bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ventral tegmental area GABA neurons mediate stress-induced anhedonia
Authors: Lowes Daniel C. , Chamberlin Linda A. , Kretsge Lisa N. , Holt Emma S. , Abbas Atheir I. , Park Alan J. , Yusufova Lyubov , Bretton Zachary H. , Firdous Ayesha , Gordon Joshua A. , Harris Alexander Z. 
Published: May 2020

AbstractStressful experiences frequently precede depressive episodes1. Depression results in anhedonia, or disrupted reward-seeking, in most patients2. In humans3,4and rodents5,6, stress can disrupt reward-seeking, providing a potential mechanism by which stress can precipitate depression7-9. Yet despite decades investigating how stress modulates dopamine neuron transmission between the ventral tegmental area (VTA) and nucleus accumbens (NAc), the underpinnings of the stress-anhedonia transition remain elusive10-13. Here we show that during restraint stress, VTA GABA neurons drive low frequency NAc LFP oscillations, rhythmically modulating NAc firing rates. The strength of these stress-induced NAc oscillations predict the degree of impaired reward-seeking upon release from restraint. Inhibiting VTA GABA neurons disrupts stress-induced NAc oscillations and reverses the effect of stress on reward-seeking. By contrast, mimicking these oscillations with rhythmic VTA GABA stimulation in the absence of stress blunts subsequent reward-seeking. These experiments demonstrate that VTA GABA inputs to the NAc are both necessary and sufficient for stress-induced decreases in reward seeking behavior, elucidating a key circuit-level mechanism underlying stress-induced anhedonia.
Population structure of the invasive golden mussel (Limnoperna fortunei) on reservoirs from five Brazilian drainage basins
Authors: Ferreira João G. R. N. , Soares-Souza Giordano Bruno , Americo Juliana A. , Dumaresq Aline , Rebelo Mauro F. 
Published: May 2020

AbstractThe golden mussel (Limnoperna fortunei) is a freshwater bivalve that was introduced in South America almost 30 years ago, likely through ballast water of Asian ships. Since then, it has spread across the continent, causing both economic and environmental impacts. The study of the population structure of an invasive species may bring valuable insights towards understanding its pattern of dispersion, which in turn will help to create more effective management plans. Here, we have compared mussel populations from 5 different Brazilian reservoirs and tested for the presence of geographic genetic structure. In order to obtain a high number of single nucleotide variants (SNVs) at good cost-benefit, we have for the first time applied the double digest restriction-site associated DNA sequencing (ddRAD-seq) protocol for the golden mussel. The ddRAD-seq protocol allowed us to obtain 2046 SNVs, which were then used to assess population structure by applying three independent methodologies: Principal Component Analysis (PCA), Bayesian Clustering and Phylogenetic Tree. All methodologies have indicated absent geographic structure.
Kin recognition in guppies uses self-referencing on olfactory cues
Authors: Daniel Mitchel J. , Rodd F. Helen 
Published: May 2020

AbstractKin recognition plays an important role in social evolution, but the proximate mechanisms by which individuals recognize kin remain poorly understood. In many species, individuals form a “kin template” that they compare against conspecifics’ phenotypes to assess phenotypic similarity–and by association, relatedness. Individuals may form a kin template through self-inspection (i.e. self-referencing) and/or by observing their rearing associates (i.e. family-referencing). However, despite much interest, few empirical studies have successfully disentangled self- and family-referencing. Here, we use a novel set of breeding crosses in the Trinidadian guppy (Poecilia reticulata) to definitively disentangle referencing systems by manipulating exposure to kin from conception onwards. We show that guppies discriminate among their full- and maternal half-siblings, which can only be explained by self-referencing. Additional behavioral experiments revealed no evidence that guppies incorporate the phenotypes of their broodmates or mother into the kin template. Finally, by manipulating the format of our behavioral tests, we show that olfactory communication is both necessary and sufficient for kin discrimination. These results demonstrate that individuals recognize kin by comparing the olfactory phenotypes of conspecifics against their own. This study resolves key questions about the proximate mechanisms underpinning kin recognition, with implications for the ontogeny and evolution of social behavior.
Macrophages drive the inflammatory phase in experimental osteoarthritis
Authors: Montgomery Anna , Fahy Niamh , Hamilton Samuel , Eckman Blair , De Almeida Lucia , Ishihara Shingo , Mayr Maximilian G , Chen Shang Yang , Gadhvi Gaurav , Cuda Carla , Malfait Anne-Marie , Bastiaansen-Jenniskens Yvonne , Winter Deborah R. 
Published: May 2020

ABSTRACTMacrophages fulfill critical functions in maintaining tissue homeostasis in steady-state, as well as in inflammation and immune response. Inflammation is not considered a major driver of osteoarthritis (OA), but macrophages have been implicated in its pathogenesis. Here, we use two mouse models of experiment OA – collagenase-induced osteoarthritis (CIOA) and destabilization of the medial meniscus (DMM) – to quantify the immune cell infiltration into the knee joint during the early stages of disease. We find that the peak of inflammation occurs at day 3 in CIOA and is characterized by a transitory increase in neutrophils and monocytes and a longer-lived expansion of synovial macrophages. Macrophage sub-populations are disproportionally expanded with CX3CR1+ cells accounting for a larger proportion of the macrophage compartment. Transcriptional profiling demonstrates that synovial macrophages up-regulate inflammatory genes coinciding with peak inflammation and down-regulate genes associated with homeostasis and tissue-residence. Female mice exhibit a similar expansion of macrophages post-CIOA indicating that the inflammatory phase is not sex-specific. Finally, we find day 7 post-DMM is also characterized by increases in neutrophil, monocyte, and macrophage sub-population numbers. These results support a role for macrophages in early stages of OA through driving the inflammatory phase. Further investigation may elucidate potential targets for the prevention or attenuation of OA-associated cartilage damage.
The immunophilin Zonda controls regulated exocytosis in endocrine and exocrine tissues
Authors: de la Riva Carrasco Rocío , Pandolfo Sebastián Perez , Freire Sofía Suarez , Romero Nuria M. , Bhujabal Zambarlal , Johansen Terje , Wappner Pablo , Melani Mariana 
Published: May 2020

ABSTRACTExocytosis is a fundamental process in physiology, communication between cells, organs and even organisms. Hormones, neuropeptides and antibodies, among other cargoes are packed in exocytic vesicles that need to reach and fuse with the plasma membrane to release their content to the extracellular milieu. Hundreds of proteins participate in this process and several others in its regulation. We report here a novel component of the exocytic machinery, theDrosophilatransmembrane immunophilin Zonda (Zda), previously found to participate in autophagy. Zda is highly expressed in secretory tissues, and regulates exocytosis in at least three of them: the ring gland, insulin-producing cells and the salivary gland. Using the salivary gland as a model system, we found that Zda is required at final steps of the exocytic process for fusion of secretory granules to the plasma membrane. In a genetic screen we identified the small GTPase RalA as a crucial regulator of secretory granule exocytosis that operates upstream of Zda in the process.
Competition and Caries on Enamel of a Dual-species Biofilm Model ofStreptococcus mutansandStreptococcus sanguinis
Authors: Díaz-Garrido Natalia , Lozano Carla P. , Kreth Jens , Giacaman Rodrigo A. 
Published: May 2020

AbstractImbalances within the dental biofilm trigger dental caries, currently considered a dysbiosis and the most prevalent non-communicable disease. There is still a gap in knowledge about the dynamics of enamel colonization by bacteria from the dental biofilm in caries. The aim, therefore, was to test whether the sequence of enamel colonization by a typically commensal and a cariogenic species modifies biofilm’s cariogenicity. Dual-species biofilms ofStreptococcus mutans(Sm) andStreptococcus sanguinis(Ss) on saliva-coated enamel slabs were inoculated in different sequences: Sm followed by Ss (Sm-Ss), Ss followed by Sm (Ss-Sm), Sm and Ss inoculated at the same time (Sm=Ss) and the single-species controls Sm followed by Sm (Sm-Sm) and Ss followed by Ss (Ss-Ss). Biofilms were exposed to 10% sucrose, 3x/day for 5 days and the slabs/biofilms were retrieved to assess demineralization, viable cells, biomass, proteins, polysaccharides and H2O2production. When compared with Sm-Sm, primary inoculation with Ss reduced demineralization (p<0.05). Both Ss-Sm and Sm=Ss sequences showed reduction in biomass, protein and polysaccharide content (p<0.05). The highestS. sanguinisviable cells and H2O2production and the lowest acidogenicity were observed when Ss colonized enamel before Sm (p<0.05). Initial enamel adherence with commensal biofilms seems to induce more intense competition against more typically cariogenic species, reducing cariogenicity.ImportanceThe concept of caries as an ecological disease implies the understanding of the intricate relationships among the populating microorganisms. Under frequent sugars exposure, some the bacteria from the oral biofilm develop pathogenic traits that lead to oral imbalances, known as dysbiosis. Depending on which microorganism colonizes the dental surface first, different competition strategies may be developed. Since the study of the interactions in the entire dental biofilm is not an easy task, in this article we model the interplay among these microorganisms using a caries-inducing (S. mutans) and a health-associated species (S. sanguinis). Initial enamel adherence with S. sanguinis seems to induce more intense competition against more typically caries-inducing species. Besides continuous exposure with sugars, early colonization of the enamel by highly cariogenic species, likeS. mutans, appears to be needed to develop caries lesions, as well. Promoting early colonization by health-associated bacteria, such asS. sanguinis, could help maintaining oral health, delaying dysbiosis.
Step-specific adaptation and trade-off over the course of an infection by GASP-mutation small colony variants
Authors: Christian Faucher , Vincent Mazana , Marion Kardacz , Nathalie Parthuisot , Jean-Baptiste Ferdy , David Duneau 
Published: May 2020

AbstractDuring an infection, parasites face a succession of challenges, each decisive for disease outcome. The diversity of challenges requires a series of parasite adaptations to successfully multiply and transmit from host to host. Thus, the pathogen genotypes which succeed during one step might be counter-selected in later stages of the infection. Using the bacteriaXenorhabdus nematophilaand adultDrosophila melanogasteras hosts, we showed that such step-specific adaptations, here linked to GASP mutations in theX. nematophilamaster gene regulatorlrp, exist and can trade-off with each other. We found that nonsenselrpmutations had lowered ability to resist the host immune response, while all classes of mutations inlrpwere associated with a decrease in the ability to proliferate during early infection. We demonstrate that reduced proliferation ofX. nematophilabest explains diminished virulence in this infection model. Finally, decreased proliferation during the first step of infection is accompanied with improved proliferation during late infection, suggesting a trade-off between the adaptations to each step. Step-specific adaptations could play a crucial role in the chronic phase of infections in any diseases that show similar small colony variants (also known as SCV) toX. nematophila.ImportanceWithin-host evolution has been described in many bacterial diseases, and the genetic basis behind the adaptations stimulated a lot of interest. Yet, the studied adaptations are generally focused on antibiotic resistance, rarely on the adaptation to the environment given by the host, and the potential trade-off hindering adaptations to each step of the infection are rarely considered. Those trade-offs are key to understand intra-host evolution, and thus the dynamics of the infection. However, the understanding of these trade-offs supposes a detailed study of host-pathogen interactions at each step of the infection process, with for each step an adapted methodology. UsingDrosophila melanogasteras host and the bacteriaXenorhabdus nematophila, we investigated the bacterial adaptations resulting from GASP mutations known to induce small colony variant (SCV) phenotype positively selected within-the-host over the course of an infection, and the trade-off between step-specific adaptations.
Analyzing Covid-19 Data using SIRD Models
Authors: Chakraborty Abhijit , Chen Jiaying , Desvars-Larrive Amélie , Klimek Peter , Tames Erwin Flores , Garcia David , Horstmeyer Leonhard , Kaleta Michaela , Lasser Jana , Reddish Jenny , Pinior Beate , Wachs Johannes , Turchin Peter 
Published: May 2020

SummaryThe goal of this analysis is to estimate the effects of the diverse government intervention measures implemented to mitigate the spread of the Covid-19 epidemic. We use a process model based on a compartmental epidemiological framework Susceptible-Infected-Recovered-Dead (SIRD). Analysis of case data with such a mechanism-based model has advantages over purely phenomenological approaches because the parameters of the SIRD model can be calibrated using prior knowledge. This approach can be used to investigate how governmental interventions have affected the Covid-19-related transmission and mortality rate during the epidemic.
Prognostic value of visual quantification of lesion severity at initial chest CT in confirmed Covid-19 infection: a retrospective analysis on 216 patients
Authors: Taieb Elias , Labani Aïssam , Ruch Yvon , Danion François , Bilbault Pascal , Oberlin Mathieu , Leyendecker Pierre , Roy Catherine , Ohana Mickaël 
Published: May 2020

AbstractRationale and ObjectivesStudies suggest an association between chest CT findings assessed with semi-quantitative CT score and gravity of Covid-19. The objective of this work is to analyze potential correlation between visual quantification of lesion severity at initial chest CT and clinical outcome in confirmed Covid-19 patients.Materials and MethodsFrom March 5th to March 21st, 2020, all consecutive patients that underwent chest CT for clinical suspicion of Covid-19 at a single tertiary center were retrospectively evaluated for inclusion. Patients with lung parenchyma lesions compatible with Covid-19 and positive RT-PCR were included.Global extensiveness of abnormal lung parenchyma was visually estimated and classified independently by 2 readers, following the European Society of Thoracic Imaging Guidelines. Death and/or mechanical ventilation within 30 days following the initial chest CT was chosen as the primary hard endpoint.Results216 patients (124 men, 62 years-old ± 16.5, range 22 – 94 yo) corresponding to 216 chest CT were included. Correlation between lesion severity and percentage of patients that met the primary endpoint was high, with a coefficient ρ of 0.87 (p = 0.05).A greater than 25% involvement was significantly associated with a higher risk of mechanical ventilation or death at 30 days, with a Risk Ratio of 5.00 (95% CI [3.59–6.99]).ConclusionThis retrospective cohort confirms a correlation between visual evaluation of lesions severity at initial chest CT and the 30 days clinical outcome of Covid-19 patients and suggests using a threshold of greater than 25% involvement to identify patients at risk.
Use of Skin Cancer Procedures, Medicare Reimbursement, and Overall Expenditures, 2012-2017
Authors: Puri Pranav , Baliga Sujith , Pittelkow Mark R. , Bhullar Puneet K. , Mangold Aaron R. 
Published: May 2020

AbstractThe treatment of skin cancers represents a growing share of healthcare expenditures. However, little is known about how variations in payment rates relate to the use of different skin cancer procedures. This study describes recent trends in payment rates, use rates, and overall expenditures for skin cancer procedures in the Medicare Part B population. In this ecological study, we used the Medicare Physician Supplier and Other Provider Public Use File (POSPUF) to analyze trends in Medicare payment rates, use rates, and overall Medicare expenditures for skin cancer procedures from 2012 to 2017. We adjusted reimbursement rates for inflation by converting payment amounts into units of 2017 dollars. From 2012 to 2017, overall inflation-adjusted Medicare expenditure on skin cancer procedures increased 9%. Over this time period, inflation-adjusted Medicare reimbursement rates declined for each procedure class, with the exception of shave excision. Concurrently, the use rate of Mohs micrographic surgery increased 21%, while the use rate for all other skin cancer procedure classes declined. In summary, the results of this study suggest that increased use of Mohs has displaced use of other skin cancer procedures in the Medicare population.
Chloroquine, hydroxychloroquine, and COVID-19: systematic review and narrative synthesis of efficacy and safety: Systematic review of (hydroxy)chloroquine efficacy and safety
Authors: Takla Michael , Jeevaratnam Kamalan 
Published: May 2020

AbstractBackgroundThe COVID-19 pandemic has required clinicians to urgently identify new treatment options or the repurposing of existing drugs. Several drugs are now being repurposed with the aim of identifying if these drugs provide some level of disease resolution. Of particular interest are chloroquine (CQ) and hydroxychloroquine (HCQ), first developed as an antimalarial therapy. There is increasing concern with regards to the efficacy and safety of these agents. The aims of this review are to systematically identify and collate studies describing the use of CQ and HCQ in human clinical trials and provide a detailed synthesis of evidence of its efficacy and safety.Methods and FindingsSearches for (“COVID” AND “chloroquine”[title/abstract] AND “outcomes”[full text]) and two (“COVID” AND “hydroxychloroquine”[title/abstract] AND “outcomes”[full text]) yielded 272 unique articles. Unique articles were manually checked for inclusion and exclusion criteria and also subjected to a quality appraisal assessment. A total of 19 articles were included in the systematic review. Seventy-five percent of observational studies employing an endpoint specific to efficacy recorded no significant difference in the attainment of outcomes, between COVID-19 patients given a range of CQ and/or HCQ doses, and the control groups. All clinical trials and 82% of observational studies examining an indicator unique to drug safety discovered a higher probability of adverse events in those treated patients suspected of, and diagnosed with, COVID-19. Seventy-five percent of the total papers focusing on cardiac side-effects found a greater incidence among patients administered a wide range of CQ and/or HCQ doses, with QTc prolongation the most common finding, in addition to its consequences of VT and cardiac arrest. Of the total studies using mortality rate as an end-point, 60% reported no significant change in the risk of death, while 30% showed an elevation, and 10% a depression, in treated relative to control patients.ConclusionThe strongest available evidence suggests that, relative to standard in-hospital management of symptoms, the use of CQ and HCQ to treat hospitalised COVID-19 patients has likely been unsafe. At the very least, the poor quality of data failing to find any significant changes in the risk of VT should preclude definitive judgment on drug safety until the completion of high-quality randomised clinical trials.
CoViD-19 in Italy: a mathematical model to analyze the epidemic containment strategy and the economic impacts
Authors: Verachi Fabio , Trussoni Luca , Lanzi Luciano 
Published: May 2020

SummaryThe objective of this paper is to evaluate the potential costs deriving from the adoption of the CoViD-19 epidemic management strategy. For this purpose, we developed a specific methodology that combines an epidemiological model, known in the literature as “SIR” (Susceptible - Infected - Recovered), and a probabilistic state model, also known as “multi-state”. The model thus conceived was then parameterized using the dataset published by the Italian Government through the Civil Protection and the Istituto Superiore di Sanità. We therefore estimated the duration of the disease and the related costs, with reference to the strategy currently under discussion between government institutions and social organizations involved. Given the flexibility of the adopted approach, the tool will also be able to provide useful indications in relation to any alternative strategies that the Government could adopt in the near future, as well as being the starting point of an analysis of the epidemic indirect costs such as losses of GDP fractions.
Predicting social distancing index during COVID-19 outbreak through online search engines trends
Authors: Lins-Filho P. C. , Araújo M. M. S. , Macêdo T. S. , Ferreira A. K. A. , Melo M. C. F. , Silva E. L. M. S. , Freitas J. L. M. , Caldas A. F. 
Published: May 2020

SummaryOnline-available information has been considered an accessory tool to estimate epidemiology and collect data on diseases and population behavior patterns. This study aimed to explore the potential use of Google and YouTube relative search volume to predict social distancing index in Brazil during COVID-19 outbreak and verify the correlation between social distancing measures with the course of the epidemic. Data concerning the social distancing index, epidemiological data on COVID-19 in Brazil and the search engines trends for “Coronavirus” were retrieved from online databases. Multiple linear regression was performed and resulted in a statistically significant model evidencing that Google and YouTube relative search volumes are predictors of the social distancing index. The Spearman correlation test revealed a weak correlation between social distancing measures and the course of the COVID-19 epidemic. Health authorities can apply these data to define the proper timing and location for practicing appropriate risk communication strategies.
COVID-19 higher morbidity and mortality in Chinese regions with lower air quality
Authors: Pansini Riccardo , Fornacca Davide 
Published: May 2020

AbstractWe investigated the geographical character of the COVID-19 infection in China and correlated it with satellite- and ground-based measurements of air quality. Controlling for population size, we found more viral infections in those areas afflicted by high Carbon Monoxide, formaldehyde, PM 2.5, and Nitrogen Dioxide values. Higher mortality was also correlated with relatively poor air quality. Air pollution appears to be a risk factor for the incidence of this disease, similar to smoking. This suggests the detrimental impact of air pollution in these types of respiratory epidemics.Short summaryThere is a significant correlation between air pollution and COVID-19 spread and mortality in China.The correlation stands at a second-order administration level, after controlling for varying population densities and removing Wuhan and Hubei from the dataset.Living in an area with low air quality is a risk factor for becoming infected and dying from this new form of coronavirus.