medRxiv : the preprint server for health sciences最新文献

{"title":"Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.","authors":"Han-Sol Park, Anna Yin, Caelan Barranta, John S Lee, Christopher A Caputo, Jaiprasath Sachithanandham, Maggie Li, Steve Yoon, Ioannis Sitaras, Anne Jedlicka, Yolanda Eby, Malathi Ram, Reinaldo E Fernandez, Owen R Baker, Aarthi G Shenoy, Giselle S Mosnaim, Yuriko Fukuta, Bela Patel, Sonya L Heath, Adam C Levine, Barry R Meisenberg, Emily S Spivak, Shweta Anjan, Moises A Huaman, Janis E Blair, Judith S Currier, James H Paxton, Jonathan M Gerber, Joann R Petrini, Patrick B Broderick, William Rausch, Marie Elena Cordisco, Jean Hammel, Benjamin Greenblatt, Valerie C Cluzet, Daniel Cruser, Kevin Oei, Matthew Abinante, Laura L Hammitt, Catherine G Sutcliffe, Donald N Forthal, Martin S Zand, Edward R Cachay, Jay S Raval, Seble G Kassaye, Christi E Marshall, Anusha Yarava, Karen Lane, Nichol A McBee, Amy L Gawad, Nicky Karlen, Atika Singh, Daniel E Ford, Douglas A Jabs, Lawrence J Appel, David M Shade, Bryan Lau, Stephan Ehrhardt, Sheriza N Baksh, Janna R Shapiro, Jiangda Ou, Yu Bin Na, Maria D Knoll, Elysse Ornelas-Gatdula, Netzahualcoyotl Arroyo-Curras, Thomas J Gniadek, Patrizio Caturegli, Jinke Wu, Nelson Ndahiro, Michael J Betenbaugh, Alyssa Ziman, Daniel F Hanley, Arturo Casadevall, Shmuel Shoham, Evan M Bloch, Kelly A Gebo, Aaron A R Tobian, Oliver Laeyendecker, Andrew Pekosz, Sabra L Klein, David J Sullivan","doi":"10.1101/2023.04.13.23288353","DOIUrl":"10.1101/2023.04.13.23288353","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 convalescent plasma (CCP) viral specific antibody levels that translate into recipient post-transfusion antibody levels sufficient to prevent disease progression is not defined.</p><p><strong>Methods: </strong>This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low post-transfusion antibody levels was established by two methods: 1) analyzing virus neutralization-equivalent anti-S-RBD IgG responses in donors or 2) receiver operating characteristic (ROC) analysis.</p><p><strong>Results: </strong>SARS-CoV-2 anti-S-RBD IgG antibody was diluted by a factor of 21.3 into post-transfusion seronegative recipients from matched donor units. Viral specific antibody delivered approximated 1.2 mg. The high antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP recipient analysis for antibody thresholds correlated to reduced hospitalizations found a significant association with Fisher's exact test between early and high antibodies versus all other CCP recipients (or control plasma) with antibody cutoffs established by both methods-donor virus neutralization-based cutoff: (0/85; 0% versus 15/276; 5.6%) p=0.03 or ROC based cutoff: (0/94; 0% versus 15/267; 5.4%) p=0.01.</p><p><strong>Conclusion: </strong>In unvaccinated, seronegative CCP recipients, early transfusion of plasma units corresponding to the upper 30% of all study donors reduced outpatient hospitalizations. These high antibody level plasma units, given early, should be reserved for therapeutic use.Trial registration: NCT04373460.</p><p><strong>Funding: </strong>Defense Health Agency and others.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a9/ba/nihpp-2023.04.13.23288353v2.PMC10153328.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10257311","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":"POTENTIATION OF CORTICO-SPINAL OUTPUT VIA TARGETED ELECTRICAL STIMULATION OF THE MOTOR THALAMUS.","authors":"Jonathan C Ho, Erinn M Grigsby, Arianna Damiani, Lucy Liang, Josep-Maria Balaguer, Sridula Kallakuri, Jessica Barrios-Martinez, Vahagn Karapetyan, Daryl Fields, Peter C Gerszten, T Kevin Hitchens, Theodora Constantine, Gregory M Adams, Donald J Crammond, Marco Capogrosso, Jorge A Gonzalez-Martinez, Elvira Pirondini","doi":"10.1101/2023.03.08.23286720","DOIUrl":"10.1101/2023.03.08.23286720","url":null,"abstract":"<p><p>Cerebral white matter lesions prevent cortico-spinal descending inputs from effectively activating spinal motoneurons, leading to loss of motor control. However, in most cases, the damage to cortico-spinal axons is incomplete offering a potential target for new therapies aimed at improving volitional muscle activation. Here we hypothesized that, by engaging direct excitatory connections to cortico-spinal motoneurons, stimulation of the motor thalamus could facilitate activation of surviving cortico-spinal fibers thereby potentiating motor output. To test this hypothesis, we identified optimal thalamic targets and stimulation parameters that enhanced upper-limb motor evoked potentials and grip forces in anesthetized monkeys. This potentiation persisted after white matter lesions. We replicated these results in humans during intra-operative testing. We then designed a stimulation protocol that immediately improved voluntary grip force control in a patient with a chronic white matter lesion. Our results show that electrical stimulation targeting surviving neural pathways can improve motor control after white matter lesions.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/58/6c/nihpp-2023.03.08.23286720v2.PMC10029067.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9602338","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":"A phenome-wide association study of methylated GC-rich repeats identifies a GCC repeat expansion in <i>AFF3</i> as a significant cause of intellectual disability.","authors":"Bharati Jadhav, Paras Garg, Joke J F A van Vugt, Kristina Ibanez, Delia Gagliardi, William Lee, Mariya Shadrina, Tom Mokveld, Egor Dolzhenko, Alejandro Martin-Trujillo, Scott L Gies, Clarissa Rocca, Mafalda Barbosa, Miten Jain, Nayana Lahiri, Katherine Lachlan, Henry Houlden, Benedict Paten, Jan Veldink, Arianna Tucci, Andrew J Sharp","doi":"10.1101/2023.05.03.23289461","DOIUrl":"10.1101/2023.05.03.23289461","url":null,"abstract":"<p><p>GC-rich tandem repeat expansions (TREs) are often associated with DNA methylation, gene silencing and folate-sensitive fragile sites and underlie several congenital and late-onset disorders. Through a combination of DNA methylation profiling and tandem repeat genotyping, we identified 24 methylated TREs and investigated their effects on human traits using PheWAS in 168,641 individuals from the UK Biobank, identifying 156 significant TRE:trait associations involving 17 different TREs. Of these, a GCC expansion in the promoter of <i>AFF3</i> was linked with a 2.4-fold reduced probability of completing secondary education, an effect size comparable to several recurrent pathogenic microdeletions. In a cohort of 6,371 probands with neurodevelopmental problems of suspected genetic etiology, we observed a significant enrichment of <i>AFF3</i> expansions compared to controls. With a population prevalence that is at least 5-fold higher than the TRE that causes fragile X syndrome, <i>AFF3</i> expansions represent a significant cause of neurodevelopmental delay.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10187445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9490615","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":"Corpus callosum abnormalities at term-equivalent age are associated with language development at two years corrected age in infants born very preterm.","authors":"Katsuaki Kojima, Julia E Kline, Mekibib Altaye, Beth M Kline-Fath, Nehal A Parikh","doi":"10.1101/2023.09.20.23295848","DOIUrl":"10.1101/2023.09.20.23295848","url":null,"abstract":"<p><p>We studied the impact of microstructural abnormalities in the corpus callosum on language development in 348 infants born very prematurely. We discovered that the fractional anisotropy of the corpus callosum anterior midbody was a significant predictor of standardized language scores at two years, independent of clinical and social risk factors.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/20/bd/nihpp-2023.09.20.23295848v1.PMC10543245.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41176681","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":"Imprecision nutrition? Duplicate meals result in unreliable individual glycemic responses measured by continuous glucose monitors across four dietary patterns in adults without diabetes.","authors":"Aaron Hengist, Jude Anthony Ong, Katherine McNeel, Juen Guo, Kevin D Hall","doi":"10.1101/2023.06.14.23291406","DOIUrl":"10.1101/2023.06.14.23291406","url":null,"abstract":"<p><strong>Background: </strong>Continuous glucose monitors (CGMs) are being used to characterize postprandial glycemic responses and thereby provide personalized dietary advice to minimize glycemic excursions. However, the efficacy of such advice depends on reliable CGM responses.</p><p><strong>Objective: </strong>To explore within-subject variability of CGM responses to duplicate meals in an inpatient setting.</p><p><strong>Methods: </strong>CGM data were collected in two controlled feeding studies (NCT03407053 and NCT03878108) in 30 participants without diabetes capturing 1056 meal responses in duplicate ~1 week apart from four dietary patterns. One study used two different CGMs (Abbott Freestyle Libre Pro and Dexcom G4 Platinum) whereas the other study used only Dexcom. We calculated the incremental area under the curve (iAUC) for each 2-h post-meal period and compared within-subject iAUCs using the same CGM for the duplicate meals using linear correlations, intra-class correlation coefficients (ICC), Bland-Altman analyses, and compared individual variability of glycemic responses to duplicate meals versus different meals using standard deviations (SDs).</p><p><strong>Results: </strong>There were weak to moderate positive linear correlations between within- subject iAUCs for duplicate meals (Abbott r=0.47, p<0.0001, Dexcom r=0.43, p<0.0001), with low within-participant reliability indicated by ICC (Abbott 0.31, Dexcom 0.14). Bland-Altman analyses indicated wide limits of agreement (Abbott -31.3 to 31.5 mg/dL, Dexcom -30.8 to 30.4 mg/dL) but no significant bias of mean iAUCs for duplicate meals (Abbott 0.1 mg/dL, Dexcom -0.2 mg/dL). Individual variability of glycemic responses to duplicate meals was similar to that of different meals evaluated each diet week for both Abbott (SD_duplicate = 10.7 mg/dL , SD_{week 1} =12.4 mg/dL, SD_{week 2} =11.6 mg/dL, <i>p</i>=0.38) and Dexcom (SD_duplicate = 11.1 mg/dL, SD_{week 1} = 11.5 mg/dL, SD_{week 2} =11.9 mg/dL, <i>p</i>=0.60).</p><p><strong>Conclusions: </strong>Individual postprandial CGM responses to duplicate meals were unreliable in adults without diabetes. Personalized diet advice based on CGM measurements in adults without diabetes requires more reliable methods involving aggregated repeated measurements.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10119917","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":"Meta-analysis of CYP2C19 and CYP2D6 metabolic activity on antidepressant response from 13 clinical studies using genotype imputation.","authors":"Danyang Li, Oliver Pain, Chiara Fabbri, Win Lee Edwin Wong, Chris Wai Hang Lo, Stephan Ripke, Annamaria Cattaneo, Daniel Souery, Mojca Z Dernovsek, Neven Henigsberg, Joanna Hauser, Glyn Lewis, Ole Mors, Nader Perroud, Marcella Rietschel, Rudolf Uher, Wolfgang Maier, Bernhard T Baune, Joanna M Biernacka, Guido Bondolfi, Katharina Domschke, Masaki Kato, Yu-Li Liu, Alessandro Serretti, Shih-Jen Tsai, Richard Weinshilboum, Andrew M McIntosh, Cathryn M Lewis","doi":"10.1101/2023.06.26.23291890","DOIUrl":"10.1101/2023.06.26.23291890","url":null,"abstract":"<p><p>Cytochrome P450 enzymes including CYP2C19 and CYP2D6 are important for antidepressant metabolism and polymorphisms of these genes have been determined to predict metabolite levels. Nonetheless, more evidence is needed to understand the impact of genetic variations on antidepressant response. In this study, individual clinical and genetic data from 13 studies of European and East Asian ancestry populations were collected. The antidepressant response was clinically assessed as remission and percentage improvement. Imputed genotype was used to translate genetic polymorphisms to metabolic phenotypes (poor, intermediate, normal, and rapid+ultrarapid) of CYP2C19 and CYP2D6. The association of CYP2C19 and CYP2D6 metabolic phenotypes with treatment response was examined using normal metabolizers as the reference. Among 5843 depression patients, a higher remission rate was found in CYP2C19 poor metabolizers compared to normal metabolizers at nominal significance but did not survive after multiple testing correction (OR=1.46, 95% CI [1.03, 2.06], p=0.033, heterogeneity I²=0%, subgroup difference p=0.72). No metabolic phenotype was associated with percentage improvement from baseline. After stratifying by antidepressants primarily metabolized by CYP2C19 and CYP2D6, no association was found between metabolic phenotypes and antidepressant response. Metabolic phenotypes showed differences in frequency, but not effect, between European- and East Asian-ancestry studies. In conclusion, metabolic phenotypes imputed from genetic variants using genotype were not associated with antidepressant response. CYP2C19 poor metabolizers could potentially contribute to antidepressant efficacy with more evidence needed. CYP2D6 structural variants cannot be imputed from genotype data, limiting inference of pharmacogenetic effects. Sequencing and targeted pharmacogenetic testing, alongside information on side effects, antidepressant dosage, depression measures, and diverse ancestry studies, would more fully capture the influence of metabolic phenotypes.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/28/5a/nihpp-2023.06.26.23291890v1.PMC10327261.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10189029","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":"Early underdetected dissemination across countries followed by extensive local transmission propelled the 2022 mpox epidemic.","authors":"Miguel I Paredes, Nashwa Ahmed, Marlin Figgins, Vittoria Colizza, Philippe Lemey, John T McCrone, Nicola Müller, Cécile Tran-Kiem, Trevor Bedford","doi":"10.1101/2023.07.27.23293266","DOIUrl":"10.1101/2023.07.27.23293266","url":null,"abstract":"<p><p>The World Health Organization declared mpox a public health emergency of international concern in July 2022. To investigate global mpox transmission and population-level changes associated with controlling spread, we built phylogeographic and phylodynamic models to analyze MPXV genomes from five global regions together with air traffic and epidemiological data. Our models reveal community transmission prior to detection, changes in case-reporting throughout the epidemic, and a large degree of transmission heterogeneity. We find that viral introductions played a limited role in prolonging spread after initial dissemination, suggesting that travel bans would have had only a minor impact. We find that mpox transmission in North America began declining before more than 10% of high-risk individuals in the USA had vaccine-induced immunity. Our findings highlight the importance of broader routine specimen screening surveillance for emerging infectious diseases and of joint integration of genomic and epidemiological information for early outbreak control.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418578/pdf/nihpp-2023.07.27.23293266v2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10028932","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":"Accuracy of digital chest x-ray analysis with artificial intelligence software as a triage and screening tool in hospitalized patients being evaluated for tuberculosis in Lima, Peru.","authors":"Amanda Biewer, Christine Tzelios, Karen Tintaya, Betsabe Roman, Shelley Hurwitz, Courtney M Yuen, Carole D Mitnick, Edward Nardell, Leonid Lecca, Dylan B Tierney, Ruvandhi R Nathavitharana","doi":"10.1101/2023.05.17.23290110","DOIUrl":"10.1101/2023.05.17.23290110","url":null,"abstract":"<p><strong>Introduction: </strong>Tuberculosis (TB) transmission in healthcare facilities is common in high-incidence countries. Yet, the optimal approach for identifying inpatients who may have TB is unclear. We evaluated the diagnostic accuracy of qXR (Qure.ai, India) computer-aided detection (CAD) software versions 3.0 and 4.0 (v3 and v4) as a triage and screening tool within the FAST (Find cases Actively, Separate safely, and Treat effectively) transmission control strategy.</p><p><strong>Methods: </strong>We prospectively enrolled two cohorts of patients admitted to a tertiary hospital in Lima, Peru: one group had cough or TB risk factors (triage) and the other did not report cough or TB risk factors (screening). We evaluated the sensitivity and specificity of qXR for the diagnosis of pulmonary TB using culture and Xpert as primary and secondary reference standards, including stratified analyses based on risk factors.</p><p><strong>Results: </strong>In the triage cohort (n=387), qXR v4 sensitivity was 0.91 (59/65, 95% CI 0.81-0.97) and specificity was 0.32 (103/322, 95% CI 0.27-0.37) using culture as reference standard. There was no difference in the area under the receiver-operating-characteristic curve (AUC) between qXR v3 and qXR v4 with either a culture or Xpert reference standard. In the screening cohort (n=191), only one patient had a positive Xpert result, but specificity in this cohort was high (>90%). A high prevalence of radiographic lung abnormalities, most notably opacities (81%), consolidation (62%), or nodules (58%), was detected by qXR on digital CXR images from the triage cohort.</p><p><strong>Conclusions: </strong>qXR had high sensitivity but low specificity as a triage in hospitalized patients with cough or TB risk factors. Screening patients without cough or risk factors in this setting had a low diagnostic yield. These findings further support the need for population and setting-specific thresholds for CAD programs.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10246158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9707840","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":"Simultaneous detection and quantification of multiple pathogen targets in wastewater.","authors":"Gouthami Rao, Drew Capone, Kevin Zhu, Abigail Knoble, Yarrow Linden, Ryan Clark, Amanda Lai, Juhee Kim, Ching-Hua Huang, Aaron Bivins, Joe Brown","doi":"10.1101/2023.06.23.23291792","DOIUrl":"10.1101/2023.06.23.23291792","url":null,"abstract":"<p><p>Wastewater-based epidemiology has emerged as a critical tool for public health surveillance, building on decades of environmental surveillance work for pathogens such as poliovirus. Work to date has been limited to monitoring a single pathogen or small numbers of pathogens in targeted studies; however, few studies consider simultaneous quantitative analysis of a wide variety of pathogens, which could greatly increase the utility of wastewater surveillance. We developed a novel quantitative multi-pathogen surveillance approach (35 pathogen targets including bacteria, viruses, protozoa, and helminths) using TaqMan Array Cards (TAC) and applied the method on concentrated wastewater samples collected at four wastewater treatment plants in Atlanta, GA from February to October of 2020. From sewersheds serving approximately 2 million people, we detected a wide range of targets including many we expected to find in wastewater (e.g., enterotoxigenic <i>E. coli</i> and <i>Giardia</i> in 97% of 29 samples at stable concentrations) as well as unexpected targets including <i>Strongyloides stercoralis</i> (a human threadworm rarely observed in the USA). Other notable detections included SARS-CoV-2, but also several pathogen targets that are not commonly included in wastewater surveillance like <i>Acanthamoeba</i> spp., <i>Balantidium coli, Entamoeba histolytica</i>, astrovirus, norovirus, and sapovirus. Our data suggest broad utility in expanding the scope of enteric pathogen surveillance in wastewaters, with potential for application in a variety of settings where pathogen quantification in fecal waste streams can inform public health surveillance and selection of control measures to limit infections.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10186962","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":"Patient Phenotyping for Atopic Dermatitis with Transformers and Machine Learning.","authors":"Andrew Wang, Rachel Fulton, Sy Hwang, David J Margolis, Danielle L Mowery","doi":"10.1101/2023.08.25.23294636","DOIUrl":"10.1101/2023.08.25.23294636","url":null,"abstract":"<p><strong>Background: </strong>Atopic dermatitis (AD) is a chronic skin condition that millions of people around the world live with each day. Performing research studies into identifying the causes and treatment for this disease has great potential to provide benefit for these individuals. However, AD clinical trial recruitment is a non-trivial task due to variance in diagnostic precision and phenotypic definitions leveraged by different clinicians as well as time spent finding, recruiting, and enrolling patients by clinicians to become study subjects. Thus, there is a need for automatic and effective patient phenotyping for cohort recruitment.</p><p><strong>Objective: </strong>Our study aims to present an approach for identifying patients whose electronic health records suggest that they may have AD.</p><p><strong>Methods: </strong>We created a vectorized representation of each patient and trained various supervised machine learning methods to classify when a patient has AD. Each patient is represented by a vector of either probabilities or binary values where each value indicates whether they meet a different criteria for AD diagnosis.</p><p><strong>Results: </strong>The most accurate AD classifier performed with a class-balanced accuracy of 0.8036, a precision of 0.8400, and a recall of 0.7500 when using XGBoost (Extreme Gradient Boosting).</p><p><strong>Conclusions: </strong>Creating an automated approach for identifying patient cohorts has the potential to accelerate, standardize, and automate the process of patient recruitment for AD studies; therefore, reducing clinician burden and informing knowledge discovery of better treatment options for AD.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10261912","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}