Communications medicine最新文献

{"title":"Medical ontology learning framework to investigate daytime impairment in insomnia disorder and treatment effects.","authors":"Alexander J Büsser, Renato Durrer, Moritz Freidank, Matteo Togninalli, Antonio Olivieri, Michael A Grandner, William V McCall","doi":"10.1038/s43856-024-00698-2","DOIUrl":"10.1038/s43856-024-00698-2","url":null,"abstract":"<p><strong>Background: </strong>Specificity challenges frequently arise in medical ontology used for the representation of real-world data, particularly in defining mental health disorders within widely used classification systems such as the International Classification of Diseases (ICD). This study aims to address these challenges by introducing the Disease-Specific Medical Ontology Learning (DiSMOL) framework, designed to generate precise disease representations from clinical physician notes, with a focus on daytime impairment in insomnia disorder.</p><p><strong>Methods: </strong>The study applied the Disease-Specific Medical Ontology Learning framework to clinical notes to better represent daytime impairment. The framework's performance was compared to insomnia expert-selected codes from ICD. Key statistical methods included sensitivity and F1-score comparisons, as well as analysis of symptom changes after the use of various medications, including benzodiazepines, non-benzodiazepine receptor agonists, and trazodone.</p><p><strong>Results: </strong>The DiSMOL framework significantly enhances the identification of daytime impairment in people with insomnia. Sensitivity increases from 17% to 98%, and the F1-score improves from 28% to 86%, compared with expert-selected ICD codes. Additionally, the framework reveals significant increases in daytime impairment symptoms following benzodiazepine use (18.9%), while traditional ICD codes do not detect any significant change.</p><p><strong>Conclusions: </strong>The study demonstrates that DiSMOL offers a more accurate method for identifying specific disease aspects, such as daytime impairment in insomnia, than traditional coding systems. These findings highlight the potential of specialized ontologies to enhance the representation and analysis of real-world clinical data, with important implications for healthcare policy and personalized medicine.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"5 1","pages":"54"},"PeriodicalIF":5.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urinary metabolite model to predict the dying process in lung cancer patients.","authors":"Séamus Coyle, Elinor Chapman, David M Hughes, James Baker, Rachael Slater, Andrew S Davison, Brendan P Norman, Ivayla Roberts, Amara C Nwosu, James A Gallagher, Lakshminarayan R Ranganath, Mark T Boyd, Catriona R Mayland, Douglas B Kell, Stephen Mason, John Ellershaw, Chris Probert","doi":"10.1038/s43856-025-00764-3","DOIUrl":"10.1038/s43856-025-00764-3","url":null,"abstract":"<p><strong>Background: </strong>Accurately recognizing that a person may be dying is central to improving their experience of care at the end-of-life. However, predicting dying is frequently inaccurate and often occurs only hours or a few days before death.</p><p><strong>Methods: </strong>We performed urinary metabolomics analysis on patients with lung cancer to create a metabolite model to predict dying over the last 30 days of life.</p><p><strong>Results: </strong>Here we show a model, using only 7 metabolites, has excellent accuracy in the Training cohort n = 112 (AUC = 0·85, 0·85, 0·88 and 0·86 on days 5, 10, 20 and 30) and Validation cohort n = 49 (AUC = 0·86, 0·83, 0·90, 0·86 on days 5, 10, 20 and 30). These results are more accurate than existing validated prognostic tools, and uniquely give accurate predictions over a range of time points in the last 30 days of life. Additionally, we present changes in 125 metabolites during the final four weeks of life, with the majority exhibiting statistically significant changes within the last week before death.</p><p><strong>Conclusions: </strong>These metabolites identified offer insights into previously undocumented pathways involved in or affected by the dying process. They not only imply cancer's influence on the body but also illustrate the dying process. Given the similar dying trajectory observed in individuals with cancer, our findings likely apply to other cancer types. Prognostic tests, based on the metabolites we identified, could aid clinicians in the early recognition of people who may be dying and thereby influence clinical practice and improve the care of dying patients.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"5 1","pages":"49"},"PeriodicalIF":5.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alzheimer's disease biological PET staging using plasma p217+tau.","authors":"Azadeh Feizpour, Vincent Doré, Natasha Krishnadas, Pierrick Bourgeat, James D Doecke, Ziad S Saad, Gallen Triana-Baltzer, Simon M Laws, Rosita Shishegar, Kun Huang, Christopher Fowler, Larry Ward, Colin L Masters, Jurgen Fripp, Hartmuth C Kolb, Victor L Villemagne, Christopher C Rowe","doi":"10.1038/s43856-025-00768-z","DOIUrl":"10.1038/s43856-025-00768-z","url":null,"abstract":"<p><strong>Background: </strong>Plasma phospho-tau biomarkers, such as p217+tau, excel at identifying Alzheimer's disease (AD) neuropathology. However, their ability to substitute for tau PET to identify AD biological stage is unclear.</p><p><strong>Methods: </strong>Participants included 248 cognitively unimpaired (CU) and 227 cognitively impaired (CI) individuals, with Janssen plasma p217+tau Simoa® assay, ¹⁸F-NAV4694 Aβ-PET (A) and ¹⁸F-MK6240 tau-PET (T) data. Biological PET stages were defined according to the Revised Criteria for Diagnosis and Staging of Alzheimer's Disease (2024): Initial (A + T-), Early (A + T_MTL + ), Intermediate (A + T_MOD + ), and Advanced (A + T_HIGH + ). The threshold for A+ was 25 Centiloid and for T_HIGH + , the 75th percentile SUVR_{temporo-parietal} in A + CI. Sixty percent were A + , 36% Intermediate/Advanced, and 9% Advanced. The performance of p217+tau in discriminating AD stages was assessed using Receiver Operating Characteristic (ROC) analysis and logistic regression.</p><p><strong>Results: </strong>Plasma p217+tau concentrations increase across the AD biological PET stages, except between Initial and Early stages. Screening for all AD stages (vs. A-T-), combined Intermediate/Advanced stages, or Advanced stage yields AUC of 0.92, 0.92, and 0.91, respectively (CI only: AUC 0.93, 0.89, 0.83). Plasma p217+tau Youden threshold provides sensitivity of 0.77 [0.73-0.90], specificity 0.91 [0.80-0.95], PPV 0.84 [0.71-0.89], and NPV 0.88 [0.85-0.93] for combined Intermediate/Advanced stages. For the Advanced stage alone, sensitivity is 0.89 [0.79-0.97], specificity 0.82 [0.75-0.9], NPV 0.99 [0.98-1.0], but PPV is only 0.33 [0.25-0.47].</p><p><strong>Conclusions: </strong>In addition to accurately screening for A+ individuals, plasma p217+tau is useful for identifying a combined Intermediate/Advanced stage AD cohort or pre-screening to reduce the tau-PET required to identify Advanced stage AD individuals.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"5 1","pages":"53"},"PeriodicalIF":5.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disparities in telemedicine use and payment policies in the United States between 2019 and 2023.","authors":"Anna D Gage, Megan A Knight, Corinne Bintz, Robert W Aldridge, Olivia Angelino, Joseph L Dieleman, M Ashworth Dirac, Laura Dwyer-Lindgren, Simon I Hay, Rafael Lozano, Ali H Mokdad, Annie Haakenstad","doi":"10.1038/s43856-025-00757-2","DOIUrl":"10.1038/s43856-025-00757-2","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic induced an increase in telemedicine use in the American health care system. We assess disparities in telemedicine usage, the diseases and conditions it is used for, and the association of payment parity policies with telemedicine use for January 2019-March 2023.</p><p><strong>Methods: </strong>We include health systems which reported electronic health record data to the Healthjump database. The outcomes of interest are the percentage of outpatient consultations conducted via telemedicine in each health system and the distribution of outpatient and telemedicine consultations across 31 diseases and conditions. We use a difference-in-difference observational design to assess the association of state level payment parity mandates with telemedicine use.</p><p><strong>Results: </strong>We show telemedicine use grew from less than 0.05% of outpatient consultations in 2019 to 25% in April 2020 and 4% in March 2023. Health systems in urban areas used telemedicine 2.4 times more than health systems in rural areas since April 2020 at the median. In March 2023, 29% of all mental health care visits and 21% of substance use disorder care were provided via telemedicine. Payment parity mandates are associated with a 2.5 percentage point increase in telemedicine use in the first quarter of 2023 compared to states without mandates.</p><p><strong>Conclusions: </strong>The pandemic resulted in a sustained change in the use of telemedicine. The predominance of mental health care in telemedicine suggests that this mode of service delivery could be instrumental to increasing access to mental health services in the United States.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"5 1","pages":"52"},"PeriodicalIF":5.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11865567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LRP5 promotes adipose progenitor cell fitness and adipocyte insulin sensitivity.","authors":"Nellie Y Loh, Senthil K Vasan, Daniel B Rosoff, Emile Roberts, Andrea D van Dam, Manu Verma, Daniel Phillips, Agata Wesolowska-Andersen, Matt J Neville, Raymond Noordam, David W Ray, Jonathan H Tobias, Celia L Gregson, Fredrik Karpe, Constantinos Christodoulides","doi":"10.1038/s43856-025-00774-1","DOIUrl":"10.1038/s43856-025-00774-1","url":null,"abstract":"<p><strong>Background: </strong>WNT signaling plays a key role in postnatal bone formation. Individuals with gain-of-function mutations in the WNT co-receptor LRP5 exhibit increased lower-body fat mass and potentially enhanced glucose metabolism, alongside high bone mass. However, the mechanisms by which LRP5 regulates fat distribution and its effects on systemic metabolism remain unclear. This study aims to explore the role of LRP5 in adipose tissue biology and its impact on metabolism.</p><p><strong>Methods: </strong>Metabolic assessments and imaging were conducted on individuals with gain- and loss-of-function LRP5 mutations, along with age- and BMI-matched controls. Mendelian randomization analyses were used to investigate the relationship between bone, fat distribution, and systemic metabolism. Functional studies and RNA sequencing were performed on abdominal and gluteal adipose cells with LRP5 knockdown.</p><p><strong>Results: </strong>Here we show that LRP5 promotes lower-body fat distribution and enhances systemic and adipocyte insulin sensitivity through cell-autonomous mechanisms, independent of its bone-related functions. LRP5 supports adipose progenitor cell function by activating WNT/β-catenin signaling and preserving valosin-containing protein (VCP)-mediated proteostasis. LRP5 expression in adipose progenitors declines with age, but gain-of-function LRP5 variants protect against age-related fat loss in the lower body.</p><p><strong>Conclusions: </strong>Our findings underscore the critical role of LRP5 in regulating lower-body fat distribution and insulin sensitivity, independent of its effects on bone. Pharmacological activation of LRP5 in adipose tissue may offer a promising strategy to prevent age-related fat redistribution and metabolic disorders.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"5 1","pages":"51"},"PeriodicalIF":5.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11862225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using wearable sensors and machine learning to assess upper limb function in Huntington's disease.","authors":"Adonay S Nunes, İlkay Yıldız Potter, Ram Kinker Mishra, Jose Casado, Nima Dana, Andrew Geronimo, Christopher G Tarolli, Ruth B Schneider, E Ray Dorsey, Jamie L Adams, Ashkan Vaziri","doi":"10.1038/s43856-025-00770-5","DOIUrl":"10.1038/s43856-025-00770-5","url":null,"abstract":"<p><strong>Background: </strong>Huntington's disease, a neurodegenerative disorder, impairs both upper and lower limb function, typically assessed in clinical settings. However, wearable sensors offer the opportunity to monitor real-world data that complements clinical assessments, providing a more comprehensive understanding of disease symptoms.</p><p><strong>Methods: </strong>In this study, we monitor upper limb function in individuals with Huntington's disease (HD, n = 16), prodromal HD (pHD, n = 7), and controls (CTR, n = 16) using a wrist-worn wearable sensor over a 7-day period. Goal-directed hand movements are detected through a deep learning model, and kinematic features of each movement are analyzed. The collected data is used to predict disease groups and clinical scores using statistical and machine learning models.</p><p><strong>Results: </strong>Here we show that significant differences in goal-directed movement features exist between the groups. Additionally, several of these features strongly correlate with clinical scores. Classification models accurately distinguish between HD, pHD, and CTR individuals, achieving a balanced accuracy of 67% and a recall of 0.72 for the HD group. Regression models effectively predict clinical scores.</p><p><strong>Conclusions: </strong>This study demonstrates the potential of wearable sensors and machine learning to monitor upper limb function in Huntington's disease, offering a tool for early detection, remote monitoring, and assessing treatment efficacy in clinical trials.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"5 1","pages":"50"},"PeriodicalIF":5.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of the Covid-19 pandemic on cerebrovascular diseases in the Sao Paulo region of Brazil.","authors":"Raiene Telassin Abbas-Kayano, Yara Hahr Marques Hökerberg, Raquel de Vasconcellos Carvalhaes de Oliveira","doi":"10.1038/s43856-025-00766-1","DOIUrl":"10.1038/s43856-025-00766-1","url":null,"abstract":"<p><strong>Background: </strong>The rapid spread of covid-19 overwhelmed healthcare systems. This study aimed to investigate the impact of the covid-19 pandemic on hospitalizations and hospital deaths due to cerebrovascular diseases (CVD) in São Paulo state, Brazil.</p><p><strong>Methods: </strong>This ecologic study evaluated the CVD hospitalizations and hospital deaths (2017-2021) by demographic features and CVD type. During the pandemic (2020-2021), segmented regression models were used to detect changes in CVD trends. We also evaluated the detrended cross-correlation between CVD deaths and hospitalization with the SARS-Cov-2 infection series.</p><p><strong>Results: </strong>During the pandemic, there is a 35% reduction in CVD hospitalizations, mainly in elective admissions and ischemic stroke, but a 6.5% increase in deaths, especially in Black and Brown individuals, and those aged 20-29 years. From 2020 to 2021, Black and Brown individuals experience an earlier and more prolonged increase in hospital deaths. Ischemic CVD hospitalizations decrease in the first quarter of 2020. Older people exhibit a monthly increase of 2.9% in hospitalizations and 5.3% in deaths in the 2nd and 3rd quarters of 2021. SARS-Cov-2 infections are inversely correlated to CVD hospitalizations and directly correlated to CVD hospital deaths.</p><p><strong>Conclusions: </strong>Covid-19 pandemic negatively affects CVD hospitalizations and deaths, particularly in Black and Brown individuals. The decrease in hospitalizations and increase in hospital deaths of ischemic CVD highlights vulnerability in accessing healthcare resources during the pandemic.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"5 1","pages":"48"},"PeriodicalIF":5.4,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Excess of rare noncoding variants in several type 2 diabetes candidate genes among Asian Indian families.","authors":"Madhusmita Rout, Deepika Ramu, Mendez Mariana, Teena Koshy, Vettriselvi Venkatesan, Juan C Lopez-Alvarenga, Rector Arya, Umarani Ravichandran, Surendra K Sharma, Sailesh Lodha, Amaresh Reddy Ponnala, Krishna Kumar Sharma, Mahaboob Vali Shaik, Roy G Resendez, Priyanka Venugopal, Parthasarathy R, Noelta S, Juliet A Ezeilo, Marcio Almeida, Juan Paralta, Srinivas Mummidi, Chidambaram Natesan, Narinder K Mehra, Jai Rup Singh, Gurpreet S Wander, Sarju Ralhan, Piers R Blackett, John Blangero, Krishna M Medicherla, Sadagopan Thanikachalam, Thyagarajan Sadras Panchatcharam, Dileep Kumar K, Rajeev Gupta, Solomon Franklin D Paul, Asish K Ghosh, Christopher E Aston, Ravindranath Duggirala, Dharambir K Sanghera","doi":"10.1038/s43856-025-00750-9","DOIUrl":"10.1038/s43856-025-00750-9","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes (T2D) etiology is highly complex due to its multiple roots of origin. Polygenic risk scores (PRS) based on genome-wide association studies (GWAS) can partially explain T2D risk. Asian Indian people have up to six times higher risk of developing T2D than European people, and underlying causes of this disparity are unknown.</p><p><strong>Methods: </strong>We have performed targeted sequencing of ten T2D GWAS/candidate regions using endogamous Punjabi Sikh families and replication studies using unrelated Sikh people and families from three other Indian endogamous ethnic groups (EEGs).</p><p><strong>Results: </strong>We detect rare and ultra-rare variants (RVs) in KCNJ11-ABCC8 and HNF4A (MODY genes) cosegregated with late-onset T2D. We also identify RV enrichment in two new genes, SLC38A11 and ANPEP, associated with T2D. Gene-burden analysis reveals the highest RV burden contributed by HNF4A (p = 0.0003), followed by KCNJ11/ABCC8 (p = 0.0061) and SLC38A11 (p = 0.03). Some RVs detected in Sikh people are also found in Agarwals from Jaipur, both from Northern India, but were monomorphic in other two EEGs from South Indian people. Despite carrying a high burden of T2D and RVs, most families have a significantly lower burden of PRS. Functional studies show that an intronic regulatory variant (RV) in ABCC8 affects the binding of Pax4 and NF-kB transcription factors, influencing downstream gene regulation.</p><p><strong>Conclusions: </strong>The high burden of T2D in these families may stem from the enrichment of noncoding RVs in a small number of major known genes (including MODY genes) with oligogenic inheritance alongside RVs from genes associated with polygenic susceptibility. These findings highlight the need to conduct deeper evaluations of families from non-European ancestries to identify potential novel therapeutics and implement preventative strategies.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"5 1","pages":"47"},"PeriodicalIF":5.4,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of decision analytic modelling to cardiovascular disease prevention in Sub-Saharan Africa: a systematic review.","authors":"James Odhiambo Oguta, Penny Breeze, Elvis Wambiya, Peter Kibe, Catherine Akoth, Peter Otieno, Peter J Dodd","doi":"10.1038/s43856-025-00772-3","DOIUrl":"10.1038/s43856-025-00772-3","url":null,"abstract":"<p><strong>Background: </strong>This systematic review sought to examine the application of decision analytic models (DAMs) to evaluate cardiovascular disease (CVD) prevention interventions in sub-Saharan Africa (SSA), a region that has experienced an increasing CVD burden in the last two decades.</p><p><strong>Methods: </strong>We searched seven databases and identified model-based economic evaluations of interventions targeting CVD prevention among adult populations in SSA. All articles were screened by two reviewers, data was extracted, and narrative synthesis was performed. Quality assessment was performed using the Philips checklist.</p><p><strong>Results: </strong>The review included 27 articles from eight SSA countries. The majority of the studies evaluated interventions for primary CVD prevention, with primordial prevention interventions being the least evaluated. Markov models were the most commonly used modelling method. Seven studies incorporated equity dimensions in the modelling, which were assessed mainly through subgroup analysis. The mean quality score of the papers was 68.9% and most studies reported data challenges while only three studies conducted model validation.</p><p><strong>Conclusions: </strong>The review finds few studies modelling the impact of interventions targeting primordial prevention and those evaluating equitable strategies for improving access to CVD prevention. There is a need for increased transparency in model building, validation and documentation.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"5 1","pages":"46"},"PeriodicalIF":5.4,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TFF3 facilitates dormancy of anti-estrogen treated ER+ mammary carcinoma.","authors":"Shu Chen, Xi Zhang, Basappa Basappa, Tao Zhu, Vijay Pandey, Peter E Lobie","doi":"10.1038/s43856-024-00710-9","DOIUrl":"10.1038/s43856-024-00710-9","url":null,"abstract":"<p><strong>Background: </strong>Tumor dormancy is a substantial clinical obstacle in treatment of estrogen receptor positive mammary carcinoma (ER+MC), contributing to drug resistance, metastatic outgrowth, relapse, and consequent mortality.</p><p><strong>Methods: </strong>Preclinical models mimicking clinical anti-estrogen-induced ER+MC dormancy were generated in vivo. Function and a mechanism-based combination treatment were determined in the generated dormancy-like models in vitro, ex vivo, and in vivo.</p><p><strong>Results: </strong>The dormancy models display molecular features of dormancy and tumor mass and cellular dormancy with associated clinical dormancy behavior. Both serum and cancer tissue expression of Trefoil factor 3 (TFF3) are identified as prognostic indicators of dormant ER+MC with TFF3 functioning as an epigenetically regulated driver of dormancy-associated behaviors. BCL2-dependent pro-survival functions of TFF3 coupled with enhanced attributes of stemness designates TFF3 as an actionable target. Moreover, combination screening of a TFF3 small-molecule-inhibitor (AMPC) with compounds used clinically to treat anti-estrogen-resistant ER+MC identifies strong synergism between AMPC and CDK4/6 inhibitors in the dormancy-like models. The combination results in concomitant suppression of CCND1 expression and CDK4/6 kinase activity to decrease RB phosphorylation, with reduced BCL2 expression, leading to both ER + MC cell cycle arrest and apoptosis. The combined TFF3-CDK4/6 inhibition impedes metastatic outgrowth and ameliorates host animal survival in the dormancy-like models, producing a complete response in a percentage of animals.</p><p><strong>Conclusions: </strong>Hence, in vivo models of anti-estrogen induced dormancy of ER+MC generated herein, identify TFF3 as a driver of this process. The combined inhibition of TFF3 and CDK4/6 may potentially alleviate the clinical challenges posed by anti-estrogen-induced dormancy in ER+MC.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"5 1","pages":"45"},"PeriodicalIF":5.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}