Keeping up to date with the latest clinical advances in prostate cancer can be challenging. We investigated the impact of guideline use on quality of treatment decisions as well as the impact of a novel, CE-certified clinical decision support tool (Siemens AIPC software) on the amount of time clinicians spend on decision-making in a multicenter setting. Ten urologists assessed ten clinical cases (screening and localized prostate cancer) in three settings: without support, using a digital version of the EAU guidelines, and with the AIPC tool, resulting in 300 clinical decisions. Comparison involved time spent, decision correct- and completeness. Using AIPC compared to digital guidelines led to a significant reduction of expenditure of time at a per case level (3.57 min and 0:14 min, p < 0.01) and for overall time per urologist (39.45 min and 02:20 min, p < 0.01). Decision options without guidelines support, online guideline usage and usage of AIPC were complete in 61%, 80% and 100%, respectively (p < 0.01). Decision making without guidelines support, online guideline usage and usage of AIPC was correct including all options in 28%, 66% and 100%, respectively (p < 0.01).Clinical decision support systems have the potential to reduces decision-making time and to enhance decision quality.

This manuscript describes the development of a resource module that is part of a learning platform named \'NIGMS Sandbox for Cloud-based Learning\' (https://github.com/NIGMS/NIGMS-Sandbox). The module delivers learning materials on Cloud-based Consensus Pathway Analysis in an interactive format that uses appropriate cloud resources for data access and analyses. Pathway analysis is important because it allows us to gain insights into biological mechanisms underlying conditions. But the availability of many pathway analysis methods, the requirement of coding skills, and the focus of current tools on only a few species all make it very difficult for biomedical researchers to self-learn and perform pathway analysis efficiently. Furthermore, there is a lack of tools that allow researchers to compare analysis results obtained from different experiments and different analysis methods to find consensus results. To address these challenges, we have designed a cloud-based, self-learning module that provides consensus results among established, state-of-the-art pathway analysis techniques to provide students and researchers with necessary training and example materials. The training module consists of five Jupyter Notebooks that provide complete tutorials for the following tasks: (i) process expression data, (ii) perform differential analysis, visualize and compare the results obtained from four differential analysis methods (limma, t-test, edgeR, DESeq2), (iii) process three pathway databases (GO, KEGG and Reactome), (iv) perform pathway analysis using eight methods (ORA, CAMERA, KS test, Wilcoxon test, FGSEA, GSA, SAFE and PADOG) and (v) combine results of multiple analyses. We also provide examples, source code, explanations and instructional videos for trainees to complete each Jupyter Notebook. The module supports the analysis for many model (e.g. human, mouse, fruit fly, zebra fish) and non-model species. The module is publicly available at https://github.com/NIGMS/Consensus-Pathway-Analysis-in-the-Cloud. This manuscript describes the development of a resource module that is part of a learning platform named ``NIGMS Sandbox for Cloud-based Learning\'\' https://github.com/NIGMS/NIGMS-Sandbox. The overall genesis of the Sandbox is described in the editorial NIGMS Sandbox [1] at the beginning of this Supplement. This module delivers learning materials on the analysis of bulk and single-cell ATAC-seq data in an interactive format that uses appropriate cloud resources for data access and analyses.

OBJECTIVE: Gene Regulatory Network (GRN) inference is a fundamental task in biology and medicine, as it enables a deeper understanding of the intricate mechanisms of gene expression present in organisms. This bioinformatics problem has been addressed in the literature through multiple computational approaches. Techniques developed for inferring from expression data have employed Bayesian networks, ordinary differential equations (ODEs), machine learning, information theory measures and neural networks, among others. The diversity of implementations and their respective customization have led to the emergence of many tools and multiple specialized domains derived from them, understood as subsets of networks with specific characteristics that are challenging to detect a priori. This specialization has introduced significant uncertainty when choosing the most appropriate technique for a particular dataset. This proposal, named MO-GENECI, builds upon the basic idea of the previous proposal GENECI and optimizes consensus among different inference techniques, through a carefully refined multi-objective evolutionary algorithm guided by various objective functions, linked to the biological context at hand.
METHODS: MO-GENECI has been tested on an extensive and diverse academic benchmark of 106 gene regulatory networks from multiple sources and sizes. The evaluation of MO-GENECI compared its performance to individual techniques using key metrics (AUROC and AUPR) for gene regulatory network inference. Friedman\'s statistical ranking provided an ordered classification, followed by non-parametric Holm tests to determine statistical significance.
RESULTS: MO-GENECI\'s Pareto front approximation facilitates easy selection of an appropriate solution based on generic input data characteristics. The best solution consistently emerged as the winner in all statistical tests, and in many cases, the median precision solution showed no statistically significant difference compared to the winner.
CONCLUSIONS: MO-GENECI has not only demonstrated achieving more accurate results than individual techniques, but has also overcome the uncertainty associated with the initial choice due to its flexibility and adaptability. It is shown intelligently to select the most suitable techniques for each case. The source code is hosted in a public repository at GitHub under MIT license: https://github.com/AdrianSeguraOrtiz/MO-GENECI. Moreover, to facilitate its installation and use, the software associated with this implementation has been encapsulated in a Python package available at PyPI: https://pypi.org/project/geneci/.

BACKGROUND: Guideline adherence in the medical field leaves room for improvement. Digitalised decision support helps improve compliance. However, the complex nature of the guidelines makes implementation in clinical practice difficult.
METHODS: This single-centre prospective study included 204 adult ASA physical status 3-4 patients undergoing elective noncardiac surgery at a German university hospital. Agreement of clearance for surgery between a guideline expert and a digital guideline support tool was investigated. The decision made by the on-duty anaesthetists (standard approach) was assessed for agreement with the expert in a cross-over design. The main outcome was the level of agreement between digital guideline support and the expert.
RESULTS: The digital guideline support approach cleared 18.1% of the patients for surgery, the standard approach cleared 74.0%, and the expert approach cleared 47.5%. Agreement of the expert decision with digital guideline support (66.7%) and the standard approach (67.6%) was fair (Cohen\'s kappa 0.37 [interquartile range 0.26-0.48] vs 0.31 [0.21-0.42], P=0.6). Taking the expert decision as a benchmark, correct clearance using digital guideline support was 50.5%, and correct clearance using the standard approach was 44.6%. Digital guideline support incorrectly asked for additional examinations in 31.4% of the patients, whereas the standard approach did not consider conditions that would have justified additional examinations before surgery in 29.4%.
CONCLUSIONS: Strict guideline adherence for clearance for surgery through digitalised decision support inadequately considered patients, clinical context. Vague formulations, weak recommendations, and low-quality evidence complicate guideline translation into explicit rules.
BACKGROUND: NCT04058769.

Single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (SRT) have led to groundbreaking advancements in life sciences. To develop bioinformatics tools for scRNA-seq and SRT data and perform unbiased benchmarks, data simulation has been widely adopted by providing explicit ground truth and generating customized datasets. However, the performance of simulation methods under multiple scenarios has not been comprehensively assessed, making it challenging to choose suitable methods without practical guidelines.
We systematically evaluated 49 simulation methods developed for scRNA-seq and/or SRT data in terms of accuracy, functionality, scalability, and usability using 152 reference datasets derived from 24 platforms. SRTsim, scDesign3, ZINB-WaVE, and scDesign2 have the best accuracy performance across various platforms. Unexpectedly, some methods tailored to scRNA-seq data have potential compatibility for simulating SRT data. Lun, SPARSim, and scDesign3-tree outperform other methods under corresponding simulation scenarios. Phenopath, Lun, Simple, and MFA yield high scalability scores but they cannot generate realistic simulated data. Users should consider the trade-offs between method accuracy and scalability (or functionality) when making decisions. Additionally, execution errors are mainly caused by failed parameter estimations and appearance of missing or infinite values in calculations. We provide practical guidelines for method selection, a standard pipeline Simpipe ( https://github.com/duohongrui/simpipe ; https://doi.org/10.5281/zenodo.11178409 ), and an online tool Simsite ( https://www.ciblab.net/software/simshiny/ ) for data simulation.
No method performs best on all criteria, thus a good-yet-not-the-best method is recommended if it solves problems effectively and reasonably. Our comprehensive work provides crucial insights for developers on modeling gene expression data and fosters the simulation process for users.

Enhancing the reproducibility and comprehension of adaptive immune receptor repertoire sequencing (AIRR-seq) data analysis is critical for scientific progress. This study presents guidelines for reproducible AIRR-seq data analysis, and a collection of ready-to-use pipelines with comprehensive documentation. To this end, ten common pipelines were implemented using ViaFoundry, a user-friendly interface for pipeline management and automation. This is accompanied by versioned containers, documentation and archiving capabilities. The automation of pre-processing analysis steps and the ability to modify pipeline parameters according to specific research needs are emphasized. AIRR-seq data analysis is highly sensitive to varying parameters and setups; using the guidelines presented here, the ability to reproduce previously published results is demonstrated. This work promotes transparency, reproducibility, and collaboration in AIRR-seq data analysis, serving as a model for handling and documenting bioinformatics pipelines in other research domains.

This paper extends the FAIR (Findable, Accessible, Interoperable, Reusable) guidelines to provide criteria for assessing if software conforms to best practices in open source. By adding \"USE\" (User-Centered, Sustainable, Equitable), software development can adhere to open source best practice by incorporating user-input early on, ensuring front-end designs are accessible to all possible stakeholders, and planning long-term sustainability alongside software design. The FAIR-USE4OS guidelines will allow funders and researchers to more effectively evaluate and plan open-source software projects. There is good evidence of funders increasingly mandating that all funded research software is open source; however, even under the FAIR guidelines, this could simply mean software released on public repositories with a Zenodo DOI. By creating FAIR-USE software, best practice can be demonstrated from the very beginning of the design process and the software has the greatest chance of success by being impactful.

Identifying impacted pathways is important because it provides insights into the biology underlying conditions beyond the detection of differentially expressed genes. Because of the importance of such analysis, more than 100 pathway analysis methods have been developed thus far. Despite the availability of many methods, it is challenging for biomedical researchers to learn and properly perform pathway analysis. First, the sheer number of methods makes it challenging to learn and choose the correct method for a given experiment. Second, computational methods require users to be savvy with coding syntax, and comfortable with command-line environments, areas that are unfamiliar to most life scientists. Third, as learning tools and computational methods are typically implemented only for a few species (i.e., human and some model organisms), it is difficult to perform pathway analysis on other species that are not included in many of the current pathway analysis tools. Finally, existing pathway tools do not allow researchers to combine, compare, and contrast the results of different methods and experiments for both hypothesis testing and analysis purposes. To address these challenges, we developed an open-source R package for Consensus Pathway Analysis (RCPA) that allows researchers to conveniently: (1) download and process data from NCBI GEO; (2) perform differential analysis using established techniques developed for both microarray and sequencing data; (3) perform both gene set enrichment, as well as topology-based pathway analysis using different methods that seek to answer different research hypotheses; (4) combine methods and datasets to find consensus results; and (5) visualize analysis results and explore significantly impacted pathways across multiple analyses. This protocol provides many example code snippets with detailed explanations and supports the analysis of more than 1000 species, two pathway databases, three differential analysis techniques, eight pathway analysis tools, six meta-analysis methods, and two consensus analysis techniques. The package is freely available on the CRAN repository. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Processing Affymetrix microarrays Basic Protocol 2: Processing Agilent microarrays Support Protocol: Processing RNA sequencing (RNA-Seq) data Basic Protocol 3: Differential analysis of microarray data (Affymetrix and Agilent) Basic Protocol 4: Differential analysis of RNA-Seq data Basic Protocol 5: Gene set enrichment analysis Basic Protocol 6: Topology-based (TB) pathway analysis Basic Protocol 7: Data integration and visualization.

In recent years, there has been a surge in the development of AI-based Software as a Medical Device (SaMD), particularly in visual specialties such as dermatology. In Australia, the Therapeutic Goods Administration (TGA) regulates AI-based SaMD to ensure its safe use. Proper labelling of these devices is crucial to ensure that healthcare professionals and the general public understand how to use them and interpret results accurately. However, guidelines for labelling AI-based SaMD in dermatology are lacking, which may result in products failing to provide essential information about algorithm development and performance metrics. This review examines existing labelling guidelines for AI-based SaMD across visual medical specialties, with a specific focus on dermatology. Common recommendations for labelling are identified and applied to currently available dermatology AI-based SaMD mobile applications to determine usage of these labels. Of the 21 AI-based SaMD mobile applications identified, none fully comply with common labelling recommendations. Results highlight the need for standardized labelling guidelines. Ensuring transparency and accessibility of information is essential for the safe integration of AI into health care and preventing potential risks associated with inaccurate clinical decisions.

This chapter describes procedures for the use of DNA sequence data to obtain and compare taxonomic identification using the public databases GenBank and Barcode of Life Data System (BOLD). The chapter begins by describing procedures used to prepare quality sequences for uploading into GenBank and BOLD. Next, steps used to query the DNA sequences against the public databases are described using GenBank BLAST and BOLD identification engines. Interpretation guidelines for the taxonomic identification assignments are presented. Finally, a procedure for evaluating the accuracy and reliability of sequences from GenBank and BOLD is provided.