bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonuniform UV-C dose across N95 facepieces can cause 2.9-log variation in SARS-CoV-2 inactivation
Authors: Geldert Alisha , Su Alison , Roberts Allison W. , Golovkine Guillaume , Grist Samantha M. , Stanley Sarah A. , Herr Amy E. 
Published: March 2021

AbstractDuring public health crises like the COVID-19 pandemic, ultraviolet-C (UV-C) decontamination of N95 respirators for emergency reuse has been implemented to mitigate shortages. However, decontamination efficacy across N95s is poorly understood, due to the dependence on received UV-C dose, which varies across the complex three-dimensional N95 shape. Robust quantification of UV-C dose across N95 facepieces presents challenges, as few UV-C measurement tools have sufficient 1) small, flexible form factor, and 2) angular response. To address this gap, we combine optical modeling and quantitative photochromic indicator (PCI) dosimetry with viral inactivation assays to generate high-resolution maps of “on-N95” UV-C dose and concomitant SARS-CoV-2 viral inactivation across N95 facepieces within a commercial decontamination chamber. Using modeling to rapidly identify on-N95 locations of interest, in-situ measurements report a 17.4 ± 5.0-fold dose difference across N95 facepieces in the chamber, yielding 2.9 ± 0.2-log variation in SARS-CoV-2 inactivation. UV-C dose at several on-N95 locations was lower than the lowest-dose locations on the chamber floor, highlighting the importance of on-N95 dose validation. Overall, we couple optical simulation with in-situ PCI dosimetry to relate UV-C dose and viral inactivation at specific on-N95 locations, informing the design of safe and effective decontamination protocols.
Combined landscape of single-nucleotide variants and copy-number alterations in clonal hematopoiesis
Authors: Saiki Ryunosuke , Momozawa Yukihide , Nannya Yasuhito , Nakagawa Masahiro M , Ochi Yotaro , Yoshizato Tetsuichi , Terao Chikashi , Kuroda Yutaka , Shiraishi Yuichi , Chiba Kenichi , Tanaka Hiroko , Niida Atsushi , Imoto Seiya , Matsuda Koichi , Morisaki Takayuki , Murakami Yoshinori , Kamatani Yoichiro , Matsuda Shuichi , Kubo Michiaki , Miyano Satoru , Makishima Hideki , Ogawa Seishi 
Published: March 2021

AbstractImplicated in the development of hematological malignancies (HM) and cardiovascular mortality, clonal hematopoiesis (CH) in apparently healthy individuals has been investigated by detecting either single-nucleotide variants and indels (SNVs/indels) or copy number alterations (CNAs), but not both. Here by combining targeted sequencing of 23 CH-related genes and array-based CNA detection of blood-derived DNA, we have delineated the landscape of CH-related SNVs/indels and CNAs in a general population of 11,234 individuals, including 672 with subsequent HM development. Both CH-related lesions significantly co-occurred, which combined, affected blood count, hypertension, and the mortality from HM and cardiovascular diseases depending on the total number of both lesions, highlighting the importance of detecting both lesions in the evaluation of CH.
Genomic prediction in an outcrossing and autotetraploid fruit crop: lessons from blueberry breeding
Authors: Ferrão Luís Felipe V. , Amadeu Rodrigo R. , Benevenuto Juliana , de Bem Oliveira Ivone , Munoz Patricio R. 
Published: March 2021

AbstractBlueberry (Vaccinium corymbosumand hybrids) is a specialty crop, with expanding production and consumption worldwide. The blueberry breeding program at the University of Florida (UF) has greatly contributed to the expansion of production areas by developing low-chilling cultivars better adapted to subtropical and Mediterranean climates of the globe. The breeding program has historically focused on phenotypic recurrent selection. As an autopolyploid, outcrossing, perennial, long juvenile phase crop, blueberry’s breeding cycles are costly and time-consuming, which results in low genetic gains per unit of time. Motivated by the application of molecular markers for a more accurate selection in early stages of breeding, we performed pioneering genomic prediction studies and optimization for implementation in the blueberry breeding program. We have also addressed some complexities of sequence-based geno- typing and model parametrization for an autopolyploid crop, providing empirical contributions that can be extended to other polyploid species. We herein revisited some of our previous genomic prediction studies and described the current achievements in the crop. In this paper, our contribution for genomic prediction in an autotetraploid crop is three-fold: i) summarize previous results on the relevance of model parametrizations, such as diploid or polyploid methods, and inclusion of dominance effects; ii) assess the importance of sequence depth of coverage and genotype dosage calling steps; iii) demonstrate the real impact of genomic selection on leveraging breeding decisions by using an independent validation set. Altogether, we propose a strategy for the use of genomic selection in blueberry, with potential to be applied to other polyploid species of a similar background.
Choice of pre-processing pipeline influences clustering quality of scRNA-seq datasets
Authors: Shainer Inbal , Stemmer Manuel 
Published: March 2021

AbstractBackgroundSingle-cell RNA sequencing (scRNA-seq) has quickly become one of the most dominant techniques in modern transcriptome assessment. In particular, 10X Genomics’ Chromium system, with its high throughput approach, turn key and thorough user guide made this cutting-edge technique accessible to many laboratories using diverse animal models. However, standard pre-processing, including the alignment and cell filtering pipelines might not be ideal for every organism or tissue. Here we applied an alternative strategy, based on the pseudoaligner kallisto, on twenty-two publicly available single cell sequencing datasets from a wide range of tissues of eight organisms and compared the results with the standard 10X Genomics’ Cell Ranger pipeline.ResultsIn most of the tested samples, kallisto produced higher sequencing read alignment rates and total gene detection rates in comparison to Cell Ranger. Although datasets processed with Cell Ranger had higher cell counts, outside of human and mouse datasets, these additional cells were routinely of low quality, containing low gene detection rates. Thorough downstream analysis of one kallisto processed dataset, obtained from the zebrafish pineal gland, revealed clearer clustering, allowing the identification of an additional photoreceptor cell type that previously went undetected. The finding of the new cluster suggests that the photoreceptive pineal gland is essentially a bi-chromatic tissue containing both green and red cone-like photoreceptors and implies that the alignment and pre-processing pipeline can affect the discovery of biologically-relevant cell types.ConclusionWhile Cell Ranger favors higher cell numbers, using kallisto results in datasets with higher median gene detection per cell. We could demonstrate that cell type identification was not hampered by the lower cell count, but in fact improved as a result of the high gene detection rate and the more stringent filtering. Depending on the acquired dataset, it can be beneficial to favor high quality cells and accept a lower cell count, leading to an improved classification of cell types.
Hepatic Leukemia Factor supports the propagation of leukemia and hematopoietic stem cell function during stress-induced regeneration
Authors: Baudet Aurélie , Komorowska Karolina , Hultmark Simon , Chapellier Marion , Miharada Kenichi , Larsson Jonas , Bryder David , Järås Marcus , Juliusson Gunnar , Magnusson Mattias 
Published: March 2021

AbstractThe processes regulating hematopoietic stem cells (HSC) during aging are not fully understood1, but it is clear that the incidence of hematological malignancies increases with age, highlighting the importance of unravelling the cellular and molecular networks involved. Recently, we identified Hepatic Leukemia Factor (HLF) as an essential transcription factor in maintaining the HSC pool during regeneration2and showed that failure to downregulate HLF leads to disrupted differentiation3.Here, we found that HLF is dispensable for hematopoiesis during systemic aging, but needed during stress-induced hematopoietic recovery of aged HSC after transplantation. Additionally, HLF was dispensable for leukemic initiation but required for disease propagation. Taken together, our findings demonstrate the existence of a HLF-dependent mechanism that uncouples stress-induced regeneration from hematopoietic homeostasis during aging, that can be used by malignant cells to gain stem cell properties to propagate the disease.Key pointsHLF is dispensable for HSC function and hematopoietic homeostasis during physiological aging, but crucial during stress induced regeneration.HLF supports the propagation of leukemia-initiating cells
Transcriptional census of epithelial-mesenchymal plasticity in cancer
Authors: Cook David P. , Vanderhyden Barbara C. 
Published: March 2021

ABSTRACTEpithelial-mesenchymal plasticity (EMP) contributes to tumour progression, promoting therapy resistance and immune cell evasion. Definitive molecular features of this plasticity have largely remained elusive due to the limited scale of most studies. Leveraging scRNA-seq data from 160 tumours spanning 8 different cancer types, we identify expression patterns associated with intratumoural EMP. Integrative analysis of these programs confirmed a high degree of diversity among tumours. These diverse programs are associated with combinations of various common regulatory mechanisms initiated from cues within the tumour microenvironment. We highlight that inferring regulatory features can inform effective therapeutics to restrict EMP.
More than the eye can see – shedding new light on SARS-CoV-2 Lateral Flow Device-based immunoassays
Authors: Koller Garrit , Morrell Alexander P , Galão Rui Pedro , Pickering Suzanne , MacMahon Eithne , Johnson Joanna , Ignatyev Konstantin , Neil Stuart JD , Elsharkawy Sherif , Fleck Roland , Pereira Machado Pedro Miguel , Addison Owen 
Published: March 2021

AbstractContaining the global SARS-CoV-2 pandemic has been an unprecedented challenge due to high horizontal transmissivity and asymptomatic carriage rates. Lateral Flow Device (LFD) immunoassays were introduced in late 2020 to detect SARS-CoV-2 infection in asymptomatic or pre-symptomatic individuals rapidly. Whilst LFD technologies have been used for over 60 years, their widespread use as a public health tool during a pandemic is unprecedented. By the end of 2020, data from studies into the efficacy of the LFDs emerged and showed these point-of-care devices to have very high specificity (ability to identify true negatives) but inadequate sensitivity with high false-negative rates. The low sensitivity (<50%) shown in several studies is a critical public health concern, as asymptomatic or pre-symptomatic carriers may wrongly be assumed to be non-infectious, posing a significant risk of further spread in the community. Here we show that the direct visual readout of SARS-CoV-2 LFDs is an inadequate approach to discriminate a potentially infective viral concentration in a bio-sample. We quantified significant immobilized antigen-antibody-label conjugate complexes within the LFDs visually scored as negative using high-sensitivity synchrotron X-ray fluorescence imaging. Correlating quantitative X-ray fluorescence measurements and qRT-PCR determined numbers of viral copies, we identified that negatively scored samples could contain up to 100 PFU (equivalent here to ∼10,000 RNA copies/test). The study demonstrates where the shortcomings arise in many of the current direct-readout SARS-CoV-2 LFDs, namely being a deficiency in the readout as opposed to the potential level of detection of the test, which is orders of magnitude higher. The present findings are of importance, both to public health monitoring during the COVID-19 pandemic and to the rapid refinement of these tools for immediate and future applications.
An Automated Radio-Telemetry System (ARTS) for Monitoring Small Mammals
Authors: Wallace Gerard , Elden (née Gorinshteyn) Marija , Boucher (née Sheely) Rachel , Phelps Steven 
Published: March 2021

AbstractPoint 1: The study of animals in nature is essential for developing an ecologically valid understanding of behavior. Small mammals, however, are often fossorial and exceedingly difficult to monitor in the wild. This limits both the taxonomic scope of field observation, and excludes species that are powerful models for the study of behavioral mechanisms.Point 2: Here, we implement an automated radio telemetry system (ARTS) designed to track small fossorial mammals. Our ARTS uses an isotropic antenna array coupled with broadband receivers. We characterized transmission at our study site and tested the ARTS’ ability to track 48 prairie voles.Point 3: We compared position estimates from nonlinear least squares, nonparameteric, and Bayesian trilateration methods and found Bayesian trilateration to have the smallest error. To examine the ability of the system to track biologically significant behavior we used ARTS data to investigate circadian rhythms of freely behaving prairie voles. We used Lomb-Scargle analysis to estimate periodic patterns from irregularly sampled time series of speed. Prairie voles demonstrated ultradian movement at periods of approximately 45 and 90 min, observations on a time scale not possible using data from traditional methods.Point 4: This ARTS offers a new tool to observe rodent field behavior at time scales and in environments which have not been previously possible, such as investigating social and spatial behaviors on the scale of minutes, hours, and days in natural environments.
COVID-19 vaccine hesitancy in care home staff: a survey of Liverpool care homes
Authors: Tulloch John S P , Lawrenson Karen , Gordon Adam L , Ghebrehewet Sam , Ashton Matthew , Peddie Steve , Parvulescu Paula 
Published: March 2021

AbstractBackgroundCOVID-19 has caused high morbidity and mortality in UK care homes. Vaccinating staff members and residents will protect care homes from severe clinical cases. Uptake of COVID-19 vaccine first doses in care homes has been higher among residents compared to staff members.MethodsWe aimed to identify causes of lower COVID-19 vaccine uptake amongst care home staff members within the Liverpool City Council region. An anonymised online survey was distributed to all care home managers between the 21st and the 29th of January 2021. Descriptive analysis was performed on responses.Results46/87 (53%) of Liverpool care homes responded. The mean staff vaccination rate per home was 51.4% (95% CI 43.9-58.8%). The most common reasons for staff not receiving the vaccine were: concerns about lack of vaccine research (37.0%), staff being off-site during vaccination sessions (36.5%), pregnancy and fertility concerns (5.6%), and concerns about allergic reactions (3.2%). Care home managers reported the necessity to combat vaccine hesitancy through meetings and conversations with health professionals, and provision of supporting evidence to dispel vaccine misinformation.ConclusionsVaccine hesitancy was the main cause for reduced vaccine uptake among care home staff members. These concerns could be addressed by targeted evidence-based training, and a public health communication campaign to build vaccine confidence and increase acceptance of COVID-19 vaccines. The speed of vaccination roll-out has also led to unexpected logistical issues that lowered vaccine uptake rates. Addressing both these challenges could increase uptake by more than 40%.Key PointsCOVID-19 vaccine uptake rates are lower in staff than residentsThree main causes of reduced uptake have been identified: vaccine hesitancy, logistical issues, and medical concerns.The main reasons for vaccine hesitancy were concerns about limited research into vaccine safety, and concerns about long-term impact on pregnancy and fertility.Addressing care home staff vaccination concerns should be given priority in these settings.
Label free sensing with Terahertz multiple ring resonators
Authors: Bai Xaing , Zhe Lujun 
Published: March 2021

AbstractApart from their relevance for spectroscopy and imaging, terahertz signals have attracted a lot of interest for sensing. In this paper, a label free terahertz sensor is proposed, which can be employed to detect the presence of molecules in the environment. The proposed sensor consists of an array of ring resonators, resonating at the frequency off=1.2 THz. By providing full-wave numerical simulations, it is shown that the proposed sensor is able to sense the variation of the refractive index in the environment. The proposed structure is found to show larger sensitivity compared to previous reports. Our findings provide a novel platform to realize label free terahertz sensors with extremely large sensitivity.
Increased disease burden in Interleukin-3 deficient mice afterMycobacterium tuberculosisand herpes simplex virus infections
Authors: Kunnath-Velayudhan Shajo , Ng Tony W. , Saini Neeraj K. , Goldberg Michael F. , Arora Pooja , Xu Jiayong , Kim John , Herold Betsy C. , Chan John , Jacobs William R. , Porcelli Steven A. 
Published: March 2021

AbstractInterleukin-3 (IL-3) is produced during infections caused by parasites, bacteria and viruses, but its contribution to immunity in this context remains largely unknown. In mouse models of parasitic infections, in which the effects of IL-3 have been most extensively studied, IL-3 has been variously reported as protective, detrimental or inconsequential. Similarly, mixed results have been reported in viral and bacterial infection models. Here, we investigated the effects of IL-3 in mouse models ofMycobacterium tuberculosisand herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections by assessing the pathogen burden, disease manifestations and survival following infection. After infection withM. tuberculosis,IL-3 deficient mice showed higher bacillary burden, increased lung pathology and reduced survival compared to wild type mice. After infection with HSV-1 through cutaneous route and HSV-2 through vaginal route, IL-3 deficient mice showed higher viral burden, increased disease manifestations and reduced survival compared to wild type mice. Our results show that IL-3 makes a subtle but significant contribution to protective immunity in these mouse models of bacterial and viral infections.
Revision and annotation of DNA barcode records for marine invertebrates: report of the 8thiBOL conference hackathon
Authors: Radulovici Adriana E. , Vieira Pedro E. , Duarte Sofia , Teixeira Marcos A. L. , Borges Luisa M. S. , Deagle Bruce , Majaneva Sanna , Redmond Niamh , Schultz Jessica A. , Costa Filipe O. 
Published: March 2021

AbstractThe accuracy of the identification of unknown specimens using DNA barcoding and metabarcoding relies on reference libraries containing records with reliable taxonomy and sequence quality. A rampant growth in barcode data led to a stringent need for data curation, especially in taxonomically difficult groups such as marine invertebrates. A major effort in curating marine barcode data deposited in the Barcode of Life Data Systems (BOLD) has been undertaken during the 8thInternational Barcode of Life Conference (Trondheim, Norway, 2019). For practical reasons, only major taxonomic groups were reviewed and annotated (crustaceans, echinoderms, molluscs, and polychaetes). The congruence of Linnean names with Barcode Index Numbers (BINs) was investigated, and the records deemed uncertain were annotated with four tags: a) MIS-ID (misidentified, mislabeled or contaminated records), b) AMBIG (ambiguous records unresolved with the current data), c) COMPLEX (species occurring in multiple BINs), and d) SHARE (barcodes shared between species). A total of 83,712 specimen records corresponding to 7,576 species were reviewed and 39% of the species were tagged (7% MIS-ID, 17% AMBIG, 14% COMPLEX, and 1% SHARE). High percentages (>50%) of AMBIG tags were recorded in gastropods, whereas COMPLEX tags dominated in crustaceans and polychaetes. This high proportion of tagged species reflects either flaws in the barcoding workflow (e.g., misidentification, cross -contamination) or taxonomic difficulties (e.g., synonyms, undescribed species). Although data curation is crucial for barcode applications, such manual efforts of reviewing large datasets are not sustainable and the implementation of automated solutions to the furthest possible extent is hi ghly desirable.
Clustering-based time series analysis on insulin response in the blood-brain barrier
Authors: Kalari Krishna R. , Wang Zengtao , Tang Xiaojia , Swaminathan Suresh K. , Kandimalla Karunya K. 
Published: March 2021

ABSTRACTBackgroundCritical functions of the blood-brain barrier (BBB), including cerebral blood flow and vascular response, are regulated by insulin signaling pathways. Therefore, endothelial insulin resistance could lead to vascular dysfunction, which is associated with neurodegenerative diseases such as Alzheimer’s disease (AD).ObjectiveThe objective of the current study is to map the dynamics of insulin-responsive pathways in polarized human cerebral microvascular endothelial cells (hCMEC/D3) cell monolayers, a widely used BBB cell culture model, to identify molecular mechanisms underlying BBB dysfunction in AD.MethodsRNA-Sequencing (RNA-Seq) was performed on hCMEC/D3 cell monolayers with and without insulin treatment at various time points. The Short Time-series Expression Miner (STEM) method was used to identify clusters of genes with distinct and representative patterns. Functional annotation and pathway analysis of the genes from top clusters were conducted using the Webgestalt and Ingenuity Pathway Analysis (IPA) software, respectively.ResultsQuantitative expression differences of 19,971 genes between the insulin-treated and control monolayers at five-time points were determined. STEM software identified 11 clusters with 3061 genes across that displayed various temporal patterns. Gene ontology enrichment analysis performed using the top 5 clusters demonstrated that these genes were enriched in various biological processes associated with AD pathophysiology. The IPA analyses revealed that signaling pathways exacerbating AD pathology such as inflammation were downregulated after insulin treatment (clusters 1 to 3). In contrast, pathways attenuating AD pathology were upregulated, including synaptogenesis and BBB repairment (clusters 4 and 5).ConclusionsThese findings unravel the dynamics of insulin action on the BBB endothelium and inform about downstream signaling cascades that potentially regulate neurovascular unit (NVU) functions that are disrupted in AD.
Fluidics System for Resolving Concentration-Dependent Effects of Dissolved Gases on Tissue Metabolism
Authors: Kamat Varun , Robbings Brian M. , Jung Seung-Ryoung , Kelly John , Hurley James B. , Bube Kenneth P. , Sweet Ian R. 
Published: March 2021

ABSTRACTOxygen (O2) and other dissolved gases such as the gasotransmitters H2S, CO and NO affect cell metabolism and function. To evaluate effects of dissolved gases on processes in tissue, we developed a fluidics system that controls dissolved gases while simultaneously measuring parameters of electron transport, metabolism and secretory function. We use pancreatic islets, retina and liver to highlight its ability to assess effects of O2and H2S. Protocols aimed at emulating hypoxia-reperfusion conditions resolved a previously unrecognized transient spike in O2consumption rate (OCR) following replenishment of O2, and tissue-specific recovery of OCR following hypoxia. The system revealed both inhibitory and stimulatory effects of H2S on insulin secretion rate from isolated islets. The unique ability of this new system to quantify metabolic state and cell function in response to precise changes in dissolved gases provides a powerful platform for cell physiologists to study a wide range of disease states.