bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Exercise Interventions on Aerobic Capacity and Health-Related Quality of Life in People Living With HIV/AIDS: Systematic Review and Network Meta-Analysis
Authors: Gomes-Neto Mansueto , Saquetto Micheli Bernardone , Alves Iura Gonzalez , Martinez Bruno Prata , Vieira João Paulo B , Brites Carlos 
Published: March 2021

AbstractObjectiveExercise is a recommended component of care for people living with HIV/AIDS; however, it is unclear which type of exercise is most effective. The purpose of this study was to investigate the relative effects of different types of exercise interventions on aerobic capacity measured by peak oxygen consumption (peak VO2) and health-related quality of life (HRQoL) in this population.MethodsFor this systematic review and indirect-comparisons meta-analysis (network meta-analysis), different electronic databases were searched up to February 2020 for randomized controlled trials that evaluated the effects of different types of exercise interventions on peak VO2 and HRQoL of people living with HIV/AIDS. Mean differences, standardized mean difference (SMD), and 95% CI were calculated. Fixed- and random-effects Bayesian network meta-analysis were used to compare the relative effectiveness of the different exercise interventions.ResultsForty studies met the study criteria, reporting on a total of 1518 patients. When comparing the exercise interventions with usual care (control group) for the peak VO2 outcome, combined aerobic and resistance exercise was the highest ranked exercise intervention with an SMD of 4.2 (95% CI = 2.5 to 5.9), followed by aerobic exercise (SMD = 3.1; 95% CI = 1.4 to 5.1). Compared with aerobic exercise, resistance training, and yoga, combined aerobic and resistance exercise was the best exercise intervention to promote improvement on physical function, general health, mental health, and energy/vitality domains HRQoL.ConclusionThe combined aerobic and resistance exercise was the highest ranked exercise intervention to improve peak VO2 and HRQoL. Combined aerobic and resistance exercise should be considered as a component of care for people living with HIV/AIDS.
Self-reported real-world safety and reactogenicity of COVID-19 vaccines: An international vaccine-recipient survey
Authors: Mathioudakis Alexander G. , Ghrew Murad , Ustianowski Andrew , Ahmad Shazaad , Borrow Ray , Papavasileiou Lida Pieretta , Petrakis Dimitrios , Bakerly Nawar Diar 
Published: March 2021

AbstractBackgroundThe safety of COVID-19 vaccines has been demonstrated in selected populations in recent studies, but more data in specific groups is needed to inform vaccine choice and health policy.ObjectivesAn international, online survey was conducted to compare the safety, tolerability and reactogenicity of available COVID-19 vaccines in different recipient groups.MethodsThis survey was launched in February 2021, for 11 days. Recipients of a first COVID-19 vaccine dose ≥7 days prior to survey completion were eligible. The incidence and severity of vaccination side effects were assessed.ResultsSurvey was completed by 2,002 respondents, of whom 26.6% had prior COVID-19 infection (68.8% laboratory confirmed). Prior COVID-19 infection was associated with increased risk of any side effect (risk ratio 1.08, 95% confidence intervals [1.05-1.11]), fever (2.24 [1.86-2.70]), breathlessness (2.05 [1.28-3.29]), flu-like illness (1.78 [1.51-2.10]), fatigue (1.34 [1.20-1.49]) and local reactions (1.10 [1.06-1.15]). It was also associated with increased risk of severe side effects, leading to hospital care (1.56 [1.14-2.12]).While mRNA vaccines were associated with a higher incidence of any side effect (1.06 [1.01-1.11]) compared to viral vector-based vaccines, these were generally milder (p<0.001), mostly local reactions. Importantly, mRNA vaccine-recipients reported considerably lower incidence of systemic reactions (RR<0.6) including anaphylaxis, swelling, flu-like illness, breathlessness and fatigue, and of side effects requiring hospital care (0.42 [0.31-0.58]).ConclusionFor the first time, our study links prior COVID-19 illness with increased incidence of vaccination side effects and demonstrates that mRNA vaccines cause milder, less frequent systemic side effects, but more local reactions.Key messages–People with prior COVID-19 illness appear to experience significantly increased incidence and severity of side effects after receiving the COVID-19 vaccine.–In this first head-to-head comparison of the safety and reactogenicity of different types of vaccines, it was demonstrated that mRNA vaccines cause milder, less frequent systemic side effects, compared to viral vector vaccines, but more local reactions.Tweetable SummaryA survey of >2000 COVID-19 vaccine-recipients links prior COVID-19 illness with increased incidence of vaccination side effects; mRNA vaccines cause milder, less frequent systemic side effects, but more local reactions.
Impact of remdesivir on 28 day mortality in hospitalized patients with COVID-19: February 2021 Meta-analysis
Authors: Robinson Robert , Prakash Vidhya , Al Tamimi Raad , Albast Nour , Al-Bast Basma , Wieland Elizabeth , Garcia Carlos 
Published: March 2021

AbstractBackgroundThe COVID-19 pandemic has stimulated worldwide investigation into a myriad of potential therapeutic agents, including antivirals such as remdesivir. The first RCT reporting results on the impact of remdesivir on COVID-19 in a peer reviewed journal was the ACTT-1 trial published in November, 2020. The ACTT-1 trial showed more rapid clinical improvement and a reduced risk of 28-day mortality in patients who received remdesivir.This study is a meta-analysis of peer reviewed RCTs aims to estimate the association of remdesivir therapy compared to the usual care or placebo on all-cause mortality in hospitalized patients with COVID-19. Software based tools to accelerate the analysis process.MethodsMeta-analysis of peer reviewed RCTs comparing remdesivir to usual care or placebo. The protocol for this meta-analysis was registered and published in the PROSPERO database (CRD42021229985) on February 5, 2021.ResultsFour English language RCTs were identified, including data from 7,333 hospitalized patients worldwide using remdesivir in COVID-19 positive patients.Meta-analysis of all identified RCTs showed no difference in survival in patients who received remdesivir therapy compared to usual care or placebo. The random effects meta-analysis has a summary odd ratio is 0.89 (95% CI 0.65-1.21, p = 0.30). Considerable variability in the severity of illness is noted with the rates of IMV at the time of randomization ranging from 0% to 27%.ConclusionsThis meta-analysis of randomized controlled trials published in peer-reviewed literature by February 1, 2021 did not show reduced mortality in hospitalized patients with COVID-19 who received remdesivir. Further research is needed to clarify the role of remdesivir therapy in the management of COVID-19.
Comparison of IgG and neutralizing antibody responses after one or two doses of COVID-19 mRNA vaccine in previously infected and uninfected persons
Authors: Demonbreun Alexis R. , Sancilio Amelia , Velez Matt E. , Ryan Daniel T. , Saber Rana , Vaught Lauren A. , Reiser Nina L. , Hsieh Ryan R. , D’Aquila Richard T. , Mustanski Brian , McNally Elizabeth M. , McDade Thomas W. 
Published: March 2021

ABSTRACTObjectiveTo compare anti-SARS-CoV-2 spike receptor binding domain (RBD) IgG antibody concentrations and antibody-mediated neutralization of spike-ACE2 receptor binding in vitro following vaccination of non-hospitalized participants by sero-status and acute virus diagnosis history.MethodsParticipants were studied before and after mRNA vaccination in a community-based, home-collected, longitudinal serosurvey; none reported hospitalization for COVID-19. Prior to vaccination, some reported prior positive acute viral diagnostic testing and were seropositive (COVID-19+). Participants who did not report acute viral diagnostic testing were categorized as seropositive or seronegative based on anti-spike RBD IgG test results. Primary measures were anti-spike RBD IgG concentration and percent antibody-mediated neutralization of spike protein-ACE2 interaction prior to vaccination, and after one or two doses of vaccine.ResultsOf 290 unique vaccine recipients, 42 reported a prior COVID-19 diagnosis and were seropositive (COVID-19+). Of the 248 with no history of acute viral diagnostic testing, 105 were seropositive and 143 seronegative before vaccination. The median age was 38yrs (range 21-83) with 65% female and 35% male; 40% were non-white. Responses were evaluated after one (n=140) or two (n=170) doses of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine. After one dose, median post-vaccine IgG concentration and percent neutralization were each significantly higher among the COVID-19+ group (median 47.7 µg/ml, IgG; >99.9% neutralization) compared to the seropositives (3.4 µg /ml IgG; 62.8% neutralization) and seronegatives (2.2 µg /ml IgG; 39.5% neutralization). The latter two groups reached >95% neutralization after the second vaccine dose.ConclusionsA prior outpatient COVID-19 diagnosis was associated with strong anti-spike RBD IgG and in vitro neutralizing responses after one vaccine dose. Persons seropositive for anti-spike RBD IgG in the absence of acute viral diagnostic testing, and those who were seronegative, required two doses to achieve equivalently high levels of IgG and neutralization activity. One mRNA vaccine dose is not sufficient to generate in vitro evidence of strong protection against COVID-19 among most persons previously infected with SARS-CoV-2, nor among seronegative persons.
Revealing Spatiotemporal Circuit Information of Olfactory Bulb in Large-scale Neural Recordings
Authors: Hu Xin , Khanzada Shahrukh , Klütsch Diana , Calegari Federico , Amin Hayder 
Published: March 2021

ABSTRACTLarge-scale multi-site biosensors are essential to probe the olfactory bulb (OB) circuitry for understanding the spatiotemporal dynamics of simultaneous discharge patterns. Current ex-vivo electrophysiological techniques are limited to recording a small set of neurons and cannot provide an inadequate resolution, which hinders revealing the fast dynamic underlying the information coding mechanisms in the OB circuit. Here, we demonstrate a novel biohybrid OB-CMOS platform to decipher the cross-scale dynamics of OB electrogenesis and quantify the distinct neuronal coding properties. The approach with 4096-microelectrodes offers a non-invasive, label-free, bioelectrical imaging to decode simultaneous firing patterns from thousands of connected neuronal ensembles in acute OB slices. The platform can measure spontaneous and drug-induced extracellular field potential activity. We employ our OB-CMOS recordings to perform multidimensional analysis to instantiate specific neurophysiological metrics underlying the olfactory spatiotemporal coding that emerged from the OB interconnected layers. Our results delineate the computational implications of large-scale activity patterns in functional olfactory processing. The high-content characterization of the olfactory circuit could benefit better functional interrogations of the olfactory spatiotemporal coding, connectivity mapping, and, further, the designing of reliable and advanced olfactory cell-based biosensors for diagnostic biomarkers and drug discovery.
Odor-evoked Increases in Olfactory Bulb Mitral Cell Spiking Variability
Authors: Ly Cheng , Barreiro Andrea K. , Gautam Shree Hari , Shew Woodrow L. 
Published: March 2021

AbstractAt the onset of sensory stimulation, the variability and co-variability of spiking activity is widely reported to decrease, especially in cortex. Considering the potential benefits of such decreased variability for coding, it has been suggested that this could be a general principle governing all sensory systems. Here we show that this is not so. We recorded mitral cells in olfactory bulb (OB) of anesthetized rats and found increased variability and co-variability of spiking at the onset of olfactory stimulation. Using models and analysis, we predicted that these increases arise due to network interactions within OB, without increasing variability of input from the nose. We tested and confirmed this prediction in awake animals with direct optogenetic stimulation of OB to circumvent the pathway through the nose. Our results establish increases in spiking variability at stimulus onset as a viable alternative coding strategy to the more commonly observed decreases in variability in many cortical systems.SummaryThe spiking variability of neural networks has important implications for how information is encoded to higher brain regions. It has been well documented by numerous labs in many cortical and motor regions that spiking variability decreases with stimulus onset, yet whether this principle holds in the olfactory bulb has not been tested. In stark contrast to this common view, we demonstrate that the onset of sensory input can cause an increase in the variability of neural activity in the mammalian olfactory bulb. We show this in both anesthetized and awake rodents. Furthermore, we use computational models to describe the mechanisms of this phenomenon. Our finding establish sensory evoked increases in spiking variability as a viable alternative.
BoolSim, a Graphical Interface for Open Access Boolean Network Simulations and Use in Guard Cell CO2Signaling
Authors: Karanam Aravind , He David , Hsu Po-Kai , Schulze Sebastian , Dubeaux Guillaume , Karmakar Richa , Schroeder Julian I. , Rappel Wouter-Jan 
Published: March 2021

ABSTRACTSignaling networks are at the heart of almost all biological processes. Most of these networks contain a large number of components and often the connections between these components are either not known, or the rate equations that govern the dynamics of soluble signaling components are not quantified. This uncertainty in network topology and parameters can make it challenging to formulate detailed mathematical models. Boolean networks, in which all components are either on or off, have emerged as viable alternatives to more detailed mathematical models but can be difficult to implement. Therefore, open source format of such models for community use is desirable. Here we present BoolSim, a freely available graphical user interface (GUI) that allows users to easily construct and analyze Boolean networks. BoolSim can be applied to any Boolean network. We demonstrate BoolSim’s application using a previously published network for abscisic acid-driven stomatal closure inArabidopsis.We also show how BoolSim can be used to generate testable predictions by extending the network to include CO2regulation of stomatal movements. Predictions of the model were experimentally tested and the model was iteratively modified based on experiments showing that ABA closes stomata even at near zero CO2concentrations (1.5 ppm CO2).One Sentence SummaryThis study presents an open-source, graphical interface for the simulation of Boolean networks and applies it to an abscisic acid signaling network in guard cells, extended to include input from CO2.
Proteogenomic characterization of hepatocellular carcinoma
Authors: Ng Charlotte K Y , Dazert Eva , Boldanova Tuyana , Coto-Llerena Mairene , Nuciforo Sandro , Ercan Caner , Suslov Aleksei , Meier Marie-Anne , Bock Thomas , Schmidt Alexander , Ketterer Sylvia , Wang Xueya , Wieland Stefan , Matter Matthias S , Colombi Marco , Piscuoglio Salvatore , Terracciano Luigi M , Hall Michael N , Heim Markus H 
Published: March 2021

SUMMARYWe performed a proteogenomic analysis of hepatocellular carcinomas (HCCs) across clinical stages and etiologies. We identified pathways differentially regulated on the genomic, transcriptomic, proteomic and phosphoproteomic levels. These pathways are involved in the organization of cellular components, cell cycle control, signaling pathways, transcriptional and translational control and metabolism. Analyses of CNA-mRNA and mRNA-protein correlations identified candidate driver genes involved in epithelial-to-mesenchymal transition, the Wnt-β-catenin pathway, transcriptional control, cholesterol biosynthesis and sphingolipid metabolism. The activity of targetable kinases aurora kinase A and CDKs was upregulated. We found thatCTNNB1mutations are associated with altered phosphorylation of proteins involved in actin filament organization, whereasTP53mutations are associated with elevated CDK1/2/5 activity and altered phosphorylation of proteins involved in lipid and mRNA metabolism. Integrative clustering identified HCC subgroups with distinct regulation of biological processes, metabolic reprogramming and kinase activation. Our analysis provides insights into the molecular processes underlying HCCs.
Deletion disrupts a conserved antibody epitope in a SARS-CoV-2 variant of concern
Authors: Rennick Linda J. , Robinson-McCarthy Lindsey R. , Nambulli Sham , Duprex W. Paul , McCarthy Kevin R. 
Published: March 2021

AbstractMultiple SARS-CoV-2 variants with altered antigenicity have emerged and spread internationally. In one lineage of global concern, we identify a transmitted variant with a deletion in its receptor binding domain (RBD) that disrupts an epitope which is conserved across sarbecoviruses. Overcoming antigenic variation by selectively focusing immune pressure on this conserved site may, ultimately, drive viral resistance.
Secondary attack rates of COVID-19 in Norwegian families: A nation-wide
register-based study
Authors: Telle Kjetil , Jørgensen Silje B. , Hart Rannveig , Greve-Isdahl Margrethe , Kacelnik Oliver 
Published: March 2021

Background
Reported transmission rates of SARS-CoV-2 within families vary widely,
and there are few reports on transmission from children to other family
members. More knowledge is needed to guide infection control
measures.

Objective
To characterize the family index case for detected SARS-CoV-2 and
describe testing and secondary attack rates in the family.

Design
Register-based cohort study.

Setting
Individual-level administrative data of all families and all PCR tests
for SARS-CoV-2 in Norway in 2020.

Participants
All families with at least one parent and one child below the age of 20,
who lived at the same address (N=662 582), where at least one member tested
positive for SARS-CoV-2 in 2020.

Main outcome measures
Secondary attack rates (SAR7) were defined as the share of non-index
family members with a positive PCR test within seven days of the index case.
SARs were calculated separately for parent- and child-index cases, and for
parent- and child-secondary cases.

Results
We identified 7548 index cases, comprising 26 991 individuals, of which
12184 were parents and 14808 children. The index was a parent in 66% of the
cases. Among the children, 42% of the index cases were in the age group
17-20 and only 8% 0-6 years. When the index was a parent, SAR7 was 24%
(95%CI 24 to 25), whilst SAR7 was 14% (95%CI 13 to 15) when the index was a
child. However, SAR7 was 24% (95%CI 20 to 28) when the index was a child
aged 0-6 years and declined steeply with increasing age of the index child.
SAR7 from index parent to other parents was 35% (95%CI 33 to 36), and from
index child to other children 12% (95%CI 11 to 13). SAR7 from index child
aged 0-6 to parents was 27% (95%CI 22 to 33). The percent of non-index
family members tested within 7 days after the index case, increased from
about 20% in April to 80% in December, however, SAR7 stabilized at about 20%
from May.

Conclusion
Parents and older children are most often index cases for SARS-CoV-2 in
families in Norway, while parents and young children more often transmit the
virus within the families. This study suggests that whilst the absolute
infection numbers are low for young children because of their low
introduction rate, when infected, young children and parents transmit the
virus to the same extent within the family.
Translational activation by an alternative sigma factor inBacillus subtilis
Authors: McCormick Dylan M. , Lalanne Jean-Benoît , Lan Tammy C. T. , Rouskin Silvi , Li Gene-Wei 
Published: March 2021

ABSTRACTSigma factors are an important class of bacterial transcription factors that lend specificity to RNA polymerases by binding to distinct promoter elements for genes in their regulons. Here we show that activation of the general stress sigma factor, σB, inBacillus subtilisparadoxically leads to dramatic induction of translation for a subset of its regulon genes. These genes are translationally repressed when transcribed by the housekeeping sigma factor, σA, owing to extended RNA secondary structures as determinedin vivousing DMS-MaPseq. Transcription from σB-dependent promoters liberates the secondary structures and activates translation, leading to dual induction. Translation efficiencies between σB- and σA-dependent RNA isoforms can vary by up to 100-fold, which in multiple cases exceeds the magnitude of transcriptional induction. These results highlight the role of long-range RNA folding in modulating translation and demonstrate that a transcription factor can regulate protein synthesis beyond its effects on transcript levels.
Conditional Stomatal Closure in a Fern Shares Molecular Features with Flowering Plant Active Stomatal Responses
Authors: Plackett Andrew R.G. , Emms David M. , Kelly Steven , Hetherington Alistair M. , Langdale Jane A. 
Published: March 2021

AbstractStomata evolved as plants transitioned from water to land, enabling carbon dioxide uptake and water loss to be controlled. In flowering plants, the most recently divergent land plant lineage, stomatal pores actively close in response to drought. In this response, the phytohormone abscisic acid (ABA) triggers signalling cascades that lead to ion and water loss in the guard cells of the stomatal complex, causing a reduction in turgor and pore closure. Whether this stimulus-response coupling pathway acts in other major land plant lineages is unclear, with some investigations reporting that stomatal closure involves ABA but others concluding that closure is passive. Here we show that in the model fernCeratopteris richardiiactive stomatal closure is conditional on sensitisation by pre-exposure to either low humidity or exogenous ABA and is promoted by ABA. RNA-seq analysis andde novotranscriptome assembly reconstructed the protein coding complement of theC. richardiigenome with coverage comparable to other plant models, enabling transcriptional signatures of stomatal sensitisation and closure to be identified. In both cases, changes in abundance of homologs of ABA, Ca2+and ROS-related signalling components were observed, suggesting that the closure response pathway is conserved in ferns and flowering plants. These signatures further suggested that sensitisation is achieved by lowering the threshold required for a subsequent closure-inducing signal to trigger a response. We conclude that the canonical signalling network for active stomatal closure functioned in at least a rudimentary form in the stomata of the last common ancestor of ferns and flowering plants.Significance StatementStomata are valve-like pores that control the uptake of CO2and the loss of water vapour in almost all land plants. In flowering plants, stomatal opening and closure is actively regulated by a stimulus-response coupling network. Whether active stomatal responses are present in other land plant lineages such as ferns has been hotly debated. Here we show that stomatal responses in the fernCeratopteris richardiiare active but depend on their past growth environment, and demonstrate that fern stomatal closure and sensitisation are associated with the altered expression of genes whose homologs function in the canonical stomatal regulatory network of flowering plants. Genetic pathways for active stomatal regulation therefore most likely evolved before the divergence of ferns and flowering plants.