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This paper discusses some overlooked challenges faced when working with machine learning models for histopathology and presents a novel opportunity to support “Learning Health Systems” with them. Initially, the authors elaborate on these challenges after separating them according to their mitigation strategies: those that need innovative approaches, time, or future technological capabilities and those that require a conceptual reappraisal from a critical perspective. Then, a novel opportunity to support ''Learning Health Systems'' by integrating hidden information extracted by ML models from digitalized histopathology slides with other healthcare big data is presented.

Numerous machine learning (ML) models have been developed for breast cancer using various types of data. Successful external validation (EV) of ML models is important evidence of their generalizability. The aim of this systematic review was to assess the performance of externally validated ML models based on histopathology images for diagnosis, classification, prognosis, or treatment outcome prediction in female breast cancer. A systematic search of MEDLINE, EMBASE, CINAHL, IEEE, MICCAI, and SPIE conferences was performed for studies published between January 2010 and February 2022. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was employed, and the results were narratively described. Of the 2011 non-duplicated citations, 8 journal articles and 2 conference proceedings met inclusion criteria. Three studies externally validated ML models for diagnosis, 4 for classification, 2 for prognosis, and 1 for both classification and prognosis. Most studies used Convolutional Neural Networks and one used logistic regression algorithms. For diagnostic/classification models, the most common performance metrics reported in the EV were accuracy and area under the curve, which were greater than 87% and 90%, respectively, using pathologists' annotations/diagnoses as ground truth. The hazard ratios in the EV of prognostic ML models were between 1.7 (95% CI, 1.2–2.6) and 1.8 (95% CI, 1.3–2.7) to predict distant disease-free survival; 1.91 (95% CI, 1.11–3.29) for recurrence, and between 0.09 (95% CI, 0.01–0.70) and 0.65 (95% CI, 0.43–0.98) for overall survival, using clinical data as ground truth. Despite EV being an important step before the clinical application of a ML model, it hasn't been performed routinely. The large variability in the training/validation datasets, methods, performance metrics, and reported information limited the comparison of the models and the analysis of their results. Increasing the availability of validation datasets and implementing standardized methods and reporting protocols may facilitate future analyses.

Abstract Purpose In a learning health system (LHS), data gathered from clinical practice informs care and scientific investigation. To demonstrate how a novel data and analytics platform can enable an LHS at a regional cancer center by characterizing the care provided to breast cancer patients. Methods Socioeconomic information, tumor characteristics, treatments and outcomes were extracted from the platform and combined to characterize the patient population and their clinical course. Oncologists were asked to identify examples where clinical practice guidelines (CPGs) or policy changes had varying impacts on practice. These constructs were evaluated by extracting the corresponding data. Results Breast cancer patients (5768) seen at the Juravinski Cancer Centre between January 2014 and June 2022 were included. The average age was 62.5 years. The commonest histology was invasive ductal carcinoma (74.6%); 77% were estrogen receptor‐positive and 15.5% were HER2 Neu positive. Breast‐conserving surgery (BCS) occurred in 56%. For the 4294 patients who received systemic therapy, the initial indications were adjuvant (3096), neoadjuvant (828) and palliative (370). Metastases occurred in 531 patients and 495 patients died. Lowest‐income patients had a higher mortality rate. For the adoption of CPGs, the uptake for adjuvant bisphosphonate was very low, 8% as predicted, compared to 64% for pertuzumab, a HER2 targeted agent and 40.2% for CD4/6 inhibitors in metastases. During COVID‐19, the provincial cancer agency issued a policy to shorten the duration of radiation after BCS. There was a significant reduction in the average number of fractions to the breast by five fractions. Conclusion Our platform characterized care and the clinical course of breast cancer patients. Practice changes in response to regulatory developments and policy changes were measured. Establishing a data platform is important for an LHS. The next step is for the data to feedback and change practice, that is, close the loop.

Introduction Large language model (LLM)-linked chatbots are being increasingly applied in healthcare due to their impressive functionality and public availability. Studies have assessed the ability of LLM-linked chatbots to provide accurate clinical advice. However, the methods applied in these Chatbot Assessment Studies are inconsistent due to the lack of reporting standards available, which obscures the interpretation of their study findings. This protocol outlines the development of the Chatbot Assessment Reporting Tool (CHART) reporting guideline.Methods and analysis The development of the CHART reporting guideline will consist of three phases, led by the Steering Committee. During phase one, the team will identify relevant reporting guidelines with artificial intelligence extensions that are published or in development by searching preprint servers, protocol databases, and the Enhancing the Quality and Transparency of health research Network. During phase two, we will conduct a scoping review to identify studies that have addressed the performance of LLM-linked chatbots in summarising evidence and providing clinical advice. The Steering Committee will identify methodology used in previous Chatbot Assessment Studies. Finally, the study team will use checklist items from prior reporting guidelines and findings from the scoping review to develop a draft reporting checklist. We will then perform a Delphi consensus and host two synchronous consensus meetings with an international, multidisciplinary group of stakeholders to refine reporting checklist items and develop a flow diagram.Ethics and dissemination We will publish the final CHART reporting guideline in peer-reviewed journals and will present findings at peer-reviewed meetings. Ethical approval was submitted to the Hamilton Integrated Research Ethics Board and deemed “not required” in accordance with the Tri-Council Policy Statement (TCPS2) for the development of the CHART reporting guideline (#17025).Registration This study protocol is preregistered with Open Science Framework: https://doi.org/10.17605/OSF.IO/59E2Q.

Recent years have witnessed a significant advancement in brain imaging techniques that offer a non-invasive approach to mapping the structure and function of the brain. Concurrently, generative artificial intelligence (AI) has experienced substantial growth, involving using existing data to create new content with a similar underlying pattern to real-world data. The integration of these two domains, generative AI in neuroimaging, presents a promising avenue for exploring various fields of brain imaging and brain network computing, particularly in the areas of extracting spatiotemporal brain features and reconstructing the topological connectivity of brain networks. Therefore, this study reviewed the advanced models, tasks, challenges, and prospects of brain imaging and brain network computing techniques and intends to provide a comprehensive picture of current generative AI techniques in brain imaging. This review is focused on novel methodological approaches and applications of related new methods. It discussed fundamental theories and algorithms of four classic generative models and provided a systematic survey and categorization of tasks, including co-registration, super-resolution, enhancement, classification, segmentation, cross-modality, brain network analysis, and brain decoding. This paper also highlighted the challenges and future directions of the latest work with the expectation that future research can be beneficial.

Various natural language processing (NLP) algorithms have been applied in the literature to analyze radiology reports pertaining to the diagnosis and subsequent care of cancer patients. Applications of this technology include cohort selection for clinical trials, population of large-scale data registries, and quality improvement in radiology workflows including mammography screening. This scoping review is the first to examine such applications in the specific context of breast cancer. Out of 210 identified articles initially, 44 met our inclusion criteria for this review. Extracted data elements included both clinical and technical details of studies that developed or evaluated NLP algorithms applied to free-text radiology reports of breast cancer. Our review illustrates an emphasis on applications in diagnostic and screening processes over treatment or therapeutic applications and describes growth in deep learning and transfer learning approaches in recent years, although rule-based approaches continue to be useful. Furthermore, we observe increased efforts in code and software sharing but not with data sharing.

The Traumatic Brain Injury Model Systems (TBIMS) is the largest longitudinal TBI data set in the world. Our study reviews the works using TBIMS data for analysis in the last 5 years. A search (2015?2020) was conducted across PubMed, EMBASE, and Google Scholar for studies that used the National Institute on Disability, Independent Living and Rehabilitation Research NIDILRR/VA-TBIMS data. Search terms were as follows: [?TBIMS? national database] within PubMed and Google Scholar, and [?TBIMS? AND national AND database] on EMBASE. Data sources, study foci (in terms of data processing and outcomes), study outcomes, and follow-up information usage were collected to categorize the studies included in this review. Variable usage in terms of TBIMS' form-based variable groups and limitations from each study were also noted. Assessment was made on how TBIMS' objectives were met by the studies. Of the 74 articles reviewed, 23 used TBIMS along with other data sets. Fifty-four studies focused on specific outcome measures only, 6 assessed data aspects as a major focus, and 13 explored both. Sample sizes of the included studies ranged from 11 to 15,835. Forty-two of the 60 longitudinal studies assessed follow-up from 1 to 5 years, and 15 studies used 10 to 25 years of the same. Prominent variable groups as outcome measures were ?Employment,? ?FIM,? ?DRS,? ?PART-O,? ?Satisfaction with Life,? ?PHQ-9,? and ?GOS-E.? Limited numbers of studies were published regarding tobacco consumption, the Brief Test of Adult Cognition by Telephone (BTACT), the Supervision Rating Scale (SRS), general health, and comorbidities as variables of interest. Generalizability was the most significant limitation mentioned by the studies. The TBIMS is a rich resource for large-sample longitudinal analyses of various TBI outcomes. Future efforts should focus on under-utilized variables and improving generalizability by validation of results across large-scale TBI data sets to better understand the heterogeneity of TBI.

Although homeless persons experience traumatic brain injury (TBI) frequently, little is known about the structural and functional brain changes in this group. We aimed to describe brain volume changes and related cognitive/motor deficits in homeless persons with or without TBI versus controls. Participants underwent T1-weighted magnetic resonance imaging (MRI), neuropsychological (NP) tests (the Grooved Pegboard Test [GPT]/Finger Tapping Test [FTT]), alcohol/drug use screens (the Alcohol Use Disorders Identification Test [AUDIT]/Drug Abuse Screening Test [DAST]), and questionnaires (the Brain Injury Screening Questionnaire [BISQ]/General Information Questionnaire [GIQ]) to determine TBI. Normalized volumes of brain substructures from MRI were derived from FreeSurfer. Comparisons were tested by Mann-Whitney U and Kruskal-Wallis rank sum tests. Leave-one-out cross-validation using random forest classifier was applied to determine the ability of predicting TBI. Diagnostic ability of this classifier was assessed using area under the receiver operating characteristic curve (AUC). Fifty-one participants?25 homeless persons (9 with TBI) and 26 controls?were included. The homeless group had higher AUDIT scores and smaller thalamus and brainstem volumes (p < 0.001) than controls. Within homeless participants, the TBI group had reduced normalized volumes of nucleus accumbens, thalamus, ventral diencephalon, and brainstem compared with the non-TBI group (p < 0.001). Homeless participants took more time on the GPT compared with controls using both hands (p < 0.0001); but the observed effects were more pronounced in the homeless group with TBI in the non-dominant hand. Homeless persons with TBI had fewer dominant hand finger taps than controls (p?=?0.0096), and homeless participants with (p?=?0.0148) or without TBI (p?=?0.0093) tapped less than controls with their non-dominant hand. In all participants, TBI was predicted with an AUC of 0.95 (95% confidence interval [CI]: 0.89-1.00) by the classifier modeled on MRI, NP tests, and screening data combined. The MRI-data-based classifier was the best predictor of TBI within the homeless group (AUC: 0.76, 95% CI: 0.53-0.99). Normalized volumes of specific brain substructures were important indicators of TBI in homeless participants and they are important indicators of TBI in the state of homelessness itself. They may improve predictive ability of NP and screening tests in determining these outcomes.

IntroductionMeningiomas are the most common brain tumor, with prevalence of approximately 3%. Histological grading has a major role in determining treatment choice and predicting outcome. While indolent grade 1 and aggressive grade 3 meningiomas exhibit relatively homogeneous clinical behavior, grade 2 meningiomas are far more heterogeneous, making outcome prediction challenging. We hypothesized two subgroups of grade 2 meningiomas which biologically resemble either World Health Organization (WHO) grade 1 or WHO grade 3. Our aim was to establish gene expression signatures that separate grade 2 meningiomas into two homogeneous subgroups: a more indolent subtype genetically resembling grade 1 and a more aggressive subtype resembling grade 3.MethodsWe carried out an observational meta-analysis on 212 meningiomas from six distinct studies retrieved from the open-access platform Gene Expression Omnibus. Microarray data was analyzed with systems-level gene co-expression network analysis. Fuzzy C-means clustering was employed to reclassify 34 of the 46 grade 2 meningiomas (74%) into a benign “grade 1-like” (13/46), and malignant “grade 3-like” (21/46) subgroup based on transcriptomic profiles. We verified shared biology between matching subgroups based on meta-gene expression and recurrence rates. These results were validated further using an independent RNA-seq dataset with 160 meningiomas, with similar results.ResultsRecurrence rates of “grade 1-like” and “grade 3- like” tumors were 0 and 75%, respectively, statistically similar to recurrence rates of grade 1 (17%) and 3 (85%). We also found overlapping biological processes of new subgroups with their adjacent grades 1 and 3.ConclusionThese results underpin molecular signatures as complements to histological grading systems. They may help reshape prediction, follow-up planning, treatment decisions and recruitment protocols for future and ongoing clinical trials.