medRxiv (Cold Spring Harbor Laboratory)最新文献

{"title":"Diagnosis in Bytes: Comparing the Diagnostic Accuracy of Google and ChatGPT 3.5 as Diagnostic Support Tools","authors":"Guilherne Guimaraes, Caroline Santos Silva, Jean Carlos Z Contreras, Ricardo G Figueiredo, Ricardo B Tiraboschi, Cristiano M Gomes, Jose Bessa","doi":"10.1101/2023.11.10.23294668","DOIUrl":"https://doi.org/10.1101/2023.11.10.23294668","url":null,"abstract":"Objective: Adopting digital technologies as diagnostic support tools in medicine is unquestionable. However, the accuracy in suggesting diagnoses remains controversial and underexplored. We aimed to evaluate and compare the diagnostic accuracy of two primary and accessible internet search tools: Google and ChatGPT 3.5. Method: We used 60 clinical cases related to urological pathologies to evaluate both platforms. These cases were divided into two groups: one with common conditions (constructed from the most frequent symptoms, following EAU and UpToDate guidelines) and another with rare disorders - based on case reports published between 2022 and 2023 in Urology Case Reports. Each case was inputted into Google Search and ChatGPT 3.5, and the results were categorized as \"correct diagnosis,\" \"likely differential diagnosis,\" or \"incorrect diagnosis.\" A team of researchers evaluated the responses blindly and randomly. Results: In typical cases, Google achieved 53.3% accuracy, offering a likely differential diagnosis in 23.3% and errors in the rest. ChatGPT 3.5 exhibited superior performance, with 86.6% accuracy, and suggested a reasonable differential diagnosis in 13.3%, without mistakes. In rare cases, Google did not provide correct diagnoses but offered a likely differential diagnosis in 20%. ChatGPT 3.5 achieved 16.6% accuracy, with 50% differential diagnoses. Conclusion: ChatGPT 3.5 demonstrated higher diagnostic accuracy than Google in both contexts. The platform showed acceptable accuracy in common cases; however, limitations in rare cases remained evident.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"4 10","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135037452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Impact of Diagnostic Stewardship in Community-Acquired Pneumonia with Syndromic Molecular Testing: A Randomized Clinical Trial","authors":"Dagfinn L. Markussen, Sondre Serigstad, Christian Ritz, Siri T. Knoop, Marit H. Ebbesen, Daniel Faurholt-Jepsen, Lars Heggelund, Henri van Werkhoven, Tristan W. Clark, Rune O. Bjørneklett, Øyvind Kommedal, Elling Ulvestad, Harleen M. S. Grewal","doi":"10.1101/2023.11.11.23298408","DOIUrl":"https://doi.org/10.1101/2023.11.11.23298408","url":null,"abstract":"Importance: Lower respiratory tract infections, including community-acquired pneumonia (CAP), are a leading cause of hospital admissions and mortality. An aetiological diagnosis of CAP is delayed due to long turnaround times with laboratory testing. Rapid microbiologic diagnosis is imperative for the management of CAP and may limit antibiotic overuse. Molecular tests have the potential to optimize treatment decisions and management of CAP, but limited evidence exists to support their routine use. Objective: To determine whether the use of a syndromic PCR-based panel for rapid testing of CAP in the emergency department (ED) leads to faster and more accurate microbiology-result-based treatment. Design, Setting, and Participants: A pragmatic, parallel-arm, single-blinded, single-centre, randomised controlled superiority trial conducted in the emergency department of a large tertiary care Norwegian hospital, where adult patients with suspected CAP were recruited. Intervention: Patients were randomly assigned 1:1 to rapid syndromic molecular panel testing (FAP-plus) of lower respiratory tract (LRT) samples and standard of care, or standard of care alone. Main Outcomes and Measures: Primary outcomes were the provision of pathogen-directed treatment based on a microbiological test result and the time to provision of pathogen-directed treatment (within 48h from randomization). Results: Between Sep 25, 2020, and Jun 21, 2022, 374 patients were enrolled, with 187 in each arm. Analysis of primary outcomes showed that 66 (35%) of 187 patients in the FAP-plus arm and 24 (13%) of 187 patients in the standard-of-care arm received pathogen-directed treatment corresponding to a reduction in absolute risk of 21.9%, 95% CI (13.5, 30.3%), and an OR for the FAP-plus arm of 3.53, 95% CI (2.13, 6.02), p<0.0001). The mean time to provision of pathogen-directed treatment within 48h was 34.5h in the FAP-plus arm and 43.8h in the standard-of-care arm (mean difference -9.4h, 95% CI (-12.7, -6.0h), p<0.0001). The corresponding hazard ratio for FAP-plus compared to standard of care was 3.08, 95% CI (1.95, 4.89). Findings remained unaltered after adjustment for season. Conclusions and Relevance: The routine deployment of PCR testing for LRT pathogens enables faster and more targeted microbial treatment for patients with suspected CAP. Rapid molecular testing could complement or replace selected standard time-consuming laboratory-based diagnostics.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"5 9","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135037630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Anti-VEGF Treatment for Diabetic Macular Oedema on Progression to Proliferative Diabetic Retinopathy: Data-driven Insights from a Multicentre Study","authors":"Abraham Olvera-Barrios, Watjana Lilaonitkul, Tjebo FC Heeren, Assaf Rozenberg, Darren Thomas, Alasdair N Warwick, Taha Somroo, Abdulrahman H Alsaedi, Roy Schwartz, Usha Chakravarthy, Haralabos Eleftheriadis, Ashish Patwardhan, Faruque Ghanchi, Paul Taylor, Adnan Tufail, Catherine Egan","doi":"10.1101/2023.11.10.23298261","DOIUrl":"https://doi.org/10.1101/2023.11.10.23298261","url":null,"abstract":"Background: To report insights on proliferative-diabetic-retinopathy (PDR) risk modification with repeated anti-vascular endothelial-growth-factor (VEGF) injections for the treatment of diabetic-macular-oedema (DMO) in routine care, and present data-driven PDR screening recommendations for injection clinics. Methods: Multicentre study (27 UK-NHS centres) of patients with non-PDR with and without DMO. Primary outcome was PDR development. Repeated anti-VEGF injections were modelled as time-dependent covariates using Cox regression and weighted cumulative exposure (WCE) adjusting for baseline diabetic retinopathy (DR) grade, age, sex, ethnicity, type of diabetes, and deprivation. A propensity score matched cohort was used to estimate the treatment effect on PDR incidence rates (IR). Results: We included 5716 NPDR eyes (5716 patients, 2858 DMO eyes). The WCE method showed a better model fit. Anti-VEGF injections showed a protective effect on risk of PDR during the most recent 4-weeks from exposure which rapidly decreased. There was a 20% reduction in risk of PDR (p0.006) in treated eyes. Severe-NPDR had a 4.6-fold increase in PDR hazards when compared with mild-NPDR (p<0.001). The annual IR of untreated mild-NPDR cases was 2.3 [95%CI 1.57-3.23] per 100 person-years). In NPDR DMO cases treated with anti-VEGF, similar IR would occur with annual review for mild, 6-monthly for moderate, and 3-monthly for severe-NPDR. Conclusion: The WCE method is a better modelling strategy than traditional Cox models for repeated exposures in ophthalmology. Injections are protective against PDR predominantly within the most recent 4 weeks. Based on observed data, we suggest follow-up recommendations for PDR detection according to retinopathy grade at first injection.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"5 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135037669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-Wide Interaction Analysis with DASH Diet Score Identified Novel Loci for Systolic Blood Pressure","authors":"Melanie Guirette, Jessie Lan, Nicola M Mckeown, Michael R. Brown, Han Chen, Paul S De Vries, Hyunju Kim, Casey M. Rebholz, Alanna C. Morrison, Traci Mae Bartz, Amanda Fretts, Xiuqing Guo, Rozenn N Lemaitre, Ching-Ti Liu, Raymond Noordam, Renée de Mutsert, Frits R. Rosendaal, Carol A Wang, Lawrence J. Beilin, Trevor A. Mori, Wendy H Oddy, Craig E Pennell, Jin-Fang Chai, Clare Whitton, Rob M. van Dam, Jianjun Liu, E Shyong Tai, Xueling Sim, Marian L. Neuhouser, Charles Kooperberg, Lesley F. Tinker, Nora Franceschini, TianXiao Huan, Thomas W Winkler, Amy R. Bentley, W. James Gauderman, Luc Heerkens, Toshiko Tanaka, Jeroen Van Rooij, Patricia B. Munroe, Helen R. Warren, Trudy Voortman, Honglei Chen, D.C. Rao, Daniel Levy, Jiantao Ma","doi":"10.1101/2023.11.10.23298402","DOIUrl":"https://doi.org/10.1101/2023.11.10.23298402","url":null,"abstract":"Objective: We examined interactions between genotype and a Dietary Approaches to Stop Hypertension (DASH) diet score in relation to systolic blood pressure (SBP). Methods: We analyzed up to 9,420,585 biallelic imputed single nucleotide polymorphisms (SNPs) in up to 127,282 individuals of six population groups (91% of European population) from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (CHARGE; n=35,660) and UK Biobank (n=91,622) and performed European population-specific and cross-population meta-analyses. Results: We identified three loci in European-specific analyses and an additional four loci in cross-population analyses at P for interaction < 5e-8. We observed a consistent interaction between rs117878928 at 15q25.1 (minor allele frequency = 0.03) and the DASH diet score (P for interaction = 4e-8; P for heterogeneity = 0.35) in European population, where the interaction effect size was 0.42±0.09 mm Hg (P for interaction = 9.4e-7) and 0.20±0.06 mm Hg (P for interaction = 0.001) in CHARGE and the UK Biobank, respectively. The 1 Mb region surrounding rs117878928 was enriched with cis-expression quantitative trait loci (eQTL) variants (P = 4e-273) and cis-DNA methylation quantitative trait loci (mQTL) variants (P = 1e-300). While the closest gene for rs117878928 is MTHFS, the highest narrow sense heritability accounted by SNPs potentially interacting with the DASH diet score in this locus was for gene ST20 at 15q25.1. Conclusion: We demonstrated gene-DASH diet score interaction effects on SBP in several loci. Studies with larger diverse populations are needed to validate our findings.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"77 22","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135036720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Travel surveillance uncovers dengue virus dynamics and introductions in the Caribbean","authors":"Emma Taylor-Salmon, Verity Hill, Lauren M. Paul, Robert T. Koch, Mallery I. Breban, Chrispin Chaguza, Afeez Sodeinde, Joshua L. Warren, Sylvia Bunch, Natalia Cano, Marshall Cone, Sarah Eysoldt, Alezaundra Garcia, Nicadia Gilles, Andrew Hagy, Lea Heberlein, Rayah Jaber, Elizabeth Kassens, Pamela Colarusso, Amanda Davis, Samantha Baudin, Edhelene Rico, Alvaro Mejia-Echeverri, Blake Scott, Danielle Stanek, Rebecca Zimler, Jorge L. Munoz-Jordan, Gilberto A. Santiago, Laura E. Adams, Gabriela Paz-Bailey, Melanie Spillane, Volha Katebi, Robert Paulino-Ramirez, Sayira Mueses, Armando Peguero, Nelissa Sanchez, Francesca F. Norman, Juan-Carlos Galan Galan, Ralph Huits Huits, Davidison H. Hamer, Chantal B.F. Vogels, Andrea Morrison Morrison, Scott F. Michael, Nathan D. Grubaugh","doi":"10.1101/2023.11.11.23298412","DOIUrl":"https://doi.org/10.1101/2023.11.11.23298412","url":null,"abstract":"Dengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean. To investigate this, we used travel surveillance and genomic epidemiology to reconstruct outbreak dynamics, DENV serotype turnover, and patterns of spread within the region from 2009-2022. We uncovered two recent DENV-3 introductions from Asia, one of which resulted in a large outbreak in Cuba, which was previously under-reported. We also show that while outbreaks can be synchronized between islands, they are often caused by different serotypes. Our study highlights the importance of surveillance of infected travelers to provide a snapshot of local introductions and transmission in areas with limited local surveillance and suggests that the recent DENV-3 introductions may pose a major public health threat in the region.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"10 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135036934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathophysiological Mechanisms of the Onset, Development, and Disappearance Phases of Skin Eruptions in Chronic Spontaneous Urticaria","authors":"Sungrim Seirin-Lee, Shunsuke Takahagi, Michihiro Hide","doi":"10.1101/2023.11.11.23298424","DOIUrl":"https://doi.org/10.1101/2023.11.11.23298424","url":null,"abstract":"Chronic spontaneous urticaria (CSU) is a typical example of an intractable skin dis- ease with no clear cause and significantly affects daily life of patients. Because CSU is a human-specific disease and lacks proper animal model, there are many questions regarding its pathophysiological dynamics. On the other hand, most clinical symptoms of urticaria are notable as dynamic appearance of skin eruptions (wheals). In this study, we explored dynamics of wheal by dividing it into three phases using a mathematical model: onset, development, and disappearance. Our results suggest that CSU onset is critically associated with endovascular dynamics triggered by basophils positive feedback. In contrast, the de- velopment phase is regulated by mast cell dynamics via vascular gap formation. We also suggest a disappearance mechanism of skin eruptions in CSU through an extension of the mathematical model using qualitative and quantitative comparisons of wheal expansion data of real patients with urticaria. Our results suggest that the wheal dynamics of the three phases and CSU development are hierarchically related to endovascular and extravascular pathophysiological networks.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"7 8","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135037983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Role of NK Cells and Monocytes in Promoting Atherogenesis in Severe COVID-19 Patients.","authors":"Manuja Gunasena, Mario Alles, Yasasvi Wijewantha, Will Mulhern, Emily Bowman, Janelle Gabriel, Aaren Kettelhut, Amrendra Kumar, Krishanthi Weragalaarachchi, Dhanuja Kasturiratna, Jeffrey C Horowitz, Scott Scrape, Sonal R Pannu, Shan-Lu Liu, Anna Vilgelm, Saranga Wijeratne, Joseph S Bednash, Thorsten Demberg, Nicholas T Funderburg, Namal Liyanage","doi":"10.1101/2023.11.10.23298322","DOIUrl":"https://doi.org/10.1101/2023.11.10.23298322","url":null,"abstract":"Clinical data demonstrate an increased predisposition to cardiovascular disease (CVD) following severe COVID-19 infection. This may be driven by a dysregulated immune response associated with severe disease. Monocytes and vascular tissue resident macrophages play a critical role in atherosclerosis, the main pathology leading to ischemic CVD. Natural killer (NK) cells are a heterogenous group of cells that are critical during viral pathogenesis and are known to be dysregulated during severe COVID-19 infection. Their role in atherosclerotic cardiovascular disease has recently been described. However, the contribution of their altered phenotypes to atherogenesis following severe COVID-19 infection is unknown. We demonstrate for the first time that during and after severe COVID-19, circulating proinflammatory monocytes and activated NK cells act synergistically to increase uptake of oxidized low-density lipoprotein (Ox-LDL) into vascular tissue with subsequent foam cell generation leading to atherogenesis despite recovery from acute infection. Our data provide new insights, revealing the roles of monocytes/macrophages, and NK cells in COVID-19-related atherogenesis.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"9 7","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135038176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Christianson Syndrome across the Lifespan: An International Longitudinal Study in Children, Adolescents, and Adults","authors":"Brian C Kavanaugh, Jennifer Elacio, Carrie R Best, Danielle G St Pierre, Matthew F Pescosolido, Qing Ouyang, Paul Caruso, Karen Buch, John Biedermann, Rebecca S Bradley, Judy S Liu, Richard N Jones, Eric M Morrow","doi":"10.1101/2023.11.11.23298218","DOIUrl":"https://doi.org/10.1101/2023.11.11.23298218","url":null,"abstract":"Mutations in the X-linked endosomal Na+/H+ Exchanger 6 (NHE6) causes Christianson Syndrome (CS). In the largest study to date, we examine genetic diversity and clinical progression, including cerebellar degeneration, in CS into adulthood. Data were collected as part of the International Christianson Syndrome and NHE6 (SLC9A6) Gene Network Study. Forty-four individuals with 31 unique NHE6 mutations, age 2 to 32 years, were followed prospectively, herein reporting baseline, 1-year follow-up, and retrospective natural history. We present data on the CS phenotype with regard to physical growth, adaptive and motor regression, and across the lifespan, including information on mortality. Longitudinal data on body weight and height were examined using a linear mixed model: the rate of growth across development was slow and resulted in prominently decreased age-normed height and weight by adulthood. Adaptive functioning was longitudinally examined: a majority of adult (18+ years) participants lost gross and fine motor skills over a 1-year follow-up. Previously defined core diagnostic criteria for CS (present in &gt;85%) – namely nonverbal status, intellectual disability, epilepsy, postnatal microcephaly, ataxia, hyperkinesia – were universally present in age 6 to 16; however, an additional core feature of high pain tolerance was added (present in 91%), and furthermore, evolution of symptoms were noted across the lifespan, such that postnatal microcephaly, ataxia and high pain threshold were often not apparent prior to age 6, and hyperkinesis decreased after age 16. While neurologic exams were consistent with cerebellar dysfunction, importantly, a majority of individuals (&gt;50% older than 10) also had corticospinal tract abnormalities. Three participants died during the period of the study. In this large and longitudinal study of CS, we begin to define the trajectory of symptoms and the adult phenotype, thereby identifying critical targets for treatment.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"10 7","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135036931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic discovery and risk prediction for type 1 diabetes in individuals without high-risk HLA-DR3/DR4 haplotypes","authors":"Carolyn McGrail, Joshua Chiou, Ruth Elgamal, Amber Luckett, Richard Oram, Paola Benaglio, Kyle Gaulton","doi":"10.1101/2023.11.11.23298405","DOIUrl":"https://doi.org/10.1101/2023.11.11.23298405","url":null,"abstract":"Over 10% of individuals with type 1 diabetes (T1D) do not have high-risk HLA-DR3 or -DR4 haplotypes, and whether they carry distinct genetic risk is unknown. To identify genetic drivers of T1D in the absence of DR3/DR4, we performed T1D association and fine-mapping analyses in 12,316 non-DR3/DR4 samples. We identified risk variants at the MHC locus and genome-wide with evidence for heterogeneity in effects on T1D compared to DR3/DR4. T1D-associated variants in non-DR3/DR4 individuals were enriched for loci, regulatory elements, and pathways related to antigen presentation, innate immunity, and beta cells, and depleted in T cells, compared to DR3/DR4. Most non-DR3/DR4 T1D cases are poorly classified based on the existing T1D GRS2, and we created a new GRS which highly discriminated non-DR3/DR4 T1D from non-diabetes and T2D and outperformed GRS2. In total we identified heterogeneity in T1D genetic risk dependent on high-risk HLA haplotype which revealed distinct disease mechanisms and enabled more accurate risk prediction for T1D a non-DR3/DR4 background.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"5 9","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135037802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring ESBL-Escherichia coli in Swiss wastewater between November 2021 and November 2022: insights into population carriage","authors":"Sheena Conforti, Aurelie Holschneider, Emile Sylvestre, Timothy R. Julian","doi":"10.1101/2023.11.12.23298428","DOIUrl":"https://doi.org/10.1101/2023.11.12.23298428","url":null,"abstract":"Background: Antimicrobial resistance (AMR) poses a global health threat, causing millions of deaths annually, with expectations of increased impact in the future. Wastewater surveillance offers a cost-effective, non-invasive tool to understand AMR carriage trends within a population. Aim: We monitored extended-spectrum β-lactamase producing Escherichia coli (ESBL-E. coli) weekly in influent wastewater from six wastewater treatment plants (WWTPs) in Switzerland (November 2021 to November 2022) to investigate spatio-temporal variations, explore correlations with environmental variables, develop a predictive model for ESBL-E. coli carriage in the community, and detect the most prevalent ESBL-genes. Methods: We cultured total and ESBL-E. coli in 300 wastewater samples to quantify daily loads and percentage of ESBL-E. coli. Additionally, we screened 234 ESBL-E. coli isolates using molecular-methods for the presence of 18 ESBL-gene families. Results: We found a population-weighted mean percentage of ESBL-E. coli of 1.9% (95%CI 1.8%, 2%) across all sites and weeks, which can inform ESBL-E. coli carriage. Concentrations of ESBL-E. coli varied across WWTPs and time, with higher values observed in WWTPs serving larger populations. Recent precipitations (previous 24-/96-hours) showed no significant association with ESBL-E. coli, while temperature occasionally had a moderate impact (p<0.05, correlation coefficients approximately 0.40) in some locations. We identified blaCTX-M-1, blaCTX-M-9 and blaTEM as the predominant ESBL-gene families. Conclusions: Our study demonstrates that wastewater-based surveillance of culturable ESBL-E. coli provides insights into AMR trends in Switzerland and may also inform resistance. These findings establish a foundation for long-term, nationally established monitoring protocols and provide information that may help inform targeted public health interventions.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"8 8","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135037975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}