm/s to 50 μm/s at room temperature. Additionally, experiments were conducted at high temperatures to compare the tribological behavior under ambient conditions. The results indicated that the GH4169 superalloy exhibited abrasive furrow wear during rubbing at both room temperature and high temperature. Furthermore, at elevated temperatures, some of the GH4169 superalloy adhered to the surface of the SiC/SiC. The analysis of the experiments conducted at ambient temperatures revealed that the friction coefficient increased with higher blade tip velocities (100~350 m/s). However, the coefficient was lower at high temperatures compared to room temperature. Furthermore, significant temperature increases were observed during rubbing at room temperature, whereas minimal temperature changes were detected on the rubbing surface at high temperatures.
Preweaning Purified Fucoidan Drench: Effects on Growth, Immune Response, and Intestinal Morphology in Weaned Piglets
Authors: Homer Bonnie , Barekatain Reza , Petrovski Kiro R. , Plush Kate J. , Dwan Corinna , D’Souza Darryl N. , Verma Paul J. , Kirkwood Roy N. , Tucker Bryony S.
Published: May 2024

Weaning stress imposes considerable physiological challenges on piglets, often manifesting in intestinal disturbances, such as inflammation and compromised barrier function, ultimately affecting growth and health outcomes. While conventional interventions, including antimicrobials, have effectively mitigated these sequelae, concerns surrounding antimicrobial resistance necessitate the exploration of alternatives. Fucoidan, derived from brown seaweed, offers promise due to its antioxidant and anti-inflammatory effects. Previous research has been limited to the in-feed supplementation of partially purified fucoidan extracted from brown seaweed. The focus of the present study is assessing the effect of a preweaning drench with highly purified (85%) fucoidan on piglet growth, immune response, and intestinal morphology post-weaning. Forty-eight male piglets at 17 ± 3 days of age (5.67 ± 0.16 kg) were assigned to a saline (control), fucoidan, or antimicrobial group, receiving treatment as a single 18 mL oral drench three days before weaning. Monitoring for seven days post-weaning included body weight measurements, blood sample collection for the inflammatory protein assay, and small intestine morphological analysis. The findings revealed that the preweaning fucoidan drench did not elicit adverse effects on piglets. However, neither fucoidan nor antimicrobial drenches significantly enhanced growth parameters, immune markers, or intestinal morphology compared to that of the control-treated piglets (p > 0.05). The lack of response may be attributed to the high health status of the experimental cohort and the limitation of a single dosage. Future research should consider a more challenging production setting to evaluate the viability and optimal application of fucoidan as an antimicrobial alternative in the pig industry.
White Isthmus Transcriptome Analysis Reveals the Mechanism of Translucent Eggshell Formation
Authors: Ma Ying , Luo Yuxing , Li Wen , Wang Dehe , Ning Zhonghua
Published: May 2024

The presence of translucent eggshells is a type of egg quality issue that impacts egg sales. While many researchers have studied them, the exact mechanisms behind their formation remain unclear. In this study, we conducted a transcriptomic differential expression analysis of the isthmus region of the oviduct in both normal egg- and translucent egg-laying hens. The analysis revealed that differentially expressed gene pathways were predominantly concentrated in the synthesis, modification, and transport of eggshell membrane proteins, particularly collagen proteins, which provide structural support. These findings suggest that variations in the physical structure of the eggshell membrane, resulting from changes in its chemical composition, are the fundamental cause of translucent eggshell formation. This research provides a theoretical reference for reducing the occurrence of translucent eggs.
The Tick Saliva Peptide HIDfsin2 TLR4-Dependently Inhibits the Tick-Borne Severe Fever with Thrombocytopenia Syndrome Virus in Mouse Macrophages
Authors: Wang Luyao , Liu Yishuo , Pang Rui , Guo Yiyuan , Ren Yingying , Wu Yingliang , Cao Zhijian
Published: May 2024

Ticks transmit a variety of pathogens to their hosts by feeding on blood. The interactions and struggle between tick pathogens and hosts have evolved bilaterally. The components of tick saliva can directly or indirectly trigger host biological responses in a manner that promotes pathogen transmission; however, host cells continuously develop strategies to combat pathogen infection and transmission. Moreover, it is still unknown how host cells develop their defense strategies against tick-borne viruses during tick sucking. Here, we found that the tick saliva peptide HIDfsin2 enhanced the antiviral innate immunity of mouse macrophages by activating the Toll-like receptor 4 (TLR4) signaling pathway, thereby restricting tick-borne severe fever with thrombocytopenia syndrome virus (SFTSV) replication. HIDfsin2 was identified to interact with lipopolysaccharide (LPS), a ligand of TLR4, and then depolymerize LPS micelles into smaller particles, effectively enhancing the activation of the nuclear factor kappa-B (NF-κB) and type I interferon (IFN-I) signaling pathways, which are downstream of TLR4. Expectedly, TLR4 knockout completely eliminated the promotion effect of HIDfsin2 on NF-κB and type I interferon activation. Moreover, HIDfsin2 enhanced SFTSV replication in TLR4-knockout mouse macrophages, which is consistent with our recent report that HIDfsin2 hijacked p38 mitogen-activated protein kinase (MAPK) to promote the replication of tick-borne SFTSV in A549 and Huh7 cells (human cell lines) with low expression of TLR4. Together, these results provide new insights into the innate immune mechanism of host cells following tick bites. Our study also shows a rare molecular event relating to the mutual antagonism between tick-borne SFTSV and host cells mediated by the tick saliva peptide HIDfsin2 at the tick–host–virus interface.
Eminent Antimicrobial Peptide Resistance in Zymomonas mobilis: A Novel Advantage of Intrinsically Uncoupled Energetics
Authors: Rutkis Reinis , Lasa Zane , Rubina Marta , Strazdina Inese , Kalnenieks Uldis
Published: May 2024

Relative to several model bacteria, the ethanologenic bacterium Zymomonas mobilis is shown here to have elevated resistance to exogenous antimicrobial peptides (AMPs)— with regard to both peptide bulk concentration in the medium and the numbers of peptide molecules per cell. By monitoring the integration of AMPs in the bacterial cell membrane and observing the resulting effect on membrane energy coupling, it is concluded that the membranotropic effects of the tested AMPs in Z. mobilis and in Escherichia coli are comparable. The advantage of Z. mobilis over E. coli apparently results from its uncoupled mode of energy metabolism that, in contrast to E. coli, does not rely on oxidative phosphorylation, and hence, is less vulnerable to the disruption of its energy-coupling membrane by AMPs. It is concluded that the high resistance to antimicrobial peptides (AMPs) observed in Z. mobilis not only proves crucial for its survival in its natural environment but also offers a promising platform for AMP production and sheds light on potential strategies for novel resistance development in clinical settings.
PlanetiQ Radio Occultation: Preliminary Comparative Analysis of Neutral Profiles vs. COSMIC and NWP Models
Authors: Ahmed Ibrahim F. , Alheyf Mohammed , Yamany Mohamed S.
Published: May 2024

Radio Occultation (RO) is pivotal for profiling the neutral and ionized atmosphere, with the PlanetiQ mission, via its GNOMES satellites, striving to establish an advanced atmospheric observing system. However, an assessment of the spatiotemporal distributions of PlanetiQ observations and comparisons with reliable datasets are lacking. This study addresses this gap by examining the temporal and spatial distribution of RO observations from PlanetiQ during its initial 198 operational days in 2023, alongside comparisons with COSMIC and Numerical Weather Prediction (NWP) models. Data from GN02, GN03, and GN04 satellites, yielding 1099, 1313, and 1843 RO events per day, respectively, were analyzed. The satellite constellation’s observations demonstrate a generally well-distributed pattern, albeit minor deficiencies in equatorial and polar regions. Single-profile comparisons with COSMIC data reveal strong correlations for pressure, temperature, Water Vapor Pressure (WVP), and refractivity profiles, with temperature exhibiting larger variations (RMSE = 1.24 °C). Statistical analyses confirm statistically insignificant differences between the PlanetiQ and COSMIC profiles at the same spatio-temporal coordinates. Comparisons with NWP models show slight differences with GFS, with overall RMSE values of 0.23 mb (WVP), 0.6 mb (pressure), 1.3 (refractivity), and 1.5 °C (temperature). However, assessments against GFS/ECMWF models indicate overall compatibility, with insignificant differences between PlanetiQ profiles and model observations.
GAT-ABiGRU Based Prediction Model for AUV Trajectory
Authors: Zhao Mingxiu , Zhang Jing , Li Qin , Yang Junzheng , Siga Estevao , Zhang Tianchi
Published: May 2024

Autonomous underwater vehicles (AUVs) are critical components of current maritime operations. However, because of the complicated marine environment, AUVs are at significant risk of being lost, and such losses significantly impact the continuity and safety of aquatic activities. This article suggests a methodology for forecasting the trajectory of lost autonomous underwater vehicles (AUVs) based on GAT-ABiGRU. Firstly, the time-series data of the AUV are transformed into a graph structure to represent the dependencies between data points. Secondly, a graph attention network is utilized to capture the spatial features of the trajectory data, while an attention-based bidirectional gated recurrent unit network learns the temporal features of the trajectory data; finally, the predicted drift trajectory is obtained. The findings show that the GAT-ABiGRU model outperforms previous trajectory prediction models, is highly accurate and robust in drift trajectory prediction, and presents a new method for forecasting the trajectory of wrecked AUVs.
Analysis and Applications of the Two Phases Closed Thermosyphon Technology in the Highways in Permafrost Regions: A Review
Authors: Du Shuai , Ye Zeliang
Published: May 2024

Permafrost spans approximately 23–25% of the land in the northern hemisphere, primarily found in Russia, Canada, USA, and China. Numerous engineering projects, particularly those related to transportation, are situated within these permafrost regions. Due to the impact of highway construction and global warming, the permafrost beneath the infrastructure is deteriorating, leading to significant damage. Two phases closed thermosyphon (TPCT) is a widely accepted green countermeasure against the problem in permafrost regions. Although it has been applied to prevent permafrost degradation, their application presents significant challenges on account of the stronger endothermic action of asphalt pavement. This paper focused on a review of the thermosyphon technology and application in the permafrost. Moreover, the article highlighted the excellent working performance of the TPCT that improves the stability of the infrastructures and prevents it degrading due its excellent efficiency in terms of heat transfer. The industrial applications of the TPCT were also summarized, along with their limitations. Ultimately, the findings presented in this paper can offer crucial insights for future TPCT design and development in permafrost areas.
Exploring the Efficacy of Binary Surveys versus Likert Scales in Assessing Student Perspectives Using Bayesian Analysis
Authors: Suárez-García Andrés , Álvarez-Hernández María , Arce Elena , Ribas José Roberto
Published: May 2024

Likert-scale surveys are the undeniable protagonists of online evaluations. They ask the respondent to express their degree of agreement with a series of statements related to the development of a subject. In contrast, in social networks, dichotomous surveys are mostly used. They force respondents to polarize their opinions by selecting “like” or “dislike”. This study compares the efficacy of binary and Likert surveys in gathering student opinions on mechanical engineering program subjects. Using Bayesian analysis, it analyzes the similarity of responses obtained from both formats. For each question and scale, the ratio of “I like” among the total responses collected was calculated. The Bayesian factor method was used to compare the ratios obtained. The null hypothesis was equality between the ratios obtained by the different scales for the same question. This hypothesis was rejected in only 7 of the 49 questions evaluated—less than 15%. Finally, the students were surveyed on the preference for use of both scales. More than 80% stated a preference for the use of the dichotomous format. In view of the results obtained, we recommend more frequent use of the dichotomous scale to gather students’ opinions.
Influence of the Parameters of an Agricultural Biogas Plant on the Amount of Power Generated
Authors: Kuboń Maciej , Skibko Zbigniew , Borusiewicz Andrzej , Romaniuk Wacław , Gajda Jakub St. , Kłosowska Olivia , Wasąg Zbigniew
Published: May 2024

Energy from biogas is widely available, inexpensive, and often contributes to waste management, making it one of the most promising renewable energy sources. The main factors influencing this process’ efficiency include the substrates’ chemical composition, temperature, and digester load. This paper presents the possibilities offered by a biogas plant built at a farm specialising in dairy cows. The dependence of the power generated in the micro biogas plant on its technical parameters was analysed in detail. Studies carried out by the authors in an agricultural microgas plant (with an electrical output of 40 kW) have shown that they are designed to maintain continuous energy production, despite changing process parameters such as digester mass level, biogas height, temperature or slurry flow into the digester. However, from the point of view of the amount of electricity generated, changes would have to be made to the design of the biogas plant. Firstly, a more powerful generator would have to be installed to cover the electricity requirements of the equipment installed in the biogas plant so that power close to the rated capacity of the biogas plant is still sent to the grid. Secondly, replacing the two existing agitators of the digestion mass (9 kW each) with more agitators of lower power (e.g., four agitators of 4.5 kW each) would be necessary. These should be programmed so that one of the agitators operates at any given time (the operating time of a given agitator should depend on the composition of the digestate).
Effects of Bacillus subtilis on Cucumber Seedling Growth and Photosynthetic System under Different Potassium Ion Levels
Authors: Li Chun , Zeng Qingpan , Han Yuzhu , Zhou Xiaofu , Xu Hongwei
Published: May 2024

Potassium deficiency is one of the important factors restricting cucumber growth and development. This experiment mainly explored the effect of Bacillus subtilis (B. subtilis) on cucumber seedling growth and the photosynthetic system under different potassium levels, and the rhizosphere bacteria (PGPR) that promote plant growth were used to solubilize potassium in soil, providing theoretical support for a further investigation of the effect of biological bacteria fertilizer on cucumber growth and potassium absorption. “Xinjin No. 4” was used as the test material for the pot experiment, and a two-factor experiment was designed. The first factor was potassium application treatment, and the second factor was bacterial application treatment. The effects of different treatments on cucumber seedling growth, photosynthetic characteristics, root morphology, and chlorophyll fluorescence parameters were studied. The results showed that potassium and B. subtilis had obvious promotion effects on the cucumber seedling growth and the photosynthesis of leaves. Compared with the blank control, the B. subtilis treatment had obvious effects on the cucumber seedling height, stem diameter, leaf area, total root length, total root surface area, total root volume, branch number, crossing number, gs, WUE, Ci, and A; the dry weight of the shoot and root increased significantly (p ≤ 0.05). Potassium application could significantly promote cucumber growth, and the effect of B. subtilis and potassium application was greater than that of potassium application alone, and the best effect was when 0.2 g/pot and B. subtilis were applied. In conclusion, potassium combined with B. subtilis could enhance the photosynthesis of cucumber leaves and promote the growth of cucumber.
Novel Angiotensin-Converting Enzyme-Inhibitory Peptides Obtained from Trichiurus lepturus: Preparation, Identification and Potential Antihypertensive Mechanism
Authors: Cao Jiaming , Xiang Boyuan , Dou Baojie , Hu Jingfei , Zhang Lei , Kang Xinxin , Lyu Mingsheng , Wang Shujun
Published: May 2024

Peptides possessing antihypertensive attributes via inhibiting the angiotensin-converting enzyme (ACE) were derived through the enzymatic degradation of Trichiurus lepturus (ribbonfish) using alkaline protease. The resulting mixture underwent filtration using centrifugation, ultrafiltration tubes, and Sephadex G-25 gels. Peptides exhibiting ACE-inhibitory properties and DPPH free-radical-scavenging abilities were isolated and subsequently purified via LC/MS-MS, leading to the identification of over 100 peptide components. In silico screening yielded five ACE inhibitory peptides: FAGDDAPR, QGPIGPR, IFPRNPP, AGFAGDDAPR, and GPTGPAGPR. Among these, IFPRNPP and AGFAGDDAPR were found to be allergenic, while FAGDDAPRR, QGPIGPR, and GPTGPAGP showed good ACE-inhibitory effects. IC50 values for the latter peptides were obtained from HUVEC cells: FAGDDAPRR (IC50 = 262.98 μM), QGPIGPR (IC50 = 81.09 μM), and GPTGPAGP (IC50 = 168.11 μM). Peptide constituents derived from ribbonfish proteins effectively modulated ACE activity, thus underscoring their therapeutic potential. Molecular docking and modeling corroborated these findings, emphasizing the utility of functional foods as a promising avenue for the treatment and prevention of hypertension, with potential ancillary health benefits and applications as substitutes for synthetic drugs.
BK Polyomavirus in Pediatric Renal Transplantation—What We Know and What We Do Not
Authors: Chiodini Benedetta , Guillaume-Gentil Pauline , Vanhomwegen Charlotte , Hennaut Elise , Lolin Ksenija , Tram Nathalie , Le Moine Alain , Ismaili Khalid
Published: May 2024

BK polyomavirus (BKPyV) is still a real threat in the management of kidney transplantation. Immunosuppressive treatment disrupts the equilibrium between virus replication and immune response, and uncontrolled BKPyV replication leads to nephropathy (BKPyV nephropathy). The first evidence of BKPyV reactivation in transplant recipients is the detection of viral shedding in urine, which appears in 20% to 60% of patients, followed by BKPyV viremia in 10–20% of kidney transplant recipients. BKPyV nephropathy eventually occurs in 1–10% of this population, mainly within the first 2 years post-transplantation, causing graft loss in about half of those patients. Few data exist regarding the pediatric population and we focus on them. In this paper, we review the existing diagnostic methods and summarize the evidence on the role of BKPyV humoral and cellular immunity in modulating the clinical course of BKPyV infection and as potential predictors of the outcome. We look at the known risk factors for BKPyV nephropathy in the immunosuppressed patient. Finally, we propose a sensible clinical attitude in order to screen and manage BKPyV infection in kidney transplant children.
Frequent Lucid Dreaming Is Associated with Meditation Practice Styles, Meta-Awareness, and Trait Mindfulness
Authors: Gerhardt Elena , Baird Benjamin
Published: May 2024

Lucid dreaming involves becoming aware that one’s current experience is a dream, which has similarities with the notion of mindfulness—becoming aware of moment-to-moment changes in experience. Additionally, meta-awareness, the ability to explicitly notice the current content of one’s own mental state, has also been proposed to play an important role both in lucid dreaming and mindfulness meditation practices. However, research has shown conflicting strengths of associations between mindfulness, meditation, and lucid dreaming frequency, and the link between lucid dreaming and meta-awareness has not yet been empirically studied. This study evaluated the associations between lucid dreaming frequency and different meditation practice styles, mindfulness traits, and individual differences in meta-awareness through an online survey (n = 635). The results suggest that daily frequent meditators experience more lucid dreams than non-frequent meditators. However, weekly frequent meditators did not have a higher lucid dreaming frequency. A positive association was observed between open monitoring styles of meditation and lucid dreaming. The findings also indicate that meta-awareness is higher for meditators and weekly lucid dreamers. Furthermore, frequent lucid dreaming was commonly associated with a non-reactive stance and experiencing transcendence. Overall, the findings suggest a positive relationship between specific meditation practices and lucid dreaming as well as the importance of meta-awareness as a cognitive process linking meditation, mindfulness, and lucid dreaming.
Decoding Subject-Driven Cognitive States from EEG Signals for Cognitive Brain–Computer Interface
Authors: Huang Dingyong , Wang Yingjie , Fan Liangwei , Yu Yang , Zhao Ziyu , Zeng Pu , Wang Kunqing , Li Na , Shen Hui
Published: May 2024

In this study, we investigated the feasibility of using electroencephalogram (EEG) signals to differentiate between four distinct subject-driven cognitive states: resting state, narrative memory, music, and subtraction tasks. EEG data were collected from seven healthy male participants while performing these cognitive tasks, and the raw EEG signals were transformed into time–frequency maps using continuous wavelet transform. Based on these time–frequency maps, we developed a convolutional neural network model (TF-CNN-CFA) with a channel and frequency attention mechanism to automatically distinguish between these cognitive states. The experimental results demonstrated that the model achieved an average classification accuracy of 76.14% in identifying these four cognitive states, significantly outperforming traditional EEG signal processing methods and other classical image classification algorithms. Furthermore, we investigated the impact of varying lengths of EEG signals on classification performance and found that TF-CNN-CFA demonstrates consistent performance across different window lengths, indicating its strong generalization capability. This study validates the ability of EEG to differentiate higher cognitive states, which could potentially offer a novel BCI paradigm.
No Consistent Antidepressant Effects of Deep Brain Stimulation of the Bed Nucleus of the Stria Terminalis
Authors: Fitzgerald Paul B. , Hoy Kate , Richardson Karyn E. , Gainsford Kirsten , Segrave Rebecca , Herring Sally E. , Daskalakis Zafiris J. , Bittar Richard G.
Published: May 2024

Background: Applying deep brain stimulation (DBS) to several brain regions has been investigated in attempts to treat highly treatment-resistant depression, with variable results. Our initial pilot data suggested that the bed nucleus of the stria terminalis (BNST) could be a promising therapeutic target. Objective: The aim of this study was to gather blinded data exploring the efficacy of applying DBS to the BNST in patients with highly refractory depression. Method: Eight patients with chronic severe treatment-resistant depression underwent DBS to the BNST. A randomised, double-blind crossover study design with fixed stimulation parameters was followed and followed by a period of open-label stimulation. Results: During the double-blind crossover phase, no consistent antidepressant effects were seen with any of the four stimulation parameters applied, and no patients achieved response or remission criteria during the blinded crossover phase or during a subsequent period of three months of blinded stimulation. Stimulation-related side effects, especially agitation, were reported by a number of patients and were reversible with adjustment of the stimulation parameters. Conclusions: The results of this study do not support the application of DBS to the BNST in patients with highly resistant depression or ongoing research utilising stimulation at this brain site. The blocked randomised study design utilising fixed stimulation parameters was poorly tolerated by the participants and does not appear suitable for assessing the efficacy of DBS at this location.
Heterogeneous Profile of ROR1 Protein Expression across Tumor Types
Authors: Raso Maria Gabriela , Barrientos Toro Elizve , Evans Kurt , Rizvi Yasmeen , Lazcano Rossana , Akcakanat Argun , Sini Patrizia , Trapani Francesca , Madlener Eva Johanna , Waldmeier Lorenz , Lazar Alexander , Meric-Bernstam Funda
Published: May 2024

The Wnt receptor ROR1 has generated increased interest as a cancer therapeutic target. Research on several therapeutic approaches involving this receptor is ongoing; however, ROR1 tissue expression remains understudied. We performed an immunohistochemistry analysis of ROR1 protein expression in a large cohort of multiple tumor and histologic types. We analyzed 12 anonymized multi-tumor tissue microarrays (TMAs), including mesothelioma, esophageal and upper gastrointestinal carcinomas, and uterine endometrioid carcinoma, among other tumor types. Additionally, we studied 5 different sarcoma types of TMAs and 6 patient-derived xenografts (PDX) TMAs developed from 19 different anatomic sites and tumor histologic types. A total of 1142 patient cases from different histologic types and 140 PDXs placed in TMAs were evaluated. Pathologists assessed the percentage of tumor cells in each case that were positive for ROR1 and the intensity of staining. For determining the prevalence of staining for each tumor type, a case was considered positive if >1% of its tumor cells showed ROR1 staining. Our immunohistochemistry assays revealed a heterogeneous ROR1 expression profile. A high prevalence of ROR1 expression was found in mesothelioma (84.6%), liposarcoma (36.1%), gastrointestinal stromal tumors (33.3%), and uterine endometrioid carcinoma (28.9%). Other histologic types such as breast, lung, renal cell, hepatocellular, urothelial carcinoma, and colon carcinomas; glioblastoma; cholangiocarcinoma; and leiomyosarcoma showed less ROR1 overall expression, ranging between 0.9 and 13%. No ROR1 expression was seen in mesenchymal chondrosarcoma, rhabdomyosarcoma, or gastric adenocarcinoma cases. Overall, ROR1 expression was relatively infrequent and low in most tumor types investigated; however, ROR1 expression was infrequent but high in selected tumor types, such as gastroesophageal GIST, suggesting that ROR1 prescreening may be preferable for those indications. Further, mesothelioma exhibited frequent and high levels of ROR1 expression, which represents a previously unrecognized therapeutic opportunity. These findings can contribute to the development of ROR1-targeted therapies.
Dysregulation of lncRNA MALAT1 Contributes to Lung Cancer in African Americans by Modulating the Tumor Immune Microenvironment
Authors: Li Jin , Dhilipkannah Pushpa , Holden Van K. , Sachdeva Ashutosh , Todd Nevins W. , Jiang Feng
Published: May 2024

African American (AA) populations present with notably higher incidence and mortality rates from lung cancer in comparison to other racial groups. Here, we elucidated the contribution of long non-coding RNAs (lncRNAs) in the racial disparities and their potential clinical applications in both diagnosis and therapeutic strategies. AA patients had elevated plasma levels of MALAT1 and PVT1 compared with cancer-free smokers. Incorporating these lncRNAs as plasma biomarkers, along with smoking history, achieved 81% accuracy in diagnosis of lung cancer in AA patients. We observed a rise in MALAT1 expression, correlating with increased levels of monocyte chemoattractant protein-1 (MCP-1) and CD68, CD163, CD206, indicative of tumor-associated macrophages in lung tumors of AA patients. Forced MALAT1 expression led to enhanced growth and invasiveness of lung cancer cells, both in vitro and in vivo, accompanied by elevated levels of MCP-1, CD68, CD163, CD206, and KI67. Mechanistically, MALAT1 acted as a competing endogenous RNA to directly interact with miR-206, subsequently affecting MCP-1 expression and macrophage activity, and enhanced the tumorigenesis. Targeting MALAT1 significantly reduced tumor sizes in animal models. Therefore, dysregulated MALAT1 contributes to lung cancer disparities in AAs by modulating the tumor immune microenvironment through its interaction with miR-206, thereby presenting novel diagnostic and therapeutic targets.
Effects of KEAP1 Silencing on NRF2 and NOTCH Pathways in SCLC Cell Lines
Authors: Fabrizio Federico Pio , Sparaneo Angelo , Gorgoglione Giusy , Battista Pierpaolo , Centra Flavia , Delli Muti Francesco , Trombetta Domenico , Centonza Antonella , Graziano Paolo , Rossi Antonio , Fazio Vito Michele , Muscarella Lucia Anna
Published: May 2024

The KEAP1/NRF2 pathway is a master regulator of several redox-sensitive genes implicated in the resistance of tumor cells against therapeutic drugs. The dysfunction of the KEAP1/NRF2 system has been correlated with neoplastic patients’ outcomes and responses to conventional therapies. In lung tumors, the growth and the progression of cancer cells may also involve the intersection between the molecular NRF2/KEAP1 axis and other pathways, including NOTCH, with implications for antioxidant protection, survival of cancer cells, and drug resistance to therapies. At present, the data concerning the mechanism of aberrant NRF2/NOTCH crosstalk as well as its genetic and epigenetic basis in SCLC are incomplete. To better clarify this point and elucidate the contribution of NRF2/NOTCH crosstalk deregulation in tumorigenesis of SCLC, we investigated genetic and epigenetic dysfunctions of the KEAP1 gene in a subset of SCLC cell lines. Moreover, we assessed its impact on SCLC cells’ response to conventional chemotherapies (etoposide, cisplatin, and their combination) and NOTCH inhibitor treatments using DAPT, a γ-secretase inhibitor (GSI). We demonstrated that the KEAP1/NRF2 axis is epigenetically controlled in SCLC cell lines and that silencing of KEAP1 by siRNA induced the upregulation of NRF2 with a consequent increase in SCLC cells’ chemoresistance under cisplatin and etoposide treatment. Moreover, KEAP1 modulation also interfered with NOTCH1, HES1, and DLL3 transcription. Our preliminary data provide new insights about the downstream effects of KEAP1 dysfunction on NRF2 and NOTCH deregulation in this type of tumor and corroborate the hypothesis of a cooperation of these two pathways in the tumorigenesis of SCLC.
Protein Quality Control of NKCC2 in Bartter Syndrome and Blood Pressure Regulation
Authors: Laghmani Kamel
Published: May 2024

Mutations in NKCC2 generate antenatal Bartter syndrome type 1 (type 1 BS), a life-threatening salt-losing nephropathy characterized by arterial hypotension, as well as electrolyte abnormalities. In contrast to the genetic inactivation of NKCC2, inappropriate increased NKCC2 activity has been associated with salt-sensitive hypertension. Given the importance of NKCC2 in salt-sensitive hypertension and the pathophysiology of prenatal BS, studying the molecular regulation of this Na-K-2Cl cotransporter has attracted great interest. Therefore, several studies have addressed various aspects of NKCC2 regulation, such as phosphorylation and post-Golgi trafficking. However, the regulation of this cotransporter at the pre-Golgi level remained unknown for years. Similar to several transmembrane proteins, export from the ER appears to be the rate-limiting step in the cotransporter’s maturation and trafficking to the plasma membrane. The most compelling evidence comes from patients with type 5 BS, the most severe form of prenatal BS, in whom NKCC2 is not detectable in the apical membrane of thick ascending limb (TAL) cells due to ER retention and ER-associated degradation (ERAD) mechanisms. In addition, type 1 BS is one of the diseases linked to ERAD pathways. In recent years, several molecular determinants of NKCC2 export from the ER and protein quality control have been identified. The aim of this review is therefore to summarize recent data regarding the protein quality control of NKCC2 and to discuss their potential implications in BS and blood pressure regulation.
The Imperative for Innovative Enteric Nervous System–Intestinal Organoid Co-Culture Models: Transforming GI Disease Modeling and Treatment
Authors: Llorente Cristina
Published: May 2024

This review addresses the need for innovative co-culture systems integrating the enteric nervous system (ENS) with intestinal organoids. The breakthroughs achieved through these techniques will pave the way for a transformative era in gastrointestinal (GI) disease modeling and treatment strategies. This review serves as an introduction to the companion protocol paper featured in this journal. The protocol outlines the isolation and co-culture of myenteric and submucosal neurons with small intestinal organoids. This review provides an overview of the intestinal organoid culture field to establish a solid foundation for effective protocol application. Remarkably, the ENS surpasses the number of neurons in the spinal cord. Referred to as the “second brain”, the ENS orchestrates pivotal roles in GI functions, including motility, blood flow, and secretion. The ENS is organized into myenteric and submucosal plexuses. These plexuses house diverse subtypes of neurons. Due to its proximity to the gut musculature and its cell type complexity, there are methodological intricacies in studying the ENS. Diverse approaches such as primary cell cultures, three-dimensional (3D) neurospheres, and induced ENS cells offer diverse insights into the multifaceted functionality of the ENS. The ENS exhibits dynamic interactions with the intestinal epithelium, the muscle layer, and the immune system, influencing epithelial physiology, motility, immune responses, and the microbiome. Neurotransmitters, including acetylcholine (ACh), serotonin (5-HT), and vasoactive intestinal peptide (VIP), play pivotal roles in these intricate interactions. Understanding these dynamics is imperative, as the ENS is implicated in various diseases, ranging from neuropathies to GI disorders and neurodegenerative diseases. The emergence of organoid technology presents an unprecedented opportunity to study ENS interactions within the complex milieu of the small and large intestines. This manuscript underscores the urgent need for standardized protocols and advanced techniques to unravel the complexities of the ENS and its dynamic relationship with the gut ecosystem. The insights gleaned from such endeavors hold the potential to revolutionize GI disease modeling and treatment paradigms.
Glioblastoma Phagocytic Cell Death: Balancing the Opportunities for Therapeutic Manipulation
Authors: Du Ruochen , Tripathi Shashwat , Najem Hinda , Brat Daniel J. , Lukas Rimas V. , Zhang Peng , Heimberger Amy B.
Published: May 2024

Macrophages and microglia are professional phagocytes that sense and migrate toward “eat-me” signals. The role of phagocytic cells is to maintain homeostasis by engulfing senescent or apoptotic cells, debris, and abnormally aggregated macromolecules. Usually, dying cells send out “find-me” signals, facilitating the recruitment of phagocytes. Healthy cells can also promote or inhibit the phagocytosis phenomenon of macrophages and microglia by tuning the balance between “eat-me” and “don’t-eat-me” signals at different stages in their lifespan, while the “don’t-eat-me” signals are often hijacked by tumor cells as a mechanism of immune evasion. Using a combination of bioinformatic analysis and spatial profiling, we delineate the balance of the “don’t-eat-me” CD47/SIRPα and “eat-me” CALR/STC1 ligand–receptor interactions to guide therapeutic strategies that are being developed for glioblastoma sequestered in the central nervous system (CNS).
Transcriptome and Metabolome Reveal Key Genes from the Plant Hormone Signal Transduction Pathway Regulating Plant Height and Leaf Size in Capsicum baccatum
Authors: Xing Na , Li Xiaoqi , Wu Shuhua , Wang Zhiwei
Published: May 2024

Plant structure-related agronomic traits like plant height and leaf size are critical for growth, development, and crop yield. Defining the types of genes involved in regulating plant structure size is essential for the molecular-assisted breeding of peppers. This research conducted comparative transcriptome analyses using Capsicum baccatum germplasm HNUCB0112 and HNUCB0222 and their F2 generation as materials. A total of 6574 differentially expressed genes (DEGs) were detected, which contain 379 differentially expressed transcription factors, mainly including transcription factor families such as TCP, WRKY, AUX/IAA, and MYB. Seven classes of DEGs were annotated in the plant hormone signal transduction pathway, including indole acetic acid (IAA), gibberellin (GA), cytokinin (CK), abscisic acid (ABA), jasmonic acid (JA), ethylene (ET), and salicylic acid (SA). The 26 modules were obtained by WGCNA analysis, and the MEpink module was positively correlated with plant height and leaf size, and hub genes associated with plant height and leaf size were anticipated. Differential genes were verified by qRT-PCR, which was consistent with the RNA-Seq results, demonstrating the accuracy of the sequencing results. These results enhance our understanding of the developmental regulatory networks governing pepper key traits like plant height and leaf size and offer new information for future research on the pepper plant architecture system.