bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying Promising Themes for Adolescent Vaping Warnings: A National Experiment
Authors: Rohde Jacob A , Noar Seth M , Sheldon Jennifer Mendel , Hall Marissa G , Kieu Talia , Brewer Noel T 
Published: April 2022

Abstract

Introduction
Adolescent vaping remains a problem in the United States, yet little is known about what health warning themes most discourage vaping among adolescents. We sought to identify the most compelling themes for vaping warnings for US adolescents.

Methods
Participants were a national probability sample of 623 US adolescents aged 13–17 years, recruited in the summer of 2020. Adolescents were randomized to one of the five warning message themes about the potential health effects of vaping: 1. chemical harms, 2. lung harms, 3. Coronavirus Disease 2019 (COVID-19) harms, 4. nicotine addiction, or 5. control (messages about vape litter). The primary outcome was perceived message effectiveness (PME; 3-item scale). Secondary outcomes were negative affect (fear), attention, anticipated social interactions, and message novelty.

Results
Adolescents rated the chemical, lung, and COVID-19 harms warning messages higher on PME than nicotine addiction and control (all p &lt; .05), while nicotine addiction was rated higher than control (p &lt; .05). The chemical, lung, and COVID-19 harms warning themes also elicited greater negative affect than nicotine addiction and control (all p &lt; .05). For all other secondary outcomes, the COVID-19 harms warning message theme was rated higher than nicotine addiction and control (all p &lt; .05).

Conclusion
Adolescents perceived warning message themes about lung, chemical and COVID-19 health effects of vaping as more effective than nicotine addiction. To discourage vaping, the FDA and others should communicate to youth about the health effects of vaping beyond nicotine addiction.

Implications
Adolescents rated warning message themes about the lung, chemical, and COVID-19 health effects of vaping as more effective than nicotine addiction, while nicotine addiction was rated as more effective than control themes about vaping litter. To discourage vaping among adolescents, health messaging should expand message themes to communicate about a broader set of health effects of vaping beyond nicotine addiction.
Sleep irregularity and nonsuicidal self-injurious urges and behaviors
Authors: Burke Taylor A , Hamilton Jessica L , Seigel David , Kautz Marin , Liu Richard T , Alloy Lauren B , Barker David H 
Published: April 2022

Abstract

Study Objectives
The objectives of this study were to examine the relationships between sleep regularity and nonsuicidal self-injury (NSSI), including lifetime NSSI history and daily NSSI urges.

Methods
Undergraduate students (N = 119; 18–26 years), approximately half of whom endorsed a lifetime history of repetitive NSSI, completed a 10-day actigraphy and ecological momentary assessment (EMA) protocol. A Sleep Regularity Index was calculated for all participants using scored epoch by epoch data to capture rapid changes in sleep schedules. Participants responded to EMA prompts assessing NSSI urge severity and negative affect three times daily over the 10-day assessment period.

Results
Results indicate that individuals with a repetitive NSSI history were more likely to experience sleep irregularity than those without a history of NSSI. Findings also suggest that sleep irregularity was associated with more intense urges to engage in NSSI on a daily basis, even after accounting for average daily sleep duration, sleep timing, negative affect, and NSSI history. Neither sleep duration nor sleep timing was associated with NSSI history nor daily NSSI urge intensity.

Conclusions
Findings suggest that sleep irregularity is linked with NSSI, including NSSI history and intensity of urges to engage in NSSI. The present study not only supports the growing evidence linking sleep disturbance with the risk for self-injury but also demonstrates this relationship using actigraphy and real-time assessments of NSSI urge severity. Findings highlight the importance of delineating the nuances in sleep irregularity that are proximally associated with NSSI risk and identifying targets for intervention.
A formalism for sequential estimation of neural membrane time constant and input–output curve towards selective and closed-loop transcranial magnetic stimulation⋆
Authors: Alavi S.M.Mahdi , Vila-Rodriguez Fidel , Mahdi Adam , Goetz Stefan M. 
Published: April 2022

AbstractObjectiveTo obtain a formalism for real-time concurrent sequential estimation of neural membrane time constant and input–output (IO) curve with transcranial magnetic stimulation (TMS).ApproachFirst, the neural membrane response and depolarization factor, which leads to motor evoked potentials (MEPs) with TMS are analytically computed and discussed. Then, an integrated model is developed which combines the neural membrane time constant and input–output curve. Identifiability of the proposed integrated model is discussed. A condition is derived, which assures estimation of the proposed integrated model. Finally, sequential parameter estimation (SPE) of the neural membrane time constant and IO curve is described through closed-loop optimal sampling and open-loop uniform sampling TMS. Without loss of generality, this paper focuses on a specific case of commercialized TMS pulse shapes. The proposed formalism and SPE method are directly applicable to other pulse shapes.Main resultsThe results confirm satisfactory estimation of the membrane time constant and IO curve parameters. By defining a stopping rule based on five times consecutive convergence of the estimation parameters with a tolerances of 0.01, the membrane time constant and IO curve parameters are estimated with 82 TMS pulses with absolute relative estimation errors (AREs) of less than 4% with the optimal sampling SPE method. At this point, the uniform sampling SPE method leads to AREs up to 16%. The uniform sampling method does not satisfy the stopping rule due to the large estimation variations.SignificanceThis paper provides a tool for real-time closed-loop SPE of the neural time constant and IO curve, which can contribute novel insights in TMS studies. SPE of the membrane time constant enables selective stimulation, which can be used for advanced brain research, precision medicine and personalized medicine.
[18F]ROStrace detects oxidative stress in vivo and predicts progression of Alzheimer’s disease pathology in APP/PS1 mice
Authors: Hsieh Chia-Ju , Hou Catherine , Zhu Yi , Lee Ji Youn , Kohli Neha , Gallagher Evan , Xu Kuiying , Lee Hsiaoju , Li Shihong , McManus Meagan J. , Mach Robert H. 
Published: April 2022

AbstractPurposeOxidative stress is implicated in the pathogenesis of the most common neurodegenerative diseases, such as Alzheimer’s disease (AD). However, tracking oxidative stress in the brain has proven difficult and impeded its use as a biomarker. Herein, we investigate the utility of a novel positron emission tomography (PET) tracer, [18F]ROStrace, as a biomarker of oxidative stress throughout the course of AD in the well-established APP/PS1 double mutant mouse model.MethodsPET imaging studies were conducted in wild-type (WT) and APP/PS1 mice at 3 different time points, representing early (5 mo.), middle (10 mo.), and advanced (16 mo.) life (n = 6-12, per sex). Semi-quantitation SUVRs of the plateau phase (40-60min post-injection; SUVR40-60) of ten brain subregions were designated by the Mirrione atlas and analyzed by Pmod. Statistical parametric mapping (SPM) was used to distinguish brain regions with elevated ROS in APP/PS1 relative to WT in both sexes. The PET studies were validated by ex vivo autoradiography and immunofluorescence with the parent compound, dihydroethidium.Results[18F]ROStrace retention was increased in the APP/PS1 brain compared to age-matched controls by 10 mo. of age (p < 0.0001), and preceded the accumulation of oxidative damage in APP/PS1 neurons at 16mo. (p < 0.005). [18F]ROStrace retention and oxidative damages were higher and occurred earlier in female APP/PS1 mice as measured by PET (p < 0.001), autoradiography and immunohistochemistry (p < 0.05). [18F]ROStrace differences emerged mid-life, temporally and spatially correlating with increased Aβ burden (r2 = 0.36; p = 0.0003), which was also greatest in the female brain (p < 0.001).Conclusions[18F]ROStrace identifies increased oxidative stress and neuroinflammation in APP/PS1 female mice, concurrent with increased amyloid burden mid-life. Differences in oxidative stress during this crucial time may partially explain the sexual dimorphism in AD. [18F]ROStrace may provide a long-awaited tool to stratify at-risk patients who may benefit from antioxidant therapy prior to irreparable neurodegeneration.
Cochlear Neurotrophin-3 overexpression at mid-life prevents age-related cochlear synaptopathy and slows age-related hearing loss
Authors: Cassinotti Luis R. , Ji Lingchao , Borges Beatriz C. , Cass Nathan D. , Desai Aditi S. , Kohrman David C. , Liberman M. Charles , Corfas Gabriel 
Published: April 2022

ABSTRACTAge-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly. This progressive pathology often has psychological and medical comorbidities, including social isolation, depression, and cognitive decline. Despite ARHL’s enormous impact, no therapies to prevent or slow its progression exist. Loss of synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs), a.k.a. cochlear synaptopathy, is an early event in ARHL, preceding neuronal and hair cell loss. To determine if age-related cochlear synaptopathy can be prevented, and if this impacts the time-course of ARHL, we tested the effects of cochlear overexpression of neurotrophin-3 (Ntf3) starting at middle-age. We chose Ntf3 because this neurotrophin regulates the formation of IHC-SGN synapses in the neonatal period. We now show that triggering Ntf3 overexpression by cochlear supporting cells starting in middle age rapidly increases the amplitude of sound-evoked neural potentials, indicating that Ntf3 improves cochlear function when pathology is minimal. Furthermore, near the end of their lifespan, Ntf3-overexpressing mice have milder ARHL, with enhanced cochlear neural function and reduced cochlear synaptopathy. Our results provide evidence that age-related decrease in cochlear Ntf3 expression contributes to ARHL. and Ntf3 supplementation could serve as a therapeutic for this prevalent disorder. Furthermore, these findings suggest that increased expression of factors that regulate synaptogenesis during development might prevent age-related synaptopathy, a process involved in several central nervous system degenerative disorders.
The natural diversity of the yeast proteome reveals chromosome-wide dosage compensation in aneuploids
Authors: Muenzner Julia , Trébulle Pauline , Agostini Federica , Messner Christoph B. , Steger Martin , Lehmann Andrea , Caudal Elodie , Egger Anna-Sophia , Amari Fatma , Barthel Natalie , De Chiara Matteo , Mülleder Michael , Demichev Vadim , Liti Gianni , Schacherer Joseph , Gossmann Toni , Berman Judith , Ralser Markus 
Published: April 2022

SummaryAneuploidy, an imbalance in chromosome copy numbers, causes genetic disorders, and drives cancer progression, drug tolerance, and antimicrobial resistance. While aneuploidy can confer stress resistance, it is not well understood how cells overcome the fitness burden caused by aberrant chromosomal copy numbers. Studies using both systematically generated1–5and natural aneuploid yeasts6–8triggered an intense debate about the role of dosage compensation, concluding that aneuploidy is transmitted to the transcriptome and proteome without significant buffering at the chromosome-wide level, and is, at least in lab strains, associated with significant fitness costs. Conversely, systematic sequencing and phenotyping of large collections of natural isolates revealed that aneuploidy is frequent and has few – if any – fitness costs in nature9. To address these discrepant findings at the proteomic level, we developed a platform that yields highly precise proteomic measurements across large numbers of genetically diverse samples, and applied it to natural isolates collected as part of the 1011 genomes project9. For 613 of the isolates, we were able to match the proteomes to their corresponding transcriptomes and genomes, subsequently quantifying the effect of aneuploidy on gene expression by comparing 95 aneuploid with 518 euploid strains. We find, as in previous studies, that aneuploid gene dosage is not buffered chromosome-wide at the transcriptome level. Importantly, in the proteome, we detect an attenuation of aneuploidy by about 25% below the aneuploid gene dosage in natural yeast isolates. Furthermore, this chromosome-wide dosage compensation is associated with the ubiquitin-proteasome system (UPS), which is expressed at higher levels and has increased activity across natural aneuploid strains. Thus, through systematic exploration of the species-wide diversity of the yeast proteome, we shed light on a long-standing debate about the biology of aneuploids, revealing that aneuploidy tolerance is mediated through chromosome-wide dosage compensation at the proteome level.
Plant-produced RBD and cocktail-based vaccine candidates are highly effective against SARS-CoV-2, independently of its emerging variants
Authors: Mamedov Tarlan , Yuksel Damla , Gürbüzaslan Irem , Ilgın Merve , Gulec Burcu , Mammadova Gulshan , Ozdarendeli Aykut , Pavel Shaikh Terkis Islam , Yetiskin Hazel , Kaplan Busra , Uygut Muhammet Ali , Hasanova Gulnara 
Published: April 2022

AbstractSARS-CoV-2 is a novel and highly pathogenic coronavirus, which has caused an outbreak in Wuhan City, China, in 2019 and then spread rapidly throughout the world. Although several COVID-19 vaccines are currently available for mass immunization, they are less effective against emerging SARS-CoV-2 variants, especially the Omicron (B.1.1.529). Recently, we successfully produced receptor-binding domain (RBD) variants of spike (S) protein of SARC-CoV-2 and an antigen cocktail in Nicotiana benthamiana, which are highly produced in plants and elicited high-titer antibodies with potent neutralizing activity against SARS-CoV-2. In this study, we demonstrate that these protein-based vaccine candidates are highly effective against Delta and Omicron variants. These data support that plant produced RBD and cocktail-based antigens are most promising vaccine candidates and may protect against Delta and Omicron-mediated COVID-19. Based on the neutralization ability, plant produced RBD and cocktail-based vaccine candidates are highly effective against SARS-CoV-2, independently of its emerging variants.
Hippo Signaling Pathway Activation during SARS-CoV-2 Infection Contributes to Host Antiviral Response
Authors: Garcia Gustavo , Wang Yijie , Irudayam Joseph Ignatius , Jeyachandran Arjit Vijey , Cario Sebastian Castillo , Sen Chandani , Li Shen , Li Yunfeng , Kumar Ashok , Nielsen-Saines Karin , French Samuel W. , Shah Priya S , Morizono Kouki , Gomperts Brigitte , Deb Arjun , Ramaiah Arunachalam , Arumugaswami Vaithilingaraja 
Published: April 2022

ABSTRACTSARS-CoV-2, responsible for the COVID-19 pandemic, causes respiratory failure and damage to multiple organ systems. The emergence of viral variants poses a risk of vaccine failures and prolongation of the pandemic. However, our understanding of the molecular basis of SARS-CoV-2 infection and subsequent COVID-19 pathophysiology is limited. In this study, we have uncovered a critical role for the evolutionarily conserved Hippo signaling pathway in COVID-19 pathogenesis. Given the complexity of COVID-19 associated cell injury and immunopathogenesis processes, we investigated Hippo pathway dynamics in SARS-CoV-2 infection by utilizing COVID-19 lung samples, and human cell models based on pluripotent stem cell-derived cardiomyocytes (PSC-CMs) and human primary lung air-liquid interface (ALI) cultures. SARS-CoV-2 infection caused activation of the Hippo signaling pathway in COVID-19 lung and in vitro cultures. Both parental and Delta variant of concern (VOC) strains induced Hippo pathway. The chemical inhibition and gene knockdown of upstream kinases MST1/2 and LATS1 resulted in significantly enhanced SARS-CoV-2 replication, indicating antiviral roles. Verteporfin a pharmacological inhibitor of the Hippo pathway downstream transactivator, YAP, significantly reduced virus replication. These results delineate a direct antiviral role for Hippo signaling in SARS-CoV-2 infection and the potential for this pathway to be pharmacologically targeted to treat COVID-19.
Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike
Authors: Stalls Victoria , Lindenberger Jared , Gobeil Sophie M-C. , Henderson Rory , Parks Rob , Barr Maggie , Deyton Margaret , Martin Mitchell , Janowska Katarzyna , Huang Xiao , May Aaron , Speakman Micah , Beaudoin Esther , Kraft Bryan , Lu Xiaozhi , Edwards Robert J , Eaton Amanda , Montefiori David C. , Williams Wilton , Saunders Kevin O. , Wiehe Kevin , Haynes Barton F. , Acharya Priyamvada 
Published: April 2022

SummaryThe BA.2 sub-lineage of the SARS-CoV-2 Omicron variant has gained in proportion relative to BA.1. As differences in spike (S) proteins may underlie differences in their pathobiology, here we determine cryo-EM structures of a BA.2 S ectodomain and compare these to previously determined BA.1 S structures. BA.2 Receptor Binding Domain (RBD) mutations induced remodeling of the internal RBD structure resulting in its improved thermostability and tighter packing within the 3-RBD-down spike. In the S2 subunit, the fusion peptide in BA.2 was less accessible to antibodies than in BA.1. Pseudovirus neutralization and spike binding assays revealed extensive immune evasion while defining epitopes of two RBD-directed antibodies, DH1044 and DH1193, that bound the outer RBD face to neutralize both BA.1 and BA.2. Taken together, our results indicate that stabilization of the 3-RBD-down state through interprotomer RBD-RBD packing is a hallmark of the Omicron variant, and reveal differences in key functional regions in the BA.1 and BA.2 S proteins.
Hepatobiliary organoids derived from leporids support the replication of hepatotropic lagoviruses
Authors: Kardia Egi , Fakhri Omid , Pavy Megan , Mason Hugh , Huang Nina , Smertina Elena , Estes Mary K. , Strive Tanja , Frese Michael , Hall Robyn N. 
Published: April 2022

AbstractLagoviruses, family Caliciviridae, are some of the most virulent vertebrate viruses known. They infect leporids, i.e., rabbits (Oryctolagus spp.), hares (Lepus spp.) and cottontails (Sylvilagus spp.) and rapidly kill over 95% of susceptible animals. Pathogenic lagoviruses are hepatotropic and induce a fulminant hepatitis that typically leads to disseminated intravascular coagulation within 24–72 hours of infection. However, the pathophysiological mechanisms governing this extreme phenotype and other aspects of the fundamental biology of these viruses are poorly understood due to a lack of cell culture systems. Here, we report on a robust and reliable ex vivo model for the cultivation of hepatotropic lagoviruses. We show that three rabbit haemorrhagic disease virus (RHDV) variants, RHDV1, RHDV2 and RHDVa-K5, replicate in monolayer cultures derived from rabbit hepatobiliary organoids. Viral replication was demonstrated by a (i) increase in viral RNA levels of greater than one log10 over a 23-hour period, (ii) detection of viral structural and non-structural proteins, and (iii) detection of double-stranded RNA viral replication intermediates. Furthermore, we generated hepatobiliary organoids from a feral cat (Felis domesticus), a wild mouse (Mus musculus) and a European brown hare (Lepus europaeus) and showed that monolayer cultures derived from the cat and mouse organoids were not permissive for lagovirus infection, while those derived from the hare organoids only supported replication of RHDV2, recapitulating the species tropism that has been observed with these viruses. Our organoid culture system will facilitate future studies into the molecular biology of lagoviruses, which will have considerable import for the conservation of endangered leporid species in Europe and North America and the biocontrol of overabundant rabbit populations in Australia and New Zealand.
A new microfluidic device for simultaneous detection of enzyme secretion and elongation of a single hypha
Authors: Itani Ayaka , Shida Yosuke , Ogasawara Wataru 
Published: April 2022

ABSTRACTFungal cells perform enzyme secretion and elongation by exocytosis in the apical region. The widespread branching of hyphae and the inability to control environmental conditions over long periods make it difficult to observe and analyze single hyphae with conventional assays. Therefore, although hyphal morphology is closely linked to productivity, no real-time measurements of morphology and exoenzymes have been carried out. In this study, a microfluidic system was developed to compartmentalize a single hypha germinated from a single spore. This allowed detailed observation of a single hypha and provided new insights, such as the fact that enlarged vacuoles inhibit nuclear movement. Furthermore, a cellulase detection assay based on subtle differences in molecular polarity was developed to detect hyphal growth and enzyme secretion in real-time using Trichoderma reesei, a potent cellulase-producing hypha, as a model. When the fluorescence from the detection assay was compared with the GFP fluorescence intensity using a strain fused with cellulase CBHI and GFP, a strong correlation was observed. As T. reesei secretes a series of cellulases, these results prove that the extracellular enzymes can be measured in real time. This microfluidic system has enabled real-time visualization and analysis of cellular heterogeneity, hyphal and enzyme dynamics associated with carbon source exchange, and quantitative dynamics of gene expression. The technology can be applied to a wide range of other biosystems exhibiting similar polar cell growth, from bioenergy production to human health.IMPORTANCEHyphal morphology and productivity of filamentous fungi are linked by exocytosis. Conventional assay methods make it difficult to observe and analyze single hyphae. Here, a robust and high-performance microfluidic system was developed to compartmentalize single hyphae germinated from a single spore, enabling their long-term observation. Using the potent cellulase-producing fungus Trichoderma reesei, the system made it possible to visualize and analyze cell heterogeneity, hyphae, enzyme dynamics, and quantitative gene expression dynamics associated with carbon source exchange. The technique can be immediately extended to various other biosystems exhibiting similar polar cell growth and is expected to contribute significantly to the elucidation of filamentous fungi production systems.