The roles of Growth Hormone dependent JAK-STAT5 and Lyn kinase signalling in determining lifespan and cancer incidence.

In rodents, loss of GH or its receptor is associated with extended lifespan. We aimed to determine the signalling process resulting in this longevity using GH receptor (GHR) mutant mice with key signalling pathways deleted and correlate this with cancer incidence and expression of genes associated with longevity. GHR uses both canonical JAK2-STAT signalling as well as signalling via LYN-ERK1/2 pathway. We utilised C57BL/6 mice with loss of key receptor tyrosines and truncation resulting in (1) loss of most STAT5 response to GH or (2) total inability to generate STAT5 to GH or (3) loss of Box1 to prevent activation of JAK2 but not LYN kinase or (4) total knockout of the receptor. For each mutant we analysed lifespan, histopathology to determine likely cause of death, and hepatic gene and protein expression. The extended lifespan is evident in the Box1 mutant males (retains Lyn activation) have median lifespan of 1016 days compared to 890 days for the Ghr-/- males. In the females, GhrBox1-/- mice have a median lifespan of 970 days compared to 911 days for the knockout females. Sexually dimorphic GHR-STAT5 is repressive for longevity, since its removal results in a median lifespan of 1003 days in females compared to 734 days for wild type females. Numerous transcripts related to insulin sensitivity, oxidative stress response and mitochondrial function are regulated by GHR-STAT5, however LYN responsive genes involve DNA repair, cell cycle control, and anti-inflammatory response. There appears to be a yin-yang relationship between JAK2 and LYN that determines lifespan.

Recommendations of the Queensland children's gender service external evaluation and their implications for health policy in Australia.

OBJECTIVE: To review the evaluation process and the implications for Australian health policy of the 2024 external clinical service evaluation of the Queensland Children's Gender Service (QCGS) and its recommendations. CONCLUSIONS: Failing to perform a systematic review of the relevant literature, and adhering to discredited and ideologically based guidelines, the Review made recommendations lacking evidentiary support that have major implications for Queensland and other Australian health services. The evaluation report's recommendations reveal eight areas of concern about the clinic's functioning.

The Hemodynamic Effects of Bolus Dose Calcium in Patients Undergoing Pulmonary Artery Reconstruction and Unifocalization Surgery: A Pilot Study.

OBJECTIVES: To determine if bolus administration of calcium increases pulmonary artery pressures after unifocalization procedures or pulmonary artery reconstruction surgery. DESIGN: Retrospective cohort study using Stanford University's data warehouse. SETTING: A large pediatric heart center within an academic quaternary care facility. PARTICIPANTS: All patients undergoing pulmonary artery reconstruction or unifocalization procedures identifiable in the data warehouse. INTERVENTIONS: Data were collected from Stanford University's data repository and formatted and analyzed using RStudio (v 2023.06.1+524). MEASUREMENTS AND MAIN RESULTS: The primary outcome was the change in pulmonary artery systolic pressure (PASP) after a bolus administration of calcium. Secondary endpoints include changes in pulmonary arterial-to-systemic arterial pressure ratio, mean arterial pressure, right-sided filling pressure, and left atrial pressure. The Friedman test was used to assess differences and the Durbin-Conover rank-sum for pairwise comparisons. A difference in PASP after a bolus dose of calcium was found (Friedman X2 = 13.67, p = 0.003), with a higher PASP 5 minutes after calcium administration compared with 2 minutes before administration (35 mmHg v 33 mmHg, p = 0.01), and a higher PASP 10 minutes after calcium administration compared with2 minutes before administration (35 mmHg v 33 mmHg, p = 0.008). CONCLUSIONS: Calcium bolus administration led to an increase in pulmonary arterial pressure in patients after pulmonary artery reconstruction or unifocalization surgeries. It may be prudent to avoid bolus administration in this patient population immediately after repair or in patients with right ventricular dysfunction.

Implications of the Cass Review for health policy governing gender medicine for Australian minors.

OBJECTIVE: To summarize the key recommendations of England's independent inquiry into gender identity services for children and young people (the Cass Review) and to evaluate their relevance to Australian health policy. CONCLUSIONS: The Cass Review's findings and recommendations have clear applicability to Australian health policy. As a matter of priority, Australian health authorities need to seriously engage with the Cass Review's findings and recommendations. To not do so will put the health and well-being of vulnerable children and young people at risk.

Perturbation-based balance training of older adults and effects on physiological, cognitive and sociopsychological factors: a secondary analysis from a randomised controlled trial with 12-month follow-up.

BACKGROUND: Perturbation-based balance training (PBT) has shown promising, although diverging, fall-preventive effects; however, the effects on important physical, cognitive and sociopsychological factors are currently unknown. The study aimed to evaluate these effects on PBT at three different time points (post-training, 6-months and 12-months) in community-dwelling older adults compared with regular treadmill walking. METHODS: This was a preplanned secondary analysis from a randomised, controlled trial performed in Aalborg, Denmark, between March 2021 and November 2022. Community-dwelling older adults aged ≥65 were randomly assigned to participate in four sessions (lasting 20 min each) of either PBT (intervention) or regular treadmill walking (control). All participants were assigned to four testing sessions: pretraining, post-training, 6-month follow-up and 12-month follow-up. At these sessions, physical, cognitive and sociopsychological measures were assessed. RESULTS: In total, 140 participants were randomly allocated to either the PBT or control group. Short-term (pretraining to post-training) between-group differences were seen for choice stepping reaction time (-49 ms, 95% CI -80 to -18), dual-task gait speed (0.05 m/s, 95% CI 0.01 to 0.09) favouring the PBT group. However, these improvements were not sustained at the 6-month and 12-month follow-up. No significant between-group differences were found in other physical, cognitive or sociopsychological factors. CONCLUSIONS: This study showed that PBT, in the short term, improved choice stepping reaction time and dual-task gait speed among community-dwelling older adults. Yet, these improvements were not retained for 6- or 12-months. The healthy state of the study's population may have imposed a ceiling effect limiting the ability to show any clinically relevant effects of PBT. TRIAL REGISTRATION NUMBER: NCT04733222.

Expanding molecular diagnostic coverage for tuberculosis by combining computer-aided chest radiography and sputum specimen pooling: a modeling study from four high-burden countries.

Background: In 2022, fewer than half of persons with tuberculosis (TB) had access to molecular diagnostic tests for TB due to their high costs. Studies have found that the use of artificial intelligence (AI) software for chest X-ray (CXR) interpretation and sputum specimen pooling can each reduce the cost of testing. We modeled the combination of both strategies to estimate potential savings in consumables that could be used to expand access to molecular diagnostics. Methods: We obtained Xpert testing and positivity data segmented into deciles by AI probability scores for TB from the community- and healthcare facility-based active case finding conducted in Bangladesh, Nigeria, Viet Nam, and Zambia. AI scores in the model were based on CAD4TB version 7 (Zambia) and qXR (all other countries). We modeled four ordinal screening and testing approaches involving AI-aided CXR interpretation to indicate individual and pooled testing. Setting a false negative rate of 5%, for each approach we calculated additional and cumulative savings over the baseline of universal Xpert testing, as well as the theoretical expansion in diagnostic coverage. Results: In each country, the optimal screening and testing approach was to use AI to rule out testing in deciles with low AI scores and to guide pooled vs individual testing in persons with moderate and high AI scores, respectively. This approach yielded cumulative savings in Xpert tests over baseline ranging from 50.8% in Zambia to 57.5% in Nigeria and 61.5% in Bangladesh and Viet Nam. Using these savings, diagnostic coverage theoretically could be expanded by 34% to 160% across the different approaches and countries. Conclusions: Using AI software data generated during CXR interpretation to inform a differentiated pooled testing strategy may optimize TB diagnostic test use, and could extend molecular tests to more people who need them. The optimal AI thresholds and pooled testing strategy varied across countries, which suggests that bespoke screening and testing approaches may be needed for differing populations and settings. Supplementary Information: The online version contains supplementary material available at 10.1186/s44263-024-00081-2.

Deep Learning to Detect Intracranial Hemorrhage in a National Teleradiology Program and the Impact on Interpretation Time.

The diagnostic performance of an artificial intelligence (AI) clinical decision support solution for acute intracranial hemorrhage (ICH) detection was assessed in a large teleradiology practice. The impact on radiologist read times and system efficiency was also quantified. A total of 61 704 consecutive noncontrast head CT examinations were retrospectively evaluated. System performance was calculated along with mean and median read times for CT studies obtained before (baseline, pre-AI period; August 2021 to May 2022) and after (post-AI period; January 2023 to February 2024) AI implementation. The AI solution had a sensitivity of 75.6%, specificity of 92.1%, accuracy of 91.7%, prevalence of 2.70%, and positive predictive value of 21.1%. Of the 56 745 post-AI CT scans with no bleed identified by a radiologist, examinations falsely flagged as suspected ICH by the AI solution (n = 4464) took an average of 9 minutes 40 seconds (median, 8 minutes 7 seconds) to interpret as compared with 8 minutes 25 seconds (median, 6 minutes 48 seconds) for unremarkable CT scans before AI (n = 49 007) (P < .001) and 8 minutes 38 seconds (median, 6 minutes 53 seconds) after AI when ICH was not suspected by the AI solution (n = 52 281) (P < .001). CT scans with no bleed identified by the AI but reported as positive for ICH by the radiologist (n = 384) took an average of 14 minutes 23 seconds (median, 13 minutes 35 seconds) to interpret as compared with 13 minutes 34 seconds (median, 12 minutes 30 seconds) for CT scans correctly reported as a bleed by the AI (n = 1192) (P = .04). With lengthened read times for falsely flagged examinations, system inefficiencies may outweigh the potential benefits of using the tool in a high volume, low prevalence environment. Keywords: Artificial Intelligence, Intracranial Hemorrhage, Read Time, Report Turnaround Time, System Efficiency Supplemental material is available for this article. © RSNA, 2024.

Conceptualisation of health among young people: a protocol for systematic review and thematic synthesis of qualitative studies.

BACKGROUND: Self-reported health is a widely used health indicator in surveys and questionnaires. The measure gained attention when research identified its association with mortality in the 1970s and 1980s. The measure is also associated with morbidity and other health outcomes such as the utilisation of health services. Self-reported health is a particularly useful measure for young people because this age group is generally clinically healthy. However, it is known that many chronic conditions have long latency periods that are initiated early in life. Because of its predictive nature, self-reported health can be used to estimate young people's current and future health. Despite its widespread use, however, self-reported health remains a poorly understood concept. This paper presents the protocol for a systematic review that will identify and synthesise qualitative studies that investigate the factors that are considered by young people when they assess their health, and when they talk about health overall. METHODS: The population of the review is young people aged 10-24 years, with or without health conditions. We will search the databases of MEDLINE (Ovid®), PsycINFO (APA PsycNet), ProQuest Sociology Collection, and Web of Science Core Collection™. We will also utilise techniques of reference checking and forward citation searching, as this strategy has been shown to result in a higher number of high-quality studies in social science systematic reviews. Google Scholar and Google Search were used during preliminary searches; Google Scholar will be utilised for forward citation searching. We will include studies written in English, German, or Finnish; there will be no lower date limit. One reviewer will screen all citations. A second reviewer will independently screen a sample of 20% of the abstracts. Data will be extracted by one researcher, two other researchers will independently review all data extracted, and quality appraisal will be completed by the first reviewer. We will utilise the Quality Framework for the appraisal of included articles and thematic synthesis of qualitative studies. DISCUSSION: The results of this systematic review will improve the understanding of the factors that are considered during the self-assessments of health; this will improve the interpretation of the results of quantitative research. Also, an improved understanding of the conceptualisation of health will inform the development of health policies and interventions that support young people's health. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022367519.

Meniscal Transplant surgery or Optimised Rehabilitation full randomised trial (MeTeOR2): a study protocol.

INTRODUCTION: Pain and disability after meniscectomy can be a substantial lifelong problem. There are few treatment options, especially for young people. Non-surgical management (rehabilitation) is an option but increasingly surgeons are performing meniscal allograft transplants (MATs) for these individuals. However, this is still an uncommon procedure, and availability and usage of MAT vary widely both in the UK and internationally. It is not known which treatment option is the most effective and cost-effective. METHODS AND ANALYSIS: The Meniscal Transplant surgery or Optimised Rehabilitation trial is an international, multicentre, randomised controlled trial. The aim is to compare the clinical and cost effectiveness of MAT versus an optimised package of individualised, progressive, rehabilitation that we have called personalised knee therapy (PKT).Participants will be recruited from sites across the UK, Australia, Canada and Belgium. The planned 144 participants provide at least 90% power to detect a 10-point difference in the Knee injury and Osteoarthritis Outcome Score (KOOS4) at 24-months post randomisation (primary outcome). A prospectively planned economic evaluation will be conducted from a healthcare system and personal social services perspective. Secondary outcome data including health utility, occupational status, sports participation, mental well-being, further treatment, and adverse events will be collected at 3, 6, 12, 18, and 24 months. Analysis will be on an intention-to-treat basis and reported in-line with the Consolidated Standards of Reporting Trials statement. ETHICS AND DISSEMINATION: The trial was approved by the London-Bloomsbury Research Ethics Committee on 19 August 2022 (22/LO/0327) and Northern Sydney Local Health District Human Research Ethics Committee, NSW, Australia on the 13 March 2023 (2022/ETH01890).Trial results will be disseminated via peer-reviewed publications, presentations at international conferences, in lay summaries and using social media as appropriate.This protocol adheres to the recommended Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist. TRIAL REGISTRATION NUMBER: ISRCTN87336549.

The loss of DNA polymerase epsilon accessory subunits POLE3-POLE4 leads to BRCA1-independent PARP inhibitor sensitivity.

The clinical success of PARP1/2 inhibitors (PARPi) prompts the expansion of their applicability beyond homologous recombination deficiency. Here, we demonstrate that the loss of the accessory subunits of DNA polymerase epsilon, POLE3 and POLE4, sensitizes cells to PARPi. We show that the sensitivity of POLE4 knockouts is not due to compromised response to DNA damage or homologous recombination deficiency. Instead, POLE4 loss affects replication speed leading to the accumulation of single-stranded DNA gaps behind replication forks upon PARPi treatment, due to impaired post-replicative repair. POLE4 knockouts elicit elevated replication stress signaling involving ATR and DNA-PK. We find POLE4 to act parallel to BRCA1 in inducing sensitivity to PARPi and counteracts acquired resistance associated with restoration of homologous recombination. Altogether, our findings establish POLE4 as a promising target to improve PARPi driven therapies and hamper acquired PARPi resistance.

Patterns and Drivers of Antifungal Prescribing in Acute Leukemia: A Retrospective Cohort Study.

Background: Patients with hematological malignancy are at high risk of invasive fungal infections (IFIs). Diagnosis is challenging, which can lead to overtreatment. Reducing exposure to inappropriate antifungal prescribing is likely to improve patient safety, but modifying prescribing behavior is difficult. We aimed to describe patterns and drivers of therapeutic antifungal prescribing in a large tertiary hemato-oncology center in the United Kingdom. Methods: We studied adults receiving treatment for acute leukemia at our center between 1 April 2019 and 14 October 2022. We developed a reproducible method to analyze routinely collected data on antifungal therapy episodes in a widely used electronic health record system. We report antifungal use in days of therapy stratified by level of diagnostic confidence, as defined by consensus diagnostic guidelines (European Organisation for Research and Treatment of Cancer/Mycoses Study Group). Results: Two hundred ninety-eight patients were included in the analysis; 21.7% of inpatient antifungal use occurred in cases of proven/probable IFI. Substantial antifungal use occurred in the absence of strong evidence of infection in patients receiving high-intensity first-line chemotherapy or approaching death (81.0% and 77.9%, respectively). Approximately 33% of high-resolution computed tomography (HRCT) reports were indeterminate for IFI. Indeterminate reports were around 8 times more likely to be followed by a new antifungal therapy episode than a negative report. Conclusions: Antifungal stewardship remains challenging in the absence of reliable diagnostics, particularly in more unwell patients. The proportion of antifungal therapy given for proven/probable infection is a new metric that will likely be useful to target antifungal stewardship programs. The thoracic HRCT report is an important contributor to diagnostic uncertainty.

Effect of 20 mph speed limits on traffic injuries in Edinburgh, UK: a natural experiment and modelling study.

INTRODUCTION: There is limited research evaluating 20 mph speed limit interventions, and long-term assessments are seldom conducted either globally or within the UK. This study evaluated the impact of the phased 20 mph speed limit implementation on road traffic collisions and casualties in the City of Edinburgh, UK over approximately 3 years post implementation. METHODS: We used four sets of complementary analyses for collision and casualty rates. First, we compared rates for road segments changing to 20 mph against those at 30 mph. Second, we compared rates for the seven implementation zones in the city against paired control zones. Third, we investigated citywide casualty rate trends using generalised additive model. Finally, we used simulation modelling to predict casualty rate changes based on changes in observed speeds. RESULTS: We found a 10% (95% CI -19% to 0%) greater reduction in casualties (8% for collisions) for streets that changed to 20 mph compared with those staying at 30 mph. However, the reduction was similar, 8% (95% CI -22% to 5%) for casualties (10% collisions), in streets that were already at 20 mph. In the implementation zones, we found a 20% (95% CI -22% to -8%) citywide reduction in casualties (22% for collisions) compared with control zones; this compared with a predicted 10% (95% CI -18% to -2%) reduction in injuries based on the changes in speed and traffic volume. Citywide casualties dropped 17% (95% CI 13% to 22%) 3 years post implementation, accounting for trend. CONCLUSION: Our results indicate that the introduction of 20 mph limits resulted in a reduction in collisions and casualties 3 years post implementation. However, the effect exceeded expectations from changes in speed alone, possibly due to a wider network effect.

Rapidly expanding gender-affirming care based on consensus instead of evidence justifies rigorous governance and transparency.

OBJECTIVE: Public services offering gender-affirming care to minors have rapidly expanded across Australia. Despite limited evidence of safety and efficacy, no public information about these services is routinely available. Data from freedom of information requests sent to Australian public gender services for minors is summarised. Gender service numbers increased rapidly in Queensland (2017:190 - 2022:922) and in Victoria (2019:472 - 2023:1290). Limited transparency prevented strong confidence in the number of patients receiving hormone therapy. Staff FTE employed by gender services jumped after 2020 in NSW (to 16.7 across two sites in 2023), Queensland (to 11.4 in 2023), Victoria (to 9.4 in 2022), and WA (to 10.2 in 2023). CONCLUSIONS: Despite low confidence in their safety and efficacy, the number of patients seen by public gender services has expanded rapidly since 2018. Limited transparency makes it difficult to judge the number of patients seen, treatments provided, and outcomes achieved. Safe, effective care of this vulnerable group requires clear treatment goals, and annual reporting.

[177Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trial.

BACKGROUND: Enzalutamide and lutetium-177 [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 both improve overall survival in patients with metastatic castration-resistant prostate cancer. Androgen and PSMA receptors have a close intracellular relationship, with data suggesting complementary benefit if targeted concurrently. In this study, we assessed the activity and safety of enzalutamide plus adaptive-dosed [177Lu]Lu-PSMA-617 versus enzalutamide alone as first-line treatment for metastatic castration-resistant prostate cancer. METHODS: ENZA-p was an open-label, randomised, controlled phase 2 trial done at 15 hospitals in Australia. Participants were men aged 18 years or older with metastatic castration-resistant prostate cancer not previously treated with docetaxel or androgen receptor pathway inhibitors for metastatic castration-resistant prostate cancer, gallium-68 [68Ga]Ga-PSMA-PET-CT (PSMA-PET-CT) positive disease, Eastern Cooperative Oncology Group performance status of 0-2, and at least two risk factors for early progression on enzalutamide. Participants were randomly assigned (1:1) by a centralised, web-based system using minimisation with a random component to stratify for study site, disease burden, use of early docetaxel, and previous treatment with abiraterone acetate. Patients were either given oral enzalutamide 160 mg daily alone or with adaptive-dosed (two or four doses) intravenous 7·5 GBq [177Lu]Lu-PSMA-617 every 6-8 weeks dependent on an interim PSMA-PET-CT (week 12). The primary endpoint was prostate-specific antigen (PSA) progression-free survival, defined as the interval from the date of randomisation to the date of first evidence of PSA progression, commencement of non-protocol anticancer therapy, or death. The analysis was done in the intention-to-treat population, using stratified Cox proportional hazards regression. This trial is registered with ClinicalTrials.gov, NCT04419402, and participant follow-up is ongoing. FINDINGS: 162 participants were randomly assigned between Aug 17, 2020, and July 26, 2022. 83 men were assigned to the enzalutamide plus [177Lu]Lu-PSMA-617 group, and 79 were assigned to the enzalutamide group. Median follow-up in this interim analysis was 20 months (IQR 18-21), with 32 (39%) of 83 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 16 (20%) of 79 patients in the enzalutamide group remaining on treatment at the data cutoff date. Median age was 71 years (IQR 64-76). Median PSA progression-free survival was 13·0 months (95% CI 11·0-17·0) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 7·8 months (95% CI 4·3-11·0) in the enzalutamide group (hazard ratio 0·43, 95% CI 0·29-0·63, p<0·0001). The most common adverse events (all grades) were fatigue (61 [75%] of 81 patients), nausea (38 [47%]), and dry mouth (32 [40%]) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and fatigue (55 [70%] of 79), nausea (21 [27%]), and constipation (18 [23%]) in the enzalutamide group. Grade 3-5 adverse events occurred in 32 (40%) of 81 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 32 (41%) of 79 patients in the enzalutamide group. Grade 3 events that occurred only in the enzalutamide plus [177Lu]Lu-PSMA-617 group included anaemia (three [4%] of 81 participants) and decreased platelet count (one [1%] participant). No grade 4 or 5 events were attributed to treatment on central review in either group. INTERPRETATION: The addition of [177Lu]Lu-PSMA-617 to enzalutamide improved PSA progression-free survival providing evidence of enhanced anticancer activity in patients with metastatic castration-resistant prostate cancer with risk factors for early progression on enzalutamide and warrants further evaluation of the combination more broadly in metastatic prostate cancer. FUNDING: Prostate Cancer Research Alliance (Movember and Australian Federal Government), St Vincent's Clinic Foundation, GenesisCare, Roy Morgan Research, and Endocyte (a Novartis company).

Identification of Human-Generated vs AI-Generated Research Abstracts by Health Care Professionals.

This survey study assesses the ability of health care professionals to discern whether abstracts were written by investigators or by an artificial intelligence (AI) chatbot.

Tumor-Tailored Ionizable Lipid Nanoparticles Facilitate IL-12 Circular RNA Delivery for Enhanced Lung Cancer Immunotherapy.

The advancement of message RNA (mRNA) -based immunotherapies for cancer is highly dependent on the effective delivery of RNA (Ribonucleic) payloads using ionizable lipid nanoparticles (LNPs). However, the clinical application of these therapies is hindered by variable mRNA expression among different cancer types and the risk of systemic toxicity. The transient expression profile of mRNA further complicates this issue, necessitating frequent dosing and thus increasing the potential for adverse effects. Addressing these challenges, a high-throughput combinatorial method is utilized to synthesize and screen LNPs that efficiently deliver circular RNA (circRNA) to lung tumors. The lead LNP, H1L1A1B3, demonstrates a fourfold increase in circRNA transfection efficiency in lung cancer cells over ALC-0315, the industry-standard LNPs, while providing potent immune activation. A single intratumoral injection of H1L1A1B3 LNPs, loaded with circRNA encoding interleukin-12 (IL-12), induces a robust immune response in a Lewis lung carcinoma model, leading to marked tumor regression. Immunological profiling of treated tumors reveals substantial increments in CD45+ leukocytes and enhances infiltration of CD8+ T cells, underscoring the ability of H1L1A1B3 LNPs to modulate the tumor microenvironment favorably. These results highlight the potential of tailored LNP platforms to advance RNA drug delivery for cancer therapy, broadening the prospects for RNA immunotherapeutics.

Validating the knowledge represented by a self-organizing map with an expert-derived knowledge structure.

BACKGROUND: Professionals are reluctant to make use of machine learning results for tasks like curriculum development if they do not understand how the results were generated and what they mean. Visualizations of peer reviewed medical literature can summarize enormous amounts of information but are difficult to interpret. This article reports the validation of the meaning of a self-organizing map derived from the Medline/PubMed index of peer reviewed medical literature by its capacity to coherently summarize the references of a core psychiatric textbook. METHODS: Reference lists from ten editions of Kaplan and Sadock's Comprehensive Textbook of Psychiatry were projected onto a self-organizing map trained on Medical Subject Headings annotating the complete set of peer reviewed medical research articles indexed in the Medline/PubMed database (MedSOM). K-means clustering was applied to references from every edition to examine the ability of the self-organizing map to coherently summarize the knowledge contained within the textbook. RESULTS: MedSOM coherently clustered references into six psychiatric knowledge domains across ten editions (1967-2017). Clustering occurred at the abstract level of broad psychiatric practice including General/adult psychiatry, Child psychiatry, and Administrative psychiatry. CONCLUSIONS: The uptake of visualizations of published medical literature by medical experts for purposes like curriculum development depends upon validation of the meaning of the visualizations. The current research demonstrates that a self-organizing map (MedSOM) can validate the stability and coherence of the references used to support the knowledge claims of a standard psychiatric textbook, linking the products of machine learning to a widely accepted standard of knowledge.