bluuebunny/crossref_metadata_2025 huggingface dataset:
Matrix Metalloproteinase 10 Contributes to Choroidal Neovascularisation
Authors: González-Zamora Jorge , Hernandez María , Recalde Sergio , Bezunartea Jaione , Montoliu Ana , Bilbao-Malavé Valentina , Orbe Josune , Rodríguez José A. , Llorente-González Sara , Fernández-Robredo Patricia , García-Layana Alfredo
Published: July 2022

Age-related macular degeneration (AMD) is currently the main cause of severe visual loss among older adults in developed countries. The pathophysiology has not been clarified, but oxidative stress is believed to play a major role. Matrix metalloproteinases (MMP) may play a prominent role in several steps of the pathophysiology of AMD, especially in its neovascular form; therefore, there is of great interest in understanding their role in choroidal neovascularisation. This study aimed to elucidate the role of MMP10 in the development of choroidal neovascularisation (CNV). We have demonstrated that MMP10 was expressed by retinal pigment epithelium cells and endothelial cells of the neovascular membrane, in cell culture, mouse and human retina. MMP10 expression and activity increased under oxidative stress conditions in ARPE-19 cells. MMP10-/- mice developed smaller laser-induced areas of CNV. Furthermore, to exclude a systemic MMP10 imbalance in these patients, plasma MMP10 concentrations were assessed in an age- and sex-matched sample of 52 control patients and 52 patients with neovascular AMD and no significant differences were found between the groups, demonstrating that MMP10 induction is a local phenomenon. Our findings suggest that MMP10 participates in the development of choroidal neovascularisation and promotes MMP10 as a possible new therapeutic target.
High Diagnostic Accuracy of a Novel Lateral Flow Assay for the Point-of-Care Detection of SARS-CoV-2
Authors: Giberti Irene , Costa Elisabetta , Domnich Alexander , Ricucci Valentina , De Pace Vanessa , Garzillo Giada , Guarona Giulia , Icardi Giancarlo
Published: July 2022

Highly accurate lateral flow immunochromatographic tests (LFTs) are an important public health tool to tackle the ongoing COVID-19 pandemic. The aim of this study was to assess the comparative diagnostic performance of the novel ND COVID-19 LFT under real-world conditions. A total of 400 nasopharyngeal swab specimens with a wide range of viral loads were tested in both reverse-transcription polymerase chain reaction and ND LFT. The overall sensitivity and specificity were 85% (95% CI: 76.7–90.7%) and 100% (95% CI: 98.7–100%), respectively. There was a clear association between the false-negative rate and sample viral load: the sensitivity parameters for specimens with cycle threshold values of <25 (>3.95 × 106 copies/mL) and ≥30 (≤1.29 × 105 copies/mL) were 100% and 50%, respectively. The performance was maximized in testing samples with viral loads ≥1.29 × 105 copies/mL. These findings suggest that the ND LFT is sufficiently accurate and useful for mass population screening programs, especially in high-prevalence and resource-constrained settings or during periods when the epidemic curve is rising. Other public health implications were also discussed.
3D Printed Hydrogels for Ocular Wound Healing
Authors: Aghamirsalim Mohamadreza , Mobaraki Mohammadmahdi , Soltani Madjid , Kiani Shahvandi Mohammad , Jabbarvand Mahmoud , Afzali Elham , Raahemifar Kaamran
Published: July 2022

Corneal disease is one of the most significant causes of blindness around the world. Presently, corneal transplantation is the only way to treat cornea blindness. It should be noted that the amount of cornea that people donate is so much less than that required (1:70). Therefore, scientists have tried to resolve this problem with tissue engineering and regenerative medicine. Fabricating cornea with traditional methods is difficult due to their unique properties, such as transparency and geometry. Bioprinting is a technology based on additive manufacturing that can use different biomaterials as bioink for tissue engineering, and the emergence of 3D bioprinting presents a clear possibility to overcome this problem. This new technology requires special materials for printing scaffolds with acceptable biocompatibility. Hydrogels have received significant attention in the past 50 years, and they have been distinguished from other materials because of their unique and outstanding properties. Therefore, hydrogels could be a good bioink for the bioprinting of different scaffolds for corneal tissue engineering. In this review, we discuss the use of different types of hydrogel for bioink for corneal tissue engineering and various methods that have been used for bioprinting. Furthermore, the properties of hydrogels and different types of hydrogels are described.
Evaluation of Pro/Antioxidant Imbalance in Blood of Women with Polycystic Ovary Syndrome Based on Determination of Oxidized Low-Density Lipoproteins and Ferric Reducing Ability of Plasma Values
Authors: Niepsuj Justyna , Franik Grzegorz , Madej Paweł , Piwowar Agnieszka , Bizoń Anna
Published: July 2022

We investigated selected pro/antioxidant parameters in a group of women with polycystic ovary syndrome (PCOS) divided according to age, body mass index (BMI), waist-to-hip ratio (WHR), homeostatic model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (Quicki). We chose oxidized low-density lipoproteins (oxLDL-C) as a marker of oxidative stress and the ferric reducing ability of plasma (FRAP) as a marker of antioxidant status. In women with PCOS, the values of BMI, WHR, age and concentration of glucose significantly affected oxLDL-C concentration and FRAP values. FRAP correlated with oxLDL-C level in the whole group and in women who were insulin sensitive (HOMA-IR < 2.0). There was a negative relationship between the concentration of Anti-Müllerian hormone and both oxLDL-C and FRAP. Furthermore, the value of FRAP was inversely correlated with luteinizing hormone (LH), follicle-stimulating hormone (FSH) and androstenedione, whereas it was positively correlated with the LH/FSH ratio. The concentration of oxLDL and the value of FRAP are significantly associated with selected metabolic and hormonal parameters in the course of PCOS.
Re-Definition of the Epidemiology of Cardiac Amyloidosis
Authors: Rossi Maddalena , Varrà Guerino Giuseppe , Porcari Aldostefano , Saro Riccardo , Pagura Linda , Lalario Andrea , Dore Franca , Bussani Rossana , Sinagra Gianfranco , Merlo Marco
Published: July 2022

The epidemiology of cardiac amyloidosis (CA), traditionally considered a rare and incurable disease, has changed drastically over the last ten years, particularly due to the advances in diagnostic methods and therapeutic options in the field of transthyretin CA (ATTR-CA). On the one hand, the possibility of employing cardiac scintigraphy with bone tracers to diagnose ATTR-CA without a biopsy has unveiled the real prevalence of the disease; on the other, the emergence of effective treatments, such as tafamidis, has rendered an early and accurate diagnosis critical. Interestingly, the following subgroups of patients have been found to have a higher prevalence of CA: elderly subjects > 75 years, patients with cardiac hypertrophy hospitalized for heart failure with preserved ejection fraction, subjects operated on for bilateral carpal tunnel syndrome, patients with cardiac hypertrophy not explained by concomitant factors and individuals with aortic valve stenosis. Many studies investigating the prevalence of CA in these particular populations have contributed to rewriting the epidemiology of the disease, increasing the awareness of the medical community for a previously underappreciated condition. In this review, we summarized the latest evidence on the epidemiology of CA according to the different clinical settings typically associated with the disease.
Heterostructures Based on Cobalt Phthalocyanine Films Decorated with Gold Nanoparticles for the Detection of Low Concentrations of Ammonia and Nitric Oxide
Authors: Dorovskikh Svetlana I. , Klyamer Darya D. , Maksimovskiy Evgeny A. , Volchek Victoria V. , Zharkov Sergey M. , Morozova Natalia B. , Basova Tamara V.
Published: July 2022

This work is aimed at the development of new heterostructures based on cobalt phthalocyanines (CoPc) and gold nanoparticles (AuNPs), and the evaluation of the prospects of their use to determine low concentrations of ammonia and nitric oxide. For this purpose, CoPc films were decorated with AuNPs by gas-phase methods (MOCVD and PVD) and drop-casting (DC), and their chemiresistive sensor response to low concentrations of NO (10–50 ppb) and NH3 (1–10 ppm) was investigated. A comparative analysis of the characteristics of heterostructures depending on the preparation methods was carried out. The composition, structure, and morphology of the resulting hybrid films were studied by X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma atomic emission (ICP-AES) spectroscopy, as well as electron microscopy methods to discuss the effect of these parameters on the sensor response of hybrid films to ammonia and nitric oxide. It was shown that regardless of the fabrication method, the response of Au/CoPc heterostructures to NH3 and NO gases increased with an increase in the concentration of gold. The sensor response of Au/CoPc heterostructures to NH3 increased 2–3.3 times compared to CoPc film, whereas in the case of NO it increased up to 16 times. The detection limits of the Au/CoPc heterostructure with a gold content of ca. 2.1 µg/cm2 for NH3 and NO were 0.1 ppm and 4 ppb, respectively. It was shown that Au/CoPc heterostructures can be used for the detection of NH3 in a gas mixture simulating exhaled air (N2—74%, O2—16%, H2O—6%, CO2—4%).
Applications of Smartphone-Based Aptasensor for Diverse Targets Detection
Authors: Lan Ying , He Baixun , Tan Cherie S. , Ming Dong
Published: July 2022

Aptamers are a particular class of functional recognition ligands with high specificity and affinity to their targets. As the candidate recognition layer of biosensors, aptamers can be used to sense biomolecules. Aptasensors, aptamer-based biosensors, have been demonstrated to be specific, sensitive, and cost-effective. Furthermore, smartphone-based devices have shown their advantages in binding to aptasensors for point-of-care testing (POCT), which offers an immediate or spontaneous responding time for biological testing. This review describes smartphone-based aptasensors to detect various targets such as metal ions, nucleic acids, proteins, and cells. Additionally, the focus is also on aptasensors-related technologies and configurations.
Dual-Mode Tumor Imaging Using Probes That Are Responsive to Hypoxia-Induced Pathological Conditions
Authors: Subasinghe S. A. Amali S. , Pautler Robia G. , Samee Md. Abul Hassan , Yustein Jason T. , Allen Matthew J.
Published: July 2022

Hypoxia in solid tumors is associated with poor prognosis, increased aggressiveness, and strong resistance to therapeutics, making accurate monitoring of hypoxia important. Several imaging modalities have been used to study hypoxia, but each modality has inherent limitations. The use of a second modality can compensate for the limitations and validate the results of any single imaging modality. In this review, we describe dual-mode imaging systems for the detection of hypoxia that have been reported since the start of the 21st century. First, we provide a brief overview of the hallmarks of hypoxia used for imaging and the imaging modalities used to detect hypoxia, including optical imaging, ultrasound imaging, photoacoustic imaging, single-photon emission tomography, X-ray computed tomography, positron emission tomography, Cerenkov radiation energy transfer imaging, magnetic resonance imaging, electron paramagnetic resonance imaging, magnetic particle imaging, and surface-enhanced Raman spectroscopy, and mass spectrometric imaging. These overviews are followed by examples of hypoxia-relevant imaging using a mixture of probes for complementary single-mode imaging techniques. Then, we describe dual-mode molecular switches that are responsive in multiple imaging modalities to at least one hypoxia-induced pathological change. Finally, we offer future perspectives toward dual-mode imaging of hypoxia and hypoxia-induced pathophysiological changes in tumor microenvironments.
Electrochemical Biosensors Based on Convectively Assembled Colloidal Crystals
Authors: Shiohara Amane , Easton Christopher D. , Prieto-Simon Beatriz , Voelcker Nicolas H.
Published: July 2022

Rapid, sensitive, selective and portable virus detection is in high demand globally. However, differentiating non-infectious viral particles from intact/infectious viruses is still a rarely satisfied sensing requirement. Using the negative space within monolayers of polystyrene (PS) spheres deposited directly on gold electrodes, we fabricated tuneable nanochannels decorated with target-selective bioreceptors that facilitate the size-selective detection of intact viruses. Detection occurred through selective nanochannel blockage of diffusion of a redox probe, [Fe(CN)6]3/4−, allowing a quantifiable change in the oxidation current before and after analyte binding to the bioreceptor immobilised on the spheres. Our model system involved partial surface passivation of the mono-assembled PS spheres, by silica glancing angle deposition, to confine bioreceptor immobilisation specifically to the channels and improve particle detection sensitivity. Virus detection was first optimised and modelled with biotinylated gold nanoparticles, recognised by streptavidin immobilised on the PS layer, reaching a low limit of detection of 37 particles/mL. Intact, label-free virus detection was demonstrated using MS2 bacteriophage (~23–28 nm), a marker of microbiological contamination, showing an excellent limit of detection of ~1.0 pfu/mL. Tuneable nanochannel geometries constructed directly on sensing electrodes offer label-free, sensitive, and cost-efficient point-of-care biosensing platforms that could be applied for a wide range of viruses.
Spiking Neural Networks and Their Applications: A Review
Authors: Yamazaki Kashu , Vo-Ho Viet-Khoa , Bulsara Darshan , Le Ngan
Published: July 2022

The past decade has witnessed the great success of deep neural networks in various domains. However, deep neural networks are very resource-intensive in terms of energy consumption, data requirements, and high computational costs. With the recent increasing need for the autonomy of machines in the real world, e.g., self-driving vehicles, drones, and collaborative robots, exploitation of deep neural networks in those applications has been actively investigated. In those applications, energy and computational efficiencies are especially important because of the need for real-time responses and the limited energy supply. A promising solution to these previously infeasible applications has recently been given by biologically plausible spiking neural networks. Spiking neural networks aim to bridge the gap between neuroscience and machine learning, using biologically realistic models of neurons to carry out the computation. Due to their functional similarity to the biological neural network, spiking neural networks can embrace the sparsity found in biology and are highly compatible with temporal code. Our contributions in this work are: (i) we give a comprehensive review of theories of biological neurons; (ii) we present various existing spike-based neuron models, which have been studied in neuroscience; (iii) we detail synapse models; (iv) we provide a review of artificial neural networks; (v) we provide detailed guidance on how to train spike-based neuron models; (vi) we revise available spike-based neuron frameworks that have been developed to support implementing spiking neural networks; (vii) finally, we cover existing spiking neural network applications in computer vision and robotics domains. The paper concludes with discussions of future perspectives.
Postural Correlates of Pollution Perception
Authors: Akounach Mbarka , Lelard Thierry , Beaumont Anaïs , Granon Sylvie , Mouras Harold
Published: July 2022

In our contemporary societies, environmental issues are more and more important. An increasing number of studies explore the biological processes involved in environment perception and in particular try to highlight the mechanisms underlying the perception of environmental scenes by our brain. The main objective of the present study was to establish whether the visualization of clean and polluted environmental scenes would lead to differential postural reactions. Our hypothesis was based on a differential postural modulation that could be recorded when the subject is confronted with images representing a “polluted” environment, differential modulation which has been reported in previous studies in response to painful-scenes compared to non-painful scenes visualization.Thirty-one subjects participated in this study. Physiological measurements [heart rate variability (HRV) and electrodermal activity] and postural responses (Center Of Pression—COP—displacements) were recorded in response to perception of polluted or clean environmental scenes. We show, for the first time, that images representing polluted scenes evoke a weaker approach movement than images representing clean scenes. The displacement of the COP in the anteroposterior axis reflects an avoidance when subjects visualize “polluted” scenes. Our results demonstrate a clear distinction between “clean” and “polluted” environments according to the postural change they induce, correlated with the ratings of pleasure and approach evoked by images.
Model of Demand of Human Settlement Environment for Rural Houses in North China: A Structural Equation Modeling Approach
Authors: Chen Bin , Chen Yajing , Chen Yu , Gao Jin
Published: July 2022

Numerous studies have shown that the technology used to improve the living environment in rural areas often loses its effect in a few years, and farmers return to their familiar and habitual way of life. The failure to consider the basic needs of farmers is an important reason for these problems. Therefore, this study conducted qualitative and quantitative analyses on the factors that influence the demand on the human settlement environment through visits, field measurements, a questionnaire survey (which involved more than 20 households in 14 villages in seven provinces and cities in northern China), and the construction of a structural equation model based on demand. The survey included (amongst other factors) personal attributes, daily living, diet and environmental preferences, living customs and energy consumption, housing construction methods, and the surrounding environment. The results showed that, compared with mental happiness (0.084) and physical health (0.119), socioeconomic status (0.260) had a greater influence on the weight of the overall demand satisfaction among the various demand indicators. Farmers prioritized yard planning (0.135), toilets (0.126), and living rooms (0.095). They also gave importance to the indoor thermal environment (0.088), air quality (0.088), and food problems (0.087). The findings of this study provide a theoretical reference for the inception of technical approaches to improve human settlement environment centered on rural houses in North China, and the realization of sustainable development in the future.
Development of Lightweight Steel Framed Construction Systems for Nearly-Zero Energy Buildings
Authors: Jelčić Rukavina Marija , Skejić Davor , Kralj Anton , Ščapec Tomislav , Milovanović Bojan
Published: July 2022

Light steel frame (LSF) building systems offer high structural resilience, lower costs due to fast prefabrication, and high ability to recycle and reuse. The main goal of this paper was to provide state-of-the-art main components for such systems with the intention to be implemented for use in nearly-zero energy buildings (NZEBs). A brief historical outline of the development of LSF systems was given, and the key parameters affecting the design and use of LSF systems were discussed. The influence of the individual components of the LSF system (steel studs, sheathing boards, and insulation materials) was then thoroughly discussed in light of relevant research on energy efficiency and other important properties (such as sound protection and fire resistance). Web of Science and Scopus databases were used for this purpose, using relevant key words: LSF, energy efficiency, sheathing boards, steel studs, insulation, etc. Several research gaps were identified that could be used for development and future research on new LSF systems. Finally, based on the analysis of each component, an innovative LSF composite wall panel was proposed which will be the subject of the authors’ future research. Conducted preliminary analysis showed low thermal transmittance of the system and indicates the path of its further research.
Development of an FEM-DEM Model to Investigate Preliminary Compaction of Asphalt Pavements
Authors: Liu Pengfei , Wang Chonghui , Lu Wei , Moharekpour Milad , Oeser Markus , Wang Dawei
Published: July 2022

Variations in pavement density have been widely monitored and investigated, both in laboratory and in field experiments, since the compaction of pavement is so critical to its long-term performance quality. In contrast to field testing, laboratory tests are simpler to produce but less accurate. Destructive drilled samples are used to conduct field testing; however, they are limited in their ability to assess density information at specific areas. The use of computationally aided approaches, such as the Finite Element Method (FEM) and the Discrete Element Method (DEM), in research involving asphalt mixtures is increasing, since these methods simulate and evaluate the characteristics of asphalt mixtures at macroscopic and microscopic scales. Individual particle behavior at the microscopic level cannot be fully represented using the FEM alone, and the computing cost of utilizing the DEM approach alone is prohibitively high. The objective of this work is to simulate the pre-compaction process by using the coupled FEM-DEM approach. In order to investigate the impact of the asphalt mixtures’ gradation, a dense-graded asphalt mixture (AC 11) and a gap graded asphalt mixture (PA 11) were simulated. Different paving speeds (4, 5, and 6 m/min) were applied on the preliminary compaction model of AC 11 to study the effect of the paving speeds on the compaction process. By comparing the angular velocity, which worked as a reference of compaction quality, it was demonstrated that the grade AC 11 asphalt mixtures performed better in the preliminary compaction process compared to the grade PA 11 asphalt mixtures. Moreover, since it has an effect on compaction, paving speed was carefully monitored and kept within a reasonable range in order to maximize both pavement quality and project efficiency.
Tri-Compartmental Restriction Spectrum Imaging Breast Model Distinguishes Malignant Lesions from Benign Lesions and Healthy Tissue on Diffusion-Weighted Imaging
Authors: Besser Alexandra H. , Fang Lauren K. , Tong Michelle W. , Sjaastad Andreassen Maren M. , Ojeda-Fournier Haydee , Conlin Christopher C. , Loubrie Stéphane , Seibert Tyler M. , Hahn Michael E. , Kuperman Joshua M. , Wallace Anne M. , Dale Anders M. , Rodríguez-Soto Ana E. , Rakow-Penner Rebecca A.
Published: July 2022

Diffusion-weighted MRI (DW-MRI) offers a potential adjunct to dynamic contrast-enhanced MRI to discriminate benign from malignant breast lesions by yielding quantitative information about tissue microstructure. Multi-component modeling of the DW-MRI signal over an extended b-value range (up to 3000 s/mm2) theoretically isolates the slowly diffusing (restricted) water component in tissues. Previously, a three-component restriction spectrum imaging (RSI) model demonstrated the ability to distinguish malignant lesions from healthy breast tissue. We further evaluated the utility of this three-component model to differentiate malignant from benign lesions and healthy tissue in 12 patients with known malignancy and synchronous pathology-proven benign lesions. The signal contributions from three distinct diffusion compartments were measured to generate parametric maps corresponding to diffusivity on a voxel-wise basis. The three-component model discriminated malignant from benign and healthy tissue, particularly using the restricted diffusion C1 compartment and product of the restricted and intermediate diffusion compartments (C1 and C2). However, benign lesions and healthy tissue did not significantly differ in diffusion characteristics. Quantitative discrimination of these three tissue types (malignant, benign, and healthy) in non-pre-defined lesions may enhance the clinical utility of DW-MRI in reducing excessive biopsies and aiding in surveillance and surgical evaluation without repeated exposure to gadolinium contrast.
Machine Learning Based on MRI DWI Radiomics Features for Prognostic Prediction in Nasopharyngeal Carcinoma
Authors: Hu Qiyi , Wang Guojie , Song Xiaoyi , Wan Jingjing , Li Man , Zhang Fan , Chen Qingling , Cao Xiaoling , Li Shaolin , Wang Ying
Published: July 2022

Purpose: This study aimed to explore the predictive efficacy of radiomics analyses based on readout-segmented echo-planar diffusion-weighted imaging (RESOLVE-DWI) for prognosis evaluation in nasopharyngeal carcinoma in order to provide further information for clinical decision making and intervention. Methods: A total of 154 patients with untreated NPC confirmed by pathological examination were enrolled, and the pretreatment magnetic resonance image (MRI)—including diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) maps, T2-weighted imaging (T2WI), and contrast-enhanced T1-weighted imaging (CE-T1WI)—was collected. The Random Forest (RF) algorithm selected radiomics features and established the machine-learning models. Five models, namely model 1 (DWI + ADC), model 2 (T2WI + CE-T1WI), model 3 (DWI + ADC + T2WI), model 4 (DWI + ADC + CE-T1WI), and model 5 (DWI + ADC + T2WI + CE-T1WI), were constructed. The average area under the curve (AUC) of the validation set was determined in order to compare the predictive efficacy for prognosis evaluation. Results: After adjusting the parameters, the RF machine learning models based on extracted imaging features from different sequence combinations were obtained. The invalidation sets of model 1 (DWI + ADC) yielded the highest average AUC of 0.80 (95% CI: 0.79–0.81). The average AUCs of the model 2, 3, 4, and 5 invalidation sets were 0.72 (95% CI: 0.71–0.74), 0.66 (95% CI: 0.64–0.68), 0.74 (95% CI: 0.73–0.75), and 0.75 (95% CI: 0.74–0.76), respectively. Conclusion: A radiomics model derived from the MRI DWI of patients with nasopharyngeal carcinoma was generated in order to evaluate the risk of recurrence and metastasis. The model based on MRI DWI can provide an alternative approach for survival estimation, and can reveal more information for clinical decision-making and intervention.
Non-Operative Management of Patients with Rectal Cancer: Lessons Learnt from the OPRA Trial
Authors: Goffredo Paolo , Quezada-Diaz Felipe F. , Garcia-Aguilar Julio , Smith J. Joshua
Published: July 2022

Over the past decade, the management of locally advanced rectal cancer (LARC) has progressively become more complex. The introduction of total neoadjuvant treatment (TNT) has increased the rates of both clinical and pathological complete response, resulting in excellent long-term oncological outcomes. As a result, non-operative management (NOM) of LARC patients with a clinical complete response (cCR) after neoadjuvant therapy has gained acceptance as a potential treatment option in selected cases. NOM is based on replacement of surgical resection with safe and active surveillance. However, the identification of appropriate candidates for a NOM strategy without compromising oncologic safety is currently challenging due to the lack of an objective standardization. NOM should be part of the treatment plan discussion with LARC patients, considering the increasing rates of cCR, patient preference, quality of life, expectations, and the potential avoidance of surgical morbidity. The recently published OPRA trial showed that organ preservation is achievable in half of rectal cancer patients treated with TNT, and that chemoradiotherapy followed by consolidation chemotherapy may an appropriate strategy to maximize cCR rates. Ongoing trials are investigating optimal algorithms of TNT delivery to further expand the pool of patients who may benefit from NOM of LARC.
New Perspectives on the Role of Integrin-Linked Kinase (ILK) Signaling in Cancer Metastasis
Authors: McDonald Paul C. , Dedhar Shoukat
Published: July 2022

Cancer metastasis is a major barrier to the long-term survival of cancer patients. In cancer cells, integrin engagement downstream of cell-extracellular matrix (ECM) interactions results in the recruitment of cytoskeletal and signaling molecules to form multi-protein complexes to promote processes critical for metastasis. One of the major functional components of these complexes is Integrin Linked Kinase (ILK). Here, we discuss recent advances in our understanding of the importance of ILK as a signaling effector in processes linked to tumor progression and metastasis. New mechanistic insights as to the role of ILK in cellular plasticity, epithelial mesenchymal transition (EMT), migration, and invasion, including the impact of ILK on the formation of invadopodia, filopodia-like protrusions (FLPs), and Neutrophil Extracellular Trap (NET)-induced motility are highlighted. Recent findings detailing the contribution of ILK to therapeutic resistance and the importance of ILK as a potentially therapeutically tractable vulnerability in both solid tumors and hematologic malignancies are discussed. Indeed, pharmacologic inhibition of ILK activity using specific small molecule inhibitors is effective in curtailing the contribution of ILK to these processes, potentially offering a novel therapeutic avenue for inhibiting critical steps in the metastatic cascade leading to reduced drug resistance and increased therapeutic efficacy.
Could We Predict the Response of Immune Checkpoint Inhibitor Treatment in Hepatocellular Carcinoma?
Authors: Lee Choong-kun , Chan Stephen L. , Chon Hong Jae
Published: July 2022

The use of anti-programmed cell-death protein (ligand)-1 (PD-[L]1) is an important strategy for treating hepatocellular carcinoma (HCC). However, the treatment only benefits 10–20% of patients when used as a monotherapy. Therefore, the selection of patients for anti-PD-1/PD-L1 treatment is crucial for both patients and clinicians. This review aimed to explore the existing literature on tissue or circulating markers for the identification of responders or non-responders to anti-PD-1/PD-L1 in HCC. For the clinically available markers, both etiological factors (viral versus non-viral) and disease extent (intra-hepatic vs. extrahepatic) impact the responses to anti-PD-1/PD-L1, warranting further studies. Preliminary data suggested that inflammatory indices (e.g., neutrophil-lymphocyte ratio) may be associated with clinical outcomes of HCC during the anti-PD-1/PD-L1 treatment. Finally, although PD-L1 expression in tumor tissues is a predictive marker for multiple cancer types, its clinical application is less clear in HCC due to the lack of a clear-cut association with responders to anti-PD-1/PD-L1 treatment. Although all translational markers are not routinely measured in HCC, recent data suggest their potential roles in selecting patients for anti-PD-1/PD-L1 treatment. Such markers, including the immune classification of HCC, selected signaling pathways, tumor-infiltrating lymphocytes, and auto-antibodies, were discussed in this review.
Analysis of Exosomal Cargo Provides Accurate Clinical, Histologic and Mutational Information in Non-Small Cell Lung Cancer
Authors: Duréndez-Sáez Elena , Calabuig-Fariñas Silvia , Torres-Martínez Susana , Moreno-Manuel Andrea , Herreros-Pomares Alejandro , Escorihuela Eva , Mosqueda Marais , Gallach Sandra , Guijarro Ricardo , Serna Eva , Suárez-Cabrera Cristian , Paramio Jesús M. , Blasco Ana , Camps Carlos , Jantus-Lewintre Eloisa
Published: July 2022

Lung cancer is a malignant disease with high mortality and poor prognosis, frequently diagnosed at advanced stages. Nowadays, immense progress in treatment has been achieved. However, the present scenario continues to be critical, and a full comprehension of tumor progression mechanisms is required, with exosomes being potentially relevant players. Exosomes are membranous vesicles that contain biological information, which can be transported cell-to-cell and modulate relevant processes in the hallmarks of cancer. The present research aims to characterize the exosomes’ cargo and study their role in NSCLC to identify biomarkers. We analyzed exosomes secreted by primary cultures and cell lines, grown in monolayer and tumorsphere formations. Exosomal DNA content showed molecular alterations, whereas RNA high-throughput analysis resulted in a pattern of differentially expressed genes depending on histology. The most significant differences were found in XAGE1B, CABYR, NKX2-1, SEPP1, CAPRIN1, and RIOK3 genes when samples from two independent cohorts of resected NSCLC patients were analyzed. We identified and validated biomarkers for adenocarcinoma and squamous cell carcinoma. Our results could represent a relevant contribution concerning exosomes in clinical practice, allowing for the identification of biomarkers that provide information regarding tumor features, prognosis and clinical behavior of the disease.
The Role of microRNAs in Multidrug Resistance of Glioblastoma
Authors: Mahinfar Parvaneh , Mansoori Behnaz , Rostamzadeh Davoud , Baradaran Behzad , Cho William C. , Mansoori Behzad
Published: July 2022

Glioblastoma (GBM) is an aggressive brain tumor that develops from neuroglial stem cells and represents a highly heterogeneous group of neoplasms. These tumors are predominantly correlated with a dismal prognosis and poor quality of life. In spite of major advances in developing novel and effective therapeutic strategies for patients with glioblastoma, multidrug resistance (MDR) is considered to be the major reason for treatment failure. Several mechanisms contribute to MDR in GBM, including upregulation of MDR transporters, alterations in the metabolism of drugs, dysregulation of apoptosis, defects in DNA repair, cancer stem cells, and epithelial–mesenchymal transition. MicroRNAs (miRNAs) are a large class of endogenous RNAs that participate in various cell events, including the mechanisms causing MDR in glioblastoma. In this review, we discuss the role of miRNAs in the regulation of the underlying mechanisms in MDR glioblastoma which will open up new avenues of inquiry for the treatment of glioblastoma.
Deep Learning Model for Grading Metastatic Epidural Spinal Cord Compression on Staging CT
Authors: Hallinan James Thomas Patrick Decourcy , Zhu Lei , Zhang Wenqiao , Kuah Tricia , Lim Desmond Shi Wei , Low Xi Zhen , Cheng Amanda J. L. , Eide Sterling Ellis , Ong Han Yang , Muhamat Nor Faimee Erwan , Alsooreti Ahmed Mohamed , AlMuhaish Mona I. , Yeong Kuan Yuen , Teo Ee Chin , Barr Kumarakulasinghe Nesaretnam , Yap Qai Ven , Chan Yiong Huak , Lin Shuxun , Tan Jiong Hao , Kumar Naresh , Vellayappan Balamurugan A. , Ooi Beng Chin , Quek Swee Tian , Makmur Andrew
Published: July 2022

Background: Metastatic epidural spinal cord compression (MESCC) is a disastrous complication of advanced malignancy. Deep learning (DL) models for automatic MESCC classification on staging CT were developed to aid earlier diagnosis. Methods: This retrospective study included 444 CT staging studies from 185 patients with suspected MESCC who underwent MRI spine studies within 60 days of the CT studies. The DL model training/validation dataset consisted of 316/358 (88%) and the test set of 42/358 (12%) CT studies. Training/validation and test datasets were labeled in consensus by two subspecialized radiologists (6 and 11-years-experience) using the MRI studies as the reference standard. Test sets were labeled by the developed DL models and four radiologists (2–7 years of experience) for comparison. Results: DL models showed almost-perfect interobserver agreement for classification of CT spine images into normal, low, and high-grade MESCC, with kappas ranging from 0.873–0.911 (p < 0.001). The DL models (lowest κ = 0.873, 95% CI 0.858–0.887) also showed superior interobserver agreement compared to two of the four radiologists for three-class classification, including a specialist (κ = 0.820, 95% CI 0.803–0.837) and general radiologist (κ = 0.726, 95% CI 0.706–0.747), both p < 0.001. Conclusion: DL models for the MESCC classification on a CT showed comparable to superior interobserver agreement to radiologists and could be used to aid earlier diagnosis.
The Comparative Safety of Epirubicin and Cyclophosphamide versus Docetaxel and Cyclophosphamide in Lymph Node-Negative, HR-Positive, HER2-Negative Breast Cancer (ELEGANT): A Randomized Trial
Authors: Liu Deyue , Wu Jiayi , Lin Caijin , Ding Shuning , Lu Shuangshuang , Fang Yan , Huang Jiahui , Hong Jin , Gao Weiqi , Zhu Siji , Chen Xiaosong , Huang Ou , He Jianrong , Chen Weiguo , Li Yafen , Shen Kunwei , Zhu Li
Published: July 2022

Background: In adjuvant settings, epirubicin and cyclophosphamide (EC) and docetaxel and cyclophosphamide (TC) are both optional chemotherapy regimens for lymph node-negative, hormone receptor (HR)-positive, human epidermal receptor 2 (HER2)-negative breast cancer patients. Neutropenia is one of the most common adverse events (AEs) of these regimens. The rate of grade 3–4 neutropenia varies in different studies, and direct comparisons of safety profiles between EC and TC are lacking. Method: ELEGANT (NCT02549677) is a prospective, randomized, open-label, noninferior hematological safety trial. Eligible patients with lymph node-negative HR+/HER2-tumors (1:1) were randomly assigned to received four cycles of EC (90/600 mg/m2) or TC (75/600 mg/m2) every three weeks as adjuvant chemotherapy. The primary endpoint was the incidence of grade 3 or 4 neutropenia defined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 on an intention-to-treat basis. Noninferiority was defined as an upper 95% CI less than a noninferiority margin of 15%. Results: In the intention-to-treat population, 140 and 135 patients were randomized into the EC and TC arms, respectively. For the primary endpoint, the rate of grade 3 or 4 neutropenia is 50.71% (95% CI: 42.18%, 59.21%) in the EC arm and 48.15% (95% CI: 39.53%, 56.87%) in the TC arm (95%CI risk difference: −0.100, 0.151), showing the noninferiority of the EC arm. For secondary endpoints, the rate of all-grade anemia is higher in the EC arm (EC 42.86% versus TC 22.96%, p = 0.0007), and more patients suffer from nausea/vomiting, hair loss, and nail changes (p < 0.01) in the EC arm. No statistically different disease-free survival was observed between the two arms (p = 0.13). Conclusion: EC is not inferior to TC in the rate of grade 3 or 4 neutropenia, but more other AEs were observed in the EC group.
Oxidative-Stress-Sensitive microRNAs in UV-Promoted Development of Melanoma
Authors: Pecorelli Alessandra , Valacchi Giuseppe
Published: July 2022

Melanoma is the most aggressive and life-threatening form of skin cancer. Key molecular events underlying the melanocytic transformation into malignant melanoma mainly involve gene mutations in which exposure to ultraviolet (UV) radiation plays a prominent role. However, several aspects of UV-induced melanomagenesis remain to be explored. Interestingly, redox-mediated signaling and perturbed microRNA (miRNA) profiles appear to be interconnected contributing factors able to act synergistically in melanoma initiation and progression. Since UV radiation can promote both redox imbalance and miRNA dysregulation, a harmful crosstalk between these two key cellular networks, with UV as central hub among them, is likely to occur in skin tissue. Therefore, decoding the complex circuits that orchestrate the interaction of UV exposure, oxidative stress, and dysregulated miRNA profiling can provide a deep understanding of the molecular basis of the melanomagenesis process. Furthermore, these mechanistic insights into the reciprocal regulation between these systems could have relevant implications for future therapeutic approaches aimed at counteracting UV-induced redox and miRNome imbalances for the prevention and treatment of malignant melanoma. In this review, we illustrate current information on the intricate connection between UV-induced dysregulation of redox-sensitive miRNAs and well-known signaling pathways involved in the malignant transformation of normal melanocytes to malignant melanoma.
New Insights into the Multivariate Analysis of SER Spectra Collected on Blood Samples for Prostate Cancer Detection: Towards a Better Understanding of the Role Played by Different Biomolecules on Cancer Screening: A Preliminary Study
Authors: Munteanu Vlad Cristian , Munteanu Raluca Andrada , Gulei Diana , Mărginean Radu , Schițcu Vlad Horia , Onaciu Anca , Toma Valentin , Știufiuc Gabriela Fabiola , Coman Ioan , Știufiuc Rareș Ionuț
Published: July 2022

It is possible to obtain diagnostically relevant data on the changes in biochemical elements brought on by cancer via the use of multivariate analysis of vibrational spectra recorded on biological fluids. Prostate cancer and control groups included in this research generated almost similar SERS spectra, which means that the values of peak intensities present in SERS spectra can only give unspecific and limited information for distinguishing between the two groups. Our diagnostic algorithm for prostate cancer (PCa) differentiation was built using principal component analysis and linear discriminant analysis (PCA-LDA) analysis of spectral data, which has been widely used in spectral data management in many studies and has shown promising results so far. In order to fully utilize the entire SERS spectrum and automatically determine the most meaningful spectral features that can be used to differentiate PCa from healthy patients, we perform a multivariate analysis on both the entire and specific spectral intervals. Using the PCA-LDA model, the prostate cancer and control groups are clearly distinguished in our investigation. The separability of the following two data sets is also evaluated using two alternative discrimination techniques: principal least squares discriminant analysis (PLS-DA) and principal component analysis—support vector machine (PCA-SVM).
Body Mass Index Is Inversely Associated with Risk of Postmenopausal Interval Breast Cancer: Results from the Women’s Health Initiative
Authors: Zhang Zhenzhen , Curran Grace , Shannon Jackilen , Velie Ellen M. , Irvin Veronica L. , Manson JoAnn E. , Simon Michael S. , Altinok Dindar Duygu , Pyle Chelsea , Schedin Pepper , Tabung Fred K.
Published: July 2022

Interval breast cancer refers to cancer diagnosed after a negative screening mammogram and before the next scheduled screening mammogram. Interval breast cancer has worse prognosis than screening-detected cancer. Body mass index (BMI) influences the accuracy of mammography and overall postmenopausal breast cancer risk, yet how is obesity associated with postmenopausal interval breast cancer incidence is unclear. The current study included cancer-free postmenopausal women aged 50–79 years at enrollment in the Women’s Health Initiative who were diagnosed with breast cancer during follow-up. Analyses include 324 interval breast cancer cases diagnosed within one year after the participant’s last negative screening mammogram and 1969 screening-detected breast cancer patients. Obesity (BMI ≥ 30 kg/m2) was measured at baseline. Associations between obesity and incidence of interval cancer were determined by sequential logistic regression analyses. In multivariable-adjusted models, obesity was inversely associated with interval breast cancer risk [OR (95% CI) = 0.65 (0.46, 0.92)]. The inverse association persisted after excluding women diagnosed within 2 years [OR (95% CI) = 0.60 (0.42, 0.87)] or 4 years [OR (95% CI) = 0.56 (0.37, 0.86)] of enrollment, suggesting consistency of the association regardless of screening practices prior to trial entry. These findings warrant confirmation in studies with body composition measures.
Tumor Microenvironment and Immunotherapy-Based Approaches in Mantle Cell Lymphoma
Authors: Saleh Khalil , Cheminant Morgane , Chiron David , Burroni Barbara , Ribrag Vincent , Sarkozy Clémentine
Published: July 2022

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) characterized by the translocation t(11;14) (q13;q32) and a poor response to rituximab–anthracycline-based chemotherapy. High-dose cytarabine-based regimens offer a durable response, but an important number of MCL patients are not eligible for intensive treatment and are ideal candidates for novel targeted therapies (such as BTK, proteasome or BCL2 inhibitors, Immunomodulatory Drugs (IMiDs), bispecific antibodies, or CAR-T cell therapy). On the bench side, several studies aiming to integrate the tumor within its ecosystem highlighted a critical role of the tumor microenvironment (TME) in the expansion and resistance of MCL. This led to important insights into the role of the TME in the management of MCL, including potential targets and biomarkers. Indeed, targeted agents often have a combined mechanism of action on the tumor B cell but also on the tumor microenvironment. The aim of this review is to briefly describe the current knowledge on the biology of the TME in MCL and expose the results of the different therapeutic strategies integrating the TME in this disease.
Current Status and Perspectives of Dual-Targeting Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Hematological Malignancies
Authors: Xie Bailu , Li Zhengdong , Zhou Jianfeng , Wang Wen
Published: July 2022

Single-targeted chimeric antigen receptor (CAR) T cells tremendously improve outcomes for patients with relapsed/refractory hematological malignancies and are considered a breakthrough therapy. However, over half of treated patients experience relapse or refractory disease, with antigen escape being one of the main contributing mechanisms. Dual-targeting CAR T-cell therapy is being developed to minimize the risk of relapse or refractory disease. Preclinical and clinical data on five categories of dual-targeting CAR T-cell therapies and approximately fifty studies were summarized to offer insights and support the development of dual-targeting CAR T-cell therapy for hematological malignancies. The clinical efficacy (durability and survival) is validated and the safety profiles of dual-targeting CAR T-cell therapy are acceptable, although there is still room for improvement in the bispecific CAR structure. It is one of the best approaches to optimize the bispecific CAR structure by boosting T-cell transduction efficiency and leveraging evidence from preclinical activity and clinical efficacy.