bluuebunny/crossref_metadata_2025 huggingface dataset:
Short-Term Effects of Temperature and Thyrotropin-Releasing Hormone Stimulation on Adrenocorticotropin Stability in Horses
Authors: Hinrichsen Sophia L. , Yuen Ka Y. , Dryburgh Elizabeth L. , Bertin François-René , Stewart Allison J.
Published: January 2022

Pituitary pars intermedia dysfunction (PPID) is diagnosed by increased basal or post thyrotropin-releasing hormone (TRH) stimulation ACTH concentrations. ACTH is known to be unstable; however, the effect of different temperatures and TRH stimulation on equine ACTH stability is poorly described. In total, 15 horses, including 8 PPID positive (ACTH > 35 pg/mL at baseline or >65 pg/mL 30 min after TRH stimulation), were divided into 2 groups: 9, including 5 PPID positive, with basal ACTH concentrations and 6, including 3 PPID positive, with post TRH stimulation ACTH concentrations. Whole blood was stored for 1 h at 4, 20, 30, 40, or 70 °C. After centrifugation, immunoreactive ACTH concentrations were determined using a chemiluminescent assay. Linear mixed effect models were used to detect the effects of temperature, PPID status, and TRH stimulation on the immunoreactive ACTH concentration. Temperature had a significant effect (p = 0.003) on immunoreactive ACTH concentrations, and this effect was greater in PPID-negative horses (p = 0.01), with the changes in immunoreactive ACTH concentrations being slightly unpredictably higher or lower than samples stored at 4 °C. Even at 20 °C, mean immunoreactive ACTH concentrations minimally changed by 5% in PPID horses and 12% in non-PPID horses after 1 h. No significant effect of TRH stimulation was identified. Although ACTH concentrations should ideally be determined from samples kept at 4 °C, samples inadvertently left at temperatures of up to 40 °C can provide valid results if analyzed within 1 h; however, this increases the risks of altered ACTH concentrations, occasionally influencing the diagnosis of PPID.
Novel Phage Lysin Abp013 against Acinetobacter baumannii
Authors: Chu Joash Jun Keat , Poh Wee Han , Hasnuddin Nabilah Taqiah Binte , Hew En Yi , Dam Linh Chi , Sahili Abbas El , Rice Scott A. , Goh Boon Chong
Published: January 2022

As antimicrobial resistance (AMR) continues to pose an ever-growing global health threat, propelling us into a post-antibiotic era, novel alternative therapeutic agents are urgently required. Lysins are bacteriophage-encoded peptidoglycan hydrolases that display great potential as a novel class of antimicrobials for therapeutics. While lysins against Gram-positive bacteria are highly effective when applied exogenously, it is challenging for lysins to access and cleave the peptidoglycan of Gram-negative bacteria due to their outer membrane. In this study, we identify a novel phage lysin Abp013 against Acinetobacter baumannii. Abp013 exhibited significant lytic activity against multidrug-resistant strains of A. baumannii. Notably, we found that Abp013 was able to tolerate the presence of human serum by up to 10%. Using confocal microscopy and LIVE/DEAD staining, we show that Abp013 can access and kill the bacterial cells residing in the biofilm. These results highlight the intrinsic bacteriolytic property of Abp013, suggesting the promising use of Abp013 as a novel therapeutic agent.
Fluoroquinolones and Other Antibiotics Redeemed for Cystitis—A Swedish Nationwide Cohort Follow-Up Study (2006–2018)
Authors: Li Xinjun , Sundquist Kristina , Jansåker Filip
Published: January 2022

Background: Antibiotics are commonly prescribed for outpatient management of cystitis. Previous evidence suggests that certain factors likely beyond the infection seem to influence the choice of antimicrobial treatment. However, studies on the specific antibiotic treatments for cystitis are lacking. This study aimed to explore the antibiotic treatments for cystitis using nationwide primary healthcare data and investigate if factors beyond the infection could be associated with fluoroquinolone treatment. Methods: This nationwide follow-up cohort study consisted of 352,507 women with cystitis. The primary aim was to investigate what specific classes of antibiotics were redeemed by patients within five days from the cystitis diagnosis. Each patient could only be included once. Logistic regression models were also used to examine the relationship between fluoroquinolone (FQ) treatment, parity, and sociodemographic factors. Results: In total, 192,065 antibiotic prescriptions were redeemed. Pivmecillinam (58.4%) followed by nitrofurantoin (22.2%), trimethoprim (12.0%), fluoroquinolone (5.6%), and cephalosporins (1.5%) were the most redeemed antibiotics. Sociodemographic factors were weakly associated with fluoroquinolone treatment; young age was inversely associated with fluoroquinolone treatment. Parity and cervical cancer history were not associated with fluoroquinolone treatment. The proportion of fluoroquinolone and trimethoprim treatments decreased over time, while pivmecillinam and nitrofurantoin increased. Conclusions: The treatment trends of antibiotics redeemed within five days from a cystitis diagnosis were similar to the national surveillance program of these antibiotics (not diagnosis linked). Fluoroquinolones were weakly associated with sociodemographic factors, which likely is only of historical relevance.
Efficacy of Vancomycin and Meropenem in Central Nervous System Infections in Children and Adults: Current Update
Authors: Schneider Franziska , Gessner André , El-Najjar Nahed
Published: January 2022

The current antimicrobial therapy of bacterial infections of the central nervous system (CNS) in adults and pediatric patients is faced with many pitfalls as the drugs have to reach necessary levels in serum and cross the blood-brain barrier. Furthermore, several studies report that different factors such as the structure of the antimicrobial agent, the severity of disease, or the degree of inflammation play a significant role. Despite the available attempts to establish pharmacokinetic (PK) modeling to improve the required dosing regimen for adults and pediatric patients, conclusive recommendations for the best therapeutic strategies are still lacking. For instance, bacterial meningitis, the most common CNS infections, and ventriculitis, a severe complication of meningitis, are still associated with 10% and 30% mortality, respectively. Several studies report on the use of vancomycin and meropenem to manage meningitis and ventriculitis; therefore, this review aims to shed light on the current knowledge about their use in adults and pediatric patients. Consequently, studies published from 2015 until mid-July 2021 are included, and data about the study population, levels of drugs in serum and cerebrospinal fluid (CSF), and measured PK data in serum and CSF are provided. The overall aim is to provide the readers a recent reference that summarizes the pitfalls and success of the current therapy and emphasizes the importance of performing more studies to improve the clinical outcome of the current therapeutical approach.
Nrf2/ARE Signaling Directly Regulates SOX9 to Potentially Alter Age-Dependent Cartilage Degeneration
Authors: Kubo Yusuke , Beckmann Rainer , Fragoulis Athanassios , Conrads Claudius , Pavanram Prathyusha , Nebelung Sven , Wolf Michael , Wruck Christoph Jan , Jahr Holger , Pufe Thomas
Published: January 2022

Oxidative stress is implicated in osteoarthritis, and nuclear factor erythroid 2–related factor 2 (Nrf2)/antioxidant response element (ARE) pathway maintains redox homeostasis. We investigated whether Nrf2/ARE signaling controls SOX9. SOX9 expression in human C-28/I2 chondrocytes was measured by RT–qPCR after shRNA-mediated knockdown of Nrf2 or its antagonist the Kelch-like erythroid cell-derived protein with cap ‘‘n’’ collar homology-associated protein 1 (Keap1). To verify whether Nrf2 transcriptionally regulates SOX9, putative ARE-binding sites in the proximal SOX9 promoter region were inactivated, cloned into pGL3, and co-transfected with phRL–TK for dual-luciferase assays. SOX9 promoter activities without and with Nrf2-inducer methysticin were compared. Sox9 expression in articular chondrocytes was correlated to cartilage thickness and degeneration in wild-type (WT) and Nrf2-knockout mice. Nrf2-specific RNAi significantly decreased SOX9 expression, whereas Keap1-specific RNAi increased it. Putative ARE sites (ARE1, ARE2) were identified in the SOX9 promoter region. ARE2 mutagenesis significantly reduced SOX9 promoter activity, but ARE1 excision did not. Functional ARE2 site was essential for methysticin-mediated induction of SOX9 promoter activity. Young Nrf2-knockout mice revealed significantly lower Sox9-positive chondrocytes, and old Nrf2-knockout animals showed thinner cartilage and more cartilage degeneration. Our results suggest Nrf2 directly regulates SOX9 in articular cartilage, and Nrf2-loss can develop mild osteoarthritis at old age. Pharmacological Nrf2 induction may hold the potential to diminish age-dependent cartilage degeneration through improving SOX9 expression.
Exploring the Age Effects on European Portuguese Vowel Production: An Ultrasound Study
Authors: Albuquerque Luciana , Valente Ana Rita , Barros Fábio , Teixeira António , Silva Samuel , Martins Paula , Oliveira Catarina
Published: January 2022

For aging speech, there is limited knowledge regarding the articulatory adjustments underlying the acoustic findings observed in previous studies. In order to investigate the age-related articulatory differences in European Portuguese (EP) vowels, the present study analyzes the tongue configuration of the nine EP oral vowels (isolated context and pseudoword context) produced by 10 female speakers of two different age groups (young and old). From the tongue contours automatically segmented from the US images and manually revised, the parameters (tongue height and tongue advancement) were extracted. The results suggest that the tongue tends to be higher and more advanced for the older females compared to the younger ones for almost all vowels. Thus, the vowel articulatory space tends to be higher, advanced, and bigger with age. For older females, unlike younger females that presented a sharp reduction in the articulatory vowel space in disyllabic sequences, the vowel space tends to be more advanced for isolated vowels compared with vowels produced in disyllabic sequences. This study extends our pilot research by reporting articulatory data from more speakers based on an improved automatic method of tongue contours tracing, and it performs an inter-speaker comparison through the application of a novel normalization procedure.
UCLAONT: Ontology-Based UML Class Models Verification Tool
Authors: Rajab Adel , Hafeez Abdul , Shaikh Asadullah , Alghamdi Abdullah , Al Reshan Mana Saleh , Hamdi Mohammed , Rajab Khairan
Published: January 2022

The software design model performs an important role in modern software engineering methods. Especially in Model-Driven Engineering (MDE), it is treated as an essential asset of software development; even programming language code is produced by the models. If the model has errors, then they can propagate into the code. Model verification tools check the presence of errors in the model. This paper shows how a UML class model verification tool has been built to support complex models and unsupported elements such as XOR constraints and dependency relationships. This tool uses ontology for verifying the UML class model. It takes a class model in XMI format and generates the OWL file. Performs verification of model in two steps: (1) uses the ontology-based algorithm to verify association multiplicity constraints; and (2) uses ontology reasoner for the verification of XOR constraints and dependency relationships. The results show the proposed tool improves the verification efficiency and supports the verification of UML class model elements that have not been supported by any existing tool.
Extreme Learning Machine Using Bat Optimization Algorithm for Estimating State of Health of Lithium-Ion Batteries
Authors: Ge Dongdong , Zhang Zhendong , Kong Xiangdong , Wan Zhiping
Published: January 2022

An accurate estimation of the state of health (SOH) of lithium-ion batteries is essential for the safe and reliable operation of electric vehicles. As a single hidden-layer feedforward neural network, extreme learning machine (ELM) has the advantages of a fast learning speed and good generalization performance. The bat algorithm (BA) is a swarm intelligence optimization algorithm based on bat echolocation for foraging. In this study, BA was creatively applied to improve the ELM neural network, forming a BA-ELM model, and it was applied to SOH estimation for the first time. First, through Pearson and Spearman correlation analysis, six variables were determined as the input variables of the model. The actual remaining capacity of the battery was determined as the output variable. Second, BA was used to optimize the connection weights and bias in ELM to construct the BA-ELM model. Third, the battery data set was trained and tested with BA-ELM, ELM, Elman, back propagation (BP), radial basis function (RBF), and general regression neural network (GRNN) models. Five statistical error indicators, and the radar chart, scatter plot, and violin diagram were used to compare the estimation effects. The results show that the evaluation function of BA-ELM can converge quickly and effectively optimize the network model of ELM. The RMSE of the BA-ELM model was 0.5354%, and the MAE was 0.4326%, which is the smallest among the 6 models. The RMSE values of the other model were 2.27%, 3.53%, 3.07%, 3.86%, 3.24%, respectively, indicating the BA-ELM has good potential for future applications.
Investigating Particulate and Nitrogen Oxides Emissions of a Plug-In Hybrid Electric Vehicle for a Real-World Driving Scenario
Authors: Feinauer Mario , Ehrenberger Simone , Epple Fabius , Schripp Tobias , Grein Tobias
Published: January 2022

Plug-in hybrid electric vehicles (PHEVs) show a high pollutant emission variability that strongly depends on the operating conditions of the internal combustion engine. Additionally, studies indicate that driving situations outside of the real driving emissions boundary conditions can lead to substantial pollutant emission increases. The objective of this study is to measure and analyze the particulate number (PN) and nitrogen oxides (NOx) emissions of a Euro 6 PHEV for a selected real-world driving test route in the Stuttgart metropolitan area. For this purpose, the vehicle is set out with multiple measurement devices to monitor vehicle internal and external parameters. Particle distribution results show an overall uniform pattern, which allows a comparative analysis of the different test scenarios on the basis of the PN concentration. While the trip-average PN emissions are in good agreement, transient effects during highway driving can substantially increase emissions, whereas the fuel consumption does not necessarily increase in such situations. PN measurements including ultrafine particles (UFP) show a significant increase in urban emissions due to higher cold start emission peaks. Additionally, low ambient temperatures raise the uncertainty of NOx and PN cold start emissions. With regard to future emission regulations, which claim that vehicles need to be as clean as possible in all driving situations, PHEV emission investigations for further situations outside of the current legislations are required.
Members of the AP-1 Family of Transcription Factors Regulate the Expression of Gja1 in Mouse GC-1 Spermatogonial Cells
Authors: Najih Mustapha , Basque Audrey , Nguyen Ha Tuyen , Diawara Mariama , Martin Luc J.
Published: January 2022

Gap junctions, mainly formed by Gja1 (Connexin43), play an essential role in the regulation of proliferation and differentiation of spermatogonia in the testis. Regulation of the abundance of Gja1 in spermatogonia involves various processes, including gene transcription, mRNA maturation, protein synthesis, post-translational modifications, plasma membrane integration and protein degradation. However, gene expression of Gja1 is abnormally decreased in most testicular germ cell tumors. Hence, a better understanding of the mechanisms of transcriptional regulation of Gja1 in spermatogonia is essential to understand how the loss of its expression occurs during the development of testicular cancer. As in other cell types, activator protein-1 (AP-1) transcription factors may be involved in such regulatory process. Thus, AP-1 members were overexpressed in GC-1 cells to assess their impact on Gja1 expression. We showed that Jun and Fosl2 cooperate to activate the Gja1 promoter in GC-1 cells. Furthermore, the recruitment of Jun to the proximal region (−153 to +46 bp) of the Gja1 promoter has been confirmed via chromatin immunoprecipitation. Protein kinase A and calcium-calmodulin protein kinase I also contribute to the activation of Gja1 expression by improving the cooperation between AP-1 factors. Therefore, the reduction in Gja1 expression in testicular germ cell tumors may involve a loss of cooperation between AP-1 factors.
Psychological Stress Level Detection Based on Heartbeat Mode
Authors: Hu Dun , Gao Lifu
Published: January 2022

The effective detection and quantification of mental health has always been an important research topic. Heart rate variability (HRV) analysis is a useful tool for detecting psychological stress levels. However, there is no consensus on the optimal HRV metrics in psychological assessments. This study proposes an HRV analysis method that is based on heartbeat modes to detect drivers’ stress. We used statistical tools for linguistics to detect and quantify the structure of the heart rate time series and summarized different heartbeat modes in the time series. Based on the k-nearest neighbors (k-NN) classification algorithm, the probability of each heartbeat mode was used as a feature to detect and recognize stress caused by the driving environment. The results indicated that the stress from the driving environment changed the heartbeat mode. Stress-related heartbeat modes were determined, facilitating detection of the stress state with an accuracy of 93.7%. We also concluded that the heartbeat mode was correlated to the galvanic skin response (GSR) signal, reflecting real-time abnormal mood fluctuations. The proposed method revealed HRV characteristics that made quantifying and detecting different mental conditions possible. Thus, it would be feasible to achieve personalized analyses to further study the interaction between physiology and psychology.
An Investigation to Reduce the Effect of Moisture on Injection-Molded Parts through Optimization of Plasticization Parameters
Authors: Chen Shia-Chung , Su Han , Mathew Jibin Jose , Gunawan Hariyanto , Huang Chun-Wei , Feng Ching-Te
Published: January 2022

Plastic materials can absorb moisture from the atmosphere even after drying. This absorbed moisture can cause many defects in the molding process. Conventionally, a dryer is used to reduce the moisture content. However, the use of a drying unit involves huge daily power consumption and is also time-consuming. Therefore, this study proposed a new method to reduce the impact of moisture on molded product part quality through the optimization of plasticization parameters while reducing drying time. Two plastic materials, polyurethane (TPU) and polycarbonate (PC), were used for the experimental verification. Key plasticization parameters, including back pressure, screw rotation speed, and barrel temperature were chosen; their influence was investigated by the design of experiments (DOE). Moisture-induced defects, such as air bubble area, part surface gloss, and appearance were measured and correlated with the plasticization parameters. It was found, after optimization via a three-level DOE and factorial design multivariate statistical analysis using TPU, that the gloss (GU) of the PC part without drying was very close to that (98.4 GU) of the fully dried PC. The proposed methodology may help molders to improve production efficiency and achieve cost savings.
Patent Analysis Using Bayesian Data Analysis and Network Modeling
Authors: Park Sangsung , Jun Sunghae
Published: January 2022

Patent analysis is to analyze patent data to understand target technology. Patent data contains various detailed information about the developed technology. Therefore, many studies concerning patent analysis have been carried out in the technology analysis fields. Most traditional methods for technology analysis were based on qualitative approaches such as Delphi survey. However, the patent analysis methods based on statistics and machine learning have been introduced recently. In this paper, we proposed a statistical method for quantitative patent analysis. Moreover, we selected drone technology as the target technology for patent analysis. To understand drone technology, we analyzed the patents on drone technology. We searched the patent documents related to drone technology and transformed them to structured data using text mining techniques. First, we visualized the patent keywords to identify the technological structure of a drone. Next, using Bayesian additive regression trees, we analyzed the structured patent data to construct technology scenarios for drones. To illustrate the performance and validity of our proposed research, we presented the experimental results of patent analysis using patent documents related to drone technology.
Time-Lapse Electrical Resistivity Tomography (TL-ERT) for Landslide Monitoring: Recent Advances and Future Directions
Authors: Lapenna Vincenzo , Perrone Angela
Published: January 2022

To date, there is a growing interest for challenging applications of time-lapse electrical resistivity tomography (TL-ERT) in Earth sciences. Tomographic algorithms for resistivity data inversion and innovative technologies for sensor networks have rapidly transformed the TL-ERT method in a powerful tool for the geophysical time-lapse imaging. In this paper, we focus our attention on the application of this method in landslide monitoring. Firstly, an overview of recent methodological advances in TL-ERT data processing and inversion is presented. In a second step, a critical analysis of the main results obtained in different field experiments and lab-scale simulations are discussed. The TL-ERT appears to be a robust and cost-effective method for mapping the water-saturated zones, and for the identification of the groundwater preferential pathways in landslide bodies. Furthermore, it can make a valuable contribution to following time-dependent changes in top-soil moisture, and the spatio-temporal dynamics of wetting fronts during extreme rainfall events. The critical review emphasizes the limits and the advantages of this geophysical method and discloses a way to identify future research activities to improve the use of the TL-ERT method in landslide monitoring.
Haptic Teleoperation of Impact Hammers in Underground Mining
Authors: Correa Mauricio , Cárdenas Daniel , Carvajal Diego , Ruiz-del-Solar Javier
Published: January 2022

Impact hammers are used to reduce the size of blasted ore in mining operations. In underground mines, tele-operated impact hammers are used to reduce the size of boulders placed on the orepass’s grizzlies. An impact hammer consists of a hydraulic arm with 4 degrees of freedom, powered with a hydraulic impact hammer as an end-effector. The tele-operation of impact hammers is difficult due to the latency of communications, the poor visibility of the environment, and the used 2D interfaces. This may result in a collision with the hammer and the infrastructure, idle strokes, and non-optimal operation. To address these issues, this paper proposes the haptic tele-operation of impact hammers. The proposed haptic tele-operation system is based on a 3D model of the environment, which is used to estimate repulsion forces that are transferred to the operator via a haptic device, so that the hammer does not collide with the structures of the mine. The system also allows identifying the oversized boulders deposited on the grizzly and notifying the operator every time the orepass is blocked, as well as providing different 3D views of the environment. A proof of concept is presented using a scaled setup, where it is validated that the use of the proposed system allows for providing a better and more efficient tele-operation experience.
Separation of Lignocellulose and Preparation of Xylose from Miscanthus lutarioriparius with a Formic Acid Method
Authors: Ouyang Jia , He Wen-Qiang , Li Qing-Ming , Chen Liang , Wu Xiao-Fen , Su Xiao-Jun
Published: January 2022

Efficient component separation technology is one of the key ways to improve the efficiency of lignocellulose bioconversion. In this study, the formic acid method was used to separate the components of lignocellulose from Miscanthus lutarioriparius, hemicellulose was degraded into xylose simultaneously, and the composition and structure of the separated components were analyzed. Then, xylose was further purified with activated carbon for decolorization and resins for the removal of formic acid and other monosaccharide impurities. The results showed that formic acid could effectively separate the cellulose, hemicellulose, and lignin of lignocellulose with recoveries of 91.7%, 80.2%, and 85.3%, respectively. Structural analyses revealed that the cellulose and lignin underwent different degrees of formylation during the formic acid treatment, yet their primary structures remained intact, and the crystallinity of cellulose increased significantly. By GC–MS and HPLC analysis, xylose was the main component of hemicellulose extract, accounting for 74.90%. The activated carbon treatment decolorized the xylose extract more than 93.66% and gave a xylose recovery of 88.58%. D301 resin could effectively remove more than 99% of the formic acid residue in xylose. The xylose extract was further purified by removing arabinose and other monosaccharide impurities with Dowex 50wx4 resin, which increased the purity to 95%. The results demonstrated that the formic acid method is an effective method to separate lignocellulose and prepare xylose, and it has broad application prospects in the field of bio-refining lignocellulose resources such as Miscanthus lutarioriparius
Modeling of the Drying Process of Apple Pomace
Authors: Tulej Weronika , Głowacki Szymon
Published: January 2022

Understanding biological materials is quite complicated. The material apple pomace is biologically unstable has been dried under certain conditions. Modeling the pomace drying is necessary to understand the heat and mass transport mechanism and is a prerequisite for the mathematical description of the entire process. Such a model plays an important role in the optimization or control of working conditions. Modeling of the pomace drying process is difficult as apple pomace is highly heterogeneous, as it consists of flesh, seeds, seed covers, and petioles of various sizes, shapes and proportions. A simple mathematical model (Page) was used, which describes well the entire course of the drying process. This is used to control the process. In turn, complex mathematical models describe the phenomena and scientifically explain the essence of drying. Mathematical modeling of the dewatering process is an indispensable part of the design, development and optimization of drying equipment.
Correction: Riccio et al. Effects of Curing on Photosensitive Resins in SLA Additive Manufacturing. Appl. Mech. 2021, 2, 942–955
Authors: Riccio Carmela , Civera Marco , Grimaldo Ruiz Oliver , Pedullà Perla , Rodriguez Reinoso Mariana , Tommasi Giulia , Vollaro Martina , Burgio Vito , Surace Cecilia
Published: January 2022

The Authors of the paper “Effects of Curing on Photosensitive Resins in SLA Additive Manufacturing” [...]
Nosocomial Infections and Role of Nanotechnology
Authors: Ananda Thripthi , Modi Ankita , Chakraborty Ishita , Managuli Vishwanath , Mukhopadhyay Chiranjay , Mazumder Nirmal
Published: January 2022

Nosocomial infections, termed hospital-acquired infections (HAIs), are acquired from a healthcare or hospital setting. HAI is mainly caused by bacteria, such as Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Enterococci spp., Methicillin-resistant Staphylococcus aureus (MRSA), and many more. Due to growing antibacterial resistance, nanotechnology has paved the way for more potent and sensitive methods of detecting and treating bacterial infections. Nanoparticles have been used with molecular beacons for identifying bactericidal activities, targeting drug delivery, and anti-fouling coatings, etc. This review addresses the looming threat of nosocomial infections, with a focus on the Indian scenario, and major initiatives taken by medical bodies and hospitals in spreading awareness and training. Further, this review focuses on the potential role nanotechnology can play in combating the spread of these infections.
Photocurable GelMA Adhesives for Corneal Perforations
Authors: Barroso Inês A. , Man Kenny , Robinson Thomas E. , Cox Sophie C. , Ghag Anita K.
Published: January 2022

The current treatments for the management of corneal and scleral perforations include sutures and adhesives. While sutures are invasive, induce astigmatism and carry a risk of infection, cyanoacrylate glues are toxic, proinflammatory and form an opaque and rough surface that precludes vision. Consequently, the clinical need for a fast curing and strong tissue adhesive with minimised cytotoxicity and host inflammation remains unmet. In this paper, we engineer a gelatine methacryloyl (GelMA) adhesive that can be crosslinked in situ within 2 min using UV or visible light and a riboflavin (RF)/sodium persulfate (SPS) system. Optical coherence tomography (OCT) images demonstrated that the flowable GelMA adhesive could completely fill corneal wounds and restore the ocular curvature by forming a smooth contour on the ocular surface. Further, ex vivo studies in porcine eyes showed that GelMA bioadhesives exhibited burst pressures that were comparable to cyanoacrylates (49 ± 9 kPa), with the hydrogels exhibiting a transmittance (90%), water content (85%) and storage modulus (5 kPa) similar to the human cornea. Finally, using human dermal fibroblasts, we showed that our GelMA adhesive was non-toxic and could effectively support cell adhesion and proliferation. Taken together, the adhesive’s performance, injectability and ease of administration, together with gelatin’s availability and cost-effectiveness, make it a potential stromal filler or sealant for corneal and conjunctival applications.
A Broad Review of Soybean Research on the Ongoing Race to Overcome Soybean Cyst Nematode
Authors: Nissan Nour , Mimee Benjamin , Cober Elroy R. , Golshani Ashkan , Smith Myron , Samanfar Bahram
Published: January 2022

Plant pathogens greatly impact food security of the ever-growing human population. Breeding resistant crops is one of the most sustainable strategies to overcome the negative effects of these biotic stressors. In order to efficiently breed for resistant plants, the specific plant–pathogen interactions should be understood. Soybean is a short-day legume that is a staple in human food and animal feed due to its high nutritional content. Soybean cyst nematode (SCN) is a major soybean stressor infecting soybean worldwide including in China, Brazil, Argentina, USA and Canada. There are many Quantitative Trait Loci (QTLs) conferring resistance to SCN that have been identified; however, only two are widely used: rhg1 and Rhg4. Overuse of cultivars containing these QTLs/genes can lead to SCN resistance breakdown, necessitating the use of additional strategies. In this manuscript, a literature review is conducted on research related to soybean resistance to SCN. The main goal is to provide a current understanding of the mechanisms of SCN resistance and list the areas of research that could be further explored.
Growth Factors Do Not Improve Muscle Function in Young or Adult mdx Mice
Authors: Nielsen Tue L. , Hornsyld Tessa M. , Pinós Tomàs , Brolin Camilla , Vissing John , Krag Thomas O.
Published: January 2022

Muscular dystrophies constitute a broad group of genetic disorders leading to muscle wasting. We have previously demonstrated that treating a muscular atrophy mouse model with growth factors resulted in increased muscle mass. In the present study, we treated the Duchenne mouse model mdx for 12 weeks with myogenic growth factors peri- and post-onset of muscular degeneration to explore the effects in the oxidative muscle soleus and the glycolytic muscle extensor digitorum longus (EDL). We found no overall beneficial effect in the peri-onset group at the conclusion of the study. In the post-onset group, the functional improvement by means of electrophysiological examinations ex vivo was mostly confined to the soleus. EDL benefitted from the treatment on a molecular level but did not improve functionally. Histopathology revealed signs of inflammation at the end of treatment. In conclusion, the growth factor cocktail failed to improve the mdx on a functional level.
Neuroimaging of Mouse Models of Alzheimer’s Disease
Authors: Jullienne Amandine , Trinh Michelle V. , Obenaus Andre
Published: January 2022

Magnetic resonance imaging (MRI) and positron emission tomography (PET) have made great strides in the diagnosis and our understanding of Alzheimer’s Disease (AD). Despite the knowledge gained from human studies, mouse models have and continue to play an important role in deciphering the cellular and molecular evolution of AD. MRI and PET are now being increasingly used to investigate neuroimaging features in mouse models and provide the basis for rapid translation to the clinical setting. Here, we provide an overview of the human MRI and PET imaging landscape as a prelude to an in-depth review of preclinical imaging in mice. A broad range of mouse models recapitulate certain aspects of the human AD, but no single model simulates the human disease spectrum. We focused on the two of the most popular mouse models, the 3xTg-AD and the 5xFAD models, and we summarized all known published MRI and PET imaging data, including contrasting findings. The goal of this review is to provide the reader with broad framework to guide future studies in existing and future mouse models of AD. We also highlight aspects of MRI and PET imaging that could be improved to increase rigor and reproducibility in future imaging studies.
Enhanced Chimeric Antigen Receptor T Cell Therapy through Co-Application of Synergistic Combination Partners
Authors: Stock Sophia , Kluever Anna-Kristina , Endres Stefan , Kobold Sebastian
Published: January 2022

Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable response rates and revolutionized the treatment of patients suffering from defined hematological malignancies. However, many patients still do not respond to this therapy or relapse after an initial remission, underscoring the need for improved efficacy. Insufficient in vivo activity, persistence, trafficking, and tumor infiltration of CAR T cells, as well as antigen escape and treatment-associated adverse events, limit the therapeutic success. Multiple strategies and approaches have been investigated to further improve CAR T cell therapy. Besides genetic modification of the CAR itself, the combination with other treatment modalities has the potential to improve this approach. In particular, combining CAR T cells with clinically approved compounds such as monoclonal antibodies and small molecule inhibitors might be a promising strategy. Combination partners could already be applied during the production process to influence the cellular composition and immunophenotype of the final CAR T cell product. Alternatively, simultaneous administration of clinically approved compounds with CAR T cells would be another feasible avenue. In this review, we will discuss current strategies to combine CAR T cells with compounds to overcome recent limitations and further enhance this promising cancer therapy, potentially broadening its application beyond hematology.
The Relationships between Gut Microbiota and Diabetes Mellitus, and Treatments for Diabetes Mellitus
Authors: Craciun Cristian-Ioan , Neag Maria-Adriana , Catinean Adrian , Mitre Andrei-Otto , Rusu Adriana , Bala Cornelia , Roman Gabriela , Buzoianu Anca-Dana , Muntean Dana-Maria , Craciun Anca-Elena
Published: January 2022

Diabetes mellitus is considered to be a global epidemic. The combination of genetic susceptibility and an unhealthy lifestyle is considered to be the main trigger of this metabolic disorder. Recently, there has been increased interest in the roles of gut microbiota as a new potential contributor to this epidemic. Research, in recent years, has contributed to an in-depth characterization of the human microbiome and its associations with various diseases, including metabolic diseases and diabetes mellitus. It is known that diet can change the composition of gut microbiota, but it is unclear how this, in turn, may influence metabolism. The main objective of this review is to evaluate the pathogenetic association between microbiota and diabetes and to explore any new therapeutic agents, including nutraceuticals that may modulate the microbiota. We also look at several mechanisms involved in this process. There is a clear, bidirectional relationship between microbiota and diabetes. Current treatments for diabetes influence microbiota in various ways, some beneficial, but others with still unclear effects. Microbiota-aimed treatments have seen no real-world significant effects on the progression of diabetes and its complications, with more studies needed in order to find a really beneficial agent.
Inhibitor of Hyaluronic Acid Synthesis 4-Methylumbelliferone Suppresses the Secretory Processes That Ensure the Invasion of Neutrophils into Tissues and Induce Inflammation
Authors: Galkina Svetlana I. , Fedorova Natalia V. , Ksenofontov Alexander L. , Golenkina Ekaterina A. , Serebryakova Marina V. , Stadnichuk Vladimir I. , Baratova Ludmila A. , Sud’ina Galina F.
Published: January 2022

Integrin-dependent adhesion of neutrophils to tissue, accompanied by the development of neutrophil-induced inflammation, occurs both in the focus of infection and in the absence of infection in metabolic disorders such as reperfusion after ischemia, diabetes mellitus, or the development of pneumonia in patients with cystic fibrosis or viral diseases. Hyaluronic acid (HA) plays an important role in the recruitment of neutrophils to tissues. 4-methylumbilliferon (4-MU), an inhibitor of HA synthesis, is used to treat inflammation, but its mechanism of action is unknown. We studied the effect of 4-MU on neutrophil adhesion and concomitant secretion using adhesion to fibronectin as a model for integrin-dependent adhesion. 4-MU reduced the spreading of neutrophils on the substrate and the concomitant secretion of granule proteins, including pro-inflammatory components. 4-MU also selectively blocked adhesion-induced release of the free amino acid hydroxylysine, a product of lysyl hydroxylase, which can influence cell invasion by modifying the extracellular matrix. Finally, 4-MU inhibited the formation of cytonemes, the extracellular membrane secretory structures containing the pro-inflammatory bactericides of the primary granules. The anti-inflammatory effect of 4-MU may be associated with the suppression of secretory processes that ensure the neutrophil invasion and initiate inflammation. We suggest that HA, due to the peculiarities of its synthesis, can promote the release of secretory carriers from the cell and 4-MU can block this process.
Graphene Quantum Dots-Based Electrochemical Biosensing Platform for Early Detection of Acute Myocardial Infarction
Authors: Tabish Tanveer A. , Hayat Hasan , Abbas Aumber , Narayan Roger J.
Published: January 2022

Heart failure resulting from acute myocardial infarction (AMI) is an important global health problem. Treatments of heart failure and AMI have improved significantly over the past two decades; however, the available diagnostic tests only give limited insights into these heterogeneous conditions at a reversible stage and are not precise enough to evaluate the status of the tissue at high risk. Innovative diagnostic tools for more accurate, more reliable, and early diagnosis of AMI are urgently needed. A promising solution is the timely identification of prognostic biomarkers, which is crucial for patients with AMI, as myocardial dysfunction and infarction lead to more severe and irreversible changes in the cardiovascular system over time. The currently available biomarkers for AMI detection include cardiac troponin I (cTnI), cardiac troponin T (cTnT), myoglobin, lactate dehydrogenase, C-reactive protein, and creatine kinase and myoglobin. Most recently, electrochemical biosensing technologies coupled with graphene quantum dots (GQDs) have emerged as a promising platform for the identification of troponin and myoglobin. The results suggest that GQDs-integrated electrochemical biosensors can provide useful prognostic information about AMI at an early, reversible, and potentially curable stage. GQDs offer several advantages over other nanomaterials that are used for the electrochemical detection of AMI such as strong interactions between cTnI and GQDs, low biomarker consumption, and reusability of the electrode; graphene-modified electrodes demonstrate excellent electrochemical responses due to the conductive nature of graphene and other features of GQDs (e.g., high specific surface area, π–π interactions with the analyte, facile electron-transfer mechanisms, size-dependent optical features, interplay between bandgap and photoluminescence, electrochemical luminescence emission capability, biocompatibility, and ease of functionalization). Other advantages include the presence of functional groups such as hydroxyl, carboxyl, carbonyl, and epoxide groups, which enhance the solubility and dispersibility of GQDs in a wide variety of solvents and biological media. In this perspective article, we consider the emerging knowledge regarding the early detection of AMI using GQDs-based electrochemical sensors and address the potential role of this sensing technology which might lead to more efficient care of patients with AMI.
Long-Term Outcomes of Surgical Resection of Pathologically Confirmed Isolated Para-Aortic Lymph Node Metastases in Colorectal Cancer: A Systematic Review
Authors: Zizzo Maurizio , Dorma Maria Pia Federica , Zanelli Magda , Sanguedolce Francesca , Bassi Maria Chiara , Palicelli Andrea , Ascani Stefano , Giunta Alessandro
Published: January 2022

Background: Para-aortic lymph node (PALN) metastases represent patterns of initial recurrence in only 2–6% CRC patients, after an estimated 23–28 month time interval. An increasing trend towards curative surgery has been witnessed in patients presenting with controlled PALN recurrence. Nevertheless, lack of consensus has impaired an unambiguous statement for PALN recurrence resection. Methods: We performed a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines, which led us to gain deeper insight into the prognostic factors and long-term outcomes after resection for synchronous or metachronous pathologically confirmed CRC isolated para-aortic lymph node metastases (PALNM). Pubmed/MEDLINE, Embase, Scopus, Cochrane Library and Web of Science databases were used to search all related literature. Results: The nine articles included covered a study period of 30 years (1988–2018), with a total of 161 patients. At presentation, most primary CRCs were located in the colon (74%) and 95.6%, 87.1% and 76.9% patients had T3–T4, N1–N2 and well/moderately differentiated CRC, respectively. We identified a 59.4–68% 3-year OS rate and 53.4–87.5% 5-year OS rate, with a 25–84 months median OS, 26.3–61% 3-year DFS rate and 0–60.5% 5-year DFS rate, with a 14–24 month median DFS. Overall, 62.1% re-recurrence rate ranged from 43.8% to 100%. Conclusions: Although PALNMs resection in CRC patients may be considered a feasible and beneficial option, no conclusions or recommendations can be made taking into account the current evidence. Therefore, further randomized, possibly multicenter trials are strongly recommended and mandatory if we want to have our results confirmed and patient selection criteria clearly identified.
Carcinoid Crisis: A Misunderstood and Unrecognized Oncological Emergency
Authors: Bardasi Camilla , Benatti Stefania , Luppi Gabriele , Garajovà Ingrid , Piacentini Federico , Dominici Massimo , Gelsomino Fabio
Published: January 2022

Carcinoid Crisis represents a rare and extremely dangerous manifestation that can occur in patients with Neuroendocrine Tumors (NETs). It is characterized by a sudden onset of hemodynamic instability, sometimes associated with the classical symptoms of carcinoid syndrome, such as bronchospasm and flushing. Carcinoid Crisis seems to be caused by a massive release of vasoactive substances, typically produced by neuroendocrine cells, and can emerge after abdominal procedures, but also spontaneously in rare instances. To date, there are no empirically derived guidelines for the management of this cancer-related medical emergency, and the available evidence essentially comes from single-case reports or dated small retrospective series. A transfer to the Intensive Care Unit may be necessary during the acute setting, when the severe hypotension becomes unresponsive to standard practices, such as volemic filling and the infusion of vasopressor therapy. The only effective strategy is represented by prevention. The administration of octreotide, anxiolytic and antihistaminic agents represents the current treatment approach to avoid hormone release and prevent major complications. However, no standard protocols are available, resulting in great variability in terms of schedules, doses, ways of administration and timing of prophylactic treatments.
Targeting Oncogenic Pathways in the Era of Personalized Oncology: A Systemic Analysis Reveals Highly Mutated Signaling Pathways in Cancer Patients and Potential Therapeutic Targets
Authors: Karagiannakos Alexandros , Adamaki Maria , Tsintarakis Antonis , Vojtesek Borek , Fåhraeus Robin , Zoumpourlis Vassilis , Karakostis Konstantinos
Published: January 2022

Cancer is the second leading cause of death globally. One of the main hallmarks in cancer is the functional deregulation of crucial molecular pathways via driver genetic events that lead to abnormal gene expression, giving cells a selective growth advantage. Driver events are defined as mutations, fusions and copy number alterations that are causally implicated in oncogenesis. Molecular analysis on tissues that have originated from a wide range of anatomical areas has shown that mutations in different members of several pathways are implicated in different cancer types. In recent decades, significant efforts have been made to incorporate this knowledge into daily medical practice, providing substantial insight towards clinical diagnosis and personalized therapies. However, since there is still a strong need for more effective drug development, a deep understanding of the involved signaling mechanisms and the interconnections between these pathways is highly anticipated. Here, we perform a systemic analysis on cancer patients included in the Pan-Cancer Atlas project, with the aim to select the ten most highly mutated signaling pathways (p53, RTK-RAS, lipids metabolism, PI-3-Kinase/Akt, ubiquitination, b-catenin/Wnt, Notch, cell cycle, homology directed repair (HDR) and splicing) and to provide a detailed description of each pathway, along with the corresponding therapeutic applications currently being developed or applied. The ultimate scope is to review the current knowledge on highly mutated pathways and to address the attractive perspectives arising from ongoing experimental studies for the clinical implementation of personalized medicine.