bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Innovative Processing Methods on Microalgae Cell Wall: Prospects towards Digestibility of Protein-Rich Biomass
Authors: Machado Luís , Carvalho Gonçalo , Pereira Ricardo N.
Published: April 2022

Microalgae are known to have higher photosynthetic efficiencies when compared to land-based plants. The use of microalgae biomass as a protein source is attracting attention due to its interesting protein composition and sustainable character when compared to conventional animal and plant protein-based sources. Nonetheless, the existence of a rigid cell wall is typical for most microalgae species, and this presents a serious obstacle to a higher bioaccessibility of their valuable protein fractions. Depending on the cell wall composition, the gastrointestinal digestion process itself can result in different pathways of protein absorption. It is then important to understand how microalgae cell wall structure can be affected during traditional and industrial production of its biomass once these questions are often overlooked. This review intends to fulfill this gap by addressing the major impacts of innovative sustainable processing of microalgae biomass, giving particular attention to drying operations and cellular disruption methods based on electric field application—such as pulsed electric fields (PEF) and moderate electric fields (MEF). Using microalgae biomass as food supplements at its full potential depends on its protein digestibility patterns, and subsequently their bioaccessibility and bioavailability. The importance of using in vitro gastrointestinal systems to understand the impact of innovative downstream processing of microalgae biomass will be addressed.
Feasibility of a Full-Field Measurements-Based Protocol for the Biomechanical Study of a Lumbar Belt: A Case Study
Authors: Bonnaire Rébecca , Han Woo Suck , Convert Reynald , Calmels Paul , Molimard Jérôme
Published: April 2022

Low back pain represents a major economic and societal challenge due to its high prevalence. Lumbar orthoses are one of the recommended treatments. Even if previous results showed their clinical effects, the detailed mode of action is still poorly known, making the device design difficult. A renewed instrumentation and experimental protocol should bring better insight into the lumbar brace–trunk mechanical interaction. This instrumentation should give detailed information on the basic physical or geometrical parameters: the pressure applied on the trunk, the body shape and the strain in the belt. The principal objective of this study was to propose and validate a new measurement protocol, based on pressure mapping systems and full-field shape and strain measurement. The feasibility of the protocol was tested along with its validity and repeatability. The influence of various parameters, which could cause changes in the measurements, was tested with six different belt configurations on one subject. Measurements were also performed to study the impact of posture on pressure and strain. Both pressure and strain appeared to be asymmetric from left to right. The pressure applied by the lumbar belt on the back varies with breathing and with posture. This study showed that full-field measurements were necessary to render the high variability of pressure or strain around the trunk, under recommendations of their use to guarantee a satisfying repeatability.
Augmented Sensitivity of At-Home Rapid SARS-CoV-2 Antigen Test (RAT) Kits with Computer Vision: A Framework and Proof of Concept
Authors: Miikki Kim , Miikki Lars , Wiklund Jenny , Karakoç Alp
Published: April 2022

At-home rapid antigen test (RAT) kits for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are valuable public health tools during the present coronavirus disease (COVID-19) pandemic. They provide fast identification of coronavirus infection, which can help to reduce the transmission rates and burden on the healthcare system. However, they have lower sensitivity compared to the reverse transcription polymerase chain reaction (RT-PCR) tests. One of the reasons for the lower sensitivity is due to the RAT color indicators being indistinct or invisible to the naked eye after the measurements. For this reason, we present a proof of concept of a novel approach, through which we investigated anonymously provided at-home RAT kit results by using our in-house open-source image processing scripts developed for affordable Raspberry Pi computer and Raspberry Pi HQ camera systems. Therefore, we aimed at minimizing the human-related analysis errors for such kits and believe that the present computer vision-based assessment framework can contribute to reducing delayed quarantines of infected individuals and the spread of the current infectious disease.
Vitamin D Impacts on Skeletal Muscle Dysfunction in Patients with COPD Promoting Mitochondrial Health
Authors: Russo Cristina , Valle Maria Stella , Casabona Antonino , Spicuzza Lucia , Sambataro Gianluca , Malaguarnera Lucia
Published: April 2022

Skeletal muscle dysfunction is frequently associated with chronic obstructive pulmonary disease (COPD), which is characterized by a permanent airflow limitation, with a worsening respiratory disorder during disease evolution. In COPD, the pathophysiological changes related to the chronic inflammatory state affect oxidant–antioxidant balance, which is one of the main mechanisms accompanying extra-pulmonary comorbidity such as muscle wasting. Muscle impairment is characterized by alterations on muscle fiber architecture, contractile protein integrity, and mitochondrial dysfunction. Exogenous and endogenous sources of reactive oxygen species (ROS) are present in COPD pathology. One of the endogenous sources of ROS is represented by mitochondria. Evidence demonstrated that vitamin D plays a crucial role for the maintenance of skeletal muscle health. Vitamin D deficiency affects oxidative stress and mitochondrial function influencing disease course through an effect on muscle function in COPD patients. This review will focus on vitamin-D-linked mechanisms that could modulate and ameliorate the damage response to free radicals in muscle fibers, evaluating vitamin D supplementation with enough potent effect to contrast mitochondrial impairment, but which avoids potential severe side effects.
Potential Therapeutic Targets and Promising Agents for Combating NAFLD
Authors: Umemura Atsushi , Kataoka Seita , Okuda Keiichiro , Seko Yuya , Yamaguchi Kanji , Moriguchi Michihisa , Okanoue Takeshi , Itoh Yoshito
Published: April 2022

Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), is a growing cause of liver cirrhosis and liver cancer worldwide because of the global increases in obesity, dyslipidemia, hypertension, and type 2 diabetes mellitus. Contrary to the advancements in therapies for viral hepatitis, effective treatments remain unestablished for patients with NAFLD. NAFLD, including NASH, is characterized by steatosis, inflammation, hepatic necrosis, and fibrosis. Despite our understanding of its pathophysiology, there are currently no effective treatments for NAFLD. In this review, we provide an update on the known pathophysiological mechanisms involved in the development of NAFLD and the role of hepatic stellate cells, and summarize the potential therapeutic agents, including natural products, for NAFLD.
Translational Applications of Extracorporeal Shock Waves in Dental Medicine: A Literature Review
Authors: Alshihri Abdulmonem
Published: April 2022

Extracorporeal shock wave therapy (ESWT) has been studied and applied extensively in medical practice for various applications including musculoskeletal, dermal, vascular, and cardiac indications. These indications have emerged from primary ESWT use in treating urolithiasis and cholelithiasis. Likewise, dental medicine has had its share of utilizing ESWT in various investigations. This review aimed to provide an up-to-date summary of ESWT use in preclinical and clinical dental medicine. There is growing interest in ESWT use stemming from its non-invasiveness, low cost, and safe qualities in addition to its proven regenerative biostimulating aspects. Targeted tissue and parameters of ESWT delivery continue to be an integral part of successful ESWT treatment to attain the clinical value of the anticipated dose’s effect.
Optimization Strategies Used for Boosting Piezoelectric Response of Biosensor Based on Flexible Micro-ZnO Composites
Authors: Zhang Xiaoting , Villafuerte Jose , Consonni Vincent , Sarigiannidou Eirini , Capsal Jean-Fabien , Bruhat Alexis , Grinberg Daniel , Petit Lionel , Cottinet Pierre-Jean , Le Minh-Quyen
Published: April 2022

Piezoelectric ZnO-based composites have been explored as a flexible and compact sensor for the implantable biomedical systems used in cardio surgery. In this work, a progressive development route was investigated to enhance the performance of piezoelectric composites incorporated with different shape, concentration and connectivity of ZnO fillers. ZnO microrods (MRs) have been successfully synthesized homogeneously in aqueous solution using a novel process-based on chemical bath deposition (CBD) method. The morphological analysis along with Raman scattering and cathodoluminescence spectroscopy of ZnO MRs confirm their high crystalline quality, their orientation along the polar c-axis and the presence of hydrogen-related defects acting as shallow donors in their center. The experimental characterizations highlight that ZnO MR-based composites, with a higher aspect ratio (AR), lead to a significant improvement in the mechanical, dielectric and piezoelectric properties as opposed to the ZnO microparticles (MP) counterparts. The dielectrophoretic (DEP) process is then subjected to both ZnO MP- and MR-based composites, whose performance is expected to be improved as compared to the randomly dispersed composites, thanks to the creation of chain-like structures along the electric field direction. Furthermore, a numerical simulation using COMSOL software is developed to evaluate the influence of the material structuration as well as the filler’s shape on the electric field distribution within different phases (filler, matrix and interface) of the composites. Finally, the aligned MR piezoelectric composites are revealed to be high potential in the development of innovative compact and biocompatible force-sensing devices. Such a technological breakthrough allows the achievement of a real-time precise characterization of mitral valve (MV) coaptation to assist surgeons during MV repair surgery.
Circulating Exosomal-DNA in Glioma Patients: A Quantitative Study and Histopathological Correlations—A Preliminary Study
Authors: Piazza Amedeo , Rosa Paolo , Ricciardi Luca , Mangraviti Antonella , Pacini Luca , Calogero Antonella , Raco Antonino , Miscusi Massimo
Published: April 2022

Glial neoplasms are a group of diseases with poor prognoses. Not all risk factors are known, and no screening tests are available. Only histology provides certain diagnosis. As already reported, DNA transported by exosomes can be an excellent source of information shared by cells locally or systemically. These vesicles seem to be one of the main mechanisms of tumor remote intercellular signaling used to induce immune deregulation, apoptosis, and both phenotypic and genotypic modifications. In this study, we evaluated the exosomal DNA (exoDNA) concentration in blood samples of patients affected by cerebral glioma and correlated it with histological and radiological characteristics of tumors. From 14 patients with diagnosed primary or recurrent glioma, we obtained MRI imaging data, histological data, and preoperative blood samples that were used to extract circulating exosomal DNA, which we then quantified. Our results demonstrate a relationship between the amount of circulating exosomal DNA and tumor volume, and mitotic activity. In particular, a high concentration of exoDNA was noted in low-grade gliomas. Our results suggest a possible role of exoDNAs in the diagnosis of brain glioma. They could be particularly useful in detecting early recurrent high-grade gliomas and asymptomatic low-grade gliomas.
Sequential Semiology of Seizures and Brain Perfusion Patterns in Patients with Drug-Resistant Focal Epilepsies: A Perspective from Neural Networks
Authors: Arocha Pérez Jorge L. , Morales Chacón Lilia M. , Batista García Ramo Karla , Galán García Lídice
Published: April 2022

Ictal semiology and brain single-photon emission computed tomography have been performed in approaching the epileptogenic zone in drug-resistant focal epilepsies. The authors aim to describe the brain structures involved in the ictal and interictal epileptogenic network from sequential semiology and brain perfusion quantitative patterns analysis. A sequential representation of seizures was performed (n = 15). A two-level analysis (individual and global) was carried out for the analysis of brain perfusion quantification and estimating network structures from the perfusion indexes. Most of the subjects started with focal seizures without impaired consciousness, followed by staring, automatisms, language impairments and evolution to a bilateral tonic-clonic seizure (temporal lobe and posterior quadrant epilepsy). Frontal lobe epilepsy seizures continued with upper limb clonus and evolution to bilateral tonic-clonic. The perfusion index of the epileptogenic zone ranged between 0.439–1.362 (mesial and lateral structures), 0.826–1.266 in dorsolateral frontal structures and 0.678–1.507 in the occipital gyrus. The interictal epileptogenic network proposed involved the brainstem and other subcortical structures. For the ictal state, it included the rectus gyrus, putamen and cuneus. The proposed methodology provides information about the brain structures in the neural networks in patients with drug-resistant focal epilepsies.
Influence of the Construction Risks on the Cost and Duration of a Project
Authors: Lapidus Azariy , Topchiy Dmitriy , Kuzmina Tatyana , Chapidze Otari
Published: April 2022

Recent years have witnessed active construction of multi-storey residential buildings. The scale of construction, its timing and limitations in financing contribute to the emergence of risk factors affecting the key parameters of cost and duration of projects. The purpose of this research is to develop the most effective mathematical model to reveal, study and estimate in a timely manner the influence of risk factors on stable implementation of a construction project during its life cycle. The mathematical model of the study is based on the theory of fuzzy sets, including 25 rules used to estimate the influence of a risk factor. An expert survey of leading specialists in the construction industry was performed and risk factors distributed over the stages of the life cycle were listed. Risk factors affecting the sustainability of the life cycle of a multi-storey residential building were identified and ranked. The result of the study shows that the application of the mathematical model will significantly increase the success of construction projects by identifying the critical risk factors in the phases of their life cycle. Since the proposed model is relatively new in Russia, it should be considered as a starting point for a new assessment of the impact of risk factors on projects. The methodology can be improved, and many aspects are still to be analyzed.
Influence of Elevated Temperatures on the Mechanical Performance of Sustainable-Fiber-Reinforced Recycled Aggregate Concrete: A Review
Authors: Ahmed Wisal , Lim C. W. , Akbar Arslan
Published: April 2022

In recent times, the applications of fiber-reinforced recycled aggregate concrete (FRAC) in practical engineering have gained greater popularity due to its superior mechanical strength and fracture properties. To apply FRAC in buildings and other infrastructures, a thorough understanding of its residual mechanical properties and durability after exposure to fire is highly important. According to the established research, the properties and volume fractions of reinforcing fiber materials, replacement levels of recycled concrete aggregate (RCA), and heating condition would affect the thermal–mechanical properties of FRAC. This review paper aims to present a thorough and updated review of the mechanical performance at an elevated temperature and post-fire durability of FRAC reinforced with various types of fiber material, specifically steel fiber (SF), polypropylene (PP) fiber, and basalt fiber (BF). More explicitly, in this review article the residual mechanical properties of FRAC, such as compressive strength, splitting tensile capacity, modulus of elasticity, mass loss, spalling, and durability after exposure to elevated temperatures, are discussed. Furthermore, this study also encompasses the relationship among the dosages of fibers, replacement levels of recycled aggregate, and the relative residual mechanical properties of FRAC that would help in the optimum selection of the fiber content. Conclusively, this study elaborately reviews and summarizes the relevant and recent literature on recycled aggregate concrete containing SF, PP fiber, and BF. The study further provides a realistic comparison of these fibers in terms of the residual mechanical performance and durability of FRAC that would help in their future enhancements and applications in practical engineering.
A Seismic Checking Method of Engineering Structures Based on the Stochastic Semi-Physical Model of Seismic Ground Motions
Authors: Ding Yanqiong , Xu Yazhou , Miao Huiquan
Published: April 2022

A seismic checking method of engineering structures based on the stochastic semi-physical model of seismic ground motions is developed. Four groups of stochastic ground motions are generated using the stochastic semi-physical model of seismic ground motions. In conjunction with the probability density evolution method (PDEM) and the idea of the equivalent extreme-value event, the dynamic reliabilities of an engineering structure are evaluated. The dynamic reliability of the structure is taken as an index for seismic checking. A five-story reinforced concrete frame structure is analyzed using both the response spectrum method and the proposed method. Some features of the instantaneous probability density function (PDF) and its evolution, the extreme value distribution, and the dynamic reliability are discussed and compared with the results of the response spectrum method in the Chinese seismic code. The seismic checking results of the response spectrum method show that the structure is safe, while the results of the proposed method reveal a failure probability as high as 35.39%. Moreover, the structure has such different reliabilities when it is excited by different groups of simulated seismic ground motions. It reveals that a structure designed according to the seismic code may carry a high risk of failure. The proposed method provides a more accurate way for the evaluation of the reliabilities of engineering structures.
Impacts of COVID-19 on the Use of Digital Technology in Construction Projects in the UAE
Authors: Elrefaey Omar , Ahmed Salma , Ahmad Irtishad , El-Sayegh Sameh
Published: April 2022

The construction industry has been incorporating digital technology over the last two decades, albeit gradually, as “technology-push” continues to overcome customary and traditional passivity typical in the sector. The objective of the study presented in this paper is to investigate how digital technology is making a headway in the construction industry as a consequence of COVID-19. For the purpose of this paper, digital technology applications are divided into three groups: data acquisition, processing, and communication. The methodology involved conducting a questionnaire survey among the construction professionals in the UAE. The survey included questions on the extent of use and level of investment on the three types of technology in three periods—pre-COVID, during COVID, and post-COVID. The results clearly show the increasing level of usage of digital technology in the construction industry from pre-COVID to during COVID and post-COVID periods. Among the three categories, communication technology indicated higher extent of use as compared to the other two. In addition, a marked difference was observed between the “small” project organizations and the “large” ones. Unsurprisingly, both usage and investment in digital technology, in smaller organizations, indicated higher extent of increase in during and post-pandemic periods when compared to the larger organizations.
Development of an Open Government Data (OGD) Evaluation Framework for BIM
Authors: Park Jong Jin , Kim Eonyong , Jun Han Jong
Published: April 2022

Open government data (OGD) provide an opportunity for developing various services by disclosing information monopolized by the government to the public so that the private sector can use it. The private sector is utilizing this to improve the work efficiency and productivity by collecting, analyzing, and reprocessing OGD for various work steps of a BIM-based design project. However, most studies on OGD focus on the functionality and usability of data portals and the factors for evaluating the data itself such as openness, accountability, and transparency. This study aims to provide an evaluation framework for OGD for the AEC industry to assess the data utilization environment in order to improve the productivity of BIM-based projects. Several OGD principles found within related literature are discussed, and from them we extract evaluation framework levels. Then, we validate the proposed framework by applying it to a case of developing a BIM-based design support system using OGD datasets. This research concludes by suggesting that to effectively utilize OGD in the construction industry, the private sector should simply view data after collecting them, create an institutional environment for creating new values by reprocessing data, and build an active data utilization roadmap based on this environment.
Influence of Water-Binder Ratio on the Mechanical Strength and Microstructure of Arch Shell Interface Transition Zone
Authors: He Tao , Xiang Weiheng , Zhang Jian , Hu Cheng , Zhang Gaozhan , Kou Bin
Published: April 2022

To prepare lightweight ultra high performance concretes used in the large-span and super-tall structure engineering fields, the effects of water-binder ratio on the mechanical performances, hydration products, and microstructure of the arched shell interface transition zone between the prewetting spherical lightweight aggregates and cement matrix were studied. The experimental results showed that adding prewetting spherical lightweight aggregates promoted the formation of an arched shell interface transition zone. And the hydration degree, microhardness, and elastic modulus values of the arched shell interface transition zone were still higher than the cement matrix. With the reduction of the water-binder ratio, the microhardness, elastic modulus, thickness, and compactness of the interface transition zone had an increase, and the internal curing action of the prewetting spherical lightweight aggregates was more obvious. Especially when the water-binder ratio was 0.18, the hydration degree of the arch shell interface transition zone increased by 18.27% compared with the cement matrix after 28 days curing time. It was concluded that the prewetting spherical lightweight aggregates could have better internal curing and arched shell effects in cement-based materials with a low water-binder ratio. Therefore, adding prewetting spherical lightweight aggregates was regarded as a potential measure to fabricate the lightweight ultra high performance concretes.
Tumor Innervation: History, Methodologies, and Significance
Authors: Baraldi James H. , Martyn German V. , Shurin Galina V. , Shurin Michael R.
Published: April 2022

The role of the nervous system in cancer development and progression has been under experimental and clinical investigation since nineteenth-century observations in solid tumor anatomy and histology. For the first half of the twentieth century, methodological limitations and opaque mechanistic concepts resulted in ambiguous evidence of tumor innervation. Differential spatial distribution of viable or disintegrated nerve tissue colocalized with neoplastic tissue led investigators to conclude that solid tumors either are or are not innervated. Subsequent work in electrophysiology, immunohistochemistry, pathway enrichment analysis, neuroimmunology, and neuroimmunooncology have bolstered the conclusion that solid tumors are innervated. Regulatory mechanisms for cancer-related neurogenesis, as well as specific operational definitions of perineural invasion and axonogenesis, have helped to explain the consensus observation of nerves at the periphery of the tumor signifying a functional role of nerves, neurons, neurites, and glia in tumor development.
Intake Patterns of Specific Alcoholic Beverages by Prostate Cancer Status
Authors: Lin Hui-Yi , Tseng Tung-Sung , Wang Xinnan , Fang Zhide , Zea Arnold H. , Wang Liang , Pow-Sang Julio , Tangen Catherine M. , Goodman Phyllis J. , Wolk Alicja , Håkansson Niclas , Kogevinas Manolis , Llorca Javier , Brenner Hermann , Schöttker Ben , Castelao Jose Esteban , Gago-Dominguez Manuela , Gamulin Marija , Lessel Davor , Claessens Frank , Joniau Steven ,   the PRACTICAL Consortium, Park Jong Y.
Published: April 2022

Background: Previous studies have shown that different alcoholic beverage types impact prostate cancer (PCa) clinical outcomes differently. However, intake patterns of specific alcoholic beverages for PCa status are understudied. The study’s objective is to evaluate intake patterns of total alcohol and the three types of beverage (beer, wine, and spirits) by the PCa risk and aggressiveness status. Method: This is a cross-sectional study using 10,029 men (4676 non-PCa men and 5353 PCa patients) with European ancestry from the PCa consortium. Associations between PCa status and alcohol intake patterns (infrequent, light/moderate, and heavy) were tested using multinomial logistic regressions. Results: Intake frequency patterns of total alcohol were similar for non-PCa men and PCa patients after adjusting for demographic and other factors. However, PCa patients were more likely to drink wine (light/moderate, OR = 1.11, p = 0.018) and spirits (light/moderate, OR = 1.14, p = 0.003; and heavy, OR = 1.34, p = 0.04) than non-PCa men. Patients with aggressive PCa drank more beer than patients with non-aggressive PCa (heavy, OR = 1.48, p = 0.013). Interestingly, heavy wine intake was inversely associated with PCa aggressiveness (OR = 0.56, p = 0.009). Conclusions: The intake patterns of some alcoholic beverage types differed by PCa status. Our findings can provide valuable information for developing custom alcohol interventions for PCa patients.
Predictive Value of 18F-FDG PET/CT Using Machine Learning for Pathological Response to Neoadjuvant Concurrent Chemoradiotherapy in Patients with Stage III Non-Small Cell Lung Cancer
Authors: Yoo Jang , Lee Jaeho , Cheon Miju , Woo Sang-Keun , Ahn Myung-Ju , Pyo Hong Ryull , Choi Yong Soo , Han Joung Ho , Choi Joon Young
Published: April 2022

We investigated predictions from 18F-FDG PET/CT using machine learning (ML) to assess the neoadjuvant CCRT response of patients with stage III non-small cell lung cancer (NSCLC) and compared them with predictions from conventional PET parameters and from physicians. A retrospective study was conducted of 430 patients. They underwent 18F-FDG PET/CT before initial treatment and after neoadjuvant CCRT followed by curative surgery. We analyzed texture features from segmented tumors and reviewed the pathologic response. The ML model employed a random forest and was used to classify the binary outcome of the pathological complete response (pCR). The predictive accuracy of the ML model for the pCR was 93.4%. The accuracy of predicting pCR using the conventional PET parameters was up to 70.9%, and the accuracy of the physicians’ assessment was 80.5%. The accuracy of the prediction from the ML model was significantly higher than those derived from conventional PET parameters and provided by physicians (p < 0.05). The ML model is useful for predicting pCR after neoadjuvant CCRT, which showed a higher predictive accuracy than those achieved from conventional PET parameters and from physicians.
Novel Targeted Therapeutic Strategies for Ewing Sarcoma
Authors: Fayzullina Daria , Tsibulnikov Sergey , Stempen Mikhail , Schroeder Brett A. , Kumar Naveen , Kharwar Rajesh Kumar , Acharya Arbind , Timashev Peter , Ulasov Ilya
Published: April 2022

Ewing sarcoma (ES) is an uncommon cancer that arises in mesenchymal tissues and represents the second most widespread malignant bone neoplasm after osteosarcoma in children. Amplifications in genomic, proteomic, and metabolism are characteristics of sarcoma, and targeting altered cancer cell molecular processes has been proposed as the latest promising strategy to fight cancer. Recent technological advancements have elucidated some of the underlying oncogenic characteristics of Ewing sarcoma. Offering new insights into the physiological basis for this phenomenon, our current review examines the dynamics of ES signaling as it related to both ES and the microenvironment by integrating genomic and proteomic analyses. An extensive survey of the literature was performed to compile the findings. We have also highlighted recent and ongoing studies integrating metabolomics and genomics aimed at better understanding the complex interactions as to how ES adapts to changing biochemical changes within the tumor microenvironment.
Tunneling Nanotubes between Cells Migrating in ECM Mimicking Fibrous Environments
Authors: Jana Aniket , Ladner Katherine , Lou Emil , Nain Amrinder S.
Published: April 2022

Tunneling nanotubes (TNTs) comprise a unique class of actin-rich nanoscale membranous protrusions. They enable long-distance intercellular communication and may play an integral role in tumor formation, progression, and drug resistance. TNTs are three-dimensional, but nearly all studies have investigated them using two-dimensional cell culture models. Here, we applied a unique 3D culture platform consisting of crosshatched and aligned fibers to fabricate synthetic suspended scaffolds that mimic the native fibrillar architecture of tumoral extracellular matrix (ECM) to characterize TNT formation and function in its native state. TNTs are upregulated in malignant mesothelioma; we used this model to analyze the biophysical properties of TNTs in this 3D setting, including cell migration in relation to TNT dynamics, rate of TNT-mediated intercellular transport of cargo, and conformation of TNT-forming cells. We found that highly migratory elongated cells on aligned fibers formed significantly longer but fewer TNTs than uniformly spread cells on crossing fibers. We developed new quantitative metrics for the classification of TNT morphologies based on shape and cytoskeletal content using confocal microscopy. In sum, our strategy for culturing cells in ECM-mimicking bioengineered scaffolds provides a new approach for accurate biophysical and biologic assessment of TNT formation and structure in native fibrous microenvironments.
Treatment of Neuropathic Pain Directly Due to Cancer: An Update
Authors: Shkodra Morena , Caraceni Augusto
Published: April 2022

Neuropathic pain can be defined as pain related to abnormal somatosensory processing in either the peripheral or central nervous system. In this review article, with neuropathic cancer pain (NCP), we refer to pain due to nervous tissue lesions caused by the tumor or its metastases. Nervous tissue damage is the cause of cancer pain in approximately 40% of those experiencing cancer pain. Recognizing a neuropathic pathophysiology in these cases may be difficult and requires specific criteria that are not homogenously applied in clinical practice. The management of this type of pain can be challenging, requiring the use of specific non-opioid adjuvant drugs. The majority of the criteria for NCP diagnosis and management have been based mainly on results from the noncancer population, risking the failure of addressing the specific needs of this population of patients. In this review, we summarize current management options available for NCP and provide some insights on new promising treatments.
A Model to Detect Significant Prostate Cancer Integrating Urinary Peptide and Extracellular Vesicle RNA Data
Authors: O’Connell Shea P. , Frantzi Maria , Latosinska Agnieszka , Webb Martyn , Mullen William , Pejchinovski Martin , Salji Mark , Mischak Harald , Cooper Colin S. , Clark Jeremy , Brewer Daniel S. ,   on behalf of The Movember GAP1 Urine Biomarker Consortium
Published: April 2022

There is a clinical need to improve assessment of biopsy-naïve patients for the presence of clinically significant prostate cancer (PCa). In this study, we investigated whether the robust integration of expression data from urinary extracellular vesicle RNA (EV-RNA) with urine proteomic metabolites can accurately predict PCa biopsy outcome. Urine samples collected within the Movember GAP1 Urine Biomarker study (n = 192) were analysed by both mass spectrometry-based urine-proteomics and NanoString gene-expression analysis (167 gene-probes). Cross-validated LASSO penalised regression and Random Forests identified a combination of clinical and urinary biomarkers for predictive modelling of significant disease (Gleason Score (Gs) ≥ 3 + 4). Four predictive models were developed: ‘MassSpec’ (CE-MS proteomics), ‘EV-RNA’, and ‘SoC’ (standard of care) clinical data models, alongside a fully integrated omics-model, deemed ‘ExoSpec’. ExoSpec (incorporating four gene transcripts, six peptides, and two clinical variables) is the best model for predicting Gs ≥ 3 + 4 at initial biopsy (AUC = 0.83, 95% CI: 0.77–0.88) and is superior to a standard of care (SoC) model utilising clinical data alone (AUC = 0.71, p < 0.001, 1000 resamples). As the ExoSpec Risk Score increases, the likelihood of higher-grade PCa on biopsy is significantly greater (OR = 2.8, 95% CI: 2.1–3.7). The decision curve analyses reveals that ExoSpec provides a net benefit over SoC and could reduce unnecessary biopsies by 30%.
Dissecting Tumor-Immune Microenvironment in Breast Cancer at a Spatial and Multiplex Resolution
Authors: Tzoras Evangelos , Zerdes Ioannis , Tsiknakis Nikos , Manikis Georgios C. , Mezheyeuski Artur , Bergh Jonas , Matikas Alexios , Foukakis Theodoros
Published: April 2022

The tumor immune microenvironment (TIME) is an important player in breast cancer pathophysiology. Surrogates for antitumor immune response have been explored as predictive biomarkers to immunotherapy, though with several limitations. Immunohistochemistry for programmed death ligand 1 suffers from analytical problems, immune signatures are devoid of spatial information and histopathological evaluation of tumor infiltrating lymphocytes exhibits interobserver variability. Towards improved understanding of the complex interactions in TIME, several emerging multiplex in situ methods are being developed and gaining much attention for protein detection. They enable the simultaneous evaluation of multiple targets in situ, detection of cell densities/subpopulations as well as estimations of functional states of immune infiltrate. Furthermore, they can characterize spatial organization of TIME—by cell-to-cell interaction analyses and the evaluation of distribution within different regions of interest and tissue compartments—while digital imaging and image analysis software allow for reproducibility of the various assays. In this review, we aim to provide an overview of the different multiplex in situ methods used in cancer research with special focus on breast cancer TIME at the neoadjuvant, adjuvant and metastatic setting. Spatial heterogeneity of TIME and importance of longitudinal evaluation of TIME changes under the pressure of therapy and metastatic progression are also addressed.
Consensus Recommendations for the Clinical Management of Hematological Malignancies in Patients with DNA Double Stranded Break Disorders
Authors: Pastorczak Agata , Attarbaschi Andishe , Bomken Simon , Borkhardt Arndt , van der Werff ten Bosch Jutte , Elitzur Sarah , Gennery Andrew R. , Hlavackova Eva , Kerekes Arpád , Křenová Zdenka , Mlynarski Wojciech , Szczepanski Tomasz , Wassenberg Tessa , Loeffen Jan
Published: April 2022

Patients with double stranded DNA repair disorders (DNARDs) (Ataxia Telangiectasia (AT) and Nijmegen Breakage syndrome (NBS)) are at a very high risk for developing hematological malignancies in the first two decades of life. The most common neoplasms are T-cell lymphoblastic malignancies (T-cell ALL and T-cell LBL) and diffuse large B cell lymphoma (DLBCL). Treatment of these patients is challenging due to severe complications of the repair disorder itself (e.g., congenital defects, progressive movement disorders, immunological disturbances and progressive lung disease) and excessive toxicity resulting from chemotherapeutic treatment. Frequent complications during treatment for malignancies are deterioration of pre-existing lung disease, neurological complications, severe mucositis, life threating infections and feeding difficulties leading to significant malnutrition. These complications make modifications to commonly used treatment protocols necessary in almost all patients. Considering the rarity of DNARDs it is difficult for individual physicians to obtain sufficient experience in treating these vulnerable patients. Therefore, a team of experts assembled all available knowledge and translated this information into best available evidence-based treatment recommendations.
Synergetic Effects of Mixed-Metal Polyoxometalates@Carbon-Based Composites as Electrocatalysts for the Oxygen Reduction and the Oxygen Evolution Reactions
Authors: Marques Inês S. , Jarrais Bruno , Mbomekallé Israël-Martyr , Teillout Anne-Lucie , de Oliveira Pedro , Freire Cristina , Fernandes Diana M.
Published: April 2022

The smart choice of polyoxometalates (POMs) and the design of POM@carbon-based composites are promising tools for producing active electrocatalysts for both the oxygen reduction (ORR) and the oxygen evolution reactions (OER). Hence, herein, we report the preparation, characterization and application of three composites based on doped, multi-walled carbon nanotubes (MWCNT_N6) and three different POMs (Na12[(FeOH2)2Fe2(As2W15O56)2]·54H2O, Na12[(NiOH2)2Ni2(As2W15O56)2]·54H2O and Na14[(FeOH2)2Ni2(As2W15O56)2]·55H2O) as ORR and OER electrocatalysts in alkaline medium (pH = 13). Overall, the three POM@MWCNT_N6 composites showed good ORR performance with onset potentials between 0.80 and 0.81 V vs. RHE and diffusion-limiting current densities ranging from −3.19 to −3.66 mA cm−2. Fe4@MWCNT_N6 and Fe2Ni2@MWCNT_N6 also showed good stability after 12 h (84% and 80% of initial current). The number of electrons transferred per O2 molecule was close to three, suggesting a mixed regime. Moreover, the Fe2Ni2@MWCNT_N6 presented remarkable OER performance with an overpotential of 0.36 V vs. RHE (for j = 10 mA cm−2), a jmax close to 135 mA cm−2 and fast kinetics with a Tafel slope of 45 mV dec−1. More importantly, this electrocatalyst outperformed not only most POM@carbon-based composites reported so far but also the state-of-the-art RuO2 electrocatalyst. Thus, this work represents a step forward towards bifunctional electrocatalysts using less expensive materials.
Expanding the Range: AuCu Metal Aerogels from H2O and EtOH
Authors: Georgi Maximilian , Kresse Johannes , Hiekel Karl , Hübner René , Eychmüller Alexander
Published: April 2022

Due to their self-supporting and nanoparticulate structure, metal aerogels have emerged as excellent electrocatalysts, especially in the light of the shift to renewable energy cycles. While a large number of synthesis parameters have already been studied in depth, only superficial attention has been paid to the solvent. In order to investigate the influence of this parameter with respect to the gelation time, crystallinity, morphology, or porosity of metal gels, AuxCuy aerogels were prepared in water and ethanol. It was shown that although gelation in water leads to highly porous gels (60 m2g−1), a CuO phase forms during this process. The undesired oxide could be selectively removed using a post-washing step with formic acid. In contrast, the solvent change to EtOH led to a halving of the gelation time and the suppression of Cu oxidation. Thus, pure Cu aerogels were synthesized in addition to various bimetallic Au3X (X = Ni, Fe, Co) gels. The faster gelation, caused by the lower permittivity of EtOH, led to the formation of thicker gel strands, which resulted in a lower porosity of the AuxCuy aerogels. The advantage given by the solvent choice simplifies the preparation of metal aerogels and provides deeper knowledge about their gelation.
Catalytic Conversion of High Fructose Corn Syrup to Methyl Lactate with CoO@silicalite-1
Authors: Jiang Yuxi , Lyu Xilei , Chen Hao , Wei Xiwen , Zhang Zihao , Lu Xiuyang
Published: April 2022

Methyl lactate (MLA), a versatile biomass platform, was typically produced from the catalytic conversion of high-priced fructose. High fructose corn syrup (HFCS) is a mixture of glucose, fructose, water, etc., which is viewed as an economical substitute for fructose to produce MLA due to the much lower cost of separation and drying processes. However, the transformation of HFCS to MLA is still a challenge due to its complex components and the presence of water. In this work, the catalytic conversion of HFCS to MLA over CoO@silicalite-1 catalyst synthesized via a straightforward post citric acid treatment approach was reported. The maximum MLA yield reached 43.8% at 180 °C for 18 h after optimizing the reaction conditions and Co loading. Interestingly, adding extra 3% water could further increase the MLA yield, implying that our CoO@silicalite-1 catalyst is also capable for upgrading wet HFCS. As a result, the costly drying process of wet HFCS can be avoided. Moreover, the activity of CoO@silicalite-1 catalyst can be regenerated for at least four cycles via facile calcination in air. This study, therefore, will provide a new opportunity to not only solve the HFCS-overproduction issues but also produce value-added MLA.
Research Status of the Orphan G Protein Coupled Receptor 158 and Future Perspectives
Authors: Fu Xianan , Wei Shoupeng , Wang Tao , Fan Hengxin , Zhang Ying , Costa Clive Da , Brandner Sebastian , Yang Guang , Pan Yihang , He Yulong , Li Ningning
Published: April 2022

G-protein-coupled receptors (GPCRs) remain one of the most successful targets for therapeutic drugs approved by the US Food and Drug Administration (FDA). Many novel orphan GPCRs have been identified by human genome sequencing and considered as putative targets for refractory diseases. Of note, a series of studies have been carried out involving GPCR 158 (or GPR158) since its identification in 2005, predominantly focusing on the characterization of its roles in the progression of cancer and mental illness. However, advances towards an in-depth understanding of the biological mechanism(s) involved for clinical application of GPR158 are lacking. In this paper, we clarify the origin of the GPR158 evolution in different species and summarize the relationship between GPR158 and different diseases towards potential drug target identification, through an analysis of the sequences and substructures of GPR158. Further, we discuss how recent studies set about unraveling the fundamental features and principles, followed by future perspectives and thoughts, which may lead to prospective therapies involving GPR158.
Impact of microRNA Regulated Macrophage Actions on Adipose Tissue Function in Obesity
Authors: Matz Alyssa , Qu Lili , Karlinsey Keaton , Zhou Beiyan
Published: April 2022

Obesity-induced adipose tissue dysfunction is bolstered by chronic, low-grade inflammation and impairs systemic metabolic health. Adipose tissue macrophages (ATMs) perpetuate local inflammation but are crucial to adipose tissue homeostasis, exerting heterogeneous, niche-specific functions. Diversified macrophage actions are shaped through finely regulated factors, including microRNAs, which post-transcriptionally alter macrophage activation. Numerous studies have highlighted microRNAs’ importance to immune function and potential as inflammation-modulatory. This review summarizes current knowledge of regulatory networks governed by microRNAs in ATMs in white adipose tissue under obesity stress.
Conditions That Simulate the Environment of Atopic Dermatitis Enhance Susceptibility of Human Keratinocytes to Vaccinia Virus
Authors: Brewer Matthew G. , Monticelli Stephanie R. , Moran Mary C. , Miller Benjamin L. , Beck Lisa A. , Ward Brian M.
Published: April 2022

Individuals with underlying chronic skin conditions, notably atopic dermatitis (AD), are disproportionately affected by infections from members of the herpesviridae, papovaviridae, and poxviridae families. Many patients with AD experience recurrent, widespread cutaneous viral infections that can lead to viremia, serious organ complications, and even death. Little is known about how the type 2 inflammatory environment observed in the skin of AD patients impacts the susceptibility of epidermal cells (keratinocytes) to viral pathogens. Herein, we studied the susceptibility of keratinocytes to the prototypical poxvirus, vaccinia virus (VV)—the causative agent of eczema vaccinatum—under conditions that simulate the epidermal environment observed in AD. Treatment of keratinocytes with type 2 cytokines (IL-4 and -13) to simulate the inflammatory environment or a tight junction disrupting peptide to mirror the barrier disruption observed in AD patients, resulted in a differentiation-dependent increase in susceptibility to VV. Furthermore, pan JAK inhibition was able to diminish the VV susceptibility occurring in keratinocytes exposed to type 2 cytokines. We propose that in AD, the increased viral susceptibility of keratinocytes leads to enhanced virus production in the skin, which contributes to the rampant dissemination and pathology seen within patients.
Ibrutinib in the Treatment of Solid Tumors: Current State of Knowledge and Future Directions
Authors: Szklener Katarzyna , Michalski Adam , Żak Klaudia , Piwoński Michał , Mańdziuk Sławomir
Published: April 2022

Bruton’s Tyrosine Kinase (BTK) is considered crucial in the activation and survival of both physiological and malignant B-cells. In recent years, ibrutinib, an oral BTK inhibitor, became a breakthrough therapy for hematological malignancies, such as chronic lymphocytic. However, ibrutinib’s feasibility might not end there. Several other kinases with established involvement with solid malignancies (i.e., EGFR, HER2) have been found to be inhibited by this agent. Recent discoveries indicate that BTK is a potential anti-solid tumor therapy target. Consequently, ibrutinib, a BTK-inhibitor, has been studied as a therapeutic option in solid malignancies. While most preclinical studies indicate ibrutinib to be an effective therapeutic option in some specific indications, such as NSCLC and breast cancer, clinical trials contradict these observations. Nevertheless, while ibrutinib failed as a monotherapy, it might become an interesting part of a multidrug regime: not only has a synergism between ibrutinib and other compounds, such as trametinib or dactolisib, been observed in vitro, but this BTK inhibitor has also been established as a radio- and chemosensitizer. This review aims to describe the milestones in translating BTK inhibitors to solid tumors in order to understand the future potential of this agent better.