bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistence of neuropsychiatric symptoms associated with SARS-CoV-2 positivity among a cohort of children and adolescents
Authors: Castro Victor M. , Gunning Faith M. , Perlis Roy H. 
Published: September 2021

AbstractBackgroundPost-acute sequelae of COVID-19 are common among adults. The prevalence of such syndromes among community samples of children and adolescents remains less well characterized.MethodWe identified all individuals age 5-18 across 2 New England health systems who had a positive SARS-CoV-2 PCR test between 3/12/2020 and 4/18/2021 and at least 90 days of follow-up visits documented in electronic health records. We identified neuropsychiatric symptoms in intervals prior to, and following, this testing using a previously-derived set of ICD-10 codes and natural language processing terms. Primary analysis examined sociodemographic features associated with presence of at least one incident (i.e., new-onset) neuropsychiatric symptom between 90 and 150 days after an initial positive test for COVID-19.ResultsAmong 5058 children (50% female, 2.9% Asian, 6.3% Black, and 63% White; 30% Hispanic; mean age was 12.4 (IQR 8.9-15.6), 366 (7.2%) exhibited at least one new-onset neuropsychiatric symptom between 90 and 150 days following initial SARS-CoV-2 test positivity. The most common incident symptoms at 90-150 days were headache (2.4%), mood and anxiety symptoms (2.4%), cognitive symptoms (2.3%), and fatigue (1.1%). In regression models, older children, girls, those with Hispanic ethnicity, those with public versus private insurance, and those with greater overall burden of medical comorbidity were more likely to exhibit subsequent symptoms.ConclusionThe prevalence of neuropsychiatric symptoms between 3- and 5-months following SARS-CoV-2 test positivity is similar to that observed in the period prior to infection. Prospective controlled studies will be needed to further refine these estimates.
Excess Deaths associated with the COVID-19 Pandemic in Ukraine in 2020
Authors: Mehta Neil K. , Honchar Ihor , Doroshenko Olena , Brovchenko Igor , Pak Khrystyna , Danyuk Maria , Polikarchuk Pavlo 
Published: September 2021

AbstractCOVID-19 related mortality has been understudied in Ukraine. As part of a World Bank project, we estimated excess mortality in Ukraine during 2020. Data on all deaths registered in government-controlled Ukraine from 2016-2020 (N=2,946,505) were utilized. We predicted deaths in 2020 by five-year age groups, sex, and month and calculated the number of deaths that deviated from expected levels (excess deaths). We compared excess deaths with the number of recorded COVID-19 deaths on death certificates and with published estimates for 30 European countries. We estimated 38,095 excess deaths in 2020 (6% of all deaths). Death rates were above expected levels in February and from June-December and lower in January and March-May. From June-December, we estimated 52,124 excess deaths with a peak in November (16,891 deaths). COVID-19 recorded deaths were approximately one-third of excess deaths in June-December (18,959 vs. 52,124). Higher than expected mortality was detected for all age groups 40-44 years and above and for those ages 0-4, 15-19, and 20-24. Ukraine’s excess mortality was about average compared to 30 other European countries. Excess deaths may be attributed directly to SARS-COV2 infection or indirectly to death causes associated with social and economic upheavals resulting in from the pandemic. Lower than expected mortality during the early part of 2020 is consistent with low influenza activity and reductions in deaths from restricted movement. Further studies are required to examine the causes of death that have contributed to positive excess mortality, particularly among younger aged groups.Key MessagesUkraine has experienced sizeable changes in its recent demography and the impact of the COVID-19 pandemic on the country’s aggregate mortality patterns is understudiedBased on recent death trends, we found that Ukraine experienced lower than expected mortality during the early part of 2020 and consistently higher than expected mortality from June-December with peak levels occurring in NovemberPositive excess mortality was observed for all age groups beginning at ages 40-44 as well as some younger age groups.
Temporal analysis of enhancers during mouse brain development reveals dynamic regulatory function and identifies novel regulators of cerebellar development
Authors: Ramirez Miguel , Badayeva Yuliya , Yeung Joanna , Wu Joshua , Yang Erin ,   FANTOM 5 Consortium, Trost Brett , Scherer Stephen W. , Goldowitz Daniel 
Published: September 2021

AbstractIn this study, we identified active enhancers in the mouse cerebellum at embryonic and postnatal stages establishing the first catalog of enhancers active during embryonic cerebellum development. The majority of cerebellar enhancers have dynamic activity between embryonic and postnatal development. Cerebellar enhancers were enriched for neural transcription factor binding sites with temporally specific expression. Putative gene targets displayed spatially restricted expression patterns, indicating cell-type specific expression regulation. Functional analysis of target genes indicated that enhancers regulate processes spanning several developmental epochs such as specification, differentiation and maturation. We use these analyses to discover one novel regulator and one novel marker of cerebellar development: Bhlhe22 and Pax3, respectively. We identified an enrichment of de novo mutations and variants associated with autism spectrum disorder in cerebellar enhancers. Our study provides insight into the dynamics of gene expression regulation by enhancers in the developing brain and delivers a rich resource of novel gene-enhancer associations providing a basis for future in-depth studies in the cerebellum.
Specific Detection of Endogenous S129 Phosphorylated α-Synuclein in Tissue Using Proximity Ligation Assay
Authors: Arlinghaus Ryan , Iba Michiyo , Masliah Eliezer , Cookson Mark R , Landeck Natalie 
Published: September 2021

AbstractBACKGROUNDSynucleinopathies are a group of neurodegenerative disorders that are pathologically characterized by the accumulation of protein aggregates called Lewy Bodies. Lewy bodies are primarily composed of α-synuclein (asyn) protein, which is phosphorylated at serine 129 (pS129) when aggregated. Currently available commercial antibodies used to stain for pS129 asyn can cross react with other proteins, thus making it difficult to specifically detect endogenous pS129 asyn and to interpret pS129 asyn staining.OBJECTIVETo develop a staining procedure that detects pS129 asyn with high specificity and low background.METHODSWe use the fluorescent and brightfield in situ Proximity Ligation Assay (PLA) to specifically detect pS129 asyn in cell culture, mouse and human brain sections.RESULTSThe pS129 asyn PLA specifically stained for endogenous, soluble pS129 asyn in cell culture, mouse brain sections, and human brain tissue without significant cross-reactivity or background signal.CONCLUSIONSThis PLA method can be used to specifically detect pS129 asyn in order to further explore and understand its role in health and disease.
Beneficial Effects of Celastrol on Immune Balance by Modulating Gut Microbiota in Dextran Sodium Sulfate-Induced Ulcerative Colitis
Authors: Li Mingyue , Guo Weina , Dong Yalan , Wang Wenzhu , Tian Chunxia , Zhang Zili , Yu Ting , Zhou Haifeng , Gui Yang , Xue Kaming , Li Junyi , Jiang Feng , Sarapultsev Alexey , Luo Shanshan , Fan Heng , Hu Desheng 
Published: September 2021

AbstractUlcerative colitis (UC) is a chronic inflammatory bowel disease caused by multi-factors including colonic inflammation and microbiota dysbiosis. Previous studies have indicated that Celastrol (CSR) has strong anti-inflammatory and immune-inhibitory effects. Here, we investigated the effects of CSR on colonic inflammation and the mucosal immunity in an experimental colitis model, and addressed the mechanism by which CSR preforms the protective effect. We characterized the therapeutic effects and the potential mechanism of CSR in treating UC using histological staining, intestinal permeability assay, cytokine assay, flow cytometry, fecal microbiota transplantation (FMT), 16S rRNA sequencing, untargeted metabolomics, and cell differentiation approaches. CSR administration significantly ameliorated DSS-induced colitis, as evidenced by the recovery of body weight and colon length, decreased disease activity index (DAI) score, as well as decreased intestinal permeability. CSR down-regulated the secretion of proinflammatory cytokines, upregulated the anti-inflammatory mediators, and improved the balances of Treg/Th1 and Treg/Th17 to maintain colonic immune homeostasis. However, the protective effects of CSR disappeared when the antibiotic cocktail was applied to deplete the gut microbiota, and the gut microbiota-mediated effect was confirmed by FMT. Furthermore, CSR treatment increased the gut microbiota diversity and composition, and raised the metabolic productions of pyruvate and adenosine, which probably involve in gut microbiota mediated protective effect. In conclusion, CSR ameliorates colonic inflammation in a gut microbiota-dependent manner. The underlying protective mechanism is associated with the rectified Treg/Th1 and Treg/Th17 balance, and increased pyruvate and adenosine production. The study provided the solid evidence that CSR might be a promising therapeutic drug for UC.
A Chimeric Peptide Inhibits Red Blood Cell Invasion by Plasmodium falciparum with Hundredfold Increased Efficacy
Authors: Mannuthodikayil Jamsad , Sinha Suman , Singh Sameer , Biswas Anamika , Ali Irshad , Mashurabad Purna Chandra , Tabassum Wahida , Vydyam Pratap , Bhattacharyya Mrinal Kanti , Mandal Kalyaneswar 
Published: September 2021

AbstractInhibition of tight junction formation between two malaria parasite proteins, apical membrane antigen 1 and rhoptry neck protein 2, crucial for red blood cell invasion, prevents the disease progression. In this work, we have utilized a unique approach to design a chimeric peptide, prepared by fusion of the best features of two peptide inhibitors, that has displayed parasite growth inhibition, in-vitro, with nanomolar IC50, which is hundredfold better than any of its parent peptides. Further, to gain structural insights, we computationally modeled the hybrid peptide on its receptor.
Temporal transcriptional response of Candida glabrata during macrophage infection reveals a multifaceted transcriptional regulator CgXbp1 important for macrophage response and drug resistance
Authors: Rai Maruti Nandan , Parsania Chirag , Rai Rikky , Shirgaonkar Niranjan , Tan Kaeling , Wong Koon Ho 
Published: September 2021

AbstractCandida glabrata can thrive inside macrophages and tolerate high levels of azole antifungals. These innate abilities render infections by this human pathogen a clinical challenge. How C. glabrata reacts inside macrophages and what is the molecular basis of its drug tolerance are not well understood. Here, we mapped genome-wide RNA polymerase II (RNAPII) occupancy in C. glabrata to delineate its transcriptional responses during macrophage infection in high temporal resolution. RNAPII profiles revealed dynamic C. glabrata responses to macrophage with genes of specialized pathways activated chronologically at different times of infection. We identified an uncharacterized transcription factor (CgXbp1) important for the chronological macrophage response, survival in macrophages, and virulence. Genome-wide mapping of CgXbp1 direct targets further revealed its multi-faceted functions, regulating not only virulence-related genes but also genes associated with drug resistance. Finally, we showed that CgXbp1 indeed also affects azole resistance. Overall, this work presents a powerful approach for examining host-pathogen interaction and uncovers a novel transcription factor important for C. glabrata’s survival in macrophages and drug tolerance.
Influenza A virus undergoes compartmentalized replication in vivo dominated by stochastic bottlenecks
Authors: Amato Katherine A. , Haddock Luis A. , Braun Katarina M. , Meliopoulos Victoria , Livingston Brandi , Honce Rebekah , Schaack Grace A. , Boehm Emma , Higgins Christina A. , Barry Gabrielle L. , Koelle Katia , Schultz-Cherry Stacey , Friedrich Thomas C. , Mehle Andrew 
Published: September 2021

AbstractTransmission of influenza A viruses (IAV) between hosts is subject to numerous physical and biological barriers that impose genetic bottlenecks, constraining viral diversity and adaptation. The presence of bottlenecks within individual hosts and their potential impacts on evolutionary pathways taken during infection and subsequent transmission are poorly understood. To address this knowledge gap, we created highly diverse IAV libraries bearing molecular barcodes on two independent gene segments, enabling high-resolution tracking and quantification of unique virus lineages within hosts. Here we show that IAV infection in lungs is characterized by multiple within-host bottlenecks that result in “islands” of infection in lung lobes, each with genetically distinct populations. We performed site-specific inoculation of barcoded IAV in the upper respiratory tract of ferrets and tracked viral diversity as infection spread to the trachea and lungs. We observed compartmentalized replication of discrete barcoded populations within the lobes of the lung. Bottlenecks stochastically sampled individual viruses from the upper respiratory tract or the trachea that became the dominant genotype in a particular lobe. These populations are shaped strongly by founder effects, with no evidence for positive selection. The segregated sites of replication highlight the jackpot-style events that contribute to within-host influenza virus evolution and may account for low rates of intrahost adaptation.
Long-term experimental evolution decouples size and production costs in Escherichia coli
Authors: Marshall Dustin J. , Malerba Martino , Lines Thomas , Sezmis Aysha L. , Hasan Chowdhury M. , Lenski Richard E. , McDonald Michael J. 
Published: September 2021

AbstractBody size covaries with population dynamics across life’s domains. Theory holds that metabolism imposes fundamental constraints on the coevolution of size and demography. However, studies of interspecific patterns are confounded by other factors that covary with size and demography, and experimental tests of the causal links remain elusive. Here we leverage a 60,000-generation experiment in which Escherichia coli populations evolved larger cells to examine intraspecific metabolic scaling and correlations with demographic parameters. Metabolic theory successfully predicted the relations among size, metabolism, and maximum population density, with strong support for Damuth’s law of energy equivalence in this experiment. In contrast, populations of larger cells grew faster than those of smaller cells, contradicting the fundamental assumption that costs of production should increase proportionately with size. The finding that the costs of production are substantially decoupled from size requires re-examining the evolutionary drivers and ecological consequences of biological size more generally.
In silico screening of TMPRSS2 SNPs that affect its binding with SARS-CoV2 spike protein and directly involved in the interaction affinity changes
Authors: Nouira Fatma , Hamdi Manel , Redissi Alaeddine , Kouidhi Soumaya , Charfeddine Cherine , M’saad Meriem , Cherif Ameur , Messaoudi Sabri , Aldulaijan Sarah , Raouafi Noureddine , Dhouib Adnene , Mosbah Amor 
Published: September 2021

AbstractIn this paper, we used in silico analysis to shed light on the possible interaction between TMPRSS2 and SARS-CoV2 spike (S) protein by examining the role of TMPRSS2 single nucleotide polymorphisms (SNPs) in relation with susceptibility and inter-individual variability of SARS-CoV2 infection. First, we used molecular docking of human TMPRSS2 protein to predict the binding site of TMPRSS2, especially the TMPRSS2 link loops, in order to assess the effect TMPRSS2 SNPs. The latter lead to missense variants on the interaction between TMPRSS2 and SARS-CoV2 S protein. In a second step, we further refine our analysis by performing a structure-function analysis of the complexes using PyMol software, and finally by MD simulations to validate the as-obtained results. Our findings show that 17 SNPs among the 692 natural TMPRSS2 coding variants are in positions to influence the binding of TMPRSS2 with the viral S protein. All of them give more important interaction energy as assessed by docking. Among the 17 SNPs, four missense variants E389A, K392Q, T393S and Q438E lead to “directly increasing” the interaction affinity and 2 missense variants R470I and Y416C cause it “directly decreasing”. The R470I and Y416C present in African and American population, respectively. While the other 4 SNP variants (E389A; K392Q; T393S and Q438E) are present only in the European population, which could link the viral infection susceptibility to demographic, geographic and genetic factors.
mTOR inhibition enhances delivery and activity of antisense oligonucleotides in uveal melanoma cells
Authors: Dewaele Shanna , Delhaye Louis , De Paepe Boel , Bogaert Bram , Martinez Ramiro , Anckaert Jasper , Yigit Nurten , Nuytens Justine , Van Coster Rudy , Eyckerman Sven , Raemdonck Koen , Mestdagh Pieter 
Published: September 2021

AbstractUveal melanoma (UM) is the most common primary intraocular malignancy in adults. Due to a lack of effective treatments, patients with metastatic disease have a median survival time of 6-12 months. We recently demonstrated that the SAMMSON long non-coding RNA (lncRNA) is essential for uveal melanoma cell survival and that antisense oligonucleotide (ASO)-mediated silencing of SAMMSON impaired cell viability and tumor growth in vitro and in vivo. By screening a library of 2911 clinical stage compounds, we identified the mTOR inhibitor GDC-0349 to synergize with SAMMSON inhibition in UM. Mechanistic studies revealed that mTOR inhibition enhanced uptake and reduced lysosomal accumulation of lipid complexed SAMMSON ASOs, improving SAMMSON knockdown and further decreasing UM cell viability. We found mTOR inhibition to also enhance target knockdown in other cancer cell lines as well as normal cells when combined with lipid nanoparticle complexed or encapsulated ASOs or small interfering RNAs (siRNAs). Our results are relevant to nucleic acid treatment in general and highlight the potential of mTOR inhibition to enhance ASO and siRNA mediated target knockdown.
Protection of Hamsters Challenged with SARS-CoV-2 Variants of Concern by Two Doses of MVC-COV1901 Vaccine Followed by a Single Dose of Beta Variant Version of MVC-COV1901
Authors: Kuo Tsun-Yung , Lien Chia-En , Lin Yi-Jiun , Lin Meei-Yun , Wu Chung-Chin , Tang Wei-Hsuan , Campbell John D. , Traquina Paula , Chuang Ya-Shan , Liu Luke Tzu-Chi , Cheng Jinyi , Chen Charles 
Published: September 2021

AbstractThe current fight against COVID-19 is compounded by the Variants of Concern (VoCs), which can diminish the effectiveness of vaccines and potentially increase viral transmission and severity of disease. MVC-COV1901 is a protein subunit vaccine based on the prefusion SARS-CoV-2 spike protein (S-2P) and is adjuvanted with CpG 1018 and aluminum hydroxide. In this study, we used the Delta variant to challenge hamsters inoculated with S-2P from the Wuhan wildtype and the Beta variant in two-dose or three-dose regimens. Two doses of wildtype S-2P followed by the third dose of Beta variant was shown to induce the highest neutralizing antibody titer against live SARS-CoV-2 of the wildtype and all current VoCs, as well as improved neutralization against Omicron variant pseudovirus compared to three doses of wildtype S-P. All regimens of vaccination were able to protect hamsters from SARS-CoV-2 Delta variant challenge and resulted in reduced lung live virus titer and pathology. Three doses of vaccination also significantly reduced lung viral RNA titer, regardless of whether the wildtype or Beta variant S-2P was used as the third dose. Based on the immunogenicity and viral challenge data, two doses of wildtype S-2P followed by the third dose of Beta variant S-2P induced potent antibody immune responses against the VoCs.
Flooded with too many messages? Predictors and consequences of instant messaging fatigue
Authors: Sun Juhyung , Lee Sun Kyong 
Published: September 2021

PurposeDuring the digital media era with an explosion of messages, the prevalence of what is known as “message fatigue” has grown. However, there is a lack of understanding toward message fatigue in using instant messengers. Based on the stressor-strain-outcome framework, this study provides a theoretical model to explore possible predictors and consequences of instant messaging fatigue.Design/methodology/approachThe hypothesized model includes communication overload, social overload, instant messaging fatigue, technology and behavioral intention to use instant messaging. Three hundred and eleven responses are collected using an online survey. The authors conduct structural equation modeling to evaluate the hypothesized model and test the hypotheses.FindingsThis study reveals that (1) communication overload and social overload are positively associated with instant messaging fatigue and technostress; (2) higher levels of instant messaging fatigue and technostress are also related to a higher level of intention to discontinue usage; (3) technostress significantly mediates the relationship between instant messaging fatigue and intention to discontinue usage of instant messaging.Research limitations/implicationsThis study is limited to collect data from one university in the United States with a cross-sectional design. Future research should include other countries, different age groups and longitudinal methods to examine instant messaging fatigue.Originality/valueThis study extends existing findings on fatigue in using mobile communication by applying the stressor-strain-outcome framework to IM fatigue and improves the understanding of the potential negative aspects of instant messaging.
How e-wallets encourage excessive spending behavior among young adult consumers?
Authors: Aji Hendy Mustiko , Adawiyah Wiwiek Rabiatul 
Published: September 2021

Purpose
As it gains more popularity, e-wallets drive its users to spend more. Therefore, the purpose of this paper is to explore how and why e-wallets may encourage excessive spending behavior among young adult consumers.

Design/methodology/approach
An exploratory sequential or QUAL-QUANT design, combining qualitative and quantitative, is used in this study. It is a type of mixed-method design consisting of both the core and supplementary methods. The qualitative method is conducted in Study 1 using online focus group discussion to answer “why” and “how” questions, whereas the quantitative method is used in Study 2 to test or examine the hypothetical model. The questionnaires are extracted from focus group discussion in Study 1, which is further tested for validity and reliability and model estimation in Study 2. The model is evaluated using structural equation modeling.

Findings
Study 1 extracted four keywords to affect young adults spending behavior, easiness, promotions, self-control and perception of having more money (the illusion of liquidity). In Study 2, it is found that those four variables significantly affect spending behavior. Interestingly, it is also found in Study 2 that the illusion of liquidity mediates the relationship between self-control and spending behavior.

Research limitations/implications
During the COVID-19 pandemic, where a physical meeting is not encouraged, focus group discussion is conducted online via Zoom. Perhaps, this condition can be one limitation this study faced.

Originality/value
This study offers a theoretical contribution to the literature by exploring how and why e-wallet payment is connected to excessive spending behavior among young adult consumers. This study also provides a model that further explains the relationship between young adults’ spending behavior by adding the illusion of liquidity as the mediating variable.