medRxiv : the preprint server for health sciences最新文献

{"title":"Measures of population immunity can predict the dominant clade of influenza A (H3N2) in the 2017-2018 season and reveal age-associated differences in susceptibility and antibody-binding specificity.","authors":"Kangchon Kim, Marcos C Vieira, Sigrid Gouma, Madison E Weirick, Scott E Hensley, Sarah Cobey","doi":"10.1101/2023.10.26.23297569","DOIUrl":"10.1101/2023.10.26.23297569","url":null,"abstract":"<p><strong>Background: </strong>For antigenically variable pathogens such as influenza, strain fitness is partly determined by the relative availability of hosts susceptible to infection with that strain compared to others. Antibodies to the hemagglutinin (HA) and neuraminidase (NA) confer substantial protection against influenza infection. We asked if a cross-sectional antibody-derived estimate of population susceptibility to different clades of influenza A (H3N2) could predict the success of clades in the following season.</p><p><strong>Methods: </strong>We collected sera from 483 healthy individuals aged 1 to 90 years in the summer of 2017 and analyzed neutralizing responses to the HA and NA of representative strains using Focus Reduction Neutralization Tests (FNRT) and Enzyme-Linked Lectin Assays (ELLA). We estimated relative population-average and age-specific susceptibilities to circulating viral clades and compared those estimates to changes in clade frequencies in the following 2017-18 season.</p><p><strong>Results: </strong>The clade to which neutralizing antibody titers were lowest, indicating greater population susceptibility, dominated the next season. Titer correlations between viral strains varied by age, suggesting age-associated differences in epitope targeting driven by shared past exposures. Yet substantial unexplained variation remains within age groups.</p><p><strong>Conclusions: </strong>This study indicates how representative measures of population immunity might improve evolutionary forecasts and inform selective pressures on influenza.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10635207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92158192","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":"Alpha coherence is a network signature of cognitive recovery from disorders of consciousness.","authors":"David W Zhou, Mary M Conte, William H Curley, Camille A Spencer-Salmon, Camille Chatelle, Eric S Rosenthal, Yelena G Bodien, Jonathan D Victor, Nicholas D Schiff, Emery N Brown, Brian L Edlow","doi":"10.1101/2024.10.08.24314953","DOIUrl":"10.1101/2024.10.08.24314953","url":null,"abstract":"<p><p>Alpha (8-12 Hz) frequency band oscillations are among the most informative features in electroencephalographic (EEG) assessment of patients with disorders of consciousness (DoC). Because interareal alpha synchrony is thought to facilitate long-range communication in healthy brains, coherence measures of resting-state alpha oscillations may provide insights into a patient's capacity for higher-order cognition beyond channel-wise estimates of alpha power. In multi-channel EEG, global coherence methods may be used to augment standard spectral analysis methods by both estimating the strength and identifying the structure of coherent oscillatory networks. We performed global coherence analysis in 95 separate clinical EEG recordings (28 healthy controls and 33 patients with acute or chronic DoC, 25 of whom returned for follow-up) collected between two academic medical centers. We found that posterior alpha coherence is associated with recovery of higher-level cognition. We developed a measure of network organization, based on the distance between eigenvectors of the alpha cross-spectral matrix, that detects recovery of posterior alpha networks. In patients who have emerged from a minimally conscious state, we showed that coherence-based alpha networks are reconfigured prior to restoration of alpha power to resemble those seen in healthy controls. This alpha network measure performs well in classifying recovery from DoC (AUC = 0.78) compared to common representations of functional connectivity using the weighted phase lag index (AUC = 0.50 - 0.57). Lastly, we observed that activity within these alpha networks is suppressed during positive responses to task-based EEG command-following paradigms, supporting the potential utility of this biomarker to detect covert cognition. Our findings suggest that restored alpha networks may represent a sensitive early signature of cognitive recovery in patients with DoC. Therefore, network detection methods may augment the utility of EEG assessments for DoC.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484844","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":"Eleven Years of Change: Disease Progression in Biomarker-Defined Sporadic Parkinson's Disease.","authors":"Paulina Gonzalez-Latapi, Caroline Gochanour, Hyunkeun Cho, Seung Ho Choi, Chelsea Caspell-Garcia, Christopher Coffey, Michael Brumm, David-Erick Lafontant, Yuge Xiao, Caroline Tanner, Charles S Venuto, Karl Kieburtz, Lana M Chahine, Kathleen L Poston, Andrew Siderowf, Ken Marek, Tanya Simuni","doi":"10.1101/2024.10.09.24315191","DOIUrl":"https://doi.org/10.1101/2024.10.09.24315191","url":null,"abstract":"<p><p>Long-term longitudinal data on outcomes in sporadic Parkinson's Disease are limited, especially from cohorts with extensive biological characterization. Recent advances in biomarkers characterization of Parkinson's Disease necessitate an updated examination of long-term progression within contemporary cohorts like the Parkinson's Progression Markers Initiative, which enrolled individuals within 2 years of clinical diagnosis of Parkinson's Disease. Our study leverages the Neuronal Synuclein Disease framework, which defines the disease based on biomarker assessed presence of neuronal alpha-synuclein and dopamine deficit, rather than based on conventional clinical diagnostic criteria. In this study we aimed to provide a comprehensive long-term description of disease progression using the integrated biological and clinical staging system framework. We analyzed data from 344 participants from the sporadic Parkinson's Disease cohort in the Parkinson's Progression Markers Initiative, who met Neuronal Synuclein Disease criteria. We assessed 11-year progression in a spectrum of clinical measures. We used Cox proportional hazards models to assess the association between baseline stage and time to key outcomes, including survival, postural instability (Hoehn & Yahr ≥ 3), loss of independence (Schwab & England < 80%), cognitive decline, and domain-based milestones such as walking and balance, motor complications, autonomic dysfunction, and activities of daily living. Additional analyses were completed to account for death and participant dropout. Biomarker analysis included dopamine transporter binding measures, as well as serum urate, neurofilament light chain and CSF amyloid-beta, phosphorylated tau and total tau. At baseline, despite the cohort consisting of individuals within 2 years of clinical diagnosis, there was clear separation of participants in Neuronal Synuclein Disease Stages (23% Stage 2b, 67% Stage 3, 10% Stage 4). At 11 years, data were available for 153 participants; 35 participants had died over the follow up period. Of retained participants, 59% presented normal cognition, 24% had evidence of postural instability and mean Schwab & England score was 78.5. Serum neurofilament light chain consistently increased over time. No other biofluids had a consistent change in trajectory. Of importance, baseline Neuronal Synuclein Disease Stage predicted progression to clinically meaningful milestones. This study provides data on longitudinal, 11-year progression in Neuronal Synuclein Disease participants within 2 years of clinical diagnosis. We observed better long-term outcomes in this contemporary observational study cohort. It highlights the heterogeneity in the early Parkinson's Disease population as defined by clinical diagnostic criteria and underscores the importance of shifting from clinical to biologically and functionally based inclusion criteria in the design of new clinical trials.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484870","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":"Organizational resilience and its implications for healthcare workers in the COVID-19 pandemic: A literature review.","authors":"Karolina Kaczmarski, Atena Pasha, Abdul-Hanan Saani Inusah, Xiaoming Li, Shan Qiao","doi":"10.1101/2024.10.10.24315244","DOIUrl":"https://doi.org/10.1101/2024.10.10.24315244","url":null,"abstract":"<p><strong>Background: </strong>Organizational resilience is crucial in supporting the well-being of healthcare workers and ensuring the quality of healthcare services during crises like the COVID-19 pandemic. This study aims to comprehensively review organizational resilience of healthcare facilities in terms of its conception, measurement, and impacts on healthcare workers during the COVID-19 pandemic.</p><p><strong>Methods: </strong>A search was conducted in four databases (PubMed, ScienceDirect, PsycINFO, and Web of Science) for empirical articles considering organizational resilience among healthcare facilities during the COVID-19 pandemic from 2019 to 2024. Several keywords from three categories (\"COVID-19\", \"organizational resilience,\" and \"healthcare facilities\") were used, and RAYYAN was used to manage references.</p><p><strong>Results: </strong>Four empirical articles from 172 studies were included, which encompassed a total sample of 6,606 healthcare workers from Switzerland, Saudi Arabia, Iran, and Türkiye. Organizational resilience could influence the individual resilience of healthcare practitioners, enhance crisis management and ensure safety performance. The strategies of enhancing organizational resilience at healthcare worker level included staff training, crisis management protocols, collaboration promotion, and stress management approaches. The ones at health facility level included government intervention, funds for hospital preparedness, competency-based crisis management, and mental health programs for healthcare workers. Our review also suggests a lack of empirical studies, no commonly used measurement instruments, and the heterogeneity of study contexts in the research of organizational resilience in public health.</p><p><strong>Conclusions: </strong>This review highlights effective strategies to enhance the organizational resilience of healthcare workers and examines their impact during the COVID-19 pandemic. Immediate government action, funding to support hospital preparedness, and the formation of flexible healthcare teams are essential to strengthen organizational resilience among healthcare workers for future crises.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484944","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":"Associations of PFASs and Pesticides with Lung Function Changes from Adolescence to Young Adulthood in the ESPINA study.","authors":"Kayleigh Kornher, Carlos F Gould, Jomel Meeko Manzano, Katie Baines, Georgia Kayser, Xin Tu, Jose Suarez-Torres, Danilo Martinez, Jose R Suarez-Lopez","doi":"10.1101/2024.10.09.24315189","DOIUrl":"10.1101/2024.10.09.24315189","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFASs) and pesticides are ubiquitous environmental exposures with increasingly recognized adverse health outcomes; however, their impact on lung function, particularly in combination, remains poorly understood. We included 381 adolescent participants from a prospective cohort study in Ecuador who underwent measurements of serum PFAS (perfluorooctanoic acid [PFOA], perfluorooctanesulfonic acid [PFOS] and perfluorononanoic acid [PFNA]) and urinary herbicides (glyphosate, 2,4D) and fungicides (ethylene thiourea) and had spirometric measurements in either 2016 or 2022. We characterized the association between each PFAS or pesticide and each lung function measure in log-log models estimated via ordinary least squares regression. We used quantile g-computation to assess the association of the mixture of PFAS and pesticides with lung function outcomes. After accounting for multiple hypothesis testing, and in models adjusting for household income, parental education, and exposure to tobacco, we found that, individually, PFOA, glyphosate, and ETU were associated with slight increases in FEV₁/FVC between 2016 and 2022. No other individual associations were significant. In mixtures analyses, a one quartile increase in all PFASs and pesticides simultaneously was also not associated with statistically significant changes in lung function outcomes after accounting for multiple hypothesis testing. In large part, we do not provide evidence for associations of PFAS and herbicide and fungicide pesticides with lung function among adolescents in moderate-to-high-altitude agricultural communities in Ecuador.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of a new highly multiplexed amplicon sequencing tool to evaluate <i>Plasmodium falciparum</i> antimalarial resistance and relatedness in individual and pooled samples from Dschang, Cameroon.","authors":"Jacob M Sadler, Alfred Simkin, Valery P K Tchuenkam, Isabela Gerdes Gyuricza, Abebe A Fola, Kevin Wamae, Ashenafi Assefa, Karamoko Niaré, Kyaw Thwai, Samuel J White, William J Moss, Rhoel R Dinglasan, Sandrine Nsango, Christopher B Tume, Jonathan B Parr, Innocent Mbulli Ali, Jeffrey A Bailey, Jonathan J Juliano","doi":"10.1101/2024.10.03.24314715","DOIUrl":"10.1101/2024.10.03.24314715","url":null,"abstract":"<p><strong>Background: </strong>Resistance to antimalarial drugs remains a major obstacle to malaria elimination. Multiplexed, targeted amplicon sequencing is being adopted for surveilling resistance and dissecting the genetics of complex malaria infections. Moreover, genotyping of parasites and detection of molecular markers drug resistance in resource-limited regions requires open-source protocols for processing samples, using accessible reagents, and rapid methods for processing numerous samples including pooled sequencing.</p><p><strong>Methods: </strong><i>P</i> <i>lasmodium</i> <i>f</i> <i>alciparum</i> Streamlined Multiplex Antimalarial Resistance and Relatedness Testing (<i>Pf</i>-SMARRT) is a PCR-based amplicon panel consisting of 15 amplicons targeting antimalarial resistance mutations and 9 amplicons targeting hypervariable regions. This assay uses oligonucleotide primers in two pools and a non-proprietary library and barcoding approach.</p><p><strong>Results: </strong>We evaluated <i>Pf</i>-SMARRT using control mocked dried blood spots (DBS) at varying levels of parasitemia and a mixture of 3D7 and Dd2 strains at known frequencies, showing the ability to genotype at low parasite density and recall within-sample allele frequencies. We then piloted <i>Pf</i>-SMARRT to genotype 100 parasite isolates collected from uncomplicated malaria cases at three health facilities in Dschang, Western Cameroon. Antimalarial resistance genotyping showed high levels of sulfadoxine-pyrimethamine resistance mutations, including 31% prevalence of the DHPS A613S mutation. No K13 candidate or validated artemisinin partial resistance mutations were detected, but one low-level non-synonymous change was observed. <i>Pf</i>-SMARRT's hypervariable targets, used to assess complexity of infections and parasite diversity and relatedness, showed similar levels and patterns compared to molecular inversion probe (MIP) sequencing. While there was strong concordance of antimalarial resistance mutations between individual samples and pools, low-frequency variants in the pooled samples were often missed.</p><p><strong>Conclusion: </strong>Overall, <i>Pf</i>-SMARRT is a robust tool for assessing parasite relatedness and antimalarial drug resistance markers from both individual and pooled samples. Control samples support that accurate genotyping as low as 1 parasite per microliter is routinely possible.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484860","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":"BREATH TEST TO DETECT WOMEN AT LOW RISK FOR BREAST CANCER: POTENTIAL CLINICAL AND ECONOMIC BENEFITS.","authors":"Michael Phillips, Therese B Bevers, Linda Hovanessian Larsen, Nadine Pappas, Sonali Pathak","doi":"10.1101/2024.10.09.24315190","DOIUrl":"10.1101/2024.10.09.24315190","url":null,"abstract":"<p><strong>Background: </strong>A breath test for volatile organic compounds has identified biomarkers associated with breast cancer. We evaluated the potential clinical and economic benefits of a breath test to detect women at low risk for breast cancer by comparing its negative predictive value (NPV) to the NPV of screening mammography.</p><p><strong>Methods: </strong>Sensitivity and specificity values for screening mammography were obtained from the Food & Drug Administration Mammography Quality Standards Act; Amendments to Part 900 Regulations Docket No. FDA-2013-N-0134. The high values were sensitivity = 79.0%, specificity = 88.9% and the low values were sensitivity = 66.0%, specificity = 88.9%. In two previous studies of 771 women undergoing mammography, breath testing identified breast cancer with sensitivity=84% and specificity = 68.6% in 178 asymptomatic women, and sensitivity=82% and specificity = 77% in 593 who were symptomatic. These values were projected to a hypothetical screening population of 100,000 asymptomatic women with average breast cancer prevalence of 450/100,000, in order to estimate the NPV and PPV (positive predictive value) for breath testing and screening mammography respectively.</p><p><strong>Results: </strong>Breath test in asymptomatic women: NPV = 99.895% and PPV = 1.19%; in symptomatic women: NPV = 99.895% and PPV = 1.59%. For screening mammography, NPV = 99.83% and PPV = 2.82% (low values), increasing to NPV= 99.89% and PPV = 3.12% (high values). A negative breath test identified 68.3% of the screening population as having low risk of breast cancer, with NPV similar to mammography. Based on Medicare reimbursement rates, elimination of mammography in women with a negative breath test could reduce the annual cost of breast cancer screening by 38.9.</p><p><strong>Conclusions: </strong>In a hypothetical screening population, a negative breath test ruled out breast cancer with the same accuracy as a negative mammogram. A screening breath test could potentially eliminate the need for two thirds of all mammograms and reduce the costs of screening without increasing the risk of false-negative findings. If applied in clinical practice, this approach could potentially reduce the costs and burdens of breast cancer screening services, and benefit women by lessening the discomfort, anxiety, radiation exposure, and costs associated with mammography.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484882","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":"Quantitative EEG Spectral Features Differentiate Genetic Epilepsies and Predict Neurologic Outcomes.","authors":"Peter D Galer, Jillian L McKee, Sarah M Ruggiero, Michael C Kaufman, Ian McSalley, Shiva Ganesan, William K S Ojemann, Alexander K Gonzalez, Quy Cao, Brian Litt, Ingo Helbig, Erin C Conrad","doi":"10.1101/2024.10.09.24315105","DOIUrl":"10.1101/2024.10.09.24315105","url":null,"abstract":"&lt;p&gt;&lt;p&gt;EEG plays an integral part in the diagnosis and management of children with genetic epilepsies. Nevertheless, how quantitative EEG features differ between genetic epilepsies and neurological outcomes remains largely unknown. Here, we aimed to identify quantitative EEG biomarkers in children with epilepsy and a genetic diagnosis in &lt;i&gt;STXBP1&lt;/i&gt;, &lt;i&gt;SCN1A&lt;/i&gt;, or &lt;i&gt;SYNGAP1&lt;/i&gt;, and to assess how quantitative EEG features associate with neurological outcomes in genetic epilepsies more broadly. We analyzed individuals with pathogenic variants in &lt;i&gt;STXBP1&lt;/i&gt; (95 EEGs, &lt;i&gt;n&lt;/i&gt;=20), &lt;i&gt;SCN1A&lt;/i&gt; (154 EEGs, &lt;i&gt;n&lt;/i&gt;=68), and &lt;i&gt;SYNGAP1&lt;/i&gt; (46 EEGs, &lt;i&gt;n&lt;/i&gt;=21) and a control cohort of individuals without epilepsy or known cerebral disease (847 EEGs, &lt;i&gt;n&lt;/i&gt;=806). After removing artifacts and epochs with excess noise or altered state from EEGs, we extracted spectral features. We validated our preprocessing pipeline by comparing automatically-detected posterior dominant rhythm (PDR) to annotations from clinical EEG reports. Next, as a coarse measure of pathological slowing, we compared the alpha-delta bandpower ratio between controls and the different genetic epilepsies. We then trained random forest models to predict a diagnosis of &lt;i&gt;STXBP1&lt;/i&gt;, &lt;i&gt;SCN1A&lt;/i&gt;, and &lt;i&gt;SYNGAP1&lt;/i&gt;. Finally, to understand how EEG features vary with neurological outcomes, we trained random forest models to predict seizure frequency and motor function. There was strong agreement between the automatically-calculated PDR and clinical EEG reports (&lt;i&gt;R&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt;=0.75). Individuals with &lt;i&gt;STXBP1&lt;/i&gt;-related epilepsy have a significantly lower alpha-delta ratio than controls (&lt;i&gt;P&lt;/i&gt;&lt;0.001) across all age groups. Additionally, individuals with a missense variant in &lt;i&gt;STXBP1&lt;/i&gt; have a significantly lower alpha-delta ratio than those with a protein-truncating variant in toddlers (&lt;i&gt;P&lt;/i&gt;&lt;0.001), children (&lt;i&gt;P&lt;/i&gt;=0.02), and adults (&lt;i&gt;P&lt;/i&gt;&lt;0.001). Models accurately predicted a diagnosis of &lt;i&gt;STXBP1&lt;/i&gt; (AUC=0.91), &lt;i&gt;SYNGAP1&lt;/i&gt; (AUC=0.82), and &lt;i&gt;SCN1A&lt;/i&gt; (AUC=0.86) against controls and from each other in a three-class model (accuracy=0.74). From these models, we isolated highly correlated biomarkers for these respective genetic disorders, including alpha-theta ratio in frontal, occipital, and parietal electrodes with &lt;i&gt;STXBP1&lt;/i&gt;, &lt;i&gt;SYNGAP1&lt;/i&gt;, and &lt;i&gt;SCN1A&lt;/i&gt;, respectively. Models were unable to predict seizure frequency (AUC=0.53). Random forest models predicted motor scores significantly better than age-based null models (&lt;i&gt;P&lt;/i&gt;&lt;0.001), suggesting spectral features contain information pertinent to gross motor function. In summary, we demonstrate that &lt;i&gt;STXBP1&lt;/i&gt;-, &lt;i&gt;SYNGAP1&lt;/i&gt;-, and &lt;i&gt;SCN1A&lt;/i&gt;-related epilepsies have distinct quantitative EEG signatures. Furthermore, EEG spectral features are predictive of some functional outcome measures in patients with genetic epilepsies. Large-scale retrospective quantitative analysis of clinical EEG ","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484956","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":"Association of Anxiety with Uncinate Fasciculus Lesion Burden in Multiple Sclerosis.","authors":"Erica B Baller, Audrey C Luo, Matthew K Schindler, Elena C Cooper, Margaret K Pecsok, Matthew C Cieslak, Melissa Lynne Martin, Amit Bar-Or, Ameena Elahi, Christopher M Perrone, Donovan Reid, Bailey C Spangler, Theodore D Satterthwaite, Russell T Shinohara","doi":"10.1101/2024.10.08.24315108","DOIUrl":"10.1101/2024.10.08.24315108","url":null,"abstract":"<p><strong>Importance: </strong>Multiple sclerosis (MS) is an immune-mediated neurological disorder that affects 2.4 million people world-wide, and up to 60% experience anxiety.</p><p><strong>Objective: </strong>We investigated how anxiety in MS is associated with white matter lesion burden in the uncinate fasciculus (UF).</p><p><strong>Design: </strong>Retrospective case-control study of participants who received research-quality 3-tesla (3T) neuroimaging as part of MS clinical care from 2010-2018. Analyses were performed from June 1^st to September 30^th, 2024.</p><p><strong>Setting: </strong>Single-center academic medical specialty MS clinic.</p><p><strong>Participants: </strong>Participants were identified from the electronic medical record. All participants were diagnosed by an MS specialist and completed research-quality MRI at 3T. After excluding participants with poor image quality, 372 were stratified into three groups which were balanced for age and sex: 1) MS without anxiety (MS+noA, n=99); 2) MS with mild anxiety (MS+mildA, n=249); and 3) MS with severe anxiety (MS+severeA, n=24).</p><p><strong>Exposure: </strong>Anxiety diagnosis and anxiolytic medication.</p><p><strong>Main outcome and measure: </strong>We first evaluated whether MS+severeA patients had greater lesion burden in the UF than MS+noA. Next, we examined whether increasing anxiety severity was associated with greater UF lesion burden. Generalized additive models were employed, with the burden of lesions (e.g. proportion of fascicle impacted) within the UF as the outcome measure and sex and spline of age as covariates.</p><p><strong>Results: </strong>UF burden was higher in MS+severeA as compared to MS+noA (T=2.02, P=0.045, Cohen's <i>f</i> ²=0.19). A dose-response effect was also found, where higher mean UF burden was associated with higher anxiety severity (T=2.08, P=0.038, Cohen's <i>f</i> ²=0.10).</p><p><strong>Conclusions and relevance: </strong>We demonstrate that overall lesion burden in UF was associated with the presence and severity of anxiety in patients with MS. Future studies linking white matter lesion burden in UF with treatment prognosis are warranted.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484862","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":"Cost-effectiveness of screening with transcriptional signatures for incipient TB among U.S. migrants.","authors":"Yuli Lily Hsieh, C Robert Horsburgh, Ted Cohen, Jeffrey W Miller, Joshua A Salomon, Nicolas A Menzies","doi":"10.1101/2024.10.09.24315062","DOIUrl":"10.1101/2024.10.09.24315062","url":null,"abstract":"<p><strong>Introduction: </strong>Host-response-based transcriptional signatures (HrTS) have been developed to identify \"incipient tuberculosis (TB)\". No study has reported the cost-effectiveness of HrTS for post-arrival migrant screening programs in low-incidence countries.</p><p><strong>Objectives: </strong>To assess the potential health impact and cost-effectiveness of HrTS for post-arrival TB infection screening among new migrants in the United States.</p><p><strong>Methods: </strong>We used a discrete-event simulation model to compare four strategies: (1) no screening for TB infection or incipient TB; (2) 'IGRA-only', screen all with interferon gamma release assay (IGRA), provide TB preventive treatment for IGRA-positives; (3) 'IGRA-HrTS', screen all with IGRA followed by HrTS for IGRA-positives, provide incipient TB treatment for individuals testing positive with both tests; and (4) 'HrTS-only', screen all with HrTS, provide incipient TB treatment for HrTS-positives. We assessed outcomes over the lifetime of migrants entering the U.S. in 2019, assuming HrTS met the WHO Target Product Profile (TPP) optimal criteria. We conducted sensitivity analyses to evaluate the robustness of results.</p><p><strong>Results: </strong>The IGRA-only strategy dominated the HrTS-based strategies under both healthcare sector and societal perspectives, with an incremental cost-effectiveness ratio of $78,943 and $89,431 per quality-adjusted life-years (QALY) gained, respectively. This conclusion was robust to varying costs ($15-300) and characteristics of HrTS, and the willingness-to-pay threshold ($30,000-150,000/ QALY gained), but sensitive to the rate of decline in TB progression risk after U.S. entry.</p><p><strong>Conclusions: </strong>Our findings suggest that HrTS meeting the WHO TPP is unlikely to be a cost-effective component of post-arrival screening for migrants entering the U.S.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484896","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}