medRxiv : the preprint server for health sciences最新文献

{"title":"Long-term performance of intracortical microelectrode arrays in 14 BrainGate clinical trial participants.","authors":"Nick V Hahn, Elias Stein, John P Donoghue, John D Simeral, Leigh R Hochberg, Francis R Willett","doi":"10.1101/2025.07.02.25330310","DOIUrl":"10.1101/2025.07.02.25330310","url":null,"abstract":"<p><p>Brain-computer interfaces have enabled people with paralysis to control computer cursors, operate prosthetic limbs, and communicate through handwriting, speech, and typing. Most high-performance demonstrations have used silicon microelectrode \"Utah\" arrays to record brain activity at single neuron resolution. However, reports so far have typically been limited to one or two individuals, with no systematic assessment of the longevity, decoding accuracy, and day-to-day stability properties of chronically implanted Utah arrays. Here, we present a comprehensive evaluation of 20 years of neural data from the BrainGate and BrainGate2 pilot clinical trials. This dataset spans 2,319 recording sessions and 20 arrays from the first 14 participants in these trials. On average, arrays successfully recorded neural spiking waveforms on 35.6% of electrodes, with only a 7% decline over the study enrollment period (up to 7.6 years, with a mean of 2.8 years). We assessed movement intention decoding performance using a \"decoding signal-to-noise ratio\" (dSNR) metric, and found that 11 of 14 arrays provided meaningful movement decoding throughout study enrollment (dSNR > 1). Three arrays reached a peak dSNR greater than 4.5, approaching that achieved during able-bodied computer mouse control (6.29). We also found that dSNR increases logarithmically with the number of electrodes, providing a pathway for scaling performance. Longevity and reliability of Utah array recordings in this study were better than in prior nonhuman primate studies. However, achieving peak performance consistently will require addressing unknown sources of variability.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593374","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":"Genomic alterations in the YAP/TAZ pathway are associated with stem cell-like castration-resistant prostate cancer.","authors":"Marjorie L Roskes, Alexander Martinez-Fundichely, Sandra Cohen, Metin Balaban, Chen Khuan Wong, Weiling Li, Tonatiuh A Gonzalez, Anisha B Tehim, Hao Xu, Shahd ElNaggar, Matthew Myers, Rohan Bareja, Princesca Dorsaint, Kathryn Gorski, Muhammad Asad, Majd Al Assaad, Brian D Robinson, Michael Sigouros, Ethan Barnett, Jyothi Manohar, Scott Tagawa, David Nanus, Ana Molina, Jones T Nauseef, Cora N Sternberg, Juan Miguel Mosquera, Howard I Scher, Andrea Sboner, Benjamin J Raphael, Yu Chen, Ekta Khurana","doi":"10.1101/2025.07.01.25330467","DOIUrl":"10.1101/2025.07.01.25330467","url":null,"abstract":"<p><p>Castration-resistant prostate cancer (CRPC) is an aggressive disease exhibiting multiple epigenomic subtypes: androgen receptor-dependent CRPC-AR, and lineage plastic subtypes CRPC-SCL (stem cell-like), CRPC-WNT (Wnt-dependent), and CRPC-NE (neuroendocrine). By transcriptomic profiling of tissue, and whole-genome sequencing (WGS) of tissue and cell-free DNA (cfDNA) from 500 samples, we relate genomic variants with epigenomic state. We find lineage plasticity is associated with higher epigenomic and genomic heterogeneity. Samples with CRPC-SCL show higher chromosomal instability. We find DNA alterations, particularly chromosomal rearrangements, in the YAP/TAZ pathway associated with CRPC-SCL. For example, complex rearrangements on chromosome 4, which are supported by patient-matched 3D genome architecture data, decrease promoter interactions of <i>MOB1B</i> , a YAP/TAZ pathway inhibitor, with its enhancers. Together, the genomic variants in the pathway can predict CRPC-SCL with 79% accuracy. We show the utility of cfDNA WGS for joint inference of epigenomic state and genomic variants, which can guide patient stratification for clinical decisions.</p><p><strong>Significance: </strong>This study reveals genomic variants associated with the presence of lineage-plastic CRPC stem cell-like state. We leverage the utility of minimally invasive cfDNA sequencing to obtain genomic and epigenomic insights about CRPC heterogeneity, which have implications for patient stratification for treatment decisions.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593332","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":"Different antigenic distance metrics generate similar predictions of influenza vaccine response breadth despite moderate correlation.","authors":"W Zane Billings, Yang Ge, Amanda L Skarlupka, Savannah L Miller, Hayley Hemme, Murphy John, Natalie E Dean, Sarah Cobey, Benjamin J Cowling, Ye Shen, Ted M Ross, Andreas Handel","doi":"10.1101/2025.07.01.25330674","DOIUrl":"10.1101/2025.07.01.25330674","url":null,"abstract":"<p><strong>Introduction: </strong>Influenza continuously evolves to escape population immunity, which makes formulating a vaccine challenging. Antigenic differences between vaccine strains and circulating strains can affect vaccine effectiveness (VE). Quantifying the antigenic difference between vaccine strains and circulating strains can aid interpretation of VE, and several antigenic distance metrics have been discussed in the literature. Here, we compare how the predicted breadth of vaccine-induced antibody response varies when different metrics are used to calculate antigenic distance.</p><p><strong>Methods: </strong>We analyzed data from a seasonal influenza vaccine cohort which collected serum samples from 2013/14 - 2017/18 at three study sites. The data include pre- and post-vaccination HAI titers to the vaccine strains and a panel of heterologous strains. We used that data to calculate four different antigenic distance measures between assay strains and vaccine strains: difference in year of isolation (temporal), <i>p</i>-Epitope (sequence), Grantham's distance (biophysical), and antigenic cartography distance (serological). We analyzed agreement between the four metrics using Spearman's correlation and intraclass correlation. We then fit Bayesian generalized additive mixed-effects models to predict the effect of antigenic distance on post-vaccination titer after controlling for confounders and analyzed the pairwise difference in predictions between metrics.</p><p><strong>Results: </strong>The four antigenic distance metrics had low or moderate correlation for influenza subtypes A(H1N1), B/Victoria, and B/Yamagata. A(H3N2) distances were highly correlated. We found that after accounting for pre-vaccination titer, study site, and repeated measurements across individuals, the predicted post-vaccination titers conditional on antigenic distance and subtype were nearly identical across antigenic distance metrics, with A(H1N1) showing the only notable deviation between metrics.</p><p><strong>Discussion: </strong>Despite moderate correlation among metrics, we found that different antigenic distance metrics generated similar predictions about breadth of vaccine response. Costly titer assays for antigenic cartography may not be needed when simpler sequence-based metrics suffice for quantifying vaccine breadth.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593337","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":"Assessing equity in effects of nutritional supplementation for child growth, development, and anemia.","authors":"Pearl Anne Ante-Testard, Charles D Arnold, K Ryan Wessells, Seth Adu-Afarwuah, Per Ashorn, Elodie Becquey, Kenneth H Brown, Parul Christian, John M Colford, Lia C H Fernald, Emanuela Galasso, Sonja Y Hess, Jean H Humphrey, Lieven Huybregts, Lora L Iannotti, Stephen P Luby, Kenneth Maleta, Clair Null, Andrew J Prendergast, Ann M Weber, Hasmot Ali, Shahjahan Ali, Ulla Ashorn, Jaden Bendabenda, Bernard Chasekwa, Loty Diop, Sherlie Jean-Louis Dulience, Kaniz Jannat, Chiza Kumwenda, Anna Lartey, Agnes Le Port, Jef L Leroy, Charles Mangani, Susana Matias, Malay Kanti Mridha, Robert Ntozini, Harriet Okronipa, Jean-Bosco Ouedraogo, John Phuka, Mahbubur Rahman, Lisy Ratsifandrihamanana, Saijuddin Shaikh, Abu Ahmed Shamim, Naume Tavengwa, Mariama Touré, Patricia Wolff, Tarik Benmarhnia, Christine P Stewart, Kathryn G Dewey, Benjamin F Arnold","doi":"10.1101/2025.06.05.25329064","DOIUrl":"10.1101/2025.06.05.25329064","url":null,"abstract":"<p><p>Undernutrition in early childhood causes stunted growth, cognitive delays, and anemia, with effects often magnified among children from the poorest households. Small-quantity lipid-based nutrient supplements (SQ-LNS) are effective in addressing undernutrition and improving child development. As momentum builds to scale up SQ-LNS for children aged 6-24 months in the Global South, a key concern is achieving equity in its distribution and outcomes. We performed equity analysis of individual participant data from 14 randomized controlled trials in nine countries (N=37,707 children) to assess SQ-LNS effects on child growth, development, and anemia across levels of an international wealth index. Benefits of SQ-LNS were consistent across the wealth spectrum, leading to similar improvements in child growth, development, and anemia regardless of wealth. However, such equal benefits of SQ-LNS did not erase large inequities in child growth and development between the poorest and wealthier households.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12154980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277243","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":"Conducting MRI trials in Alzheimer's patients: Challenges and Guidelines.","authors":"Maria Dobrushina, Sayyeda Chandni, Linda Dietrich, Wenzel Glanz, Michaela Butryn, Dorothea Hämmerer, Lucía Penalba-Sánchez","doi":"10.1101/2025.07.02.25330723","DOIUrl":"10.1101/2025.07.02.25330723","url":null,"abstract":"<p><p>Combining pharmaceutical interventions with neuroimaging in Alzheimer's disease (AD) research presents logistical and methodological challenges. This perspective paper outlines early-phase experiences from a 7-tesla (7T) fMRI clinical trial involving individuals with mild cognitive impairment (MCI) and mild AD, highlighting recruitment hurdles and practical recommendations. From a pool of 1,000 patients, 475 had MCI or AD clinically diagnosed; following pre-selection and screening, only 6% met all inclusion criteria. Major barriers included exclusion due to comorbidities, difficulties with blood draws, miscommunication about study procedures, and unreported medical conditions discovered during MRI. Effective communication, often requiring caregiver involvement, was essential for obtaining accurate medical histories and improving adherence. Internally, clear team coordination helped manage scheduling and protocol compliance. While strict eligibility criteria enhance data quality, they significantly impede recruitment and feasibility in high-field MRI drug studies. We offer recommendations to optimize recruitment and screening, improve protocol execution, and better balance scientific rigor with real-world clinical constraints.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593334","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":"Germline predisposition to oncogenic alkylating damage in colorectal cancer.","authors":"Carino Gurjao, Jules Cazaubiel, Chichun Tan, Brendan Reardon, Matan Hofree, Tomotaka Ugai, Jeffrey A Meyerhardt, Jonathan A Nowak, Edward L Giovannucci, Jeffrey P Townsend, Shuji Ogino, Marios Giannakis","doi":"10.1101/2025.06.30.25330572","DOIUrl":"https://doi.org/10.1101/2025.06.30.25330572","url":null,"abstract":"<p><strong>Background: </strong>Red meat consumption is a risk factor for colorectal cancer (CRC) and has been linked to tumor alkylating DNA damage. <i>rs16906252</i> -T is a cis expression quantitative trait locus (eQTL) variant associated with silencing of <i>MGMT</i> , a central alkylating damage repair gene. We hypothesize that <i>rs16906252</i> -T carriers are predisposed to alkylating damage mutations.</p><p><strong>Methods: </strong>We conducted mutational signature deconvolution of CRC whole-exome sequencing data from The Cancer Genome Atlas (TCGA, n = 540), the Nurses' Health Studies/ Health Professional Follow-up Study (NHS/HPFS, n = 900) as well as non-western samples from the Pan-Cancer Analysis of Whole Genomes (COCA-CN, n = 295); and examined the relationship of <i>rs16906252</i> -T with putative alkylation-dependent tumor mutations. Leveraging lifestyle data from NHS/HPFS, we also investigated the interaction between red meat consumption and <i>rs16906252</i> -T.</p><p><strong>Results: </strong>Among CRC patients, <i>rs16906252</i> -T carriers exhibited higher tumor alkylating damage compared to non-carriers. In the general population <i>, rs16906252</i> -T is largely absent in individuals with East Asian ancestries, and we consistently find a negligible contribution of alkylating damage in CRC patients with East Asian ancestries. We show that the alkylating mutational signature's carcinogenicity is mainly mediated by <i>KRAS</i> G12D and G13D mutations. We also observe a synergistic effect of <i>rs16906252</i> -T with high pre-diagnosis red meat intake for tumor alkylating damage.</p><p><strong>Conclusions: </strong><i>MGMT rs16906252</i> -T carriers are predisposed to CRC oncogenic alkylating damage which is potentiated by red meat intake.</p><p><strong>Impact: </strong>Our results support a causal relationship between red meat and CRC and can lead to tailored dietary and screening guidelines for CRC prevention.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593367","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":"Interrelations of aortic spring function, cardiovascular disease risk factors, and left ventricular diastolic function: The Framingham Heart Study.","authors":"Leroy L Cooper, Brenton R Prescott, Vanessa Xanthakis, Jian Rong, Martin G Larson, Emelia J Benjamin, Naomi M Hamburg, Ramachandran S Vasan, Gary F Mitchell","doi":"10.1101/2025.06.30.25330569","DOIUrl":"10.1101/2025.06.30.25330569","url":null,"abstract":"<p><strong>Background: </strong>Energy associated with proximal aortic stretch during systole is recovered as diastolic elastic recoil of the aorta that facilitates left ventricular filling. Impairment of this aortic spring mechanism may contribute to left ventricular diastolic dysfunction. However, cross-sectional and longitudinal inter-relations of cardiovascular disease risk factors, aortic stretch, and left ventricular diastolic function have not been examined. The goal of this study was to assess the cross-sectional and longitudinal associations of cardiovascular disease risk factors and systolic atrioventricular plane displacement (AVPD), a surrogate measure of stretch of the mechanically coupled ascending aorta, with measures of left ventricular diastolic function.</p><p><strong>Methods: </strong>At two examinations (14±1 years apart) in Framingham Heart Study participants (N=7117; mean age 50 years, 55% women), we assessed AVPD and left ventricular diastolic function using echocardiography. We measured systolic AVPD using the integral of the tissue Doppler s' wave. Additionally, we assessed e' (the peak early diastolic tissue velocity of the lateral mitral annulus) and E/e' (the ratio of peak early mitral inflow velocity and e').</p><p><strong>Results: </strong>In cross-sectional analyses, higher AVPD was associated with higher e' (<i>β</i> per SD±standard error=0.43±0.01; <i>P</i><0.001) and lower E/e' (<i>β</i>=-0.35±0.01; <i>P</i><0.001). In longitudinal models (between two examinations), greater change in (Δ) AVPD between visits was associated with higher Δe' (<i>β</i>=0.40±0.01; <i>P</i><0.001) and lower ΔE/e' (<i>β</i>=-0.23±0.01; <i>P</i><0.001). We observed significant effect modification (interaction <i>P</i>-values: <0.001 to 0.045) for cross-sectional and longitudinal associations by median age, sex, obesity status, hypertension treatment, and the extent of aortic stiffness (assessed via carotid-femoral pulse wave velocity).</p><p><strong>Conclusion: </strong>The aortic spring function, as assessed via AVPD, may play an important role in maintaining left ventricular diastolic function, with putative effects modified by aortic stiffness, obesity, age, and sex.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593373","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":"Spatial and Temporal Patterns of Community Utilization of a Tribally Run Shellfish Toxin Testing Program in the Gulf of Alaska.","authors":"Esther G Kennedy, John R Harley, Shannon M Cellan, Kari Lanphier, Jeff Feldpausch, Christopher Whitehead, Matthew O Gribble, Hugh B Roland","doi":"10.1101/2025.07.01.25330576","DOIUrl":"10.1101/2025.07.01.25330576","url":null,"abstract":"<p><p>Rural shellfish harvesters, including many Alaska Native peoples, require safe access to wild shellfish for subsistence, food security, and cultural practices. However, wild shellfish may be contaminated with paralytic shellfish toxins, leaving harvesters with increased risks of significant illness or death. To manage these risks, the Sitka Tribe of Alaska Environmental Research Lab (STAERL) was established to test shellfish samples sent in by harvesters in the community and to support regular monitoring of select local beaches by tribal governments. Here, we investigated harvester utilization of this shellfish testing service from 2016-2024, comprising 299 samples sent in by local harvesters, and used generalized linear models to examine how annual testing rates varied by year, location, species, and species-based detoxification rates. We pay particular attention to differences that may reflect the influence of risk perceptions and accessibility of harvesting and testing on utilization (DOI: 10.5061/dryad.dfn2z35dr). We find that testing utilization has increased through time (1.278, 95% CI: 1.161, 1.407), testing rates are highest in spring and broadly similar between the other three seasons, testing rates in Sitka are much higher than those outside of it, and neither road accessibility nor species-based detoxification rates strongly affect testing rate ratios. These findings suggest that shellfish testing behavior is consistent despite seasonal variations in risk and convenience, but that the STAERL individual testing program provides a pathway to maintain established subsistence harvest practices while reducing poisoning risks.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593381","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":"Dynamic frame-by-frame motion correction for ¹⁸F-flurpiridaz PET-MPI using convolution neural network.","authors":"Meghana Urs, Aditya Killekar, Valerie Builoff, Mark Lemley, Chih-Chun Wei, Giselle Ramirez, Paul Kavanagh, Christopher Buckley, Piotr J Slomka","doi":"10.1101/2025.06.27.25330436","DOIUrl":"10.1101/2025.06.27.25330436","url":null,"abstract":"<p><strong>Purpose: </strong>Precise quantification of myocardial blood flow (MBF) and flow reserve (MFR) in ¹⁸F-flurpiridaz PET significantly relies on motion correction (MC). However, the manual frame-by-frame correction leads to significant inter-observer variability, time-consuming, and requires significant experience. We propose a deep learning (DL) framework for automatic MC of ¹⁸F-flurpiridaz PET.</p><p><strong>Methods: </strong>The method employs a 3D ResNet based architecture that takes 3D PET volumes and outputs motion vectors. It was validated using 5-fold cross-validation on data from 32 sites of a Phase III clinical trial (NCT01347710). Manual corrections from two experienced operators served as ground truth, and data augmentation using simulated vectors enhanced training robustness. The study compared the DL approach to both manual and standard non-AI automatic MC methods, assessing agreement and diagnostic accuracy using minimal segmental MBF and MFR.</p><p><strong>Results: </strong>The area under the receiver operating characteristic curves (AUC) for significant CAD were comparable between DL-MC MBF, manual-MC MBF from Operators (AUC=0.897, 0.892 and 0.889, respectively; p>0.05), standard non-AI automatic MC (AUC=0.877; p>0.05) and significantly higher than No-MC (AUC=0.835; p<0.05). Similar findings were observed with MFR. The 95% confidence limits for agreement with the operator were ±0.49ml/g/min (mean difference = 0.00) for MFR and ±0.24ml/g/min (mean difference = 0.00) for MBF.</p><p><strong>Conclusion: </strong>DL-MC is significantly faster but diagnostically comparable to manual-MC. The quantitative results obtained with DL-MC for MBF and MFR are in excellent agreement with those manually corrected by experienced operators compared to standard non-AI automatic MC in patients undergoing ¹⁸F-flurpiridaz PET-MPI.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593339","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":"Prioritising Follow-Up for People with Suspected Epilepsy Using a Digital EEG Biomarker.","authors":"Rosie Charles, Emanuela De Falco, Elizabeth Galizia, David Martin-Lopez, Kay Meiklejohn, David Allen, Lydia E Staniaszek, Chris Price, Sophie Georgiou, Manny Bagary, Sakh Khalsa, Charlotte Lawthom, Rohit Shankar, John Terry, Wessel Woldman","doi":"10.1101/2025.06.30.25330550","DOIUrl":"10.1101/2025.06.30.25330550","url":null,"abstract":"<p><p>Lengthy waits for follow-up testing are common for people with suspected epilepsy. This delays diagnosis, prolongs uncertainty and increases seizure risk. Initial EEGs are frequently inconclusive, yet follow-ups are typically dictated by referral date, rather than risk. Here, we tested whether a digital EEG biomarker could help prioritise those most likely to have epilepsy for expedited EEG testing. We analysed 196 non-contributory (non-diagnostic) initial EEGs collected from six National Health Service (NHS) sites in England. From these recordings, we extracted eight computational features and derived a digital biomarker that quantifies the likelihood of the EEG was recorded from someone with active epilepsy. We used this information to reorder follow-up lists and compared outcomes against standard referral-based scheduling. We found that ordering for follow-up testing based upon the digital biomarker consistently prioritised people subsequently diagnosed with epilepsy. The diagnostic yield of each subsequent EEG performed was increased relative to orderings based on time of referral. Our study indicates that a routine EEG may furnish an objective risk metric that could accelerate second-line investigations and so reduce diagnostic delay whilst improving resource allocation in clinical practice.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593379","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}