Protein Function Analysis through Machine Learning.

Machine learning (ML) has been an important arsenal in computational biology used to elucidate protein function for decades. With the recent burgeoning of novel ML methods and applications, new ML approaches have been incorporated into many areas of computational biology dealing with protein function. We examine how ML has been integrated into a wide range of computational models to improve prediction accuracy and gain a better understanding of protein function.

Functional Dynamics of Substrate Recognition in TEM Beta-Lactamase.

The beta-lactamase enzyme provides effective resistance to beta-lactam antibiotics due to substrate recognition controlled by point mutations. Recently, extended-spectrum and inhibitor-resistant mutants have become a global health problem. Here, the functional dynamics that control substrate recognition in TEM beta-lactamase are investigated using all-atom molecular dynamics simulations.

JEDi: java essential dynamics inspector - a molecular trajectory analysis toolkit.

Background: Principal component analysis (PCA) is commonly applied to the atomic trajectories of biopolymers to extract essential dynamics that describe biologically relevant motions. Although application of PCA is straightforward, specialized software to facilitate workflows and analysis of molecular dynamics simulation data to fully harness the power of PCA is lacking. The Java Essential Dynamics inspector (JEDi) software is a major upgrade from the previous JED software.

Molecular function recognition by supervised projection pursuit machine learning.

Identifying mechanisms that control molecular function is a significant challenge in pharmaceutical science and molecular engineering. Here, we present a novel projection pursuit recurrent neural network to identify functional mechanisms in the context of iterative supervised machine learning for discovery-based design optimization. Molecular function recognition is achieved by pairing experiments that categorize systems with digital twin molecular dynamics simulations to generate working hypotheses.

Nationwide randomised trial evaluating elective neck dissection for early stage oral cancer (SEND study) with meta-analysis and concurrent real-world cohort.

Background: Guidelines remain unclear over whether patients with early stage oral cancer without overt neck disease benefit from upfront elective neck dissection (END), particularly those with the smallest tumours.

Methods: We conducted a randomised trial of patients with stage T1/T2 N0 disease, who had their mouth tumour resected either with or without END. Data were also collected from a concurrent cohort of patients who had their preferred surgery.

Evaluation of five years of nursing home inspection forms: structural and hygiene-related violation trends.

Health inspections are performed at nursing homes to identify and reduce risk and to help maintain a safe environment for nursing home residents. The study described in this article aimed to identify the most frequent violations, types of violations (hygiene or structural), and repeat violations in nursing home facilities during health inspections; and to determine if the age of the facility influenced inspection scores. Nursing home health inspection forms (N = 131) completed between 2005 and 2011 in Pitt County, North Carolina, were analyzed.

Matching capacity to demand: a regional dashboard reduces ambulance avoidance and improves accessibility of receiving hospitals.

Objectives: ambulance diversion is a dangerous repercussion of emergency department (ED) crowding and can reflect fragmentation and a lack of coordination in designating optimal patient offload sites for prehospital providers. The objective of this study was to evaluate whether proactive destination selection through the Regional Emergency Patient Access and Coordination (REPAC) program would enhance capacity and ED flow management.

Methods: the REPAC system provides a dashboard that synthesizes real-time capacity and acuity data for all three adult EDs in the city of Calgary, assigning a color code to reflect receiving status.