bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the number of deaths in Brazil between 2003 and 2020 and possible inferences about the COVID-19 pandemic and history of other diseases
Authors: Sosman Lilian P. , Papa Andrés R. R. 
Published: January 2021

ABSTRACTThis work explores data on the number of deaths in Brazil since the beginning of the historical series of IBGE, 2003, together with data for the period 2015-2020 of the Transparency Portal. The graphs for total deaths, deaths from violence and deaths in hospitals are discussed. The relationship between them leads to conclusions about the real dimension of the effect of COVID-19 in Brazilian society during the year 2020 and its relative importance to other diseases that had a lesser impact. Hypotheses are also made about the number of deaths in future years.
Tumor Microenvironment Alters Chemoresistance of Hepatocellular Carcinoma Through CYP3A4 Metabolic Activity
Authors: Özkan Alican , Stolley Danielle L. , Cressman Erik N. K. , McMillin Matthew , DeMorrow Sharon , Yankeelov Thomas E. , Rylander Marissa Nichole 
Published: January 2021

AbstractVariations in tumor biology from patient to patient combined with the low overall survival rate of hepatocellular carcinoma (HCC) present significant clinical challenges. During the progression of chronic liver diseases from inflammation to the development of HCC, microenvironmental properties, including tissue stiffness and oxygen concentration, change over time. This can potentially impact drug metabolism and subsequent therapy response to commonly utilized therapeutics, such as doxorubicin, multi-kinase inhibitors (e.g., sorafenib), and other drugs, including immunotherapies. In this study, we utilized four common HCC cell lines embedded in 3D collagen type-I gels of varying stiffnesses to mimic normal and cirrhotic livers with environmental oxygen regulation to quantify the impact of these microenvironmental factors on HCC chemoresistance. In general, we found that HCC cells with higher baseline levels of cytochrome p450-3A4 (CYP3A4) enzyme expression, HepG2 and C3Asub28, exhibited a cirrhosis-dependent increase in doxorubicin chemoresistance. Under the same conditions, HCC cell lines with lower CYP3A4 expression, HuH-7 and Hep3B2, showed a decrease in doxorubicin chemoresistance in response to an increase in microenvironmental stiffness. This differential therapeutic response was correlated with the regulation of CYP3A4 expression levels under the influence of stiffness and oxygen variation. In all tested HCC cell lines, the addition of sorafenib lowered the required doxorubicin dose to induce significant levels of cell death, demonstrating its potential to help reduce systemic doxorubicin toxicity when used in combination. These results suggest that patient-specific tumor microenvironmental factors, including tissue stiffness, hypoxia, and CYP3A4 activity levels, may need to be considered for more effective use of chemotherapeutics in HCC patients.
Tapping into the aging brain:In vivomicrodialysis reveals mirroring pathology between preclinical models and patients with Alzheimer’s disease
Authors: Bjorkli C. , Louet C. , Flo T.H. , Hemler M. , Sandvig A. , Sandvig I. 
Published: January 2021

SUMMARYPreclinical models of Alzheimer’s disease (AD) can provide valuable insights into the onset and progression of the disease, such as changes in concentrations of amyloid-β (Aβ) and tau in cerebrospinal fluid (CSF). However, such models are currently underutilized due to limited advancement in techniques that allow for longitudinal monitoring of CSF akin to methods employed in AD patients. An elegant way to understand the biochemical environment in the diseased brain is intracerebral microdialysis, a method that has until now been limited to short-term observations, or snapshots, of the brain microenvironment. Our novel push-pull microdialysis method in AD mice permitsin vivolongitudinal monitoring of dynamic changes of Aβ and tau in CSF and allows for better translational understanding of CSF biomarkers. Specifically, we demonstrate that CSF concentrations of Aβ and tau along disease progression in transgenic mice mirror what is observed in patients, with a decrease in CSF Aβ observed when plaques are deposited, and an increase in CSF tau once tau pathology is present in the brain. We found that a high molecular weight cut-off membrane allowed for simultaneous sampling of Aβ and tau, comparable to lumbar puncture CSF collection in patients. We furthermore provide specific recommendations for optimal application of our novel microdialysis method, such as achieving optimal recovery of analytes, which depends heavily on the flow rate of perfusion, probe properties and perfusate composition. Our approach can further advance AD research by following evolving neuropathology along the disease cascade via consecutive sampling from the same animal, and can additionally be used to administer pharmaceutical compounds and assess their efficacy in treating AD.
Dynamics of sex-biased gene expression during development in the stick insectTimema californicum
Authors: Jelisaveta Djordjevic , Zoé Dumas , Marc Robinson-Rechavi , Tanja Schwander , James Parker Darren 
Published: January 2021

AbstractSexually dimorphic phenotypes are thought to arise primarily from sex-biased gene expression during development. Major changes in developmental strategies, such as the shift from hemimetabolous to holometabolous development, are therefore expected to have profound consequences for the dynamics of sex-biased gene expression. However, no studies have previously examined sex-biased gene expression during development in hemimetabolous insects, precluding comparisons between developmental strategies. Here we characterized sex-biased gene expression at three developmental stages in a hemimetabolous stick insect (Timema californicum): hatchlings, juveniles, and adults. As expected, the proportion of sex-biased genes gradually increased during development, mirroring the gradual increase of phenotypic sexual dimorphism. Sex-biased genes identified at early developmental stages were generally consistently male- or female-biased at later stages, suggesting their importance in sexual differentiation. Additionally, we compared the dynamics of sex-biased gene expression during development inT. californicumto those of the holometabolous flyDrosophila melanogasterby reanalyzing publicly available RNA-seq data from third instar larval, pupal and adult stages. InD. melanogaster, 84% of genes were sex-biased at the adult stage (compared to only 20% inT. californicum), and sex-biased gene expression increased abruptly at the adult stage when morphological sexual dimorphism is manifested. Our findings are consistent with the prediction that the dynamics of sex-biased gene expression during development differ extensively between holometabolous and hemimetabolous insect species.
SENP1 in the retrosplenial agranular cortex regulates core autistic-like symptoms in mice
Authors: Yang Kan , Shi Yuhan , Du Xiujuan , Wang Jincheng , Zhang Yuefang , Shan Shifang , Yuan Yiting , Wang Ruoqing , Zhou Chenhuan , Liu Yuting , Cai Zilin , Wang Yanzhi , Fan Liu , Xu Huatai , Yu Juehua , Cheng Jinke , Li Fei , Qiu Zilong 
Published: January 2021

AbstractAutism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder, in which core symptoms are defects of social interaction and evidently repetitive behaviors. Although around 50-70 % of ASD patients have comorbidity of intellectual disabilities (ID) or developmental delay (DD), there are some ASD patients who exhibit only core symptoms but without ID/DD, raising the question whether there are genetic components and neural circuits specific for core symptoms of ASD. Here, by focusing on ASD patients who do not show compound ID or DD, we identified ade novoheterozygous gene-truncating mutation of the Sentrin-specific peptidase1 (SENP1) gene, coding the small ubiquitin-like modifiers (SUMO) deconjugating enzyme, as a potentially new candidate gene for ASD. We found thatSenp1haploinsufficient mice exhibited core symptoms of autism such as deficits in social interaction and repetitive behaviors, but normal learning and memory ability. Moreover, we found that the inhibitory and excitatory synaptic functions were severely affected in the retrosplenial agranular (RSA) cortex ofSenp1haploinsufficient mice. Lack ofSenp1led to over SUMOylation and degradation of fragile X mental retardation protein (FMRP) proteins, which is coded by theFMR1gene, also implicated in syndromic ASD. Importantly, re-introducing SENP1 or FMRP specifically in RSA fully rescued the defects of synaptic functions and core autistic-like symptoms ofSenp1haploinsufficient mice. Together, these results demonstrated that disruption of the SENP1-FMRP regulatory axis in the RSA may cause core autistic symptoms, which provide a candidate brain region of ASD for potential therapeutic intervene by neural modulation approaches.
The brain clock portal system: SCN-OVLT
Authors: Yao Yifan , Taub Alana , LeSauter Joseph , Silver Rae 
Published: January 2021

AbstractVascular portal systems are key structures, necessary for transporting products directly from the capillary bed of one region to the capillary bed of another region in high concentrations, without first returning to the heart. The only known portal systems in the brain is the hypophyseal-pituitary portal system, a structure necessary for survival and reproduction. Secretions from specific populations of hypothalamic neurons travel into fenestrated capillaries of the median eminence (ME) and thence drain into portal veins which break up into the secondary capillary plexus of the anterior pituitary. Neurons of the hypothalamic suprachiasmatic nucleus (SCN), locus of the brain’s master clock, also produces secretions deeply implicated in health and survival (Karatsoreos, 2019; Musiek & Holtzman, 2016). Here we describe a portal system connecting the SCN and organum vasculosum of the lamina terminalis (OVLT) - a circumventricular organ (CVO). CVOs lie around ventricles and lack a blood-brain barrier, enabling communication between the blood, brain, and cerebrospinal fluid. This “clock portal system” points to entirely new routes and targets for secreted signals, restructuring our understanding of brain communication pathways. Whether any of the remaining six CVOs in the mammalian brain bear portal systems is yet to be determined.
Sea of Electrodes Array (SEA): Extremely Dense and High-Count Silicon-Based Electrode Array Technology for High-Resolution High-Bandwidth Interfacing with 3D Neural Structures
Authors: Zardini Amin Sandoughsaz , Rostami Behnoush , Najafi Khalil , Hetrick Vaughn L. , Ahmed Omar J. 
Published: January 2021

AbstractIn this work, we propose a new silicon-based micro-fabrication technology to fabricate 3D high-density high-electrode-count neural micro-probe arrays scalable to thousands and even millions of individual electrodes with user-defined length, width, shape, and tip profile. This unique technology utilizes DRIE of ultra-high aspect-ratio holes in silicon and refilling them with multiple films to form thousands of individual needles with metal tips making up the “sea-of-electrodes” array (SEA). World-record density of 400 electrodes/mm2in a 5184-needle array is achieved. The needles are ~0.5-1.2mm long, <20μm wide at the base, and <1μm at the tip. The silicon-based structure of these 3D array probes with sharp tips, makes them stiff enough and easily implantable in the brain to reach a targeted region without failing. Moreover, the high aspect ratio of these extremely fine needles reduces the tissue damage and improves the chronic stability. Functionality of the electrodes is investigated using acutein vivorecording in a rat barrel field cortex under isoflurane anesthesia.
Profile hidden Markov model sequence analysis can help remove putative pseudogenes from DNA barcoding and metabarcoding datasets
Authors: Porter T. M. , Hajibabaei M. 
Published: January 2021

AbstractBackgroundPseudogenes are non-functional copies of protein coding genes that typically follow a different molecular evolutionary path as compared to functional genes. The inclusion of pseudogene sequences in DNA barcoding and metabarcoding analysis can lead to misleading results. None of the most widely used bioinformatic pipelines used to process marker gene (metabarcode) high throughput sequencing data specifically accounts for the presence of pseudogenes in protein-coding marker genes. The purpose of this study is to develop a method to screen for obvious pseudogenes in large COI metabarcode datasets. We do this by: 1) describing gene and pseudogene characteristics from a simulated DNA barcode dataset, 2) show the impact of two different pseudogene removal methods on mock metabarcode datasets with simulated pseudogenes, and 3) incorporate a pseudogene filtering step in a bioinformatic pipeline that can be used to process Illumina paired-end COI metabarcode sequences. Open reading frame length and sequence bit scores from hidden Markov model (HMM) profile were used to detect pseudogenes.ResultsOur simulations showed that it was more difficult to identify pseudogenes from shorter amplicon sequences such as those typically used in metabarcoding (∼300 bp) compared with full length DNA barcodes that are used in construction of barcode libraries (∼ 650 bp). It was also more difficult to identify pseudogenes in datasets where there is a high percentage of pseudogene sequences. We show that existing bioinformatic pipelines used to process metabarcode sequences already remove some apparent pseudogenes, especially in the rare sequence removal step, but the addition of a pseudogene filtering step can remove more.ConclusionsThe combination of open reading frame length and hidden Markov model profile analysis can be used to effectively screen out obvious pseudogenes from large datasets. There is more to learn from COI pseudogenes such as their frequency in DNA barcode and metabarcoding studies, their taxonomic distribution, and evolution. Thus, we encourage the submission of verified COI pseudogenes to public databases to facilitate future studies.
Large-scale analysis of interindividual variability in single and paired-pulse TMS data: results from the ‘Big TMS Data Collaboration’
Authors: Corp Daniel T. , Bereznicki Hannah G. K. , Clark Gillian M. , Youssef George J. , Fried Peter J. , Jannati Ali , Davies Charlotte B. , Gomes-Osman Joyce , Kirkovski Melissa , Albein-Urios Natalia , Fitzgerald Paul B. , Koch Giacomo , Lazzaro Vincenzo Di , Pascual-Leone Alvaro , Enticott Peter G. ,   the Big TMS Data Collaboration
Published: January 2021

AbstractObjectiveInterindividual variability of single and paired-pulse TMS data has limited the clinical and experimental applicability of these methods. This study brought together over 60 TMS researchers to create the largest known sample of individual participant single and paired-pulse TMS data to date, enabling a more comprehensive evaluation of factors driving response variability.Methods118 corresponding authors provided deidentified individual TMS data. Mixed-effects regression investigated a range of individual and study level variables for their contribution to variability in response to single and pp TMS data.Results687 healthy participant’s TMS data was pooled across 35 studies. Target muscle, pulse waveform, neuronavigation use, and TMS machine significantly predicted an individual’s single pulse TMS amplitude. Baseline MEP amplitude, M1 hemisphere, and biphasic AMT significantly predicted SICI response. Baseline MEP amplitude, test stimulus intensity, interstimulus interval, monophasic RMT, monophasic AMT, and biphasic RMT significantly predicted ICF response. Age, M1 hemisphere, and TMS machine significantly predicted motor threshold.ConclusionsThis large-scale analysis has identified a number of factors influencing participants’ responses to single and paired pulse TMS. We provide specific recommendations to increase the standardisation of TMS methods within and across laboratories, thereby minimising interindividual variability in single and pp TMS data.Highlights687 healthy participant’s TMS data was pooled across 35 studiesSignificant relationships between age and resting motor thresholdSignificant relationships between baseline MEP amplitude and SICI/ICF
The quorum sensing system NprR-NprRB contributes to spreading and fitness in colony biofilms ofBacillus thuringiensis
Authors: Verdugo-Fuentes Abel , de la Torre Mayra , Rocha Jorge 
Published: January 2021

AbstractQuorum sensing (QS) are intercellular communication mechanisms to coordinate bacterial gene expression in response to signaling molecules. InBacillus thuringiensisthe QS system NprR-NprRB (receptor protein-signaling peptide) regulates the expression of genes related to nutrient scavenging during necrotrophism and also modulates sporulation onset. However, the relevance of QS in free-living stages ofB. thuringiensisis less known. In this work, we depict the contribution of this QS system to spreading in colony biofilms. Through a spreading assay in spotted colonies ofB. thuringiensisBt8741 Wt and derived mutants, we find that the spreading phenotype depends on the NprR regulator and on the extracellular signaling NprRB peptide. We also show that this phenotype is associated to an increased fitness of the bacterium in these experimental conditions. Exogenous addition of a lipopeptide surfactant was sufficient to recover spreading in the ΔnprR-nprRBmutant, indicating that the phenotype could be mediated by the lipopeptide kurstakin. Finally, we suggest that the spreading is relevant in nature, since it occurs in the sole presence of soil nutrients, and it is conserved in several species ofBacilluscommonly found in soil. This novel function of NprR-NprRB highlights the relevance of this QS system on the evolution and on the free-lifestyle ecology ofB. thuringiensis.
Near real-time surveillance of the SARS-CoV-2 epidemic with incomplete data
Authors: De Salazar PM , Lu F , Hay JA , Gómez-Barroso D , Fernández-Navarro P , Martínez E , Astray-Mochales J , Amillategui R , García-Fulgueiras A , Chirlaque MD , Sánchez-Migallón A , Larrauri A , Sierra MJ , Lipsitch M , Simón F , Santillana M , Hernán MA 
Published: January 2021

AbstractDesigning public health responses to outbreaks requires close monitoring of population-level health indicators in real-time. Thus, an accurate estimation of the epidemic curve is critical. We propose an approach to reconstruct epidemic curves in near real time. We apply this approach to characterize the early SARS-CoV-2 outbreak in two Spanish regions between March and April 2020.We address two data collection problems that affected the reliability of the available real-time epidemiological data, namely, the frequent missing information documenting when a patient first experienced symptoms, and the frequent retrospective revision of historical information (including right censoring). This is done by using a novel back-calculating procedure based on imputing patients’ dates of symptom onset from reported cases, according to a dynamically-estimated “backward” reporting delay conditional distribution, and adjusting for right censoring using an existing package, NobBS, to estimate in real time (nowcast) cases by date of symptom onset. This process allows us to obtain an approximation of the time-varying reproduction number (Rt) in real-time.At each step, we evaluate how different assumptions affect the recovered epidemiological events and compare the proposed approach to the alternative procedure of merely using curves of case counts, by report day, to characterize the time-evolution of the outbreak. Finally, we assess how these real-time estimates compare with subsequently documented epidemiological information that is considered more reliable and complete that became available later in time. Our approach may help improve accuracy, quantify uncertainty, and evaluate frequently unstated assumptions when recovering the epidemic curves from limited data obtained from public health surveillance systems in other locations.
Prevalence of Iron Deficiency, Iron Deficiency Anaemia and General Anaemia in Male Gambian Blood Donors Residing in Greater Banjul Region
Authors: Dibbasey Mustapha , Lawal Bolarinde , Umukoro Solomon , Mitchel Peter 
Published: January 2021

AbstractObjectiveThe objective of this study is to determine the prevalence of iron deficiency (ID) and iron deficiency anaemia (IDA) as well as general anaemia in male blood donors and their association with ageing process.Methodology and ResultsA total of two hundred and one (201) serum samples were analysed for ferritin in male Gambian blood donors. The ferritin measurement was achieved with COBAS® INTEGRA 400 plus. At the same time, haemoglobin values were retrospectively obtained from the archived haematological full blood count result in the GARIS database. IDA was defined as (Haemoglobin <13.0g/dL+ Ferritin<15ng/ml) whilst ID was defined as (Haemoglobin ≥13.0g/dL+ Ferritin<15ng/ml) and general anaemia was defined as haemoglobin <13.0g/dL in males. The prevalence of anaemia (20%, n=41), ID (22%, n=44) and IDA (10%, n=21), were recorded in male donors. The results show no relationship between ferritin and haemoglobin among the blood donors (collection coefficient (r) = 0.04). Besides, no linear association of having anaemia and ID with ageing was reported among the blood donor population.Conclusion and potential application of findingsID and IDA as well as general anaemia are highly prevalent among blood donors in the Gambia. Besides, no predisposition to ID and anaemia was observed in term of age, thus all blood donors from 18-60 should be considered for blood donation without any age preference.