bluuebunny/crossref_metadata_2025 huggingface dataset:
Premature Cardiovascular Death and its Modifiable Risk Factors: Protocol of a Systematic Review and Meta-Analysis
Authors: Rodzlan Hasani Wan Shakira , Muhamad Nor Asiah , Maamor Hasnah , Hanis Tengku Muhammad , Wee Chen Xin , Musa Kamarul Imran
Published: March 2022

Introduction

The burden of cardiovascular disease (CVDs), in the number of premature deaths, continues to increase globally and alarmingly, especially in almost all countries outside high-income countries. An accurate estimate of premature CVD death is of crucial importance for planning, implementing, and evaluating cardiovascular prevention and care interventions. However, existing literature reported the evidence on premature CVD death from selected regions, and there has been less evidence of systematic review with meta-analysis estimating the global premature death. This paper reports the protocol for a systematic review and meta-analysis to derive solid and updated estimates on global and setting-specific premature CVD death prevalence and its associated risk factors.

Methods and analysis

PUBMED, EMBASE, Web of Science, CINAHL, and Cochrane Central Register of Controlled Trials (CENTRAL) will be used as the literature database. Retrieved records will be independently screened by two authors and relevant data will be extracted from studies that report data on premature mortality (death before the age of 70 years) related to CVD. Study selection and reporting will follow the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guideline. Pooled estimates of premature CVD mortality (based on standardised mortality ratio and years of life lost) and the effect size of modifiable risk factors will be computed applying random-effects meta-analysis. Heterogeneity among selected studies will be assessed using the I2 statistic and explored through meta-regression and subgroup analyses. Depending on data availability, we propose to conduct subgroup analyses by geographical area, CVD events, and socio-demographic variables of interest study. The risk of bias for the studies included in the systematic review or meta-analysis will be assessed by the Newcastle–Ottawa Quality Assessment Scale.

Ethics and dissemination

Ethics approval is not required as the data used in this systematic review will be extracted from published studies. The systematic review will focus on the premature CVD mortality rate and its associated factors. The findings of the final report will be disseminated to the scientific community through publication in a peer-reviewed journal and presentation at conferences.

PROSPERO registration number

CRD42021288415
Anti-spike antibody response to natural infection with SARS-CoV-2 and its activity against emerging variants
Authors: Chen Cheng-Pin , Huang Kuan-Ying A. , Shih Shin-Ru , Lin Yi-Chun , Cheng Chien-Yu , Huang Yhu-Chering , Lin Tzou-Yien , Cheng Shu-Hsing
Published: March 2022

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has substantially impacted human health globally. Spike-specific antibody response plays a major role in protection against SARS-CoV-2. Here, we demonstrated that acute SARS-CoV-2 infection elicits rapid and robust spike-binding and ACE2-blocking antibody responses, which wane approximately 11 months after infection. Serological responses were found to be correlated with the frequency of spike-specific memory B cell responses to natural infections. Further, significantly higher spike-binding, ACE2-blocking, and memory B cell responses were detected in patients with fever and pneumonia. Spike-specific antibody responses were found to be greatly affected by spike mutations in emerging variants, especially the Beta and Omicron variants. These results warrant continued surveillance of spike-specific antibody responses to natural infections and highlight the importance of maintaining functional anti-spike antibodies through immunization.

Importance

As spike protein-specific antibody responses play a major role in protection against SARS-CoV-2, we examined the spike-binding and ACE2-blocking antibody responses in SARS-CoV-2 infection at different time points. We found robust responses following acute infection, which waned approximately 11 months after infection. Further, the serological responses were correlated with the frequency of spike-specific memory B cell responses to natural infections. Patients with fever and pneumonia showed significantly stronger spike-binding, ACE2-blocking antibody, and memory B cell responses. Moreover, the spike-specific antibody responses were substantially affected by the emerging variants, especially the Beta and Omicron variants. These results warrant continued surveillance of spike-specific antibody responses to natural infections and highlight the importance of maintaining functional anti-spike antibodies through immunization.
Skeletal Muscle TFEB Signaling Promotes Central Nervous System Function and Reduces Neuroinflammation during Aging and Neurodegenerative Disease
Authors: Matthews Ian , Birnbaum Allison , Gromova Anastasia , Huang Amy W. , Liu Kailin , Liu Eleanor A. , Coutinho Kristen , McGraw Megan , Patterson Dalton C. , Banks Macy T. , Nobles Amber C. , Nguyen Nhat , Merrihew Gennifer E. , Wang Lu , Baeuerle Eric , Fernandez Elizabeth , Musi Nicolas , MacCoss Michael J. , Miranda Helen C. , La Spada Albert R. , Cortes Constanza J.
Published: March 2022

Skeletal muscle has recently arisen as a novel regulator of Central Nervous System (CNS) function and aging, secreting bioactive molecules known as myokines with metabolism-modifying functions in targeted tissues, including the CNS. Here we report the generation of a novel transgenic mouse with enhanced skeletal muscle lysosomal and mitochondrial function via targeted overexpression of Transcription Factor E-B (TFEB). We have discovered that the resulting geroprotective effects in skeletal muscle reduce neuroinflammation and the accumulation of tau-associated pathological hallmarks in a mouse model of tau pathology. Muscle-specific TFEB overexpression also significantly ameliorates proteotoxicity, reduces neuroinflammation and promotes transcriptional remodeling of the aged CNS, preserving cognition and memory in aged mice. Our results implicate the maintenance of skeletal muscle function throughout aging to direct regulation of CNS health and disease, and suggest that skeletal-muscle originating factors may act as novel therapeutic targets against age-associated neurodegenerative disorders.
The genomic landscapes of desert birds form over multiple time scales
Authors: Provost Kaiya , Shue Stephanie Yun , Forcellati Meghan , Smith Brian Tilston
Published: March 2022

Spatial models show that genetic differentiation between populations can be explained by factors ranging from geographic distance to environmental resistance across the landscape. However, genomes exhibit a landscape of differentiation, which could indicate that multiple spatial models better explain divergence in different portions of the genome. We test whether alternative geographic predictors of intraspecific differentiation vary across the genome in ten bird species that co-occur in Sonoran and Chihuahuan Deserts of North America. Using population-level genomic data, we characterized the genomic landscapes across species and modeled five predictors that represented historical and contemporary mechanisms. The characteristics of genomic landscapes differed across the ten species, influenced by varying levels of population structuring and admixture between deserts. General dissimilarity matrix modeling indicated that the best-fit models differed from the whole genome and partitions along the genome. Almost all of the historical and contemporary mechanisms were important in explaining genetic distance, but particularly historical and contemporary environment, while contemporary abundance, position of the barrier to gene flow, and distance explained relatively less. Individual species have significantly different patterns of genomic variation. These results illustrate that the genomic landscape of differentiation was influenced by alternative geographic factors operating on different portions of the genome.
Gender-based disparities and biases in science: an observational study of a virtual conference
Authors: Zhang Junhanlu , Torchet Rachel , Julienne Hanna
Published: March 2022

Success in STEM (Science, Technology, Engineering, and Math) remains influenced by race, gender, and socioeconomic status. Here, we focus on the impact of gender on question-asking behavior during the 2021 JOBIM virtual conference (Journées Ouvertes en Biologie et Mathématiques). We gathered quantitative and qualitative data including : demographic information, question asking motivations, live observations and interviews of participants. Quantitative analyses include unprecedented figures such as the fraction of the audience identifying as LGBTQIA+ and an increased attendance of women in virtual conferences. Although parity was reached in the audience, women asked half as many questions as men. This under-representation persisted after accounting for seniority of the asker. Interviews of participants highlighted several barriers to oral expression encountered by women and gender minorities : negative reactions to their speech, discouragement to pursue a career in research, and gender discrimination/sexual harassment. Informed by the study,guidelinesfor conference organizers have been written.
Alnustone inhibits Streptococcus pneumoniae virulence by targeting pneumolysin and sortase A
Authors: Zhang Can , Wang Xinyu , Shi Linlin , Zhan Baihe , Hou NaNa , Liu Suohong , Bao Manjie , Chi Gefu , Fang Tianqi
Published: March 2022

Streptococcus pneumoniae (S. pneumoniae) is a significant Gram-positive opportunistic pathogen responsible for a variety of lethal infections. This bacterium accounts for more deaths from diseases than any other single pathogen worldwide. Distinctively, these symptoms arise despite effective antibiotic therapy. This study unveiled a novel mechanism of resistance to S. pneumoniae infection by targeting pneumolysin (PLY) and sortase A (Srt A), the key virulence factors of S. pneumoniae. Through protein phenotype assays, we found alnustone to be a potent drug that inhibits both PLY and Srt A. Using a PLY-mediated hemolysis assay, we found that albumin can effectively reduce Srt A peptidase activity by blocking PLY oligomerization, thereby directly inhibiting PLY-expressing cytolysis. Co-incubation of S. pneumoniae D39 Srt A with small-molecule inhibitors reduces cell wall-bound Nan A (pneumococcal-anchored surface protein Srt A), inhibits biofilm formation, and significantly reduces biomass. But more interestingly, the protective effect of invasive pneumococcal disease (IPD) on murine streptococcus pneumoniae was further demonstrated. Our study proposes a detailed bacteriostatic mechanism of pneumococcal and highlights the major translational potential of targeting circulating PLY and Srt A to protect against pneumococcal infections. Our results suggest that the antiviral strategy of directly targeting PLY and Srt A with alnustone is a promising treatment option for Streptococcus pneumoniae and that alnustone can be used as an effective inhibitor of PLY and Srt A.
Aerosolized Ad5-nCoV booster vaccination elicited potent immune response against the SARS-CoV-2 Omicron variant after inactivated COVID-19 vaccine priming
Authors: Zhang Zhe , Wu Shipo , Liu Yawei , Li Kailiang , Fan Pengfei , Song Xiaohong , Wang Yudong , Zhao Zhenghao , Zhang Xianwei , Shang Jin , Zhang Jinlong , Xu Jinghan , Li Yao , Li Yaohui , Zhang Jipeng , Fu Kefan , Wang Busen , Hao Meng , Zhang Guanying , Long Pengwei , Qiu Ziyu , Zhu Tao , Liu Shuling , Zhang Yue , Shao Fangze , Lv Peng , Yang Yilong , Zhao Xiaofan , Sun Yufa , Hou Lihua , Chen Wei
Published: March 2022

The SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant around the world and exhibits immune escape to current COVID-19 vaccines to some extent due to its numerous spike mutations. Here, we evaluated the immune responses to booster vaccination with intramuscular adenovirus-vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines 6 months prior. We found that the Ad5-nCoV booster induced potent neutralizing activity against the wild-type virus and Omicron variant, while aerosolized Ad5-nCoV generated the greatest neutralizing antibody responses against the Omicron variant at day 28 after booster vaccination, at 14.1-fold that of CoronaVac, 5.6-fold that of ZF2001 and 2.0-fold that of intramuscular Ad5-nCoV. Similarly, the aerosolized Ad5-nCoV booster produced the greatest IFNγ T-cell response at day 14 after booster vaccination. The IFNγ T-cell response to aerosolized Ad5-nCoV was 12.8-fold for CoronaVac, 16.5-fold for ZF2001, and 5.0-fold for intramuscular Ad5-nCoV. Aerosolized Ad5-nCoV booster also produced the greatest spike-specific B cell response. Our findings suggest that inactivated vaccine recipients should consider adenovirus-vectored vaccine boosters in China and that aerosolized Ad5-nCoV may provide a more efficient alternative in response to the spread of the Omicron variant.
Trends and factors associated with initiation of HIV treatment and uptake of viral load testing among PLHIV in Jamaica
Authors: Cushnie Anya , Reintjes Ralf , Artama Miia , Figueroa J. Peter
Published: March 2022

Introduction

Jamaica did not achieve the UNAIDS 90-90-90 targets in 2020. This study aims to examine trends and factors associated with uptake of HIV treatment and viral load testing among people living with HIV (PLHIV) in Jamaica, to make recommendations for improving patient management and outcomes.

Methods

This secondary analysis uses patient-level data from the National Treatment Service Information System. The baseline sample is PLHIV initiating anti-retroviral treatment (ART) between January 2015-December 2019. Descriptive statistics are used to summarize demographic and clinical variables. Multivariable logistic regression is used to assess factors associated with ART initiation (31+ days vs. same day) and viral load testing uptake (viral load test vs. no test), using categorical variables for age group, gender and regional health authority. Adjusted odds ratios and 95% confidence intervals are reported.

Results

Same day ART initiation increased by 72% over 5 years. The coverage of 1st viral load test was 90% but declined to 79% for the 2nd test. Testing occurred mostly after 0-6 months on ART (n=3047, 55%) and uptake was highest in the South-East Region (n=2885, 53%). Those virally suppressed were significantly more likely to have same day ART initiation compared to those non-suppressed (aOR=1.58, CI=1.43-1.75). Males were significantly more likely to have same day ART initiation (aOR=1.46, CI=1.32-1.62) but no first viral load test (aOR=1.55, CI=1.27-1.90) compared to females.

Conclusion

The goal of immediate ART initiation is increasingly being met and is significantly associated with viral suppression at the first viral load test. Males were less likely to have a viral load test after ART initiation. A qualitative assessment should be conducted to understand important challenges faced to access routine viral load testing, followed by implementation of differentiated service care models, targeting males.
Self-injury, suicidal ideation and -attempt and eating disorders in young people following the initial and second COVID-19 lockdown
Authors: Danielsen Stine , Joensen Andrea , Andersen Per Kragh , Madsen Trine , Strandberg-Larsen Katrine
Published: March 2022

Background

The initial COVID-19 lockdowns have had negative effect on different mental health measures, especially in young women. However, the impact on self-injury, suicidality and eating disorder (ED) are less elucidated and remains inconsistent. We compare self-reported self-injury, suicide ideation and -attempt and symptoms of EDs from before through different pandemic periods until spring 2021.

Methods

Young participants in the Danish National Birth Cohort reported these measures in an 18-year follow-up in 2015-2021 and in a COVID-19 survey in spring 2021 when participants were aged 19-24 years. Changes in measures from pre to post lockdown were estimated with longitudinal data (N=7,597) and with repeated cross-sectional data (N=24,625) by linear regression.

Findings

In the longitudinal comparisons 14% of women and 7% of men reported self-injury pre lockdown, which decreased 6%-points (95% CI:-7%;-5%) for women and 3%-points (95% CI:-4%;-2%) for men during lockdown. For suicide ideation, the pre lockdown proportions were 25% and 18% for women and men respectively, and decreased 7%-points (95% CI:-8%;-6%) for women and 3%-points (95% CI:-5%;-1%) for men. For suicide attempt no change was observed. Pre lockdown 15% and 3% of women and men, respectively, had symptoms of EDs, which decreased 2%-points (95% CI:-3%;-1%) for women. We observed no changes in proportions of self-injury, suicide ideation or EDs in the repeated cross-sectional data.

Interpretation

Our findings provide no support for increase in self-injury, suicidality and EDs following the lockdowns, and if anything, indicate a reduction in self-injury and suicide ideation as well as EDs in women.
Donor whole blood DNA methylation is not a strong predictor of acute graft versus host disease in unrelated donor allogeneic haematopoietic cell transplantation
Authors: Webster Amy P. , Ecker Simone , Moghul Ismail , Dhami Pawan , Marzi Sarah , Paul Dirk S. , Kuxhausen Michelle , Lee Stephanie J. , Spellman Stephen R. , Wang Tao , Feber Andrew , Rakyan Vardhman , Peggs Karl S. , Beck Stephan
Published: March 2022

Allogeneic hematopoietic cell transplantation (HCT) is used to treat many blood-based disorders and malignancies. While this is an effective treatment, it can result in serious adverse events, such as the development of acute graft-versus-host disease (aGVHD). This study aimed to develop a donor-specific epigenetic classifier that could be used in donor selection in HCT to reduce the incidence of aGVHD.

The discovery cohort of the study consisted of 288 donors from a population receiving HLA-A, -B, -C and -DRB1 matched unrelated donor HCT with T cell replete peripheral blood stem cell grafts for treatment of acute leukaemia or myelodysplastic syndromes after myeloablative conditioning. Donors were selected based on recipient aGVHD outcome; this cohort consisted of 144 cases with aGVHD grades III-IV and 144 controls with no aGVHD that survived at least 100 days post-HCT matched for sex, age, disease and GVHD prophylaxis.

Genome-wide DNA methylation was assessed using the Infinium Methylation EPIC BeadChip (Illumina), measuring CpG methylation at >850,000 sites across the genome. Following quality control, pre-processing and exploratory analyses, we applied a machine learning algorithm (Random Forest) to identify CpG sites predictive of aGVHD. Receiver operating characteristic (ROC) curve analysis of these sites resulted in a classifier with an encouraging area under the ROC curve (AUC) of 0.91.

To test this classifier, we used an independent validation cohort (n=288) selected using the same criteria as the discovery cohort. Different attempts to validate the classifier using the independent validation cohort failed with the AUC falling to 0.51. These results indicate that donor DNA methylation may not be a suitable predictor of aGVHD in an HCT setting involving unrelated donors, despite the initial promising results in the discovery cohort.

Our work highlights the importance of independent validation of machine learning classifiers, particularly when developing classifiers intended for clinical use.
The origins and molecular evolution of SARS-CoV-2 lineage B.1.1.7 in the UK
Authors: Hill Verity , Du Plessis Louis , Peacock Thomas P. , Aggarwal Dinesh , Colquhoun Rachel , Carabelli Alesandro M. , Ellaby Nicholas , Gallagher Eileen , Groves Natalie , Jackson Ben , McCrone JT , O’Toole Áine , Price Anna , Sanderson Theo , Scher Emily , Southgate Joel , Volz Erik ,   The COVID-19 genomics UK (COG-UK) consortium, Barclay Wendy S. , Barrett Jeffrey C. , Chand Meera , Connor Thomas , Goodfellow Ian , Gupta Ravindra K. , Harrison Ewan M. , Loman Nicholas , Myers Richard , Robertson David L , Pybus Oliver G , Rambaut Andrew
Published: March 2022

The first SARS-CoV-2 variant of concern (VOC) to be designated was lineage B.1.1.7, later labelled by the World Health Organisation (WHO) as Alpha. Originating in early Autumn but discovered in December 2020, it spread rapidly and caused large waves of infections worldwide. The Alpha variant is notable for being defined by a long ancestral phylogenetic branch with an increased evolutionary rate, along which only two sequences have been sampled. Alpha genomes comprise a well-supported monophyletic clade within which the evolutionary rate is more typical of SARS-CoV-2. The Alpha epidemic continued to grow despite the continued restrictions on social mixing across the UK, and the imposition of new restrictions, in particular the English national lockdown in November 2020. While these interventions succeeded in reducing the absolute number of cases, the impact of these non-pharmaceutical interventions was predominantly to drive the decline of the SARS-CoV-2 lineages which preceded Alpha. We investigate the only two sampled sequences that fall on the branch ancestral to Alpha. We find that one is likely to be a true intermediate sequence, providing information about the order of mutational events that led to Alpha. We explore alternate hypotheses that can explain how Alpha acquired a large number of mutations yet remained largely unobserved in a region of high genomic surveillance: an under-sampled geographical location, a non-human animal population, or a chronically-infected individual. We conclude that the last hypothesis provides the best explanation of the observed behaviour and dynamics of the variant, although we find that the individual need not be immunocompromised, as persistently-infected immunocompetent hosts also display a higher within-host rate of evolution. Finally, we compare the ancestral branches and mutation profiles of other VOCs to each other, and identify that Delta appears to be an outlier both in terms of the genomic locations of its defining mutations, and its lack of rapid evolutionary rate on the ancestral branch. As new variants, such as Omicron, continue to evolve (potentially through similar mechanisms) it remains important to investigate the origins of other variants to identify ways to potentially disrupt their evolution and emergence.
Geneticin shows selective antiviral activity against SARS-CoV-2 by interfering with programmed -1 ribosomal frameshifting
Authors: Varricchio Carmine , Mathez Gregory , Pillonel Trestan , Bertelli Claire , Kaiser Laurent , Tapparel Caroline , Brancale Andrea , Cagno Valeria
Published: March 2022

SARS-CoV-2 is currently causing an unprecedented pandemic. While vaccines are massively deployed, we still lack effective large-scale antiviral therapies. In the quest for antivirals targeting conserved structures, we focused on molecules able to bind viral RNA secondary structures. Aminoglycosides are a class of antibiotics known to interact with the ribosomal RNA of both prokaryotes and eukaryotes and have previously been shown to exert antiviral activities by interacting with viral RNA. Here we show that the aminoglycoside geneticin is endowed with antiviral activity against all tested variants of SARS-CoV-2, in different cell lines and in a respiratory tissue model at non-toxic concentrations. The mechanism of action is an early inhibition of RNA replication and protein expression related to a decrease in the efficiency of the -1 programmed ribosomal frameshift (PRF) signal of SARS-CoV-2. Using in silico modelling, we have identified a potential binding site of geneticin in the pseudoknot of frameshift RNA motif. Moreover, we have selected, through virtual screening, additional RNA binding compounds, interacting with the same site with increased potency.
Flexible estimation of biodiversity with short-range multispectral imaging in a temperate grassland
Authors: Jackson J. , Lawson C. S. , Adelmant C. , Huhtala E. , Fernandes P. , Hodgson R. , King H. , Williamson L. , Maseyk K. , Hawes N. , Hector A. , Salguero-Gómez R
Published: March 2022

Image sensing technologies are rapidly increasing the cost-effectiveness of biodiversity monitoring efforts. Species differences in the reflectance of electromagnetic radiation have recently been highlighted as a promising target to estimate plant biodiversity using multispectral image data.

However, these efforts are currently hampered by logistical difficulties in broad-scale implementation and their use in characterizing biodiversity at different spatial scales.

Here, we investigate the utility of multispectral imaging technology from commercially available unmanned aerial vehicles (UAVs, or drones) in estimating biodiversity metrics at short-range (<10 m image recording height) in a temperate calcareous grassland ecosystem in Oxfordshire, UK. We calculate a suite of moments (coefficient of variation, standard deviation, skew, kurtosis) for the distribution of radiance from multispectral images at five wavelength bands (Blue 450±16 nm; Green 560±16 nm; Red 650±16 nm; Red Edge 730±16 nm; Near Infrared 840±16 nm) and test their effectiveness at estimating ground-truthed biodiversity metrics fromin-situbotanical surveys for 37 - 1 m × 1 m quadrats.

We find positive associations between the average coefficient of variation in spectral radiance and both the Shannon-Weiner and Simpsons biodiversity indices. Furthermore, we find that the average coefficient of variation in spectral radiance is consistent and highly repeatable, across sampling days and recording heights. Positive associations with biodiversity indices hold irrespective of the image recording height (2-8 m), but we report reductions in estimates of spectral diversity with increases to UAV recording height. UAV imaging reduced sampling time by 16-fold relative toin-situbotanical surveys.

Synthesis- We demonstrate the utility of multispectral radiance moments as an indicator of grassland biodiversity metrics at high spatial resolution using a widely available UAV monitoring system at a coarse spectral resolution. The use of UAV technology with multispectral sensors has far-reaching potential to provide cost-effective and high-resolution monitoring of biodiversity in complex environments.
BMAL1 and MEX3A co-regulate intestinal stem cell succession
Authors: Chang Fang-Pei , Wang Cheng-Kai , Chou Yu-Chi , Chen Tzu-Jou , Wu Ya-Wen , Sridharan Samyuktha , Hsu Pang-Hung , Hwang-Verslues Wendy W.
Published: March 2022

Chemotherapeutic agents, such as 5-fluorouracil (5-FU), often induce intestinal mucositis due to toxicity to rapidly dividing intestinal stem cells (ISCs). Drug delivery at different times of day can alter 5-FU toxicity; however, the underlying biology is unclear. We found that homeostasis and succession between two ISC types, fast proliferating Lgr5+crypt base columnar (CBC) cells and stress-resistant +4 cells (Bmi1+), are controlled by the circadian clock transcription factor BMAL1 and the BMAL1-regulated RNA-binding protein MEX3A via both direct transcriptional regulation and post-transcriptional control ofLgr5mRNA stability.Bmal1knockout in Lgr5+CBCs reduced MEX3A expression and CBC numbers but increased Bmi1 expression in the crypts. Timing 5-FU delivery when crypt cells had lowLgr5but peak level ofBmi1protected ISCs from apoptosis. Together, these findings identify a novel role of BMAL1 in ISC homeostasis and provide a biological explanation for chronotherapeutic chemoprotection.
Lingering neural representations of past task features adversely affect future behavior
Authors: Rangel Benjamin O. , Hazeltine Eliot , Wessel Jan R.
Published: March 2022

During goal-directed behavior, humans purportedly form and retrieve so called ‘event files’ – conjunctive representations that link context-specific information about stimuli, their associated actions, and the expected action-outcomes. The automatic formation – and later retrieval – of such conjunctive ‘event file’ representations can substantially facilitate efficient action selection. However, recent behavioral work suggests that these event-files may also adversely affect future behavior, especially when action requirements have changed between successive instances of the same task context (e.g., during task-switching). Here, we directly tested this hypothesis through a recently developed method that allows measuring the strength of the neural representations of context-specific stimulus-action conjunctions (i.e., event files). Thirty-five male and female adult humans performed a task-switching paradigm while undergoing EEG recordings. Replicating previous behavioral work, we found that changes in action requirements between two spaced repetitions of the same task incurred a significant reaction time cost. By combining multi-variate pattern analysis and representational similarity analysis of the EEG recordings with linear mixed-effects modeling of trial-to-trial behavior, we then found that the magnitude of this behavioral cost was directly proportional to the strength of the conjunctive representation formed during the most recent previous exposure to the same task – i.e., the most recent ‘event file’. This confirms that the formation of conjunctive representations of specific task contexts, stimuli, and actions in the brain can indeed adversely affect future behavior. Moreover, these findings demonstrate the potential of neural decoding of complex task set representations towards the prediction of behavior beyond the current trial.
Introducing RELAX (the Reduction of Electroencephalographic Artifacts): A fully automated pre-processing pipeline for cleaning EEG data - Part 1: Algorithm and Application to Oscillations
Authors: Bailey NW , Biabani M , Hill AT , Miljevic A , Rogasch NC , McQueen B , Murphy OW , Fitzgerald PB
Published: March 2022

Electroencephalographic (EEG) data is typically contaminated with non-neural artifacts which can confound the results of experiments. Artifact cleaning approaches are available, but often require time-consuming manual input and significant expertise. Advancements in artifact cleaning often only address a single artifact, are only compared against a small selection of pre-existing methods, and seldom assess whether a proposed advancement improves experimental outcomes. To address these issues, we developed RELAX (the Reduction of Electroencephalographic Artifacts), an automated EEG cleaning pipeline implemented within EEGLAB that reduces all artifact types. RELAX cleans continuous data using Multiple Wiener filtering [MWF] and/or wavelet enhanced independent component analysis [wICA] applied to artifacts identified by ICLabel [wICA_ICLabel]). Several versions of RELAX were tested using three datasets containing a mix of cognitive and resting recordings (N = 213, 60 and 23 respectively). RELAX was compared against six commonly used EEG cleaning approaches across a wide range of artifact cleaning quality metrics, including signal-to-error and artifact-to-residue ratios, measures of remaining blink and muscle activity, and the amount of variance explained by experimental manipulations after cleaning. RELAX with MWF and wICA_ICLabel showed amongst the best performance for cleaning blink and muscle artifacts while still preserving neural signal. RELAX with wICA_ICLabel (and no MWF) may perform better at detecting the effect of experimental manipulations on alpha oscillations in working memory tasks. The pipeline is easy to implement in MATLAB and freely available on GitHub. Given its high cleaning performance, objectivity, and ease of use, we recommend RELAX for data cleaning across EEG studies.
The Plasmodium falciparum CCCH zinc finger protein ZNF4 plays an important role in gametocyte exflagellation through the regulation of male gametocyte enriched transcripts
Authors: Hanhsen Borja , Farrukh Afia , Pradel Gabriele , Ngwa Che Julius
Published: March 2022

CCCH zinc finger proteins (ZFPs) function mainly as RNA-binding proteins (RBPs) where they play a central role in the mRNA metabolism. Over 27 CCCH-ZFPs are encoded in the genome of the human malaria parasite Plasmodium falciparum, the causative agent of malaria tropica. However, little is known about their functions. In this study, we characterize one member of the PfCCCH-ZFP named ZNF4. We show that ZNF4 is highly expressed in mature gametocytes where it predominantly localizes to the cytoplasm. Targeted gene disruption of ZNF4 showed no significant effect in asexual blood stage replication and gametocyte development while male gametocyte exflagellation was significantly impaired leading to reduced malaria transmission in the mosquito. Comparative transcriptomics between wildtype (WT) and the ZNF4-deficient line (ZNF4-KO) demonstrated the de-regulation of about 473 genes (274-upregulated and 199 down-regulated) in mature gametocytes. Most of the down-regulated genes show peak expression in mature gametocyte with male enriched genes associated to the axonemal dynein complex formation and cell projection organization highly affected, pointing to the phenotype in male gametocyte exflagellation. Up-regulated genes are associated to ATP synthesis. Our combine data therefore indicate that ZNF4 is a CCCH zinc finger protein which plays an important role in male gametocyte exflagellation through the regulation of male gametocyte enriched genes.

Author Summary

CCCH ZFPs have gained significant interest due to their ability to interact with RNA and control different RNA metabolic processes. The role of CCCH ZFPs in the malaria parasite Plasmodium falciparum has not been well studied. In this study we report the functional characterization of a PfCCCH-ZFP named ZNF4. Using mouse anti-ZNF4 antisera and a ZNF4-HA tag parasite line we show that the protein is mainly expressed in the cytosol of mature gametocytes. To determine the function of ZNF4, we generated a ZNF4 knockout parasite line and we found that the asexual blood stages and gametocytes developed normally while the ability of the male gametocytes to exflagellate as well as the further development of the parasite in the mosquito was significantly impaired. Interestingly, when the transcriptome of mature gametocytes of the ZNF4-KO was compared to the WT, down-regulated genes were mainly male gametocyte enriched genes associated to processes involved in gametocyte exflagellation such axonemal dynein complex formation and cell projection organization indicating that ZNF4 plays an important role in male gametocyte exflagellation through the regulation of male gametocyte enriched transcripts.
Sepsis-induced brain state instability
Authors: Kala Annu , Leemburg Susan , Jezek Karel
Published: March 2022

Sepsis-associated brain dysfunction (SABD) is a frequent severe complication of sepsis and the systemic inflammatory response syndrome. It is associated with high mortality and a majority of survivors suffer long-term neurological consequences. Here, we aimed at better understanding the effects of SABD on oscillatory brain states in an acute rat model of sepsis induced by high dose LPS (10 mg/kg). To focus on intrinsically generated brain state dynamics, we used a urethane model that spares oscillatory activity in REM- and NREM-like sleep states. Soon after the intraperitoneal LPS injection we observed a robust instability of both oscillatory states resulting in tripling amount of state transitions that lasted for several hours, although the overall time spent in either state did not change. Analysis of power spectra showed opposing shifts in low frequency oscillations (1-9 Hz) that resulted in increased similarity between both states in 2-D state space. The described spectral characteristics of sepsis-induced EEG state instability might point to a mechanism underlying severe sleep fragmentation as described both in sepsis patients and in SABD animal models.
A Dynamic Bottom-Up Saliency Detection Method for Still Images
Authors: Sadeghi Leila , Kamkar Shiva , Moghaddam Hamid Abrishami
Published: March 2022

Introduction

Existing saliency detection algorithms in the literature have ignored the importance of time. They create a static saliency map for the whole recording time. However, bottom-up and top-down attention continuously compete and the salient regions change through time. In this paper, we propose an unsupervised algorithm to predict the dynamic evolution of bottom-up saliency in images.

Method

We compute the variation of low-level features within non-overlapping patches of the input image. A patch with higher variation is considered more salient. We use a threshold to ignore less salient parts and create a map. A weighted sum of this map and its center of mass is calculated to provide the saliency map. The threshold and weights are set dynamically. We use the MIT1003 and DOVES datasets for evaluation and break the recording to multiple 100ms or 500ms-time intervals. A separate ground-truth is created for each interval. Then, the predicted dynamic saliency map is compared to the ground-truth using Normalized Scanpath Saliency, Kullback-Leibler divergence, Similarity, and Linear Correlation Coefficient metrics.

Results

The proposed method outperformed the competitors on DOVES dataset. It also had an acceptable performance on MIT1003 especially within 0-400ms after stimulus onset.

Conclusion

This dynamic algorithm can predict an image’s salient regions better than the static methods as saliency detection is inherently a dynamic process. This method is biologically-plausible and in-line with the recent findings of the creation of a bottom-up saliency map in the primary visual cortex or superior colliculus.
SARS-CoV-2 Omicron variant is more stable than the ancestral strain on various surfaces
Authors: Hong Chin Alex Wing , Yuk Lai Alison Man , Peiris Malik , Man Poon Leo Lit
Published: March 2022

The Omicron BA.1 SARS-CoV-2 variant of concern spreads quickly around the world and outcompetes other circulating strains. We examined the stability of this SARS-CoV-2 variant on various surfaces and revealed that the Omicron variant is more stable than its ancestral strain on smooth and porous surfaces.
Dissecting the Role of the Human Microbiome in COVID-19 via Metagenome-assembled Genomes
Authors: Ke Shanlin , Weiss Scott T. , Liu Yang-Yu
Published: March 2022

Coronavirus disease 2019 (COVID-19), primarily a respiratory disease caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is often accompanied by gastrointestinal symptoms. However, little is known about the relation between the human microbiome and COVID-19, largely due to the fact that previous studies fail to provide high taxonomic resolution to identify microbes that likely interact with SARS-CoV-2 infection. Here we used whole-metagenome shotgun sequencing data together with assembly and binning strategies to reconstruct metagenome-assembled genomes (MAGs) from a total of 514 nasopharyngeal and fecal samples of patients with COVID-19 and controls. We reconstructed a total of 11,584 medium-and high-quality microbial MAGs and obtained 5,403 non-redundant MAGs (nrMAGs) with strain-level resolution. We found that, thanks to the high taxonomic resolution of nrMAGs, the gut microbiome signatures can accurately distinguish COVID-19 cases from healthy controls and predict the progression of COVID-19. Moreover, we identified a set of nrMAGs with a putative causal role in the clinical manifestations of COVID-19 and revealed their functional pathways that potentially interact with SARS-CoV-2 infection. The presented results highlight the importance of incorporating the human gut microbiome in our understanding of SARS-CoV-2 infection and disease progression. The genomic content of nrMAGs presented here has the potential to inform microbiome-based therapeutic developments for COVID-19 progression and post-COVID conditions.
Open modification searching of SARS-CoV-2–human protein interaction data reveals novel viral modification sites
Authors: Adams Charlotte , Boonen Kurt , Laukens Kris , Bittremieux Wout
Published: March 2022

The outbreak of the SARS-CoV-2 coronavirus, the causative agent of the COVID-19 disease, has led to an ongoing global pandemic since 2019. Mass spectrometry can be used to understand the molecular mechanisms of viral infection by SARS-CoV-2, for example, by determining virus–host protein–protein interactions (PPIs) through which SARS-CoV-2 hijacks its human hosts during infection, and to study the role of post-translational modifications (PTMs). We have reanalyzed public affinity purification mass spectrometry data using open modification searching to investigate the presence of PTMs in the context of the SARS-CoV-2 virus–host PPI network. Based on an over two-fold increase in identified spectra, our detected protein interactions show a high overlap with independent mass spectrometry-based SARS-CoV-2 studies and virus–host interactions for alternative viruses, as well as previously unknown protein interactions. Additionally, we identified several novel modification sites on SARS-CoV-2 proteins that we investigated in relation to their interactions with host proteins. A detailed analysis of relevant modifications, including phosphorylation, ubiquitination, and S-nitrosylation, provides important hypotheses about the functional role of these modifications during viral infection by SARS-CoV-2.
Crystal structure of 2-(benzo[d]thiazol-2-yl)-3,3-bis(ethylsulfanyl)acrylonitrile
Authors: Azzam Rasha A. , Elgemeie Galal H. , Elsayed Rasha E. , Gad Nagwa M. , Jones Peter G.
Published: March 2022

In the title compound, C14H14N2S3, the double-bond system of the acrylonitrile moiety is significantly non-planar, with absolute cis torsion angles of 13.9 (2) and 15.1 (2)°. The ring system and the double bond system subtend an interplanar angle of 11.16 (4)°. The wide angle C—C(CN)=C of 129.40 (12)° may be associated with a balance between planarity and avoidance of a very short S...S contact.
1-(Methyl-α-D-glucopyranosid-6-yl)-3-vinylimidazolium iodide dimethylformamide monosolvate
Authors: Lambrecht Sina , Villinger Alexander , Jopp Stefan
Published: March 2022

The title solvated molecular salt, [MeGluVIm]I (MeGluVIm = 1-(methyl-α-D-glucopyranosid-6-yl)-3-vinylimidazolium), or C12H19N2O5
+·I−·C3H7NO, was synthesized from methyl-α-D-6-iodoglucopyranoside and vinylimidazole in DMF. It crystallizes through precipitation from ethyl acetate solution directly after the reaction procedure. The crystal structure consists of an iodide anion and a [MeGluVIm] cation. Furthermore, the crystal structure contains one molecule of DMF, which accepts two O—H...H hydrogen bonds from the OH groups of the glucopyranoside.
The moderating role of complaint handling on brand hate in the cancel culture
Authors: Abbasi Amir Zaib , Fayyaz Muhammad Shahzeb , Ting Ding Hooi , Munir Maira , Bashir Shahid , Zhang Chun
Published: March 2022

Purpose

This study investigates the moderating role of complaint handling between ideological incompatibility, symbolic incongruity, negative past experience and corporate social irresponsibility on brand hate.

Design/methodology/approach

The study employs the Duplex Hate theory which assumes that hate is the manifestation of multiple factors. A survey-based self-administered questionnaire was used to collect data from 400 smartphone users at Rawalpindi and Islamabad, Pakistan.

Findings

The findings suggest that ideological incompatibility, symbolic incongruity, negative past experience and corporate social irresponsibility contributes to brand hate. The complaint handling (moderator) weakens the effects of ideological incompatibility and symbolic incongruity on brand hate.

Practical implications

The research provides insights into the cancel culture and clarifies how brand hate can be controlled.

Originality/value

Empirical study on the antecedents of brand hate remains insufficient. The current study contributes to the brand hate literature by providing an understanding of the phenomenon of brand hate and by empirically examining the different antecedents responsible for causing the behavior. The study has also provided an additional determinant of brand hate, which is corporate social irresponsibility. The role of moderators for controlling brand hate is greatly ignored in the existing literature. The current work also extends previous studies by investigating a moderating factor for reducing brand hate, which is complaint handling.
Fruit-related lifestyles as a segmentation tool for fruit consumers
Authors: Ahmadi Kaliji Sina , Imami Drini , Canavari Maurizio , Gjonbalaj Mujë , Gjokaj Ekrem
Published: March 2022

Purpose

This study develops a modified food-related lifestyle (FRL) instrument to analyse Kosovo consumers' fruit consumption behaviour and attitudes.

Design/methodology/approach

The research study is based on a structured questionnaire designed using a reduced version of the FRL instrument, including evaluation factors related to fruit consumption, which is useful to describe a fruit-related lifestyle. Data were collected through a face-to-face survey with 300 consumers in three main cities in Kosovo. A principal component analysis (PCA) with Varimax rotation and Kaiser Normalisation was performed to interpret and investigate fruit-related lifestyles. Cluster analysis was performed to analyse market segments, using the identified factors obtained from the PCA, a hierarchical clustering algorithm with a Ward linkage method and the K-means clustering technique.

Findings

Consumption behaviour is motivated by health concerns (perceived), fruit (nutrition) content and consumption habits. Four distinct consumer clusters were identified based on the fruit-related lifestyle instrument and analysed considering the different fruit purchase and consumption behaviour, attitudes towards health, quality, taste and safety.

Research limitations/implications

The authors adapted a survey tool based on a reduced FRL instrument to elaborate a specific survey instrument suitable to describe the fruit-related consumer's lifestyles. The instrument was not designed according to the standard scales design procedure, but it is a first step towards creating a fruit-related lifestyle instrument.

Originality/value

The fruit-related lifestyle instrument can be used in studies focused on fruit consumer segmentation. Results provide insight into fruit marketing and distribution companies, which can adjust their marketing strategies and customer-oriented initiatives tailored for specific consumer segments. Results can be useful also for policymakers to promote increased fruit consumption.