bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemotherapy-based versus chemotherapy-free stem cell mobilization (± plerixafor) in multiple myeloma patients: an Italian cost-effectiveness analysis
Authors: Lazzaro Carlo , Castagna Luca , Lanza Francesco , Laszlo Daniele , Milone Giuseppe , Pierelli Luca , Saccardi Riccardo 
Published: March 2021

AbstractGiven the availability and efficacy of the mobilizing agent plerixafor in augmenting hematopoietic progenitor cell mobilization with granulocyte colony-stimulating factor (G-CSF), there is a strong case for comparing the cost-effectiveness of mobilization with G-CSF + cyclophosphamide versus G-CSF alone. This study investigated the cost and effectiveness (i.e., successful 4 million-CD34+collection) of G-CSF alone versus high-dose cyclophosphamide (4 g/m2) + G-CSF mobilization (± on-demand plerixafor) in patients with multiple myeloma (MM) eligible for autograft in Italy. A decision tree-supported cost-effectiveness analysis (CEA) model in MM patients was developed from the societal perspective. The CEA model compared G-CSF alone with cyclophosphamide 4 g/m2 + G-CSF (± on-demand plerixafor) and was populated with demographic, healthcare and non-healthcare resource utilization data collected from a questionnaire administered to six Italian oncohematologists. Costs were expressed in Euro (€) 2019. The CEA model showed that G-CSF alone was strongly dominant versus cyclophosphamide + G-CSF ( ± on-demand plerixafor), with incremental savings of €1198.59 and an incremental probability of a successful 4 million-CD34+apheresis (+0.052). Sensitivity analyses confirmed the robustness of the base-case results. In conclusion, chemotherapy-free mobilization (± on-demand plerixafor) is a “good value for money” option for MM patients eligible for autograft.
Unraveling a fine-scale high genetic heterogeneity and recent continental connections of an Arabian Peninsula population
Authors: Eaaswarkhanth Muthukrishnan , Pathak Ajai K. , Ongaro Linda , Montinaro Francesco , Hebbar Prashantha , Alsmadi Osama , Metspalu Mait , Al-Mulla Fahd , Thanaraj Thangavel Alphonse 
Published: March 2021

AbstractRecent studies have showed the diverse genetic architecture of the highly consanguineous populations inhabiting the Arabian Peninsula. Consanguinity coupled with heterogeneity is complex and makes it difficult to understand the bases of population-specific genetic diseases in the region. Therefore, comprehensive genetic characterization of the populations at the finest scale is warranted. Here, we revisit the genetic structure of the Kuwait population by analyzing genome-wide single nucleotide polymorphisms data from 583 Kuwaiti individuals sorted into three subgroups. We envisage a diverse demographic genetic history among the three subgroups based on drift and allelic sharing with modern and ancient individuals. Furthermore, our comprehensive haplotype-based analyses disclose a high genetic heterogeneity among the Kuwaiti populations. We infer the major sources of ancestry within the newly defined groups; one with an obvious predominance of sub-Saharan/Western Africa mostly comprising Kuwait-B individuals, and other with West Eurasia including Kuwait-P and Kuwait-S individuals. Overall, our results recapitulate the historical population movements and reaffirm the genetic imprints of the legacy of continental trading in the region. Such deciphering of fine-scale population structure and their regional genetic heterogeneity would provide clues to the uncharted areas of disease-gene discovery and related associations in populations inhabiting the Arabian Peninsula.
Retroviral gene therapy in Germany with a view on previous experience and future perspectives
Authors: Morgan Michael A. , Galla Melanie , Grez Manuel , Fehse Boris , Schambach Axel 
Published: March 2021

AbstractGene therapy can be used to restore cell function in monogenic disorders or to endow cells with new capabilities, such as improved killing of cancer cells, expression of suicide genes for controlled elimination of cell populations, or protection against chemotherapy or viral infection. While gene therapies were originally most often used to treat monogenic diseases and to improve hematopoietic stem cell transplantation outcome, the advent of genetically modified immune cell therapies, such as chimeric antigen receptor modified T cells, has contributed to the increased numbers of patients treated with gene and cell therapies. The advancement of gene therapy with integrating retroviral vectors continues to depend upon world-wide efforts. As the topic of this special issue is “Spotlight on Germany,” the goal of this review is to provide an overview of contributions to this field made by German clinical and research institutions. Research groups in Germany made, and continue to make, important contributions to the development of gene therapy, including design of vectors and transduction protocols for improved cell modification, methods to assess gene therapy vector efficacy and safety (e.g., clonal imbalance, insertion sites), as well as in the design and conduction of clinical gene therapy trials.
Delivery of functional exogenous proteins by plant-derived vesicles to human cells in vitro
Authors: Garaeva Luiza , Kamyshinsky Roman , Kil Yury , Varfolomeeva Elena , Verlov Nikolai , Komarova Elena , Garmay Yuri , Landa Sergey , Burdakov Vladimir , Myasnikov Alexander , Vinnikov Ilya A. , Margulis Boris , Guzhova Irina , Kagansky Alexander , Konevega Andrey L. , Shtam Tatiana 
Published: March 2021

AbstractPlant-derived extracellular vesicles (EVs) gain more and more attention as promising carriers of exogenous bioactive molecules to the human cells. Derived from various edible sources, these EVs are remarkably biocompatible, biodegradable and highly abundant from plants. In this work, EVs from grapefruit juice were isolated by differential centrifugation followed by characterization of their size, quantity and morphology by nanoparticle tracking analysis, dynamic light scattering, atomic force microscopy and cryo-electron microscopy (Cryo-EM). In Cryo-EM experiments, we visualized grapefruit EVs with the average size of 41 ± 13 nm, confirmed their round-shaped morphology and estimated the thickness of their lipid bilayer as 5.3 ± 0.8 nm. Further, using cell culture models, we have successfully demonstrated that native grapefruit-derived extracellular vesicles (GF-EVs) are highly efficient carriers for the delivery of the exogenous Alexa Fluor 647 labeled bovine serum albumin (BSA) and heat shock protein 70 (HSP70) into both human peripheral blood mononuclear cells and colon cancer cells. Interestingly, loading to plant EVs significantly ameliorated the uptake of exogenous proteins by human cells compared to the same proteins without EVs. Most importantly, we have confirmed the functional activity of human recombinant HSP70 in the colon cancer cell culture upon delivery by GF-EVs. Analysis of the biodistribution of GF-EVs loaded with 125I-labeled BSA in mice demonstrated a significant uptake of the grapefruit-derived extracellular vesicles by the majority of organs. The results of our study indicate that native plant EVs might be safe and effective carriers of exogenous proteins into human cells.
Comprehensive characterization of motor and coordination functions in three adolescent wild-type mouse strains
Authors: Eltokhi Ahmed , Kurpiers Barbara , Pitzer Claudia 
Published: March 2021

AbstractNeuropsychiatric disorders are often associated with motor and coordination abnormalities that have important implications on the etiology, pathophysiology, and management of these disorders. Although the onset of many neuropsychiatric disorders including autism spectrum disorder, schizophrenia, and attention-deficit hyperactivity disorder emerges mainly during infancy and adolescence, most of the behavioral studies in mice modeling neuropsychiatric phenotypes are performed in adult animals, possibly missing valuable phenotypic information related to the effect of synaptic maturation during development. Here, we examined which behavioral tests assessing both motor and coordination functions can be performed in mice at two different adolescent stages. As strain and sex affect mouse behavior, our experiments covered both male and female mice of three inbred wild-type strains, C57BL/6N, DBA/2, and FVB/N. Adolescent mice of both postnatal days (P)22–30 and P32–40 developmental stages were capable of mastering common motor and coordination tests. However, results differed significantly between strains and sexes. Moreover, the 10-day interval between the two tested cohorts uncovered a strong difference in the behavioral results, confirming the significant impact of maturation on behavioral patterns. Interestingly, the results of distinct behavioral experiments were directly correlated with the weight of mice, which may explain the lack of reproducibility of some behavioral results in genetically-modified mice. Our study paves the way for better reproducibility of behavioral tests by addressing the effect of the developmental stage, strain, sex, and weight of mice on achieving the face validity of neuropsychiatric disorder-associated motor dysfunctions.
Selection for high levels of resistance to double-stranded RNA (dsRNA) in Colorado potato beetle (Leptinotarsa decemlineata Say) using non-transgenic foliar delivery
Authors: Mishra Swati , Dee James , Moar William , Dufner-Beattie Jodi , Baum James , Dias Naymã Pinto , Alyokhin Andrei , Buzza Aaron , Rondon Silvia I. , Clough Mark , Menasha Sandy , Groves Russell , Clements Justin , Ostlie Ken , Felton Gary , Waters Tim , Snyder William E. , Jurat-Fuentes Juan Luis 
Published: March 2021

AbstractInsecticidal double-stranded RNAs (dsRNAs) silence expression of vital genes by activating the RNA interference (RNAi) mechanism in insect cells. Despite high commercial interest in insecticidal dsRNA, information on resistance to dsRNA is scarce, particularly for dsRNA products with non-transgenic delivery (ex. foliar/topical application) nearing regulatory review. We report the development of the CEAS 300 population of Colorado potato beetle (Leptinotarsa decemlineata Say) (Coleoptera: Chrysomelidae) with > 11,100-fold resistance to a dsRNA targeting the V-ATPase subunit A gene after nine episodes of selection using non-transgenic delivery by foliar coating. Resistance was associated with lack of target gene down-regulation in CEAS 300 larvae and cross-resistance to another dsRNA target (COPI β; Coatomer subunit beta). In contrast, CEAS 300 larvae showed very low (~ 4-fold) reduced susceptibility to the Cry3Aa insecticidal protein from Bacillus thuringiensis. Resistance to dsRNA in CEAS 300 is transmitted as an autosomal recessive trait and is polygenic. These data represent the first documented case of resistance in an insect pest with high pesticide resistance potential using dsRNA delivered through non-transgenic techniques. Information on the genetics of resistance and availability of dsRNA-resistant L. decemlineata guide the design of resistance management tools and allow research to identify resistance alleles and estimate resistance risks.
Capsular polysaccharide switching in Streptococcus suis modulates host cell interactions and virulence
Authors: Okura Masatoshi , Auger Jean-Philippe , Shibahara Tomoyuki , Goyette-Desjardins Guillaume , Van Calsteren Marie-Rose , Maruyama Fumito , Kawai Mikihiko , Osaki Makoto , Segura Mariela , Gottschalk Marcelo , Takamatsu Daisuke 
Published: March 2021

AbstractThe capsular polysaccharide (CPS) of Streptococcus suis defines various serotypes based on its composition and structure. Though serotype switching has been suggested to occur between S. suis strains, its impact on pathogenicity and virulence remains unknown. Herein, we experimentally generated S. suis serotype-switched mutants from a serotype 2 strain that express the serotype 3, 4, 7, 8, 9, or 14 CPS. The effects of serotype switching were then investigated with regards to classical properties conferred by presence of the serotype 2 CPS, including adhesion to/invasion of epithelial cells, resistance to phagocytosis by macrophages, killing by whole blood, dendritic cell-derived pro-inflammatory mediator production and virulence using mouse and porcine infection models. Results demonstrated that these properties on host cell interactions were differentially modulated depending on the switched serotypes, although some different mutations other than loci of CPS-related genes were found in each the serotype-switched mutant. Among the serotype-switched mutants, the mutant expressing the serotype 8 CPS was hyper-virulent, whereas mutants expressing the serotype 3 or 4 CPSs had reduced virulence. By contrast, switching to serotype 7, 9, or 14 CPSs had little to no effect. These findings suggest that serotype switching can drastically alter S. suis virulence and host cell interactions.
Vibrational communication and mating behavior of the greenhouse whitefly Trialeurodes vaporariorum (Westwood) (Hemiptera: Aleyrodidae)
Authors: Fattoruso Valeria , Anfora Gianfranco , Mazzoni Valerio 
Published: March 2021

AbstractThe greenhouse whitefly (GW), Trialeurodes vaporariorum is considered one of the most harmful insect pests in greenhouses worldwide. The GW mating behavior has been partially investigated and its vibrational communication is only in part known. A deeper knowledge of its intraspecific communication is required to evaluate the applicability of control methods based on techniques of behavioral manipulation. In this study, for the first time, we provided a detailed ethogram of the GW mating behavior and we characterized the vibrational signals emitted during the process of pair formation. We characterized two types of male vibrational emissions (“chirp” and “pulses”), differently arranged according to the behavioral stage to form stage-specific signals, and a previously undescribed Male Rivalry Signal. We recorded and characterized two new female signals: The Female Responding Signal and the Female Rejective Signal. The mating behavior of GW can be divided into six different stages that we named “call”, “alternated duet”, “courtship”, “overlapped duet”, “mating”, “failed mating attempt”. The analysis performed with the Markovian behavioral transition matrix showed that the “courtship” is the key stage in which male exhibits its quality and can lead to the “overlapped duet” stage. The latter is strictly associated to the female acceptance and therefore it plays a crucial role to achieve mating success. Based on our findings, we consider the use of vibrational playbacks interfering with GW mating communication a promising option for pest control in greenhouses. We discuss the possibility to start a research program of behavioral manipulation to control the populations of GW.
Characteristics and comparative clinical outcomes of prisoner versus non-prisoner populations hospitalized with COVID-19
Authors: Altibi Ahmed M. , Pallavi Bhargava , Liaqat Hassan , Slota Alexander A. , Sheth Radhika , Al Jebbawi Lama , George Matthew E. , LeDuc Allison , Abdallah Enas , Russell Luke R. , Jain Saniya , Shirvanian Nariné , Masri Ahmad , Kak Vivek 
Published: March 2021

AbstractPrisons in the United States have become a hotbed for spreading COVID-19 among incarcerated individuals. COVID-19 cases among prisoners are on the rise, with more than 143,000 confirmed cases to date. However, there is paucity of data addressing clinical outcomes and mortality in prisoners hospitalized with COVID-19. An observational study of all patients hospitalized with COVID-19 between March 10 and May 10, 2020 at two Henry Ford Health System hospitals in Michigan. Clinical outcomes were compared amongst hospitalized prisoners and non-prisoner patients. The primary outcomes were intubation rates, in-hospital mortality, and 30-day mortality. Multivariable logistic regression and Cox-regression models were used to investigate primary outcomes. Of the 706 hospitalized COVID-19 patients (mean age 66.7 ± 16.1 years, 57% males, and 44% black), 108 were prisoners and 598 were non-prisoners. Compared to non-prisoners, prisoners were more likely to present with fever, tachypnea, hypoxemia, and markedly elevated inflammatory markers. Prisoners were more commonly admitted to the intensive care unit (ICU) (26.9% vs. 18.7%), required vasopressors (24.1% vs. 9.9%), and intubated (25.0% vs. 15.2%). Prisoners had higher unadjusted inpatient mortality (29.6% vs. 20.1%) and 30-day mortality (34.3% vs. 24.6%). In the adjusted models, prisoner status was associated with higher in-hospital death (odds ratio, 2.32; 95% confidence interval (CI), 1.33 to 4.05) and 30-day mortality (hazard ratio, 2.00; 95% CI, 1.33 to 3.00). In this cohort of hospitalized COVID-19 patients, prisoner status was associated with more severe clinical presentation, higher rates of ICU admissions, vasopressors requirement, intubation, in-hospital mortality, and 30-day mortality.
Social categorization based on permanent versus transient visual traits in neurotypical children and children with autism spectrum disorder
Authors: Kiss Orsolya , Oláh Katalin , Fehér Lili Julia , Topál József 
Published: March 2021

AbstractThe present study was designed to test the relative weight of different types of category markers in children’s representations of social and biological kinds. We reasoned that in order to efficiently navigate through the mesh network of overlapping social categories, the representational system dedicated to processing information about social groups should be prepared to flexibly switch between potential ways of categorizing fellow humans. Thus, we hypothesized that children would assign more relevance to transient but symbolic features, such as shirt colour, when categorizing humans than other animal species. Across two experiments, we investigated whether typically developing children as well as children diagnosed with Autism Spectrum Disorder would categorize drawings of humans and dogs along a transient or a biologically set, permanent marker. The results show that both groups of children overwhelmingly selected the permanent feature to categorize dogs, however, they were more likely to categorize fellow humans based on transient features. We suggest that this tendency lays the ground for humans’ ability to efficiently represent the complex structure of societies.
Functional foregut anatomy of the blue–green sharpshooter illustrated using a 3D model
Authors: White Daniel , Backus Elaine A. , Marcus Ian M. , Walker Sharon L. , Roper M. Caroline 
Published: March 2021

AbstractSharpshooter leafhoppers (Hemiptera: Cicadellidae: Cicadellinae) are important vectors of the plant pathogenic bacterium Xylella fastidiosa Wells et al. (Xanthomonadales: Xanthomonadaceae). This pathogen causes economically significant diseases in olive, citrus, and grapes on multiple continents. Bacterial acquisition and inoculation mechanisms are linked to X. fastidiosa biofilm formation and fluid dynamics in the functional foregut of sharpshooters, which together result in egestion (expulsion) of fluids likely carrying bacteria. One key X. fastidiosa vector is the blue–green sharpshooter, Graphocephala atropunctata (Signoret, 1854). Herein, a 3D model of the blue–green sharpshooter functional foregut is derived from a meta-analysis of published microscopy images. The model is used to illustrate preexisting and newly defined anatomical terminology that is relevant for investigating fluid dynamics in the functional foregut of sharpshooters. The vivid 3D illustrations herein and supplementary interactive 3D figures are suitable resources for multidisciplinary researchers who may be unfamiliar with insect anatomy. The 3D model can also be used in future fluid dynamic simulations to better understand acquisition, retention, and inoculation of X. fastidiosa. Improved understanding of these processes could lead to new targets for preventing diseases caused by X. fastidiosa.
A surface plasmon resonance based approach for measuring response to pneumococcal vaccine
Authors: Garrido-Jareño Marta , Puchades-Carrasco Leonor , Orti-Pérez Leticia , Sahuquillo-Arce José Miguel , del Carmen Meyer-García María , Mollar-Maseres Joan , Lloret-Sos Carmina , Gil-Brusola Ana , López-Hontangas José Luis , Beltrán-Garrido José Manuel , Pemán-García Javier , Pineda-Lucena Antonio 
Published: March 2021

AbstractIncidence of pneumococcal disease has increased worldwide in recent years. Response to pneumococcal vaccine is usually measured using the multiserotype enzyme-linked immunosorbent assay (ELISA) pneumococcal test. However, this approach presents several limitations. Therefore, the introduction of new and more robust analytical approaches able to provide information on the efficacy of the pneumococcal vaccine would be very beneficial for the clinical management of patients. Surface plasmon resonance (SPR) has been shown to offer a valuable understanding of vaccines’ properties over the last years. The aim of this study is to evaluate the reliability of SPR for the anti-pneumococcal capsular polysaccharides (anti-PnPs) IgGs quantification in vaccinated. Fast protein liquid chromatography (FPLC) was used for the isolation of total IgGs from serum samples of vaccinated patients. Binding-SPR assays were performed to study the interaction between anti-PnPs IgGs and PCV13. A robust correlation was found between serum levels of anti-PnPs IgGs, measured by ELISA, and the SPR signal. Moreover, it was possible to correctly classify patients into “non-responder”, “responder” and “high-responder” groups according to their specific SPR PCV13 response profiles. SPR technology provides a valuable tool for reliably characterize the interaction between anti-PnPs IgGs and PCV13 in a very short experimental time.
Rainfall increasing offsets the negative effects of nighttime warming on GHGs and wheat yield in North China Plain
Authors: Zhang Yaojun , Shou Wenkai , Maucieri Carmelo , Lin Feng 
Published: March 2021

AbstractThe effects of nighttime warming and rainfall increasing on crop productivity and soil greenhouse gas emissions are few studied. This study was conducted with a field experiment to investigate the effects of nighttime warming, rainfall increasing and their interaction on wheat grain yield, methane (CH4) and nitrous oxide (N2O) emissions during a winter wheat growing season in the North China Plain (NCP). The results showed that nighttime warming and rainfall increasing significantly altered soil temperature and moisture, and thus the CH4and N2O emissions from the soil. Nighttime warming significantly promoted soil CH4uptake by 21.2% and increased soil N2O emissions by 22.4%. Rainfall increasing stimulated soil N2O emissions by 15.7% but decreased soil CH4uptake by 18.6%. Nighttime warming significantly decreased wheat yield by 5.5%, while rainfall increasing enhanced wheat yield by 4.0%. The results indicate that the positive effect of nighttime warming on CH4uptake and negative effect on wheat yield can be offset by rainfall increasing in the NCP. Generally, rainfall increasing significantly raised the global warming potential and greenhouse gas intensity induced by CH4and N2O emissions. Overall, this study improves our understanding of agroecosystem C and N cycling in response to nighttime warming and rainfall increasing under future climate change.