bluuebunny/crossref_metadata_2025 huggingface dataset:
Unpacking the dynamics of a contested practice: the case of executive compensation and the shareholder value orientation in the USA
Authors: Carberry Edward J , Zajac Edward J
Published: May 2020

The corporate scandals and market crashes of the 2000s generated significant criticism of the shareholder value orientation (SVO) in the USA. We offer a sociopolitical analysis of how this criticism triggered changes in stock-based executive compensation, a central practice associated with the SVO. We first analyze how corporate stakeholders redefined different forms of stock-based compensation, motivated new regulations and wielded direct challenges to specific firms. We then predict how firm-specific differences in external challenges and intra-firm power relationships were related to changes in the use of stock options and restricted stock grants (RSGs), testing our predictions using a longitudinal dataset of S&P 500 executives between 2002 and 2012. We find that firms facing negative media coverage of their executive compensation practices made less use of both forms of stock-based compensation, while firms facing shareholder activism only made less use of stock options, the form that was more heavily criticized. In addition, firms with more powerful CEOs utilized RSGs more heavily and did so even when facing media criticism. Our findings demonstrate that while stock options were vulnerable to change, stock-based compensation remained resilient because the structural power of CEOs, a core corporate governance feature of the SVO, also remained resilient.
The global deregulation hypothesis
Authors: Oatley Thomas , Petrova Bilyana
Published: May 2020

The growth of the American financial services remains a bit of a puzzle. The standard approach, the deregulation hypothesis, posits that the industry expanded in response to national deregulation. Yet, when viewed in a comparative context, US finance was deregulated significantly less than other national financial systems and yet grew significantly more than most. We propose the global deregulation hypothesis as a solution to this puzzle. The hypothesis posits that American finance grew in response to deregulation in Europe and the emerging market economies. The article develops two theoretical mechanisms that link global deregulation to US financialization. It reports statistical tests that support two central implications of the global deregulation hypothesis. First, global deregulation is positively associated with the growth of US financial services, while US deregulation is not. Second, global deregulation is not systematically related to the growth of financial services in other industrial democracies.
Resin ducts as resistance traits in conifers: linking dendrochronology and resin-based defences
Authors: Vázquez-González Carla , Zas Rafael , Erbilgin Nadir , Ferrenberg Scott , Rozas Vicente , Sampedro Luis
Published: May 2020

Conifers have evolved different chemical and anatomical defences against a wide range of antagonists. Resin ducts produce, store and translocate oleoresin, a complex terpenoid mixture that acts as both a physical and a chemical defence. Although resin duct characteristics (e.g., number, density, area) have been positively related to biotic resistance in several conifer species, the literature reporting this association remains inconclusive. Axial resin ducts recorded in annual growth rings are an archive of annual defensive investment in trees. This whole-life record of defence investment can be analysed using standard dendrochronological procedures, which allows us to assess interannual variability and the effect of understudied drivers of phenotypic variation on resin-based defences. Understanding the sources of phenotypic variation in defences, such as genetic differentiation and environmental plasticity, is essential for assessing the adaptive potential of forest tree populations to resist pests under climate change. Here, we reviewed the evidence supporting the importance of resin ducts in conifer resistance, and summarized current knowledge about the sources of variation in resin duct production. We propose a standardized methodology to measure resin duct production by means of dendrochronological procedures. This approach will illuminate the roles of resin ducts in tree defence across species, while helping to fill pivotal knowledge gaps in plant defence theory, and leading to a robust understanding of the patterns of variation in resin-based defences throughout the tree’s lifespan.
Teach-Back Training for Nursing Students: Knowledge and Beliefs After Training for Health Literate Communication
Authors: Feinberg Iris , Hendry Terri , Tighe Elizabeth , Ogrodnick Michelle , Czarnonycz Catherine
Published: May 2020

For nurses to communicate effectively, they must understand how patients obtain, understand, and use health information to make health decisions, that is, their health literacy (HL) level. A gap in teaching HL communication skills exists in nursing curricula. This study explored nursing students’ knowledge and beliefs about HL communication before and after an HL training. Analysis revealed a significant increase in knowledge after training (M
pre = 9.00, M
post = 9.89), t(36) = 3.75, p < .001. Participants (84.6 percent) used teach-back technique with simulated patients and identified additional training as an aid to skill building.
Bilateral Leukemic Infiltration of the Lacrimal Sac in a Child
Authors: Levitt Alexandra E. , Choi Catherine J. , Johnson Thomas E.
Published: May 2020

An 8-year-old boy with a history of refractory acute lymphoblastic leukemia presented with left-sided periorbital erythema and painless enlargement of the lacrimal sac. MRI revealed a soft tissue mass on the floor of the left orbit, extending into the nasolacrimal sac and duct. Lacrimal sac biopsy was consistent with B-lymphoblastic leukemia. The patient was treated with chemotherapy and radiation with satisfactory remission of local disease. However, similar symptoms emerged shortly after on the contralateral side, and repeat MRI was concerning for new leukemic infiltration of the right lacrimal sac. Bone marrow biopsy revealed concurrent medullary relapse. Systemic chemotherapy was adjusted and radiation therapy of the right orbit was initiated. This is the first reported pediatric case of bilateral leukemic involvement of the lacrimal sac.
Impact of Personal Protective Equipment on Pediatric Cardiopulmonary Resuscitation Performance
Authors: Donoghue Aaron J. , Kou Maybelle , Good Grace L. , Eiger Carmel , Nash Mark , Henretig Fred M. , Stacks Helen , Kochman Adam , Debski Julie , Chen Jia-Yuh , Sharma Gaurav , Hornik Christoph P. , Gosnell Leigh , Siegel David , Krug Steven , Adler Mark D.
Published: May 2020

Objectives

This study aimed to determine whether personal protective equipment (PPE) results in deterioration in chest compression (CC) quality and greater fatigue for administering health care providers (HCPs).

Methods

In this multicenter study, HCPs completed 2 sessions. In session 1 (baseline), HCPs wore normal attire; in session 2, HCPs donned full PPE. During each session, they performed 5 minutes of uninterrupted CCs on a child manikin. Chest compression rate, depth, and release velocity were reported in ten 30-second epochs. Change in CC parameters and self-reported fatigue were measured between the start and 2- and 5-minute epochs.

Results

We enrolled 108 HCPs (prehospital and in-hospital providers). The median CC rate did not change significantly between epochs 1 and 10 during baseline sessions. Median CC depth and release velocity decreased for 5 minutes with PPE. There were no significant differences in CC parameters between baseline and PPE sessions in any provider group. Median fatigue scores during baseline sessions were 2 (at start), 4 (at 2 minutes), and 6 (at 5 minutes). There was a significantly higher median fatigue score between 0 and 5 minutes in both study sessions and in all groups. Fatigue scores were significantly higher for providers wearing PPE compared with baseline specifically among prehospital providers.

Conclusions

During a clinically appropriate 2-minute period, neither CC quality nor self-reported fatigue worsened to a significant degree in providers wearing PPE. Our data suggest that Pediatric Basic Life Support recommendations for CC providers to switch every 2 minutes need not be altered with PPE use.
Population-level viral suppression among pregnant and postpartum women in a universal test and treat trial
Authors: Kabami Jane , Balzer Laura B. , Saddiki Hachem , Ayieko James , Kwarisiima Dalsone , Atukunda Mucunguzi , Charlebois Edwin D. , Clark Tamara D. , Koss Catherine A. , Ruel Theodore , Bukusi Elizabeth A. , Cohen Craig R. , Musoke Phillipa , Petersen Maya L. , Havlir Diane V. , Kamya Moses R. , Chamie Gabriel
Published: May 2020

Objective(s):

We sought to determine whether universal ‘test and treat’ (UTT) can achieve gains in viral suppression beyond universal antiretroviral treatment (ART) eligibility during pregnancy and postpartum, among women living with HIV.

Design:

A community cluster randomized trial.

Methods:

The SEARCH UTT trial compared an intervention of annual population testing and universal ART with a control of baseline population testing with ART by country standard, including ART eligibility for all pregnant/postpartum women, in 32 communities in Kenya and Uganda. When testing, women were asked about current pregnancy and live births over the prior year and, if HIV-infected, had their viral load measured. Between arms, we compared population-level viral suppression (HIV RNA <500 copies/ml) among all pregnant/postpartum HIV-infected women at study close (year 3). We also compared year-3 population-level viral suppression and predictors of viral suppression among all 15 to 45-year-old women by arm.

Results:

At baseline, 92 and 93% of 15 to 45-year-old women tested for HIV: HIV prevalence was 12.6 and 12.3%, in intervention and control communities, respectively. Among HIV-infected women self-reporting pregnancy/live birth, prevalence of viral suppression was 42 and 44% at baseline, and 81 and 76% (P = 0.02) at year 3, respectively. Among all 15 to 45-year-old HIV-infected women, year-3 population-level viral suppression was higher in intervention (77%) versus control (68%; P < 0.001). Pregnancy/live birth was a predictor of year-3 viral suppression in control (P = 0.016) but not intervention (P = 0.43). Younger age was a risk factor for nonsuppression in both arms.

Conclusion:

The SEARCH intervention resulted in higher population viral suppression among pregnant/postpartum women than a control of baseline universal testing with ART eligibility for pregnant/postpartum women.
Association of Dementia and Vascular Risk Scores With Cortical Thickness and Cognition in Low-risk Middle-aged Adults
Authors: Gourley Drew , Pasha Evan P. , Kaur Sonya S. , Haley Andreana P. , Tanaka Hirofumi
Published: May 2020

Background:

Increased risk for the future development of Alzheimer disease begins as early as midlife. Algorithm-based scores, such as the Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) dementia risk score, and the Framingham general cardiovascular disease (CVD) risk score, have been used to determine future risk for the development of cognitive decline and dementia. We evaluated the association between neuroimaging and cognitive measures with the 2 risk scores in middle-aged, cognitively intact adults (49±6 y).

Methods:

In a cohort of 132 participants collected in 2014, magnetic resonance imaging was used to determine measures of cortical thickness in a priori regions of interest and a neuropsychological battery to assess memory and executive function.

Results:

The CAIDE dementia risk score was significantly and inversely associated with the cortical thickness of the parahippocampal (r=−0.266; P=0.002) and superior frontal gyrus (r=−0.261; P=0.002) despite a considerable percentage of individuals (99.3%) at low risk for CVD. There was a significant negative association between CAIDE and memory (r=−0.251; P=0.003). Framingham general CVD score was not associated with brain structure or cognitive function.

Conclusions:

These results indicate that the CAIDE dementia risk score is associated with cortical thickness and cognitive function at midlife in a low-risk population. These data provide insight into subclinical structural and functional changes occurring during midlife associated with future risk for the development of dementia.
Feeling and Looking Down: Impact of Depressive Symptoms on the Allocation of Vertical Attention
Authors: Mańkowska Aleksandra , Harciarek Michał , Heilman Kenneth M.
Published: May 2020

Background:

Emotions and moods are often expressed using verbal, vertical spatial metaphors (eg, “I’m feeling down”). The reason for using these vertical metaphors is unknown; however, when individuals experience depressive symptoms, they often become self-reflective and ruminative. These mental activities are associated with activation of the default network, including the parietal lobes. The parietal lobes are a critical component of the dorsal visual attentional network, which allocates attention downward. Therefore, activation of the default network may create a downward bias of vertical attention.

Objective:

To investigate whether depressive mood disposition, as measured by the number of depressive symptoms experienced by an individual, influences their allocation of vertical attention.

Methods:

We used the Hospital Anxiety and Depression Scale to evaluate depressive symptoms in 48 right-handed individuals with a mean age of 57.31 (±17.14) years. We also asked the participants to mark the center (bisect) of 24 vertical and 24 horizontal lines.

Results:

Overall, the individuals deviated their bisections of vertical lines upward (M=2.66 mm; SD=3.85). A stepwise linear regression analysis revealed that the number of depressive symptoms an individual experienced was significantly associated with a reduction in the magnitude of this upward vertical bias (P=0.009; R
2=0.138), such that the number of depressive symptoms was associated with the reduction (lowering) of their upward bias.

Conclusion:

Depressive symptoms may be associated with a relative lowering of the vertical attentional bias, and this lowering may be related to increased activation of portions of the default network.
Potential RNA-dependent RNA polymerase inhibitors as prospective therapeutics against SARS-CoV-2
Authors: Pokhrel Rudramani , Chapagain Prem , Siltberg-Liberles Jessica
Published: May 2020

Introduction. The emergence of SARS-CoV-2 has taken humanity off guard. Following an outbreak of SARS-CoV in 2002, and MERS-CoV about 10 years later, SARS-CoV-2 is the third coronavirus in less than 20 years to cross the species barrier and start spreading by human-to-human transmission. It is the most infectious of the three, currently causing the COVID-19 pandemic. No treatment has been approved for COVID-19. We previously proposed targets that can serve as binding sites for antiviral drugs for multiple coronaviruses, and here we set out to find current drugs that can be repurposed as COVID-19 therapeutics.

Aim. To identify drugs against COVID-19, we performed an in silico virtual screen with the US Food and Drug Administration (FDA)-approved drugs targeting the RNA-dependent RNA polymerase (RdRP), a critical enzyme for coronavirus replication.

Methodology. Initially, no RdRP structure of SARS-CoV-2 was available. We performed basic sequence and structural analysis to determine if RdRP from SARS-CoV was a suitable replacement. We performed molecular dynamics simulations to generate multiple starting conformations that were used for the in silico virtual screen. During this work, a structure of RdRP from SARS-CoV-2 became available and was also included in the in silico virtual screen.

Results. The virtual screen identified several drugs predicted to bind in the conserved RNA tunnel of RdRP, where many of the proposed targets were located. Among these candidates, quinupristin is particularly interesting because it is expected to bind across the RNA tunnel, blocking access from both sides and suggesting that it has the potential to arrest viral replication by preventing viral RNA synthesis. Quinupristin is an antibiotic that has been in clinical use for two decades and is known to cause relatively minor side effects.

Conclusion. Quinupristin represents a potential anti-SARS-CoV-2 therapeutic. At present, we have no evidence that this drug is effective against SARS-CoV-2 but expect that the biomedical community will expeditiously follow up on our in silico findings.
Illegal trade of morphologically distinct populations prior to taxonomic assessment and elevation, with recommendations for future prevention
Authors: van den Burg Matthijs P. , Weissgold Bruce J.
Published: May 2020

The negative impacts of international wildlife trafficking are well known, and such negative impacts can be even more pronounced for insular species. This dynamic market needs close monitoring, and when novel species appear in the commercial trade relevant authorities should be able to react in order to reduce negative impacts on wild populations. Here we describe a novel case where an insular endemic form of theIguana iguanacomplex has entered the international commercial trade, likely stimulated by efforts to elevate the form taxonomically. Despite the absence of authorized export permits from the relevant CITES authority, we identify animals that are sold in a range of countries and the likely pathway and methods of importation. We provide recommendations to prevent future illegal collection and trafficking that could be implemented for other taxa. We call for increased awareness of the higher economic value of taxa considered for future taxonomic elevation, and increased monitoring of the commercial trade in order to act promptly when illegal activity is detected.
Learning Clique Subgraphs in Structural Brain Network Classification with Application to Crystallized Cognition
Authors: Wang Lu , Lin Feng Vankee , Cole Martin , Zhang Zhengwu
Published: May 2020

Structural brain networks constructed from diffusion MRI are important biomarkers for understanding human brain structure and its relation to cognitive functioning. There is increasing interest in learning differences in structural brain networks between groups of subjects in neuroimaging studies, leading to a variable selection problem in network classification. Traditional methods often use independent edgewise tests or unstructured generalized linear model (GLM) with regularization on vectorized networks to select edges distinguishing the groups, which ignore the network structure and make the results hard to interpret. In this paper, we develop a symmetric bilinear logistic regression (SBLR) with elastic-net penalty to identify a set of small clique subgraphs in network classification. Clique subgraphs, consisting of all the interconnections among a subset of brain regions, have appealing neurological interpretations as they may correspond to some anatomical circuits in the brain related to the outcome. We apply this method to study differences in the structural connectome between adolescents with high and low crystallized cognitive ability, using the crystallized cognition composite score, picture vocabulary and oral reading recognition tests from NIH Toolbox. A few clique subgraphs containing several small sets of brain regions are identified between different levels of functioning, indicating their importance in crystallized cognition.
Sustained Androgen Receptor signaling is a determinant of melanoma cell growth potential and tumorigenesis
Authors: Ma Min , Ghosh Soumitra , Tavernari Daniele , Katarkar Atul , Clocchiatti Andrea , Mazzeo Luigi , Samarkina Anastasia , Epiney Justine , Yu Yi-Ru , Ho Ping-Chih , Levesque Mitchell P. , Özdemir Berna C. , Ciriello Giovanni , Dummer Reinhard , Dotto G. Paolo
Published: May 2020

Melanoma is a benchmark of major clinical significance for cancer development with greater aggressiveness in the male than the female population. Surprisingly little is known on the role of androgen receptor (AR) signaling in the disease. Irrespectively of expression levels, genetic and pharmacological suppression of AR activity in a large panel of melanoma cells, derived from both male and female patients, suppresses proliferation and self-renewal potential while, conversely, increased AR expression or ligand stimulation enhance proliferation. AR gene silencing in multiple melanoma lines elicits a shared gene expression signature related to interferon- and inflammatory cytokines signaling with an inverse association with DNA repair-associated genes, which is significantly linked with better patients’ survival. AR plays an essential function in maintenance of genome integrity: in both cultured melanoma cells and tumors, loss of AR activity leads to chromosomal DNA breakage, leakage into the cytoplasm, and stimulator of interferon genes (STING) activation.In vivo, reduced tumorigenesis resulting from AR gene silencing or pharmacological inhibition is associated with intratumor macrophage infiltration and, in an immune competent mouse model, cytotoxic T cell activation. Although at different levels, androgens are produced in both male and female individuals and AR targeting provides an attractive therapy approach for improved management of melanoma irrespective of patients’ sex and gender.

Significance

The study uncovers an essential role of androgen receptor (AR) signaling in melanoma cell expansion and tumorigenesis, with loss of AR activity inducing cellular senescence, genomic DNA breakage, a STING dependent inflammatory cascade and immune cells recruitment. Use of AR inhibitors as growth inhibitory and DNA damaging agents in melanoma cells can provide an attractive venue for new combination approaches for management of the disease.
Deep learning predicts non-coding RNA functions from only raw sequence data
Authors: Noviello Teresa M.R. , Ceccarelli Michele , Cerulo Luigi
Published: May 2020

Non-coding RNAs (ncRNAs) are small non-coding sequences involved in gene regulation in many biological processes and diseases. The lack of a complete comprehension of their biological functionality, especially in a genome-wide scenario, has demanded new computational approaches to annotate their roles. It is widely known that secondary structure is determinant to know RNA function and machine learning based approaches have been successfully proven to predict RNA function from secondary structure information.

Here we show that RNA function can be predicted with good accuracy from raw sequence information without the necessity of computing secondary structure features which is computationally expensive. This finding appears to go against the dogma of secondary structure being a key determinant of function in RNA. Compared to recent secondary structure based methods, the proposed solution is more robust to sequence boundary noise and reduces drastically the computational cost allowing for large data volume annotations.

Scripts and datasets to reproduce the results of experiments proposed in this study are available at:https://github.com/bioinformatics-sannio/ncrna-deep
Imaging ATP Consumption in Resting Skeletal Muscle: One Molecule at a Time
Authors: Nelson Shane R. , Li Amy , Beck-Previs Samantha , Kennedy Guy G. , Warshaw David M.
Published: May 2020

Muscle contraction is driven by sarcomere shortening and powered by cyclic hydrolysis of ATP by myosin molecular motors. However, myosin in relaxed muscle continues to slowly hydrolyze ATP, analogous to an idling engine. Utilizing super-resolution microscopy to directly image single molecule fluorescent ATP turnover in relaxed rat soleus skeletal muscle sarcomeres, we observed two rates of myosin ATP consumption that differed 5-fold. These distinct hydrolysis rates were spatially segregated, with the slower or “super relaxed” rate localized predominantly to the sarcomere C-zone, where Myosin Binding Protein-C (MyBP-C), a known modulator of muscle contractile function, exists. This super relaxed hydrolysis rate and its location suggest that MyBP-C can sequester myosin motors to regulate muscle metabolism and heat production in resting muscle and force generation upon activation.

One Sentence Summary

Super relaxed skeletal muscle myosin is stabilized by Myosin-Binding Protein C as imaged by single ATP molecule consumption.
Genotypic diversity between surgical and nasalStaphylococcus aureusisolates
Authors: Ma Dongzhu , Maher Patrick L. , Brothers Kimberly M. , Phillips Nathan J. , Simonetti Deborah , Pasculle A. William , Richardson Anthony R. , Cooper Vaughn S. , Urish Kenneth L.
Published: May 2020

Staphylococcus aureusis a common organism in periprosthetic joint infection (PJI). Little is known aboutS. aureusgenetic diversity in PJI as compared to nasal carriage. We hypothesized PJIS. aureusstrains would be associated with increased virulence as compared to those from nasal carriage. Whole genome sequencing and multilocus sequence typing (MLST) was performed to genotype these two populations at high resolution. MLST revealed a variety of genotypes in both populations but many belonged to the most common clonal complexes. In nasal cultures, 69% of strains were of clonal complexes CC5, CC8, and CC30. In PJI cultures, only 51% could be classified in these common clonal complexes. Remaining strains were atypical, and these atypical strains in PJI were associated with poor host status and compromised immune conditions. Mutations in genes involved in fibronectin binding (ebh, fnbA, clfA, clfB) systematically distinguished later PJI isolates from the first PJI isolate from each patient.S. aureusisolated from nasal carriage and PJI specimens differ significantly, with the latter being more diverse. Strains associated with lower pathogenicity tended to be found in immunocompromised patients, suggesting the host immune system plays an important role in preventing PJI. Repeated mutations inS. aureusgenes associated with extracellular matrix binding were identified suggesting an adaptive, parallel evolution inS. aureusduring the development of PJI.
Identifying the measurements required to estimate rates of COVID-19 transmission, infection, and detection, using variational data assimilation
Authors: Armstrong Eve , Runge Manuela , Gerardin Jaline
Published: May 2020

We demonstrate the ability of statistical data assimilation to identify the measurements required for accurate state and parameter estimation in an epidemiological model for the novel coronavirus disease COVID-19. Our context is an effort to inform policy regarding social behavior, to mitigate strain on hospital capacity. The model unknowns are taken to be: the time-varying transmission rate, the fraction of exposed cases that require hospitalization, and the time-varying detection probabilities of new asymptomatic and symptomatic cases. In simulations, we obtain accurate estimates of undetected (that is, unmeasured) infectious populations, by measuring the detected cases together with the recovered and dead - and without assumed knowledge of the detection rates. These state estimates require a measurement of the recovered population, and are tolerant to low errors in that measurement. Further, excellent estimates of all quantities are obtained using a temporal baseline of 112 days, with the exception of the time-varying transmission rate at times prior to the implementation of social distancing. The estimation of this transmission rate is sensitive to contamination in the data, highlighting the need for accurate and uniform methods of reporting. Finally, we employ the procedure using real data from Italy reported by Johns Hopkins. The aim of this paper is not to assign extreme significance to the results of these specific experimentsper se. Rather, we intend to exemplify the power of SDA to determine what properties of measurements will yield estimates of unknown model parameters to a desired precision - all set within the complex context of the COVID-19 pandemic.
Management and Outcomes of Critically-Ill Patients with COVID-19 Pneumonia at a Safety-net Hospital in San Francisco, a Region with Early Public Health Interventions: A Case Series
Authors: Vanderburg Sky , Alipanah Narges , Crowder Rebecca , Yoon Christina , Wang Richard , Thakur Neeta , Slown Kristin , Shete Priya B. , Rofael Martin , Metcalfe John Z. , Merrifield Cindy , Marquez Carina , Malcolm Katherine , Lipnick Michael , Jain Vivek , Gomez Antonio , Burns Gregory , Brown Lillian B. , Berger Christopher , Auyeung Vincent , Cattamanchi Adithya , Hendrickson Carolyn M.
Published: May 2020

Background

Following early implementation of public health measures, San Francisco has experienced a slow rise and a low peak level of coronavirus disease 2019 (COVID-19) cases and deaths.

Methods and Findings

We included all patients with COVID-19 pneumonia admitted to the intensive care unit (ICU) at the safety net hospital for San Francisco through April 8, 2020. Each patient had ≥15 days of follow-up. Among 26 patients, the median age was 54 years (interquartile range, 43 to 62), 65% were men, and 77% were Latinx. Mechanical ventilation was initiated for 11 (42%) patients within 24 hours of ICU admission and 20 patients (77%) overall. The median duration of mechanical ventilation was 13.5 days (interquartile range, 5 to 20). Patients were managed with lung protective ventilation (tidal volume ≤8 ml/kg of ideal body weight and plateau pressure ≤30 cmH2O on 98% and 78% of ventilator days, respectively). Prone positioning was used for 13 of 20 (65%) ventilated patients for a median of 5 days (interquartile range, 2 to 10). Seventeen (65%) patients were discharged home, 1 (4%) was discharged to nursing home, 3 (12%) were discharged from the ICU, and 2 (8%) remain intubated in the ICU at the time of this report. Three (12%) patients have died.

Conclusions

Good outcomes were achieved in critically ill patients with COVID-19 by using standard therapies for acute respiratory distress syndrome (ARDS) such as lung protective ventilation and prone positioning. Ensuring hospitals can deliver sustained high-quality and evidence-based critical care to patients with ARDS should remain a priority.
Legionnaires’ disease on the rise in Switzerland: A denominator-based analysis of national diagnostic data, 2007-2016
Authors: Fischer Fabienne B. , Schmutz Claudia , Gaia Valeria , Mäusezahl Daniel
Published: May 2020

Purpose

The risk of Legionnaires’ disease (LD) is suggested to increase, but the global burden of disease is unknown due to lack of appropriate diagnosis and surveillance systems. In Switzerland, the number of LD cases, captured by the National Notification System for Infectious Diseases, has more than doubled since 2008. The aim of this study is to evaluate disease surveillance data using denominator data i.e. the number of tests performed for Legionella. spp.

Methods

We collected the testing data for Legionella spp. of 14 Swiss diagnostic laboratories and calculated the positivity rate, which is the rate of the number of positive tests to the number of tests performed.

Results

The number of positive tests increased proportionally to the number of tests performed; hence the positivity remained stable. However, the cause of the increase in test volume is unclear and has a large impact on the interpretation of the positivity curve. Further, the test outcome was found to be dependent on regional determinants and the diagnostic method applied.

Conclusion

In concert with the lack of understanding if and at which stage LD is considered in current case management of pneumonia patients, it is difficult to interpret heterogeneities in incidence or underestimation in Switzerland.
Evidence for two main domestication trajectories inSaccharomyces cerevisiaelinked to distinct bread-making processes
Authors: Bigey Frédéric , Segond Diego , Friedrich Anne , Guezenec Stephane , Bourgais Aurélie , Huyghe Lucie , Agier Nicolas , Nidelet Thibault , Sicard Delphine
Published: May 2020

Despite bread being one of the most historically and culturally important fermented products, its history and influence on the evolution of associated microbial species remains largely unknown. The first evidence of leavened bread dates to the second millenium BCE in Egypt and since, the art of bread-making developed and spread worldwide. Nowadays, leavened bread is made either by using a pure commercial culture of the yeastSaccharomyces cerevisiaeor by propagating a sourdough, which is a mix of flour and water spontaneously fermented by yeast and bacteria. We studied the domestication ofS. cerevisiaepopulations originating from industry and sourdough and tested whether these different bread-making processes led to population divergence. We found that the origin ofS. cerevisiaebakery strains is polyphyletic with 67 % of strains clustering in two main clades: most commercial strains were tetraploid and clustered with strains having diverse origins, including beer. By contrast, most sourdough strains were diploids and found in a second clade of strains having mosaic genomes and diverse origins including fruits, or clinical and wild environments. When compared to the others, sourdough strains harboured in average a higher copy number of genes involved in maltose utilization, a common sugar produced from dough starch. Overall, a high level of gene flow from multiple contributors was detected. Phenotyping of bakery and non bakery strains further showed that sourdough and industrial bakery populations have undergone human selection for rapidly starting fermentations and for high CO2production. Interestingly, sourdough strains also showed a better adaptation to a sourdough mimicking environment, suggesting that natural selection occurred as well. In summary, our results revealed that the domestication of bakery yeast populations has been accompanied by dispersion, hybridization and divergent selection through industrial and artisanal bakery processes. In addition, they unveiled for the first time a case of fungus domestication where species divergence occurred through autotetraploidisation.
Investigation of thein vitroandin vivoactivity of the type IV pilus extension ATPase BfpD
Authors: Zhao Jinlei , Nisa Shahista , Donnenberg Michael S.
Published: May 2020

Type IV pili (T4Ps) are multifunctional protein fibers found in many bacteria and archaea. All T4P systems have an extension ATPase, which provides the energy required to push structural subunits out of the membrane. We previously reported that the BfpD T4P ATPase from enteropathogenicE. coli(EPEC) has the expected hexameric structure and ATPase activity, the latter enhanced by the presence of the N-terminal cytoplasmic domains of its partner proteins BfpC and BfpE. In this study, we further investigated the kinetics of the BfpD ATPase. Despite high purity of the proteins, the reported enhanced ATPase activity was found to be from (an) ATPase(s) contaminating the N-BfpC preparation. Furthermore, although two mutations in highly conservedbfpDsites led to loss of functionin vivo, the purified mutant proteins retained some ATPase activity, albeit less than the wild-type protein. Therefore, the observed ATPase activity of BfpD was also affected by (a) contaminating ATPase(s). Expression of the mutantbfpDalleles did not interfere with BfpD function in bacteria that also expressed wild-type BfpD. However, a similar mutation ofbfpF, which encodes the retraction ATPase, blocked the function of wild-type BfpF when both were present. These results highlight similarities and differences in function and activity of T4P extension and retraction ATPases in EPEC.
Characterisation of the bacterial microbiota of a landfill-contaminated confined aquifer undergoing intrinsic remediation
Authors: Abiriga Daniel , Jenkins Andrew , Alfsnes Kristian , Vestgarden Live S. , Klempe Harald
Published: May 2020

Literature on microbiome of landfill leachate-contaminated aquifers is scarce despite groundwater contaminations from landfills being common globally. In this study, a combination of microbiological techniques was applied to groundwater samples from an aquifer contaminated by a municipal landfill and undergoing intrinsic bioremediation. Groundwater samples were obtained from three multilevel sampling wells placed along the groundwater flow path in the contaminated aquifer and additionally from a background well located in a nearby uncontaminated aquifer. The samples were subjected to chemical analysis, microbial culturing and characterisation, cell counting by fluorescence microscopy and 16S rRNA metabarcoding. Good concordance was realised with the results from the different microbiological techniques. Samples from the uncontaminated aquifer had both lower cell density and lower microbial diversity compared to samples from the contaminated aquifer. Among the wells located in the contaminated aquifer, microbial diversity increased between the well closest to the landfill and the intermediate well, but was lower at the most distant well. The majority of the cultured microbes represented taxa frequently recovered from contaminated environments, with 47% belonging to taxa with previously documented bioremediation potential. Multivariate redundancy analysis showed that microbial composition was most similar in wells located closer to the landfill, although beta diversity analysis indicated a significant difference in microbial composition across the wells. Taken together with the results of cell counting, culture and metabarcoding, these findings illustrate the effect of landfill leachate on the microbial community and indicate that microbes are capable of hydrocarbon, sulphur, nitrogen, iron and manganese metabolism.
Laminin N-terminus α31 is upregulated in invasive ductal breast cancer and changes the mode of tumour invasion
Authors: Troughton Lee D. , Zech Tobias , Hamill Kevin J.
Published: May 2020

Laminin N-terminus α31 (LaNt α31) is an alternative splice isoform derived from the laminin α3 gene. The LaNt α31 protein is enriched around the terminal duct lobular units in normal breast tissue. In the skin and cornea the protein influences epithelial cell migration and tissue remodelling. However, LaNt α31 has never been investigated in a tumour environment. Here we analysed LaNt α31 in invasive ductal carcinoma and determined its contribution to breast carcinoma invasion. LaNt α31 expression and distribution were analysed by immunohistochemistry in human breast tissue biopsy sections and tissue microarrays covering 232 breast cancer samples. This analysis revealed LaNt α31 to be upregulated in 56 % of invasive ductal carcinoma specimens compared with matched normal tissue, and further increased in nodal metastasis compared with the tumour mass in 45 % of samples. 65.8 % of triple negative cases displayed medium to high LaNt α31 expression. To study LaNt α31 function, an adenoviral system was used to induce expression in MCF-7 and MDA-MB-231 cells. Metabolic activity, 2D cell migration, and invasion into collagen hydrogels were not significantly different between LaNt α31 overexpressing cells and control treated cells. However, LaNt α31 overexpressing MDA-MB-231 cells displayed a striking change in their mode of invasion into laminin-containing Matrigel; changing from multicellular streaming to individual cellular-invasion. In agreement with these results, 66.7% of the tumours with the highest LaNt α31 expression were non-cohesive. Together these findings indicate that breast cancer-associated changes in LaNt α31 expression could directly contribute to tumour invasiveness, and that this little-studied protein may become a therapeutic target.
Single-dose replicating RNA vaccine induces neutralizing antibodies against SARS-CoV-2 in nonhuman primates
Authors: Erasmus Jesse H. , Khandhar Amit P. , Walls Alexandra C. , Hemann Emily A. , O’Connor Megan A. , Murapa Patience , Archer Jacob , Leventhal Shanna , Fuller Jim , Lewis Thomas , Draves Kevin E. , Randall Samantha , Guerriero Kathryn A. , Duthie Malcolm S. , Carter Darrick , Reed Steven G. , Hawman David W. , Feldmann Heinz , Gale Michael , Veesler David , Berglund Peter , Fuller Deborah Heydenburg
Published: May 2020

The ongoing COVID-19 pandemic, caused by infection with SARS-CoV-2, is having a dramatic and deleterious impact on health services and the global economy. Grim public health statistics highlight the need for vaccines that can rapidly confer protection after a single dose and be manufactured using components suitable for scale-up and efficient distribution. In response, we have rapidly developed repRNA-CoV2S, a stable and highly immunogenic vaccine candidate comprised of an RNA replicon formulated with a novel Lipid InOrganic Nanoparticle (LION) designed to enhance vaccine stability, delivery and immunogenicity. We show that intramuscular injection of LION/repRNA-CoV2S elicits robust anti-SARS-CoV-2 spike protein IgG antibody isotypes indicative of a Type 1 T helper response as well as potent T cell responses in mice. Importantly, a single-dose administration in nonhuman primates elicited antibody responses that potently neutralized SARS-CoV-2. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection from SARS-CoV-2 infection.
Crystal structure and Hirshfeld surface analysis of 4-(naphthalen-2-yl)-N-[(Z)-4-propoxybenzylidene]-1,3-thiazol-2-amine
Authors: Sheakh Mohamad Ropak A. , Hamad Wali M. , Aziz Hashim J.
Published: May 2020

The asymmetric unit of the title compound, C23H20N2OS, contains one slightly bent molecule. The naphthalene ring system and the thiazole ring are twisted with respect to each other, making a dihedral angle of 13.69 (10)°; the anisole ring is inclined to the plane of the naphthalene ring system, the dihedral angle being 14.22 (12)°. In the crystal structure, molecules are linked by C—H...π interactions, resulting in the formation of sheets parallel to (100). Within the sheets, very weak π–π stacking interactions lead to additional stabilization. Hirshfeld surface analysis and fingerprint plots reveal that the cohesion in the crystal structure is dominated by H...H (42.5%) and C...H/H...C (37.2%) contacts.
Crystal structure of catena-poly[[[diaqua[1,2-bis(pyridin-4-yl)ethene]{4-[2-(pyridin-4-yl)ethenyl]pyridinium}gold(I)iron(II)]-di-μ-cyanido] bis[dicyanidogold(I)] 1,2-bis(pyridin-4-yl)ethene dihydrate]
Authors: Partsevska Sofiia V. , Naumova Dina D. , Matushko Igor P. , Shova Sergiu , Gural'skiy Il'ya A.
Published: May 2020

In the title compound [Fe(bpe)(Hbpe)Au(CN)2][Au(CN)2]2·bpe·2H2O}
n
[where bpe = 1,2-bis(pyridin-4-yl)ethene, C12H10N2], the FeII ion is coordinated in a distorted octahedral [FeN4O2] environment by two dicyanoaurate anions, two water molecules and two partially protonated 1,2-di(4-pyridyl)ethylene molecules. Dicyanoaurate anions bridge the FeII cations, forming infinite chains, which propagate along the a-axis direction. The chains are connected via aurophilic interactions with two non-coordinated dicyanoaurate anions for each FeII ion. The polymeric chains interact with each other via π–π stacking between the guest bpe molecules and multiple hydrogen bonds.
Molecular and crystal structure, optical properties and DFT studies of 1,4-dimethoxy-2,5-bis[2-(4-nitrophenyl)ethenyl]benzene
Authors: Bogdanov Georgii , Oskolkov Evgenii , Bustos Jenna , Glebov Viktor , Tillotson John P. , Timofeeva Tatiana V.
Published: May 2020

The title compound DBNB, C24H20N2O6, has been crystallized and studied by X-ray diffraction, spectroscopic and computational methods. In the title molecule, which is based on a 1,4-distyryl-2,5-dimethoxybenzene core with p-nitro-substituted terminal benzene rings, the dihedral angle between mean planes of the central fragment and the terminal phenyl ring is 16.46 (6)°. The crystal packing is stabilized by π–π interactions. DFT calculations at the B3LYP/6–311 G(d,p) level of theory were used to compare the optimized structures with the experimental data. Energy parameters, including HOMO and LUMO energies, their difference, and vertical excitation and emission energies were obtained.
2-[Carbamothioyl(2-hydroxyethyl)amino]ethyl benzoate: crystal structure, Hirshfeld surface analysis and computational study
Authors: Tan Sang Loon , Tiekink Edward R. T.
Published: May 2020

The title di-substituted thiourea, C12H16N2O3S, has the hydroxylethyl and ethyl benzoate substituents bound to the same amine-N atom, and is twisted, having a (+)syn-clinal conformation with the Namine—C—C—O(hydroxyl, carbonyl)torsion angles of 49.39 (13) and 59.09 (12)°, respectively; the dihedral angle between the almost planar CN2S core and the pendent benzene ring is 69.26 (4)°. In the crystal, supramolecular layers propagating in theacplane are formedviaa combination of hydroxyl-O—H...S(thione), amine-N—H...O(hydroxyl, carbonyl) hydrogen-bonds. The layers stack along thebaxis with inter-digitation of the benzene rings allowing the formation of π–π stacking [inter-centroid separation = 3.8722 (7) Å] and parallel C=O...π interactions. A computational chemistry study shows the conventional hydrogen bonding in the crystal leads to significant electrostatic stabilization but dispersion terms are also apparent, notably through the interactions involving the benzene residue.
High-resolution crystal structure of Trypanosoma brucei pteridine reductase 1 in complex with an innovative tricyclic-based inhibitor
Authors: Landi Giacomo , Linciano Pasquale , Tassone Giusy , Costi Maria Paola , Mangani Stefano , Pozzi Cecilia
Published: May 2020

The protozoan parasite Trypanosoma brucei is the etiological agent of human African trypanosomiasis (HAT). HAT, together with other neglected tropical diseases, causes serious health and economic issues, especially in tropical and subtropical areas. The classical antifolates targeting dihydrofolate reductase (DHFR) are ineffective towards trypanosomatid parasites owing to a metabolic bypass by the expression of pteridine reductase 1 (PTR1). The combined inhibition of PTR1 and DHFR activities in Trypanosoma parasites represents a promising strategy for the development of new effective treatments for HAT. To date, only monocyclic and bicyclic aromatic systems have been proposed as inhibitors of T. brucei PTR1 (TbPTR1); nevertheless, the size of the catalytic cavity allows the accommodation of expanded molecular cores. Here, an innovative tricyclic-based compound has been explored as a TbPTR1-targeting molecule and its potential application for the development of a new class of PTR1 inhibitors has been evaluated. 2,4-Diaminopyrimido[4,5-b]indol-6-ol (1) was designed and synthesized, and was found to be effective in blocking TbPTR1 activity, with a K
i in the low-micromolar range. The binding mode of 1 was clarified through the structural characterization of its ternary complex with TbPTR1 and the cofactor NADP(H), which was determined to 1.30 Å resolution. The compound adopts a substrate-like orientation inside the cavity that maximizes the binding contributions of hydrophobic and hydrogen-bond interactions. The binding mode of 1 was compared with those of previously reported bicyclic inhibitors, providing new insights for the design of innovative tricyclic-based molecules targeting TbPTR1.