medRxiv : the preprint server for health sciences最新文献

{"title":"Artificial Intelligence in Pancreatic Intraductal Papillary Mucinous Neoplasm Imaging: A Systematic Review.","authors":"Muhammad Ibtsaam Qadir, Jackson A Baril, Michele T Yip-Schneider, Duane Schonlau, Thi Thanh Thoa Tran, C Max Schmidt, Fiona R Kolbinger","doi":"10.1101/2025.01.08.25320130","DOIUrl":"10.1101/2025.01.08.25320130","url":null,"abstract":"<p><strong>Background: </strong>Based on the Fukuoka and Kyoto international consensus guidelines, the current clinical management of intraductal papillary mucinous neoplasm (IPMN) largely depends on imaging features. While these criteria are highly sensitive in detecting high-risk IPMN, they lack specificity, resulting in surgical overtreatment. Artificial Intelligence (AI)-based medical image analysis has the potential to augment the clinical management of IPMNs by improving diagnostic accuracy.</p><p><strong>Methods: </strong>Based on a systematic review of the academic literature on AI in IPMN imaging, 1041 publications were identified of which 25 published studies were included in the analysis. The studies were stratified based on prediction target, underlying data type and imaging modality, patient cohort size, and stage of clinical translation and were subsequently analyzed to identify trends and gaps in the field.</p><p><strong>Results: </strong>Research on AI in IPMN imaging has been increasing in recent years. The majority of studies utilized CT imaging to train computational models. Most studies presented computational models developed on single-center datasets (n=11,44%) and included less than 250 patients (n=18,72%). Methodologically, convolutional neural network (CNN)-based algorithms were most commonly used. Thematically, most studies reported models augmenting differential diagnosis (n=9,36%) or risk stratification (n=10,40%) rather than IPMN detection (n=5,20%) or IPMN segmentation (n=2,8%).</p><p><strong>Conclusion: </strong>This systematic review provides a comprehensive overview of the research landscape of AI in IPMN imaging. Computational models have potential to enhance the accurate and precise stratification of patients with IPMN. Multicenter collaboration and datasets comprising various modalities are necessary to fully utilize this potential, alongside concerted efforts towards clinical translation.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019469","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":"The Role of <i>de novo</i> and Ultra-Rare Variants in Hirschsprung Disease (HSCR): Extended Gene Discovery for Risk Profiling of Patients.","authors":"Mingzhou Fu, Hanna E Berk-Rauch, Sumantra Chatterjee, Aravinda Chakravarti","doi":"10.1101/2025.01.07.25320162","DOIUrl":"10.1101/2025.01.07.25320162","url":null,"abstract":"<p><strong>Background: </strong>Hirschsprung disease (HSCR) is a rare neurodevelopmental disorder caused by disrupted migration and proliferation of enteric neural crest cells during enteric nervous system development. Genetic studies suggest a complex etiology involving both rare and common variants, but the contribution of ultra-rare pathogenic variants (PAs) remains poorly understood.</p><p><strong>Methods: </strong>We perform whole-exome sequencing (WES) on 301 HSCR probands and 109 family trios, employing advanced statistical methods and gene prioritization strategies to identify genes carrying <i>de novo</i> and ultra-rare coding pathogenic variants. Multiple study designs, including case-control, <i>de novo</i> mutation analysis and joint test, are used to detect associated genes. Candidate genes are further prioritized based on their biological and functional relevance to disease associated tissues and onset period (i.e., human embryonic colon).</p><p><strong>Results: </strong>We identify 19 risk genes enriched with ultra-rare coding pathogenic variants in HSCR probands, including four known genes (<i>RET</i>, <i>EDNRB</i>, <i>ZEB2</i>, <i>SOX10</i>) and 15 novel candidates (e.g., <i>COLQ</i>, <i>NES</i>, <i>FAT3</i>) functioning in neural proliferation and neuromuscular synaptic development. These genes account for 17.5% of the population-attributable risk (PAR), with novel candidates contributing 6.5%. Notably, a positive correlation between pathogenic mutational burden and disease severity is observed. Female cases exhibit at least 42% higher ultra-rare pathogenic variant burden than males (P = 0.05).</p><p><strong>Conclusions: </strong>This first-ever genome-wide screen of ultra-rare variants in a large, phenotypically diverse HSCR cohort highlights the substantial contribution of ultra-rare pathogenic variants to the disease risk and phenotypic variability. These findings enhance our understanding of the genetic architecture of HSCR and provide potential targets for genetic screening and personalized interventions.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019476","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":"Evaluation of Photon-Counting CT for Spectral Imaging in Cardiovascular Applications: Impact of Lumen Size, Dose, and Patient Habitus.","authors":"Martin V Rybertt, Leening P Liu, Manoj Mathew, Pooyan Sahbaee, Harold I Litt, Peter B Noël","doi":"10.1101/2025.01.07.25320150","DOIUrl":"https://doi.org/10.1101/2025.01.07.25320150","url":null,"abstract":"<p><strong>Objectives: </strong>This study evaluates the performance of a clinical dual-source photon-counting computed tomography (PCCT) system in quantifying iodine within calcified vessels, using 3D- printed phantoms with vascular-like structures lined with calcium.</p><p><strong>Methods: </strong>Parameters assessed include lumen diameters (4, 6, 8, 10, and 12 mm), phantom sizes (S: 20×20 cm, M: 25×25 cm, L: 30×40 cm, XL: 40×50 cm, representing the 99th percentile of US patient sizes), and iodine concentrations (2, 5, and 10 mg/mL). Scans were performed at radiation dose levels of 5, 10, 15, and 20 mGy to systematically evaluate iodine quantification accuracy and spectral imaging performance.</p><p><strong>Results: </strong>The results indicate that for lumen diameters ≥6 mm, iodine quantification remains stable across all dose levels and phantom sizes, with deviations consistently below 0.6 mg/mL. Whereas, for 4 mm lumens, stability is observed primarily in smaller to medium phantoms, highlighting the influence of patient size and radiation dose on quantification accuracy. Virtual Monoenergetic Imaging (VMI) at 70 keV showed stable performance for larger lumens (≥6 mm) with variations of 13 ± 2 HU across all conditions, while smaller lumens remained stable in medium to small phantoms.</p><p><strong>Conclusions: </strong>These findings highlight the influence of lumen diameter, patient size, and radiation dose in optimizing PCCT protocols for spectral imaging. Importantly, the study demonstrates that PCCT delivers stable and highly accurate imaging across nearly the entire range of patient sizes in the U.S..</p><p><strong>Advances in knowledge: </strong>This study demonstrates PCCT's potential to enhance spectral imaging in vascular applications, surpassing conventional or Dual Energy CT.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019492","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":"Measurement and interpretation of the Harare HIV combination prevention cascade in priority populations: A population survey of adolescent girls and young women and young men in Zimbabwe.","authors":"Louisa Moorhouse, Jeffrey W Imai-Eaton, Tawanda Dadirai, Rufurwokuda Maswera, Tafadzwa Museka, Phyllis Mandizvidza, Freedom Dzamatira, Blessing Tsenesa, Timothy B Hallett, Constance Nyamukapa, Simon Gregson","doi":"10.1101/2025.01.08.25320195","DOIUrl":"10.1101/2025.01.08.25320195","url":null,"abstract":"<p><strong>Introduction: </strong>HIV-negative adolescent girls and young women (AGYW), and male partners, have disproportionately high HIV incidence in many African countries. We used a new HIV Prevention Cascade (HPC) approach to quantify levels of, and barriers to, prevention method use to guide interventions to increase effective uptake of primary HIV prevention.</p><p><strong>Methods: </strong>Data from the Manicaland HPC pilot study (2018-19; N=9803) in Zimbabwe were used to measure levels of sexual risk behaviour and construct HPCs for male condom, PrEP (females), VMMC (males) and combination prevention use by HIV-negative sexually-active AGYW (15-24-years) and male partners (15-29-years).</p><p><strong>Results: </strong>19% of AGYW (N=1140) and 37% of young men (N=955) who had started sex reported one or more HIV risk behaviour and met the definition of the priority populations for HIV prevention. Of these, 63% of females and 87% of males were motivated to use an HIV prevention method, 28% and 63% had access to a method, and 16% and 53% used a method. Male condoms were the most commonly used prevention method, accounting for 97% of use in females and 55% in males. Barriers to motivation, access and capacity to use were reported for all priority populations and methods. Some barriers were common across HPCs (e.g. lack of risk perception, social unacceptability, and lack of acceptable provision); others were specific to particular prevention methods or priority populations (e.g. lack of availability).</p><p><strong>Conclusion: </strong>HIV risk behaviours were commonly reported, but use of prevention methods is low in young people in Manicaland. Population survey measurements of HPCs revealed large gaps in all steps in the cascade (lack of motivation, lack of access and lack of capacity to use prevention) but also provided information on the reasons for these gaps that can aid in designing interventions that reduce new infections.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019363","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":"Long-term mortality outcomes among immunotherapy recipients treated with dupilumab for the management of cutaneous immune-related adverse events.","authors":"Sara Khattab, Guihong Wan, Suzanne Xu, Cameron Moseley, Matthew Tran, Emma Beagles, Chuck Lin, Bonnie Leung, Marjan Azin, Ninghui Hao, Kerry L Reynolds, Shadmehr Demehri, Nicole R LeBoeuf, Yevgeniy R Semenov","doi":"10.1101/2025.01.07.25320156","DOIUrl":"https://doi.org/10.1101/2025.01.07.25320156","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Dupilumab has been added to National Cancer Comprehensive Network (NCCN) guidelines as a therapeutic strategy for managing certain cutaneous immune-related adverse events (cirAEs) from immune checkpoint inhibitor (ICI) therapy. However, little is known about the implications of dupilumab for cancer outcomes in this population. In this multi-institutional study, we evaluate the impact of dupilumab treatment on survival among ICI recipients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a muti-institutional retrospective cohort study of ICI recipients from the Mass General Brigham Healthcare System and Dana-Farber Cancer Institute. The dupilumab group was compared to two control groups who did not receive dupilumab: with and without cirAEs (control groups 1 and 2, respectively) that were 1:2 matched on sex, race, age at ICI initiation, Charlson Comorbidity Score, year of ICI initiation, and ICI type. Manual chart review was performed to obtain cirAE characteristics, systemic glucocorticoid use, dupilumab treatment, vital status, and last contact date. Time-varying multivariable Cox proportional hazards regressions were used to evaluate the impact of dupilumab on overall survival, adjusted for sex, race, age at ICI initiation, ICI type, Charlson Comorbidity Index score, cancer type, cancer stage at ICI initiation, and systemic glucocorticoid use.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 53 cirAE patients treated with dupilumab were compared to two control groups of 106 patients each. Most patients receiving dupilumab demonstrated either complete or partial resolution of their cirAE (88.7%). In multivariable modeling, the overall survival of the dupilumab group was not significantly different from control group 1 (HR=0.74, 95% CI:0.35-1.60, p=0.5) or control group 2 (HR=0.70, 95% CI:0.32-1.51, p=0.4). However, the use of systemic glucocorticoids within two years after ICI initiation was associated with poorer overall survival when comparing the dupilumab group to control group 1 (HR=2.03, 95% CI:1.04-3.96, p=0.039) and control group 2 (HR=2.21, 95% CI:1.25-3.91, p=0.006).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study suggests that dupilumab is an effective therapeutic option for recalcitrant cirAEs and does not adversely impact mortality. Due to the observed detrimental effects of systemic glucocorticoid therapy, this study supports the need to shift away from systemic glucocorticoid immunosuppression and towards targeted immune modulators for irAE management that are less detrimental to ICI response.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;• what is already known on this topic: &lt;/strong&gt;Current guidelines recommend the use of dupilumab in the treatment of certain moderate to severe cutaneous immune related adverse events (cirAE) and systemic glucocorticoids for others. Previous studies have shown dupilumab to be effective for steroid refractory cirAEs; &lt;sup&gt;1&lt;/sup&gt; however, the impact dupilumab on survival outcomes among recipients of immune","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019316","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":"Pregnenolone Reduces Provoked Craving and Cocaine Use in Men and Women with Cocaine Use Disorder: A Pilot Trial.","authors":"Elcin Sakmar, Stephanie Wemm, Nia Fogelman, Gretchen Hermes, Rajita Sinha, Verica Milivojevic","doi":"10.1101/2025.01.07.25320141","DOIUrl":"https://doi.org/10.1101/2025.01.07.25320141","url":null,"abstract":"<p><strong>Aim: </strong>Chronic cocaine use is associated with decreases in neuroactive steroid levels. These adaptations may contribute to continued cocaine use and high relapse risk in individuals with cocaine use disorder (CUD). Thus, this pilot study assessed chronic treatment with 2 supraphysiologic doses of the neuroactive steroid precursor pregnenolone (PREG, 300 mg/day; 500 mg/day) to boost endogenous neuroactive steroid levels and assess its impact on provoked craving and cocaine use outcomes in an 8-week trial in men and women with CUD.</p><p><strong>Methods: </strong>Fifty-five treatment-seeking individuals with CUD were randomly assigned to receive either placebo (PLA; n=18; 12M/6F), 300mg PREG/day (n=20; 15M/5F) or 500mg PREG/day (n=17; 12M/5F) for 8 weeks, along with outpatient weekly relapse prevention treatment. Plasma was collected at weeks 2, 5 and 7 to assess circulating pregnenolone levels. A subset of subjects participated in a 3-day experimental component of guided imagery exposure to stress, cocaine cue and neutral conditions in about week 2 of the trial to assess craving response. Cocaine use outcomes was also assessed over the 8-week treatment period. Intent-to-treat analyses were conducted using linear mixed effects models.</p><p><strong>Results: </strong>There were no differences between treatment groups on demographic variables and baseline cocaine use. Plasma pregnenolone levels were higher in the 300mg and 500mg PREG groups compared to PLA ( <i>p's</i> < 0.032). Participant trial completion rates were 100% for PLA, 90% for 300mg and 94% for 500mg PREG groups. Placebo group had increased craving in response to stress ( <i>p</i> < .001) and cocaine cue ( <i>p</i> < .001) provocation, whereas the PREG groups showed no increased in provoked cocaine craving. For cocaine use outcomes during the 8-week trial, a significant main effect of treatment group ( <i>p</i> = .005) on the weekly amounts of cocaine use showed e significantly lower amounts used in the 300mg PREG compared to the 500mg PREG group ( <i>p</i> = 0.01) and to PLA ( <i>p</i> = .047). There was also a trend for a treatment group main effect for days of cocaine used (p<.12).</p><p><strong>Conclusions: </strong>These pilot findings suggest that supraphysiologic neuroactive steroid PREG doses reduces cocaine craving and may also improve cocaine use outcomes in treatment seeking individuals with CUD. Findings support further assessment and development of PREG in the treatment of CUD.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019442","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":"Non-Contact Optical Blood Pressure Biometry Using AI-Based Analysis of Non-Mydriatic Fundus Imaging.","authors":"Idan Bressler, Dolev Dollberg, Rachelle Aviv, Danny Margalit, Alon Harris, Brent Siesky, Tsontcho Ianchulev, Zack Dvey-Aharon","doi":"10.1101/2025.01.06.25320084","DOIUrl":"10.1101/2025.01.06.25320084","url":null,"abstract":"<p><strong>Background: </strong>This study was developed to determine whether a machine learning model could be developed to assess blood pressure with accuracy comparable to arm cuff measurements.</p><p><strong>Methods: </strong>A deep learning model was developed based on the UK Biobank dataset and was trained to detect both systolic and diastolic pressure. The hypothesis was formulated after data collection and before the development of the model. Comparison was conducted between arm cuff measurements, as ground truth, and results from the model, using Mean Absolute Error, Mean Squared Error, and Coefficient of Determination (R^2).</p><p><strong>Results: </strong>Systolic pressure was measured with 9.81 Mean Absolute Error, 165.13 Mean Squared Error and 0.36 R^2. Diastolic pressure was measured with 6.00 Mean Absolute Error, 58.21 and 0.30 R^2.</p><p><strong>Conclusions: </strong>This model improves on existing research and shows errors comparable to the variability of hand cuff measurements. The use of fundus images to assess blood pressure may be more indicative of long-term hypertension. Additional trials in clinical settings may be necessary, as well as additional prospective studies to validate results.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019399","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":"Protocol for the development and validation of machine-learning models for predicting the risk of hypertriglyceridemia in critically ill patients receiving propofol sedation using retrospective data.","authors":"Jiawen Deng, Kiyan Heybati, Hemang Yadav","doi":"10.1101/2024.08.17.24312159","DOIUrl":"10.1101/2024.08.17.24312159","url":null,"abstract":"<p><strong>Introduction: </strong>Propofol is a widely used sedative-hypnotic agent for critically-ill patients requiring invasive mechanical ventilation (IMV). Despite its clinical benefits, propofol is associated with increased risks of hypertriglyceridemia. Early identification of patients at risk for propofol-associated hypertriglyceridemia is crucial for optimizing sedation strategies and preventing adverse outcomes. Machine learning (ML) models offer a promising approach for predicting individualized patient risks of propofol-associated hypertriglyceridemia.</p><p><strong>Methods and analysis: </strong>We propose the development of a ML model aimed at predicting the risk of propofol-associated hypertriglyceridemia in ICU patients receiving IMV. The study will utilize retrospective data from four Mayo Clinic sites. Nested cross-validation (CV) will be employed, with a 10-fold inner CV loop for model tuning and selection as well as an outer loop using leave-one-site-out CV for external validation. Feature selection will be conducted using Boruta and LASSO-penalized logistic regression. Data preprocessing steps include missing data imputation, feature scaling, and dimensionality reduction techniques. Six ML algorithms will be tuned and evaluated. Bayesian optimization will be used for hyperparameter selection. Global model explainability will be assessed using permutation importance, and local model explainability will be assessed using SHapley Additive exPlanations (SHAP).</p><p><strong>Ethics and dissemination: </strong>The proposed ML model aims to provide a reliable and interpretable tool for clinicians to predict the risk of propofol-associated hypertriglyceridemia in ICU patients. The final model will be deployed in a web-based clinical risk calculator. The model development process and performance measures obtained during nested cross-validation will be described in a study publication to be disseminated in a peer-reviewed journal. The proposed study has received ethics approval from the Mayo Clinic Institutional Review Board (IRB #23-007416).</p><p><strong>Strengths and limitations of this study: </strong>Robust external validation using a nested cross-validation (CV) framework will help assess the generalizability of models produced from the modeling pipeline across different hospital settings.A diverse set of machine learning (ML) algorithms and advanced hyperparameter tuning techniques will be employed to identify the most optimal model configuration.Integration of feature explainability will enhance the clinical applicability of the ML models by providing transparency in predictions, which can improve clinician trust and encourage adoption.Reliance on retrospective data may introduce biases due to inconsistent or erroneous data collection, and the computational intensity of the validation approach may limit replication and future model expansion in resource-constrained settings.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127850","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":"Systemic Metabolic Alterations after Aneurysmal Subarachnoid Hemorrhage: A Plasma Metabolomics Approach.","authors":"Bosco Seong Kyu Yang, Jude P J Savarraj, Hua Chen, Sarah N Hinds, Glenda L Torres, Alice S Ryan, Folefac D Atem, Philip L Lorenzi, Xuefang S Ren, Neeraj Badjatia, Huimahn A Choi, Aaron M Gusdon","doi":"10.1101/2025.01.06.25320083","DOIUrl":"10.1101/2025.01.06.25320083","url":null,"abstract":"<p><strong>Background: </strong>Aneurysmal subarachnoid hemorrhage (aSAH) causes systemic changes that contribute to delayed cerebral ischemia (DCI) and morbidity. Circulating metabolites reflecting underlying pathophysiological mechanisms warrant investigation as biomarker candidates.</p><p><strong>Methods: </strong>Blood samples, prospectively collected within 24 hours (T1) of admission and 7-days (T2) post ictus, from patients with acute aSAH from two tertiary care centers were retrospectively analyzed. Samples from healthy subjects and patients with non-neurologic critical illness served as controls. A validated external analysis platform was used to perform untargeted metabolomics. Bioinformatics analyses were conducted to identify metabolomic profiles defining each group and delineate metabolic pathways altered in each group. Machine learning (ML) models were developed incorporating key metabolites to improve DCI prediction.</p><p><strong>Results: </strong>Among 70 aSAH, 30 healthy control, and 17 sick control subjects, a total of 1,117 metabolites were detected. Groups were matched among key clinical variables. DCI occurred in 36% of aSAH subjects, and poor functional outcome was observed in 70% at discharge. Metabolomic profiles readily discriminated the groups. aSAH subjects demonstrated a robust mobilization of lipid metabolites, with increased levels of free fatty acids (FFAs), mono- and diacylglycerols (MAG, DAG) compared with both control groups. aSAH subjects also had decreased circulating amino acid derived metabolites, consistent with increased catabolism. DCI was associated with increased sphingolipids (sphingosine and sphinganine) and decreased acylcarnitines and S-adenosylhomocysteine at T1. Decreased lysophospholipids and acylcarnitines were associated with poor outcomes. Incorporating metabolites into ML models improved prediction of DCI compared with clinical variables alone.</p><p><strong>Conclusions: </strong>Profound metabolic shifts occur after aSAH with characteristic increases in lipid and decreases in amino acid metabolites. Key lipid metabolites associated with outcomes (sphingolipids, lysophospholipids, and acylcarnitines) provide insight into systemic changes driving secondary complications. These metabolites may also prove to be useful biomarkers to improve prognostication and personalize aSAH care.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019411","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":"Perspectives on Cervical Cancer Prevention Strategies and a Combination Treatment for Cervical Precancer in South African Women Living with HIV and Male Partners.","authors":"Nicholas S Teodoro, Nkosinathi Ngcobo, Milenka Jean-Baptiste, Masangu Mulongo, Cecilia Milford, Malgorzata Beksinska, Jaqueline Burgess, Sibusisiwe Luvuno, Jermina Nkoana, Nonkululeko Mayisela, Lisa Rahangdale, Carla J Chibwesha","doi":"10.1101/2025.01.07.25320108","DOIUrl":"https://doi.org/10.1101/2025.01.07.25320108","url":null,"abstract":"<p><strong>Introduction: </strong>Cervical cancer remains the second most common cancer among women worldwide, with 85% of cases occurring in low-and middle-income countries (LMIC). Women living with HIV (WLWH) are at a particularly high risk of developing for high-grade cervical intraepithelial neoplasia (CIN2/3) and cervical cancer, and the standard surgical treatment is far less effective in this population. Thus, research on medical therapies and combination treatment options remain a priority. In preparation for a clinical trial involving adjuvant intravaginal 5-fluorouracil (5FU) cream following surgical treatment for CIN2/3, we explored the acceptability of our proposed intervention among WLWH and male partners.</p><p><strong>Methods: </strong>We conducted qualitative interviews with WLWH and male partners in Johannesburg, South Africa between April 2022 and September 2022. We invited WLWH to participate in semi-structured focus group discussions (FGDs), while male partners were invited to participate in semi-structured in-depth interviews (IDIs). The analysis utilized a rapid, deductive approach in which quotations were identified and categorized into relevant domains: factors affecting cervical cancer screening, the initiation of 5FU vaginal cream, and adherence to 5FU.</p><p><strong>Results: </strong>We conducted 9 FGDs comprising 48 WLWH and 18 IDIs with male partners. The mean age of participants was 43 years, and the majority (75%) had completed secondary education. Most women (75%) had also undergone Pap smear screening and 50% had a prior abnormal Pap smear. Qualitative analysis revealed that education on HPV and cervical cancer, prior experience with the health system, and social perceptions/stigma influenced cervical cancer screening uptake and were important factors in the initiation of and adherence to 5FU. Men's knowledge about cervical cancer was extremely limited. Overall, participants' perceptions of the proposed trial intervention were positive, with most participants expressing confidence that women would be able to use and adhere to the intravaginal 5FU cream. Concerns raised included possible effects of 5FU on fertility, contraceptive requirements, and the recommendation for brief periods of abstinence following cream use to prevent partner side effects.</p><p><strong>Conclusions: </strong>Although participants had some cervical cancer knowledge, misperceptions about HPV and cervical cancer were common and prevented follow-up for abnormal Pap results. Participants emphasized the need for thorough counseling about 5FU, citing this as integral for uptake. Utilizing stakeholder input to design the clinical trial is necessary to promote acceptability and adherence to the trial intervention.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019427","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}