bluuebunny/crossref_metadata_2025_split huggingface dataset:
Customize Deep Learning-based De-Identification Systems Using Local Clinical Notes - A Study of Sample Size
Authors: Yang Xi , Bian Jiang , Wu Yonghui 
Published: August 2020

ABSTRACTElectronic Health Records (EHRs) are a valuable resource for both clinical and translational research. However, much detailed patient information is embedded in clinical narratives, including a large number of patients’ identifiable information. De-identification of clinical notes is a critical technology to protect the privacy and confidentiality of patients. Previous studies presented many automated de-identification systems to capture and remove protected health information from clinical text. However, most of them were tested only in one institute setting where training and test data were from the same institution. Directly adapting these systems without customization could lead to a dramatic performance drop. Recent studies have shown that fine-tuning is a promising method to customize deep learning-based NLP systems across different institutes. However, it’s still not clear how much local data is required. In this study, we examined the customizing of a deep learning-based de-identification system using different sizes of local notes from UF Health. Our results showed that the fine-tuning could significantly improve the model performance even on a small local dataset. Yet, when the local data exceeded a threshold (e.g., 700 notes in this study), the performance improvement became marginal.
Mutual anticipation can contribute to self-organization in human crowds
Authors: Murakami Hisashi , Feliciani Claudio , Nishiyama Yuta , Nishinari Katsuhiro 
Published: August 2020

AbstractHuman crowds provide paradigmatic examples of collective behavior emerging through self-organization. Although the underlying interaction has been considered to obey the distance-dependent law, resembling physical particle systems, recent findings emphasized that pedestrian motions are fundamentally influenced by the anticipated future positions of their neighbors rather than their current positions. Therefore, anticipatory interaction may play a crucial role in collective patterning. However, whether and how individual anticipation functionally benefits the group is not well-understood. We suggest that collective patterning in human crowds is promoted by anticipatory path-seeking behavior resulting in a scale-free movement pattern, called the Lévy walk. In our experiments of lane formation, a striking example of self-organized patterning in human crowds where people moving in opposite directions spontaneously segregate into several unidirectional lanes, we manipulated some pedestrians’ ability to anticipate by having them type on a mobile phone while walking. The manipulation slowed overall walking speeds and delayed the onset of global patterning, and the distracted pedestrians sometimes failed to achieve their usual walking strategy. Moreover, we observed that the delay of global patterning depends on decisions made by pedestrians who were moving toward the distracted ones and had no choice but to take sudden large steps, presumably because of difficulty in anticipating the motions of their counterparts. These results imply that mutual anticipation between pedestrians facilitates efficient transition to emergent patterning in situations where nobody within a crowd is distracted. Our findings may contribute to efficient crowd management and inform future models of self-organizing systems.
A novel, dichloromethane-fermenting bacterium in thePeptococcaceaefamily, ‘CandidatusFormamonas warabiya’, gen. nov. sp. nov.
Authors: Holland Sophie I , Ertan Haluk , Manefield Michael J , Lee Matthew 
Published: August 2020

AbstractDichloromethane (DCM; CH2Cl2) is a toxic groundwater pollutant that also has a detrimental effect on atmospheric ozone levels. As a dense non-aqueous phase liquid, DCM migrates vertically through groundwater to low redox zones, yet information on anaerobic microbial DCM transformation remains scarce due to a lack of cultured organisms. We report here the characterisation of strain DCMF, the dominant organism in an anaerobic enrichment culture (DFE) that is capable of fermenting DCM to the environmentally benign product acetate. Stable carbon isotope experiments demonstrated that the organism assimilated carbon from DCM and bicarbonate via the Wood-Ljungdahl pathway. Strain DCMF is the first anaerobic DCM-degrading bacterium also shown to metabolise non-chlorinated substrates. It appears to be a methylotroph utilising the Wood-Ljungdahl pathway for metabolism of methyl groups from methanol, choline, and glycine betaine, which has implications for the flux of climate-active compounds from subsurface environments. Community profiling and enrichment of the cohabiting taxa in culture DFE to the exclusion of strain DCMF suggest that it is the sole organism in this culture responsible for substrate metabolism, while the cohabitants persist via necromass recycling. Genomic and physiological evidence support placement of strain DCMF in a novel genus, ‘CandidatusFormamonas warabiya’.
Post-exertion oxygen saturation as a prognostic factor for adverse outcome in patients attending the emergency department with suspected COVID-19: Observational cohort study
Authors: Goodacre Steve 
Published: August 2020

AbstractBackgroundMeasurement of post-exertion oxygen saturation has been proposed to assess illness severity in suspected COVID-19 infection. We aimed to determine the accuracy of post-exertional oxygen saturation for predicting adverse outcome in suspected COVID-19.MethodsWe undertook an observational cohort study across 70 emergency departments during first wave of the COVID-19 pandemic in the United Kingdom. We collected data prospectively, using a standardised assessment form, and retrospectively, using hospital records, from patients with suspected COVID-19, and reviewed hospital records at 30 days for adverse outcome (death or receiving organ support). Patients with post-exertion oxygen saturation recorded were selected for this analysis.ResultsWe analysed data from 817 patients with post-exertion oxygen saturation recorded after excluding 54 in whom measurement appeared unfeasible. The c-statistic for post-exertion change in oxygen saturation was 0.589 (95% confidence interval 0.465 to 0.713), and the positive and negative likelihood ratios of a 3% or more desaturation were respectively 1.78 (1.25 to 2.53) and 0.67 (0.46 to 0.98). Multivariable analysis showed that post-exertion oxygen saturation was not a significant predictor of adverse outcome when baseline clinical assessment was taken into account (p=0.368). Secondary analysis excluding patients in whom post-exertion measurement appeared inappropriate resulted in a c-statistic of 0.699 (0.581 to 0.817), likelihood ratios of 1.98 (1.26 to 3.10) and 0.61 (0.35 to 1.07), and some evidence of additional prognostic value on multivariable analysis (p=0.019).ConclusionsPost-exertion oxygen saturation provides modest prognostic information in the assessment of patients attending the emergency department with suspected COVID-19.RegistrationISRCTN registry, ISRCTN56149622, http://www.isrctn.com/ISRCTN28342533Key messagesWhat is already known on this subject?Post exertional decrease in oxygen saturation can be used to predict prognosis in chronic lung diseasesPost exertional desaturation has been proposed as a way of predicting adverse outcome in people with suspected COVID-19What this study adds:Post-exertion oxygen saturation provides modest prognostic information in the assessment of patients attending the emergency department with suspected COVID-19
Application of Optimal Control to the Dynamics of COVID-19 Disease in South Africa
Authors: Gatyeni S. P. , Chukwu C.W. , Chirove F. , Fatmawati  , Nyabadza F. 
Published: August 2020

AbstractSARS-CoV-2 (COVID-19) belongs to the beta-coronavirus family, which include: the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV). Since its outbreak in South Africa in March 2020, it has lead to high mortality and thousands of people contracting the virus. Mathematical analysis of a model without controls was done and the basic reproduction number (ℛ0) of the COVID-19 for the South African pandemic determined. We introduced permissible controls and formulate an optimal control problem using the Pontraygain Maximum Principle. Our numerical findings suggest that joint implementation of effective mask usage, physical distancing and active screening and testing, are effective measures to curtail the spread of the disease in the human population. The results obtained in this paper are of public health importance in the control and management of the spread for the novel coronavirus, SARS-CoV-2, in South Africa.
Janus Kinase-Inhibitor and Type I Interferon Ability to Produce Favorable Clinical Outcomes in COVID-19 Patients: A Systematic Review and Meta-Analysis
Authors: Walz Lucas , Cohen Avi J. , Rebaza Andre P. , Vanchieri James , Slade Martin D. , Dela Cruz Charles S. , Sharma Lokesh 
Published: August 2020

ABSTRACTBackgroundNovel coronavirus (SARS-CoV-2) has infected over 17 million. Novel therapies are urgently needed. Janus-kinase (JAK) inhibitors and Type I interferons have emerged as potential antiviral candidates for COVID-19 patients for their proven efficacy against diseases with excessive cytokine release and by their ability to promote viral clearance in past coronaviruses, respectively. We conducted a systemic review and meta-analysis to evaluate role of these therapies in COVID-19 patients.MethodsMEDLINE and MedRxiv were searched until July 30th, 2020, including studies that compared treatment outcomes of humans treated with JAK-inhibitor or Type I interferon against controls. Inclusion necessitated data with clear risk estimates or those that permitted back-calculation.ResultsWe searched 733 studies, ultimately including four randomized and eleven non-randomized clinical trials. JAK-inhibitor recipients had significantly reduced odds of mortality (OR, 0.12; 95%CI, 0.03–0.39, p=0.0005) and ICU admission (OR, 0.05; 95%CI, 0.01–0.26, p=0.0005), and had significantly increased odds of hospital discharge (OR, 22.76; 95%CI, 10.68–48.54, p<0.00001), when compared to standard treatment group. Type I interferon recipients had significantly reduced odds of mortality (OR, 0.19; 95%CI, 0.04–0.85, p=0.03), and increased odds of discharge bordering significance (OR, 1.89; 95%CI, 1.00–3.59, p=0.05).ConclusionsJAK-inhibitor treatment is significantly associated with positive clinical outcomes regarding mortality, ICU admission, and discharge. Type I interferon treatment is associated with positive clinical outcomes regarding mortality and discharge. While these data show promise, additional randomized clinical trials are needed to further elucidate the efficacy of JAK-inhibitors and Type I interferons and clinical outcomes in COVID-19.KEY MESSAGESKey QuestionCan treatment of hospitalized COVID-19 patients with JAK-inhibitor or Type I interferon confer favorable clinical outcomes?Bottom LineMeta-analysis demonstrates that JAK-inhibitor treatment was significantly associated with favorable clinical outcomes in terms of mortality, requiring mechanical ventilation, and hospital discharge, while treatment with Type I interferon was significantly associated with decreased mortality.Why Read On?This study conducted a systematic review of human trials that treated patients with JAK-inhibitors or Type I interferon, and it elaborates on the potential benefits of administering these therapies at different moments of the disease course despite apparently opposite mechanism of action of these two interventions.
Lying in wait: the resurgence of dengue virus after the Zika epidemic in Brazil
Authors: Brito Anderson Fernandes , Machado Lais Ceschini , Siconelli Márcio Junio Lima , Oidtman Rachel J. , Fauver Joseph R. , de Oliveira Carvalho Rodrigo Dias , Dezordi Filipe Zimmer , Pereira Mylena Ribeiro , de Castro-Jorge Luiza Antunes , Minto Elaine Cristina Manini , Passos Luzia Márcia Romanholi , Kalinich Chaney C. , Petrone Mary E. , Allen Emma , España Guido Camargo , Huang Angkana T. , Cummings Derek A. T. , Baele Guy , Franca Rafael Freitas Oliveira , Perkins T. Alex , da Fonseca Benedito Antônio Lopes , Wallau Gabriel Luz , Grubaugh Nathan D. 
Published: August 2020

AbstractAfter Zika virus (ZIKV) emerged and caused an epidemic in the Americas in 2016, both Zika and dengue incidence declined in the following years (2017-2018) to a record low in many countries. Following this period of low incidence, dengue resurged in 2019 in Brazil, causing ~2.1 million cases. The reasons for the recent fluctuations in dengue incidence and the maintenance of dengue virus (DENV) through periods of low transmission are unknown. To investigate this, we used a combination of epidemiological and climatological data to estimate dengue force of infection (FOI) and model mosquito-borne transmission suitability since the early 2000s in Brazil. Our estimates of FOI revealed that the rate of DENV transmission in 2018-2019 was exceptionally low, due to a low proportion of susceptible population rather than changes to ecological conditions. This supports the hypothesis that the synchronous decline of dengue in Brazil may be explained by protective immunity from pre-exposure to ZIKV and/or DENV in prior years. Furthermore, we sequenced 69 genomes of dengue virus serotype 1 (DENV-1) and DENV-2 circulating in Northeast and Southeast Brazil, and performed phylogeographic analyses to uncover patterns of viral spread. We found that the outbreaks in Brazil in 2019 were caused by DENV lineages that were circulating locally prior to the Zika epidemic and spread cryptically during the period of low transmission. Despite the period of low transmission, endemic DENV lineages persisted for 5-10 years in Brazil before causing major outbreaks. Our study challenges the paradigm that dengue outbreaks are caused by recently introduced new lineages, but rather they may be driven by established lineages circulating at low levels until the conditions are conducive for outbreaks.
Is there reporting and citation bias for completed phase III interventional brain tumor trials?
Authors: Rayi Appaji , Alnahhas Iyad , Giglio Pierre , Puduvalli Vinay 
Published: August 2020

AbstractAimsReporting and citation bias based on positive versus negative outcome among completed phase III interventional brain tumor trials (IBTTs) have not been previously reported. Thus, we aimed to assess the evidence.MethodsClinicaltrials.gov was used to obtain all phase III IBTTs completed prior to December 31st 2016. Trials closed due to poor accrual or non-phase III were excluded. Data about the funding source, type of intervention, conducted at U.S or Non-U.S locations, patients enrolled, primary completion date, time to dissemination of results in months (either reported on Clinicaltrials.gov or published in a journal), citations per year (from web of science) and outcome (positive or neutral/negative) were abstracted. Median time to dissemination was estimated using Kaplan-Meier estimates and a log rank test for statistical significance. The number of citations per year for positive and negative/neutral studies was compared using a t-test.Results67 studies were analyzed. The median time from primary completion to dissemination of results for trials with a positive outcome was 20 months (n = 20; 95% CI: 12-31) compared to 30 months for trials with a negative outcome (n=35; 95 % CI: 22 – 37) (p = 0.095). The average number of citations per year for trials with a positive outcome is 62.4 (n = 21; range 1.1 – 614.8) compared to 25.0 for trials with a negative outcome (n=35; range 0.14 - 158.8) (p = 0.213). There was no significant difference in time to dissemination based on the funding source, type of intervention or the location where the trial was conducted.ConclusionThere was no evidence of reporting or citation bias among completed phase III IBTTs. Nevertheless, positive phase III IBTTs were reported more promptly and cited more often compared to negative or neutral trials. These findings might need consideration for risk of bias assessment while conducting systematic reviews.
Probability of elimination for COVID-19 in Aotearoa New Zealand
Authors: Binny Rachelle N. , Hendy Shaun C. , James Alex , Lustig Audrey , Plank Michael J. , Steyn Nicholas 
Published: August 2020

AbstractOn 25th March 2020, New Zealand implemented stringent lockdown measures (Alert Level 4, in a four-level alert system) with the goal of eliminating community transmission of COVID-19. Once new cases are no longer detected over consecutive days, the probability of elimination is an important measure for informing decisions on when certain COVID-19 restrictions should be relaxed. Our model of COVID-19 spread in New Zealand estimates that after 2-3 weeks of no new reported cases, there is a 95% probability that COVID-19 has been eliminated. We assessed the sensitivity of this estimate to varying model parameters, in particular to different likelihoods of detection of clinical cases and different levels of control effectiveness. Under an optimistic scenario with high detection of clinical cases, a 95% probability of elimination is achieved after 10 consecutive days with no new reported cases, while under a more pessimistic scenario with low case detection it is achieved after 22 days.
Antigen-Specific T Cell Recall Assay To Screen Drugs For Off-Target Effects
Authors: Kleiman Eden , Sierra Gloria , Magcase Dennie , George Marybeth V , Daftarian Pirouz M 
Published: August 2020

ABSTRACTExtracellular adenosine suppresses T cell immunity in the tumor microenvironment. We have developed an in vitro recall assay utilizing a sequential adenosine dosing regimen guide for testing drug off-target effects on memory T cell expansion/function. As a proof of principle, we show low dose adenosine analog GS-5734, a monophosphoramidate prodrug of an adenosine analog, does not alter memory T cell recall whereas toxicity observed at high dose favors antigen-specific memory T cell survival/proliferation over non-specific CD8+T cells. Parent drug GS-445124 at high dosage interferes with antigen-specific T cell recall without cellular toxicity. Despite similar chemical structure, these drugs displayed opposing effects on memory T cell expansion. This assay platform has broad utility in screening memory T cell off-target effects.
Resolving the data asynchronicity in high-speed atomic force microscopy measurement via the Kalman Smoother
Authors: Kubo Shintaroh , Kato Suguru , Nakamura Kazuyuki , Kodera Noriyuki , Takada Shoji 
Published: August 2020

AbstractHigh-speed atomic force microscopy (HS-AFM) is a scanning probe microscopy that can capture structural dynamics of biomolecules in real time at single molecule level near physiological condition. Albeit much improvement of the instruments, while scanning one frame of HS-AFM movies, biomolecules often change their conformations largely. Thus, the obtained frame images can be hampered by the time-difference, the asynchronicity, in the data acquisition. Here, to resolve this data asynchronicity in the HS-AFM movie, we developed Kalman filter and smoother methods, some of the sequential Bayesian filtering approaches. The Kalman filter/smoother methods use alternative steps of a short time-propagation by a linear dynamical system and a correction by the likelihood of AFM data acquired pixel by pixel. We first tested the method using a toy model of a diffusing cone, showing that the Kalman smoother method outperforms to reproduce the ground-truth movie, compared to that mimics the raw AFM movie, and the Kalman filter result. We then applied the Kalman smoother to a synthetic movie for conformational change dynamics of a motor protein, i.e., dynein, confirming the superiority of the Kalman smoother. Finally, we applied the Kalman smoother to two real HS-AFM movies, FlhAc and centralspindlin, reducing distortion and noise in the AFM movies. The method is general and can be applied to any HS-AFM movies.
The PNUTS-PP1 axis regulates endothelial aging and barrier function via SEMA3B suppression
Authors: Lozano-Vidal Noelia , Stanicek Laura , Bink Diewertje I. , Kremer Veerle , MacInnes Alyson W. , Dimmeler Stefanie , Boon Reinier A. 
Published: August 2020

ABSTRACTAge-related diseases pose great challenges to health care systems worldwide. During aging, endothelial senescence increases the risk for cardiovascular disease. Recently, it was described that Phosphatase 1 Nuclear Targeting Subunit (PNUTS) has a central role in cardiomyocyte aging and homeostasis. Here, we determined the role of PNUTS in endothelial cell aging. We confirmed that PNUTS is repressed in senescent endothelial cells (ECs). Moreover, PNUTS silencing elicits several of the hallmarks of endothelial aging: senescence, reduced angiogenesis and loss of barrier function. To validate our findings in vivo, we generated an endothelial-specific inducible PNUTS-deficient mouse line (Cdh5-CreERT2;PNUTSfl/fl), termed PNUTSEC-KO. Two weeks after PNUTS deletion, PNUTSEC-KOmice presented severe multiorgan failure and vascular leakage. We showed that the PNUTS binding motif for protein phosphatase 1 (PP1) is essential to maintain endothelial barrier function. Transcriptomic analysis of PNUTS-silenced HUVECs and lungs of PNUTSEC-KOmice revealed that the PNUTS-PP1 axis tightly regulates the expression of semaphorin 3B (SEMA3B). Indeed, silencing of SEMA3B completely restored barrier function after PNUTS loss-of-function. These results reveal a pivotal role for PNUTS in endothelial homeostasis through a PP1-SEMA3B downstream pathway that provides a potential target against the effects of aging in ECs.
Rapid endothelial infection, endothelialitis and vascular damage characterise SARS-CoV-2 infection in a human lung-on-chip model
Authors: Thacker Vivek V , Sharma Kunal , Dhar Neeraj , Mancini Gian-Filippo , Sordet-Dessimoz Jessica , McKinney John D 
Published: August 2020

AbstractSevere cases of COVID-19 present with hypercoagulopathies and systemic endothelialitis of the lung microvasculature. The dynamics of vascular damage, and whether it is a direct consequence of endothelial infection or an indirect consequence of immune cell mediated cytokine storms is unknown. This is in part becausein vitromodels are typically epithelial cell monocultures or fail to recapitulate vascular physiology. We use a vascularised lung-on-chip model where, consistent with monoculture reports, low numbers of SARS-CoV-2 virions are released apically from alveolar epithelial cells. However, rapid infection of the underlying endothelial layer leads to the generation of clusters of endothelial cells with low or no CD31 expression, a progressive loss of endothelial barrier integrity, and a pro-coagulatory microenvironment. These morphological changes do not occur if these cells are exposed to the virus apically. Viral RNA persists in individual cells, which generates a response that is skewed towards NF-KB mediated inflammation, is typified by IL-6 secretion even in the absence of immune cells, and is transient in epithelial cells but persistent in endothelial cells. Perfusion with Tocilizumab, an inhibitor of trans IL-6 signalling slows the loss of barrier integrity but does not prevent the formation of endothelial cell clusters with reduced CD31 expression. SARS-CoV-2 mediated endothelial cell damage occurs despite a lack of rapid viral replication, in a cell-type specific manner and independently of immune-cell mediated cytokine storms, whose effect would only exacerbate the damage.