bluuebunny/crossref_metadata_2025_split huggingface dataset:
FACT- Frankfurt adjusted COVID-19 testing- a novel method enables high-throughput SARS-CoV-2 screening without loss of sensitivity
Authors: Schmidt Michael , Hoehl Sebastian , Berger Annemarie , Zeichhardt Heinz , Hourfar Kai , Ciesek Sandra , Seifried Erhard 
Published: May 2020

AbstractBackgroundIn the pandemic, testing for SARS-CoV-2 by RT-PCR in one of the pillars on which countermeasures are based. Factors limiting the output of laboratories interfere with the effectiveness of public health measures. Conserving reagents by pooling samples in low-probability settings is proposed, but may cause dilution and loss of sensitivity.MethodsWe tested an alternate approach (FACT) by simultaneously incubating multiple respiratory swabs in a single tube. This protocol was evaluated by serial incubation of a respiratory swab in up to 10 tubes. The analytics validity of this concept was demonstrated in a five-sample mini pool set-up. It was consequently applied in the testing of 50 symptomatic patients (five-sample pools) as well as 100 asymptomatic residents of a nursing home (ten-sample pools).ResultsSerial incubation of a respiratory swab in up to 10 tubes did not lead to a significant decline in viral concentration. The novel FACT-protocol did not cause a false negative result in a five-sample mini-pool setup, with non-significantly differing Ct values between single sample and mini-pool NAT. In two routine applications, all mini pools containing positive patient samples were correctly identified.ConclusionsOur proposed FACT-protocol did not cause a significant loss in analytic or diagnostic sensitivity compared to single sample testing in multiple setups. It reduced the amount of reagents needed by up to 40%, and also reduced hands-on time. This method could enhance testing efficiency, especially in groups with a low pretest-probability, such as systemically relevant professional groups.
Curbing the AI-induced enthusiasm in diagnosing COVID-19 on chest X-Rays: the present and the near-future
Authors: Burlacu Alexandru , Crisan-Dabija Radu , Popa Iolanda Valentina , Artene Bogdan , Birzu Vasile , Pricop Mihai , Plesoianu Cristina , Generali Daniele 
Published: May 2020

AbstractIn the current context of COVID-19 pandemic, a rapid and accessible screening tool based on image processing of chest X-rays (CXRs) using machine learning (ML) approaches would be much needed. Initially, we intended to create and validate an ML software solution able to discriminate on the basis of the CXR between SARS-CoV-2-induced bronchopneumonia and other bronchopneumonia etiologies.A systematic search of PubMed, Scopus and arXiv databases using the following search terms [“artificial intelligence” OR “deep learning” OR “neural networks”], AND [“COVID-19” OR “SARS-CoV-2”] AND [“chest X-ray” OR “CXR” OR “X-ray”] found 14 recent studies. Most of them declared to be able to confidently identify COVID-19 based on CXRs using deep neural networks. Firstly, weaknesses of artificial intelligence (AI) solutions were analyzed, tackling the issues with datasets (from both medical and technical points of view) and the vulnerability of used algorithms. Then, arguments were provided for why our study design is stronger and more realistic than the previously quoted papers, balancing the possible false expectations with facts.The authors consider that the potential of AI use in COVID-19 diagnosis on CXR is real. However, scientific community should be careful in interpreting statements, results and conclusions regarding AI use in imaging. It is therefore necessary to adopt standards for research and publication of data, because it seems that in the recent months scientific reality suffered manipulations and distortions. Also, a call for responsible approaches to the imaging methods in COVID-19 is raised. It seems mandatory to follow some rigorous approaches in order to provide with adequate results in daily routine. In addition, the authors intended to raise public awareness about the quality of AI protocols and algorithms and to encourage public sharing of as many CXR images with common quality standards.
COVID-19 versus non-COVID-19 pneumonia: A retrospective cohort study in Chengdu, China
Authors: Li Xiao-Jin , Shuai Bing-Xing , Zhang Zhong-Wei , Kang Yan 
Published: May 2020

Background and ObjectiveSince the outbreak of coronavirus disease 2019 (COVID-19) in December 2019 in Wuhan, Hubei Province, China, it has spread throughout the world and become a global public health emergency. It is important to distinguish COVID-19 from other viral pneumonias to properly screen and diagnose patients, reduce nosocomial infections, and complement the inadequacy of nucleic acid testing. In this study, we retrospectively analysed the clinical data of COVID-19 versus non-COVID-19 patients treated at our hospital between January 17 and February 27, 2020 to summarize our clinical experience in the differential diagnosis of COVID-19.MethodsIn this retrospective cohort study, 23 confirmed COVID-19 patients were consecutively enrolled from January 17 to February 27, 2020, and 29 confirmed non-COVID-19 patients were enrolled in the West China Hospital of Sichuan University. We collected baseline data, epidemiological data, clinical characteristics, imaging findings, viral nucleic acid test results, and survival data. SPSS v22.0 was used for the statistical analysis. Outcomes were followed-up until March 25.ResultsA total of 52 patients were included in this study, including 23 COVID-19 patients and 29 non-COVID-19 patients. No significant between-group differences were observed for age, sex, primary signs or symptoms, cellular immunity, or platelet count. Significant between-group differences were observed in clinical characteristics such as dry cough, contact with individuals from Wuhan, some underlying diseases, nucleated cell count, chest imaging findings, viral nucleic acid test results, 28-day mortality, and 28-day survival.ConclusionEpidemiological data, clinical symptoms, nucleic acid test results for COVID-19 and chest CT manifestation may help distinguish COVID-19 from non-COVID-19 cases, prevent imported cases and nosocomial infections.
Gap junction protein INNEXIN2 modulates the period of free-running rhythms inDrosophila melanogaster
Authors: Ramakrishnan Aishwarya , Sheeba Vasu 
Published: May 2020

AbstractThe circadian neuronal circuit ofDrosophila melanogasteris made up of about 150 neurons, distributed bilaterally and distinguished into 7 clusters. Multiple lines of evidence suggest that coherent rhythms in behaviour are brought about when these clusters function as a network. Although chemical modes of communication amongst circadian neurons have been well-studied, there has been no report of communication via electrical synapses made up of gap junctions. Here, we report for the first time that gap junction proteins – Innexins play crucial roles in determining the period of free-running activity rhythms in flies. Our experiments reveal the presence of gap junction protein INNEXIN2 in the ventral lateral neurons. RNA-interference based knockdown of its expression in circadian pacemakers slows down the speed of locomotor activity rhythm. Concomitantly, we find alterations in the oscillation of a core-clock protein PERIOD and in the output molecule Pigment Dispersing Factor in the circadian pacemaker neuron network.
Durable memories and efficient neural coding through mnemonic training using the method of loci
Authors: Wagner Isabella C. , Konrad Boris N. , Schuster Philipp , Weisig Sarah , Repantis Dimitris , Ohla Kathrin , Kühn Simone , Fernández Guillén , Steiger Axel , Lamm Claus , Czisch Michael , Dresler Martin 
Published: May 2020

AbstractMnemonic techniques, such as the method of loci, can powerfully boost memory. Here, we compared memory athletes ranked among the world’s top 50 in memory sports to mnemonics-naïve controls. In a second study, participants completed a six-weeks memory training, working memory training, or no intervention. Behaviorally, memory training enhanced durable, longer-lasting memories. fMRI during encoding and recognition revealed task-based activation decreases in lateral prefrontal, as well as in parahippocampal and retrosplenial cortices in both memory athletes and participants after memory training, partly associated with better performance after four months. This was complemented by hippocampal-neocortical coupling during consolidation, which was stronger the more durable memories participants formed. Our findings are the first to demonstrate that mnemonic training boosts durable memory formation via decreased task-based activation and increased consolidation thereafter. This is in line with conceptual accounts of neural efficiency and highlights a complex interplay of neural processes critical for extraordinary memory.
Gene expression profiling reveals subgenome dominance duringBrassica napusseed development
Authors: Khan Deirdre , Ziegler Dylan J. , Kalichuk Jenna L. , Hoi Vanessa , Hyunh Nina , Hajihasani Abolfazl , Parkin Isobel A.P. , Robinson Stephen J. , Belmonte Mark F. 
Published: May 2020

AbstractWe profiled the gene regulatory landscape ofBrassica napusreproductive development using RNA sequencing. Comparative analysis of this nascent amphidiploid across the plant lifecycle revealed the contribution of each subgenome to plant reproduction. Global mRNA profiling revealed lower accumulation of Cnsubgenome transcripts relative to the Ansubgenome. Subgenome-specific transcriptional networks identified distinct transcription factor families enriched in each of the Anand Cnsubgenome early in seed development. Global gene expression profiling of laser-microdissected seed subregions further reveal subgenome expression dynamics in the embryo, endosperm, and seed coat of early stage seeds. Transcription factors predicted to be regulators encoded by the Ansubgenome are expressed primarily in the seed coat whereas regulators encoded by the Cnsubgenome were expressed primarily in the embryo. Data suggest subgenome bias are characteristic features of theB. napusseed throughout development, and that such bias might not be universal across the embryo, endosperm, and seed coat of the developing seed. Whole genome transcription factor networks identified BZIP11 as a transcriptional regulator of earlyB. napusseed development. Knockdown ofBZIP11using RNA interference resulted in a similar reduction in gene activity of predicted gene targets, and a reproductive-lethal phenotype. Taken together, transcriptional networks spanning both the Anand Cngenomes of theB. napusseed can identify valuable targets for seed development research and that-omics level approaches to studying gene regulation inB. napuscan benefit from both broad and high-resolution analyses.One Sentence SummaryGlobal RNA sequencing coupled with laser microdissection provides a critical resource to study subgenome bias in whole seeds and specific tissues of polyploid plants.
Differential Effects of Two Early Life Stress Paradigms on Cerebellar-Dependent Delay Eyeblink Conditioning
Authors: Moussa-Tooks Alexandra B. , Hetrick William P. , Green John T. 
Published: May 2020

AbstractEarly life stress paradigms have become prominent in the animal literature to model atypical development. Currently, two models have prevailed within the literature: (1) limited bedding or nesting and (2) maternal separation or deprivation. Both models have produced aberrations spanning behavior and neural circuitry. Surprisingly, these two models have yet to be directly compared. The current study utilized delay eyeblink conditioning, an associative learning task with a well-defined cerebellar circuit, to compare the behavioral effects of standard limited bedding (postnatal day 2-9, n=15) and maternal separation (60 minutes per day during postnatal day 2-14, n=13) early life stress paradigms. Animals in all groups exhibited robust learning curves. Surprisingly, facilitated conditioning was observed in the maternal separation group. Rats that underwent limited bedding did not differ from the control or maternal separation groups on any conditioning measures. This study contributes to a clearer understanding of early life stress paradigms and the claims made about their mechanisms, which if better clarified can be properly leveraged to increase translational value.
The Spatial Scale of Synaptic Protein Allocation during Homeostatic Plasticity
Authors: Sun Chao , Nold Andreas , Tchumatchenko Tatjana , Heilemann Mike , Schuman Erin M. 
Published: May 2020

AbstractAn individual neuron hosts up to 10,000 individual synapses that can be made stronger or weaker by local and cell-wide plasticity mechanisms, both of which require protein synthesis. To address over what spatial scale a neuron allocates synaptic resources, we quantified the distribution of newly synthesized proteins after global homeostatic upscaling using metabolic labeling and single-molecule localization (DNA-PAINT). Following upscaling, we observed a global increase in locally synthesized nascent protein in synapses and at dendrites, with a high degree of variability between individual synapses. We determined the smallest spatial scale over which nascent proteins were evenly distributed and found that it is best described by synaptic neighborhoods (~ 10 microns in length)-smaller than a dendritic branch and larger than an individual synapse. Protein allocation at the level of neighborhoods thus represents a solution to the problem of protein allocation within a neuron that balances local autonomy and global homeostasis.
Longitudinal Quantification of Metabolites and Macromolecules Reveals Age- and Sex-Related Changes in the Healthy Fischer 344 Rat Brain
Authors: Fowler Caitlin F. , Madularu Dan , Dehghani Masoumeh , Devenyi Gabriel A. , Near Jamie 
Published: May 2020

ABSTRACTNormal aging is associated with numerous biological changes including altered brain metabolism and tissue chemistry.In vivocharacterization of the neurochemical profile during aging is possible using magnetic resonance spectroscopy, a powerful non-invasive technique capable of quantifying brain metabolites involved in physiological processes that become impaired with age. A prominent macromolecular signal underlies those of brain metabolites and is particularly visible at high fields; parameterization of this signal into components improves quantification and expands the number of biomarkers comprising the neurochemical profile. The present study reports, for the first time, the simultaneous absolute quantification of brain metabolites and individual macromolecules in aging male and female Fischer 344 rats, measured longitudinally using proton magnetic resonance spectroscopy at 7T. We identified age- and sex-related changes in neurochemistry, with prominent differences in metabolites implicated in anaerobic energy metabolism, antioxidant capacity, and neuroprotection, as well as numerous macromolecule changes. These findings contribute to our understanding of the neurobiological processes associated with healthy aging, critical for the proper identification and management of pathological aging trajectories.HIGHLIGHTS→ Magnetic resonance spectroscopy reveals altered chemistry in the aging rat brain→ Age- and sex-dependent differences in metabolites and macromolecules are present→ Metabolites and macromolecules are markers of processes involved in healthy aging→ This study clarifies normative progression of brain chemistry and metabolismin vivo→ Improved understanding will inform future studies in pathological aging
Longevity, clonal relationship and transcriptional program of celiac disease-specific plasma cells
Authors: Lindeman Ida , Zhou Chunyan , Eggesbø Linn M. , Miao Zhichao , Polak Justyna , Lundin Knut E. A. , Jahnsen Jørgen , Qiao Shuo-Wang , Iversen Rasmus , Sollid Ludvig M. 
Published: May 2020

ABSTRACTDisease-specific plasma cells (PCs) reactive with transglutaminase 2 (TG2) or deamidated gluten peptides (DGP) are abundant in celiac disease (CeD) gut lesions. Their contribution toward CeD pathogenesis is unclear. We assessed expression of markers associated with PC longevity in 15 untreated and 26 treated CeD patients in addition to 13 non-CeD controls, and performed RNA-sequencing with clonal inference and transcriptomic analysis of 3251 single PCs. We observed antigen-dependent V-gene selection and stereotypic antibodies. Generation of recombinant DGP-specific antibodies revealed a key role of a heavy-chain residue that displays polymorphism, suggesting that immunoglobulin gene polymorphisms may influence CeD-specific antibody responses. We identified transcriptional differences between CeD-specific vs non-disease-specific PCs and between short-lived vs long-lived PCs. The short-lived CD19+CD45+phenotype dominated in untreated and short-term-treated CeD, in particular among disease-specific PCs but also in the general PC population. Thus, the disease lesion of untreated CeD is characterized by massive accumulation of short-lived PCs that are not only directed against disease-specific antigens.
A machine learning approach to optimizing cell-free DNA sequencing panels: with an application to prostate cancer
Authors: Cario Clinton L. , Chen Emmalyn , Leong Lancelote , Emami Nima C. , Lopez Karen , Tenggara Imelda , Simko Jeffry P. , Friedlander Terence W. , Li Patricia S. , Paris Pamela L. , Carroll Peter R. , Witte John S. 
Published: May 2020

AbstractBackgroundCell-free DNA’s (cfDNA) use as a biomarker in cancer is challenging due to genetic heterogeneity of malignancies and rarity of tumor-derived molecules. Here we describe and demonstrate a novel machine-learning guided panel design strategy for improving the detection of tumor variants in cfDNA. Using this approach, we first generated a model to classify and score candidate variants for inclusion on a prostate cancer targeted sequencing panel. We then used this panel to screen tumor variants from prostate cancer patients with localized disease in bothin silicoand hybrid capture settings.MethodsWhole Genome Sequence (WGS) data from 550 prostate tumors was analyzed to build a targeted sequencing panel of single point and small (<200bp) indel mutations, which was subsequently screenedin silicoagainst prostate tumor sequences from 5 patients to assess performance against commonly used alternative panel designs. The panel’s ability to detect tumor-derived cfDNA variants was then assessed using prospectively collected cfDNA and tumor foci from a test set 18 prostate cancer patients with localized disease undergoing radical proctectomy.ResultsThe panel generated from this approach identified as top candidates mutations in known driver genes (e.g. HRAS) and prostate cancer related transcription factor binding sites (e.g. MYC, AR). It outperformed two commonly used designs in detecting somatic mutations found in the cfDNA of 5 prostate cancer patients when analyzed in anin silicosetting. Additionally, hybrid capture and 2,500X sequencing of cfDNA molecules using the panel resulted in detection of tumor variants in all 18 patients of a test set, where 15 of the 18 patients had detected variants found in multiple foci.ConclusionMachine learning-prioritized targeted sequencing panels may prove useful for broad and sensitive variant detection in the cfDNA of heterogeneous diseases. This strategy has implications for disease detection and monitoring when applied to the cfDNA isolated from prostate cancer patients.
A biomimetic liver model recapitulating bio-physical properties and tumour stroma interactions in hepatocellular carcinoma
Authors: Calitz C. , Pavlovic N. , Rosenquist J. , Zagami C. , Samanta A. , Heindryckx F. 
Published: May 2020

ABSTRACTHepatocellular carcinoma (HCC) is a primary liver tumor developing in the wake of chronic liver disease. Chronic liver disease and inflammation leads to a fibrotic environment actively supporting and driving hepatocarcinogenesis. Insight into hepatocarcinogenesis in terms of the interplay between the tumor stroma micro-environment and tumor cells is thus of considerable importance. Three-dimensional (3D) cell culture models are proposed as the missing link between currentin vitro2D cell culture models andin vivoanimal models. Our aim was to design a novel 3D biomimetic HCC model with accompanying fibrotic stromal compartment and vasculature. Physiologically relevant hydrogels such as collagen and fibrinogen were incorporated to mimicking the bio-physical properties of the tumor ECM. In our model LX2 and HepG2 cells embedded in a hydrogel matrix were seeded onto the inverted insert membrane of a Transwell™ system. HUVEC cells were then seeded onto the opposite side of the membrane. Three formulations consisting of ECM-hydrogels embedded with cells were prepared and the bio-physical properties determined by rheology. Cell viability was determined by the AlamarBlue®assay over 21-days. The effect of the chemotherapeutic drug doxorubicin was evaluated in both a 2D co-culture and our 3D model for a period of 72h. We show that this model is viable for 25-days and gives rise to metastatic tumor nodules after 17 days in culture. Rheology results show that bio-physical properties of a fibrotic, cirrhotic and HCC liver can be successfully mimicked. Overall, results indicate that this 3D model is more representative of thein vivosituation compared to traditional 2D cultures. Our 3D tumor model showed a decreased response to chemotherapeutics, mimicking drug resistance typically seen in HCC patients. This model could in future provide a valuable new platform to study multifocal HCC or to identify mechanisms that contribute to early stages of metastasis.SUMMARYA protocol for a novel 3D biomimetic HCC model with accompanying fibrotic stromal compartment and vasculature, to study endocrine and paracrine signaling in liver cancer. The model uses physiological relevant hydrogels in ratios mimicking the bio-physical properties of the stromal extracellular matrix, which is an active mediator of cellular interactions, tumor growth and metastasis.
Earlier springs enable High-Arctic wolf spiders to produce a second clutch
Authors: Høye Toke T. , Kresse Jean-Claude , Koltz Amanda M. , Bowden Joseph J. 
Published: May 2020

ABSTRACTSpiders at southern latitudes commonly produce multiple clutches, but this has not been observed at high latitudes where activity seasons are much shorter. Yet the timing of snowmelt is advancing in the Arctic, and may allow some species to produce an additional clutch. To determine if this is already happening, we used specimens of the wolf spiderPardosa glacialiscaught by pitfall traps from the long-term (1996-2014) monitoring program at Zackenberg, Northeast Greenland. We dissected individual egg sacs and counted the number of eggs and partially developed juveniles, and measured carapace width of the mothers. Upon discovery of a bimodal frequency distribution of clutch sizes, as is typical for wolf spiders at lower latitudes producing a second clutch, we assigned egg sacs to being a first or second clutch depending on clutch size. We tested whether the median capture date differed among first and second clutches, whether clutch size was correlated to female size, and whether the proportion of second clutches produced within a season was related to climate. We found that assigned second clutches appeared significantly later in the season than first clutches. In years with earlier snowmelt, first clutches occurred earlier and the proportion of second clutches produced was larger. This result, likely a result of female spiders producing first clutches earlier in those years, which allowed time for another clutch. Clutch size for first clutches was correlated to female size, while this was not the case for second clutches. Our results provide the first evidence for Arctic invertebrates producing additional clutches in response to warming. This could be a common but overlooked phenomenon due to the challenges associated with long-term collection of life history data in the Arctic. Moreover, given that wolf spiders are a widely distributed, important tundra predator, we may expect to see population and food web consequences of their increased reproductive rates.