bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanistic models of Rift Valley fever virus transmission dynamics: A systematic review
Authors: Cecilia Hélène , Drouin Alex , Métras Raphaëlle , Balenghien Thomas , Durand Benoit , Chevalier Véronique , Ezanno Pauline 
Published: March 2022

AbstractRift Valley fever (RVF) is a zoonotic arbovirosis which has been reported across Africa including the northernmost edge, South West Indian Ocean islands, and the Arabian Peninsula. The virus is responsible for high abortion rates and mortality in young ruminants, with economic impacts in affected countries. To this day, RVF epidemiological mechanisms are not fully understood, due to the multiplicity of implicated vertebrate hosts, vectors and ecosystems. In this context, mathematical models are useful tools to develop our understanding of complex systems, and mechanistic models are particularly suited to data-scarce settings. In this work, we performed a systematic review of mechanistic models studying RVF, to explore their diversity and their contribution to the understanding of this disease epidemiology. Researching Pubmed and Scopus databases (October 2021), we eventually selected 48 papers, which needed to provide a clear description of a mechanistic model with numerical application to RVF. We categorized models as theoretical, applied or grey, according to their will to represent a specific geographical context and their use of data to fulfill this intention. We discussed their contributions to the understanding of RVF epidemiology, and highlighted that theoretical and applied models can use different tools to meet common objectives. Through the examination of model features, we identified research questions left unexplored across scales, along with a substantial lack of justification when choosing a functional form for the force of infection. Overall, we showed a great diversity in RVF models, leading to substantial progress in our comprehension of epidemiological mechanisms. To go further, data gaps must be fulfilled, and modelers need to go the extra mile regarding transparency.Authors summaryRift Valley fever (RVF) affects humans and livestock across Africa, South West Indian Ocean islands, and in the Arabian Peninsula. This disease is one of the World Health Organization priorities, and is caused by a virus transmitted by Aedes and Culex spp. mosquitoes, but also directly from livestock to humans. Mathematical models have been used in the last 20 years to disentangle RVF virus transmission dynamics. These models can further our understanding of processes driving outbreaks, test the efficiency of control strategies, or even anticipate possible emergence. Provided with detailed datasets, models can tailor their conclusions to specific geographical contexts and aid in decision-making in the field. This review provides a general overview of mathematical models developed to study RVF virus transmission dynamics. We describe their main results and methodological choices, and identify hurdles to be lifted. To offer innovative animal and public health value, we recommend that future models focus on the relative contribution of host species to transmission, and the role of animal mobility.
Unravelling the link between sleep and mental health during the COVID-19 pandemic
Authors: González-Hijón Juan , Kähler Anna K. , Frans Emma M. , Valdimarsdóttir Unnur A. , Sullivan Patrick F. , Fang Fang , Lovik Anikó 
Published: March 2022

AbstractBackgroundThe emergence of COVID-19 brought unparalleled changes in people’s lifestyle, including sleep. We aimed to assess the bidirectional association between sleep quality and mental health and describe how sleep and mental health were affected in Sweden during the COVID-19 pandemic (between June 2020 and September 2021).MethodsData were obtained from the Omtanke2020 study. Participants who completed the baseline survey and 8 monthly follow-up surveys were included (N=9035). We described the distribution of sleep and mental health in the different Swedish regions using maps and over the study period with longitudinal graphs adjusting for sex, age, recruitment type (self-recruitment or invitation), and COVID-19 status. The inner relationships between mental health, sleep and covid infection were described through relative importance networks. Finally, we modelled how mental health affects sleep and vice versa using generalized estimating equations with different adjustments.ResultsSeasonal and north-south regional variations were found in sleep and mental health outcomes at baseline and attenuated over time. The seasonal variation of sleep and mental health correlated moderately with the incidence rate of COVID-19 in the sample. Networks indicate that the relationship between COVID-19 incidence and mental health varies over time. We observed a bidirectional relationship between sleep quality and quantity at baseline and mental health at follow-up and vice versa.ConclusionSleep quality and quantity at baseline was associated with adverse symptom trajectories of mental health at follow-up, and vice versa, during the COVID-19 pandemic. There is also a weak relationship between COVID-19 incidence, sleep, and mental health.
SARS-CoV-2 spike-binding antibody longevity and protection from re-infection with antigenically similar SARS-CoV-2 variants
Authors: Kubale John , Gleason Charles , Carreño Juan Manuel , Srivastava Komal ,   PARIS Study Team, Gordon Aubree , Krammer Florian , Simon Viviana 
Published: March 2022

AbstractThe PARIS (Protection Associated with Rapid Immunity to SARS-CoV-2) cohort follows health care workers with and without documented coronavirus disease 2019 (COVID-19) since April 2020. We report our findings regarding SARS-CoV-2 spike binding antibody stability and protection from infection in the pre-variant era. We analyzed data from 400 healthcare workers (150 seropositive and 250 seronegative at enrollment) for a median of 84 days. The SARS-CoV-2 spike binding antibody titers were highly variable with antibody levels decreasing over the first three months, followed by a relative stabilization. We found that both more advanced age (>40 years) and female sex were associated with higher antibody levels (1.6-fold and 1.4-fold increases, respectively). Only six percent of the initially seropositive participants “seroreverted”. We documented a total of 11 new SARS-CoV-2 infections (ten naïve participants, one previously infected participant without detectable antibodies, p<0.01) indicating that spike antibodies limit the risk of re-infection. These observations, however, only apply to SARS-CoV-2 variants antigenically similar to the ancestral SARS-CoV-2 ones. In conclusion, SARS-CoV-2 antibody titers mounted upon infection are stable over several months in most people and provide protection from infection with antigenically similar viruses.summaryThe levels of SARS-CoV-2 spike binding antibodies mounted upon infection with ancestral SARS-CoV-2 variants are highly variable, stabilize at an individual level after three months and provide protection from infection with homologous virus.
HIV co-infection is associated with lower tuberculosis bacterial burden independent of time to diagnosis in Botswana, a setting with widespread ART use
Authors: Chalfin Juliana S. , Baker Chelsea R. , Kizito Balladiah , Otukile Dimpho , Ogopotse Matsiri T. , Shin Sanghyuk S. , Modongo Chawangwa 
Published: March 2022

AbstractHIV co-infection has been shown to be associated with lower tuberculosis (TB) bacterial load in studies conducted prior to widespread availability of antiretroviral therapy (ART). We investigated associations between HIV co-infection and TB bacterial load, accounting for differences in time to TB diagnosis, in a high prevalence setting with widespread ART use. In Gaborone, Botswana, 268 sputum samples from people with newly diagnosed TB were tested with Xpert MTB/RIF Ultra (Xpert). TB bacterial load and time to TB diagnosis were estimated using mean Xpert cycle threshold (CT) and symptom duration, respectively. Multiple linear regression models and causal mediation analysis were used to determine the associations between HIV and Xpert CT and assess the mediating effect of symptom duration. Mean CT values were higher in people living with HIV compared to people without HIV (22.7 vs 20.3, p < 0.001). Among those living with HIV, there was a negative relationship between CD4 count and mean CT value (Spearman’s rho -0.20, p = 0.06). After controlling for gender, age, and symptom duration, HIV status remained associated with CT value, with an average increase of 1.6 cycles (p = 0.009) among people with HIV and CD4 count > 200 cells/mm3and 2.1 cycles (p = 0.002) in those with a CD4 count ≤ 200 cells/mm3compared to individuals without HIV. Symptom duration was also found to be associated with CT value (p < 0.05). We found an indirect effect of HIV status on Xpert CT through the mediator, symptom duration (β = 0.33, p = 0.048), accounting for 13.5% of the relationship. Our findings suggest that time to TB diagnosis partially mediates the relationship between HIV status and CT value, but differences in pathophysiology between people with and without HIV likely play a dominant role in affecting TB bacterial burden.
Insights into the limited global spread of the immune evasive SARS-CoV-2 variant Mu
Authors: Petrone Mary E. , Lucas Carolina , Menasche Bridget , Breban Mallery I. , Yildirim Inci , Campbell Melissa , Omer Saad B. , Ko Albert I. , Grubaugh Nathan D. , Iwasak Akiko , Wilen Craig B. , Vogels Chantal B.F. , Fauver Joseph R. 
Published: March 2022

ABSTRACTSARS-CoV-2 ‘Variants of Concern’ (VOCs) continue to reshape the trajectory of the COVID-19 pandemic. However, why some VOCs, like Omicron, become globally dominant while the spread of others is limited is not fully understood. To address this question, we investigated the VOC Mu, which was first identified in Colombia in late 2020. Our study demonstrates that, although Mu is less sensitive to neutralization compared to variants that preceded it, it did not spread significantly outside of South and Central America. Additionally, we find evidence that the response to Mu was impeded by reporting delays and gaps in the global genomic surveillance system. Our findings suggest that immune evasion alone was not sufficient to outcompete highly transmissible variants that were circulating concurrently with Mu. Insights into the complex relationship between genomic and epidemiological characteristics of previous variants should inform our response to variants that are likely to emerge in the future.
SARS-CoV-2 and other respiratory pathogens are detected in continuous air samples from congregate settings
Authors: Ramuta Mitchell D. , Newman Christina M. , Brakefield Savannah F. , Stauss Miranda R. , Wiseman Roger W. , Kita-Yarbro Amanda , O’Connor Eli J. , Dahal Neeti , Lim Ailam , Poulsen Keith P. , Safdar Nasia , Marx John A. , Accola Molly A. , Rehrauer William M. , Zimmer Julia A. , Khubbar Manjeet , Beversdorf Lucas J. , Boehm Emma C. , Castañeda David , Rushford Clayton , Gregory Devon A. , Yao Joseph D. , Bhattacharyya Sanjib , Johnson Marc C. , Aliota Matthew T. , Friedrich Thomas C. , O’Connor David H. , O’Connor Shelby L. 
Published: March 2022

AbstractTwo years after the emergence of SARS-CoV-2, there is still a need for better ways to assess the risk of transmission in congregate spaces. We deployed active air samplers to monitor the presence of SARS-CoV-2 in real-world settings across communities in the Upper Midwestern states of Wisconsin and Minnesota. Over 29 weeks, we collected 527 air samples from 15 congregate settings and detected 106 SARS-CoV-2 positive samples, demonstrating SARS-CoV-2 can be detected in air collected from daily and weekly sampling intervals. We expanded the utility of air surveillance to test for 40 other respiratory pathogens. Surveillance data revealed differences in timing and location of SARS-CoV-2 and influenza A virus detection in the community. In addition, we obtained SARS-CoV-2 genome sequences from air samples to identify variant lineages. Collectively, this shows air surveillance is a scalable, cost-effective, and high throughput alternative to individual testing for detecting respiratory pathogens in congregate settings.
Emerging Therapies for COVID-19: the value of information from more clinical trials
Authors: Dijk Stijntje W. , Krijkamp Eline , Kunst Natalia , Gross Cary P. , Wong John B. , Myriam Hunink M.G. 
Published: March 2022

AbstractObjectivesThe COVID-19 pandemic necessitates time-sensitive policy and implementation decisions regarding new therapies in the face of uncertainty. The aim of this study was to quantify consequences of approving therapies or pursuing further research: either immediate approval, use only in research, approval with research (e.g., Emergency Use Authorization), or reject.MethodsUsing a cohort state-transition model for hospitalized COVID-19 patients, we estimated quality-adjusted life years (QALYs) and costs associated with the following interventions: Hydroxychloroquine, Remdesivir, Casirivimab-Imdevimab, Dexamethasone, Baricitinib-Remdesivir, Tocilizumab, Lopinavir-Ritonavir, and Interferon beta-1a, and usual care. We used the model outcomes to conduct cost-effectiveness and value of information analyses from a US healthcare perspective and a lifetime horizon.ResultsAssuming a $100,000-per-QALY willingness-to-pay-threshold, only Remdesivir, Casirivimab-Imdevimab, Dexamethasone, Baricitinib-Remdesivir and Tocilizumab were (cost-) effective (incremental net health benefit 0.252, 0.164, 0.545, 0.668 and 0.524 QALYs and incremental net monetary benefit $25,249, $16,375, $54,526, $66,826 and $52,378). Our value of information analyses suggest that most value can be obtained if these 5 therapies are approved for immediate use rather than requiring additional RCTs (net value $20.6 Billion, $13.4 Billion, $7.4 Billion, $54.6 Billion and $7.1 Billion); Hydroxychloroquine (net value $198 Million) only used in further RCTs if seeking to demonstrate decremental cost-effectiveness, and otherwise rejected; and Interferon beta-1a and Lopinavir-Ritonavir are rejected (i.e., neither approved nor additional RCTs).Conclusions and RelevanceEstimating the real-time value of collecting additional evidence during the pandemic can inform policymakers and clinicians about the optimal moment to implement therapies and whether to perform further research.
The origin of diffuse noxious inhibitory controls
Authors: Kucharczyk Mateusz Wojciech , Di Domenico Francesca , Bannister Kirsty 
Published: March 2022

AbstractPain alerts us to actual or potential tissue damage. During acute pain, our central nervous system acts endogenously to modulate pain processing, thus reducing or enhancing pain perception. However, during chronic pain, the balance between inhibitory and facilitatory processes are tipped in favour of pro-pain modulation.Diffuse noxious inhibitory controls (DNIC) is a naturally occurring pain inhibitory pathway that projects from the brainstem to the spinal cord to inhibit neuronal activity therein in a manner that is 1) subserved by noradrenaline, and 2) dysfunctional in chronicity. To harness its high therapeutic potential, we aimed to anatomically and functionally define DNIC.Through employing an intersectional opto- and chemogenetic approach to modulate activity in brainstem noradrenergic nuclei, here we show that spinal neuronal firing observed upon DNIC activation during electrophysiological experiments, and animal pain thresholds observed during behavioural experiments, are modulated in a pro-pain manner upon opto-manipulation of A5 spinally projecting noradrenergic neurons, thus evidencing the DNIC origin.Given the plasticity of the functional expression of DNIC in disease, and the success of back and forward translation of paradigms that evoke DNIC in pre-clinical and clinical models, our findings offer an attractive avenue of studies for disease specific analgesic interventions.
Novel Adult Cortical Neuron Processing and Screening method illustrates Sex- and Age-dependent effects of pharmaceutical compounds
Authors: Sefiani Arthur , Rusyn Ivan , Geoffroy Cédric G. 
Published: March 2022

AbstractNeurodegenerative diseases and neurotraumatic injuries are typically age-associated disorders that can reduce neuron survival, neurite outgrowth, and synaptic plasticity leading to loss of cognitive capacity, executive function, and motor control. In pursuit of reducing the loss of said neurological functions, novel compounds are sought that promote neuron viability, neuritogenesis, and/or synaptic plasticity. Current high content in vitro screenings typically use cells that are iPSC-derived, embryonic, or originate from post-natal tissues; however, most patients suffering from neurodegenerative diseases and neurotrauma are of middle-age and older. The chasm in maturity between the neurons used in drug screens and those in a target population is a barrier for translational success of in vitro results. It has been historically challenging to culture adult neurons let alone conduct screenings; therefore, age-appropriate drug screenings have previously not been plausible. We have modified Miltenyi’s protocol to increase neuronal yield, neuron purity, and neural viability at a reduced cost to expand our capacity to screen compounds directly in primary adult neurons. Furthermore, we have developed the first morphology-based screening system using adult cortical neurons. By using primary adult cortical neurons from mice that were 4 to 48 weeks old for screening of a library of pharmaceuticals, we have demonstrated age- and sex-dependent effects on neuritogenesis and neuron survival in vitro. Utilizing age- and sex-appropriate in vitro models to find novel compounds increasing neuron survival and neurite outgrowth, made possible by our modified adult neuron processing method, will greatly increase the relevance of in vitro screening for finding neuroprotective compounds.
On the Geometry of Interacting Axon Tracts in Relation to Their Functional Properties
Authors: Chawla Aman , Morgera Salvatore Domenic 
Published: March 2022

AbstractIt is well known that demyelination associated with multiple sclerosis alters coupling between axons in a diseased nerve tract due to exposure of ion channels. In this work we ask the question whether the presence of electric fields as a coupling mechanism between nerve axons, has any impact on the expected conduction properties of the nerve under focal demyelination. Using an approximate geometry for a bundle of three axons, we allow electric fields generated at a node of Ranvier to influence other nodes of Ranvier on different axons. In order to introduce focal demyelination, we allow a new type of structure, intermediate between a node and an internodal segment. We find that the nerve’s conduction profiles are different with and without field-based coupling. This is important because it opens up the possibility for an experimental investigation to study whether field-based coupling predominates over current-based coupling. Fields and currents may also be measured using different methods and so there are implications for bio-instrumentation. From a systems perspective, the study is based on a novel equation which allows electric fields to act as sources of current at axons’ nodes of Ranvier, thereby generating new behaviors from the set of coupled partial differential equations that model the electrodynamics of the nerve. In addition to our simulation study of focal demyelination, we present a justification for a certain geometric W-matrix used in our phenomenological 2019 model. We also provide the first simulations of a tract of tortuous axons, showing the impact of tract tortuosity on conduction velocity. The tortuous model is analyzed geometrically to illustrate the mechanism of synchronization. Finally, this same model is shown to be castable as a learning machine - a formulation that has neuroscience implications.
Behavioral and imaging analysis of Foxg1 heterozygous mice
Authors: Erickson Kirsty R. , Lifer Rebekah , Merritt Jonathan K. , Lanaghan Zeljka Miletic , Does Mark D. , Ramadass Karthik , Landman Bennett A. , Cutting Laurie E. , Neul Jeffrey L. 
Published: March 2022

AbstractFOXG1 Syndrome (FS) is a devastating neurodevelopmental disorder that is caused by a heterozygous loss-of-function (LOF) mutation of theFOXG1gene, which encodes a transcriptional regulator important for telencephalic brain development. People with FS have marked developmental delays, impaired ambulation, movement disorders, seizures, and behavior abnormalities including autistic features. Current therapeutic approaches are entirely symptomatic, however the ability to rescue phenotypes in mouse models of other genetic neurodevelopmental disorders such as Rett syndrome, Angelman syndrome, and Phelan-McDermid syndrome by postnatal expression of gene products has led to hope that similar approaches could help modify the disease course in other neurodevelopmental disorders such as FS. While FoxG1 protein function plays a critical role in embryonic brain development, the ongoing adult expression of FoxG1 and behavioral phenotypes that present when FoxG1 function is removed postnatally provides support for opportunity for improvement with postnatal treatment. Here we generated a new mouse allele ofFoxg1that disrupts protein expression and characterized the behavioral and structural brain phenotypes in heterozygous mutant animals. These mutant animals display changes in locomotor behavior, gait, anxiety, social interaction, aggression, and learning and memory compared to littermate controls. Additionally, they have structural brain abnormalities reminiscent of people with FS. This information provides the framework for future studies to evaluate the potential for post-natal expression of FoxG1 to modify the disease course in this severe neurodevelopmental disorder.