bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long Term Follow-Up of Pediatric Mandibular Reconstruction With Human Transforming Growth Factor-β3
Authors: Ferretti Carlo , Ripamonti Ugo 
Published: June 2020

Abstract
Translating bone regeneration induced by recombinant human bone morphogenetic proteins from animal models to human patients has proven inexplicably inconsistent. This prompted us to test in 5 pediatric patients, an alternative osteoinductive morphogen, recombinant human transforming growth factor β3 (hTGF-β3), to reconstruct mandibular defects of such a size to preclude reconstruction with autologous bone. An osteoinductive implant of human demineralized bone matrix (DBM) loaded with 125 μg hTGF-β3 per gram of DBM was implanted into one defect, and 250 μg hTGF-β3 per gram of DBM in another. Thereafter in 3 patients limited amounts of particulate cortico-cancellous bone graft harvested from the posterior iliac crest were combined with 250 μg hTGF-β3 per gram of DBM. Patients were followed up for 3 to 6 years. Three patients achieved clinically significant osteoinduction, 1 patient with hTGF-β3 only, and 2 by combining hTGF-β3 with a small supplement of autologous bone. One patient with hTGF-β3 only and followed up for 5 years retains a viable reconstruction but has had sub-optimal bone regeneration. One patient had osteoinductive failure due to sepsis although the plate reconstruction remains viable. Recombinant human TGF-β3 initiates osteoinduction in humans and potentiates autologous bone graft activity allowing the reconstruction of large mandibular defects in pediatric patients.
Paediatric Dentistry and the coronavirus (COVID-19) response in the North East of England and North Cumbria
Authors: Simpson S , Sumner O , Holliday R , Currie CC , Hind V , Lush N , Burbridge LA , Cole BOI 
Published: June 2020

AbstractIntroductionCoronavirus (COVID-19) has dramatically changed the landscape of dentistry including Paediatric Dentistry. This paper explores paediatric patient data within a wider service evaluation completed within an Urgent Dental Care Centre in the North East of England and North Cumbria over a 6-week period.AimTo assess demand for the service, patient demographics and inform paediatric urgent dental care pathways.Main outcome methodsData collected included key characteristics of paediatric patients accessing Paediatric Dental Services from 23rd March to 3rd May 2020. Descriptive statistics were used for analysis.ResultsThere were 369 consultations (207 telephone, 124 face-to-face and 38 Out of Hours consultations). The mean age of children accessing the service was 7 years old. 7% of those attending face-to-face visits were reattenders. The most common diagnoses were irreversible pulpitis and dental trauma. 49% of face-to-face consultations resulted in extractions, 28% with General Anaesthetic, and 21% with Local Anaesthetic.ConclusionManagement of dental emergencies provided by the Urgent Dental Care Centre for paediatric patients has largely been effective and confirmed the efficacy of patient pathways established.Three in Brief Points⍰ Describes the approach adopted in the North East of England and North Cumbria to managing paediatric dental emergencies during the coronavirus pandemic⍰ Provides an overview of dental problems and management provided to paediatric patients in the first 6 weeks of the coronavirus pandemic⍰ Confirms the need for general anaesthetic services for exodontia in the paediatric population
Early phase of the COVID-19 outbreak in Hungary and post-lockdown scenarios
Authors: Röst Gergely , Bartha Ferenc A. , Bogya Norbert , Boldog Péter , Dénes Attila , Ferenci Tamás , Horváth Krisztina J. , Juhász Attila , Nagy Csilla , Tekeli Tamás , Vizi Zsolt , Oroszi Beatrix 
Published: June 2020

AbstractCOVID-19 epidemic has been suppressed in Hungary due to timely non-pharmaceutical interventions, prompting a huge reduction in the number of contacts and transmission of the virus. This strategy was effective in preventing epidemic growth and reducing the incidence of COVID-19 to low levels. In this report, we present the first epidemiological and statistical analysis of the early phase of the COVID-19 outbreak in Hungary. Then, we establish an age-structured compartmental model to explore alternative post-lockdown scenarios. We incorporate various factors, such as age-specific measures, seasonal effects, and spatial heterogeneity to project the possible peak size and disease burden of a COVID-19 epidemic wave after the current measures are relaxed.
SpikeShip: A method for fast, unsupervised discovery of high-dimensional neural spiking patterns
Authors: Sotomayor-Gómez Boris , Battaglia Francesco P. , Vinck Martin 
Published: June 2020

AbstractNeural coding and memory formation depend on temporal spiking sequences that span high-dimensional neural ensembles. The unsupervised discovery and characterization of these spiking sequences requires a suitable dissimilarity measure to spiking patterns, which can then be used for clustering and decoding. Here, we present a new dissimilarity measure based on optimal transport theory called SpikeShip, which compares multineuron spiking patterns based on all the relative spike-timing relationships among neurons. SpikeShip computes the optimal transport cost to make all the relative spike-timing relationships (across neurons) identical between two spiking patterns. We show that this transport cost can be decomposed into a temporal rigid translation term, which captures global latency shifts, and a vector of neuron-specific transport flows, which reflect inter-neuronal spike timing differences. SpikeShip can be effectively computed for high-dimensional neuronal ensembles, has a low (linear) computational cost that has the same order as the spike count, and is sensitive to higher-order correlations. Furthermore SpikeShip is binless, can handle any form of spike time distributions, is not affected by firing rate fluctuations, can detect patterns with a low signal-to-noise ratio, and can be effectively combined with a sliding window approach. We compare the advantages and differences between SpikeShip and other measures like SPIKE and Victor-Púrpura distance. We applied SpikeShip to large-scale Neuropixel recordings during spontaneous activity and visual encoding. We show that high-dimensional spiking sequences detected via SpikeShip reliably distinguish between different natural images and different behavioral states. These spiking sequences carried complementary information to conventional firing rate codes. SpikeShip opens new avenues for studying neural coding and memory consolidation by rapid and unsupervised detection of temporal spiking patterns in high-dimensional neural ensembles.
Glutamatergic adaptation to stress in medial prefrontal cortex underlies risk and resilience for pessimistic beliefs
Authors: Cooper Jessica A. , Nuutinen Makiah R. , Lawlor Victoria M. , DeVries Brittany A. M. , Barrick Elyssa M. , Hossein Shabnam , Cole Daniel C. , Leonard Chelsea V. , Teer Andrew P. , Shields Grant S. , Slavich George M. , Ongur Dost , Jensen J. Eric , Du Fei , Pizzagalli Diego A. , Treadway Michael T. 
Published: June 2020

ABSTRACTStress is a major risk factor for the development of mental illness, including major depressive disorder (MDD), yet the underlying biological mechanisms remain unclear. Particular challenges lie in disentangling adaptive versus maladaptive responses to repeated stress exposure. Preclinically, stress-induced changes in glutamatergic function have been frequently observed in the medial prefrontal cortex (mPFC), a key region for mediating adaptive stress responses. Here, we examined stress-induced changes in mPFC glutamate using magnetic resonance spectroscopy (MRS) in four human samples varying in perceived stress exposure. Changes in mPFC glutamate following an acute stressor were reliably moderated by recent perceived stress in healthy controls. This adaptive glutamate response was absent in unmedicated individuals with MDD and was associated with excessively pessimistic beliefs as assessed via ecological momentary assessments over a 1-month follow-up period. Taken together, these data provide novel evidence for glutamatergic adaptation to stress in mPFC that is significantly disrupted in MDD.
Confidence in action: differences between perceived accuracy of decision and motor response
Authors: Siedlecka Marta , Koculak Marcin , Paulewicz Borysław 
Published: June 2020

AbstractEach of our decisions is associated with a degree of confidence. This confidence can change once we have acted as we might start doubting our choice or even become convinced that we made a mistake. In this study, we explore the relations between action and our confidence that our decision was correct or erroneous. Fifty-six volunteers took part in a perceptual decision task in which their decisions could either lead to action or not. At the end of each trial, participants rated their confidence that their decision was correct, or they reported that they had made an error. The main results showed that when given after a response, confidence ratings were higher and more strongly related to decision accuracy, and post-response reports of errors more often indicated actual errors. The results support the view that error awareness and confidence might be partially based on post-action processing.
Do male and female heterogamety really differ in expression regulation? Lack of global dosage balance in pygopodid geckos
Authors: Rovatsos Michail , Gamble Tony , Nielsen Stuart V. , Georges Arthur , Ezaz Tariq , Kratochvíl Lukáš 
Published: June 2020

AbstractDifferentiation of sex chromosomes is thought to have evolved with cessation of recombination and subsequent loss of genes from the degenerated partner (Y and W) of sex chromosomes, which in turn leads to imbalance of gene dosage between sexes. Based on work with traditional model species, theory suggests that unequal gene copy numbers lead to the evolution of mechanisms to counter this imbalance. Dosage compensation, or at least achieving dosage balance in expression of sex-linked genes between sexes, has largely been documented in lineages with male heterogamety (XX/XY sex determination), while ZZ/ZW systems are assumed to be usually associated with the lack of chromosome-wide gene dose regulatory mechanisms. Here we document that although the pygopodid geckos evolved male heterogamety with a degenerated Y chromosome 32-72 million years ago, one species in particular, Burton’s legless lizard (Lialis burtonis), does not possess dosage balance in the expression of genes in its X-specific region. We summarize studies on gene dose regulatory mechanisms in animals and conclude that there is in them no significant dichotomy between male and female heterogamety. We speculate that gene dose regulatory mechanisms are likely to be related to the general mechanisms of sex determination instead of type of heterogamety.
Pitfalls in SARS-CoV-2 PCR diagnostics
Authors: Wernike Kerstin , Keller Markus , Conraths Franz J. , Mettenleiter Thomas C. , Groschup Martin H. , Beer Martin 
Published: June 2020

AbstractTo combat the COVID-19 pandemic, millions of PCR tests are performed worldwide. Any deviation of the diagnostic sensitivity and specificity will reduce the predictive values of the test. Here, we report the occurrence of contaminations of commercial primers/probe sets with the SARS-CoV-2 target sequence of the RT-qPCR as an example for pitfalls during PCR diagnostics affecting diagnostic specificity. In several purchased in-house primers/probe sets, quantification cycle values as low as 17 were measured for negative control samples. However, there were also primers/probe sets that displayed very low-level contaminations, which were detected only during thorough internal validation. Hence, it appears imperative to pre-test each batch of reagents extensively before use in routine diagnosis, to avoid false-positive results and low positive predictive value in low-prevalence situations. As such, contaminations may have happened more widely, COVID-19 diagnostic results should be re-assessed retrospectively to validate the epidemiological basis for control measures.
Brief sensory deprivation triggers plasticity of dopamine-synthesising enzyme expression in genetically labelled olfactory bulb dopaminergic neurons
Authors: Byrne Darren J , Lipovsek Marcela , Crespo Andres , Grubb Matthew S 
Published: June 2020

AbstractIn the glomerular layer of the olfactory bulb, local dopaminergic interneurons play a key role in regulating the flow of sensory information from nose to cortex. These dual dopamine- and GABA-releasing cells are capable of marked experience-dependent changes in the expression of neurotransmitter-synthesising enzymes, including tyrosine hydroxylase (TH). However, such plasticity has most commonly been studied in cell populations identified by their expression of the enzyme being studied, and after long periods of sensory deprivation. Here, instead, we used brief 1- or 3-day manipulations of olfactory experience in juvenile mice, coupled with a conditional genetic approach that labelled neurons contingent upon their expression of the dopamine transporter (DAT-tdTomato). This enabled us to evaluate the potential for rapid changes in neurotransmitter-synthesising enzyme expression in an independently identified neuronal population. Our labelling strategy showed good specificity for olfactory bulb dopaminergic neurons, whilst revealing a minority sub-population of non-dopaminergic DAT-tdTomato cells that expressed the calcium-binding protein calretinin. Crucially, the proportions of these neuronal subtypes were not affected by brief alterations in sensory experience. Short-term olfactory manipulations also produced no significant changes in immunofluorescence or whole-bulb mRNA for the GABA-synthesising enzyme GAD67/Gad1. However, in bulbar DAT-tdTomato neurons brief sensory deprivation was accompanied by a transient, small drop in immunofluorescence for the dopamine-synthesising enzyme dopa decarboxylase (DDC), and a sustained decrease for TH. Deprivation also produced a sustained decrease in whole-bulbThmRNA. Careful characterisation of an independently identified, genetically labelled neuronal population therefore enabled us to uncover rapid experience-dependent changes in dopamine-synthesising enzyme expression.
Precision genetic cellular models identify therapies protective against endoplasmic reticulum stress
Authors: Lebedeva Irina V. , Wagner Michelle V. , Sahdeo Sunil , Lu Yi-Fan , Anyanwu-Ofili Anuli , Harms Matthew B. , Wadia Jehangir S. , Rajagopal Gunaretnam , Boland Michael J. , Goldstein David B. 
Published: June 2020

AbstractCongenital disorders of glycosylation (CDG) and deglycosylation (CDDG) are a collection of rare pediatric disorders with symptoms that range from mild to life threatening. They typically affect multiple organ systems and usually present with neurological abnormalities including hypotonia, cognitive impairment, and intractable seizures. Several genes have been implicated in the thirty-six types of CDG, but currentlyNGLY1is the only known CDDG gene. A common biological mechanism among CDG types and in CDDG is endoplasmic reticulum (ER) stress. Here, we develop two isogenic human cellular models of CDG (PMM2, the most prevalent type of CDG, andDPAGT1) and of the only CDDG (NGLY1) in an effort to identify drugs that can alleviate ER stress. Systematic phenotyping identified elevated ER stress and autophagy levels among other cellular and morphological phenotypes in each of the cellular models. We screened a complex drug library for compounds able to correct aberrant morphological phenotypes in each of the models using an agnostic phenotypic cell painting assay based on >300 cellular features. The image-based screen identified multiple candidate compounds able to correct aberrant morphology, and we show a subset of these are able to correct cellular and molecular defects in each of the models. These results provide new directions for the treatment of rare diseases of glycosylation and deglycosylation and a framework for new drug screening paradigms for more common neurodegenerative diseases characterized by ER stress.Summary sentenceNovel drug screening modality identifies compounds that correct aberrant molecular phenotypes in precision cellular models of glycosylation defects.
Reduced intra- and inter-individual diversity of semantic representations in the brains of schizophrenia patients
Authors: Nishida Satoshi , Matsumoto Yukiko , Yoshikawa Naganobu , Son Shuraku , Murakami Akio , Hayashi Ryusuke , Nishimoto Shinji , Takahashi Hidehiko 
Published: June 2020

AbstractSchizophrenia patients often manifest semantic processing deficits. It has been proposed that these deficits stem from disorganized semantic representations in the brain. However, no study has yet examined the neural correlates of semantic disorganization by directly evaluating semantic representations in the brain. We used voxelwise modeling on functional magnetic resonance imaging signals to evaluate the semantic representations associated with several thousand words in individual patient brains. We then compared the structural properties of semantic representations to those in healthy controls. The variability of semantic representations was smaller both within individual patients and across patients compared to controls. Surrogate data analysis suggests that the observed reduction in representational variability is associated with disorganization of categorical information. To our knowledge, these findings provide the first evidence for sematic disorganization in schizophrenia at the level of brain representations.
Microdiversity and phylogeographic diversification of bacterioplankton in pelagic freshwater systems revealed through long-read amplicon sequencing
Authors: Okazaki Yusuke , Fujinaga Shohei , Salcher Michaela M. , Callieri Cristiana , Tanaka Atsushi , Kohzu Ayato , Oyagi Hideo , Tamaki Hideyuki , Nakano Shin-ichi 
Published: June 2020

AbstractFreshwater ecosystems are inhabited by members of cosmopolitan bacterioplankton lineages despite the disconnected nature of these habitats. The lineages are delineated based on >97% 16S rRNA gene sequence similarity, but their intra-lineage microdiversity and phylogeography, which are key to understanding the eco-evolutional processes behind their ubiquity, remain unresolved. Here, we applied long-read amplicon sequencing targeting nearly full-length 16S rRNA genes and the adjacent ribosomal internal transcribed spacer sequences to reveal the intra-lineage diversities of pelagic bacterioplankton assemblages in 11 deep freshwater lakes in Japan and Europe. Our single nucleotide-resolved analysis, which was validated using shotgun metagenomic sequencing, uncovered 7–101 amplicon sequence variants for each of the 11 predominant bacterial lineages and demonstrated sympatric, allopatric, and temporal microdiversities that could not be resolved through conventional approaches. Clusters of samples with similar intra-lineage population compositions were identified, which consistently supported genetic isolation between Japan and Europe. At a regional scale (up to hundreds of kilometers), dispersal between lakes was unlikely to be a limiting factor, and environmental factors were potential determinants of population composition. The extent of microdiversification varied among lineages, suggesting that highly diversified lineages (e.g., Iluma-A2 and acI-A1) achieve their ubiquity by containing a consortium of genotypes specific to each habitat, while less diversified lineages (e.g., CL500-11) may be ubiquitous due to a small number of widespread genotypes. The lowest extent of intra-lineage diversification was observed among the dominant hypolimnion-specific lineage (CL500-11), suggesting that their dispersal among lakes is not limited despite the hypolimnion being a more isolated habitat than the epilimnion. Our novel approach complemented the limited resolution of short-read amplicon sequencing and limited sensitivity of the metagenome assembly-based approach, and highlighted the complex ecological processes underlying the ubiquity of freshwater bacterioplankton lineages.
Systems-level immunomonitoring from acute to recovery phase of severe COVID-19
Authors: Rodriguez Lucie , Pekkarinen Pirkka , Lakshmikanth Tadepally , Tan Ziyang , Consiglio Camila Rosat , Pou Christian , Chen Yang , Mugabo Constantin Habimana , Quoc Anh Nguyen , Nowlan Kirsten , Strandin Tomas , Levanov Lev , Mikes Jaromir , Wang Jun , Kantele Anu , Hepojoki Jussi , Vapalahti Olli , Heinonen Santtu , Kekäläinen Eliisa , Brodin Petter 
Published: June 2020

SUMMARYThe immune response to SARS-CoV2 is under intense investigation, but not fully understood att this moment. Severe disease is characterized by vigorous inflammatory responses in the lung, often with a sudden onset after 5–7 days of stable disease. Efforts to modulate this hyperinflammation and the associated acute respiratory distress syndrome, rely on the unraveling of the immune cell interactions and cytokines that drive such responses. Systems-level analyses are required to simultaneously capture all immune cell populations and the many protein mediators by which cells communicate. Since every patient analyzed will be captured at different stages of his or her infection, longitudinal monitoring of the immune response is critical. Here we report on a systems-level blood immunomonitoring study of 39 adult patients, hospitalized with severe COVID-19 and followed with up to 14 blood samples from acute to recovery phases of the disease. We describe an IFNγ – Eosinophil axis activated prior to lung hyperinflammation and changes in cell-cell coregulation during different stages of the disease. We also map an immune trajectory during recovery that is shared among patients with severe COVID-19.HIGHLIGHTSSystems-level immunomonitoring from acute to recovery in severe COVID-19An IFNγ - Eosinophil axis involved in lung hyperinflammationCell-cell coregulation differ during four disease stagesBasophils and hyperinflammation modulate humoral responsesA shared trajectory of immunological recovery in severe COVID-19
Coronavirus Disease 2019 (COVID-19) Dynamics Considering the Influence of Hospital Infrastructure
Authors: Pacheco Pedro M.C.L. , Savi Marcelo A. , Savi Pedro V. 
Published: June 2020

ABSTRACTThis paper deals with the mathematical modeling and numerical simulations related to the coronavirus dynamics. A description is developed based on the framework of susceptible-exposed-infectious-removed model. Removed population is split into recovered and death populations allowing a better comprehension of real situations. Besides, total population is reduced based on the number of deaths. Hospital infrastructure is also included into the mathematical description allowing the consideration of collapse scenarios. Initially, a model verification is carried out calibrating system parameters with data from China outbreak that is considered a benchmark due the availability of data for the entire cycle. Afterward, numerical simulations are performed to analyze COVID-19 dynamics in Brazil. Results show several scenarios showing the importance of social isolation. System dynamics has a strong sensitivity to transmission rate showing the importance of numerical simulations to guide public health decision strategies.