bluuebunny/crossref_metadata_2025 huggingface dataset:
Emulating Agricultural Disease Management: Comparing Risk Preferences Between Industry Professionals and Online Participants Using Experimental Gaming Simulations and Paired Lottery Choice Surveys
Authors: Clark Eric M. , Merrill Scott C. , Trinity Luke , Bucini Gabriela , Cheney Nicholas , Langle-Chimal Ollin , Shrum Trisha , Koliba Christopher , Zia Asim , Smith Julia M.
Published: January 2021

Mitigating the spread of disease is crucial for the well-being of agricultural production systems. Implementing biosecurity disease prevention measures can be expensive, so producers must balance the costs of biosecurity investments with the expected benefits of reducing the risk of infections. To investigate the risk associated with this decision making process, we developed an online experimental game that simulates biosecurity investment allocation of a pork production facility during an outbreak. Participants are presented with several scenarios that vary the visibility of the disease status and biosecurity protection implemented at neighboring facilities. Certain rounds allowed participants to spend resources to reduce uncertainty and reveal neighboring biosecurity and/or disease status. We then test how this uncertainty affects the decisions to spend simulation dollars to increase biosecurity and reduce risk. We recruited 50 attendees from the 2018 World Pork Expo to participate in our simulation. We compared their performance to an opportunity sample of 50 online participants from the survey crowdsourcing tool, Amazon Mechanical Turk (MTurk). With respect to biosecurity investment, we did not find a significant difference between the risk behaviors of industry professionals and those of MTurk participants for each set of experimental scenarios. Notably, we found that our sample of industry professionals opted to pay to reveal disease and biosecurity information more often than MTurk participants. However, the biosecurity investment decisions were not significantly different during rounds in which additional information could be purchased. To further validate these findings, we compared the risk associated with each group's responses using a well-established risk assessment survey implementing paired lottery choices. Interestingly, we did not find a correlation in risk quantified with simulated biosecurity investment in comparison to the paired lottery choice survey. This may be evidence that general economic risk preferences may not always translate into simulated behavioral risk, perhaps due to the contextual immersion provided by experimental gaming simulations. Online recruitment tools can provide cost effective research quality data that can be rapidly assembled in comparison to industry professionals, who may be more challenging to sample at scale. Using a convenience sample of industry professionals for validation can also provide additional insights into the decision making process. These findings lend support to using online experimental simulations for interpreting risk associated with a complex decision mechanism.
Controlled Over-Expression of AtDREB1A Enhances Tolerance against Drought and Salinity in Rice
Authors: Muthurajan Raveendran , Ramanathan Valarmathi , Bansilal Shillak Abhijeet , Madhuri Pralhad Suryawanshi , Shankarrao Chavan Neha , Rahman Hifzur , Kambale Rohit , Nallathambi Jagadeeshselvam , Tamilselvan Sudha , Madasamy Parani
Published: January 2021

Engineering transcription factors (TF) hold promise in enhancing abiotic stress tolerance in plants. In this study, one of the popular rice varieties of South India, namely ADT 43, was engineered with a TF AtDREB1A driven by a stress-inducible rd29A promoter. PCR and Southern hybridization were employed to confirm the integration and copy number of the transgene. Transgenic lines (T1) of ADT 43 showed enhanced tolerance to drought and salinity compared to the non-transgenic ADT 43. Transgenic lines were found to maintain higher RWC %, lower leaf temperature, and partially closed stomata, enabling better survival under stress conditions. qRT-PCR analysis revealed the strong induction of AtDREB1A transcripts during drought. Transgenic lines of ADT 43 exhibited increased germination and retention of chlorophyll in their leaves under salinity. Evaluation of transgenic lines under transgenic screen house conditions revealed that line # A16 exhibited on par agronomic performance against its non-transgenic counterpart under normal conditions. Under drought, non-transgenic ADT 43 showed >20% reduction in the total number of spikelets per panicle, whereas transgenic line # A16 registered only a 2% reduction. Non-transgenic ADT 43 recorded 80% yield reduction under drought, whereas line # A16 recorded only 54% yield loss. The above results demonstrated the effectiveness of controlled expression of DREB1A in regulating dehydration responses in rice.
Contribution of Agro-Environmental Factors to Yield and Plant Diversity of Olive Grove Ecosystems (Olea europaea L.) in the Mediterranean Landscape
Authors: Solomou Alexandra D. , Sfougaris Athanassios
Published: January 2021

Olive cultivation (Olea europaea L.) is one of the most significant sources of income for agricultural areas in the Mediterranean basin, and the olive oil industry as well as the environmental protection are an important part of the Greek agricultural sector. Generalized Linear Models were applied in order to investigate the predictive strength of several biodiversity components and agro-environmental factors for yield and herbaceous plant diversity (species richness) in organic and conventional olive groves of Greece. Our study highlights an increase in yields of organic olive groves by increasing manure application and the earthworms’ density. In the conventional olive groves, yields increase by increasing soil organic matter and the application of inorganic fertilizer N. Also, the herbaceous plant species richness increases with increasing the Shannon diversity index of herbaceous plants, the field area, the application of organic fertilizer K and the manure in organic olive groves. As for the conventional ones, herbaceous plant species richness increases with the increase of the application of inorganic fertilizer N. Moreover, some plant species could be regarded as indicators of the differently managed olive groves. Conclusively, this study contributes to the integration of biodiversity conservation with ecologically sustainable agriculture and conservation of agroecosystem. Finally, it could be utilized as a decision and management tool to the scientific and agricultural community reinforcing the knowledge about the agro-environmental impact in olive grove management systems.
Cover Crop and Pruning Residue Management to Reduce Nitrogen Mineral Fertilization in Mediterranean Vineyards
Authors: Pisciotta Antonino , Di Lorenzo Rosario , Novara Agata , Laudicina Vito Armando , Barone Ettore , Santoro Antonino , Gristina Luciano , Barbagallo Maria Gabriella
Published: January 2021

This paper aimed to study the effect of temporary cover crop and vine pruning residue burial as alternative practices to conventional tillage on soil nitrate (NO3-N) availability and grapevine performance in the short term. The trial was carried out in a rain-fed vineyard (Vitis vinifera L., cv Grecanico dorato/140 Ruggeri) located in a traditional Mediterranean viticultural area (37°32′48′′ N; 13°00′15′′ E) in Sicily (Italy). Conventional tillage (CT) soil management was compared with winter cover crop (CC), conventional tillage plus buried pruning residue (CT + PR), and winter cover crop plus buried pruning residue (CC + PR) management treatments. Two fertilizer treatments (92 kg ha−1 of N as urea and 0 kg ha−1) were applied to the four soil management treatments. Vicia faba L. was the selected leguminous cover crop species, which was seeded in autumn and buried in spring at the same time as vine pruning residues. The soil NO3-N content was monitored, and vine vegetative growth, yield, and must quality were assessed over two seasons. Results showed that NO3-N availability strongly differed between fertilized (F) and unfertilized (UF) plots and years and among treatments. A positive effect of winter leguminous CC + PR on the Grecanico dorato grapevine performance was observed. In the UF vineyard, grape fertility, yield, Ravaz index, and total soluble solids were significantly higher in CC + PR vines than in other treatments, thus showing the reliability of reducing N mineral fertilization and related risks of excess nitrate in groundwater. The possibility of increasing the overall sustainability of rain-fed vineyards in a semiarid agro-ecosystem, without negative effects on grape and must quality, is also demonstrated.
Effects of Feed Removal during Acute Heat Stress on the Cytokine Response and Short-Term Growth Performance in Finishing Pigs
Authors: Kpodo Kouassi R. , Duttlinger Alan W. , Maskal Jacob M. , McConn Betty R. , Johnson Jay S.
Published: January 2021

The study objective was to evaluate the effects of feed removal during acute heat stress (HS) on the cytokine response and its short-term effect on growth performance in finishing pigs. Thirty-two pigs (93.29 ± 3.14 kg initial body weight; 50% barrows and 50% gilts) were subjected to thermoneutral (TN; 23.47 ± 0.10 °C; n = 16 pigs) or HS (cycling of 25 to 36 °C; n = 16 pigs) conditions for 24 h. Within each temperature treatment, 50% of the pigs were provided with feed (AF; n = 8 pigs/temperature treatment) and 50% of the pigs had no feed access (NF; n = 8 pigs/temperature treatment). Following the 24 h temperature and feeding treatment (TF) period, all pigs had ad libitum access to feed and water and were maintained under TN conditions for 6 d. During the first 12 h of the TF period, gastrointestinal (TGI) and skin (Tsk) temperatures were recorded every 30 min. Serum cytokines were determined at 0, 4, 8, 12, and 24 h during the TF period and on Days 3 and 6 of the post-TF period. Average daily gain (ADG) and average daily feed intake were measured on Days 1, 3, and 6 of the post-TF period. Behavioral data were collected from Days 1 to 6 of the post-TF period. Heat stress increased (p < 0.02) the TGI and Tsk. During the post-TF period, interleukin-1α was greater (p < 0.01) in HS + NF compared to HS + AF and TN + NF pigs. From Days 1 to 2 of the post-TF period, the ADG was reduced (p < 0.01) in TN + AF compared to HS + AF, HS + NF, and TN + NF pigs. In conclusion, feed removal during an acute HS challenge did not reduce the cytokine response or improve short-term growth performance in finishing pigs.
Training with Multiple Structurally Related Odorants Fails to Improve Generalization of Ammonium Nitrate Detection in Domesticated Dogs (Canis familiaris)
Authors: Dorman David C. , Foster Melanie L. , Lazarowski Lucia
Published: January 2021

A critical aspect of canine scent detection involves the animal’s ability to respond to odors based on prior odor training. In the current study, dogs (n = 12) were initially trained on an olfactory simple discrimination task using vanillin as the target odorant. Based on their performance on this task, dogs were assigned to experimental groups. Dogs in group 1 and 2 (n = 5 dogs/group; 1 dog/group were removed due to low motivation or high error rates) were trained with either two or six forms of ammonium nitrate (AN), respectively. Dogs were then assessed with a mock explosive with AN and powdered aluminum. Dogs in both groups failed to respond to the novel AN-aluminum odor. Mean success rates were 56 ± 5 and 54 ± 4% for groups 1 and 2, respectively. Overall, and individual dog performance was not statistically higher than chance indicating that dogs did not generalize from AN to a similar AN-based odorant at reliable levels desired for explosive detection dogs. These results suggest the use of authentic explosive materials, without the added complication of including category-learning methods, likely remains a cost-effective and efficient way to train explosive scent detection dogs.
Laparoscopic Ovum Pick-Up Followed by In Vitro Embryo Production and Transfer in Assisted Breeding Programs for Ruminants
Authors: Baldassarre Hernan
Published: January 2021

The potential of laparoscopic ovum pick-up (LOPU) followed by in vitro embryo production (IVEP) as a tool for accelerated genetic programs in ruminants is reviewed in this article. In sheep and goats, the LOPU-IVEP platform offers the possibility of producing more offspring from elite females, as the procedure is minimally invasive and can be repeated more times and more frequently in the same animals compared with conventional surgical embryo recovery. On average, ~10 and ~14 viable oocytes are recovered by LOPU from sheep and goats, respectively, which results in 3–5 transferable embryos and >50% pregnancy rate after transfer. LOPU-IVEP has also been applied to prepubertal ruminants of 2–6 months of age, including bovine and buffalo calves. In dairy cattle, the technology has gained momentum in the past few years stemming from the development of genetic marker selection that has allowed predicting the production phenotype of dairy females from shortly after birth. In Holstein calves, we obtained an average of ~22 viable oocytes and ~20% transferable blastocyst rate, followed by >50% pregnancy rate after transfer, declaring the platform ready for commercial application. The present and future of this technology are discussed with a focus on improvements and research needed.
Current Aspects Regarding the Clinical Relevance of Electroacupuncture in Dogs with Spinal Cord Injury: A Literature Review
Authors: Dragomir Madalina Florina , Pestean Cosmin Petru , Melega Iulia , Danciu Cecilia Gabriella , Purdoiu Robert Cristian , Oana Liviu
Published: January 2021

In recent years, the use of acupuncture and electroacupuncture has been increasing as more clinical research has been conducted showing positive results in the treatment of animals, particularly dogs. Electroacupuncture is a more complex and specific acupuncture technique that involves electrical stimulation on acupuncture needles. Most of the studies have shown that the beneficial effects of electroacupuncture are more evident than in acupuncture alone. This review included studies focused only on dogs with spinal cord injury. Research facility animals (mice, rats, and rabbits) were avoided. Titles and abstracts of identified articles were read, and outlines were made to be better understood. Clinical applications are discussed and suggested in each section. When specialists use this method, electroacupuncture can be an excellent complementary therapy for veterinary patients’ pain control.
Back to Nature: Combating Candida albicans Biofilm, Phospholipase and Hemolysin Using Plant Essential Oils
Authors: El-Baz Ahmed M. , Mosbah Rasha A. , Goda Reham M. , Mansour Basem , Sultana Taranum , Dahms Tanya E. S. , El-Ganiny Amira M.
Published: January 2021

Candida albicans is the causative agent of fatal systemic candidiasis. Due to limitations of antifungals, new drugs are needed. The anti-virulence effect of plant essential oils (EOs) was evaluated against clinical C. albicans isolates including cinnamon, clove, jasmine and rosemary oils. Biofilm, phospholipase and hemolysin were assessed phenotypically. EOs were evaluated for their anti-virulence activity using phenotypic methods as well as scanning electron microscopy (SEM) and atomic force microscopy (AFM). Among the C. albicans isolates, biofilm, phospholipase and hemolysins were detected in 40.4, 86.5 and 78.8% of isolates, respectively. Jasmine oil showed the highest anti-biofilm activity followed by cinnamon, clove and rosemary oils. SEM and AFM analysis showed reduced adherence and roughness in the presence of EOs. For phospholipase, rosemary oil was the most inhibitory, followed by jasmine, cinnamon and clove oils, and for hemolysins, cinnamon had the highest inhibition followed by jasmine, rosemary and clove oils. A molecular docking study revealed major EO constituents as promising inhibitors of the Als3 adhesive protein, with the highest binding for eugenol, followed by 1,8-cineole, 2-phenylthiolane and cinnamaldehyde. In conclusion, EOs have a promising inhibitory impact on Candida biofilm, phospholipase and hemolysin production, hence EOs could be used as potential antifungals that impact virulence factors.
Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in Staphylococcus aureus
Authors: Liu Liping , Ingmer Hanne , Vestergaard Martin
Published: January 2021

Resveratrol has been extensively studied due to its potential health benefits in multiple diseases, for example, cancer, obesity and cardiovascular diseases. Besides these properties, resveratrol displays inhibitory activity against a wide range of bacterial species; however, the cellular effects of resveratrol in bacteria remain incompletely understood, especially in the human pathogen, Staphylococcus aureus. In this study, we aimed to identify intrinsic resistance genes that aid S. aureus in tolerating the activity of resveratrol. We screened the Nebraska Transposon Mutant Library, consisting of 1920 mutants with inactivation of non-essential genes in S. aureus JE2, for increased susceptibly to resveratrol. On agar plates containing 0.5× the minimum inhibitory concentration (MIC), 17 transposon mutants failed to grow. Of these, four mutants showed a two-fold reduction in MIC, being the clpP protease mutant and three mutants with deficiencies in the electron transport chain (menD, hemB, aroC). The remaining 13 mutants did not show a reduction in MIC, but were confirmed by spot-assays to have increased susceptibility to resveratrol. Several genes were associated with DNA damage repair (recJ, xerC and xseA). Treatment of S. aureus JE2 with sub-inhibitory concentrations of resveratrol did not affect the expression of recJ, xerC and xseA, but increased expression of the SOS–stress response genes lexA and recA, suggesting that resveratrol interferes with DNA integrity in S. aureus. Expression of error-prone DNA polymerases are part of the SOS–stress response and we could show that sub-inhibitory concentrations of resveratrol increased overall mutation frequency as measured by formation of rifampicin resistant mutants. Our data show that DNA repair systems are important determinants aiding S. aureus to overcome the inhibitory activity of resveratrol. Activation of the SOS response by resveratrol could potentially facilitate the development of resistance towards conventional antibiotics in S. aureus.
Clavulanic Acid Production by Streptomyces clavuligerus: Insights from Systems Biology, Strain Engineering, and Downstream Processing
Authors: López-Agudelo Víctor A. , Gómez-Ríos David , Ramirez-Malule Howard
Published: January 2021

Clavulanic acid (CA) is an irreversible β-lactamase enzyme inhibitor with a weak antibacterial activity produced by Streptomyces clavuligerus (S. clavuligerus). CA is typically co-formulated with broad-spectrum β‑lactam antibiotics such as amoxicillin, conferring them high potential to treat diseases caused by bacteria that possess β‑lactam resistance. The clinical importance of CA and the complexity of the production process motivate improvements from an interdisciplinary standpoint by integrating metabolic engineering strategies and knowledge on metabolic and regulatory events through systems biology and multi-omics approaches. In the large-scale bioprocessing, optimization of culture conditions, bioreactor design, agitation regime, as well as advances in CA separation and purification are required to improve the cost structure associated to CA production. This review presents the recent insights in CA production by S. clavuligerus, emphasizing on systems biology approaches, strain engineering, and downstream processing.
Grapefruit Seed Extract as a Natural Derived Antibacterial Substance against Multidrug-Resistant Bacteria
Authors: Han Hee-Won , Kwak Jin-Hwan , Jang Tae-Su , Knowles Jonathan Campbell , Kim Hae-Won , Lee Hae-Hyoung , Lee Jung-Hwan
Published: January 2021

Multidrug-resistant (MDR) bacteria are increasing due to the abuse and misuse of antibiotics, and nosocomial infections by MDR bacteria are also increasing. The aim of this study was to identify new substances that can target MDR bacteria among 12 plant extracts that are known to have antibacterial effects. The experiments were performed by the disk diffusion test and microdilution minimum inhibitory concentration (MIC) test, as described by the Clinical and Laboratory Standards Institute (CLSI). By screening against methicillin-sensitive Staphylococcus aureus (MSSA), grapefruit seed extract (GSE) was selected from 12 plant extracts for subsequent experiments. GSE showed antibacterial effects against methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) in the disk diffusion test. Even at the lowest concentration, GSE showed antibacterial activity in the microdilution MIC test. As a result, we can conclude that GSE is a naturally derived antibacterial substance that exhibits a favorable antibacterial effect even at a very low concentration, so it is a good candidate for a natural substance that can be used to prevent or reduce nosocomial infections as coating for materials used in medical contexts or by mixing a small amount with other materials.
Modeling, Assessment and Design of an Emergency Department of a Public Hospital through Discrete-Event Simulation
Authors: Castanheira-Pinto Alexandre , Gonçalves Bruno S. , Lima Rui M. , Dinis-Carvalho José
Published: January 2021

Emergency departments in hospitals are having many difficulties in achieving the performance levels required by health regulators and society. The waiting times as well as the total throughput time are examples of performance indicators that emergency departments need to improve in order to provide a better service to the community. To achieve improvement of performance, the present paper shows a methodology to assist the design process of an emergency department using simulation techniques. In this study, the emergency department of a hospital located in the northern region of Portugal was considered to test the proposed simulation technique. The emergency department initial state was assessed, in terms of patient flow, as well as the human resources needed at every stage of the service. In order to understand in depth the process that a patient goes through during an emergency episode, a comprehensive study was performed on the hospital database. This allowed the analytical description of an emergency episode, which was further used as an input to the simulation model. After developing the simulation model with the information obtained by the hospital’s database, a validation stage was performed. Finally, in order to achieve an optimized design for the emergency department several variant scenarios were considered and evaluated. This methodology proved to be very useful in determining an optimized operation for complex, and non-linear systems.
Generalizability of Deep Learning System for the Pathologic Diagnosis of Various Cancers
Authors: Jang Hyun-Jong , Song In Hye , Lee Sung Hak
Published: January 2021

The deep learning (DL)-based approaches in tumor pathology help to overcome the limitations of subjective visual examination from pathologists and improve diagnostic accuracy and objectivity. However, it is unclear how a DL system trained to discriminate normal/tumor tissues in a specific cancer could perform on other tumor types. Herein, we cross-validated the DL-based normal/tumor classifiers separately trained on the tissue slides of cancers from bladder, lung, colon and rectum, stomach, bile duct, and liver. Furthermore, we compared the differences between the classifiers trained on the frozen or formalin-fixed paraffin-embedded (FFPE) tissues. The Area under the curve (AUC) for the receiver operating characteristic (ROC) curve ranged from 0.982 to 0.999 when the tissues were analyzed by the classifiers trained on the same tissue preparation modalities and cancer types. However, the AUCs could drop to 0.476 and 0.439 when the classifiers trained for different tissue modalities and cancer types were applied. Overall, the optimal performance could be achieved only when the tissue slides were analyzed by the classifiers trained on the same preparation modalities and cancer types.
Emerging Information Technologies for Next Generation Communications and Networks
Authors: Kim Byung-Seo
Published: January 2021

Our lives can be said to be in an era with information and communication devices, and we are pursuing a hyperconnected society with advanced information and communication devices [...]
Numerical and Experimental Studies of the Attenuation Characteristics of Friction Torque in a Wet Multidisc Clutch
Authors: Chen Man , Zhang Bin , Feng Yuqing , Wang Liang , Wang He
Published: January 2021

A numerical model is proposed to calculate both the contact pressure and the friction torque (FT) of the friction components considering the spline friction in a wet multidisc clutch, which is verified by the bench test. The results indicate that the spline friction of components is an important factor causing the axial attenuation of contact pressure on friction pairs. As the applied pressure increases, the attenuation amplitude of contact pressure increases gradually. In addition, the average single-pair FT decreases with the increasing number of friction pairs, thus leading to the decrease of the growth rate of total FT. Therefore, when the number of friction pairs reaches a certain number, it is not reliable to obtain a good torque enhancement, indicating that the effect of spline friction needs to be weakened to reduce the attenuation of contact pressure.
Deep Learning-Based Applications for Safety Management in the AEC Industry: A Review
Authors: Hou Lei , Chen Haosen , Zhang Guomin (Kevin) , Wang Xiangyu
Published: January 2021

Safety is an essential topic to the architecture, engineering and construction (AEC) industry. However, traditional methods for structural health monitoring (SHM) and jobsite safety management (JSM) are not only inefficient, but also costly. In the past decade, scholars have developed a wide range of deep learning (DL) applications to address automated structure inspection and on-site safety monitoring, such as the identification of structural defects, deterioration patterns, unsafe workforce behaviors and latent risk factors. Although numerous studies have examined the effectiveness of the DL methodology, there has not been one comprehensive, systematic, evidence-based review of all individual articles that investigate the effectiveness of using DL in the SHM and JSM industry to date, nor has there been an examination of this body of evidence in regard to these methodological problems. Therefore, the objective of this paper is to disclose the state of the art of current research progress and determine the relevant gaps, challenges and future work. Methodically, CiteSpace was employed to summarize the research trends, advancements and frontiers of DL applications from 2010 to 2020. Next, an application-focused literature review was conducted, which led to a summary of research gaps, recommendations and future research directions. Overall, this review gains insight into SHM and JSM and aims to help researchers formulate more types of effective DL applications which have not been addressed sufficiently for the time being.
A Machine Learning Tool to Predict the Response to Neoadjuvant Chemotherapy in Patients with Locally Advanced Cervical Cancer
Authors: Arezzo Francesca , La Forgia Daniele , Venerito Vincenzo , Moschetta Marco , Tagliafico Alberto Stefano , Lombardi Claudio , Loizzi Vera , Cicinelli Ettore , Cormio Gennaro
Published: January 2021

Despite several studies having identified factors associated with successful treatment outcomes in locally advanced cervical cancer, there is the lack of accurate predictive modeling for progression-free survival (PFS) in patients who undergo radical hysterectomy after neoadjuvant chemotherapy (NACT). Here we investigated whether machine learning (ML) may have the potential to provide a tool to predict neoadjuvant treatment response as PFS. In this retrospective observational study, we analyzed patients with locally advanced cervical cancer (FIGO stages IB2, IB3, IIA1, IIA2, IIB, and IIIC1) who were followed in a tertiary center from 2010 to 2018. Demographic and clinical characteristics were collected at either treatment baseline or at 24-month follow-up. Furthermore, we recorded data about magnetic resonance imaging (MRI) examinations and post-surgery histopathology. Proper feature selection was used to determine an attribute core set. Three different machine learning algorithms, namely Logistic Regression (LR), Random Forest (RFF), and K-nearest neighbors (KNN), were then trained and validated with 10-fold cross-validation to predict 24-month PFS. Our analysis included n. 92 patients. The attribute core set used to train machine learning algorithms included the presence/absence of fornix infiltration at pre-treatment MRI as well as of either parametrium invasion and lymph nodes involvement at post-surgery histopathology. RFF showed the best performance (accuracy 82.4%, precision 83.4%, recall 96.2%, area under receiver operating characteristic curve (AUROC) 0.82). We developed an accurate ML model to predict 24-month PFS.
Semantic Scene Graph Generation Using RDF Model and Deep Learning
Authors: Kim Seongyong , Jeon Tae Hyeon , Rhiu Ilsun , Ahn Jinhyun , Im Dong-Hyuk
Published: January 2021

Over the last several years, in parallel with the general global advancement in mobile technology and a rise in social media network content consumption, multimedia content production and reproduction has increased exponentially. Therefore, enabled by the rapid recent advancements in deep learning technology, research on scene graph generation is being actively conducted to more efficiently search for and classify images desired by users within a large amount of content. This approach lets users accurately find images they are searching for by expressing meaningful information on image content as nodes and edges of a graph. In this study, we propose a scene graph generation method based on using the Resource Description Framework (RDF) model to clarify semantic relations. Furthermore, we also use convolutional neural network (CNN) and recurrent neural network (RNN) deep learning models to generate a scene graph expressed in a controlled vocabulary of the RDF model to understand the relations between image object tags. Finally, we experimentally demonstrate through testing that our proposed technique can express semantic content more effectively than existing approaches.
Nanoscale Topographies for Corneal Endothelial Regeneration
Authors: Formisano Nello , Sahin Gozde , Català Pere , Truckenmüller Roman , Nuijts Rudy M. M. A. , Dickman Mor M. , LaPointe Vanessa L. S. , Giselbrecht Stefan
Published: January 2021

The corneal endothelium is the innermost layer of the cornea that selectively pumps ions and metabolites and regulates the hydration level of the cornea, ensuring its transparency. Trauma or disease affecting human corneal endothelial cells (hCECs) can result in major imbalances of such transport activity with consequent deterioration or loss of vision. Since tissue transplantation from deceased donors is only available to a fraction of patients worldwide, alternative solutions are urgently needed. Cell therapy approaches, in particular by attempting to expand primary culture of hCECs in vitro, aim to tackle this issue. However, existing cell culture protocols result in limited expansion of this cell type. Recent studies in this field have shown that topographical features with specific dimensions and shapes could improve the efficacy of hCEC expansion. Therefore, potential solutions to overcome the limitation of the conventional culture of hCECs may include recreating nanometer scale topographies (nanotopographies) that mimic essential biophysical cues present in their native environment. In this review, we summarize the current knowledge and understanding of the effect of substrate topographies on the response of hCECs. Moreover, we also review the latest developments for the nanofabrication of such bio-instructive cell substrates.
Role of Collagen in Airway Mechanics
Authors: Liu Lumei , Stephens Brooke , Bergman Maxwell , May Anne , Chiang Tendy
Published: January 2021

Collagen is the most abundant airway extracellular matrix component and is the primary determinant of mechanical airway properties. Abnormal airway collagen deposition is associated with the pathogenesis and progression of airway disease. Thus, understanding how collagen affects healthy airway tissue mechanics is essential. The impact of abnormal collagen deposition and tissue stiffness has been an area of interest in pulmonary diseases such as cystic fibrosis, asthma, and chronic obstructive pulmonary disease. In this review, we discuss (1) the role of collagen in airway mechanics, (2) macro- and micro-scale approaches to quantify airway mechanics, and (3) pathologic changes associated with collagen deposition in airway diseases. These studies provide important insights into the role of collagen in airway mechanics. We summarize their achievements and seek to provide biomechanical clues for targeted therapies and regenerative medicine to treat airway pathology and address airway defects.
A Universal Model for the Log-Normal Distribution of Elasticity in Polymeric Gels and Its Relevance to Mechanical Signature of Biological Tissues
Authors: Millet Arnaud
Published: January 2021

The mechanosensitivity of cells has recently been identified as a process that could greatly influence a cell’s fate. To understand the interaction between cells and their surrounding extracellular matrix, the characterization of the mechanical properties of natural polymeric gels is needed. Atomic force microscopy (AFM) is one of the leading tools used to characterize mechanically biological tissues. It appears that the elasticity (elastic modulus) values obtained by AFM presents a log-normal distribution. Despite its ubiquity, the log-normal distribution concerning the elastic modulus of biological tissues does not have a clear explanation. In this paper, we propose a physical mechanism based on the weak universality of critical exponents in the percolation process leading to gelation. Following this, we discuss the relevance of this model for mechanical signatures of biological tissues.
Covalently Labeled Fluorescent Exosomes for In Vitro and In Vivo Applications
Authors: González María Isabel , González-Arjona Mario , Santos-Coquillat Ana , Vaquero Javier , Vázquez-Ogando Elena , de Molina Antonio , Peinado Héctor , Desco Manuel , Salinas Beatriz
Published: January 2021

The vertiginous increase in the use of extracellular vesicles and especially exosomes for therapeutic applications highlights the necessity of advanced techniques for gaining a deeper knowledge of their pharmacological properties. Herein, we report a novel chemical approach for the robust attachment of commercial fluorescent dyes to the exosome surface with covalent binding. The applicability of the methodology was tested on milk and cancer cell-derived exosomes (from U87 and B16F10 cancer cells). We demonstrated that fluorescent labeling did not modify the original physicochemical properties of exosomes. We tested this nanoprobe in cell cultures and healthy mice to validate its use for in vitro and in vivo applications. We confirmed that these fluorescently labeled exosomes could be successfully visualized with optical imaging.
Therapeutic Targeting of Autoreactive B Cells: Why, How, and When?
Authors: Stensland Zachary C. , Cambier John C. , Smith Mia J.
Published: January 2021

B lymphocytes play critical roles in the development of autoimmunity, acting as autoantibody manufacturers, antigen-presenting cells, and producers of cytokines. Pan-B cell depletion has demonstrated efficacy in treatment of many autoimmune disorders, but carries with it an unfavorable safety profile due to global immune suppression. Hence, attention has turned to the potential of autoantigen-specific B cell targeted therapies, which would deplete or silence pathogenic self-antigen-reactive cells while sparing B cells needed for immune defense. Here, we discuss the antigen-specific B cell-targeted approaches that are under development or are under consideration, that could be employed to allow for more precise therapy in the treatment of autoimmunity. Lastly, we discuss some of the challenges associated with antigen-specific B cell targeting that may impact their clinical applicability.
M2 Monocyte Polarization in Dialyzed Patients Is Associated with Increased Levels of M-CSF and Myeloperoxidase-Associated Oxidative Stress: Preliminary Results
Authors: Pireaux Valérie , Delporte Cédric , Rousseau Alexandre , Desmet Jean-Marc , Van Antwerpen Pierre , Raes Martine , Zouaoui Boudjeltia Karim
Published: January 2021

Cardiovascular diseases represent a major issue in terms of morbidity and mortality for dialysis patients. This morbidity is due to the accelerated atherosclerosis observed in these patients. Atherosclerosis is a chronic inflammatory disease characterized by key players such as monocytes, macrophages, or oxidized LDLs. Monocytes-macrophages are classified into subsets of polarized cells, with M1 and M2 macrophages considered, respectively, as pro- and anti-inflammatory. (1) Methods: The monocyte subsets and phenotypes were analyzed by flow cytometry. These data were completed by the quantification of plasma M-CSF, IL-8, CRP, Mox-LDLs, Apo-B, Apo-AI, chloro-tyrosine, and homocitrulline concentrations. The statistical differences and associations between two continuous variables were assessed using the Mann–Whitney U test and Spearman’s correlation coefficient, respectively. (2) Results: Hemodialyzed patients showed a significant increase in their concentrations of CRP, M-CSF, and IL-8 (inflammation biomarkers), as well as chloro-tyrosine and homocitrulline (myeloperoxidase-associated oxidative stress biomarkers). Moreover, we observed a higher percentage of M2 monocytes in the plasma of hemodialysis patients as compared to the controls. (3) Conclusions: Our data suggest that oxidative stress and an inflammatory environment, which is amplified in hemodialysis patients, seems to favor an increase in the concentration of circulating M-CSF, therefore leading to an increase in M2 polarization among circulating monocytes.
Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme
Authors: González-Casimiro Carlos M. , Merino Beatriz , Casanueva-Álvarez Elena , Postigo-Casado Tamara , Cámara-Torres Patricia , Fernández-Díaz Cristina M. , Leissring Malcolm A. , Cózar-Castellano Irene , Perdomo Germán
Published: January 2021

Insulin-degrading enzyme (IDE) is a highly conserved and ubiquitously expressed metalloprotease that degrades insulin and several other intermediate-size peptides. For many decades, IDE had been assumed to be involved primarily in hepatic insulin clearance, a key process that regulates availability of circulating insulin levels for peripheral tissues. Emerging evidence, however, suggests that IDE has several other important physiological functions relevant to glucose and insulin homeostasis, including the regulation of insulin secretion from pancreatic β-cells. Investigation of mice with tissue-specific genetic deletion of Ide in the liver and pancreatic β-cells (L-IDE-KO and B-IDE-KO mice, respectively) has revealed additional roles for IDE in the regulation of hepatic insulin action and sensitivity. In this review, we discuss current knowledge about IDE’s function as a regulator of insulin secretion and hepatic insulin sensitivity, both evaluating the classical view of IDE as an insulin protease and also exploring evidence for several non-proteolytic functions. Insulin proteostasis and insulin sensitivity have both been highlighted as targets controlling blood sugar levels in type 2 diabetes, so a clearer understanding the physiological functions of IDE in pancreas and liver could led to the development of novel therapeutics for the treatment of this disease.
Immunogenicity of Viral Vaccines in the Italian Military
Authors: Ferlito Claudia , Biselli Roberto , Visco Vincenzo , Cattaruzza Maria Sofia , Capobianchi Maria Rosaria , Castilletti Concetta , Lapa Daniele , Nicoletti Loredana , Marchi Antonella , Magurano Fabio , Ciccaglione Anna Rita , Chionne Paola , Madonna Elisabetta , Donatelli Isabella , Calzoletti Laura , Fabiani Concetta , Biondo Michela Ileen , Teloni Raffaela , Mariotti Sabrina , Salerno Gerardo , Picchianti-Diamanti Andrea , Salemi Simonetta , Caporuscio Sara , Autore Alberto , Lulli Patrizia , Borelli Francesco , Lastilla Marco , Nisini Roberto , D’Amelio Raffaele
Published: January 2021

Military personnel of all armed forces receive multiple vaccinations and have been doing so since long ago, but relatively few studies have investigated the possible negative or positive interference of simultaneous vaccinations. As a contribution to fill this gap, we analyzed the response to the live trivalent measles/mumps/rubella (MMR), the inactivated hepatitis A virus (HAV), the inactivated trivalent polio, and the trivalent subunits influenza vaccines in two cohorts of Italian military personnel. The first cohort was represented by 108 students from military schools and the second by 72 soldiers engaged in a nine-month mission abroad. MMR and HAV vaccines had never been administered before, whereas inactivated polio was administered to adults primed at infancy with a live trivalent oral polio vaccine. Accordingly, nearly all subjects had baseline antibodies to polio types 1 and 3, but unexpectedly, anti-measles/-mumps/-rubella antibodies were present in 82%, 82%, and 73.5% of subjects, respectively (43% for all of the antigens). Finally, anti-HAV antibodies were detectable in 14% and anti-influenza (H1/H3/B) in 18% of the study population. At mine months post-vaccination, 92% of subjects had protective antibody levels for all MMR antigens, 96% for HAV, 69% for the three influenza antigens, and 100% for polio types 1 and 3. An inverse relationship between baseline and post-vaccination antibody levels was noticed with all the vaccines. An excellent vaccine immunogenicity, a calculated long antibody persistence, and apparent lack of vaccine interference were observed.
Surface Plasmon Resonance Based on Molecularly Imprinted Polymeric Film for l-Phenylalanine Detection
Authors: Çimen Duygu , Bereli Nilay , Denizli Adil
Published: January 2021

In this study, we designed a simple, rapid, sensitive and selective surface plasmon resonance (SPR) sensor for detection of L-phenylalaine by utilizing molecular imprinting technology. l-phenylalanine imprinted and non-imprinted poly(2-hydroxyethyl methacrylate-methacryloyl-l-phenylalanine) polymeric films were synthesized onto SPR chip surfaces using ultraviolet polymerization. l-phenyalanine imprinted and non-imprinted SPR sensors were characterized by using contact angle, atomic force microscopy and ellipsometry. After characterization studies, kinetic studies were carried out in the concentration range of 5.0–400.0 μM. The limit of detection and quantification were obtained as 0.0085 and 0.0285 μM, respectively. The response time for the test including equilibration, adsorption and desorption was approximately 9 min. The selectivity studies of the l-phenylalanine imprinted SPR sensor was performed in the presence of d-phenylalanine and l-tryptophan. Validation studies were carried out via enzyme-linked immunosorbent analysis technique in order to demonstrate the applicability and superiority of the l-phenylalanine imprinted SPR sensor.
Ipsi- and Contralateral Oligo- and Polysynaptic Reflexes in Humans Revealed by Low-Frequency Epidural Electrical Stimulation of the Lumbar Spinal Cord
Authors: Hofstoetter Ursula S. , Danner Simon M. , Freundl Brigitta , Binder Heinrich , Lackner Peter , Minassian Karen
Published: January 2021

Epidural electrical stimulation (EES) applied over the human lumbosacral spinal cord provides access to afferent fibers from virtually all lower-extremity nerves. These afferents connect to spinal networks that play a pivotal role in the control of locomotion. Studying EES-evoked responses mediated through these networks can identify some of their functional components. We here analyzed electromyographic (EMG) responses evoked by low-frequency (2–6 Hz) EES derived from eight individuals with chronic, motor complete spinal cord injury. We identified and separately analyzed three previously undescribed response types: first, crossed reflexes with onset latencies of ~55 ms evoked in the hamstrings; second, oligosynaptic reflexes within 50 ms post-stimulus superimposed on the monosynaptic posterior root-muscle reflexes in the flexor muscle tibialis anterior, but with higher thresholds and no rate-sensitive depression; third, polysynaptic responses with variable EMG shapes within 50–450 ms post-stimulus evoked in the tibialis anterior and triceps surae, some of which demonstrated consistent changes in latencies with graded EES. Our observations suggest the activation of commissural neurons, lumbar propriospinal interneurons, and components of the late flexion reflex circuits through group I and II proprioceptive afferent inputs. These potential neural underpinnings have all been related to spinal locomotion in experimental studies.
A Phase 1/2 Study of Flavocoxid, an Oral NF-κB Inhibitor, in Duchenne Muscular Dystrophy
Authors: Vita Gian Luca , Sframeli Maria , Licata Norma , Bitto Alessandra , Romeo Sara , Frisone Francesca , Ciranni Annamaria , Pallio Giovanni , Mannino Federica , Aguennouz M’Hammed , Rodolico Carmelo , Squadrito Francesco , Toscano Antonio , Messina Sonia , Vita Giuseppe
Published: January 2021

Flavocoxid is a blended extract containing baicalin and catechin with potent antioxidant and anti-inflammatory properties due to the inhibition of the cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) enzymes, nuclear factor-κB (NF-κB), tumor necrosis factor (TNF)-alpha, and the mitogen-activated protein kinases (MAPKs) pathways. This phase 1/2 study was designed to assess the safety and tolerability of flavocoxid in patients with Duchenne muscular dystrophy (DMD). Thirty-four patients were recruited: 17 were treated with flavocoxid at an oral dose of 250 or 500 mg, according to body weight, for one year; 17 did not receive flavocoxid and served as controls. The treatment was well tolerated and nobody dropped out. Flavocoxid induced a significant reduction in serum interleukin (IL)-1 beta and TNF-alpha only in the group of DMD boys on add-on therapy (flavocoxid added to steroids for at least six months). The decrease in IL-1 beta was higher in younger boys. The serum H2O2 concentrations significantly decreased in patients treated with flavocoxid alone with a secondary reduction of serum glutathione peroxidase (GPx) levels, especially in younger boys. The exploratory outcome measures failed to show significant effects but there was a trend showing that the younger boys who received treatment were faster at performing the Gowers’ maneuver, while the older boys who received treatment were faster at doing the 10-m walk test (10MWT). Therefore, a double-blind, placebo-controlled study for at least two/three years is warranted to verify flavocoxid as a steroid substitute or as add-on therapy to steroids.