bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural Stimulation in vitro and in vivo by Photoacoustic Nanotransducers
Authors: Huang Yimin , Jiang Ying , Luo Xuyi , Wu Jiayingzi , Zong Haonan , Shi Linli , Cheng Ran , Jiang Shan , Jia Xiaoting , Mei Jianguo , Man Heng-Ye , Cheng Ji-Xin , Yang Chen 
Published: May 2020

AbstractNeuromodulation is an invaluable approach for study of neural circuits and clinical treatment of neurological diseases. Here, we report semiconducting polymer nanoparticles based photoacoustic nanotransducers (PANs) for neural stimulation. Our PANs strongly absorb light in the near-infrared second window and generate localized acoustic waves. PANs can also be surface-modified to selectively bind onto neurons. PAN-mediated activation of primary neurons in vitro is achieved with ten 3-nanosecond laser pulses at 1030 nm over a 3 millisecond duration. In vivo neural modulation of mouse brain activities and motor activities is demonstrated by PANs directly injected into brain cortex. With millisecond-scale temporal resolution, sub-millimeter spatial resolution and negligible heat deposition, PAN stimulation is a new non-genetic method for precise control of neuronal activities, opening potentials in non-invasive brain modulation.
The emergence of SARS-CoV-2 in Europe and the US
Authors: Worobey Michael , Pekar Jonathan , Larsen Brendan B. , Nelson Martha I. , Hill Verity , Joy Jeffrey B. , Rambaut Andrew , Suchard Marc A. , Wertheim Joel O. , Lemey Philippe 
Published: May 2020

AbstractAccurate understanding of the global spread of emerging viruses is critically important for public health response and for anticipating and preventing future outbreaks. Here, we elucidate when, where and how the earliest sustained SARS-CoV-2 transmission networks became established in Europe and the United States (US). Our results refute prior findings erroneously linking cases in January 2020 with outbreaks that occurred weeks later. Instead, rapid interventions successfully prevented onward transmission of those early cases in Germany and Washington State. Other, later introductions of the virus from China to both Italy and Washington State founded the earliest sustained European and US transmission networks. Our analyses reveal an extended period of missed opportunity when intensive testing and contact tracing could have prevented SARS-CoV-2 from becoming established in the US and Europe.
SARS-CoV-2 RNA detected in blood samples from patients with COVID-19 is not associated with infectious virus
Authors: Andersson Monique I , Arancibia-Cárcamo Carolina V , Auckland Kathryn , Baillie J Kenneth , Barnes Eleanor , Beneke Tom , Bibi Sagida , Carroll Miles , Crook Derrick , Dingle Kate , Dold Christina , Downs Louise O , Dunn Laura , Eyre David W , Jaramillo Javier Gilbert , Harvala Heli , Hoosdally Sarah , Ijaz Samreen , James Tim , James William , Jeffery Katie , Justice Anita , Klenerman Paul , Knight Julian , Knight Michael , Liu Xu , Lumley Sheila F , Matthews Philippa C , McNaughton Anna L , Mentzer Alexander J , Mongkolsapaya Juthathip , Oakley Sarah , Oliveira Marta S , Peto Timothy , Ploeg Rutger J , Ratcliff Jeremy , Roberts David J , Rudkin Justine , Russell Rebecca A , Screaton Gavin , Semple Malcolm G , Skelly Donal , Simmonds Peter , Stoesser Nicole , Turtle Lance , Wareing Sue , Zambon Maria 
Published: May 2020

ABSTRACTBackgroundLaboratory diagnosis of SARS-CoV-2 infection (the cause of COVID-19) uses PCR to detect viral RNA (vRNA) in respiratory samples. SARS-CoV-2 RNA has also been detected in other sample types, but there is limited understanding of the clinical or laboratory significance of its detection in blood.MethodsWe undertook a systematic literature review to assimilate the evidence for the frequency of vRNA in blood, and to identify associated clinical characteristics. We performed RT-PCR in serum samples from a UK clinical cohort of acute and convalescent COVID-19 cases (n=212), together with convalescent plasma samples collected by NHS Blood and Transplant (NHSBT) (n=111 additional samples). To determine whether PCR-positive blood samples could pose an infection risk, we attempted virus isolation from a subset of RNA-positive samples.ResultsWe identified 28 relevant studies, reporting SARS-CoV-2 RNA in 0-76% of blood samples; pooled estimate 10% (95%CI 5-18%). Among serum samples from our clinical cohort, 27/212 (12.7%) had SARS-CoV-2 RNA detected by RT-PCR. RNA detection occurred in samples up to day 20 post symptom onset, and was associated with more severe disease (multivariable odds ratio 7.5). Across all samples collected ≥28 days post symptom onset, 0/143 (0%, 95%CI 0.0-2.5%) had vRNA detected. Among our PCR-positive samples, cycle threshold (ct) values were high (range 33.5-44.8), suggesting low vRNA copy numbers. PCR-positive sera inoculated into cell culture did not produce any cytopathic effect or yield an increase in detectable SARS-CoV-2 RNA.ConclusionsvRNA was detectable at low viral loads in a minority of serum samples collected in acute infection, but was not associated with infectious SARS-CoV-2 (within the limitations of the assays used). This work helps to inform biosafety precautions for handling blood products from patients with current or previous COVID-19.
Sleep in disorders of consciousness: Behavioral and polysomnographic recording
Authors: Mertel Isabella , Pavlov Yuri G. , Barner Christine , Müller Friedemann , Diekelmann Susanne , Kotchoubey Boris 
Published: May 2020

AbstractBackgroundSleep-wakefulness cycles are an essential diagnostic criterion for Disorders of Consciousness (DOC), differentiating prolonged DOC from coma. Specific sleep features, like the presence of sleep spindles, are an important marker for the prognosis of recovery from DOC. Based on increasing evidence for a link between sleep and neuronal plasticity, understanding sleep in DOC might facilitate the development of novel methods for rehabilitation. Yet, well-controlled studies of sleep in DOC are lacking. Here, we aimed to quantify, on a reliable evaluation basis, the distribution of behavioral and neurophysiological sleep patterns in DOC over a 24h period while controlling for environmental factors (by recruiting a group of conscious tetraplegic patients who resided in the same hospital).MethodsWe evaluated the distribution of sleep and wakefulness by means of polysomnography (EEG, EOG, EMG) and video recordings in 32 DOC patients (16 Unresponsive Wakefulness Syndrome [UWS], 16 Minimally Conscious State [MCS]) and 10 clinical control patients with severe tetraplegia. Three independent raters scored the patients’ polysomnographic recordings.ResultsAll but one patient (UWS) showed behavioral and electrophysiological signs of sleep. Control and MCS patients spent significantly more time in sleep during the night than during daytime, a pattern that was not evident in UWS. DOC patients (particularly UWS) exhibited less REM sleep than control patients. 44% of UWS patients and 12% of MCS patients did not have any REM sleep, while all control patients (100%) showed signs of all sleep stages and sleep spindles. Furthermore, no sleep spindles were found in 62% of UWS patients and 21% of MCS patients. In the remaining DOC patients who had spindles, their number and amplitude were significantly lower than in controls.ConclusionsThe distribution of sleep signs in DOC over 24 hours differs significantly from the normal sleep-wakefulness pattern. These abnormalities of sleep in DOC are independent of external factors such as severe immobility and hospital environment.
Assessment of small pulmonary blood vessels in COVID-19 patients using HRCT
Authors: Lins Muriel , Vandevenne Jan , Thillai Muhunthan , Lavon Ben R. , Lanclus Maarten , Bonte Stijn , Godon Rik , Kendall Irvin , De Backer Jan , De Backer Wilfried 
Published: May 2020

AbstractBackgroundMounting evidence supports the role of pulmonary hemodynamic alternations in the pathogenesis of COVID-19. Previous studies have demonstrated that changes in pulmonary blood volumes measured on CT are associated with histopathological markers of pulmonary vascular pruning, suggesting that quantitative HRCT analysis may eventually be useful in the assessment pulmonary vascular dysfunction more broadly.MethodsBuilding upon previous work, automated HRCT measures of small blood vessel volume and pulmonary vascular density were developed. Scans from 103 COVID-19 patients and 108 healthy volunteers were analyzed and their results compared, with comparisons made both on lobar and global levels.ResultsCompared to healthy volunteers, COVID-19 patients showed significant reduction in BV5 (pulmonary blood volume contained in blood vessels of <5 mm2) expressed as BV5/(Total pulmonary blood volume) (p<0.0001), and significant increases in BV5_10 and BV 10 (pulmonary blood volumes contained in vessels between 5 and 10 mm2 and above 10 mm2, respectively) (p<0.0001). These changes were consistent across lobes.ConclusionsCOVID-19 patients display striking anomalies in the distribution of blood volume within the pulmonary vascular tree, consistent with increased pulmonary vasculature resistance in the pulmonary vessels below the resolution of HRCT.
The lower COVID-19 related mortality and incidence rates in Eastern European countries are associated with delayed start of community circulation
Authors: Ylli Alban , Wu Yan Yan , Burazeri Genc , Pirkle Catherine , Sentell Tetine 
Published: May 2020

AbstractBackgroundThe purpose of this analysis was to assess the variations in COVID-19 related mortality and incidence rates in relation to the time differences in the commencement of virus circulation and containment measures in different countries of the European Region.MethodsThe data for the current analysis (N=50 countries) were retrieved from the John Hopkins University dataset on the 7th of May 2020, with countries as study units. A piecewise regression analysis was conducted with mortality and cumulative incidence rates introduced as dependent variables and time interval (days from the 22nd of January to the date when 100 first cases were reported) as the main predictor. The country average life expectancy at birth was statistically adjusted for in the regression model.ResultsMortality and incidence were strongly and inversely intercorrelated with days from January 22, respectively −0.83 (p<.0001) and −0.73 (p<.0001). Adjusting for average life expectancy, between days 33 to 50 from the 22th of the January, the average mortality rate decreased by 30.4/million per day (95% CI: 23.2, 37.1, p<0.0001). During interval 51 to 73 days, the change in mortality was no longer statistically significant but still showed a decreasing trend. A similar relationship with time interval was found in incidence. Life expectancy was not associated with mortality rate.ConclusionCountries in Europe which observed the earliest COVID-19 circulation, suffered the worst consequences in terms of health outcomes, specifically mortality. The drastic social isolation measures, undertaken especially in Eastern European countries, where community circulation started after March 11th, may have been timely. This may explain their significantly lower COVID-related mortality compared with the Western European countries.
Uncertainty Quantification in Radiogenomics: EGFR Amplification in Glioblastoma
Authors: Hu Leland S. , Wang Lujia , Hawkins-Daarud Andrea , Eschbacher Jennifer M. , Singleton Kyle W. , Jackson Pamela R. , Clark-Swanson Kamala , Sereduk Christopher P. , Peng Sen , Wang Panwen , Wang Junwen , Baxter Leslie C. , Smith Kris A. , Mazza Gina L. , Stokes Ashley M. , Bendok Bernard R. , Zimmerman Richard S. , Krishna Chandan , Porter Alyx B. , Mrugala Maciej M. , Hoxworth Joseph M. , Wu Teresa , Tran Nhan L. , Swanson Kristin R. , Li Jing 
Published: May 2020

ABSTRACTBACKGROUNDRadiogenomics uses machine-learning (ML) to directly connect the morphologic and physiological appearance of tumors on clinical imaging with underlying genomic features. Despite extensive growth in the area of radiogenomics across many cancers, and its potential role in advancing clinical decision making, no published studies have directly addressed uncertainty in these model predictions.METHODSWe developed a radiogenomics ML model to quantify uncertainty using transductive Gaussian Processes (GP) and a unique dataset of 95 image-localized biopsies with spatially matched MRI from 25 untreated Glioblastoma (GBM) patients. The model generated predictions for regional EGFR amplification status (a common and important target in GBM) to resolve the intratumoral genetic heterogeneity across each individual tumor - a key factor for future personalized therapeutic paradigms. The model used probability distributions for each sample prediction to quantify uncertainty, and used transductive learning to reduce the overall uncertainty. We compared predictive accuracy and uncertainty of the transductive learning GP model against a standard GP model using leave-one-patient-out cross validation.RESULTSPredictive uncertainty informed the likelihood of achieving an accurate sample prediction. When stratifying predictions based on uncertainty, we observed substantially higher performance in the group cohort (75% accuracy, n=95) and amongst sample predictions with the lowest uncertainty (83% accuracy, n=72) compared to predictions with higher uncertainty (48% accuracy, n=23), due largely to data interpolation (rather than extrapolation).CONCLUSIONWe present a novel approach to quantify radiogenomics uncertainty to enhance model performance and clinical interpretability. This should help integrate more reliable radiogenomics models for improved medical decision-making.
Anterior Cingulate Cortex Directs Exploration of Alternative Strategies
Authors: Tervo D. Gowanlock R. , Kuleshova Elena , Manakov Maxim , Proskurin Mikhail , Karlsson Mattias , Lustig Andy , Behnam Reza , Karpova Alla Y. 
Published: May 2020

SummaryThe ability to adjust one’s behavioral strategy in complex environments is at the core of cognition. Doing so efficiently requires monitoring the reliability of the ongoing strategy and switching away from it to evaluate alternatives when appropriate. Studies in humans and non-human primates have uncovered signals in the anterior cingulate cortex (ACC) that track the pressure to switch away from the ongoing strategy, and others that relate to the pursuit of alternatives. However, whether these signals underlie computations that actually underpin strategy switching, or merely reflect tracking of related variables remains unclear. Here we provide causal evidence that rodent ACC actively arbitrates between persisting with ongoing behavioral choice and switching away temporarily to re-evaluate alternatives. Furthermore, by individually perturbing distinct output pathways, we establish that the two associated computations – whether to switch away from the current choice, and the pursuit of alternatives – are segregated within ACC micro-circuitry.
Intolerance of uncertainty is associated with heightened responding in the prefrontal cortex during instructed outcome uncertainty of threat
Authors: Morriss Jayne , Bell Tiffany , Biagi Nicolò , Johnstone Tom , van Reekum Carien M. 
Published: May 2020

AbstractHeightened responding to uncertain threat is considered a hallmark of anxiety disorder pathology. Here, we sought to determine if individual differences in self-reported intolerance of uncertainty (IU), a key transdiagnostic dimension in anxiety-related pathology, underlies differential recruitment of neural circuitry during instructed outcome uncertainty of threat (n= 42). In an instructed threat of shock task, cues signalled uncertain threat of shock (50%) or certain safety from shock outcomes. Ratings of arousal and valence, skin conductance response (SCR) and functional magnetic resonance imaging were acquired. Overall, participants displayed greater ratings of arousal and negative valence, SCR, and amygdala activation to uncertain threat vs. safe cues. IU was not associated with greater arousal ratings, SCR or amygdala activation to uncertain threat vs. safe cues. However, we found that high IU was associated with greater ratings of negative valence and greater activity in the medial prefrontal cortex and dorsomedial rostral prefrontal cortex to uncertain threat vs safe cues. These findings suggest that during instructed outcome uncertainty of threat, individuals high in IU rate uncertain threat as aversive and engage prefrontal cortical regions known to be involved in safety-signalling and conscious threat appraisal. Taken together, these findings highlight the potential of IU in modulating safety-signalling and conscious appraisal mechanisms in situations with instructed outcome uncertainty of threat, which may be relevant to models of anxiety-related pathology.
The Outcome Impact of Early vs Late HFNC Oxygen Therapy in Elderly Patients with COVID-19 and ARDS
Authors: Deng Liehua , Lei Shaoqing , Jiang Fang , Lubarsky David A. , Zhang Liangqing , Liu Danyong , Han Conghua , Zhou Dunrong , Wang Zheng , Sun Xiaocong , Zhang Yuanli , Cheung Chi Wai , Wang Sheng , Xia Zhong-yuan , Applegate Richard L , Liu Hong , Tang Jing , Xia Zhengyuan 
Published: May 2020

AbstractCoronavirus disease-2019 (COVID-19) has rapidly spread worldwide. High-flow nasal cannula therapy (HFNC) is a major oxygen supporting therapy for severely ill patients, but information regarding the timing of HFNC application is scarce, especially in elderly patients. We retrospectively analyzed the clinical data of 110 elderly patients (≥65 years) who received HFNC from Renmin Hospital of Wuhan University, People’s Hospital of Xiantao City and Chinese Medicine Hospital of Shishou City in Hubei Province, China, and from Affiliated Hospital of Guangdong Medical University, People’s Hospital of Yangjiang City, People’s Hospital of Maoming City in Guangdong Province, China.Of the 110 patients, the median age was 71 years (IQR, 68-78) and 59.1% was male. Thirty-eight patients received HFNC when 200 mmHg < PO2/FiO2 ≤ 300 mmHg (early HFNC group), and 72 patients received HFNC treatment when 100 mmHg < PaO2/FiO2 ≤ 200 mmHg (late HFNC group). Compared with the late HFNC group, patients in the early HFNC group had a lower likelihood of developing severe ARDS, longer time from illness onset to severe ARDS and shorter duration of viral shedding after illness onset, as well as shorter lengths of ICU and hospital stay. Twenty-four patients died during hospitalization, of whom 22 deaths (30.6%) were in the late HFNC group and 2(5.3%) in the early HFNC group. It is concluded that the Prognosis was better in severely ill elderly patients with COVID-19 receiving early compared to late HFNC. This suggests HFNC could be considered early in this disease process.
Time delay epidemic model for COVID-19
Authors: Maleewong Montri 
Published: May 2020

AbstractA time delay epidemic model is presented for the spread of the Coronavirus 2019 (COVID-19) in China. The time delay effects affect infected individuals. Monte Carlo simulation is performed to estimate the transmission and recovery rates. The basic reproduction number is estimated in terms of the average infected ratio. This ratio can be used to monitor the policy performance of disease control during the spread of the disease.
A comparative study of isothermal nucleic acid amplification methods for SARS-CoV-2 detection at point-of-care
Authors: Tran Diem Hong , Cuong Hoang Quoc , Tran Hau Thi , Le Uyen Phuong , Do Hoang Dang Khoa , Bui Le Minh , Hai Nguyen Duc , Linh Hoang Thuy , Thao Nguyen Thi Thanh , Anh Nguyen Hoang , Hieu Nguyen Trung , Thang Cao Minh , Vu Van Van , Phung Huong Thi Thu 
Published: May 2020

AbstractCOVID-19, caused by the novel coronavirus SARS-CoV-2, has spread worldwide and put most of the world under lockdown. Despite that there have been emergently approved vaccines for SARS-CoV-2, COVID-19 cases, hospitalizations, and deaths have remained rising. Thus, rapid diagnosis and necessary public health measures are still key parts to contain the pandemic. In this study, the colorimetric isothermal nucleic acid amplification tests (iNAATs) for SARS-CoV-2 detection based on loop-mediated isothermal amplification (LAMP), cross-priming amplification (CPA), and polymerase spiral reaction (PSR) were designed and evaluated. The three methods showed the same limit of detection (LOD) value of 1 copy of the targeted gene per reaction. However, for the direct detection of SARS-CoV-2 genomic-RNA, LAMP outperformed both CPA and PSR, exhibiting the LOD value of roughly 43.14 genome copies/reaction. The results can be read with the naked eye within 45 minutes, without cross-reactivity to closely related coronaviruses. Moreover, the direct detection of SARS-CoV-2 RNA in simulated patient specimens by iNAATs was also successful. Finally, the ready-to-use lyophilized reagents for LAMP reactions were shown to maintain the sensitivity and LOD value of the liquid assays. The results indicate that the colorimetric lyophilized LAMP kit developed herein is highly suitable for detecting SARS-CoV-2 nucleic acids at point-of-care.
HSP90 inhibition modulates NFκB signaling in airway goblet cell metaplasia
Authors: Tudas Rosarie A. , Gannon Ryan M. , Thurman Andrew L. , Stroik Mallory R. , Zabner Joseph , Pezzulo Alejandro A. 
Published: May 2020

AbstractGoblet cell metaplasia and mucus hyper-production are key features of chronic muco-obstructive lung diseases such as asthma, chronic bronchitis, and cystic fibrosis. Various mechanisms lead to goblet cell metaplasia in the airways; the driving mechanism for goblet cell metaplasia in a specific patient may be unknown. We recently found that heat shock protein 90 (HSP90) is important for both IL-13- and IL-17- induced airway goblet cell metaplasia. HSP90 interacts with multiple clients that are important in goblet cell metaplasia including Akt, Jak/STAT, IRS, Notch, and various kinases involved in NFκB signaling. Here, we used a targeted phospho-proteomic approach to identify candidate HSP90 clients modulated by the HSP90-inhibitor geldanamycin. NFκB family members were enriched amongst the top candidate targets of HSP90 inhibition in IL-13 an organotypic model of human airway epithelia. We hypothesized that HSP90 inhibition modulated goblet cell metaplasia by interfering with NFκB signaling. We used transcription factor activation, nuclear translocation, and phospho-specific immunofluorescence assays to investigate how IL-13 exposure and HSP90 inhibition modulated NFκB. We found that HSP90 inhibition prevented goblet cell metaplasia by non-canonically blocking NFκB p100/p52 function in human airway epithelia. NFκB modulation via its interaction with HSP90 is a pharmaceutically feasible therapeutic target for goblet cell metaplasia; this approach may enable treatment of patients with chronic muco-inflammatory lung diseases with both known or unidentified disease-driving mechanisms.