bluuebunny/crossref_metadata_2025_split huggingface dataset:
Remdesivir for the Treatment of COVID-19: An Updated Systematic Review and Meta-Analysis
Authors: Lee Todd C. , Murthy Srinivas , Del Corpo Olivier , Senécal Julien , Butler-Laporte Guillaume , Sohani Zahra N , Brophy James M. , McDonald Emily G. 
Published: January 2022

AbstractBackgroundThe benefits of remdesivir in the treatment of hospitalized patients with Covid-19 remain debated with the National Institutes of Health and the World Health Organization providing contradictory recommendations for and against use.MethodsWe performed a systematic review of randomized controlled trials (RCTs) of remdesivir for the treatment of hospitalized patients with COVID-19. The primary outcome was mortality, stratified by oxygen use (none, supplemental oxygen without mechanical ventilation, and mechanical ventilation). We conducted a frequentist random effects meta-analysis on the risk ratio (RR) scale and, to better contextualize the probabilistic benefits, we also performed a bayesian random effects meta-analysis on the risk difference scale.ResultsWe identified 8 randomized trials, totaling 9157 participants. The RR for mortality comparing remdesivir versus control was 0.71 (95% confidence interval [CI] 0.42-1.22; I2=0.0%) in the patients who did not require supplemental oxygen; 0.83 (95%CI 0.73-0.95; I2=0.0%) for nonventilated patients requiring oxygen; and 1.19 (95%CI 0.98-1.44 I2=0.0%) in the setting of mechanical ventilation. Using neutral priors, the probabilities that remdesivir reduces mortality were 74.7%, 96.9% and 8.9%, respectively. The probability that remdesivir reduced mortality by more than 1% was 88.1% for nonventilated patients requiring oxygen.ConclusionBased on this meta-analysis, there is a high probability that remdesivir reduces mortality for nonventilated patients with COVID-19 requiring supplemental oxygen therapy.
Genetic Associations with Polycystic Ovary Syndrome: The Role of The Mitochondrial Genome; A Systematic Review and Meta-analysis
Authors: Moosa Almira , Ghani Meeladah , O’Neill Helen 
Published: January 2022

1.ABSTRACTBackgroundPolycystic Ovary Syndrome (PCOS) remains the most common female reproductive endocrine disorder. Genetic studies have predominantly focused on the role of the nuclear genome, whilst the contribution of mitochondrial genetics in PCOS remains largely unknown.AimThis study aims to systematically evaluate the literature regarding the associations between the mitochondrial genome and PCOS.MethodsA literature search focused on PCOS and mitochondrial genetics was conducted on (1) MEDLINE (2) EMBASE and (3) The Cochrane Library (CENTRAL and Cochrane Reviews). Search results were screened for eligibility, and data involving genetic variants of mitochondrial DNA (mtDNA) was extracted. Quantitative data was presented in forest plots, and where this was not possible, data was analysed in a qualitative manner. Quality of studies was assessed using the Q-Genie tool.ResultsOf the 13,812 identified studies, 15 studies were eligible for inclusion, with 8 studies suitable for meta-analysis. Women with PCOS showed higher frequencies of a 9-bp deletion, and aberrant SNPs in the ND5, A6, and 7 tRNA-encoding genes. They also showed lower frequencies of two SNPs in the D-Loop of the genome. Women with PCOS also exhibited significantly lowered mtDNA copy number.ConclusionWomen with PCOS harbour genetic variants in coding and non-coding regions of the mitochondrial genome. This may disrupt the electron transport chain and lead to oxidative stress, causing apoptosis of cells and further genetic damage. However, further studies of higher quality are required to confirm these associations.
Population-Based Model of the Fraction of Incidental COVID-19 Hospitalizations During the Omicron BA.1 Wave in the United States
Authors: Harris Jeffrey E. 
Published: January 2022

AbstractBackgroundSome reports have suggested that as many as one-half of all hospital inpatients identified as COVID-19-positive during the Omicron BA.1 variant-driven wave were incidental cases admitted primarily for reasons other than their viral infections. To date, however, there are no prospective longitudinal studies of a representative panel of hospitals based on pre-established criteria for determining whether a patient was in fact admitted as a result of the disease.Materials and MethodsTo fill this gap, we developed a formula to estimate the fraction of incidental COVID-19 hospitalizations that relies upon measurable, population-based parameters. We applied our approach to a longitudinal panel of 164 counties throughout the United States, covering a 4-week interval ending in the first week of January 2022.ResultsWithin this panel, we estimated that COVID-19 incidence was rising exponentially at a rate of 9.34% per day (95% CI, 8.93-9.87). Assuming that only one-quarter of all Omicron BA.1 infections had been reported by public authorities, we further estimated the aggregate prevalence of active SARS-CoV-2 infection during the first week of January to be 3.45%. During the same week, among 250 high-COVID-volume hospitals within our 164-county panel, an estimated 1 in 4 inpatients was COVID-positive. Based upon these estimates, we computed that 10.6% of such COVID-19-positive hospitalized patients were incidental infections. Across individual counties, the median fraction of incidental COVID-19 hospitalizations was 9.5%, with an interquartile range of 6.7 to 12.7%.ConclusionIncidental COVID-19 infections appear to have been a nontrivial fraction of all COVID-19-positive hospitalized patients during the Omicron BA.1 wave. In the aggregate, however, the burden of patients admitted for complications of their viral infections was far greater.
Bacteriophage-derived dsRNA exerts anti-SARS-CoV-2 activity in vitro and in Golden Syrian hamsters in vivo
Authors: Kristine Vaivode , Irina Verhovcova , Dace Skrastina , Ramona Petrovska , Madara Kreismane , Daira Lapse , Diana Rubene , Zane Kalnina , Dace Pjanova 
Published: January 2022

AbstractPurposeBacteriophage-derived dsRNA, also known as Larifan, is nationally well-known broad-spectrum antiviral medication. The goal of this study was to ascertain the antiviral activity of Larifan against the novel SARS-CoV-2.MethodsThe antiviral activity of Larifan against SARS-CoV-2 in vitro was measured in human lung adenocarcinoma (Calu3) and primary human small airway epithelial cells (HSAEC) using cytopathic effect assay, viral RNA copy number detection by digital droplet PCR (ddPCR) and infectious virus titration in cells supernatants in Vero E6 cells by end-point titration method. The antiviral effect of Larifan in vivo was detected in SARS-CoV-2 infection model in Golden Syrian hamsters. Larifan (5 mg/kg) was administered either subcutaneously or intranasally twice before and after virus infection with a 24-hour interval between doses. The viral RNA copies and infectious virus titre were detected in animal lungs at day three and five post-infection using ddPCR and end-point titration in Vero E6 cells, respectively. Histopathology of lungs was analysed as well.ResultsLarifan inhibited SARS-CoV-2 replication in Calu3 cells both after the drug addition pre- and post-infection with a substantial drop in the supernatant viral RNA copy numbers from eight (p = 0.0013) to twenty (p = 0.0042) times, respectively. Similarly, infectious virus titre in Vero E6 cells dropped by 3.6log10 TCID50 and 2.8log10 TCID50 after the drug addition pre- and post-infection, respectively. In HSAEC, Larifan inhibited SARS-CoV-2 replication at the similar level. Larifan also markedly reduced virus numbers in the lungs of infected hamsters (p = 0.0032) both at day three and five post-infection with a more pronounced effect after intranasal administration reaching a drop by 2.7log10 at day three and 2.0log10 at day five. The administration of Larifan also reduced the amount of infections virus titer in lungs (p = 0.0039) by 4.3log10 TCID50 and 2.8log10 TCID50 at day three and five post-infection, respectively. Improvements in the infection-induced pathological lesion severity in the lungs of animals treated with Larifan were also demonstrated by histological analyses.ConclusionsThe inhibition of SARS-CoV-2 replication in vitro and the reduction of the viral load in the lungs of infected hamsters treated with Larifan alongside the improved lung histopathology, suggests a potential use of Larifan in controlling the COVID-19 disease in humans.
Amacrine cells differentially balance zebrafish colour circuits in the central and peripheral retina
Authors: Wang Xinwei , Roberts Paul A , Yoshimatsu Takeshi , Lagnado Leon , Baden Tom 
Published: January 2022

SUMMARYIn vertebrate vision, the feature-extracting circuits of the inner retina are driven by photoreceptors whose outputs are already pre-processed. In zebrafish, for example, outer retinal circuits split “colour” from “greyscale” information across all four cone-photoreceptor types. How does the inner retina process this incoming spectral information while also combining cone-signals to shape new greyscale functions?We address this question by imaging the light driven responses of amacrine cells (ACs) and bipolar cells (BCs) in larval zebrafish, in the presence and pharmacological absence of inner retinal inhibition. We find that amacrine cells exert distinct effects on greyscale processing depending on retinal region, as well as contributing to the generation of colour opponency in the central retina. However, in the peripheral retina amacrine cells enhanced opponency in some bipolar cells while at the same time suppressing pre-existing opponency in others, such that the net change in the number of colour-opponent units was essentially zero. To achieve this ‘dynamic balance’ ACs counteracted intrinsic colour opponency of BCs via the On-channel. Consistent with these observations, Off-stratifying ACs were exclusively achromatic, while all colour opponent ACs stratified in the On-sublamina.This study reveals that the central and peripheral retina of larval zebrafish employ fundamentally distinct inhibitory circuits to control the interaction between greyscale- and colour-processing. Differential actions on the On- and Off-channels control the transmission of colour-opponent signals in the periphery.
An in vitro neuronal model replicating the in vivo maturation and heterogeneity of perineuronal nets
Authors: Dickens S , Goodenough A , Kwok JCF 
Published: January 2022

AbstractThe perineuronal net (PNN) is a condensed form of extracellular matrix (ECM) that enwraps specific populations of neurons and regulates plasticity. To create a PNN, only three classes of components are needed: membrane bound hyaluronan by its synthetic enzyme hyaluronan synthases (HASs), a link protein and a CSPG. However, there is redundancy within the classes as multiple HAS isoforms, link proteins and CSPGs have been found in the PNN in vivo. The effect of this heterogeneity has on PNN function is unresolved. Currently, the most common way to address this question is through the creation and study of PNN component in knockout animals. Here, we reported the development of a primary neuronal culture model which reproduces the in vivo maturation and heterogeneity of PNNs. This model accurately replicated mature cortical PNNs, both in terms of the heterogeneity in PNN composition and its maturation. PNNs transitioned from an immature punctate morphology to the reticular morphology as observed in the mature CNS. We also observed a small population of PNNs that were mature at an earlier time point and a distinct composition, highlighting further heterogeneity. This model will provide a valuable tool for the study of PNN biology, their roles in diseases and the development of PNN focused plasticity treatment.
LITERATUR REVIEW : DEVELOPMENT OF DISASTER EDUCATION IN MULTI AGENT BASED EARLY EMERGENCY HANDLING IN THE PRE-HOSPITALS AREA
Authors: Winoto Priyo Mukti Pribadi , Wijayanti Lono , Pandin Moses Glorino Rumambo 
Published: January 2022

ABSTRACTBackgroundDisaster risk reduction involves several sectors, legal, social, structural, economic, technological, educational, environmental health, with improved preparedness will be able to reduce the impact of disasters. Capacity that continues to be added with knowledge about rapid disaster response to disasters can make resilience dealing with disasters and preventing the emergence of disaster risks.PurposeConduct a literature review on articles that examine the importance of disaster education in the initial handling of emergencies in the hospital areaDesignLiterature reviewMethodUsing databases with electronic search on ProQuest, SAGE, and Science Direct published in 2017-2021Results100 articles were used in the review. These articles discuss the importance of disaster education in the initial handling of emergencies in the hospital area. The 15 articles reviewed are original research.ConclusionLocal communities are well placed to play a central role in hazard identification, development of preparedness plans, detection and response to emergencies, and implementation of recovery efforts. Community leaders and local health workers (e.g. family doctors, nurses, midwives, pharmacists, community health workers) can build public trust, disseminate information, and identify people at risk
Values and preferences of the general population in Indonesia in relation to COVID-19 self-testing: A cross-sectional survey
Authors: Thomas Caroline , Shilton Sonjelle , Thomas Catherine , Batheja Deepshikha , Goel Srishti , Iye Claudius Mone , Ivanova Elena , Martínez-Pérez Guillermo Z. 
Published: January 2022

ABSTRACTObjectivesInnovative diagnostics are essential to assist members of the general population become active agents of case detection. In Indonesia, a country with an over-burdened healthcare system, individuals could use self-tests for SARS-CoV-2 to determine their COVID-19 status. To assess the acceptability of SARS-CoV-2 self-testing among the general population in Indonesia, a cross-sectional, population-based survey was conducted in mid-2021 in Jakarta and the provinces of Banten and North Sulawesi.MethodsThis was a survey that approached respondents in >600 randomly selected street-points in the three study geographies. A 35-item questionnaire was used to collect data on key variables, such as willingness to use and to pay for a SARS-CoV-2 self-test and likely actions following a positive result. Bivariate and multivariate regression analyses were performed.ResultsOf 630 respondents, (318 were female), 14% knew about COVID-19 self-testing, while 62.7% agreed with the concept of people being able to self-test at home, unassisted, for COVID-19. If self-tests were available in Indonesia, >60% of respondents would use them if they felt it necessary and would undertake regular self-testing e.g., weekly if recommended. Upon receiving a positive self-test result, most respondents would communicate it (86.03%), request post-test counseling (80.79%), self-isolate (97.46%), and/or warn their close contacts (n=570, 90.48%).ConclusionsSARS-CoV-2 self-testing would be acceptable to a majority of the Indonesian public, to learn whether they have COVID-19. Self-testing could contribute to an over-burdened healthcare system by helping COVID-19-infected people become agents of change in epidemiological surveillance of SARS-CoV-2 in their communities.
Vaccinia virus attenuation by codon deoptimization of the A24R gene for vaccine development
Authors: Lorenzo María M , Nogales Aitor , Chiem Kevin , Blasco Rafael , Martínez-Sobrido Luis 
Published: January 2022

ABSTRACTPoxviruses have large DNA genomes and they are able to infect multiple vertebrate and invertebrate animals, including humans. Despite the eradication of smallpox, poxvirus infections still remain a significant public health concern. Vaccinia virus (VV) is the prototypic member in the poxviridae family and it has been used extensively for different therapeutic applications, including the generation of vaccines against multiple infectious diseases and/or for oncolytic treatment. Many attempts have been pursued to develop novel attenuated forms of VV with improved safety profiles for their implementation as vaccines and/or vaccines vectors. We and others have previously demonstrated how RNA viruses encoding codon-deoptimized viral genes are attenuated, immunogenic and able to protect, upon a single administration, against challenge with parental viruses. In this study, we employed the same experimental approach based on the use of misrepresented codons for the generation of a recombinant (r)VV encoding a codon-deoptimized A24R gene, which is a key component of the viral RNA polymerase. Similar to our previous studies with RNA viruses, the A24R codon-deoptimized rVV (v-A24cd) was highly attenuated in vivo but able to protect, after a single intranasal dose administration, against an otherwise lethal challenge with parental VV. These results indicate that poxviruses can be effectively attenuated by synonymous codon deoptimization and open the possibility of using this methodology alone or in combination with other experimental approaches for the development of attenuated vaccines for the treatment of poxvirus infection, or to generate improved VV-based vectors. Moreover, this approach could be applied to other DNA viruses.IMPORTANCEThe family poxviridae includes multiple viruses of medical and veterinary relevance, being vaccinia virus (VV) the prototypic member in the family. VV was used during the smallpox vaccination campaign to eradicate variola virus (VARV), which is considered a credible bioterrorism threat. Because of novel innovations in genetic engineering and vaccine technology, VV has gained popularity as a viral vector for the development of vaccines against several infectious diseases. Several approaches have been used to generate attenuated VV for its implementation as vaccine and/or vaccine vector. Here, we generated a rVV containing a codon-deoptimized A24R gene (v-A24cd), which encodes a key component of the viral RNA polymerase. v-A24cd was stable in culture cells and highly attenuated in vivo but able to protect against a subsequent lethal challenge with parental VV. Our findings support the use of this approach for the development of safe, stable, and protective live-attenuated VV and/or vaccine vectors.
The interplay of active and passive mechanisms in slow axonal transport
Authors: Maiya Reshma , Dey Swagata , Ray Krishanu , Menon Gautam I. 
Published: January 2022

ABSTRACTA combination of intermittent active movement of transient aggregates and a paused state that intervenes between periods of active transport has been proposed to underly the slow, directed transport of soluble proteins in axons. A component of passive diffusion in the axoplasm may also contribute to slow axonal transport, although quantitative estimates of the relative contributions of diffusive and active movement in the slow transport of a soluble protein, and in particular how they might vary across developmental stages, are lacking. Here, we propose and study a model for slow axonal transport, addressing data from bleach-recovery measurements on a small, soluble, protein, Choline Acetyltransferase (ChAT), in thin axons of the lateral chordotonal (lch5) sensory neurons of Drosophila. ChAT is mainly present in soluble form in the axon and catalyses the acetylation of choline at the synapse. It does not form particulate structures in axons and moves at rates characteristic of slow component b (≈ 1-10 mm/day or 0.01-0.1 μm/s). Using our model, which incorporates active transport, paused and diffusive states, we predict bleach recovery and cargo trajectories obtained through kymographs, comparing these to experimental observations at different developmental stages. We show that changes in the diffusive fraction of cargo during these developmental stages dominate bleach recovery and that a combination of active motion with a paused state alone cannot reproduce the data. We compared predictions of the model with results from photoactivation experiments. The importance of the diffusive state in reproducing the bleach recovery signal in the slow axonal transport of small soluble proteins is our central result.STATEMENT OF SIGNIFICANCEWhile the fast axonal transport of cargo in axons is by now well-understood, the nature of slow transport remains controversial. A number of different models having been proposed for slow axonal transport, including models which allow for transitions between an intermittently moving molecular-motor driven state and a stalled state. How mechanisms for slow axonal transport are modulated during development is unexplored. We study a number of different models for slow axonal transport, comparing their predictions to data on transport of the enzyme Choline Acetyltransferase (ChAT) in thin lateral chordotonal (lch5) sensory neurons of Drosophila larva, across developmental stages where flux increases significantly. We show that accounting for changes in the diffusive fraction of cargo during these developmental stages is essential and diffusion cannot be neglected in the modelling of the slow axonal transport of small soluble proteins.
PyRodentTracks: flexible computer vision and RFID based system for multiple rodent tracking and behavioral assessment
Authors: Fong Tony , Jury Braeden , Hu Hao , Murphy Timothy H. 
Published: January 2022

AbstractPyRodentTracks (PRT) is a scalable and customizable computer vision and RFID- based system for multiple rodent tracking and behavior assessment that can be set up within minutes in any user-defined arena at minimal cost. PRT is composed of the online Raspberry Pi-based video and RFID acquisition and the subsequent offline analysis tools. The system is capable of tracking up to 6 mice in experiments ranging from minutes to days. PRT maintained a minimum of 88% detections tracked with an overall accuracy >85% when compared to manual validation of videos containing 1-4 mice in a modified home-cage. As expected, chronic recording in home-cage revealed diurnal activity patterns. Moreover, it was observed that novel non-cagemate mice pairs exhibit more similarity in travel trajectory patterns over a 10-minute period in the openfield than cagemates. Therefore, shared features within travel trajectories between animals may be a measure of sociability that has not been previously reported. Moreover, PRT can interface with open-source packages such as Deeplabcut and Traja for pose estimation and travel trajectory analysis, respectively. In combination with Traja, PRT resolved motor deficits exhibited in stroke animals. Overall, we present an affordable, open-sourced, and customizable/scalable rodent-specific behavior recording and analysis system.Statement of SignificanceAn affordable, customizable, and easy-to-use open-source rodent tracking system is described. To tackle the increasingly complex questions in neuroscience, researchers need a flexible system to track rodents of different coat colors in various complex experimental paradigms. The majority of current tools, commercial or otherwise, can only be fully automated to track multiple animals of the same type in a single defined environment and are not easily setup within custom arenas or cages. Moreover, many tools are not only expensive but are also difficult to set up and use, often requiring users to have extensive hardware and software knowledge. In contrast, PRT is easy to install and can be adapted to track rodents of any coat color in any user-defined environment with few restrictions. We believe that PRT will be an invaluable tool for researchers that are quantifying behavior in identified animals.