bluuebunny/crossref_metadata_2025_split huggingface dataset:
ATP serves as a nucleotide switch coupling the genome maturation and packaging motor complexes of a virus assembly machine
Authors: Yang Qin , Catalano Carlos E 
Published: April 2020

AbstractThe assembly of double-stranded DNA viruses, from phages to herpesviruses, is strongly conserved. Terminase enzymes processively excise and package monomeric genomes from a concatemeric DNA substrate. The enzymes cycle between a stable maturation complex that introduces site-specific nicks into the duplex and a dynamic motor complex that rapidly translocates DNA into a procapsid shell, fueled by ATP hydrolysis. These tightly coupled reactions are catalyzed by terminase assembled into two functionally distinct nucleoprotein complexes; the maturation complex and the packaging motor complex, respectively. We describe the effects of nucleotides on the assembly of a catalytically competent maturation complex on viral DNA, their effect on maturation complex stability and their requirement for the transition to active packaging motor complex. ATP plays a major role in regulating all of these activities and may serve as a ‘nucleotide switch’ that mediates transitions between the two complexes during processive genome packaging. These biological processes are recapitulated in all of the dsDNA viruses that package monomeric genomes from concatemeric DNA substrates and the nucleotide switch mechanism may have broad biological implications with respect to virus assembly mechanisms.
Deacetylation enhances ParB–DNA interactions affecting chromosome segregation in Streptomyces coelicolor
Authors: Li Peng , Zhang Hong , Zhao Guo-Ping , Zhao Wei 
Published: April 2020

Abstract
Reversible lysine acetylation plays regulatory roles in diverse biological processes, including cell metabolism, gene transcription, cell apoptosis and ageing. Here, we show that lysine acetylation is involved in the regulation of chromosome segregation, a pivotal step during cell division in Streptomyces coelicolor. Specifically, deacetylation increases the DNA-binding affinity of the chromosome segregation protein ParB to the centromere-like sequence parS. Both biochemical and genetic experiments suggest that the deacetylation process is mainly modulated by a sirtuin-like deacetylase ScCobB1. The Lys-183 residue in the helix-turn-helix region of ParB is the major deacetylation site responsible for the regulation of ParB-parS binding. In-frame deletion of SccobB1 represses formation of ParB segregation complexes and leads to generation of abnormal spores. Taken together, these observations provide direct evidence that deacetylation participates in the regulation of chromosome segregation by targeting ParB in S. coelicolor.
Structural and functional characterization of the severe fever with thrombocytopenia syndrome virus L protein
Authors: Vogel Dominik , Thorkelsson Sigurdur Rafn , Quemin Emmanuelle R J , Meier Kristina , Kouba Tomas , Gogrefe Nadja , Busch Carola , Reindl Sophia , Günther Stephan , Cusack Stephen , Grünewald Kay , Rosenthal Maria 
Published: April 2020

Abstract
The Bunyavirales order contains several emerging viruses with high epidemic potential, including Severe fever with thrombocytopenia syndrome virus (SFTSV). The lack of medical countermeasures, such as vaccines and antivirals, is a limiting factor for the containment of any virus outbreak. To develop such antivirals a profound understanding of the viral replication process is essential. The L protein of bunyaviruses is a multi-functional and multi-domain protein performing both virus transcription and genome replication and, therefore, is an ideal drug target. We established expression and purification procedures for the full-length L protein of SFTSV. By combining single-particle electron cryo-microscopy and X-ray crystallography, we obtained 3D models covering ∼70% of the SFTSV L protein in the apo-conformation including the polymerase core region, the endonuclease and the cap-binding domain. We compared this first L structure of the Phenuiviridae family to the structures of La Crosse peribunyavirus L protein and influenza orthomyxovirus polymerase. Together with a comprehensive biochemical characterization of the distinct functions of SFTSV L protein, this work provides a solid framework for future structural and functional studies of L protein–RNA interactions and the development of antiviral strategies against this group of emerging human pathogens.
Diagnostic Accuracy of Non-Invasive Thermal Evaluation of Ventriculoperitoneal Shunt Flow in Shunt Malfunction: A Prospective, Multi-Site, Operator-Blinded Study
Authors: Madsen Joseph R , Boyle Tehnaz P , Neuman Mark I , Park Eun-Hyoung , Tamber Mandeep S , Hickey Robert W , Heuer Gregory G , Zorc Joseph J , Leonard Jeffrey R , Leonard Julie C , Keating Robert , Chamberlain James M , Frim David M , Zakrzewski Paula , Klinge Petra , Merck Lisa H , Piatt Joseph , Bennett Jonathan E , Sandberg David I , Boop Frederick A , Hameed Mustafa Q 
Published: April 2020

Abstract

BACKGROUND
Thermal flow evaluation (TFE) is a non-invasive method to assess ventriculoperitoneal shunt function. Flow detected by TFE is a negative predictor of the need for revision surgery. Further optimization of testing protocols, evaluation in multiple centers, and integration with clinical and imaging impressions prompted the current study.

OBJECTIVE
To compare the diagnostic accuracy of 2 TFE protocols, with micropumper (TFE+MP) or without (TFE-only), to neuro-imaging in patients emergently presenting with symptoms concerning for shunt malfunction.

METHODS
We performed a prospective multicenter operator-blinded trial of a consecutive series of patients who underwent evaluation for shunt malfunction. TFE was performed, and preimaging clinician impressions and imaging results were recorded. The primary outcome was shunt obstruction requiring neurosurgical revision within 7 d. Non-inferiority of the sensitivity of TFE vs neuro-imaging for detecting shunt obstruction was tested using a prospectively determined a priori margin of −2.5%.

RESULTS
We enrolled 406 patients at 10 centers. Of these, 68/348 (20%) evaluated with TFE+MP and 30/215 (14%) with TFE-only had shunt obstruction. The sensitivity for detecting obstruction was 100% (95% CI: 88%-100%) for TFE-only, 90% (95% CI: 80%-96%) for TFE+MP, 76% (95% CI: 65%-86%) for imaging in TFE+MP cohort, and 77% (95% CI: 58%-90%) for imaging in the TFE-only cohort. Difference in sensitivities between TFE methods and imaging did not exceed the non-inferiority margin.

CONCLUSION
TFE is non-inferior to imaging in ruling out shunt malfunction and may help avoid imaging and other steps. For this purpose, TFE only is favored over TFE+MP.
Plasminogen improves lung lesions and hypoxemia in patients with COVID-19
Authors: Wu Y , Wang T , Guo C , Zhang D , Ge X , Huang Z , Zhou X , Li Y , Peng Q , Li J 
Published: April 2020

Abstract

Background
Lungs from patients with coronavirus disease 2019 (COVID-19) have shown typical signs of acute respiratory distress syndrome (ARDS), formation of hyaline membrane mainly composed of fibrin and ‘ground-glass’ opacity. Previously, we showed plasminogen itself is a key regulator in fibrin degradation, wound healing and infection.

Aim
We aimed to investigate whether plasminogen can improve lung lesions and hypoxemia of COVID-19.

Design
Thirteen clinically moderate, severe or critical COVID-19 patients were treated with atomization inhalation of freeze-dried plasminogen.

Methods
Levels of their lung lesions, oxygen saturation and heart rates were compared before and after treatment by computed tomography scanning images and patient monitor.

Results
After plasminogen inhalation, conditions of lung lesions in five clinically moderate patients have quickly improved, shown as the decreased range and density of ‘ground glass’ opacity. Improvements of oxygen saturation were observed in six clinically severe patients. In the two patients with critical conditions, the oxygen levels have significantly increased from 79–82% to 91% just about 1 h after the first inhalation. In 8 of 13 patients, the heart rates had slowed down. For the five clinically moderate patients, the difference is even statistically significant. Furthermore, a general relief of chest tightness was observed.

Conclusion
Whereas it is reported that plasminogen is dramatically increased in adults with ARDS, this study suggests that additional plasminogen may be effective and efficient in treating lung lesions and hypoxemia during COVID-19 infections. Although further studies are needed, this study highlights a possible hope of efficiently combating this rapid epidemic emergency.
Changing research on research evaluation: A critical literature review to revisit the agenda
Authors: Thomas Duncan A , Nedeva Maria , Tirado Mayra M , Jacob Merle 
Published: April 2020

Abstract
The current range and volume of research evaluation-related literature is extensive and incorporates scholarly and policy/practice-related perspectives. This reflects academic and practical interest over many decades and trails the changing funding and reputational modalities for universities, namely increased selectivity applied to institutional research funding streams and the perceived importance of university rankings and other reputational devices. To make sense of this highly diverse body of literature, we undertake a critical review of over 350 works constituting, in our view, the ‘state-of-the-art’ on institutional performance-based research evaluation arrangements (PREAs). We focus on PREAs because they are becoming the predominant means world-wide to allocate research funds and accrue reputation for universities. We highlight the themes addressed in the literature and offer critical commentary on the balance of scholarly and policy/practice-related orientations. We then reflect on five limitations to the state-of-the-art and propose a new agenda, and a change of perspective, to progress this area of research in future studies.
An objective and reliable electrophysiological marker for implicit trustworthiness perception
Authors: Swe Derek C , Palermo Romina , Gwinn O Scott , Rhodes Gillian , Neumann Markus , Payart Shanèle , Sutherland Clare A M 
Published: April 2020

AbstractTrustworthiness is assumed to be processed implicitly from faces, despite the fact that the overwhelming majority of research has only involved explicit trustworthiness judgements. To answer the question whether or not trustworthiness processing can be implicit, we apply an electroencephalography fast periodic visual stimulation (FPVS) paradigm, where electrophysiological cortical activity is triggered in synchrony with facial trustworthiness cues, without explicit judgements. Face images were presented at 6 Hz, with facial trustworthiness varying at 1 Hz. Significant responses at 1 Hz were observed, indicating that differences in the trustworthiness of the faces were reflected in the neural signature. These responses were significantly reduced for inverted faces, suggesting that the results are associated with higher order face processing. The neural responses were reliable, and correlated with explicit trustworthiness judgements, suggesting that the technique is capable of picking up on stable individual differences in trustworthiness processing. By demonstrating neural activity associated with implicit trustworthiness judgements, our results contribute to resolving a key theoretical debate. Moreover, our data show that FPVS is a valuable tool to examine face processing at the individual level, with potential application in pre-verbal and clinical populations who struggle with verbalization, understanding or memory.
Adjuvant and neoadjuvant chemotherapy in pancreatic ductal adenocarcinoma
Authors: Leonhardt Carl S. , Traub Benno , Hackert Thilo , Klaiber Ulla , Strobel Oliver , Büchler Markus W. , Neoptolemos John P. 
Published: April 2020

Abstract
The management of pancreatic cancer has dramatically changed since the first major randomized trial published in 2001 by the European Study Group for Pancreatic Cancer (ESPAC) stimulated the development of multimodality oncosurgical therapies. ESPAC-1 demonstrated a survival improvement from upfront surgery of only 8%, increasing to 21% 5-year survival for 5-fluorouracil/folinic acid but only 10.8% for chemoradiotherapy. ESPAC-4 has shown a 5-year survival rate of 30% for all patients without restriction of 30% using a combination of gemcitabine and capecitabine, rising to 40% in those with an R0 resection margin, or nearly 50% in those with N0 lymph node status. In selected patients with favorable prognostic features mFOLFIRINOX can produce a 50% 5-year survival rate but with added toxicity. While a positive resection margin is associated with an increased likelihood of local recurrence, this of itself is not the contributor to reduced survival, but rather reflects the increased probability of systemic disease. Thus, strategies aimed at local control, may reduce subsequent local progression, but will not improve overall survival. Neoadjuvant chemotherapy is increasingly utilized in cases of borderline resectable or locally advanced pancreatic cancer, but there is still a lack of proof of concept studies. High-quality evidence from randomized controlled trials to identify the indications and benefits of neoadjuvant therapy in pancreatic cancer are required. The use of patient-derived tumor organoids may predict response to chemotherapy which could open a new opportunity in pancreatic cancer treatment, stratifying patients into treatment groups based on their response to these therapies in the laboratory.
Automated Pupillometry as an Adjunct to Clinical Examination in Patients With Acute Vision Loss
Authors: Bhatnagar Roshni , Birnbaum Andrea D. , Baqai Jeanine , Volpe Nicholas J. 
Published: April 2020

Background:
Despite automated pupillometry's (AP) improved detection of relative afferent pupillary defects (RAPDs) compared with the Swinging Flashlight Test (SFT), AP remains uncommon in clinical practice. This study examined barriers to routine use of AP in evaluation of acute vision loss.

Methods:
(1) Ophthalmologists and optometrists' perceptions of AP were captured via electronic survey. (2) Ophthalmologists were presented with clinical vignettes to assess their use of AP in clinical decision-making. (3) Patients presenting with decreased vision to an ophthalmology urgent care clinic underwent manual SFT and AP screening to evaluate ophthalmologists' perceptions of the device.

Results:
Surveys indicated that clinicians were “neutral” to “somewhat likely” to use AP. In clinical vignettes, more physicians proceeded with workup for optic nerve pathology when presented with an RAPD by AP than SFT (77% vs 26%, P = 0.003). When SFT and AP results were discordant, more physicians proceeded with workup for optic nerve disease when AP was positive and SFT was negative than vice versa (61% vs 18%, P = 0.008). In the clinical study of 21 patients, 50% of RAPDs detected by AP were not detected by SFT, although ophthalmologists rated AP's usefulness as only “neutral” to “somewhat useful.”

Conclusion:
Clinicians value pupillary examination and trust AP over SFT; however, widespread adoption and perceived value of AP may depend on its impact on clinical outcomes. Within a comprehensive diagnostic device, AP may be an important tool, but is not necessary to screen for optic nerve disease or evaluate acute vision loss.
Clinical features, Diagnosis, and Treatment of COVID-19: A systematic review of case reports and case series
Authors: Tahvildari Azin , Arbabi Mahta , Farsi Yeganeh , Jamshidi Parnian , Hasanzadeh Saba , Calcagno Tess Moore , Nasiri Mohammad Javad , Mirsaeidi Mehdi 
Published: April 2020

AbstractObjectivesThe 2019 novel coronavirus (COVID-19) has been declared a public health emergency worldwide. The objective of this systematic review was to characterize the clinical, diagnostic, and treatment characteristics of patients presenting with COVID-19.MethodsWe conducted a structured search using PubMed/Medline, Embase, Web of Science and the Cochrane Library to collect both case reports and case series on COVID-19 published up to February 30, 2020.ResultsThirty-four articles were included analyzing a total of 99 patients with a mean age of 46.2 years. The most common presenting symptom in patients who tested positive for COVID-19 was fever, reported in up to 83% of patients from 76.4% of the analyzed studies. Other symptoms including rhinorrhea, dizziness, and chills were less frequently reported. Additionally, in studies which reported C-reactive protein (CRP) measurements (44%), a large majority of patients displayed an elevated CRP (73%). Progression to acute respiratory distress syndrome (ARDS) was the most common complication of patients testing positive for COVID-19 (33%). CT images displayed ground-glass opacification (GGO) patterns (80%) as well as bilateral lung involvement (71.0%). The most commonly used antiviral treatment modalities included, lopinavir (HIV protease inhibitor), arbidiol hydrochloride (influenza fusion inhibitor), and oseltamivir (neuraminidase inhibitor).ConclusionsDevelopment of ARDS may play a role in estimating disease progression and mortality risk. Early detection of elevations in serum CRP, combined with a clinical COVID-19 symptom presentation may be used as a surrogate marker for presence and severity of disease. There is a paucity of data surrounding the efficacy of treatments. There is currently not a well-established gold standard therapy for the treatment of diagnosed COVID-19. Further prospective investigations are necessary.
deepMINE - Natural Language Processing based Automatic Literature Mining and Research Summarization for Early-Stage Comprehension in Pandemic Situations specifically for COVID-19
Authors: Joshi Bhrugesh , Bakarola Vishvajit , Shah Parth , Krishnamurthy Ramar 
Published: April 2020

AbstractThe recent pandemic created due to Novel Coronavirus (nCOV-2019) from Wuhan, China demanding a large scale of a general health emergency. This demands novel research on the vaccine to fight against this pandemic situation, re-purposing of the existing drugs, phylogenetic analysis to identify the origin and determine the similarity with other known viruses, etc. The very preliminary task from the research community is to analyze the wide verities of existing related research articles, which is very much time-consuming in such situations where each minute counts for saving hundreds of human lives. The entire manual processing is even lower down the efficiency in mining the information. We have developed a complete automatic literature mining system that delivers efficient and fast mining from existing biomedical literature databases. With the help of modern-day deep learning algorithms, our system also delivers a summarization of important research articles that provides ease and fast comprehension of critical research articles. The system is currently scanning nearly 1,46,115,136 English words from 29,315 research articles in not greater than 1.5 seconds with multiple search keywords. Our research article presents the criticality of literature mining, especially in pandemic situations with the implementation and online deployment of the system.
Predicting Mortality Risk in Patients with COVID-19 Using Artificial Intelligence to Help Medical Decision-Making
Authors: Pourhomayoun Mohammad , Shakibi Mahdi 
Published: April 2020

AbstractIn the wake of COVID-19 disease, caused by the SARS-CoV-2 virus, we designed and developed a predictive model based on Artificial Intelligence (AI) and Machine Learning algorithms to determine the health risk and predict the mortality risk of patients with COVID-19. In this study, we used documented data of 117,000 patients world-wide with laboratory-confirmed COVID-19. This study proposes an AI model to help hospitals and medical facilities decide who needs to get attention first, who has higher priority to be hospitalized, triage patients when the system is overwhelmed by overcrowding, and eliminate delays in providing the necessary care. The results demonstrate 93% overall accuracy in predicting the mortality rate. We used several machine learning algorithms including Support Vector Machine (SVM), Artificial Neural Networks, Random Forest, Decision Tree, Logistic Regression, and K-Nearest Neighbor (KNN) to predict the mortality rate in patients with COVID-19. In this study, the most alarming symptoms and features were also identified. Finally, we used a separate dataset of COVID-19 patients to evaluate our developed model accuracy, and used confusion matrix to make an in-depth analysis of our classifiers and calculate the sensitivity and specificity of our model.
In silicoapproach for designing of a multi-epitope based vaccine against novel Coronavirus (SARS-COV-2)
Authors: Saha Ratnadeep , Prasad Burra V L S 
Published: April 2020

AbstractA novel Coronavirus (SARS-COV-2) has now become a global pandemic. Considering the severity of infection and the associated mortalities, there is an urgent need to develop an effective preventive measure against this virus. In this study, we have designed a novel vaccine construct using computational strategies. Spike (S) glycoprotein is the major antigenic component that trigger the host immune responses. Detailed investigation of S protein with various immunoinformatics tools enabled us to identify 5 MHC I and 5 MHC II B-cell derived T-cell epitopes with VaxiJen score > 1 and IC50value < 100nM. These epitopes were joined with a suitable adjuvant and appropriate linkers to form a multi-epitope based vaccine construct. Further, in silico testing of the vaccine construct for its antigenicity, allergenicity, solubility, and other physicochemical properties showed it to be safe and immunogenic. Suitable tertiary structure of the vaccine protein was generated using 3Dpro of SCRATCH suite, refined with GalaxyRefine, and validated with ProSA, PROCHECK, and ERRAT server. Finally, molecular docking studies were performed to ensure a favorable binding affinity between the vaccine construct and TLR3 receptor. The designed multi-epitope vaccine showed potential to elicit specific immune responses against the SARS-COV-2. However, further wet lab validation is necessary to confirm the actual effectiveness, safety and immunogenic potency of the vaccine construct against derived in this study.
A SARS-CoV-2 Vaccination Strategy Focused on Population-Scale Immunity
Authors: Yarmarkovich Mark , Warrington John M. , Farrel Alvin , Maris John M. 
Published: April 2020

SummaryHere we propose a vaccination strategy for SARS-CoV-2 based on identification of both highly conserved regions of the virus and newly acquired adaptations that are presented by MHC class I and II across the vast majority of the population, are highly dissimilar from the human proteome, and are predicted B cell epitopes. We present 65 peptide sequences that we expect to result in a safe and effective vaccine which can be rapidly tested in DNA, mRNA, or synthetic peptide constructs. These include epitopes that are contained within evolutionarily divergent regions of the spike protein reported to increase infectivity through increased binding to the ACE2 receptor, and within a novel furin cleavage site thought to increase membrane fusion. This vaccination strategy specifically targets unique vulnerabilities of SARS-CoV-2 and should engage a robust adaptive immune response in the vast majority of the human population.