bluuebunny/crossref_metadata_2025 huggingface dataset:
A Methodology to Quantify Resilience in Growing Pigs
Authors: Laghouaouta Houda , Pena Ramona N. , Ros-Freixedes Roger , Reixach Josep , Díaz Marta , Estany Joan , Armengol Ramon , Bassols Anna , Fraile Lorenzo
Published: October 2021

There is a growing concern about the genetic determinism of resilience and its possible implementation in breeding programs. The objective of our study was to elaborate novel resilience indicators in growing pigs based on the deviation from the expected growth curve and the increment of the acute-phase protein haptoglobin (HP) after applying a common vaccine. A total of 445 pigs were vaccinated with an attenuated Aujeszky vaccine at 12 weeks of age. Deviation from the expected body weight (ΔBW) given the growth curve of unvaccinated pigs at 28 days post-vaccination (DPV) and the increment of HP at 4 DPV (ΔHP) were suggested as resilience indicators. Challenged pigs that maintained their productivity and had a minor activation of HP were deemed resilient, whereas pigs that had low ∆BW values and a high activation of HP were deemed susceptible. Pigs were also classified based on ∆BW and ∆HP relative to the expected BW at 28 DPV and to the basal level of HP, respectively. The concordance was high between both methods, indicating that ΔBW and ΔHP are not sensitive to the animal’s expected BW nor the basal level of HP. The heritability estimates were moderate for ∆BW (0.33) and low-to-moderate for ∆HP (0.16). Our study suggests ΔBW and ΔHP as novel resilience indicators in pigs. The suggested indicators capture different aspects of resilience, are easy to measure, and are genetically controlled. Thus, they may be improved through selective breeding. Further analyses are needed to validate our findings.
Classic and Non-Classic Effects of the Duration of Supplementation of 25-Hydroxicholecalciferol in Broiler Chicken Diets
Authors: Prokoski Karen , Bittencourt Leticia C. , Teixeira Levy V. , Bortoluzzi Cristiano , Vanroo Elisangela , Palma Sabrina , Fernandes Jovanir I. M.
Published: October 2021

The present study aimed to determine the effect of different times of supplementation of 25-hydroxycholecalciferol (25(OH)D3) in broiler chickens on the performance, carcass and cuts yield, bone resistance, plasma concentration of 25(OH)D3, and expression of the mTOR gene. The treatments were a control diet (CD) supplemented with 3000 IU vitamin D3/kg of feed from 1 to 46 d, or the CD + 2760 IU (69 mcg) of 25(OH)D3/kg of feed from 1 to 21 d, from 1 to 35 d, or from 1 to 46 d. The period of supplementation of 25(OH)D3 did not affect the growth performance of broilers, but the breast meat yield was linearly increased in response to increasing days of supplementation (p < 0.05). Birds supplemented with 25(OH)D3 at the time of the analysis showed an increase (p < 0.05) in the plasma concentration of 25(OH)D3 when compared to non-supplemented birds. The mTOR gene expression (p < 0.05), and breast protein deposition (p < 0.05) presented a quadratic response related to the supplementation period of 25(OH)D3. The fat content of the breast linearly decreased (p < 0.05) as the period of supplementation was extended. The results also showed a positive linear correlation between mTOR expression and 25(OH)D3 plasma levels (r = 0.593; p < 0.05).
Machine Learning to Detect Posture and Behavior in Dairy Cows: Information from an Accelerometer on the Animal’s Left Flank
Authors: Balasso Paolo , Marchesini Giorgio , Ughelini Nicola , Serva Lorenzo , Andrighetto Igino
Published: October 2021

The aim of the present study was to develop a model to identify posture and behavior from data collected by a triaxial accelerometer located on the left flank of dairy cows and evaluate its accuracy and precision. Twelve Italian Red-and-White lactating cows were equipped with an accelerometer and observed on average for 136 ± 29 min per cow by two trained operators as a reference. The acceleration data were grouped in time windows of 8 s overlapping by 33.0%, for a total of 35,133 rows. For each row, 32 different features were extracted and used by machine learning algorithms for the classification of posture and behavior. To build up a predictive model, the dataset was split in training and testing datasets, characterized by 75.0 and 25.0% of the observations, respectively. Four algorithms were tested: Random Forest, K Nearest Neighbors, Extreme Boosting Algorithm (XGB), and Support Vector Machine. The XGB model showed the best accuracy (0.99) and Cohen’s kappa (0.99) in predicting posture, whereas the Random Forest model had the highest overall accuracy in predicting behaviors (0.76), showing a balanced accuracy from 0.96 for resting to 0.77 for moving. Overall, very accurate detection of the posture and resting behavior were achieved.
Animal-Based Indicators for On-Farm Welfare Assessment in Sheep
Authors: Zufferey Romane , Minnig Adrian , Thomann Beat , Zwygart Sibylle , Keil Nina , Schüpbach Gertraud , Miserez Raymond , Zanolari Patrik , Stucki Dimitri
Published: October 2021

The value society assigns to animal welfare in agricultural productions is increasing, resulting in ever-enhancing methods to assess the well-being of farm animals. The aim of this study was to review the scientific literature to obtain an overview of the current knowledge on welfare assessments for sheep and to extract animal-based welfare indicators as well as welfare protocols with animal-based indicators. By title and abstract screening, we identified five protocols and 53 potential indicators from 55 references. Three out of the five protocols include animal-based as well as resource-based indicators. All of them were assessed as being practicable on-farm but lacking reliability. Some of the single indicators are endorsed by the literature and widely used in the field like assessment of behaviour, lameness or body condition score. Others (e.g., Faffa Malan Chart FAMACHA©, dag score or pain assessment) are regularly mentioned in the literature, but their reliability and usefulness are still subject of discussion. Several indicators, such as pruritic behaviour, eye condition, lying time or tooth loss are relatively new in the literature and still lack evidence for their validity and usefulness. This literature review serves as a starting point for the development of valid and practicable welfare protocols for sheep.
Metabolomics of Chlorophylls and Carotenoids: Analytical Methods and Metabolome-Based Studies
Authors: Roca María , Pérez-Gálvez Antonio
Published: October 2021

Chlorophylls and carotenoids are two families of antioxidants present in daily ingested foods, whose recognition as added-value ingredients runs in parallel with the increasing number of demonstrated functional properties. Both groups include a complex and vast number of compounds, and extraction and analysis methods evolved recently to a modern protocol. New methodologies are more potent, precise, and accurate, but their application requires a better understanding of the technical and biological context. Therefore, the present review compiles the basic knowledge and recent advances of the metabolomics of chlorophylls and carotenoids, including the interrelation with the primary metabolism. The study includes material preparation and extraction protocols, the instrumental techniques for the acquisition of spectroscopic and spectrometric properties, the workflows and software tools for data pre-processing and analysis, and the application of mass spectrometry to pigment metabolomics. In addition, the review encompasses a critical description of studies where metabolomics analyses of chlorophylls and carotenoids were developed as an approach to analyzing the effects of biotic and abiotic stressors on living organisms.
Effect of the Concentration of Extracellular Polymeric Substances (EPS) and Aeration Intensity on Waste Glycerol Valorization by Docosahexaenoic Acid (DHA) Produced in Heterotrophic Culture of Schizochytrium sp
Authors: Kujawska Natalia , Talbierz Szymon , Dębowski Marcin , Kazimierowicz Joanna , Zieliński Marcin
Published: October 2021

The study aimed to determine the effectiveness of docosahexaenoic acid (DHA) production by Schizochytrium sp. biomass fed with waste glycerol depending on the concentration of extracellular polymeric substances (EPS) in the culture medium and medium aeration effectiveness. The microalgae from the genus Schizochytrium sp. were proved to be capable of producing EPS composed of glucose, galactose, mannose, fucose, and xylose. The highest EPS concentration, reaching 8.73 ± 0.09 g/dm3, was determined at the stationary growth phase. A high EPS concentration caused culture medium viscosity to increase, contributing to diminished oxygen availability for cells, lower culture effectiveness, and reduced waste glycerol conversion to DHA. The Schizochytrium sp. culture variant found optimal in terms of the obtained technological effects and operating costs was performed at the volumetric oxygen mass transfer coefficient of kLa = 600 1/h, which enabled obtaining dry cell weight (DCW) of 147.89 ± 4.77 g/dm3, lipid concentration of 69.44 ± 0.76 g/dm3, and DHA concentration in the biomass reaching 29.44 ± 0.36 g/dm3. The effectiveness of waste glycerol consumption in this variant reached 3.76 ± 0.31 g/dm3·h and 3.16 ± 0.22 g/gDCW.
Methodology to Assess Sustainable Mobility in LATAM Cities
Authors: Huertas José I. , Stöffler Sonja , Fernández Trinidad , García Xanin , Castañeda Roberto , Serrano-Guevara Oscar , Mogro Antonio E. , Alvarado Duván A.
Published: October 2021

As the first step toward implementing strategies to improve mobility in urban centers, governmental authorities must assess their present situation in order to identify the most effective actions that should be included in their short and long-term plans. However, there is not a well-established methodology to carry out such an assessment. The already existing ones are subjective, incomplete, costly, and hard to implement, especially for the case of Latin American (LATAM) countries. This paper proposes a comprehensive methodology to carry out this assessment. It uses recent advances in information technologies and includes the use of web map services, telematics data, and low-cost vehicle emission tests. As an example of application, a mobility assessment was carried out for Saltillo, a medium-sized city in northeastern Mexico, which is considered a typical city in LATAM countries. Results indicate that this methodology can be replicated at a low incremental cost and that it leads towards the identification of the most sustainable (economic, environmental, and social) actions that should be implemented in these cities considering their local circumstances.
Seismic Damage Probability Assessment of Isolated Girder Bridges Based on Performance under Near-Field Earthquakes
Authors: Liu Qiang , Yang Chunyan
Published: October 2021

This paper presents a copula technique for developing seismic fragility curves for an RC (reinforced concrete) isolated continuous girder bridge, by considering earthquake damage indicators such as bridge piers, isolated bearing components, and the main girder of collision damage. The results of this method are compared with those of the limit method of the first-order reliability theory. Meanwhile, the incremental dynamic analysis of the bridge structure under different failure conditions is carried out, and the randomness of the near-fault ground motion and the structural parameters are accounted. Based on the damage index of the isolated bridge under different damage conditions, the seismic fragility curves of each component and the whole isolated bridge are obtained. The research shows that the safety control of the isolated continuous girder bridge structure is mainly affected by the seismic fragility of the isolated bearing, the influence of bridge pier seismic fragility is relatively small, and the probability of beam collision in an isolated bridge is lower than that of a general bridge without isolation bearing. By applying the isolation scheme, the probability of different damage state of the bridge structure is greatly reduced, thus the seismic performance is improved. It also verifies the efficiency and superiority of copula technology. The results will provide a reference for future seismic damage prediction.
Smart Grid Data Management in a Heterogeneous Environment with a Hybrid Load Forecasting Model
Authors: Albayati Ammar , Abdullah Nor Fadzilah , Abu-Samah Asma , Mutlag Ammar Hussein , Nordin Rosdiadee
Published: October 2021

The power consumption model can be represented in multiple dimensions, and it is proliferating to include structured and unstructured data. Dealing with such heterogeneous data and analyzing it in real-time is an ongoing challenge in the energy sector. Moreover, converting these data into useful information remains an open research area. This study focuses on modeling realistic and efficient power consumption data management in the heterogeneous environment for the Iraq energy sector and suggested a novel hybrid load forecasting model. The proposed system is named the Power Consumption Information and Analytics System (PIAS), which can perform various roles such as data acquisition from mechanical and smart meters, data federation, data management, data visualization, data analysis, and load forecasting. The proposed system has a four-tier framework (Data, Analytics, Application, and Presentation). Each layer is discussed in detail in this study to overcome the anticipated challenges. Furthermore, this study discusses the proposed system by applying two case studies. The first case study discusses power consumption data management, while the second introduces a novel hybrid load forecasting model using Fuzzy C-Means clustering, Auto Regressive Integrated Moving Average (ARIMA), and Gradient Boosted Tree Learner. The dataset used in this forecasting is based on a 1-year duration dated 1 January 2019 to 31 December 2019, on an hourly basis (365 * 24) for the Baghdad governorate. The results showed high accuracy in load forecasting with improved error rates (MAPE, MAE, and RMSE) achievements in comparison with other evaluated models such as standalone ARIMA and Gradient Boosted Trees methods.
Approach for Calibrated Measurement of the Frequency Response for Characterization of Compliant Interface Elements on Vibration Test Benches
Authors: Heyden Emil , Lindenmann Andreas , Matthiesen Sven , Krause Dieter
Published: October 2021

In vibration tests, the behavior of the structure depends on its mechanical boundary conditions, which are represented in physical tests by connecting elements with mechanical properties. Adjustable impedance elements are machine elements fulfilling the task of an adjustable connection on a vibration test bench and therefore represent a variety of properties. Their mechanical properties must be known over wider ranges than comparable compliant structures tested in the literature. This paper is dedicated to vibration testing of the adjustable impedance elements themselves, taking the influences of fixtures and measuring devices of the test bench into account. Different approaches for measuring the frequency response functions are applied to freely vibrating masses at a hydraulic and an electrodynamic test bench. Mass cancellation and the frequency-dependent measurement systems function have shown their usefulness in characterizing the biodynamic response of hand–arm models before. This measurement method is extended to be transferable to machine elements to obtain reliable results under a wider range of test conditions. The necessity for dynamically calibrated measurement of the frequency response functions is demonstrated for different free vibration masses and for two compliant elements on two different test benches to provide results over a wide range of test conditions.
The Contribution of Ecosystem Regulating Services Based on Their Interrelationship in the Urban Ecosystem
Authors: Kim Hyunsu , Oh Kyushik , Lee Dongwoo
Published: October 2021

The urban ecosystem provides many services that help humans lead physically and mentally healthy lives. The quality of such urban ecosystem services is closely related to various urban forms, such as land cover, land use, buildings, infrastructure, population, and type and scale of green space. This study aims to promote the overall improvement and balance of an urban ecosystem’s regulating services. Initially, ecosystem regulating services are assessed according to the type of the urban space, and their contributions are analyzed based on linear regression slope and pairwise comparison of the ecosystem services. The contribution of ecosystem regulating services of Suwon City in South Korea was assessed through the following process: (1) selection of assessment indices and assessment methods for urban ecosystem regulating services; (2) urban space classification; (3) ecosystem regulating service assessment by type of urban space; and (4) pairwise comparison of ecosystem regulating services by type and for the entire study area. The study areas are classified into six type areas: forests (type A), agricultural land (type B), low-rise residential areas (type C), mid-rise mixed (residential and commercial) areas (type D), high-rise residential areas (type E), and industrial and barren land (type F). By studying representative regulating services, such as vegetation vitality, flood reduction capacity, carbon storage capacity, and heat reduction capacity, this study confirmed that type A provided the best service, while type C provided the worst. In addition, the relative contribution analysis between the regulating services based on pairwise comparison showed that the standard deviation between the contributions was 0.04 when diagnosing the entire study area, but apparently no types except type A were balanced. The reason such regulating services are imbalanced is that their vegetation vitality was calculated to be the lowest compared with the assessment indices of type A. Additionally, this imbalance was found to be most severe in the mid-rise mixed (residential and commercial) districts. Through this study, the spatial types in which the ecosystem regulating services in Suwon City are imbalanced could be determined. It was also revealed that regulating services should be prioritized for improvement in order to achieve greater balance in urban ecosystem. Such pairwise comparison results can be effectively utilized in determining the area and supply needed when formulating urban greening plans and forest restoration plans.
Antisense-Mediated Down-Regulation of Factor V-Short Splicing in a Liver Cell Line Model
Authors: Todaro Alice M. , Hackeng Tilman M. , Castoldi Elisabetta
Published: October 2021

Coagulation factor V (FV) is a liver-derived protein encoded by the F5 gene. Alternative splicing of F5 exon 13 produces a low-abundance splicing isoform, known as FV-short, which binds the anticoagulant protein tissue factor pathway inhibitor (TFPIα) with high affinity, stabilising it in the circulation and potently enhancing its anticoagulant activity. Accordingly, rare F5 gene mutations that up-regulate FV-short splicing are associated with bleeding. In this study we have explored the possibility of decreasing FV-short splicing by antisense-based splicing modulation. To this end, we have designed morpholino antisense oligonucleotides (MAOs) targeting the FV-short-specific donor and acceptor splice sites and tested their efficacy in a liver cell line (HepG2) that naturally expresses full-length FV and FV-short. Cells were treated with 0–20 µM MAO, and full-length FV and FV-short mRNA expression was analysed by RT-(q)PCR. Both MAOs, alone or in combination, decreased the FV-short/full-length FV mRNA ratio down to ~50% of its original value in a specific and dose-dependent manner. This pilot study provides proof-of-principle for the possibility to decrease FV-short expression by antisense-mediated splicing modulation. In turn, this may form the basis for novel therapeutic approaches to bleeding disorders caused by FV-short over-expression and/or elevated TFPIα (activity) levels.
Simulation and Optimization for a Closed-Loop Vessel Dispatching Problem in the Middle East Considering Various Uncertainties
Authors: An Heungjo , Bahamaish Fatima , Lee Dong-Wook
Published: October 2021

The downstream sectors of the hydrocarbon industry in the Middle East are growing quickly. Due to their geographical locations, they need to transport products from manufacturing plants at one port to other hub ports for international shipping, forming complex closed-loop shipping systems. Such domestic shipping systems are also typical logistics structures in many energy and heavy industries near coastal regions. The operations in such systems are frequently lagging due to uncertainties, such as weather and unexpected events, and the lack of effective management techniques. More reliable and efficient systems require a better vessel operations management policy than one based on a first-available-first-use policy and constant voyage speed. This study develops a detailed and realistic simulation model to evaluate the economic and environmental performance of a closed-loop vessel shipping system, considering various uncertainties from weather and port operations. Furthermore, the optimization model has been incorporated into the simulation model to prescribe the optimal number of vessels and voyage speed to minimize the total costs. A new vessel dispatching policy, large-vessel-first-use, has been proposed and compared with the first-available-first-use policy using the developed model. Increased use of large vessels and slower voyage speeds significantly benefited the total costs and environmental effects. The optimal solution presented the potential to save 26.8% of the total cost and reduce greenhouse gas emissions up to 39% compared with the current operating condition.
Development of a Commercial Screed Mortar with Low OPC Content by Incorporation of Biomass Fly Ash
Authors: Capela Marinélia N. , Tobaldi David M. , Tarelho Luís A. C. , Seabra Maria P. , Labrincha João A.
Published: October 2021

Substitute Ordinary Portland Cement (OPC) by biomass fly ash (BFA) reduce the environmental impact produced by cement-based materials, and at the same time, decreased the economic and environmental burden associated with the landfilling of this waste. This study aims to evaluate the recycling of BFA as supplementary cementitious materials (SCMs) in a commercial screed mortar formulation. Two BFA varieties, both resulting from fluidized bed combustion of forest residues, were used to replace 17, 50, and 67 wt.% of OPC. The influence of simple pre-treatment processes of the BFA, such as sieving and grinding, in the fresh and hardened state properties of the mortars, was evaluated. The BFAs were characterized in terms of chemical (XRF) and mineralogical (XRD) composition, particle size distribution (laser diffraction-COULTER) and morphology (SEM). The prepared formulations were characterized in terms of workability, mass loss upon curing, bulk density, sorptivity (by immersion and capillary), flexural and compressive strength and durability to 25 freeze–thaw cycles. Both of the BFAs are potential SCMs. Substitution of 17 wt.% OPC with BFA complied with the product technical requirements for compressive and flexural strength (10 and 3 MPa, respectively), with the ground and sieved and just sieved BFAs perform slightly better than the as-received BFA.
Lowest-Order Thermal Correction to the Hydrogen Recombination Cross-Section in Presence of Blackbody Radiation
Authors: Triaskin Jaroslav , Zalialiutdinov Timur , Anikin Aleksei , Solovyev Dmitrii
Published: October 2021

In the present paper, the correction of the recombination and ionization processes of the hydrogen atom due to the thermal interaction of two charges was considered. The evaluation was based on a rigorous quantum electrodynamic (QED) approach within the framework of perturbation theory. The lowest-order radiative correction to the recombination/ionization cross-section was examined for a wide range of temperatures corresponding to laboratory and astrophysical conditions. The found thermal contribution was discussed both for specific states and for the total recombination and ionization coefficients.
Exotic Pet Trade as a Cause of Biological Invasions: The Case of Tree Squirrels of the Genus Callosciurus
Authors: Mazzamuto Maria Vittoria , Wauters Lucas A. , Koprowski John L.
Published: October 2021

The trade of non-native pets, especially of non-domesticated and exotic animals, and their subsequent release and establishment of populations is one of the major pathways of introduction for invasive alien reptiles, amphibia, birds and mammals. Here, we use a group of arboreal mammals, tree squirrels of the genus Callosciurus, as a well-documented case study, reviewing the pathways of introduction, the current areas of non-native distribution, the rate of establishment success and the challenge and legal importance of species identification. We further illustrate the importance of early detection and effective monitoring methods and plans. Next, we document how they interfere with native species, their risk of acting as vectors for emerging infectious diseases and their potential role in maintaining parasitic infections that can affect human health. We conclude by reviewing the current management, or the lack of it, and highlight the diverse biological, social, political and economic reasons that make control/eradication of these charismatic species difficult or even impractical in most countries. However, reviewing the only two successful eradications of the IAS, we highlight the need to acknowledge the public opinion and the importance of communication, transparency and the engagement of a diversity of stakeholders to create a consensus about the actions to undertake.
Network Analysis Integrating microRNA Expression Profiling with MRI Biomarkers and Clinical Data for Prostate Cancer Early Detection: A Proof of Concept Study
Authors: Panebianco Valeria , Paci Paola , Pecoraro Martina , Conte Federica , Carnicelli Giorgia , Besharat Zein , Catanzaro Giuseppina , Splendiani Elena , Sciarra Alessandro , Farina Lorenzo , Catalano Carlo , Ferretti Elisabetta
Published: October 2021

The MRI of the prostate is the gold standard for the detection of clinically significant prostate cancer (csPCa). Nonetheless, MRI still misses around 11% of clinically significant disease. The aim was to comprehensively integrate tissue and circulating microRNA profiling, MRI biomarkers and clinical data to implement PCa early detection. In this prospective cohort study, 76 biopsy naïve patients underwent MRI and MRI directed biopsy. A sentinel sample of 15 patients was selected for a pilot molecular analysis. Weighted gene coexpression network analysis was applied to identify the microRNAs drivers of csPCa. MicroRNA–target gene interaction maps were constructed, and enrichment analysis performed. The ANOVA on ranks test and ROC analysis were performed for statistics. Disease status was associated with the underexpression of the miRNA profiled; a correlation was found with ADC (r = −0.51, p = 0.02) and normalized ADC values (r = −0.64, p = 0.002). The overexpression of miRNAs from plasma was associated with csPCa (r = 0.72; p = 0.02), and with PI-RADS assessment score (r = 0.73; p = 0.02); a linear correlation was found with biomarkers of diffusion and perfusion. Among the 800 profiled microRNA, eleven were identified as correlating with PCa, among which miR-548a-3p, miR-138-5p and miR-520d-3p were confirmed using the RT-qPCR approach on an additional cohort of ten subjects. ROC analysis showed an accuracy of >90%. Provided an additional validation set of the identified miRNAs on a larger cohort, we propose a diagnostic paradigm shift that sees molecular data and MRI biomarkers as the prebiopsy triage of patients at risk for PCa. This approach will allow for accurate patient allocation to biopsy, and for stratification into risk group categories, reducing overdiagnosis and overtreatment.
Antitumoral Activities of Curcumin and Recent Advances to ImProve Its Oral Bioavailability
Authors: Nocito Marta Claudia , De Luca Arianna , Prestia Francesca , Avena Paola , La Padula Davide , Zavaglia Lucia , Sirianni Rosa , Casaburi Ivan , Puoci Francesco , Chimento Adele , Pezzi Vincenzo
Published: October 2021

Curcumin, a main bioactive component of the Curcuma longa L. rhizome, is a phenolic compound that exerts a wide range of beneficial effects, acting as an antimicrobial, antioxidant, anti-inflammatory and anticancer agent. This review summarizes recent data on curcumin’s ability to interfere with the multiple cell signaling pathways involved in cell cycle regulation, apoptosis and the migration of several cancer cell types. However, although curcumin displays anticancer potential, its clinical application is limited by its low absorption, rapid metabolism and poor bioavailability. To overcome these limitations, several curcumin-based derivatives/analogues and different drug delivery approaches have been developed. Here, we also report the anticancer mechanisms and pharmacokinetic characteristics of some derivatives/analogues and the delivery systems used. These strategies, although encouraging, require additional in vivo studies to support curcumin clinical applications.
Topographical Vacuum Sealing of 3D-Printed Multiplanar Microfluidic Structures
Authors: Heidt Benjamin , Rogosic Renato , Leoné Nils , Brás Eduardo , Cleij Thomas , Harings Jules , Diliën Hanne , Eersels Kasper , van Grinsven Bart
Published: October 2021

We demonstrate a novel way of creating three-dimensional microfluidic channels capable of following complex topographies. To this end, substrates with open channels and different geometries were 3D-printed, and the open channels were consecutively closed with a thermoplastic using a low-resolution vacuum-forming approach. This process allows the sealing of channels that are located on the surface of complex multiplanar topographies, as the thermoplastic aligns with the surface-shape (the macrostructure) of the substrate, while the microchannels remain mostly free of thermoplastic as their small channel size resists thermoplastic inflow. This new process was analyzed for its capability to consistently close different substrate geometries, which showed reliable sealing of angles >90°. Furthermore, the thermoplastic intrusion into channels of different widths was quantified, showing a linear effect of channel width and percentage of thermoplastic intrusion; ranging from 43.76% for large channels with 2 mm width to only 5.33% for channels with 500 µm channel width. The challenging sealing of substrate ‘valleys’, which are created when two large protrusions are adjacent to each other, was investigated and the correlation between protrusion distance and height is shown. Lastly, we present three application examples: a serpentine mixer with channels spun around a cuboid, increasing the usable surface area; a cuvette-inspired flow cell for a 2-MXP biosensor based on molecular imprinted polymers, fitting inside a standard UV/Vis-Spectrophotometer; and an adapter system that can be manufactured by one-sided injection molding and is self-sealed before usage. These examples demonstrate how this novel technology can be used to easily adapt microfluidic circuits for application in biosensor platforms.
Emotional Processing and Experience in Amyotrophic Lateral Sclerosis: A Systematic and Critical Review
Authors: Carelli Laura , Solca Federica , Tagini Sofia , Torre Silvia , Verde Federico , Ticozzi Nicola , Consonni Monica , Ferrucci Roberta , Pravettoni Gabriella , Poletti Barbara , Silani Vincenzo
Published: October 2021

Even though increasing literature describes changes in emotional processing in Amyotrophic Lateral Sclerosis (ALS), efforts to summarize relevant findings are lacking in the field. A systematic literature review was performed to provide a critical and up-to-date account of emotional abilities in ALS. References were identified by searches of PubMed, Web of Science and Scopus (1980–2021, English literature), with the following key terms: (“Amyotrophic Lateral Sclerosis” or “Primary Lateral Sclerosis” or “Motor Neuron”) and “Emotion*” and (“Processing” or “Attribution” or “Elaboration” or “Perception” or “Recognition”). Studies concerning only caregivers, pseudobulbar affect, and social cognition were excluded. Forty-one articles were included, all concerning ALS, and seven topics were identified: Emotion recognition, Emotional responsiveness, Emotional reactivity, Faces approachability rating, Valence rating, Memory for emotional materials and Alexithymia. The majority of these aspects have only been sparsely addressed. The evidence confirms altered emotional processing in ALS. The most consistent findings regard the recognition of facial expressions for negative emotions, but also alterations in the subjective responsiveness to emotional stimuli (arousal, valence and approachability), in psychophysiological and cerebral reactivity and in emotional memory, together with alexithymia traits, were reported. According to this evidence, emotional abilities should be included in the clinical assessment and therapeutic interventions.
Socioeconomic Environment and Survival in Patients with Digestive Cancers: A French Population-Based Study
Authors: Tron Laure , Fauvernier Mathieu , Bouvier Anne-Marie , Robaszkiewicz Michel , Bouvier Véronique , Cariou Mélanie , Jooste Valérie , Dejardin Olivier , Remontet Laurent , Alves Arnaud ,   FRANCIM Group, Molinié Florence , Launoy Guy
Published: October 2021

Social inequalities are an important prognostic factor in cancer survival, but little is known regarding digestive cancers specifically. We aimed to provide in-depth analysis of the contextual social disparities in net survival of patients with digestive cancer in France, using population-based data and relevant modeling. Digestive cancers (n = 54,507) diagnosed between 2006–2009, collected through the French network of cancer registries, were included (end of follow-up 30 June 2013). Social environment was assessed by the European Deprivation Index. Multidimensional penalized splines were used to model excess mortality hazard. We found that net survival was significantly worse for individuals living in a more deprived environment as compared to those living in a less deprived one for esophageal, liver, pancreatic, colon and rectal cancers, and for stomach and bile duct cancers among females. Excess mortality hazard was up to 57% higher among females living in the most deprived areas (vs. least deprived) at 1 year of follow-up for bile duct cancer, and up to 21% higher among males living in the most deprived areas (vs. least deprived) regarding colon cancer. To conclude, we provide a better understanding of how the (contextual) social gradient in survival is constructed, offering new perspectives for tackling social inequalities in digestive cancer survival.
A Unified Transcriptional, Pharmacogenomic, and Gene Dependency Approach to Decipher the Biology, Diagnostic Markers, and Therapeutic Targets Associated with Prostate Cancer Metastasis
Authors: Bacolod Manny D. , Barany Francis
Published: October 2021

Our understanding of metastatic prostate cancer (mPrCa) has dramatically advanced during the genomics era. Nonetheless, many aspects of the disease may still be uncovered through reanalysis of public datasets. We integrated the expression datasets for 209 PrCa tissues (metastasis, primary, normal) with expression, gene dependency (GD) (from CRISPR/cas9 screen), and drug viability data for hundreds of cancer lines (including PrCa). Comparative statistical and pathways analyses and functional annotations (available inhibitors, protein localization) revealed relevant pathways and potential (and previously reported) protein markers for minimally invasive mPrCa diagnostics. The transition from localized to mPrCa involved the upregulation of DNA replication, mitosis, and PLK1-mediated events. Genes highly upregulated in mPrCa and with very high average GD (~1) are potential therapeutic targets. We showed that fostamatinib (which can target PLK1 and other over-expressed serine/threonine kinases such as AURKA, MELK, NEK2, and TTK) is more active against cancer lines with more pronounced signatures of invasion (e.g., extracellular matrix organization/degradation). Furthermore, we identified surface-bound (e.g., ADAM15, CD276, ABCC5, CD36, NRP1, SCARB1) and likely secreted proteins (e.g., APLN, ANGPT2, CTHRC1, ADAM12) that are potential mPrCa diagnostic markers. Overall, we demonstrated that comprehensive analyses of public genomics data could reveal potentially clinically relevant information regarding mPrCa.
Impact of the Presenting Symptom on Time Intervals and Diagnostic Routes of Patients with Symptomatic Oral Cancer
Authors: Varela-Centelles Pablo Ignacio , López Daniel Pérez , López-Cedrún José Luis , García-Rozado Álvaro , Baz Pablo Castelo , Romero-Méndez Amparo , Seoane Juan
Published: October 2021

This investigation was aimed at determining the time intervals from the presenting symptoms until the beginning of oral cancer treatment and their relative contribution to the total time, and to assess the impact of the presenting symptom on diagnostic timelines and patient referral routes. A cross-sectional, ambispective study was designed to investigate symptomatic incident cases. The Aarhus statement was used as a conceptual framework. Strategies for minimizing potential recall biases were implemented. A sample of 181 patients was recruited (power: 99.5%; α = 0.05). The patient interval reached 58.2 days (95% CI, 40.3–76.2), which accounted for 74% of the whole prereferral interval and for more than one third of the total time interval. The presenting symptom (trigger for consultation) influenced both the number of primary care consultations and the length of time to diagnosis. General dental practitioners generated longer intervals to diagnosis (p < 0.005) and needed more consultations before referring a patient (RR = 0.76; 95% CI, 0.61–0.93), than general medical practitioners. The current study identifies the patient as the main target for interventions to improve awareness and reinforces the need for increased alertness amongst healthcare professionals about presenting symptoms of oral cancer and to diminish the number of prereferral consultations in order to optimize the primary care interval.
Global Methylome Scores Correlate with Histological Subtypes of Colorectal Carcinoma and Show Different Associations with Common Clinical and Molecular Features
Authors: Turpín-Sevilla María del Carmen , Pérez-Sanz Fernando , García-Solano José , Sebastián-León Patricia , Trujillo-Santos Javier , Carbonell Pablo , Estrada Eduardo , Tuomisto Anne , Herruzo Irene , Fennell Lochlan J. , Mäkinen Markus J. , Rodríguez-Braun Edith , Whitehall Vicki L. J. , Conesa Ana , Conesa-Zamora Pablo
Published: October 2021

Background. The typical methylation patterns associated with cancer are hypermethylation at gene promoters and global genome hypomethylation. Aberrant CpG island hypermethylation at promoter regions and global genome hypomethylation have not been associated with histological colorectal carcinomas (CRC) subsets. Using Illumina’s 450 k Infinium Human Methylation beadchip, the methylome of 82 CRCs were analyzed, comprising different histological subtypes: 40 serrated adenocarcinomas (SAC), 32 conventional carcinomas (CC) and 10 CRCs showing histological and molecular features of microsatellite instability (hmMSI-H), and, additionally, 35 normal adjacent mucosae. Scores reflecting the overall methylation at 250 bp, 1 kb and 2 kb from the transcription starting site (TSS) were studied. Results. SAC has an intermediate methylation pattern between CC and hmMSI-H for the three genome locations. In addition, the shift from promoter hypermethylation to genomic hypomethylation occurs at a small sequence between 250 bp and 1 Kb from the gene TSS, and an asymmetric distribution of methylation was observed between both sides of the CpG islands (N vs. S shores). Conclusion. These findings show that different histological subtypes of CRC have a particular global methylation pattern depending on sequence distance to TSS and highlight the so far underestimated importance of CpGs aberrantly hypomethylated in the clinical phenotype of CRCs.
Pulmonary Nodule and Mass: Superiority of MRI of Diffusion-Weighted Imaging and T2-Weighted Imaging to FDG-PET/CT
Authors: Usuda Katsuo , Ishikawa Masahito , Iwai Shun , Yamagata Aika , Iijima Yoshihito , Motono Nozomu , Matoba Munetaka , Doai Mariko , Hirata Keiya , Uramoto Hidetaka
Published: October 2021

The purpose of this retrospective study was to compare the diagnostic efficacy of FDG-PET/CT and MRI in discriminating malignant from benign pulmonary nodules and masses (PNMs). There were 278 lung cancers and 50 benign PNMs that were examined by FDG-PET/CT and MRI. The T2 contrast ratio (T2 CR) was designated as the ratio of T2 signal intensity of PNM divided by T2 signal intensity of the rhomboid muscle. The optimal cut-off values (OCVs) for differential diagnosis were 3.605 for maximum standardized uptake value (SUVmax), 1.459 × 10−3 mm2/s for apparent diffusion coefficient (ADC), and 2.46 for T2 CR. Areas under the receiver operating characteristics curves were 67.5% for SUVmax, 74.3% for ADC, and 72.4% for T2 CR, respectively. The sensitivity (0.658) of SUVmax was significantly lower than that (0.838) of ADC (p < 0.001) and that (0.871) of T2 CR (p < 0.001). The specificity (0.620) of SUVmax was that the same as (0.640) ADC and (0.640) of T2 CR. The accuracy (0.652) of SUVmax was significantly lower than that (0.808) of ADC (p < 0.001) and that (0.835) of T2 CR (p < 0.001). The sensitivity and accuracy of DWI and T2WI in MRI were significantly higher than those of FDG-PET/CT. Ultimately, MRI can replace FDG PET/CT for differential diagnosis of PNMs saving healthcare systems money while not sacrificing the quality of care.
A Mathematical Modeling Approach for Targeted Radionuclide and Chimeric Antigen Receptor T Cell Combination Therapy
Authors: Adhikarla Vikram , Awuah Dennis , Brummer Alexander B. , Caserta Enrico , Krishnan Amrita , Pichiorri Flavia , Minnix Megan , Shively John E. , Wong Jeffrey Y. C. , Wang Xiuli , Rockne Russell C.
Published: October 2021

Targeted radionuclide therapy (TRT) has recently seen a surge in popularity with the use of radionuclides conjugated to small molecules and antibodies. Similarly, immunotherapy also has shown promising results, an example being chimeric antigen receptor T cell (CAR-T) therapy in hematologic malignancies. Moreover, TRT and CAR-T therapies possess unique features that require special consideration when determining how to dose as well as the timing and sequence of combination treatments including the distribution of the TRT dose in the body, the decay rate of the radionuclide, and the proliferation and persistence of the CAR-T cells. These characteristics complicate the additive or synergistic effects of combination therapies and warrant a mathematical treatment that includes these dynamics in relation to the proliferation and clearance rates of the target tumor cells. Here, we combine two previously published mathematical models to explore the effects of dose, timing, and sequencing of TRT and CAR-T cell-based therapies in a multiple myeloma setting. We find that, for a fixed TRT and CAR-T cell dose, the tumor proliferation rate is the most important parameter in determining the best timing of TRT and CAR-T therapies.
PET with Different Radiopharmaceuticals in Neuroendocrine Neoplasms: An Umbrella Review of Published Meta-Analyses
Authors: Treglia Giorgio , Sadeghi Ramin , Giovinazzo Francesco , Galiandro Federica , Annunziata Salvatore , Muoio Barbara , Kroiss Alexander Stephan
Published: October 2021

Background: Several meta-analyses have reported quantitative data about the diagnostic performance, the prognostic value, the impact on management and the safety of positron emission tomography (PET) including related hybrid modalities (PET/CT or PET/MRI) using different radiopharmaceuticals in patients with neuroendocrine neoplasms. We performed an umbrella review of published meta-analyses to provide an evidence-based summary. Methods: A comprehensive literature search of meta-analyses listed in PubMed/MEDLINE and Cochrane Library databases was carried out (last search date: 30 June 2021). Results: Thirty-four published meta-analyses were selected and summarized. About the diagnostic performance: 68Ga-SSA PET yields high diagnostic performance in patients with NETs and PGL; 18F-FDOPA PET yields good diagnostic performance in patients with intestinal NETs, PGL, NB, being the best available PET method in detecting rMTC; 68Ga-exendin-4 PET has good diagnostic accuracy in detecting insulinomas; 18F-FDG PET has good diagnostic performance in detecting aggressive neuroendocrine neoplasms. About the prognostic value: 68Ga-SSA PET has a recognized prognostic value in well-differentiated NETs, whereas 18F-FDG PET has a recognized prognostic value in aggressive neuroendocrine neoplasms. A significant clinical impact of 68Ga-SSA PET and related hybrid modalities in patients with NETs was demonstrated. There are no major toxicities or safety issues related to the use of PET radiopharmaceuticals in patients with neuroendocrine neoplasms. Conclusions: Evidence-based data support the use of PET with different radiopharmaceuticals in patients with neuroendocrine neoplasms with specific indications for each radiopharmaceutical.
Could Photodynamic Therapy Be a Promising Therapeutic Modality in Hepatocellular Carcinoma Patients? A Critical Review of Experimental and Clinical Studies
Authors: Kumar Abhishek , Moralès Olivier , Mordon Serge , Delhem Nadira , Boleslawski Emmanuel
Published: October 2021

Photodynamic Therapy (PDT) relies on local or systemic administration of a light-sensitive dye, called photosensitizer, to accumulate into the target site followed by excitation with light of appropriate wavelength and fluence. This photo-activated molecule reacts with the intracellular oxygen to induce selective cytotoxicity of targeted cells by the generation of reactive oxygen species. Hepatocellular carcinoma (HCC), one of the leading causes of cancer-associated mortality worldwide, has insufficient treatment options available. In this review, we discuss the mechanism and merits of PDT along with its recent developments as an anti-cancerous therapy. We also highlight the application of this novel therapy for diagnosis, visualization, and treatment of HCC. We examine the underlying challenges, some pre-clinical and clinical studies, and possibilities of future studies associated with PDT. Finally, we discuss the mechanism of an active immune response by PDT and thereafter explored the role of PDT in the generation of anti-tumor immune response in the context of HCC, with an emphasis on checkpoint inhibitor-based immunotherapy. The objective of this review is to propose PDT as a plausible adjuvant to existing therapies for HCC, highlighting a feasible combinatorial approach for HCC treatment.