bluuebunny/crossref_metadata_2025 huggingface dataset:
Positively Charged Lipid as Potential Tool to Influence the Fate of Ethosomes
Authors: Mancuso Antonia , Cristiano Maria Chiara , Fresta Massimo , Torella Daniele , Paolino Donatella
Published: July 2021

Ethosomes® are one of the main deformable vesicles proposed to overcome the stratum corneum. They are composed of lecithin, ethanol and water, resulting in round vesicles characterized by a narrow size distribution and a negative surface charge. Taking into account their efficiency to deliver drugs into deeper skin layers, the current study was designed to evaluate the influence of different lipids on the physico-chemical features of traditional ethosomes in the attempt to influence their fate. Three lipids (DOPE, DSPE and DOTAP) were used for the study, but only DOTAP conferred a net positive charge to ethosomes, maintaining a narrow mean size lower than 300 nm and a good polydispersity index. Stability and in vitro cytotoxic studies have been performed using Turbiscan Lab analysis and MTT dye exclusion assay, respectively. Data recorded demonstrated the good stability of modified ethosomes and a reasonable absence of cell mortality when applied to human keratinocytes, NCTC 2544, which are used as a cell model. Finally, the best formulations were selected to evaluate their ability to encapsulate drugs, through the use of model compounds. Cationic ethosomes encapsulated oil red o and rhodamine b in amounts comparable to those recorded from conventional ethosomes (over 50%). Results recorded from this study are encouraging as cationic ethosomes may open new opportunities for skin delivery.
Performance Evaluation of an Inflatable Solar Dryer for Maize and the Effect on Product Quality Compared with Direct Sun Drying
Authors: Ntwali Janvier , Schock Steffen , Romuli Sebastian , Chege Christine , Banadda Noble , Aseru Gloria , Müller Joachim
Published: July 2021

Maize is an important staple in Africa, which necessitates immediate drying to preserve the postharvest quality. The traditional drying of maize in the open sun is prone to adverse weather and extraneous contamination. In this study, the drying performance of an inflatable solar dryer (ISD) was compared to direct sun drying (DSD) in Gombe Town, Wakiso District (Uganda) by analysing the moisture content, yeasts, moulds, aflatoxin, and colour. The maximum temperature inside the ISD reached 63.7 °C and averaged 7 °C higher than the ambient temperature. Maize was dried using both methods to a moisture content below 14% after two days. In one of the received maize lots that was already heavily contaminated after harvest, drying with DSD and ISD reduced the aflatoxin content from 569.6 µg kg−1 to 345.5 µg kg−1 and 299.2 µg kg−1, respectively. Although the drying performance in terms of drying time and product quality regarding colour, yeast, and mould was similar for both drying methods, the advantage of ISD in reducing the risk of spoilage due to sudden rain is obvious. A strategy for the early detection of aflatoxins in maize is recommended to avoid contaminated maize in the food chain.
Temperature Control of Spring CO2 Fluxes at a Coniferous Forest and a Peat Bog in Central Siberia
Authors: Park Sung-Bin , Knohl Alexander , Migliavacca Mirco , Thum Tea , Vesala Timo , Peltola Olli , Mammarella Ivan , Prokushkin Anatoly , Kolle Olaf , Lavrič Jošt , Park Sang Seo , Heimann Martin
Published: July 2021

Climate change impacts the characteristics of the vegetation carbon-uptake process in the northern Eurasian terrestrial ecosystem. However, the currently available direct CO2 flux measurement datasets, particularly for central Siberia, are insufficient for understanding the current condition in the northern Eurasian carbon cycle. Here, we report daily and seasonal interannual variations in CO2 fluxes and associated abiotic factors measured using eddy covariance in a coniferous forest and a bog near Zotino, Krasnoyarsk Krai, Russia, for April to early June, 2013–2017. Despite the snow not being completely melted, both ecosystems became weak net CO2 sinks if the air temperature was warm enough for photosynthesis. The forest became a net CO2 sink 7–16 days earlier than the bog. After the surface soil temperature exceeded ~1 °C, the ecosystems became persistent net CO2 sinks. Net ecosystem productivity was highest in 2015 for both ecosystems because of the anomalously high air temperature in May compared with other years. Our findings demonstrate that long-term monitoring of flux measurements at the site level, particularly during winter and its transition to spring, is essential for understanding the responses of the northern Eurasian ecosystem to spring warming.
Correction: Bates et al. Vector Fields and Differential Forms on the Orbit Space of a Proper Action. Axioms 2021, 10, 118
Authors: Bates Larry , Cushman Richard , Śniatycki Jędrzej
Published: July 2021

There was an error in the original article [...]
RETRACTED: Zipper Is Necessary for Branching Morphogenesis of the Terminal Cells in the Drosophila melanogaster’s Tracheal System
Authors: Shin Jong-Hyeon , Jeong Chan-Woo
Published: July 2021

Branching morphogenesis and seamless tube formation in Drosophila melanogaster are essential for the development of vascular and tracheal systems, and instructive in studying complex branched structures such as human organs. Zipper is a myosin II’s actin-binding heavy chain; hence, it is important for contracting actin, cell proliferation, and cell sheet adhesion for branching of the tracheal system in post-larval development of the D. melanogaster. Nevertheless, the specific role of Zipper in the larva is still in question. This paper intended to investigate the specific role of Zipper in branching morphogenesis and lumenogenesis in early developmental stages. It did so by checking the localization of the protein in the cytoplasm of the terminal cells and also by analyzing the morphology of zipper RNAi loss-of-function mutants in regard to branching and lumen formation in the terminal cells. A rescue experiment of RNAi mutants was also performed to check the sufficiency of Zipper in branching morphogenesis. Confocal imaging showed the localization of Zipper in the cytoplasm of the terminal cells, and respective quantitative analyses demonstrated that zipper RNAi terminal cells develop significantly fewer branches. Such a result hinted that Zipper is required for the regulation of branching in the terminal cells of D. melanogaster. Nevertheless, Zipper is not significantly involved in the formation of seamless tubes. One hypothesis is that Zipper’s contractility at the lateral epidermis’ leading edge allows cell sheet movement and respective elongation; as a result of such an elongation, further branching may occur in the elongated region of the cell, hence defining branching morphogenesis in the terminal cells of the tracheal system.
Relevance of BET Family Proteins in SARS-CoV-2 Infection
Authors: Lara-Ureña Nieves , García-Domínguez Mario
Published: July 2021

The recent pandemic we are experiencing caused by the coronavirus disease 2019 (COVID-19) has put the world’s population on the rack, with more than 191 million cases and more than 4.1 million deaths confirmed to date. This disease is caused by a new type of coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A massive proteomic analysis has revealed that one of the structural proteins of the virus, the E protein, interacts with BRD2 and BRD4 proteins of the Bromodomain and Extra Terminal domain (BET) family of proteins. BETs are essential to cell cycle progression, inflammation and immune response and have also been strongly associated with infection by different types of viruses. The fundamental role BET proteins play in transcription makes them appropriate targets for the propagation strategies of some viruses. Recognition of histone acetylation by BET bromodomains is essential for transcription control. The development of drugs mimicking acetyl groups, and thereby able to displace BET proteins from chromatin, has boosted interest on BETs as attractive targets for therapeutic intervention. The success of these drugs against a variety of diseases in cellular and animal models has been recently enlarged with promising results from SARS-CoV-2 infection studies.
Role of Occupational Footwear and Prolonged Walking on Lower Extremity Muscle Activation during Maximal Exertions and Postural Stability Tasks
Authors: Chander Harish , Kodithuwakku Arachchige Sachini N. K. , Turner Alana J. , Burch V Reuben F. , Knight Adam C. , Wade Chip , Garner John C.
Published: July 2021

Background: Occupational footwear and a prolonged duration of walking have been previously reported to play a role in maintaining postural stability. The purpose of this paper was to analyze the impact of three types of occupational footwear: the steel-toed work boot (ST), the tactical work boot (TB), and the low-top work shoe (LT) on previously unreported lower extremity muscle activity during postural stability tasks. Methods: Electromyography (EMG) muscle activity was measured from four lower extremity muscles (vastus medialis (VM), medial hamstrings (MH), tibialis anterior (TA), and medial gastrocnemius (MG) during maximal voluntary isometric contractions (MVIC) and during a sensory organization test (SOT) every 30 min over a 4 h simulated workload while wearing ST, TB, and LT footwear. The mean MVIC and the mean and percentage MVIC during each SOT condition from each muscle was analyzed individually using a repeated measures ANOVA at an alpha level of 0.05. Results: Significant differences (p < 0.05) were found for maximal exertions, but this was limited to only the time main effect. No significant differences existed for EMG measures during the SOT. Conclusion: The findings suggest that occupational footwear type does not influence lower extremity muscle activity during both MVIC and SOT. Significantly lower muscle activity during maximal exertions over the course of the 4 h workload was evident, which can be attributed to localized muscular fatigue, but this was not sufficient to impact muscle activity during postural stability tasks.
Nature-Inspired Unconventional Approaches to Develop 3D Bioceramic Scaffolds with Enhanced Regenerative Ability
Authors: Ruffini Andrea , Sandri Monica , Dapporto Massimiliano , Campodoni Elisabetta , Tampieri Anna , Sprio Simone
Published: July 2021

Material science is a relevant discipline in support of regenerative medicine. Indeed, tissue regeneration requires the use of scaffolds able to guide and sustain the natural cell metabolism towards tissue regrowth. This need is particularly important in musculoskeletal regeneration, such as in the case of diseased bone or osteocartilaginous regions for which calcium phosphate-based scaffolds are considered as the golden solution. However, various technological barriers related to conventional ceramic processing have thus far hampered the achievement of biomimetic and bioactive scaffolds as effective solutions for still unmet clinical needs in orthopaedics. Driven by such highly impacting socioeconomic needs, new nature-inspired approaches promise to make a technological leap forward in the development of advanced biomaterials. The present review illustrates ion-doped apatites as biomimetic materials whose bioactivity resides in their unstable chemical composition and nanocrystallinity, both of which are, however, destroyed by the classical sintering treatment. In the following, recent nature-inspired methods preventing the use of high-temperature treatments, based on (i) chemically hardening bioceramics, (ii) biomineralisation process, and (iii) biomorphic transformations, are illustrated. These methods can generate products with advanced biofunctional properties, particularly biomorphic transformations represent an emerging approach that could pave the way to a technological leap forward in medicine and also in various other application fields.
Oxidative Stress, Mitochondrial Dysfunction, and Neuroprotection of Polyphenols with Respect to Resveratrol in Parkinson’s Disease
Authors: Kung Heng-Chung , Lin Kai-Jung , Kung Chia-Te , Lin Tsu-Kung
Published: July 2021

Parkinson’s disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic neuronal loss. The exact pathogenesis of PD is complex and not yet completely understood, but research has established the critical role mitochondrial dysfunction plays in the development of PD. As the main producer of cytosolic reactive oxygen species (ROS), mitochondria are particularly susceptible to oxidative stress once an imbalance between ROS generation and the organelle’s antioxidative system occurs. An overabundance of ROS in the mitochondria can lead to mitochondrial dysfunction and further vicious cycles. Once enough damage accumulates, the cell may undergo mitochondria-dependent apoptosis or necrosis, resulting in the neuronal loss of PD. Polyphenols are a group of natural compounds that have been shown to offer protection against various diseases, including PD. Among these, the plant-derived polyphenol, resveratrol, exhibits neuroprotective effects through its antioxidative capabilities and provides mitochondria protection. Resveratrol also modulates crucial genes involved in antioxidative enzymes regulation, mitochondrial dynamics, and cellular survival. Additionally, resveratrol offers neuroprotective effects by upregulating mitophagy through multiple pathways, including SIRT-1 and AMPK/ERK pathways. This compound may provide potential neuroprotective effects, and more clinical research is needed to establish the efficacy of resveratrol in clinical settings.
The Role of Non-Coding RNAs in the Regulation of the Proto-Oncogene MYC in Different Types of Cancer
Authors: Stasevich Ekaterina Mikhailovna , Murashko Matvey Mikhailovich , Zinevich Lyudmila Sergeevna , Demin Denis Eriksonovich , Schwartz Anton Markovich
Published: July 2021

Alterations in the expression level of the MYC gene are often found in the cells of various malignant tumors. Overexpressed MYC has been shown to stimulate the main processes of oncogenesis: uncontrolled growth, unlimited cell divisions, avoidance of apoptosis and immune response, changes in cellular metabolism, genomic instability, metastasis, and angiogenesis. Thus, controlling the expression of MYC is considered as an approach for targeted cancer treatment. Since c-Myc is also a crucial regulator of many cellular processes in healthy cells, it is necessary to find ways for selective regulation of MYC expression in tumor cells. Many recent studies have demonstrated that non-coding RNAs play an important role in the regulation of the transcription and translation of this gene and some RNAs directly interact with the c-Myc protein, affecting its stability. In this review, we summarize current data on the regulation of MYC by various non-coding RNAs that can potentially be targeted in specific tumor types.
Mask R-CNN Based C. Elegans Detection with a DIY Microscope
Authors: Fudickar Sebastian , Nustede Eike Jannik , Dreyer Eike , Bornhorst Julia
Published: July 2021

Caenorhabditis elegans (C. elegans) is an important model organism for studying molecular genetics, developmental biology, neuroscience, and cell biology. Advantages of the model organism include its rapid development and aging, easy cultivation, and genetic tractability. C. elegans has been proven to be a well-suited model to study toxicity with identified toxic compounds closely matching those observed in mammals. For phenotypic screening, especially the worm number and the locomotion are of central importance. Traditional methods such as human counting or analyzing high-resolution microscope images are time-consuming and rather low throughput. The article explores the feasibility of low-cost, low-resolution do-it-yourself microscopes for image acquisition and automated evaluation by deep learning methods to reduce cost and allow high-throughput screening strategies. An image acquisition system is proposed within these constraints and used to create a large data-set of whole Petri dishes containing C. elegans. By utilizing the object detection framework Mask R-CNN, the nematodes are located, classified, and their contours predicted. The system has a precision of 0.96 and a recall of 0.956, resulting in an F1-Score of 0.958. Considering only correctly located C. elegans with an AP@0.5 IoU, the system achieved an average precision of 0.902 and a corresponding F1 Score of 0.906.
The Anterior Attentional–Intentional System in Patients with Parkinson’s Disease—A Pilot and Feasibility Study
Authors: Golińska Paulina Beata , Sawicki Artur Józef , Bieleninik Łucja , Bidzan Mariola
Published: July 2021

(1) Background: This study compared anterior attentional–intentional system performance between three groups: Parkinson’s disease (PD) patients with normal cognition (PD-NC), with mild cognitive impairment (PD-MCI), and a comparison group (CG). It also evaluated the feasibility of the recruitment and study procedures; (2) Methods: From 45 participants recruited, 39 were allocated (mean age 65.31; 43.59% men) to PD-NC, PD-MCI and CG (13 per group). To assess attention, we used three tasks from the ROtman–Baycrest Battery for Investigating Attention: Simple Reaction time (RT), Choice RT, and Prepare RT. We conducted a mixed-model analysis of variance with a 3 (groups) × 4 (tasks) design to compare reaction times; (3) Results: PD-MCI had slower reaction times than PD-NC (p = 0.028) and the CG (p = 0.052); there was no difference between PD-NC and CG. PD-MCI might perform worse on monitoring tasks than PD-NC, Z = −1.68, p = 0.092. Nearly half the volunteers from the CG and 87% of all eligible patients were enrolled in the study and completed all neuropsychological procedures; (4) Conclusions: General cognitive decline appears related to partial deficits in energization and tends to impair attentional monitoring. Furthermore, PD-NC exhibited similar reaction times to the CG. Results from the feasibility study contributed to the definitive study.
Neural Alterations in Interpersonal Distance (IPD) Cognition and Its Correlation with IPD Behavior: A Systematic Review
Authors: Huang Xinxin , Izumi Shin-Ichi
Published: July 2021

Background. Interpersonal distance (IPD) plays a critical role in a human being’s social life, especially during interpersonal interaction, and IPD is non-verbal social information and not only provides silent cues but also provides a secure space for personal relationships. IPD has been a research field of neural studies from the recent decade, researches had provided behavior and neural correlates of IPD. Objectives. This review aims to summarize the experimental paradigms of IPD-neural research, to reveal the neural activity processes associated with it, and to explore the correlation between IPD-neural activity and IPD-behavior. Methods. We conducted a standardized systematic review procedure, including the formal search method be adopted to seek out any type of studies related to IPD and brain, then devised them into categories to make a systematic review. Results. 17 articles met the inclusion criteria of the review, 5 event-related potential (ERP) studies measured the amplitude and latencies of ERPs, and 12 functional magnetic resonance imaging (fMRI) studies provided the neural activation during IPD tasks. In addition, the passive IPD experimental paradigm is the main experimental paradigm for exploring neural activity in IPD cognition, with the parietal lobe, motor areas, prefrontal lobe, and amygdala being the main brain areas involved. Functional connections between the identified brain regions were found and have a moderate correlation with IPD behavior. Conclusions. This review provides the neural activity of the IPD interaction process. However, the insufficient ecological validity of IPD tasks and ignore the initiative of people in IPD interaction. Therefore, there is a large research space on this topic. The work of the current systematic review contributed to linking the external performance and inner neural activities of IPD.
Prevalence and Risk Factors for Cognitive Frailty in Aging Hypertensive Patients in China
Authors: Wang Can , Zhang Jiechun , Hu Chengping , Wang Yanbo
Published: July 2021

Hypertension is one of the most common chronic diseases and a major risk factor for stroke, myocardial infarction and cardiovascular death. Cognitive frailty is an important predictor of all-cause mortality and dementia in aging individuals. Hypertension is closely related to cognitive frailty and these two conditions often coexist in aging individuals. Few studies have explored the relationship between hypertension and cognitive frailty in the Chinese population. This study investigates the epidemiological characteristics of and factors related to cognitive frailty in aging Chinese patients with hypertension. In total, cognitive function, weakness, social support, depression and sociodemographic were assessed in 305 participants aged 60 and over. Univariate and multivariate logistic regression models were constructed. The prevalence of cognitive frailty in aging Chinese hypertensive patients was 9.8% (95% CI = 6.4–13.2%). After adjusting for confounding variables, logistic regression showed that the course of hypertension (6–10 years, OR = 8.588, 95% CI = 1.608–45.859;course of more than 10 years, OR = 9.020, 95%CI = 1.854–43.892), multimorbidity (OR = 11.231, 95% CI = 2.912–43.322), depression (OR = 6.917, 95% CI = 2.424–19.738) and social support (OR = 0.187, 95% CI = 0.071–0.492) were independently associated with cognitive frailty. The prevalence of cognitive frailty in aging patients with hypertension in China should not be ignored. The course of hypertension, multimorbidity and depression are the risk factors of cognitive frailty in the aging population and a better level of social support is the protective factor for cognitive frailty.
Review of Cryogenic Carbon Capture Innovations and Their Potential Applications
Authors: Font-Palma Carolina , Cann David , Udemu Chinonyelum
Published: July 2021

Our ever-increasing interest in economic growth is leading the way to the decline of natural resources, the detriment of air quality, and is fostering climate change. One potential solution to reduce carbon dioxide emissions from industrial emitters is the exploitation of carbon capture and storage (CCS). Among the various CO2 separation technologies, cryogenic carbon capture (CCC) could emerge by offering high CO2 recovery rates and purity levels. This review covers the different CCC methods that are being developed, their benefits, and the current challenges deterring their commercialisation. It also offers an appraisal for selected feasible small- and large-scale CCC applications, including blue hydrogen production and direct air capture. This work considers their technological readiness for CCC deployment and acknowledges competing technologies and ends by providing some insights into future directions related to the R&D for CCC systems.
A Novel Combination of Bevacizumab with Chemotherapy Improves Therapeutic Effects for Advanced Biliary Tract Cancer: A Retrospective, Observational Study
Authors: Pei Sung-Nan , Liao Chun-Kai , Chen Yaw-Sen , Tseng Cheng-Hao , Hung Chao-Ming , Chiu Chong-Chi , Hsieh Meng-Che , Tsai Yu-Fen , Liao Hsiu-Yun , Liu Wei-Ching , Rau Kun-Ming
Published: July 2021

Background: Biliary tract cancer (BTC) is a heterogenous collection of biliary tract cancer at different primary sites, and the prognosis of advanced BTC is dismal. Systemic chemotherapy with gemcitabine and cisplatin (GC) has been the reference regimen since 2010. How to improve therapeutic effects of GC regimen is an urgent mission at present. Methods: Bevacizumab with a reduced dosage and modified schedule (10 mg/Kg/triweekly, 1 day before GS at the first 2 cycles) was combined with standard GC for patients with advanced BTC. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors version 1.1 every 2 months. Kaplan–Meier curves were estimated for time-to-treatment failure (TTF), progression-free survival (PFS) and overall survival (OS). Result: A total of thirty cases of advanced BTC accepted this treatment, and the overall response rate (ORR) was 50.0%, and the disease control rate was 80.0% for all patients. The median TTF was 5.8 months, the median PFS was 8.4 months, and the median OS was 13.6 months. Most responses were noted at the first evaluation. Adverse effects (AEs) were mostly tolerable. Conclusions: After modifying the schedule, adding bevacizumab to a traditional GC regimen could increase the ORR with a shorter time-to-response, a better PFS and OS than GC alone but without the addition of AE. This regimen can be applied to patients with advanced BTC, especially those who are with a big tumor burden and who need a rapid response.
Pri-miR526b and Pri-miR655 Are Potential Blood Biomarkers for Breast Cancer
Authors: Majumder Mousumi , Ugwuagbo Kingsley Chukwunonso , Maiti Sujit , Lala Peeyush K , Brackstone Muriel
Published: July 2021

We reported that two microRNAs, miR526b and miR655, are oncogenic in breast cancer (BC). Overexpression of these two miRNAs in poorly metastatic BC cells promotes aggressive BC phenotypes in vitro and in vivo. High expression of each miRNA was associated with poor patient survival. In this pilot biomarker study, we report for the first time that miRNA precursor RNAs (pri-miRNAs) are robust and sensitive biomarkers for BC, detectable in both human blood plasma and biopsy tissues. Pri-miRNA detection and quantification do not require a special enrichment procedure, thus reducing specimen quantity. Blood plasma samples from 90 malignant tumor-bearing patients and 20 benign lesion-bearing participants (control) were analyzed for pri-miRNA expression with a quantitative real-time polymerase chain reaction. Results revealed that normalized expressions of plasma pri-miR526b and pri-miR655 are significantly upregulated in malignancy compared to benign plasmas (p = 0.002 and p = 0.03, respectively). Both pri-miRNAs showed more prominent results to distinguish stage I plasmas from benign plasmas (p = 0.001 for pri-miR526b and p = 0.0001 for pri-miR655). We have also validated pri-miRNA expression in independent tumor bank tissues, showing significant upregulation of both pri-miRNAs in BC; thus, pri-miRNAs are robust markers. The diagnostic relevance of pri-miRNAs was computed with the area under the curve (AUC). Pri-miR526b is a sensitive biomarker to distinguish cancer from control plasmas (sensitivity of 86%; AUC = 71.47%, p = 0.0027) with a positive predictive value of 88.89%; however, pri-miR655 did not show significant sensitivity. Furthermore, pri-miR526b could also significantly distinguish tumors as early as stage I from control (sensitivity of 75%; AUC = 72.71%, p = 0.0037). Therefore, pri-miR526b can be used as an early diagnostic biomarker. The expression of both pri-miRNAs was significantly high in ER-positive and HER2-negative subgroups of BC; hence, these biomarkers might play a role in the management of endocrine therapy designs. Additionally, with a case–control cohort study, we identified that high expression of pri-miR526b in the blood is also a risk factor associated with breast cancer (OR = 4.3, CI = 1.39–13.34, p = 0.01). Pri-miRNAs could be considered novel breast cancer blood biomarkers.
Tissue Factor and Extracellular Vesicles: Activation of Coagulation and Impact on Survival in Cancer
Authors: Hisada Yohei , Mackman Nigel
Published: July 2021

Tissue factor (TF) is a transmembrane glycoprotein that functions as a receptor for FVII/FVIIa and initiates the extrinsic coagulation pathway. Tumors and cancer cells express TF that can be released in the form of TF positive (TF+) extracellular vesicles (EVs). In this review, we summarize the studies of tumor TF and TF + EVs, and their association with activation of coagulation and survival in cancer patients. We also summarize the role of tumor-derived TF + EVs in venous thrombosis in mouse models. Levels of tumor TF and TF + EVs are associated with venous thromboembolism in pancreatic cancer patients. In addition, levels of EVTF activity are associated with disseminated intravascular coagulation in cancer patients. Furthermore, tumor-derived TF + EVs enhance venous thrombosis in mice. Tumor TF and TF + EVs are also associated with worse survival in cancer patients, particularly in pancreatic cancer patients. These studies indicate that EVTF activity could be used as a biomarker to identify pancreatic cancer patients at risk for venous thrombosis and cancer patients at risk for disseminated intravascular coagulation. EVTF activity may also be a useful prognostic biomarker in cancer patients.
PKM2 Regulates HSP90-Mediated Stability of the IGF-1R Precursor Protein and Promotes Cancer Cell Survival during Hypoxia
Authors: Koo Han , Byun Sangwon , Seo Jieun , Jung Yuri , Lee Dong Chul , Cho Jung Hee , Park Young Soo , Yeom Young Il , Park Kyung Chan
Published: July 2021

Insulin-like growth factor-1 receptor (IGF-1R), an important factor in promoting cancer cell growth and survival, is commonly upregulated in cancer cells. However, amplification of the IGF1R gene is extremely rare in tumors. Here, we have provided insights into the mechanisms underlying the regulation of IGF-1R protein expression. We found that PKM2 serves as a non-metabolic protein that binds to and increases IGF-1R protein expression by promoting the interaction between IGF-1R and heat-shock protein 90 (HSP90). PKM2 depletion decreases HSP90 binding to IGF-1R precursor, thereby reducing IGF-1R precursor stability and the basal level of mature IGF-1R. Consequently, PKM2 knockdown inhibits the activation of AKT, the key downstream effector of IGF-1R signaling, and increases apoptotic cancer cell death during hypoxia. Notably, we clinically verified the PKM2-regulated expression of IGF-1R through immunohistochemical staining in a tissue microarray of 112 lung cancer patients, demonstrating a significant positive correlation (r = 0.5208, p < 0.0001) between PKM2 and IGF-1R expression. Together, the results of a previous report demonstrated that AKT mediates PKM2 phosphorylation at serine-202; these results suggest that IGF-1R signaling and PKM2 mutually regulate each other to facilitate cell growth and survival, particularly under hypoxic conditions, in solid tumors with dysregulated IGF-1R expression.
Quantitative Assessment and Prognostic Associations of the Immune Landscape in Ovarian Clear Cell Carcinoma
Authors: Khalique Saira , Nash Sarah , Mansfield David , Wampfler Julian , Attygale Ayoma , Vroobel Katherine , Kemp Harriet , Buus Richard , Cottom Hannah , Roxanis Ioannis , Jones Thomas , von Loga Katharina , Begum Dipa , Guppy Naomi , Ramagiri Pradeep , Fenwick Kerry , Matthews Nik , Hubank Michael , Lord Christopher , Haider Syed , Melcher Alan , Banerjee Susana , Natrajan Rachael
Published: July 2021

Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian cancer characterised by a high frequency of loss-of-function ARID1A mutations and a poor response to chemotherapy. Despite their generally low mutational burden, an intratumoural T cell response has been reported in a subset of OCCC, with ARID1A purported to be a biomarker for the response to the immune checkpoint blockade independent of micro-satellite instability (MSI). However, assessment of the different immune cell types and spatial distribution specifically within OCCC patients has not been described to date. Here, we characterised the immune landscape of OCCC by profiling a cohort of 33 microsatellite stable OCCCs at the genomic, gene expression and histological level using targeted sequencing, gene expression profiling using the NanoString targeted immune panel, and multiplex immunofluorescence to assess the spatial distribution and abundance of immune cell populations at the protein level. Analysis of these tumours and subsequent independent validation identified an immune-related gene expression signature associated with risk of recurrence of OCCC. Whilst histological quantification of tumour-infiltrating lymphocytes (TIL, Salgado scoring) showed no association with the risk of recurrence or ARID1A mutational status, the characterisation of TILs via multiplexed immunofluorescence identified spatial differences in immunosuppressive cell populations in OCCC. Tumour-associated macrophages (TAM) and regulatory T cells were excluded from the vicinity of tumour cells in low-risk patients, suggesting that high-risk patients have a more immunosuppressive microenvironment. We also found that TAMs and cytotoxic T cells were also excluded from the vicinity of tumour cells in ARID1A-mutated OCCCs compared to ARID1A wild-type tumours, suggesting that the exclusion of these immune effectors could determine the host response of ARID1A-mutant OCCCs to therapy. Overall, our study has provided new insights into the immune landscape and prognostic associations in OCCC and suggest that tailored immunotherapeutic approaches may be warranted for different subgroups of OCCC patients.
A Molecular Pinball Machine of the Plasma Membrane Regulates Plant Growth—A New Paradigm
Authors: Lamport Derek T. A. , Tan Li , Kieliszewski Marcia J.
Published: July 2021

Novel molecular pinball machines of the plasma membrane control cytosolic Ca2+ levels that regulate plant metabolism. The essential components involve: 1. an auxin-activated proton pump; 2. arabinogalactan glycoproteins (AGPs); 3. Ca2+ channels; 4. auxin-efflux “PIN” proteins. Typical pinball machines release pinballs that trigger various sound and visual effects. However, in plants, “proton pinballs” eject Ca2+ bound by paired glucuronic acid residues of numerous glycomodules in periplasmic AGP-Ca2+. Freed Ca2+ ions flow down the electrostatic gradient through open Ca2+ channels into the cytosol, thus activating numerous Ca2+-dependent activities. Clearly, cytosolic Ca2+ levels depend on the activity of the proton pump, the state of Ca2+ channels and the size of the periplasmic AGP-Ca2+ capacitor; proton pump activation is a major regulatory focal point tightly controlled by the supply of auxin. Auxin efflux carriers conveniently known as “PIN” proteins (null mutants are pin-shaped) pump auxin from cell to cell. Mechanosensitive Ca2+ channels and their activation by reactive oxygen species (ROS) are yet another factor regulating cytosolic Ca2+. Cell expansion also triggers proton pump/pinball activity by the mechanotransduction of wall stress via Hechtian adhesion, thus forming a Hechtian oscillator that underlies cycles of wall plasticity and oscillatory growth. Finally, the Ca2+ homeostasis of plants depends on cell surface external storage as a source of dynamic Ca2+, unlike the internal ER storage source of animals, where the added regulatory complexities ranging from vitamin D to parathormone contrast with the elegant simplicity of plant life. This paper summarizes a sixty-year Odyssey.
Heat Shock Proteins: Connectors between Heart and Kidney
Authors: Junho Carolina Victória Cruz , Azevedo Carolina Amaral Bueno , da Cunha Regiane Stafim , de Yurre Ainhoa Rodriguez , Medei Emiliano , Stinghen Andréa Emilia Marques , Carneiro-Ramos Marcela Sorelli
Published: July 2021

Over the development of eukaryotic cells, intrinsic mechanisms have been developed in order to provide the ability to defend against aggressive agents. In this sense, a group of proteins plays a crucial role in controlling the production of several proteins, guaranteeing cell survival. The heat shock proteins (HSPs), are a family of proteins that have been linked to different cellular functions, being activated under conditions of cellular stress, not only imposed by thermal variation but also toxins, radiation, infectious agents, hypoxia, etc. Regarding pathological situations as seen in cardiorenal syndrome (CRS), HSPs have been shown to be important mediators involved in the control of gene transcription and intracellular signaling, in addition to be an important connector with the immune system. CRS is classified as acute or chronic and according to the first organ to suffer the injury, which can be the heart (CRS type 1 and type 2), kidneys (CRS type 3 and 4) or both (CRS type 5). In all types of CRS, the immune system, redox balance, mitochondrial dysfunction, and tissue remodeling have been the subject of numerous studies in the literature in order to elucidate mechanisms and propose new therapeutic strategies. In this sense, HSPs have been targeted by researchers as important connectors between kidney and heart. Thus, the present review has a focus to present the state of the art regarding the role of HSPs in the pathophysiology of cardiac and renal alterations, as well their role in the kidney–heart axis.
May the Force Be with You (Or Not): The Immune System under Microgravity
Authors: ElGindi Mei , Sapudom Jiranuwat , Ibrahim Ibrahim Hamed , Al-Sayegh Mohamed , Chen Weiqiang , Garcia-Sabaté Anna , Teo Jeremy C. M.
Published: July 2021

All terrestrial organisms have evolved and adapted to thrive under Earth’s gravitational force. Due to the increase of crewed space flights in recent years, it is vital to understand how the lack of gravitational forces affects organisms. It is known that astronauts who have been exposed to microgravity suffer from an array of pathological conditions including an impaired immune system, which is one of the most negatively affected by microgravity. However, at the cellular level a gap in knowledge exists, limiting our ability to understand immune impairment in space. This review highlights the most significant work done over the past 10 years detailing the effects of microgravity on cellular aspects of the immune system.
The Arbuscular Mycorrhizal Fungus Glomus viscosum Improves the Tolerance to Verticillium Wilt in Artichoke by Modulating the Antioxidant Defense Systems
Authors: Villani Alessandra , Tommasi Franca , Paciolla Costantino
Published: July 2021

Verticillium wilt, caused by the fungal pathogen Verticillium dahliae, is the most severe disease that threatens artichoke (Cynara scolymus L.) plants. Arbuscular mycorrhizal fungi (AMF) may represent a useful biological control strategy against this pathogen attack, replacing chemical compounds that, up to now, have been not very effective. In this study, we evaluated the effect of the AMF Glomus viscosum Nicolson in enhancing the plant tolerance towards the pathogen V. dahliae. The role of the ascorbate-glutathione (ASC-GSH) cycle and other antioxidant systems involved in the complex network of the pathogen-fungi-plant interaction have been investigated. The results obtained showed that the AMF G. viscosum is able to enhance the defense antioxidant systems in artichoke plants affected by V. dahliae, alleviating the oxidative stress symptoms. AMF-inoculated plants exhibited significant increases in ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), and superoxide dismutase (SOD) activities, a higher content of ascorbate (ASC) and glutathione (GSH), and a decrease in the levels of lipid peroxidation and hydrogen peroxide (H2O2). Hence, G. viscosum may represent an effective strategy for mitigating V. dahliae pathogenicity in artichokes, enhancing the plant defense systems, and improving the nutritional values and benefit to human health.
Multi-Sensor Characterization of Sparkling Wines Based on Data Fusion
Authors: Izquierdo-Llopart Anais , Saurina Javier
Published: July 2021

This paper is focused on the assessment of a multi-sensor approach to improve the overall characterization of sparkling wines (cava wines). Multi-sensor, low-level data fusion can provide more comprehensive and more accurate vision of results compared with the study of simpler data sets from individual techniques. Data from different instrumental platforms were combined in an enriched matrix, integrating information from spectroscopic (UV/Vis and FTIR), chromatographic, and other techniques. Sparkling wines belonging to different classes, which differed in the grape varieties, coupages, and wine-making processes, were analyzed to determine organic acids (e.g., tartaric, lactic, malic, and acetic acids), pH, total acidity, polyphenols, total antioxidant capacity, ethanol, or reducing sugars. The resulting compositional values were treated chemometrically for a more efficient recovery of the underlaying information. In this regard, exploratory methods such as principal component analysis showed that phenolic compounds were dependent on varietal and blending issues while organic acids were more affected by fermentation features. The analysis of the multi-sensor data set provided a more comprehensive description of cavas according to grape classes, blends, and vinification processes. Hierarchical Cluster Analysis (HCA) allowed specific groups of samples to be distinguished, featuring malolactic fermentation and the chardonnay and red grape classes. Partial Least Squares-Discriminant Analysis (PLS-DA) also classified samples according to the type of grape varieties and fermentations. Bar charts and complementary statistic test were performed to better define the differences among the studied samples based on the most significant markers of each cava wine type. As a conclusion, catechin, gallic, gentisic, caftaric, caffeic, malic, and lactic acids were the most remarkable descriptors that contributed to their discrimination based on varietal, blending, and oenological factors.
Carbon Quantum Dots from Lemon Waste Enable Communication among Biodevices
Authors: Calì Federico , Cantaro Valentina , Fichera Luca , Ruffino Roberta , Trusso Sfrazzetto Giuseppe , Li-Destri Giovanni , Tuccitto Nunzio
Published: July 2021

A bioinspired method of communication among biodevices based on fluorescent nanoparticles is herein presented. This approach does not use electromagnetic waves but rather the exchange of chemical systems—a method known as molecular communication. The example outlined was based on the fluorescence properties of carbon dots and follows a circular economy approach as the method involves preparation from the juice of lemon waste. The synthesis is herein presented, and the fluorescence properties and diffusion coefficient are evaluated. The application of carbon dots to molecular communication was studied from a theoretical point of view by numerically solving the differential equation that governs the phenomenon. The theoretical results were used to develop a prototype molecular communication platform that enables the communication of simple messages via aqueous fluids to a fluorescence-detecting biodevice receiver.
Pulmonary Vein Stenosis in Children: A Programmatic Approach Employing Primary and Anatomic Therapy
Authors: Kuo James A. , Petit Christopher J.
Published: July 2021

Pulmonary vein stenosis (PVS) is a difficult condition to treat due to recurrence and progression. In 2017, we developed a comprehensive PVS Program at our center to address the multidisciplinary needs of these patients. We discuss the components of our program and our approach to these patients, using a combination of primary (medical) therapy in addition to anatomic therapy to preserve vessel patency. A multidisciplinary approach to treating these challenging patients is critical.
Extravascular MDCT Findings of Pulmonary Vein Stenosis in Children with Cardiac Septal Defect
Authors: Lee Edward Y. , Callahan Ryan , Vargas Sara O. , Jenkins Kathy J. , Park Halley J. , Gauthier Zachary , Winant Abbey J.
Published: July 2021

Purpose: To retrospectively investigate the extravascular thoracic MDCT angiography findings of pulmonary vein stenosis (PVS) in children with a cardiac septal defect. Materials and Methods: Pediatric patients (age ≤ 18 years) with cardiac septal defect and PVS, confirmed by echocardiogram and/or conventional angiography, who underwent thoracic MDCT angiography studies from April 2009 to April 2021 were included. Two pediatric radiologists independently evaluated thoracic MDCT angiography studies for the presence of extravascular thoracic abnormalities in: (1) lung and airway (ground-glass opacity (GGO), consolidation, pulmonary nodule, mass, cyst, septal thickening, fibrosis, and bronchiectasis); (2) pleura (pleural thickening, pleural effusion, and pneumothorax); and (3) mediastinum (mass and lymphadenopathy). Interobserver agreement between the two independent pediatric radiology reviewers was evaluated with kappa statistics. Results: The final study group consisted of 20 thoracic MDCT angiography studies from 20 consecutive individual pediatric patients (13 males (65%) and 7 females (35%); mean age: 7.5 months; SD: 12.7; range: 2 days to 7 months) with cardiac septal defect and PVS. The characteristic extravascular thoracic MDCT angiography findings were GGO (18/20; 90%), septal thickening (9/20; 45%), pleural thickening (16/20; 80%), and ill-defined, mildly heterogeneously enhancing, non-calcified soft tissue mass (9/20; 45%) following the contours of PVS in the mediastinum. There was a high interobserver kappa agreement between two independent reviewers for detecting extravascular abnormalities on thoracic MDCT angiography studies (k = 0.99). Conclusion: PVS in children with a cardiac septal defect has a characteristic extravascular thoracic MDCT angiography finding. In the lungs and pleura, GGO, septal thickening, and pleural thickening are frequently seen in children with cardiac septal defect and PVS. In the mediastinum, a mildly heterogeneously enhancing, non-calcified soft tissue mass in the distribution of PVS in the mediastinum is seen in close to half of the pediatric patients with cardiac septal defect and PVS.
Role of Periodontal Bacteria, Viruses, and Placental mir155 in Chronic Periodontitis and Preeclampsia—A Genetic Microbiological Study
Authors: Mahendra Jaideep , Mahendra Little , Mugri Maryam H. , Sayed Mohammed E. , Bhandi Shilpa , Alshahrani Rahaf Turki , Balaji Thodur Madapusi , Varadarajan Saranya , Tanneeru Swetha , P. Abirami Nayaki Rao , Srinivasan Sruthi , Reda Rodolfo , Testarelli Luca , Patil Shankargouda
Published: July 2021

Previous studies assessed the involvement and impact of periodontal bacteria in preeclamptic women with chronic periodontitis. To explore further, the current study aimed to associate periodontal viruses and bacteria with mir155 levels in placental tissues of preeclamptic women with generalized chronic periodontitis. Four-hundred 45 pregnant women, 18–35 years of age, were selected and divided into four groups (controls, A, B, and C) where the Controls included 145 systemically and periodontally healthy pregnant women Group A-100 systemically healthy pregnant women with chronic periodontitis, Group B- 100 preeclamptic women with chronic periodontitis, Group C- 100 preeclamptic women without chronic periodontitis. Age, BMI, SES, and periodontal parameters such as PI, BOP, PPD, and CAL were noted. Periodontal pathogens such as Tf, Td, Pg, Pi, Fn, HSV, EBV, and HCMV were tested in subgingival plaque, placental tissues, and mir155. We observed that PI, BOP, PPD, CAL, Tf, and EBV were highly significant in Group B. We found a higher number of periodontal bacteria, viruses, and mir 155 in Group B showing a higher risk of preeclampsia. More genetic studies in this field are advised to ascertain the role of periodontopathogens and mir 155 in preeclampsia and periodontal inflammation. What is already known on this subject? Periodontal diseases pose an increased risk of developing preeclampsia and delivering preterm and/or low-birth-weight babies. What do the results of this study add? Periodontal variables such as PI, pocket depth, BOP, and clinical attachment levels, were found to be increased in the preeclamptic women with chronic periodontitis. The significant difference was seen in the relative fold expression of mir155 with higher gene expression of mir155 in groups B and A as compared to group C and controls. What are the implications of these findings for clinical practice and/or further research? In our study, mir155 correlation with the periodontal parameters and periodontal pathogens further strengthen the evidence of periodontal inflammation as a risk of preeclampsia in pregnant women especially when associated with chronic periodontitis. mir155 can be considered to be one of the genetic biomarkers and can be used as a diagnostic tool for the early detection of PE.