medRxiv : the preprint server for health sciences最新文献

{"title":"Impaired speaking-induced suppression in schizophrenia predicts auditory verbal hallucinations.","authors":"Songyuan Tan, Yingxin Jia, Miriam Mathew, Namasvi Jariwala, Alvincé Pongos, Kurtis Brent, Judith Ford, Daniel Mathalon, John Houde, Srikantan Nagarajan, Karuna Subramaniam","doi":"10.1101/2024.09.30.24314623","DOIUrl":"10.1101/2024.09.30.24314623","url":null,"abstract":"<p><p>A successful efference copy self-prediction suppresses auditory signals in the primary auditory cortex (A1) is necessary for speakers to successfully compare auditory feedback during speech production with auditory feedback during passive listening, this is called speaker-induced suppression (SIS). The top-rank positive symptom in schizophrenic (SZ) patients, auditory verbal hallucination, for instance, is hypothesized to relate to failure to distinguish the internal voice and external sounds, and this deficit is thought to be associated with impaired self-prediction in comparing external and self-generated contents. In this magnetoencephalographic imaging (MEGI) study, we compared SIS M100 in the primary auditory cortex (A1) between the healthy controls (HC; N = 30) and SZ patients (N = 22). The SZ patients displayed reduced SIS and M100 in the A1, and this impairment is negatively correlated with auditory hallucinations. These outcomes suggest that the SZ patients' hallucinatory symptoms are caused by misattribution between the external and self-generated stimuli. We proposed that the weakened self-agency and neural oscillations may lead to this misattribution.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484902","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":"Misfolded alpha synuclein co-occurrence with Alzheimer's disease proteinopathy.","authors":"Erin M Jonaitis, Karen MacLeod, Jennifer Lamoureux, Beckie Jeffers, Rachel L Studer, John Middleton, Rachael E Wilson, Nathaniel A Chin, Ozioma C Okonkwo, Barbara B Bendlin, Sanjay Asthana, Cynthia M Carlsson, Catherine L Gallagher, Bruce Hermann, Sean McEvoy, Gwendlyn Kollmorgen, Henrik Zetterberg, Luis Concha-Marambio, Sterling C Johnson, Russ M Lebovitz, Rebecca E Langhough","doi":"10.1101/2024.10.11.24315349","DOIUrl":"https://doi.org/10.1101/2024.10.11.24315349","url":null,"abstract":"<p><strong>Introduction: </strong>Multi-etiology dementia necessitates in-vivo markers of copathologies including misfolded <i>α</i> -synuclein (syn). We measured misfolded syn aggregates (syn-seeds) via qualitative seed amplifcation assays (synSAA) and examined relationships with markers of Alzheimer's disease (AD).</p><p><strong>Methods: </strong>Cerebrospinal fluid (CSF) was obtained from 420 participants in two Wisconsin AD risk cohorts (35% male; 91% cognitively unimpaired; mean (SD) age, 65.42 (7.78) years; education, 16.17 (2.23) years). synSAA results were compared to phosphorylated tau (T), beta amyloid (A), and clinical outcomes. Longitudinal cognition was modeled with mixed effects.</p><p><strong>Results: </strong>Syn positivity (synSAA+) co-occurred with T (in synSAA+ vs synSAA-, 36% vs 20% T+; p=0.011) and with cognitive impairment (10% vs 7% MCI; 10% vs 0% dementia; p=0.00050). synSAA+ participants' cognitive performance declined ∼40% faster than synSAA-for Digit Symbol, but not other tests.</p><p><strong>Discussion: </strong>Findings support prevalent syn copathology in a mostly-unimpaired AD risk cohort. Future work will explore relationships with disease progression.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484923","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":"Cochlear implants with dexamethasone-eluting electrode arrays reduce foreign body response in a murine model of cochlear implantation and human subjects.","authors":"Muhammad Taifur Rahman, Brian Mostaert, Peter Eckard, Shakila Mahmuda Fatima, Rachel Scheperle, Ibrahim Razu, Bryce Hunger, Rafal T Olszewski, Shoujun Gu, Cristina Garcia, Nashwaan Ali Khan, Douglas M Bennion, Jacob Oleson, Jonathon R Kirk, Ya Lang Enke, Robert D Gay, Robert J Morell, Keiko Hirose, Michael Hoa, Alexander D Claussen, Marlan R Hansen","doi":"10.1101/2024.10.11.24315311","DOIUrl":"https://doi.org/10.1101/2024.10.11.24315311","url":null,"abstract":"<p><p>The inflammatory foreign body response (FBR) following cochlear implantation (CI) can negatively impact CI outcomes, including increased electrode impedances. This study aims to investigate the long-term efficacy of dexamethasone eluting cochlear implant and locally delivered dexamethasone, a potent anti-inflammatory glucocorticoid on the intracochlear FBR and electrical impedance post-implantation in a murine model and human subjects. The left ears of CX3CR1 ^+/GFP Thy1 ^+/YFP (macrophage-neuron dual reporter) mice were implanted with dexamethasone-eluting cochlear implants (Dex-CI) or standard implant (Standard-CI) while the right ear served as unoperated control. Another group of dual reporter mice was implanted with a standard CI electrode array followed by injection of dexamethasone in the middle ear to mimic current clinical practice (Dex-local). Mouse implants were electrically stimulated with serial measurement of electrical impedance. Human subjects were implanted with either standard or Dex-CI followed by serial impedance measurements. Dex-CI reduced electrical impedance in the murine model and human subjects and inflammatory FBR in the murine model for an extended period. Dex-local in the murine model is ineffective for long-term reduction of FBR and electrode impedance. Our data suggest that dexamethasone eluting arrays are more effective than the current clinical practice of locally applied dexamethasone in reducing FBR and electrical impedance.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484894","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 Gene Variant Type and Location with Breast Cancer Risk in the General Population.","authors":"Mwangala P Akamandisa, Nicholas J Boddicker, Siddhartha Yadav, Chunling Hu, Steven N Hart, Christine Ambrosone, Hoda Anton-Culver, Paul L Auer, Clara Bodelon, Elizabeth S Burnside, Fei Chen, Heather A Eliassen, David E Goldgar, Christopher Haiman, James M Hodge, Hongyan Huang, Esther M John, Rachid Karam, James V Lacey, Sara Lindstroem, Elana Martinez, Jie Na, Susan L Neuhausen, Katie M O'Brien, Janet E Olson, Tuya Pal, Julie R Palmer, Alpa V Patel, Tina Pesaran, Eric C Polley, Marcy E Richardson, Kathryn Ruddy, Dale P Sandler, Lauren R Teras, Amy Trentham-Dietz, Celine M Vachon, Clarice Weinberg, Stacey J Winham, Song Yao, Gary Zirpoli, Peter Kraft, Jeffrey N Weitzel, Susan M Domchek, Fergus J Couch, Katherine L Nathanson","doi":"10.1101/2024.10.11.24315237","DOIUrl":"https://doi.org/10.1101/2024.10.11.24315237","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Pathogenic variants (PVs) in &lt;i&gt;ATM, BRCA1, BRCA2, CHEK2&lt;/i&gt; , and &lt;i&gt;PALB2&lt;/i&gt; are associated with increased breast cancer risk. However, it is unknown whether breast cancer risk differs by PV type or location in carriers ascertained from the general population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To evaluate breast cancer risks associated with PV type and location in &lt;i&gt;ATM, BRCA1, BRCA2, CHEK2&lt;/i&gt; , and &lt;i&gt;PALB2&lt;/i&gt; .&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;Age adjusted case-control association analysis for all participants, subsets of PV carriers, and women with no breast cancer family history in population-based and clinical testing cohorts.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Setting: &lt;/strong&gt;Twelve US population-based studies within the Cancer Risk Estimates Related to Susceptibility (CARRIERS) Consortium, and breast cancer cases from the UK-Biobank and an Ambry Genetics clinical testing cohort.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants: &lt;/strong&gt;32,247 women with and 32,544 age-matched women without a breast cancer diagnosis from CARRIERS; 237 and 1351 women with &lt;i&gt;BRCA2&lt;/i&gt; PVs and breast cancer from the UKBB and Ambry Genetics, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Exposures: &lt;/strong&gt;PVs in ATM, BRCA1, BRCA2, CHEK2, and PALB2.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;PVs were grouped by type and location within genes and assessed for risks of breast cancer (odds ratios (OR), 95% confidence intervals (CI), and p-values) using logistic regression. Mean ages at diagnosis were compared using linear regression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Compared to women carrying &lt;i&gt;BRCA2&lt;/i&gt; exon 11 protein truncating variants (PTVs) in the CARRIERS population-based study, women with &lt;i&gt;BRCA2&lt;/i&gt; ex13-27 PTVs (OR=2.7, 95%CI 1.1-7.9) and ex1-10 PTVs (OR=1.6, 95%CI 0.8-3.5) had higher breast cancer risks, lower rates of ER-negative breast cancer (ex13-27 OR=0.5, 95%CI 0.2-0.9; ex1-10 OR=0.5, 95%CI 0.1-1.0), and earlier age of breast cancer diagnosis (ex13-27 5.5 years, p&lt;0.001; ex1-10 2.4 years, p=0.17). These associations with ER-negative breast cancer and age replicated in a high-risk clinical cohort and the population-based UK Biobank cohort. No differences in risk or age at diagnosis by gene region were observed for PTVs in other predisposition genes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;Population-based and clinical high-risk cohorts establish that PTVs in exon 11 of &lt;i&gt;BRCA2&lt;/i&gt; are associated with reduced risk of breast cancer, later age at diagnosis, and greater risk of ER-negative disease. These differential risks may improve individualized risk prediction and clinical management for women carrying &lt;i&gt;BRCA2&lt;/i&gt; PTVs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key points: &lt;/strong&gt;&lt;b&gt;Question:&lt;/b&gt; Does &lt;i&gt;ATM&lt;/i&gt; , &lt;i&gt;BRCA1&lt;/i&gt; , &lt;i&gt;BRCA2&lt;/i&gt; , &lt;i&gt;CHEK2&lt;/i&gt; and &lt;i&gt;PALB2&lt;/i&gt; pathogenic variant type and location influence breast cancer risk in population-based studies? &lt;b&gt;Findings:&lt;/b&gt; Breast cancer risk and estrogen receptor status differ based on the type and location of pa","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484864","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":"Biallelic variants in <i>MRPL49</i> cause variable clinical presentations, including sensorineural hearing loss, leukodystrophy, and ovarian insufficiency.","authors":"Huw B Thomas, Leigh A M Demain, Alfredo Cabrera-Orefice, Isabelle Schrauwen, Hanan E Shamseldin, Alessandro Rea, Thashi Bharadwaj, Thomas B Smith, Monika Oláhová, Kyle Thompson, Langping He, Namanpreet Kaur, Anju Shukla, Musaad Abukhalid, Muhammad Ansar, Sakina Rehman, Saima Riazuddin, Firdous Abdulwahab, Janine M Smith, Zornitza Stark, Samantha Carrera, Wyatt W Yue, Kevin J Munro, Fowzan S Alkuraya, Peter Jamieson, Zubair M Ahmed, Suzanne M Leal, Robert W Taylor, Ilka Wittig, Raymond T O'Keefe, William G Newman","doi":"10.1101/2024.10.10.24315152","DOIUrl":"10.1101/2024.10.10.24315152","url":null,"abstract":"<p><p>Combined oxidative phosphorylation deficiency (COXPD) is a rare multisystem disorder which is clinically and genetically heterogeneous. Genome sequencing identified biallelic <i>MRPL49</i> variants in individuals from five unrelated families with presentations ranging from Perrault syndrome (primary ovarian insufficiency and sensorineural hearing loss) to severe childhood onset of leukodystrophy, learning disability, microcephaly and retinal dystrophy. Complexome profiling of fibroblasts from affected individuals revealed reduced levels of the small and, a more pronounced reduction of, the large mitochondrial ribosomal subunits. There was no evidence of altered mitoribosomal assembly. The reductions in levels of OXPHOS enzyme complexes I and IV are consistent with a form of COXPD associated with biallelic <i>MRPL49</i> variants, expanding the understanding of how disruption of the mitochondrial ribosomal large subunit results in multi-system phenotypes.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484881","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 between Neonicotinoid, Pyrethroid, and Organophosphate Insecticide Metabolites and Neurobehavioral Performance in Ecuadorian Adolescents.","authors":"Jessica Yen, Kun Yang, Xin M Tu, Georgia Kayser, Ana Skomal, Sheila Gahagan, Jose Suarez-Torres, Suzi Hong, Raeanne C Moore, Jose R Suarez-Lopez","doi":"10.1101/2024.10.10.24315201","DOIUrl":"https://doi.org/10.1101/2024.10.10.24315201","url":null,"abstract":"<p><strong>Background: </strong>Organophosphate and pyrethroid insecticides can affect children's neurodevelopment and increase inflammation. Limited evidence exists among adolescents and on whether inflammation may mediate pesticide-neurobehavior associations. We examined the associations between insecticide metabolite concentrations and neurobehavior among adolescents in Ecuadorian agricultural communities.</p><p><strong>Methods: </strong>We included 520 participants aged 11-17 years. We measured urinary insecticide metabolites (mass spectrometry) and neurobehavior (NEPSY-II). Associations were adjusted for socio-demographic and anthropometric characteristics. The associations of insecticide mixtures with neurobehavior were evaluated using PLS regression, and mediation by inflammatory biomarkers (TNF-α, IL-6, CRP, SAA, sICAM-1, sVCAM-1 and sCD-14) was conducted.</p><p><strong>Results: </strong>Among organophosphates, para-nitrophenol (PNP) and 3,5,6-Trichloro-2-pyridinol (TCPy) were inversely associated with Social Perception (score difference per 50% increase [β _50% ] = -0.26 [95%CI: - 1.07, -0.20] and -0.10 [-0.22, 0.01], respectively). PNP and TCPy also had significant inverse associations with Attention/Inhibitory Control at concentrations >60 ^th percentile (β _50% = -0.26 [95%CI: -0.51, -0.01] and β _50% = -0.22 [95%CI: -0.43, -0.00], respectively). The pyrethroid, 3-phenoxybenzoic acid (3-PBA), was inversely associated with Language (β _50% = -0.13 [95%CI: -0.19, -0.01]) and had a negative quadratic association with Attention/Inhibitory Control. The neonicotinoid 5-Hydroxy imidacloprid (OHIM) was positively associated with Memory/Learning (β _50% = 0.20 [95%CI: 0.04, 0.37]). Mixtures of all insecticides were significantly negatively related to all domains, except for Memory/Learning, which was positively associated. No mediation by inflammatory markers on these associations was observed.</p><p><strong>Conclusions: </strong>Concurrent organophosphate, pyrethroid, and the mixtures of all metabolites were associated with lower performance in all domains except for Memory/Learning. Neonicotinoids were positively associated with Memory/Learning and Social Perception scores.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484875","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":"Genome-wide studies define new genetic mechanisms of IgA vasculitis.","authors":"Lili Liu, Li Zhu, Sara Monteiro-Martins, Aaron Griffin, Lukas J Vlahos, Masashi Fujita, Cecilia Berrouet, Francesca Zanoni, Maddalena Marasa, Jun Y Zhang, Xu-Jie Zhou, Yasar Caliskan, Oleh Akchurin, Samhar Al-Akash, Augustina Jankauskiene, Monica Bodria, Aftab Chishti, Ciro Esposito, Vittoria Esposito, Donna Claes, Vladimir Tesar, Thomas K Davis, Dmitry Samsonov, Dorota Kaminska, Tomasz Hryszko, Gianluigi Zaza, Joseph T Flynn, Franca Iorember, Francesca Lugani, Dana Rizk, Bruce A Julian, Guillermo Hidalgo, Mahmoud Kallash, Luigi Biancone, Antonio Amoroso, Luisa Bono, Laila-Yasmin Mani, Bruno Vogt, Fangming Lin, Raji Sreedharan, Patricia Weng, Daniel Ranch, Nianzhou Xiao, Alejandro Quiroga, Raed Bou Matar, Michelle N Rheault, Scott Wenderfer, Dave Selewski, Sigrid Lundberg, Cynthia Silva, Sherene Mason, John D Mahan, Tetyana L Vasylyeva, Krzysztof Mucha, Bartosz Foroncewicz, Leszek Pączek, Michał Florczak, Małgorzata Olszewska, Agnieszka Gradzińska, Maria Szczepańska, Edyta Machura, Andrzej Badeński, Helena Krakowczyk, Przemysław Sikora, Norbert Kwella, Monika Miklaszewska, Dorota Drożdż, Marcin Zaniew, Krzysztof Pawlaczyk, Katarzyna SiniewiczLuzeńczyk, Andrew S Bomback, Gerald B Appel, Claudia Izzi, Francesco Scolari, Anna Materna-Kiryluk, Malgorzata Mizerska-Wasiak, Laureline Berthelot, Evangeline Pillebout, Renato C Monteiro, Jan Novak, Todd Jason Green, William E Smoyer, M Colleen Hastings, Robert J Wyatt, Raoul Nelson, Javier Martin, Miguel A González-Gay, Philip L De Jager, Anna Köttgen, Andrea Califano, Ali G Gharavi, Hong Zhang, Krzysztof Kiryluk","doi":"10.1101/2024.10.10.24315041","DOIUrl":"10.1101/2024.10.10.24315041","url":null,"abstract":"<p><p>IgA vasculitis (IgAV) is a pediatric disease with skin and systemic manifestations. Here, we conducted genome, transcriptome, and proteome-wide association studies in 2,170 IgAV cases and 5,928 controls, generated IgAV-specific maps of gene expression and splicing from blood of 255 pediatric cases, and reconstructed myeloid-specific regulatory networks to define disease master regulators modulated by the newly identified disease driver genes. We observed significant association at the <i>HLA</i>-<i>DRB1</i> (OR=1.55, P=1.1×10^-25) and fine-mapped specific amino-acid risk substitutions in DRβ1. We discovered two novel non-HLA loci: <i>FCAR</i> (OR=1.51, P=1.0×10^-20) encoding a myeloid IgA receptor FcαR, and <i>INPP5D</i> (OR=1.34, P=2.2×10^-9) encoding a known inhibitor of FcαR signaling. The <i>FCAR</i> risk locus co-localized with a cis-eQTL increasing <i>FCAR</i> expression; the risk alleles disrupted a <i>PRDM1</i> binding motif within a myeloid enhancer of <i>FCAR</i>. Another risk locus was associated with a higher genetically predicted levels of plasma IL6R. The <i>IL6R</i> risk haplotype carried a missense variant contributing to accelerated cleavage of IL6R into a soluble form. Using systems biology approaches, we prioritized IgAV master regulators co-modulated by <i>FCAR</i>, <i>INPP5D</i> and <i>IL6R</i> in myeloid cells. We additionally identified 21 shared loci in a cross-phenotype analysis of IgAV with IgA nephropathy, including novel loci <i>PAID4, WLS</i>, and <i>ANKRD55</i>.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484889","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 COVID-19 risk factors with systemic fungal infections in hospitalized patients.","authors":"Abbygail C Wilbourn, Oleg V Tsodikov, Sylvie Garneau-Tsodikova","doi":"10.1101/2024.10.10.24315254","DOIUrl":"10.1101/2024.10.10.24315254","url":null,"abstract":"<p><strong>Purpose: </strong>A new category of systemic co-infections that emerged with the COVID-19 pandemic is known as COVID-19-associated (CA) fungal infections, which include pulmonary aspergillosis (CAPA), candidiasis (CAC), and mucormycosis (CAM). We aimed to study the association between patient characteristics of hospitalized COVID-19 patients, COVID-19 comorbidities, and COVID-19 therapies with secondary non-superficial fungal infections.</p><p><strong>Methods: </strong>We performed descriptive and regression analyses of data from 4,999 hospitalized COVID-19 patients from the University of Kentucky Healthcare (UKHC) system.</p><p><strong>Results: </strong>The patients with secondary systemic fungal infections had a 6-fold higher risk of death than those without such infections. Generally, the risk factors for severe COVID-19 (age, obesity, cardiovascular disease, diabetes, and lack of COVID-19 vaccination) were strong predictors of a secondary fungal infection. However, several characteristics had much higher risks, suggesting that a causative link may be at play: ICU admission, mechanical ventilation, length of hospital stay, and steroid use.</p><p><strong>Conclusions: </strong>In sum, this study found that the known risk factors for severe COVID-19 disease, age, diabetes, cardiovascular disease, obesity, ventilation, and high steroid doses were all predictors of a secondary fungal infection. Steroid therapy may need to be modified to account for a risk or a presence of a fungal infection in vulnerable patients.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484863","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":"Outbreak of Chikungunya Fever in the Central Valley of Chiapas, Mexico.","authors":"Ana Luz Gonzalez-Perez, Ana Vazquez, Fernando de Ory, Anabel Negredo, Kenneth S Plante, Jessica A Plante, Pedro M Palermo, Douglas Watts, Maria Paz Sanchez-Seco, Scott C Weaver, Jose Guillermo Estrada-Franco","doi":"10.1101/2024.10.09.24314897","DOIUrl":"10.1101/2024.10.09.24314897","url":null,"abstract":"<p><p>Chikungunya virus (CHIKV) was isolated from humans in an outbreak of a febrile illness during July and August 2015 in the central valleys of Chiapas, Mexico. Sera obtained from 80 patients were tested for CHIKV RNA by reverse transcriptase polymerase chain reaction (RT-PCR) and for IgM and IgG antibodies by an enzyme linked immunoassay and a commercial indirect immunofluorescence test for CHIKV and dengue virus (DENV). Of the 80 patients, 67 were positive, including 50 for RNA and 17 for IgM. In addition, one patient was coinfected with CHIKV-DENV and 40 patients were positive for IgG antibody to DENV. The clinical manifestations included a high fever, polyarthralgia, headache, myalgia, rash, digestive disorders, conjunctivitis, and adenopathy associated with cervical and axillary inguinal regions. Complete nucleotide sequences of two of the CHIKV isolates showed that they belonged to the Asian lineage but did not group with other Mexican CHIKV isolates from the Chiapas coast. Our findings documented that different Asian lineage strains of CHIKV were circulating simultaneously during the 2015 outbreak in the Central Valley of Chiapas, Mexico. The 2024 cases suggest an explosive scenario of re-emergence of thousands of new Chikungunya and dengue fever (DENF) cases associated with deaths, and a dangerous increase of the four DENV serotypes throughout the Americas, especially in South American countries that have shown a high influx of human migration to southern Mexico. In Mexico, the state of Chiapas and other southern regions are the most vulnerable.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484945","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":"2022 Sudan Ebolavirus Outbreak in Uganda: Modelling Case Burden and Outbreak Duration.","authors":"Donal Bisanzio, Henry Kyobe Bosa, Barnabas Bakamutumaho, Carolyne Nasimiyu, Diana Atwine, Daniel Kyabayinze, Charles Olaro, Robert F Breiman, M Kariuki Njenga, Henry Mwebesa, Jane Ruth Aceng, Richard Reithinger","doi":"10.1101/2024.10.11.24314870","DOIUrl":"10.1101/2024.10.11.24314870","url":null,"abstract":"<p><p>In September 2022, an outbreak of Sudan virus (SUDV) was confirmed in Uganda. Following the first case report, we developed an individual based modelling platform (IBM-SUDV) to estimate the burden of cases and deaths, as well as the duration of the unfolding SUDV outbreak, using different scenarios. Modelled projections were within the range of cases and deaths ultimately observed.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484837","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}