bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the Risk of Cascading COVID-19 Outbreaks from Prison-to-Prison Transfers
Authors: Parsons Todd L. , Worden Lee 
Published: April 2021

AbstractCOVID-19 transmission has been widespread across the California prison system, and at least two of these outbreaks were caused by transfer of infected individuals between prisons. Risks of individual prison outbreaks due to introduction of the virus and of widespread transmission within prisons due to poor conditions have been documented. We examine the additional risk potentially posed by transfer between prisons that can lead to large-scale spread of outbreaks across the prison system if the rate of transfer is sufficiently high.We estimated the threshold number of individuals transferred per prison per month to generate supercritical transmission between prisons, a condition that could lead to large-scale spread across the prison system. We obtained numerical estimates from a range of representative quantitative assumptions, and derived the percentage of transfers that must be performed with effective quarantine measures to prevent supercritical transmission given known rates of transfers occurring between California prisons.Our mean estimate of the critical threshold rate of transfers was 14.38 individuals transferred per prison per month in the absence of quarantine measures. Available data documents transfers occurring at a rate of 60 transfers per prison per month. At that rate, estimates of the threshold rate of adherence to quarantine precautions had mean 76.03%. While the impact of vaccination and possible decarceration measures is unclear, we include estimates of the above quantities given reductions in the probability and extent of outbreaks.We conclude that the risk of supercritical transmission between California prisons has been substantial, requiring quarantine protocols to be followed rigorously to manage this risk. The rate of outbreaks occurring in California prisons suggests that supercritical transmission may have occurred. We stress that the thresholds we estimate here do not define a safe level of transfers, even if supercritical transmission between prisons is avoided, since even low rates of transfer can cause very large outbreaks. We note that risks may persist after vaccination, due for example to variant strains, and in prison systems where widespread vaccination has not occurred. Decarceration remains urgently needed as a public health measure.
A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2
Authors: Fulford Thomas S. , Van Huy , Gherardin Nicholas A. , Zheng Shuning , Ciula Marcin , Drummer Heidi E. , Redmond Samuel , Tan Hyon-Xhi , Center Rob J. , Li Fan , Grimley Samantha L. , Wines Bruce D. , Nguyen Thi H.O. , Mordant Francesca L. , Rowntree Louise C. , Cheng Allen C. , Doolan Denise L. , Bond Katherine , Hogarth P. Mark , McQuilten Zoe , Subbarao Kanta , Kedzierska Katherine , Juno Jennifer A. , Wheatley Adam K. , Kent Stephen J. , Williamson Deborah A. , Purcell Damian F.J. , Anderson David A. , Godfrey Dale I. 
Published: April 2021

AbstractAs vaccines against SARS-CoV-2 are now being rolled out, a better understanding of immunity to the virus; whether through infection, or passive or active immunisation, and the durability of this protection is required. This will benefit from the ability to measure SARS-CoV-2 immunity, ideally with rapid turnaround and without the need for laboratory-based testing. Current rapid point-of-care (POC) tests measure antibodies (Ab) against the SARS-CoV-2 virus, however, these tests provide no information on whether the antibodies can neutralise virus infectivity and are potentially protective, especially against newly emerging variants of the virus. Neutralising Antibodies (NAb) are emerging as a strong correlate of protection, but most current NAb assays require many hours or days, samples of venous blood, and access to laboratory facilities, which is especially problematic in resource-limited settings. We have developed a lateral flow POC test that can measure levels of RBD-ACE2 neutralising antibodies from whole blood, with a result that can be determined by eye (semi-quantitative) or on a small instrument (quantitative), and results show high correlation with microneutralisation assays. This assay also provides a measure of total anti-RBD antibody, thereby providing evidence of exposure to SARS-CoV-2 or immunisation, regardless of whether NAb are present in the sample. By testing samples from immunised macaques, we demonstrate that this test is equally applicable for use with animal samples, and we show that this assay is readily adaptable to test for immunity to newly emerging SARS-CoV-2 variants. Lastly, using a cohort of vaccinated humans, we demonstrate that our whole-blood test correlates closely with microneutralisation assay data (R2 =0.75, p<0.0001), and that fingerprick whole blood samples are sufficient for this test. Accordingly, the COVID-19 NAb-test™ device described here can provide a rapid readout of immunity to SARS-CoV-2 at the point of care.
ClustENMD: Efficient sampling of biomolecular conformational space at atomic resolution
Authors: Kaynak Burak T. , Zhang She , Bahar Ivet , Doruker Pemra 
Published: April 2021

AbstractSummaryEfficient sampling of conformational space is essential for elucidating functional/allosteric mechanisms of proteins and generating ensembles of conformers for docking applications. However, unbiased sampling is still a challenge especially for highly flexible and/or large systems. To address this challenge, we describe the new implementation of our computationally efficient algorithm ClustENMD that is integrated with ProDy and OpenMM softwares. This hybrid method performs iterative cycles of conformer generation using elastic network model (ENM) for deformations along global modes, followed by clustering and short molecular dynamics (MD) simulations. ProDy framework enables full automation and analysis of generated conformers and visualization of their distributions in the essential subspace.Availability and implementationClustENMD is open-source and freely available under MIT License from https://github.com/prody/ProDy.Contactburak.kaynak@pitt.edu or doruker@pitt.eduSupplementary informationSupplementary materials comprise method details, figures, table and tutorial.
Sleep modulates alcohol toxicity inDrosophila
Authors: Noakes Eric J. , De Nobrega Aliza K. , Mellers Alana P. , Lyons Lisa C. 
Published: April 2021

AbstractStudy ObjectivesAlcohol abuse is a significant public health problem, particularly in populations in which sleep deprivation is common as such as shift workers and aged individuals. Although research demonstrates the effect of alcohol on sleep, little is known about the role of sleep in alcohol sensitivity and toxicity. We investigated sleep as a factor modulating alcohol toxicity usingDrosophila melanogaster, a model system ideal for studies of sleep, alcohol and aging.MethodsFollowing 24 hours of sleep deprivation using mechanical stimulation,Drosophilawere exposed to binge-like alcohol exposures. Behavioral sensitivity, tolerance, and mortality were assessed. The effects of chronic sleep deprivation on alcohol toxicity were investigated using a short sleep mutantinsomniac. Pharmacological induction of sleep for prior to alcohol exposure was accomplished using a GABAA-receptor agonist, 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP) to determine if increased sleep mitigated the effects of alcohol toxicity on middle-aged flies and flies with environmentally disrupted circadian clocks mimicking groups more vulnerable to the effects of alcohol.ResultsAcute sleep deprivation increased alcohol-induced mortality following alcohol exposure. However, sleep deprivation had no effect on alcohol absorbance or clearance. Sleep deprivation also abolished functional tolerance measured 24 hours after the initial alcohol exposure, although tolerance at 4 h was observed. Pharmacologically increasing sleep prior to alcohol exposure decreased alcohol-induced mortality.ConclusionsSleep quantity prior to alcohol exposure affects alcohol toxicity with decreased sleep increasing alcohol toxicity and dampened 24-hour alcohol tolerance. In contrast, increased sleep mitigated alcohol-induced mortality even in vulnerable groups such as aging flies and those with circadian dysfunction.Statement of significanceWith the growing incidence of sleep deprivation and sleep disorders across adolescents and adults, it is important to understand the role of sleep in alcohol toxicity to develop future therapies for prevention and treatment of alcohol-induced pathologies. UsingDrosophila melanogaster, an established model for both sleep and alcohol research, we found that acute and chronic sleep deprivation increased alcohol toxicity and eliminated long-term functional alcohol tolerance. In contrast, increased sleep prior to binge-like alcohol exposure mitigated alcohol-induced mortality even in vulnerable groups with higher susceptibility to alcohol toxicity.
Focused Ultrasound Modulation of Hepatic Neural Plexus Restores Glucose Homeostasis in Diabetes
Authors: Cotero Victoria , Miwa Hiromi , Hirschstein Zall , Qanud Khaled , Huerta Tomás S. , Tai Ningwen , Ding Yuyan , Jimenez-Cowell Kevin , Tomaio Jacquelyn-Nicole , Song Weiguo , Devarajan Alex , Tsaava Tea , Graf John , Madhavan Radhika , Wallace Kirk , Loghin Evelina , Morton Christine , Fan Ying , Kao Tzu-Jen , Akhtar Kainat , Damaraju Meghana , Barenboim Linda , Maietta Teresa , Ashe Jeffrey , Tracey Kevin J. , Coleman Thomas R. , Carlo Dino Di , Shin Damian , Zanos Stavros , Chavan Sangeeta S. , Herzog Raimund I. , Puleo Chris 
Published: April 2021

While peripheral glucose sensors are known to relay signals of substrate availability to integrative nuclei in the brain, the importance of these pathways in maintaining energy homeostasis and their contribution to disease remain unknown. Herein, we demonstrate that selective activation of the hepatoportal neural plexus via transient peripheral focused ultrasound (pFUS) induces glucose homeostasis in models of well-established insulin resistant diabetes. pFUS modulates sensory projections to the hindbrain and alters hypothalamic concentrations of neurotransmitters that regulate metabolism, resulting in potentiation of hypothalamic insulin signaling, leptin-independent inhibition of the orexigenic neuropeptide Y system, and therapeutic alteration in autonomic output to peripheral effector organs. Multiomic profiling confirms pFUS-induced modifications of key metabolic functions in liver, pancreas, muscle, adipose, kidney, and intestines. Activation of the hepatic nutrient sensing pathway not only restores nervous system coordination of peripheral metabolism in three different species but does so across these organ systems; several of which are current targets of antidiabetic drug classes. These results demonstrate the potential of hepatic pFUS as a novel/non-pharmacologic therapeutic modality to restore glucose homeostasis in metabolic diseases, including type II diabetes.One Sentence SummaryWe utilize a non-invasive ultrasound technique to activate a liver-brain sensory pathway and demonstrate its potential to induce durable normalization of glucose homeostasis in models of well-established insulin resistant diabetes.
RNase L limits host and viral protein synthesis via inhibition of mRNA export
Authors: Burke James M. , Gilchrist Alison R. , Sawyer Sara L. , Parker Roy 
Published: April 2021

AbstractRNase L is widely thought to limit viral protein synthesis by cleaving host rRNA and viral mRNA, resulting in translation arrest and viral mRNA degradation. Herein, we show that the mRNAs of dengue virus and influenza A virus largely escape RNase L-mediated mRNA decay, and this permits viral protein production. However, activation of RNase L arrests nuclear mRNA export, which strongly inhibits influenza A virus protein synthesis and reduces cytokine production. Importantly, the heterogeneous and temporal nature of the mRNA export block in individual cells permits sufficient production of antiviral cytokines from transcriptionally induced host mRNAs. This defines RNase L-mediated arrest of mRNA export as a key antiviral shutoff and cytokine regulatory pathway.One Sentence SummaryRNase L-mediated shutoff of nuclear mRNA export limits viral protein synthesis and regulates antiviral cytokine production.
An Immune Cell Atlas Reveals Dynamic COVID-19 Specific Neutrophil Programming Amenable to Dexamethasone Therapy
Authors: Sinha Sarthak , Rosin Nicole L. , Arora Rohit , Labit Elodie , Jaffer Arzina , Cao Leslie , Farias Raquel , Nguyen Angela P. , de Almeida Luiz G. N. , Dufour Antoine , Bromley Amy , McDonald Braedon , Gillrie Mark , Fritzler Marvin J. , Yipp Bryan , Biernaskie Jeff 
Published: April 2021

SummarySARS-CoV-2 is a novel coronavirus that causes acute respiratory distress syndrome (ARDS), death and long-term sequelae. Innate immune cells are critical for host defense but are also the primary drivers of ARDS. The relationships between innate cellular responses in ARDS resulting from COVID-19 compared to other causes of ARDS, such as bacterial sepsis is unclear. Moreover, the beneficial effects of dexamethasone therapy during severe COVID-19 remain speculative, but understanding the mechanistic effects could improve evidence-based therapeutic interventions. To interrogate these relationships, we developed an scRNA-Seq and plasma proteomics atlas (biernaskielab.ca/COVID_neutrophil). We discovered that compared to bacterial ARDS, COVID-19 was associated with distinct neutrophil polarization characterized by either interferon (IFN) or prostaglandin (PG) active states. Neutrophils from bacterial ARDS had higher expression of antibacterial molecules such as PLAC8 and CD83. Dexamethasone therapy in COVID patients rapidly altered the IFNactivestate, downregulated interferon responsive genes, and activated IL1R2+veneutrophils. Dexamethasone also induced the emergence of immature neutrophils expressing immunosuppressive molecules ARG1 and ANXA1, which were not present in healthy controls. Moreover, dexamethasone remodeled global cellular interactions by changing neutrophils from information receivers into information providers. Importantly, male patients had higher proportions of IFNactiveneutrophils, a greater degree of steroid-induced immature neutrophil expansion, and increased mortality benefit compared to females in the dexamethasone era. Indeed, the highest proportion of IFNactiveneutrophils was associated with mortality. These results define neutrophil states unique to COVID-19 when contextualized to other life-threatening infections, thereby enhancing the relevance of our findings at the bedside. Furthermore, the molecular benefits of dexamethasone therapy are also defined, and the identified pathways and plasma proteins can now be targeted to develop improved therapeutics.
Restoration of plant diversity in permanent grassland by seeding: Assessing the limiting factors along land‐use gradients
Authors: Freitag Martin , Klaus Valentin H. , Bolliger Ralph , Hamer Ute , Kleinebecker Till , Prati Daniel , Schäfer Deborah , Hölzel Norbert 
Published: April 2021

Abstract

Land‐use intensification has caused dramatic declines in grassland biodiversity, and in Europe this decline has not yet been halted. Therefore, a major challenge in ecological restoration is to effectively restore plant diversity in permanent grasslands, that is, long‐term managed grassland not being used as cropland. As species richness is often limited by seed dispersal, introducing locally absent species is crucial. Seeding diverse seed mixtures is an appropriate tool, but restoration outcomes are highly variable. Considering constraints by land‐use intensity and plant functional traits during restoration could improve the efficacy of restoration efforts.

We established a full‐factorial experiment with high‐diversity seeding and topsoil disturbance in 73 grasslands along land‐use intensity and productivity gradients and evaluated the restoration success over 5 years. In addition, after 5 years we assessed the number of established species and tested whether specific traits promoted the establishment of sown species in interaction with productivity.

Plant diversity increased considerably when seeding and disturbance were combined while seeding alone only slightly increased species richness. Along land‐use gradients, we found no direct effects of grazing or mowing on the establishment of sown species, but fertilization indirectly limited establishment in the combined treatment via a negative effect of productivity.

Functional traits structured the establishment of sown species, especially in the combined treatments, but effects varied with productivity. Species with low seed mass and low specific leaf area had greater establishment success in low‐productivity grasslands, whereas species with high seed mass had greater establishment in high‐productivity grasslands.

Synthesis and applications. Our results highlight the potential of using diverse seed mixtures for biodiversity restoration in a wide range of permanent grasslands, especially when combined with topsoil disturbance. However, productivity both limited restoration success and affected establishment via an interaction with plant functional traits. As productivity is a major constraint in grassland restoration, we strongly recommend to first stop fertilization and reduce soil nutrient loads in highly productive grasslands. Restoration by seeding, with or without disturbance, should only be applied when productivity is reduced and the local environment should be considered to compile site‐specific seed mixtures to maximize restoration success.

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Convicted drinking and driving offenders: Comparing alcohol use before and after the pandemic outbreak
Authors: Manning Amy R. , Romano Eduardo , Diebold Josal , Nochajski Thomas H. , Taylor Eileen , Voas Robert B. , Scherer Michael 
Published: April 2021

AbstractBackgroundBefore the COVID‐19 pandemic, very little was known about the impact of social isolation on individuals’ alcohol use and misuse. This study examines how socially isolated individuals with a history of heavy drinking used alcohol during the pandemic.MethodsData for this study came from an add‐on to the Managing Heavy Drinking (MHD) longitudinal study of drivers convicted of DWI that was conducted in Erie County, New York. Pre‐COVID information (October 2019–March 2020) was augmented with a COVID‐19 questionnaire collected between July and August 2020. A total of 92 participants completed the COVID‐19 survey.ResultsThe sample of problem drinkers showed a significant increase after the pandemic outbreak in the average number of drinking days from 1.99 to 2.49 per week (p = 0.047), but a significant decrease in the average number of drinks per drinking day, from 3.74 to 2.74 (p = 0.003). The proportion of individuals who drank more frequently was greater among those who, before the outbreak had an Alcohol Use Disorders Identification Test (AUDIT) score <8 (26% increase) compared with those with an AUDIT score of >8 (13%). Alcohol treatment was also associated with the frequency of drinking, with individuals who were not in alcohol treatment showing a 16% increase in frequency compared with a 10% increase among those in treatment. Further, individuals who, after the outbreak worried about their health (30%) or finances (37%) reported greater increases in the frequency of drinking than those who did not worry about their health (17%) or finances (10%).ConclusionsOverall, the individuals in our sample showed small changes in the frequency andheaviness of drinking after the outbreak of COVID‐19, effects that opposite in direction from one another and thus resulted in no overall change in drinks consumed. Nonetheless, we identified factors that influenced the effects of the pandemic on drinking behavior among individuals convicted of DWI, which emphasizes the need to individualize these individuals’ treatment, particularly in the context of dramatic environmental change.
Is hepatectomy an appropriate option for bilobar liver metastasis with portal vein tumor thrombus of colorectal cancer?
Authors: Paik Kwang Yeol 
Published: April 2021

AbstractThe prognosis of patients with multiple liver metastasis of colorectal cancer (CLM) on both lobes accompanied by a portal vein tumor thrombus (PVTT) remains unclear. We report two patients with multiple CLM and PVTT who underwent liver resection. A 73‐year‐old man had successful extended right hemi‐hepatectomy with a thrombectomy for a macroscopic tumor thrombus in the right portal branch and multiple CLM in both lobes. At 8 months after surgery, the patient had multiple CLM in the remnant lobe with left main PVTT and died 14 months after liver surgery. A 64‐year‐old woman who had previously undergone palliative chemotherapy for adenocarcinoma of the ascending colon presented with CLM accompanied by a macroscopic tumor thrombus in the left portal branch. Tumor and PVTT had progressed despite various regimens of chemotherapy. Left hemi‐hepatectomy with radiofrequency ablation on right lobe and right hemicolectomy were performed. However, CLM occurred again within 3 months after the liver surgery. Considering these cases, a poor prognosis may be expected even though the tumor is successfully removed by liver resection.
Suitability of endobronchial ultrasound‐guided transbronchial needle aspiration samples for programmed death ligand‐1 testing in non‐small cell lung cancer, the Bristol experience
Authors: Hardy Joanna , Bhatt Nidhi , Medford Andrew R.L. 
Published: April 2021

AbstractTreatment for non‐small cell lung cancer (NSCLC) is now personalised using molecular mutation testing. Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) biopsy suitability for anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) mutation testing is established. Less is currently known about EBUS‐TBNA suitability for PD‐L1 (programmed death ligand‐1) testing.To assess EBUS‐TBNA biopsy adequacy for ALK, EGFR and PD‐L1 testing, we conducted a prospective study of 279 consecutive NSCLC patients referred to a tertiary EBUS‐TBNA centre in South West England. One hundred eight‐four (62.6%) patients were found to have adenocarcinoma, 83 (28.2%) had squamous cell carcinoma, and 27 (9.2%) were identified as NSCLC‐not otherwise specified. EGFR testing was successful in 166 of 168 patients (98.8%), ALK testing in all 115 and PD‐L1 testing in 43 of 49 patients (88.2%).Previous EGFR and ALK testing did not affect biopsy PD‐L1 testing success. PD‐L1 testing failures occurred in three of five (60.0%) of 22G needle biopsies, one of five (20.0%) of 21G needle biopsies and two of 39 (5.1%) of 19G needle biopsies, P = .016.EBUS‐TBNA biopsies are mostly suitable for PD‐L1 testing. Larger needle size may improve PD‐L1 (but not EGFR and ALK) testing success but requires further study in a controlled trial.
Price Limit Expansion and Volatility: A Theoretical Perspective*
Authors: Lee Jeong Hwan , Su Xin , Yoo Jin 
Published: April 2021

AbstractWe theoretically examine whether and how price limit expansion changes return volatility. This study incorporates competing hypotheses regarding investor reactions to limit‐hit events into a model that considers trader irrationality; we then conduct several simulations. We find that, when price limits are widened, stock return volatility tends to increase but may also remain unchanged or decrease. We consider the implications of the study’s main findings, which shed light on the mixed empirical results found in the price limit literature so far.