bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Performance Evaluation of a SARS-CoV-2 Rapid Antibody Test for Determining Past Exposure to SARS-CoV-2
Authors: Findeisen Peter , Stiegler Hugo , Lopez-Calle Eloisa , Schneider Tanja , Urlaub Eva , Hayer Johannes , Zemmrich Claudia 
Published: September 2020

AbstractThe true prevalence and population seropositivity of SARS-CoV-2 infection remains unknown, due to the number of asymptomatic infections and limited access to high-performance antibody tests. To control the COVID-19 pandemic it is crucial to understand the true seroprevalence, but not every region has access to extensive centralized PCR and serology testing. Currently available rapid antibody tests lack the accuracy needed for recommendation by health authorities. To fill this gap, we analyzed and validated the clinical performance of a new point-of-care SARS-CoV-2 Rapid Antibody Assay, a chromatographic immunoassay for qualitative detection of IgM/IgG antibodies for use in near-patient settings. Analysis was performed using 42 Anti-SARS-Cov-2 positive (CoV+) and 92 Anti-SARS-Covid-2 negative (CoV-) leftover samples from before December 2019, using the Elecsys® Anti-SARS-CoV-2 as the reference assay. Analytical specificity was tested using leftover samples from individuals with symptoms of common cold collected before December 2019. The SARS-CoV-2 Rapid Antibody Test was 100.0% (95% CI 91.59–100.00) sensitive and 96.74% (95% CI 90.77–99.32) specific with an assay failure rate of 0.00%. No cross-reactivity was observed against the common cold panel. Method comparison was additionally conducted by two external laboratories, using 100 CoV+/275 CoV-samples, also comparing whole blood versus plasma matrix. The comparison demonstrated for plasma 96.00% positive/96.36% negative percent agreement with the Elecsys Anti-SARS-CoV-2 and overall 99.20% percent agreement between whole blood and EDTA plasma. The SARS-CoV-2 Rapid Antibody Test demonstrated similar clinical performance to the manufacturer's data and to a centralized automated immunoassay, with no cross-reactivity to common cold panels.
Historical trends of the ecotoxicological pesticide risk from the main grain crops in Rolling Pampa (Argentina)
Authors: Ferraro D.O. , Ghersa F , de Paula R. , Duarte Vera A.C. , Pessah S. 
Published: September 2020

AbstractWe showed the results of the first long-term analysis (1987-2019) of pesticide impact in the main agricultural area of Argentina. Using a clear and meaningful tool, based not only on acute toxicity but also on scaling up the results to total sown area, we identified time trends for both total pesticide impact and the ecoefficiency of modal pesticide profiles. By the end of the time series, soybean showed a pesticide impact four times greater than maize crop in the studied area. However, the time trend in the last years showed a sustainable pattern of pesticide use, with an improvement in the ecoefficiency. Oppositely, maize showed a relatively constant ecoefficiency value during most of the time series, suggesting a possible path towards an unsustainable cropping system. Findings from this study suggest that some efforts have to be made to improve the pest management decisions towards a more efficient pesticide profiles in maize crop and to keep improving the ecotoxicity pesticide profile in soybean crops because of its large sown area in the studied area.
Locus coeruleus integrity and the effect of atomoxetine on response inhibition in Parkinson’s disease
Authors: O’Callaghan Claire , Hezemans Frank H. , Ye Rong , Rua Catarina , Jones P. Simon , Murley Alexander G. , Holland Negin , Regenthal Ralf , Tsvetanov Kamen A. , Wolpe Noham , Barker Roger A. , Williams-Gray Caroline H. , Robbins Trevor W. , Passamonti Luca , Rowe James B. 
Published: September 2020

AbstractCognitive decline is a common feature of Parkinson’s disease, and many of these cognitive deficits fail to respond to dopaminergic therapy. Therefore, targeting other neuromodulatory systems represents an important therapeutic strategy. Among these, the locus coeruleus-noradrenaline system has been extensively implicated in response inhibition deficits. Restoring noradrenaline levels using the noradrenergic reuptake inhibitor atomoxetine can improve response inhibition in some patients with Parkinson’s disease, but there is considerable heterogeneity in treatment response. Accurately predicting the patients who would benefit from therapies targeting this neurotransmitter system remains a critical goal, in order to design the necessary clinical trials with stratified patient selection to establish the therapeutic potential of atomoxetine. Here, we test the hypothesis that integrity of the noradrenergic locus coeruleus explains the variation in improvement of response inhibition following atomoxetine. In a double-blind placebo-controlled randomised crossover design, 19 people with Parkinson’s disease completed an acute psychopharmacological challenge with 40 mg of oral atomoxetine or placebo. A stop-signal task was used to measure response inhibition, with stop-signal reaction times obtained through hierarchical Bayesian estimation of an ex-Gaussian race model. Twenty-six control subjects completed the same task without undergoing the drug manipulation. In a separate session, patients and controls underwent ultra-high field 7T imaging of the locus coeruleus using a neuromelanin-sensitive magnetisation transfer sequence. The principal result was that atomoxetine improved stop-signal reaction times in those patients with lower locus coeruleus integrity. This was in the context of a general impairment in response inhibition, as patients on placebo had longer stop-signal reaction times compared to controls. We also found that the caudal portion of the locus coeruleus showed the largest neuromelanin signal decrease in the patients compared to controls. Our results highlight a link between the integrity of the noradrenergic locus coeruleus and response inhibition in Parkinson’s disease patients. Furthermore, they demonstrate the importance of baseline noradrenergic state in determining the response to atomoxetine. We suggest that locus coeruleus neuromelanin imaging offers a marker of noradrenergic capacity that could be used to stratify patients in trials of noradrenergic therapy and to ultimately inform personalised treatment approaches.
Cellular and molecular phenotypes ofC9orf72ALS/FTD patient derived iPSC-microglia mono-cultures
Authors: Lorenzini Ileana , Alsop Eric , Levy Jennifer , Gittings Lauren M , Lall Deepti , Rabichow Benjamin E , Moore Stephen , Pevey Ryan , Bustos Lynette , Burciu Camelia , Bhatia Divya , Singer Mo , Saul Justin , McQuade Amanda , Tzioras Makis , Mota Thomas A , Logemann Amber , Rose Jamie , Almeida Sandra , Gao Fen-Biao , Marks Michael , Donnelly Christopher J , Hutchins Elizabeth , Hung Shu-Ting , Ichida Justin , Bowser Robert , Spires-Jones Tara , Blurton-Jones Mathew , Gendron Tania F , Baloh Robert H , Van Keuren-Jensen Kendall , Sattler Rita 
Published: September 2020

SummaryWhile motor and cortical neurons are affected inC9orf72ALS/FTD, it remains still largely unknown if and how non-neuronal cells induce or exacerbate neuronal damage. We generatedC9orf72ALS/FTD patient-derived induced pluripotent stem cells differentiated into microglia (iPSC-MG) and examined their intrinsic phenotypes. Similar to iPSC motor neurons,C9orf72ALS/FTD iPSC-MG mono-cultures form G4C2repeat RNA foci, exhibit reduced C9orf72 protein levels and generate dipeptide repeat proteins. Healthy control andC9orf72iPSC-MG equivalently express microglial specific genes and display microglial functions including inflammatory cytokine release and phagocytosis of extracellular toxic cargos such as synthetic amyloid beta peptides and healthy human brain synaptoneurosomes. SelectC9orf72iPSC-MG patient lines show inability to efficiently remove phagocytosed contents, suggesting dysfunction of the endosomal-lysosomal pathways. Finally, RNA sequencing revealed overall transcriptional changes in diseased microglia yet no significant differentially expressed microglial-enriched genes. These minimal differences in cellular, molecular and functional characteristics of microglial mono-cultures suggest that a diseased microenvironment is associated with microglial activation and subsequent regulation of neuronal dysfunction.
Single-cell Characterization of Acute Myeloid Leukemia and its Microenvironment Following PD-1 Blockade Based Therapy
Authors: Abbas Hussein A. , Hao Dapeng , Tomczak Katarzyna , Barrodia Praveen , Im Jin Seon , Reville Patrick K. , Alaniz Zoe , Wang Wei , Wang Ruiping , Wang Feng , Al-Atrash Gheath , Takahashi Koichi , Ning Jing , Ding Maomao , Mathews Jairo T. , Little Latasha , Zhang Jianhua , Basu Sreyashi , Konopleva Marina , Garcia-Manero Guillermo , Green Michael R. , Sharma Padmanee , Allison James P. , Kornblau Steven M. , Rai Kunal , Wang Linghua , Daver Naval , Futreal Andrew 
Published: September 2020

AbstractAcute myeloid leukemia (AML) and effector cells of immune checkpoint blockade (ICB) therapy co-reside in a complex bone marrow (BM) milieu. The interplay of tumor intrinsic and microenvironment (TME) mechanisms that influences the response to ICB-based therapies in AML have not been elucidated. Here we report our analyses of single cell RNA profiling of more than 127,000 BM cells from healthy donors and relapsed/refractory (R/R) AML patients at pre/post treatment with azacitidine/nivolumab, paired with single cell T cell receptor (TCR) repertoire profiles, to uncover factors impacting response and resistance. Loss of chromosome 7/7q conferred an immunosuppressive TME and was associated with resistance to ICB-based therapy in R/R AML. Our trajectory analysis revealed a continuum of CD8+ T cell phenotypes, characterized by differential expression of granzyme B (GZMB) and GZMK. GZMK expression defined a BM residing memory CD8+ T cell subset with stem-like properties likely an intermediary between naïve and cytotoxic lymphocytes. Responses to ICB-based therapy were primarily driven by novel and expanded T cell clonotypes. Our findings support an adaptable T cell plasticity in response to PD-1 blockade in AML. Disentangling AML cells from their complex, immune-rich microenvironment revealed characteristics that shaped resistance to ICB-based therapy and could inform strategies to target AML vulnerabilities.SignificanceDetermining the cellular and molecular underpinnings of response and resistance to PD-1 blockade based therapy in AML can guide immune-based therapeutic strategies. Our results reveal AML intrinsic characteristics (chromosome 7/7q status and oxidative stressors) and tumor microenvironment to modulate responses to checkpoint blockers. CD8 cells exist in the bone marrow in a continuum with GZMK expression defining a memory, stem-like T cell population that could play a role in response to therapy.
Bacterial Peptidoglycan Fragments Differentially Regulate Innate Immune Signaling
Authors: Bersch Klare L. , DeMeester Kristen E. , Zagani Rachid , Wodzanowski Kimberly A. , Reinecker Hans-Christian , Grimes Catherine L. 
Published: September 2020

ABSTRACTThe human innate immune system responds to both pathogen and commensal bacteria at the molecular level using bacterial peptidoglycan (PG) recognition elements. Traditionally, synthetic and commercially accessible PG monosaccharide units known as muramyl dipeptide (MDP) andN-glycolyl MDP (ng-MDP) have been used to probe the mechanism of innate immune activation of pattern recognition receptors (PRRs) such as NOD-like receptors (NLRs). However, bacterial PG is a dynamic and complex structure, with various chemical modifications and trimming mechanisms that result in the production of disaccharide containing elements. These molecules pose as attractive targets for immunostimulatory screening; however, studies are limited due to their synthetic accessibility. Inspired by disaccharide containing compounds produced from the gut microbe,Lactobacillus acidophilus, a robust and scalable chemical synthesis of PG-based disaccharide ligands was implemented. Together with a monosaccharide PG library, compounds were screened for their ability to stimulate proinflammatory genes in bone marrow derived macrophages (BMDMs). The data reveal a diverse gene induction pattern between monosaccharide and disaccharide PG units, suggesting that PG innate immune signaling is more complex than a one-activator-one pathway program, as biologically relevant fragments induce distinct transcriptional programs. These disaccharide molecules will serve as critical immunostimulatory tools to more precisely define specialized innate immune regulatory mechanisms that distinguish between commensal and pathogenic bacteria residing in the microbiome.
A Single Dose of Self-Transcribing and Replicating RNA Based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity In Mice
Authors: de Alwis Ruklanthi , Gan Esther S , Chen Shiwei , Leong Yan Shan , Tan Hwee Cheng , Zhang Summer L , Yau Clement , Matsuda Daiki , Allen Elizabeth , Hartman Paula , Park Jenny , Alayyoubi Maher , Bhaskaran Hari , Dukanovic Adrian , Bao Belle , Clemente Brenda , Vega Jerel , Roberts Scott , Gonzalez Jose A. , Sablad Marciano , Yelin Rodrigo , Taylor Wendy , Tachikawa Kiyoshi , Parker Suezanne , Karmali Priya , Davis Jared , Sullivan Sean M. , Hughes Steve G. , Chivukula Pad , Ooi Eng Eong 
Published: September 2020

ABSTRACTA self-transcribing and replicating RNA (STARR™) based vaccine (LUNAR®-COV19) has been developed to prevent SARS-CoV-2 infection. The vaccine encodes an alphavirus-based replicon and the SARS-CoV-2 full length spike glycoprotein. Translation of the replicon produces a replicase complex that amplifies and prolong SARS-CoV-2 spike glycoprotein expression. A single prime vaccination in mice led to robust antibody responses, with neutralizing antibody titers increasing up to day 60. Activation of cell mediated immunity produced a strong viral antigen specific CD8+T lymphocyte response. Assaying for intracellular cytokine staining for IFN-γ and IL-4 positive CD4+T helper lymphocytes as well as anti-spike glycoprotein IgG2a/IgG1 ratios supported a strong Th1 dominant immune response. Finally, single LUNAR-COV19 vaccination at both 2 μg and 10 μg doses completely protected human ACE2 transgenic mice from both mortality and even measurable infection following wild-type SARS-CoV-2 challenge. Our findings collectively suggest the potential of Lunar-COV19 as a single dose vaccine.
Increasing salinity of fibrinogen solvent generates stable fibrin hydrogels for cell delivery or tissue engineering
Authors: Jarrell Dillon K. , Vanderslice Ethan J. , Lennon Mallory L. , Lyons Anne C. , VeDepo Mitchell C. , Jacot Jeffrey G. 
Published: September 2020

AbstractFibrin has been used clinically for wound coverings, surgical glues, and cell delivery because of its affordability, cytocompatibility, and ability to modulate angiogenesis and inflammation. However, its rapid degradation rate has limited its usefulness as a scaffold for 3D cell culture and tissue engineering. Previous studies have sought to slow the degradation rate of fibrin with the addition of proteolysis inhibitors or synthetic crosslinkers that require multiple functionalization or polymerization steps. These strategies are difficult to implementin vivoand introduce increased complexity, both of which hinder the use of fibrin in research and medicine. Previously, we demonstrated that the simple inclusion of bifunctionalized poly(ethylene glycol)-n-hydroxysuccinimide (PEG-NHS) in the fibrinogen solvent slows the degradation rate of fibrin by providing additional crosslinking. In this study, we aimed to further improve the longevity of fibrin gels such that they could be used for tissue engineering in vitro or in situ without the need for proteolysis inhibitors. It is well documented that increasing the salinity of fibrin precursor solutions affects the resulting gel morphology. In this study, we investigated whether this altered morphology influences the fibrin degradation rate. Increasing the final sodium chloride (NaCl) concentration from 145 mM (physiologic level) to 250 mM resulted in fine, transparent high-salt (HS) fibrin gels that degrade 2-3 times slower than coarse, opaque physiologic-salt (PS) fibrin gels bothin vitro(when treated with proteases and when seeded with amniotic fluid stem cells) andin vivo(when injected subcutaneously into mice). Increased salt concentrations did not affect the viability of encapsulated cells, the ability of encapsulated endothelial cells to form rudimentary capillary networks, or the ability of the gels to maintain induced pluripotent stem cells. Finally, when implanted subcutaneously, PS gels degraded completely within one week while HS gels remained stable and maintained viability of seeded dermal fibroblasts. To our knowledge, this is the simplest method reported for the fabrication of fibrin gels with tunable degradation properties and will be useful for implementing fibrin gels in a wide range of research and clinical applications.
A fully defined pluripotent stem cell derived multi-liver-cell model for steatohepatitis and fibrosis
Authors: Kumar Manoj , Toprakhisar Burak , Van Haele Matthias , Antoranz Asier , Boon Ruben , Chesnais Francois , De Smedt Jonathan , Idoype Teresa Izuel , Canella Marco , Tilliole Pierre , De Boeck Jolan , Tricot Tine , Bajaj Manmohan , Ranga Adrian , Bosisio Francesca Maria , Roskams Tania , van Grunsven Leo A , Verfaillie Catherine M 
Published: September 2020

AbstractChronic liver injury, as observed in non-alcoholic steatohepatitis (NASH), progressive fibrosis, and cirrhosis, remains poorly treatable. Steatohepatitis causes hepatocyte loss in part by a direct lipotoxic insult, which is amplified by derangements in the non-parenchymal cellular (NPC) interactive network wherein hepatocytes reside, including, hepatic stellate cells, liver sinusoidal endothelial cells and liver macrophages. To create an in vitro culture model encompassing all these cells that allows studying liver steatosis, inflammation and fibrosis caused by NASH, we here developed a fully defined hydrogel microenvironment, termed hepatocyte maturation (HepMat) gel, that supports maturation and maintenance of pluripotent stem cell (PSC)-derived hepatocyte- and NPC-like cells for at least one month. The HepMat-based co-culture system modeled key molecular and functional features of TGFβ-induced liver fibrosis and fatty-acid induced inflammation and fibrosis better than monocultures its constituent cell populations. The novel co-culture system should open new avenues for studying mechanisms underlying liver steatosis, inflammation and fibrosis as well as for assessing drugs counteracting these effects.
Exploring and explaining properties of motion processing in biological brains using a neural network
Authors: Rideaux Reuben , Welchman Andrew E 
Published: September 2020

ABSTRACTVisual motion perception underpins behaviours ranging from navigation to depth perception and grasping. Our limited access to biological systems constrain our understanding of how motion is processed within the brain. Here we explore properties of motion perception in biological systems by training a neural network (‘MotionNetxy’) to estimate the velocity image sequences. The network recapitulates key characteristics of motion processing in biological brains, and we use our complete access to its structure explore and understand motion (mis)perception at the computational-, neural-, and perceptual-levels. First, we find that the network recapitulates the biological response to reverse-phi motion in terms of direction. We further find that it overestimates the speed of slow reverse-phi motion while underestimating the speed of fast reverse-phi motion because of the correlation between reverse-phi motion and the spatiotemporal receptive fields tuned to motion in opposite directions. Second, we find that the distribution of spatiotemporal tuning properties in the V1 and MT layers of the network are similar to those observed in biological systems. We then show that compared to MT units tuned to fast speeds, those tuned to slow speeds primarily receive input from V1 units tuned to high spatial frequency and low temporal frequency. Third, we find that there is a positive correlation between the pattern-motion and speed selectivity of MT units. Finally, we show that the network captures human underestimation of low coherence motion stimuli, and that this is due to pooling of noise and signal motion. These findings provide biologically plausible explanations for well-known phenomena, and produce concrete predictions for future psychophysical and neurophysiological experiments.
Broad-range RNA modification analysis of complex biological samples using rapid C18-UPLC-MS
Authors: Gregorova Pavlina , Sipari Nina H. , Sarin L. Peter 
Published: September 2020

ABSTRACTPost-transcriptional RNA modifications play an important role in cellular metabolism with homeostatic disturbances manifesting as a wide repertoire of phenotypes, reduced stress tolerance and translational perturbation, developmental defects, and diseases, such as type II diabetes, leukemia and carcinomas. Hence, there has been an intense effort to develop various methods for investigating RNA modifications and their roles in various organisms, including sequencing-based approaches and, more frequently, liquid chromatography mass spectrometry (LC-MS)-based methods. Although LC-MS offers numerous advantages, such as being highly sensitive and quantitative over a broad detection range, some stationary phase chemistries struggle to resolve positional isomers. Furthermore, the demand for detailed analyses of complex biological samples often necessitates long separation times, hampering sample-to-sample turnover and making multisample analyses time consuming. To overcome this limitation, we have developed an ultra-performance LC-MS (UPLC-MS) method that uses an octadecyl carbon chain (C18)-bonded silica matrix for the efficient separation of 50 modified ribonucleosides, including positional isomers, in a single 9 min sample-to-sample run. To validate the performance and versatility of our method, we analyzed tRNA modification patterns of representative microorganisms from each kingdom of life, namely Archaea (Methanosarcina acetivorans), Bacteria (Pseudomonas syringae) and Eukarya (Saccharomyces cerevisiae). Additionally, our method is flexible and readily applicable for detection and relative quantification using stable isotope labelling and targeted approaches like multiple reaction monitoring (MRM). In conclusion, this method represents a fast and robust tool for broad-range exploration and quantification of ribonucleosides, facilitating future homeostasis studies of RNA modification in complex biological samples.