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1.
Phytochemistry ; 226: 114206, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38972440

RESUMEN

Eighteen compounds including eleven previously undescribed diterpenes were isolated from the leaves of Croton mangelong. The structures were determined by HRESIMS, IR, NMR, X-ray diffraction and ECD spectroscopic analysis. All isolates were assayed for their anti-hyperglycemic activities in insulin resistance (IR) 3T3-L1 adipocytes, and compound 4 was tested for its anti-diabetic activity in vivo. Results suggested compound 4 could effectively reduce blood glucose level in diabetic SD rats in a dose of 30 mg/kg.

3.
Nat Commun ; 15(1): 5887, 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39003305

RESUMEN

Memory engrams are a subset of learning activated neurons critical for memory recall, consolidation, extinction and separation. While the transcriptional profile of engrams after learning suggests profound neural changes underlying plasticity and memory formation, little is known about how memory engrams are selected and allocated. As epigenetic factors suppress memory formation, we developed a CRISPR screening in the hippocampus to search for factors controlling engram formation. We identified histone lysine-specific demethylase 4a (Kdm4a) as a negative regulator for engram formation. Kdm4a is downregulated after neural activation and controls the volume of mossy fiber boutons. Mechanistically, Kdm4a anchors to the exonic region of Trpm7 gene loci, causing the stalling of nascent RNAs and allowing burst transcription of Trpm7 upon the dismissal of Kdm4a. Furthermore, the YTH domain containing protein 2 (Ythdc2) recruits Kdm4a to the Trpm7 gene and stabilizes nascent RNAs. Reducing the expression of Kdm4a in the hippocampus via genetic manipulation or artificial neural activation facilitated the ability of pattern separation in rodents. Our work indicates that Kdm4a is a negative regulator of engram formation and suggests a priming state to generate a separate memory.


Asunto(s)
Hipocampo , Memoria , Canales Catiónicos TRPM , Animales , Hipocampo/metabolismo , Ratones , Memoria/fisiología , Canales Catiónicos TRPM/metabolismo , Canales Catiónicos TRPM/genética , Histona Demetilasas con Dominio de Jumonji/metabolismo , Histona Demetilasas con Dominio de Jumonji/genética , Humanos , Regulación hacia Abajo/genética , Neuronas/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratas , Sistemas CRISPR-Cas , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Plasticidad Neuronal/genética , Células HEK293 , Histona Demetilasas
4.
BMC Med Educ ; 24(1): 736, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982429

RESUMEN

BACKGROUND: Academic paper writing holds significant importance in the education of medical students, and poses a clear challenge for those whose first language is not English. This study aims to investigate the effectiveness of employing large language models, particularly ChatGPT, in improving the English academic writing skills of these students. METHODS: A cohort of 25 third-year medical students from China was recruited. The study consisted of two stages. Firstly, the students were asked to write a mini paper. Secondly, the students were asked to revise the mini paper using ChatGPT within two weeks. The evaluation of the mini papers focused on three key dimensions, including structure, logic, and language. The evaluation method incorporated both manual scoring and AI scoring utilizing the ChatGPT-3.5 and ChatGPT-4 models. Additionally, we employed a questionnaire to gather feedback on students' experience in using ChatGPT. RESULTS: After implementing ChatGPT for writing assistance, there was a notable increase in manual scoring by 4.23 points. Similarly, AI scoring based on the ChatGPT-3.5 model showed an increase of 4.82 points, while the ChatGPT-4 model showed an increase of 3.84 points. These results highlight the potential of large language models in supporting academic writing. Statistical analysis revealed no significant difference between manual scoring and ChatGPT-4 scoring, indicating the potential of ChatGPT-4 to assist teachers in the grading process. Feedback from the questionnaire indicated a generally positive response from students, with 92% acknowledging an improvement in the quality of their writing, 84% noting advancements in their language skills, and 76% recognizing the contribution of ChatGPT in supporting academic research. CONCLUSION: The study highlighted the efficacy of large language models like ChatGPT in augmenting the English academic writing proficiency of non-native speakers in medical education. Furthermore, it illustrated the potential of these models to make a contribution to the educational evaluation process, particularly in environments where English is not the primary language.


Asunto(s)
Inteligencia Artificial , Estudiantes de Medicina , Escritura , Humanos , China , Educación de Pregrado en Medicina , Masculino , Femenino , Lenguaje
5.
J Infect Dis ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38963827

RESUMEN

BACKGROUND: Human rhinoviruses (RV) primarily cause the common cold, but infection outcomes vary from subclinical to severe cases, including asthma exacerbations and fatal pneumonia in immunocompromised individuals. To date, therapeutic strategies have been hindered by the high diversity of serotypes. Global surveillance efforts have traditionally focused on sequencing VP1 or VP2/VP4 genetic regions, leaving gaps in our understanding of RV genomic diversity. METHODS: We sequenced 1,078 RV genomes from nasal swabs of symptomatic and asymptomatic individuals to explore viral evolution during two epidemiologically distinct periods in Washington State: when the COVID-19 pandemic affected the circulation of other seasonal respiratory viruses except for RV (February - July 2021), and when the seasonal viruses reemerged with the severe RSV and influenza outbreak (November-December 2022). We constructed maximum likelihood and BEAST-phylodynamic trees to characterize intra-genotype evolution. RESULTS: We detected 99 of 168 known genotypes and observed inter-genotypic recombination and genotype cluster swapping from 2021 to 2022. We found a significant association between the presence of symptoms and viral load, but not with RV species or genotype. Phylodynamic trees, polyprotein selection pressure, and Shannon entropy revealed co-circulation of divergent clades within genotypes with high amino acid constraints throughout polyprotein. DISCUSSION: Our study underscores the dynamic nature of RV genomic epidemiology within a localized geographic region, as more than 20% of existing genotypes within each RV species co-circulated each studied month. Our findings also emphasize the importance of investigating correlations between rhinovirus genotypes and serotypes to understand long-term immunity and cross-protection.

6.
Inorg Chem ; 63(28): 13014-13021, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38943593

RESUMEN

Zwitterionic thiolate ligands have the potential to introduce novel assembly modes and functions for noble metal clusters. However, their utilization in the synthesis of silver clusters remains understudied, particularly for the clusters containing reductive Ag(0) species. In this article, we report the first synthesis of a mixed-valence silver(0/I) cluster protected by zwitterionic Tab as thiolate ligands (Tab = 4-(trimethylammonio)benzenethiolate), denoted as [Ag22(Tab)24](PF6)20·16CH3OH·6Et2O (Ag22·16CH3OH·6Et2O), alongside an Ag(I) cluster [Ag20(Tab)12(PhCOO)10(MeCN)2(H2O)](PF6)10·11MeCN (Ag20·11MeCN). Ag22 has a distinct hierarchical supratetrahedral structure with a central {Ag6} kernel surrounded by four [Ag4(Tab)6]4+ units. High-resolution electrospray ionization mass spectra demonstrate that Ag22 has two free electrons, indicating a superatomic core. Ag20 has a drum-like [Ag12(Tab)6(PhCOO)6(H2O)]6+ inner core capped by two tetrahedral-like [Ag4(Tab)3(PhCOO)2(MeCN)]2+ units. Ag20 can be transformed into Ag22 after its reaction with NaBH4 in solution. Antibacterial measurements reveal that Ag22 has a significantly lower minimum inhibitory concentration than that of the Ag20 cluster. This work not only extends the stabilization of silver(0/I) clusters to neutral thiol ligands but also offers new materials for the development of novel antibacterial materials.

7.
Sci Rep ; 14(1): 14399, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38909109

RESUMEN

Aiming at the shortcomings of the BP neural network in practical applications, such as easy to fall into local extremum and slow convergence speed, we optimized the initial weights and thresholds of the BP neural network using the particle swarm optimization (PSO). Additionally, cloud computing service, web technology, cloud database and numerical simulation were integrated to construct an intelligent feedback analysis cloud program for underground engineering safety monitoring based on the PSO-BP algorithm. The program could conveniently, quickly, and intelligently carry out numerical analysis of underground engineering and dynamic feedback analysis of surrounding rock parameters. The program was applied to the cloud inversion analysis of the surrounding rock parameters for the underground powerhouse of the Shuangjiangkou Hydropower Station. The calculated displacement simulated with the back-analyzed parameters matches the measured displacement very well. The posterior variance evaluation shows that the posterior error ratio is 0.045 and the small error probability is 0.999. The evaluation results indicate that the intelligent feedback analysis cloud program has high accuracy and can be applied to engineering practice.

8.
medRxiv ; 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38826243

RESUMEN

Pathogen genomics can provide insights into disease transmission patterns, but new methods are needed to handle modern large-scale pathogen genome datasets. Genetically proximal viruses indicate epidemiological linkage and are informative about transmission events. Here, we leverage pairs of identical sequences using 114,298 SARS-CoV-2 genomes collected via sentinel surveillance from March 2021 to December 2022 in Washington State, USA, with linked age and residence information to characterize fine-scale transmission. The location of pairs of identical sequences is highly consistent with expectations from mobility and social contact data. Outliers in the relationship between genetic and mobility data can be explained by SARS-CoV-2 transmission between postal codes with male prisons, consistent with transmission between prison facilities. Transmission patterns between age groups vary across spatial scales. Finally, we use the timing of sequence collection to understand the age groups driving transmission. This work improves our ability to characterize transmission from large pathogen genome datasets.

9.
Sci Rep ; 14(1): 13587, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38867067

RESUMEN

Longwave radiation is an important open-air environmental factor that can significantly affect the temperature of concrete, but it has often been ignored in the temperature analysis of open-air concrete structures. In this article, an improved analytical model of concrete temperature was proposed by considering solar radiation, thermal convection, thermal conduction and especially longwave radiation. Temperature monitoring of an open-air concrete block was carried out to verify the proposed model and analyze the heat energy characteristics of open-air concrete. As demonstrated by the open-air experiment, under the influence of longwave radiation, the temperature at the top of the concrete block could decrease rapidly at night and even become lower than the minimum temperature at its bottom. Compared with the analytical model that ignores longwave radiation, the improved model that includes it better matches the measured temperature. According to the energy analysis, although solar radiation controls the transient variation in heat energy, the heat exchange caused by longwave radiation were more than that caused by convection on sunlit surfaces, which indicates the importance of considering longwave radiation.

10.
Front Rehabil Sci ; 5: 1384698, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38711832

RESUMEN

Background: In the previous research, the Disability Assessment Scale based on ICF had been constructed for LTC insurance in China. To apply this scale in further studies, it is essential to establish assessment standards for disability levels. Objective: To establish standardized disability classification criteria and identify the disability statuses and levels in older people. Methods: This is a cross-sectional study, in which 1,610 older individuals in 15 long-term care institutions in China were assessed by the disability assessment scale based on ICF. Cluster analysis was used for classification of the disability levels. Mean (SD) and median (IQR) were used to describe the scores for each item and each dimension. Results: The total scores of the disability assessment scale were classified into six disability levels. The overall disability level of the 1,610 participants was moderate-to-severe. The disability in the dimension of "self-care ability and activity" was the most obvious and severe. Conclusion: The Disability Assessment Scale is capable of identifying disability statuses and levels of older people, and it can serve as a valuable tool for investigating the disabilities among old people and for conducting cross-national comparisons of disability levels.

11.
Sci Rep ; 14(1): 12045, 2024 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802502

RESUMEN

Comprehending the phylogeography of invasive organisms enhances our insight into their distribution dynamics, which is instrumental for the development of effective prevention and management strategies. In China, Pomacea canaliculata and Pomacea maculata are the two most widespread and damaging species of the non-native Pomacea spp.. Given this species' rapid spread throughout country, it is urgent to investigate the genetic diversity and structure of its different geographic populations, a task undertaken in the current study using the COI and ITS1 mitochondrial and ribosomal DNA genes, respectively. The result of this study, based on a nationwide systematic survey, a collection of Pomacea spp., and the identification of cryptic species, showed that there is a degree of genetic diversity and differentiation in P. canaliculata, and that all of its variations are mainly due to differences between individuals within different geographical populations. Indeed, this species contains multiple haplotypes, but none of them form a systematic geographical population structure. Furthermore, the COI gene exhibits higher genetic diversity than the ITS1 gene. Our study further clarifies the invasive pathways and dispersal patterns of P. canaliculata in China to provide a theoretical basis.


Asunto(s)
Complejo IV de Transporte de Electrones , Variación Genética , Genética de Población , Haplotipos , China , Animales , Complejo IV de Transporte de Electrones/genética , Filogeografía , Filogenia , Especies Introducidas , ADN Espaciador Ribosómico/genética , Gastrópodos/genética
12.
Chem Asian J ; : e202400443, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773630

RESUMEN

Two polyhedral silver-thiolate clusters, [S@Ag16(Tab)10(MeCN)8](PF6)14 (Ag16) and [Ag12(Tab)6(DMF)12](PF6)12 (Ag12), were synthesized by using electroneutral Tab species as protective ligands (Tab=4-(trimethylammonio)benzenethiolate, DMF=N,N-dimethylformamide, MeCN=acetonitrile). Ag16 has a decahedral shape composed of eight pentagon {Ag5} units and two square {Ag4} units. The structure of Ag12 is a cuboctahedron, a classical Archimedean structure composed of six triangular faces and eight square faces. The former configuration is discovered in silver-thiolate cluster for the first time, possibly benefited from the more flexible coordination between the Tab ligand and Ag+ facilitated by the electropositive -N(CH3)3 + substituent group. Third-order nonlinear optical studies show that both clusters in DMF exhibit reverse saturate absorption response under the irradiation of 532 nm laser.

13.
Biomed Pharmacother ; 175: 116689, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38703508

RESUMEN

Ischemic heart disease invariably leads to devastating damage to human health. Nicotinamide ribose (NR), as one of the precursors of NAD+ synthesis, has been discovered to exert a protective role in various neurological and cardiovascular disorders. Our findings demonstrated that pretreatment with 200 mg/kg NR for 3 h significantly reduced myocardial infarct area, decreased levels of CK-MB and LDH in serum, and improved cardiac function in the rats during myocardial ischemia-reperfusion (I/R) injury. Meanwhile, 0.5 mM NR also effectively increased the viability and decreased the LDH release of H9c2 cells during OGD/R. We had provided evidence that NR pretreatment could decrease mitochondrial reactive oxygen species (mtROS) production and MDA content, and enhance SOD activity, thereby mitigating mitochondrial damage and inhibiting apoptosis during myocardial I/R injury. Further investigations revealed that NR increased NAD+ content and upregulated SIRT3 protein expression in myocardium. Through using of SIRT3 small interfering RNA and the SIRT3 deacetylase activity inhibitor 3-TYP, we had confirmed that the cardioprotective effect of NR on cardiomyocytes was largely dependent on the inhibition of mitochondrial oxidative stress via SIRT3-SOD2 axis. Overall, our study suggested that exogenous supplementation with NR mitigated mitochondrial damage and inhibited apoptosis during myocardial I/R injury by reducing mitochondrial oxidative stress via SIRT3-SOD2-mtROS pathway.


Asunto(s)
Apoptosis , Daño por Reperfusión Miocárdica , Niacinamida , Estrés Oxidativo , Compuestos de Piridinio , Ratas Sprague-Dawley , Transducción de Señal , Sirtuina 3 , Superóxido Dismutasa , Animales , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Sirtuina 3/metabolismo , Transducción de Señal/efectos de los fármacos , Masculino , Niacinamida/farmacología , Niacinamida/análogos & derivados , Superóxido Dismutasa/metabolismo , Ratas , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Compuestos de Piridinio/farmacología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Especies Reactivas de Oxígeno/metabolismo , Línea Celular , Cardiotónicos/farmacología , Sirtuinas
14.
Am J Transl Res ; 16(4): 1246-1255, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38715804

RESUMEN

OBJECTIVE: To study the effect of nursing intervention derived from Snyder's hope theory in individuals with spinal cord injury. METHODS: We retrospectively analyzed clinical data of 80 patients with spinal cord injury who were admitted to General Hospital of Pingxiang Mining Group Co., from August 2021 to October 2023. According to different nursing methods, they were assigned into a control group (n = 40, routine curative care) and an observation group (n = 40, routine curative care plus nursing intervention derived from Snyder's hope theory). The two groups were compared in terms of emotional state, level of hope, living standard, occurrence of complications, and nursing satisfaction. According to the occurrence of complications after nursing, the patients were divided into a good prognosis group and a poor prognosis group, and the influencing factors for prognosis were analyzed by univariate analysis and logistic multivariate analysis. RESULTS: After nursing, the anxiety and depression scores decreased in both groups when compared to their pre-nursing scores, with lower scores in the observation group than in the controls (P<0.05). Also, the observation group exhibited significantly higher score of hope, higher score of quality of life, and lower occurrence of complications when compared to the control group (P<0.05). The nursing satisfaction rate in the observation group was 95.00% (38/40), which was noticeably greater than 65.00% (26/40) in the control group (P<0.05). Multivariate analysis showed that nursing methods (P = 0.007, OR = 7.828, 95% CI: 1.766-34.688) and HB after intervention (P = 0.029, OR = 0.965, 95% CI: 0.935-0.996) were the influencing factors of complications after nursing intervention in patients with SCI. CONCLUSION: The implementation of nursing intervention derived from Snyder's hope theory can decrease the anxiety and depression levels, lower the occurrence of complications, enhance the hope level, increase the satisfaction rate, and improve the overall quality of life in patients with spinal cord injury.

16.
Heliyon ; 10(10): e31137, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38778969

RESUMEN

Background: The prevalence of breast cancer (BRCA), which is common among women, is on the rise. This study applied network pharmacology to explore the potential mechanism of action of herba sarcandrae in BRCA and construct a prognostic signature composed of inflammation-related genes. Methods: The active ingredients of herba sarcandrae were screened using the SymMap, TCMID, and TCMSP platforms, and the molecular targets were determined in the UniProt database. The "drug-active compound-potential target" network was established with Cytoscape 3.7.2. The molecular targets were subjected to disease ontology, gene ontology (GO), and Kyoto Encyclopedia of Genes (KEGG) analyses. AutoDock software was used for molecular docking. Differentially expressed genes (DEGs) related to inflammation were obtained from the BRCA Cancer Genome Atlas (TCGA) database. In the training cohort, the univariate Cox regression model was applied to preliminarily screen prognostic genes. A multigene signature was built by the least absolute shrinkage and selection operator (LASSO) regression model, followed by validation through Kaplan‒Meier, Cox, and receiver operating characteristic (ROC) analyses. Results: Forty-one active compounds were identified, and 265 therapeutic targets for herba sarcandrae were predicted. GO enrichment results revealed significant enrichment of biological processes, such as response to xenobiotic stimuli, response to nutrient levels, and response to lipopolysaccharide. KEGG analysis revealed significant enrichment of pathways such as AGE-RAGE and chemical carcinogenesis receptor activation signaling pathways. In addition, the herbs Marc-Andre and rutin were shown to mediate BRCA cell proliferation and apoptosis via the interferon regulatory factor 1 (IRF1)/signal transducer and activator of transcription 3 (STAT3)/programmed death-ligand 1 (PD-L1) pathway. Sixteen inflammatory signatures, including BST2, GPR132, IL12B, IL18, IL1R1, IL2RB, IRF1, and others, were constructed, and the risk score was found to be a strong independent prognostic factor for overall survival in BRCA patients. The 16-inflammation signature was associated with several clinical features (age, clinical stage, T, and N classifications) and could reflect immune cell infiltration in tumor microenvironments with different immune cells. Conclusions: Herba sarcandrae and rutin were shown to mediate BRCA cell proliferation and apoptosis via the IRF1/STAT3/PD-L1 pathway, and the 16-member inflammatory signature might be a novel biomarker for predicting BRCA patient prognosis, providing more accurate guidance for clinical treatment prognosis evaluation and having important reference value for individualized treatment selection.

18.
ACS Appl Mater Interfaces ; 16(20): 26057-26065, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38722302

RESUMEN

To address the issue of high energy consumption associated with monoethanolamine (MEA) regeneration in the CO2 capture process, solid acid catalysts have been widely investigated due to their performance in accelerating carbamate decomposition. The recently discovered carbon nanotube (CNT) catalyst presents efficient catalytic activity for bicarbonate decomposition. In this paper, bifunctional catalysts SO42-/TiO2-CNT (STC) were prepared, which could simultaneously catalyze carbamate and bicarbonate decomposition, and outstanding catalytic performance has been exhibited. STC significantly increased the CO2 desorption amount by 82.3% and decreased the relative heat duty by 46% compared to the MEA-CO2 solution without catalysts. The excellent stability of STC was confirmed by 15 cyclic absorption-desorption experiments, showing good practical feasibility for decreasing energy consumption in an industrial CO2 capture process. Furthermore, associated with the results of experimental characterization and theoretical calculations, the synergistic catalysis of STC catalysts via proton and charge transfer was proposed. This work demonstrated the potential of STC catalysts in improving the efficiency of amine regeneration processes and reducing energy consumption, contributing to the design of more effective and economical catalysts for carbon capture.

19.
World J Hepatol ; 16(5): 800-808, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38818290

RESUMEN

BACKGROUND: In recent years, approximately half of the newly diagnosed cases and mortalities attributed to hepatocellular carcinoma (HCC) have been reported in China. Despite the high incidence of HCC, there remains a paucity of data regarding the natural growth pattern and the determination of optimal surveillance intervals specific to the Chinese population. AIM: To quantify the natural tumor growth pattern of HCC in regional China. METHODS: A retrospective analysis was performed on patients from a single institution in Southwest China who had undergone two or more serial dynamic computed tomography or magnetic resonance imaging scans between 2014 and 2020, without having received any anti-cancer therapy. Tumor growth was assessed using tumor volume doubling time (TVDT) and tumor growth rate (TGR), with volumes measured manually by experienced radiologists. Simple univariate linear regression and descriptive analysis were applied to explore associations between growth rates and clinical factors. RESULTS: This study identifies the median TVDT for HCC as 163.4 d, interquartile range (IQR) 72.1 to 302.3 d, with a daily TGR of 0.42% (IQR 0.206%-0.97%). HCC growth patterns reveal that about one-third of tumors grow indolently with TVDT exceeding 270 d, another one-third of tumors exhibit rapid growth with TVDT under 90 d, and the remaining tumors show intermediate growth rates, with TVDT ranging between 3 to 9 months. CONCLUSION: The identified TGRs support biannual surveillance and follow-up for HCC patients in certain regions of China. Given the observed heterogeneity in HCC growth, further investigation is warranted.

20.
J Infect Dis ; 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38805234

RESUMEN

BACKGROUND: The clinical severity of genital HSV-2 infection varies widely among infected persons with some experiencing frequent genital lesions while others are asymptomatic. The viral genital shedding rate is closely associated with and has been established as a surrogate marker of clinical severity. METHODS: To assess the relationship between viral genetics and shedding, we assembled a set of 145 persons who had the severity of their genital herpes quantified through determination of their HSV genital shedding rate. An HSV-2 sample from each person was sequenced and biallelic variants among these genomes were identified. RESULTS: We found no association between metrics of genome-wide variation in HSV-2 and shedding rate. A viral genome-wide association study (vGWAS) identified the minor alleles of three individual unlinked variants as significantly associated with higher shedding rate (p<8.4x10-5): C44973T (A512T), a non-synonymous variant in UL22 (glycoprotein H); A74534G, a synonymous variant in UL36 (large tegument protein); and T119283C, an intergenic variant. We also found an association between the total number of minor alleles for the significant variants and shedding rate (p=6.6x10-7). CONCLUSIONS: These results add to a growing body of literature for HSV suggesting a connection between viral genetic variation and clinically important phenotypes of infection.

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