bluuebunny/crossref_metadata_2025_split huggingface dataset:
Language Mapping With Magnetoencephalography: An Update on the Current State of Clinical Research and Practice With Considerations for Clinical Practice Guidelines
Authors: Bowyer Susan M. , Zillgitt Andrew , Greenwald Margaret , Lajiness-O'Neill Renee 
Published: November 2020

Summary:
Numerous studies have shown that language processing is not limited to a few brain areas. Visual or auditory stimuli activate corresponding cortical areas, then memory identifies the word or image, Wernicke's and Broca's areas support the processing for either reading/listening or speaking and many areas of the brain are recruited. Determining how a normal person processes language helps clinicians and scientist to understand how brain pathologies such as tumor or stroke can affect changes in language processing. Patients with epilepsy may develop atypical language organization. Over time, the chronic nature of epileptic activity, or changes from a tumor or stroke, can result in a shift of language processing area from the left to the right hemisphere, or re-routing of language pathways from traditional to non-traditional areas within the dominant left hemisphere. It is important to determine where these language areas are prior to brain surgery. MEG evoked responses reflecting cerebral activation of receptive and expressive language processing can be localized using several different techniques: Single equivalent current dipole, current distribution techniques or beamformer techniques. Over the past 20 years there have been at least 25 validated MEG studies that indicate MEG can be used to determine the dominant hemisphere for language processing. The use of MEG neuroimaging techniques is needed to reliably predict altered language networks in patients and to provide identification of language eloquent cortices for localization and lateralization necessary for clinical care.
Auditory Mapping With MEG: An Update on the Current State of Clinical Research and Practice With Considerations for Clinical Practice Guidelines
Authors: Shvarts Vladimir , Mäkelä Jyrki P. 
Published: November 2020

Summary:Auditory evoked fields (AEFs) are well suited for studies of auditory processing in patients. Their sources have been localized to Heschl's gyri and to the supratemporal auditory cortices. Auditory evoked fields are known to be modulated by peripheral and central lesions of auditory pathways and to reflect group-level pathophysiology of neurodevelopmental and psychiatric disorders. They are useful in lateralization of language processes for planning neurosurgery and for localization of language-related cortex. The recently developed artifact rejection and movement compensation methods will enhance and extend the use of AEFs in studies of clinical patients and pediatric groups. New pediatric magnetoencephalography systems will facilitate clinical AEF studies of developmental disorders. In addition to their established use in planning neurosurgery, AEF findings in several new clinical patient groups suffering, e.g., from developmental, neurodegenerative, or psychiatric disorders have been reported. Several recent investigations report the correlations with clinical symptoms and sensitivity and specificity profiles of AEFs in studies of these disorders; this development is mandatory in gaining wider clinical approval for the use of AEFs in clinical practice dealing with individual patients. Most promising future research lines of clinical applicability of AEFs focus on developmental and psychiatric disorders.
Sticks and Stones, a conserved cell surface ligand for the Type IIa RPTP Lar, regulates neural circuit wiring inDrosophila
Authors: Bali Namrata , Lee Hyung-Kook (Peter) , Zinn Kai 
Published: November 2020

AbstractControl of tyrosine phosphorylation is an essential element of many cellular processes, including proliferation, differentiation neurite outgrowth, and synaptogenesis. Receptor-like protein-tyrosine phosphatases (RPTPs) have cytoplasmic phosphatase domains and cell adhesion molecule (CAM)-like extracellular domains that interact with cell-surface ligands and/or co-receptors. We identified a new ligand for theDrosophilaLar RPTP, the immunoglobulin superfamily CAM Sticks and Stones (Sns). Lar is orthologous to the three Type IIa mammalian RPTPs, PTPRF (LAR), PTPRD (PTPδ), and PTPRS (PTPσ). Lar and Sns bind to each other in embryos andin vitro. The human Sns ortholog, Nephrin, binds to PTPRD and PTPRF. Genetic interaction studies show that Sns is essential to Lar’s functions in several developmental contexts in the larval and adult nervous systems. In the larval neuromuscular system,Larandsnstransheterozygotes (Lar/snstranshets) have synaptic defects like those seen inLarmutants and Sns knockdown animals. Lar and Sns reporters are both expressed in motor neurons and not in muscles, so Lar and Sns likely act incis(in the same neurons).Larmutants andLar/snstranshets have identical axon guidance defects in the larval mushroom body in which Kenyon cell axons fail to stop at the midline and do not branch. Pupal Kenyon cell axon guidance is similarly affected, resulting in adult mushroom body defects. Lar is expressed in larval and pupal Kenyon cells, but Sns is not, so Lar-Sns interactions in this system must be intrans(between neurons). Lastly, R7 photoreceptor axons inLarmutants andLar/snstranshets fail to innervate the correct M6 layer of the medulla in the optic lobe. Lar acts cell-autonomously in R7s, while Sns is only in lamina and medulla neurons that arborize near the R7 target layer. Therefore, the Lar-Sns interactions that control R7 targeting also occur intrans.
Direct detection of Dengue viruses without extraction of RNA on the mobile real-time PCR device
Authors: Muraoka Masaaki , Tanoi Yukiko , Tada Tetsutaro , Tabata Aya , Mizukoshi Mikio , Kawaguchi Osamu 
Published: November 2020

ABSTRACTDengue virus (DENV) is the cause of dengue / severe dengue and a virus of the Flaviviridae family, furthermore, dengue fever has rapidly spread in the world in recent decades. DENV is transmitted by female mosquitoes, mainly of the specie Aedes aegypti. The main method to control or prevent the transmission of DENV is to combat the mosquito vectors. Among these, one of important methods is to monitor the DENVs in the mosquito vectors.For the detection of DENV, nucleic acid amplification tests (NAAT) were recommended, of which criterion standard is real-time RT-PCR with highly sensitive and specific. However, it takes long time as to judge the result per a reaction, besides the necessity of the treatment of RNA in advance, example of extraction, concentration and purification.It was our object in this time to develop the method of real-time RT-PCR detecting DENVs in shorter time, moreover without especial treatment of RNA from the mosquito in advance. Besides, this work was performed with combing the mobile real-time PCR device with the one-step RT-PCR reagent.Firstly, we succeeded in shortening the time of real-time RT-PCR for the detection of DENV per one reaction, so that the judgement needed less than 20 minutes if genomic RNA treated in advance. Moreover, each value on the real-PCR device was quantitatively correlated with the positive control RNA from 1.0 × 10 ^ 3 copies to 1.0 × 10 ^ 0 copies per reaction (This correlation coefficient R2 > 0.95). Additionally, it made sure that this method could be applied to each DENV serotype.Secondly, we established the basis of procedure for the real-time RT-PCR without the treatment in advance so-called “direct”. As the result that the positive control RNA additive was utilized instead of the real DENV, spiked into the mosquito homogenized and sampled the supernatant without treatment, it was possible to detect on the real-time RT-PCR even if mosquitoes immediately after blood-feeding. For this reason, this method might be able to utilize in human sera, too.According to the results of this work, we could suggest the method is possible to detect DENV more quickly and more simply than heretofore. The Real-time “direct” RT-PCR, especially, could be performed with mobile real-time PCR PCR1100 device and one step RT-PCR reagent only. This method must help to detect some viruses other than DENV, too.
Point-of-care detection of SARS-CoV-2 in nasopharyngeal swab samples using an integrated smartphone-based centrifugal microfluidic platform
Authors: Soares Ruben R. G. , Akhtar Ahmad S. , Pinto Inês F. , Lapins Noa , Barrett Donal , Sandh Gustaf , Yin Xiushan , Pelechano Vicent , Russom Aman 
Published: November 2020

AbstractWith its origin estimated around December 2019 in Wuhan, China, the ongoing 2020 SARS-CoV-2 pandemic is a major global health challenge, resulting in more than 45 million infections and 1.2 million deaths. The demand for scalable, rapid and sensitive viral diagnostics is thus particularly pressing at present to help contain the rapid spread of infection and prevent overwhelming the capacity of health systems. While high-income countries have managed to rapidly expand diagnostic capacities, such is not the case in resource-limited settings of low- to medium-income countries.Aiming at developing cost-effective viral load detection systems for point-of-care COVID-19 diagnostics in resource-limited and resource-rich settings alike, we report the development of an integrated modular centrifugal microfluidic platform to perform loop-mediated isothermal amplification (LAMP) of viral RNA directly from heat-inactivated nasopharyngeal swab samples. The discs were pre-packed with dried n-benzyl-n-methylethanolamine modified agarose beads used as a versatile post-nucleic acid amplification signal enhancement strategy, allowing fluorescence detection via a smartphone camera and simple optics. The platform provided sample-to-answer analysis within 1 hour from sample collection and a detection limit between 100 and 1000 RNA copies in 10 μL reaction volume. Furthermore, direct detection of non-extracted SARS-CoV-2 RNA in nasopharyngeal swab samples from patients with Ct values below 26 (n=25 plus 6 PCR negative samples) was achieved with ∼94% sensitivity and 100% specificity, thus being fit-for-purpose to diagnose patients with a high risk of viral transmission. These results show significant promise towards bringing routine point-of-care COVID-19 diagnostics closer to resource-limited settings.
Biometric covariates and outcome in COVID-19 patients: Are we looking close enough?
Authors: Fritsch Sebastian , Sharafutdinov Konstantin , Marx Gernot , Schuppert Andreas , Bickenbach Johannes 
Published: November 2020

AbstractBackgroundThe impact of biometric covariates on risk for adverse outcomes of COVID-19 disease was assessed by numerous observational studies on unstratified cohorts, which show great heterogeneity. However, multilevel evaluations to find possible complex, e. g. non-monotonic multi-variate patterns reflecting mutual interference of parameters are missing. We used a more detailed, computational analysis to investigate the influence of biometric differences on mortality and disease evolution among severely ill COVID-19 patients.MethodsWe analyzed a group of COVID-19 patients requiring Intensive care unit (ICU) treatment. For further analysis, the study group was segmented into six subgroups according to BMI and age. To link the BMI/age derived subgroups with risk factors, we performed an enrichment analysis of diagnostic parameters and comorbidities. To suppress spurious patterns, multiple segmentations were analyzed and integrated into a consensus score for each analysis step.ResultsWe analyzed 81 COVID-19 patients, of whom 67 required MV. Mean mortality was 35.8 %. We found a complex, non-monotonic interaction between age, BMI and mortality. A subcohort of patients with younger age and intermediate BMI exhibited a strongly reduced mortality risk (p < 0.001), while differences in all other groups were not significant. Univariate impacts of BMI or age on mortality were missing. Comparing MV with non-MV patients, we found an enrichment of baseline CRP, PCT and D-Dimers within the MV-group, but not when comparing survivors vs. non-survivors within the MV patient group.ConclusionsThe aim of this study was to get a more detailed insight into the influence of biometric covariates on the outcome of COVID-19 patients with high degree of severity. We found that survival in MV is affected by complex interactions of covariates differing to the reported covariates, which are hidden in generic, non-stratified studies on risk factors. Hence, our study suggests that a detailed, multivariate pattern analysis on larger patient cohorts reflecting the specific disease stages might reveal more specific patterns of risk factors supporting individually adapted treatment strategies.
Post-acute COVID-19 syndrome negatively impacts health and wellbeing despite less severe acute infection
Authors: Tabacof Laura , Tosto-Mancuso Jenna , Wood Jamie , Cortes Mar , Kontorovich Amy , McCarthy Dayna , Rizk Dahlia , Mohammadi Nicki , Breyman Erica , Nasr Leila , Kellner Christopher , Putrino David 
Published: November 2020

AbstractIntroductionOne of the noted features of COVID-19 is the spectrum of expressivity in symptoms among those with the disease, ranging from no or mild symptoms that may last a small number of days, to severe and/or longer lasting symptoms. It is emerging that many patients have long lasting symptoms, several months after initial infection with COVID-19. The aim of this research was to characterize post-acute COVID-19 syndrome (PACS).MethodsThis was a retrospective cross-sectional observational study. Participants were patients recovering from COVID-19 infection, enrolled in Mount Sinai Hospital’s COVID-19 Precision Recovery Program (PRP). Inclusion criteria were confirmed or probable (based on World Health Organization criteria) initial diagnosis of COVID-19; post-acute COVID-19 syndrome (defined as experiencing symptoms > 6 weeks since acute symptom onset) and being currently enrolled in the PRP during the months of July and August 2020. Study survey data were collected using REDCap. Demographic data, COVID-19 clinical data and patient-reported outcomes for breathlessness (Medical Research Council Breathlessness Scale), fatigue and quality of life (EuroQoL 5D-5L) were collected.Results84 individuals with PACS were included. Symptoms persisted at mean (range) 151 (54 to 255) days. The most prevalent persistent symptoms were fatigue (92%), loss of concentration/memory (74%), weakness (68%), headache (65%) and dizziness (64%). Most participants reported increased levels of disability associated with breathlessness, increased fatigue and reduced quality of life.ConclusionsPersistent symptoms following COVID-19 infection are prevalent, debilitating and appear to affect individuals regardless of acute infection severity or prior health status. More detailed research is required in order to identify specific symptom clusters associated with PACS, and to devise effective interventional strategies.
Don’t wait, re-escalate: delayed action results in longer duration of COVID-19 restrictions
Authors: Hurford Amy , Watmough James 
Published: November 2020

AbstractNon-pharmaceutical public health interventions have significant economic and social costs, and minimizing their duration is paramont. Assuming that interventions are sufficient to reduce infection prevalence, we use a simple linear SIR model with case importation to determine the relationship between the timing of restrictions, duration of measures necessary to return the incidence to a set point, and the final size of the outbreak. The predictions of our linear SIR model agree well with COVID-19 data from Atlantic Canada, and are consistent with the predictions of more complex deterministic COVID-19 models. We conclude that earlier re-escalation of restrictions results in shorter disruptions, smaller outbreaks, and consequently, lower economic and social costs. Our key message is succinctly summarized as ‘don’t wait, re-escalate’ since delaying re-escalation of restrictions results in not only more infections, but also longer periods of restrictions.
SARS-Cov-2 Viral Load as an Indicator for COVID-19 Patients’ Hospital Stay
Authors: Ali Salman Al , AbdulRahman AbdulKarim , Yaghi Omar , Janahi Essam M. , Al-Qahtani Manaf 
Published: November 2020

AbstractBackground/objectiveThe novel coronavirus disease 2019 (COVID-19) pandemic poses a global threat to the public health. There is a challenge in measuring the patient’s length of hospital stay and managing the healthcare resources to handle the situation successfully. Our objective is to use the qPCR cycle of threshold (Ct) as a tool in evaluating the severity of the infection and hence the length of hospital stay to better utilize and manage the healthcare resources.MethodsThis cross sectional study was carried out on 306 patients who admitted to COVID-19 care centers in Kingdom of Bahrain from 20th March 2020 to 5th April 2020. Standard qPCR was used to estimate the viral load and data were analyzed to investigate the relationship between Ct values and various variables.ResultsOut of 306 patients, 2 deaths, 1 active stable case and 303 recovered cases were reported. Ct value was significantly and negatively associated (P value <0.001) with length of hospital stay. The viral clearance was also inversely associated with the Ct values.ConclusionCt value was inversely associated with hospital stay duration (and time to viral clearance), higher the Ct value is indicative of faster time to viral clearance. This association could help to better manage the infection and resources allocation.
Human Identical Sequences of SARS-CoV-2 Promote Clinical Progression of COVID-19 by Upregulating Hyaluronan via NamiRNA-Enhancer Network
Authors: Li Wei , Yang Shuai , Xu Peng , Zhang Dapeng , Tong Ying , Chen Lu , Jia Ben , Li Ang , Ru Daoping , Zhang Baolong , Liu Mengxing , Lian Cheng , Chen Cancan , Fu Weihui , Yuan Songhua , Ren Xiaoguang , Liang Ying , Yang Zhicong , Li Wenxuan , Wang Shaoxuan , Zhang Xiaoyan , Lu Hongzhou , Xu Jianqing , Wang Hailing , Yu Wenqiang 
Published: November 2020

SUMMARYThe COVID-19 pandemic is a widespread and deadly public health crisis. The pathogen SARS-CoV-2 replicates in the lower respiratory tract and causes fatal pneumonia. Although tremendous efforts have been put into investigating the pathogeny of SARS-CoV-2, the underlying mechanism of how SARS-CoV-2 interacts with its host is largely unexplored. Here, by comparing the genomic sequences of SARS-CoV-2 and human, we identified five fully conserved elements in SARS-CoV-2 genome, which were termed as “human identical sequences (HIS)”. HIS are also recognized in both SARS-CoV and MERS-CoV genome. Meanwhile, HIS-SARS-CoV-2 are highly conserved in the primate. Mechanically, HIS-SARS-CoV-2, behaving as virus-derived miRNAs, directly target to the human genomic loci and further interact with host enhancers to activate the expression of adjacent and distant genes, including cytokines gene and angiotensin converting enzyme II (ACE2), a well-known cell entry receptor of SARS-CoV-2, andhyaluronan synthase 2(HAS2), which further increases hyaluronan formation. Noteworthily, hyaluronan level in plasma of COVID-19 patients is tightly correlated with severity and high risk for acute respiratory distress syndrome (ARDS) and may act as a predictor for the progression of COVID-19. HIS antagomirs, which downregulate hyaluronan level effectively, and 4-Methylumbelliferone (MU), an inhibitor of hyaluronan synthesis, are potential drugs to relieve the ARDS related ground-glass pattern in lung for COVID-19 treatment. Our results revealed that unprecedented HIS elements of SARS-CoV-2 contribute to the cytokine storm and ARDS in COVID-19 patients. Thus, blocking HIS-involved activating processes or hyaluronan synthesis directly by 4-MU may be effective strategies to alleviate COVID-19 progression.
Extending the integrate-and-fire model to account for metabolic dependencies
Authors: Jaras Ismael , Harada Taiki , Orchard Marcos E. , Maldonado Pedro E. , Vergara Rodrigo C. 
Published: November 2020

AbstractIt is widely accepted that the brain, like any other physical system, is subjected to physical constraints restricting its operation. The brain’s metabolic demands are particularly critical for proper neuronal function, but the impact of these constraints is still poorly understood. Detailed single-neuron models are recently integrating metabolic constraints, but the computational resources these models need, make it difficult to explore the dynamics of extended neural networks imposed by such constraints. Thus, there is a need for a simple-enough neuron model that incorporates metabolic activity and allows us to explore neural network dynamics. This work introduces an energy-dependent leaky integrate-and-fire (LIF) neuronal model extension to account for the effects of metabolic constraints on the single-neuron behavior (EDLIF). This simple energy-dependent model shows better performance predicting real spikes trains -inspike coincidencemeasure sense-than the classical leaky integrate-and-fire model. It can describe the relationship between the average firing rate and the ATP cost, and replicate a neuron’s behavior under a clinical setting such as amyotrophic lateral sclerosis. The simplicity of the energy-dependent model presented here, makes it computationally efficient and thus, suitable to study the dynamics of large neural networks.Author summaryAny physical system or biological tissue is restricted by physical constraints bounding their behavior, and the brain is not free from these constraints. Energetic disorders in the brain have been linked to several neurodegenerative diseases, highlighting the relevance of maintaining a critical balance between energy production and consumption in neurons. These observations motivate the development of mathematical tools that can help to understand the dependence of the brain’s behavior in metabolism. One of the essential building blocks to achieve this task is the mathematical representation of neurons through models, allowing computational simulations of single-neurons and neural networks. Here we construct a simple and computational cheap energy-dependent neuron model that allows the study of neuron’s behavior under an energetic perspective. The introduced neuron model is contrasted with one of the widest-used neuron models and shows better prediction capabilities when real neuron recordings are used. Our model is suitable for replicating neuron’s behavior under a specific neurodegenerative disease, which cannot be achieved by the abovementioned popular model. Our simple model is promising because it allows the simulation and study of neuronal networks under a metabolic-dependent perspective.