bluuebunny/crossref_metadata_2025 huggingface dataset:
A Microfluidic Platform Revealing Interactions between Leukocytes and Cancer Cells on Topographic Micropatterns
Authors: Cui Xin , Liu Lelin , Li Jiyu , Liu Yi , Liu Ya , Hu Dinglong , Zhang Ruolin , Huang Siping , Jiang Zhongning , Wang Yuchao , Qu Yun , Pang Stella W. , Lam Raymond H. W.
Published: November 2022

Immunoassay for detailed analysis of immune−cancer intercellular interactions can achieve more promising diagnosis and treatment strategies for cancers including nasopharyngeal cancer (NPC). In this study, we report a microfluidic live−cell immunoassay integrated with a microtopographic environment to meet the rising demand for monitoring intercellular interactions in different tumor microenvironments. The developed assay allows: (1) coculture of immune cells and cancer cells on tunable (flat or micrograting) substrates, (2) simultaneous detection of different cytokines in a wide working range of 5–5000 pg/mL, and (3) investigation of migration behaviors of mono- and co-cultured cells on flat/grating platforms for revealing the topography-induced intercellular and cytokine responses. Cytokine monitoring was achieved on-chip by implementing a sensitive and selective microbead-based sandwich assay with an antibody on microbeads, target cytokines, and the matching fluorescent-conjugated detection antibody in an array of active peristaltic mixer-assisted cytokine detection microchambers. Moreover, this immunoassay requires a low sample volume down to 0.5 μL and short assay time (30 min) for on-chip cytokine quantifications. We validated the biocompatibility of the co-culture strategy between immune cells and NPC cells and compared the different immunological states of undifferentiated THP-1 monocytic cells or PMA-differentiated THP-1 macrophages co-culturing with NP460 and NPC43 on topographical and planar substrates, respectively. Hence, the integrated microfluidic platform provides an efficient, broad-range and precise on-chip cytokine detection approach, eliminates the manual sampling procedures and allows on-chip continuous cytokine monitoring without perturbing intercellular microenvironments on different topographical ECM substrates, which has the potential of providing clinical significance in early immune diagnosis, personalized immunotherapy, and precision medicine.
Investigating the Neural Bases of Risky Decision Making Using Multi-Voxel Pattern Analysis
Authors: Wang Yanqing , Peng Xuerui , Hu Xueping
Published: November 2022

Choices between smaller certain reward and larger riskier reward are referred to as risky decision making. Numerous functional magnetic resonance imaging (fMRI) studies have investigated the neural substrates of risky decision making via conventional univariate analytical approaches, revealing dissociable activation of decisions involving certain rewards and risky rewards. However, it is still unclear how the patterns of brain activity predict the choice that the individual will make. With the help of multi-voxel pattern analyses, which is more sensitive for evaluating information encoded in spatially distributed patterns, we showed that fMRI activity patterns represent viable signatures of certain and risky choice and individual differences. Notably, the regions involved in representation of value and risk and cognitive control play prominent roles in differentiating certain and risky choices as well as individuals with distinct risk preference. These results deepen our understanding of the neural correlates of risky decision making as well as emphasize the important roles of regions involved in representation of value and risk cognitive control in predicting risky decision making and individual differences.
Individual Cofactors and Multisensory Contributions to the Postural Sway of Adults with Diabetes
Authors: Villaseñor-Moreno Julio , Aranda-Moreno Catalina , Figueroa-Padilla Ignacio , Giraldez-Fernández María , Gresty Michael , Jáuregui-Renaud Kathrine
Published: November 2022

To assess the interactions between individual cofactors and multisensory inputs on the postural sway of adults with type 2 diabetes and healthy subjects, 69 adults accepted to participate in the study (48 with/21 without diabetes). Assessments included neuro-otology (sinusoidal-rotation and unilateral-centrifugation), ophthalmology and physiatry evaluations, body mass index (BMI), physical activity, quadriceps strength, the ankle/brachial index and polypharmacy. Postural sway was recorded on hard/soft surface, either with eyes open/closed, or without/with 30° neck extension. The proportional differences from the baseline of each condition were analyzed using Multivariate and Multivariable analyses. Patients with polyneuropathy and no retinopathy showed visual dependence, while those with polyneuropathy and retinopathy showed adaptation. Across sensory challenges, the vestibulo-ocular gain at 1.28 Hz and the BMI were mainly related to changes in sway area, while the dynamic visual vertical was mainly related to changes in sway length. The ankle/brachial index was related to the effect of neck extension, with contributions from quadriceps strength/physical activity, polyneuropathy and polypharmacy. Across conditions, men showed less sway than women did. In conclusion, in adults with diabetes, sensory inputs and individual cofactors differently contribute to postural stability according to context. Rehabilitation programs for adults with diabetes may require an individualized approach.
Central Disorders of Hypersomnolence: Association with Fatigue, Depression and Sleep Inertia Prevailing in Women
Authors: Nevsimalova Sona , Skibova Jelena , Galuskova Karolina , Prihodova Iva , Dostalova Simona , Maurovich-Horvat Eszter , Šonka Karel
Published: November 2022

Fatigue, depression, and sleep inertia are frequently underdiagnosed manifestations in narcolepsy and idiopathic hypersomnia. Our cross-sectional study design included diagnostic interview accompanied by assessment instruments and aimed to explore how these factors influence disease severity as well as to elucidate any sex predisposition. One hundred and forty-eight subjects (female 63%) were divided into narcolepsy type 1 (NT1; n = 87, female = 61%), narcolepsy type 2 (NT2; n = 22, female = 59%), and idiopathic hypersomnia (IH; n = 39, female = 69%). All subjects completed a set of questionnaires: Epworth Sleepiness Scale (ESS), Hospital Anxiety and Depression Scales (HADS), Fatigue Severity Scale (FSS), and Sleep Inertia Questionnaire (SIQ). In narcoleptic subjects, questionnaire data were correlated with the Narcolepsy Severity Scale (NSS), and in subjects with idiopathic hypersomnia, with the Idiopathic Hypersomnia Severity Scale (IHSS). The highest correlation in narcoleptic subjects was found between NSS and ESS (r = 0.658; p < 0.0001), as well as FSS (r = 0.506; p < 0.0001), while in subjects with idiopathic hypersomnia, the most prominent positive correlations were found between IHSS and SIQ (r = 0.894; p < 0.0001), FSS (r = 0.812; p < 0.0001), HADS depression scale (r = 0.649; p = 0.0005), and HADS anxiety scale (r = 0.528; p < 0.0001). ESS showed an analogic correlation with disease severity (r = 0.606; p < 0.0001). HADS anxiety and depression scores were higher in females (p < 0.05 and p < 0.01), with similar results for FSS and SIQ scales (p < 0.05 for both), and a trend toward higher ESS values in females (p = 0.057). Our study illustrates that more attention should be focused on pathophysiological mechanisms and associations of fatigue, depression, as well as sleep inertia in these diseases; they influence the course of both illnesses, particularly in women.
Motor Imagery as a Key Factor for Healthy Ageing: A Review of New Insights and Techniques
Authors: Passarello Noemi , Liparoti Marianna , Padulo Caterina , Sorrentino Pierpaolo , Alivernini Fabio , Fairfield Beth , Lucidi Fabio , Mandolesi Laura
Published: November 2022

Motor imagery (MI) describes a dynamic cognitive process where a movement is mentally simulated without taking place and holds potential as a means of stimulating motor learning and regaining motor skills. There is growing evidence that imagined and executed actions have common neural circuitry. Since MI counteracts cognitive and motor decline, a growing interest in MI-based mental exercise for older individuals has emerged. Here we review the last decade’s scientific literature on age-related changes in MI skills. Heterogeneity in the experimental protocols, as well as the use of populations with unrepresentative age, is making it challenging to draw unambiguous conclusions about MI skills preservation. Self-report and behavioural tasks have shown that some MI components are preserved, while others are impaired. Evidence from neuroimaging studies revealed that, during MI tasks, older individuals hyperactivate their sensorimotor and attentional networks. Some studies have argued that this represents a compensatory mechanism, others claim that this is a sign of cognitive decline. However, further studies are needed to establish whether MI could be used as a promotion factor to improve cognitive functioning and well-being in older people.
Improving Emergency Training for Earthquakes through Immersive Virtual Environments and Anxiety Tests: A Case Study
Authors: Rajabi Mohammad Sadra , Taghaddos Hosein , Zahrai Seyed Mehdi
Published: November 2022

Because of the occurrence of severe and large magnitude earthquakes each year, earthquake-prone countries suffer considerable financial damages and loss of life. Teaching essential safety measures will lead to a generation that can perform basic procedures during an earthquake, which is an essential and effective solution in preventing the loss of life in this natural disaster. In recent years, Virtual Reality (VR) technology has been a tool used to educate people on safety matters. This paper evaluates the effect of education and premonition on the incorrect decision-making of residents under the stressful conditions of an earthquake. For this purpose, a virtual model has been designed and modeled based on a proposed classroom in a school in the city of Tehran to simulate a virtual learning experience. In contrast, the classroom represents a realistic method of learning. Accordingly, each educational scenario, presented in reality and the virtual model, respectively, was conducted on a statistical sample of 20 students within the range of 20 to 25 years of age. Among the mentioned sample, the first group of 10 students was taught safety measures in a physical classroom. The second group of 10 students participated in a virtual classroom. Evaluation tests on safety measures against earthquakes were distributed after two weeks. Two self-reporting tests of Depression, Anxiety, Stress Scale (DASS) and Beck Anxiety Inventory (BAI) tests were assigned to the second group to evaluate the effect of foresight under two different scenarios. The results indicate that teaching through VR technology yields a higher performance level than the in-person education approach. Additionally, the ability to detect earthquakes ahead is an influential factor in controlling anxiety and determining the right decisions should the event occur.
Life-Cycle Assessment of Contemporary and Classical Seismic Retrofitting Approaches Applied to a Reinforced Concrete Building in Israel
Authors: Pushkar Svetlana , Halperin Ido , Ribakov Yuri
Published: November 2022

This study aims to select an eco-friendly earthquake-resistant design using life-cycle assessments (LCAs). The study compares LCAs of three retrofitting cases: concrete shear-wall strengthening (Case 1); reinforced concrete column jacketing with shear-wall strengthening (Case 2); and high-damping rubber bearing base isolation with viscous fluid damping devices (Case 3). These cases were applied to a five-story reinforced concrete building built according to the design principles widely used in Israel in the 1970s. The seismic-bearing capacity of the retrofitted building was improved in all three cases, where Case 3 was observed as being the most effective retrofitting measure. The environmental performance of the retrofitting measures was assessed using the ReCiPe 2016 midpoint, which indicated that Case 3 was the best with the least environmental impact, Case 1 was intermediate with moderate environmental impact, and Case 2 was the worst with the most environmental impact. However, the ReCiPe 2016 endpoint single-score results showed that Case 3 caused significantly less damage than Cases 1 and 2, which caused similar significant environmental damage. These results indicate that LCA should be used to select an eco-friendly earthquake-resistant design.
A Quantitative Study of the Impact of Organizational Culture, Communication Management, and Clarity in Project Scope on Constructions’ Project Success with Moderating Role of Project Manager’s Competencies to Enhance Constructions Management Practices
Authors: Muneer Muhammad , Khan Nawar , Awais Hussain Muhammad , Shuai Zhang , Khan Adnan Ahmad , Farooq Rashid , Moawwez Muhammad Aamir , Tariq Muhammad Atiq Ur Rehman
Published: November 2022

The construction industry is considered a driver of economic growth, especially in developing countries. However, the successful completion of construction projects is a major challenge, due to the lack of competencies. The current study explores the effects of communication management practices, clarity in the scope of the construction project, and organizational culture to enhance project success. A project manager is essential in running a project smoothly and according to the schedule. Keeping in view the predominant role of the project manager, this study aims to find the moderating impact of manager competencies to improve the construction project routine and generate successful projects. A questionnaire survey was conducted to collect the data and determine how these variables influence construction project progress. The current research results show an excellent association between a construction project’s success and the discussed independent variables. Additionally, it was found that a competent project manager can play a better role in preventing the uncomfortable influences of independent variables on the dependent variable. The obtained outcomes highlight the importance of adequately handling organizational culture, communication management, and clarity to achieve project success. These outcomes are helpful for the professionals working in the construction sector to raise the project success rate and enhance their construction management capabilities.
Experimental Comparison of Efficiency of Water-Soluble and Solvent Hydrophobic Agents for Concrete
Authors: Hodul Jakub , Hodná Jana , Mészárosová Lenka , Borg Ruben Paul
Published: November 2022

The paper presents the results and assessment of the properties and capabilities of new types of surface hydrophobic agents for the treatment of fresh and matured surfaces of concrete and other cement-bound layers. Hydrophobisation prevents the premature evaporation of water and thus plastic shrinkage, which inevitably leads to the formation of cracks in cement-based structures. The influence of the new type of hydrophobic agents, epoxy water-based (EWH) and acrylate (AH) containing solvent, on the physical and mechanical properties of the treated concrete samples was assessed, including the adhesion of hydrophobisation on the concrete surface layers. It was confirmed that surface hydrophobisation successfully prevents premature evaporation of water, and thus, plastic shrinkage (concrete treated with EWH_0.3 showed more than two times lower shrinkage than reference concrete). The concrete samples treated by hydrophobisation agents showed higher strength after 120 days (37.5 MPa) in comparison with untreated concrete (32.8 MPa). Different properties were recorded with different types of hydrophobisation agents, including compressive strength after 90 days (31.2 MPa with EWH_0.15, and 35.9 MPa with AH_0.15). Water absorption after 120 days was lowest with EWH_0.3 samples (3.77%), two times lower than AH_0.15 (6.98%). The layer of hydrophobisation agent EWH_0.3 was thicker than AH_0.15, leading to lower water absorption of treated concrete and higher resistance to defrosting chemicals—waste 8.5. g/m2 with EWH_0.3 in comparison to 35.7 g/m2 with AH_0.15. Furthermore, a difference in the hydrophobisation behaviour was shown with blocking of infiltration from the chemically aggressive environment into the concrete substrate. Deterioration of the surface concrete exposed to 10% HCl solution was worse with AH_0.15; but the concrete surface treated with AH_0.15 showed better resistance than the EWH treated surface, when exposed to 5% CH3COOH. Degradation of the hydrophobisation integrity and the loss of cohesion between the concrete and the surface treatment after exposure to acetic acid and hydrochloric acid was observed using scanning electron microscopy (SEM).
Experimental Study on the Structural Behavior of the Oldest Timber Frame in China
Authors: Jing Songfeng , Nishizawa Hidekazu
Published: November 2022

The main hall of the Nanchan Temple, the oldest wooden building of the Tang Dynasty (782 C.E.) in China, was built 1200 years ago, representing a valuable heritage building. Thus far, research on the Nanchan Temple has focused on stylistic comparisons and historical documentary evidence. This study concentrates on the oldest timber-framed structure, with our experiments designed to understand the structural behavior of the hall. In this study, a 1:10-scaled specimen of a timber-framed building was fabricated based on the construction method of Yingzao Fashi, and the main hall of the Nanchan Temple was first reviewed; then, quasi-static tests were conducted under different vertical loads to ascertain the seismic mechanism of the oldest wooden building. The stiffness, energy dissipation, vertical load transfer path, bending stress of the component, and axial force were investigated. According to the results obtained on the vertical load transfer path, the roof was found to cause stress to the structural sections. The results indicate that the vertical load of the roof above Cha Shou is transferred down through Ping Liang; it then passes through Ping Liang to Tuo Feng and eventually passes to Sichuan Fu, which causes deformation. We increased the vertical loads, resulting in the increased lateral resistance (resilience) of the Nanchan Temple, and the stability of the timber-framed building in relation to the vertical loads was investigated. Moreover, the effects of horizontal and vertical loads were studied, and thus, we provide proposals for repair and conservation.
BRCA1/2 Mutation Testing in Patients with HER2-Negative Advanced Breast Cancer: Real-World Data from the United States, Europe, and Israel
Authors: Mahtani Reshma , Niyazov Alexander , Arondekar Bhakti , Lewis Katie , Rider Alex , Massey Lucy , Lux Michael Patrick
Published: November 2022

Poly(adenosine diphosphate-ribose) polymerase inhibitors are approved to treat patients harboring a germline breast cancer susceptibility gene 1 or 2 mutation (BRCA1/2mut) with human epidermal growth factor receptor 2—negative (HER2−) advanced breast cancer (ABC). This study evaluated differences in patient demographics, clinical characteristics, and BRCA1/2mut testing within the United States (US), European Union 4 (EU4; France, Germany, Italy, and Spain), and Israel in a real-world population of patients with HER2− ABC. Oncologists provided chart data from eligible patients from October 2019 through March 2020. In the US, EU4, and Israel, 73%, 42%, and 99% of patients were tested for BRCA1/2mut, respectively. In the US and the EU4, patients who were not tested versus tested for BRCA1/2mut were more likely to have hormone receptor—positive (HR+)/HER2− ABC (US, 94% vs. 74%, p < 0.001; EU4, 96% vs. 78%, p < 0.001), less likely to have a known family history of BRCA1/2-related cancer (US, 6% vs. 19%, p = 0.002; EU4, 10% vs. 28%, p < 0.001), and were older (US, 68.9 vs. 62.5 years, p < 0.001; EU4, 66.7 vs. 58.0 years, p < 0.001). Among tested patients, genetic counseling was received by 45%, 53%, and 98% with triple-negative breast cancer, and 36%, 36%, and 98% with HR+/HER2− ABC in the US, EU4, and Israel, respectively. Efforts should be made to improve BRCA1/2 testing rates in the US and Europe.
Exploring Gut Microbiome in Predicting the Efficacy of Immunotherapy in Non-Small Cell Lung Cancer
Authors: Liu Ben , Chau Justin , Dai Qun , Zhong Cuncong , Zhang Jun
Published: November 2022

We performed various analyses on the taxonomic and functional features of the gut microbiome from NSCLC patients treated with immunotherapy to establish a model that may predict whether a patient will benefit from immunotherapy. We collected 65 published whole metagenome shotgun sequencing samples along with 14 samples from our previous study. We systematically studied the taxonomical characteristics of the dataset and used both the random forest (RF) and the multilayer perceptron (MLP) neural network models to predict patients with progression-free survival (PFS) above 6 months versus those below 3 months. Our results showed that the RF classifier achieved the highest F-score (85.2%) and the area under the receiver operating characteristic curve (AUC) (95%) using the protein families (Pfam) profile, and the MLP neural network classifier achieved a 99.9% F-score and 100% AUC using the same Pfam profile. When applying the model trained in the Pfam profile directly to predict the treatment response, we found that both trained RF and MLP classifiers significantly outperformed the stochastic predictor in F-score. Our results suggested that such a predictive model based on functional (e.g., Pfam) rather than taxonomic profile might be clinically useful to predict whether an NSCLC patient will benefit from immunotherapy, as both the F-score and AUC of functional profile outperform that of taxonomic profile. In addition, our model suggested that interactive biological processes such as methanogenesis, one-carbon, and amino acid metabolism might be important in regulating the immunotherapy response that warrants further investigation.
Physical Activity as the Best Supportive Care in Cancer: The Clinician’s and the Researcher’s Perspectives
Authors: Torregrosa Cécile , Chorin Frédéric , Beltran Eva Ester Molina , Neuzillet Cindy , Cardot-Ruffino Victoire
Published: November 2022

Multidisciplinary supportive care, integrating the dimensions of exercise alongside oncological treatments, is now regarded as a new paradigm to improve patient survival and quality of life. Its impact is important on the factors that control tumor development, such as the immune system, inflammation, tissue perfusion, hypoxia, insulin resistance, metabolism, glucocorticoid levels, and cachexia. An increasing amount of research has been published in the last years on the effects of physical activity within the framework of oncology, marking the appearance of a new medical field, commonly known as “exercise oncology”. This emerging research field is trying to determine the biological mechanisms by which, aerobic exercise affects the incidence of cancer, the progression and/or the appearance of metastases. We propose an overview of the current state of the art physical exercise interventions in the management of cancer patients, including a pragmatic perspective with tips for routine practice. We then develop the emerging mechanistic views about physical exercise and their potential clinical applications. Moving toward a more personalized, integrated, patient-centered, and multidisciplinary management, by trying to understand the different interactions between the cancer and the host, as well as the impact of the disease and the treatments on the different organs, this seems to be the most promising method to improve the care of cancer patients.
Factors and Mechanisms That Influence Chromatin-Mediated Enhancer–Promoter Interactions and Transcriptional Regulation
Authors: Ito Shinsuke , Das Nando Dulal , Umehara Takashi , Koseki Haruhiko
Published: November 2022

Eukaryotic gene expression is regulated through chromatin conformation, in which enhancers and promoters physically interact (E–P interactions). How such chromatin-mediated E–P interactions affect gene expression is not yet fully understood, but the roles of histone acetylation and methylation, pioneer transcription factors, and architectural proteins such as CCCTC binding factor (CTCF) and cohesin have recently attracted attention. Moreover, accumulated data suggest that E–P interactions are mechanistically involved in biophysical events, including liquid–liquid phase separation, and in biological events, including cancers. In this review, we discuss various mechanisms that regulate eukaryotic gene expression, focusing on emerging views regarding chromatin conformations that are involved in E–P interactions and factors that establish and maintain them.
Cancer Cachexia among Patients with Advanced Non-Small-Cell Lung Cancer on Immunotherapy: An Observational Study with Exploratory Gut Microbiota Analysis
Authors: Hakozaki Taiki , Nolin-Lapalme Alexis , Kogawa Masato , Okuma Yusuke , Nakamura Shohei , Moreau-Amaru Danielle , Tamura Taichi , Hosomi Yukio , Takeyama Haruko , Richard Corentin , Hosokawa Masahito , Routy Bertrand
Published: November 2022

Cancer cachexia exerts a negative clinical influence on patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI). The prognostic impact of body weight change during ICI treatment remains unknown. The gut microbiota (GM) is a key contributor to the response to ICI therapy in cancer patients. However, the association between cancer cachexia and GM and their association with the response to ICIs remains unexplored. This study examined the association of cancer cachexia with GM composition and assessed the impact of GM on clinical outcomes in patients with NSCLC treated with ICIs. In this observational, prospective study, which included 113 Japanese patients with advanced NSCLC treated with ICIs, the prevalence of cachexia was 50.4% (57/113). The median progression-free survival (PFS) and overall survival (OS) were significantly shorter in the cachexia group than in the non-cachexia group (4.3 vs. 11.6 months (p = 0.003) and 12.0 months vs. not reached (p = 0.02), respectively). A multivariable analysis revealed that baseline cachexia was independently associated with a shorter PFS. Moreover, a gain in body weight from the baseline (reversible cachexia) was associated with a significantly longer PFS and OS compared to irreversible cachexia. Microbiome profiling with 16S rRNA analysis revealed that the cachexia group presented an overrepresentation of the commensal bacteria, Escherichia-Shigella and Hungatella, while the non-cachexia group had a preponderance of Anaerostipes, Blautia, and Eubacterium ventriosum. Anaerostipes and E. ventriosum were associated with longer PFS and OS. Moreover, a cachexia status correlated with the systemic inflammatory marker-derived-neutrophil-to-lymphocytes ratio (dNLR) and Lung Immune Prognostic Index (LIPI) indexes. Our study demonstrates that cachexia and longitudinal bodyweight change have a prognostic impact on patients with advanced NSCLC treated with ICI therapy. Moreover, our study demonstrates that bacteria associated with ICI resistance are also linked to cachexia. Targeted microbiota interventions may represent a new type of treatment to overcome cachexia in patients with NSCLC.
CIC-Rearranged Sarcomas: An Intriguing Entity That May Lead the Way to the Comprehension of More Common Cancers
Authors: Mancarella Caterina , Carrabotta Marianna , Toracchio Lisa , Scotlandi Katia
Published: November 2022

Capicua transcriptional repressor (CIC)-rearranged sarcoma, belonging to the undifferentiated round cells sarcoma family, is characterized by high metastatic rate and poor chemo response. CIC sarcoma represents a new entity harboring the recurrent chromosomal translocation between CIC and, in most of the cases, DUX4. CIC-DUX4 imposes a CIC-specific transcriptional signature, which drives cell transformation, proliferation, and migration. While the discovery of the fusion represented the first evidence of a role of CIC in cancer, a complete comprehension of CIC-rearranged activity is still required before providing new potential avenues for therapy. To date, a specific and effective treatment for CIC sarcoma has yet to be defined. In this review, we initially highlight the clinical features and pathogenesis of CIC-rearranged sarcomas along with current therapeutic approaches and then focus on the specific oncogenic mechanisms driven by the CIC-rearrangement. We discuss novel therapeutic options evoked by the aberrant relations of CIC-DUX4 with the IGF system, DUSP6, P300/CBP, and CCNE1. We also discuss how different mutations involving CIC might converge on a common upregulation of CIC-target genes across human cancers. A deeper understanding of the oncogenic mechanisms driven by the chimera CIC-DUX4 might provide novel therapeutic opportunities with a general impact in cancer.
Structural and Socio-Spatial Determinants Influencing Care and Survival of Patients with a Pancreatic Adenocarcinoma: Results of the PANDAURA Cohort
Authors: Roth Gaël S. , Fayet Yohan , Benmameche-Medjahed Sakina , Ducimetière Françoise , Charreton Amandine , Cropet Claire , Chabaud Sylvie , Marion-Audibert Anne-Marie , Berthelet Olivier , Walter Thomas , Adham Mustapha , Baconnier Mathieu , Tavan David , Williet Nicolas , Artru Pascal , Huet-Penz Floriane , Ray-Coquard Isabelle , Farsi Fadila , Labrosse Hélène , de la Fouchardière Christelle
Published: November 2022

Background and aims: Pancreatic cancer is highly lethal and often diagnosed at an advanced stage. This cohort study analyzes the impact of care pathways, delays, and socio-spatial determinants on pancreatic cancer patients’ diagnosis, treatment, and prognosis. Method: Patients with pancreatic adenocarcinoma newly diagnosed at all stages between January and June 2016 in the AuRA French region were included. The influence on survival of delays of care, healthcare centers’ expertise, and socio-spatial determinants was evaluated. Results: Here, 538 patients were included in 76 centers including 116 patients (21.8%) with resectable, 64 (12.0%) borderline-resectable, 147 (27.6%) locally-advanced tumors, and 205 (38.5%) with metastatic disease. A delay between first symptoms and CT scans did not statistically influence overall survival (OS). In resected patients, OS was significantly higher in centers with more than 20 surgeries (HR<5 surgeries/year = 2.236 and HR5-20 surgeries/year = 1.215 versus centers with > 20 surgeries/year p = 0.0081). Regarding socio-spatial determinants, patients living in municipalities with greater access to a general practitioner (HR = 1.673, p = 0.0153) or with a population density below 795.1 people/km2 (HR = 1.881, p = 0.0057) were significantly more often resectable. Conclusion: This cohort study supports the pivotal role of general practitioner in cancer care and the importance of the centralization of pancreatic surgery to optimize pancreatic cancer patients’ care and outcomes. However, delays of care did not impact patient survival.
Glycocalyx Acts as a Central Player in the Development of Tumor Microenvironment by Extracellular Vesicles for Angiogenesis and Metastasis
Authors: Zeng Ye , Qiu Yan , Jiang Wenli , Fu Bingmei M.
Published: November 2022

Angiogenesis in tumor growth and progression involves a series of complex changes in the tumor microenvironment. Extracellular vesicles (EVs) are important components of the tumor microenvironment, which can be classified as exosomes, apoptotic vesicles, and matrix vesicles according to their origins and properties. The EVs that share many common biological properties are important factors for the microenvironmental modification and play a vital role in tumor growth and progression. For example, vascular endothelial growth factor (VEGF) exosomes, which carry VEGF, participate in the tolerance of anti-angiogenic therapy (AAT). The glycocalyx is a mucopolysaccharide structure consisting of glycoproteins, proteoglycans, and glycosaminoglycans. Both endothelial and tumor cells have glycocalyx at their surfaces. Glycocalyx at both cells mediates the secretion and uptake of EVs. On the other hand, many components carried by EVs can modify the glycocalyx, which finally facilitates the development of the tumor microenvironment. In this short review, we first summarize the role of EVs in the development of the tumor microenvironment. Then we review how the glycocalyx is associated with the tumor microenvironment and how it is modulated by the EVs, and finally, we review the role of the glycocalyx in the synthesis, release, and uptake of EVs that affect tumor microenvironments. This review aims to provide a basis for the mechanistic study of AAT and new clues to address the challenges in AAT tolerance, tumor angiogenesis and metastasis.
Crystal Structure and Properties of Gd1-xSrxCo1-yFeyO3-δ Oxides as Promising Materials for Catalytic and SOFC Application
Authors: Aksenova Tatiana V. , Mysik Darya K. , Cherepanov Vladimir A.
Published: November 2022

A series of samples with the overall composition Gd1-xSrxCo1-yFeyO3-δ (x = 0.8; 0.9 and 0.1 ≤ y ≤ 0.9), which are promising materials for catalytic and SOFC application, was prepared by a glycerol nitrate technique. X-ray diffraction analysis allowed to describe Gd0.2Sr0.8Co1-yFeyO3-δ with 0.1 ≤ y ≤ 0.5 in a tetragonal 2ap × 2ap × 4ap superstructure (SG I4/mmm), while oxides with 0.6 ≤ y ≤ 0.9 exhibit cubic disordered perovskite structure (SG Pm-3m). All Gd0.1Sr0.9Fe1-yCoyO3-δ oxides within the composition range 0.1 ≤ y ≤ 0.9 possess the cubic perovskite structure (SG Pm-3m). The structural parameters were refined using the Rietveld full-profile method. The changes of oxygen content in Gd1-xSrxCo1-yFeyO3-δ versus temperature were determined by thermogravimetric analysis. The introduction of iron into the cobalt sublattice leads to a gradual increase in the unit cell parameters and unit cell volume, accompanied with increasing oxygen content. The temperature dependency of conductivity for Gd0.2Sr0.8Co0.3Fe0.7O3-δ exhibits a maximum (284 S/cm) at ≈600 K in air. The positive value of the Seebeck coefficient indicates predominant p-type conductivity in the Gd0.2Sr0.8Co0.3Fe0.7O3-δ complex oxide.
The Advanced Synthesis of MOFs-Based Materials in Photocatalytic HER in Recent Three Years
Authors: Zhang Hao , Li Cha , Li Yang , Pang Jiandong , Bu Xianhe
Published: November 2022

Since the advent of metal–organic frameworks (MOFs), researchers have paid extensive attention to MOFs due to their determined structural composition, controllable pore size, and diverse physical and chemical properties. Photocatalysis, as a significant application of MOFs catalysts, has developed rapidly in recent years and become a research hotspot continuously. Various methods and approaches to construct and modify MOFs and their derivatives can not only affect the structure and morphology, but also largely determine their properties. Herein, we summarize the advanced synthesis of MOFs-based materials in the field of the photocatalytic decomposition of water to produce hydrogen in the recent three years. The main contents include the overview of the novel synthesis strategies in four aspects: internal modification and structure optimization of MOFs materials, MOFs/semiconductor composites, MOFs/COFs-based hybrids, and MOFs-derived materials. In addition, the problems and challenges faced in this direction and the future development goals were also discussed. We hope this review will help deepen the reader’s understanding and promote continued high-quality development in this field.
The Kinetic Simulation of Persulfate Activation by Nano-Ferrosoferric Oxide
Authors: Song Tiehong , Gao Yanjiao , Li Guanqiao , Chen Yaxin , Li Qiang
Published: November 2022

Nano-ferrosoferric-oxide (nFe3O4)-activated persulfate (PS) technology was used to remove pollutant bisphenol A (BPA) in water. The effects of nFe3O4 concentration, PS concentration, BPA concentration, temperature, and pH were investigated in terms of the degradation effect of BPA. The results showed that more PS dosage and lower BPA concentration could improve the degradation rate of BPA. When other conditions were constant, the degradation rate of BPA increased with the increase of temperature. When pH was 5, the degradation rate of BPA was the highest. When the initial PS concentration and pH were changed, the degradation rate of BPA was consistent with the pseudo-secondary kinetic model. Under other conditions, the degradation rate of BPA was consistent with the pseudo-first-order kinetic model. Sulfate radical (SO4•−) produced by nFe3O4/PS system was mainly responsible for the degradation of BPA.
Melatonin Treatment Triggers Metabolic and Intracellular pH Imbalance in Glioblastoma
Authors: Fernandez-Gil Beatriz I. , Otamendi-Lopez Andrea , Bechtle Alexandra , Vazquez-Ramos Carla A. , Qosja Neda , Suarez-Meade Paola , Sarabia-Estrada Rachel , Jentoft Mark E. , Guerrero-Cázares Hugo , Escames Germaine , Schiapparelli Paula , Quiñones-Hinojosa Alfredo
Published: November 2022

Metabolic rewiring in glioblastoma (GBM) is linked to intra- and extracellular pH regulation. In this study, we sought to characterize the role of melatonin on intracellular pH modulation and metabolic consequences to identify the mechanisms of action underlying melatonin oncostatic effects on GBM tumor initiating cells. GBM tumor initiating cells were treated at different times with melatonin (1.5 and 3.0 mM). We analyzed melatonin’s functional effects on GBM proliferation, cell cycle, viability, stemness, and chemo-radiosensitivity. We then assessed the effects of melatonin on GBM metabolism by analyzing the mitochondrial and glycolytic parameters. We also measured the intracellular and extracellular pH. Finally, we tested the effects of melatonin on a mouse subcutaneous xenograft model. We found that melatonin downregulated LDHA and MCT4, decreasing lactate production and inducing a decrease in intracellular pH that was associated with an increase in ROS and ATP depletion. These changes blocked cell cycle progression and induced cellular death and we observed similar results in vivo. Melatonin’s cytotoxic effects on GBM were due, at least in part, to intracellular pH modulation, which has emerged as a newly identified mechanism, providing new insights into the oncostatic effect of melatonin on GBM.
Natural Killer Cells Are Key Host Immune Effector Cells Affecting Survival in Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation
Authors: Porrata Luis F.
Published: November 2022

The infusion of autograft immune effector cells directly impacts the clinical outcomes of patients treated with autologous peripheral blood hematopoietic stem cell transplantation, suggesting the possibility of an autologous graft-versus tumor cells. Furthermore, the early recovery of immune effector cells also affects survival post-autologous peripheral blood hematopoietic stem cell transplantation. Natural killer cells are among the immune effector cells reported to be collected, infused, and recovered early post-autologous peripheral blood hematopoietic stem cell transplantation. In this review, I attempt to give an update on the role of natural killer cells regarding improving survival outcomes on patients treated with autologous peripheral blood hematopoietic stem cell transplantation.
Visfatin-Induced Inhibition of miR-1264 Facilitates PDGF-C Synthesis in Chondrosarcoma Cells and Enhances Endothelial Progenitor Cell Angiogenesis
Authors: Song Chang-Yu , Chang Sunny Li-Yun , Lin Chih-Yang , Tsai Chun-Hao , Yang Shang-Yu , Fong Yi-Chin , Huang Yu-Wen , Wang Shih-Wei , Chen Wei-Cheng , Tang Chih-Hsin
Published: November 2022

New treatments for chondrosarcoma are extremely important. Chondrosarcoma is a primary malignant bone tumor with a very unfavorable prognosis. High-grade chondrosarcoma has a high potential to metastasize to any organ in the body. Platelet-derived growth factor (PDGF) is a potent angiogenic factor that promotes tumor angiogenesis and metastasis. The adipocytokine visfatin promotes metastatic potential of chondrosarcoma; however, the role of visfatin in angiogenesis in human chondrosarcoma is unclear. We report that the levels of PDGF-C expression were positively correlated with tumor stages, significantly higher than the levels of expression in normal cartilage. Visfatin increased PDGF-C expression and endothelial progenitor cell (EPC) angiogenesis through the PI3K/Akt/mTOR signaling pathway, and dose-dependently down-regulated the synthesis of miR-1264, which targets the 3′-UTR of PDGF-C. Additionally, we discovered inhibition of visfatin or PDGF-C in chondrosarcoma tumors significantly reduced tumor angiogenesis and size. Our results indicate that visfatin inhibits miR-1264 production through the PI3K/Akt/mTOR signaling cascade, and thereby promotes PDGF-C expression and chondrosarcoma angiogenesis. Visfatin may be worth targeting in the treatment of chondrosarcoma angiogenesis.
Analysis of the Utilization and Prospects of CRISPR-Cas Technology in the Annotation of Gene Function and Creation New Germplasm in Maize Based on Patent Data
Authors: Wang Youhua , Tang Qiaoling , Kang Yuli , Wang Xujing , Zhang Haiwen , Li Xinhai
Published: November 2022

Maize (Zea mays L.) is a food crop with the largest planting area and the highest yield in the world, and it plays a vital role in ensuring global food security. Conventional breeding methods are costly, time-consuming, and ineffective in maize breeding. In recent years, CRISPR-Cas editing technology has been used to quickly generate new varieties with high yield and improved grain quality and stress resistance by precisely modifying key genes involved in specific traits, thus becoming a new engine for promoting crop breeding and the competitiveness of seed industries. Using CRISPR-Cas, a range of new maize materials with high yield, improved grain quality, ideal plant type and flowering period, male sterility, and stress resistance have been created. Moreover, many patents have been filed worldwide, reflecting the huge practical application prospects and commercial value. Based on the existing patent data, we analyzed the development process, current status, and prospects of CRISPR-Cas technology in dissecting gene function and creating new germplasm in maize, providing information for future basic research and commercial production.
Stem-Cell-Based Therapy: The Celestial Weapon against Neurological Disorders
Authors: Zayed Mohamed A. , Sultan Samar , Alsaab Hashem O. , Yousof Shimaa Mohammad , Alrefaei Ghadeer I. , Alsubhi Nouf H. , Alkarim Saleh , Al Ghamdi Kholoud S. , Bagabir Sali Abubaker , Jana Ankit , Alghamdi Badrah S. , Atta Hazem M. , Ashraf Ghulam Md
Published: November 2022

Stem cells are a versatile source for cell therapy. Their use is particularly significant for the treatment of neurological disorders for which no definitive conventional medical treatment is available. Neurological disorders are of diverse etiology and pathogenesis. Alzheimer’s disease (AD) is caused by abnormal protein deposits, leading to progressive dementia. Parkinson’s disease (PD) is due to the specific degeneration of the dopaminergic neurons causing motor and sensory impairment. Huntington’s disease (HD) includes a transmittable gene mutation, and any treatment should involve gene modulation of the transplanted cells. Multiple sclerosis (MS) is an autoimmune disorder affecting multiple neurons sporadically but induces progressive neuronal dysfunction. Amyotrophic lateral sclerosis (ALS) impacts upper and lower motor neurons, leading to progressive muscle degeneration. This shows the need to try to tailor different types of cells to repair the specific defect characteristic of each disease. In recent years, several types of stem cells were used in different animal models, including transgenic animals of various neurologic disorders. Based on some of the successful animal studies, some clinical trials were designed and approved. Some studies were successful, others were terminated and, still, a few are ongoing. In this manuscript, we aim to review the current information on both the experimental and clinical trials of stem cell therapy in neurological disorders of various disease mechanisms. The different types of cells used, their mode of transplantation and the molecular and physiologic effects are discussed. Recommendations for future use and hopes are highlighted.
Fabricated AIE-Based Probe to Detect the Resistance to Anoikis of Cancer Cells Detached from Tumor Tissue
Authors: Chang Ya-Nan , Liang Yuelan , Wang Jiayi , Chen Ziteng , Yan Ruyu , Chen Kui , Li Juan , Li Jiacheng , Liang Haojun , Xing Gengmei
Published: November 2022

(1) Background: Resisting anoikis is a vital and necessary characteristic of malignant cancer cells, but there is no existing quantification method. Herein, a sensitive probe for assessing anoikis resistance of cancer cells detached from the extracellular matrix was developed based on the aggregation-induced emission (AIE) of AIEgens. It has been reported that detached cancer cell endocytose activated integrin clusters, and in the endosome these clusters recruit and activate phosphorylate focal adhesion kinase (pFAK) in the cytoplasm to induce signaling that supports the growth of detached cancer cells. (2) Methods: We established a lost nest cell model of cancer cells and determined their ability to resist anoikis. The colocalization of the activated integrin, pFAK, and endosomes in model cells was observed and calculated. (3) Results: The fluorescence signal intensity of the probe was significantly higher than that of the integrin antibody in the model cells and the fluorescence signal of probe signal was better overlapped with labeled pFAK by fluorescence in endosomes in model cells. (4) Conclusions: We developed a quantitative multi-parametric image analysis program to calculate fluorescent intensity of the probe and antibodies against pFAK and Rab5 in the areas of colocalization. A positive correlation of fluorescence signal intensity between the probe and pFAK on the endosome was observed. Therefore, the probe was used to quantitatively evaluate resisting anoikis of different cancer cell lines under the lost nest condition.