bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimates of the COVID-19 pandemic dynamics in Ukraine based on two data sets
Authors: Nesteruk Igor 
Published: February 2021

ABSTRACTBackgroundTo simulate how the number of COVID-19 cases increases versus time, various data sets for the number of new cases and different mathematical models can be used. Since there are some differences in statistical data, the results of simulations can be different. Complex mathematical models contain many unknown parameters, the values of which must be determined using a limited number of observations of the disease over time. Even long-term monitoring of the epidemic may not provide reliable estimates of its parameters due to the constant change of testing conditions, isolation of infected and quarantine. Therefore, simpler approaches are necessary. In particular, previous simulations of the COVID-19 epidemic dynamics in Ukraine were based on smoothing of the dependence of the number of cases on time and the generalized SIR (susceptible-infected-removed) model. These approaches allowed to detect the waves of pandemic and to make adequate predictions of the their duration and final sizes. In particular, eight waves of the COVID-19 pandemic in Ukraine were investigated.ObjectiveWe will compare the results simulation of a new epidemic wave in Ukraine based on national statistics and data reported by Johns Hopkins University (JHU).MethodsIn this study we use the smoothing method for the dependences of the number of cases on time, the generalized SIR model for the dynamics of any epidemic wave, the exact solution of the linear differential equations, and statistical approach developed before.ResultsNinth epidemic wave in Ukraine was simulated. The optimal values of the SIR model parameters were calculated and compared with the use of two data sets. Both predictions are not very optimistic: new cases will not stop appearing until June-July 2021.ConclusionsNew waves of COVID-19 pandemic can be detected, calculated and predicted with the use of rather simple mathematical models. The results of calculations depend on the data sets for the number of confirmed cases. The expected long duration of the pandemic forces us to be careful and in solidarity. The government and all Ukrainians must strictly adhere to quarantine measures in order to avoid fatal consequences. Probably the presented results could be useful in order to estimate the efficiency of future vaccinations.
Cavernoma in septum pellucidum: descriptive analysis and review of existing literature
Authors: Haque Samiul , Islam Asraful , Rahman Tyfur , Hossain Mohammad D. , Siddik Abu Bakar , Shourav Md Manjurul Islam , Hasan Md Fayad , Ikram Samar , Rahman Masum 
Published: February 2021

AbstractBackgroundCavernomas are rare central nervous system (CNS) lesions that constitute a distinct type of vascular malformation encountered in the brain parenchyma or ventricular system. A cavernoma can be familial or sporadic forms and exhibit a range of presentation from incidental findings to seizures, headaches, hemorrhage. Septum pellucidum cavernoma is exceedingly rare and should be studied for its unique topographical location and clinical course.MethodWe performed a comprehensive literature search and review using multiple databases. the title/abstract and MeSH keywords used included “cavernoma,” “cavernous hemangioma,” “cavernous malformation,” “cavernous angioma,” “CM,” “septum pellucidum” “SP” and “intraventricular,” along with “AND” and “OR” operators. Demographic and clinical data of each patient were collected for qualitative synthesis.ResultReported cases were diagnosed at a median age of 42 years; the most frequent symptom was headaches. The incidence of hemorrhage and hydrocephalus was 30%. Gross total resection was performed in 100% of patients and exhibit clinical improvement.ConclusionThe unique location of the cavernoma exhibits clinical presentations seen and the surgical approach used. Gross total resection conveys the impression of optimum management strategy and leads to a magnificent outcome in most cases.
Impact of environmental temperature on Covid-19 spread: Model and analysis of measurements recorded during the second pandemic in Cyprus
Authors: Livadiotis G. 
Published: February 2021

AbstractThe paper investigates the effect of the environmental temperature on the spread of COVID-19. We study the daily numbers of the cases infected and deaths caused by Covid-19 during the second wave of the pandemic within 2020, and how they were affected by the daily average-high temperature for the districts of the Republic of Cyprus. Among the findings of the paper, we show that (i) the average ratio of the PCR to rapid positive tests is ∼2.57±0.25, as expected from the tests’ responses, indicating that PCR overestimates positivity by ∼2.5 times; (ii) the average age of deaths caused by Covid-19 increases with rate about a year of age per week; (iii) the probability of a person infected by Covid-19 to develop severe symptoms leading to death is strongly depended on the person’s age, while the probability of having a death on the age of ∼67 or younger is less than 1/1000; (iv) the number of infected cases and deaths declined dramatically when the environmental temperature reaches and/or climbs above the critical temperature ofTC=30.1±2.4 C0; (v) the observed negative correlation between the exponential growth rate of the infected cases and the environmental temperature can be described within the framework of chemical kinetics, with at least two competing reactions, the connection of the coronavirus towards the receptor and the dissolution of the coronavirus; the estimated activation energy difference corresponding to the competing chemical reactions, 0.212±0.25 eV, matches the known experimental value; and (vi) the infected cases will decline to zero, when the environmental temperature climbs above the critical temperature within the summery days of 2021, which is expected for the Republic of Cyprus by the 16thof May, 2021.
Losartan Increases Survival of theFbn1mgR/mgRMouse Model of Marfan Syndrome in an Age-Dependent Manner
Authors: Smith Jeffrey D. , Chen Jeff Z. , Phillips Rebecca , Daugherty Alan , Sheppard Mary B. 
Published: February 2021

AbstractClinical trials investigating angiotensin receptor blockers (ARB) for attenuation of thoracic aortic aneurysm in people with Marfan syndrome have demonstrated variable efficacy. The primary objective of this study was to determine whether the age of mice at the time of losartan initiation affected mortality in fibrillin-1 hypomorphic (Fbn1mgR/mgR) mice. Male (n=40) and female (n=28) Fbn1mgR/mgR mice were randomized to receive losartan in drinking water (0.6 g/L) starting at either 24 or 50 days of age. Controls included Fbn1mgR/mgR mice (20M, 14F) and wild type (15M, 15F) littermates who were not administered the drug. Mortality of Fbn1mgR/mgR males receiving losartan at postnatal day 24 (P24) was not different from wild type controls (p=0.138). Survival of Fbn1mgR/mgR males administered losartan at P50 was not different compared to Fbn1mgR/mgR males receiving no drug (p=0.194) and decreased compared to wild type mice (p=0.002). Survival analysis after P50 demonstrated increased survival of Fbn1mgR/mgR males administered losartan at P50 compared to Fbn1mgR/mgR mice receiving no drug (p=0.017). Age is a critical variable that affects the therapeutic efficacy of losartan in male Fbn1mgR/mgR mice. Since overall mortality in female Fbn1mgR/mgR mice was lower than in male Fbn1mgR/mgR mice, a survival benefit with losartan was not detected in females.
Unique functions for Notch4 in murine embryonic lymphangiogenesis
Authors: Muley Ajit , Uh Minji Kim , Simone Glicella Salazar-De , Swaminathan Bhairavi , James Jennifer M. , Murtomaki Aino , Youn Seock Won , McCarron Joseph D. , Kitajewski Chris , Buethe Maria Gnarra , Riitano Gloria , Mukoyama Yoh-suke , Kitajewski Jan , Shawber Carrie J. 
Published: February 2021

AbstractIn mice, embryonic dermal lymphatic development is well-understood and used to study gene functions in lymphangiogenesis. Notch signaling is an evolutionarily conserved pathway that modulates cell fate decisions, which has been shown to both inhibit and promote dermal lymphangiogenesis. Here, we demonstrate distinct roles for Notch4 signaling versus canonical Notch signaling in embryonic dermal lymphangiogenesis. Actively growing embryonic dermal lymphatics expressed NOTCH1, NOTCH4 and DLL4 which correlated with Notch activity. In lymphatic endothelial cells (LECs), DLL4 activation of Notch induced a subset of Notch effectors and lymphatic genes, which were distinctly regulated by Notch1 and Notch4 activation. Treatment of LECs with VEGF-A or VEGF-C upregulatedDll4transcripts, and differentially and temporally regulated the expression ofNotch1andHes/Heygenes. Mice nullizygous forNotch4had an increase in the closure of the lymphangiogenic fronts which correlated with reduced vessel caliber in the maturing lymphatic plexus at E14.5, and reduced branching at E16.5. Activation of Notch4 suppressed LEC migration in a wounding assay significantly more than Notch1, suggesting a dominant role for Notch4 in regulating LEC migration. UnlikeNotch4nulls, inhibition of canonical Notch signaling by expressing a dominant negative form of MAML1 (DNMAML) in Prox1+ LECs led to increased lymphatic density consistent with an increased in LEC proliferation, described for the loss of LECNotch1. Moreover, loss ofNotch4did not affect LEC canonical Notch signaling. Thus, we propose that Notch4 signaling and canonical Notch signaling have distinct functions in the coordination of embryonic dermal lymphangiogenesis.
A conserved paint box underlies color pattern diversity in Estrildid finches
Authors: Hidalgo Magdalena , Curantz Camille , Quenech’Du Nicole , Gluckman Thanh-Lan , Neguer Julia , Beck Samantha , Mohammad Ammara , Manceau Marie 
Published: February 2021

AbstractMany animals exhibit typical color patterns that have been linked to key adaptive functions, yet the developmental mechanisms establishing these crucial designs remain unclear. Here, we surveyed color distribution in the plumage across a large number of passerine finches. Despite extreme apparent pattern diversity, we identified a small set of conserved color regions whose combinatory association can explain all observed patterns. We found these domains are instructed by early embryonic landmarks, and through profiling and comparative analyses produced a molecular map marking putative color domains in the developing skin. This revealed cryptic pre-patterning common to differently colored species, uncovering a simple molecular landscape underlying extensive color pattern variation.
Behavioral deficits, learning impairment, and enhanced hippocampal excitability in co-isogenic PrnpZH3/ZH3 mice
Authors: Matamoros-Angles A. , Hervera A. , Soriano J. , Martí E. , Carulla P , Llorens F. , Nuvolone M , Aguzzi A. , Ferrer I. , Gruart A. , Delgado-García JM. , Del Río JA. 
Published: February 2021

AbstractBackgroundThe cellular prion protein (PrPC) has been associated with numerous cellular processes, such as cell differentiation and neurotransmission. Moreover, it was recently demonstrated that some functions were misattributed to PrPC since results were obtained from mouse models with genetic artifacts. Here we elucidate the role of PrPC in the hippocampal circuitry and its related functions, like learning and memory, using the new strictly co-isogenic Prnp0/0 mouse (PrnpZH3/ZH3). Behavioral and operant conditioning tests were performed to evaluate memory and learning capabilities. In vivo electrophysiological recordings were carried out at CA3-CA1 synapses in living behaving mice, and spontaneous neuronal firing and network formation were monitored in primary neuronal cultures of PrnpZH3/ZH3 vs. wild-type mice.ResultsResults showed decreased motility, impaired operant conditioning learning, and anxiety-related behavior in PrnpZH3/ZH3 animals. PrPC absence enhanced susceptibility to high-intensity stimulations and kainate-induced seizures. However, long-term potentiation (LTP) was not enhanced in the PrnpZH3/ZH3 hippocampus. In addition, we observed a delay in neuronal maturation and network formation in PrnpZH3/ZH3 cultures.ConclusionIn conclusion, PrPC mediates synaptic function and protects the synapse from excitotoxic insults. Its deletion might evoke a susceptible epileptogenic brain that would fail to perform highly cognitive-demanding tasks such as associative learning and anxiety-like behaviors.
Oxford Nanopore sequencing-based protocol to detect CpG methylation in human mitochondrial DNA
Authors: Bicci Iacopo , Calabrese Claudia , Golder Zoe J. , Gomez-Duran Aurora , Chinnery Patrick F 
Published: February 2021

SummaryMethylation on CpG residues is one of the most important epigenetic modifications of nuclear DNA, regulating gene expression. Methylation of mitochondrial DNA (mtDNA) has been studied using whole genome bisulfite sequencing (WGBS), but recent evidence has uncovered major technical issues which introduce a potential bias during methylation quantification. Here, we validate the technical concerns with WGBS, and then develop and assess the accuracy of a protocol for variant-specific methylation identification using long-read Oxford Nanopore Sequencing. Our approach circumvents mtDNA-specific confounders, while enriching for native full-length molecules over nuclear DNA. Variant calling analysis against Illumina deep re-sequencing showed that all expected mtDNA variants can be reliably identified. Methylation calling revealed negligible mtDNA methylation levels in multiple human primary and cancer cell lines. In conclusion, our protocol enables the reliable analysis of epigenetic modifications of mtDNA at single-molecule level at single base resolution, with potential applications beyond methylation.MotivationAlthough whole genome bisulfite sequencing (WGBS) is the gold-standard approach to determine base-level CpG methylation in the nuclear genome, emerging technical issues raise questions about its reliability for evaluating mitochondrial DNA (mtDNA) methylation. Concerns include mtDNA strand asymmetry rendering the C-rich light strand disproportionately vulnerable the chemical modifications introduced with WGBS. Also, short-read sequencing can result in a co-amplification of nuclear sequences originating from ancestral mtDNA with a high nucleotide similarity. Lastly, calling mtDNA alleles with varying proportions (heteroplasmy) is complicated by the C-to-T conversion introduced by WGBS on unmethylated CpGs. Here, we propose an alternative protocol to quantify methyl-CpGs in mtDNA, at single-molecule level, using Oxford Nanopore Sequencing (ONS). By optimizing the standard ONS library preparation, we achieved selective enrichment of native mtDNA and accurate single nucleotide variant and CpG methylation calling, thus overcoming previous limitations.
Intrinsic and growth-mediated cell and matrix specialization during meniscus tissue assembly
Authors: Tsinman Tonia K. , Jiang Xi , Han Lin , Koyama Eiki , Mauck Robert L. , Dyment Nathaniel A. 
Published: February 2021

ABSTRACTThe incredible mechanical strength and durability of mature fibrous tissues and their extremely limited turnover and regenerative capacity underscores the importance of proper matrix assembly during early postnatal growth. In tissues with composite extracellular matrix (ECM) structures, such as the adult knee meniscus, fibrous (Collagen-I rich) and cartilaginous (Collagen-II, proteoglycan-rich) matrix components are regionally segregated to the outer and inner portions of the tissue. While this spatial variation in composition is appreciated to be functionally important for resisting complex mechanical loads associated with gait, the establishment of these specialized zones is poorly understood. To address this issue, the following study tracked the growth of the murine meniscus from its embryonic formation through its first month of growth, encompassing the critical time-window during which animals begin to ambulate and weight bear. Using histological analysis, region specific high-throughput qPCR, and Col-1 and Col-2 fluorescent reporter mice, we found that matrix and cellular features defining specific tissue zones were already present at birth, before continuous weight-bearing had occurred. These differences were further refined with postnatal growth and maturation, resulting in specialization of mature tissue regions. Taken together, this work establishes a detailed timeline of the concurrent spatiotemporal changes that occur at both the cellular and matrix level throughout meniscus maturation. The findings of this study provide a framework for investigating the reciprocal feedback between cells and their evolving microenvironments during assembly of a mechanically robust fibrocartilage tissue, thus providing insight into mechanisms of tissue degeneration and effective regenerative strategies.
A genome-wide circular RNA transcriptome in Rat
Authors: Sharma Disha , Sehgal Paras , Sivasubbu Sridhar , Scaria Vinod 
Published: February 2021

AbstractBackgroundCircular RNAs are a novel class of non-coding RNAs that backsplice from 5’ donor site and 3’ acceptor site to form a circular structure. A number of circRNAs have been discovered in model organisms including human, mouse, Drosophila, among other organisms. There are a few candidate-based studies on circular RNAs in rat, a well studied model organism. The availability of a recent dataset of transcriptomes encompassing 11 tissues, 4 developmental stages and 2 genders motivated us to explore the landscape of circular RNAs in the organism.MethodologyIn order to understand the difference among different pipelines, we have used the same bodymap RNA sequencing dataset. A number of pipelines have been published to identify the backsplice junctions for the discovery of circRNAs but studies comparing these tools have suggested that a combination of tools would be a better approach to identify high-confidence circular RNAs. We employed 5 different combinations of tools including tophat_CIRCexplorer2, segemehl_CIRCexplorer2, star_CIRCexplorer, Bowtie2_findcirc and Bowtie2_findcirc (noHisat2) to identify circular RNAs from the dataset.ResultsOur analysis identified a number of tissue-specific, developmental stage specific and gender specific circular RNAs. We further independently validated 16 circRNA junctions out of 24 selected candidates in 5 tissue samples. We additionally estimated the quantitative expression of 5 circRNA candidates using real-time PCR and our analysis suggests 3 candidates as tissue-enrichedConclusionThis study is one of the most comprehensive studies that provides a circular RNA transcriptome as well as to understand the difference among different computational pipelines in Rat.
Microstates and power envelope hidden Markov modeling probe bursting brain activity at different timescales
Authors: Coquelet N , De Tiège X , Roshchupkina L , Peigneux P , Goldman S , Woolrich M , Wens V 
Published: February 2021

AbstractState modeling of whole-brain electroencephalography (EEG) or magnetoencephalography (MEG) allows to investigate transient, recurring neurodynamical events. Two widely-used techniques are the microstate analysis of EEG signals and hidden Markov modeling (HMM) of MEG power envelopes. Both reportedly lead to similar state lifetimes on the 100 ms timescale, suggesting a common neural basis. We addressed this issue by using simultaneous MEG/EEG recordings at rest and comparing the spatial signature and temporal activation dynamics of microstates and power envelope HMM states obtained separately from EEG and MEG. Results showed that microstates and power envelope HMM states differed both spatially and temporally. Microstates tend to exhibit spatio-temporal locality, whereas power envelope HMM states disclose network-level activity with 100–200 ms lifetimes. Further, MEG microstates do not correspond to the canonical EEG microstates but are better interpreted as split HMM states. On the other hand, both MEG and EEG HMM states involve the (de)activation of similar functional networks. Microstate analysis and power envelope HMM thus appear sensitive to neural events occurring over different spatial and temporal scales. As such, they represent complementary approaches to explore the fast, sub-second scale bursting electrophysiological dynamics in spontaneous human brain activity.
Rigid-body fitting to atomic force microscopy images for inferring probe shape and biomolecular structure
Authors: Niina Toru , Matsunaga Yasuhiro , Takada Shoji 
Published: February 2021

AbstractAtomic force microscopy (AFM) can visualize functional biomolecules near the physiological condition, but the observed data are limited to the surface height of specimens. Since the AFM images highly depend on the probe tip shape, for successful inference of molecular structures from the measurement, the knowledge of the probe shape is required, but is often missing. Here, we developed a method of the rigid-body fitting to AFM images, which simultaneously finds the shape of the probe tip and the placement of the molecular structure via an exhaustive search. First, we examined four similarity scores via twin-experiments for four test proteins, finding that the cosine similarity score generally worked best, whereas the pixel-RMSD and the correlation coefficient were also useful. We then applied the method to two experimental high-speed-AFM images inferring the probe shape and the molecular placement. The results suggest that the appropriate similarity score can differ between target systems. For an actin filament image, the cosine similarity apparently worked best. For an image of the flagellar protein FlhAC, we found the correlation coefficient gave better results. This difference may partly be attributed to the flexibility in the target molecule, ignored in the rigid-body fitting. The inferred tip shape and placement results can be further refined by other methods, such as the flexible fitting molecular dynamics simulations. The developed software is publicly available.Author SummaryObservation of functional dynamics of individual biomolecules is important to understand molecular mechanisms of cellular phenomena. High-speed (HS) atomic force microscopy (AFM) is a powerful tool that enables us to visualize the real-time dynamics of working biomolecules under near-physiological conditions. However, the information available by the AFM images is limited to the two-dimensional surface shape detected via the force to the probe. While the surface information is affected by the shape of the probe tip, the probe shape itself cannot be directly measured before each AFM measurement. To overcome this problem, we have developed a computational method to simultaneously infer the probe tip shape and the molecular placement from an AFM image. We show that our method successfully estimates the effective AFM tip shape and visualizes a structure with a more accurate placement. The estimation of a molecular placement with the correct probe tip shape enables us to obtain more insights into functional dynamics of the molecule from HS-AFM images.