bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of COVID-19 on the lives and mental health of Australian adolescents
Authors: Li Sophie H. , Beames Joanne R. , Newby Jill M. , Maston Kate , Christensen Helen , Werner-Seidler Aliza 
Published: September 2020

AbstractObjectiveThere has been significant disruption to the lives and mental health of adolescents during the COVID-19 pandemic, but the exact nature of the effects is not known. The purpose of this study was to assess the psychological and lifestyle impact of the pandemic on Australian adolescents, using an online survey, administered during and after the peak of the outbreak (June-July 2020).MethodSelf-report surveys were administered online to a sample of 760 Australian adolescents aged 12-18 years old. Surveys assessed worry about contracting COVID-19, behavioral change in response to the pandemic, impact on education, peer and family relationships, lifestyle factors including exercise, technology use and sleep, as well as mental health outcomes including psychological distress, loneliness, health anxiety and wellbeing.ResultsOverall, young people expressed significant concern and worry about contracting the virus, and most (>85%) engaged in behaviors to reduce the risk of transmission. Three quarters of the sample reported a worsening of their mental health since the pandemic began, with negative impacts reported by most respondents on learning, friendships and family relationships. More than 40% of young people reported a decrease in exercise and 70% reported an increase in technology use since the outbreak. There were high levels of uncertainty about the future reported by respondents, and their scores on validated measures indicated higher levels of sleep disturbance, psychological distress and health anxiety, and lower levels of wellbeing, relative to normative samples. Reponses on the Kessler Psychological Distress Scale indicated that 48.3% of the sample were experiencing distress consistent with a probable mental illness, which is much higher than pre-pandemic prevalence rates. Effects on mental health were worse among those who reported a previous diagnosis of depression and/or anxiety relative to those without a history of depression and/or anxiety.ConclusionThese results indicate high levels of disruption and psychological distress experienced by adolescents during the current COVID-19 pandemic. Adolescents are already vulnerable to the onset of mental illness at this developmental stage, and the current research underscores the need to find rapid and accessible ways to support adolescent mental health during times of crisis. There is a need for longitudinal research to evaluate the enduring effects of the pandemic on adolescents.
Functionalized TiO2 nanotube-based Electrochemical Biosensor for Rapid Detection of SARS-CoV-2
Authors: Vadlamani B.S. , Uppal T. , Verma S.C. , Misra M. 
Published: September 2020

ABSTRACTThe COronaVIrus Disease (COVID-19) is a newly emerging viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Rapid increase in the number of COVID-19 cases worldwide led the WHO declare pandemic within a few month after the first case of infection. Due to the lack of a prophylactic measure to control the virus infection and spread, early diagnosis and quarantining of infected as well as the asymptomatic individuals are necessary for the containment of this pandemic. However, the current methods for SARS-CoV-2 diagnosis are expensive and time consuming although some promising and inexpensive technologies are coming out for emergency use. In this work, we report the synthesis of a cheap yet highly sensitive cobalt-functionalized TiO2 nanotubes (Co-TNTs)-based electrochemical biosensor and its efficacy for rapid detection of spike glycoprotein of SARS-CoV-2 by examining S-RBD protein as the reference material. A simple, low-cost, and one-step electrochemical anodization route was used to synthesize TNTs, followed by an incipient wetting method for cobalt functionalization of the TNTs platform, which is connected to a potentiostat for data collection. This sensor specifically detected the S-RBD protein of SARS-CoV-2 even at very low concentration (range of 14 nM to 1400 nM). Additionally, our sensor showed a linear response in the detection of viral protein with concentration range. In summary, our Co-TNT sensor is highly effective in detecting SARS-CoV-2 S-RBD protein in approximately 30 seconds, which can be explored for developing a point of care diagnostics for rapid detection of SARS-CoV-2 in nasal secretions and saliva samples.AUTHOR SUMMARYSARS-COV-2 is currently a global pandemic on a scale that has not been experienced since the Spanish flu of 1918. One of the reasons why this pandemic virus has spread so quickly is because many infected individuals with SARS-CoV-2 remain asymptomatic and involuntarily transmit the virus before they come down with the symptoms. Therefore, uniform surveillance and quarantining of infected as well as the asymptomatic individuals could provide an effective measure to contain the spread of SARS-CoV-2. However, the current methods for SARS-CoV-2 diagnosis are expensive and time consuming although some inexpensive technologies are getting approvals for emergency use. Our manuscript reports the synthesis of a cheap yet highly sensitive cobalt-functionalized TiO2 nanotubes (Co-TNTs)-based electrochemical biosensor for rapid detection of spike glycoprotein of SARS-CoV-2. Our sensor is synthesized through one-step electrochemical anodization route, followed by an incipient wetting method for cobalt functionalization of TNTs platform. The readout of this sensor is an electrochemical signal collected through a potentiostat, which can be adopted for use through smartphone applications and the development of a point of care diagnostics for COVID-19.
Histone demethylase Lsd1 is required for the differentiation of neural cells in the cnidarianNematostella vectensis
Authors: Gahan James M , Kouzel Ivan U. , Rentzsch Fabian 
Published: September 2020

AbstractThe evolution of multicellularity was accompanied by the emergence of processes to regulate cell fate, identity and differentiation in a robust and faithful manner. Chromatin regulation has emerged as a key process in development and yet its contribution to the evolution of such processes is largely unexplored. Chromatin is regulated by a diverse set of proteins, which themselves are tightly regulated in order to play cell/ tissue-specific functions. Using the cnidarianNematostella vectensis, a model for basal metazoans, we explore the function of one such chromatin regulator, Lysine specific demethylase 1 (Lsd1). We generated an endogenously tagged allele and show that the expression of NvLsd1 is developmentally regulated and higher in differentiated neural cells than their progenitors. We further show, using a CRISPR/Cas9 generated mutant that loss ofNvLsd1leads to several distinct developmental abnormalities. Strikingly,NvLsd1loss leads to the almost complete loss of differentiated cnidocytes, cnidarian-specific neural cells, which we show to be the result of a cell-autonomous requirement forNvLsd1. Together this suggests that complex regulation of developmental processes by chromatin modifying proteins predates the split of the cnidarian and bilaterian lineages, approximately 600 million years ago, and may constitute an ancient feature of animal development.
Visual cortex cTBS increases mixed percept duration while a-tDCS has no effect on binocular rivalry
Authors: Abuleil Dania , McCulloch Daphne , Thompson Benjamin 
Published: September 2020

AbstractNeuromodulation of the primary visual cortex using anodal transcranial direct current stimulation (a-tDCS) can alter visual perception and enhance neuroplasticity. However, the mechanisms that underpin these effects are currently unknown. When applied to the motor cortex, a-tDCS reduces the concentration of the inhibitory neurotransmitter gamma aminobutyric acid (GABA), an effect that has been linked to increased neuroplasticity. The aim of this study was to assess whether a-tDCS also reduces GABA-mediated inhibition when applied to the human visual cortex. Changes in visual cortex inhibition were measured using the mixed percept duration in binocular rivalry. Binocular rivalry mixed percept duration has recently been advocated as a direct and sensitive measure of visual cortex inhibition whereby GABA agonists decrease mixed percept durations and agonists of the excitatory neurotransmitter acetylcholine increase them. Our hypothesis was that visual cortex a-tDCS would increase mixed percept duration by reducing GABA-mediated inhibition and increasing cortical excitation. In addition, we measured the effect of continuous theta-burst transcranial magnetic stimulation (cTBS) of the visual cortex on binocular rivalry dynamics. When applied to the motor or visual cortex, cTBS increases GABA concentration and we therefore hypothesized that visual cortex cTBS would decrease the mixed percept duration. Binocular rivalry dynamics were recorded before and after active and sham a-tDCS (N=15) or cTBS (N=15). Contrary to our hypotheses, a-tDCS had no effect, whereas cTBS significantly increased mixed percepts during rivalry. These results suggest that the neurochemical mechanisms of a-tDCS may differ between the motor and visual cortices.
TAZ-CAMTA1 and YAP-TFE3 modulate the basal TAZ/YAP transcriptional program by recruiting the ATAC histone acetyltransferase complex
Authors: Merritt Nicole , Garcia Keith , Rajendran Dushyandi , Lin Zhen-Yuan , Zhang Xiaomeng , Mitchell Katrina M. , Borcherding Nicholas , Fullenkamp Colleen , Chimenti Michael , Gingras Anne-Claude , Harvey Kieran F. , Tanas Munir R. 
Published: September 2020

AbstractEpithelioid hemangioendothelioma (EHE) is a vascular sarcoma that metastasizes early and lacks an effective medical therapy. The TAZ-CAMTA1 and YAP-TFE3 fusion proteins are chimeric transcription factors and initiating oncogenic drivers of EHE. A combined proteomic/genetic screen identified YEATS2 and ZZZ3, components of theAda2a-containing histone acetyltransferase (ATAC) complex, as key interactors of both TAZ-CAMTA1 and YAP-TFE3 despite the dissimilarity of the C terminal fusion partners CAMTA1 and TFE3. An integrative next generation sequencing approach showed the fusion proteins drive expression of a unique transcriptome distinct from TAZ and YAP by simultaneously hyperactivating a TEAD-based transcriptional program and modulating the chromatin environment via interaction with the ATAC complex. Interaction of the ATAC complex with both TAZ-CAMTA1 and YAP-TFE3 indicates the histone acetyltransferase complex is an oncogenic driver in EHE and potentially other sarcomas. Furthermore, the ATAC complex is an enzymatic transcriptional cofactor required for both fusion proteins in EHE, representing a unifying therapeutic target for this sarcoma. Gene fusions are the most common genetic alterations activating TAZ and YAP in cancer, and this study serves as a template for identifying epigenetic modifiers recruited by the C terminal fusion partners of other TAZ/YAP gene fusions occurring in gliomas, carcinomas, and other sarcomas.SummaryTAZ-CAMTA1 and YAP-TFE3 alter the TAZ/YAP transcriptional program by recruiting the ATAC complex and modifying the chromatin landscape.
UVA radiation could be a significant contributor to sunlight inactivation of SARS-CoV-2
Authors: Luzzatto-Fegiz Paolo , Temprano-Coleto Fernando , Peaudecerf François J. , Landel Julien R. , Zhu Yangying , McMurry Julie A. 
Published: September 2020

AbstractPast experiments demonstrated SARS-CoV-2 inactivation by simulated sunlight; models have considered exclusively mechanisms involving UVB acting directly on RNA. However, UVA inactivation has been demonstrated for other enveloped RNA viruses, through indirect mechanisms involving the suspension medium. We propose a model combining UVB and UVA inactivation for SARS-CoV-2, which improves predictions by accounting for effects associated with the medium. UVA sensitivities deduced for SARS-CoV-2 are consistent with data for SARS-CoV-1 under UVA only. This analysis calls for experiments to separately assess effects of UVA and UVB in different media, and for including UVA in inactivation models.Lay summaryRecent experiments have demonstrated that SARS-CoV-2 is inactivated by simulated sunlight; however, there are still many unknowns, including the mechanism of action and which part of the light spectrum is principally responsible. Our analysis indicates the need for targeted experiments that can separately assess the effects of UVA and UVB on SARS-CoV-2, and that sunlight inactivation models may need to be expanded to also include the effect of UVA. A first UVA-inclusive model is also proposed here. These findings have implications for how to improve the safety of the built environment, and for the seasonality of COVID-19.
Quinolone resistance in different uropathogens isolated from urine cultures in patients with urinary tract infection
Authors: Villegas Jorge Angel Almeida , Carrillo Iris Mellolzy Estrada , Contreras Rodolfo Garcia , Peña Silvia Patricia 
Published: September 2020

AbstractObjectiveTo identify patterns of resistance against quinolones in various uropathogens in urinary tract infections in the population of the Toluca valley, MexicoIntroductionQuinolones are antibiotics with a spectrum of activity for both gram-positives and gram-negatives and are antibiotics used for the empirical treatment of urinary tract infections. Recently, a high index of resistance to quinolones has been reported due to different mechanisms on the part of bacteria, however the one that has taken the greatest importance is the presence of extended spectrum beta-lactamasesMethods155 samples were collected from patients with suspected urinary tract infection without exclusion criteria such as age or gender. Automated equipment was used for the identification of the etiological agent and sensitivity tests to quinolones.ResultsThe results positives were divided to evaluate which of the two antibiotics studied had greater resistance. For ciprofloxacin there are 27 resistant strains 37%, 1 strain with intermediate resistance 1% and 45 susceptible strains 62%. For levofloxacin 26 strains are resistant 36%, 41 strains are sensitive 56% and 6 strains show intermediate sensitivity 8%.ConclusionDifferent microorganisms, both gram-positive and gram-negative, were isolated and it can be observed that gram-negative strains are the ones with the greatest resistance against quinolones, mainlyEscherichia coli, which produces extended-spectrum beta-lactamases, in the case of gram-positive resistance patterns are variable with a tendency towards sensitivity.
Bacteriophage uptake by Eukaryotic cell layers represents a major sink for phages during therapy
Authors: Bichet Marion C. , Chin Wai Hoe , Richards William , Lin Yu-Wei , Avellaneda-Franco Laura , Hernandez Catherine A. , Oddo Arianna , Chernyavskiy Oleksandr , Hilsenstein Volker , Neild Adrian , Li Jian , Voelcker Nicolas Hans , Patwa Ruzeen , Barr Jeremy J. 
Published: September 2020

AbstractFor over 100 years, bacteriophages have been known as viruses that infect bacteria. Yet it is becoming increasingly apparent that bacteriophages, or phages for short, have tropisms outside their bacterial hosts. During phage therapy, high doses of phages are directly administered and disseminated throughout the body, facilitating broad interactions with eukaryotic cells. Using live cell imaging across a range of cell lines we demonstrate that cell type plays a major role in phage internalisation and that smaller phages (< 100 nm) are internalised at higher rates. Uptake rates were validated under physiological shear stress conditions using a microfluidic device that mimics the shear stress to which endothelial cells are exposed to in the human body. Phages were found to rapidly adhere to eukaryotic cell layers, with adherent phages being subsequently internalised by macropinocytosis and functional phages accumulating and stably persisting intracellularly. Finally, we incorporate these results into an established pharmacokinetic model demonstrating the potential impact of phage accumulation by these cell layers, which represents a major sink for circulating phages in the body. Understanding these interactions will have important implications on innate immune responses, phage pharmacokinetics, and the efficacy of phage therapy.
The combination of Bromelain and Acetylcysteine (BromAc) synergistically inactivates SARS-CoV-2
Authors: Akhter Javed , Quéromès Grégory , Pillai Krishna , Kepenekian Vahan , Badar Samina , Mekkawy Ahmed H. , Frobert Emilie , Valle Sarah J , Morris David L. 
Published: September 2020

AbstractBackground and objectivesSARS-CoV-2 infection is the cause of a worldwide pandemic, currently with limited therapeutic options. Whilst vaccines are at the forefront of the therapeutic initiative, drug repurposing remains a promising approach for SARS-CoV-2 treatment. BromAc (Bromelain & Acetylcysteine) has synergistic action against glycoproteins by the synchronous breakage of glycosidic linkages and disulfide bonds. The spike protein of SARS-CoV-2, formed of glycoprotein and disulfide bridges for stabilization, represents an attractive target as it is essential for binding to the ACE2 receptor in host cells present in nasal mucosa. We sought to determine the effect of BromAc on the Spike and Envelope proteins and its potential to reduce infectivity in host cells.DesignRecombinant Spike and Envelope proteins were treated by single agent and combination BromAc at 50 and 100 µg/20mg/mL and analyzed by electrophoresis. Ultraviolet analysis of disulfide bond reduction was performed for both Spike and Envelope proteins after treatment with Acetylcysteine. In vitro whole virus culture inactivation of pre-treated wild type and an S1/S2 Spike mutant SARS-CoV-2 with BromAc from 25 to 250 µg/20mg/mL was measured by cytopathic effect, cell lysis assay, and replication capacity by RT-PCR.ResultsRecombinant Spike and Envelope SARS-CoV-2 proteins were fragmented by BromAc at both 50 and 100 µg/20mg/mL whilst single agents had minimal effect. Spike and Envelope protein disulfide bonds were reduced by Acetylcysteine. In vitro whole virus culture of both wild type and Spike mutant SARS-CoV-2 demonstrated a concentration-dependent inactivation from BromAc treatment but not from single agents.ConclusionBromAc disintegrates SARS-CoV-2 Spike and Envelope proteins. In vitro tests on whole virus support this finding with inactivation of its replication capacity most strongly at 100 and 250 µg/20mg/mL BromAc, even in Spike mutant virus. Clinical testing through nasal administration in patients with early SARS-CoV-2 infection is imminent.Author SummaryThere is currently no suitable therapeutic treatment for early SARS-CoV-2 aimed to prevent disease progression. BromAc is under clinical development by the authors for mucinous cancers due to its ability to alter complex glycoproteins structure. The potential of BromAc on SARS-CoV-2 Spike and Envelope glycoproteins stabilized by disulfide bonds was examined and found to disintegrate recombinant Spike and Envelope proteins whilst reducing disulfide stabilizer bridges. BromAc also showed an inhibitory effect on wild-type and Spike mutant SARS-CoV-2 by inactivation of its replication capacity in vitro. Hence, BromAc may be an effective therapeutic agent for early SARS-CoV-2 infection, despite mutations, and even have potential as a prophylactic in people at high risk of infection.
The role of NIH funding in vaccine readiness; foundational research and NIH funding underlying candidate SARS-CoV-2 vaccines
Authors: Kiszewski Anthony E , Cleary Ekaterina Galkina , Jackson Matthew J , Ledley Fred D 
Published: September 2020

ABSTRACTThis work characterizes the NIH contribution to vaccine technologies being employed in “warp speed” development of vaccines for COVID-19, as well as the lack of sustained NIH funding for published research against recognized epidemic threats. Using quantitative methods, we examined the advance of published research on ten of the vaccine technologies incorporated in the 165 candidate vaccines entering development through July 2020 as well as the NIH funding that supported this research. Live, attenuated virus, inactivated virus, and adjuvant technologies have been used in successful products since the 1950s and continue to exhibit steady advance. Synthetic (recombinant) vaccines, viral vectors, DNA, and TLR9 agonists as adjuvants emerged since the 1980s, and exhibit a logistic, “S-curve” pattern of growth characteristic of emerging technologies that have passed an analytically-definedestablishedpoint. In contrast, mRNA, virus-like particle, and nanoparticle technologies show exponential growth characteristic of technologies short of theirestablishedpoints. The body of research and NIH funding for established and emerging vaccine technologies exhibited sustained growth through the late 2010s, supported by > 16,000 project years of NIH funding totaling over $17.2 billion (2000–2019), the majority through cooperative agreements and intramural programs. NIH funding for published research on vaccines for recognized zoonotic threats including coronavirus, Zika, Ebola, and dengue, however, has been inconsistent and reactive to disease outbreaks. These data are considered in the context of the high failure rate for candidate vaccines and evidence that technological maturity is a significant factor in the efficiency of product development. Sustained funding for both enabling technologies and vaccine development is essential to ensure a rapid response to COVID and future pandemic threats.SIGNIFICANCE STATEMENTThis work examines the advance of research and NIH funding for technologies being employed in “warp speed” development of COVID-19 vaccines in the context of evidence that mature technologies have a greater likelihood of generating successful products. We show that candidate vaccines for COVID-19 employ a variety of established and still-emerging technologies, and identify $17.2 billion in NIH funding for this research from 2000–2019. In contrast, NIH funding for published research for vaccines on recognized pandemic threats has been inconsistent. This work highlights the significance and scale of the NIH contribution to vaccine technologies and the lack of sustained initiatives for vaccine development.