bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimisation and comparison of orthogonal methods for separation and characterisation of extracellular vesicles to investigate how representative infant milk formula is of milk
Authors: Mukhopadhya Anindya , Santoro Jessie , Moran Barry , Useckaite Zivile , O’Driscoll Lorraine 
Published: July 2020

AbstractThis study aimed to separate and characterise extracellular vesicles (EV) from infant milk formula (IMF) and skim milk (SM), to determine how representative the EV content of IMF is to SM. Contaminant casein micelles, due to their abundance and overlapping size, were removed followed by either differential ultracentrifugation (DUC) or gradient ultracentrifugation (GUC). Characterisation included BCA, SDS-PAGE, nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), immunoblotting, and imaging flow cytometry (IFCM). NTA reported significantly reduced concentrations of EVs/particles in IMF versus SM; TEM showed intact SM-derived EVs to sparse and disrupted EV-like structures in IMF. Compared to IMF, noticeably stronger bands for EV biomarkers were observed by immunoblotting in SM, indicating compromised EV proteins in IMF; also supported by IFCM. Altogether, we established that EVs are substantially compromised during IMF processing. Furthermore, an optimised method combining acid pre-treatment and GUC for EV separation from milk products has been established.
Biomarkers of Memory Variability in Traumatic Brain Injury
Authors: Adamovich-Zeitlin Richard , Wanda Paul A. , Solomon Ethan , Phan Tung , Lega Bradley , Jobst Barbara C. , Gross Robert E. , Ding Kan , Diaz-Arrastia Ramon , Kahana Michael J. 
Published: July 2020

AbstractTraumatic brain injury (TBI) is a leading cause of cognitive disability and is often associated with significant impairment in episodic memory. In TBI survivors, as in healthy controls, there is marked variability between individuals in memory ability. Using recordings from indwelling electrodes, we characterized and compared the oscillatory biomarkers of mnemonic variability in two cohorts of epilepsy patients: a group with a history of moderate-to-severe TBI (n= 37) and a group of non-TBI controls (n= 111) closely matched for demographics and electrode coverage. Analysis of these recordings demonstrated that increased high frequency power and decreased theta power across a broad set of brain regions mark periods of successful memory formation in both groups. As features in a logistic-regression classifier, spectral power biomarkers effectively predicted recall probability, with little difference between TBI and non-TBI controls. The two groups also displayed similar patterns of theta-frequency connectivity during successful encoding periods. These biomarkers of successful memory, highly conserved between TBI patients and controls, could serve as the basis for novel therapies that target disordered memory across diverse forms of neurological disease.
Mass cytometry analysis of the NK cell receptor-ligand repertoire reveals unique differences between dengue-infected children and adults
Authors: McKechnie Julia L. , Beltrán Davis , Ferreira Anne-Maud M. , Vergara Rosemary , Saenz Lisseth , Vergara Ofelina , Estripeaut Dora , Araúz Ana B. , Simpson Laura J. , Holmes Susan , López-Vergès Sandra , Blish Catherine A. 
Published: July 2020

AbstractDengue virus (DENV) is a significant cause of morbidity in many regions of the world, with children at the greatest risk of developing severe dengue. Natural killer (NK) cells, characterized by their ability to rapidly recognize and kill virally infected cells, are activated during acute DENV infection. However, their role in viral clearance versus pathogenesis has not been fully elucidated. Our goal was to profile the NK cell receptor-ligand repertoire to provide further insight into the function of NK cells during pediatric and adult DENV infection. We used mass cytometry (CyTOF) to phenotype isolated NK cells and peripheral blood mononuclear cells (PBMCs) from a cohort of DENV-infected children and adults. Using unsupervised clustering, we found that pediatric DENV infection leads to a decrease in total NK cell frequency with a reduction in the percentage of CD56dimCD38brightNK cells and an increase in the percentage of CD56dimperforinbrightNK cells. No such changes were observed in adults. Next, we identified markers predictive of DENV infection using a differential state test. In adults, NK cell expression of activation markers, including CD69, perforin, and Fas-L, and myeloid cell expression of activating NK cell ligands, namely Fas, were predictive of infection. In contrast, NK cell expression of the maturation marker CD57 and increased myeloid cell expression of inhibitory ligands, such as HLA class I molecules, were predictive of pediatric DENV infection. These findings suggest that acute pediatric DENV infection may result in diminished NK cell activation, which could contribute to enhanced pathogenesis and disease severity.
ERβ regulated ovarian kisspeptin plays an important role in oocyte maturation
Authors: Chakravarthi V. Praveen , Ghosh Subhra , Roby Katherine F. , Wolfe Michael W. , Rumi M. A. Karim 
Published: July 2020

AbstractKisspeptin (KISS1) signaling in the hypothalamic-pituitary (H-P) axis plays essential role in regulating gonadotropin secretion. KISS1 and KISS1 receptor (KISS1R) are also expressed in the ovary; however, the role of intraovarian KISS1 signaling remains largely unclear. Granulosa cell (GC)-specific expression of KISS1, and oocyte-specific expression of KISS1R indicate that GC-derived KISS1 may act on oocytes. Expression of KISS1 in GCs is induced by gonadotropins but it is absent in estrogen receptor β knockout (Erβnull) rats. We also observed that gonadotropin stimulation failed to induce maturation ofErβnulloocytes. Interestingly, KISS1 treatment of cumulus oocyte complexes (COCs) isolated from antral follicles promotesin vitromaturation of oocytes. Treatment of oocytes with KISS1 induced intracellular Ca2+release, and increased activation of MAP kinase ERK1/2. KISS1 treatment also induced the expression of oocyte genes that are crucial for differentiation of GCs, and maturation of oocytes. Our findings suggest that ovarian KISS1-signaling plays an important role in gonadotropin induced follicle development and oocyte maturation.
Heterogeneity in signaling pathway activity within primary and between primary and metastatic breast cancer
Authors: Inda Márcia A. , van Swinderen Paul , van Brussel Anne , Moelans Cathy B. , Verhaegh Wim , van Zon Hans , Biezen Eveline den , Bikker Jan Willem , van Diest Paul J. , van de Stolpe Anja 
Published: July 2020

AbstractBackgroundTargeted drug treatment aims to block tumor driving signaling pathways, and is generally based on analysis of one primary tumor (PT) biopsy. Phenotypic heterogeneity within primary and between primary and metastatic lesions was investigated.MethodsActivity of androgen and estrogen receptor, PI3K-FOXO, Hedgehog, TGFβ, and Wnt signaling pathways was measured in breast cancer samples using a novel mRNA-based assay platform. Macro-scale heterogeneity analysis was performed on multiple spatially distributed PT tissue blocks from 17 luminal A-like, 9 luminal B-like, and 9 ER-negative primary breast cancers; micro-scale heterogeneity analysis was performed on four “quadrant” samples of a single tissue block of respectively 9, 4, and 4 matched PT. Samples from 6 PT with matched lymph node (LN, n=23) and 9 PT with distant metastatic sites (DS, n=12) were analyzed. Statistical variance analysis was performed with linear mixed models. A “checkerboard” model was introduced to explain the observed heterogeneity in PT.ResultsWithin PT, macro-scale heterogeneity in signaling pathway activity was similar to micro-scale heterogeneity, with a possible exception of the PI3K pathway. Variation was significantly higher on microscale for Hedgehog and TGFβ pathways. While pathway activity scores correlated significantly between different locations in the PT, positive correlations decreased between PT and LN, and even more between PT and DS metastases, including the emergence of a negative correlation for the ER pathway.ConclusionWith a possible exception of the PI3K pathway, variation in signaling pathway activity within a single PT tissue block was generally representative for the whole PT, but not for DS or LN metastases. The higher variation in TGFβ and HH pathway activity on microscale suggested the presence of multiple small cancer cell clones. While analysis of multiple sub-samples of a single biopsy block may be sufficient to predict PT response to some targeted therapies, such as hormonal therapy, metastatic breast cancer treatment requires analysis of metastatic biopsies. The findings on phenotypic intra-tumor heterogeneity are compatible with currently emerging ideas on a Big Bang type of cancer evolution.
Rationing and triage of scarce, lifesaving therapy in the context of the COVID-19 pandemic - a cross-sectional, social media-driven, scenario-based online query of societal attitudes
Authors: Muensterer Oliver J. , Gianicolo Emilio A. , Paul Norbert W. 
Published: July 2020

ABSTRACTBackgroundThe recent COVID-19 pandemic made us aware that medical resources are limited. When demand for essential resources surpasses availability, difficult triaging decisions are necessary. While algorithms exist, almost nothing is known on societal attitudes regarding triage criteria.MethodsA cross-sectional survey was conducted via social media channels to query a broad sample of society. Participants were asked to make triage decisions in case-based vignettes, exploring a variety of factors. They also were asked to assess how sure they were about their decisions, and how such decisions should be reached.ResultsThe survey was completed in full by 1626 participants in April 2020. Median age was 39 years (range 12-80 years), 984 (61%) were female. Patient prognosis, responsibility towards others, the absence of behavior-induced co-morbidities, and younger age were rated the most important triage criteria, while participants found that insurance status, social status, and nationality should not play a substantial role. Ethics-committees and point systems were regarded potentially helpful for triage decision-making, while decisions based on order of presentation (first-come first-serve) or on a legal basis were viewed critically. Participants were least sure about their decision when dealing with age or behavior-induced co-morbidities. Overall, women were surer about their decisions than men, participants of Christian faith were also more secure about their decision than atheists-agnostics.ConclusionsThis study uses social media to generate insight into public opinion and attitudes regarding triage criteria and modalities. These findings may be helpful for the development of future medical triage algorithms.
Unemployment insurance and food insecurity among people who lost employment in the wake of COVID-19
Authors: Raifman Julia , Bor Jacob , Venkataramani Atheendar 
Published: July 2020

AbstractForty million U.S. residents lost their jobs in the first two months of the coronavirus disease 2019 (COVID-19) pandemic. In response, the Federal Government expanded unemployment insurance benefits in both size ($600/week supplement) and scope (to include caregivers and self-employed workers). We assessed the relationship between unemployment insurance and food insecurity among people who lost their jobs during the COVID-19 pandemic in the period when the federal unemployment insurance supplement was in place. We analyzed data from the Understanding Coronavirus in America (UAC) cohort, a longitudinal survey collected by the University of Southern California Center for Economic and Social Research (CESR) every two weeks between April 1 and July 8, 2020. We limited the sample to individuals living in households earning less than $75,000 in February 2020 who lost their jobs during COVID-19. Using difference-in-differences and event study regression models, we evaluated the association between receipt of unemployment insurance and self-reported food insecurity and eating less due to financial constraints. We found that 40.5% of those living in households earning less than $75,000 and employed in February 2020 experienced unemployment during the COVID-19 pandemic. Of those who lost their jobs, 31% reported food insecurity and 33% reported eating less due to financial constraints. Food insecurity peaked in April 2020 and declined over time, but began to increase again among people receiving unemployment insurance during the final wave of the survey ahead of the federal supplement to unemployment insurance ending. Food insecurity and eating less were more common among people who were non-White, lived in lower-income households, younger, and who were sexual or gender minorities. Receipt of unemployment insurance was associated with a 4.4 percentage point (95% CI: −7.8 to −0.9 percentage points) decline in food insecurity (a 30.3% relative decline compared to the average level of food insecurity during the study period). Receipt of unemployment insurance was also associated with a 6.1 percentage point (95% CI: −9.6 to −2.7 percentage point) decline in eating less due to financial constraints (a 42% relative decline). Estimates from event study specifications revealed that reductions in food insecurity and eating less were greatest in the four-week period immediately following receipt of unemployment insurance, with no evidence of differential pre-existing trends in either outcome. We conclude that receiving unemployment insurance benefits during the period when the $600/week federal supplement was in place was associated with large reductions in food insecurity.
Clinical validation of innovative, low cost, kit-free, RNA processing protocol for RT-PCR based COVID-19 testing
Authors: Sahajpal Nikhil Shri , Mondal Ashis K , Njau Allan , Ananth Sudha , Kothandaraman Arvind , Hegde Madhuri , Chaubey Alka , Padala Sandeep , Kota Vamsi , Caspary Kevin , Tompkins Stephen M , Ross Ted , Rojani Amyn M. , Kolhe Ravindra 
Published: July 2020

AbstractThe current gold-standard molecular diagnosis for COVID-19 is based on a multi-step assay involving RNA-extraction and RT-PCR analysis for the detection of SARS-CoV-2. RNA-extraction step has been a major rate-limiting step in implementing high-throughput screening for COVID-19 during this pandemic. Moreover, clinical laboratories are facing several challenges that include cost, reagents, instrumentation, turn-around time, trained personnel, and supply-chain constraints to efficiently implement and sustain testing. Cognizant of these limitations, we evaluated the extraction-free methods described in the literature and have developed an innovative, simplified and easy protocol employing limited reagents to extract RNA for subsequent RT-PCR analysis. Nasopharyngeal-swab samples were subjected to the following individual conditions: 65°C for 15 minutes; 80°C for 5 minutes; 90°C for 5 minutes or 80°C for 1 minute, and processed for direct RT-PCR. These groups were also compared with a supplemental protocol adding isopropanol-ethanol-water elution steps followed by RT-PCR assay. The direct RT-PCR assay did not detect SARS-CoV-2 within the various temperature incubation only groups, whereas, the 90°C for 5 minutes-isopropanol-ethanol-water method was found to be comparable to the FDA-EUA method. Evaluation of the performance metrics for 100 clinical samples demonstrated a sensitivity of 94.2% and a specificity of 100%. The limit of detection was ascertained to be ∼40 copies/ml by absolute-quantification. The protocol presented for this assay employs limited reagents and yields results with high sensitivity. Additionally, it presents a simplified methodology that would be easier to implement in laboratories in limited resource countries in order to meet the high current COVID-19 testing needs.
Optimizing antiviral treatment for seasonal influenza in the United States: A Mathematical Modeling Analysis
Authors: Yechezkel Matan , Ndeffo Mbah Martial L , Yamin Dan 
Published: July 2020

AbstractSeasonal influenza remains a major health burden in the United States. Despite recommendations of early antiviral treatment of high-risk patients, the effective treatment coverage remains very low. We developed an influenza transmission model that incorporates data on infectious viral load, social contact, and healthcare-seeking behavior, to evaluate the population-level impact of increasing antiviral treatment timeliness and coverage among high-risk patients in the US. We found that increasing the rate of early treatment among high-risk patients who received treatment more than 48 hours after symptoms onset, would substantially avert infections and influenza-induced hospitalizations. We found that treatment of the elderly has the highest impact on reducing hospitalizations, whereas treating high-risk individuals aged 5-19 years old has the highest impact on transmission. The population-level impact of increased timeliness and coverage of treatment among high-risk patients was observed regardless of seasonal influenza vaccination coverage and the severity of the influenza season.
COVID-19: Time-Dependent Effective Reproduction Number and Sub-notification Effect Estimation Modeling
Authors: de Carvalho Eduardo Atem , de Carvalho Rogerio Atem 
Published: July 2020

ABSTRACTBackgroundSince the beginning of the COVID-19 pandemic, researchers and health authorities have sought to identify the different parameters that govern their infection and death cycles, in order to be able to make better decisions. In particular, a series of reproduction number estimation models have been presented, with different practical results.ObjectiveThis article aims to present an effective and efficient model for estimating the Reproduction Number and to discuss the impacts of sub-notification on these calculations.MethodsThe concept of Moving Average Method with Initial value (MAMI) is used, as well as a model for Rt, the Reproduction Number, is derived from experimental data. The models are applied to real data and their performance is presented.ResultsAnalyses on Rt and sub-notification effects for Germany, Italy, Sweden, United Kingdom, South Korea, and the State of New York are presented to show the performance of the methods here introduced.ConclusionsWe show that, with relatively simple mathematical tools, it is possible to obtain reliable values for time-dependent, incubation period-independent Reproduction Numbers (Rt). We also demonstrate that the impact of sub-notification is relatively low, after the initial phase of the epidemic cycle has passed.
New measures of agency from an adaptive sensorimotor task
Authors: Wang Shiyun , Rajananda Sivananda , Lau Hakwan , Knotts J. D. 
Published: July 2020

AbstractSelf-agency, the sense that one is the author or owner of one’s behaviors, is impaired in multiple psychological and neurological disorders, including functional movement disorders, Parkinson’s Disease, alien hand syndrome, schizophrenia, and dystonia. Existing assessments of self-agency, many of which focus on agency of movement, can be prohibitively time-consuming and often yield ambiguous results. Here, we introduce a short online motion tracking task that quantifies movement agency through both first-order perceptual and second-order metacognitive judgments. The task assesses the degree to which a participant can distinguish between a motion stimulus whose trajectory is influenced by the participant’s cursor movements and a motion stimulus whose trajectory is random. We demonstrate the task’s reliability in healthy participants and discuss how its efficiency, reliability, and ease of online implementation make it a promising new tool for both diagnosing and understanding disorders of agency.
The construction and deconstruction of sub-optimal preferences through range-adapting reinforcement learning
Authors: Bavard Sophie , Rustichini Aldo , Palminteri Stefano 
Published: July 2020

AbstractConverging evidence suggests that economic values are rescaled as a function of the range of the available options. Critically, although locally adaptive, range adaptation has been shown to lead to suboptimal choices. This is particularly striking in reinforcement learning (RL) situations when options are extrapolated from their original context. Range adaptation can be seen as the result of an adaptive coding process aiming at increasing the signal-to-noise ratio. However, this hypothesis leads to a counter-intuitive prediction: decreasing outcome uncertainty should increase range adaptation and, consequently, extrapolation errors. Here, we tested the paradoxical relation between range adaptation and performance in a large sample of subjects performing variants of a RL task, where we manipulated task difficulty. Results confirmed that range adaptation induces systematic extrapolation errors and is stronger when decreasing outcome uncertainty. Finally, we propose a range-adapting model and show that it is able to parsimoniously capture all the observed results.
Sex-Specific Genetic Architecture Of Behavioral Traits In A Spider
Authors: Kralj-Fišer Simona , Schneider Jutta M. , Kuntner M. , Garcia-Gonzalez Francisco 
Published: July 2020

ABSTRACTSex differences in behavioral traits are common, but we know little about the role of sexual selection in shaping these traits. Estimating sex-specific genetic effects and cross-sex genetic correlations can provide insights into sex-specific selection and on whether evolution can shape independent expression of behavioral traits across the sexes. We conducted a quantitative genetic study in a sexually-size-dimorphic spider,Larinioides sclopetarius, which exhibits sex differences in adult life-styles. We observed pedigreed spiders for aggression, activity, exploration and boldness, and used animal models to disentangle genetic and environmental influences on these behaviors. We detected higher additive genetic variances in activity and aggression in males compared to females, but no sex differences in quantitative genetic estimates for exploration and boldness. The estimated mean cross-sex genetic correlation in all traits were close to zero suggesting these traits could have flexibility for sex-independent evolution. We note however, that the 95% credible intervals of cross-sex genetic correlation are large, and thus estimates uncertain. Our results imply that individual variation in aggression and activity might stem from sex-specific selection acting on these traits. The estimates of sex-specific additive genetic variation and cross-sex genetic correlation suggests their further sex-independent evolution. Taken together, our results support the notion that sexual selection can play an important role shaping behavioral traits.