bluuebunny/crossref_metadata_2025 huggingface dataset:
La psicoterapia adleriana breve: un modelo de intervención para los contextos de la salud mental pública
Authors: Ruiz Juan José , Oberst Ursula
Published: July 2021

Este artículo presenta una propuesta para una intervención psicológica breve (Psicoterapia Adleriana Breve, P.A.B.) pensada para su aplicación especialmente en contextos con recursos limitados y de salud pública. Después de una breve presentación de las nociones básicas de la Psicología Individual de Alfred Adler, se reseñan algunas propuestas previas de su aplicación en un formato de intervención breve. El artículo sigue con la descripción de un modelo propio de los autores ilustrado por un ejemplo de caso.
Estas viejas locas: envejecer gay en el buenos aires contemporáneo, una experiencia grupal
Authors: Gagliesi Pablo
Published: July 2021

El propósito de este trabajo es exponer y debatir la experiencia grupal de psicoterapia con varones homosexuales mayores de 65 años en Buenos Aires. Las hipótesis centrales que lo articulan se constituyen desde dos perspectivas, una estadística y otra de análisis narrativo. Se parte del supuesto que los grupos homogéneos son eficaces en algunos contextos, lo que queda demostrado en los resultados de las tomas de inicio y final del BDI y SAS; aunque dichos datos no se encuentran, como se suponía, vinculados consistentemente con los antecedentes históricos (abuso de poder, duelos durante las últimas dictaduras militares, duelos por la epidemia del SIDA y las dificultades en la supervivencia económica). Por otro lado, se ha evidenciado que las Narrativas Gay y Lesbianas descritas y validadas en la bibliografía contemporánea anglosajona son asumidas por este grupo. Por último, se discute el constructo de la atribución melodramática el cual está relacionado con la homofobia, y las vinculaciones de esta con el carácter patologizante de los tratamientos psicoterapéuticos anteriores.
A Modular Framework for the Life Cycle Based Evaluation of Aircraft Technologies, Maintenance Strategies, and Operational Decision Making Using Discrete Event Simulation
Authors: Pohya Ahmad Ali , Wehrspohn Jennifer , Meissner Robert , Wicke Kai
Published: July 2021

Current practices for investment and technology decision making in aeronautics largely rely on regression-based cost estimation methods. Although quick to implement and easy to use, they suffer from a variety of limitations, both in temporal space and scope of applicability. While recent research and development in this area addresses these to a certain extent, aerospace engineering still lacks a flexible and customizable valuation framework. To this end, a generic environment for economic and operational assessment of aircraft and related products named LYFE is presented. This tool employs a discrete event simulation which models the product life cycle from its order through decades of operation and maintenance until disposal. This paper introduces its key characteristics and default methods alongside its modular program architecture. The capabilities are demonstrated with a case study of on-wing engine cleaning procedures which are triggered by a customized decision making module. Thereby, the impact on engine health, fuel efficiency and overall economic viability is quantified. On the whole, the framework introduced in this paper can be used to analyze not only physical products but also operational procedures and maintenance strategies as well as specified decision making algorithms in terms of their impact on an aircraft’s or system’s life cycle.
Biosynthesis of Silver Nanoparticles Mediated by Entomopathogenic Fungi: Antimicrobial Resistance, Nanopesticides, and Toxicity
Authors: Santos Tárcio S. , Silva Tarcisio M. , Cardoso Juliana C. , Albuquerque-Júnior Ricardo L. C. de , Zielinska Aleksandra , Souto Eliana B. , Severino Patrícia , Mendonça Marcelo da Costa
Published: July 2021

Silver nanoparticles are widely used in the biomedical and agri-food fields due to their versatility. The use of biological methods for the synthesis of silver nanoparticles has increased considerably due to their feasibility and high biocompatibility. In general, microorganisms have been widely explored for the production of silver nanoparticles for several applications. The objective of this work was to evaluate the use of entomopathogenic fungi for the biological synthesis of silver nanoparticles, in comparison to the use of other filamentous fungi, and the possibility of using these nanoparticles as antimicrobial agents and for the control of insect pests. In addition, the in vitro methods commonly used to assess the toxicity of these materials are discussed. Several species of filamentous fungi are known to have the ability to form silver nanoparticles, but few studies have been conducted on the potential of entomopathogenic fungi to produce these materials. The investigation of the toxicity of silver nanoparticles is usually carried out in vitro through cytotoxicity/genotoxicity analyses, using well-established methodologies, such as MTT and comet assays, respectively. The use of silver nanoparticles obtained through entomopathogenic fungi against insects is mainly focused on mosquitoes that transmit diseases to humans, with satisfactory results regarding mortality estimates. Entomopathogenic fungi can be employed in the synthesis of silver nanoparticles for potential use in insect control, but there is a need to expand studies on toxicity so to enable their use also in insect control in agriculture.
Pomegranate Extract (POMx) Induces Mitochondrial Dysfunction and Apoptosis of Oral Cancer Cells
Authors: Peng Sheng-Yao , Lin Li-Ching , Chen Shu-Rong , Farooqi Ammad A. , Cheng Yuan-Bin , Tang Jen-Yang , Chang Hsueh-Wei
Published: July 2021

The anticancer effect of pomegranate polyphenolic extract POMx in oral cancer cells has rarely been explored, especially where its impact on mitochondrial functioning is concerned. Here, we attempt to evaluate the proliferation modulating function and mechanism of POMx against human oral cancer (Ca9-22, HSC-3, and OC-2) cells. POMx induced ATP depletion, subG1 accumulation, and annexin V/Western blotting-detected apoptosis in these three oral cancer cell lines but showed no toxicity to normal oral cell lines (HGF-1). POMx triggered mitochondrial membrane potential (MitoMP) disruption and mitochondrial superoxide (MitoSOX) generation associated with the differential downregulation of several antioxidant gene mRNA/protein expressions in oral cancer cells. POMx downregulated mitochondrial mass, mitochondrial DNA copy number, and mitochondrial biogenesis gene mRNA/protein expression in oral cancer cells. Moreover, POMx induced both PCR-based mitochondrial DNA damage and γH2AX-detected nuclear DNA damage in oral cancer cells. In conclusion, POMx provides antiproliferation and apoptosis of oral cancer cells through mechanisms of mitochondrial impairment.
Assessment of a Location-Based Mobile Augmented-Reality Game by Adult Users with the ARCS Model
Authors: Sdravopoulou Konstantina , Muñoz González Juan Manuel , Hidalgo-Ariza María Dolores
Published: July 2021

In mobile augmented reality (MAR) games, learning by doing is important to supplement the theoretical knowledge with practical exercise in order to maximize the learning outcome. However, in many fields, the users are not able to apply their knowledge in practical ways, despite having achieved a good understanding of the theoretical fundamentals and this is even more important to adult learners. The aim of this research is to examine young, middle-aged and elderly adults’ opinions about the location-based MAR game Ingress, by applying John Keller’s “ARCS learning motivation model” (Attention, Relevance, Confidence and Satisfaction). The users’ responses to closed questions related to Ingress were collected from 45 adult players aged 20–60 from Greece and were subsequently analyzed by means of pre- and post-quantitative measures of the four ARCS factors. The results show that: (a) game training improves all the factors of ARCS, primarily attention and satisfaction; (b) the responses of young people (20–35) agree more with those of elderly adults (>52) than with those of the intermediate age group of 36–51. Our findings, therefore, highlight the potential and the applicability of the ARCS model in MAR games.
Dye Schedule Optimization: A Case Study in a Textile Industry
Authors: Gomes Uiraquitan Tadeu , Pinheiro Plácido Rogério , Saraiva Rommel Dias
Published: July 2021

In a demanding and globalized market, production management plays a fundamental role in the company’s reference. Proper management of the production area allows companies to obtain productivity gains, reducing operational costs and make contributions to face the competitiveness of their competitors. When defining its strategic objectives in a productive system, it is necessary to formulate plans to manage human resources and strategies based on requirements. In this context, planning, production, and control (PPC) is an excellent ally of the organizations. The adequate development of the activities of the PPC allows companies to minimize production orders not attended, minimize stocks of raw materials, and finished products, minimize idleness of human resources by efficient allocation of work and minimize production processing times. The present work proposes a study to organize and develop a model that guides the prediction of the setup gain in the fabric dyeing process, structured by the traveling salesman problem.
Reactive Obstacle–Avoidance Systems for Wheeled Mobile Robots Based on Artificial Intelligence
Authors: Medina-Santiago A. , Morales-Rosales Luis Alberto , Hernández-Gracidas Carlos Arturo , Algredo-Badillo Ignacio , Pano-Azucena Ana Dalia , Orozco Torres Jorge Antonio
Published: July 2021

Obstacle–Avoidance robots have become an essential field of study in recent years. This paper analyzes two cases that extend reactive systems focused on obstacle detection and its avoidance. The scenarios explored get data from their environments through sensors and generate information for the models based on artificial intelligence to obtain a reactive decision. The main contribution is focused on the discussion of aspects that allow for comparing both approaches, such as the heuristic approach implemented, requirements, restrictions, response time, and performance. The first case presents a mobile robot that applies a fuzzy inference system (FIS) to achieve soft turning basing its decision on depth image information. The second case introduces a mobile robot based on a multilayer perceptron (MLP) architecture, which is a class of feedforward artificial neural network (ANN), and ultrasonic sensors to decide how to move in an uncontrolled environment. The analysis of both options offers perspectives to choose between reactive Obstacle–Avoidance systems based on ultrasonic or Kinect sensors, models that infer optimal decisions applying fuzzy logic or artificial neural networks, with key elements and methods to design mobile robots with wheels. Therefore, we show how AI or Fuzzy Logic techniques allow us to design mobile robots that learn from their “experience” by making them safe and adjustable for new tasks, unlike traditional robots that use large programs to perform a specific task.
Port Structure Inspection Based on 6-DOF Displacement Estimation Combined with Homography Formulation and Genetic Algorithm
Authors: Min Jiyoung , Bang Yuseok , Bang Hyuntae , Jeon Haemin
Published: July 2021

A vision sensor-based 6-DOF displacement evaluation method incorporating a genetic algorithm was proposed to monitor the critical defects of port infrastructure, such as deflection, slope, and slip. The 6-DOF behavior of the port structure, including subsidence, was estimated based on the specification of the target and fixed structures nearby. The method calculates the relative position of the target port structure and measures the movement of the structure over time. To improve the measurement accuracy, a genetic algorithm was used to adjust the intrinsic parameters that were previously estimated using the checkerboards. The results of measuring 6-DOF displacements based on the tuned intrinsic parameters confirmed that it has the potential to accurately measure the 6-DOF behavior of port facilities. The possibility of field application was examined through an artificial movement that was induced in the image of the port facility to create an arbitrary displacement between two points.
Adapted Use of the TRIZ System Operator
Authors: Fiorineschi Lorenzo , Frillici Francesco Saverio , Rotini Federico , Conti Leonardo , Rossi Giuseppe
Published: July 2021

The System Operator (SO), also known as Nine Boxes or Multiscreen, is classically used for analysing the undesired situation according to different perspectives. However, its logic can be suitably exploited also for other kinds of tasks. In such a context, this paper shows an alternative application of the SO. In particular, the new proposed SO approach allows us to formulate alternative problems, i.e., different from the central one, although referring to the same problem-solving task. By applying the proposed procedure to a real case study, this paper shows that the tool can be used for problem analysis and formulation purposes, aimed at better clarifying the problem-solving task. The case study concerns a preliminary set of experiments performed to evaluate the possibility of obtaining angular shapes by bending tiles made by a specific compostable composite material. The suggestions obtained using the proposed SO approach allowed us to find potentially valid solutions, thus paving the way for further validation tests. In particular, tests are still needed to validate the actual potentialities of the proposed SO. Additionally, further and more comprehensive tests are required to validate the solutions inferred in this study concerning the compostable tiles.
The Honey Bee: An Active Biosampler of Environmental Pollution and a Possible Warning Biomarker for Human Health
Authors: Martinello Marianna , Manzinello Chiara , Dainese Nicoletta , Giuliato Ilenia , Gallina Albino , Mutinelli Franco
Published: July 2021

Member states of the European Union are required to ensure the initiation of monitoring programs to verify honey bee exposure to pesticides, where and as appropriate. Based on 620 samples of dead honey bees—42 of pollen, 183 of honey and 32 of vegetables—we highlighted the presence, as analyzed by liquid and gas chromatography coupled with tandem mass spectrometric detection, of many active substances, mainly tau-fluvalinate, piperonyl butoxide, chlorpyrifos and chlorpyrifos-methyl, permethrin and imidacloprid. Among the active substances found in analyzed matrices linked to honey bee killing incidents, 38 belong to hazard classes I and II, as methiocarb, methomyl, chlorpyrifos, cypermethrin and permethrin, thus representing a potential risk for human health. We have shown that, at different times between 2015 and 2020, during implementation of the Italian national guidelines for managing reports of bee colony mortality or depopulation associated with pesticide use, pesticide pollution events occurred that could raise concern for human health. Competent authorities could, as part of a One Health approach, exploit the information provided by existing reporting programs on honey bees and their products, in view of the close correlation to human health, animal health and ecosystem health.
Survey Solutions for 3D Acquisition and Representation of Artificial and Natural Caves
Authors: Giordan Daniele , Godone Danilo , Baldo Marco , Piras Marco , Grasso Nives , Zerbetto Raffaella
Published: July 2021

A three-dimensional survey of natural caves is often a difficult task due to the roughness of the investigated area and the problems of accessibility. Traditional adopted techniques allow a simplified acquisition of the topography of caves characterized by an oversimplification of the geometry. Nowadays, the advent of LiDAR and Structure from Motion applications eased three-dimensional surveys in different environments. In this paper, we present a comparison between other three-dimensional survey systems, namely a Terrestrial Laser Scanner, a SLAM-based portable instrument, and a commercial photo camera, to test their possible deployment in natural caves survey. We presented a comparative test carried out in a tunnel stretch to calibrate the instrumentation on a benchmark site. The choice of the site is motivated by its regular geometry and easy accessibility. According to the result obtained in the calibration site, we presented a methodology, based on the Structure from Motion approach that resulted in the best compromise among accuracy, feasibility, and cost-effectiveness, that could be adopted for the three-dimensional survey of complex natural caves using a sequence of images and the structure from motion algorithm. The methods consider two different approaches to obtain a low resolution complete three-dimensional model of the cave and ultra-detailed models of most peculiar cave morphological elements. The proposed system was tested in the Gazzano Cave (Piemonte region, Northwestern Italy). The obtained result is a three-dimensional model of the cave at low resolution due to the site’s extension and the remarkable amount of data. Additionally, a peculiar speleothem, i.e., a stalagmite, in the cave was surveyed at high resolution to test the proposed high-resolution approach on a single object. The benchmark and the cave trials allowed a better definition of the instrumentation choice for underground surveys regarding accuracy and feasibility.
High Genetic Diversity and Low Population Differentiation in Wild Hop (Humulus lupulus L.) from Croatia
Authors: Grdiša Martina , Šatović Zlatko , Liber Zlatko , Jakše Jernej , Varga Filip , Erhatić Renata , Srečec Siniša
Published: July 2021

Hop (Humulus lupulus L.) is used in the brewing industry as a source of compounds responsible for the bitterness, aroma, and preservative properties of beer. In this study, we used microsatellite markers to investigate genetic diversity and genetic differentiation of wild hop populations sampled in the northwestern part of Croatia. Analysis of 12 microsatellite loci revealed high diversity and weak population differentiation among wild hop populations. A total of 152 alleles were determined with an average of 12.67 alleles per locus. Observed heterozygosity ranged from 0.689 to 0.839 (average 0.767) and expected heterozygosity ranged from 0.725 to 0.789 (average 0.760). A total of 38 private alleles were detected. The data suggest that H. lupulus populations are not affected by recent bottlenecks. The degree of genetic differentiation among populations was low and not significant for most pairwise FST values, except for the pair of geographically most distant populations. The results did not indicate the existence of genetic structure among the sampled populations. The high genetic diversity and low differentiation among populations, combined with the absence of isolation by distance, indicate the existence of substantial gene flow among wild hop populations. Therefore, extensive sampling per population is clearly required to assess the genetic diversity of hop populations. Sampling strategies involving sampling across a large number of localities represented by only a few samples could lead to erroneous conclusions.
A Cadaveric Study of Ulnar Nerve Movement and Strain around the Elbow Joint
Authors: Nagashima Mitsuyuki , Omokawa Shohei , Nakanishi Yasuaki , Mahakkanukrauh Pasuk , Hasegawa Hideo , Tanaka Yasuhito
Published: July 2021

There is a lack of data on how ulnar nerve strain varies according to the location around the elbow joint. Therefore, we measured the longitudinal movement of the ulnar nerve around the elbow joint. Four fresh-frozen cadaveric upper extremities were used. A linear displacement sensor was attached to the ulnar nerve at eight measurement points at 20-mm intervals. At each point, the longitudinal movement of the ulnar nerve was measured during elbow flexion. We calculated the strain on the ulnar nerve based on the change in movement between neighboring points. Ulnar nerve movement with elbow flexion had a maximum value (mean, 10.5 mm; p < 0.001) at 2 cm proximal to the medial epicondyle. In the site distal to the medial epicondyle, the movement was small and demonstrated no significant difference between points (p = 0.1). The change in strain between mild flexion (0–60°) and deep flexion (60–120°) significantly differed at 2–4 cm and 6–8 cm proximal to the medial epicondyle (15% versus 3%, p < 0.01; 5% versus 9%, p < 0.05, respectively). The longitudinal movement of the ulnar nerve during elbow flexion occurred mainly at the site proximal to the medial epicondyle and became smaller away from the medial epicondyle.
Change in Sediment Provenance on the Inner Slope of the Chukchi Rise and Their Paleoenvironmental Implications
Authors: Koo Hyo-Jin , Jin Young-Keun , Cho Hyen-Goo
Published: July 2021

The Arctic Ocean is one of the world’s most remarkable regions with respect to global climate change. The core ARA09C-St03 was analyzed for mineral composition and Nd isotope to determine the sediment provenance and reconstruct the paleoenvironment in the inner slope of the Chukchi Rise. Core ARA09C-St03 represents overall cycles of brown and gray color with three distinct dark brown layers and two pinkish-white layers and is divided into eight sedimentary units based on the lithological feature. The core has a continuous record of the late marine isotope stage (MIS) 5 to the Holocene and in particular provides a particularly high-resolution record from the Last Glacial Maximum (LGM). Sediment is derived mainly from the adjacent East Siberian Sea and the North American region, and changes in sediment provenance are controlled by climate-dependent particle size. During the glacial/stadial periods, sediments in Units 3, 5, and 8 were supplied by the East Siberian Sea via meltwater-derived suspension. The major ice-rafted debris (IRD) events in Units 2, 4, and 7, characterized by abundant dolomite and K/C ratio, were sourced from North America. The North America-derived materials reflect the initiation and disintegration of the Laurentide Ice Sheet and icebergs transported them across the open Arctic Ocean. The differences in provenance within these periods may be related to the scale of the Laurentide Ice Sheet. Interglacial sediments, including those from Units 1 and 6, are of mixed origin from Eurasia and the Canadian Archipelago and may have been transported by oceanic current and seasonal sea ice. These periods are likely associated with the negative Arctic Oscillation (AO) intensifying the Beaufort Gyre.
Word Categorization of Vowel Durational Changes in Speech-Modulated Bone-Conducted Ultrasound
Authors: Okayasu Tadao , Nishimura Tadashi , Yamashita Akinori , Nagatani Yoshiki , Inoue Takashi , Uratani Yuka , Yamanaka Toshiaki , Hosoi Hiroshi , Kitahara Tadashi
Published: July 2021

Ultrasound can deliver speech information when it is amplitude-modulated with speech and presented via bone conduction. This speech-modulated bone-conducted ultrasound (SM-BCU) can also transmit prosodic information. However, there is insufficient research on the recognition of vowel duration in SM-BCU. The aim of this study was to investigate the categorization of vowel durational changes in SM-BCU using a behavioral test. Eight Japanese-speaking participants with normal hearing participated in a forced-choice behavioral task to discriminate between “hato” (pigeon) and “haato” (heart). Speech signal stimuli were presented in seven duration grades from 220 ms to 340 ms. The threshold at which 50% of responses were “haato” was calculated and compared for air-conducted audible sound (ACAS) and SM-BCU. The boundary width was also evaluated. Although the SM-BCU threshold (mean: 274.6 ms) was significantly longer than the ACAS threshold (mean: 269.6 ms), there were no differences in boundary width. These results suggest that SM-BCU can deliver prosodic information about vowel duration with a similar difference limen to that of ACAS in normal hearing.
FLAME: A Web Tool for Functional and Literature Enrichment Analysis of Multiple Gene Lists
Authors: Thanati Foteini , Karatzas Evangelos , Baltoumas Fotis A. , Stravopodis Dimitrios J. , Eliopoulos Aristides G. , Pavlopoulos Georgios A.
Published: July 2021

Functional enrichment is a widely used method for interpreting experimental results by identifying classes of proteins/genes associated with certain biological functions, pathways, diseases, or phenotypes. Despite the variety of existing tools, most of them can process a single list per time, thus making a more combinatorial analysis more complicated and prone to errors. In this article, we present FLAME, a web tool for combining multiple lists prior to enrichment analysis. Users can upload several lists and use interactive UpSet plots, as an alternative to Venn diagrams, to handle unions or intersections among the given input files. Functional and literature enrichment, along with gene conversions, are offered by g:Profiler and aGOtool applications for 197 organisms. FLAME can analyze genes/proteins for related articles, Gene Ontologies, pathways, annotations, regulatory motifs, domains, diseases, and phenotypes, and can also generate protein–protein interactions derived from STRING. We have validated FLAME by interrogating gene expression data associated with the sensitivity of the distal part of the large intestine to experimental colitis-propelled colon cancer. FLAME comes with an interactive user-friendly interface for easy list manipulation and exploration, while results can be visualized as interactive and parameterizable heatmaps, barcharts, Manhattan plots, networks, and tables.
Familial Hypercholesterolemia: Do HDL Play a Role?
Authors: Pedro-Botet Juan , Climent Elisenda , Benaiges David
Published: July 2021

Cardiovascular disease (CVD) in heterozygous familial hypercholesterolemia (HeFH), the most frequent monogenic disorder of human metabolism, is largely driven by low-density lipoprotein (LDL) cholesterol concentrations. Since the CVD rate differs considerably in this population, beyond the lifetime LDL cholesterol vascular accumulation, other classical risk factors are involved in the high cardiovascular risk of HeFH. Among other lipoprotein disturbances, alterations in the phenotype and functionality of high-density lipoproteins (HDL) have been described in HeFH patients, contributing to the presence and severity of CVD. In fact, HDL are the first defensive barrier against the burden of high LDL cholesterol levels owing to their contribution to reverse cholesterol transport as well as their antioxidant and anti-inflammatory properties, among others. In this context, the present narrative review aimed to focus on quantitative and qualitative abnormalities in HDL particles in HeFH, encompassing metabolic, genetic and epigenetic aspects.
Animal Models of Autosomal Recessive Parkinsonism
Authors: Bastioli Guendalina , Regoni Maria , Cazzaniga Federico , De Luca Chiara Maria Giulia , Bistaffa Edoardo , Zanetti Letizia , Moda Fabio , Valtorta Flavia , Sassone Jenny
Published: July 2021

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder. The neuropathological hallmark of the disease is the loss of dopamine neurons of the substantia nigra pars compacta. The clinical manifestations of PD are bradykinesia, rigidity, resting tremors and postural instability. PD patients often display non-motor symptoms such as depression, anxiety, weakness, sleep disturbances and cognitive disorders. Although, in 90% of cases, PD has a sporadic onset of unknown etiology, highly penetrant rare genetic mutations in many genes have been linked with typical familial PD. Understanding the mechanisms behind the DA neuron death in these Mendelian forms may help to illuminate the pathogenesis of DA neuron degeneration in the more common forms of PD. A key step in the identification of the molecular pathways underlying DA neuron death, and in the development of therapeutic strategies, is the creation and characterization of animal models that faithfully recapitulate the human disease. In this review, we outline the current status of PD modeling using mouse, rat and non-mammalian models, focusing on animal models for autosomal recessive PD.
Thermosensory Transient Receptor Potential Ion Channels and Asthma
Authors: Kytikova Oxana Yu. , Novgorodtseva Tatyana P. , Denisenko Yulia K. , Naumov Denis E. , Gvozdenko Tatyana A. , Perelman Juliy M.
Published: July 2021

Asthma is a widespread chronic disease of the bronchopulmonary system with a heterogeneous course due to the complex etiopathogenesis. Natural-climatic and anthropogenic factors play an important role in the development and progression of this pathology. The reception of physical and chemical environmental stimuli and the regulation of body temperature are mediated by thermosensory channels, members of a subfamily of transient receptor potential (TRP) ion channels. It has been found that genes encoding vanilloid, ankyrin, and melastatin TRP channels are involved in the development of some asthma phenotypes and in the formation of exacerbations of this pathology. The review summarizes modern views on the role of high and low temperatures in airway inflammation in asthma. The participation of thermosensory TRP channels (vanilloid, ankyrin, and melastatin TRP channels) in the reaction to high and low temperatures and air humidity as well as in the formation of bronchial hyperreactivity and respiratory symptoms accompanying asthma is described. The genetic aspects of the functioning of thermosensory TRP channels are discussed. It is shown that new methods of treatment of asthma exacerbations caused by the influence of temperature and humidity should be based on the regulation of channel activity.
Hexapod Assassins’ Potion: Venom Composition and Bioactivity from the Eurasian Assassin Bug Rhynocoris iracundus
Authors: Rügen Nicolai , Jenkins Timothy P. , Wielsch Natalie , Vogel Heiko , Hempel Benjamin-Florian , Süssmuth Roderich D. , Ainsworth Stuart , Cabezas-Cruz Alejandro , Vilcinskas Andreas , Tonk Miray
Published: July 2021

Assassin bug venoms are potent and exert diverse biological functions, making them potential biomedical goldmines. Besides feeding functions on arthropods, assassin bugs also use their venom for defense purposes causing localized and systemic reactions in vertebrates. However, assassin bug venoms remain poorly characterized. We collected the venom from the assassin bug Rhynocoris iracundus and investigated its composition and bioactivity in vitro and in vivo. It caused lysis of murine neuroblastoma, hepatoma cells, and healthy murine myoblasts. We demonstrated, for the first time, that assassin bug venom induces neurolysis and suggest that it counteracts paralysis locally via the destruction of neural networks, contributing to tissue digestion. Furthermore, the venom caused paralysis and melanization of Galleria mellonella larvae and pupae, whilst also possessing specific antibacterial activity against Escherichia coli, but not Listeria grayi and Pseudomonas aeruginosa. A combinatorial proteo-transcriptomic approach was performed to identify potential toxins responsible for the observed effects. We identified neurotoxic Ptu1, an inhibitory cystin knot (ICK) toxin homologous to ω-conotoxins from cone snails, cytolytic redulysins homologous to trialysins from hematophagous kissing bugs, and pore-forming hemolysins. Additionally, chitinases and kininogens were found and may be responsible for insecticidal and cytolytic activities. We demonstrate the multifunctionality and complexity of assassin bug venom, which renders its molecular components interesting for potential biomedical applications.
The PATHFINDER Study: Assessment of the Implementation of an Investigational Multi-Cancer Early Detection Test into Clinical Practice
Authors: Nadauld Lincoln D. , McDonnell Charles H. , Beer Tomasz M. , Liu Minetta C. , Klein Eric A. , Hudnut Andrew , Whittington Richard A. , Taylor Bruce , Oxnard Geoffrey R. , Lipson Jafi , Lopatin Margarita , Shaknovich Rita , Chung Karen C. , Fung Eric T. , Schrag Deborah , Marinac Catherine R.
Published: July 2021

To examine the extent of the evaluation required to achieve diagnostic resolution and the test performance characteristics of a targeted methylation cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test, ~6200 participants ≥50 years with (cohort A) or without (cohort B) ≥1 of 3 additional specific cancer risk factors will be enrolled in PATHFINDER (NCT04241796), a prospective, longitudinal, interventional, multi-center study. Plasma cfDNA from blood samples will be analyzed to detect abnormally methylated DNA associated with cancer (i.e., cancer “signal”) and a cancer signal origin (i.e., tissue of origin). Participants with a “signal detected” will undergo further diagnostic evaluation per guiding physician discretion; those with a “signal not detected” will be advised to continue guideline-recommended screening. The primary objective will be to assess the number and types of subsequent diagnostic tests needed for diagnostic resolution. Based on microsimulations (using estimates of cancer incidence and dwell times) of the typical risk profiles of anticipated participants, the median (95% CI) number of participants with a “signal detected” result is expected to be 106 (87–128). Subsequent diagnostic evaluation is expected to detect 52 (39–67) cancers. The positive predictive value of the MCED test is expected to be 49% (39–58%). PATHFINDER will evaluate the integration of a cfDNA-based MCED test into existing clinical cancer diagnostic pathways. The study design of PATHFINDER is described here.
Early Imaging and Molecular Changes with Neoadjuvant Bevacizumab in Stage II/III Breast Cancer
Authors: López-Vega José Manuel , Álvarez Isabel , Antón Antonio , Illarramendi José Juan , Llombart Antonio , Boni Valentina , García-Velloso María José , Martí-Climent Josep María , Pina Luis , García-Foncillas Jesús
Published: July 2021

This prospective, phase II study evaluated novel biomarkers as predictors of response to bevacizumab in patients with breast cancer (BC), using serial imaging methods and gene expression analysis. Patients with primary stage II/III BC received bevacizumab 15 mg/kg (cycle 1; C1), then four cycles of neoadjuvant docetaxel doxorubicin, and bevacizumab every 3 weeks (C2–C5). Tumour proliferation and hypoxic status were evaluated using 18F-fluoro-3′-deoxy-3′-L-fluorothymidine (FLT)- and 18F-fluoromisonidazole (FMISO)-positron emission tomography (PET) at baseline, and during C1 and C5. Pre- and post-bevacizumab vascular changes were evaluated using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Molecular biomarkers were assessed using microarray analysis. A total of 70 patients were assessed for treatment efficacy. Significant decreases from baseline in tumour proliferation (FLT-PET), vascularity, and perfusion (DCE-MRI) were observed during C1 (p ≤ 0.001), independent of tumour subtype. Bevacizumab treatment did not affect hypoxic tumour status (FMISO-PET). Significant changes in the expression of 28 genes were observed after C1. Changes in vascular endothelial growth factor receptor (VEGFR)-2p levels were observed in 65 patients, with a > 20% decrease in VEGFR-2p observed in 13/65. Serial imaging techniques and molecular gene profiling identified several potentially predictive biomarkers that may predict response to neoadjuvant bevacizumab therapy in BC patients.
The Prostate Cancer Therapy Enzalutamide Compared with Abiraterone Acetate/Prednisone Impacts Motivation for Exploration, Spatial Learning and Alters Dopaminergic Transmission in Aged Castrated Mice
Authors: Nicola Celeste , Dubois Martine , Campart Cynthia , Al Sagheer Tareq , Desrues Laurence , Schapman Damien , Galas Ludovic , Lange Marie , Joly Florence , Castel Hélène
Published: July 2021

Cognitive side effects after cancer treatment threatening quality of life (QoL) constitute a major challenge in oncology. Abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) are examples of next-generation therapy (NGT) administered to metastatic castration-resistant prostate cancer (mCRPC) patients. NGT significantly improved mCRPC overall survival but neurological side effects such as fatigue and cognitive impairment were reported. We developed a behavioral 17 months-aged and castrated mouse model receiving per os AAP or ENZ for 5 days per week for six consecutive weeks. ENZ exposure reduced spontaneous activity and exploratory behavior associated with a decreased tyrosine hydroxylase (TH)-dopaminergic activity in the substantia nigra pars compacta and the ventral tegmental area. A decrease in TH+-DA afferent fibers and Phospho-DARPP32-related dopaminergic neuronal activities in the striatum and the ventral hippocampus highlighted ENZ-induced dopaminergic regulation within the nigrostriatal and mesolimbocortical pathways. ENZ and AAP treatments did not substantially modify spatial learning and memory performances, but ENZ led to a thygmotaxis behavior impacting the cognitive score, and reduced c-fos-related activity of NeuN+-neurons in the dorsal hippocampus. The consequences of the mCRPC treatment ENZ on aged castrated mouse motivation to exploration and cognition should make reconsider management strategy of elderly prostate cancer patients.
Immunotherapy Strategies for Gastrointestinal Stromal Tumor
Authors: Arshad Junaid , Costa Philippos A. , Barreto-Coelho Priscila , Valdes Brianna Nicole , Trent Jonathan C.
Published: July 2021

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal soft tissue sarcoma of the gastrointestinal tract. The management of locally advanced or metastatic unresectable GIST involves detecting KIT, PDGFR, or other molecular alterations targeted by imatinib and other tyrosine kinase inhibitors. The role of immunotherapy in soft tissue sarcomas is growing fast due to multiple clinical and pre-clinical studies with no current standard of care. The potential therapies include cytokine-based therapy, immune checkpoint inhibitors, anti-KIT monoclonal antibodies, bi-specific monoclonal antibodies, and cell-based therapies. Here we provide a comprehensive review of the immunotherapeutic strategies for GIST.
Genomic Risk Prediction for Breast Cancer in Older Women
Authors: Lacaze Paul , Bakshi Andrew , Riaz Moeen , Orchard Suzanne G. , Tiller Jane , Neumann Johannes T. , Carr Prudence R. , Joshi Amit D. , Cao Yin , Warner Erica T. , Manning Alisa , Nguyen-Dumont Tú , Southey Melissa C. , Milne Roger L. , Ford Leslie , Sebra Robert , Schadt Eric , Gately Lucy , Gibbs Peter , Thompson Bryony A. , Macrae Finlay A. , James Paul , Winship Ingrid , McLean Catriona , Zalcberg John R. , Woods Robyn L. , Chan Andrew T. , Murray Anne M. , McNeil John J.
Published: July 2021

Genomic risk prediction models for breast cancer (BC) have been predominantly developed with data from women aged 40–69 years. Prospective studies of older women aged ≥70 years have been limited. We assessed the effect of a 313-variant polygenic risk score (PRS) for BC in 6339 older women aged ≥70 years (mean age 75 years) enrolled into the ASPREE trial, a randomized double-blind placebo-controlled clinical trial investigating the effect of daily 100 mg aspirin on disability-free survival. We evaluated incident BC diagnoses over a median follow-up time of 4.7 years. A multivariable Cox regression model including conventional BC risk factors was applied to prospective data, and re-evaluated after adding the PRS. We also assessed the association of rare pathogenic variants (PVs) in BC susceptibility genes (BRCA1/BRCA2/PALB2/CHEK2/ATM). The PRS, as a continuous variable, was an independent predictor of incident BC (hazard ratio (HR) per standard deviation (SD) = 1.4, 95% confidence interval (CI) 1.3–1.6) and hormone receptor (ER/PR)-positive disease (HR = 1.5 (CI 1.2–1.9)). Women in the top quintile of the PRS distribution had over two-fold higher risk of BC than women in the lowest quintile (HR = 2.2 (CI 1.2–3.9)). The concordance index of the model without the PRS was 0.62 (95% CI 0.56–0.68), which improved after addition of the PRS to 0.65 (95% CI 0.59–0.71). Among 41 (0.6%) carriers of PVs in BC susceptibility genes, we observed no incident BC diagnoses. Our study demonstrates that a PRS predicts incident BC risk in women aged 70 years and older, suggesting potential clinical utility extends to this older age group.
IL-15 Enhances the Persistence and Function of BCMA-Targeting CAR-T Cells Compared to IL-2 or IL-15/IL-7 by Limiting CAR-T Cell Dysfunction and Differentiation
Authors: Battram Anthony M. , Bachiller Mireia , Lopez Victor , Fernández de Larrea Carlos , Urbano-Ispizua Alvaro , Martín-Antonio Beatriz
Published: July 2021

Chimeric antigen receptor (CAR)-T cell immunotherapy has revolutionized the treatment of B-lymphoid malignancies. For multiple myeloma (MM), B-cell maturation antigen (BCMA)-targeted CAR-T cells have achieved outstanding complete response rates, but unfortunately, patients often relapse within a year of receiving the therapy. Increased persistence and reduced dysfunction are crucial features that enhance the durability of CAR-T cell responses. One of the factors that influence CAR-T cell in vivo longevity and loss of function, but which has not yet been extensively studied for BCMA-directed CAR-T cells, are the cytokines used during their production. We here compared the impact of IL-2, IL-15 and a combination of IL-15/IL-7 on the phenotype and function of ARI2h, an academic BCMA-directed CAR-T cell that is currently being administered to MM patients. For this study, flow cytometry, in vitro cytotoxicity assays and analysis of cytokine release were performed. In addition, ARI2h cells expanded with IL-2, IL-15, or IL-15/IL-7 were injected into MM tumor-bearing mice to assess their in vivo efficacy. We demonstrated that each of the cytokine conditions was suitable for the expansion of ARI2h cells, with clear in vitro activity. Strikingly, however, IL-15-produced ARI2h cells had improved in vivo efficacy and persistence. When explored further, it was found that IL-15 drove a less-differentiated ARI2h phenotype, ameliorated parameters related to CAR-T cell dysfunction, and lowered the release of cytokines potentially involved in cytokine release syndrome and MM progression. Moreover, we observed that IL-15 was less potent in inducing T cell senescence and DNA damage accumulation, both of which may contribute to an unfavorable CAR-T cell phenotype. These findings show the superiority of IL-15 to IL-2 and IL-15/IL-7 in the quality of anti-BCMA CAR-T cells, particularly their efficacy and persistence, and as such, could improve the duration of responses if applied to the clinical production of CAR-T cells for patients.
Epoxidation of Terpenes
Authors: Mahamat Ahmat Yacoub , Madadi Sara , Charbonneau Luc , Kaliaguine Serge
Published: July 2021

Terpene epoxides are considered as potential primary intermediates in the synthesis of numerous green polymers including epoxy resins, polycarbonates, nonisocyanate polyurethanes and even some polyamides. In this chapter we describe recent efforts from our group to develop catalytic and noncatalytic processes for terpene epoxidation using a variety of oxidizing agents and process intensification methods. Most experimental tests deal with limonene epoxidation with applicability to some other terpenes also demonstrated.
Light-Induced Charge Accumulation in PTCDI/Pentacene/Ag(111) Heterojunctions
Authors: Costantini Roberto , Cossaro Albano , Morgante Alberto , Dell’Angela Martina
Published: July 2021

The incorporation of singlet fission (SF) chromophores in solar cells is expected to bring significant increases in the power conversion efficiency thanks to multiexciton generation. However, efficient charge generation in the device is determined by the energy level alignment (ELA) between the active materials, which should favor exciton transport and separation under illumination. By combining ultraviolet photoemission spectroscopy and optical differential reflectance measurements, we determine the ELA in a prototypical SF heterojunction between pentacene (Pc) and perylene-tetracarboxylic-diimide (PTCDI) grown on Ag(111). Time-resolved X-ray photoelectron spectroscopy on such a system reveals light-induced modifications of the ELA; by measuring the transient shift of the core level photoemission lines we observe an accumulation of long-lived holes in the PTCDI within the first hundred picoseconds after the optical pump.
Randomized Trial of Oxygen Saturation Targets during and after Resuscitation and Reversal of Ductal Flow in an Ovine Model of Meconium Aspiration and Pulmonary Hypertension
Authors: Lesneski Amy L. , Vali Payam , Hardie Morgan E. , Lakshminrusimha Satyan , Sankaran Deepika
Published: July 2021

Neonatal resuscitation (NRP) guidelines suggest targeting 85–95% preductal SpO2 by 10 min after birth. Optimal oxygen saturation (SpO2) targets during resuscitation and in the post-resuscitation management of neonatal meconium aspiration syndrome (MAS) with persistent pulmonary hypertension (PPHN) remains uncertain. Our objective was to compare the time to reversal of ductal flow from fetal pattern (right-to-left), to left-to-right, and to evaluate pulmonary (QPA), carotid (QCA)and ductal (QDA) blood flows between standard (85–94%) and high (95–99%) SpO2 targets during and after resuscitation. Twelve lambs asphyxiated by endotracheal meconium instillation and cord occlusion to induce MAS and PPHN were resuscitated per NRP guidelines and were randomized to either standard (85–94%) or high (95–99%) SpO2 targets. Out of twelve lambs with MAS and PPHN, six each were randomized to standard and high SpO2 targets. Median [interquartile range] time to change in direction of blood flow across the ductus arteriosus from right-to-left, to left-to-right was significantly shorter with high SpO2 target (7.4 (4.4–10.8) min) compared to standard SpO2 target (31.5 (21–66.2) min, p = 0.03). QPA was significantly higher during the first 10 min after birth with higher SpO2 target. At 60 min after birth, the QPA, QCA and QDA were not different between the groups. To conclude, targeting SpO2 of 95–99% during and after resuscitation may hasten reversal of ductal flow in lambs with MAS and PPHN and transiently increase QPA but no differences were observed at 60 min. Clinical studies comparing low and high SpO2 targets assessing hemodynamics and neurodevelopmental outcomes are warranted.
Associations between Perceived Child-Parent Relationships and School Engagement among 9–11 Aged Children
Authors: Markkula Pirita , Rantanen Anja , Koivisto Anna-Maija , Joronen Katja
Published: July 2021

School engagement has been shown to protect students from dropping out of education, depression and school burnout. The aim of this Finnish study was to explore the association between child-parent relationships and how much 99,686 children aged 9–11 years liked school. The data were based on the 2019 School Health Promotion Study, conducted by the Finnish Institute for Health and Welfare. This asked children whether they liked school or not and about their child-parent relationships. Univariate and multivariate analyses were used to examine the data separately for boys and girls and the results are presented as odds ratios (OR) and 95% confidence intervals (CI). According to the results, girls showed more school engagement than boys (81.9% versus 74.0%), and it was more common in children who felt that their parents communicated with them in a supportive way. This association was slightly stronger for girls than boys (OR 2.46 95% CI 2.33–2.59 versus OR 2.10 95% CI 2.02–2.20). It is important that child-parent relationships and communication are considered during school health examinations, so that children who have lower support at home can be identified.