A modeling study to define guidelines for antigen screening in schools and workplaces to mitigate COVID-19 outbreaks.

Background: In-person interaction offers invaluable benefits to people. To guarantee safe in-person activities during a COVID-19 outbreak, effective identification of infectious individuals is essential. In this study, we aim to analyze the impact of screening with antigen tests in schools and workplaces on identifying COVID-19 infections.

The impact of natural climate variability on the global distribution of Aedes aegypti: a mathematical modelling study.

Background: Aedes aegypti spread pathogens affecting humans, including dengue, Zika, and yellow fever viruses. Anthropogenic climate change is altering the spatial distribution of Ae aegypti and therefore the locations at risk of vector-borne disease. In addition to climate change, natural climate variability, resulting from internal atmospheric processes and interactions between climate system components (eg, atmosphere-land and atmosphere-ocean interactions), determines climate outcomes.

Optimizing the timing of an end-of-outbreak declaration: Ebola virus disease in the Democratic Republic of the Congo.

Following the apparent final case in an Ebola virus disease (EVD) outbreak, the decision to declare the outbreak over must balance societal benefits of relaxing interventions against the risk of resurgence. Estimates of the end-of-outbreak probability (the probability that no future cases will occur) provide quantitative evidence that can inform the timing of an end-of-outbreak declaration. An existing modeling approach for estimating the end-of-outbreak probability requires comprehensive contact tracing data describing who infected whom to be available, but such data are often unavailable or incomplete during outbreaks.

A Histone Methylation-MAPK Signaling Axis Drives Durable Epithelial-Mesenchymal Transition in Hypoxic Pancreatic Cancer.

Unlabelled: The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) plays a key role in tumor progression and response to therapy. The dense PDAC stroma causes hypovascularity, which leads to hypoxia. Here, we showed that hypoxia drives long-lasting epithelial-mesenchymal transition (EMT) in PDAC primarily through a positive-feedback histone methylation-MAPK signaling axis.

Divergent transcriptomic signatures from putative mesenchymal stimuli in glioblastoma cells.

In glioblastoma, a mesenchymal phenotype is associated with especially poor patient outcomes. Various glioblastoma microenvironmental factors and therapeutic interventions are purported drivers of the mesenchymal transition, but the degree to which these cues promote the same mesenchymal transitions and the uniformity of those transitions, as defined by molecular subtyping systems, is unknown. Here, we investigate this question by analyzing publicly available patient data, surveying commonly measured transcripts for mesenchymal transitions in glioma-initiating cells (GIC), and performing next-generation RNA sequencing of GICs.

Isolation may select for earlier and higher peak viral load but shorter duration in SARS-CoV-2 evolution.

During the COVID-19 pandemic, human behavior change as a result of nonpharmaceutical interventions such as isolation may have induced directional selection for viral evolution. By combining previously published empirical clinical data analysis and multi-level mathematical modeling, we find that the SARS-CoV-2 variants selected for as the virus evolved from the pre-Alpha to the Delta variant had earlier and higher peak in viral load dynamics but a shorter duration of infection. Selection for increased transmissibility shapes the viral load dynamics, and the isolation measure is likely to be a driver of these evolutionary transitions.

Analysis of the risk and pre-emptive control of viral outbreaks accounting for within-host dynamics: SARS-CoV-2 as a case study.

In the era of living with COVID-19, the risk of localised SARS-CoV-2 outbreaks remains. Here, we develop a multiscale modelling framework for estimating the local outbreak risk for a viral disease (the probability that a major outbreak results from a single case introduced into the population), accounting for within-host viral dynamics. Compared to population-level models previously used to estimate outbreak risks, our approach enables more detailed analysis of how the risk can be mitigated through pre-emptive interventions such as antigen testing.

Contact-number-driven virus evolution: A multi-level modeling framework for the evolution of acute or persistent RNA virus infection.

Viruses evolve in infected host populations, and host population dynamics affect viral evolution. RNA viruses with a short duration of infection and a high peak viral load, such as SARS-CoV-2, are maintained in human populations. By contrast, RNA viruses characterized by a long infection duration and a low peak viral load (e.

Understanding how transmembrane domains regulate interactions between human BST-2 and the SARS-CoV-2 accessory protein ORF7a.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID, replicates at intracellular membranes. Bone marrow stromal antigen 2 (BST-2; tetherin) is an antiviral response protein that inhibits transport of viral particles after budding within infected cells. RNA viruses such as SARS-CoV-2 use various strategies to disable BST-2, including use of transmembrane 'accessory' proteins that interfere with BST-2 oligomerization.

Generation time of the alpha and delta SARS-CoV-2 variants: an epidemiological analysis.

Background: In May, 2021, the delta (B.1.617.

Inference of the SARS-CoV-2 generation time using UK household data.

The distribution of the generation time (the interval between individuals becoming infected and transmitting the virus) characterises changes in the transmission risk during SARS-CoV-2 infections. Inferring the generation time distribution is essential to plan and assess public health measures. We previously developed a mechanistic approach for estimating the generation time, which provided an improved fit to data from the early months of the COVID-19 pandemic (December 2019-March 2020) compared to existing models (Hart et al.

High infectiousness immediately before COVID-19 symptom onset highlights the importance of continued contact tracing.

Background: Understanding changes in infectiousness during SARS-COV-2 infections is critical to assess the effectiveness of public health measures such as contact tracing.

Methods: Here, we develop a novel mechanistic approach to infer the infectiousness profile of SARS-COV-2-infected individuals using data from known infector-infectee pairs. We compare estimates of key epidemiological quantities generated using our mechanistic method with analogous estimates generated using previous approaches.

Key questions for modelling COVID-19 exit strategies.

Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement exit strategies that relax restrictions while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented.

Comparative Biochemical and Structural Analysis of Novel Cellulose Binding Proteins (Tāpirins) from Extremely Thermophilic Species.

Genomes of extremely thermophilic species encode novel cellulose binding proteins, called tāpirins, located proximate to the type IV pilus locus. The C-terminal domain of tāpirin 0844 (Calkro_0844) is structurally unique and has a cellulose binding affinity akin to that seen with family 3 carbohydrate binding modules (CBM3s). Here, full-length and C-terminal versions of tāpirins from (Athe_1870), (Calhy_0908), (Calkr_0826), and (NA10_0869) were produced recombinantly in and compared to Calkro_0844.