bluuebunny/crossref_metadata_2025 huggingface dataset:
Deposition of Titanium Dioxide Coating by the Cold-Spray Process on Annealed Stainless Steel Substrate
Authors: Omar Noor irinah , Selvami Santirraprahkash , Kaisho Makoto , Yamada Motohiro , Yasui Toshiaki , Fukumoto Masahiro
Published: October 2020

The surface of most metals is covered with thin native oxide films. It has generally been believed that to achieve bonding, the oxide covering the surface of metallic particles or metal substrates must be broken and removed by adiabatic shear instability (ASI), whether induced at the particle–substrate interface or at the particle–particle interface. The aim of the present research is to investigate the correlation between the remaining oxide amorphous layer and substrate-deformation with the adhesion strength of cold-sprayed TiO2 coatings towards the bonding mechanism involved. Relevant experiments were executed using stainless steel (SUS 304), subjected to various annealing temperatures and cold-sprayed with TiO2 powder. The results indicate an increasing trend of coating adhesion strength with increasing annealed substrate temperature. The influence of substrate plastic deformation and atomic intermixing at the remaining amorphous oxide layer is discussed as the factors contributing to the increasing adhesion strength of cold-sprayed TiO2 coatings.
In Vivo Assessment of Bone Enhancement in the Case of 3D-Printed Implants Functionalized with Lithium-Doped Biological-Derived Hydroxyapatite Coatings: A Preliminary Study on Rabbits
Authors: Duta Liviu , Neamtu Johny , Melinte Razvan P. , Zureigat Oana A. , Popescu-Pelin Gianina , Chioibasu Diana , Oktar Faik N. , Popescu Andrei C.
Published: October 2020

We report on biological-derived hydroxyapatite (HA, of animal bone origin) doped with lithium carbonate (Li-C) and phosphate (Li-P) coatings synthesized by pulsed laser deposition (PLD) onto Ti6Al4V implants, fabricated by the additive manufacturing (AM) technique. After being previously validated by in vitro cytotoxicity tests, the Li-C and Li-P coatings synthesized onto 3D Ti implants were preliminarily investigated in vivo, by insertion into rabbits’ femoral condyles. The in vivo experimental model for testing the extraction force of 3D metallic implants was used for this study. After four and nine weeks of implantation, all structures were mechanically removed from bones, by tensile pull-out tests, and coatings’ surfaces were investigated by scanning electron microscopy. The inferred values of the extraction force corresponding to functionalized 3D implants were compared with controls. The obtained results demonstrated significant and highly significant improvement of functionalized implants’ attachment to bone (p-values ≤0.05 and ≤0.00001), with respect to controls. The correct placement and a good integration of all 3D-printed Ti implants into the surrounding bone was demonstrated by performing computed tomography scans. This is the first report in the dedicated literature on the in vivo assessment of Li-C and Li-P coatings synthesized by PLD onto Ti implants fabricated by the AM technique. Their improved mechanical characteristics, along with a low fabrication cost from natural, sustainable resources, should recommend lithium-doped biological-derived materials as viable substitutes of synthetic HA for the fabrication of a new generation of metallic implant coatings.
Magnetic Diagram of the High-Pressure Stabilized Multiferroic Perovskites of the BiFe1-yScyO3 Series
Authors: Fertman Elena L. , Fedorchenko Alexey V. , Čižmár Erik , Vorobiov Serhii , Feher Alexander , Radyush Yury V. , Pushkarev Anatoli V. , Olekhnovich Nikolai M. , Stanulis Andrius , Barron Andrew R. , Khalyavin Dmitry D. , Salak Andrei N.
Published: October 2020

Magnetic properties of the high-pressure stabilized perovskite BiFe1-yScyO3 phases (0.1 ≤ y ≤ 0.9) have been studied by means of magnetization measurements and neutron diffraction. The metastable perovskites of this series undergo irreversible polymorphic transformations upon annealing, the phenomenon referred to as conversion polymorphism. It has been found that the solid solutions with y ≥ 0.70 exhibit no long-range magnetic ordering regardless of their polymorph modification, while those with y ≤ 0.60 are all antiferromagnets. Depending on the scandium content, temperature and structural distortions, three types of the antiferromagnetic orderings, involving collinear, canted and cycloidal spin arrangements, have been revealed in the phases obtained via conversion polymorphism and the corresponding magnetic phase diagram has been suggested.
Rehabilitation Improves Mitochondrial Energetics in Progressive Multiple Sclerosis: The Significant Role of Robot-Assisted Gait Training and of the Personalized Intensity
Authors: Manfredini Fabio , Straudi Sofia , Lamberti Nicola , Patergnani Simone , Tisato Veronica , Secchiero Paola , Bernardi Francesco , Ziliotto Nicole , Marchetti Giovanna , Basaglia Nino , Bonora Massimo , Pinton Paolo
Published: October 2020

Abnormal levels of pyruvate and lactate were reported in multiple sclerosis (MS). We studied the response of markers of mitochondrial function to rehabilitation in relation to type, intensity and endurance performance in severely disabled MS patients. Forty-six progressive MS patients were randomized to receive 12 walking sessions of robot-assisted gait training (RAGT, n = 23) or conventional overground therapy (CT, n = 23). Ten healthy subjects were also studied. Blood samples were collected to determine lactate, pyruvate, and glutathione levels and lactate/pyruvate ratio pre–post rehabilitation. In vivo muscle metabolism and endurance walking capacity were assessed by resting muscle oxygen consumption (rmVO2) using near-infrared spectroscopy and by six-minute walking distance (6MWD), respectively. The levels of mitochondrial biomarkers and rmVO2, altered at baseline with respect to healthy subjects, improved after rehabilitation in the whole population. In the two groups, an enhanced response was observed after RAGT compared to CT for lactate (p = 0.012), glutathione (<0.001), lactate/pyruvate ratio (p = 0.08) and rmVO2 (p = 0.07). Metabolic biomarkers and 6MWD improvements were exclusively correlated with a training speed markedly below individual gait speed. In severely disabled MS patients, rehabilitation rebalanced altered serum metabolic and muscle parameters, with RAGT being more effective than CT. A determinable slow training speed was associated with better metabolic and functional recovery. Trial Registration: ClinicalTrials.gov NCT02421731.
Transfer Entropy Analysis of Interactions between Bats Using Position and Echolocation Data
Authors: Shaffer Irena , Abaid Nicole
Published: October 2020

Many animal species, including many species of bats, exhibit collective behavior where groups of individuals coordinate their motion. Bats are unique among these animals in that they use the active sensing mechanism of echolocation as their primary means of navigation. Due to their use of echolocation in large groups, bats run the risk of signal interference from sonar jamming. However, several species of bats have developed strategies to prevent interference, which may lead to different behavior when flying with conspecifics than when flying alone. This study seeks to explore the role of this acoustic sensing on the behavior of bat pairs flying together. Field data from a maternity colony of gray bats (Myotis grisescens) were collected using an array of cameras and microphones. These data were analyzed using the information theoretic measure of transfer entropy in order to quantify the interaction between pairs of bats and to determine the effect echolocation calls have on this interaction. This study expands on previous work that only computed information theoretic measures on the 3D position of bats without echolocation calls or that looked at the echolocation calls without using information theoretic analyses. Results show that there is evidence of information transfer between bats flying in pairs when time series for the speed of the bats and their turning behavior are used in the analysis. Unidirectional information transfer was found in some subsets of the data which could be evidence of a leader–follower interaction.
Innovativeness of Industrial Processing Enterprises and Conjunctural Movement
Authors: Jakimowicz Aleksander , Rzeczkowski Daniel
Published: October 2020

Singulation of components determining the innovative activity of enterprises is a complex issue as it depends on both microeconomic and macroeconomic factors. The purpose of this article is to present the results of research on the impact of the mutual interactions between ownership and the size of companies on the achievement of the objectives of innovative activity by Polish industrial processing enterprises in changing cyclical conditions. The importance of innovation barriers was also assessed. Empirical data came from three periods that covered different phases of the business cycle: prosperity 2004–2006, global financial crisis 2008–2010, and recovery 2012–2014. The research used a cybernetic approach based on feedback loops presenting interactions between variables. In addition, two statistical methods were used: the Pearson’s χ2 independence test and correspondence analysis. The following discoveries were made during the research: (1) consideration of the combined impact of ownership and the size of companies on their innovation activities makes it possible to study phenomena that may be overlooked if the impact of these factors is considered separately; (2) public enterprises achieve significantly worse results in terms of innovation than companies from other ownership sectors; (3) the Red Queen effect, which assumes that the best innovative enterprises exert selection pressure on all other companies, applies to industrial processing companies, and in particular public enterprises; (4) the industrial processing section is more sensitive to secular trends than to cyclical fluctuations; (5) confirmation of occurrence of the Polish Green Island effect, which assumes that companies achieve good results in terms of innovation, irrespective of the phases of the business cycle; and (6) statistical evidence is provided that the global financial crisis may be associated with the turn of the Fifth and Sixth Kondratieff waves. Most likely, the role of the communication channel between the world economy and the Polish manufacturing section is fulfilled by foreign ownership, whose percentage of share capital of this section is estimated at 50%.
Requirements for Validation of Dynamic Wind Turbine Models: An International Grid Code Review
Authors: Villena-Ruiz Raquel , Honrubia-Escribano Andrés , Jiménez-Buendía Francisco , Molina-García Ángel , Gómez-Lázaro Emilio
Published: October 2020

Wind power is positioned as one of the fastest-growing energy sources today, while also being a mature technology with a strong capacity for creating employment and guaranteeing environmental sustainability. However, the stochastic nature of wind may affect the integration of power plants into power systems and the availability of generation capacity. In this sense, as in the case of conventional power plants, wind power installations should be able to help maintain power system stability and reliability. To help achieve this objective, a significant number of countries have developed so-called grid interconnection agreements. These are designed to define the technical and behavioral requirements that wind power installations, as well as other power plants, must comply with when seeking connection to the national network. These documents also detail the tasks that should be conducted to certify such installations, so these can be commercially exploited. These certification processes allow countries to assess wind turbine and wind power plant simulation models. These models can then be used to estimate and simulate wind power performance under a variety of scenarios. Within this framework, and with a particular focus on the new Spanish grid code, the present paper addresses the validation process of dynamic wind turbine models followed in three countries—Spain, Germany and South Africa. In these three countries, and as a novel option, it has been proposed that these models form part of the commissioning and certification processes of wind power plants.
Vertical and Horizontal Transmission of ESBL Plasmid from Escherichia coli O104:H4
Authors: Daniel Sandra , Goldlust Kelly , Quebre Valentin , Shen Minjia , Lesterlin Christian , Bouet Jean-Yves , Yamaichi Yoshiharu
Published: October 2020

Multidrug resistance (MDR) often results from the acquisition of mobile genetic elements (MGEs) that encode MDR gene(s), such as conjugative plasmids. The spread of MDR plasmids is founded on their ability of horizontal transference, as well as their faithful inheritance in progeny cells. Here, we investigated the genetic factors involved in the prevalence of the IncI conjugative plasmid pESBL, which was isolated from the Escherichia coli O104:H4 outbreak strain in Germany in 2011. Using transposon-insertion sequencing, we identified the pESBL partitioning locus (par). Genetic, biochemical and microscopic approaches allowed pESBL to be characterized as a new member of the Type Ib partitioning system. Inactivation of par caused mis-segregation of pESBL followed by post-segregational killing (PSK), resulting in a great fitness disadvantage but apparent plasmid stability in the population of viable cells. We constructed a variety of pESBL derivatives with different combinations of mutations in par, conjugational transfer (oriT) and pnd toxin-antitoxin (TA) genes. Only the triple mutant exhibited plasmid-free cells in viable cell populations. Time-lapse tracking of plasmid dynamics in microfluidics indicated that inactivation of pnd improved the survival of plasmid-free cells and allowed oriT-dependent re-acquisition of the plasmid. Altogether, the three factors—active partitioning, toxin-antitoxin and conjugational transfer—are all involved in the prevalence of pESBL in the E. coli population.
Developmental scRNAseq Trajectories in Gene- and Cell-State Space—The Flatworm Example
Authors: Schmidt Maria , Loeffler-Wirth Henry , Binder Hans
Published: October 2020

Single-cell RNA sequencing has become a standard technique to characterize tissue development. Hereby, cross-sectional snapshots of the diversity of cell transcriptomes were transformed into (pseudo-) longitudinal trajectories of cell differentiation using computational methods, which are based on similarity measures distinguishing cell phenotypes. Cell development is driven by alterations of transcriptional programs e.g., by differentiation from stem cells into various tissues or by adapting to micro-environmental requirements. We here complement developmental trajectories in cell-state space by trajectories in gene-state space to more clearly address this latter aspect. Such trajectories can be generated using self-organizing maps machine learning. The method transforms multidimensional gene expression patterns into two dimensional data landscapes, which resemble the metaphoric Waddington epigenetic landscape. Trajectories in this landscape visualize transcriptional programs passed by cells along their developmental paths from stem cells to differentiated tissues. In addition, we generated developmental “vector fields” using RNA-velocities to forecast changes of RNA abundance in the expression landscapes. We applied the method to tissue development of planarian as an illustrative example. Gene-state space trajectories complement our data portrayal approach by (pseudo-)temporal information about changing transcriptional programs of the cells. Future applications can be seen in the fields of tissue and cell differentiation, ageing and tumor progression and also, using other data types such as genome, methylome, and also clinical and epidemiological phenotype data.
Socio-Ecological Predictors of Frequent Bike Share Trips: Do Purposes Matter?
Authors: Chen Li-Ting , Hsu Ya-Wen
Published: October 2020

Using bike share could increase physical activity and improve health. This study used the social-ecological model to identify predictors of frequent bike share trips for different purposes. Participants residing in the U.S. were recruited via Amazon Mechanical Turk (MTurk). Self-report trip purposes were used to group participants into using bike share for commuting only (n = 260), social/entertainment only (n = 313), exercise only (n = 358), dual or triple-purpose (n = 501), and purposes other than commuting, social/entertainment, and exercise (n = 279). Results showed that at the intrapersonal level, perceived use of bike share to be helpful for increasing physical activity was a significant predictor for all groups, except for the other purpose group. Adjusting outdoor activity based on air quality was a significant predictor for the dual or triple-purpose group. At the interpersonal level, having four or more friends/family using bike share was a significant predictor for the other purpose group. At the community level, distance to the nearest bike share within acceptable range was a significant predictor for social/entertainment and dual or triple-purpose groups. The findings suggest that it is important to consider factors at multiple levels for predicting bike share usage. Moreover, health educators and policy makers should adopt different strategies for promoting bike share usage based on trip purposes.
Analysis of the Training Effect of a Nursing Undergraduate Course on the Management of Radiation-Related Health Concerns—A Single Group Experiment
Authors: Kawasaki Hiromi , Yamasaki Satoko , Kohama Natsu , Fukita Susumu , Tsunematsu Miwako , Kakehashi Masayuki
Published: October 2020

After the 2011 Fukushima Daiichi accident, demands regarding nursing staff’s management of nuclear disasters have increased. This study aimed to evaluate a basic training program to teach undergraduate nursing students on how to deal with public anxiety following a nuclear disaster. We analyzed the data of 111 third-year nursing students attending a Japanese university. We set attainment goals in three domains (cognitive, affective, psychomotor) regarding their acquisition of consultation techniques for radiation-related health concerns. We compared pre- and post-class response scores on a knowledge test and calculated word frequencies in health consultation scenarios. The pre-class mean score was 12.2 out of 27 points and the post-class mean score (directly after the course) was 21.0, a significant increase (p < 0.001). The mean level of attainment in each of the three domains increased significantly from pre-test to post-test (p < 0.001). The variety and number of words in the health consultations also increased. Students attained the program goals for radiation-related health concerns in all domains. During disasters, there is a great need for nursing staff to administer physical and mental care to the public. This program was evaluated to be one wherein nursing staff can acquire fundamental knowledge about radiation in a short time.
A Brief History of Adherons: The Discovery of Brain Exosomes
Authors: Schubert David
Published: October 2020

Although exosomes were first described in reticulocytes in 1983, many people do not realize that similar vesicles had been studied in the context of muscle and nerve, beginning in 1980. At the time of their discovery, these vesicles were named adherons, and they were found to play an important role in both cell–substrate and cell–cell adhesion. My laboratory described several molecules that are present in adherons, including heparan sulfate proteoglycans (HSPGs) and purpurin. HSPGs have since been shown to play a variety of key roles in brain physiology. Purpurin has a number of important functions in the retina, including a role in nerve cell differentiation and regeneration. In this review, I discuss the discovery of adherons and how that led to continuing studies on their role in the brain with a particular focus on HSPGs.
DNA Methylation at Birth Predicts Intellectual Functioning and Autism Features in Children with Fragile X Syndrome
Authors: Kraan Claudine M , Baker Emma K , Arpone Marta , Bui Minh , Ling Ling , Gamage Dinusha , Bretherton Lesley , Rogers Carolyn , Field Michael J , Wotton Tiffany L , Francis David , Hunter Matt F , Cohen Jonathan , Amor David J , Godler David E
Published: October 2020

Fragile X syndrome (FXS) is a leading single-gene cause of intellectual disability (ID) with autism features. This study analysed diagnostic and prognostic utility of the Fragile X-Related Epigenetic Element 2 DNA methylation (FREE2m) assessed by Methylation Specific-Quantitative Melt Analysis and the EpiTYPER system, in retrospectively retrieved newborn blood spots (NBS) and newly created dried blood spots (DBS) from 65 children with FXS (~2–17 years). A further 168 NBS from infants from the general population were used to establish control reference ranges, in both sexes. FREE2m analysis showed sensitivity and specificity approaching 100%. In FXS males, NBS FREE2m strongly correlated with intellectual functioning and autism features, however associations were not as strong for FXS females. Fragile X mental retardation 1 gene (FMR1) mRNA levels in blood were correlated with FREE2m in both NBS and DBS, for both sexes. In females, DNAm was significantly increased at birth with a decrease in childhood. The findings support the use of FREE2m analysis in newborns for screening, diagnostic and prognostic testing in FXS.
Taming the Sentinels: Microbiome-Derived Metabolites and Polarization of T Cells
Authors: Wojciech Lukasz , Tan Kevin S. W. , Gascoigne Nicholas R. J.
Published: October 2020

A global increase in the prevalence of metabolic syndromes and digestive tract disorders, like food allergy or inflammatory bowel disease (IBD), has become a severe problem in the modern world. Recent decades have brought a growing body of evidence that links the gut microbiome’s complexity with host physiology. Hence, understanding the mechanistic aspects underlying the synergy between the host and its associated gut microbiome are among the most crucial questions. The functionally diversified adaptive immune system plays a central role in maintaining gut and systemic immune homeostasis. The character of the reciprocal interactions between immune components and host-dwelling microbes or microbial consortia determines the outcome of the organisms’ coexistence within the holobiont structure. It has become apparent that metabolic by-products of the microbiome constitute crucial multimodal transmitters within the host–microbiome interactome and, as such, contribute to immune homeostasis by fine-tuning of the adaptive arm of immune system. In this review, we will present recent insights and discoveries regarding the broad landscape of microbiome-derived metabolites, highlighting the role of these small compounds in the context of the balance between pro- and anti-inflammatory mechanisms orchestrated by the host T cell compartment.
Antioxidant Supplementation in the Treatment of Neurotoxicity Induced by Platinum-Based Chemotherapeutics—A Review
Authors: Stankovic Jelena S. Katanic , Selakovic Dragica , Mihailovic Vladimir , Rosic Gvozden
Published: October 2020

Cancer represents one of the most pernicious public health problems with a high mortality rate among patients worldwide. Chemotherapy is one of the major therapeutic approaches for the treatment of various malignancies. Platinum-based drugs (cisplatin, oxaliplatin, carboplatin, etc.) are highly effective chemotherapeutic drugs used for the treatment of several types of malignancies, but their application and dosage are limited by their toxic effects on various systems, including neurotoxicity. Simultaneously, researchers have tried to improve the survival rate and quality of life of cancer patients and decrease the toxicity of platinum-containing drugs by combining them with non-chemotherapy-based drugs, dietary supplements and/or antioxidants. Additionally, recent studies have shown that the root cause for the many side effects of platinum chemotherapeutics involves the production of reactive oxygen species (ROS) in naive cells. Therefore, suppression of ROS generation and their inactivation with antioxidants represents an appropriate approach for platinum drug-induced toxicities. The aim of this paper is to present an updated review of the protective effects of different antioxidant agents (vitamins, dietary antioxidants and supplements, medicaments, medicinal plants and their bioactive compounds) against the neurotoxicity induced by platinum-based chemotherapeutics. This review highlights the high potential of plant antioxidants as adjuvant strategies in chemotherapy with platinum drugs.
Exacerbation of Neonatal Hemolysis and Impaired Renal Iron Handling in Heme Oxygenase 1-Deficient Mice
Authors: Bednarz Aleksandra , Lipiński Paweł , Starzyński Rafał R. , Tomczyk Mateusz , Kraszewska Izabela , Herman Sylwia , Kowalski Kacper , Gruca Ewelina , Jończy Aneta , Mazgaj Rafał , Szudzik Mateusz , Rajfur Zenon , Baster Zbigniew , Józkowicz Alicja , Lenartowicz Małgorzata
Published: October 2020

In most mammals, neonatal intravascular hemolysis is a benign and moderate disorder that usually does not lead to anemia. During the neonatal period, kidneys play a key role in detoxification and recirculation of iron species released from red blood cells (RBC) and filtered out by glomeruli to the primary urine. Activity of heme oxygenase 1 (HO1), a heme-degrading enzyme localized in epithelial cells of proximal tubules, seems to be of critical importance for both processes. We show that, in HO1 knockout mouse newborns, hemolysis was prolonged despite a transient state and exacerbated, which led to temporal deterioration of RBC status. In neonates lacking HO1, functioning of renal molecular machinery responsible for iron reabsorption from the primary urine (megalin/cubilin complex) and its transfer to the blood (ferroportin) was either shifted in time or impaired, respectively. Those abnormalities resulted in iron loss from the body (excreted in urine) and in iron retention in the renal epithelium. We postulate that, as a consequence of these abnormalities, a tight systemic iron balance of HO1 knockout neonates may be temporarily affected.
Mediator Complex: A Pivotal Regulator of ABA Signaling Pathway and Abiotic Stress Response in Plants
Authors: Chong Leelyn , Guo Pengcheng , Zhu Yingfang
Published: October 2020

As an evolutionarily conserved multi-protein complex, the Mediator complex modulates the association between transcription factors and RNA polymerase II to precisely regulate gene transcription. Although numerous studies have shown the diverse functions of Mediator complex in plant development, flowering, hormone signaling, and biotic stress response, its roles in the Abscisic acid (ABA) signaling pathway and abiotic stress response remain largely unclear. It has been recognized that the phytohormone, ABA, plays a predominant role in regulating plant adaption to various abiotic stresses as ABA can trigger extensive changes in the transcriptome to help the plants respond to environmental stimuli. Over the past decade, the Mediator complex has been revealed to play key roles in not only regulating the ABA signaling transduction but also in the abiotic stress responses. In this review, we will summarize current knowledge of the Mediator complex in regulating the plants’ response to ABA as well as to the abiotic stresses of cold, drought and high salinity. We will particularly emphasize the involvement of multi-functional subunits of MED25, MED18, MED16, and CDK8 in response to ABA and environmental perturbation. Additionally, we will discuss potential research directions available for further deciphering the role of Mediator complex in regulating ABA and other abiotic stress responses.
Saliva microRNA Biomarkers of Cumulative Concussion
Authors: Hicks Steven D. , Olympia Robert P. , Onks Cayce , Kim Raymond Y. , Zhen Kevin J. , Fedorchak Gregory , DeVita Samantha , Rangnekar Aakanksha , Heller Matthew , Zwibel Hallie , Monteith Chuck , Gagnon Zofia , McLoughlin Callan D. , Randall Jason , Madeira Miguel , Campbell Thomas R. , Fengler Elise , Dretsch Michael N. , Neville Christopher , Middleton Frank A.
Published: October 2020

Recurrent concussions increase risk for persistent post-concussion symptoms, and may lead to chronic neurocognitive deficits. Little is known about the molecular pathways that contribute to persistent concussion symptoms. We hypothesized that salivary measurement of microribonucleic acids (miRNAs), a class of epitranscriptional molecules implicated in concussion pathophysiology, would provide insights about the molecular cascade resulting from recurrent concussions. This hypothesis was tested in a case-control study involving 13 former professional football athletes with a history of recurrent concussion, and 18 age/sex-matched peers. Molecules of interest were further validated in a cross-sectional study of 310 younger individuals with a history of no concussion (n = 230), a single concussion (n = 56), or recurrent concussions (n = 24). There was no difference in neurocognitive performance between the former professional athletes and their peers, or among younger individuals with varying concussion exposures. However, younger individuals without prior concussion outperformed peers with prior concussion on three balance assessments. Twenty salivary miRNAs differed (adj. p < 0.05) between former professional athletes and their peers. Two of these (miR-28-3p and miR-339-3p) demonstrated relationships (p < 0.05) with the number of prior concussions reported by younger individuals. miR-28-3p and miR-339-5p may play a role in the pathophysiologic mechanism involved in cumulative concussion effects.
A New Take on Prion Protein Dynamics in Cellular Trafficking
Authors: Alves Rodrigo Nunes , Iglesia Rebeca Piatniczka , Prado Mariana Brandão , Melo Escobar Maria Isabel , Boccacino Jacqueline Marcia , Fernandes Camila Felix de Lima , Coelho Bárbara Paranhos , Fortes Ailine Cibele , Lopes Marilene Hohmuth
Published: October 2020

The mobility of cellular prion protein (PrPC) in specific cell membrane domains and among distinct cell compartments dictates its molecular interactions and directs its cell function. PrPC works in concert with several partners to organize signaling platforms implicated in various cellular processes. The scaffold property of PrPC is able to gather a molecular repertoire to create heterogeneous membrane domains that favor endocytic events. Dynamic trafficking of PrPC through multiple pathways, in a well-orchestrated mechanism of intra and extracellular vesicular transport, defines its functional plasticity, and also assists the conversion and spreading of its infectious isoform associated with neurodegenerative diseases. In this review, we highlight how PrPC traffics across intra- and extracellular compartments and the consequences of this dynamic transport in governing cell functions and contributing to prion disease pathogenesis.
Biological and Clinical Changes in a Pediatric Series Treated with Off-Label JAK Inhibitors
Authors: Pin Alessia , Tesser Alessandra , Pastore Serena , Moressa Valentina , Valencic Erica , Arbo Anna , Maestro Alessandra , Tommasini Alberto , Taddio Andrea
Published: October 2020

Off-label use of medications is still a common practice in pediatric rheumatology. JAK inhibitors are authorized in adults in the treatment of rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. Although their use is not authorized yet in children, JAK inhibitors, based on their mechanism of action and on clinical experiences in small series, have been suggested to be useful in the treatment of pediatric interferon-mediated inflammation. Accordingly, an increased interferon score may help to identify those patients who might benefit of JAK inhibitors. We describe the clinical experience with JAK inhibitors in seven children affected with severe inflammatory conditions and we discuss the correlation between clinical features and transcriptomic data. Clinical improvements were recorded in all cases. A reduction of interferon signaling was recorded in three out of seven subjects at last follow-up, irrespectively from clinical improvements. Other signal pathways with significant differences between patients and controls included upregulation of DNA repair pathway and downregulation of extracellular collagen homeostasis. Two patients developed drug-related adverse events, which were considered serious in one case. In conclusion, JAK inhibitors may offer a valuable option for children with severe interferon-mediated inflammatory disorders reducing the interferon score as well as influencing other signal pathways that deserve future studies.
Evaluation of Temporomandibular Joint by Anesthetists in Florida When Conducting Orotracheal Intubation—A Pilot Study
Authors: Gadotti Inae C. , Geronimo Melanie , Rodriguez Gabriela , Caceres Stephanie , Campbell Yasmine , Valdes Jorge , Glymph Derrick
Published: October 2020

Background: Orotracheal intubation has been considered a risk factor for the development or exacerbation of disorders related to the temporomandibular joint (TMJ). The objective of this pilot study was to evaluate TMJ assessment performed by anesthetists in Florida when conducting orotracheal intubation. Methods: An online questionnaire was created using Qualtrics. The survey included 22 questions related to demographics, TMJ related to anesthesia procedures, and education/awareness regarding TMJ related to intubation. Descriptive statistics and cross-tabulation analysis were performed. Results: One hundred and eight providers participated (mean 46 years-old ± 12; 59% female). About 50% reported to always evaluate TMJ prior non-emergency intubation. Of those, 56% used an alternative intubation technique based on the TMJ status and 60% never/rarely evaluated TMJ post-intubation. Twenty-five percent reported they did not know of possible intubation effects on TMJ and 47% reported that they did not receive adequate information/education on TMJ management related to intubation in school. After participation, 81% reported to be more aware of the importance of evaluating TMJ. Conclusions: Only half of the providers who frequently performed intubation in Florida evaluated TMJ prior to intubation. This survey increased the awareness regarding the importance of evaluating TMJ when conducting intubation. This may contribute to reducing TMJ issues associated with non-emergency intubations.
Transcultural Adaptation and Validation of the Fonseca Anamnestic Index in a Spanish Population with Temporomandibular Disorders
Authors: Sánchez-Torrelo Carmen María , Zagalaz-Anula Noelia , Alonso-Royo Roger , Ibáñez-Vera Alfonso Javier , López Collantes Jesús , Rodríguez-Almagro Daniel , Obrero-Gaitán Esteban , Lomas-Vega Rafael
Published: October 2020

Background: The Fonseca Anamnestic Index (FAI) offers a simple method to screen temporomandibular disorders (TMD). This study aimed to validate the Spanish version of the FAI in patients with TMD. Methods: The sample consisted of 125 subjects (66 TMD and 59 controls) aged over 18 years. Construct validity, internal consistency, test-retest reliability, concurrent validity and capacity to discriminate between TMD and healthy subjects were analyzed. Results: The Spanish version of the FAI showed a structure formed by three factors. Cronbach’s alpha was 0.826. The reliability of the items varied between substantial to almost perfect and was excellent for the total score (intraclass correlation coefficient = 0.937). The standard error of measurement (SEM) was 6.52, with a minimum detectable change (MDC) of 12.78. FAI score showed a significant correlation with headache, neck pain and vertigo measurements. A cut-off point >35 showed a sensitivity = 83.33% and a specificity = 77.97% in differentiating between healthy and TMD patients, with an area under the curve (AUC) = 0.865. Conclusions: The Spanish version of the FAI is a valid and reliable instrument for diagnosing people with TMD, with appropriate general clinimetric properties. Discrimination between patients with and without TMD is excellent.
Clinical Outcome and Toxicity in the Treatment of Anaplastic Thyroid Cancer in Elderly Patients
Authors: Augustin Teresa , Oliinyk Dmytro , Koehler Viktoria Florentine , Rauch Josefine , Belka Claus , Spitzweg Christine , Käsmann Lukas
Published: October 2020

Background: The present study aims to evaluate the outcomes and toxicity of elderly anaplastic thyroid cancer (ATC) patients receiving (chemo)radiotherapy, as well as to identify prognostic factors. Patients and methods: A systematic review using the MEDLINE/PubMed and Cochrane databases was performed. Individual data from all eligible studies were extracted, and a pooled analysis (n = 186) was conducted to examine patient characteristics and treatment. All consecutive ATC patients (≥65 years) treated between 2009 and 2019 at our institution were evaluated for outcomes concerning progression-free survival (PFS), overall survival (OS) probabilities and treatment-related toxicity. Results: The systematic review and pooled analysis identified age as a prognostic factor. The median OS of our patient cohort (n = 26) was three months (range = 0–125). The 6-, 12- and 24-month survival rates were 35%, 22% and 11%, respectively. In the univariate analysis, a Karnofsky performance status of >70%, the Union for International Cancer Control Tumor–Node–Metastasis classification, multimodal therapy and an EQD2 of >49 Gy were correlated with longer OS and PFS. The acute grade 3 toxicity of dysphagia, dyspnea, dermatitis, mucositis and dysphonia was found in 23%, 15%, 12%, 12% and 8% of patients. Conclusion: Age appears to be a prognostic factor in ATC. Elderly ATC patients can tolerate multimodal treatment and achieve a promising outcome. Prospective studies need to confirm our findings.
Low Serum Branched-chain Amino Acid and Insulin-Like Growth Factor-1 Levels Are Associated with Sarcopenia and Slow Gait Speed in Patients with Liver Cirrhosis
Authors: Saeki Chisato , Kanai Tomoya , Nakano Masanori , Oikawa Tsunekazu , Torisu Yuichi , Saruta Masayuki , Tsubota Akihito
Published: October 2020

Branched-chain amino acid (BCAA) and insulin-like growth factor 1 (IGF-1) are essential for muscle protein synthesis. We investigated the association of serum BCAA and IGF-1 levels with sarcopenia and gait speed in 192 patients with liver cirrhosis (LC). Sarcopenia was diagnosed according to the Japan Society of Hepatology criteria. Slow gait speed was defined as <1.0 m/s. Subjects were divided into three groups based on baseline BCAA or IGF-1 levels: low (L), intermediate (I), and high (H) groups. The L-BCAA group had the highest prevalence of sarcopenia (60.4%, p < 0.001) and slow gait speed (56.3%, p = 0.008), whereas the H-BCAA group had the lowest prevalence of sarcopenia (8.5%, p < 0.001). The L-IGF-1 group showed the highest prevalence of sarcopenia (46.9%, p < 0.001), whereas the H-IGF-1 group had the lowest prevalence of sarcopenia (10.0%, p < 0.001) and slow gait speed (18.0%, p = 0.003). Using the optimal BCAA and IGF-1 cutoff values for predicting sarcopenia (372 μmol/L and 48.5 ng/mL, respectively), the sensitivity and specificity were 0.709 and 0.759 for BCAA and 0.636 and 0.715 for IGF-1, respectively. Low serum BCAA and IGF-1 levels were associated with sarcopenia and slow gait speed in patients with LC.
Enhanced Humoral Immune Responses against Toxin A and B of Clostridium difficile is Associated with a Milder Disease Manifestation
Authors: Na’amnih Wasef , Carmeli Yehuda , Asato Valeria , Goren Sophy , Adler Amos , Cohen Dani , Muhsen Khitam
Published: October 2020

The role of the humoral immune response to Clostridium difficile in modulating the severity of C. difficile infection (CDI) is unclear. We compared the levels of serum immunoglobulin G (IgG) and immunoglobulin A (IgA) against toxin A (TcdA) and toxin B (TcdB) of C. difficile between CDI and control patients and according to disease severity. The levels of IgG and IgA antibodies against TcdA and TcdB were measured in sera from patients with CDI (n = 50; 19 had severe CDI) and control patients (n = 52), using ELISA. Patients with CDI had higher levels of IgG antibodies against TcdA and TcdB than controls (p = 0.001 and p = 0.04, respectively). Higher IgG levels against TcdA and TcdB were found in patients with mild vs. severe CDI 7–14 days after the diagnosis (p = 0.004 and 0.036, respectively). A factor analysis included both IgA and IgG levels against both toxins into one composite variable, which was of higher values in patients with mild vs. severe CDI (p = 0.026). In conclusion, the systemic humoral immune responses against TcdA and TcdB might modulate the severity of CDI. These preliminary findings provide a basis for future large-scale studies and support the development and evaluation of active and passive immunotherapies for CDI management.
Prostate Cancer Survivors’ and Caregivers’ Experiences Using Behavior Change Techniques during a Web-Based Self-Management and Physical Activity Program: A Qualitative Study
Authors: Hallward Laura , Chemtob Keryn , Lambert Sylvie D. , Duncan Lindsay R.
Published: October 2020

Both men with prostate cancer and their caregivers report experiencing a number of challenges and health consequences, and require programs to help support the cancer patient–caregiver dyad. A tailored, web-based, psychosocial and physical activity self-management program (TEMPO), which implements behavior change techniques to help facilitate behavior change for the dyads was created and its acceptability was tested in a qualitative study. The purpose of this secondary analysis was to explore the dyads’ experiences using behavior change techniques to change behavior and address current needs and challenges while enrolled in TEMPO. Multiple semi-structured interviews were conducted with 19 prostate cancer-caregiver dyads over the course of the program, resulting in 46 transcripts that were analyzed using an inductive thematic analysis. Results revealed four main themes: (1) learning new behavior change techniques, (2) engaging with behavior change techniques learned in the past, (3) resisting full engagement with behavior change techniques, and (4) experiencing positive outcomes from using behavior change techniques. The dyads’ discussions of encountering behavior change techniques provided unique insight into the process of learning and implementing behavior change techniques through a web-based self-management program, and the positive outcomes that resulted from behavior changes.
HbA1c and Aortic Calcification Index as Noninvasive Predictors of Pre-Existing Histopathological Damages in Living Donor Kidney Transplantation
Authors: Tanaka Kosuke , Yamanaga Shigeyoshi , Hidaka Yuji , Nishida Sho , Kinoshita Kohei , Kaba Akari , Ishizuka Toshinori , Hamanoue Satoshi , Okumura Kenji , Kawabata Chiaki , Toyoda Mariko , Takeda Asami , Miyata Akira , Kashima Masayuki , Yokomizo Hiroshi
Published: October 2020

We previously reported that allografts from living donors may have pre-existing histopathological damages, defined as the combination of interstitial fibrosis (ci), tubular atrophy (ct), and arteriolar hyalinosis (ah) scores of ≧1, according to the Banff classification. We examined preoperative characteristics to identify whether the degree of these damages was related to metabolic syndrome-related factors of donors. We conducted a single-center cross-sectional analysis including 183 living kidney donors. Donors were divided into two groups: chronic change (ci + ct ≧ 1 ∩ ah ≧ 1, n = 27) and control (n = 156). Preoperative characteristics, including age, sex, blood pressure, hemoglobin A1c (HbA1c), aortic calcification index (ACI), and psoas muscle index (PMI), were analyzed. Comparing the groups, the baseline estimated glomerular filtration rate was not significantly different; however, we observed a significant difference for ACI (p = 0.009). HbA1c (p = 0.016) and ACI (p = 0.006) were independent risk factors to predict pre-existing histopathological damages, whereas PMI was not. HbA1c correlated with ct scores (p = 0.035), and ACI correlated with ci (p = 0.005), ct (p = 0.021), and ah (p = 0.017). HbA1c and ACI may serve as preoperative markers for identifying pre-existing damages on the kidneys of living donors.
Prognostic Significance of Tumor Location in T2 Gallbladder Cancer: A Korea Tumor Registry System Biliary Pancreas (KOTUS-BP) Database Analysis
Authors: Lee Seung Eun , Choi Yoo Shin , Kim Yong Hoon , Heo Jin Seok , Jeong Chi-Young , Lee Woo Jung , Seo Hyung Il , Yoon Yoo-Seok , Jang Jin-Young
Published: October 2020

Background: T2 gallbladder cancer (GBC) is subdivided into T2a and T2b by the American Joint Committee on Cancer (AJCC) 8th edition. However; there is a lack of evidence for the prognostic significance of tumor location and validation with large-scale studies is needed. The aims of this study were to investigate the clinical features and clinical outcomes of T2 GBC according to tumor location and determine the prognostic significance of tumor location and an appropriate surgical strategy. Methods: Between 2000 and 2014 the Korea Tumor Registry System Biliary Pancreas (KOTUS-BP) database was used to identify and enroll a total 707 patients with pathologically diagnosed T2 GBC who underwent curative resection. Clinicopathological findings and long-term follow-up results were analyzed. Results: The incidence of lymph node metastasis in T2b was significantly higher than that of T2a tumors (37.9% vs. 29.5%, p = 0.032). The 5-year disease-specific survival of T2a was better than that of T2b tumors (74.8% vs. 65.4%, p = 0.019). There was no significant survival difference in T2a between extended cholecystectomy and simple cholecystectomy with lymph node dissection (81.8% vs. 73.7%, p = 0.361). However; there was a better survival trend for T2b tumor after extended cholecystectomy (71.7% vs. 59.3%, p = 0.057). Adjuvant chemotherapy was associated with improved survival for patients with lymph node metastasis in T2a (72.1% vs. 56.9; p = 0.022) and in T2b (68.2 vs. 48.5; p < 0.001). Multivariate analysis revealed that lymph node metastasis was the only significant poor prognostic factor (Hazard ratio 3.222; 95% confidential interval 1.960–4.489; p < 0.001). Conclusions: For T2 GBC; tumor location was not an independent prognostic factor. Lymph node metastasis was a significant poor prognostic factor and adjuvant chemotherapy should be considered for the patients with lymph node metastasis.
Adsorption of Blood Components to Extracorporeal Membrane Oxygenation (ECMO) Surfaces in Humans: A Systematic Review
Authors: Callaghan Sam , Cai Tengyi , McCafferty Conor , Van Den Helm Suelyn , Horton Steve , MacLaren Graeme , Monagle Paul , Ignjatovic Vera
Published: October 2020

The accumulation of blood proteins and cells on extracorporeal membrane oxygenation (ECMO) circuits has been proposed as a contributing factor to the coagulopathic state of many patients. This systematic review aims to summarize and discuss the existing knowledge of blood components binding to the ECMO circuits in human patients. A systematic review was conducted using the Medline, PubMed and Embase databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seven studies were included in this review. Three studies identified a leukocyte adhesion, three studies observed von Willebrand factor accumulation and four studies identified bound platelets on the surface of the circuits. Other identified components included fibrin, albumin, hemoglobin, erythrocytes, progenitor cells, fibronectin and IgG. This systematic review demonstrates the limited state of knowledge when it comes to adsorption to the ECMO circuits in humans. Most of the studies lacked insight or detail into the mechanisms of binding and the interactions between different components bound to the ECMO circuits. Further research is required to comprehensively characterize surface adsorption to ECMO circuits in humans and to define the specific mechanisms of binding, enabling improvements that increase biocompatibility between the blood-circuit interface in this important clinical setting.