bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stroke Rate, Subtype, and Cardiovascular Risk Factors in Nonarteritic Anterior Ischemic Optic Neuropathy: A Population-Based Study
Authors: Foster Robert C. , Bhatti M. Tariq , Crum Olivia M. , Lesser Elizabeth R. , Hodge David O. , Klaas James P. , Chen John J. 
Published: April 2020

Background:
Nonarteritic anterior ischemic optic neuropathy (NAION) is a common cause of acute optic neuropathy in adults and is associated with vascular risk factors. Owing to the overlapping risk factor profiles between NAION and cerebral stroke, previous studies have produced conflicting results with regard to NAION as an independent risk factor for stroke.

Methods:
A retrospective chart review was conducted using the Rochester Epidemiology Project database to identify all cases of NAION occurring among Olmsted County, Minnesota residents from January 1, 1990, through December 31, 2016. Stroke events were characterized using clinical and radiologic data. Comparison was made to an age- and sex-matched control group with similar vascular risk factors.

Results:
One-hundred four patients with NAION and 104 control subjects were analyzed. Median age at diagnosis was 65 years (range, 40–90 years). Thirteen patients (13%) with NAION and 10 controls (10%) had symptomatic strokes after the age of 40 years. Among patients with NAION, 6 (46%) suffered a stroke before the diagnosis of NAION, 5 (39%) at least 5 months after the NAION diagnosis, and 2 patients (15%) suffered strokes both before and after the NAION. The cumulative probability of symptomatic strokes for patients with NAION was not significantly different than for controls (hazard ratio = 1.50, 95% confidence interval: 0.66–3.42; P = 0.34). There were no cardioembolic strokes within 1 month of the NAION diagnosis. The mechanism of symptomatic strokes did not differ between the 2 groups.

Conclusions:
NAION does not confer an increased risk of symptomatic stroke beyond the risk posed by age and existing vascular risk factors.
Scrutinizing the SARS-CoV-2 protein information for the designing an effective vaccine encompassing both the T-cell and B-cell epitopes
Authors: Jain Neha , Shankar Uma , Majee Prativa , Kumar Amit 
Published: April 2020

ABSTRACTNovel SARS coronavirus (SARS-CoV-2) has caused a pandemic condition world-wide and has been declared as public health emergency of International concern by WHO in a very short span of time. The community transmission of this highly infectious virus has severely affected various parts of China, Italy, Spain and USA among others. The prophylactic solution against SARS-CoV-2 infection is challenging due to the high mutation rate of its RNA genome. Herein, we exploited a next generation vaccinology approach to construct a multi-epitope vaccine candidate against SARS-CoV-2 with high antigenicity, safety and efficacy to combat this deadly infectious agent. The whole proteome was scrutinized for the screening of highly conserved, antigenic, non-allergen and non-toxic epitopes having high population coverage that can elicit both humoral and cellular mediated immune response against COVID-19 infection. These epitopes along with four different adjuvants were utilized to construct a multi-epitope vaccine candidate that can generate strong immunological memory response having high efficacy in humans. Various physiochemical analyses revealed the formation of a stable vaccine product having a high propensity to form a protective solution against the detrimental SARS-CoV-2 strain with high efficacy. The vaccine candidate interacted with immunological receptor TLR3 with high affinity depicting the generation of innate immunity. Further, the codon optimization and in silico expression show the plausibility of the high expression and easy purification of the vaccine product. Thus, this present study provides an initial platform of the rapid generation of an efficacious protective vaccine for combating COVID-19.
Perception of emergent epidemic of COVID-2019 / SARS CoV-2 on the Polish Internet
Authors: Jarynowski Andrzej , Wójta-Kempa Monika , Belik Vitaly 
Published: April 2020

ProblemDue to the spread of SARS CoV-2 virus infection and COVID-2019 disease, there is an urgent need to analyze COVID-2019 epidemic perception in Poland. This would enable authorities for preparation of specific actions minimizing public health and economic risks.MethodsWe study the perception of COVID-2019 epidemic in Polish society using quantitative analysis of its digital footprints on the Internet (onTwitter, Google, YouTube, Wikipediaand electronic media represented byEvent Registry) from January 2020 to 12.03.2020 (before and after official introduction to Poland on 04.03.2020). To this end we utilize data mining, social network analysis, natural language processing techniques. Each examined internet platform was analyzed for representativeness and composition of the target group.ResultsWe identified three temporal major cluster of the interest before disease introduction on the topic COVID-2019: China- and Italy-related peaks on all platforms, as well as a peak on social media related to the recent special law on combating COVID-2019. Besides, there was a peak in interest on the day of officially confirmed introduction as well as an exponential increase of interest when the Polish government “declared war against disease” with a massive mitigation program. From sociolingistic perspective, we found that concepts and issues of threat, fear and prevention prevailed before introduction. After introduction, practical concepts about disease and epidemic dominate. We have found out that Twitter reflected the structural division of the Polish political sphere. We were able to identify clear communities of governing party, mainstream oppostition and a protestant group and potential sources of disinformation. We have also detected bluring boundaries between comminities after disease introduction.ConclusionsTraditional and social media do not only reflect reality, but also create it. Due to filter “bubbles” observed on Twitter, public information campaigns might have less impact on society than expected. For greater penetration, it might be necessary to diversify information channels to reach as many people as possible which might already be happening. Moreover, it might be necessary to prevent the spread of disinformation, which is now possible in Poland due to the special law on combating COVID-2019.
SARS-CoV-2 infection in health care workers: a retrospective analysis and model study
Authors: Bai Yansen , Wang Xuan , Huang Qimin , Wang Han , Gurarie David , Ndeffo-Mbah Martial , Fan Fei , Fu Peng , Horn Mary Ann , Xu Shuai , Mondal Anirban , Jiang Xiaobing , Zhao Hongyang 
Published: April 2020

ABSTRACTBackgroundThere had been a preliminary occurrence of human-to-human transmissions between healthcare workers (HCWs), but risk factors in the susceptibility for COVID-19, and infection patterns among HCWs have largely remained unknown.MethodsRetrospective data collection on demographics, lifestyles, contact status with infected subjects for 118 HCWs (include 12 COVID-19 HCWs) from a single-center. Sleep quality and working pressure were evaluated by Pittsburgh Sleep Quality Index (PSQI) and The Nurse Stress Index (NSI), respectively. Follow-up duration was from Dec 25, 2019, to Feb 15, 2020. Risk factors and transmission models of COVID-19 among HCWs were analyzed and constructed.FindingsA high proportion of COVID-19 HCWs had engaged in night shift-work (75.0% vs. 40.6%) and felt they were working under pressure (66.7% vs. 32.1%) than uninfected HCWs. COVID-19 HCWs had higher total scores of PSQI and NSI than uninfected HCWs. Furthermore, these scores were both positively associated with COVID-19 risk. An individual-based model (IBM) estimated the outbreak duration among HCWs in a non-typical COVID-19 ward at 62-80 days and the basic reproduction numberR0=1.27 [1.06, 1.61]. By reducing the average contact rate per HCW by a 1.35 factor and susceptibility by a 1.40 factor, we can avoid an outbreak of the basic case among HCWs.InterpretationPoor sleep quality and high working pressure were positively associated with high risks of COVID-19. A novel IBM of COVID-19 transmission is suitable for simulating different outbreak patterns in a hospital setting.FundingFundamental Research Funds for the Central Universities
Multiscale ATUM-FIB microscopy enables targeted ultrastructural analysis at isotropic resolution
Authors: Kislinger Georg , Gnägi Helmut , Kerschensteiner Martin , Simons Mikael , Misgeld Thomas , Schifferer Martina 
Published: April 2020

AbstractVolume electron microscopy enables the ultrastructural analysis of biological tissues and is essential for dense reconstructions e.g. of neuronal circuits. So far, three-dimensional analysis is based on either serial sectioning followed by sequential imaging (ATUM, ssTEM/SEM) or serial block-face imaging (SB-SEM, FIB-SEM), where imaging is intercalated with sectioning. Currently, the techniques involving ultramicrotomy allow scanning large fields of view, but afford only limited z-resolution determined by section thickness, while ion beam-milling approaches yield isotropic voxels, but are restricted in volume size. Now we present a hybrid method, named ATUM-FIB, which combines the advantages of both approaches: ATUM-FIB is based on serial sectioning of tissue into semithick (2-10 µm) resin sections that are collected onto transparent tape. 3D information obtained by serial light and electron microscopy allows identifying regions of interest that are then directly accessible for targeted FIB-SEM. The set of serial semithin sections thus represent a tissue ‘library’, which provides information about microscopic tissue context that can then be probed ‘on demand’ by local high resolution analysis. We demonstrate the potential of this technique to reveal the ultrastructure of rare but pathologically important events by identifying microglia contact sites with amyloid plaques in a mouse model for familial Alzheimer’s disease.
CeTF: an R package to Coexpression for Transcription Factors using Regulatory Impact Factors (RIF) and Partial Correlation and Information (PCIT) analysis
Authors: de Biagi Carlos Alberto Oliveira , Nociti Ricardo Perecin , Funicheli Breno Osvaldo , de Cássia Ruy Patrícia , Ximenez João Paulo Bianchi , Silva Wilson Araújo 
Published: April 2020

AbstractSummaryFinding meaningful gene-gene associations and the main Transcription Factors (TFs) in co-expression networks is one of the most important challenges in gene expression data mining. CeTF is an R package that integrates the Partial Correlation with Information Theory (PCIT) and Regulatory Impact Factors (RIF) algorithms applied to gene expression data from microarray, RNA-seq, or single-cell RNA-seq platforms. This approach allows identifying the transcription factors most likely to regulate a given network in different biological systems — for example, regulation of gene pathways in tumor stromal cells and tumor cells of the same tumor. This pipeline can be easily integrated into the high-throughput analysis.AvailabilityCeTF is available as R package in Bioconductor (https://bioconductor.org/packages/CeTF), GitHub (https://github.com/cbiagii/CeTF) and as docker image (https://hub.docker.com/r/biagii/cetf). More information on how to use the package can be found in the Supplemental File 1.
Maintained representations of the ipsilateral and contralateral limbs during bimanual control in primary motor cortex
Authors: Cross Kevin P. , Heming Ethan A. , Cook Douglas J. , Scott Stephen H. 
Published: April 2020

AbstractPrimary motor cortex (M1) almost exclusively controls the contralateral side of the body. However, M1 activity is also modulated during ipsilateral body movements. Previous work has shown that M1 activity related to the ipsilateral arm is independent of the M1 activity related to the contralateral arm. How do these patterns of activity interact when both arms move simultaneously? We explored this problem by training two monkeys (male, Macaca mulatta) in a postural perturbation task while recording from M1. Loads were applied to one arm at a time (unimanual) or both arms simultaneously (bimanual). We found 83% of neurons were responsive to both the unimanual and bimanual loads. We also observed a small reduction in activity magnitude during the bimanual loads for both limbs (25%). Across the unimanual and bimanual loads, neurons largely maintained their preferred load directions. However, there was a larger change in the preferred loads for the ipsilateral limb (~25%) than the contralateral limb (~9%). Lastly, we identified the contralateral and ipsilateral subspaces during the unimanual loads and found they captured a significant amount of the variance during the bimanual loads. However, the subspace captured more of the bimanual variance related to the contralateral limb (97%) than the ipsilateral limb (66%). Our results highlight that even during bimanual motor actions, M1 largely retains its representations of the contralateral and ipsilateral limbs.Significance StatementPrevious work has shown that primary motor cortex (M1) reflects information related to the contralateral limb, its downstream target, but also reflects information related to the ipsilateral limb. Can M1 still reflect both sources of information when performing simultaneous movements of the limbs? Here we use a postural perturbation task to show that M1 activity maintains a similar representation for the contralateral limb during bimanual motor actions, while there is only a modest change in the representation of the ipsilateral limb. Our results indicate that two orthogonal representations can be maintained and expressed simultaneously in M1.
Biophysical characterization of the SARS-CoV-2 spike protein binding with the ACE2 receptor and implications for infectivity
Authors: Chowdhury Ratul , Maranas Costas D. 
Published: April 2020

AbstractSARS-CoV-2 is a novel highly virulent pathogen which gains entry to human cells by binding with the cell surface receptor – angiotensin converting enzyme (ACE2). We computationally contrasted the binding interactions between human ACE2 and coronavirus spike protein receptor binding domain (RBD) of the 2002 epidemic-causing SARS-CoV-1, SARS-CoV-2, and bat coronavirus RaTG13 using the Rosetta energy function. We find that the RBD of the spike protein of SARS-CoV-2 is highly optimized to achieve very strong binding with human ACE2 (hACE2) which is consistent with its enhanced infectivity. SARS-CoV-2 forms the most stable complex with hACE2 compared to SARS-CoV-1 (23% less stable) or RaTG13 (11% less stable) while occupying the greatest number of residues in the ATR1 binding site. Notably, the SARS-CoV-2 RBD out-competes the angiotensin 2 receptor type I (ATR1) which is the native binding partner of ACE2 by 35% in terms of the calculated binding affinity. Strong binding is mediated through strong electrostatic attachments with every fourth residue on the N-terminus alpha-helix (starting from Ser19 to Asn53) as the turn of the helix makes these residues solvent accessible. By contrasting the spike protein SARS-CoV-2 Rosetta binding energy with ACE2 of different livestock and pet species we find strongest binding with bat ACE2 followed by human, feline, equine, canine and finally chicken. This is consistent with the hypothesis that bats are the viral origin and reservoir species. These results offer a computational explanation for the increased infectivity of SARS-CoV-2 and allude to therapeutic modalities by identifying and rank-ordering the ACE2 residues involved in binding with the virus.
High-resolution Structures of multiple 5-HT3AR-setron complexes reveal a novel mechanism of competitive inhibition
Authors: Basak Sandip , Kumar Arvind , Ramsey Steven , Gibbs Eric , Kapoor Abhijeet , Filizola Marta , Chakrapani Sudha 
Published: April 2020

AbstractSerotonin receptors (5-HT3AR) play a crucial role in regulating gut movement, and are the principal target of setrons, a class of high-affinity competitive antagonists, used in the management of nausea and vomiting associated with radiation and chemotherapies. Structural insights into setron-binding poses and their inhibitory mechanisms are just beginning to emerge. Here, we present high-resolution cryo-EM structures of full-length 5-HT3AR in complex with palonosetron, ondansetron, and alosetron. Each structure reveals a distinct interaction fingerprint between the setron and binding-pocket residues that may underlie their diverse affinities. In addition, setrons elicit varying degrees of conformational change throughout the channel that, quite surprisingly, lie along the channel activation pathway, suggesting a novel mechanism of competitive inhibition. Molecular dynamic simulations were used to assess binding-poses and the drug-target interaction dynamics. Together, this study provides a molecular basis for setron binding affinities and their inhibitory effects.
Dopamine Signaling in the Dorsomedial Striatum Promotes Compulsive Behavior
Authors: Seiler Jillian L. , Cosme Caitlin V. , Sherathiya Venus N. , Bianco Joseph M. , Bridgemohan Abigael S. , Lerner Talia N. 
Published: April 2020

SUMMARYCompulsive behavior is a defining feature of disorders such as substance use disorder and obsessive-compulsive disorder. Current evidence suggests that corticostriatal circuits control the expression of established compulsions, but little is known about the mechanisms regulating the development of compulsions. We hypothesized that dopamine, a critical modulator of striatal synaptic plasticity, could control alterations in corticostriatal circuits leading to the development of compulsions (defined as continued reward-seeking in the face of punishment). We used dual-site fiber photometry to measure dopamine axon activity in the dorsomedial striatum (DMS) and the dorsolateral striatum (DLS) as compulsions emerged. Individual variability in the speed with which compulsions emerged was predicted by DMS dopamine axon activity. Amplifying this dopamine signal accelerated animals’ transitions to compulsion, whereas inhibition led to learning delays. In contrast, amplifying DLS dopamine signaling had no effect on the emergence of compulsions. These results establish DMS dopamine signaling as a key controller of the development of compulsive reward-seeking.
Long-Term Performance of Utah Slanted Electrode Arrays and Intramuscular Electromyographic Leads Implanted Chronically in Human Arm Nerves and Muscles
Authors: George Jacob A. , Page David M. , Davis Tyler S. , Duncan Christopher C. , Hutchinson Douglas T. , Rieth Loren W. , Clark Gregory A. 
Published: April 2020

AbstractObjectiveWe explore the long-term performance and stability of seven percutanous Utah Slanted Electrode Arrays (USEAs) and intramuscular recording leads (iEMGs) implanted chronically in the residual arm nerves and muscles of three human amputees as a means to permanently restore sensorimotor function after upper-limb.ApproachWe quantify the number of functional recording and functional stimulating electrodes over time. We also calculate the signal-to-noise ratio of USEA and iEMG recordings and quantify the stimulation amplitude necessary to evoke detectable sensory percepts. Furthermore, we quantify the consistency of the sensory modality, receptive field location, and receptive field size of USEA-evoked percepts.Main ResultsIn the most recent subject, involving USEAs with technical improvements, neural recordings persisted for 502 days (entire implant duration) and the number of functional recording electrodes for one USEA increased over time. However, for six out of seven USEAs the number of functional recording electrodes decreased within the first two months after implantation. The signal-to-noise ratio of neural recordings and electromyographic recordings stayed relatively consistent over time. Sensory percepts were consistently evoked over the span of 14 months, were not significantly different in size, and highlighted the nerves’ fascicular organization. The percentage of percepts with consistent modality or consistent receptive field location between sessions (~1 month apart) varied between 0–86.2% and 9.1–100%, respectively. Stimulation thresholds and electrode impedances increased initially but then remained relatively stable over time.SignificanceThis work demonstrates improved performance of USEAs, and provides a basis for comparing the longevity and stability of USEAs to that of other neural interfaces. Although USEAs provide a rich repertoire of neural recordings and sensory percepts, performance still generally declines over time. Future work should leverage the results presented here to further improve USEA design or to develop adaptive algorithms that can maintain a high level of performance.
Female rats self-administer heroin by vapor inhalation
Authors: Gutierrez Arnold , Nguyen Jacques D. , Creehan Kevin M. , Taffe Michael A. 
Published: April 2020

AbstractOver the last two decades the United States has experienced a significant increase in the medical and non-medical use of opioid drugs, resulting in record numbers of opioid-related overdoses and deaths. There was an initial increase in non-medical use of prescription opioids around 2002, followed later by increased heroin use and then most recently fentanyl. Inhalation is a common route of administration for opioids, with a documented history spanning back to Mediterranean antiquity and up through modern use with e-cigarette devices. Unfortunately, preclinical studies using inhalation as the route of administration remain relatively few. This study was conducted to determine the efficacy of e-cigarette vapor inhalation of heroin in rats. Non-contingent exposure to heroin or methadone vapor produced anti-nociceptive efficacy in male and female rats. Female rats were trained to self-administer heroin vapor; the most-preferring half of the distribution obtained more vapor reinforcers when the concentration of heroin was reduced in the vapor vehicle and when pre-treated with the opioid receptor antagonist naloxone. The anti-nociceptive effect of heroin self-administered by vapor was identical in magnitude to that produced by intravenous self-administration. Finally, anxiety-like behavior increased 24-48 hours after last heroin vapor access, consistent with withdrawal signs observed after intravenous self-administration. In sum, these studies show that rewarding and anti-nociceptive effects of heroin are produced in rats by vapor inhalation using e-cigarette technology. Importantly, self-administration models by this route can be deployed to determine health effects of inhaled heroin or other opioids.