bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of agricultural fungicide use onAspergillus fumigatusabundance, antifungal susceptibility, and population structure
Authors: Barber Amelia E. , Riedel Jennifer , Sae-Ong Tongta , Kang Kang , Brabetz Werner , Panagiotou Gianni , Deising Holger B. , Kurzai Oliver 
Published: May 2020

ABSTRACTAntibiotic resistance is an increasing threat to human health. In the case ofAspergillus fumigatus, which is both an environmental saprobe and an opportunistic human fungal pathogen, resistance is suggested to arise from fungicide use in agriculture, as the azoles used for plant protection are almost identical to the frontline antifungals used clinically. However, limiting azole fungicide use on crop fields to preserve their activity for clinical use could threaten the global food supply via a reduction in yield. In this study we clarify the link between fungicide use on crop fields and resistance in a prototypical human pathogen through systematic soil sampling on farms in Germany and surveying fields before and after azole application. We observed a reduction in the abundance ofA. fumigatuson fields following fungicide treatment in 2017—a finding that was not observed on an organic control field applying only natural plant protection agents. However, this finding was less pronounced during our 2018 sampling, indicating that the impact of fungicides onA. fumigatuspopulation size is variable and influenced by additional factors. The overall resistance frequency among agricultural isolates is low, with only 1-3% of isolates from 2016-2018 displaying resistance to medical azoles. Isolates collected after the growing season and azole exposure show a subtle, but consistent decrease in susceptibility to medical and agricultural azoles. Whole genome sequencing indicates that, despite the alterations in antifungal susceptibility, fungicide application does not significantly affect the population structure and genetic diversity ofA. fumigatusin fields. Given the low observed resistance rate among agricultural isolates, as well the lack of genomic impact following azole application, we do not find evidence that azole use on crops is significantly driving resistance inA. fumigatusin this context.IMPORTANCEAntibiotic resistance is an increasing threat to human health. In the case ofAspergillus fumigatus, which is an environmental fungus that also causes life-threatening infections in humans, antimicrobial resistance is suggested to arise from fungicide use in agriculture, as the chemicals used for plant protection are almost identical to the antifungals used clinically. However, removing azole fungicides from crop fields threatens the global food supply via a reduction in yield. In this study, we survey crop fields before and after fungicide application. We find a low overall azole resistance rate among agricultural isolates, as well a lack of genomic and population impact following fungicide application, leading us to conclude azole use on crops does not significantly contribute to resistance inA. fumigatus.
Metformin increases tauroursodeoxycholic acid levels to improve insulin resistance in diet-induced obese mice
Authors: Zhang Ya , Cheng Yang , Liu Jian , He Dan , Zuo Jihui , Yan Liping , Thring Ronald W. , Wu Mingjiang , Gao Yitian , Tong Haibin 
Published: May 2020

AbstractMetformin is widely used to surmount insulin resistance (IR) and type 2 diabetes. Evidence indicates that metformin improves insulin resistance associated with gut microbiota, but the underlying mechanism remains unclear. In the present study, metformin effectively improved insulin sensitivity and alleviated liver inflammation and oxidative stress in high-fat diet (HFD)-fed mice. Metabolomics analysis showed that metformin increased tauroursodeoxycholic acid (TUDCA) levels both in intestinal content and liver by reducing the production and activity of bile salt hydrolase (BSH). We further found that TUDCA was able to antagonize with KEAP1 to prevent its binding to Nrf2 and activate Nrf2/ARE pathway, thereby reducing intracellular ROS and improving insulin signaling. Moreover, metformin increased the proportion ofAkkermanisia muciniphliain the HFD-fed mice, whilein vitrogrowth curve test confirmed that it’s TUDCA, not metformin, promoted the proliferation ofA. muciniphlia. Subsequently, TUDCA administration could effectively ameliorate insulin resistance, activate hepatic Nrf2/ARE pathways, and increase the abundance of intestinalA. muciniphliainob/obmice. These findings reveal that metformin remodels the gut microbiota, reduces oxidative stress and enhances insulin sensitivity partly due to increasing the production of TUDCA. This provides a novel mechanism by which metformin alleviates diet-induced insulin resistance and improves metabolism.
Adrenergic activation modulates the signal from the Reissner fiber to cerebrospinal fluid-contacting neurons during development
Authors: Yasmine Cantaut-Belarif , Margot Penru , Adeline Orts Del’Immagine , Guillaume Pézeron , Claire Wyart , Pierre-Luc Bardet 
Published: May 2020

AbstractThe cerebrospinal fluid (CSF) contains an extracellular thread that is conserved in vertebrates and referred to as the Reissner fiber. Genetic ablation in the zebrafish revealed that the Reissner fiber controls body axis morphogenesis in the embryo. Yet, the signaling cascade originating from this fiber to ensure body axis straightening is not fully understood. Here, we explore the functional link between the Reissner fiber and undifferentiated spinal neurons contacting the CSF (CSF-cNs). First, we show that the Reissner fiber is required for the expression ofurp2, a neuropeptide expressed in CSF-cNs. Usingin vivocalcium imaging, we show that the Reissner fiber is also required for embryonic calcium transients in these spinal neurons. Finally, we study how local adrenergic activation directly in the CSF can substitute for the Reissner fiber-signaling pathway to CSF-cNs and rescue body axis morphogenesis. Our results suggest that the Reissner fiber acts on CSF-cNs to establish body axis morphogensis by controlling the availability of a chemical signal in the CSF.
Developmental Phase Transitions in Spatial Organization of Spontaneous Activity in Postnatal Barrel Cortex Layer 4
Authors: Nakazawa Shingo , Yoshimura Yumiko , Takagi Masahiro , Mizuno Hidenobu , Iwasato Takuji 
Published: May 2020

AbstractSpatially-organized spontaneous activity is a characteristic feature of developing mammalian sensory systems. However, the transitions of spontaneous-activity spatial organization during development and related mechanisms remain largely unknown. We reported previously that layer 4 (L4) glutamatergic neurons in the barrel cortex exhibit spontaneous activity with a patchwork-type pattern at postnatal day 5 (P5), which is during barrel formation. In the current work, we revealed that spontaneous activity in barrel-cortex L4 glutamatergic neurons exhibits at least three phases during the first two weeks of postnatal development. Phase I activity has a patchwork-type pattern and is observed not only at P5, but also P1, prior to barrel formation. Phase II is found at P9, by which time barrel formation is completed, and exhibits broadly synchronized activity across barrel borders. Phase III emerges around P11 when L4-neuron activity is desynchronized. The Phase I activity, but not Phase II or III activity, is blocked by thalamic inhibition, demonstrating that the Phase I to II transition is associated with loss of thalamic dependency. Dominant-negative Rac1 expression in L4 neurons hampers the Phase II to III transition. It also suppresses developmental increases in spine density and excitatory synapses of L4 neurons in the second postnatal week, suggesting that Rac1-mediated synapse maturation could underlie the Phase II to III transition. Our findings revealed the presence of distinct mechanisms for Phase I to II and Phase II to III transition. They also highlighted the role of a small GTPase in the developmental desynchronization of cortical spontaneous activity.Significant statementDeveloping neocortex exhibits spatially-organized spontaneous activity, which plays a critical role in cortical circuit development. The features of spontaneous-activity spatial organization and the mechanisms underlying its changes during development remain largely unknown. In the present study, using two-photon in vivo imaging, we revealed three phases (Phase I, II, and III) of spontaneous activity in barrel-cortex layer 4 (L4) glutamatergic neurons during the first two postnatal weeks. We also demonstrated the presence of distinct mechanisms underlying phase transitions. Phase I to II shift arose from the switch in the L4-neuron driving source, and Phase II to III transition relied on L4-neuron Rac1 activity. These results provide new insights into the principles of developmental transitions of neocortical spontaneous-activity spatial patterns.
Chromatin-associated protein complexes link DNA base J and transcription termination inLeishmania
Authors: Jensen Bryan C , Phan Isabelle Q. , McDonald Jacquelyn R. , Sur Aakash , Gillespie Mark A. , Ranish Jeffrey A. , Parsons Marilyn , Myler Peter J 
Published: May 2020

AbstractUnlike most other eukaryotes,Leishmaniaand other trypanosomatid protozoa have largely eschewed transcriptional control of gene expression; relying instead on post-transcriptional regulation of mRNAs derived from polycistronic transcription units (PTUs). In these parasites, a novel modified nucleotide base (β-D-glucopyranosyloxymethyluracil) known as J plays a critical role in ensuring that transcription termination occurs only at the end of each PTU, rather than at the polyadenylation sites of individual genes. To further understand the biology of J-associated processes, we used tandem affinity purification (TAP-tagging) and mass spectrometry to reveal proteins that interact with the glucosyltransferase performing the final step in J synthesis. These studies identified four proteins reminiscent of subunits in the PTW/PP1 complex that controls transcription termination in higher eukaryotes. Moreover, bioinformatic analyses identified the DNA-binding subunit ofLeishmaniaPTW/PP1 as a novel J-binding protein (JBP3), which is also part of another complex containing proteins with domains suggestive of a role in chromatin modification/remodeling. Additionally, JBP3 associates (albeit transiently and/or indirectly) with the trypanosomatid equivalent of the PAF1 complex involved in regulation of transcription in other eukaryotes. Down-regulation of JBP3 expression levels inLeishmaniaresulted in a substantial increase in transcriptional read-through at the 3’ end of most PTUs. We propose that JBP3 recruits one or more of these complexes to the J-containing regions at the end of PTUs, where they halt progression of the RNA polymerase. This de-coupling of transcription termination from splicing of individual genes enables the parasites’ unique reliance on polycistronic transcription and post-transcriptional regulation of gene expression.ImportanceLeishmaniaparasites cause a variety of serious human diseases, with no effective vaccine and emerging resistance to current drug therapy. We have previously shown that a novel DNA base called J is critical for transcription termination at the ends of the polycistronic gene clusters that are a hallmark ofLeishmaniaand related trypanosomatids. Here, we describe a new J-binding protein (JBP3) associated with three different protein complexes that are reminiscent to those involved in control of transcription in other eukaryotes. However, the parasite complexes have been reprogrammed to regulate transcription and gene expression in trypanosomatids differently than in the mammalian hosts, providing new opportunities to develop novel chemotherapeutic treatments against these important pathogens.
Slc26a9P2ACre, a new CRE driver to regulate gene expression in the otic placode lineage and other FGFR2b-dependent epithelia
Authors: Urness Lisa D. , Wang Xiaofen , Li Chaoying , Quadros Rolen M. , Harms Donald W. , Gurumurthy Channabasavaiah B. , Mansour Suzanne L. 
Published: May 2020

AbstractPan-otic CRE drivers enable gene regulation throughout the otic placode lineage, comprising the inner ear epithelium and neurons. However, intersection of extra-otic gene-of-interest expression with the CRE lineage can compromise viability and impede auditory analyses. Furthermore, extant pan-otic CREs recombine in auditory and vestibular brain nuclei, making it difficult to ascribe resulting phenotypes solely to the inner ear. We previously identifiedSlc26a9as an otic placode-specific target of FGFR2b ligands, FGF3 and FGF10. We show here thatSlc26a9is otic-specific through E10.5, but not required for hearing. We targetedP2ACreto theSlc26a9stop codon, generatingSlc26a9P2ACremice, and observed CRE activity throughout the otic epithelium and neurons, with little activity evident in the brain. Notably, recombination was detected in many FGFR2b ligand-dependent epithelia. We generatedFgf10andFgf8conditional mutants, and activated an FGFR2b ligand trap from E17.5-P3. In contrast to analogous mice generated with other pan-otic CREs, these were viable. Auditory thresholds were elevated in mutants, and correlated with cochlear epithelial cell losses. Thus,Slc26a9P2ACreprovides a useful complement to existing pan-otic CRE drivers, particularly for postnatal analyses.Summary statementWe describe a new pan-otic CRE driver,Slc26a9P2ACre, with little activity in the brain or middle ear, and demonstrate its utility by manipulating FGF signaling and assessing hearing loss.
Comparison of Decision Modeling Approaches for Health Technology and Policy Evaluation
Authors: Graves John , Garbett Shawn , Zhou Zilu , Schildcrout Jonathan S. , Peterson Josh 
Published: May 2020

ABSTRACTWe discuss tradeoffs and errors associated with approaches to modeling health economic decisions. Through an application in pharmacogenomic (PGx) testing to guide drug selection for individuals with a genetic variant, we assessed model accuracy, optimal decisions and computation time for an identical decision scenario modeled four ways: using (1) coupled-time differential equations [DEQ]; (2) a cohort-based discrete-time state transition model [MARKOV]; (3) an individual discrete-time state transition microsimulation model [MICROSIM]; and (4) discrete event simulation [DES]. Relative to DEQ, the Net Monetary Benefit for PGx testing (vs. a reference strategy of no testing) based on MARKOV with rate-to-probability conversions using commonly used formulas resulted in different optimal decisions. MARKOV was nearly identical to DEQ when transition probabilities were embedded using a transition intensity matrix. Among stochastic models, DES model outputs converged to DEQ with substantially fewer simulated patients (1 million) vs. MICROSIM (1 billion). Overall, properly embedded Markov models provided the most favorable mix of accuracy and run-time, but introduced additional complexity for calculating cost and quality-adjusted life year outcomes due to the inclusion of “jumpover” states after proper embedding of transition probabilities. Among stochastic models, DES offered the most favorable mix of accuracy, reliability, and speed.
The Effects of Nurse Specialty Certification and Medical Treatments on Glycemic Control Outcomes: A Retrospective Study
Authors: Ojeda Maria M. 
Published: May 2020

AbstractAIMSTo describe and explore the impact of the presence of specialty certified nurses on the unit on glycemic control among non-critically ill hospitalized patients with Diabetes mellitus.BACKGROUNDPoor glycemic control during hospitalization has been associated adverse patient outcomes. Staff nurses administer much of the diabetes-specific care delivered to patients during hospitalization. Nurse specialty certification is a recognized indicator of nursing care quality.METHODSA retrospective sample of medical records data was analyzed to describe and explore the impact of specialty certified nurses on glycemic control among a group of 293 non-critically ill hospitalized patients with Diabetes mellitus. Regression analysis was performed to assess the impact of the percentage of certified nurses on the unit as a mediator or moderator of the relationship between medical treatments and glycemic control outcomes.RESULTSIncreases in the percentage of specialty certified nurses on the unit were associated with significant decreases in mean blood glucose levels among patients who received a basal-bolus insulin regimen or enteral nutritional feedings.CONCLUSIONSPatients who received specific medical treatments during hospitalization had superior outcomes when nursing care was delivered during times in which the relative proportion of certified nurses on the unit were higher.
Continuous Electroencephalography (cEEG) Characteristics and Acute Symptomatic Seizures in COVID-19 Patients
Authors: Louis Shreya , Dhawan Andrew , Newey Christopher , Nair Dileep , Jehi Lara , Hantus Stephen , Punia Vineet 
Published: May 2020

AbstractBackgroundNeurological manifestations of COVID-19 have only recently been described, with a paucity of literature reporting the potential relationship between COVID-19 and acute symptomatic seizures. Two prior studies found no clinical or electrographic seizures in their cohorts of COVID-19 patients with altered mental status (AMS) and clinical seizure-like events (SLEs).MethodsIn this retrospective cohort study, 22 critically-ill COVID-19 patients above the age of 18 years who underwent EEG (electroencephalography) monitoring between April 20th, 2020 and May 20th, 2020 were studied. 19 patients underwent continuous EEG (cEEG) for at least 24 hours, and 3 patients underwent routine EEGs (<1 hour). Demographics including age, gender, comorbid medical, and neurological conditions were collected. Clinical variables included EEG findings, anti-seizure medications, discharge disposition, and survival.Findings17 patients underwent EEG monitoring for unexplained altered mental status changes and 5 patients underwent monitoring for a seizure-like event. 5 patients had epileptiform abnormalities on EEG (4 patients on cEEG, 1 on routine EEG); and only 2 of 5 epileptic EEG patients had a prior history of epilepsy. 2 patients in our cohort had electrographic seizures in the absence of prior epilepsy history. No patients with epileptiform abnormalities or electrographic seizures had acutely abnormal neuroimaging on CT or MRI.InterpretationEncephalopathic COVID-19 positive patients had a range of EEG abnormalities, and a higher proportion of patients in this series had electrographic seizures than previous literature suggests. This may be influenced by the duration of monitoring with cEEG and the use of a 21 channel electrode system. cEEG findings may help to guide antiseizure medical therapy, as well as the workup of altered mental status in the setting of unremarkable neuroimaging.FundingNo funding was used for this study.
Predictions for Europe for the Covid-19 pandemic from a SIR model
Authors: Bhanot Gyan , DeLisi Charles 
Published: May 2020

AbstractWe develop and apply a simplified SIR model to current data for the 2019-2020 SARS-Cov-2/Covid-19 pandemic for the United Kingdom (UK) and eight European countries: Norway, Sweden, Denmark, the Netherlands, France, Germany, Italy and Spain. The most important result of the model was the identification and segregation of pandemic characteristics into two distinct groups: those that are invariant across countries, and those that are highly variable. Amongst the former is the infective period TL, which was very similar for all countries, with an average value of days. The other invariants were TR, the average time between contacts and R = NC, the average number of contacts while infective. We find days and . In contrast to these invariants, there was a highly variable time lag TD between the peak in the daily number of infected individuals and the peak in the daily number of deaths, ranging from a low of TD = 4 days for Italy and Denmark, to a high of TD = 17 for Norway. The mortality probability among identified cases was also highly variable, ranging from low values 3.5%, 5% and 5% for Norway, Denmark and Germany respectively to high values of 18%, 18% and 20% for France, Sweden and the UK respectively. Our analysis predicts that the number of deaths per million population until the pandemic ends (defined as when the daily number of deaths is less than 5) will be lowest for Norway (45 deaths/million) and highest for the United Kingdom (628 deaths/million). Finally, we observe a small but detectable effect of average temperature on the probability α of infection in each contact, with higher temperatures associated with lower infectivity.
Mental health outcomes and associations during the coronavirus disease 2019 pandemic: A cross-sectional survey of the US general population
Authors: Kantor Bella Nichole , Kantor Jonathan 
Published: May 2020

AbstractPandemic coronavirus disease 2019 (COVID-19) may lead to significant mental health stresses, potentially with modifiable risk factors. To determine the presence of and magnitude of associations between baseline associations and anxiety and depression in the US general population, we performed an internet-based cross-sectional survey of an age-, sex-, and race-stratified representative sample from the US general population. Degrees of anxiety, depression, and loneliness were assessed using the 7-item Generalized Anxiety Disorder scale (GAD-7), the 9-item Patient Health Questionnaire (PHQ-9), and the 8-item UCLA Loneliness Scale, respectively. Unadjusted and multivariable logistic regression analyses were performed to determine associations with baseline demographic characteristics. A total of 1,005 finished surveys were returned of the 1,020 started, yielding a completion rate of 98.5% in the survey panel. The mean (SD) age of respondents was 45 (16), and 494 (48.8%) were male. Baseline demographic data were similar between those that were (n=663, 66.2%) and were not (n=339, 33.8%) under a shelter in place/ stay at home order, with the exception of sex and geographic location. Overall, 264 subjects (26.8%) met criteria for an anxiety disorder based on a GAD-7 cutoff of 10; a cutoff of 7 yielded 416 subjects (41.4%) meeting clinical criteria for anxiety. On multivariable analysis, male sex (OR 0.65, 95% CI [0.49, 0.87]) and living in a larger home (OR 0.46, 95% CI [0.24, 0.88]) were associated with a decreased odds of meeting anxiety criteria. Rural location (OR 1.39, 95% CI [1.03, 1.89]), loneliness (OR 4.92, 95% CI [3.18, 7.62]), and history of hospitalization (OR 2.04, 95% CI [1.38, 3.03]), were associated with increased odds of meeting anxiety criteria. 232 subjects (23.6%) met criteria for clinical depression. On multivariable analysis, male sex (OR 0.71, 95% CI [0.53, 0.95]), increased time outdoors (OR 0.51, 95% CI [0.29, 0.92]), and living in a larger home (OR 0.35, 95% CI [0.18, 0.69]), were associated with decreased odds of meeting depression criteria. Having lost a job (OR 1.64, 95% CI [1.05, 2.54]), loneliness (OR 10.42, 95% CI [6.26, 17.36]), and history of hospitalization (OR 2.42, 95% CI [1.62, 3.62]), were associated with an increased odds of meeting depression criteria. Income, media consumption, and religiosity were not associated with mental health outcomes. Anxiety and depression are common in the US general population in the context of the COVID-19 pandemic, and are associated with potentially modifiable factors.