bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morphological colour adaptation during development: Involvement of Growth Hormone Receptor 1
Authors: Delgadin Tomás Horacio , Castañeda-Cortés Diana Carolina , Sacks Clara , Breccia Andrés , Fernandino Juan Ignacio , Vissio Paula Gabriela 
Published: June 2020

AbstractMorphological background adaptation is both an endocrine and a nervous response, involving changes in the amount and shape of chromatophores. However, if this adaptation takes place at early developmental stages is largely unknown. Somatolactin (SL) is a pituitary hormone present in fish, which has been associated to skin pigmentation. Moreover, growth hormone receptor type 1 (ghr1) has been suggested to be the SL receptor and was associated to background adaptation in adults. In this context, the aim of this work was to evaluate the ontogeny of morphological adaptation to background and the participation ofghr1in this process. We found in larval stages ofCichlasoma dimerusthat the number of head melanophores and ir-SL pituitary cells were increased in individuals reared in black backgrounds compared to fish grown in white tanks. In medaka (Oryzias latipes)larval stages a similar response was observed that is altered by aghr1biallelic mutations using CRISPR/cas9.Interestingly, melanophore and leucophore numbers are highly associated. Furthermore, we found that somatic growth is reduced inghr1biallelic mutant medaka, establishing the dual function of this growth hormone receptor. Taken together, these results show that morphological background adaptation is present at early stages during development and that is dependent uponghr1unless during this period.
Identification of polyketide biosynthetic gene clusters that harbor self-resistance target genes
Authors: Vandova Gergana A , Nivina Aleksandra , Khosla Chaitan , Davis Ronald W , Fisher Curt R , Hillenmeyer Maureen E 
Published: June 2020

AbstractBackgroundPolyketide secondary metabolites have been a rich source of antibiotic discovery for decades. Thousands of novel polyketide synthase (PKS) gene clusters have been identified in recent years with advances in DNA sequencing. However, experimental characterization of novel and useful PKS activities remains complicated. As a result, computational tools to analyze sequence data are essential to identify and prioritize potentially novel PKS activities. Here we exploit the concept of genetically-encoded self-resistance to identify and rank biosynthetic gene clusters for their potential to encode novel antibiotics.ResultsTo identify PKS genes that are likely to produce an antibacterial compound, we developed an automated method to identify and catalog clusters that harbor potential self-resistance genes. We manually curated a list of known self-resistance genes and searched all NCBI genome databases for homologs of these self-resistance genes in biosynthetic gene clusters. The algorithm takes into account (1) the distance of the potential self-resistance gene to a core enzyme in the biosynthetic gene cluster; (2) the presence of a duplicated housekeeping copy of the self-resistance gene; (3) the presence of close homologs of the biosynthetic gene cluster in diverse species also harboring the putative self-resistance gene; (4) evidence for coevolution of the self-resistance gene and core biosynthetic gene; and (5) self-resistance gene ubiquity. We generated a catalog of 190 unique PKS clusters whose products likely target known enzymes of antibacterial importance. We also present an expanded set of putative self-resistance genes that may be useful in identifying small molecules active against novel microbial targets.ConclusionsWe developed a bioinformatic approach to identify and rank biosynthetic gene clusters that likely harbor self-resistance genes and may produce compounds with antibacterial properties. We compiled a list of putative self-resistance genes for novel antibacterial targets, and of orphan PKS clusters harboring these targets. These catalogues are a resource for discovery of novel antibiotics.
Spike-frequency dependent inhibition and excitation of neural activity by high-frequency ultrasound
Authors: Prieto Martin Loynaz , Firouzi Kamyar , Khuri-Yakub Butrus T. , Madison Daniel V. , Maduke Merritt 
Published: June 2020

ABSTRACTUltrasound can modulate action-potential firingin vivoandin vitro, but the mechanistic basis of this phenomenon is not well understood. To address this problem, we used patch-clamp recording to quantify the effects of focused, high-frequency (43 MHz) ultrasound on evoked action potential firing in CA1 pyramidal neurons in acute rodent hippocampal brain slices. We find that ultrasound can either inhibit or potentiate firing in a spike-frequency-dependent manner: at low (near-threshold) input currents and low firing frequencies, ultrasound inhibits firing, while at higher input currents and higher firing frequencies, ultrasound potentiates firing. The net result of these two competing effects is that ultrasound increases the threshold current for action potential firing, the slope of frequency-input curves, and the maximum firing frequency. In addition, ultrasound slightly hyperpolarizes the resting membrane potential, decreases action potential width, and increases the depth of the afterhyperpolarization. All of these results can be explained by the hypothesis that ultrasound activates a sustained potassium conductance. According to this hypothesis, increased outward potassium currents hyperpolarize the resting membrane potential and inhibit firing at near-threshold input currents, but potentiate firing in response to higher input currents by limiting inactivation of voltage-dependent sodium channels during the action potential. This latter effect is a consequence of faster action-potential repolarization, which limits inactivation of voltage-dependent sodium channels, and deeper (more negative) afterhyperpolarization, which increases the rate of recovery from inactivation. Based on these results we propose that ultrasound activates thermosensitive and mechanosensitive two-pore-domain potassium (K2P) channels, through heating or mechanical effects of acoustic radiation force. Finite-element modelling of the effects of ultrasound on brain tissue suggests that the effects of ultrasound on firing frequency are caused by a small (less than 2°C) increase in temperature, with possible additional contributions from mechanical effectsSUMMARYPrieto et al. describe how ultrasound can either inhibit or potentiate action potential firing in hippocampal pyramidal neurons and demonstrate that these effects can be explained by increased potassium conductance.
Spatial modelling improves genetic evaluation in smallholder breeding programs
Authors: Selle Maria L. , Steinsland Ingelin , Powell Owen , Hickey John M. , Gorjanc Gregor 
Published: June 2020

AbstractBreeders and geneticists use statistical models for genetic evaluation of animals to separate genetic and environmental effects on phenotype. A common way to separate these effects is to model a descriptor of an environment, a contemporary group or herd, and account for genetic relationship between animals across the environments. However, separating the genetic and environmental effects in smallholder systems is challenging due to small herd sizes and weak genetic connectedness across herds. Our hypothesis was that accounting for spatial relationships between nearby herds can improve genetic evaluation in smallholder systems. Further, geographically referenced environmental covariates are increasingly available and could be used to model underlying sources of the spatial relationships. The objective of this study was therefore to evaluate the potential of spatial modelling to improve genetic evaluation in smallholder systems. We focus solely on dairy cattle smallholder systems.We performed simulations and real dairy cattle data analysis to test our hypothesis. We used a range of models to account for environmental variation by estimating herd and spatial effects. We compared these models using pedigree or genomic data.The results show that in smallholder systems (i) standard models are not able to separate genetic and environmental effects, (ii) spatial modelling increases accuracy of genetic evaluation for phenotyped and non-phenotyped animals, (iii) environmental covariates do not substantially improve accuracy of genetic evaluation beyond simple distance-driven spatial relationships between herds, (iv) the benefit of spatial modelling was the largest when the genetic and environmental effects were hard to separate and (v) spatial modelling was beneficial when using either pedigree or genomic data.We have demonstrated the potential of spatial modelling to improve genetic evaluation in smallholder systems. This improvement is driven by establishing environmental connectedness between herds that enhances separation of the genetic and environmental effects. We suggest routine spatial modelling in genetic evaluations, particularly for smallholder systems. Spatial modelling could also have major impact in studies of human and wild populations.
Concordance of “rapid” serological tests and IgG and IgM chemiluminescence for SARS-COV-2
Authors: Sáenz-Flor K , y Sanatafé L 
Published: June 2020

AbstarctBackgroundThe COVID-19 serological tests for IgG and IgM have been developed with several methodologies: Immunoenzymatic Assay (ELISA), Chemiluminescence, Electro Chemiluminescence, Fluorescent Lateral Flow Immunoassays and Immunochromatography. None of these tests should be used for the diagnosis or population screening of the disease, considering that the antibodies appear only on the 8th – 14th day of the disease onset. The present study evaluates a sample of immunofluorescent and immunochromatographic rapid tests to show their agreement in relation to Chemiluminescence.MethodsA diagnostic test evaluation assay was performed to establish the performance of five “rapid” tests (4 immunochromatographic and 1 immunofluorescent tests) for IgG and IgM serology for SARS-CoV-2 using a panel of 30 serum samples from patients received in the laboratory analysis routine. For the evaluation of clinical performance, the qualitative results of the “rapid” tests were compared against those obtained by chemiluminescence, dichotomized as positives (≥ 10 AU / mL) or negative (<10 UA / mL).FindingsThe best agreement is seen in the immunofluorescent assay, for the IgG contrast, with a particularly good kappa index (0.85), without positive disagreements and a negative disagreement of about 15%. In the immunochromatographic methods Kappa index was 0.61 at best, with disagreements in negative findings of ≈35% and in positive cases of up to ≈70%.The IgM concordance behavior, on the other hand, reflects a weak to moderate Kappa concordance value (Kappa 0.2 to 0.6), with negative disagreements reaching up to 55% and positives of up to 84%, without any evaluated test reaching Kappa performance equal to or greater than 0.8.InterpretationSerological studies should be used in the clinical and epidemiological context and of other diagnostic tests. Given the high demand and supply in the market of “rapid serological tests”, its evaluation against panels of serologically positive or negative samples established by Chemiluminescence or Electro chemiluminescence is essential to authorize its extensive use in populationsFundingNone
Is death from Covid-19 a multistep process?
Authors: Pearce Neil , Moirano Giovenale , Maule Milena , Kogevinas Manolis , Rodo Xavier , Lawlor Deborah A , Vandenbroucke Jan , Vandenbroucke-Grauls Christina , Polack Fernando P , Custovic Adnan 
Published: June 2020

ABSTRACTCovid-19 death has a different relationship with age than is the case for other severe respiratory pathogens. The Covid-19 death rate increases exponentially with age, and the main risk factors are age itself, as well as having underlying conditions such as hypertension, diabetes, cardiovascular disease, severe chronic respiratory disease and cancer. Furthermore, the almost complete lack of deaths in children suggests that infection alone is not sufficient to cause death; rather, one must have gone through a number of changes, either as a result of undefined aspects of aging, or as a result of chronic disease. These characteristics of Covid-19 death are consistent with the multistep model of disease, a model which has primarily been used for cancer, and more recently for amyotrophic lateral sclerosis (ALS). We applied the multi-step model to data on Covid-19 case fatality rates (CFRs) from China, South Korea, Italy, Spain and Japan. In all countries we found that a plot of ln (CFR) against ln (age) was approximately linear with a slope of about 5. As a comparison, we also conducted similar analyses for selected other respiratory diseases. SARS showed a similar log-log age-pattern to that of Covid-19, albeit with a lower slope, whereas seasonal and pandemic influenza showed quite different age-patterns. Thus, death from Covid-19 and SARS appears to follow a distinct age-pattern, consistent with a multistep model of disease that in the case of Covid-19 is probably defined by comorbidities and age producing immune-related susceptibility. Identification of these steps would be potentially important for prevention and therapy for SARS-COV-2 infection.
Continuous positive airway pressure face-mask ventilation to manage massive influx of patients requiring respiratory support during the SARS-CoV-2 outbreak
Authors: Alviset S. , Riller Q. , Aboab J. , Dilworth K. , Billy PA. , Lombardi Y. , Azzi M. , Ferreira Vargas L. , Laine L. , Lermuzeaux M. , Memain N. , Silva D. , Tchoubou T. , Ushmorova D. , Dabbagh H. , Escoda S. , Lefrançois R. , Nardi A. , Ngima A. , Ioos V. 
Published: June 2020

AbstractBackgroundSince December 2019, a global outbreak of coronavirus disease (COVID-19) is responsible for massive influx of patients with acute respiratory failure in hospitals. We describe the characteristics, clinical course, and outcomes of COVID-19 patients treated with continuous positive airway pressure (CPAP) in a large public hospital in France.MethodIt is a single centre retrospective observational cohort. From 27th March to 23rd April, consecutive patients who had signs of respiratory failure or were unable to maintain an SpO2 > 90%, despite receiving 10 to 15 l/min of oxygen with a non-rebreather mask, were treated by CPAP with a face-mask unless the ICU physician judged that immediate intubation was indicated. The main outcomes under study were reasons for CPAP discontinuation and mortality.ResultsA total of 585 patients were admitted in Delafontaine hospital for severe COVID-19. ICU was quickly overwhelmed. Fifty-nine out of 159 (37%) patients requiring ICU care had to be referred to other hospitals. CPAP therapy was initiated in 49 patients and performed out of ICU in 41 (84%). SARS-CoV2 pneumonia was confirmed by PCR from respiratory tract in 39 (79%) patients and by thoracic CT scan in the remaining patients. CPAP was performed out of ICU in 41 (84%) cases. Median age was 65 years (IQR=54-71). Median duration of CPAP treatment was 3 days (IQR=1-5). Reasons for discontinuation of CPAP were intubation for invasive ventilation in 25 (51%) patients, improvement in 16 (33%), poor tolerance in 6 (12%) and death in 2 (4%). A decision not to intubate had been taken for the 2 patients who died while on CPAP.ConclusionsTreatment with CPAP is feasible and safe in a non-ICU environment in the context of a massive influx of patients. One third of these patients with high oxygen requirements did not eventually need invasive ventilation.Key messagesWhat is the key question?What is the best respiratory support strategy to manage a massive influx of patients with hypoxemic respiratory failure despite high-flow oxygen delivered with a non-rebreather mask?What is the bottom line?Continuous positive airway pressure face mask ventilation delivered in non-ICU wards to patients who do not require immediate intubation is feasible and safe.Why read on?Face mask ventilation with CPAP should be considered as an option of respiratory support in the context of the on-going COVID-19 pandemic and limited availability of ICU beds.
Evaluation of Confocal Laser Endomicroscopy for Detection of Occult Gastric Carcinoma in CDH1 Variant Carriers
Authors: Schueler Samuel A. , Gamble Lauren A. , Curtin Bryan F. , Ruff Samantha M. , Connolly Maureen , Hannah Cathleen , Quezado Martha , Miettinen Markku , George Maureen , Blakely Andrew M. , Hernandez Jonathan M. , Heller Theo , Koh Christopher , Davis Jeremy L. 
Published: June 2020

AbstractBackground & AimsHereditary diffuse gastric cancer, attributed to inactivating germline CDH1 variants, is characterized by signet ring cell (SRC) morphology. We sought to evaluate the occult cancer detection rate using probe-based confocal laser endomicroscopy (pCLE) during endoscopic surveillance.MethodsA prospective, single-institution study was conducted in asymptomatic adults with pathogenic or likely pathogenic (P/LP) CDH1 variants. Subjects received endoscopic gastric surveillance using pCLE in conjunction with the consensus Cambridge method (CM) of non-targeted mucosal biopsies. Systematic examination was performed with white light endoscopy (WLE) and pCLE. Abnormalities visualized by pCLE were biopsied, followed by non-targeted mucosal biopsies according to the CM. Pathologists were blinded to clinical and endomicroscopic findings. Primary endpoint was to determine pCLE sensitivity for detection of occult SRC carcinoma compared to CM.ResultsThirty-six patients with P/LP CDH1 variants underwent endoscopy using pCLE and CM. Majority were female (75%) with median age 47 years. Median procedure time was 52.5 minutes, without serious adverse events. Targeted biopsies of focal abnormalities on WLE were negative for carcinoma. Overall, 19.4% (7/36) patients had SRC detected on ≥1 biopsy. Non-targeted CM biopsies revealed SRC in 11.1% (4/36), whereas pCLE revealed SRC in 16.7% (6/36). Fifteen patients, 5 of whom had SRC at endoscopy, underwent total gastrectomy; all 15 explants contained occult carcinoma. In those 15 patients, the false-negative SRC detection rates for pCLE and CM were 67% and 87%, respectively.ConclusionsConfocal endomicroscopy alone has low sensitivity for occult cancer detection in CDH1 variant carriers. Reliable endoscopic surveillance is lacking as an alternative to prophylactic surgery in this high-risk population. (http://ClinicalTrials.gov, Number: NCT03648879).
The COVID-19 Pandemic in Africa: Predictions using the SIR Model
Authors: Sinkala Musalula , Nkhoma Panji , Zulu Mildred , Kafita Doris , Tembo Rabecca , Daka Victor 
Published: June 2020

AbstractSince the earliest reports of the Coronavirus disease - 2019 (COVID-19) in Wuhan, China in December 2019, the disease has rapidly spread worldwide, attaining pandemic levels in early March 2020. However, the spread of COVID-19 has differed in the African setting compared to countries on other continents. To predict the spread of COVID-19 in Africa and within each country on the continent, we applied a Susceptible-Infectious-Recovered mathematical model. Here, our results show that, overall, Africa is currently (July 24, 2020) at the peak of the COVID-19 pandemic, after which we predict the number of cases would begin to fall in August 2020. Furthermore, we predict that the ending phase of the pandemic would be in Late-November 2020 and that decreasing cases of COVID-19 infections would be detected until around August 2021 and September 2021. Our results also reveal that of the 51 countries with reported COVID-19 cases, only eight, including Algeria, Morocco and Zambia, are likely to report higher monthly COVID-19 cases in the coming months of 2020 than those reported in the previous months. Overall, at the end of this pandemic, we predict that approximately 2,201,849 (about 1,451,567 future cases) individuals in Africa would have been infected with the COVID-19 virus. Here, our predictions are data-driven and based on the previously observed trends in the spread of the COVID-19 pandemic. Shifts in the population dynamics and/or changes in the infectiousness of the COVID-19 virus may require new forecasts of the disease spread.
Who do not wash their hands during the Covid-19 pandemic? Social media use as a potential predictor
Authors: Zhang Stephen X. , Graf-Vlachy Lorenz , Su Rui , Li Jizhen , Looi Kim Hoe 
Published: June 2020

AbstractThis study predicts handwashing behavior during the Covid-19 pandemic. An analysis of 674 adults in Malaysia identifies their time spent on social media per day as a key predictor of handwashing. The association between time spent on social media and handwashing substantially depends on gender and the number of children in the same household. Additional predictors include age and health condition. This study helps identify specific target groups for health communication on hand hygiene via people’s use of social media, which can be a key channel for health communication campaigns during a pandemic.
ANGPTL4 from adipose, but not liver, is responsible for regulating plasma triglyceride partitioning
Authors: Spitler Kathryn M. , Shetty Shwetha K. , Cushing Emily M. , Sylvers-Davie Kelli L. , Davies Brandon S.J. 
Published: June 2020

ABSTRACTElevated plasma triglyceride levels are associated with metabolic disease. Angiopoietin-like protein 4 (ANGPTL4) regulates plasma triglyceride levels by inhibiting lipoprotein lipase (LPL). Our aim was to investigate the role of tissue-specific ANGPTL4 expression in the setting of high fat diet. Adipocyte- and hepatocyte-specific ANGPTL4 deficient mice were fed a high fat diet (60% kCal from fat) for either 12 weeks or 6 months. We performed plasma metabolic measurements, triglyceride clearance and uptake assays, LPL activity assays, and assessed glucose homeostasis. Mice lacking adipocyte ANGPTL4 recapitulated the triglyceride phenotypes of whole-body ANGPTL4 deficiency, whereas mice lacking hepatocyte ANGPTL4 had few triglyceride phenotypes. When fed a high fat diet (HFD), mice deficient in adipocyte ANGPTL4 gained more weight, had enhanced adipose LPL activity, and initially had improved glucose and insulin sensitivity. However, this improvement was largely lost after 6 months on HFD. Conversely, mice deficient in hepatocyte ANGPTL4 initially displayed no differences in glucose homeostasis, but began to manifest improved glucose tolerance after 6 months on HFD. We conclude that it is primarily adipocyte-derived ANGPTL4 that is responsible for regulating plasma triglyceride levels. Deficiency in adipocyte- or hepatocyte-derived ANGPTL4 may confer some protections against high fat diet induced dysregulation of glucose homeostasis.