bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment with Arbidol and Moxifloxacin in Ordinary and Severe Adult Patients Infected with COVID-19
Authors: Xi Wen-Na , Jin Di , Sun Ke , Yu Rong-Yan , Yao Xue-Bing , Zou Biao-Shu , Song Zhi-Ying , Yang AO-Yu , Luo Rui-Xia , liu Yun , Li Yan-hua , Sun Shui-Lin , Yu Dong-Shan 
Published: June 2020

AbstractBackgroundAn outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread. We aim to investigate the therapeutic effect of arbidol and moxifloxacin in patients infected with SARS-CoV-2.MethodsWe collected and analyzed data on 94 patients with COVID-19 including 27 severe patients at the Intensive Care Unit (ICU) and 74 ordinary patients at general isolation ward in Wuhan Xiehe Hospital, from February 15, 2020 to March 15, 2020. All patients were treated with arbidol (100mg each time, three times a day for 14 days) and moxifloxacin (0.4g each time, once a day for 7-14 days). Other data was also collected including demographic data, symptoms, laboratory findings, treatments and clinical outcomes.ResultsIn basic characteristics, compared with the ordinary patients, the severe patients were older (median age was 63.0 years V.S 57.0 years, p=0.03), had higher proportion of hypertension (30% V.S 9%, p=0.03), higher possibility of getting fatigue and/or myalgia (26% V.S 6%, p=0.03), and had more obvious dyspnea symptom (26% V.S 3%, p=0.006). In regarding to laboratory results, we found the severe patients have higher white blood cell counts (p=0.003), neutrophil counts (p=0.007), higher levels of D-dimer (p<0.001), ALT (p<0.001) and AST (p=0.013) than the ordinary patients. After treatment of arbidol and moxifloxacin for one week, the rates of SARS-CoV-2 nucleic acid turning negative were 69.2% in the severe group and 77.8% in the ordinary group. A peculiar phenomenon was that IL-6 stands out among the cytokines in both groups, and higher in severe group than the ordinary one (p=0.011). After treating with arbidol and moxifloxacin for one week, IL-6 decreased significantly in severe group (p=0.023).ConclusionIn summary, we proved the treatment of arbidol and moxifloxacin could be helpful in reducing viral load and inflammation during SARS-CoV2 infection, especially for negatively regulating fatal inflammation in severe COVID-19 patients. However, more evidence awaits further clinical verification.
Hospitalist perspectives of available tests to monitor volume status in patients with heart failure: a qualitative study
Authors: Maw Anna M , Ortiz-lopez Carolina , Morris Megan A , Jones Christine , Gee Elaine , Tchernodrinski Stephan , Kramer Henry , Galen Benjamin T , Dempsey Amanda F , Soni Nilam 
Published: June 2020

AbstractAcute decompensated heart failure is the leading admitting diagnosis in patients 65 and older with more than 1 million hospitalizations per year in the US alone. Traditional tools to evaluate for and monitor volume status in patients with heart failure, including symptoms and physical exam findings, are known to have limited accuracy. In contrast, point of care lung ultrasound is a practical and evidenced-based tool for monitoring of volume status in patients with heart failure. However, few inpatient clinicians currently use this tool to monitor diuresis. We performed semi-structured interviews of 23 hospitalists practicing in 5 geographically diverse academic institutions in the US to better understand how hospitalists currently assess and monitor volume status in patients hospitalized with heart failure. We also explored their perceptions and attitudes toward adoption of lung ultrasound. Hospitalist participants reported poor reliability and confidence in the accuracy of traditional tools to monitor diuresis and expressed interest in learning or were already using lung ultrasound for this purpose. The time required for training and access to equipment that does not impede workflow were considered important barriers to its adoption by interviewees.
SARS-CoV2 Testing: The Limit of Detection Matters
Authors: Arnaout Ramy , Lee Rose A. , Lee Ghee Rye , Callahan Cody , Yen Christina F. , Smith Kenneth P. , Arora Rohit , Kirby James E. 
Published: June 2020

AbstractResolving the COVID-19 pandemic requires diagnostic testing to determine which individuals are infected and which are not. The current gold standard is to perform RT-PCR on nasopharyngeal samples. Best-in-class assays demonstrate a limit of detection (LoD) of ~100 copies of viral RNA per milliliter of transport media. However, LoDs of currently approved assays vary over 10,000-fold. Assays with higher LoDs will miss more infected patients, resulting in more false negatives. However, the false-negative rate for a given LoD remains unknown. Here we address this question using over 27,500 test results for patients from across our healthcare network tested using the Abbott RealTime SARS-CoV-2 EUA. These results suggest that each 10-fold increase in LoD is expected to increase the false negative rate by 13%, missing an additional one in eight infected patients. The highest LoDs on the market will miss a majority of infected patients, with false negative rates as high as 70%. These results suggest that choice of assay has meaningful clinical and epidemiological consequences. The limit of detection matters.
iSCAN: An RT-LAMP-coupled CRISPR-Cas12 module for rapid, sensitive detection of SARS-CoV-2
Authors: Ali Zahir , Aman Rashid , Mahas Ahmed , Rao Gundra Sivakrishna , Tehseen Muhammad , Marsic Tin , Salunke Rahul , Subudhi Amit K. , Hala Sharif M. , Hamdan Samir M. , Pain Arnab , Hassan Norhan , Mahfouz Magdy M. 
Published: June 2020

AbstractThe COVID-19 pandemic caused by SARS-CoV-2 affects all aspects of human life. Detection platforms that are efficient, rapid, accurate, specific, sensitive, and user friendly are urgently needed to manage and control the spread of SARS-CoV-2. RT-qPCR based methods are the gold standard for SARS-CoV-2 detection. However, these methods require trained personnel, sophisticated infrastructure, and a long turnaround time, thereby limiting their usefulness. Reverse transcription-loop-mediated isothermal amplification (RT-LAMP), a one-step nucleic acid amplification method conducted at a single temperature, has been used for colorimetric virus detection. CRISPR-Cas12 and CRISPR-Cas13 systems, which possess collateral activity against ssDNA and RNA, respectively, have also been harnessed for virus detection. Here, we built an efficient, rapid, specific, sensitive, user-friendly SARS-CoV-2 detection module that combines the robust virus amplification of RT-LAMP with the specific detection ability of SARS-CoV-2 by CRISPR-Cas12. Furthermore, we combined the RT-LAMP-CRISPR-Cas12 module with lateral flow cells to enable highly efficient point-of-care SARS-CoV-2 detection. Our iSCAN SARS-CoV-2 detection module, which exhibits the critical features of a robust molecular diagnostic device, should facilitate the effective management and control of COVID-19.
Adverse events associated with nifurtimox treatment for Chagas disease in children and adults
Authors: Berenstein A.J. , Falk N. , Moscatelli G. , Moroni S. , González N. , Garcia-Bournissen F. , Ballering G. , Freilij H. , Altcheh J. 
Published: June 2020

ABSTRACTBACKGROUNDNifurtimox (NF) is one of the only two drugs currently available for Chagas disease (ChD) treatment. However, there is scarce data on NF safety, and many physicians defer or refuse NF treatment because of concerns about drug tolerance.METHODSProspective cohort study with retrospective data collection of adverse drug reactions (ADRs) associated with NF treatment of ChD. Children received NF doses of 10-15 mg/kg/day for 60-90 days, and adults 8-10 mg/kg/day for 30 days.RESULTS215 children (median age: 2.6yrs, range 0-17) and 105 adults (median age: 34yrs, range 18-57) were enrolled. Overall, 127/320 (39.7%) patients developed ADRs, with an incidence of 64/105 in adults, and 63/215 in children (OR = 3.7, 95%CI [2.2;6.3]). We observed 215 ADRs, 131 in adults (median: 2 events/patient (IQR25-75= 1-3) and 84 in children (median: 1 event/patient (IQR25-75= 1-1.5) (Wilcoxon-Test, PAdjusted < 8.10-5). ADRs were mainly mild and moderate. Severe ADRs were infrequent (1.2% in children and 0.9% in adults). Nutritional, central nervous and digestive systems were the most frequently affected, without differences between both groups.Treatment was discontinued in 31/320 (9.7%) patients without differences between groups. However, ADR-related discontinuations occurred more frequently in adults than in children (OR = 5.5, 95%CI = [1.5;24]).CONCLUSIONSOur study supports the safety of NF for ChD treatment. Delaying NF treatment due to safety concerns does not seem to be supported by the evidence.
A Model for the Testing and Tracing Needed to Suppress COVID-19
Authors: Wang Victor 
Published: June 2020

AbstractThis paper presents the first analytical model for calculating how many tests and tracing needed to suppress COVID-19 transmission. The number of people needs to be tested daily is given by:

WhereN is the size of the population in considerationAr is the attack rate at any given timeTp is the test-positive rateρ is the percentage of infectious people that have to be detected per day. To make the effective reproduction number Re below 1, ρ must satisfy the following equation:
WhereR0 is the basic reproduction number,S/N is the percentage of the susceptible population over the entire population,D is the length of the infectious period, andη is the percentage of close contacts that have to be traced.This model provides insights and guidance to deploy the testing and tracing resources optimally. An Excel model is attached to facilitate easy calculation of the number of tests and tracing needed. This model is also applicable to any infectious disease that can be suppressed by testing and tracing.
Estimating excess visual loss in people with neovascular age-related macular degeneration during the COVID-19 pandemic
Authors: Thomas Darren S. , Warwick Alasdair N , Olvera-Barrios Abraham , Egan Catherine , Schwartz Roy , Patra Sudeshna , Eleftheriadis Haralabos , Khawaja Anthony P. , Lotery Andrew , Müeller Philipp L. , Hamilton Robin , Preston Ella , Taylor Paul , Tufail Adnan ,   UK EMR Users Group
Published: June 2020

ABSTRACTObjectivesTo report the reduction in new neovascular age-related macular degeneration (nAMD) referrals during the COVID-19 pandemic and estimate the impact of delayed treatment on visual outcomes at one year.DesignRetrospective clinical audit and simulation model.SettingMultiple UK NHS ophthalmology centres.ParticipantsData on the reduction in new nAMD referrals was obtained from four NHS Trusts in England comparing April 2020 to April 2019. To estimate the potential impact on one-year visual outcomes, a stratified bootstrap simulation model was developed drawing on an electronic medical records dataset of 20,825 nAMD eyes from 27 NHS Trusts.Main outcome measuresSimulated mean visual acuity and proportions of eyes with vision ≤6/60, ≤6/24 and ≥6/12 at one year under four hypothetical scenarios: no treatment delay, 3, 6 and 9-month treatment delays. Estimated additional number of eyes with vision ≤6/60 at one year nationally.ResultsThe number of nAMD referrals at four major eye treatment hospital groups based in England dropped on average by 72% (range 65 to 87%) in April 2020 compared to April 2019. Simulated one-year visual outcomes for 1000 nAMD eyes with a 3-month treatment delay suggested an increase in the proportion of eyes with vision ≤6/60 from 15.5% (13.2 to 17.9) to 23.3% (20.7 to25.9), and a decrease in the proportion of eyes with vision ≥6/12 (driving vision) from 35.1% (32.1 to 38.1) to 26.4% (23.8 to29.2). Outcomes worsened incrementally with longer modelled delays. Assuming nAMD referrals are reduced to this level at the national level for only one month, these simulated results suggest an additional 186-365 eyes with vision ≤6/60 at one-year with even a short treatment delay.ConclusionsWe report a large decrease in nAMD referrals during the first month of COVID-19 lockdown and provide an important public health message regarding the risk of delayed treatment. As a conservative estimate, a treatment delay of 3 months could lead to a >50% relative increase in the number of eyes with vision ≤6/60 and 25% relative decrease in the number of eyes with driving vision at one year.
VipariNama: RNA vectors to rapidly reprogram plant morphology and metabolism
Authors: Khakhar Arjun , Wang Cecily , Swanson Ryan , Stokke Sydney , Rizvi Furva , Sarup Surbhi , Hobbs John , Voytas Daniel F. 
Published: June 2020

AbstractSynthetic transcription factors have great promise as tools to explore biological processes. By allowing precise alterations in gene expression, they can help elucidate relationships between gene expression and plant morphology or metabolism. However, the years-long timescales, high cost, and technical skill associated with plant transformation have dramatically slowed their use. In this work, we developed a new platform technology called VipariNama (ViN) in which RNA vectors are used to rapidly deploy synthetic transcription factors and reprogram gene expressionin planta. We demonstrate how ViN vectors can direct activation or repression of multiple genes, systemically and persistently over several weeks, and in multiple plant species. We also show how this transcriptional reprogramming can create predictable changes to metabolic and morphological phenotypes in the model plantsNicotiana benthamianaandArabidopsis thalianain a matter of weeks. Finally, we show how a model of gibberellin signaling can guide ViN vector-based reprogramming to rapidly engineer plant size in both model species as well as the cropSolanum lycopersicum(tomato). In summary, using VipariNama accelerates the timeline for generating phenotypes from over a year to just a few weeks, providing an attractive alternative to transgenesis for synthetic transcription factor-enabled hypothesis testing and crop engineering.
In silico saturation mutagenesis of cancer genes
Authors: Muiños Ferran , Martinez-Jimenez Francisco , Pich Oriol , Gonzalez-Perez Abel , Lopez-Bigas Nuria 
Published: June 2020

SummaryExtensive bioinformatics analysis of datasets of tumor somatic mutations data have revealed the presence of some 500-600 cancer driver genes. The identification of all potential driver mutations affecting cancer genes is essential to implement precision cancer medicine and to understand the interplay of mutation probability and selection in tumor development. Here, we present an in silico saturation mutagenesis approach to identify all driver mutations in 568 cancer genes across 66 tumor types. For most cancer genes the mutation probability across tissues --underpinned by active mutational processes-- influences which driver variants have been observed, although this differs significantly between tumor suppressor and oncogenes. The role of selection is apparent in some of the latter, the observed and unobserved driver mutations of which are equally likely to occur. The number of potential driver mutations in a cancer gene roughly determines how many mutations are available for detection across newly sequenced tumors.
Group II metabotropic glutamate receptors modulate sound evoked and spontaneous activity in the mouse inferior colliculus
Authors: Kristaponyte Inga , Beebe Nichole L. , Young Jesse W. , Shanbhag Sharad J. , Schofield Brett R. , Galazyuk Alexander V. 
Published: June 2020

AbstractLittle is known about the functions of group II metabotropic glutamate receptors (mGluRs2/3) in the inferior colliculus (IC)—a midbrain structure that is a major integration region of the central auditory system. We investigated how these receptors modulate sound-evoked and spontaneous firing in the mouse ICin vivo. We first performed immunostaining and tested hearing thresholds to validate VGAT-ChR2 transgenic mice on a mixed CBA/CaJ x C57BL/6J genetic background. Transgenic animals allowed for optogenetic cell type identification. Extracellular single neuron recordings were obtained before and after pharmacological mGluR2/3 activation. We observed increased sound-evoked firing—as assessed by the rate-level functions—in a subset of both GABAergic and non-GABAergic IC neurons following mGluR2/3 pharmacological activation. These neurons also displayed elevated spontaneous excitability and were distributed throughout the IC area tested, suggesting a widespread mGluR2/3 distribution in the mouse IC.
Multi-Omic Analysis Reveals Disruption of Cholesterol Homeostasis by Cannabidiol in Human Cell Lines
Authors: Guard Steven E. , Chapnick Douglas A. , Poss Zachary C. , Ebmeier Christopher C. , Jacobsen Jeremy , Nemkov Travis , Ball Kerri A. , Webb Kristofor J. , Simpson Helen L. , Coleman Stephen , Bunker Eric , Ramirez Adrian , Reisz Julie A. , Sievers Robert , Stowell Michael H.B. , D’Alessandro Angelo , Liu Xuedong , Old William M. 
Published: June 2020

AbstractThe non-psychoactive cannabinoid, cannabidiol (CBD), is FDA-approved for treatment of two drug-resistant epileptic disorders, and is seeing increased use among the general public, yet the mechanisms that underlie its therapeutic effects and side-effect profiles remain unclear. Here, we report a systems-level analysis of CBD action in human cell lines using temporal multi-omic profiling. FRET-based biosensor screening revealed that CBD treatment resulted in a sharp rise in cytosolic calcium, and activation of AMPK and ERK kinases in human keratinocyte and neuroblastoma cell lines. CBD treatment led to alterations in the abundance of metabolites, mRNA transcripts, and proteins consistent with activation of cholesterol biosynthesis, transport and storage. We found that CBD rapidly incorporated into cellular membranes and altered cholesterol chemical activity, suggesting direct perturbation of cholesterol-dependent membrane properties. CBD treatment induced apoptosis in a dose-dependent manner in multiple human cell lines, which was rescued by inhibition of cholesterol synthesis, and potentiated by compounds that disrupt cholesterol trafficking and storage. Our data point to a pharmacological interaction of CBD with cholesterol homeostasis pathways, with potential implications in its therapeutic use.
Spatio-temporal surveys of the brown meagreSciaena umbrausing passive acoustics for management and conservation
Authors: Di Iorio Lucia , Bonhomme Patrick , Michez Noëmie , Ferrari Bruno , Gigou Alexandra , Panzalis Pieraugusto , Desiderà Elena , Navone Augusto , Boissery Pierre , Lossent Julie , Cadville Benjamin , Bravo-Monin Marie , Charbonnel Eric , Gervaise Cédric 
Published: June 2020

AbstractConservation of exploited fish populations is a priority for environmental managers. Spatio-temporal knowledge on reproductive sites is mandatory for species and habitat conservation but is often difficult to assess, particularly over vast geographic areas. Regular and long-term standardized surveys are necessary to identify reproductive sites, assess population trends and their distribution. Here we emphasize the utility of Passive Acoustic Monitoring (PAM) for the survey and management of a depleted vulnerable Mediterranean fish species, the brown meagre,Sciaena umbra. Acoustic surveys of reproductive calls were conducted combining 1) spatial data from standardized surveys within three MPAs and from 49 unprotected sites throughout the Northwestern Mediterranean basin, as well as 2) temporal data from a two-year-long survey at a presumed spawning location. The MPA surveys, which rapidly scanned ~30-50 km of the rocky coastlines per MPA, unveiled maps of distribution and reproductive activity of the brown meagre, including potential spawning sites. They were also effective in emphasizing effects linked to management actions: Full-protection zones had a higher number of vocalizations (70% of the listening sites) compared to less protected zones (30% of the sites) or sites outside MPAs (45% of the sites). This was also reflected in the number of singers that was generally low (< 3 individuals) in less protected zones and outside MPAs, implying lower fish densities. Highest calling aggregations were observed in potential spawning areas that represented only 0.04% of all listening sites, and were almost all in older, fully protected MPAs, which thus play a key role for fish stock recovery. The two-year survey revealed a 5-month reproductive season (from May to October) with a strong positive correlation between calling activity and temperature. Overall this study confirms the role of PAM as an efficient, replicable and standardized non-invasive method for population management that can identify functional sites and key protection zones, provide valuable information on reproduction, spatial and temporal occurrence, but also on population trends and climate-driven changes.HighlightsMonitoring of threatened species and their key habitats is critical for environmental managers.Management requires methods to assess population trends at large spatial and temporal scales.Passive acoustics (PA) is efficient in mapping and monitoring vulnerable fish species.Distribution, reproductive sites and population dynamics can be assessed over vast geographical areas.We show the utility of PA to identify key conservation zones and assess effects of management actions.
Decomposition of reinforcement learning deficits in gambling disorder via drift diffusion modeling and functional magnetic resonance imaging
Authors: Wiehler Antonius , Peters Jan 
Published: June 2020

AbstractGambling disorder is associated with deficits in feedback-based learning tasks, but the computational mechanisms underlying these learning impairments are still poorly understood. Here, we examined this question using a combination of computational modeling and functional resonance imaging (fMRI) in individuals that regular participate in gambling (n=23, seven fulfilled 1-3 DSM 5 criteria, sixteen fulfilled 4 or more) and matched controls (n=23). Participants performed a stationary reinforcement learning task with two pairs of stimuli (80% vs. 20% reinforcement rates per pair). As predicted, the gambling group made significantly fewer selections of the optimal stimulus, while overall response times (RTs) were not significantly different between groups. We then used comprehensive modeling using reinforcement learning drift diffusion models (RLDDMs) in combination with hierarchical Bayesian parameter estimation to shed light on the computational underpinnings of this performance impairment. In both groups, an RLDDM in which both non-decision time and response threshold (boundary separation) changed over the course of the experiment accounted for the data best. The model showed good parameter and model recovery, and posterior predictive checks revealed that in both groups, the model reproduced the evolution of both accuracy and RTs over time. The learning impairment in the gambling group was attributable to a more rapid reduction in boundary separation over time, and a reduced effect of value-differences on the drift rate, compared to controls. The gambling group also exhibted substantially shorter non-decision times. Imaging analyses replicated earlier effects of prediction error coding in the ventral striatum and value coding in the ventro-medial prefrontal cortex, but there was no credible evidence for group differences in these regions. Taken together, our findings highlight the computational mechanisms underlying reinforcement learning impairments in gambling disorder.