bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of vaccine type on HIV-1 vaccine elicited antibody durability and B cell gene signature
Authors: Palli Rohith , Seaton Kelly E. , Piepenbrink Michael S. , Hural John , Goepfert Paul A. , Laher Fatima , Buchbinder Susan P. , Churchyard Gavin , Gray Glenda E. , Robinson Harriet L. , Huang Yunda , Janes Holly , Kobie James J. , Keefer Michael C. , Tomaras Georgia D. , Thakar Juilee 
Published: August 2020

AbstractEfficacious HIV-1 vaccination requires elicitation of long-lived antibody responses. However, our understanding of how different vaccine types elicit durable antibody responses is lacking. To assess the impact of vaccine type on antibody responses, we measured IgG isotypes against four consensus HIV antigens from 2 weeks to 10 years post HIV-1 vaccination and used mixed effects models to estimate half-life of responses in four human clinical trials. Compared to protein-boosted regimens, half-lives of gp120-specific antibodies were longer but peak magnitudes were lower in Modified Vaccinia Ankara (MVA)-boosted regimens. Furthermore, gp120-specific B cell transcriptomics from MVA-boosted and protein-boosted vaccines revealed a distinct signature at a peak (2 weeks after last vaccination) including CD19, CD40, and FCRL2-5 activation along with increased B cell receptor signaling. Additional analysis revealed contributions of RIG-I-like receptor pathway and genes such as SMAD5 and IL-32 to antibody durability. Thus, this study provides novel insights into vaccine induced antibody durability and B-cell receptor signaling.
Single nucleotide polymorphisms in tinnitus patients exhibiting severe distress
Authors: Watabe Takahisa , Kanzaki Sho , Sato Noriko , Matsunaga Tatsuo , Muramatsu Masaaki , Ogawa Kaoru 
Published: August 2020

AbstractThe association between distress caused by tinnitus and psychological factors such as depression and anxiety has been examined and reported. However, prognostic factors remain poorly understood because there are only a few reports on genetic associations. We theorized there might be an association between the grade of tinnitus distress and the genetic background related to psychological factors which might lead us to identify prognostic markers. We enrolled 138 patients who had suffered from tinnitus for over 3 months. Using Tinnitus Handicap Inventory (THI) scores, we examined the association between tinnitus distress and a genetic background related to depression or anxiety. A significant association between single nucleotide polymorphism rs131702 of the Breakpoint Cluster Region (BCR) gene and the severe THI score was identified. In addition, there was an association with the severity of the State-Trait Anxiety Inventory, an index of state anxiety severity. No association was found with the Self-Rating Depression Scale, an index of depression severity. It is reported that rs131702 of BCR in Japanese patients are related to bipolar II depression characterized by fluctuation between abnormal mood states of mania and depression. Our results indicate that rs131702 of BCR is independent of depression in this study and is, therefore, a prognostic factor unique to tinnitus. We conclude that the severity of tinnitus is associated with genes related to depression.
Accuracy of older adults in judging self-generated elbow torques during multi-joint isometric tasks
Authors: Cai Ninghe M. , Dewald Julius P. A. , Gurari Netta 
Published: August 2020

AbstractSuccessful execution of daily activities requires accurate perception of the torques one generates about multiple joints. Even so, previous studies are mostly limited to an individual’s perception when torques are generated about a single joint. Consequently, this study investigates how accurately individuals judge torques at their arm during a multi-joint task. The accuracy of fifteen right-hand dominant participants (age: 60 ± 10 years) in matching isometric elbow torques, within the same arm, was quantified during single- and/or multi-joint tasks. Participants generated and matched elbow torques when the shoulder was: (1) not abducted (single-to-single-joint), (2) abducted (multi-to-multi-joint), and (3) abducted and then not abducted (multi-to-single-joint). The constant error for the multi-to-single-joint condition (dominant: 6.9 ± 5.9 Nm, non-dominant: 6.0 ± 5.5 Nm) was greater than that for the single-to-single-joint condition (dominant: 2.7 ± 3.1 Nm, non-dominant: 3.4 ± 2.8 Nm) (p < 0.001) and multi-to-multi-joint condition (dominant: 3.0 ± 2.8 Nm, non-dominant: 3.9 ± 2.7 Nm) (p < 0.001). The constant error for the multi-to-multi-joint condition did not significantly differ from that of the single-to-single-joint condition (p $$=$$
=
0.780). Findings indicate that in older adults the perception of a self-generated torque during a 2-degree-of-freedom (DOF), multi-joint task is largely influenced by the motor commands associated with the 2-DOF task and is not specific to the DOF at each joint.
Batrachochytrium salamandrivorans (Bsal) not detected in an intensive survey of wild North American amphibians
Authors: Waddle J. Hardin , Grear Daniel A. , Mosher Brittany A. , Grant Evan H. Campbell , Adams Michael J. , Backlin Adam R. , Barichivich William J. , Brand Adrianne B. , Bucciarelli Gary M. , Calhoun Daniel L. , Chestnut Tara , Davenport Jon M. , Dietrich Andrew E. , Fisher Robert N. , Glorioso Brad M. , Halstead Brian J. , Hayes Marc P. , Honeycutt R. Ken , Hossack Blake R. , Kleeman Patrick M. , Lemos-Espinal Julio A. , Lorch Jeffrey M. , McCreary Brome , Muths Erin , Pearl Christopher A. , Richgels Katherine L. D. , Robinson Charles W. , Roth Mark F. , Rowe Jennifer C. , Sadinski Walt , Sigafus Brent H. , Stasiak Iga , Sweet Samuel , Walls Susan C. , Watkins-Colwell Gregory J. , White C. LeAnn , Williams Lori A. , Winzeler Megan E. 
Published: August 2020

AbstractThe salamander chytrid fungus (Batrachochytrium salamandrivorans [Bsal]) is causing massive mortality of salamanders in Europe. The potential for spread via international trade into North America and the high diversity of salamanders has catalyzed concern about Bsal in the U.S. Surveillance programs for invading pathogens must initially meet challenges that include low rates of occurrence on the landscape, low prevalence at a site, and imperfect detection of the diagnostic tests. We implemented a large-scale survey to determine if Bsal was present in North America designed to target taxa and localities where Bsal was determined highest risk to be present based on species susceptibility and geography. Our analysis included a Bayesian model to estimate the probability of occurrence of Bsal given our prior knowledge of the occurrence and prevalence of the pathogen. We failed to detect Bsal in any of 11,189 samples from 594 sites in 223 counties within 35 U.S. states and one site in Mexico. Our modeling indicates that Bsal is highly unlikely to occur within wild amphibians in the U.S. and suggests that the best proactive response is to continue mitigation efforts against the introduction and establishment of the disease and to develop plans to reduce impacts should Bsal establish.
Human pluripotent stem cell-derived cardiomyocytes as a target platform for paracrine protection by cardiac mesenchymal stromal cells
Authors: Constantinou Chrystalla , Miranda Antonio M. A. , Chaves Patricia , Bellahcene Mohamed , Massaia Andrea , Cheng Kevin , Samari Sara , Rothery Stephen M. , Chandler Anita M. , Schwarz Richard P. , Harding Sian E. , Punjabi Prakash , Schneider Michael D. , Noseda Michela 
Published: August 2020

AbstractIschemic heart disease remains the foremost cause of death globally, with survivors at risk for subsequent heart failure. Paradoxically, cell therapies to offset cardiomyocyte loss after ischemic injury improve long-term cardiac function despite a lack of durable engraftment. An evolving consensus, inferred preponderantly from non-human models, is that transplanted cells benefit the heart via early paracrine signals. Here, we tested the impact of paracrine signals on human cardiomyocytes, using human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) as the target of mouse and human cardiac mesenchymal stromal cells (cMSC) with progenitor-like features. In co-culture and conditioned medium studies, cMSCs markedly inhibited human cardiomyocyte death. Little or no protection was conferred by mouse tail tip or human skin fibroblasts. Consistent with the results of transcriptomic profiling, functional analyses showed that the cMSC secretome suppressed apoptosis and preserved cardiac mitochondrial transmembrane potential. Protection was independent of exosomes under the conditions tested. In mice, injecting cMSC-conditioned media into the infarct border zone reduced apoptotic cardiomyocytes > 70% locally. Thus, hPSC-CMs provide an auspicious, relevant human platform to investigate extracellular signals for cardiac muscle survival, substantiating human cardioprotection by cMSCs, and suggesting the cMSC secretome or its components as potential cell-free therapeutic products.
Uniaxial films of maximally controllable response under visible light
Authors: Tulegenov Dias , Valagiannopoulos Constantinos 
Published: August 2020

AbstractThe controllability of photonic setups is strongly related to how coherently their outputs react to changes in their inputs; such a generic concept is treated in the case of films comprising multilayers of tilted optical axes, under visible light. The optimized designs incorporate ordinary metals or semiconductors while being able to achieve practically all the combinations of reflected, transmitted and absorbed power within the passivity limits. Importantly, most of the proposed structures exhibit substantial robustness to manufacturing defects and are fabricable with various methods. Therefore, they can make indispensable pieces of integrated photonic systems by improving their light-controlling operation for applications ranging from steering and electrodynamic switching to filtering and optical signal processing.
Rogue waves in disordered 1D photonic lattices
Authors: Rivas Danilo , Szameit Alexander , Vicencio Rodrigo A. 
Published: August 2020

AbstractIn this work, we study the phenomena of Rogue waves (RW) on one-dimensional (1D) photonic lattices presenting diagonal and non-diagonal disorder. Our results show the appearance of extreme events coming from the superposition of different, extended and localized, linear waves for weak disorder. We perform experiments on femtosecond laser written waveguide arrays having disorder in coupling constants, which is originated from a random waveguide distribution. Both, numerics and experiments, are in good agreement and show that RW are generically present in 1D lattices for weak disorder only, after a mandatory data filtering process.
Identification of adolescent girls and young women for targeted HIV prevention: a new risk scoring tool in KwaZulu Natal, South Africa
Authors: Ayton Sarah Gabrielle , Pavlicova Martina , Abdool Karim Quarraisha 
Published: August 2020

AbstractThe ongoing spread of human immunodeficiency virus (HIV) has driven novel interventions, such as antiretrovirals, for pre-exposure prophylaxis. Interventions have overlooked a high-risk Sub-Saharan African population: adolescent girls and young women (AGYW), particularly those under 18. We apply the Balkus risk tool among rural South African AGYW (n = 971) in a hyper-endemic setting, identify limitations, and assess deficiencies with modern statistical techniques. We apply the “Ayton” tool, the first risk tool applicable to sub-Saharan African AGYW, and compare performance of Balkus and Ayton tools under varying conditions. The Ayton tool more effectively predicted HIV acquisition. In low and high-risk AGYW, the Ayton tool out-performed the Balkus tool, which did not distinguish between risk classes. The Ayton tool better captured HIV acquisition risk and risk heterogeneities due to its AGYW-focused design. Findings support use of the Ayton tool for AGYW and underscore the need for diverse prognostic tools considering epidemic severity, age, sex and transmission.Clinical Trial Number ClinicalTrials.gov (NCT01187979) and the South African National Clinical Trials Registry (SANCTR) (DOH-27-0812-3345).
Exploring the molecular determinants for subtype-selectivity of 2-amino-1,4,5,6-tetrahydropyrimidine-5-carboxylic acid analogs as betaine/GABA transporter 1 (BGT1) substrate-inhibitors
Authors: Kickinger Stefanie , Al-Khawaja Anas , Haugaard Anne Stæhr , Lie Maria E. K. , Bavo Francesco , Löffler Rebekka , Damgaard Maria , Ecker Gerhard F. , Frølund Bente , Wellendorph Petrine 
Published: August 2020

AbstractWe have previously identified 2-amino-1,4,5,6-tetrahydropyrimidine-5-carboxylic acid (ATPCA) as the most potent substrate-inhibitor of the betaine/GABA transporter 1 (BGT1) (IC502.5 µM) reported to date. Herein, we characterize the binding mode of 20 novel analogs and propose the molecular determinants driving BGT1-selectivity. A series ofN1-, exocyclic-N-, andC4-substituted analogs was synthesized and pharmacologically characterized in radioligand-based uptake assays at the four human GABA transporters (hGATs) recombinantly expressed in mammalian cells. Overall, the analogs retained subtype-selectivity for hBGT1, though with lower inhibitory activities (mid to high micromolar IC50values) compared to ATPCA. Further characterization of five of these BGT1-active analogs in a fluorescence-based FMP assay revealed that the compounds are substrates for hBGT1, suggesting they interact with the orthosteric site of the transporter. In silico-guided mutagenesis experiments showed that the non-conserved residues Q299 and E52 in hBGT1 as well as the conformational flexibility of the compounds potentially contribute to the subtype-selectivity of ATPCA and its analogs. Overall, this study provides new insights into the molecular interactions governing the subtype-selectivity of BGT1 substrate-inhibitors. The findings may guide the rational design of BGT1-selective pharmacological tool compounds for future drug discovery.
Highly synergistic drug combination prevents vaginal HIV infection in humanized mice
Authors: Baum Marc M. , Ramirez Christina M. , Moss John A. , Gunawardana Manjula , Bobardt Michael , Gallay Philippe A. 
Published: August 2020

AbstractThe HIV-1 epidemic remains an urgent global health concern. Young women are disproportionately at risk of acquiring the virus. A range of highly effective, female-controlled, discrete vaginal products therefore is needed to help curb the epidemic. Oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are effective in HIV-1 pre-exposure prophylaxis (PrEP) and form a promising basis for a vaginal product. Here, we evaluate TDF and FTC in combination with the broadly neutralizing antibody VRC01-N using a highly reproducible humanized mouse model. The agents were vaginally dosed individually and in combination, and the efficacy of HIV-1 prevention was analyzed using the established, rigorous median-effect model. Surprisingly, the triple combination showed a high degree of synergism, unprecedented for in vivo HIV-1 PrEP, leading to a possible fivefold dose reduction for some of the agents. Vaginal administration of the TDF-FTC-VRC01-N combination holds significant promise for HIV-1 PrEP.
Development of a miniaturized 96-Transwell air–liquid interface human small airway epithelial model
Authors: Bluhmki Teresa , Bitzer Sarah , Gindele Julia Anna , Schruf Eva , Kiechle Tobias , Webster Megan , Schymeinsky Jürgen , Ries Robert , Gantner Florian , Bischoff Daniel , Garnett James , Heilker Ralf 
Published: August 2020

AbstractIn order to overcome the challenges associated with a limited number of airway epithelial cells that can be obtained from clinical sampling and their restrained capacity to divide ex vivo, miniaturization of respiratory drug discovery assays is of pivotal importance. Thus, a 96-well microplate system was developed where primary human small airway epithelial (hSAE) cells were cultured at an air–liquid interface (ALI). After four weeks of ALI culture, a pseudostratified epithelium containing basal, club, goblet and ciliated cells was produced. The 96-well ALI cultures displayed a cellular composition, ciliary beating frequency, and intercellular tight junctions similar to 24-well conditions. A novel custom-made device for 96-parallelized transepithelial electric resistance (TEER) measurements, together with dextran permeability measurements, confirmed that the 96-well culture developed a tight barrier function during ALI differentiation. 96-well hSAE cultures were responsive to transforming growth factor β1 (TGF-β1) and tumor necrosis factor α (TNF-α) in a concentration dependent manner. Thus, the miniaturized cellular model system enables the recapitulation of a physiologically responsive, differentiated small airway epithelium, and a robotic integration provides a medium throughput approach towards pharmaceutical drug discovery, for instance, in respect of fibrotic distal airway/lung diseases.
Platypus predation has differential effects on aquatic invertebrates in contrasting stream and lake ecosystems
Authors: McLachlan-Troup Tanya A. , Nicol Stewart C. , Dickman Christopher R. 
Published: August 2020

AbstractPredators can have strong impacts on prey populations, with cascading effects on lower trophic levels. Although such effects are well known in aquatic ecosystems, few studies have explored the influence of predatory aquatic mammals, or whether the same predator has similar effects in contrasting systems. We investigated the effects of platypus (Monotremata:Ornithorhynchus anatinus) on its benthic invertebrate prey, and tested predictions that this voracious forager would more strongly affect invertebrates—and indirectly, epilithic algae—in a mesotrophic lake than in a dynamic stream ecosystem. Hypotheses were tested using novel manipulative experiments involving platypus-exclusion cages. Platypuses had strongly suppressive effects on invertebrate prey populations, especially detritivores and omnivores, but weaker or inconsistent effects on invertebrate taxon richness and composition. Contrary to expectation, predation effects were stronger in the stream than the lake; no effects were found on algae in either ecosystem due to weak effects of platypuses on herbivorous invertebrates. Platypuses did not cause redistribution of sediment via their foraging activities. Platypuses can clearly have both strong and subtle effects on aquatic food webs that may vary widely between ecosystems and locations, but further research is needed to replicate our experiments and understand the contextual drivers of this variation.
A possible beneficial effect of Bacteroides on faecal lipopolysaccharide activity and cardiovascular diseases
Authors: Yoshida Naofumi , Yamashita Tomoya , Kishino Shigenobu , Watanabe Hikaru , Sasaki Kengo , Sasaki Daisuke , Tabata Tokiko , Sugiyama Yuta , Kitamura Nahoko , Saito Yoshihiro , Emoto Takuo , Hayashi Tomohiro , Takahashi Tomoya , Shinohara Masakazu , Osawa Ro , Kondo Akihiko , Yamada Takuji , Ogawa Jun , Hirata Ken-ichi 
Published: August 2020

AbstractFaecal lipopolysaccharides (LPS) have attracted attention as potent elements to explain a correlation between the gut microbiota and cardiovascular disease (CVD) progression. However, the underlying mechanism of how specific gut bacteria contribute to faecal LPS levels remains unclear. We retrospectively analysed the data of 92 patients and found that the abundance of the genus Bacteroides was significantly and negatively correlated with faecal LPS levels. The controls showed a higher abundance of Bacteroides than that in the patients with CVD. The endotoxin units of the Bacteroides LPS, as determined by the limulus amoebocyte lysate (LAL) tests, were drastically lower than those of the Escherichia coli LPS; similarly, the Bacteroides LPS induced relatively low levels of pro-inflammatory cytokine production and did not induce sepsis in mice. Fermenting patient faecal samples in a single-batch fermentation system with Bacteroides probiotics led to a significant increase in the Bacteroides abundance, suggesting that the human gut microbiota could be manipulated toward decreasing the faecal LPS levels. In the clinical perspective, Bacteroides decrease faecal LPS levels because of their reduced LAL activity; therefore, increasing Bacteroides abundance might serve as a novel therapeutic approach to prevent CVD via reducing faecal LPS levels and suppressing immune responses.
Crossover from BKT-rough to KPZ-rough surfaces for interface-limited crystal growth/recession
Authors: Akutsu Noriko 
Published: August 2020

AbstractThe crossover from a Berezinskii–Kosterlitz–Thouless (BKT) rough surface to a Kardar–Parisi–Zhang (KPZ) rough surface on a vicinal surface is studied using the Monte Carlo method in the non-equilibrium steady state in order to address discrepancies between theoretical results and experiments. The model used is a restricted solid-on-solid model with a discrete Hamiltonian without surface or volume diffusion (interface limited growth/recession). The temperature, driving force for growth, system size, and surface slope dependences of the surface width are calculated for vicinal surfaces tilted between the (001) and (111) surfaces. The surface velocity, kinetic coefficient of the surface, and mean height of the locally merged steps are also calculated. In contrast to the accepted theory for (2 + 1) surfaces, we found that the crossover point from a BKT (logarithmic) rough surface to a KPZ (algebraic) rough surface is different from the kinetic roughening point for the (001) surface. The driving force for crystal growth was found to be a relevant parameter for determining whether the system is in the BKT class or the KPZ class. It was also determined that ad-atoms, ad-holes, islands, and negative-islands block surface fluctuations, which contributes to making a BKT-rough surface.
Identification of resistance in Escherichia coli and Klebsiella pneumoniae using excitation-emission matrix fluorescence spectroscopy and multivariate analysis
Authors: Costa Fernanda S. L. , Bezerra Caio C. R. , Neto Renato M. , Morais Camilo L. M. , Lima Kássio M. G. 
Published: August 2020

AbstractKlebsiella pneumoniae and Escherichia coli are part of the Enterobacteriaceae family, being common sources of community and hospital infections and having high antimicrobial resistance. This resistance profile has become the main problem of public health infections. Determining whether a bacterium has resistance is critical to the correct treatment of the patient. Currently the method for determination of bacterial resistance used in laboratory routine is the antibiogram, whose time to obtain the results can vary from 1 to 3 days. An alternative method to perform this determination faster is excitation-emission matrix (EEM) fluorescence spectroscopy combined with multivariate classification methods. In this paper, Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA) and Support Vector Machines (SVM), coupled with dimensionality reduction and variable selection algorithms: Principal Component Analysis (PCA), Genetic Algorithm (GA), and the Successive Projections Algorithm (SPA) were used. The most satisfactory models achieved sensitivity and specificity rates of 100% for all classes, both for E. coli and for K. pneumoniae. This finding demonstrates that the proposed methodology has promising potential in routine analyzes, streamlining the results and increasing the chances of treatment efficiency.