bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reinstatement of cortical outcome representations during higher-order learning
Authors: Luettgau Lennart , Porcu Emanuele , Tempelmann Claus , Jocham Gerhard 
Published: June 2020

AbstractNaturalistic learning scenarios are characterized by infrequent experience of external feedback to guide behavior. Higher-order learning mechanisms like second-order conditioning (SOC) may allow stimuli that were never experienced together with reinforcement to acquire motivational value. Despite its explanatory potential for real-world learning, surprisingly little is known about the neural mechanism underlying such associative transfer of value in SOC. Here, we used multivariate cross-session, cross-modality searchlight classification on functional magnetic resonance imaging data obtained from humans during SOC. We show that visual first-order conditioned stimuli (CS) reinstate cortical patterns representing previously paired gustatory outcomes in the lateral orbitofrontal cortex (OFC). During SOC, this OFC region showed increased functional covariation with amygdala, where neural pattern similarity between second-order CS and outcomes increased from early to late stages of SOC. Our data suggest a mechanism by which motivational value is conferred to stimuli that were never paired with reinforcement.
Viral Dynamics Matter in COVID-19 Pneumonia: the success of early treatment with hydroxychloroquine and azithromycin in Lebanon
Authors: Chamieh Amanda , Afif Claude , El-Hajj Gerard , Zmerli Omar , Djaffar-Jureidini Isabelle , Raad Roy A. , Ashou Raja , Juvelekian Georges , Rolain Jean-Marc , Azar Eid 
Published: June 2020

1.Abstract1.1.Background/PurposeWe share our experience in COVID-19 pneumonia management at Saint George Hospital University Medical Center (SGHUMC) in Lebanon. In the absence of a standard of care, early diagnosis and opt-in therapy with Hydroxychloroquine and Azithromycin were offered.1.2.MethodsWe reviewed records of COVID-19 pneumonia patients from March 16-April 26 2020. Based on NEWS score, we stratified patients as A: low B: medium, and C: high clinical severity and obtained pharmacotherapy data. Chest-CT-severity-score (CTSS) was used. We defined clinical cure as resolution of symptoms and biomarkers and virologic cure as a PCR above 35 cycles(Ct).1.3.ResultsWe recorded 21 COVID-19 pneumonia patients of whom 19 opted for treatment. Clinical symptoms and laboratory markers at presentation did not significantly correlate with severity. Lower initial viral load significantly correlated with lower levels of clinical and radiological severity (p=0.038). Virologic cure, Ct>35, by day 10, was only 33% in high severity significantly less than categories A and B. We observed 100% clinical cure at day 10 in Category-A, 67% in B, and 33% in C(p<0.05). Patients with the lowest severity had the fastest virologic cure in a mean of 5.8 days from diagnosis, shortest hospitalization and earlier radiological improvement(p<0.005). Ultimately, 18 patients were discharged home in good condition and one remains in the ICU.1.4.ConclusionViral dynamics matter in COVID-19 pneumonia. An early control of replication may be crucial in averting complications. Early administration of Hydroxychloroquine and Azithromycin potentially explains our 94.7% success rate in treating a fairly complex cohort of COVID-19 pneumonia.
Early CPAP reduced mortality in covid-19 patients. Audit results from Wrightington, Wigan and Leigh Teaching Hospitals NHS Foundation Trust
Authors: Ashish Abdul , Unsworth Alison , Martindale Jane , Sedda Luigi , Sundar Ramachandran , Farrier Martin 
Published: June 2020

AbstractCOVID-19 infection typically causes pneumonia with bilateral changes on Chest radiograph. There is significant hypoxia and use of oxygen for patients admitted to hospital is standard. The use of Continuous Positive Airway Pressure (CPAP) in patients with COVID-19 has now become established as a common clinical practice based on recent experience. It is given as part of “best endeavours” treatment in the absence of sufficient evidence to guide best practice. The use of CPAP as a step up in clinical care is now common but has a poor evidence base.Using routinely collected data, the use of CPAP as a supportive non-invasive ventilatory treatment is described in 35 patients with COVID infection. Patients given early CPAP and in particular within 48 hours of admission, are shown to have a better outcome (a significant probability of lower mortality) than patients who received late CPAP (more than 48 hours after admission).Although the analysis is affected by a small sample size, the results have shown good evidence that supports the early use of CPAP in patients with COVID-19 infection.
Dynamic regulation of translation quality control associated with ribosome stalling
Authors: Goldman Daniel H. , Livingston Nathan M. , Movsik Jonathan , Wu Bin , Green Rachel 
Published: June 2020

AbstractTranslation of problematic mRNA sequences induces ribosome stalling. Collided ribosomes at the stall site are recognized by cellular quality control machinery, resulting in dissociation of the ribosome from the mRNA and subsequent degradation of the nascent polypeptide and in some organisms, decay of the mRNA. However, the timing and regulation of these processes are unclear. We developed a SunTag-based reporter to monitor translation in real time on single mRNAs harboring difficult-to-translate poly(A) stretches. This reporter recapitulates previous findings in human cells that an internal poly(A) stretch reduces protein output ∼10-fold, while mRNA levels are relatively unaffected. Long-term imaging of translation indicates that poly(A)-containing mRNAs are robustly translated in the absence of detectable mRNA cleavage. However, quantification of ribosome density reveals a ∼3-fold increase in the number of ribosomes on poly(A)-containing mRNAs compared to a control mRNA, consistent with queues of many stalled ribosomes. Using single-molecule harringtonine runoff experiments, we observe the resolution of these queues in real-time by the cellular quality control machinery, and find that rescue is very slow compared to both elongation and termination. We propose that the very slow clearance of stalled ribosomes provides the basis for the cell to distinguish between transient and deleterious stalls, and that the human quality control apparatus predominantly targets the nascent protein rather than the mRNA.
Synergistic effects of anionic surfactants on coronavirus (SARS-CoV-2) virucidal efficiency of sanitizing fluids to fight COVID-19
Authors: Jahromi Reza , Mogharab Vahid , Jahromi Hossein , Avazpour Arezoo 
Published: June 2020

AbstractOur surrounding environment, especially often-touched contaminated surfaces, plays an important role in the transmission of pathogens in society. The shortage of effective sanitizing fluids, however, became a global challenge quickly after the coronavirus disease-19 (COVID-19) outbreak in December 2019. In this study, we present the effect of surfactants on coronavirus (SARS-CoV-2) virucidal efficiency in sanitizing fluids. Sodium dodecylbenzenesulfonate (SDBS), sodium laureth sulfate (SLS), and two commercial dish soap and liquid hand soap were studied with the goal of evaporation rate reduction in sanitizing liquids to maximize surface contact time. Twelve fluids with different recipes composed of ethanol, isopropanol, SDBS, SLS, glycerin, and water of standardized hardness (WSH) were tested for their evaporation time and virucidal efficiency. Evaporation time increased by 17-63% when surfactant agents were added to the liquid. In addition, surfactant incorporation enhanced the virucidal efficiency between 15-27% according to the 4-field test in the EN 16615:2015 European Standard method. Most importantly, however, we found that surfactant addition provides a synergistic effect with alcohols to inactivate the SARS-CoV-2 virus. This study provides a simple, yet effective solution to improve the virucidal efficiency of commonly used sanitizers.
Endotoxemia and circulating bacteriome in severe COVID-19 patients
Authors: Sirivongrangson Phatadon , Kulvichit Win , Payungporn Sunchai , Pisitkun Trairak , Chindamporn Ariya , Peerapornratana Sadudee , Pisitkun Prapaporn , Chitcharoen Suwalak , Sawaswong Vorthon , Worasilchai Navaporn , Kampunya Sarinya , Putcharoen Opass , Thawitsri Thammasak , Leelayuwatanakul Nophol , Kongpolprom Napplika , Phoophiboon Vorakamol , Sriprasart Thitiwat , Samransamruajkit Rujipat , Tungsanga Somkanya , Tiankanon Kanitha , Lumlertgul Nuttha , Leelahavanichkul Asada , Sriphojanart Tueboon , Tantawichien Terapong , Thisyakorn Usa , Chirathaworn Chintana , Praditpornsilpa Kearkiat , Tungsanga Kriang , Eiam-Ong Somchai , Sitprija Visith , Kellum John A. , Srisawat Nattachai 
Published: June 2020

AbstractPurposeWhen severe, COVID-19 shares many clinical features with bacterial sepsis. Yet, secondary bacterial infection is uncommon. However, as epithelium are injured and barrier function is lost, bacterial products entering the circulation might contribute to the pathophysiology of COVID-19.MethodsWe studied 19 adults, severely ill patients with COVID-19 infection, who were admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 13th March and 17th April 2020. Blood samples on day 1, 3, and 7 of enrollment were analyzed for endotoxin activity assay (EAA), (1→3)-β-D-Glucan (BG), and 16S rRNA gene sequencing to determine the circulating bacteriome.ResultsOf the 19 patients, 14 were in intensive care and 10 patients received mechanical ventilation. We found 8 patients with high EAA (≥ 0.6) and about half of the patients had high serum BG levels which tended to be higher in later in the illness. Although only 1 patient had a positive blood culture, 18 of 19 patients were positive for 16S rRNA gene amplification. Proteobacteria was the most abundant phylum. The diversity of bacterial genera was decreased overtime.ConclusionsBacterial DNA and toxins were discovered in virtual all severely ill COVID-19 pneumonia patients. This raises a previously unrecognized concern for significant contribution of bacterial products in the pathogenesis of this disease
Efficacy and Safety of Leflunomide for Refractory COVID-19: An Open-label Controlled Study
Authors: Wang Qiang , Guo Haipeng , Li Yu , Jian Xiangdong , Hou Xinguo , Zhong Ning , Fei Jianchun , Su Dezhen , Bian Zhouyan , Zhang Yi , Hu Yingying , Sun Yan , Yu Xueyuan , Li Yuan , Jiang Bei , Li Yan , Qin Fengping , Wu Yingying , Gao Yanxia , Hu Zhao 
Published: June 2020

ABSTRACTOBJECTIVETo evaluate the safety and efficacy of leflunomide for the treatment of refractory COVID-19 in adult patients.DESIGNOpen-label controlled studySETTINGA designated hospital for patients with refractory COVID-19 in Wuhan, China.PARTICIPANTS27 hospitalized adult patients (≥18 years of age) with radiologically confirmed pneumonia and SARS-CoV-2 positive for more than 28 days despite standard care were assigned to receive standard of care (SOC, grp I) or leflunomide + SOC (grp 2). After 2 weeks, grp 1 and grp 2 patients who continued to be SARS-CoV-2-positive received leflunomide for 14 days while continuing SOC.MAIN OUTCOME MEASURESThe primary outcomes were the rate of and time to SARS-CoV-2 clearance and the 14-day and 30-day hospital discharge rate.RESULTSTwelve patients enrolled in grp 1 and 15 patients were in grp 2. The 14 days SARS-CoV-2 viral clearance rate was 80.0% (12/15) for grp 2 patients receiving leflunomide versus 16.7% for grp 1 patients (2/12) (P=0.002). By day 14, the median time to SARS-CoV-2 clearance was 6.0 days (range 1-12, IQR 1-12) for grp 2 patients. In grp 1, two patients converted to viral negative on days 1 and 6 (P=0.002). The 14-day discharge rate was 73.3% (11/15) for the grp 2 versus 8.3% (1/12) for grp 1 (P=0.001). The 30-day discharge rate was 100% (15/15) for the grp 2 versus 66.7% (8/12) for grp 1. No severe adverse events or deaths were reported.CONCLUSIONLeflunomide is effective in enhancing SARS-CoV-2 clearance and hospital discharge in refractory COVID-19 patients. The addition of leflunomide to SOC did not increase adverse events versus SOC. These preliminary observations underscore a need for a randomized clinical study of leflunomide in SARS-CoV-2 infection.WHAT IS ALREADY KNOWN ON THIS TOPICBased on the large numbers of global infected patients of SARS-CoV-2, there will be many patients on persist viral positive which is named refractory covid-19. Specific medication for the treatment of the refractory covid-19 has been approved.Leflunomide has been widely used in rheumatoid arthritis and psoriatic arthritis with good safety and tolerance. Recently, it is found an activity of anti-SARS-CoV-2 in vitro and the effective concentration of leflunomide is within the recognized therapeutic level for rheumatoid arthritis.WHAT THIS STUDY ADDSLeflunomide is effective in enhancing SARS-CoV-2 clearance and hospital discharge in refractory COVID-19 patients. The safety and tolerability of the 14-28-day course of treatment with leflunomide is acceptable.
The COVID-19 Critical Care Consortium observational study: Design and rationale of a prospective, international, multicenter, observational study
Authors: Li Bassi Gianluigi , Suen Jacky Y. , Barnett Adrian G. , Corley Amanda , Millar Jonathan E. , Fanning Jonathon P. , Lye India , Colombo Sebastiano , Wildi Karin , Livingstone Samantha , Abbate Gabriella , Hinton Samuel , Liquet Benoit , Shrapnel Sally , Dalton Heidi J. , Fraser John F. 
Published: June 2020

ABSTRACTImportanceThere is a paucity of data that can be used to guide the management of critically ill patients with coronavirus disease 2019 (COVID-19). Global collaboration offers the best chance of obtaining these data, at scale and in time. In the absence of effective therapies, insights derived from real-time observational data will be a crucial means of improving outcomes.ObjectiveIn response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, a research and data-sharing collaborative has been assembled to harness the cumulative experience of intensive care units (ICUs) worldwide. The resulting observational study provides a platform to rapidly disseminate detailed data and insights.DesignThe COVID-19 Critical Care Consortium observational study is an international, multicenter, prospective, observational study of patients with confirmed or suspected SARSCoV-2 infection admitted to ICUs.SettingThis is an evolving, open-ended study that commenced on January 1st, 2020 and currently includes more than 350 sites in over 48 countries. The study enrolls patients at the time of ICU admission and follows them to the time of death, hospital discharge, or 28 days post-ICU admission, whichever occurs last.ParticipantsAll subjects, without age limit, requiring admission to an ICU for SARS-CoV-2 infection, confirmed by real-time polymerase chain reaction (PCR) and/or next-generation sequencing or with high clinical suspicion of the infection. Patients admitted to an ICU for any other reason are excluded.Main outcomes and measuresKey data, collected via an electronic case report form devised in collaboration with the ISARIC/SPRINT-SARI networks, include: patient demographic data and risk factors, clinical features, severity of illness and respiratory failure, need for non-invasive and/or mechanical ventilation and/or extracorporeal membrane COVID–19 CCC observational study protocol oxygenation (ECMO), and associated complications, as well as data on adjunctive therapies. Final outcomes of in-hospital death, discharge or continuing admissions at 28 days.DiscussionThis large-scale, observational study of COVID-19 in the critically ill will provide rapid international characterization. Open-ended accrual will increase the power to answer hypothesis-led questions over time. Several sub-studies have already been initiated, examining hemostasis, neurological, cardiac, and long-term outcomes.
Is India heading towards a new high? : An optimistic approach to estimate ending life-cycle and cumulative cases by the end of the major COVID-19 pandemic wave in India and some of its states
Authors: Gupta P. , Sharma K. K. , Joshi S.D. , Goyal S. 
Published: June 2020

AbstractProjecting the COVID-19 curve parameters such as ending-lifecycle and cumulative cases are helpful in guiding the policy makers to mitigate the outbreak. However, overestimating these parameters may put the public and policy makers in a muddle. In this paper, an optimistic scenario is simulated, wherein the dynamics of the COVID-19 curve is allowed to spread to such an extent that the projections of the COVID-19 parameters do not take excessively high values. Based on this scenario, the ending life-cycle and cumulative cases for India and some of its states, are predicted. Our study, suggests that the fall of the peak amplitude (95%) of the major COVID-19 wave in India may take place by the 8th of September 2020 with a total count of 655000 cases. Simulation results, also indicate that Maharashtra, Tamil Nadu, Delhi, Gujarat, Uttar Pradesh, Bihar, Madhya Pradesh, and Rajasthan may end up with 263700, 18140, 50600, 21130, 24420, 44170, 27080, and 28200 cumulative cases respectively.
Large-scale color biases in the retinotopic functional architecture are region specific and shared across human brains
Authors: Bannert Michael M. , Bartels Andreas 
Published: June 2020

AbstractDespite the functional specialization in visual cortex, there is growing evidence that the processing of chromatic and spatial visual features is intertwined. While past studies focused on visual field biases in retina and behaviour, large-scale dependencies between coding of color and retinotopic space are largely unexplored in the cortex. Here we asked whether spatial color biases are shared across different human observers, and whether they are idiosyncratic for distinct areas. We tested this by predicting the color a person was seeing using a linear classifier that has never been trained on chromatic responses from that same brain, solely by taking into account: (1) the chromatic responses in other individuals’ brains and (2) commonalities between the spatial coding in brains used for training and the test brain. We were able to predict the color (and luminance) of stimuli seen by an observer based on other subjects’ activity patterns in areas V1-V3, hV4 and LO1. In addition, we found that different colors elicited systematic, large-scale retinotopic biases that were idiosyncratic for distinct areas and common across brains. The area-specific spatial color codes and their conservation across individuals suggest functional or evolutionary organization pressures that remain to be elucidated.Significance statementDoes a color elicit comparable neural activity in two different observers? We addressed these questions, which involved the central test to predict what color someone is seeing based on their brain activity if it is only known how other brains respond to color. We estimated the commonalities across brains in the way they respond to achromatic, spatial stimulation, which allowed us to retinotopically align different brain responses to each other in a common response space. In this space derived without any color responses we could decode across brains what color an observer was seeing and found that spatial color biases differed between areas. Our results demonstrate systematic dependencies between chromatic and visual field representations that are area-specific and preserved across observers.
Patient ancestry significantly contributes to molecular heterogeneity of systemic lupus erythematosus
Authors: Catalina Michelle D. , Bachali Prathyusha , Yeo Anthony E. , Geraci Nicholas S. , Petri Michelle A. , Grammer Amrie C. , Lipsky Peter E. 
Published: June 2020

AbstractGene expression signatures can stratify patients with heterogeneous diseases, such as Systemic Lupus Erythematosus (SLE), yet understanding the contributions of ancestral background to this heterogeneity is not well elucidated. We hypothesized that ancestry would significantly influence gene expression signatures and measured 34 gene modules in 1566 SLE patients of african (AA), european (EA) or native american (NAA) ancestry to determine the impact of ancestry on gene expression. Healthy subject ancestry-specific gene expression provided the transcriptomic background upon which the SLE patient signatures were built. Although standard therapy affected every gene signature, and significantly increased myeloid cell signatures, logistic regression analysis determined that ancestral background significantly changed 23/34 gene signatures. Additionally, the strongest association to gene expression changes was autoantibodies and this also had etiology in ancestry; the AA predisposition to have both RNP and dsDNA autoantibodies compared to EA predisposition to have only antidsDNA. A machine learning approach was used to determine a gene signature characteristic to distinguish AA SLE and was most influenced by genes characteristic of the perturbed B cell axis in AA SLE patients.
Summer vacation and COVID-19: effects of metropolitan people going to summer provinces
Authors: Britton Tom , Ball Frank 
Published: June 2020

AbstractMany countries are now investigating what the effects of summer vacation might be on the COVID-19 pandemic. Here one particular such question is addressed: what will happen if large numbers of metropolitan people visit a less populated province during the summer vacation? By means of a simple epidemic model, allowing for both short and long-term visitors to the province, it is studied which features are most influential in determining if such summer movements will result in large number of infections among the province population. The method is applied to the island of Gotland off the South East coast of Sweden. It is shown that the amount of mixing between the metropolitan and province groups and the fraction of metropolitan people being infectious upon arrival are most influential. Consequently, minimizing events gathering both the province and metropolitan groups and/or reducing the number of short-term visitors could substantially decrease spreading, as could measures to lower the fraction initially infectious upon arrival.
Tension promotes kinetochore-microtubule release in response to Aurora B activity
Authors: Chen Geng-Yuan , Renda Fioranna , Zhang Huaiying , Gokden Alper , Wu Daniel Z. , Chenoweth David M. , Khodjakov Alexey , Lampson Michael A. 
Published: June 2020

AbstractAurora B kinase regulates kinetochore-microtubule interactions to ensure accurate chromosome segregation in cell division. Tension provides a signal to discriminate attachment errors from bi-oriented kinetochores with sisters correctly attached to opposite spindle poles. Current models focus on tension as an input to locally regulate Aurora B activity. Here we show that the outcome of Aurora B activity depends on tension. Using an optogenetic approach to manipulate Aurora B at individual kinetochores, we find that kinase activity promotes microtubule release when tension is high. Conversely, when tension is low, Aurora B activity promotes depolymerization of kinetochore-microtubule bundles while maintaining attachment. We propose that tension is a signal inducing distinct error-correction mechanisms, with release or depolymerization advantageous for typical errors characterized by high or low tension, respectively.