bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding signaling and metabolic paths using semantified and harmonized information about biological interactions
Authors: Miller Ryan A , Kutmon Martina , Bohler Anwesha , Waagmeester Andra , Evelo Chris T , Willighagen Egon L 
Published: August 2020

AbstractBackgroundTo grasp the complexity of biological processes, the biological knowledge is often translated into schematic diagrams of biological pathways, such as signalling and metabolic pathways. These pathway diagrams describe relevant connections between biological entities and incorporate domain knowledge in a visual format that is easier for humans to interpret. It has already been established that these diagrams can be represented in machine readable formats, as done in KEGG, Reactome, and WikiPathways. However, while humans are good at interpreting the message of the creator of such a diagram, algorithms struggle when the diversity in drawing approaches increases. WikiPathways supports multiple drawing styles, and therefore needs to harmonize this to offer semantically enriched access via the Resource Description Framework format. Particularly challenging in the normalization of diagrams are the interactions between the biological entities, so that we can glean information about the connectivity of the entities represented. These interactions include information about the type of interaction (metabolic conversion, inhibition, etc.), the direction, and the participants. Availability of the interactions in a semantic and harmonized format enables searching the full network of biological interactions and integration with the linked data cloud.ResultsWe here study how the graphically modelled biological knowledge in diagrams can be semantified and harmonized efficiently, and exemplify how the resulting data can be used to programmatically answer biological questions. We find that we can translate graphically modelled biological knowledge to a sufficient degree into a semantic model of biological knowledge and discuss some of the current limitations. Furthermore, we show how this interaction knowledge base can be used to answer specific biological questions.ConclusionThis paper demonstrates that most of the graphical biological knowledge from WikiPathways is modelled in the semantic layer of WikiPathways with the semantic information intact and connectivity information preserved. The usability of the WikiPathways pathway and connectivity information has shown to be useful and has been integrated into other platforms. Being able to evaluate how biological elements affect each other is useful and allows, for example, the identification of up or downstream targets that will have a similar effect when modified.
DLDTI: A learning-based framework for identification of drug-target interaction using neural networks and network representation
Authors: Zhao Yihan , Zheng Kai , Guan Baoyi , Guo Mengmeng , Song Lei , Gao Jie , Qu Hua , Wang Yuhui , Zhang Ying , Shi Dazhuo 
Published: August 2020

AbstractTo elucidate novel molecular mechanisms of known drugs, efficient and feasible computational methods for predicting potential drug-target interactions (DTI) would be of great importance. A novel calculation model called DLDTI was generated for predicting DTI based on network representation learning and convolutional neural networks. The proposed approach simultaneously fuses the topology of complex networks and diverse information from heterogeneous data sources and copes with the noisy, incomplete, and high-dimensional nature of large-scale biological data by learning low-dimensional and rich depth features of drugs and proteins. Low-dimensional feature vectors were used to train DLDTI to obtain optimal mapping space and infer new DTIs by ranking DTI candidates based on their proximity to optimal mapping space. DLDTI achieves promising performance under 5-fold cross-validation with AUC values of 0.9172, which was higher than that of the method based on different classifiers or different feature combination technique. Moreover, biomedical experiments were also completed to validate DLDTI’s performance. Consistent with the predicted result, tetramethylpyrazine, a member of pyrazines, reduced atherosclerosis progression and inhibited signal transduction in platelets, via PI3K/Akt, cAMP and calcium signaling pathways. The source code and datasets explored in this work are available athttps://github.com/CUMTzackGit/DLDTI
Computing the daily reproduction number of COVID-19 by inverting the renewal equation using a variational technique
Authors: Alvarez Luis , Colom Miguel , Morel Jean-David , Morel Jean-Michel 
Published: August 2020

The COVID-19 pandemic has undergone frequent and rapid changes in its local and global infection rates, driven by governmental measures, or the emergence of new viral variants. The reproduction number Rt indicates the average number of cases generated by an infected person at time t and is a key indicator of the spread of an epidemic. A timely estimation of Rt is a crucial tool to enable governmental organizations to adapt quickly to these changes and assess the consequences of their policies. The EpiEstim method is the most widely accepted method for estimating Rt. But it estimates Rt with a significant temporal delay. Here, we propose a new method, EpiInvert, that shows good agreement with EpiEstim, but that provides estimates of Rt several days in advance. We show that Rt can be estimated by inverting the renewal equation linking Rt with the observed incidence curve of new cases, it. Our signal processing approach to this problem yields both Rt and a restored it corrected for the “weekend effect” by applying a deconvolution + denoising procedure. The implementations of the EpiInvert and EpiEstim methods are fully open-source and can be run in real-time on every country in the world, and every US state through a web interface at www.ipol.im/epiinvert.Significance StatementBased on a signal processing approach we propose a method to compute the reproduction number Rt, the transmission potential of an epidemic over time. Rt is estimated by minimizing a functional that enforces: (i) the ability to produce an incidence curve it corrected of the weekly periodic bias produced by the “weekend effect”, obtained from Rt through a renewal equation; (ii) the regularity of Rt. A good agreement is found between our Rt estimate and the one provided by the currently accepted method, EpiEstim, except our method predicts Rt several days closer to present. We provide the mathematical arguments for this shift. Both methods, applied every day on each country, can be compared at www.ipol.im/epiinvert.
Outcome of COVID-19 with co-existing surgical emergencies in children: our initial experiences and recommendations
Authors: Hasan Md Samiul , Ali Md Ayub , Huq Umama 
Published: August 2020

AbstractBackgroundCOVID-19 has changed the practice of surgery vividly all over the world. Pediatric surgery is not an exception. Prioritization protocols allowing us to provide emergency surgical care to the children in need while controlling the pandemic spread. The aim of this study is to share our experiences with the outcome of children with COVID-19 who had a co-existing surgical emergency.MethodsThis is a retrospective observational study. We reviewed the epidemiological, clinical, and laboratory data of all patients admitted in our surgery department through the emergency department and later diagnosed to have COVID-19 by RT-PCR. The study duration was 3 months (April 2020 – June 2020). A nasopharyngeal swab was taken from all patients irrespective of symptoms to detect SARS CoV 2 by RT-PCR with the purpose of detecting asymptomatic patients and patients with atypical symptoms. Emergency surgical services were provided immediately without delay and patients with positive test results were isolated according to the hospital protocol. We divided the test positive patients into 4 age groups for the convenience of data analysis. Data were retrieved from hospital records and analyzed using SPSS (version 25) software. Ethical permission was taken from the hospital ethical review board.ResultsTotal patients were 32. Seven (21.9%) of them were neonates. Twenty-four (75%) patients were male. The predominant diagnosis was acute abdomen followed by infantile hypertrophic pyloric stenosis (IHPS), myelomeningocele, and intussusception. Only two patients had mild respiratory symptoms (dry cough). Fever was present in 13 (40.6%) patients. Fourteen (43.8%) patients required surgical treatment. The mean duration of hospital stay was 5.5 days. One neonate with ARM died in the post-operative ward due to cardiac arrest. No patient had hypoxemia or organ failure. Seven health care workers (5.51%) including doctors & nurses got infected with SARS Co V2 during this period.ConclusionOur study has revealed a milder course of COVID-19 in children with minimal infectivity even when present in association with emergency surgical conditions. This might encourage a gradual restart to mitigate the impact of COVID-19 on children’s surgery.
Sensitivity of nasopharyngeal, oropharyngeal and nasal washes specimens for SARS-CoV-2 detection in the setting of sampling device shortage
Authors: Adrien Calame , Léna Mazza , Adriana Renzoni , Laurent Kaiser , Manuel Schibler 
Published: August 2020

AbstractIn the context of an unprecedented shortage of nasopharyngeal swabs (NPS) or sample transport media during the coronavirus disease 2019 (COVID-19) crisis, alternative methods for sample collection are needed. To address this need, we validated a cell culture medium as a viral transport medium, and compared the analytical sensitivity of SARS-CoV-2 real-time RT-PCR in nasal wash (NW), oropharyngeal swab (OPS) and NPS specimens. Both the clinical and analytical sensitivity were comparable in these three sample types. OPS and NW specimens may therefore represent suitable alternatives to NPS for SARS-CoV-2 detection.
Physical activity, BMI and COVID-19: an observational and Mendelian randomisation study
Authors: Zhang Xiaomeng , Li Xue , Sun Ziwen , He Yazhou , Xu Wei , Campbell Harry , Dunlop Malcolm G , Timofeeva Maria , Theodoratou Evropi 
Published: August 2020

AbstractPhysical activity (PA) is known to be a protective lifestyle factor against several non-communicable diseases while its impact on infectious diseases, including Coronavirus Disease 2019 (COVID-19) is not as clear. We performed univariate and multivariate logistic regression to identify associations between body mass index (BMI) and both objectively and subjectively measured PA collected prospectively and COVID-19 related outcomes (Overall COVID-19, inpatient COVID-19, outpatient COVID-19, and COVID-19 death) in the UK Biobank (UKBB) cohort. Subsequently, we tested causality by using two-sample Mendelian randomisation (MR) analysis. In the multivariable model, the increased acceleration vector magnitude PA (AMPA) was associated with a decreased probability of overall and outpatient COVID-19. No association was found between self-reported moderate-to-vigorous PA (MVPA) or BMI and COVID-19 related outcomes. Although no causal association was found by MR analyses, this may be due to limited power and we conclude policies to encourage and facilitate exercise at a population level during the pandemic should be considered.
Perinatal Risk and Protective Factors in the Development of Diffuse White Matter Abnormality on Term-Equivalent Age MRI in Infants Born Very Preterm
Authors: Parikh Nehal A. , Sharma Puneet , He Lili , Li Hailong , Altaye Mekibib , Priyanka Illapani Venkata Sita ,   for the Cincinnati Imaging & Neurodevelopment Early Prediction Study (CINEPS)
Published: August 2020

AbstractImportanceDiffuse white matter abnormality (DWMA) is the most common brain MRI finding in very preterm infants and is predictive of neurodevelopmental impairments. However, its etiology remains elusive and identifying perinatal risk and protective factors may allow clinicians to reduce the burden of DWMA.ObjectiveTo identify perinatal clinical factors that are associated with the development of objectively diagnosed DWMA in very preterm infants.DesignA prospective cohort was enrolled between September 2016 and November 2019. Brain MRIs were collected at 39 to 45 weeks postmenstrual age (PMA) to evaluate DWMA volume. A pre-defined list of pertinent maternal characteristics, pregnancy/delivery data, and neonatal ICU data was collected for enrolled patients to identify antecedents of objectively diagnosed DWMA.SettingFive level III/IV NICUs in the greater Cincinnati, Ohio area.ParticipantsA population-based sample of 392 very preterm infants born before 33 weeks gestational age.ExposureVery preterm birth with associated diseases and treatments.Main Outcome and MeasureObjectively diagnosed DWMA volume on brain MRI at term-equivalent age.Results377 of the 392 very preterm infants (96%) had high quality MRI data. Mean (SD) gestational age was 29.3 (2.5) weeks. In multivariable linear regression analyses, pneumothorax (p=.027), severe bronchopulmonary dysplasia (BPD) (p=.009), severe retinopathy of prematurity (ROP) (p<0.001), and male sex (p=.041) were associated with increasing volume of DWMA. The following factors were associated with decreased risk of DWMA – dexamethasone for severe BPD (p=.004), duration of caffeine for severe BPD (p = 0.009), and exclusive maternal milk at NICU discharge (p=.049).Conclusions and RelevanceSevere ROP and BPD exhibited the strongest adverse association with the development of DWMA. Caffeine and dexamethasone treatments for infants with severe BPD exhibited a protective effect against development of DWMA. The beneficial association with maternal milk is also a modifiable factor that has clinical implications.Key PointsQuestionWhat perinatal clinical factors are independently associated with the development of diffuse white matter abnormality (DWMA) in very preterm infants?FindingsIn this prospective cohort study, pneumothorax, severe bronchopulmonary dysplasia (BPD), severe retinopathy of prematurity, and male sex were significantly associated with an increased risk of DWMA. Significant protective factors included dexamethasone for severe BPD, duration of caffeine for severe BPD, and exclusive maternal milk diet at NICU discharge.MeaningKnowledge of these common and modifiable neonatal diseases and treatments may allow clinicians to reduce the burden of DWMA development through targeted prevention or treatments approaches.
Mucosal versus systemic antibody responses to SARS-CoV-2 antigens in COVID-19 patients
Authors: Isho Baweleta , Abe Kento T. , Zuo Michelle , Jamal Alainna J. , Rathod Bhavisha , Wang Jenny H. , Li Zhijie , Chao Gary , Rojas Olga L. , Bang Yeo Myong , Pu Annie , Christie-Holmes Natasha , Gervais Christian , Ceccarelli Derek , Samavarchi-Tehrani Payman , Guvenc Furkan , Budylowski Patrick , Li Angel , Paterson Aimee , Yun Yue Feng , Marin Lina M. , Caldwell Lauren , Wrana Jeffrey L. , Colwill Karen , Sicheri Frank , Mubareka Samira , Gray-Owen Scott D. , Drews Steven J. , Siqueira Walter L. , Barrios-Rodiles Miriam , Ostrowski Mario , Rini James M. , Durocher Yves , McGeer Allison J. , Gommerman Jennifer L. , Gingras Anne-Claude 
Published: August 2020

AbstractWhile the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the mucosal immune response and its relationship to systemic antibody levels. Since SARS-CoV-2 initially replicates in the upper airway, the antibody response in the oral cavity is likely an important parameter that influences the course of infection, but how it correlates to the antibody response in serum is not known. Here, we profile by enzyme linked immunosorbent assays (ELISAs) IgG, IgA and IgM responses to the SARS-CoV-2 spike protein (full length trimer) and its receptor binding domain (RBD) in serum (n=496) and saliva (n=90) of acute and convalescent patients with laboratory-diagnosed COVID-19 ranging from 3–115 days post-symptom onset (PSO), compared to negative controls. Anti-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16–30 days PSO. Whereas anti-CoV-2 IgA and IgM antibodies rapidly decayed, IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. In a surrogate neutralization ELISA (snELISA), neutralization activity peaks by 31–45 days PSO and slowly declines, though a clear drop is detected at the last blood draw (105–115 days PSO). Lastly, IgG, IgM and to a lesser extent IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that systemic and mucosal humoral IgG antibodies are maintained in the majority of COVID-19 patients for at least 3 months PSO. Based on their correlation with each other, IgG responses in saliva may serve as a surrogate measure of systemic immunity.One Sentence SummaryIn this manuscript, we report evidence for sustained SARS-CoV-2-specific IgG and transient IgA and IgM responses both at the site of infection (mucosae) and systemically in COVID-19 patients over 3 months and suggest that saliva could be used as an alternative biofluid for monitoring IgG to SARS-CoV-2 spike and RBD antigens.
Low-Cost Enhancement of Facial Mask Filtration to Prevent Transmission of COVID-19
Authors: Bhimaraju Hari , Jain Ramesh , Nag Nitish 
Published: August 2020

AbstractThe use of face masks is recommended worldwide to reduce the spread of COVID-19. A plethora of facial coverings and respirators, both commercial and homemade, pervade the market, but the true filtration capabilities of many homemade measures against the virus are unclear and continue to be unexplored. In this work, we compare the efficacy of the following masks in keeping out particulate matter below 2.5 microns: N95 respirators, surgical masks, cloth masks, cloth masks with activated carbon air filters, cloth masks with HVAC air filters, lightly starch-enhanced cloth masks, and heavily-starched cloth masks. The experiments utilize an inhalation system and aerosol chamber to simulate a masked individual respiring aerosolized air. COVID-19 disproportionately affects people in low-income communities, who often lack the resources to acquire appropriate personal protective equipment and tend to lack the flexibility to shelter in place due to their public-facing occupations. This work tests low-cost enhancements to homemade masks to assist these communities in making better masks to reduce viral transmission. Experimental results demonstrate that the filtration efficacy of cloth masks with either a light or heavy starch can approach the performance of much costlier masks. This discovery supports the idea of low-cost enhancements to reduce transmission and protect individuals from contracting COVID-19.
Effect of Handedness on Learned Controllers and Sensorimotor Noise During Trajectory-Tracking
Authors: Yamagami Momona , Peterson Lauren N. , Howell Darrin , Roth Eatai , Burden Samuel A. 
Published: August 2020

AbstractIn human-in-the-loop control systems, operators can learn to manually control dynamic machines with either hand using a combination of reactive (feedback) and predictive (feed-forward) control. This paper studies the effect of handedness on learned controllers and performance during a trajectory-tracking task. In an experiment with 18 participants, subjects perform an assay of unimanual trajectory-tracking and disturbance-rejection tasks through second-order machine dynamics, first with one hand then the other. To assess how hand preference (or dominance) affects learned controllers, we extend, validate, and apply a non-parametric modeling method to estimate the concurrent feedback and feedforward controllers. We find that performance improves because feedback adapts, regardless of the hand used. We do not detect statistically significant differences in performance or learned controllers between hands. Adaptation to reject disturbances arising exogenously (i.e. applied by the experimenter) and endogenously (i.e. generated by sensorimotor noise) explains observed performance improvements.
Control of aperture closure during reach-to-grasp movements in immersive haptic-free virtual reality
Authors: Mangalam Madhur , Yarossi Mathew , Furmanek Mariusz P. , Tunik Eugene 
Published: August 2020

AbstractVirtual reality (VR) has garnered much interest as a training environment for motor skill acquisition, including for neurological rehabilitation of upper extremities. While the focus has been on gross upper limb motion, VR applications that involve reaching for, and interacting with, virtual objects are growing. The absence of true haptics in VR when it comes to hand-object interactions raises a fundamentally important question: can haptic-free immersive virtual environments (hf-VEs) support naturalistic coordination of reach-to-grasp movements? This issue has been grossly understudied, and yet is of significant importance in the development and application of VR across a number of sectors. In a previous study (Furmanek et al. 2019), we reported that reach-to-grasp movements are similarly coordinated in both the physical environment (PE) and hf-VE. The most noteworthy difference was that the closure phase—which begins at maximum aperture and lasts through the end of the movement—was longer in hf-VE than in PE, suggesting that different control laws might govern the initiation of closure between the two environments. To do so, we reanalyzed data from Furmanek et al. (2019), in which the participants reached to grasp three differently sized physical objects, and matching 3D virtual object renderings, placed at three different locations. Our analysis revealed two key findings pertaining to the initiation of closure in PE and hf-VE. First, the respective control laws governing the initiation of aperture closure in PE and hf-VE both included state estimates of transport velocity and acceleration, supporting a general unified control policy for implementing reach-to-grasp across physical and virtual environments. Second, aperture was less informative to the control law in hf-VE. We suggest that the latter was likely because transport velocity at closure onset and aperture at closure onset were less independent in hf-VE than in PE, ultimately resulting in aperture at closure onset having a weaker influence on the initiation of closure. In this way, the excess time and muscular effort needed to actively bring the fingers to a stop at the interface of a virtual object was factored into the control law governing the initiation of closure in hf-VE. Critically, this control law remained applicable, albeit with different weights in hf-VE, despite the absence of terminal haptic feedback and potential perceptual differences.