Publications by authors named "Charles King"

Dengue virus (DENV) is the most common arbovirus globally, with its incidence growing dramatically in recent decades. Although the effects of DENV infection during pregnancy are unclear, reported associations with adverse health outcomes include miscarriage, prematurity, and low birth weight. In this study, we used an IgG ELISA to identify mothers exposed to DENV during pregnancy by testing samples obtained from a previous study that followed a cohort of pregnant women in Kenya to investigate parasitic infections during pregnancy.

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GLTSCR1, a protein encoded by the Bicra gene, is a defining subunit of the SWI/SNF (also called mammalian BAF) chromatin remodeling subcomplex called GBAF/ncBAF. To determine the role of GLTSCR1 during mouse development, we generated a Bicra germline knockout mouse using CRISPR/Cas9. Mice with homozygous loss of Bicra were born at Mendelian ratios but were small, pale and died within 24 hours after birth.

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The volume of nucleic acid sequence data has exploded recently, amplifying the challenge of transforming data into meaningful information. Processing data can require an increasingly complex ecosystem of customized tools, which increases difficulty in communicating analyses in an understandable way yet is of sufficient detail to enable informed decisions or repeats. This can be of particular interest to institutions and companies communicating computations in a regulatory environment.

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Sucralose and acesulfame-potassium consumption alters gut microbiota in rodents, with unclear effects in humans. We examined effects of three-times daily sucralose- and acesulfame-potassium-containing diet soda consumption for 1 ( = 17) or 8 ( = 8) weeks on gut microbiota composition in young adults. After 8 weeks of diet soda consumption, the relative abundance of Proteobacteria, specifically , increased; and, increased abundance of two Proteobacteria taxa was also observed after 1 week of diet soda consumption compared with sparkling water.

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Poor access to diagnostic testing in resource limited settings restricts surveillance for emerging infections, such as dengue virus (DENV), to clinician suspicion, based on history and exam observations alone. We investigated the ability of machine learning to detect DENV based solely on data available at the clinic visit. We extracted symptom and physical exam data from 6,208 pediatric febrile illness visits to Kenyan public health clinics from 2014-2019 and created a dataset with 113 clinical features.

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Article Synopsis
  • Urogenital schistosomiasis can lead to both acute and chronic issues in the urinary tract, with chronic damage often overlooked in assessments of disease burden.
  • A study tracking 93 women over 14 years found that while active infections decreased significantly, urinary tract issues actually increased, particularly related to bladder thickening.
  • The findings suggest that chronic changes induced by schistosomiasis can persist even after active infections are treated, highlighting the need for improved disease management strategies to reduce long-term impacts.
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Article Synopsis
  • The WHO's 2021-30 road map focuses on controlling, eliminating, and eradicating neglected tropical diseases, particularly highlighting the case of schistosomiasis and its prevalence benchmarks for public health.
  • The current criterion for eliminating schistosomiasis as a public health concern is deemed inadequate due to changing patterns of disease severity and the need for updated guidelines.
  • To effectively monitor and evaluate schistosomiasis, there is a call for more precise measures, such as using overall infection prevalence, age-and-species-specific morbidity markers, and a standardized evaluation protocol.
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Background: Vaccine and sufficient food availability are key factors for reducing pneumonia outbreaks in sub-Saharan Africa.

Methods: In this study, the 10-valent pneumococcal conjugate vaccine (Synflorix® or PCV10) was administered to a child cohort (5-7 years old, = 237) in Msambweni, Kenya, to determine relationships between dietary intake, nutritional/socioeconomic status of mothers/caregivers, and vaccine response. 7-day food frequency questionnaire (FFQ), dietary diversity score (DDS) and single 24-h dietary recall were used to address participants' dietary assessment and nutritional status.

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Schistosomiasis is a helminthiasis infecting approximately 250 million people worldwide. In 2001, the World Health Assembly (WHA) 54.19 resolution defined a new global strategy for control of schistosomiasis through preventive chemotherapy programmes.

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Article Synopsis
  • * This initiative encourages data-sharing and collaborative analysis to build strong evidence on the effectiveness and safety of treatments for these diseases.
  • * A Research Agenda has been developed to engage researchers and highlight important questions, with an emphasis on ethical data sharing as a means to help eliminate NTDs in the future.
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This project demonstrates the use of the IEEE 2791-2020 Standard (BioCompute Objects [BCO]) to enable the complete and concise communication of results from next generation sequencing (NGS) analysis. One arm of a clinical trial was replicated using synthetically generated data made to resemble real biological data and then two independent analyses were performed. The first simulated a pharmaceutical regulatory submission to the US Food and Drug Administration (FDA) including analysis of results and a BCO.

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Background: Rift Valley fever virus (RVFV) is a lethal threat to humans and livestock in many parts of Africa, the Arabian Peninsula, and the Indian Ocean. This systematic review's objective was to consolidate understanding of RVFV epidemiology during 1999-2021 and highlight knowledge gaps relevant to plans for human vaccine trials.

Methodology/principal Findings: The review is registered with PROSPERO (CRD42020221622).

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Secondary bacterial infection in COVID-19 patients is associated with increased mortality and disproportionately affects critically ill patients. This single-centre retrospective observational study investigates the comparative efficacy of change in procalcitonin (PCT) and other commonly available biomarkers in revealing or predicting microbiologically proven secondary infection in critical COVID-19 patients. Adult patients admitted to an intensive care unit (ICU) with confirmed SARS-CoV-2 infection between 9 March 2020 and 5 June 2020 were recruited to the study.

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Background: We sought to determine if there was a difference in the longitudinal inflammatory response measured by white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), and ferritin levels between the first and the second COVID-19 wave of ICU patients.

Methods: In a single-center retrospective observational study, ICU patients were enrolled during the first and second waves of the COVID-19 pandemic. Data were collected on patient demographics, comorbidities, laboratory results, management strategies, and complications during the ICU stay.

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Elimination of schistosomiasis as a public health problem among all disease-endemic countries in 2030 is an ambitious goal. Recent achievements resulting from mass drug administration (MDA) with praziquantel is promising but may need to be complemented with also other means. Schistosomiasis was highly prevalent in China before the initiation of the national schistosomiasis control program in the mid-1950s, and, at that time, the country bore the world's highest burden of schistosomiasis.

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Background: Current World Health Organization guidelines utilize prevalence of heavy-intensity infections (PHIs), that is, ≥50 eggs per 10 mL of urine for and ≥400 eggs per gram of stool for , to determine whether a targeted area has controlled schistosomiasis morbidity or eliminated schistosomiasis as a public health problem. The relationship between these PHI categories and morbidity is not well understood.

Methods: School-age participants enrolled in schistosomiasis monitoring and evaluation cohorts from 2003 to 2008 in Burkina Faso, Mali, Niger, Tanzania, Uganda, and Zambia were surveyed for infection and morbidity at baseline and after 1 and 2 rounds of preventive chemotherapy.

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Background: World Health Organization (WHO) guidelines for measuring global progress in schistosomiasis control classify individuals with Schistosoma spp. infections based on the concentration of excreted eggs. We assessed the associations between WHO infection intensity categories and morbidity prevalence for selected S.

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Background: Healthcare workers (HCWs) are at the forefront of fighting against the COVID-19 pandemic. However, they are at high risk of acquiring the pathogen from infected patients and transmitting to other HCWs. We aimed to investigate risk factors for nosocomial COVID-19 infection among HCWs in a non-COVID-19 hospital yard.

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The complex mTORC2 is accepted to be the kinase that controls the phosphorylation of the hydrophobic motif, a key regulatory switch for AGC kinases, although whether mTOR directly phosphorylates this motif remains controversial. Here, we identified an mTOR-mediated phosphorylation site that we termed the TOR interaction motif (TIM; F-x-F-pT), which controls the phosphorylation of the hydrophobic motif of PKC and Akt and the activity of these kinases. The TIM is invariant in mTORC2-dependent AGC kinases, is evolutionarily conserved, and coevolved with mTORC2 components.

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Developments in high-throughput sequencing (HTS) result in an exponential increase in the amount of data generated by sequencing experiments, an increase in the complexity of bioinformatics analysis reporting and an increase in the types of data generated. These increases in volume, diversity and complexity of the data generated and their analysis expose the necessity of a structured and standardized reporting template. BioCompute Objects (BCOs) provide the requisite support for communication of HTS data analysis that includes support for workflow, as well as data, curation, accessibility and reproducibility of communication.

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Objective: Pegloticase is used for the treatment of severe gout, but its use is limited by immunogenicity. This study was undertaken to evaluate whether mycophenolate mofetil (MMF) prolongs the efficacy of pegloticase.

Methods: Participants were randomized 3:1 to receive 1,000 mg MMF twice daily or placebo for 14 weeks, starting 2 weeks before receiving pegloticase and continuing while receiving intravenous pegloticase 8 mg biweekly for 12 weeks.

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Throughout the last decade, chikungunya virus (CHIKV) and Zika virus (ZIKV) infections have spread globally, causing a spectrum of disease that ranges from self-limited febrile illness to permanent severe disability, congenital anomalies, and early death. Nevertheless, estimates of their aggregate health impact are absent from the literature and are currently omitted from the Global Burden of Disease (GBD) reports. We systematically reviewed published literature and surveillance records to evaluate the global burden caused by CHIKV and ZIKV between 2010 and 2019, to calculate estimates of their disability-adjusted life year (DALY) impact.

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PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) is a tumor suppressor that directly dephosphorylates a wide array of substrates, most notably the prosurvival kinase Akt. However, little is known about the molecular mechanisms governing PHLPP1 itself. Here, we report that PHLPP1 is dynamically regulated in a cell cycle-dependent manner and deletion of PHLPP1 results in mitotic delays and increased rates of chromosomal segregation errors.

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