Publications by authors named "Evan Johnson"

191 Publications

Recognizing and treating trigger finger.

J Fam Pract 2021 09;70(7):334-340

University of Central Florida College of Medicine, Orlando (Drs. Johnson, Romero, and Stelzer); US Department of Veteran Affairs, Orlando VAMC, FL (Dr. Werntz); University of Connecticut, Department of Orthopaedic Surgery, Farmington (Dr. Stelzer); Department of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee-Campbell Clinic, Memphis (Dr. Johnson); Department of Orthopaedic Surgery, University of Central Florida/HCA Healthcare GME Consortium, Ocala (Dr. Romero).

This inflammatory condition can leave your patient in pain and with impaired function. Here's what you need to know about the diagnosis and Tx options to provide relief.
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http://dx.doi.org/10.12788/jfp.0239DOI Listing
September 2021

The oral microbiome in relation to pancreatic cancer risk in African Americans.

Br J Cancer 2021 Oct 30. Epub 2021 Oct 30.

Slone Epidemiology Center, Boston University, Boston, MA, USA.

Background: African Americans have the highest pancreatic cancer incidence of any racial/ethnic group in the United States. The oral microbiome was associated with pancreatic cancer risk in a recent study, but no such studies have been conducted in African Americans. Poor oral health, which can be a cause or effect of microbial populations, was associated with an increased risk of pancreatic cancer in a single study of African Americans.

Methods: We prospectively investigated the oral microbiome in relation to pancreatic cancer risk among 122 African-American pancreatic cancer cases and 354 controls. DNA was extracted from oral wash samples for metagenomic shotgun sequencing. Alpha and beta diversity of the microbial profiles were calculated. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between microbes and pancreatic cancer risk.

Results: No associations were observed with alpha or beta diversity, and no individual microbial taxa were differentially abundant between cases and control, after accounting for multiple comparisons. Among never smokers, there were elevated ORs for known oral pathogens: Porphyromonas gingivalis (OR = 1.69, 95% CI: 0.80-3.56), Prevotella intermedia (OR = 1.40, 95% CI: 0.69-2.85), and Tannerella forsythia (OR = 1.36, 95% CI: 0.66-2.77).

Conclusions: Previously reported associations between oral taxa and pancreatic cancer were not present in this African-American population overall.
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http://dx.doi.org/10.1038/s41416-021-01578-5DOI Listing
October 2021

Novel temporal and spatial patterns of metastatic colonization from breast cancer rapid-autopsy tumor biopsies.

Genome Med 2021 10 28;13(1):170. Epub 2021 Oct 28.

Utah Center for Genetic Discovery, University of Utah, Salt Lake City, USA.

Background: Metastatic breast cancer is a deadly disease with a low 5-year survival rate. Tracking metastatic spread in living patients is difficult and thus poorly understood.

Methods: Via rapid autopsy, we have collected 30 tumor samples over 3 timepoints and across 8 organs from a triple-negative metastatic breast cancer patient. The large number of sites sampled, together with deep whole-genome sequencing and advanced computational analysis, allowed us to comprehensively reconstruct the tumor's evolution at subclonal resolution.

Results: The most unique, previously unreported aspect of the tumor's evolution that we observed in this patient was the presence of "subclone incubators," defined as metastatic sites where substantial tumor evolution occurs before colonization of additional sites and organs by subclones that initially evolved at the incubator site. Overall, we identified four discrete waves of metastatic expansions, each of which resulted in a number of new, genetically similar metastasis sites that also enriched for particular organs (e.g., abdominal vs bone and brain). The lung played a critical role in facilitating metastatic spread in this patient: the lung was the first site of metastatic escape from the primary breast lesion, subclones at this site were likely the source of all four subsequent metastatic waves, and multiple sites in the lung acted as subclone incubators. Finally, functional annotation revealed that many known drivers or metastasis-promoting tumor mutations in this patient were shared by some, but not all metastatic sites, highlighting the need for more comprehensive surveys of a patient's metastases for effective clinical intervention.

Conclusions: Our analysis revealed the presence of substantial tumor evolution at metastatic incubator sites in a patient, with potentially important clinical implications. Our study demonstrated that sampling of a large number of metastatic sites affords unprecedented detail for studying metastatic evolution.
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http://dx.doi.org/10.1186/s13073-021-00989-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555066PMC
October 2021

Tuberculosis-Learning the Impact of Nutrition (TB LION): protocol for an interventional study to decrease TB risk in household contacts.

BMC Infect Dis 2021 Oct 12;21(1):1058. Epub 2021 Oct 12.

Department of Medicine, Section of Infectious Diseases, Boston Medical Center, Boston, MA, USA.

Background: Comorbidities such as undernutrition and parasitic infections are widespread in India and other tuberculosis (TB)-endemic countries. This study examines how these conditions as well as food supplementation and parasite treatment might alter immune responses to Mycobacterium tuberculosis (Mtb) infection and risk of progression to TB disease.

Methods: This is a 5-year prospective clinical trial at Jawaharlal Institute of Post Graduate Medical Education and Research in Puducherry, Tamil Nadu, India. We aim to enroll 760 household contacts (HHC) of adults with active TB in order to identify 120 who are followed prospectively for 2 years: Thirty QuantiFERON-TB Gold Plus (QFT-Plus) positive HHCs ≥ 18 years of age in four proposed groups: (1) undernourished (body mass index [BMI] < 18.5 kg/m); (2) participants with a BMI ≥ 18.5 kg/m who have a parasitic infection (3) undernourished participants with a parasitic infection and (4) controls-participants with BMI ≥ 18.5 kg/m and without parasitic infection. We assess immune response at baseline and after food supplementation (for participants with BMI < 18.5 kg/m) and parasite treatment (for participants with parasites). Detailed nutritional assessments, anthropometry, and parasite testing through polymerase chain reaction (PCR) and microscopy are performed. In addition, at serial time points, these samples will be further analyzed using flow cytometry and whole blood transcriptomics to elucidate the immune mechanisms involved in disease progression.

Conclusions: This study will help determine whether undernutrition and parasite infection are associated with gene signatures that predict risk of TB and whether providing nutritional supplementation and/or treating parasitic infections improves immune response towards this infection. This study transcends individual level care and presents the opportunity to benefit the population at large by analyzing factors that affect disease progression potentially reducing the overall burden of people who progress to TB disease. Trial registration ClinicalTrials.gov; NCT03598842; Registered on July 26, 2018; https://clinicaltrials.gov/ct2/show/NCT03598842.
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http://dx.doi.org/10.1186/s12879-021-06734-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506078PMC
October 2021

Wolframin-1-expressing neurons in the entorhinal cortex propagate tau to CA1 neurons and impair hippocampal memory in mice.

Sci Transl Med 2021 09 15;13(611):eabe8455. Epub 2021 Sep 15.

Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA.

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http://dx.doi.org/10.1126/scitranslmed.abe8455DOI Listing
September 2021

Sugarcane Workweek Study: Risk Factors for Daily Changes in Creatinine.

Kidney Int Rep 2021 Sep 22;6(9):2404-2414. Epub 2021 Jun 22.

Center for Health, Work, & Environment, Colorado School of Public Health, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.

Introduction: Agricultural workers laboring in thermally stressful environments are at increased risk for kidney injury and chronic kidney disease of unknown origin (CKDu), and their environmental and occupational exposures have been considered to be important risk factors. This study examined the effects of repeated kidney stress from the simultaneous strain of work and other factors experienced by workers in Guatemala during a typical workweek.

Methods: We collected data from 107 sugarcane workers across 7 consecutive work shifts. Data included information on daily occupational, meteorological, environmental, and lifestyle factors. We used multivariable linear mixed models to evaluate associations of these factors with percent change in creatinine.

Results: We observed that increasing wet bulb globe temperature (β = 2.5%, 95% confidence interval [CI] = 0.3%, 4.7%) and increasing diastolic blood pressure (β = 6.2%, 95% CI = 0.9%, 11.6%) were associated with increases in creatinine across the shift, whereas consumption of water from chlorinated dormitory tanks as compared to artesian well water (β = -17.5%, 95% CI = -29.6%, -5.4%) and increasing number of rest breaks (β = -5.8%, 95% CI = -9.0%, -2.6%) were found to be protective against increases in creatinine. Workers reporting drinking tank water had lower concentrations of urine creatinine-corrected arsenic, lead, uranium, and glyphosate compared to workers reporting the use of well water or municipal water.

Conclusion: These results reinforce the need to focus on preventive actions that reduce kidney injury among this worker population, including strategies to reduce heat stress, managing blood pressure, and examining water sources of workers for nephrotoxic contaminants.
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http://dx.doi.org/10.1016/j.ekir.2021.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418948PMC
September 2021

Multifunctional Surface, Subsurface, and Systemic Therapeutic (MS3T) Formulation for the Control of Citrus Canker.

J Agric Food Chem 2021 Sep 10;69(37):10807-10818. Epub 2021 Sep 10.

Citrus Research and Education Center, University of Florida, 700 Experiment Station Road, Lake Alfred, Florida 33850, United States.

A multifunctional surface, subsurface and systemic therapeutic (MS3T) formulation comprised of two bactericides, both didecyldimethylammonium chloride (DDAC) and a zinc (Zn)-chelate, was developed as an alternative to copper pesticides for crop protection. Agricultural grade chemicals were used to prepare MS3T formulations. Minimal inhibitory concentration (MIC) was determined to be tested in vitro against subsp. (herein called ), (), and (Ps). Assessment of the phytotoxic potential was carried out on tomato under greenhouse conditions. Moreover, field trials were conducted during three consecutive years on grapefruit () groves to evaluate efficacy against citrus canker ( subsp. citri), scab (), and melanose (). In addition to disease control, improvements to both fruit yield and quality were observed likely due to the nutritional activity of MS3T via the sustained release of plant nutrients (Zn and nitrogen). Zn residues of leaf tissues were analyzed via atomic absorption spectroscopy (AAS) at various time points before and after MS3T foliar applications throughout the duration of the 2018 field trial. Field trial results demonstrated MS3T to be an effective alternative to copper (Cu)-based formulations for the control of citrus canker.
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http://dx.doi.org/10.1021/acs.jafc.1c03323DOI Listing
September 2021

Detection and PI-RADS classification of focal lesions in prostate MRI: Performance comparison between a deep learning-based algorithm (DLA) and radiologists with various levels of experience.

Eur J Radiol 2021 Sep 5;142:109894. Epub 2021 Aug 5.

Digital Technology and Innovation, Siemens Healthineers, Princeton, NJ, USA. Electronic address:

Purpose: To compare the performance of lesion detection and Prostate Imaging-Reporting and Data System (PI-RADS) classification between a deep learning-based algorithm (DLA), clinical reports and radiologists with different levels of experience in prostate MRI.

Methods: This retrospective study included 121 patients who underwent prebiopsy MRI and prostate biopsy. More than five radiologists (Reader groups 1, 2: residents; Readers 3, 4: less-experienced radiologists; Reader 5: expert) independently reviewed biparametric MRI (bpMRI). The DLA results were obtained using bpMRI. The reference standard was based on pathologic reports. The diagnostic performance of the PI-RADS classification of DLA, clinical reports, and radiologists was analyzed using AUROC. Dichotomous analysis (PI-RADS cutoff value ≥ 3 or 4) was performed, and the sensitivities and specificities were compared using McNemar's test.

Results: Clinically significant cancer [CSC, Gleason score ≥ 7] was confirmed in 43 patients (35.5%). The AUROC of the DLA (0.828) for diagnosing CSC was significantly higher than that of Reader 1 (AUROC, 0.706; p = 0.011), significantly lower than that of Reader 5 (AUROC, 0.914; p = 0.013), and similar to clinical reports and other readers (p = 0.060-0.661). The sensitivity of DLA (76.7%) was comparable to those of all readers and the clinical reports at a PI-RADS cutoff value ≥ 4. The specificity of the DLA (85.9%) was significantly higher than those of clinical reports and Readers 2-3 and comparable to all others at a PI-RADS cutoff value ≥ 4.

Conclusions: The DLA showed moderate diagnostic performance at a level between those of residents and an expert in detecting and classifying according to PI-RADS. The performance of DLA was similar to that of clinical reports from various radiologists in clinical practice.
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http://dx.doi.org/10.1016/j.ejrad.2021.109894DOI Listing
September 2021

Validity and Reliability of a Water Frequency Questionnaire to Estimate Daily Total Water Intake in Adults.

Front Nutr 2021 14;8:676697. Epub 2021 Jun 14.

Hydration Science Lab, College of Health Solutions, Arizona State University, Phoenix, AZ, United States.

The purpose of this investigation was to assess the validity and reliability of a seven-day water frequency questionnaire (TWI-FQ) to estimate daily total water intake (TWI) in comparison to a water turnover objective reference value via deuterium oxide (DO). Data collection occurred over 3 weeks, with a wash-out period during week two. Healthy adults ( = 98; 52% female; 41 ± 14 y; BMI, 26.4 ± 5.5 kg·m) retrospectively self-reported consumption frequencies of 17 liquids and 35 foods with specified volumes/amounts for weeks one and three via TWI-FQ. Standard water content values were utilized to determine the volume of water consumed from each liquid and food for calculation of mean daily TWI for each week. Diet records were completed daily during week two to estimate metabolic water production. To assess validity of the TWI-FQ, participants consumed DO at the start of each week and provided urine samples immediately before ingestion, the following day, and at the end of the week to calculate water turnover. Metabolic water was subtracted from water turnover to estimate TWI. TWI-FQ validity was assessed via Bland-Altman plot for multiple observations. Reliability was assessed via intraclass correlation and Pearson's correlation between weeks. TWI-FQ significantly underestimated DO TWI by -350 ± 1,431 mL·d (95% confidence interval (CI): -551, -149 mL·d). TWI-FQ TWI was significantly correlated ( = 0.707, <0.01) and not different (198 ± 1,180 mL·d, 95% CI: -38, 435 mL·d) between weeks. TWI-FQ intraclass correlation = 0.706 was significant [95% CI: 0.591, 0.793; = 5.799], indicating moderate test-retest reliability. While this tool would not be suitable for individual TWI assessment, the magnitude of bias may be acceptable for assessment at the sample-level.
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http://dx.doi.org/10.3389/fnut.2021.676697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236537PMC
June 2021

Respiratory syncytial virus M2-1 protein associates non-specifically with viral messenger RNA and with specific cellular messenger RNA transcripts.

PLoS Pathog 2021 05 18;17(5):e1009589. Epub 2021 May 18.

Department of Microbiology, Boston University School of Medicine; National Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts, United States of America.

Respiratory syncytial virus (RSV) is a major cause of respiratory disease in infants and the elderly. RSV is a non-segmented negative strand RNA virus. The viral M2-1 protein plays a key role in viral transcription, serving as an elongation factor to enable synthesis of full-length mRNAs. M2-1 contains an unusual CCCH zinc-finger motif that is conserved in the related human metapneumovirus M2-1 protein and filovirus VP30 proteins. Previous biochemical studies have suggested that RSV M2-1 might bind to specific virus RNA sequences, such as the transcription gene end signals or poly A tails, but there was no clear consensus on what RSV sequences it binds. To determine if M2-1 binds to specific RSV RNA sequences during infection, we mapped points of M2-1:RNA interactions in RSV-infected cells at 8 and 18 hours post infection using crosslinking immunoprecipitation with RNA sequencing (CLIP-Seq). This analysis revealed that M2-1 interacts specifically with positive sense RSV RNA, but not negative sense genome RNA. It also showed that M2-1 makes contacts along the length of each viral mRNA, indicating that M2-1 functions as a component of the transcriptase complex, transiently associating with nascent mRNA being extruded from the polymerase. In addition, we found that M2-1 binds specific cellular mRNAs. In contrast to the situation with RSV mRNA, M2-1 binds discrete sites within cellular mRNAs, with a preference for A/U rich sequences. These results suggest that in addition to its previously described role in transcription elongation, M2-1 might have an additional role involving cellular RNA interactions.
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http://dx.doi.org/10.1371/journal.ppat.1009589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162694PMC
May 2021

Effects of a 14-Day Hydration Intervention on Individuals with Habitually Low Fluid Intake.

Ann Nutr Metab 2020 29;76 Suppl 1:67-68. Epub 2021 Mar 29.

Exercise Science Research Center, University of Arkansas-Fayetteville, Fayetteville, Arkansas, USA.

Background: Debate continues over whether or not individuals with low total water intake (TWI) are in a chronic fluid deficit (i.e., low total body water) [1]. When women with habitually low TWI (1.6 ± 0.5 L/day) increased their fluid intake (3.5 ± 0.1 L/day) for 4 days 24-h urine osmolality decreased, but there was no change in body weight, a proxy for total body water (TBW) [2]. In a small (n = 5) study of adult men, there were no observable changes in TBW, as measured by bioelectrical impedance, after increasing TWI for 4 weeks [3]. However, body weight increased and salivary osmolality decreased indicating that the study may have been underpowered to detect changes in TBW. Further, no studies to date have measured changes in blood volume (BV) when TWI is increased.

Objectives: Therefore, the purpose of this study was to identify individuals with habitually low fluid intake and determine if increasing TWI, for 14 days, resulted in changes in TBW or BV.

Methods: In order to identify individuals with low TWI, 889 healthy adults were screened. Participants with a self-reported TWI less than 1.8 L/day (men) or 1.2 L/day (women), and a 24-h urine osmolality greater than 800 mOsm were included in the intervention phase of the study. For the intervention phase, 15 participants were assigned to the experimental group and 8 participants were assigned to the control group. The intervention period lasted for 14 days and consisted of 2 visits to our laboratory: one before the intervention (baseline) and 14 days into the intervention (14-day follow-up). At these visits, BV was measured using a CO-rebreathe procedure and deuterium oxide (D2O) was administered to measure TBW. Urine samples were collected immediately prior, and 3-8 h after the D2O dose to allow for equilibration. Prior to each visit, participants collected 24-h urine to measure 24-h hydration status. After the baseline visit, the experimental group increased their TWI to 3.7 L for males and 2.7 L for females in order to meet the current Institute of Medicine recommendations for TWI.

Results: Twenty-four-hour urine osmolality decreased (-438.7 ± 362.1 mOsm; p < 0.001) and urine volume increased (1,526 ± 869 mL; p < 0.001) in the experimental group from baseline, while there were no differences in osmolality (-74.7 ± 572 mOsm; p = 0.45), or urine volume (-32 ± 1,376 mL; p = 0.89) in the control group. However, there were no changes in BV (Fig. 1a) or changes in TBW (Fig. 1b) in either group.

Conclusions: Increasing fluid intake in individuals with habitually low TWI increases 24-h urine volume and decreases urine osmolality but does not result in changes in TBW or BV. These findings are in agreement with previous work indicating that TWI interventions lasting 3 days [2] to 4 weeks [3] do not result in changes in TBW. Current evidence would suggest that the benefits of increasing TWI are not related changes in TBW.
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http://dx.doi.org/10.1159/000515375DOI Listing
October 2021

animalcules: interactive microbiome analytics and visualization in R.

Microbiome 2021 03 28;9(1):76. Epub 2021 Mar 28.

Section of Computational Biomedicine, Boston University School of Medicine, Boston, MA, USA.

Background: Microbial communities that live in and on the human body play a vital role in health and disease. Recent advances in sequencing technologies have enabled the study of microbial communities at unprecedented resolution. However, these advances in data generation have presented novel challenges to researchers attempting to analyze and visualize these data.

Results: To address some of these challenges, we have developed animalcules, an easy-to-use interactive microbiome analysis toolkit for 16S rRNA sequencing data, shotgun DNA metagenomics data, and RNA-based metatranscriptomics profiling data. This toolkit combines novel and existing analytics, visualization methods, and machine learning models. For example, the toolkit features traditional microbiome analyses such as alpha/beta diversity and differential abundance analysis, combined with new methods for biomarker identification are. In addition, animalcules provides interactive and dynamic figures that enable users to understand their data and discover new insights. animalcules can be used as a standalone command-line R package or users can explore their data with the accompanying interactive R Shiny interface.

Conclusions: We present animalcules, an R package for interactive microbiome analysis through either an interactive interface facilitated by R Shiny or various command-line functions. It is the first microbiome analysis toolkit that supports the analysis of all 16S rRNA, DNA-based shotgun metagenomics, and RNA-sequencing based metatranscriptomics datasets. animalcules can be freely downloaded from GitHub at https://github.com/compbiomed/animalcules or installed through Bioconductor at https://www.bioconductor.org/packages/release/bioc/html/animalcules.html . Video abstract.
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http://dx.doi.org/10.1186/s40168-021-01013-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006385PMC
March 2021

NaCl and KCl mediate log increase in AAV vector particles and infectious titers in a specific/timely manner with the HSV platform.

Mol Ther Methods Clin Dev 2021 Jun 24;21:1-13. Epub 2021 Feb 24.

Department of Pediatrics, Powell Gene Therapy Center, University of Florida, 1200 Newell Drive, Academic Research Building, RG-187, Gainesville, FL 32610, USA.

The increasing demand for adeno-associated virus (AAV) vectors, a result from the surging interest for their potential to cure human genetic diseases by gene transfer, tumbled on low-performing production systems. Innovative improvements to increase both yield and quality of the vector produced have become a priority undertaking in the field. In a previous study, we showed that adding a specific concentration of sodium chloride (NaCl) to the production medium resulted in a dramatic increase of AAV vector particle and infectious titers when using the herpes simplex virus (HSV) production system, both in adherent or suspension platforms. In this work, we studied additional salts and their impact on AAV vector production. We found that potassium chloride (KCl), or a combination of KCl and NaCl, resulted in the highest increase in AAV vector production. We determined that the salt-mediated effect was the most impactful when the salt was present between 8 and approximately 16 h post-infection, with the highest rate increase occurring within the first 24 h of the production cycle. We showed that the AAV vector yield increase did not result from an increase in cell growth, size, or viability. Furthermore, we demonstrated that the impact on AAV vector production was specifically mediated by NaCl and KCl independently of their impact on the osmolality of the production media. Our findings convincingly showed that NaCl and KCl were uniquely efficacious to promote up to a 10-fold increase in the production of highly infectious AAV vectors when produced in the presence of HSV. We think that this study will provide unique and important new insights in AAV biology toward the establishment of more successful production protocols.
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http://dx.doi.org/10.1016/j.omtm.2021.02.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960503PMC
June 2021

Eleventh Annual Hydration for Health Scientific Conference: From Water Resources to Metabolic Health and Drinking Behavior.

Ann Nutr Metab 2020 24;76 Suppl 1:1-3. Epub 2021 Mar 24.

Freelance Dietitian, London, United Kingdom,

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http://dx.doi.org/10.1159/000515017DOI Listing
October 2021

Tophaceous gout of the atlantoaxial joint: a case report.

J Med Case Rep 2021 Feb 15;15(1):74. Epub 2021 Feb 15.

Department of Orthopaedic Surgery, Orlando VA Medical Center, Orlando, FL, 32827, USA.

Background: To report the occurrence of tophaceous gout in the cervical spine and to review the literature on spinal gout.

Case Presentation: This report details the occurrence of a large and clinically significant finding of tophaceous gout in the atlantoaxial joint of the cervical spine in an 82-year-old Caucasian man with a 40-year history of crystal-proven gout and a 3-month history of new-onset progressive myelopathy. The patient's American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria score was 15.0.

Conclusion: Spinal gout is more common than previously thought, and it should be considered in patients who present with symptoms of myelopathy. Diagnosis can be made without a tissue sample of the affected joint(s) with tools like the ACR/EULAR criteria and the use of the "diagnostic clinical rule" for determining the likelihood of gout. Early conservative management with neck immobilization and medical management can avoid the need for surgical intervention.
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http://dx.doi.org/10.1186/s13256-020-02638-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885401PMC
February 2021

Comparing tuberculosis gene signatures in malnourished individuals using the TBSignatureProfiler.

BMC Infect Dis 2021 Jan 22;21(1):106. Epub 2021 Jan 22.

Boston Medical Center, Boston, MA, USA.

Background: Gene expression signatures have been used as biomarkers of tuberculosis (TB) risk and outcomes. Platforms are needed to simplify access to these signatures and determine their validity in the setting of comorbidities. We developed a computational profiling platform of TB signature gene sets and characterized the diagnostic ability of existing signature gene sets to differentiate active TB from LTBI in the setting of malnutrition.

Methods: We curated 45 existing TB-related signature gene sets and developed our TBSignatureProfiler software toolkit that estimates gene set activity using multiple enrichment methods and allows visualization of single- and multi-pathway results. The TBSignatureProfiler software is available through Bioconductor and on GitHub. For evaluation in malnutrition, we used whole blood gene expression profiling from 23 severely malnourished Indian individuals with TB and 15 severely malnourished household contacts with latent TB infection (LTBI). Severe malnutrition was defined as body mass index (BMI) < 16 kg/m2 in adults and based on weight-for-height Z scores in children < 18 years. Gene expression was measured using RNA-sequencing.

Results: The comparison and visualization functions from the TBSignatureProfiler showed that TB gene sets performed well in malnourished individuals; 40 gene sets had statistically significant discriminative power for differentiating TB from LTBI, with area under the curve ranging from 0.662-0.989. Three gene sets were not significantly predictive.

Conclusion: Our TBSignatureProfiler is a highly effective and user-friendly platform for applying and comparing published TB signature gene sets. Using this platform, we found that existing gene sets for TB function effectively in the setting of malnutrition, although differences in gene set applicability exist. RNA-sequencing gene sets should consider comorbidities and potential effects on diagnostic performance.
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http://dx.doi.org/10.1186/s12879-020-05598-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821401PMC
January 2021

Combining urine color and void number to assess hydration in adults and children.

Eur J Clin Nutr 2021 08 18;75(8):1262-1266. Epub 2021 Jan 18.

Hydration Science Lab, College of Health Solutions, Arizona State University, Phoenix, AZ, USA.

Background/objectives: To test the diagnostic ability of two combined practical markers for elevated urine osmolality (underhydration) in free-living adults and children.

Subjects/methods: One hundred and one healthy adults (females n = 52, 40 ± 14 y, 1.70 ± 0.95 m, 76.7 ± 17.4 kg, 26.5 ± 5.5 kg/m) and 210 children (females = 105, 1.49 ± 0.13 m, 43.4 ± 12.6 kg, 19.2 ± 3.2 kg m) collected urine for 24-h. Urine was analyzed for urine osmolality (UOsm), color (UC), while the number of voids (void) was also recorded. Receiver Operating Characteristic (ROC) analysis was performed for UC, void, and combination of UC and void, to determine markers' diagnostic ability for detecting underhydration based on elevated UOsm (UOsm ≥ 800 mmol kg).

Results: Linear regression analysis revealed that UC was significantly associated with UOsm in both adults (R = 0.38; P < 0.001) and children (R = 0.45; P < 0.001). Void was significantly associated with UOsm in both adults (R = 0.13; P < 0.001) and children (R = 0.15; P < 0.001). In adults, when UC > 3 and void <7 were combined, the overall diagnostic ability for underhydration was 97% with sensitivity and specificity of 100% and 88%, respectively. In children, UC > 3 and void <5 had an overall diagnostic ability for underhydration of 89% with sensitivity and specificity of 100% and 62%, respectively.

Conclusions: Urine color alone and the combination of urine color with void number can a valid and simple field-measure to detect underhydration based on elevated urine osmolality.
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http://dx.doi.org/10.1038/s41430-020-00834-wDOI Listing
August 2021

Systematic evaluation of transcriptomic disease risk and diagnostic biomarker overlap between COVID-19 and tuberculosis: a patient-level meta-analysis.

medRxiv 2020 Nov 26. Epub 2020 Nov 26.

Background: The novel coronavirus, SARS-CoV-2, has increased the burden on healthcare systems already strained by a high incidence of tuberculosis (TB) as co-infection and dual presentation are occurring in syndemic settings. We aimed to understand the interaction between these diseases by profiling COVID-19 gene expression signatures on RNA-sequencing data from TB-infected individuals.

Methods: We performed a systematic review and patient-level meta-analysis by querying PubMed and pre-print servers to derive eligible COVID-19 gene expression signatures from human whole blood (WB), PBMCs or BALF studies. A WB influenza dataset served as a control respiratory disease signature. Three large TB RNA-seq datasets, comprising multiple cohorts from the UK and Africa and consisting of TB patients across the disease spectrum, were chosen to profile these signatures. Putative "COVID-19 risk scores" were generated for each sample in the TB datasets using the TBSignatureProfiler package. Risk was stratified by time to TB diagnosis in progressors and contacts of pulmonary and extra-pulmonary TB. An integrative analysis between TB and COVID-19 single-cell RNA-seq data was performed and a population-level meta-analysis was conducted to identify shared gene ontologies between the diseases and their relative enrichment in COVID-19 disease severity states.

Results: 35 COVID-19 gene signatures from nine eligible studies comprising 98 samples were profiled on TB RNA-seq data from 1181 samples from 853 individuals. 25 signatures had significantly higher COVID-19 risk in active TB (ATB) compared with latent TB infection (p <0·005), 13 of which were validated in two independent datasets. - and -expressing macrophages enriched in BALF during severe COVID-19 were identified in circulation during ATB. Shared perturbed ontologies included antigen presentation, epigenetic regulation, platelet activation, and ROS/RNS production were enriched with increasing COVID-19 severity. Finally, we demonstrate that the overlapping transcriptional responses may complicate development of blood-based diagnostic signatures of co-infection.

Interpretation: Our results identify shared dysregulation of immune responses in COVID-19 and TB as a dual risk posed by co-infection to COVID-19 severity and TB disease progression. These individuals should be followed up for TB in the months subsequent to SARS-CoV-2 diagnosis.
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http://dx.doi.org/10.1101/2020.11.25.20236646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709192PMC
November 2020

Robustifying genomic classifiers to batch effects via ensemble learning.

Bioinformatics 2021 07;37(11):1521-1527

Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

Motivation: Genomic data are often produced in batches due to practical restrictions, which may lead to unwanted variation in data caused by discrepancies across batches. Such 'batch effects' often have negative impact on downstream biological analysis and need careful consideration. In practice, batch effects are usually addressed by specifically designed software, which merge the data from different batches, then estimate batch effects and remove them from the data. Here, we focus on classification and prediction problems, and propose a different strategy based on ensemble learning. We first develop prediction models within each batch, then integrate them through ensemble weighting methods.

Results: We provide a systematic comparison between these two strategies using studies targeting diverse populations infected with tuberculosis. In one study, we simulated increasing levels of heterogeneity across random subsets of the study, which we treat as simulated batches. We then use the two methods to develop a genomic classifier for the binary indicator of disease status. We evaluate the accuracy of prediction in another independent study targeting a different population cohort. We observed that in independent validation, while merging followed by batch adjustment provides better discrimination at low level of heterogeneity, our ensemble learning strategy achieves more robust performance, especially at high severity of batch effects. These observations provide practical guidelines for handling batch effects in the development and evaluation of genomic classifiers.

Availability And Implementation: The data underlying this article are available in the article and in its online supplementary material. Processed data is available in the Github repository with implementation code, at https://github.com/zhangyuqing/bea_ensemble.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btaa986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485848PMC
July 2021

A realism-based approach to an ontological representation of symbiotic interactions.

BMC Med Inform Decis Mak 2020 10 8;20(1):258. Epub 2020 Oct 8.

Department of Health Outcomes and Biomedical Informatics, University of Florida, Gainesville, FL, USA.

Background: The symbiotic interactions that occur between humans and organisms in our environment have a tremendous impact on our health. Recently, there has been a surge in interest in understanding the complex relationships between the microbiome and human health and host immunity against microbial pathogens, among other things. To collect and manage data about these interactions and their complexity, scientists will need ontologies that represent symbiotic interactions as they occur in reality.

Methods: We began with two papers that reviewed the usage of 'symbiosis' and related terms in the biology and ecology literature and prominent textbooks. We then analyzed several prominent standard terminologies and ontologies that contain representations of symbiotic interactions, to determine if they appropriately defined 'symbiosis' and related terms according to current scientific usage as identified by the review papers. In the process, we identified several subtypes of symbiotic interactions, as well as the characteristics that differentiate them, which we used to propose textual and axiomatic definitions for each subtype of interaction. To both illustrate how to use the ontological representations and definitions we created and provide additional quality assurance on key definitions, we carried out a referent tracking analysis and representation of three scenarios involving symbiotic interactions among organisms.

Results: We found one definition of 'symbiosis' in an existing ontology that was consistent with the vast preponderance of scientific usage in biology and ecology. However, that ontology changed its definition during the course of our work, and discussions are ongoing. We present a new definition that we have proposed. We also define 34 subtypes of symbiosis. Our referent tracking analysis showed that it is necessary to define symbiotic interactions at the level of the individual, rather than at the species level, due to the complex nature in which organisms can go from participating in one type of symbiosis with one organism to participating in another type of symbiosis with a different organism.

Conclusion: As a result of our efforts here, we have developed a robust representation of symbiotic interactions using a realism-based approach, which fills a gap in existing biomedical ontologies.
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http://dx.doi.org/10.1186/s12911-020-01273-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542735PMC
October 2020

: batch effect adjustment for RNA-seq count data.

NAR Genom Bioinform 2020 Sep 21;2(3):lqaa078. Epub 2020 Sep 21.

Division of Computational Biomedicine, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA.

The benefit of integrating batches of genomic data to increase statistical power is often hindered by batch effects, or unwanted variation in data caused by differences in technical factors across batches. It is therefore critical to effectively address batch effects in genomic data to overcome these challenges. Many existing methods for batch effects adjustment assume the data follow a continuous, bell-shaped Gaussian distribution. However in RNA-seq studies the data are typically skewed, over-dispersed counts, so this assumption is not appropriate and may lead to erroneous results. Negative binomial regression models have been used previously to better capture the properties of counts. We developed a batch correction method, ComBat-seq, using a negative binomial regression model that retains the integer nature of count data in RNA-seq studies, making the batch adjusted data compatible with common differential expression software packages that require integer counts. We show in realistic simulations that the ComBat-seq adjusted data results in better statistical power and control of false positives in differential expression compared to data adjusted by the other available methods. We further demonstrated in a real data example that ComBat-seq successfully removes batch effects and recovers the biological signal in the data.
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http://dx.doi.org/10.1093/nargab/lqaa078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518324PMC
September 2020

Electrolyte Beverage Intake to Promote Hydration and Maintain Kidney Function in Guatemalan Sugarcane Workers Laboring in Hot Conditions.

J Occup Environ Med 2020 12;62(12):e696-e703

Center for Health, Work, & Environment (Ms Krisher, Dr Butler-Dawson, Ms Dally, Ms Jaramillo, Dr Newman); Colorado Consortium on Climate Change and Human Health (Ms Krisher, Dr Butler-Dawson, Ms Dally, Ms Jaramillo, Dr Newman); Department of Environmental and Occupational Health (Ms Krisher, Dr Butler-Dawson, Ms Dally, Dr Newman), Colorado School of Public Health, University of Colorado Denver, Anschutz Medical Campus; Division of Kinesiology & Health, University of Wyoming, Laramie, Wyoming (Ms Yoder, Dr Johnson); Pantaleon, Guatemala (Dr Pilloni, Dr Cruz, Dr Asensio); Department of Epidemiology, Colorado School of Public Health (Dr Newman); Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, School of Medicine (Dr Newman), University of Colorado Denver, Aurora, Colorado.

Objectives: To evaluate impact of electrolyte supplementation on hydration status and health outcomes in Guatemalan agricultural workers performing heavy work under hot climatic conditions.

Methods: A 3-week pragmatic trial was conducted with a group of 50 workers during the 2017 to 2018 sugarcane harvest. Workers received an electrolyte hydration intervention during 2 of the 3 weeks. Blood and urine samples were collected each week.

Results: Increased electrolyte intake resulted in less muscle injury. Kidney function was maintained across the intervention period. Workers were adequately hydrated and average electrolyte levels remained in normal ranges. Mild indications of hyponatremia occurred at higher levels of fluid intake.

Conclusions: This trial demonstrates the feasibility of maintaining workers' electrolyte levels under extremely hot and humid conditions while mitigating muscle injury. Electrolyte supplementation should be added to standard workplace water, rest, and shade interventions to protect workers.
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http://dx.doi.org/10.1097/JOM.0000000000002033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720870PMC
December 2020

Assessment of the Effect of Thermotherapy on ' Liberibacter asiaticus' Viability in Woody Tissue of Citrus via Graft-Based Assays and RNA Assays.

Phytopathology 2021 May 19;111(5):808-818. Epub 2021 Apr 19.

Plant Pathology Department, Citrus Research and Education Center, University of Florida, 700 Experiment Station Road, Lake Alfred, FL 33850.

In 2019, citrus production in Florida declined by more than 70%, mostly because of Huanglongbing (HLB), which is caused by the bacterium ' Liberibacter asiaticus' (CLas). Thermotherapy for HLB-affected trees was proposed as a short-term management solution to maintain field productivity. It was hypothesized that thermotherapy could eliminate HLB from affected branches; therefore, the study objectives were to show which time-temperature combinations eliminated CLas from woody tissues. Hardening, rounded Valencia twigs collected from HLB-affected field trees were treated in a steam chamber at different time-temperature combinations (50°C for 60 s; 55°C for 0, 30, 60, 90, and 120 s; 60°C for 30 s; and an untreated control). Three independent repetitions of 13 branches per treatment were grafted onto healthy rootstocks and tested to detect CLas after 6, 9, and 12 months. For the RNA-based CLas viability assay, three branches per treatment were treated and bark samples were peeled for RNA extraction and subsequent gene expression analyses. During the grafting study, at 12 months after grafting, a very low frequency of trees grafted with twigs treated at 55°C for 90 s and 55°C for 120 s had detectable CLas DNA. In the few individuals with CLas, titers were significantly lower ( ≤ 0.0001) and could have been remnants of degrading DNA. Additionally, there was a significant decrease ( ≤ 0.0001) in CLas 16S rRNA expression at 55°C for 90 s, 55°C for 120 s, and 60°C for 30 s (3.4-fold change, 3.4-fold change, and 2.3-fold change, respectively) in samples 5 days after treatment. Heat injury, not total CLas kill, could explain the limited changes in transcriptional activity; however, failed recovery and eventual death of CLas resulted in no CLas detection in most of the grafted trees treated with the highest temperatures or longest durations.
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http://dx.doi.org/10.1094/PHYTO-04-20-0152-RDOI Listing
May 2021

Exploring changes in the human gut microbiota and microbial-derived metabolites in response to diets enriched in simple, refined, or unrefined carbohydrate-containing foods: a post hoc analysis of a randomized clinical trial.

Am J Clin Nutr 2020 12;112(6):1631-1641

Cardiovascular Nutrition, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.

Background: Dietary carbohydrate type may influence cardiometabolic risk through alterations in the gut microbiome and microbial-derived metabolites, but evidence is limited.

Objectives: We explored the relative effects of an isocaloric exchange of dietary simple, refined, and unrefined carbohydrate on gut microbiota composition/function, and selected microbial metabolite concentrations.

Methods: Participants [n = 11; age: 65 ± 8 y; BMI (in kg/m2): 29.8 ± 3.2] were provided with each of 3 diets for 4.5 wk with 2-wk washout, according to a randomized, crossover design. Diets [60% of energy (%E) carbohydrate, 15%E protein, and 25%E fat] differed in type of carbohydrate. Fecal microbial composition, metatranscriptomics, and microbial-derived SCFA and secondary bile acid (SBA) concentrations were assessed at the end of each phase and associated with cardiometabolic risk factors (CMRFs).

Results: Roseburia abundance was higher (11% compared with 5%) and fecal SBA concentrations were lower (lithocolic acid -50% and deoxycholic acid -64%) after consumption of the unrefined carbohydrate diet relative to the simple carbohydrate diet [false discovery rate (FDR): all P < 0.05), whereas Anaerostipes abundance was higher (0.35% compared with 0.12%; FDR: P = 0.04) after the simple carbohydrate diet relative to the refined carbohydrate diet. Metatranscriptomics indicated upregulation of 2 cellular stress genes (FDR: P < 0.1) after the unrefined carbohydrate diet compared with the simple carbohydrate or refined carbohydrate diets. The microbial expression of 3 cellular/oxidative stress and immune response genes was higher (FDR: P < 0.1) after the simple carbohydrate diet relative to the refined carbohydrate diet. No significant diet effect was observed in fecal SCFA concentrations. Independent of diet, we observed 16 associations (all FDR: P < 0.1) of taxon abundance (15 phylum and 1 genera) with serum inflammatory markers and also with fecal SCFA and SBA concentrations.

Conclusions: Consuming an unrefined carbohydrate-rich diet had a modest effect on the gut microbiome and SBAs, resulting in favorable associations with selected CMRFs. Simple carbohydrate- and refined carbohydrate-rich diets have distinctive effects on the gut microbiome, suggesting differential mechanisms mediate their effects on cardiometabolic health. This trial was registered at clinicaltrials.gov as NCT01610661.
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http://dx.doi.org/10.1093/ajcn/nqaa254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727488PMC
December 2020

Evaluation of computational methods for human microbiome analysis using simulated data.

PeerJ 2020 11;8:e9688. Epub 2020 Aug 11.

Center for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile.

Background: Our understanding of the composition, function, and health implications of human microbiota has been advanced by high-throughput sequencing and the development of new genomic analyses. However, trade-offs among alternative strategies for the acquisition and analysis of sequence data remain understudied.

Methods: We assessed eight popular taxonomic profiling pipelines; MetaPhlAn2, metaMix, PathoScope 2.0, Sigma, Kraken, ConStrains, Centrifuge and Taxator-tk, against a battery of metagenomic datasets simulated from real data. The metagenomic datasets were modeled on 426 complete or permanent draft genomes stored in the Human Oral Microbiome Database and were designed to simulate various experimental conditions, both in the design of a putative experiment; read length (75-1,000 bp reads), sequence depth (100K-10M), and in metagenomic composition; number of species present (10, 100, 426), species distribution. The sensitivity and specificity of each of the pipelines under various scenarios were measured. We also estimated the relative root mean square error and average relative error to assess the abundance estimates produced by different methods. Additional datasets were generated for five of the pipelines to simulate the presence within a metagenome of an unreferenced species, closely related to other referenced species. Additional datasets were also generated in order to measure computational time on datasets of ever-increasing sequencing depth (up to 6 × 10).

Results: Testing of eight pipelines against 144 simulated metagenomic datasets initially produced 1,104 discrete results. Pipelines using a marker gene strategy; MetaPhlAn2 and ConStrains, were overall less sensitive, than other pipelines; with the notable exception of Taxator-tk. This difference in sensitivity was largely made up in terms of runtime, significantly lower than more sensitive pipelines that rely on whole-genome alignments such as PathoScope2.0. However, pipelines that used strategies to speed-up alignment between genomic references and metagenomic reads, such as kmerization, were able to combine both high sensitivity and low run time, as is the case with Kraken and Centrifuge. Absent species genomes in the database mostly led to assignment of reads to the most closely related species available in all pipelines. Our results therefore suggest that taxonomic profilers that use kmerization have largely superseded those that use gene markers, coupling low run times with high sensitivity and specificity. Taxonomic profilers using more time-consuming read reassignment, such as PathoScope 2.0, provided the most sensitive profiles under common metagenomic sequencing scenarios. All the results described and discussed in this paper can be visualized using the dedicated R Shiny application (https://github.com/microgenomics/HumanMicrobiomeAnalysis). All of our datasets, pipelines and results are made available through the GitHub repository for future benchmarking.
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http://dx.doi.org/10.7717/peerj.9688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427543PMC
August 2020

Zinkicide Is a ZnO-Based Nanoformulation with Bactericidal Activity against Liberibacter crescens in Batch Cultures and in Microfluidic Chambers Simulating Plant Vascular Systems.

Appl Environ Microbiol 2020 08 3;86(16). Epub 2020 Aug 3.

Department of Entomology and Plant Pathology, Auburn University, Auburn, Alabama, USA

Phloem-limited bacterial " Liberibacter" species are associated with incurable plant diseases worldwide. Antimicrobial treatments for these pathogens are challenging due to the difficulty of reaching the vascular tissue they occupy at bactericidal concentrations. Here, antimicrobial mechanisms of Zinkicide TMN110 (ZnK), a nonphytotoxic zinc oxide (ZnO)-based nanoformulation, were compared to those of bulk ZnO (b-ZnO) using as a model the only culturable species of the genus, Minimum bactericidal concentration (MBC) determination and time-kill assays showed that ZnK has a bactericidal effect against , whereas b-ZnO is bacteriostatic. When ZnK was used at the MBC (150 ppm), its antimicrobial mechanisms included an increase in Zn solubility, generation of intracellular reactive oxygen species, lipid peroxidation, and cell membrane disruption; all of these were of greater intensity than those of b-ZnO. Inhibition of biofilms, which are important during insect vector colonization, was stronger by ZnK than by b-ZnO at concentrations between 2.5 and 10 ppm in batch cultures; however, neither ZnK nor b-ZnO removed preformed biofilms when applied between 100 and 400 ppm. In microfluidic chambers simulating source-to-sink phloem movement, ZnK significantly outperformed b-ZnO in Zn mobilization and bactericidal activity against planktonic cells in sink reservoirs. In microfluidic chamber assays assessing antibiofilm activity, ZnK displayed a significantly enhanced bactericidal activity against individual attached cells as well as preformed biofilms compared to that of b-ZnO. The superior mobility and antimicrobial activity of ZnK in microenvironments make this formulation a promising product to control plant diseases caused by " Liberibacter" species and other plant vascular pathogens. " Liberibacter" species are associated with incurable plant diseases that have caused billions of dollars of losses for United States and world agriculture. Chemical control of these pathogens is complicated, because their life cycle combines intracellular vascular stages in plant hosts with transmission by highly mobile insect vectors. To date, " Liberibacter" species are mostly unculturable, except for , a member of the genus that has been used as a model for assays. Here, we evaluated the potential of Zinkicide (ZnK) as an antimicrobial against " Liberibacter" species in batch cultures and under flow conditions, using as a biological model. ZnK displayed bactericidal activity against in batch cultures and showed increased mobility and bactericidal activity in microfluidic devices resembling " Liberibacter" species natural habitats. ZnK performance observed here against makes this compound a promising candidate to control plant diseases caused by vascular pathogens.
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http://dx.doi.org/10.1128/AEM.00788-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414956PMC
August 2020

Leclercia adecarboxylata: An Emerging Pathogen Among Pediatric Infections.

Cureus 2020 May 10;12(5):e8049. Epub 2020 May 10.

Inpatient Pediatrics, Nemours Children's Hospital, Orlando, USA.

is a gram-negative bacillus of the Enterobacteriaceae family. It is a rare human pathogen that is often acquired via wound and/or contact with aquatic environment. Although multiple cases of infections are described in the adult population, few have been documented in pediatrics. We will present two cases of infections in the pediatric population. The first is a case of cellulitis in an 11-year-old male patient after a penetrating wound. The second is a first-documented urinary tract infection in a 16-year-old male patient with chronic kidney disease. Both patients were successfully treated with antibiotics and surgical intervention, if necessary. These cases highlight the growing emergence of this bacterium in the pediatric population and the need to become more aware of its threat even in patients who are immunocompetent.
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http://dx.doi.org/10.7759/cureus.8049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286590PMC
May 2020

Impact of Nutrient Intake on Hydration Biomarkers Following Exercise and Rehydration Using a Clustering-Based Approach.

Nutrients 2020 Apr 30;12(5). Epub 2020 Apr 30.

University of Connecticut, Storrs, CT 06269, USA.

We investigated the impact of nutrient intake on hydration biomarkers in cyclists before and after a 161 km ride, including one hour after a 650 mL water bolus consumed post-ride. To control for multicollinearity, we chose a clustering-based, machine learning statistical approach. Five hydration biomarkers (urine color, urine specific gravity, plasma osmolality, plasma copeptin, and body mass change) were configured as raw- and percent change. Linear regressions were used to test for associations between hydration markers and eight predictor terms derived from 19 nutrients merged into a reduced-dimensionality dataset through serial k-means clustering. Most predictor groups showed significant association with at least one hydration biomarker: 1) Glycemic Load + Carbohydrates + Sodium, 2) Protein + Fat + Zinc, 3) Magnesium + Calcium, 4) Pinitol, 5) Caffeine, 6) Fiber + Betaine, and 7) Water; potassium + three polyols, and mannitol + sorbitol showed no significant associations with any hydration biomarker. All five hydration biomarkers were associated with at least one nutrient predictor in at least one configuration. We conclude that in a real-life scenario, some nutrients may serve as mediators of body water, and urine-specific hydration biomarkers may be more responsive to nutrient intake than measures derived from plasma or body mass.
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http://dx.doi.org/10.3390/nu12051276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282025PMC
April 2020

Infection of Citrus Leaves and Host Defense Activation Compared to Root Infection.

Phytopathology 2020 Aug 11;110(8):1437-1448. Epub 2020 Jun 11.

Citrus Research and Education Center, University of Florida, 700 Experiment Station Road, Lake Alfred, FL, U.S.A.

Currently, little is known about the host pathogen interaction between spp. and citrus roots versus leaves. Therefore, we compared the molecular events occurring in citrus roots and leaves after zoospore inoculation with . We analyzed the physical characteristics and genetic responses to infection of leaves and roots for susceptible and tolerant citrus rootstocks to examine the potential for leaves to model root responses to infection. Leaves responded faster and stronger to infection than roots, and leaves showed greater differential response than roots. In addition to differences in hormonal responses, sugar, phospholipase D (PLD), and phospholipase A (PLA) involvement in the interaction between citrus and was identified. This work, for the first time, creates a solid zoospore infection protocol, reports infection on citrus leaves through stomata, and provides evidence that different host organs respond to the pathogen differentially in timing and magnitude. This work identifies the hormones, sugars, pathogenesis-related genes, PLDs, and PLAs that are involved in the molecular events occurring in citrus under infection of zoospore, and advances our understanding of the mechanisms underlying the interaction.
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http://dx.doi.org/10.1094/PHYTO-09-19-0343-RDOI Listing
August 2020

Malignant Hidradenocarcinoma of the Axilla.

Cureus 2020 Feb 24;12(2):e7091. Epub 2020 Feb 24.

Surgery, Flagler Hospital, St. Augustine, USA.

Malignant hidradenocarcinoma is a very rare and highly aggressive primary skin neoplasm that arises in the eccrine sweat glands. Diagnosis is typically made with histopathological evaluation after excisional biopsy. Reports of this tumor are scarce in the literature, thus making its characterization and management particularly challenging. A 71-year-old male presented in the clinic with swelling of the left lateral axilla on routine dermatological examination. Clinically, the lesion was suspected to be a capillary hemangioma. Upon surgical excision, the specimen was diagnosed as malignant hidradenocarcinoma based on histological characterization with immunohistochemical staining. Subsequent wide excision with sentinel lymph node biopsy was performed, which came back negative for residual tumor and metastasis. Due to the low incidence of this cancer and the markedly poor prognosis, accurate diagnosis of these tumors is highly important. Wide excisional biopsy and sentinel lymph node biopsy appear to be the most common initial treatment plans based on the available literature. With high rates of recurrence and metastasis, there remains the need to characterize effective adjuvant therapy for the post-operative management of hidradenocarcinoma.
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http://dx.doi.org/10.7759/cureus.7091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096074PMC
February 2020
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