bluuebunny/crossref_metadata_2025 huggingface dataset:
Solving Engineering Optimization Problems Based on Multi-Strategy Particle Swarm Optimization Hybrid Dandelion Optimization Algorithm
Authors: Tang Wenjie , Cao Li , Chen Yaodan , Chen Binhe , Yue Yinggao
Published: May 2024

In recent years, swarm intelligence optimization methods have been increasingly applied in many fields such as mechanical design, microgrid scheduling, drone technology, neural network training, and multi-objective optimization. In this paper, a multi-strategy particle swarm optimization hybrid dandelion optimization algorithm (PSODO) is proposed, which is based on the problems of slow optimization speed and being easily susceptible to falling into local extremum in the optimization ability of the dandelion optimization algorithm. This hybrid algorithm makes the whole algorithm more diverse by introducing the strong global search ability of particle swarm optimization and the unique individual update rules of the dandelion algorithm (i.e., rising, falling and landing). The ascending and descending stages of dandelion also help to introduce more changes and explorations into the search space, thus better balancing the global and local search. The experimental results show that compared with other algorithms, the proposed PSODO algorithm greatly improves the global optimal value search ability, convergence speed and optimization speed. The effectiveness and feasibility of the PSODO algorithm are verified by solving 22 benchmark functions and three engineering design problems with different complexities in CEC 2005 and comparing it with other optimization algorithms.
Development of a Flexible Sensor-Integrated Tissue Patch to Monitor Early Organ Rejection Processes Using Impedance Spectroscopy
Authors: Ertl Peter , Wladimir Tibor , Sticker Drago , Schuller Patrick , Rothbauer Mario , Wieselthaler Georg , Frauenlob Martin
Published: May 2024

Heart failure represents a primary cause of hospitalization and mortality in both developed and developing countries, often necessitating heart transplantation as the only viable recovery path. Despite advances in transplantation medicine, organ rejection remains a significant post-operative challenge, traditionally monitored through invasive endomyocardial biopsies (EMB). This study introduces a rapid prototyping approach to organ rejection monitoring via a sensor-integrated flexible patch, employing electrical impedance spectroscopy (EIS) for the non-invasive, continuous assessment of resistive and capacitive changes indicative of tissue rejection processes. Utilizing titanium-dioxide-coated electrodes for contactless impedance sensing, this method aims to mitigate the limitations associated with EMB, including procedural risks and the psychological burden on patients. The biosensor’s design features, including electrode passivation and three-dimensional microelectrode protrusions, facilitate effective monitoring of cardiac rejection by aligning with the heart’s curvature and responding to muscle contractions. Evaluation of sensor performance utilized SPICE simulations, scanning electron microscopy, and cyclic voltammetry, alongside experimental validation using chicken heart tissue to simulate healthy and rejected states. The study highlights the potential of EIS in reducing the need for invasive biopsy procedures and offering a promising avenue for early detection and monitoring of organ rejection, with implications for patient care and healthcare resource utilization.
Development of Non-Invasive Biosensors for Neonatal Jaundice Detection: A Review
Authors: Hazarika Chandan Jyoti , Borah Alee , Gogoi Poly , Ramchiary Shrimanta S. , Daurai Bethuel , Gogoi Manashjit , Saikia Manob Jyoti
Published: May 2024

One of the most common problems many babies encounter is neonatal jaundice. The symptoms are yellowing of the skin or eyes because of bilirubin (from above 2.0 to 2.5 mg/dL in the blood). If left untreated, it can lead to serious neurological complications. Traditionally, jaundice detection has relied on invasive blood tests, but developing non-invasive biosensors has provided an alternative approach. This systematic review aims to assess the advancement of these biosensors. This review discusses the many known invasive and non-invasive diagnostic modalities for detecting neonatal jaundice and their limitations. It also notes that the recent research and development on non-invasive biosensors for neonatal jaundice diagnosis is still in its early stages, with the majority of investigations being in vitro or at the pre-clinical level. Non-invasive biosensors could revolutionize neonatal jaundice detection; however, a number of issues still need to be solved before this can happen. These consist of in-depth validation studies, affordable and user-friendly gadgets, and regulatory authority approval. To create biosensors that meet regulatory requirements, additional research is required to make them more precise and affordable.
The Effect of Rhythmic Audio-Visual Stimulation on Inhibitory Control: An ERP Study
Authors: Wang Yifan , Wu Di , Sun Kewei , Zhu Yan , Chen Xianglong , Xiao Wei
Published: May 2024

Inhibitory control, as an essential cognitive ability, affects the development of higher cognitive functions. Rhythmic perceptual stimulation has been used to improve cognitive abilities. It is unclear, however, whether it can be used to improve inhibitory control. This study used the Go/NoGo task and the Stroop task to assess various levels of inhibitory control using rhythmic audio-visual stimuli as the stimulus mode. Sixty subjects were randomly divided into three groups to receive 6 Hz, 10 Hz, and white noise stimulation for 30 min. Two tasks were completed by each subject both before and after the stimulus. Before and after the task, closed-eye resting EEG data were collected. The results showed no differences in behavioral and EEG measures of the Go/NoGo task among the three groups. While both 6 Hz and 10 Hz audio-visual stimulation reduced the conflict effect in the Stroop task, only 6 Hz audio-visual stimulation improved the amplitude of the N2 component and decreased the conflict score. Although rhythmic audio-visual stimulation did not enhance response inhibition, it improved conflict inhibition.
Study on the Mechanical Performance of RC Beams under Load Reinforced by a Thin Layer of Reactive Powder Concrete on Four Sides
Authors: Liao Wei , Yang Weijun , Yang Jianyu
Published: May 2024

To repair reinforced concrete beams efficiently in a limited building space, the four-sided application of a reinforcing thin layer of reactive powder concrete (“RPCTL”) was proposed to improve the bending capacity of the members. Static flexural tests of one comparison beam and five reinforced beams were completed on a four-point centralized loading device. Changes in deflection, cracks, stresses, and damage characteristics of the specimens were measured under various levels of loading. The test results showed that the damage patterns of the reinforced specimens were dominated by the yielding of longitudinal tensile reinforcement at the bottoms of the beams and the crushing of the cementitious material in the top compression zones of the beams. The cracking load greatly increased by 1.42 to 7.12 times, and the ultimate bearing capacity increased by 0.29 to 1.41 times. The distribution characteristics and dynamic changes in the displacement, stress, and damage of the specimens were dynamically simulated by finite element software. The effects of reinforcement and initial load-holding level on the reinforcement effect were investigated. A bending capacity calculation formula for RPCTL reinforcement technology is proposed that aligns with the test results and can provide a reference for the design of RPCTL reinforcement.
Experimental Study on Using Synthetic Images as a Portion of Training Dataset for Object Recognition in Construction Site
Authors: Kim Jaemin , Wang Ingook , Yu Jungho
Published: May 2024

The application of Artificial Intelligence (AI) across various industries necessitates the acquisition of relevant environmental data and the implementation of AI recognition learning based on this data. However, the data available in real-world environments are limited and difficult to obtain. Construction sites represent dynamic and hazardous environments with a significant workforce, making data acquisition challenging and labor-intensive. To address these issues, this experimental study explored the potential of generating synthetic data to overcome the challenges of obtaining data from hazardous construction sites. Additionally, this research investigated the feasibility of hybrid dataset in securing construction-site data by creating synthetic data for scaffolding, which has a high incidence of falls but low object recognition rates due to its linear object characteristics. We generated a dataset by superimposing scaffolding objects, from which the backgrounds were removed, onto various construction site background images. Using this dataset, we produced a hybrid dataset to assess the feasibility of synthetic data for construction sites and to evaluate improvements in object recognition performance. By finding the optimal composition ratio with real data and conducting model training, the highest accuracy was achieved at an 8:2 ratio, with a construction object recognition accuracy of 0.886. Therefore, this study aims to reduce the risk and labor associated with direct data collection at construction sites through a hybrid dataset, achieving data generation at a low cost and high efficiency. By generating synthetic data to find the optimal ratio and constructing a hybrid dataset, this research demonstrates the potential to address the problems of data scarcity and data quality on construction sites. The improvement in recognition accuracy of the construction safety management system is anticipated, suggesting that the creation of synthetic data for constructing a hybrid dataset can reduce construction safety-accident issues.
Flexural Behavior of Cross-Laminated Timber Panels with Environmentally Friendly Timber Edge Connections
Authors: Ren Honghao , Bahrami Alireza , Cehlin Mathias , Wallhagen Marita
Published: May 2024

As a sustainable construction material, timber is more promoted than steel, concrete, and aluminum nowadays. The building industry benefits from using timber based on several perspectives, including decarbonization, improved energy efficiency, and easier recycling and disposal processes. The cross-laminated timber (CLT) panel is one of the widely utilized engineered wood products in construction for floors, which is an ideal alternative option for replacing reinforced concrete. One single CLT panel has an outstanding flexural behavior. However, CLT cannot be extended independently without external connections, which are normally made of steel. This article proposes two innovative adhesive-free edge connections made of timber, the double surface (DS) and half-lapped (HL) connections. These connections were designed to connect two CLT panels along their weak direction. Parametric studies consisting of twenty models were conducted on the proposed edge connections to investigate the effects of different factors and the flexural behavior of CLT panels with these edge connections under a four-point bending test. Numerical simulations of all the models were done in the current study by using ABAQUS 2022. Furthermore, the employed material properties and other relevant inputs (VUSDFLD subroutines, time steps, meshes, etc.) of the numerical models were validated through existing experiments. The results demonstrated that the maximum and minimum load capacities among the studied models were 6.23 kN and 0.35 kN, respectively. The load–displacement responses, strain, stress, and defection distributions were collected and analyzed, as well as their failure modes. It was revealed that the CLT panels’ load capacity was distinctly improved due to the increment of the connectors’ number (55.05%) and horizontal length (80.81%), which also reinforced the stability. Based on the findings, it was indicated that adhesive-free timber connections could be used for CLT panels in buildings and replace traditional construction materials, having profound potential for improving buildings’ sustainability and energy efficiency.
A Novel Calculate Model of Shear Deformation and Relative Displacement of Pile–Soil Interface in Warm Frozen Soil Foundation
Authors: Sun Gaochen , Gu Lijun , Li Long , Huo Yufan , Wang Zhengzhong , Dang Hongzu
Published: May 2024

In permafrost regions with warm frozen soil, the pile foundation is commonly used, but most currently available models for the WFS foundation pile–soil system are either highly empirical or overcomplicated, without a simplified theoretical manner in engineering. This study derives a novel and simplified calculated model of the WFS pile–soil system. The model is formulated in terms of the shear deformation theory and load transfer method based on the rigorous deformation mechanism of the WFS foundation soil around the pile. Considering the different depth soil features and the equilibrium state of the pile–soil system, dividing warm frozen soil foundation into three regions (TPPR, ER, and BPPR) to calculate the Dp and Ds can simply obtain the total displacement of pile under different loads. The results demonstrate that the present theoretical model can well predict the WFS foundation load–displacement response of the pile. The present model provides a simple, practical, and effective approach for the estimation of the load–displacement behavior of piles installed in the WFS foundation.
Segmentation of Apparent Multi-Defect Images of Concrete Bridges Based on PID Encoder and Multi-Feature Fusion
Authors: Liao Yanna , Huang Chaoyang , Yin Yafang
Published: May 2024

To address the issue of insufficient deep contextual information mining in the semantic segmentation task of multiple defects in concrete bridges, due to the diversity in texture, shape, and scale of the defects as well as significant differences in the background, we propose the Concrete Bridge Apparent Multi-Defect Segmentation Network (PID-MHENet) based on a PID encoder and multi-feature fusion. PID-MHENet consists of a PID encoder, skip connection, and decoder. The PID encoder adopts a multi-branch structure, including an integral branch and a proportional branch with a “thick and long” design principle and a differential branch with a “thin and short” design principle. The PID Aggregation Enhancement (PAE) combines the detail information of the proportional branch and the semantic information of the differential branch to enhance the fusion of contextual information and, at the same time, introduces the self-learning parameters, which can effectively extract the information of the boundary details of the lesions, the texture, and the background differences. The Multi-Feature Fusion Enhancement Decoding Block (MFEDB) in the decoding stage enhances the information and globally fuses the different feature maps introduced by the three-channel skip connection, which improves the segmentation accuracy of the network for the background similarity and the micro-defects. The experimental results show that the mean Pixel accuracy (mPa) and mean Intersection over Union (mIoU) values of PID-MHENet on the concrete bridge multi-defect semantic segmentation dataset improved by 5.17% and 5.46%, respectively, compared to the UNet network.
Preparation and Performance of Cement-Stabilized Base External Curing Agent in a Desert Environment
Authors: Wei Chenhao , He Zewen , Ma Jiachen , Sun Xiaohui , Shi Yana , Yi Qiang , Li Maoqing
Published: May 2024

To explore and deal with the difficulty in curing cement-stabilized bases in desert environments, curing agents were prepared to enhance the curing effect on the base in this research. The composite curing agent was prepared through orthogonal experiments and the durability of the curing agent coating were studied by simulating a desert environment. Subsequently, the curing effect on the performance of bases was analyzed. Finally, the hydration degree of cement was studied via scanning electron microscope (SEM), thermogravimetric analysis (TG), and X-ray diffraction analysis (XRD), and the curing mechanism of the curing agent was explored. The results show that the composite (paraffin emulsion is the main component of the film, vinyl acetate-ethylene copolymer dosage is 20%, ethanol ester-12 dosage is 10%, and sodium silicate dosage is 18%) could effectively improve the water-retention performance (water-loss ratio: 2.36%) and mechanical properties of the specimen (7 d compressive strength: 7.48 MPa; 7 d indirect tensile strength: 0.70 MPa). The dry shrinkage coefficient of the specimen with composite curing agent was reduced by 116.26% at 28 days. The compressive strength of dry and wet freeze could reach 7.48 MPa and 6.88 MPa, respectively. The durability of the curing agent-coated base met the requirements of pavement performance in desert areas. The results of XRD, TG, and SEM indicated that the curing agent promoted hydration. In addition, the number of C-S-H gel and AFt crystals significantly increased. The curing difficulty of road bases in desert areas could be reduced effectively through the application presented in this study, which contributes to the conservation of natural and human resources.
‘The Reports of My Death Are Greatly Exaggerated’—Evaluating the Effect of Necrosis on MGMT Promoter Methylation Testing in High-Grade Glioma
Authors: Satgunaseelan Laveniya , Lee Maggie , Iannuzzi Sebastian , Hallal Susannah , Deang Kristine , Stanceski Kristian , Wei Heng , Mason Sofia , Shivalingam Brindha , Sim Hao-Wen , Buckland Michael E. , Alexander Kimberley L.
Published: May 2024

(1) Background: MGMT (O-6-methylguanine-DNA methyltransferase) promoter methylation remains an important predictive biomarker in high-grade gliomas (HGGs). The influence of necrosis on the fidelity of MGMT promoter (MGMTp) hypermethylation testing is currently unknown. Therefore, our study aims to evaluate the effect of varying degrees of necrosis on MGMTp status, as determined by pyrosequencing, in a series of primary and recurrent HGGs; (2) Methods: Within each case, the most viable blocks (assigned as ‘true’ MGMTp status) and the most necrotic block were determined by histopathology review. MGMTp status was determined by pyrosequencing. Comparisons of MGMTp status were made between the most viable and most necrotic blocks. (3) Results: 163 samples from 64 patients with HGGs were analyzed. MGMTp status was maintained in 84.6% of primary and 78.3% of recurrent HGGs between the most viable and necrotic blocks. A threshold of ≥60% tumor cellularity was established at which MGMTp status was unaltered, irrespective of the degree of necrosis. (4) Conclusions: MGMTp methylation status, as determined by pyrosequencing, does not appear to be influenced by necrosis in the majority of cases at a cellularity of at least 60%. Further investigation into the role of intratumoral heterogeneity on MGMTp status will increase our understanding of this predictive marker.
The Utility of Contrast-Enhanced Ultrasound (CEUS) in Assessing the Risk of Malignancy in Thyroid Nodules
Authors: Żyłka Agnieszka , Dobruch-Sobczak Katarzyna , Piotrzkowska-Wróblewska Hanna , Jędrzejczyk Maciej , Bakuła-Zalewska Elwira , Góralski Piotr , Gałczyński Jacek , Dedecjus Marek
Published: May 2024

Background: Ultrasonography is a primary method used in the evaluation of thyroid nodules, but no single feature of this method predicts malignancy with high accuracy. Therefore, this paper aims to assess the utility of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of thyroid nodules. Methods: The study group comprised 188 adult patients (155 women and 33 men) who preoperatively underwent CEUS of a thyroid nodule classified as Bethesda categories II–VI after fine-needle aspiration biopsy. During the CEUS examination, 1.5 mL of SonoVue contrast was injected intravenously, after which 15 qualitative CEUS enhancement patterns were analysed. Results: The histopathologic results comprised 65 benign thyroid nodules and 123 thyroid carcinomas. The dominant malignant CEUS features, such as hypo- and heterogeneous enhancement and slow wash-in phase, were evaluated, whereas high enhancement, ring enhancement, and a slow wash-out phase were assessed as predictors of benign lesions. Two significant combinations of B-mode and CEUS patterns were noted, namely, hypoechogenicity with heterogeneous enhancement and non-smooth margins with hypo- or iso-enhancement. Conclusions: The preliminary results indicate that CEUS is a useful tool in assessing the risk of malignancy of thyroid lesions. The combination of the qualitative enhancement parameters and B-mode sonographic features significantly increases the method’s usefulness.
A Preparatory Virtual Reality Experience Reduces Anxiety before Surgery in Gynecologic Oncology Patients: A Randomized Controlled Trial
Authors: Schmid Bernd C. , Marsland Dominic , Jacobs Eilish , Rezniczek Günther A.
Published: May 2024

Perioperative anxiety is common among patients undergoing surgery, potentially leading to negative outcomes. Immersive virtual reality (VR) has shown promise in reducing anxiety in various clinical settings. This study aimed to evaluate the effectiveness of VR in reducing perioperative anxiety in patients undergoing gynecological oncology surgery and was conducted as a single-center, double-arm, single-blinded randomized controlled trial at the Gold Coast University Hospital, Queensland, Australia. Participants were randomized into the VR intervention + care as usual (CAU) group (n = 39) and the CAU group (n = 41). Anxiety scores were assessed using a six-tier visual facial anxiety scale at baseline, after the intervention/CAU on the same day, and, several days up to weeks later, immediately before surgery. There was no significant difference in baseline anxiety scores, type of operation, or suspected cancer between the two groups. The VR intervention significantly reduced anxiety scores from baseline to preoperative assessment (p < 0.001). The median anxiety score in the VR intervention group decreased from 3 (interquartile range 2 to 5) at baseline to 2 (2 to 3) prior to surgery, while the control group’s scores were 4 (2 to 5) and 4 (3 to 5), respectively. Multivariate analysis showed that group assignment was the sole outcome predictor, not age, type of procedure, or the time elapsed until surgery. Thus, VR exposure was effective in reducing perioperative anxiety in patients undergoing gynecological oncology surgery. The use of VR as a preparation tool may improve patient experience and contribute to better surgical outcomes, warranting further research into exploring the potential benefits of VR in other surgical specialties and its long-term impact on patient recovery.
Pathogenicity Prediction of Gene Fusion in Structural Variations: A Knowledge Graph-Infused Explainable Artificial Intelligence (XAI) Framework
Authors: Murakami Katsuhiko , Tago Shin-ichiro , Takishita Sho , Morikawa Hiroaki , Kojima Rikuhiro , Yokoyama Kazuaki , Ogawa Miho , Fukushima Hidehito , Takamori Hiroyuki , Nannya Yasuhito , Imoto Seiya , Fuji Masaru
Published: May 2024

When analyzing cancer sample genomes in clinical practice, many structural variants (SVs), other than single nucleotide variants (SNVs), have been identified. To identify driver variants, the leading candidates must be narrowed down. When fusion genes are involved, selection is particularly difficult, and highly accurate predictions from AI is important. Furthermore, we also wanted to determine how the prediction can make more reliable diagnoses. Here, we developed an explainable AI (XAI) suitable for SVs with gene fusions, based on the XAI technology we previously developed for the prediction of SNV pathogenicity. To cope with gene fusion variants, we added new data to the previous knowledge graph for SVs and we improved the algorithm. Its prediction accuracy was as high as that of existing tools. Moreover, our XAI could explain the reasons for these predictions. We used some variant examples to demonstrate that the reasons are plausible in terms of pathogenic basic mechanisms. These results can be seen as a hopeful step toward the future of genomic medicine, where efficient and correct decisions can be made with the support of AI.
An Investigative Analysis of Therapeutic Strategies in Hepatocellular Carcinoma: A Raetrospective Examination of 23 Biopsy-Confirmed Cases Emphasizing the Significance of Histopathological Insights
Authors: Zgura Anca , Grasu Mugur Cristian , Dumitru Radu Lucian , Toma Letitia , Iliescu Laura , Baciu Cosmin
Published: May 2024

Background: The Liver Imaging Reporting and Data System (LI-RADS) combines standardized terminology with a classification system for imaging findings in patients with HCC, therefore rendering diagnostic biopsy unnecessary in many cases. This retrospective study included 23 patients with a biopsy diagnosis of HCC, performed either before or after local interventional procedures, in order to evaluate the histopathologic changes induced by previous procedures and their potential influence on the response to immune therapy. Material and Methods: The study encompassed a cohort of patients diagnosed with Hepatocellular Carcinoma (HCC). Diagnosis was established via contrast-enhanced computer tomography or magnetic resonance imaging that identified LI-RADS-5 nodules in conjunction with historical liver disease and elevated alpha-fetoprotein (AFP) levels or via histological examination confirming positivity for glypican3, heat shock protein 70, and glutamine synthetase. The study detailed the liver disease etiology, LI-RADS scores, characteristics and dimensions of HCC nodules, serum AFP concentrations, Edmondson–Steiner grading, and the expression of programmed cell death ligand 1 (PD-L1) in the tumor cells. Results: Among the study’s cohort of Hepatocellular Carcinoma (HCC) patients, a portion had not received any prior treatments, while the remainder experienced local HCC recurrence following trans-arterial chemoembolization or radiofrequency ablation. Observations indicated elevated alpha-fetoprotein (AFP) levels in those who had not undergone any previous interventions, showing statistical significance. The Edmondson–Steiner classification predominantly identified grade III differentiation across patients, irrespective of their treatment history. Furthermore, an increase in intra-tumoral programmed cell death ligand 1 (PD-L1) expression was noted in patients who had not been subjected to previous therapies. Conclusion: Liver biopsy offers valuable insights for patients with Hepatocellular Carcinoma (HCC), assisting in the tailoring of immune therapy strategies, particularly in cases of recurrence following prior local interventions.
Controllable Synthesis of Fe2O3/Nickel Cobaltite Electrocatalyst to Enhance Oxidation of Small Molecules
Authors: Alamro Fowzia S. , Medany Shymaa S. , Al-Kadhi Nada S. , Mostafa Ayman M. , Zaher Walaa F. , Ahmed Hoda A. , Hefnawy Mahmoud A.
Published: May 2024

Nickel-based catalysts have been widely recognized as highly promising electrocatalysts for oxidation. Herein, we designed a catalyst surface based on iron oxide electrodeposited on NiCo2O4 spinel oxide. Nickel foam was used as a support for the prepared catalysts. The modified surface was characterized by different techniques like electron microscopy and X-ray photon spectroscopy. The activity of the modified surface was investigated through the electrochemical oxidation of different organic molecules such as urea, ethanol, and ethylene glycol. Therefore, the modified Fe@ NiCo2O4/NF current in 1.0 M NaOH and 1.0 M fuel concentrations reached 31.4, 27.1, and 17.8 mA cm−2 for urea, ethanol, and ethylene glycol, respectively. Moreover, a range of kinetic characteristics parameters were computed, such as the diffusion coefficient, Tafel slope, and transfer coefficient. Chronoamperometry was employed to assess the electrode’s resistance to long-term oxidation. Consequently, the electrode’s activity exhibited a reduction ranging from 17% to 30% over a continuous oxidation period of 300 min.
The Role of TLR-2 in Lethal COVID-19 Disease Involving Medullary and Resident Lung Megakaryocyte Up-Regulation in the Microthrombosis Mechanism
Authors: Pannone Giuseppe , Pedicillo Maria Carmela , De Stefano Ilenia Sara , Angelillis Francesco , Barile Raffaele , Pannone Chiara , Villani Giuliana , Miele Francesco , Municinò Maurizio , Ronchi Andrea , Serviddio Gaetano , Zito Marino Federica , Franco Renato , Colangelo Tommaso , Zamparese Rosanna
Published: May 2024

Patients with COVID-19 have coagulation and platelet disorders, with platelet alterations and thrombocytopenia representing negative prognostic parameters associated with severe forms of the disease and increased lethality. Methods: The aim of this study was to study the expression of platelet glycoprotein IIIa (CD61), playing a critical role in platelet aggregation, together with TRL-2 as a marker of innate immune activation. Results: A total of 25 patients were investigated, with the majority (24/25, 96%) having co-morbidities and dying from a fatal form of SARS-CoV-2(+) infection (COVID-19+), with 13 men and 12 females ranging in age from 45 to 80 years. When compared to a control group of SARS-CoV-2 (−) negative lungs (COVID-19−), TLR-2 expression was up-regulated in a subset of patients with deadly COVID-19 fatal lung illness. The proportion of Spike-1 (+) patients found by PCR and ISH correlates to the proportion of Spike-S1-positive cases as detected by digital pathology examination. Furthermore, CD61 expression was considerably higher in the lungs of deceased patients. In conclusion, we demonstrate that innate immune prolonged hyperactivation is related to platelet/megakaryocyte over-expression in the lung. Conclusions: Microthrombosis in deadly COVID-19+ lung disease is associated with an increase in the number of CD61+ platelets and megakaryocytes in the pulmonary interstitium, as well as their functional activation; this phenomenon is associated with increased expression of innate immunity TLR2+ cells, which binds the SARS-CoV-2 E protein, and significantly with the persistence of the Spike-S1 viral sequence.
Emerging Strategies in Mesenchymal Stem Cell-Based Cardiovascular Therapeutics
Authors: Kumar Rishabh , Mishra Nitin , Tran Talan , Kumar Munish , Vijayaraghavalu Sivakumar , Gurusamy Narasimman
Published: May 2024

Cardiovascular diseases continue to challenge global health, demanding innovative therapeutic solutions. This review delves into the transformative role of mesenchymal stem cells (MSCs) in advancing cardiovascular therapeutics. Beginning with a historical perspective, we trace the development of stem cell research related to cardiovascular diseases, highlighting foundational therapeutic approaches and the evolution of cell-based treatments. Recognizing the inherent challenges of MSC-based cardiovascular therapeutics, which range from understanding the pro-reparative activity of MSCs to tailoring patient-specific treatments, we emphasize the need to refine the pro-regenerative capacity of these cells. Crucially, our focus then shifts to the strategies of the fourth generation of cell-based therapies: leveraging the secretomic prowess of MSCs, particularly the role of extracellular vesicles; integrating biocompatible scaffolds and artificial sheets to amplify MSCs’ potential; adopting three-dimensional ex vivo propagation tailored to specific tissue niches; harnessing the promise of genetic modifications for targeted tissue repair; and institutionalizing good manufacturing practice protocols to ensure therapeutic safety and efficacy. We conclude with reflections on these advancements, envisaging a future landscape redefined by MSCs in cardiovascular regeneration. This review offers both a consolidation of our current understanding and a view toward imminent therapeutic horizons.
Role of Vasoactive Hormone-Induced Signal Transduction in Cardiac Hypertrophy and Heart Failure
Authors: Dhalla Naranjan S. , Mota Karina O. , Elimban Vijayan , Shah Anureet K. , de Vasconcelos Carla M. L. , Bhullar Sukhwinder K.
Published: May 2024

Heart failure is the common concluding pathway for a majority of cardiovascular diseases and is associated with cardiac dysfunction. Since heart failure is invariably preceded by adaptive or maladaptive cardiac hypertrophy, several biochemical mechanisms have been proposed to explain the development of cardiac hypertrophy and progression to heart failure. One of these includes the activation of different neuroendocrine systems for elevating the circulating levels of different vasoactive hormones such as catecholamines, angiotensin II, vasopressin, serotonin and endothelins. All these hormones are released in the circulation and stimulate different signal transduction systems by acting on their respective receptors on the cell membrane to promote protein synthesis in cardiomyocytes and induce cardiac hypertrophy. The elevated levels of these vasoactive hormones induce hemodynamic overload, increase ventricular wall tension, increase protein synthesis and the occurrence of cardiac remodeling. In addition, there occurs an increase in proinflammatory cytokines and collagen synthesis for the induction of myocardial fibrosis and the transition of adaptive to maladaptive hypertrophy. The prolonged exposure of the hypertrophied heart to these vasoactive hormones has been reported to result in the oxidation of catecholamines and serotonin via monoamine oxidase as well as the activation of NADPH oxidase via angiotensin II and endothelins to promote oxidative stress. The development of oxidative stress produces subcellular defects, Ca2+-handling abnormalities, mitochondrial Ca2+-overload and cardiac dysfunction by activating different proteases and depressing cardiac gene expression, in addition to destabilizing the extracellular matrix upon activating some metalloproteinases. These observations support the view that elevated levels of various vasoactive hormones, by producing hemodynamic overload and activating their respective receptor-mediated signal transduction mechanisms, induce cardiac hypertrophy. Furthermore, the occurrence of oxidative stress due to the prolonged exposure of the hypertrophied heart to these hormones plays a critical role in the progression of heart failure.
Lung Transplant Immunomodulation with Genetically Engineered Mesenchymal Stromal Cells—Therapeutic Window for Interleukin-10
Authors: Nykänen Antti I. , Mariscal Andrea , Duong Allen , Ali Aadil , Takahagi Akihiro , Bai Xiaohui , Zehong Guan , Joe Betty , Takahashi Mamoru , Chen Manyin , Gokhale Hemant , Shan Hongchao , Hwang David M. , Estrada Catalina , Yeung Jonathan , Waddell Tom , Martinu Tereza , Juvet Stephen , Cypel Marcelo , Liu Mingyao , Davies John E. , Keshavjee Shaf
Published: May 2024

Lung transplantation results are compromised by ischemia–reperfusion injury and alloimmune responses. Ex vivo lung perfusion (EVLP) is used to assess marginal donor lungs before transplantation but is also an excellent platform to apply novel therapeutics. We investigated donor lung immunomodulation using genetically engineered mesenchymal stromal cells with augmented production of human anti-inflammatory hIL-10 (MSCsIL-10). Pig lungs were placed on EVLP for 6 h and randomized to control (n = 7), intravascular delivery of 20 × 106 (n = 5, low dose) or 40 × 106 human MSCs IL-10 (n = 6, high dose). Subsequently, single-lung transplantation was performed, and recipient pigs were monitored for 3 days. hIL-10 secretion was measured during EVLP and after transplantation, and immunological effects were assessed by cytokine profile, T and myeloid cell characterization and mixed lymphocyte reaction. MSCIL-10 therapy rapidly increased hIL-10 during EVLP and resulted in transient hIL-10 elevation after lung transplantation. MSCIL-10 delivery did not affect lung function but was associated with dose-related immunomodulatory effects, with the low dose resulting in a beneficial decrease in apoptosis and lower macrophage activation, but the high MSCIL-10 dose resulting in inflammation and cytotoxic CD8+ T cell activation. MSCIL-10 therapy during EVLP results in a rapid and transient perioperative hIL-10 increase and has a therapeutic window for its immunomodulatory effects.
Antibody–Drug Conjugate Made of Zoledronic Acid and the Anti-CD30 Brentuximab–Vedotin Exert Anti-Lymphoma and Immunostimulating Effects
Authors: Morelli Feliciana , Matis Serena , Benelli Roberto , Salvini Laura , Zocchi Maria Raffaella , Poggi Alessandro
Published: May 2024

Relevant advances have been made in the management of relapsed/refractory (r/r) Hodgkin Lymphomas (HL) with the use of the anti-CD30 antibody–drug conjugate (ADC) brentuximab–vedotin (Bre–Ved). Unfortunately, most patients eventually progress despite the excellent response rates and tolerability. In this report, we describe an ADC composed of the aminobisphosphonate zoledronic acid (ZA) conjugated to Bre–Ved by binding the free amino groups of this antibody with the phosphoric group of ZA. Liquid chromatography–mass spectrometry, inductively coupled plasma–mass spectrometry, and matrix-assisted laser desorption ionization–mass spectrometry analyses confirmed the covalent linkage between the antibody and ZA. The novel ADC has been tested for its reactivity with the HL/CD30+ lymphoblastoid cell lines (KMH2, L428, L540, HS445, and RPMI6666), showing a better titration than native Bre–Ved. Once the HL-cells are entered, the ADC co-localizes with the lysosomal LAMP1 in the intracellular vesicles. Also, this ADC exerted a stronger anti-proliferative and pro-apoptotic (about one log fold) effect on HL-cell proliferation compared to the native antibody Bre–Ved. Eventually, Bre–Ved–ZA ADC, in contrast with the native antibody, can trigger the proliferation and activation of cytolytic activity of effector-memory Vδ2 T-lymphocytes against HL-cell lines. These findings may support the potential use of this ADC in the management of r/r HL.
Cytosolic and Acrosomal pH Regulation in Mammalian Sperm
Authors: Chávez Julio C. , Carrasquel-Martínez Gabriela , Hernández-Garduño Sandra , Matamoros Volante Arturo , Treviño Claudia L. , Nishigaki Takuya , Darszon Alberto
Published: May 2024

As in most cells, intracellular pH regulation is fundamental for sperm physiology. Key sperm functions like swimming, maturation, and a unique exocytotic process, the acrosome reaction, necessary for gamete fusion, are deeply influenced by pH. Sperm pH regulation, both intracellularly and within organelles such as the acrosome, requires a coordinated interplay of various transporters and channels, ensuring that this cell is primed for fertilization. Consistent with the pivotal importance of pH regulation in mammalian sperm physiology, several of its unique transporters are dependent on cytosolic pH. Examples include the Ca2+ channel CatSper and the K+ channel Slo3. The absence of these channels leads to male infertility. This review outlines the main transport elements involved in pH regulation, including cytosolic and acrosomal pH, that participate in these complex functions. We present a glimpse of how these transporters are regulated and how distinct sets of them are orchestrated to allow sperm to fertilize the egg. Much research is needed to begin to envision the complete set of players and the choreography of how cytosolic and organellar pH are regulated in each sperm function.
Uncovering miRNA–mRNA Regulatory Networks Related to Olaparib Resistance and Resensitization of BRCA2MUT Ovarian Cancer PEO1-OR Cells with the ATR/CHK1 Pathway Inhibitors
Authors: Biegała Łukasz , Kołat Damian , Gajek Arkadiusz , Płuciennik Elżbieta , Marczak Agnieszka , Śliwińska Agnieszka , Mikula Michał , Rogalska Aneta
Published: May 2024

Resistance to olaparib is the major obstacle in targeted therapy for ovarian cancer (OC) with poly(ADP-ribose) polymerase inhibitors (PARPis), prompting studies on novel combination therapies to enhance olaparib efficacy. Despite identifying various mechanisms, understanding how OC cells acquire PARPi resistance remains incomplete. This study investigated microRNA (miRNA) expression in olaparib-sensitive (PEO1, PEO4) and previously established olaparib-resistant OC cell lines (PEO1-OR) using high-throughput RT-qPCR and bioinformatic analyses. The role of miRNAs was explored regarding acquired resistance and resensitization with the ATR/CHK1 pathway inhibitors. Differentially expressed miRNAs were used to construct miRNA–mRNA regulatory networks and perform functional enrichment analyses for target genes with miRNet 2.0. TCGA-OV dataset was analyzed to explore the prognostic value of selected miRNAs and target genes in clinical samples. We identified potential processes associated with olaparib resistance, including cell proliferation, migration, cell cycle, and growth factor signaling. Resensitized PEO1-OR cells were enriched in growth factor signaling via PDGF, EGFR, FGFR1, VEGFR2, and TGFβR, regulation of the cell cycle via the G2/M checkpoint, and caspase-mediated apoptosis. Antibody microarray analysis confirmed dysregulated growth factor expression. The addition of the ATR/CHK1 pathway inhibitors to olaparib downregulated FGF4, FGF6, NT-4, PLGF, and TGFβ1 exclusively in PEO1-OR cells. Survival and differential expression analyses for serous OC patients revealed prognostic miRNAs likely associated with olaparib resistance (miR-99b-5p, miR-424-3p, and miR-505-5p) and resensitization to olaparib (miR-324-5p and miR-424-3p). Essential miRNA–mRNA interactions were reconstructed based on prognostic miRNAs and target genes. In conclusion, our data highlight distinct miRNA profiles in olaparib-sensitive and olaparib-resistant cells, offering molecular insights into overcoming resistance with the ATR/CHK1 inhibitors in OC. Moreover, some miRNAs might serve as potential predictive signature molecules of resistance and therapeutic response.
Prognostic Factors of Pediatric Acute Myeloid Leukemia Patients with t(8;21) (q22;q22): A Single-Center Retrospective Study
Authors: Yang Jiapeng , Zhu Xiaohua , Zhang Honghong , Fu Yang , Li Zifeng , Xing Ziping , Yu Yi , Cao Ping , Le Jun , Jiang Junye , Li Jun , Wang Hongsheng , Zhai Xiaowen
Published: May 2024

This retrospective study aimed to analyze the treatment effect and prognostic factors of pediatric acute myeloid leukemia (AML) patients with t(8;21). A total of 268 newly diagnosed pediatric AML (pAML) enrolled from 1 January 2005 to 31 December 2022 were retrospectively reviewed, and 50 (18.7%) patients harbored t(8;21) translocation. CR rate, OS, EFS, and RFS were assessed by multivariate Logistic and Cox regression models in these patients. Of the 50 patients, 2 patients abandoned treatment during the first induction course. Of the remaining 48 patients who received double-induction therapy and were included in the final analyses, CR1 and CR2 were 75.0% (36/48) and 95.8% (46/48), respectively. The overall three-year OS, EFS, and RFS were 68.4% (95% CI, 55.0–85.1), 64.2% (95% CI, 50.7–81.4), and 65.5% (95% CI, 51.9–82.8), respectively. The presence of loss of sex chromosome (LOS) at diagnosis (n = 21) was associated with a better 3-year OS [87.5% (95% CI, 72.7–100) vs. 52.7% (95% CI, 35.1–79.3), p = 0.0089], 3-year EFS [81.6% (95% CI, 64.7–100) vs. 49.7% (95% CI, 32.4–76.4), p = 0.023], and 3-year RFS [81.6% (95% CI, 64.7–100) vs. 51.7% (95% CI, 33.9–78.9), p = 0.036] than those without LOS (n = 27), and it was also an independent good prognostic factor of OS (HR, 0.08 [95% CI, 0.01–0.48], p = 0.005), EFS (HR, 0.22 [95% CI, 0.05–0.85], p = 0.029), and RFS (HR, 0.21 [95% CI, 0.05–0.90], p = 0.035). However, extramedullary leukemia (EML) featured the independent risk factors of inferior OS (HR, 10.99 [95% CI, 2.08–58.12], p = 0.005), EFS (HR, 4.75 [95% CI, 1.10–20.61], p = 0.037), and RFS (HR, 6.55 [95% CI, 1.40–30.63], p = 0.017) in pediatric individuals with t(8;21) AML. Further analysis of combining LOS with EML indicated that the EML+LOS− subgroup had significantly inferior OS (92.9%, [95% CI, 80.3–100]), EFS (86.2%, [95% CI, 70.0–100]), and RFS (86.2%, [95% CI, 80.3–100]) compared to the other three subgroups (all p < 0.001). LOS and EML are independent prognostic factors of OS, EFS, and RFS with t(8;21) pAML patients. LOS combined with EML may help improve risk stratification.
Polyhexamethylene Biguanide Reduces High-Risk Human Papilloma Virus Viral Load in Cervical Cell Samples Derived from ThinPrep Pap Test
Authors: Di Fraia Ludovica , Babalini Carla , Calcagno Marco , Proietti Sara , Lepore Elisa , Di Fraia Pietro
Published: May 2024

Human papilloma virus (HPV) infection and its progression still represent a great medical challenge worldwide. Clinical evidence has demonstrated the beneficial effects of polyhexamethylene biguanide (PHMB) on HPV clinical manifestations; however, evidence of the effect of this molecule on HPV viral load is still lacking. In this in vitro study, 13 ThinPrep Papanicolaou (Pap) tests were treated with a PHMB solution (0.10 g/100 mL) for 2 h. We observed no cytological changes but a significant reduction in the viral load of high-risk (HR) HPV after PHMB treatment, also revealing a dose-dependent antiviral effect. In addition, by stratifying the obtained results according to HR-HPV genotype, we observed a significant reduction in the viral load of HPV 16, P2 (56, 59, 66), 31, and P3 (35, 39, 68) and a strong decrease in the viral load of HPV 45, 52, and P1 (33, 58). Overall, 85% of the analyzed cervical cell samples exhibited an improvement in HPV viral load after PHMB exposure, while only 15% remain unchanged. For the first time, the data from this pilot study support the activity of PHMB on a specific phase of the HPV viral lifecycle, the one regarding the newly generated virions, reducing viral load and thus blocking the infection of other cervical cells.
People’s Perception of Climate Change Impacts on Subtropical Climatic Region: A Case Study of Upper Indus, Pakistan
Authors: Ahmad Bashir , Nadeem Muhammad Umar , Hussain Saddam , Hussain Abid , Virik Zeeshan Tahir , Jamil Khalid , Raza Nelufar , Kamran Ali , Dogar Salar Saeed
Published: May 2024

In developing countries like Pakistan, the preservation of the environment, as well as people’s economies, agriculture, and way of life, are believed to be hampered by climate change. Understanding how people perceive climate change and its signs is essential for creating a variety of adaptation solutions. In this study, we aim to bridge the gap in current research within this area, which predominantly relies on satellite data, by integrating qualitative assessments of people’s perceptions of climate change, thereby providing valuable ground-based observations of climate variability and its impacts on local communities. Field-based data were collected at different altitudes (upstream (US), midstream (MS), and downstream (DS)) of the Upper Indus Basin using both quantitative and qualitative assessments in 2017. The result shows that these altitudes are highly variable in many contexts: socioeconomic indicators of education, agriculture, income, women empowerment, health, access to basic resources, and livelihood diversifications are highly variable in the Indus Basin. The inhabitants of the Indus Basin perceive the climate changing around them and report impacts of this change as increase in overall temperatures (US 96.9%, MS 97%, DS 93.6%) and erratic rainfall patterns (US 44.1%, MS 73.3%, DS 51.0%) resulting in increased water availability for crops (US 38.6%, MS 39.7%, DS 54.8%) but also increasing number of dry days (US 56.7%, MS 85.5%, DS 67.1%). Communities at these altitudes said that agriculture was their primary source of income, making them particularly vulnerable to the effects of climate change and the dangers that go along with it. The insights are useful for determining what information and actions are required to support local climate-related hazard management in subtropical climate regions. Moreover, it is vital to launch a campaign to raise awareness of potential hazards, as well as to provide training and an early warning system.