Abstract Constructing gene regulatory networks is a widely adopted approach for investigating gene regulation, offering diverse applications in biology and medicine. A great deal of research focuses ...on using time series data or single-cell RNA-sequencing data to infer gene regulatory networks. However, such gene expression data lack either cellular or temporal information. Fortunately, the advent of time-lapse confocal laser microscopy enables biologists to obtain tree-shaped gene expression data of Caenorhabditis elegans, achieving both cellular and temporal resolution. Although such tree-shaped data provide abundant knowledge, they pose challenges like non-pairwise time series, laying the inaccuracy of downstream analysis. To address this issue, a comprehensive framework for data integration and a novel Bayesian approach based on Boolean network with time delay are proposed. The pre-screening process and Markov Chain Monte Carlo algorithm are applied to obtain the parameter estimates. Simulation studies show that our method outperforms existing Boolean network inference algorithms. Leveraging the proposed approach, gene regulatory networks for five subtrees are reconstructed based on the real tree-shaped datatsets of Caenorhabditis elegans, where some gene regulatory relationships confirmed in previous genetic studies are recovered. Also, heterogeneity of regulatory relationships in different cell lineage subtrees is detected. Furthermore, the exploration of potential gene regulatory relationships that bear importance in human diseases is undertaken. All source code is available at the GitHub repository https://github.com/edawu11/BBTD.git.
Abstract Pseudomonas aeruginosa is a complex nosocomial infectious agent responsible for numerous illnesses, with its growing resistance variations complicating treatment development. Studies have ...emphasized the importance of virulence factors OprE and OprF in pathogenesis, highlighting their potential as vaccine candidates. In this study, B-cell, MHC-I, and MHC-II epitopes were identified, and molecular linkers were active to join these epitopes with an appropriate adjuvant to construct a vaccine. Computational tools were employed to forecast the tertiary framework, characteristics, and also to confirm the vaccine’s composition. The potency was weighed through population coverage analysis and immune simulation. This project aims to create a multi-epitope vaccine to reduce P. aeruginosa–related illness and mortality using immunoinformatics resources. The ultimate complex has been determined to be stable, soluble, antigenic, and non-allergenic upon inspection of its physicochemical and immunological properties. Additionally, the protein exhibited acidic and hydrophilic characteristics. The Ramachandran plot, ProSA-web, ERRAT, and Verify3D were employed to ensure the final model’s authenticity once the protein’s three-dimensional structure had been established and refined. The vaccine model showed a significant binding score and stability when interacting with MHC receptors. Population coverage analysis indicated a global coverage rate of 83.40%, with the USA having the highest coverage rate, exceeding 90%. Moreover, the vaccine sequence underwent codon optimization before being cloned into the Escherichia coli plasmid vector pET-28a (+) at the EcoRI and EcoRV restriction sites. Our research has developed a vaccine against P. aeruginosa that has strong binding affinity and worldwide coverage, offering an acceptable way to mitigate nosocomial infections.
Abstract Somatic variation is a major type of genetic variation contributing to human diseases including cancer. Of the vast quantities of somatic variants identified, the functional impact of many ...somatic variants, in particular the missense variants, remains unclear. Lack of the functional information prevents the translation of rich variation data into clinical applications. We previously developed a method named Ramachandran Plot–Molecular Dynamics Simulations (RP-MDS), aiming to predict the function of germline missense variants based on their effects on protein structure stability, and successfully applied to predict the deleteriousness of unclassified germline missense variants in multiple cancer genes. We hypothesized that regardless of their different genetic origins, somatic missense variants and germline missense variants could have similar effects on the stability of their affected protein structure. As such, the RP-MDS method designed for germline missense variants should also be applicable to predict the function of somatic missense variants. In the current study, we tested our hypothesis by using the somatic missense variants in TP53 as a model. Of the 397 somatic missense variants analyzed, RP-MDS predicted that 195 (49.1%) variants were deleterious as they significantly disturbed p53 structure. The results were largely validated by using a p53–p21 promoter–green fluorescent protein (GFP) reporter gene assay. Our study demonstrated that deleterious somatic missense variants can be identified by referring to their effects on protein structural stability.
The COVID-19 outbreak compelled countries to take swift actions across various domains amidst substantial uncertainties. In Israel, significant COVID-19-related efforts were assigned to the Israeli ...Home Front Command (HFC). HFC faced the challenge of anticipating adequate resources to efficiently and timely manage its numerous assignments despite the absence of a COVID-19 spread forecast. This paper describes the initiative of a group of motivated, though nonexpert, people to provide the needed COVID-19 rate of spread of the epidemic forecasts.ObjectiveThe COVID-19 outbreak compelled countries to take swift actions across various domains amidst substantial uncertainties. In Israel, significant COVID-19-related efforts were assigned to the Israeli Home Front Command (HFC). HFC faced the challenge of anticipating adequate resources to efficiently and timely manage its numerous assignments despite the absence of a COVID-19 spread forecast. This paper describes the initiative of a group of motivated, though nonexpert, people to provide the needed COVID-19 rate of spread of the epidemic forecasts.To address this challenge, the Planning Chamber, reporting to the HFC Medical Commander, undertook the task of mapping HFC healthcare challenges and resource requirements. The nonexpert team continuously collected public COVID-19-related data published by the Israeli Ministry of Health (MoH) of verified cases, light cases, mild cases, serious condition cases, life-support cases, and deaths, and despite lacking expertise in statistics and healthcare and having no sophisticated statistical packages, generated forecasts using Microsoft® Excel.MethodsTo address this challenge, the Planning Chamber, reporting to the HFC Medical Commander, undertook the task of mapping HFC healthcare challenges and resource requirements. The nonexpert team continuously collected public COVID-19-related data published by the Israeli Ministry of Health (MoH) of verified cases, light cases, mild cases, serious condition cases, life-support cases, and deaths, and despite lacking expertise in statistics and healthcare and having no sophisticated statistical packages, generated forecasts using Microsoft® Excel.The analysis methods and applications successfully demonstrated the desired outcome of the lockdown by showing a transition from exponential to polynomial growth in the spread of the virus. These forecasting activities enabled decision-makers to manage resources effectively, supporting the HFC's operations during the pandemic.ResultsThe analysis methods and applications successfully demonstrated the desired outcome of the lockdown by showing a transition from exponential to polynomial growth in the spread of the virus. These forecasting activities enabled decision-makers to manage resources effectively, supporting the HFC's operations during the pandemic.Nonexpert forecasting may become a necessity and be beneficial, and similar analysis efforts can be easily replicated in future events. However, they are inherently short-lived and should persist only until knowledge centers can bridge the expertise gap. It is crucial to identify major events, such as lockdowns, during forecasting due to their potential impact on spread rates. Despite the expertise gap, the Planning Chamber's approach provided valuable resource management insights for HFC's COVID-19 response.ConclusionsNonexpert forecasting may become a necessity and be beneficial, and similar analysis efforts can be easily replicated in future events. However, they are inherently short-lived and should persist only until knowledge centers can bridge the expertise gap. It is crucial to identify major events, such as lockdowns, during forecasting due to their potential impact on spread rates. Despite the expertise gap, the Planning Chamber's approach provided valuable resource management insights for HFC's COVID-19 response.
Hand-foot-and-mouth disease (HFMD), which is typically seen in the younger pediatric population, is uncommon in older adolescent and young adult populations. We report on an atypical outbreak of HFMD ...among college students at a mid-size university in the mid-Atlantic U.S. The outbreak included 138 qualifying cases of HFMD among students at the institution between August and November 2018. All tested samples were positive for CVA6, a less common cause of HFMD. Signs and symptoms and campus mitigation strategies are described. This case report aims to highlight an atypical outbreak of HFMD for clinicians who care for older adolescent and college-aged patients in primary care and community settings, and may see cases and/or outbreaks of HFMD in these populations.
Low back pain is the most common musculoskeletal complaint accounting for over 30 million visits to primary care physicians annually. Serious pathology is found in less than 1% of these visits. ...Therefore it is often a challenge to distinguish worrisome findings requiring further workup and treatment from common complaints of pain. Gout is an inflammatory arthritis that most commonly affects the appendicular skeleton. It is characterized by the saturation of uric acid and deposition of monosodium urate crystals in joints and tissues. Spinal involvement is rare and is not typically considered on the differential diagnosis for a patient presenting with acute low back pain. We present such a case of a 35-year-old male who presented with intractable back pain, highlighting the need to recognize signs and symptoms that raise suspicion for spinal gout.
PUBLIC HEALTH AND CARE DELIVERY THEME ISSUE: Through partnerships with trusted community-based organizations, health systems and public health are able to expand access to care for the vulnerable ...segments of the population. The experience of Saint Paul – Ramsey County Public Health, Fairview Health Services, and many local community and faith-based partners has implications for ongoing teamwork in care delivery.
In Minnesota, age-adjusted case incidence rates of Covid-19 infection were significantly higher among Black and Latine communities compared with non-Hispanic white communities. The siloed nature of public health and health care delivery emerged as a critical obstacle to equitable Covid-19 testing and vaccination. Fragmented care delivery due to varying funding models, complicated administrative frameworks, and systemic barriers to accessing services impeded a rapid, equity-focused response. Saint Paul – Ramsey County Public Health (SPRCPH), Fairview Health Services (Fairview), and many local community and faith-based partners recognized the need to work together to ensure that underserved populations had equitable access to Covid-19 testing and vaccination. The authors describe how these entities, collectively serving a population of about 550,000, sought to establish equitable, low-barrier Covid-19 testing and vaccinations that were accessible, free, and available within a trusted space and given appropriate language and cultural considerations to address long-standing health disparities revealed and exacerbated by the pandemic. The partnership’s strength lay in integrating SPRCPH’s logistics capability with Fairview’s clinical expertise and the community partners’ trusted status, enhancing the credibility and effectiveness of public health initiatives. SPRCPH provided the supplies and operations personnel needed to establish drive-through testing sites capable of serving more than 1,500 patients in a 6-hour operational period. Fairview brought teams of medical staff and colleagues who supported in nonclinical roles and engaged with community partners. Over the course of the response, this cadre of participants learned to function less as a partnership between separate entities and more like one team with staff from multiple organizations. From 2020 to 2023, this initiative set up 38 community mass-testing clinics and organized 210 Covid-19 vaccination clinics across 71 diverse community-based sites, including fire stations, consulates, schools, shelters, and faith-based organizations. Notably, 56 of the sites were situated within census tracts exhibiting a social vulnerability index (SVI) of 0.500 or higher, with 35 sites having an SVI score surpassing 0.800, indicating greater vulnerability. Through this effort, 18,059 Covid-19 tests were conducted and processed, and 16,367 Covid-19 vaccinations were administered, averaging 78 per clinic. Many community members who received services were recent immigrants and persons whose preferred language was not English. The success of this pandemic response depended largely on a common mission and shared sense of purpose among previously infrequent or unfamiliar partners. However, operations were not seamless; if these relationships had existed and been fostered during nonemergency periods, the responsiveness among participants could have produced better results. Although much was accomplished, it is sobering to remember the many lives lost during the pandemic. The authors describe an approach to eliminate silos to maintain and strengthen teamwork between public health and care delivery to improve care and be better prepared for future public health emergencies.
Poser le diagnostic de crise non épileptique est difficile en absence de vidéo-électroencéphalogramme. La commission d´expert de la ligue international contre l´épilepsie propose une démarche ...diagnostic permettant de poser le diagnostic selon un degré de certitude avec ou en absence de vidéo-électroencéphalogramme. Notre objectif était de déterminer la fréquence hospitalière des crises non épileptiques psychogènes en absence de vidéo-électroencéphalogramme. A l´aide du registre de consultation externe, nous avons identifié les patients suivis pour épilepsie avec deux électroencéphalographies inter-critiques normaux, entre janvier 2020 et octobre 2021. Un examen des dossiers médicaux des patients et une évaluation de la validité du diagnostic ont été effectués. Sur 64 patients évalués avec électroencéphalogramme intercritique normal, 19 ont été inclus comme souffrant de crise non épileptique psychogène, soit 26,68%. La moyenne d´âge était de 23,94 +/- 9,4 ans. Les femmes représentaient 68,4%. Les patients suivis en neurologie ont représenté 84%. Un antécédent de traumatisme dans l´enfance était retrouvé dans (47,4 %). La première crise était précédée d´événements stressants dans 47,36%. Le trouble stress posttraumatique était le plus représenté avec 73,7% des cas. L´âge moyen était de 20,95 +/-9,8 ans pour la première la crise et la durée moyenne d´évolution des crises était de 3 ans +/- 2 ans. Cette étude illustre la possibilité de poser un diagnostic présomptif de crise non-épileptique psychogène en absence de vidéo-EEG.
