medRxiv : the preprint server for health sciences最新文献

{"title":"USING ARTIFICIAL INTELLIGENCE TO PREDICT TREATMENT OUTCOMES IN PATIENTS WITH NEUROGENIC OVERACTIVE BLADDER AND MULTIPLE SCLEROSIS.","authors":"Oliva H Chang, Jaylen Lee, Felicia Lane, Michael Demetriou, Peter D Chang","doi":"10.1101/2025.06.17.25329802","DOIUrl":"https://doi.org/10.1101/2025.06.17.25329802","url":null,"abstract":"<p><strong>Introduction and objectives: </strong>Many women with multiple sclerosis (MS) experience neurogenic overactive bladder (NOAB) characterized by urinary frequency, urinary urgency and urgency incontinence. The objective of the study was to create machine learning (ML) models utilizing clinical and imaging data to predict NOAB treatment success stratified by treatment type.</p><p><strong>Methods: </strong>This was a retrospective cohort study of female patients with diagnosis of NOAB and MS seen at a tertiary academic center from 2017-2022. Clinical and imaging data were extracted. Three types of NOAB treatment options evaluated included behavioral therapy, medication therapy and minimally invasive therapies. The primary outcome - treatment success was defined as > 50% reduction in urinary frequency, urinary urgency or a subjective perception of treatment success. For the construction of the logistic regression ML models, bivariate analyses were performed with backward selection of variables with p-values of < 0.10 and clinically relevant variables applied. For ML, the cohort was split into a training dataset (70%) and a test dataset (30%). Area under the curve (AUC) scores are calculated to evaluate model performance.</p><p><strong>Results: </strong>The 110 patients included had a mean age of patients were 59 years old (SD 14 years), with a predominantly White cohort (91.8%), post-menopausal (68.2%). Patients were stratified by NOAB treatment therapy type received with 70 patients (63.6%) at behavioral therapy, 58 (52.7%) with medication therapy and 44 (40%) with minimally invasive therapies. On MRI brain imaging, 63.6% of patients had > 20 lesions though majority were not active lesions. The lesions were mostly located within the supratentorial (94.5%), infratentorial (68.2%) and 58.2 infratentorial brain (63.8%) as well as in the deep white matter (53.4%). For MRI spine imaging, most of the lesions were in the cervical spine (71.8%) followed by thoracic spine (43.7%) and lumbar spine (6.4%).10.3%). After feature selection, the top 10 highest ranking features were used to train complimentary LASSO-regularized logistic regression (LR) and extreme gradient-boosted tree (XGB) models. The top-performing LR models for predicting response to behavioral, medication, and minimally invasive therapies yielded AUC values of 0.74, 0.76, and 0.83, respectively.</p><p><strong>Conclusions: </strong>Using these top-ranked features, LR models achieved AUC values of 0.74-0.83 for prediction of treatment success based on individual factors. Further prospective evaluation is needed to better characterize and validate these identified associations.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532348","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":"Investigating biomarkers of exposure to jet aircraft oil fumes using mass spectrometry.","authors":"Clement E Furlong, Rebecca Richter, Judit Marsillach, Alex Zelter, Matthew McDonald, Allan Rettie, Oksana Lockridge, Rachel Lundeen, Dale Whittington","doi":"10.1101/2025.04.17.25326021","DOIUrl":"10.1101/2025.04.17.25326021","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Most commercial passenger jet aircraft use compressed engine air after cooling as a source for ventilation and cabin pressurization onboard. This \"bleed air\" design means that engine oil and/or hydraulic fluid can contaminate the ventilation supply air during otherwise normal flights, exposing onboard crewmembers and passengers to the fumes. The oils and hydraulic fluids contain a complex mixture of triaryl phosphates (TAPs) and decomposition products. Although the health and flight safety consequences of inhaling these fumes have been widely documented, measures of onboard inhalation exposure have been lacking. An approach is presented for documenting exposure to engine oil fumes by using high-resolution mass spectrometry (MS) to monitor and quantify post-translational modifications of subjects' butyrylcholinesterase (BChE) that are consistent with exposure to the engine oil TAPs. We hypothesized that plasma from exposed individuals would show modifications or adducts on the active site serine (Ser198) of BChE. Plasma BChE from 81 exposed subjects was purified to near homogeneity and concentrated using antibodies immobilized on paramagnetic beads. The purified BChE was eluted at low pH, neutralized, digested with trypsin, and analyzed by liquid chromatography (LC)-MS. In subjects reporting onboard oil fume exposures, the most consistent adduct modifying the Ser198-containing tryptic peptide had a mass value of +154.0031 Da. The normalized peak area (NPA) of the +154Da modification was determined by comparing the relative MS1 intensities of the +154Da-modified Ser198 containing peptide to the total observable peptides containing the active site, including missed cleavages. Notably, adducts from &lt;i&gt;in vitro&lt;/i&gt; exposures of bioactivated TAPs to purified BChE conducted in this study (i.e., +80Da, +156Da, +170Da, and +186Da) as well as adducts reported in other earlier in vitro studies (i.e., +65Da, +80Da, +91Da, +107Da, +165Da, +180Da, +181Da, and +277Da) were not detected in exposed subjects. Of the 81 subjects in this study, the average NPA of +154Da-Ser198 resulted from fume event exposures that pre-dated 2013 (N=59); range = 0.46%-17.8%, &lt;i&gt;with X̅&lt;/i&gt; =4.84% which was 9.7 times higher than control subjects ( &lt;i&gt;X̅&lt;/i&gt; = 0.50%) These data are uncorrected for the time lag between the reported exposure and the blood draw. Samples from the remaining 16 subjects with exposures from 2016-2024 showed only the 154Da modification at background levels (0.24%-1.13%; &lt;i&gt;X̅&lt;/i&gt; =0.55%), as confirmed in control plasma samples from individuals who had not flown in at least three months. The observed reduction in the 154Da adduct over time in exposed individuals is likely a function of the change in the formulation of the OP blends added to engine oils during the course of the study. Further investigation into other protein biomarkers and adducts correlated with exposure to the current oil additives and hydraulic fluid fumes on aircraft is warranted. Th","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060134","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":"Clinicogenomic landscape and function of <i>PIK3CA</i> , <i>AKT1</i> , and <i>PTEN</i> mutations in breast cancer.","authors":"Jacqueline J Tao, Saumya D Sisoudiya, Hanna Tukachinsky, Alexa Schrock, Smruthy Sivakumar, Ethan S Sokol, Neil Vasan","doi":"10.1101/2025.06.18.25329632","DOIUrl":"https://doi.org/10.1101/2025.06.18.25329632","url":null,"abstract":"<p><strong>Purpose: </strong>To comprehensively characterize the clinical and genomic landscapes of <i>PIK3CA, AKT1,</i> and <i>PTEN</i> alterations and examine their functional implications in AKT-driven breast cancer.</p><p><strong>Experimental design: </strong>Comprehensive genomic profiling of 51,767 breast tumors was performed with FoundationOne ^® CDx or FoundationOne ^® . We examined the genomic landscape of <i>PIK3CA</i> , <i>PTEN</i> , and <i>AKT1</i> alterations and their distribution across clinical variables of interest. Prior deep mutational scanning (DMS) data was used to functionally characterize clinical <i>PTEN</i> variants.</p><p><strong>Results: </strong>There were 29,157 total variants across <i>PIK3CA, AKT1,</i> and <i>PTEN</i> , including pathogenic variants and VUS. The most frequently altered gene was <i>PIK3CA</i> (37.4% of cases), followed by <i>PTEN</i> (13.5%), then <i>AKT1</i> (5.4%). The most common alterations in each gene were <i>PIK3CA</i> H1047R (35.6% of <i>PIK3CA</i> -altered cases), E545K (19.7%), and E542K (11.7%); <i>AKT1</i> E17K (69.7%); and <i>PTEN</i> homozygous copy number deletion (37.3%). <i>PIK3CA</i> alterations were less prevalent in patients of African genetic ancestry (27.1% vs 38.6% in European genetic ancestry), while <i>AKT1</i> and <i>PTEN</i> alterations were balanced across ancestries. <i>PIK3CA</i> , <i>AKT1</i> , and <i>PTEN</i> pathogenic alterations were all mutually exclusive to each other. Using available DMS data on missense <i>PTEN</i> mutations, we found that 32.5% showed discordant effects on protein stability and phosphatase activity, underscoring the need for functional validation beyond predicted loss-of-function.</p><p><strong>Conclusions: </strong>Here we present the landscape of <i>PIK3CA</i> , <i>AKT1</i> , and <i>PTEN</i> alterations in the largest clinical cohort examined to date. The functional implications of lesser-known variants in each gene warrant further investigation by tools such as deep mutational scanning.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532289","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":"Is cognitive motor dissociation just a minimally conscious state \"plus\" by another name?","authors":"Martin M Monti","doi":"10.1101/2025.06.11.25329346","DOIUrl":"10.1101/2025.06.11.25329346","url":null,"abstract":"<p><p>Cognitive Motor Dissociation (CMD) describes a condition whereby brain injury patients can demonstrate response to command through advanced electrophysiology and imaging assessments but are unable to do so through in standard, behavior-based, clinical assessments. Rightfully, significant emphasis has been placed on the fact that despite a similar behavioral phenotype, patients with CMD show better outcomes than patients without CMD. Yet, this finding is not overly surprising when considering that patients with CMD might <i>just</i> be minimally conscious state \"plus\" patients (MCS+; i.e., patients capable of response to command) who were misdiagnoses due to the known limitations of behavioral assessments in the presence of sensory, cognitive, or motor comorbidities. The present work brings together 131 DOC patients, from two separate longitudinal studies, to assess whether patients able demonstrate response to command <i>via</i> brain responses but not behavioral responses (i.e., CMD patients) are \"just\" misdiagnosed MCS+ patients, in terms of short-term outcomes, or whether they represent a separate diagnostic entity. Robust general linear modelling reveals that, while CMD patients show greater short-term gains than patients with no evidence of CMD, consistent with prior work, these gains are not different from those seen in patients who can demonstrate response to command behaviorally (i.e., MCS+ patients). This pattern of results remains unchanged when separately analyzing Vegetative State (VS; i.e., entirely unresponsive) and Minimally Conscious State \"minus\" patients (MCS-; i.e., patients only able to show non-language-mediated response) with and without CMD, and when restricting analyses to traumatic brain injury patients only. These findings suggest that, at least in terms of short-term outcomes, patients with CMD are not meaningfully different from MCS+ patients. Rather, CMD patients are best understood as MCS+ patients who were misdiagnosed likely due to the well-known limitations of behavioral assessments in the presence of comorbidities affecting sensory input, cognitive processing, and/or motor output. These results thus support the suggestion by the European Union practice guidelines to assign diagnoses based on the highest level of response obtained in a patient across behavioral and non-behavioral assessments, as well as the use of advanced assessments not only in behaviorally VS patients, consistent with the US guidelines, but also in MCS- patients. Finally, from a nosological perspective, these findings suggest that patients with CMD might best be described as \"MCS+ patients with CMD,\" to convey at once their true level of consciousness (i.e., MCS+) and the presence of motor output limitations (i.e., CMD).</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532232","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":"Ranked placement of phage predation as a determinant of dehydration severity among cholera patients in Bangladesh.","authors":"N Madi, Md Abu Sayeed, E T Cato, A Creasy-Marrazzo, K Islam, Md I Ul Khabir, Md T R Bhuiyan, Y Begum, E Freeman, A Vustepalli, L Brinkley, M Kamat, L S Bailey, K B Basso, F Qadri, A I Khan, B J Shapiro, E J Nelson","doi":"10.1101/2025.06.17.25329780","DOIUrl":"10.1101/2025.06.17.25329780","url":null,"abstract":"<p><p>Phage predation is inversely associated with severe cholera yet its importance as a determinant of dehydration severity is unknown relative to other factors. Here we used machine learning to assess and rank potential host, microbial, and environmental factors as determinants of severe dehydration among a cohort of cholera patients enrolled at hospital admission across Bangladesh. We found the phage to pathogen ratio ranked among the top classifying features, placing just behind patient age and admission location. We advocate that phage predation is a key factor to include in the characterization of cholera for scientific, clinical and epidemiological applications.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532325","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":"From aging to Alzheimer's disease: concordant brain DNA methylation changes in late life.","authors":"David Lukacsovich, Juan I Young, Lissette Gomez, Michael A Schmidt, Wei Zhang, Brian W Kunkle, X Steven Chen, Eden R Martin, Lily Wang","doi":"10.1101/2025.06.17.25329345","DOIUrl":"https://doi.org/10.1101/2025.06.17.25329345","url":null,"abstract":"<p><p>Aging is the strongest risk factor for Alzheimer's disease (AD), yet the molecular mechanisms linking aging to AD remain poorly understood. DNA methylation (DNAm) is an epigenetic modification that plays a critical role in gene regulation and has been implicated in both aging and AD. In this study, we performed a meta-analysis of DNAm profiles in the prefrontal cortex using two large, independent postmortem brain cohorts, the Religious Orders Study and Memory and Aging Project (ROSMAP) and Brains for Dementia Research (BDR), to identify DNAm differences associated with aging in late life. We identified 3,264 CpGs significantly associated with aging, the majority of which were hypermethylated and enriched in promoter regions and CpG islands. These aging-associated DNAm changes were significantly overrepresented in genes involved in immune regulation and metabolic pathways. When compared with AD-associated DNAm changes, we found a significant overlap, with nearly all CpGs and differentially methylated regions (DMRs) that were associated with both aging and AD Braak stage displaying concordant directionality. This supports the hypothesis that aging and AD are interconnected at the molecular level. Further integrative analyses indicated that a number of these DNAm variants may have functional relevance in AD. By integrating blood DNAm data, we identified multiple CpGs that showed significant brain-to-blood correlations and were involved in both aging and AD pathogenesis. Co-localization analyses with genome-wide association study (GWAS) data revealed shared genetic regulation of DNAm and dementia at several AD risk loci. Out-of-sample validation using the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset demonstrated that, among 334 CpGs showing concordant DNAm changes in aging and AD, baseline DNAm levels at cg10752406 in the <i>AZU1</i> promoter were significantly associated with AD progression at a 5% false discovery rate, even after adjusting for age, sex, <i>APOE</i> ε4 allele status, years of education, and baseline MMSE. Notably, this CpG also showed a strong brain-blood DNAm correlation, further supporting its potential as a peripheral biomarker for AD. Our study provides valuable insights into the epigenetic landscape of aging and its implications for AD, suggesting that aging-related epigenetic modifications may provide a viable source of biomarkers for AD.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532303","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":"Ancestry Calibration of Polygenic Risk Scores Improves Risk Stratification and Effect Estimation in African American Adults.","authors":"Luciana B Vargas, Mariah C Meyer, Iain R Konigsberg, Aastha Kakar, Patrick M Carry, Yun Li, Alana C Jones, Hemant K Tiwari, Vinodh Srinivasasainagendra, Nicole D Armstrong, Eimear E Kenny, Bogdan Pasaniuc, Marguerite R Irvin, Michael H Cho, Maggie A Stanislawski, Sridharan Raghavan, Jonathan A Shortt, Leslie A Lange, Ethan M Lange","doi":"10.1101/2025.06.18.25329573","DOIUrl":"https://doi.org/10.1101/2025.06.18.25329573","url":null,"abstract":"<p><p>Polygenic risk score (PRS) distributions vary across populations, complicating PRS risk assessment. We evaluated the impact of <i>post-hoc</i> PRS calibration according to individualized genetic ancestry estimates on PRS performance using two large multi-ethnic PRS for type 2 diabetes (T2D) (PRS _T2D ) and height (PRS _height ), in 8,841 African American (AA) individuals from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. We calibrated each participant's score as a function of estimated genetic similarity to the Yoruba (GSYRI) cohort in the 1000 Genomes Project. Uncalibrated PRSs were significantly skewed by GSYRI. After calibration, 33.6% of individuals in the top decile of PRS _T2D were reclassified and performance in the top PRS _T2D decile improved from an OR of 7.97 [6.31-10.13] to 10.77 [8.41- 13.91] when compared to the lowest decile. Similarly, 55.0% of individuals in the top PRS _height decile were reclassified with GSYRI calibration. The calibrated PRS _height showed higher correlation with height (from 0.24 to 0.32, <i>p</i> <10 ^-7 ), and increased mean height in the top PRS _height decile ( <i>p</i> =5.7×10 ^-5 ) when compared to the uncalibrated PRS _height . Lastly, we show that evaluating uncalibrated PRS while adjusting for GSYRI in regression models can lead to inflated and unstable effect size estimates for both the PRS and GSYRI.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532240","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 machine learning to identify subgroups with the highest expected benefit in a population-based water, sanitation, handwashing, and nutrition intervention.","authors":"Caitlin Hemlock, Laura H Kwong, Lia C H Fernald, Alan E Hubbard, John M Colford, Fahmida Tofail, Md Mahbubur Rahman, Sarker Parvez, Stephen P Luby, Andrew N Mertens","doi":"10.1101/2025.06.17.25329796","DOIUrl":"https://doi.org/10.1101/2025.06.17.25329796","url":null,"abstract":"<p><strong>Background: </strong>Understanding who benefits most from investments in water, sanitation, and hygiene (WaSH) interventions can elucidate causal pathways, uncover complex interactions between population characteristics and interventions, and inform targeted implementation. We applied machine learning to identify and describe households of children that benefited most from WaSH and nutrition interventions.</p><p><strong>Methods: </strong>We used causal forests and baseline characteristics of pregnant women enroled in a trial in Bangladesh (2013-2015) to test for heterogenous treatment effects of the primary trial outcomes at two years (length-for-age Z-score [LAZ-score] and diarrhoea prevalence) and one secondary outcome (child development [EASQ Z-score]) for each treatment-outcome combination. We split households into three groups based on predicted treatment effect magnitude and compared characteristics of those that benefitted the most (Tercile 3) versus the least (Tercile 1).</p><p><strong>Results: </strong>Heterogeneity was detected in the effect of Sanitation on EASQ Z-score, compared to Control; children in Tercile 3 were estimated to gain 0.51 SD (95% CI: 0.35, 0.67) whereas children in Tercile 1 were estimated to have no benefit. At baseline, households of children in Tercile 3 were more likely to report that chickens always entered the house (85% vs. 4%) and had animal feces observed in the child's play area (84% vs. 18%) when compared with Tercile 1. Tercile 3 households also owned less land and assets and lived further from Dhaka, any population center, or a market. We did not detect heterogeneity for any other treatment-outcome comparison.</p><p><strong>Conclusions: </strong>We did not detect heterogeneity in any treatment arms for the outcomes of diarrhoea or LAZ-score, showing that children from all backgrounds benefit from effective interventions equally based on household characteristics. We found heterogeneity in the effect of receiving sanitation improvements on child development, where poorer households located in more remote areas and potentially with higher levels of animal fecal contamination had the highest expected benefit.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532350","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":"Demographic Composition of Participants in Sex Chromosome Aneuploidy Studies across the Globe: a 20-year Systematic Review.","authors":"Karli S Swenson, Samantha Bothwell, Anastasia Zhivotov, Amanda Sieverts, Shalika Devireddy, Kira Shuff, Kayla Nocon, Alexandra Carl, Kayla Molison, Lidia Grzybacz, Brisa Avila, Chijioke Ikomi, Lilian Cohen, Ellie Svoboda, Shanlee Davis","doi":"10.1101/2025.06.17.25329799","DOIUrl":"10.1101/2025.06.17.25329799","url":null,"abstract":"<p><strong>Background: </strong>Sex chromosome aneuploidies (SCAs), including Klinefelter syndrome (47,XXY), Turner syndrome (45,X), XYY syndrome, trisomy X (47,XXX), and rarer tetrasomies and pentasomies, affect approximately 1 in 400 births and are associated with a wide range of developmental, cognitive, and physical health outcomes. While clinical research on SCAs has expanded over the past two decades, it is unclear whether the populations included in these studies reflect the demographic diversity of those affected. Assessing representation is critical to ensuring research findings are generalizable and applicable to diverse patient populations.</p><p><strong>Methods: </strong>We conducted a systematic review of global clinical research on SCAs published in English between January 2004 and May 2024. Searches were performed in Ovid MEDLINE^® ALL, Embase, and Web of Science. Studies were included if they enrolled ≥10 participants and excluded if they were case reports, reviews, or meta-analyses. We extracted data from 1,474 studies on geographic location, participant karyotypes, and demographic metrics, including race, ethnicity, and socioeconomic status (SES) reported. Trends in demographic reporting were examined over time and by geographic region. For U.S.-based studies reporting race/ethnicity, we compared pooled participant demographics to national census data.</p><p><strong>Results: </strong>SCA research is concentrated within a small number of geographic areas, primarily in Europe (51.4%) and the U.S. (23.6%). Reporting rates of race or ethnicity for U.S. papers increased over the 20-year observation period, with an average increase of 1.5% ± 0.4% per year (p = 0.003), peaking in 2024 with 61.4% of U.S.-based papers presenting demographics. When reported, studies consistently overrepresented non-Hispanic White (p<0.001) and college-educated (p<0.001) participants relative to U.S. census benchmarks.</p><p><strong>Conclusions: </strong>This systematic review reveals persistent gaps in the demographic reporting and representation of participants in SCA research. Even in the U.S., where population diversity is high, published studies do not reflect the expected racial, ethnic, and socioeconomic makeup of affected individuals. To ensure that research findings are equitable and clinically relevant, future studies should adopt standardized demographic reporting and prioritize inclusive enrollment strategies to reflect the full spectrum of individuals with SCAs.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532253","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":"Quantifying Effects of Lifestyle Changes on Progression to Advanced Age-Related Macular Degeneration in High Genetic Risk Individuals.","authors":"Johanna M Seddon, Dikha De, Bernard Rosner","doi":"10.1101/2025.06.18.25329367","DOIUrl":"10.1101/2025.06.18.25329367","url":null,"abstract":"<p><strong>Purpose: </strong>We examined the extent to which adopting healthy lifestyle behaviors could offset high genetic risk for progression to advanced age-related macular degeneration (AMD), to address concerns of family members of affected patients.</p><p><strong>Design: </strong>Prospective longitudinal study.</p><p><strong>Participants: </strong>Eyes with early or intermediate AMD at baseline were defined based on the Age-Related Eye Disease Study severity scale. High genetic risk was defined as the third tertile of a genetic risk score for progression, adjusted for age, race and sex.</p><p><strong>Methods: </strong>Information on lifestyle behaviors was obtained from baseline risk and food frequency questionnaires. Risk-inducing and health-promoting lifestyle profiles were defined based on dichotomous categorizations of smoking, body-mass index (BMI), and dietary caloric intake, green leafy vegetables and fish, in never and ever smokers. Cox proportional hazard ratios (HRs), relative risks (RRs) and population attributable risks (PARs) were calculated, adjusting for inter-eye correlation, demographic factors, macular status and family history.</p><p><strong>Main outcome measures: </strong>Progression to advanced AMD (AAMD) and subtypes geographic atrophy (GA) and neovascular (NV), confirmed at 2 consecutive visits over 5 years of follow-up.</p><p><strong>Results: </strong>Among 898 high genetic risk eyes, 207 eyes progressed to AAMD (23%). Among never smokers, a high risk-inducing lifestyle profile conferred a 3-fold increased incidence of AAMD, compared to an ideal health-promoting lifestyle profile [HR = 3.3 (CI 1.8, 6.4), P <0.001]. In ever smokers, a risk-inducing profile was independently associated with a 5-fold increased incidence of AAMD [HR = 5.3 (CI 2.3,11.9), P <0.001]. Stronger effects of these lifestyle behaviors were seen for GA compared to NV. Estimated PARs suggested adopting an ideal health-promoting profile could prevent 56% of incident AAMD in never smokers and 60% in ever smokers.</p><p><strong>Conclusion: </strong>Unhealthy behaviors increased incidence of AAMD by 3 to 5-fold among a highly genetically susceptible population, and 56-60% of AAMD incidence was attributed to the modifiable factors of smoking, high BMI, high caloric intake and low intake of foods rich in lutein-zeaxanthin and omega-3 fatty acids. These results underscore the importance of lifestyle interventions even in high genetic risk populations, such as relatives of affected patients, to reduce progression from early and intermediate AMD to advanced vision-threatening stages.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532323","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}