Publications by authors named "Jennifer Anderson"

341 Publications

Transparency in risk-disproportionate regulation of modern crop-breeding techniques.

GM Crops Food 2021 Jan;12(1):376-381

Global Academy of Agriculture and Food Security, the University of Edinburgh, Midlothian, UK.

Despite over 25 years of safe deployment of genetically engineered crops, the number, complexity, and scope of regulatory studies required for global approvals continue to increase devoid of adequate scientific justification. Recently, there have been calls to further expand the scope of study and data requirements to improve public acceptance. However, increased regulation can actually generate consumer distrust due to the misperception that risks are high. We believe risk-disproportionate regulation as a means to advocate for acceptance of technology is counterproductive, even though some regulatory authorities believe it part of their mandate. To help avoid public distrust, the concept of regulatory transparency to demystify regulatory decision-making should be extended to clearly justifying specific regulatory requirements as: 1) risk-driven (i.e., proportionately addressing increased risk compared with traditional breeding), or 2) advocacy-driven (i.e., primarily addressing consumer concerns and acceptance). Such transparency in the motivation for requiring risk-disproportionate studies would: 1) lessen over-prescriptive regulation, 2) save public and private resources, 3) make beneficial products and technologies available to society sooner, 4) reduce needless animal sacrifice, 5) improve regulatory decision-making regarding safety, and 6) lessen public distrust that is generated by risk-disproportionate regulation.
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http://dx.doi.org/10.1080/21645698.2021.1934353DOI Listing
January 2021

Clinically Actionable Findings Derived From Predictive Genomic Testing Offered in a Medical Practice Setting.

Mayo Clin Proc 2021 06 21;96(6):1407-1417. Epub 2020 Oct 21.

Center for Individualized Medicine, Mayo Clinic, Rochester, MN; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN. Electronic address:

Objective: To assess the presence of clinically actionable results and other genetic findings in an otherwise healthy population of adults seen in a medical practice setting and offered "predictive" genomic testing.

Patients And Methods: In 2014, a predictive genomics clinic for generally healthy adults was launched through the Mayo Clinic Executive Health Program. Self-identified interested patients met with a genomic nurse and genetic counselor for pretest advice and education. Two genome sequencing platforms and one gene panel-based health screen were offered. Posttest genetic counseling was available for patients who elected testing. From March 1, 2014, through June 1, 2019, 1281 patients were seen and 301 (23.5%) chose testing. Uptake rates increased to 36.3% [70 of 193]) in 2019 from 11.8% [2 of 17] in 2014. Clinically actionable results and genetic findings were analyzed using descriptive statistics.

Results: Clinically actionable results were detected in 11.6% of patients (35 of 301), and of those, 51.7% (15 of 29) with a cancer or cardiovascular result = did not have a personal or family history concerning for a hereditary disorder. The most common actionable results were in the BCHE, BRCA2, CHEK2, LDLR, MUTYH, and MYH7 genes. A carrier of at least one recessive condition was found in 53.8% of patients (162 of 301). At least one variant associated with multifactorial disease was found in 44.5% (134 of 301) (eg, 25 patients were heterozygous for the F5 factor V Leiden variant associated with thrombophilia risk).

Conclusion: Our predictive screening revealed that 11.6% of individuals will test positive for a clinically actionable, likely pathogenic/pathogenic variant. This finding suggests that wider knowledge and adoption of predictive genomic services could be beneficial in medical practice, although additional studies are needed.
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http://dx.doi.org/10.1016/j.mayocp.2020.08.051DOI Listing
June 2021

Clinical presentation and autonomic profile in Ross syndrome.

J Neurol 2021 Apr 3. Epub 2021 Apr 3.

Department of Neurology, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA.

Background: Ross syndrome is a rare disorder characterized by tonic pupils, hyporeflexia, and segmental anhidrosis. We sought to characterize the clinical presentation, associated autoimmune disorders, and autonomic profile in patients with Ross syndrome to further elucidate its pathophysiology.

Methods: We performed a retrospective chart review of all patients who underwent a thermoregulatory sweat test (TST) between 1998 and 2020 and had confirmation of the diagnosis of Ross syndrome by an autonomic disorders specialist. Standardized autonomic reflex testing was reviewed when available.

Results: Twenty-six patients with Ross syndrome were identified. The most common initial reported manifestation was an abnormal segmental sweating response in 16 patients (described as hyperhidrosis in 12 patients and anhidrosis in 4 patients) while a tonic pupil was the initial manifestation in 10 patients. Other commonly reported symptoms included fatigue, chronic cough, and increased urinary frequency. An associated autoimmune disorder was identified in one patient. Positive autoantibodies were found in a minority of patients often with unclear clinical significance. Distributions of anhidrosis encountered were segmental (n = 15), widespread (n = 7), and global (n = 4). Well-circumscribed small areas of preserved sweating within areas of anhidrosis were observed in the majority of patients (88.5%). Anhidrosis progressed slowly over time and sudomotor dysfunction was predominantly (post)ganglionic. Cardiovagal and adrenergic functions were preserved in most patients.

Conclusions: The pattern of autonomic dysfunction in Ross syndrome is suggestive of a limited autonomic ganglioneuropathy. Sudomotor impairment is prominent and should be the focus of symptomatic management; however, clinicians should be aware of symptoms beyond the classic triad.
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http://dx.doi.org/10.1007/s00415-021-10531-8DOI Listing
April 2021

Otolaryngology Consult Protocols in the Setting of COVID-19: The University of Pittsburgh Approach.

Ann Otol Rhinol Laryngol 2021 Mar 29:34894211005937. Epub 2021 Mar 29.

Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Objective: To analyze trends in otolaryngology consultations and provide algorithms to guide management during the COVID-19 pandemic.

Methods: A retrospective cohort study at a single institution tertiary care hospital. A total of 95 otolaryngology consultations were performed from March 1, 2020 to April 26, 2020 (COVID-era) and 363 were performed from September 1, 2019 to February 29, 2020 (pre-COVID-era) at the UPMC Oakland campus. Data collected included patient demographics, COVID-19 status, reason for consult, location of consult, type of consult, procedures performed, need for surgical intervention, length of hospital stay and recommended follow up.

Results: Patient populations in the pre-COVID-era and COVID-era were similar in terms of their distribution of demographics and chief complaints. Craniofacial trauma was the most common reason for consultation in both periods, followed by vocal fold and airway-related consults. We saw a 21.5% decrease in the rate of consults seen per month during the COVID-era compared to the 6 months prior. Review of trends in the consult workflow allowed for development of several algorithms to safely approach otolaryngology consults during the COVID-19 pandemic.

Conclusions: Otolaryngology consultations provide valuable services to inpatients and patients in the emergency department ranging from evaluation of routine symptoms to critical airways. Systematic otolaryngology consult service modifications are required in order to reduce risk of exposure to healthcare providers while providing comprehensive patient care.
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http://dx.doi.org/10.1177/00034894211005937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010376PMC
March 2021

Direct Tissue PCR and Genotyping for Species Identification in a Case of Laryngeal Blastomycosis.

Ear Nose Throat J 2021 Mar 8:145561321991342. Epub 2021 Mar 8.

Integrated Research and Development Laboratory, Marshfield Clinic Research Institute, Marshfield Clinic Health System, Marshfield, WI, USA.

Otolaryngologic manifestations of infection with species are extremely rare and restricted geographically to recognized endemic regions. Here, we describe a case of laryngeal blastomycosis that presented as slowly progressive dysphonia. While a preliminary diagnosis was made using routine histopathology, a species identification of was made using polymerase chain reaction amplification and rapid genotyping without the need for fungal culture. All symptoms resolved following 1 month of antifungal therapy. Rapid molecular differentiation of from provides important insights into pathogenesis given recent recognition of differences in clinical spectra.
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http://dx.doi.org/10.1177/0145561321991342DOI Listing
March 2021

RADSex: A computational workflow to study sex determination using restriction site-associated DNA sequencing data.

Mol Ecol Resour 2021 Jul 9;21(5):1715-1731. Epub 2021 Mar 9.

Physiological Chemistry, Biocenter, University of Wuerzburg, Wuerzburg, Germany.

The study of sex determination and sex chromosome organization in nonmodel species has long been technically challenging, but new sequencing methodologies now enable precise and high-throughput identification of sex-specific genomic sequences. In particular, restriction site-associated DNA sequencing (RAD-Seq) is being extensively applied to explore sex determination systems in many plant and animal species. However, software specifically designed to search for and visualize sex-biased markers using RAD-Seq data is lacking. Here, we present RADSex, a computational analysis workflow designed to study the genetic basis of sex determination using RAD-Seq data. RADSex is simple to use, requires few computational resources, makes no prior assumptions about the type of sex-determination system or structure of the sex locus, and offers convenient visualization through a dedicated R package. To demonstrate the functionality of RADSex, we re-analysed a published data set of Japanese medaka, Oryzias latipes, where we uncovered a previously unknown Y chromosome polymorphism. We then used RADSex to analyse new RAD-Seq data sets from 15 fish species spanning multiple taxonomic orders. We identified the sex determination system and sex-specific markers in six of these species, five of which had no known sex-markers prior to this study. We show that RADSex greatly facilitates the study of sex determination systems in nonmodel species thanks to its speed of analyses, low resource usage, ease of application and visualization options. Furthermore, our analysis of new data sets from 15 species provides new insights on sex determination in fish.
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http://dx.doi.org/10.1111/1755-0998.13360DOI Listing
July 2021

Regenerative tissue filler for breast conserving surgery and other soft tissue restoration and reconstruction needs.

Sci Rep 2021 Feb 1;11(1):2711. Epub 2021 Feb 1.

Weldon School of Biomedical Engineering, College of Engineering, Purdue University, West Lafayette, IN, 47907, USA.

Complete removal of cancerous tissue and preservation of breast cosmesis with a single breast conserving surgery (BCS) is essential for surgeons. New and better options would allow them to more consistently achieve this goal and expand the number of women that receive this preferred therapy, while minimizing the need for re-excision and revision procedures or more aggressive surgical approaches (i.e., mastectomy). We have developed and evaluated a regenerative tissue filler that is applied as a liquid to defects during BCS prior to transitioning to a fibrillar collagen scaffold with soft tissue consistency. Using a porcine simulated BCS model, the collagen filler was shown to induce a regenerative healing response, characterized by rapid cellularization, vascularization, and progressive breast tissue neogenesis, including adipose tissue and mammary glands and ducts. Unlike conventional biomaterials, no foreign body response or inflammatory-mediated "active" biodegradation was observed. The collagen filler also did not compromise simulated surgical re-excision, radiography, or ultrasonography procedures, features that are important for clinical translation. When post-BCS radiation was applied, the collagen filler and its associated tissue response were largely similar to non-irradiated conditions; however, as expected, healing was modestly slower. This in situ scaffold-forming collagen is easy to apply, conforms to patient-specific defects, and regenerates complex soft tissues in the absence of inflammation. It has significant translational potential as the first regenerative tissue filler for BCS as well as other soft tissue restoration and reconstruction needs.
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http://dx.doi.org/10.1038/s41598-021-81771-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851166PMC
February 2021

Hypothesis-based food, feed, and environmental safety assessment of GM crops: A case study using maize event DP-202216-6.

GM Crops Food 2021 Jan;12(1):282-291

Corteva Agriscience™ , Johnston, Iowa, USA.

Event DP-2Ø2216-6 (referred to as DP202216 maize) was genetically modified to increase and extend the expression of the introduced gene relative to endogenous gene expression, resulting in plants with enhanced grain yield potential. The gene expresses the ZMM28 protein, a MADS-box transcription factor. The safety assessment of DP202216 maize included an assessment of the potential hazard of the ZMM28 protein, as well as an assessment of potential unintended effects of the genetic insertion on agronomics, composition, and nutrition. The history of safe use (HOSU) of the ZMM28 protein was evaluated and a bioinformatics approach was used to compare the deduced amino acid sequence of the ZMM28 protein to databases of known allergens and toxins. Based on HOSU and the bioinformatics assessment, the ZMM28 protein was determined to be unlikely to be either allergenic or toxic to humans. The composition of DP202216 maize forage and grain was comparable to non-modified forage and grain, with no unintended effects on nutrition or food and feed safety. Additionally, feeding studies with broiler chickens and rats demonstrated a low likelihood of unintentional alterations in nutrition and low potential for adverse effects. Furthermore, the agronomics observed for DP202216 maize and non-modified maize were comparable, indicating that the likelihood of increased weediness or invasiveness of DP202216 maize in the environment is low. This comprehensive review serves as a reference for regulatory agencies and decision-makers in countries where authorization of DP202216 maize will be pursued, and for others interested in food, feed, and environmental safety.
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http://dx.doi.org/10.1080/21645698.2020.1869492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833765PMC
January 2021

Animal Model Dependent Response to Pentagalloyl Glucose in Murine Abdominal Aortic Injury.

J Clin Med 2021 Jan 9;10(2). Epub 2021 Jan 9.

Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.

Abdominal aortic aneurysms (AAAs) are a local dilation of the aorta and are associated with significant mortality due to rupture and treatment complications. There is a need for less invasive treatments to prevent aneurysm growth and rupture. In this study, we used two experimental murine models to evaluate the potential of pentagalloyl glucose (PGG), which is a polyphenolic tannin that binds to and crosslinks elastin and collagen, to preserve aortic compliance. Animals underwent surgical aortic injury and received 0.3% PGG or saline treatment on the adventitial surface of the infrarenal aorta. Seventeen mice underwent topical elastase injury, and 14 mice underwent topical calcium chloride injury. We collected high-frequency ultrasound images before surgery and at 3-4 timepoints after. There was no difference in the in vivo effective maximum diameter due to PGG treatment for either model. However, the CaCl model had significantly higher Green-Lagrange circumferential cyclic strain in PGG-treated animals ( < 0.05). While ex vivo pressure-inflation testing showed no difference between groups in either model, histology revealed reduced calcium deposits in the PGG treatment group with the CaCl model. These findings highlight the continued need for improved understanding of PGG's effects on the extracellular matrix and suggest that PGG may reduce arterial calcium accumulation.
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http://dx.doi.org/10.3390/jcm10020219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827576PMC
January 2021

Genetic evaluation of patients and families with concern for hereditary endocrine tumor syndromes.

Fam Cancer 2021 Jan 7. Epub 2021 Jan 7.

Division of Human Genetics, Department of Internal Medicine and James Comprehensive Cancer Center, The Ohio State University, 2012 Kenny Road, Columbus, OH, 43202, USA.

Hereditary endocrine tumor syndromes are rare conditions with overlapping features. It is imperative that healthcare providers differentiate between these syndromes for proper patient care. Advances in genetic testing technologies have increased utilization of genetic counseling and testing in this field; however, few endocrine cancer genetics clinics exist. Two years ago, a genetic counselor (GC) specializing in endocrine cancer genetics was added to the multidisciplinary team of the James Neuroendocrine/Thyroid Clinic at The Ohio State University. Here, we report on this experience. In total, 358 patients were seen. The majority were referred by medical oncology (n = 204; 57%) for a personal history of disease (n = 249; 81%). The most common referral indications were pancreatic neuroendocrine tumors (n = 44; 17%), multiple primary tumors (n = 37; 14%), and pheochromocytoma/paraganglioma (n = 35; 14%). Most patients completed genetic testing after genetic counseling (n = 200; 65%). Targeted gene panel testing was the most common testing ordered (n = 98; 32%). Thirty-one patients (15.5%) had ≥ one likely pathogenic variant (LPV) or pathogenic variant (PV) identified. Approximately 37% (n = 11) did not meet genetic testing guidelines for the gene they tested positive for. The most common genes with LPV/PVs were the SDH genes (n = 8) and MEN1 (n = 7). Referral indications with the highest likelihood of LPV/PVs were paraganglioma, medullary thyroid carcinoma, and multiple primary tumors. We believe this data can provide valuable guidance to healthcare providers who see patients with endocrine neoplasia or who are seeking to establish hereditary endocrine cancer clinics.
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http://dx.doi.org/10.1007/s10689-020-00222-0DOI Listing
January 2021

The Developmental and Genetic Architecture of the Sexually Selected Male Ornament of Swordtails.

Curr Biol 2021 Mar 3;31(5):911-922.e4. Epub 2020 Dec 3.

Institute of Neuroscience, University of Oregon, Eugene, OR 97401, USA. Electronic address:

Sexual selection results in sex-specific characters like the conspicuously pigmented extension of the ventral tip of the caudal fin-the "sword"-in males of several species of Xiphophorus fishes. To uncover the genetic architecture underlying sword formation and to identify genes that are associated with its development, we characterized the sword transcriptional profile and combined it with genetic mapping approaches. Results showed that the male ornament of swordtails develops from a sexually non-dimorphic prepattern of transcription factors in the caudal fin. Among genes that constitute the exclusive sword transcriptome and are located in the genomic region associated with this trait we identify the potassium channel, Kcnh8, as a sword development gene. In addition to its neural function kcnh8 performs a known role in fin growth. These findings indicate that during evolution of swordtails a brain gene has been co-opted for an additional novel function in establishing a male ornament.
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http://dx.doi.org/10.1016/j.cub.2020.11.028DOI Listing
March 2021

The Tailgate Study: Differing metabolic effects of a bout of excessive eating and drinking.

Alcohol 2021 02 21;90:45-55. Epub 2020 Nov 21.

Department of Nutrition and Exercise Physiology, School of Medicine, University of Missouri, Columbia, MO, United States; Department of Medicine, Division of Gastroenterology and Hepatology, School of Medicine, University of Missouri, Columbia, MO, United States. Electronic address:

Introduction: Excess energy intake by spectators at a sporting event (i.e., a tailgate) might cause acute negative health effects. However, limited data exist regarding the effects of overeating and alcohol consumption on lipid metabolism and the potential to gain intrahepatic triacylglycerols (IHTG). We tested the hypothesis that overconsumption of food and alcohol would significantly increase both hepatic de novo lipogenesis (DNL) and IHTG.

Methods: Eighteen males (mean ± SD, age: 31.4 ± 7.3 years, BMI: 32.1 ± 5.9 kg/m) were given alcoholic drinks to elevate blood alcohol for 5 h, while highly palatable food was presented. Blood samples were collected and DNL in TG-rich lipoproteins (TRL) was measured by GC/MS, IHTG was measured via MRS (n = 15), and substrate oxidation was measured via indirect calorimetry.

Results: Subjects consumed 5087 ± 149 kcal (191 ± 25% excess of total daily energy needs including 171 ± 24 g alcohol), which increased plasma insulin, glucose, TG, and decreased NEFA (ANOVA p ≤ 0.003 for all). Both DNL and TRL-TG increased (p < 0.001), while IHTG did not change in the group as a whole (p = 0.229). Individual subject data revealed remarkably differing responses for IHTG (nine increased, five decreased, one did not change). Despite maintaining equal breath alcohol levels, subjects with IHTG elevations exhibited higher DNL, consumed 90% less alcohol (p = 0.048), tended to consume more carbohydrates, and exhibited lower whole-body fat oxidation (not significant) compared to those whose IHTG was reduced.

Discussion: This study demonstrates that acute excess energy intake may have differing effects on an individual's DNL and IHTG, and dietary carbohydrate may influence DNL more than alcohol.
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http://dx.doi.org/10.1016/j.alcohol.2020.11.001DOI Listing
February 2021

Spontaneous resolution of blastomycosis symptoms caused by .

Med Mycol Case Rep 2020 Dec 24;30:43-45. Epub 2020 Oct 24.

Integrated Research and Development aLaboratory, Marshfield Clinic Research Institute, Marshfield Clinic Health System, Marshfield, WI, 54449, USA.

Given the propensity of blastomycosis to disseminate or reoccur and the inability to predict which infections will experience severe manifestations, nearly all cases of blastomycosis are treated. Although, spontaneous resolution of symptoms is referred to generally in the literature, to our knowledge an individual case of this has not been previously reported. We report the spontaneous resolution of blastomycosis symptoms in a 40 year-old Caucasian male.
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http://dx.doi.org/10.1016/j.mmcr.2020.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599114PMC
December 2020

Élaboration d'un énoncé de position national sur la navigation des patients atteints de cancer au Canada.

Can Oncol Nurs J 2020 1;30(2):83-92. Epub 2020 Apr 1.

Au Canada, le paysage des soins du cancer évolue et les infirmières en oncologie sont appelées à jouer de nouveaux rôles afin d'améliorer l'expérience des patients et des familles et de répondre à leurs besoins toujours changeants. L'un de ces rôles, la navigation des patients atteints de cancer (NPC), vise principalement à coordonner les soins centrés sur la personne et à guider les patients dans le système de santé. Dans plusieurs provinces et territoires du Canada, la navigation est devenue essentielle pour offrir des soins de grande qualité aux patients cancéreux. Depuis 2016, des chefs de file des soins infirmiers oncologiques se réunissent au sein d'un groupe national pour synthétiser leur compréhension de la navigation des patients en contexte canadien afin d'élaborer un énoncé de position national sur la NPC. Dans le présent article, nous analyserons l'historique de l'élaboration de l'énoncé de position sur la NPC que publiera prochainement l'Association canadienne des infirmières en oncologie (ACIO/CANO). Nous analyserons également les commentaires des participants aux ateliers tenus dans le cadre des congrès de 2016, 2017 et 2018, de même que les comptes rendus des réunions du groupe de travail national qui ont eu lieu pendant cette même période. Le présent article se veut un sommaire historique concis de l'évolution de la NPC au Canada, ainsi qu'un modèle pour les autres groupes aspirant à rédiger un énoncé de position consensuel.
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http://dx.doi.org/10.5737/236880763028392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586701PMC
April 2020

Development of a national position statement on cancer patient navigation in Canada.

Can Oncol Nurs J 2020 1;30(2):73-82. Epub 2020 Apr 1.

As the landscape of cancer care in Canada evolves, oncology nursing roles are developed to enhance the patient experience and address the changing needs of patients and families. Cancer Patient Navigation (CPN), an oncology nursing role focusing primarily on person-centred care coordination and system navigation, has become integral to providing high-quality cancer care in many Canadian jurisdictions. Since 2016, a national group of oncology nursing leaders have been engaged in convening and catalyzing our understanding of the role of patient navigation in the Canadian cancer context with the purpose of developing a national position statement on CPN. In this paper, we provide a historical analysis of the development of the forthcoming Canadian Association of Nurses in Oncology (CANO) position statement on CPN. We present an analysis of participant feedback from workshops at the 2016, 2017, and 2018 conferences, and meeting minutes from the National working group over this same time period. This paper serves as a concise historical summary of the evolution of CPN in Canada while providing a template for other groups looking to develop a consensus-based position statement.
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http://dx.doi.org/10.5737/236880763027382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586707PMC
April 2020

Effects of Braiding Parameters on Tissue Engineered Vascular Graft Development.

Adv Healthc Mater 2020 12 15;9(24):e2001093. Epub 2020 Oct 15.

Nationwide Children's Hospital, Abagail Wexner Research Institute, 575 Children's Crossroad, Columbus, OH, 43215, USA.

Tissue engineered vascular grafts (TEVGs) using scaffolds fabricated from braided poly(glycolic acid) (PGA) fibers coated with poly(glycerol sebacate) (PGS) are developed. The approach relies on in vivo tissue engineering by which neotissue forms solely within the body after a scaffold has been implanted. Herein, the impact of altering scaffold braid design and scaffold coating on neotissue formation is investigated. Several combinations of braiding parameters are manufactured and evaluated in a Beige mouse model in the infrarenal abdominal aorta. Animals are followed with 4D ultrasound analysis, and 12 week explanted vessels are evaluated for biaxial mechanical properties as well as histological composition. Results show that scaffold parameters (i.e., braiding angle, braiding density, and presence of a PGS coating) have interdependent effects on the resulting graft performance, namely, alteration of these parameters influences levels of inflammation, extracellular matrix production, graft dilation, neovessel distensibility, and overall survival. Coupling carefully designed in vivo experimentation with regression analysis, critical relationships between the scaffold design and the resulting neotissue that enable induction of favorable cellular and extracellular composition in a controlled manner are uncovered. Such an approach provides a potential for fabricating scaffolds with a broad range of features and the potential to manufacture optimized TEVGs.
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http://dx.doi.org/10.1002/adhm.202001093DOI Listing
December 2020

Building the vertebrate codex using the gene breaking protein trap library.

Elife 2020 08 11;9. Epub 2020 Aug 11.

Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, United States.

One key bottleneck in understanding the human genome is the relative under-characterization of 90% of protein coding regions. We report a collection of 1200 transgenic zebrafish strains made with the gene-break transposon (GBT) protein trap to simultaneously report and reversibly knockdown the tagged genes. Protein trap-associated mRFP expression shows previously undocumented expression of 35% and 90% of cloned genes at 2 and 4 days post-fertilization, respectively. Further, investigated alleles regularly show 99% gene-specific mRNA knockdown. Homozygous GBT animals in , , , and phenocopied established mutants. 204 cloned lines trapped diverse proteins, including 64 orthologs of human disease-associated genes with 40 as potential new disease models. Severely reduced skeletal muscle Ca transients in GBT homozygous animals validated the ability to explore molecular mechanisms of genetic diseases. This GBT system facilitates novel functional genome annotation towards understanding cellular and molecular underpinnings of vertebrate biology and human disease.
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http://dx.doi.org/10.7554/eLife.54572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486118PMC
August 2020

Blue Light Laser Results in Less Vocal Fold Scarring Compared to KTP Laser in Normal Rat Vocal Folds.

Laryngoscope 2021 04 4;131(4):853-858. Epub 2020 Aug 4.

Department of Otolaryngology-Head & Neck Surgery, Laryngology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.

Objectives: Preliminary investigations suggest that a novel blue light (BL) laser with a wavelength of 445 nm is comparable to the commonly utilized potassium titanyl phosphate (KTP) laser (532 nm) for treatment of various laryngeal pathologies. The objective of the current study is to make a direct histological comparison of the degree of vocal fold scarring after either BL or KTP laser treatment in an animal model.

Study Design: This was a randomized controlled study using rats.

Methods: Twenty-four Sprague-Dawley rats were randomized to BL or KTP laser treatment. Laser was delivered in non-overlapping pulses to normal rat vocal folds. Larynges in each group were harvested at three time points: post-operative day 1, 30, and 90. Three animals served as negative controls. The excised whole larynges were sectioned transversely and stained with hematoxylin/eosin and trichrome. Presence of subepithelial inflammation and protein deposition/fibrosis indicative of scarring were scored semi-quantitatively (from grade 1-3) by two pathologists blinded to treatment groups.

Results: Between-group comparison showed that both laser treatments resulted in significantly elevated subepithelial protein deposition/fibrosis 90 days after treatment compared to negative controls (BL: 2 ± 0; KTP: 2.67 ± 0.29; control: 1.17 ± 0.29; P < .05). However, the degree of protein deposition/fibrosis was significantly higher in the KTP group compared to the BL group (P = .016). Within-group comparison showed that the KTP group showed evidence of fibrosis as early as 30 days after treatment, which was not observed in the BL group.

Conclusions: The current study suggests that the degree of scarring is significantly less after BL laser treatment compared to KTP in normal rat vocal fold tissue.

Level Of Evidence: NA Laryngoscope, 131:853-858, 2021.
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http://dx.doi.org/10.1002/lary.28892DOI Listing
April 2021

The role of steroid injection for vocal folds lesions in professional voice users.

J Otolaryngol Head Neck Surg 2020 Jul 20;49(1):50. Epub 2020 Jul 20.

Department of Otolaryngology-Head and Neck Surgery, St. Michaels Hospital, Department of Otolaryngology-Head and Neck Surgery, University of Toronto, 30 Bond St 8CC, Toronto, ON, M5B 1W8, Canada.

Background: Benign vocal fold lesions identified in professional voice users, frequently require further treatment after failure of conservative measures. The role of vocal fold steroid injection as a treatment option for select benign lesions is the focus of this study. Steroid injection may avoid phonosurgery in some individuals thereby reducing the potential for adverse side effects associated with surgery.

Objective: The purpose of the study is to review the effect of steroid injection on vocal function in professional voice users associated with a benign lesion(s) using the Voice Handicap Index-10.

Method: This study is a retrospective review of patients (professional voice users) that underwent 1 or more steroid injection(s) between July 2014-December 2018. The Voice Handicap Index-10 was compared from pre to post treatment. Patients were identified using billing code data for laryngeal injection. Patient demographics (age, gender, profession), previous phonosurgery, date of steroid injection and follow up dates as well as VHI-10 scores were collected from the electronic medical record.

Results: Twenty four patients were identified. The mean Voice HandicapIndex-10 score decreased from 23.5 pre injection to 17.8 post injection which represented a reduction of 24.3%. Vocal fold steroid injection procedure in our series was associated with one complication.

Conclusion: Vocal fold steroid injection for benign lesions is a safe, well-tolerated procedure with an improvement in vocal function without surgical intervention. Steroid injection should be considered as a treatment option to avoid surgery in patients with select vocal fold lesions.
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http://dx.doi.org/10.1186/s40463-020-00434-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370469PMC
July 2020

Development and evaluation of a dual density insole for people standing for long periods of time at work.

J Foot Ankle Res 2020 Jul 8;13(1):42. Epub 2020 Jul 8.

School of Health and Society, University of Salford, Salford, M5 4WT, UK.

Background: Appropriate footwear is important for those who stand for prolonged periods of time at work, enabling them to remain comfortable, healthy and safe. Preferences for different footwear cushioning or hardness are often person specific and one shoe or insole will not be the choice for all. The aim of this study was to develop a range of insole options to maintain comfort during long periods of standing at work and test insole material preferences in the workplace.

Methods: The study consisted of two parts. Part one evaluated 9 insoles of the same geometry that varied in hardness under 2 different plantar regions (n = 34). Insole preference, plantar pressure and selected anthropometric foot measures were taken. Three insole designs based on the most preferred options were identified from this part. In part two, these three insoles were evaluated with 22 workers immediately after trying them on (1 min) and after a working day. Foot anthropometric measures and subjective questions concerning material hardness preferences and self-reported foot characteristics were used to investigate whether either had a relationship with insole preference.

Results: Part one found insole preference predominantly varied according to material hardness under the medial arch rather than the heel/forefoot. Softer material under the heel and forefoot was associated with a reduction in peak pressures in these regions (p < 0.05). The most preferred insole had lower pressures under the hallux and first metatarsal phalangeal joint, and greater pressures and contact area under the medial midfoot (p < 0.05) compared to the least preferred insole. Height and foot anthropometrics were related to insole preference. In part two, under real world conditions, insole preference changed for 65% of participants between the immediate assessment (1 min) and after a whole workday, with dorsum height related to the latter (p < 0.05). Subjective questions for self-assessed arch height and footwear feel identified 66.7% of the insole preferences after 1 day at work, compared to 36% using immediate assessment of insole preference.

Conclusion: Preference for material hardness varies underneath the medial arch of the foot and is time dependent. Simple foot measures and questions about comfort can guide selection of preferred insoles.
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http://dx.doi.org/10.1186/s13047-020-00402-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341629PMC
July 2020

Urine Antigen Testing is Equally Sensitive to and Infections.

Clin Med Res 2020 12 22;18(4):133-139. Epub 2020 Jun 22.

Integrated Research and Development Laboratory, Marshfield Clinic Research Institute, Marshfield Clinic Health System, Marshfield, WI 54449

Introduction: Blastomycosis is endemic in Wisconsin with and responsible for infections. Urine antigen testing is a non-invasive diagnostic method for blastomycosis with up to 93% test sensitivity. However, the test's sensitivity has not been evaluated with relationship to infections.

Methods: We aimed to assess physician use of the urine antigen assay and its sensitivity to and infections in a retrospective study. Culture confirmed clinical cases of blastomycosis from 2008-2016 were identified within Marshfield Clinic Health System (MCHS) and UW Hospital and Clinics (UWHC) medical records. Clinical data were abstracted from each medical record and included the following: patient demographics, presence of immune compromising and underlying medical conditions, treatment drugs, presence of isolated pulmonary or disseminated disease, death, urine antigen testing, timeframe of testing, and quantitative test values (EIA units or ng/mL).

Results: A total of 140 blastomycosis cases were included in this study, with MCHS contributing 114 cases to the study and UWHC contributing 26 cases. The majority of UWHC cases (n=22; 85%) were caused by and the majority of MCHS cases (n=73; 64%) were caused by . UWHC physicians were significantly more likely to treat with multiple drugs during the course of infection and were more likely to prescribe amphotericin B and voriconazole. Urine antigen testing was more frequently used at UWHC (n=24; 92%) than MCHS (n=51; 45%; < 0.00001). In this study, the urine antigen assay demonstrated 79% sensitivity. Sensitivity was significantly associated with the timeframe of testing ( < 0.05), with most true positive urine antigen tests (83%) being performed ≤ 7 days from diagnosis. In this study, the urine antigen assay was capable of detecting both and at about equal sensitivity. Urine antigen concentration (ng/mL) trended higher in infections.

Conclusion: This study found that the urine antigen assay is capable of detecting both species of at about the same sensitivity. We recommend continued use of the urine antigen assay for diagnosis of blastomycosis and recommend that the assay be used early in the diagnostic process to minimize the chance of false negative results.
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http://dx.doi.org/10.3121/cmr.2020.1534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735445PMC
December 2020

Data-Driven Development of an Institutional "Gross-Only" Policy for the Examination of Select Surgical Pathology Specimens.

Am J Clin Pathol 2020 09;154(4):486-493

Medical College of Wisconsin, Department of Pathology, Milwaukee.

Objectives: To determine diagnostic, workflow, and economic implications of instituting a gross-only policy at our institution.

Methods: Retrospective (2017) key word searches were performed to identify "gross-only" cases for which microscopic evaluation could potentially be omitted, but was performed, and those who underwent gross evaluation per surgeon request. Cases were evaluated for type(s), part(s), block volume, turnaround time, demographics, and diagnosis. Laboratory costs and reimbursement were evaluated.

Results: In total, 448 potential gross-only cases with 472 specimens consisted of atherosclerotic plaques (33.5%), bariatric stomach/bowel (32.6%), hernia (15.7%), heart valves (12.7%), and other (5.9%). Four (2.6%) bariatric surgery cases had Helicobacter pylori infection; these were the only cases with "significant" histologic findings. Cost analysis revealed that converting all potential gross-only specimens to gross only would result in overall losses based on average reimbursements, most influenced by bariatric specimens (Current Procedural Terminology code 88307), comprising 65.2% of estimated loss.

Conclusions: Establishing a gross-only policy should be guided by established recommendations but institutionally individualized and data driven. It was reasonable for us to establish a gross-only policy for most evaluated specimens, while excluding bariatric stomach specimens in which microscopic pathology could be missed, given the lack of H pylori screening at our institution.
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http://dx.doi.org/10.1093/ajcp/aqaa065DOI Listing
September 2020

Agronomic and compositional assessment of genetically modified DP23211 maize for corn rootworm control.

GM Crops Food 2020 Oct 17;11(4):206-214. Epub 2020 Jun 17.

Corteva Agriscience™ , Johnston, Iowa, USA.

DP23211 maize was genetically modified (GM) to express DvSSJ1 double-stranded RNA and the IPD072Aa protein for control of corn rootworm ( spp.). DP23211 maize also expresses the phosphinothricin acetyltransferase (PAT) protein for tolerance to glufosinate herbicide, and the phosphomannose isomerase (PMI) protein that was used as a selectable marker. A multi-location field trial was conducted during the 2018 growing season at 12 sites selected to be representative of the major maize-growing regions of the U.S. and Canada. Standard agronomic endpoints as well as compositional analytes from grain and forage (e.g., proximates, fibers, minerals, amino acids, fatty acids, vitamins, anti-nutrients, secondary metabolites) were evaluated and compared to non-GM near-isoline control maize (control maize) and non-GM commercial maize (reference maize). A small number of agronomic endpoints were statistically significant compared to the control maize, but were not considered to be biologically relevant when adjusted using the false discovery rate method (FDR) or when compared to the range of natural variation established from in-study reference maize. A small number of composition analytes were statistically significant compared to the control maize. These analytes were not statistically significant when adjusted using FDR, and all analyte values fell within the range of natural variation established from in-study reference range, literature range or tolerance interval, indicating that the composition of DP23211 maize grain and forage is substantially equivalent to conventional maize represented by non-GM near-isoline control maize and non-GM commercial maize.
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http://dx.doi.org/10.1080/21645698.2020.1770556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518745PMC
October 2020

Transition to a virtual multidisciplinary tumor board during the COVID-19 pandemic: University of Pittsburgh experience.

Head Neck 2020 06 27;42(6):1310-1316. Epub 2020 Apr 27.

Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Multidisciplinary conferences (MDC) are an important component of head and neck oncologic care including diagnosis, treatment, and survivorship. Virtual MDC allows for improved collaboration between providers at distant sites and proper allocation of health care resources in a time of crisis. When approached systematically, a virtual MDC is feasible to design and implement in a large academic medical center with multiple satellite hospitals.
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http://dx.doi.org/10.1002/hed.26195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264555PMC
June 2020

Toward Automation of the Supine Pressor Test for Preeclampsia.

J Eng Sci Med Diagn Ther 2019 Nov 19;2(4). Epub 2019 Nov 19.

Weldon School of Biomedical Engineering, Purdue Center for Cancer Research, Purdue University, 206 South Martin Jischke Drive, West Lafayette, IN 47907.

Preeclampsia leads to increased risk of morbidity and mortality for both mother and fetus. Most previous studies have largely neglected mechanical compression of the left renal vein by the gravid uterus as a potential mechanism. In this study, we first used a murine model to investigate the pathophysiology of left renal vein constriction. The results indicate that prolonged renal vein stenosis after 14 days can cause renal necrosis and an increase in blood pressure (BP) of roughly 30 mmHg. The second part of this study aimed to automate a diagnostic tool, known as the supine pressor test (SPT), to enable pregnant women to assess their preeclampsia development risk. A positive SPT has been previously defined as an increase of at least 20 mmHg in diastolic BP when switching between left lateral recumbent and supine positions. The results from this study established a baseline BP increase between the two body positions in nonpregnant women and demonstrated the feasibility of an autonomous SPT in pregnant women. Our results demonstrate that there is a baseline increase in BP of roughly 10-14 mmHg and that pregnant women can autonomously perform the SPT. Overall, this work in both rodents and humans suggests that (1) stenosis of the left renal vein in mice leads to elevation in BP and acute renal failure, (2) nonpregnant women experience a baseline increase in BP when they shift from left lateral recumbent to supine position, and (3) the SPT can be automated and used autonomously.
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http://dx.doi.org/10.1115/1.4045203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045991PMC
November 2019

Persistent and nonprogressive cutaneous blastomycosis in a pregnant adolescent.

JAAD Case Rep 2020 Mar 12;6(3):169-171. Epub 2020 Feb 12.

Integrated Research and Development Laboratory, Marshfield Clinic Research Institute, Marshfield Clinic Health System, Marshfield, Wisconsin.

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http://dx.doi.org/10.1016/j.jdcr.2019.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019037PMC
March 2020

Racial Differences in Clinical Phenotype and Hospitalization of Blastomycosis Patients.

Open Forum Infect Dis 2019 Nov 4;6(11):ofz438. Epub 2019 Oct 4.

Integrated Research and Development Laboratory, Marshfield Clinic Research Institute, Marshfield Clinic Health System, Marshfield, Wisconsin.

Background: Dimorphic fungal infections, such as blastomycosis, cause significant morbidity and mortality. Historically, blastomycosis studies have focused on non-Hispanic whites, which limits our understanding of the clinical presentation and outcomes for patients of other races and ethnicities. We evaluated whether clinical presentation and disease severity varied across racial and ethnic groups.

Methods: Blastomycosis patients were identified from Marshfield Clinic Health System and data were abstracted from electronic medical records. genotyping was performed for cases with available isolates. Bivariate analyses (χ  tests/analysis of variance) assessed associations of race and/or ethnicity, spp, and hospitalization status with demographics and clinical presentation. Multivariable logistic regression was used to evaluate the association of race and/or ethnicity and hospitalization.

Results: In total, 477 patients were included. Age differences were observed across race and ethnicity categories ( < .0001). Non-Hispanic whites were oldest (median, 48 years; interquartile range [IQR], 31-62) and Asians were youngest (26 years; IQR, 19-41). Non-Hispanic whites (55%) and African Americans (52%) had underlying medical conditions more frequently than Hispanic whites (27%) and Asians (29%). Odds of hospitalization were 2 to 3 times higher for Hispanic whites (adjusted odds ratio [aOR], 2.9; 95% confidence interval [CI], 1.2-1.7), American Indian or Alaska Native (AIAN) (aOR, 2.4; 95% CI, 1.0-5.5), and Asian (aOR, 1.9; 95% CI, 1.0-3.6) patients compared with non-Hispanic white patients. Ninety percent of infections occurred in non-Hispanic whites, whereas blastomycosis in Hispanic whites, AIAN, and Asian patients was frequently caused by ( < .0001).

Conclusions: Hispanic whites, AIAN, and Asian blastomycosis patients were younger and healthier but more frequently hospitalized. Patients in these racial and ethnic groups may need more aggressive treatment and closer therapeutic monitoring.
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http://dx.doi.org/10.1093/ofid/ofz438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824527PMC
November 2019

Adapterama I: universal stubs and primers for 384 unique dual-indexed or 147,456 combinatorially-indexed Illumina libraries (iTru & iNext).

PeerJ 2019 11;7:e7755. Epub 2019 Oct 11.

Department of Biological Sciences and Museum of Natural Science, Louisiana State University, Baton Rouge, LA, United States of America.

Massively parallel DNA sequencing offers many benefits, but major inhibitory cost factors include: (1) start-up (i.e., purchasing initial reagents and equipment); (2) buy-in (i.e., getting the smallest possible amount of data from a run); and (3) sample preparation. Reducing sample preparation costs is commonly addressed, but start-up and buy-in costs are rarely addressed. We present dual-indexing systems to address all three of these issues. By breaking the library construction process into universal, re-usable, combinatorial components, we reduce all costs, while increasing the number of samples and the variety of library types that can be combined within runs. We accomplish this by extending the Illumina TruSeq dual-indexing approach to 768 (384 + 384) indexed primers that produce 384 unique dual-indexes or 147,456 (384 × 384) unique combinations. We maintain eight nucleotide indexes, with many that are compatible with Illumina index sequences. We synthesized these indexing primers, purifying them with only standard desalting and placing small aliquots in replicate plates. In qPCR validation tests, 206 of 208 primers tested passed (99% success). We then created hundreds of libraries in various scenarios. Our approach reduces start-up and per-sample costs by requiring only one universal adapter that works with indexed PCR primers to uniquely identify samples. Our approach reduces buy-in costs because: (1) relatively few oligonucleotides are needed to produce a large number of indexed libraries; and (2) the large number of possible primers allows researchers to use unique primer sets for different projects, which facilitates pooling of samples during sequencing. Our libraries make use of standard Illumina sequencing primers and index sequence length and are demultiplexed with standard Illumina software, thereby minimizing customization headaches. In subsequent papers, we use these same primers with different adapter stubs to construct amplicon and restriction-site associated DNA libraries, but their use can be expanded to any type of library sequenced on Illumina platforms.
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http://dx.doi.org/10.7717/peerj.7755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791352PMC
October 2019

Evaluation of the History of Safe Use of the Maize ZMM28 Protein.

J Agric Food Chem 2019 Jul 25;67(26):7466-7474. Epub 2019 Jun 25.

Corteva Agriscience , Agriculture Division of DowDuPont , Johnston , Iowa 50131 , United States.

The ZMM28 protein encoded by the zmm28 gene is endogenous to maize. DP202216 maize was genetically modified to increase and extend expression of the zmm28 gene relative to native zmm28 gene expression, resulting in plants with enhanced grain yield potential. Evaluation of the history of safe use (HOSU) is one component of the safety assessment framework for a newly expressed protein in a GM crop. The deduced amino acid sequence of the introduced ZMM28 protein in DP202216 maize is identical to the ZMM28 protein in nonmodified conventional maize. The ZMM28 protein has also been found in selected varieties of sweet corn kernels, and closely related proteins are found in other commonly consumed food crops. Concentrations of the ZMM28 protein in event DP202216 maize, conventional maize, and sweet corn are reported. This information supports, in part, the evaluation of HOSU, which can be leveraged in the safety assessment of the ZMM28 protein. Additional studies will be considered in the food and feed safety assessment of the DP202216 maize event.
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http://dx.doi.org/10.1021/acs.jafc.9b00391DOI Listing
July 2019