Showing papers by "University of Oklahoma published in 2021"

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults.

Abstract: Background Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness. Methods We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible. Results A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P = 0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed. Conclusions Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. (Funded by the Bill and Melinda Gates Foundation and the Fundacion INFANT Pandemic Fund; Direccion de Sangre y Medicina Transfusional del Ministerio de Salud number, PAEPCC19, Plataforma de Registro Informatizado de Investigaciones en Salud number, 1421, and ClinicalTrials.gov number, NCT04479163.).

Climate warming enhances microbial network complexity and stability

Abstract: Unravelling the relationships between network complexity and stability under changing climate is a challenging topic in theoretical ecology that remains understudied in the field of microbial ecology. Here, we examined the effects of long-term experimental warming on the complexity and stability of molecular ecological networks in grassland soil microbial communities. Warming significantly increased network complexity, including network size, connectivity, connectance, average clustering coefficient, relative modularity and number of keystone species, as compared with the ambient control. Molecular ecological networks under warming became significantly more robust, with network stability strongly correlated with network complexity, supporting the central ecological belief that complexity begets stability. Furthermore, warming significantly strengthened the relationships of network structure to community functional potentials and key ecosystem functioning. These results indicate that preserving microbial ‘interactions’ is critical for ecosystem management and for projecting ecological consequences of future climate warming. The authors examine the effect of long-term experimental warming on the complexity and stability of molecular ecological networks in grassland soil microbial communities. They find warming increases network complexity, which is strongly correlated with network stability.

Software for the frontiers of quantum chemistry: An overview of developments in the Q-Chem 5 package

Abstract: This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange-correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear-electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an "open teamware" model and an increasingly modular design.

Origin of the heaviest elements: The rapid neutron-capture process

Abstract: The production of about half of the heavy elements found in nature is assigned to a specific astrophysical nucleosynthesis process: the rapid neutron capture process (r-process). Although this idea has been postulated more than six decades ago, the full understanding faces two types of uncertainties/open questions: (a) The nucleosynthesis path in the nuclear chart runs close to the neutron-drip line, where presently only limited experimental information is available, and one has to rely strongly on theoretical predictions for nuclear properties. (b) While for many years the occurrence of the r-process has been associated with supernovae, more recent studies have cast substantial doubts on this environment. Alternative scenarios include the mergers of neutron stars, neutron-star black hole mergers, but possibly also rare classes of supernovae as well as hypernovae/collapsars with polar jet ejecta and also accretion disk outflows related to the collapse of fast rotating massive stars with high magnetic fields. Stellar r-process abundance observations, have provided insights into, and constraints on the frequency of and conditions in the responsible stellar production sites. One of them, neutron star mergers, was just identified and related to the Gravitational Wave event GW170817. High resolution observations, increasingly more precise due to improved experimental atomic data, have been particularly important in defining the heavy element abundance patterns of the old halo stars, and thus determining the extent, and nature, of the earliest nucleosynthesis in our Galaxy. Combining new results and important breakthroughs in the related nuclear, atomic and astronomical fields of science, this review attempts to provide an answer to the question "How Were the Elements from Iron to Uranium Made?" (Abridged)

Aspirin Use Is Associated With Decreased Mechanical Ventilation, Intensive Care Unit Admission, and In-Hospital Mortality in Hospitalized Patients With Coronavirus Disease 2019.

Abstract: Background Coronavirus disease-2019 (COVID-19) is associated with hypercoagulability and increased thrombotic risk in critically ill patients. To our knowledge, no studies have evaluated whether aspirin use is associated with reduced risk of mechanical ventilation, intensive care unit (ICU) admission, and in-hospital mortality. Methods A retrospective, observational cohort study of adult patients admitted with COVID-19 to multiple hospitals in the United States between March 2020 and July 2020 was performed. The primary outcome was the need for mechanical ventilation. Secondary outcomes were ICU admission and in-hospital mortality. Adjusted hazard ratios (HRs) for study outcomes were calculated using Cox-proportional hazards models after adjustment for the effects of demographics and comorbid conditions. Results Four hundred twelve patients were included in the study. Three hundred fourteen patients (76.3%) did not receive aspirin, while 98 patients (23.7%) received aspirin within 24 hours of admission or 7 days before admission. Aspirin use had a crude association with less mechanical ventilation (35.7% aspirin versus 48.4% nonaspirin, P = .03) and ICU admission (38.8% aspirin versus 51.0% nonaspirin, P = .04), but no crude association with in-hospital mortality (26.5% aspirin versus 23.2% nonaspirin, P = .51). After adjusting for 8 confounding variables, aspirin use was independently associated with decreased risk of mechanical ventilation (adjusted HR, 0.56, 95% confidence interval [CI], 0.37-0.85, P = .007), ICU admission (adjusted HR, 0.57, 95% CI, 0.38-0.85, P = .005), and in-hospital mortality (adjusted HR, 0.53, 95% CI, 0.31-0.90, P = .02). There were no differences in major bleeding (P = .69) or overt thrombosis (P = .82) between aspirin users and nonaspirin users. Conclusions Aspirin use may be associated with improved outcomes in hospitalized COVID-19 patients. However, a sufficiently powered randomized controlled trial is needed to assess whether a causal relationship exists between aspirin use and reduced lung injury and mortality in COVID-19 patients.

Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial.

Abstract: Summary Background Chemoradiotherapy is the standard of care for unresected locally advanced squamous cell carcinoma of the head and neck. We aimed to assess if addition of avelumab (anti-PD-L1) to chemoradiotherapy could improve treatment outcomes for this patient population. Methods In this randomised, double-blind, placebo-controlled, phase 3 study, patients were recruited from 196 hospitals and cancer treatment centres in 22 countries. Patients aged 18 years or older, with histologically confirmed, previously untreated, locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, larynx, or oral cavity (unselected for PD-L1 status), an Eastern Cooperative Oncology Group performance status score of 0 or 1, and who could receive chemoradiotherapy were eligible. Patients were randomly assigned (1:1) centrally by means of stratified block randomisation with block size four (stratified by human papillomavirus status, tumour stage, and nodal stage, and done by an interactive response technology system) to receive 10 mg/kg avelumab intravenously every 2 weeks plus chemoradiotherapy (100 mg/m2 cisplatin every 3 weeks plus intensity-modulated radiotherapy with standard fractionation of 70 Gy [35 fractions during 7 weeks]; avelumab group) or placebo plus chemoradiotherapy (placebo group). This was preceded by a single 10 mg/kg avelumab or placebo lead-in dose given 7 days previously and followed by 10 mg/kg avelumab or placebo every 2 weeks maintenance therapy for up to 12 months. The primary endpoint was progression-free survival by investigator assessment per modified Response Evaluation Criteria in Solid Tumors, version 1.1, in all randomly assigned patients. Adverse events were assessed in patients who received at least one dose of avelumab or placebo. This trial is registered with ClinicalTrials.gov , NCT02952586 . Enrolment is no longer ongoing, and the trial has been discontinued. Findings Between Dec 12, 2016, and Jan 29, 2019, from 907 patients screened, 697 patients were randomly assigned to the avelumab group (n=350) or the placebo group (n=347). Median follow-up for progression-free survival was 14·6 months (IQR 8·5–19·6) in the avelumab group and 14·8 months (11·6–18·8) in the placebo group. Median progression-free survival was not reached (95% CI 16·9 months–not estimable) in the avelumab group and not reached (23·0 months–not estimable) in the placebo group (stratified hazard ratio 1·21 [95% CI 0·93–1·57] favouring the placebo group; one-sided p=0·92). The most common grade 3 or worse treatment-related adverse events were neutropenia (57 [16%] of 348 patients in the avelumab group vs 52 [15%] of 344 patients in the placebo group), mucosal inflammation (50 [14%] vs 45 [13%]), dysphagia (49 [14%] vs 47 [14%]), and anaemia (41 [12%] vs 44 [13%]). Serious treatment-related adverse events occurred in 124 (36%) patients in the avelumab group and in 109 (32%) patients in the placebo group. Treatment-related deaths occurred in two (1%) patients in the avelumab group (due to general disorders and site conditions, and vascular rupture) and one ( Interpretation The primary objective of prolonging progression-free survival with avelumab plus chemoradiotherapy followed by avelumab maintenance in patients with locally advanced squamous cell carcinoma of the head and neck was not met. These findings may help inform the design of future trials investigating the combination of immune checkpoint inhibitors plus CRT. Funding Pfizer and Merck KGaA, Darmstadt, Germany.

Targeting SARS-CoV-2 spike protein of COVID-19 with naturally occurring phytochemicals: an in silico study for drug development.

Abstract: Spike glycoprotein, a class I fusion protein harboring the surface of SARS-CoV-2 (SARS-CoV-2S), plays a seminal role in the viral infection starting from recognition of the host cell surface receptor, attachment to the fusion of the viral envelope with the host cells. Spike glycoprotein engages host Angiotensin-converting enzyme 2 (ACE2) receptors for entry into host cells, where the receptor recognition and attachment of spike glycoprotein to the ACE2 receptors is a prerequisite step and key determinant of the host cell and tissue tropism. Binding of spike glycoprotein to the ACE2 receptor triggers a cascade of structural transitions, including transition from a metastable pre-fusion to a post-fusion form, thereby allowing membrane fusion and internalization of the virus. From ancient times people have relied on naturally occurring substances like phytochemicals to fight against diseases and infection. Among these phytochemicals, flavonoids and non-flavonoids have been the active sources of different anti-microbial agents. We performed molecular docking studies using 10 potential naturally occurring compounds (flavonoids/non-flavonoids) against the SARS-CoV-2 spike protein and compared their affinity with an FDA approved repurposed drug hydroxychloroquine (HCQ). Further, our molecular dynamics (MD) simulation and energy landscape studies with fisetin, quercetin, and kamferol revealed that these molecules bind with the hACE2-S complex with low binding free energy. The study provided an indication that these molecules might have the potential to perturb the binding of hACE2-S complex. In addition, ADME analysis also suggested that these molecules consist of drug-likeness property, which may be further explored as anti-SARS-CoV-2 agents. Communicated by Ramaswamy H. Sarma.

Widespread deoxygenation of temperate lakes

Abstract: The concentration of dissolved oxygen in aquatic systems helps to regulate biodiversity1,2, nutrient biogeochemistry3, greenhouse gas emissions4, and the quality of drinking water5. The long-term declines in dissolved oxygen concentrations in coastal and ocean waters have been linked to climate warming and human activity6,7, but little is known about the changes in dissolved oxygen concentrations in lakes. Although the solubility of dissolved oxygen decreases with increasing water temperatures, long-term lake trajectories are difficult to predict. Oxygen losses in warming lakes may be amplified by enhanced decomposition and stronger thermal stratification8,9 or oxygen may increase as a result of enhanced primary production10. Here we analyse a combined total of 45,148 dissolved oxygen and temperature profiles and calculate trends for 393 temperate lakes that span 1941 to 2017. We find that a decline in dissolved oxygen is widespread in surface and deep-water habitats. The decline in surface waters is primarily associated with reduced solubility under warmer water temperatures, although dissolved oxygen in surface waters increased in a subset of highly productive warming lakes, probably owing to increasing production of phytoplankton. By contrast, the decline in deep waters is associated with stronger thermal stratification and loss of water clarity, but not with changes in gas solubility. Our results suggest that climate change and declining water clarity have altered the physical and chemical environment of lakes. Declines in dissolved oxygen in freshwater are 2.75 to 9.3 times greater than observed in the world’s oceans6,7 and could threaten essential lake ecosystem services2,3,5,11. Analysis of temperate lakes finds a widespread decline in dissolved oxygen concentrations in surface and deep waters, which is associated with reduced solubility at warmer surface water temperatures and increased stratification at depth.

Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial

Abstract: Summary Background BCG is the most effective therapy for high-risk non-muscle-invasive bladder cancer. Nadofaragene firadenovec (also known as rAd-IFNa/Syn3) is a replication-deficient recombinant adenovirus that delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non-muscle-invasive bladder cancer. We aimed to evaluate its efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer. Methods In this phase 3, multicentre, open-label, repeat-dose study done in 33 centres (hospitals and clinics) in the USA, we recruited patients aged 18 years or older, with BCG-unresponsive non-muscle-invasive bladder cancer and an Eastern Cooperative Oncology Group status of 2 or less. Patients were excluded if they had upper urinary tract disease, urothelial carcinoma within the prostatic urethra, lymphovascular invasion, micropapillary disease, or hydronephrosis. Eligible patients received a single intravesical 75 mL dose of nadofaragene firadenovec (3 × 1011 viral particles per mL). Repeat dosing at months 3, 6, and 9 was done in the absence of high-grade recurrence. The primary endpoint was complete response at any time in patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour). The null hypothesis specified a complete response rate of less than 27% in this cohort. Efficacy analyses were done on the per-protocol population, to include only patients strictly meeting the BCG-unresponsive definition. Safety analyses were done in all patients who received at least one dose of treatment. The study is ongoing, with a planned 4-year treatment and monitoring phase. This study is registered with ClinicalTrials.gov , NCT02773849 . Findings Between Sept 19, 2016, and May 24, 2019, 198 patients were assessed for eligibility. 41 patients were excluded, and 157 were enrolled and received at least one dose of the study drug. Six patients did not meet the definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were included in the per-protocol efficacy analyses. 55 (53·4%) of 103 patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 25 (45·5%) of 55 patients at 12 months. Micturition urgency was the most common grade 3–4 study drug-related adverse event (two [1%] of 157 patients, both grade 3), and there were no treatment-related deaths. Interpretation Intravesical nadofaragene firadenovec was efficacious, with a favourable benefit:risk ratio, in patients with BCG-unresponsive non-muscle-invasive bladder cancer. This represents a novel treatment option in a therapeutically challenging disease state. Funding FKD Therapies Oy.

Jet energy scale and resolution measured in proton-proton collisions at s =13 TeV with the ATLAS detector

Abstract: Jet energy scale and resolution measurements with their associated uncertainties are reported for jets using 36-81 fb$^{-1}$ of proton-proton collision data with a centre-of-mass energy of $\sqrt{s}=13$ TeV collected by the ATLAS detector at the LHC. Jets are reconstructed using two different input types: topo-clusters formed from energy deposits in calorimeter cells, as well as an algorithmic combination of charged-particle tracks with those topo-clusters, referred to as the ATLAS particle-flow reconstruction method. The anti-$k_t$ jet algorithm with radius parameter $R=0.4$ is the primary jet definition used for both jet types. Jets are initially calibrated using a sequence of simulation-based corrections. Next, several $\textit{in situ}$ techniques are employed to correct for differences between data and simulation and to measure the resolution of jets. The systematic uncertainties in the jet energy scale for central jets ($|\eta| 2.5$ TeV). The relative jet energy resolution is measured and ranges from ($24 \pm 1.5$)% at 20 GeV to ($6 \pm 0.5$)% at 300 GeV.

Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High-Grade Gliomas

Abstract: Background Outcomes in children and adolescents with recurrent or progressive high-grade glioma are poor, with a historical median overall survival of 56 months Pediatric high-grade glio

An overview of the ORACLES (ObseRvations of Aerosols above CLouds and their intEractionS) project: aerosol–cloud–radiation interactions in the southeast Atlantic basin

Abstract: . Southern Africa produces almost a third of the Earth’s biomass burning (BB) aerosol particles, yet the fate of these particles and their influence on regional and global climate is poorly understood. ORACLES (ObseRvations of Aerosols above CLouds and their intEractionS) is a five-year NASA EVS-2 (Earth Venture Suborbital-2) investigation with three Intensive Observation Periods designed to study key atmospheric processes that determine the climate impacts of these aerosols. During the Southern Hemisphere winter and spring (June-October), aerosol particles reaching 3–5 km in altitude are transported westward over the South-East Atlantic, where they interact with one of the largest subtropical stratocumulus subtropical stratocumulus (Sc) cloud decks in the world. The representation of these interactions in climate models remains highly uncertain in part due to a scarcity of observational constraints on aerosol and cloud properties, and due to the parameterized treatment of physical processes. Three ORACLES deployments by the NASA P-3 aircraft in September 2016, August 2017 and October 2018 (totaling ~350 science flight hours), augmented by the deployment of the NASA ER-2 aircraft for remote sensing in September 2016 (totaling ~100 science flight hours), were intended to help fill this observational gap. ORACLES focuses on three fundamental science questions centered on the climate effects of African BB aerosols: (a) direct aerosol radiative effects; (b) effects of aerosol absorption on atmospheric circulation and clouds; (c) aerosol-cloud microphysical interactions. This paper summarizes the ORACLES science objectives, describes the project implementation, provides an overview of the flights and measurements in each deployment, and highlights the integrative modeling efforts from cloud to global scales to address science objectives. Significant new findings on the vertical structure of BB aerosol physical and chemical properties, chemical aging, cloud condensation nuclei, rain and precipitation statistics, and aerosol indirect effects are emphasized, but their detailed descriptions are the subject of separate publications. The main purpose of this paper is to familiarize the broader scientific community with the ORACLES project and the data set it produced.

Carbon loss from forest degradation exceeds that from deforestation in the Brazilian Amazon

Abstract: Spatial–temporal dynamics of aboveground biomass (AGB) and forest area affect the carbon cycle, climate and biodiversity in the Brazilian Amazon. Here we investigate interannual changes in AGB and forest area by analysing satellite-based annual AGB and forest area datasets. We found that the gross forest area loss was larger in 2019 than in 2015, possibly due to recent loosening of forest protection policies. However, the net AGB loss was three times smaller in 2019 than in 2015. During 2010–2019, the Brazilian Amazon had a cumulative gross loss of 4.45 Pg C against a gross gain of 3.78 Pg C, resulting in a net AGB loss of 0.67 Pg C. Forest degradation (73%) contributed three times more to the gross AGB loss than deforestation (27%), given that the areal extent of degradation exceeds that of deforestation. This indicates that forest degradation has become the largest process driving carbon loss and should become a higher policy priority. Carbon loss from forests occurs through deforestation or the degradation of existing forest. The loss of forest area in the Brazilian Amazon was higher in 2019 than following drought and an El Nino event in 2015, yet degradation drove three times more biomass loss than deforestation from 2010 to 2019.

Renewable energy for whom? A global systematic review of the environmental justice implications of renewable energy technologies

Abstract: Renewable energy transitions are essential for decarbonizing the world economy and mitigating global climate change. Yet many energy technologies classified as renewable have human health and livelihood implications that jeopardize the lives and wellbeing of those already most vulnerable to the impacts of climate change. The purpose of this study is thus to summarize the documented environmental justice (EJ) impacts associated with renewable energy technologies included in many renewable energy policies globally. Our motivation for this study is to ensure that renewable energy policies incorporate concerns for justice into their formulation and implementation. We provide a systematic review of the literature assessing renewable energy technologies from the perspective of distributive, procedural, recognition, and capability interpretations of environmental justice. Our review finds that there are ten common renewable energy technologies that have EJ implications documented in the current literature, and that future energy transition policy development needs to ensure these justice concerns are addressed.

Genomic mechanisms of climate adaptation in polyploid bioenergy switchgrass.

Abstract: Long-term climate change and periodic environmental extremes threaten food and fuel security1 and global crop productivity2-4. Although molecular and adaptive breeding strategies can buffer the effects of climatic stress and improve crop resilience5, these approaches require sufficient knowledge of the genes that underlie productivity and adaptation6-knowledge that has been limited to a small number of well-studied model systems. Here we present the assembly and annotation of the large and complex genome of the polyploid bioenergy crop switchgrass (Panicum virgatum). Analysis of biomass and survival among 732 resequenced genotypes, which were grown across 10 common gardens that span 1,800 km of latitude, jointly revealed extensive genomic evidence of climate adaptation. Climate-gene-biomass associations were abundant but varied considerably among deeply diverged gene pools. Furthermore, we found that gene flow accelerated climate adaptation during the postglacial colonization of northern habitats through introgression of alleles from a pre-adapted northern gene pool. The polyploid nature of switchgrass also enhanced adaptive potential through the fractionation of gene function, as there was an increased level of heritable genetic diversity on the nondominant subgenome. In addition to investigating patterns of climate adaptation, the genome resources and gene-trait associations developed here provide breeders with the necessary tools to increase switchgrass yield for the sustainable production of bioenergy.

COVID-Classifier: an automated machine learning model to assist in the diagnosis of COVID-19 infection in chest X-ray images.

Abstract: Chest-X ray (CXR) radiography can be used as a first-line triage process for non-COVID-19 patients with pneumonia. However, the similarity between features of CXR images of COVID-19 and pneumonia caused by other infections makes the differential diagnosis by radiologists challenging. We hypothesized that machine learning-based classifiers can reliably distinguish the CXR images of COVID-19 patients from other forms of pneumonia. We used a dimensionality reduction method to generate a set of optimal features of CXR images to build an efficient machine learning classifier that can distinguish COVID-19 cases from non-COVID-19 cases with high accuracy and sensitivity. By using global features of the whole CXR images, we successfully implemented our classifier using a relatively small dataset of CXR images. We propose that our COVID-Classifier can be used in conjunction with other tests for optimal allocation of hospital resources by rapid triage of non-COVID-19 cases.

Root exudates drive soil-microbe-nutrient feedbacks in response to plant growth.

Abstract: Although interactions between plants and microbes at the plant-soil interface are known to be important for plant nutrient acquisition, relatively little is known about how root exudates contribute to nutrient exchange over the course of plant development. In this study, root exudates from slow- and fast-growing stages of Arabidopsis thaliana plants were collected, chemically analysed and then applied to a sandy nutrient-depleted soil. We then tracked the impacts of these exudates on soil bacterial communities, soil nutrients (ammonium, nitrate, available phosphorus and potassium) and plant growth. Both pools of exudates shifted bacterial community structure. GeoChip analyses revealed increases in the functional gene potential of both exudate-treated soils, with similar responses observed for slow-growing and fast-growing plant exudate treatments. The fast-growing stage root exudates induced higher nutrient mineralization and enhanced plant growth as compared to treatments with slow-growing stage exudates and the control. These results suggest that plants may adjust their exudation patterns over the course of their different growth phases to help tailor microbial recruitment to meet increased nutrient demands during periods demanding faster growth.

Social Entrepreneurship and COVID-19

Abstract: COVID-19 has changed the world. The pandemic is a public health crisis with profound implications for society. It follows that research efforts focused on addressing societal issues such as social entrepreneurship (SE) – ‘the practice of addressing social problems by means of markets’ (Mair, 2020, p. 333) – will also be deeply altered. In this commentary, we reflect on how the current COVID-19 pandemic and future pandemics have affected, and will affect, research on the topic of SE. We unearth five fundamental assumptions underlying the field of SE that have been challenged by this crisis, consider their implications for research in the space, and propose future research questions to guide SE scholarship. First, SE researchers assume that it is social entrepreneurs’ prosocial motives that lead to positive social outcomes. However, to tackle social problems caused by COVID-19, many businesses stepped-up to create solutions benefitting the public good, without regard to their initial motives – e.g., manufacturers made plastic shields and ventilators, distilleries produced highly sought-after hand sanitizer – often offering these solutions below cost. While there is little doubt that these ventures helped others (the essence of the term ‘prosocial’), their founders did not necessarily express prosocial motives at venture inception. As such, the global COVID-19 pandemic has revealed the assumed link between prosocial motives and social outcomes to be potentially tenuous. If entrepreneurial ventures and established businesses can achieve positive social outcomes regardless of their motivations – for example, by rapidly deploying solutions in the face of a global crisis such as COVID-19 – and if social entrepreneurs driven by social motives do not always achieve intended social outcomes, this suggests challenging questions about the overlap between SE and entrepreneurship as research domains: (1) To what extent are Journal of Management Studies ••:•• 2020 doi:10.1111/joms.12641

Muon reconstruction and identification efficiency in ATLAS using the full Run 2 pp collision data set at √ s = 13 TeV

Abstract: This article documents the muon reconstruction and identification efficiency obtained by the ATLAS experiment for 139 $$\hbox {fb}^{-1}$$ fb - 1 of pp collision data at $$\sqrt{s}=13$$ s = 13 TeV collected between 2015 and 2018 during Run 2 of the LHC. The increased instantaneous luminosity delivered by the LHC over this period required a reoptimisation of the criteria for the identification of prompt muons. Improved and newly developed algorithms were deployed to preserve high muon identification efficiency with a low misidentification rate and good momentum resolution. The availability of large samples of $$Z\rightarrow \mu \mu $$ Z → μ μ and $$J/\psi \rightarrow \mu \mu $$ J / ψ → μ μ decays, and the minimisation of systematic uncertainties, allows the efficiencies of criteria for muon identification, primary vertex association, and isolation to be measured with an accuracy at the per-mille level in the bulk of the phase space, and up to the percent level in complex kinematic configurations. Excellent performance is achieved over a range of transverse momenta from 3 GeV to several hundred GeV, and across the full muon detector acceptance of $$|\eta |<2.7$$ | η | < 2.7 .

The differing pathophysiologies that underlie COVID-19 associated perniosis and thrombotic retiform purpura: a case series.

Abstract: Background There are two distinctive acral manifestations of COVID-19 embodying disparate clinical phenotypes. One is perniosis occurring in mildly symptomatic patients, typically children and young adults; the second is the thrombotic retiform purpura of critically ill adults with COVID-19. Objectives To compare the clinical and pathological profiles of these two different cutaneous manifestations of COVID-19. Methods We compared the light microscopic, phenotypic, cytokine and SARS-CoV-2 protein and RNA profiles of COVID-19-associated perniosis with that of thrombotic retiform purpura in critical patients with COVID-19. Results Biopsies of COVID-19-associated perniosis exhibited vasocentric and eccrinotropic T-cell- and monocyte-derived CD11c+ , CD14+ and CD123+ dendritic cell infiltrates. Both COVID-associated and idiopathic perniosis showed striking expression of the type I interferon-inducible myxovirus resistance protein A (MXA), an established marker for type I interferon signalling in tissue. SARS-CoV-2 RNA, interleukin-6 and caspase 3 were minimally expressed and confined to mononuclear inflammatory cells. The biopsies from livedo/retiform purpura showed pauci-inflammatory vascular thrombosis without any MXA decoration. Blood vessels exhibited extensive complement deposition with endothelial cell localization of SARS-CoV-2 protein, interleukin-6 and caspase 3; SARS-CoV-2 RNA was not seen. Conclusions COVID-19-associated perniosis represents a virally triggered exaggerated immune reaction with significant type I interferon signaling. This is important to SARS-CoV-2 eradication and has implications in regards to a more generalized highly inflammatory response. We hypothesize that in the thrombotic retiform purpura of critically ill patients with COVID-19, the vascular thrombosis in the skin and other organ systems is associated with a minimal interferon response. This allows excessive viral replication with release of viral proteins that localize to extrapulmonary endothelium and trigger extensive complement activation.

Trapped in a Double Bind: Chinese Overseas Student Anxiety during the COVID-19 Pandemic.

Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), the COVID-19 disease cases stemming from it, and the resulting pandemic have imposed severe, distressing, physical, and psychologic...