Cystine urolithiasis-free duration after first occurrence and treatment is longer for castrated dogs than for sexually intact male dogs.

Objective: To evaluate outcome in 60 dogs with cystine urolithiasis treated with surgical removal with and without castration and postoperative therapeutic diet to determine frequency of recurrence and urolith-free duration.

Methods: Patient records were reviewed for dogs with documented cystine urolithiasis from September 2010 to December 2020. Medical records, client interviews, and referring veterinarians were contacted to document the absence of clinical signs associated with subsequent urolith formation and to evaluate risk factors for urolith reoccurrence.

Comparative effectiveness of dexamethasone in treatment of hospitalized COVID-19 patients in the United States during the first year of the pandemic: Findings from the National COVID Cohort Collaborative (N3C) data repository.

Background: Dexamethasone was approved for use in hospitalized COVID-19 patients early in the pandemic based on the RECOVERY trial, but evidence is still needed to support its real-world effectiveness in heterogeneous populations of patients with a wide range of comorbidities.

Methods: COVID-19 inpatients represented within the National COVID Cohort Collaborative (N3C) Data Enclave, prior to vaccine availability, were studied. Primary outcome was in-hospital death; secondary outcome was combined in-hospital death and severe outcome defined by use of ECMO or mechanical ventilation.

Optimizing COVID-19 testing strategies on college campuses: Evaluation of the health and economic costs.

Colleges and universities in the US struggled to provide safe in-person education throughout the COVID-19 pandemic. Testing coupled with isolation is a nimble intervention strategy that can be tailored to mitigate the changing health and economic risks associated with SARS-CoV-2. We developed a decision-support tool to aid in the design of university-based screening strategies using a mathematical model of SARS-CoV-2 transmission.

Disproportionate impacts of COVID-19 in a large US city.

COVID-19 has disproportionately impacted individuals depending on where they live and work, and based on their race, ethnicity, and socioeconomic status. Studies have documented catastrophic disparities at critical points throughout the pandemic, but have not yet systematically tracked their severity through time. Using anonymized hospitalization data from March 11, 2020 to June 1, 2021 and fine-grain infection hospitalization rates, we estimate the time-varying burden of COVID-19 by age group and ZIP code in Austin, Texas.

Optimizing COVID-19 testing strategies on college campuses: evaluation of the health and economic costs.

Colleges and universities in the US struggled to provide safe in-person education throughout the COVID-19 pandemic. Testing coupled with isolation is a nimble intervention strategy that can be tailored to mitigate health and economic costs, as the virus and our arsenal of medical countermeasures continue to evolve. We developed a decision-support tool to aid in the design of university-based testing strategies using a mathematical model of SARS-CoV-2 transmission.

Superficial digital flexor tendon luxation repaired with abrasion calcaneoplasty and primary retinaculum repair in dogs.

Surgical treatment of a superficial digital flexor tendon luxation is the treatment of choice, since nonsurgical treatment has been shown to be unsuccessful in dogs in which it has been attempted. The objectives of this study were to report complications and short- to long-term outcomes in dogs with superficial digital flexor tendon luxation treated with abrasion calcaneoplasty, an adjunctive surgical technique, in addition to traditional repair. In total, 12 client-owned dogs with superficial digital flexor tendon luxations were examined in this retrospective case series (from 2010 to 2020) of a novel surgical technique using abrasion calcaneoplasty, in addition to retinaculum imbrication.

Comparative Effectiveness of Dexamethasone in Treatment of Hospitalized COVID-19 Patients during the First Year of the Pandemic: The N3C Data Repository.

Background: Dexamethasone, a widely available glucocorticoid, was approved for use in hospitalized COVID-19 patients early in the pandemic based on the RECOVERY trial; however, evidence is still needed to support its real-world effectiveness in patients with a wide range of comorbidities and in diverse care settings.

Objectives: To conduct a comparative effectiveness analysis of dexamethasone use with and without remdesivir in hospitalized COVID-19 patients using electronic health record data.

Methods: We conducted a retrospective real-world effectiveness analysis using the harmonized, highly granular electronic health record data of the National COVID Cohort Collaborative (N3C) Data Enclave.

SARS-CoV-2 viral load is associated with risk of transmission to household and community contacts.

Background: Factors that lead to successful SARS-CoV-2 transmission are still not well described. We investigated the association between a case's viral load and the risk of transmission to contacts in the context of other exposure-related factors.

Methods: Data were generated through routine testing and contact tracing at a large university.

Real-Time Projections of SARS-CoV-2 B.1.1.7 Variant in a University Setting, Texas, USA.

We used the incidence of spike gene target failures identified during PCR testing to provide an early projection of the prevalence of severe acute respiratory syndrome coronavirus 2 variant B.1.1.

Effects of COVID-19 Vaccination Timing and Risk Prioritization on Mortality Rates, United States.

During rollout of coronavirus disease vaccination, policymakers have faced critical trade-offs. Using a mathematical model of transmission, we found that timing of vaccination rollout would be expected to have a substantially greater effect on mortality rate than risk-based prioritization and uptake and that prioritizing first doses over second doses may be lifesaving.

Detecting in-school transmission of SARS-CoV-2 from case ratios and documented clusters.

Claims that in-person schooling has not amplified SARS-CoV-2 transmission are based on similar infection rates in schools and their surrounding communities and limited numbers of documented in-school transmission events. Simulations assuming high in-school transmission suggest that these metrics cannot exclude the possibility that transmission in schools exacerbated overall pandemic risks.

Individually optimal choices can be collectively disastrous in COVID-19 disease control.

Background: The word 'pandemic' conjures dystopian images of bodies stacked in the streets and societies on the brink of collapse. Despite this frightening picture, denialism and noncompliance with public health measures are common in the historical record, for example during the 1918 Influenza pandemic or the 2015 Ebola epidemic. The unique characteristics of SARS-CoV-2-its high basic reproduction number (R), time-limited natural immunity and considerable potential for asymptomatic spread-exacerbate the public health repercussions of noncompliance with interventions (such as vaccines and masks) to limit disease transmission.

In the long shadow of our best intentions: Model-based assessment of the consequences of school reopening during the COVID-19 pandemic.

As the world grapples with the ongoing COVID-19 pandemic, a particularly thorny set of questions surrounds the reopening of primary and secondary (K-12) schools. The benefits of in-person learning are numerous, in terms of education quality, mental health, emotional well-being, equity and access to food and shelter. Early reports suggested that children might have reduced susceptibility to COVID-19, and children have been shown to experience fewer complications than older adults.

The impacts of COVID-19 vaccine timing, number of doses, and risk prioritization on mortality in the US.

As COVID-19 vaccination begins worldwide, policymakers face critical trade-offs. Using a mathematical model of COVID-19 transmission, we find that timing of the rollout is expected to have a substantially greater impact on mortality than risk-based prioritization and uptake and that prioritizing first doses over second doses may be life saving.

Integrating Quantitative Assays with Biologically Based Mathematical Modeling for Predictive Oncology.

We provide an overview on the use of biological assays to calibrate and initialize mechanism-based models of cancer phenomena. Although artificial intelligence methods currently dominate the landscape in computational oncology, mathematical models that seek to explicitly incorporate biological mechanisms into their formalism are of increasing interest. These models can guide experimental design and provide insights into the underlying mechanisms of cancer progression.

Integrating transcriptomics and bulk time course data into a mathematical framework to describe and predict therapeutic resistance in cancer.

A significant challenge in the field of biomedicine is the development of methods to integrate the multitude of dispersed data sets into comprehensive frameworks to be used to generate optimal clinical decisions. Recent technological advances in single cell analysis allow for high-dimensional molecular characterization of cells and populations, but to date, few mathematical models have attempted to integrate measurements from the single cell scale with other types of longitudinal data. Here, we present a framework that actionizes static outputs from a machine learning model and leverages these as measurements of state variables in a dynamic model of treatment response.

Comparison of diagnosis and prescribing practices between virtual visits and office visits for adults diagnosed with uncomplicated urinary tract infections within a primary care network.

Objectives: Telemedicine visits are an increasingly popular method of care for mild infectious complaints, including uncomplicated urinary tract infections (UTIs), and they are an important target for antimicrobial stewardship programs (ASPs) to evaluate quality of prescribing. In this study, we compared antimicrobial prescribing in a primary care network for uncomplicated UTIs treated through virtual visits and at in-office visits.

Design: Retrospective cohort study comparing guideline-concordant antibiotic prescribing for uncomplicated UTI between virtual visits and office visits.

Cancer cell population growth kinetics at low densities deviate from the exponential growth model and suggest an Allee effect.

Most models of cancer cell population expansion assume exponential growth kinetics at low cell densities, with deviations to account for observed slowing of growth rate only at higher densities due to limited resources such as space and nutrients. However, recent preclinical and clinical observations of tumor initiation or recurrence indicate the presence of tumor growth kinetics in which growth rates scale positively with cell numbers. These observations are analogous to the cooperative behavior of species in an ecosystem described by the ecological principle of the Allee effect.

Directional inconsistency between Response Evaluation Criteria in Solid Tumors (RECIST) time to progression and response speed and depth.

Aim: We seek to characterize how faster tumour shrinkage rate (k) can lead to paradoxically shorter Response Evaluation Criteria in Solid Tumors (RECIST) time to progression ('TTP20' - tumour size exceeding its minimum by 5 mm and 20%) [1] and, therefore, progression-free survival (PFS). Specifically, we investigate under what conditions this paradoxical behaviour occurs, what fraction of patients satisfy these conditions, whether this phenomenon can invert population-level PFS hazard ratio, and consistency of an alternative time-to-event benefit metric with k.

Methods: We use a mathematical model treating tumour burden as decreasing drug-sensitive and increasing drug-resistant cell subpopulations.

A multi-state model of chemoresistance to characterize phenotypic dynamics in breast cancer.

The development of resistance to chemotherapy is a major cause of treatment failure in breast cancer. While mathematical models describing the dynamics of resistant cancer cell subpopulations have been proposed, experimental validation has been difficult due to the complex nature of resistance that limits the ability of a single phenotypic marker to sufficiently identify the drug resistant subpopulations. We address this problem with a coupled experimental/modeling approach to reveal the composition of drug resistant subpopulations changing in time following drug exposure.

AIF promotes a JNK1-mediated cadherin switch independently of respiratory chain stabilization.

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein occasionally involved in cell death that primarily regulates mitochondrial energy metabolism under normal cellular conditions. AIF catalyzes the oxidation of NADH , yet the significance of this redox activity in cells remains unclear. Here, we show that through its enzymatic activity AIF is a critical factor for oxidative stress-induced activation of the mitogen-activated protein kinases JNK1 (c-Jun N-terminal kinase), p38, and ERK (extracellular signal-regulated kinase).

Optimization and scale up of microfluidic nanolipomer production method for preclinical and potential clinical trials.

Background: The process of optimization and fabrication of nanoparticle synthesis for preclinical studies can be challenging and time consuming. Traditional small scale laboratory synthesis techniques suffer from batch to batch variability. Additionally, the parameters used in the original formulation must be re-optimized due to differences in fabrication techniques for clinical production.