bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Secretory Mucins in the Occurrence and Development of Cholelithiasis
Authors: Zhao Zeying , Yang Ye , Wu Shuodong , Yao Dianbo
Published: June 2024

Cholelithiasis is a common biliary tract disease. However, the exact mechanism underlying gallstone formation remains unclear. Mucin plays a vital role in the nuclear formation and growth of cholesterol and pigment stones. Excessive mucin secretion can result in cholestasis and decreased gallbladder activity, further facilitating stone formation and growth. Moreover, gallstones may result in inflammation and the secretion of inflammatory factors, which can further increase mucin expression and secretion to promote the growth of gallstones. This review systematically summarises and analyses the role of mucins in gallstone occurrence and development and its related mechanisms to explore new ideas for interventions in stone formation or recurrence.
Quality of Life in Follow-Up up to 9 Months after COVID-19 Hospitalization among the Polish Population—A Prospective Single Center Study
Authors: Pietruszka-Wałęka Ewa , Rząd Michał , Rożyńska Renata , Miklusz Piotr , Zieniuk-Lesiak Emilia , Żabicka Magdalena , Jahnz-Różyk Karina
Published: June 2024

The consequences of COVID-19 constitute a significant burden to healthcare systems worldwide. Conducting an HRQoL assessment is an important aspect of the evaluation of the impact of the disease. The aim of this study was to investigate the prevalence of persistent symptoms and their impact on HRQoL and health status in COVID-19 convalescents. The study group consists of 46 patients who required hospitalization due to respiratory failure and who were subsequently evaluated 3 and 9 months after hospital discharge. At the follow-up visits, the patients were asked to assess their HRQoL using the EQ-5D-5L questionnaire. The results of chest CT, 6MWT, as well as the severity of the course of COVID-19 were also considered in the analysis. The obtained results have identified fatigue as the most common persistent symptom. The majority of the convalescents reported an impairment of HRQoL in at least one domain (80% and 82% after 3 and 9 months, respectively), of which the most common was that of pain/discomfort. The presence of ongoing symptoms may affect HRQoL in particular domains. The 6MWT outcome correlates with HRQoL 3 months after hospital discharge. Therefore, it may be useful in identifying patients with reduced HRQoL, allowing early interventions aimed at its improvement.
Graphical Insight: Revolutionizing Seizure Detection with EEG Representation
Authors: Awais Muhammad , Belhaouari Samir Brahim , Kassoul Khelil
Published: June 2024

Epilepsy is characterized by recurring seizures that result from abnormal electrical activity in the brain. These seizures manifest as various symptoms including muscle contractions and loss of consciousness. The challenging task of detecting epileptic seizures involves classifying electroencephalography (EEG) signals into ictal (seizure) and interictal (non-seizure) classes. This classification is crucial because it distinguishes between the states of seizure and seizure-free periods in patients with epilepsy. Our study presents an innovative approach for detecting seizures and neurological diseases using EEG signals by leveraging graph neural networks. This method effectively addresses EEG data processing challenges. We construct a graph representation of EEG signals by extracting features such as frequency-based, statistical-based, and Daubechies wavelet transform features. This graph representation allows for potential differentiation between seizure and non-seizure signals through visual inspection of the extracted features. To enhance seizure detection accuracy, we employ two models: one combining a graph convolutional network (GCN) with long short-term memory (LSTM) and the other combining a GCN with balanced random forest (BRF). Our experimental results reveal that both models significantly improve seizure detection accuracy, surpassing previous methods. Despite simplifying our approach by reducing channels, our research reveals a consistent performance, showing a significant advancement in neurodegenerative disease detection. Our models accurately identify seizures in EEG signals, underscoring the potential of graph neural networks. The streamlined method not only maintains effectiveness with fewer channels but also offers a visually distinguishable approach for discerning seizure classes. This research opens avenues for EEG analysis, emphasizing the impact of graph representations in advancing our understanding of neurodegenerative diseases.
Choice Function-Based Hyper-Heuristics for Causal Discovery under Linear Structural Equation Models
Authors: Dang Yinglong , Gao Xiaoguang , Wang Zidong
Published: June 2024

Causal discovery is central to human cognition, and learning directed acyclic graphs (DAGs) is its foundation. Recently, many nature-inspired meta-heuristic optimization algorithms have been proposed to serve as the basis for DAG learning. However, a single meta-heuristic algorithm requires specific domain knowledge and empirical parameter tuning and cannot guarantee good performance in all cases. Hyper-heuristics provide an alternative methodology to meta-heuristics, enabling multiple heuristic algorithms to be combined and optimized to achieve better generalization ability. In this paper, we propose a multi-population choice function hyper-heuristic to discover the causal relationships encoded in a DAG. This algorithm provides a reasonable solution for combining structural priors or possible expert knowledge with swarm intelligence. Under a linear structural equation model (SEM), we first identify the partial v-structures through partial correlation analysis as the structural priors of the next nature-inspired swarm intelligence approach. Then, through partial correlation analysis, we can limit the search space. Experimental results demonstrate the effectiveness of the proposed methods compared to the earlier state-of-the-art methods on six standard networks.
Modal Analysis of Cerebrovascular Effects for Digital Health Integration of Neurostimulation Therapies—A Review of Technology Concepts
Authors: Stefanski Marcel , Arora Yashika , Cheung Mancheung , Dutta Anirban
Published: June 2024

Transcranial electrical stimulation (tES) is increasingly recognized for its potential to modulate cerebral blood flow (CBF) and evoke cerebrovascular reactivity (CVR), which are crucial in conditions like mild cognitive impairment (MCI) and dementia. This study explores the impact of tES on the neurovascular unit (NVU), employing a physiological modeling approach to simulate the vascular response to electric fields generated by tES. Utilizing the FitzHugh–Nagumo model for neuroelectrical activity, we demonstrate how tES can initiate vascular responses such as vasoconstriction followed by delayed vasodilation in cerebral arterioles, potentially modulated by a combination of local metabolic demands and autonomic regulation (pivotal locus coeruleus). Here, four distinct pathways within the NVU were modeled to reflect the complex interplay between synaptic activity, astrocytic influences, perivascular potassium dynamics, and smooth muscle cell responses. Modal analysis revealed characteristic dynamics of these pathways, suggesting that oscillatory tES may finely tune the vascular tone by modulating the stiffness and elasticity of blood vessel walls, possibly by also impacting endothelial glycocalyx function. The findings underscore the therapeutic potential vis-à-vis blood-brain barrier safety of tES in modulating neurovascular coupling and cognitive function needing the precise modulation of NVU dynamics. This technology review supports the human-in-the-loop integration of tES leveraging digital health technologies for the personalized management of cerebral blood flow, offering new avenues for treating vascular cognitive disorders. Future studies should aim to optimize tES parameters using computational modeling and validate these models in clinical settings, enhancing the understanding of tES in neurovascular health.
Childhood Environmental Instabilities and Their Behavioral Implications: A Machine Learning Approach to Studying Adverse Childhood Experiences
Authors: Codjoe Priscilla Mansah , Tawiah Nii Adjetey , Alhassan Daniel
Published: June 2024

Adverse childhood experiences (ACEs) include a range of abusive, neglectful, and dysfunctional household behaviors that are strongly associated with long-term health problems, mental health conditions, and societal difficulties. The study aims to uncover significant factors influencing ACEs in children aged 0–17 years and to propose a predictive model that can be used to forecast the likelihood of ACEs in children. Machine learning models are applied to identify and analyze the relationships between several predictors and the occurrence of ACEs. Key performance metrics such as AUC, F1 score, recall, and precision are used to evaluate the predictive strength of different factors on ACEs. Family structures, especially non-traditional forms such as single parenting, and the frequency of relocating to a new address are determined as key predictors of ACEs. The final model, a neural network, achieved an AUC of 0.788, a precision score of 0.683, and a recall of 0.707, indicating its effectiveness in accurately identifying ACE cases. The model’s ROC and PR curves showed a high true positive rate for detecting children with two or more ACEs while also pointing to difficulties in classifying single ACE instances accurately. Furthermore, our analysis revealed the intricate relationship between the frequency of relocation and other predictive factors. The findings highlight the importance of familial and residential stability in children’s lives, with substantial implications for child welfare policies and interventions. The study emphasizes the need for targeted educational and healthcare support to promote the well-being and resilience of at-risk children.
A Digital Math Game and Multiple-Try Use with Primary Students: A Sex Analysis on Motivation and Learning
Authors: Cubillos Claudio , Roncagliolo Silvana , Cabrera-Paniagua Daniel , Vicari Rosa Maria
Published: June 2024

Sex differences have been a rarely addressed aspect in digital game-based learning (DGBL). Likewise, mixed results have been presented regarding the effects according to sex and the conditions that generate these effects. The present work studied the effects of a drill-and-practice mathematical game on primary students. The study focused on an analysis by sex, measuring motivation and learning in the practice activity. Also, two instructional mechanics were considered regarding the question answering to search for possible differences: a multiple-try feedback (MTF) condition and a single-try feedback (STF) condition. A total of 81 students from four courses and two schools participated in the intervention. The study’s main findings were as follows: (a) the girls outperformed the boys in terms of the students’ learning gains; (b) the girls presented lower levels of competence and autonomy than the boys; (c) under MTF, the girls presented lower levels of autonomy but no differences in competence contrasted with the boys; (d) under STF, the girls presented lower levels of competence but no differences in autonomy contrasted with the boys; (e) no sex differences existed in interest, effort, and value, in general, as per the instructional condition. This study enhances the knowledge of sex differences under diverse instructional settings, in particular providing insights into the possible differences by sex when varying the number of attempts provided to students.
Patients’ UX Impact on Medication Adherence in Czech Pilot Study for Chronically Ill
Authors: Gergely Ondrej , Mazalová Romana , Štýbnar Michal , Hlavinka Antonín , Goodfellow Nicola , Scott Michael , Fleming Glenda , Jochmannová Leona , Stanke Ladislav
Published: June 2024

This article presents a comprehensive and multistage approach to the development of the user experience (UX) for an mHealth application targeting older adult patients with chronic diseases, specifically chronic heart failure and chronic obstructive pulmonary disease. The study adopts a mixed methods approach, incorporating both quantitative and qualitative components. The underlying hypothesis posits that baseline medicine adherence knowledge (measured by the MARS questionnaire), beliefs about medicines (measured by the BMQ questionnaire), and level of user experience (measured by the SUS and UEQ questionnaires) act as predictors of adherence change after a period of usage of the mHealth application. However, contrary to our expectations, the results did not demonstrate the anticipated relationship between the variables examined. Nevertheless, the qualitative component of the research revealed that patients, in general, expressed satisfaction with the application. It is important to note that the pilot testing phase revealed a notable prevalence of technical issues, which may have influenced participants’ perception of the overall UX. These findings contribute to the understanding of UX development in the context of mHealth applications for older adults with chronic diseases and emphasise the importance of addressing technical challenges to enhance user satisfaction and engagement.
Effects of Prolonged Leaching on the Acute Ecotoxicity of Spruce-Pine Oriented Strand Board for Plants
Authors: Kobetičová Klára , Sedláčková Hana , Böhm Martin , Brich Jiří , Nábělková Jana , Černý Robert
Published: June 2024

In this study, the ecotoxicological effects of a selected OSB material on three model plants (green freshwater algae Desmodesmus subspicatus, duckweed Lemna minor, and seeds of lettuce Lactuca sativa) were tested. A 24 h and 168 h leachate of the same OSB material was prepared. Mg, Si, Ca, K, Fe, Zn, Mn, and Na were found in the samples. Their higher residues were measured in the 168 h leachate. Biogenic elements (N, P, C) were not detected. The acute effect was relatively slow (for algae up to 26%, for duckweed up to 20%, and for lettuce seeds with stimulation up to 37%). Prolongation of the leaching time did not show any effect on the results of the plant tests. Acute toxicity for the three plant species used was slow.
Two-Stage Optimal Design Method for Asymmetric Base-Isolated Structures Subject to Pulse-Type Earthquakes
Authors: Zhang Jiayu , Qi Ai , Yang Mianyue
Published: June 2024

Asymmetric base-isolated structures subjected to severe torsion may suffer further aggravation of their torsional and translational responses under pulse-type earthquakes. To counteract these detrimental impacts, this study introduces a two-stage optimal design method. The first stage involved the application of the NSGA-II algorithm for determining an optimal isolator arrangement—namely, position and category—with the objective of reducing both the maximum interstory rotation of the superstructure and the isolation layer. In the second stage, the inclusion of viscous dampers served to minimize the excessive translational response triggered by pulse-type earthquakes. The influence of these dampers’ positions on the structural response was carefully evaluated. The final application of this optimal design method was demonstrated on an asymmetric base-isolated structure. The results indicated a significant reduction in the translational and torsional responses of the asymmetric base-isolated structure when the two-stage optimal design method was utilized, compared to those of structures designed using traditional conceptual methods. It was found that by installing viscous dampers in the isolation layer along both the x and the y directions—specifically, underneath the mass center of the superstructure (CMS)—the effectiveness of the torsional resistance from the first stage could be effectively maintained.
Assessment of Glass-Fiber-Reinforced Polymer (GFRP)–Concrete Interface Durability Subjected to Simulated Seawater Environment
Authors: Ma Deliang , Liu Jie , Wang Libin , Wang Qiudong
Published: June 2024

Fiber-reinforced polymer (FRP)-retrofitted concrete structures are extensively utilized, and they have attracted growing research interest due to their combined performance in marine environments. To investigate the effect of seawater exposure, a total of 20 single-shear GFRP (glass-FRP)-bonded concrete structures were tested. Three corrosion conditions, i.e., exposure to single-salinity and triple-salinity seawater through wet–dry cycles as well as continuous immersion in triple-salinity seawater, were simulated and tested. The minimum shear strength (13,006 N) was tested using specimen B150-T-DW-90, which was cured in triple-salinity seawater with wet–dry cyclic exposure. The results of the shear strengths, load–displacement curves, interfacial shear stresses, and fracture energies indicated that seawater exposure degraded the bonding strength of the GFRP–concrete interface. Notably, the wet–dry cycles in triple-salinity seawater resulted in the most significant interface degradation, which could exacerbate with prolonged exposure. By introducing a parameter, the residual coefficient α, a new strength calculation model for GFRP–concrete exposed to a seawater environment was proposed and discussed.
Correlation between Vegetation Landscape and Subjective Human Perception: A Systematic Review
Authors: Xie Xiaohuan , Jiang Qiao , Wang Ruobing , Gou Zhonghua
Published: June 2024

Environmental perception is a key indicator for evaluating green space preference and satisfaction. The shift in urban green space research towards emphasizing human benefits over functionality has caused a gradual increase in the number of articles on green space perception in recent years. Studying the relationship between the vegetation landscape (a fundamental aspect of urban green spaces) and subjective perceptual dimensions have become a pivotal research topic. This paper delves into the correlations and influencing relationships between these two dimensions with the main focus being on vegetation landscape indicators and subjective perception. The perceived green benefits were categorized into four main groups in the 80 articles reviewed: perceived safety, visual aesthetics, restoration benefits, and preferences. In this study, green indicators were also defined and categorized. The results indicated that the guiding indicators had a higher frequency and that species diversity improved the perceived benefits in all aspects. Among the control indicators, plant color, plant height, and the vegetation composition structure received the most attention. Plant color accounted for the largest proportion of studies on perceived visual aesthetics. Vegetation characteristics related to perceived safety had a shared trait, and there was a lack of correlation studies between safety and aesthetics in perceptual dimensions. In the common methods for assessing human perception, a shift from subjective measurements to mixed measurements using emerging technologies is underway. As a pioneering scope review of how vegetation landscapes influence subjective human perceptions, this study has not only provided evidence of the perceived benefits of urban green spaces but also offers valuable insights and tools for future research and policymaking.
Clinker-Free Cement Manufactured with Metallurgical Slags
Authors: Demarco Marcel , Vernilli Fernando , Zago Sara Carvalho
Published: June 2024

Steel slag is a significant environmental liability generated by pyrometallurgical processes. Residue generation, such as granulated blast furnace slag and basic oxygen slag (BOF), is intrinsic in steel production. Blast furnace slag, generated in the carbothermal reduction of iron ore, is almost entirely used as a supplementary cement material in Portland cement. BOF slag, produced in the conversion of pig iron into steel in a basic oxygen converter, is still not consolidated or valued for reuse. This research proposes the reuse and valorization of BOF slag combined with blast furnace slag in clinker-free cement production. Cement formulations were produced with different slag and gypsum contents, ranging from 80 to 90% blast furnace slag, 10 to 20% gypsum, and 10 to 15% BOF slag. All formulations were evaluated for compressive strength at ages of 3, 7, 14, 28, 91, and 180 days of curing. At the initial ages, the cement formulations exhibited high resistance. On the 3rd day, the cement formulations reached up to 10 MPa, and on the 7th day, 40 MPa. At late ages, the best-performing formulation, ECO2, showed, after 28 days of hydration, a compressive strength greater than 50 MPa, and at 180 days, a compressive strength greater than 80 MPa. It was possible to understand that BOF slag acts in cement alkaline activation with pH increase, more or less actively due to the presence of lime, portlandite, and calcite.
Wind-Induced Response Analysis and Fatigue Reliability Study of a Steel–Concrete Composite Wind Turbine Tower
Authors: Zhang Meng , Liu Bing , Gao Chongqi , Hossain Md Nayim , Zhao Guifeng
Published: June 2024

Taking an actual 3MW steel–concrete composite wind turbine tower as an example, a finite element model of the tower structure was established, and static bearing capacity and dynamic time history response analyses were performed to identify the locations where the structure is prone to failure. On this basis, the fatigue lives of the turbine tower at the most unfavorable locations were predicted using linear cumulative damage theory, and the fatigue reliability at the corresponding locations of the structure was calculated using the kriging–subset simulation method. The most dangerous locations of the tower that are most prone to failure are as follows: the bottom of the leeward side of the upper steel tube, the flange of the steel tube, the bolt-hole imprinting surface of the flange, the leeward side of the transition tube, and the top of the leeward side of the concrete tube. The failure risk of the flange and bolt-hole imprinting surface of the upper steel tube is relatively high, followed by that of the transition tube. This indicates that special attention should be given to the design and daily maintenance of this part. The fatigue resistance of the tower can be enhanced by improving the strength of the flange plate or increasing the number of bolts and strengthening the transition tube.
The Seismic Evaluation of Existing Buildings for Energy Renovation—A Case Study for the Residential Building Stock in Bucharest (Romania)
Authors: Pavel Florin , Nica George
Published: June 2024

This study focuses on an overview of two programs applied to the residential building stock of Bucharest (Romania), namely, the seismic strengthening program and the thermal rehabilitation program. The methodology for seismic risk assessment given in the current generation of Romanian codes, as well as in previous regulations, is examined. A brief review of other seismic risk assessment methodologies currently applied in various seismically prone countries is also presented. Examples of high-rise buildings in Bucharest that suffered significant damage during the Vrancea 1977 earthquake and that were thermally rehabilitated without any strengthening works are shown in this paper. The consistent differences between the current outcomes of the two programs are presented and discussed. Finally, this review paper highlights the lack of coherence in terms of seismic risk assessments for the same class of buildings, inducing, in some situations, a false feeling of safety in the building inhabitants. In addition, a combined procedure for both seismic strengthening and thermal rehabilitation is mandatory, considering the seismicity of Romania, as well as ongoing climate change.
G9a in Cancer: Mechanisms, Therapeutic Advancements, and Clinical Implications
Authors: Ni Yuchao , Shi Mingchen , Liu Liangliang , Lin Dong , Zeng Hao , Ong Christopher , Wang Yuzhuo
Published: June 2024

G9a, also named EHMT2, is a histone 3 lysine 9 (H3K9) methyltransferase responsible for catalyzing H3K9 mono- and dimethylation (H3K9me1 and H3K9me2). G9a contributes to various aspects of embryonic development and tissue differentiation through epigenetic regulation. Furthermore, the aberrant expression of G9a is frequently observed in various tumors, particularly in prostate cancer, where it contributes to cancer pathogenesis and progression. This review highlights the critical role of G9a in multiple cancer-related processes, such as epigenetic dysregulation, tumor suppressor gene silencing, cancer lineage plasticity, hypoxia adaption, and cancer progression. Despite the increased research on G9a in prostate cancer, there are still significant gaps, particularly in understanding its interactions within the tumor microenvironment and its broader epigenetic effects. Furthermore, this review discusses the recent advancements in G9a inhibitors, including the development of dual-target inhibitors that target G9a along with other epigenetic factors such as EZH2 and HDAC. It aims to bring together the existing knowledge, identify gaps in the current research, and suggest future directions for research and treatment strategies.
The Clinical Role of Adjuvant Chemotherapy after Sublobar Resection for Non-Small-Cell Lung Cancer ≤ 20 mm with Lymph Node Metastases: A Propensity-Matched Analysis of the National Cancer Database
Authors: Takamori Shinkichi , Zhu Junjia , Hashinokuchi Asato , Komiya Takefumi
Published: June 2024

Sublobar resection is a standard surgical procedure for small-sized non-small-cell lung cancer (NSCLC). However, the clinical role of adjuvant chemotherapy for small-sized NSCLC with pathological lymph node (LN) metastasis after sublobar resection is unknown. The National Cancer Database was queried for NSCLC patients between 2004 and 2018. Eligibility included sublobar resection with pathological LN metastasis, R0 resection, Charlson comorbidity score = 0, clinical stage T1a-b, and tumor size ≤ 20 mm. The Kaplan–Meier method with a log-rank test and multivariable Cox proportional hazards analyses were used for assessing survival. The samples were evaluated before and after propensity score matching (PSM) with respect to age, sex, histologic type, and pathological LN status. Of 810 patients who met the eligibility criteria, 567 (70.0%) underwent adjuvant chemotherapy. After PSM, patients with adjuvant chemotherapy had a significantly longer survival than those without (median survival: 64.3 vs. 34.0 months, hazard ratio for death: 0.61, p < 0.0001). Multivariate analyses after PSM showed that younger age (p = 0.0206), female (p = 0.0005), and adjuvant chemotherapy (p < 0.0001) were independent prognostic factors for longer survival. Adjuvant chemotherapy has a prognostic impact in patients with small-sized NSCLC and pathological lymph node metastasis who undergo sublobar resection.
Quantification of Resection Margin following Sublobar Resection in Lung Cancer Patients through Pre- and Post-Operative CT Image Comparison: Utilizing a CT-Based 3D Reconstruction Algorithm
Authors: Lin Yu-Hsuan , Chen Li-Wei , Wang Hao-Jen , Hsieh Min-Shu , Lu Chao-Wen , Chuang Jen-Hao , Chang Yeun-Chung , Chen Jin-Shing , Chen Chung-Ming , Lin Mong-Wei
Published: June 2024

Sublobar resection has emerged as a standard treatment option for early-stage peripheral non-small cell lung cancer. Achieving an adequate resection margin is crucial to prevent local tumor recurrence. However, gross measurement of the resection margin may lack accuracy due to the elasticity of lung tissue and interobserver variability. Therefore, this study aimed to develop an objective measurement method, the CT-based 3D reconstruction algorithm, to quantify the resection margin following sublobar resection in lung cancer patients through pre- and post-operative CT image comparison. An automated subvascular matching technique was first developed to ensure accuracy and reproducibility in the matching process. Following the extraction of matched feature points, another key technique involves calculating the displacement field within the image. This is particularly important for mapping discontinuous deformation fields around the surgical resection area. A transformation based on thin-plate spline is used for medical image registration. Upon completing the final step of image registration, the distance at the resection margin was measured. After developing the CT-based 3D reconstruction algorithm, we included 12 cases for resection margin distance measurement, comprising 4 right middle lobectomies, 6 segmentectomies, and 2 wedge resections. The outcomes obtained with our method revealed that the target registration error for all cases was less than 2.5 mm. Our method demonstrated the feasibility of measuring the resection margin following sublobar resection in lung cancer patients through pre- and post-operative CT image comparison. Further validation with a multicenter, large cohort, and analysis of clinical outcome correlation is necessary in future studies.
Combined Treatment of Uterine Leiomyosarcoma with Gamma Secretase Inhibitor MK-0752 and Chemotherapeutic Agents Decreases Cellular Invasion and Increases Apoptosis
Authors: Abedin Yasmin , Fife Alexander , Samuels Cherie-Ann , Wright Rasheena , Murphy Trystn , Zhang Xusheng , Alpert Emily , Cheung Emma , Zhao Qingshi , Einstein Mark H. , Douglas Nataki C.
Published: June 2024

Due to limited effective therapeutics for uterine leiomyosarcoma (uLMS), the impact of the gamma secretase inhibitor (GSI) MK-0752 with common chemotherapeutics was explored in uLMS. MTT assays were performed on two human uLMS cell lines, SK-UT-1B and SK-LMS-1, using MK-0752, docetaxel, doxorubicin, and gemcitabine, individually and in combination, to determine cell viability after treatment. Synergistic combinations were used in transwell invasion assays, cell cycle flow cytometry, proliferation assays, and RNA sequencing. In SK-UT-1B, MK-0752 was synergistic with doxorubicin and gemcitabine plus docetaxel. In SK-LMS-1, MK-0752 was synergistic with all individual agents and with the combination of gemcitabine plus docetaxel. MK-0752, gemcitabine, and docetaxel decreased invasion in SK-UT-1B 2.1-fold* and in SK-LMS-1 1.7-fold*. In SK-LMS-1, invasion decreased 1.2-fold* after treatment with MK-0752 and docetaxel and 2.2-fold* after treatment with MK-0752 and doxorubicin. Cell cycle analysis demonstrated increases in the apoptotic sub-G1 population with MK-0752 alone in SK-UT-1B (1.4-fold*) and SK-LMS-1 (2.7-fold**), along with increases with all combinations in both cell lines. The combination treatments had limited effects on proliferation, while MK-0752 alone decreased proliferation in SK-LMS-1 (0.63-fold**). Both MK-0752 alone and in combination altered gene expression and KEGG pathways. In conclusion, the combinations of MK-0752 with either doxorubicin, docetaxel, or gemcitabine plus docetaxel are potential novel therapeutic approaches for uLMS. (* p < 0.05, ** p < 0.01).
Facile Abatement of Oxygenated Volatile Organic Compounds via Hydrogen Co-Combustion over Pd/Al2O3 Catalyst as Onsite Heating Source
Authors: Ullah Lutf , Munsif Sehrish , Cao Long , Zhang Jing-Cai , Li Wei-Zhen
Published: June 2024

Catalytic combustion of volatile organic compounds (VOCs) usually requires external energy input to hold the desired reaction temperature via electric heating. This work presents an example of internal onsite heating of the catalytic active sites via hydrogen catalytic combustion with air over a conventional Pd/Al2O3 catalyst. Hydrogen combustion was ignited by the catalyst at room temperature without electric heating, and thus the temperatures were readily varied with the concentrations of H2. Representative oxygenated VOCs such as methanol, formaldehyde and formic acid can be completely oxidized into CO2 and water by co-feeding with H2 below its low explosion limit of 4% using Pd/Al2O3 as shared catalyst. The catalytic performance apparently is not sensitive to the sizes of Pd nanoparticles in fresh and spent states, as revealed by XRD and STEM. This provides an option for using renewable green hydrogen to eliminate VOC pollutants in an energy-efficient way.
The Immune Checkpoint Protein PD-L1 Regulates Ciliogenesis and Hedgehog Signaling
Authors: Agborbesong Ewud , Li Xiaogang
Published: June 2024

The primary cilium, an antenna-like sensory organelle that protrudes from the surface of most eukaryotic cell types, has become a signaling hub of growing interest given that defects in its structure and/or function are associated with human diseases and syndromes, known as ciliopathies. With the continuously expanding role of primary cilia in health and diseases, identifying new players in ciliogenesis will lead to a better understanding of the function of this organelle. It has been shown that the primary cilium shares similarities with the immune synapse, a highly organized structure at the interface between an antigen-presenting or target cell and a lymphocyte. Studies have demonstrated a role for known cilia regulators in immune synapse formation. However, whether immune synapse regulators modulate ciliogenesis remains elusive. Here, we find that programmed death ligand 1 (PD-L1), an immune checkpoint protein and regulator of immune synapse formation, plays a role in the regulation of ciliogenesis. We found that PD-L1 is enriched at the centrosome/basal body and Golgi apparatus of ciliated cells and depleting PD-L1 enhanced ciliogenesis and increased the accumulation of ciliary membrane trafficking proteins Rab8a, BBS5, and sensory receptor protein PC-2. Moreover, PD-L1 formed a complex with BBS5 and PC-2. In addition, we found that depletion of PD-L1 resulted in the ciliary accumulation of Gli3 and the downregulation of Gli1. Our results suggest that PD-L1 is a new player in ciliogenesis, contributing to PC-2-mediated sensory signaling and the Hh signaling cascade.
Characterization of Organic Anion and Cation Transport in Three Human Renal Proximal Tubular Epithelial Models
Authors: Meijer Tamara , da Costa Pereira Daniel , Klatt Olivia C. , Buitenhuis Joanne , Jennings Paul , Wilmes Anja
Published: June 2024

The polarised expression of specific transporters in proximal tubular epithelial cells is important for the renal clearance of many endogenous and exogenous compounds. Thus, ideally, the in vitro tools utilised for predictions would have a similar expression of apical and basolateral xenobiotic transporters as in vivo. Here, we assessed the functionality of organic cation and anion transporters in proximal tubular-like cells (PTL) differentiated from human induced pluripotent stem cells (iPSC), primary human proximal tubular epithelial cells (PTEC), and telomerase-immortalised human renal proximal tubular epithelial cells (RPTEC/TERT1). Organic cation and anion transport were studied using the fluorescent substrates 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP) and 6-carboxyfluorescein (6-CF), respectively. The level and rate of intracellular ASP accumulation in PTL following basolateral application were slightly lower but within a 3-fold range compared to primary PTEC and RPTEC/TERT1 cells. The basolateral uptake of ASP and its subsequent apical efflux could be inhibited by basolateral exposure to quinidine in all models. Of the three models, only PTL showed a modest preferential basolateral-to-apical 6-CF transfer. These results show that organic cation transport could be demonstrated in all three models, but more research is needed to improve and optimise organic anion transporter expression and functionality.
Efficient Generation of Pancreatic Progenitor Cells from Induced Pluripotent Stem Cells Derived from a Non-Invasive and Accessible Tissue Source—The Plucked Hair Follicle
Authors: Fatehi Amatullah , Sadat Marwa , Fayyad Muneera , Tang Jean , Han Duhyun , Rogers Ian M. , Taylor Drew
Published: June 2024

The advent of induced pluripotent stem cell (iPSC) technology has brought about transformative advancements in regenerative medicine, offering novel avenues for disease modeling, drug testing, and cell-based therapies. Patient-specific iPSC-based treatments hold the promise of mitigating immune rejection risks. However, the intricacies and costs of producing autologous therapies present commercial challenges. The hair follicle is a multi-germ layered versatile cell source that can be harvested at any age. It is a rich source of keratinocytes, fibroblasts, multipotent stromal cells, and the newly defined Hair Follicle-Associated Pluripotent Stem Cells (HAP). It can also be obtained non-invasively and transported via regular mail channels, making it the ideal starting material for an autologous biobank. In this study, cryopreserved hair follicle-derived iPSC lines (HF-iPS) were established through integration-free vectors, encompassing a diverse cohort. These genetically stable lines exhibited robust expression of pluripotency markers, and showcased tri-lineage differentiation potential. The HF-iPSCs effectively differentiated into double-positive cKIT+/CXCR4+ definitive endoderm cells and NKX6.1+/PDX1+ pancreatic progenitor cells, affirming their pluripotent attributes. We anticipate that the use of plucked hair follicles as an accessible, non-invasive cell source to obtain patient cells, in conjunction with the use of episomal vectors for reprogramming, will improve the future generation of clinically applicable pancreatic progenitor cells for the treatment of Type I Diabetes.
Injection Drug Use Alters Plasma Regulation of the B Cell Response
Authors: Sarkar Sanghita , Hill Dave D. , Rosenberg Alexander F. , Eaton Ellen F. , Kutsch Olaf , Kobie James J.
Published: June 2024

The opioid epidemic continues to be a major public health issue that includes millions of people who inject drugs (PWID). PWID have increased incidence of serious infections, including HIV as well as metabolic and inflammatory sequelae. We sought to discern the extent of systemic alterations in humoral immunity associated with injection drug use, including alterations in the plasma proteome and its regulation of B cell responsiveness. Comprehensive plasma proteomics analysis of HIV negative/hepatitis C negative individuals with a history of recent injection heroin use was performed using mass spectrometry and ELISA. The effects of plasma from PWID and healthy controls on the in vitro proliferation and transcriptional profile of B cell responses to stimulation were determined by flow cytometry and RNA-Seq. The plasma proteome of PWID was distinct from healthy control individuals, with numerous immune-related analytes significantly altered in PWID, including complement (C3, C5, C9), immunoglobulin (IgD, IgM, kappa light chain), and other inflammatory mediators (CXCL4, LPS binding protein, C-reactive protein). The plasma of PWID suppressed the in vitro proliferation of B cells. Transcriptome analysis indicated that PWID plasma treatment increased B cell receptor and CD40 signaling and shifted B cell differentiation from plasma cell-like toward germinal center B cell-like transcriptional profiles. These results indicate that the systemic inflammatory milieu is substantially altered in PWID and may impact their B cell responses.
Cannabinerol Prevents Endoplasmic Reticulum and Mitochondria Dysfunctions in an In Vitro Model of Alzheimer’s Disease: A Network-Based Transcriptomic Analysis
Authors: Chiricosta Luigi , Minuti Aurelio , Gugliandolo Agnese , Salamone Stefano , Pollastro Federica , Mazzon Emanuela , Artimagnella Osvaldo
Published: June 2024

Neurodegenerative disorders are affecting millions of people worldwide, impacting the healthcare system of our society. Among them, Alzheimer’s disease (AD) is the most common form of dementia, characterized by severe cognitive impairments. Neuropathological hallmarks of AD are β-amyloid (Aβ) plaques and neurofibrillary tangles, as well as endoplasmic reticulum and mitochondria dysfunctions, which finally lead to apoptosis and neuronal loss. Since, to date, there is no definitive cure, new therapeutic and prevention strategies are of crucial importance. In this scenario, cannabinoids are deeply investigated as promising neuroprotective compounds for AD. In this study, we evaluated the potential neuroprotective role of cannabinerol (CBNR) in an in vitro cellular model of AD via next-generation sequencing. We observed that CBNR pretreatment counteracts the Aβ-induced loss of cell viability of differentiated SH-SY5Y cells. Moreover, a network-based transcriptomic analysis revealed that CBNR restores normal mitochondrial and endoplasmic reticulum functions in the AD model. Specifically, the most important genes regulated by CBNR are related mainly to oxidative phosphorylation (COX6B1, OXA1L, MT-CO2, MT-CO3), protein folding (HSPA5) and degradation (CUL3, FBXW7, UBE2D1), and glucose (G6PC3) and lipid (HSD17B7, ERG28, SCD) metabolism. Therefore, these results suggest that CBNR could be a new neuroprotective agent helpful in the prevention of AD dysfunctions.
Transcriptome Analysis Reveals That FvPAP1 Genes Are Related to the Prolongation of Red-Leaf Period in Ficus virens
Authors: Ma Qingchao , Zhong Shuhua , Ma Tianci , Yue Yajie , Zou Shihui , Sui Shunzhao , Ai Lijiao , Guo Yulong
Published: June 2024

Ficus virens is a deciduous tree that is highly valuable both economically and medicinally. Like other plants with ‘red young leaves’, the red-leaf period of most F. virens trees lasts only a few days, and the red leaves have little ornamental value. However, in recent years, some lines of F. virens with bright red young leaves and a prolonged red-leaf period have been utilized for urban greening. To explore the mechanism of the different lengths of the duration of F. virens leaves, we analyzed the physiology and changes in gene expression during the development of two varieties of leaves. The detection of anthocyanin in different developmental stages of the F. virens leaves showed that the changes in color of the red leaves of F. virens were primarily caused by the change in anthocyanin content. A transcriptome analysis showed that the expression of genes related to the biosynthesis of anthocyanin changed significantly during the development of leaves. A MYB gene FvPAP1, which was consistent with the change in anthocyanin content, was identified. A real-time quantitative reverse transcription PCR analysis and heterologous expression transgenic studies showed that FvPAP1 promoted the biosynthesis of anthocyanins. The difference in the expression of FvPAP1 in time and intensity in the young leaves may be the reason for the difference in the duration of the red-leaf period in different lines of F. virens. A sequence analysis showed that the cDNA sequence of FvPAP1 was polymorphic, and possible reasons were discussed. These results can provide insight for similar studies on the mechanism of the formation of red coloring in other woody plant leaves and provide molecular targets to breed new materials with more prolonged red-leaf periods in F. virens.
Determination of Volatile Organic Compounds in Some Epipactis, Neottia, and Limodorum Orchids Growing in Basilicata (Southern Italy)
Authors: D’Auria Maurizio , Lorenz Richard , Racioppi Rocco , Romano Vito Antonio
Published: June 2024

SPME analysis of the scent of Epipactis microphylla showed the presence of limonene as the main component of the scent. Other components were 2,4,4,6,6,8,8-heptamethyl-1-nonene, pentadecane, and heptadecane. The scent of Epipactis palustris was characterized by pentadecane, 2,4,4,6,6,8,8-heptamethyl-1-nonene, and heptadecane. The scent of Neottia nidus avis showed the presence of kaur-16-ene as the main component of the scent. Other components were heinecosane, tetradecane, pentadecane, hexadecane, heptadecane, and 5,9,13-trimethyl-4,8,12-tetradecanal. The scent of Neottia ovata is due to pentadecane, hexadecane, and heptadecane. The scent of Limodorum abortivum showed the presence of 2,4,4,6,6,8,8-heptamethyl-1-nonene, pentadecane, hexadecane, heptadecane, and 2-(dodecyloxy)-ethanol.
ARPocketLab—A Mobile Augmented Reality System for Pedagogic Applications
Authors: Nunes Miguel , Adão Telmo , Shahrabadi Somayeh , Capela António , Carneiro Diana , Branco Pedro , Magalhães Luís , Morais Raul , Peres Emanuel
Published: June 2024

The widespread adoption of digital technologies in educational systems has been globally reflecting a shift in pedagogic content delivery that seems to fit modern generations of students while tackling relevant challenges faced by the current scholar context, e.g., progress traceability, pedagogic content fair access and intuitive visual representativeness, mobility issue mitigation, and sustainability in crisis situations. Among these technologies, augmented reality (AR) emerges as a particularly promising approach, allowing the visualization of computer-generated interactive data on top of real-world elements, thus enhancing comprehension and intuition regarding educational content, often in mobile settings. While the application of AR to education has been widely addressed, issues related to performance interaction and cognitive performance are commonly addressed, with lesser attention paid to the limitations associated with setup complexity, mostly related to experiences configurating tools, or contextual range, i.e., technical/scientific domain targeting versatility. Therefore, this paper introduces ARPocketLab, a digital, mobile, flexible, and scalable solution designed for the dynamic needs of modern tutorship. With a dual-interface system, it allows both educators and students to interactively design and engage with AR content directly tied to educational outcomes. Moreover, ARPocketLab’s design, aimed at handheld operationalization using a minimal set of physical resources, is particularly relevant in environments where educational materials are scarce or in situations where remote learning becomes necessary. Its versatility stems from the fact that it only requires a marker or a surface (e.g., a table) to function at full capacity. To evaluate the solution, tests were conducted with 8th-grade Portuguese students within the context of Physics and Chemistry subject. Results demonstrate the application’s effectiveness in providing didactic assistance, with positive feedback not only in terms of usability but also regarding learning performance. The participants also reported openness for the adoption of AR in pedagogic contexts.
Use of Deep-Amplicon Sequencing (DAS), Real-Time PCR and In Situ Hybridization to Detect H. pylori and Other Pathogenic Helicobacter Species in Feces from Children
Authors: Moreno Trigos Yolanda , Tortajada-Girbés Miguel , Simó-Jordá Raquel , Hernández Pérez Manuel , Hortelano Irene , García-Ferrús Miguel , Ferrús Pérez María Antonia
Published: June 2024

Background: Detecting Helicobacter pylori in fecal samples is easier and more comfortable than invasive techniques, especially in children. Thus, the objective of the present work was to detect H. pylori in feces from children by molecular methods as an alternative for diagnostic and epidemiological studies. Methods: Forty-five fecal samples were taken from pediatric patients who presented symptoms compatible with H. pylori infection. HpSA test, culture, real-time quantitative PCR (qPCR), fluorescence in situ hybridization (FISH), direct viable count associated with FISH (DVC-FISH), and Illumina-based deep-amplicon sequencing (DAS) were applied. Results: No H. pylori colonies were isolated from the samples. qPCR analysis detected H. pylori in the feces of 24.4% of the patients. In comparison, DVC-FISH analysis showed the presence of viable H. pylori cells in 53.3% of the samples, 37% of which carried 23S rRNA mutations that confer resistance to clarithromycin. After DAS, H. pylori-specific 16S rDNA sequences were detected in 26 samples. In addition, DNA from H. hepaticus was identified in 10 samples, and H. pullorum DNA was detected in one sample. Conclusion: The results of this study show the presence of H. pylori, H. hepaticus, and H. pullorum in children’s stools, demonstrating the coexistence of more than one Helicobacter species in the same patient. The DVC-FISH method showed the presence of viable, potentially infective H. pylori cells in a high percentage of the children’s stools. These results support the idea that fecal–oral transmission is probably a common route for H. pylori and suggest possible fecal–oral transmission of other pathogenic Helicobacter species.