bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain Basis of Psychopathy in Criminal Offenders and General Population
Authors: Nummenmaa Lauri , Lukkarinen Lasse , Sun Lihua , Putkinen Vesa , Seppälä Kerttu , Karjalainen Tomi , Karlsson Henry K , Hudson Matthew , Venetjoki Niina , Salomaa Marja , Rautio Päivi , Hirvonen Jussi , Lauerma Hannu , Tiihonen Jari
Published: March 2021

Psychopathy is characterized by persistent antisocial behavior, impaired empathy, and egotistical traits. These traits vary also in normally functioning individuals. Here, we tested whether such antisocial personalities are associated with similar structural and neural alterations as those observed in criminal psychopathy. Subjects were 100 non-convicted well-functioning individuals, 19 violent male offenders, and 19 matched controls. Subjects underwent T1-weighted magnetic resonance imaging and viewed movie clips with varying violent content during functional magnetic resonance imaging. Psychopathic traits were evaluated with Levenson Self-Report Psychopathy Scale (controls) and Psychopathy Checklist-Revised (offenders). Psychopathic offenders had lower gray matter density (GMD) in orbitofrontal cortex and anterior insula. In the community sample, affective psychopathy traits were associated with lower GMD in the same areas. Viewing violence increased brain activity in periaqueductal grey matter, thalamus, somatosensory, premotor, and temporal cortices. Psychopathic offenders had increased responses to violence in thalamus and orbitofrontal, insular, and cingulate cortices. In the community sample, impulsivity-related psychopathy traits were positively associated with violence-elicited responses in similar areas. We conclude that brain characteristics underlying psychopathic spectrum in violent psychopathy are related to those observed in well-functioning individuals with asocial personality features.
Unmet needs for CKD care: from the general population to the CKD clinics—how many patients are we missing?
Authors: Torreggiani Massimo , Chatrenet Antoine , Fois Antioco , Coindre Jean Philippe , Crochette Romain , Sigogne Mickael , Wacrenier Samuel , Seret Guillaume , Mazé Béatrice , Lecointre Léna , Breuer Conrad , Fessi Hafedh , Piccoli Giorgina Barbara
Published: March 2021

Introduction

Prevalence of chronic kidney disease (CKD) varies around the world. Little is known about the discrepancy between the general population's needs and nephrology care offered. We aimed to contribute to filling this gap and propose a means to infer the number of patients needing follow-up.

Methods

All patients undergoing at least one nephrology consultation in 2019 were enrolled. We used the ratio between CKD Stages 3 and 4 reported in the literature, and considered that only 25–50% of CKD Stage 3 patients have progressive CKD, to hypothesize different scenarios to estimate the number of CKD Stage 3 patients still needing nephrology follow-up.

Results

The 1992 CKD patients were followed-up in our centre (56.93% males; age 66.71 ± 18.32 years; 16.82% Stage 1; 14.66% Stage 2; 39.46% Stage 3; 19.88% Stage 4; 7.68% Stage 5). The ratio between Stages 3 and 4 in population studies ranged from 7.72 to 51.29, being 1.98 in our centre. Hypothesizing that we followed-up 100, 70 or 50% of CKD Stage 4 patients, 528–2506 CKD Stage 3 patients in our area would need nephrology follow-up [1885–8946 per million population (p.m.p.)]. Three to 17 additional nephrologists p.m.p. would be necessary to fully cover the need for care.

Conclusions

The number of patients with CKD Stage 3 who would benefit from nephrology care is high. Considering that one patient-year of delay of dialysis could cover a nephrologist’s annual salary, interventions aimed to improve the care of advanced CKD may be economically sound.
Multimodality cardiac imaging for management of a cardiac mass in the era of COVID-19: a case report
Authors: Ranjan Pragya , LaRocca Gina , Sanz Javier , Croft Lori
Published: March 2021

Background 

Atrial myxomas are the most common benign cardiac tumours. This case highlights an unusual presentation and complex management of a patient who was incidentally found to have a left atrial tumour concerning for a myxoma.

Case summary 

A 54-year-old-woman presented with symptoms of nausea and vomiting and was found to have a left atrial mass incidentally in addition to a renal infarct. She was also found to have COVID-19 and the mass was initially thought to be a thrombus. With the help of multimodality imaging, it was determined that the mass was an atrial myxoma and she was started on short-term anticoagulation to prevent recurrent embolization. After 6 weeks of anticoagulation, she successfully underwent elective resection of the mass which was confirmed to be myxoma with superimposed thrombus.

Discussion 

It is difficult to differentiate cardiac tumours from intracardiac thrombus and multimodality cardiac imaging is crucial to make an accurate diagnosis. While the treatment of atrial myxomas involves early surgical resection, it becomes more complicated with concurrent COVID-19 infection.
The Standard Portfolio Choice Problem in Germany
Authors: Breunig Christoph , Huck Steffen , Schmidt Tobias , Weizsäcker Georg
Published: March 2021

We study an investment experiment with a representative sample of German households. Respondents invest in a safe asset and a risky asset whose return is tied to the German stock market. Experimental investments correlate with beliefs about stock market returns and exhibit desirable external validity at least in one respect: they predict real-life stock market participation. But many households are unresponsive to an exogenous increase in the risky asset’s return. The data analysis and a series of additional laboratory experiments suggest that task complexity decreases the responsiveness to incentives. Modifying the safe asset’s return has a larger effect on behaviour than modifying the risky asset’s return.
Heat-killed Lactobacillus acidophilus mediates Fusobacterium nucleatum induced pro-inflammatory responses in epithelial cells
Authors: Ding Qinfeng , Sun Xuecheng , Cao Shuai , Zhao Cancan , Wang Yitong , Wang Xudong
Published: March 2021

Probiotics is widespreadly used nowadays. However, the safety issue with the use of live probiotics is still a matter of contention. In recent years, an expanding body of evidence supports the beneficial role of heat-killed probiotics in the maintenance of systemic health, whereas the role of these heat-killed bacteria on periodontal health remains unclear. This study aimed to evaluate the effects of heat-killed probiotics on periodontal pathogen virulence and associated mechanisms. We demonstrated that heat-killed Lactobacillus acidophilus was able to coaggregate with Fusobacterium nucleatum, the bridging bacteria of oral biofilm, and inhibit the adhesion and invasion of F. nucleatum, leading to a subsequent elimination of pro-inflammatory cytokine production in oral epithelial cells. This coaggregation further caused a suppression of the virulence gene fap2 expression in F. nucleatum. Therefore, heat-killed L. acidophilus might downregulate the pro-inflammatory cytokine expression in epithelial cells via coaggregation with F. nucleatum and suppression of F. nucleatum fap2 expression, which was the first demonstration that heat-killed probiotics modulate periodontal disease pathogenesis via coaggregation. Collectively, this finding provides new evidence that heat-killed probiotics might exert beneficial effects to periodontal health by coaggregating with periodontal pathogens and modulating their virulence.
Interactions between the WEE-1.3 kinase and the PAM-1 aminopeptidase in oocyte maturation and the earlyC. elegansembryo
Authors: Benton Dorothy , Jaeger Eva C , Kilner Arielle , Kimble Ashley , Lowry Josh , Schleicher Emily M , Power Kaiden M , Uibel Danielle , Eisele Caprice , Bowerman Bruce , Lyczak Rebecca
Published: March 2021

Puromycin-sensitive aminopeptidases are found across phyla and are known to regulate the cell-cycle and play a protective role in neurodegenerative disease. PAM-1 is a puromycin-sensitive aminopeptidase important for meiotic exit and polarity establishment in the one-cell Caenorhabditis elegans embryo. Despite conservation of this aminopeptidase, little is known about its targets during development. In order to identify novel interactors, we conducted a suppressor screen and isolated four suppressing mutations in three genes that partially rescued the maternal-effect lethality of pam-1 mutants. Suppressed strains show improved embryonic viability and polarization of the anterior–posterior axis. We identified a missense mutation in wee-1.3 in one of these suppressed strains. WEE-1.3 is an inhibitory kinase that regulates maturation promoting factor. Although the missense mutation suppressed polarity phenotypes in pam-1, it does so without restoring centrosome–cortical contact or altering the cortical actomyosin cytoskeleton. To see if PAM-1 and WEE-1.3 interact in other processes, we examined oocyte maturation. Although depletion of wee-1.3 causes sterility due to precocious oocyte maturation, this effect was lessened in pam-1 worms, suggesting that PAM-1 and WEE-1.3 interact in this process. Levels of WEE-1.3 were comparable between wild-type and pam-1 strains, suggesting that WEE-1.3 is not a direct target of the aminopeptidase. Thus, we have established an interaction between PAM-1 and WEE-1.3 in multiple developmental processes and have identified suppressors that are likely to further our understanding of the role of puromycin-sensitive aminopeptidases during development.
Solution-Focused Brief Therapy for Substance Use: A Review of the Literature
Authors: Franklin Cynthia , Hai Audrey Hang
Published: March 2021

Substance use is a prevalent public health issue. Most social workers may encounter substance use in their work with clients and need effective therapeutic strategies for this issue. Since the 1980s, solution-focused brief therapy (SFBT) has been practiced with clients who have substance use problems, and clinical training materials have been developed to help practitioners learn and use SFBT in substance use treatment. Despite the longevity of the use of SFBT in practice, there are no published reviews of outcome studies to guide practitioners using SFBT. This article fills a gap in current literature on SFBT and substance use treatment by reviewing the published studies on SFBT where the focus was on substance use treatment. Five databases were searched to identify eligible studies. Experts and reference lists of relevant studies were also consulted. Nine studies were identified and included in the review. All studies reviewed found promising evidence on SFBT’s effectiveness in improving substance use behaviors and related psychosocial problems. Five of the nine studies reviewed showed that SFBT can change substance use and comorbid mental health and psychosocial problems such as depression, trauma, and school- and work-related behavior problems. The article concludes with a discussion of the study results’ implications for clinical practice and future research.
Mental Health Service Utilization among Adults with Head Injury with Loss of Consciousness: Implications for Social Work
Authors: Coxe Kathryn A , Lee Guijin , Kagotho Njeri , Eads Ray
Published: March 2021

The purpose of this study was to identify factors associated with mental health service utilization among adults with head injury with loss of consciousness (LOC) using Andersen’s model of health. This secondary data analysis used the 2011–2014 National Health and Nutrition Examination Survey with data collected from 7,399 adults. Binary logistic regression was conducted to determine odds associated with predisposing, enabling, and needs factors on head injury with LOC and mental health service utilization. A total of  948 (12.8 percent) adults 40 years and older self-reported head injury with LOC. Head injury with LOC was higher among men and people with lower income, illicit drug use history, and moderate to severe depression. Mental health service utilization for people with head injury with LOC was lower among older-age adults and those with no health insurance. However, utilization was higher among adults with military service, history of drug use, and moderate to severe depression. Social workers in health care settings play critical roles serving adults with traumatic brain injury (TBI) through mental health and substance use disorder treatment and bridging gaps in service access. Social workers should recognize the complex needs of clients with TBI and factors affecting mental health service use.
Use of a Contained Mycobacterium tuberculosis Mouse Infection Model to Predict Active Disease and Containment in Humans
Authors: Duffy Fergal J , Olson Gregory S , Gold Elizabeth S , Jahn Ana , Aderem Alan , Aitchison John D , Rothchild Alissa C , Diercks Alan H , Nemeth Johannes
Published: March 2021

Previous studies have identified whole-blood transcriptional risk and disease signatures for tuberculosis; however, several lines of evidence suggest that these signatures primarily reflect bacterial burden, which increases before symptomatic disease. We found that the peripheral blood transcriptome of mice with contained Mycobacterium tuberculosis infection (CMTI) has striking similarities to that of humans with active tuberculosis and that a signature derived from these mice predicts human disease with accuracy comparable to that of signatures derived directly from humans. A set of genes associated with immune defense are up-regulated in mice with CMTI but not in humans with active tuberculosis, suggesting that their up-regulation is associated with bacterial containment. A signature comprising these genes predicts both protection from tuberculosis disease and successful treatment at early time points where current signatures are not predictive. These results suggest that detailed study of the CMTI model may enable identification of biomarkers for human tuberculosis.
Implicit-based computer-aided design for additively manufactured functionally graded cellular structures
Authors: Nguyen Cong Hong Phong , Kim Youngdoo , Do Quang Thang , Choi Young
Published: March 2021

Additive manufacturing has enabled the fabrication of complex structures such as cellular structures. Although numerous design frameworks have been proposed for cellular structures, their effectiveness was limited owing to the use of B-rep-based representation. To address the limitations in previous research, this study proposes an implicit-based computer-aided design framework customized for additively manufactured functionally graded cellular structures (AM-FGCSs). The proposed design framework effectively aids in both single- and multiscale structural optimization for designing FGCSs. Moreover, implicit-based modeling afforded a reliable geometric representation that could efficiently assist computation tasks such as visualization, validation, and process planning for fabrication. In addition, two case studies were conducted to demonstrate the effectiveness of the proposed framework for designing FGCSs. The first case study on a three-point bending beam design problem proved the practicality of implicit-based representation in multiscale structural design. Meanwhile, the second case study validated the proficiency of the proposed framework in process planning for fabrication and engineering analysis, the two most vital computation tasks in designing cellular structures.
Spatial Distribution of Chesapeake Bay Riparian Hemlock Forests Threatened by Hemlock Woolly Adelgid
Authors: Fajvan Mary Ann , Morin Randall S
Published: March 2021

Landscape-scale maps of tree species densities are important tools for managing ecosystems threatened by forest pests. Eastern hemlock dominates riparian forests throughout its range. As a conifer in a deciduous landscape, hemlock plays an ecohydrological role, especially when other species are dormant. The nonnative, hemlock woolly adelgid has caused widespread hemlock decline and mortality. We used two existing basal area raster layers first to identify Chesapeake Bay subwatersheds with ≥6 percent hemlock basal area and second to quantify hemlock basal area densities within fixed-width riparian buffers of 50 m, 100 m, 250 m, and 500 m. Hemlock densities were higher in riparian zones compared with entire subwatersheds. In five subwatersheds, 50 m and 100 m zones had higher percentages of pixels with ≥25 percent hemlock basal area. We produced maps identifying hemlock riparian densities in the Pine Creek Watershed, which managers can use to prioritize sites for supplemental conifer planting under anticipated hemlock decline.
Delayed chylothorax in the absence of radiological evidence of rib or vertebral body fractures following blunt trauma
Authors: Mazhar Khurum , Mohamed Saifullah , Patel Akshay Jatin , Berger-Veith Sarah , Abid Qamar , Ghosh Shilajit
Published: March 2021

Our case report illustrates effective implementation of conservative measures without the need for more invasive procedures, which can be required in refractory cases. Our patient was a 42-year-old female who fell from a horse and presented with a 1-week history of dyspnoea. Investigations revealed her to have a large right chylothorax, which was treated conservatively with chest drainage and octreotide. The patient remained in hospital for a total of 3 days prior to being discharged home without further complications. Blunt traumatic chylothorax should be considered as part of the differential diagnosis in patients who present with ongoing dyspnoea or chest discomfort within a 2-week preceding history of blunt trauma. Radiological imaging should be mandatory and the absence of posterior thoracic fractures does not exclude the diagnosis. Conservative management with pleural drainage, medium-chain triglyceride diet and octreotide yielded excellent results in our case.
Kozak Sequence Acts as a Negative Regulator for De Novo Transcription Initiation of Newborn Coding Sequences in the Plant Genome
Authors: Hata Takayuki , Satoh Soichirou , Takada Naoto , Matsuo Mitsuhiro , Obokata Junichi
Published: March 2021

The manner in which newborn coding sequences and their transcriptional competency emerge during the process of gene evolution remains unclear. Here, we experimentally simulated eukaryotic gene origination processes by mimicking horizontal gene transfer events in the plant genome. We mapped the precise position of the transcription start sites (TSSs) of hundreds of newly introduced promoterless firefly luciferase (LUC) coding sequences in the genome of Arabidopsis thaliana cultured cells. The systematic characterization of the LUC-TSSs revealed that 80% of them occurred under the influence of endogenous promoters, while the remainder underwent de novo activation in the intergenic regions, starting from pyrimidine-purine dinucleotides. These de novo TSSs obeyed unexpected rules; they predominantly occurred ∼100 bp upstream of the LUC inserts and did not overlap with Kozak-containing putative open reading frames (ORFs). These features were the output of the immediate responses to the sequence insertions, rather than a bias in the screening of the LUC gene function. Regarding the wild-type genic TSSs, they appeared to have evolved to lack any ORFs in their vicinities. Therefore, the repulsion by the de novo TSSs of Kozak-containing ORFs described above might be the first selection gate for the occurrence and evolution of TSSs in the plant genome. Based on these results, we characterized the de novo type of TSS identified in the plant genome and discuss its significance in genome evolution.
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

Objective

Exercise 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.

Methods

For 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.

Results

Forty 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.

Conclusion

The 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.
Comparative transcriptomic analysis of the mechanisms underpinning ageing and fecundity in social insects
Authors: Korb Judith , Meusemann Karen , Aumer Denise , Bernadou Abel , Elsner Daniel , Feldmeyer Barbara , Foitzik Susanne , Heinze Jürgen , Libbrecht Romain , Lin Silu , Majoe Megha , Monroy Kuhn José Manuel , Nehring Volker , Negroni Matteo A. , Paxton Robert J. , Séguret Alice C. , Stoldt Marah , Flatt Thomas ,   the So-Long consortium
Published: March 2021

The exceptional longevity of social insect queens despite their lifelong high fecundity remains poorly understood in ageing biology. To gain insights into the mechanisms that might underlie ageing in social insects, we compared gene expression patterns between young and old castes (both queens and workers) across different lineages of social insects (two termite, two bee and two ant species). After global analyses, we paid particular attention to genes of the insulin/insulin-like growth factor 1 signalling (IIS)/target of rapamycin (TOR)/juvenile hormone (JH) network, which is well known to regulate lifespan and the trade-off between reproduction and somatic maintenance in solitary insects. Our results reveal a major role of the downstream components and target genes of this network (e.g. JH signalling, vitellogenins, major royal jelly proteins and immune genes) in affecting ageing and the caste-specific physiology of social insects, but an apparently lesser role of the upstream IIS/TOR signalling components. Together with a growing appreciation of the importance of such downstream targets, this leads us to propose the TI–J–LiFe (
T
OR/
I
IS–
J
H–
Li
fespan and
Fe
cundity) network as a conceptual framework for understanding the mechanisms of ageing and fecundity in social insects and beyond.

This article is part of the theme issue ‘Ageing and sociality: why, when and how does sociality change ageing patterns?’
The effect of environmental stress on ageing in a termite species with low social complexity
Authors: Rau Veronika , Korb Judith
Published: March 2021

Social insects seem to have overcome the almost universal trade-off between fecundity and longevity as queens can be highly fecund and at the same time reach lifespans of decades. By contrast, their non-reproducing workers are often short-lived. One hypothesis to explain the long lifespan of queens is that they are better protected against stress than their workers. However, evidence is controversial and experimental studies are scarce. We aimed at manipulating environmental stress and ageing by exposing colonies of the less-socially complex termite
Cryptotermes secundus
to temperature regimes that differed in variance. In contrast with expectation, constant temperatures imposed more stress than variable temperatures. Survival of queens and workers as well as queens' fecundity were partly reduced under constant conditions and both castes showed signs of ageing in the transcriptome signature under constant conditions. There was a clear oxidative stress defence signal under constant conditions that was, surprisingly, stronger for workers than queens. We discuss how our results relate to social complexity. We argue that workers that are totipotent to become reproductives, like in
C. secundus
, should invest more in ‘anti-ageing' mechanisms than sterile workers because the former can still reproduce and have not reached maturity yet.

This article is part of the theme issue ‘Ageing and sociality: why, when and how does sociality change ageing patterns?’
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

Background

The 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.

Objectives

An international, online survey was conducted to compare the safety, tolerability and reactogenicity of available COVID-19 vaccines in different recipient groups.

Methods

This 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.

Results

Survey 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]).

Conclusion

For 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 Summary

A 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

Background

The 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.

Methods

Meta-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.

Results

Four 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%.

Conclusions

This 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

Objective

To 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.

Methods

Participants 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.

Results

Of 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.

Conclusions

A 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.
Within-sibship GWAS improve estimates of direct genetic effects
Authors: Howe Laurence J , Nivard Michel G , Morris Tim T , Hansen Ailin F , Rasheed Humaira , Cho Yoonsu , Chittoor Geetha , Lind Penelope A , Palviainen Teemu , van der Zee Matthijs D , Cheesman Rosa , Mangino Massimo , Wang Yunzhang , Li Shuai , Klaric Lucija , Ratliff Scott M , Bielak Lawrence F , Nygaard Marianne , Reynolds Chandra A , Balbona Jared V , Bauer Christopher R , Boomsma Dorret I , Baras Aris , Campbell Archie , Campbell Harry , Chen Zhengming , Christofidou Paraskevi , Dahm Christina C , Dokuru Deepika R , Evans Luke M , de Geus Eco JC , Giddaluru Sudheer , Gordon Scott D , Harden K. Paige , Havdahl Alexandra , Hill W. David , Kerr Shona M , Kim Yongkang , Kweon Hyeokmoon , Latvala Antti , Li Liming , Lin Kuang , Martikainen Pekka , Magnusson Patrik KE , Mills Melinda C , Lawlor Deborah A , Overton John D , Pedersen Nancy L , Porteous David J , Reid Jeffrey , Silventoinen Karri , Southey Melissa C , Mallard Travis T , Tucker-Drob Elliot M , Wright Margaret J ,   Social Science Genetic Association Consortium,   Within Family Consortium, Hewitt John K , Keller Matthew C , Stallings Michael C , Christensen Kaare , Kardia Sharon LR , Peyser Patricia A , Smith Jennifer A , Wilson James F , Hopper John L , Hägg Sara , Spector Tim D , Pingault Jean-Baptiste , Plomin Robert , Bartels Meike , Martin Nicholas G , Justice Anne E , Millwood Iona Y , Hveem Kristian , Naess Øyvind , Willer Cristen J , Åsvold Bjørn Olav , Koellinger Philipp D , Kaprio Jaakko , Medland Sarah E , Walters Robin G , Benjamin Daniel J , Turley Patrick , Evans David M , Smith George Davey , Hayward Caroline , Brumpton Ben , Hemani Gibran , Davies Neil M
Published: March 2021

Estimates from genome-wide association studies (GWAS) represent a combination of the effect of inherited genetic variation (direct effects), demography (population stratification, assortative mating) and genetic nurture from relatives (indirect genetic effects). GWAS using family-based designs can control for demography and indirect genetic effects, but large-scale family datasets have been lacking. We combined data on 159,701 siblings from 17 cohorts to generate population (between-family) and within-sibship (within-family) estimates of genome-wide genetic associations for 25 phenotypes. We demonstrate that existing GWAS associations for height, educational attainment, smoking, depressive symptoms, age at first birth and cognitive ability overestimate direct effects. We show that estimates of SNP-heritability, genetic correlations and Mendelian randomization involving these phenotypes substantially differ when calculated using within-sibship estimates. For example, genetic correlations between educational attainment and height largely disappear. In contrast, analyses of most clinical phenotypes (e.g. LDL-cholesterol) were generally consistent between population and within-sibship models. We also report compelling evidence of polygenic adaptation on taller human height using within-sibship data. Large-scale family datasets provide new opportunities to quantify direct effects of genetic variation on human traits and diseases.
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

Large-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

At 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.

The 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

Signaling 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 Summary

This 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

We 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

Multiple 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

Sigma 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.