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"Bryant, William"
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Creation and analysis of biochemical constraint-based models using the COBRA Toolbox v.3.0
Constraint-based reconstruction and analysis (COBRA) provides a molecular mechanistic framework for integrative analysis of experimental molecular systems biology data and quantitative prediction of physicochemically and biochemically feasible phenotypic states. The COBRA Toolbox is a comprehensive desktop software suite of interoperable COBRA methods. It has found widespread application in biology, biomedicine, and biotechnology because its functions can be flexibly combined to implement tailored COBRA protocols for any biochemical network. This protocol is an update to the COBRA Toolbox v.1.0 and v.2.0. Version 3.0 includes new methods for quality-controlled reconstruction, modeling, topological analysis, strain and experimental design, and network visualization, as well as network integration of chemoinformatic, metabolomic, transcriptomic, proteomic, and thermochemical data. New multi-lingual code integration also enables an expansion in COBRA application scope via high-precision, high-performance, and nonlinear numerical optimization solvers for multi-scale, multi-cellular, and reaction kinetic modeling, respectively. This protocol provides an overview of all these new features and can be adapted to generate and analyze constraint-based models in a wide variety of scenarios. The COBRA Toolbox v.3.0 provides an unparalleled depth of COBRA methods.The COBRA toolbox provides quality-controlled reconstruction, modeling, topological analysis, and network visualization, as well as network integration of chemoinformatic, metabolomic, transcriptomic, proteomic, and thermochemical data.
Journal Article
Increasing diagnoses per patient admission at a specialist children’s hospital: A retrospective study
In adult practice there is recognition that average patient complexity is increasing, with a greater proportion of patients having multiple diagnoses or comorbidities. This study aims to examine whether there has been a change in number of recorded coexisting diagnoses per patient over a 24-year period for children attending as in-patients to a specialist children's hospital in England.
Following all in-patient admissions, patient episodes are allocated specific diagnosis codes (ICD-10) by a specialist clinical coding team according to standard NHS criteria and guidance. We examine the number of coexisting diagnoses allocated per patient admission over a 24-year period.
From a total of 278,579 overnight in-patient admissions during the study period (2000-2023) there were 1,023,276 ICD-10 patient diagnoses. The mean number of diagnoses per admission increased from 2.72 to 10.43 over the period (Kendall's tau statistic of 0.93; p-value < 0.001), an increase of 284% (95% confidence interval 275% - 293%).
Over recent decades, the recorded complexity of patients attending a specialist children's hospital appear to have increased significantly, with an almost 3-fold increase in the number of coexisting diagnoses present per admission. The cause of this finding cannot be determined from the data; however, it appears to be gradual and consistent, and across all speciality areas suggesting biological or referral factors rather than artefactual coding issues. Recognition of such a trend is important when interpreting retrospective data for AI, research, and planning purposes.
Journal Article
Romeo & Juliet : the graphic novel : original text version
Presents in graphic novel format an easy-to-follow adaptation of Shakespeare's play of the tragic consequences of a deadly feud between two rival families in Renaissance Verona.
BOOK
Of mice and human-specific long noncoding RNAs
The number of human LncRNAs has now exceeded all known protein-coding genes. Most studies of human LncRNAs have been conducted in cell culture systems where various mechanisms of action have been worked out. On the other hand, efforts to elucidate the function of human LncRNAs in an in vivo setting have been limited. In this brief review, we highlight some strengths and weaknesses of studying human LncRNAs in the mouse. Special consideration is given to bacterial artificial chromosome transgenesis and genome editing. The integration of these technical innovations offers an unprecedented opportunity to complement and extend the expansive literature of cell culture models for the study of human LncRNAs. Two different examples of how BAC transgenesis and genome editing can be leveraged to gain insight into human LncRNA regulation and function in mice are presented: the random integration of a vascular cell-enriched LncRNA and a targeted approach for a new LncRNA immediately upstream of the ACE2 gene, which encodes the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent underlying the coronavirus disease-19 (COVID-19) pandemic.
Journal Article
A midsummer night's dream : the graphic novel : original text version
The entire Shakespeare play as a graphic novel.
BOOK
Evolving phenotypes of non-hospitalized patients that indicate long COVID
Background
For some SARS-CoV-2 survivors, recovery from the acute phase of the infection has been grueling with lingering effects. Many of the symptoms characterized as the post-acute sequelae of COVID-19 (PASC) could have multiple causes or are similarly seen in non-COVID patients. Accurate identification of PASC phenotypes will be important to guide future research and help the healthcare system focus its efforts and resources on adequately controlled age- and gender-specific sequelae of a COVID-19 infection.
Methods
In this retrospective electronic health record (EHR) cohort study, we applied a computational framework for knowledge discovery from clinical data, MLHO, to identify phenotypes that positively associate with a past positive reverse transcription-polymerase chain reaction (RT-PCR) test for COVID-19. We evaluated the post-test phenotypes in two temporal windows at 3–6 and 6–9 months after the test and by age and gender. Data from longitudinal diagnosis records stored in EHRs from Mass General Brigham in the Boston Metropolitan Area was used for the analyses. Statistical analyses were performed on data from March 2020 to June 2021. Study participants included over 96 thousand patients who had tested positive or negative for COVID-19 and were not hospitalized.
Results
We identified 33 phenotypes among different age/gender cohorts or time windows that were positively associated with past SARS-CoV-2 infection. All identified phenotypes were newly recorded in patients’ medical records 2 months or longer after a COVID-19 RT-PCR test in non-hospitalized patients regardless of the test result. Among these phenotypes, a new diagnosis record for anosmia and dysgeusia (OR 2.60, 95% CI [1.94–3.46]), alopecia (OR 3.09, 95% CI [2.53–3.76]), chest pain (OR 1.27, 95% CI [1.09–1.48]), chronic fatigue syndrome (OR 2.60, 95% CI [1.22–2.10]), shortness of breath (OR 1.41, 95% CI [1.22–1.64]), pneumonia (OR 1.66, 95% CI [1.28–2.16]), and type 2 diabetes mellitus (OR 1.41, 95% CI [1.22–1.64]) is one of the most significant indicators of a past COVID-19 infection. Additionally, more new phenotypes were found with increased confidence among the cohorts who were younger than 65.
Conclusions
The findings of this study confirm many of the post-COVID-19 symptoms and suggest that a variety of new diagnoses, including new diabetes mellitus and neurological disorder diagnoses, are more common among those with a history of COVID-19 than those without the infection. Additionally, more than 63% of PASC phenotypes were observed in patients under 65 years of age, pointing out the importance of vaccination to minimize the risk of debilitating post-acute sequelae of COVID-19 among younger adults.
Journal Article
Macbeth : the graphic novel : plain text version
In graphic novel format, presents an adaptation of Shakespeare's classic tale about a man who kills his king after hearing the prophesies of three witches.
BOOK
Experiences with Negative Behavior and Incivility: Perspectives of Unlicensed Assistive Personnel and Registered Nurses
Healthcare professionals experience negative behaviors such as incivility from various sources within the hospital environment. However, little is known regarding the experience of unlicensed assistive personnel with these behaviors. Using a cross-sectional survey design, the research team aimed to examine the presence, sources, and impact of negative behaviors among registered nurses and unlicensed assistive personnel within a US hospital. Descriptive and inferential statistics were used to analyze quantitative data, while thematic analysis was used to analyze the qualitative responses. A total of 309 participants completed the survey, and 135 participants responded to three qualitative questions. Most respondents identified inadequate staffing/resources to handle workload (87%) and job stress leading to loss of control over behavior as contributing factors to lateral/vertical aggression in the work environment (71%). Impacts of negative behavior on job performance were related to both personal well-being and the work environment. Demoralization was identified as a common consequence of negative behaviors for individuals and within the work environment. The results suggested that registered nurses, unlicensed assistive personnel, and nursing leadership may benefit from system-wide approaches addressing negative behaviors such as incivility within the clinical environment. Specifically, efforts and policies aimed at aiding clinicians in responding to negative behaviors could potentially improve the clinical environment.
Journal Article