Publications by authors named "Samuel Yoon"

10 Publications

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Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia patients.

J Exp Med 2021 Jul 5;218(7). Epub 2021 May 5.

Department of Genetics, University of Alabama at Birmingham, Birmingham, AL.

The pioneer transcription factor (TF) PU.1 controls hematopoietic cell fate by decompacting stem cell heterochromatin and allowing nonpioneer TFs to enter otherwise inaccessible genomic sites. PU.1 deficiency fatally arrests lymphopoiesis and myelopoiesis in mice, but human congenital PU.1 disorders have not previously been described. We studied six unrelated agammaglobulinemic patients, each harboring a heterozygous mutation (four de novo, two unphased) of SPI1, the gene encoding PU.1. Affected patients lacked circulating B cells and possessed few conventional dendritic cells. Introducing disease-similar SPI1 mutations into human hematopoietic stem and progenitor cells impaired early in vitro B cell and myeloid cell differentiation. Patient SPI1 mutations encoded destabilized PU.1 proteins unable to nuclear localize or bind target DNA. In PU.1-haploinsufficient pro-B cell lines, euchromatin was less accessible to nonpioneer TFs critical for B cell development, and gene expression patterns associated with the pro- to pre-B cell transition were undermined. Our findings molecularly describe a novel form of agammaglobulinemia and underscore PU.1's critical, dose-dependent role as a hematopoietic euchromatin gatekeeper.
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http://dx.doi.org/10.1084/jem.20201750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105723PMC
July 2021

Validating Data-driven Methods to Identify Transgender Individuals in the Veterans Affairs.

Am J Epidemiol 2021 Apr 12. Epub 2021 Apr 12.

Center for Healthcare Organization and Implementation Research (CHOIR), VA Bedford Healthcare System, Bedford, Massachusetts, United States.

We sought to operationalize and validate data-driven approaches to identify transgender individuals in the U.S. Department of Veteran Affairs (VA) health care system through a retrospective analysis using VA administrative data from 2006 to 2018. Besides gender identity disorder (GID) diagnoses, a combination of non-GID data elements were used to identify potential transgender veterans, including: 1) endocrine disorder, unspecified or not otherwise specified codes, 2) receipt of sex hormones not associated with the sex documented in the veteran's records (gender-affirming hormone therapy), and 3) change in the administratively recorded sex. Both GID and non-GID data elements were applied to a sample of 13,233,529 veterans utilizing the VA healthcare system between January 2006 and December 2018. We identified 10,769 potential transgender veterans. Based on a high positive predictive value of GID (83%, 95% Confidence Interval (CI)=77-89%) versus non-GID-coded veterans (2%, 95% CI=1-11%) from chart review validation, the final analytical sample comprised of only veterans with a GID diagnosis code (n=9,608). In the absence of self-identified gender identity, findings suggest that relying entirely on GID diagnosis codes are the most reliable approach to identify transgender individuals in the VA.
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http://dx.doi.org/10.1093/aje/kwab102DOI Listing
April 2021

Impact of electronic consultation (e-consult) on timeliness and guideline concordance of workups leading to thyroid nodule fine-needle aspiration biopsy.

Endocr Pract 2021 Mar 22. Epub 2021 Mar 22.

Center for Healthcare Organization and Implementation Research, VA Bedford Healthcare System, 200 Springs Road, Bedford MA 01730, Section of Endocrinology, Diabetes, Nutrition and Weight Management, Boston University School of Medicine, 720 Harrison Avenue, Suite 8100, Boston, MA 02118.

Objective: Electronic consultations (e-consults) are commonly used to obtain endocrinology input on clinical questions without a face-to-face visit, but there are sparse data on quality of care resulting from e-consults for specific conditions. We examined workups resulting in thyroid nodule fine-needle aspiration (FNA) biopsy to examine whether endocrinology e-consults were more timely and similarly guideline concordant as compared to endocrinology face-to-face visits, and whether endocrinology e-consults were more guideline concordant as compared to workups without endocrinology input.

Methods: We conducted a retrospective chart review of 302 thyroid FNA biopsies conducted in the Veterans Affairs (VA) health system between 5/1/2017 and 2/4/2020 (e-consult, N=99; face-to-face visit, N=100; no endocrinology input, N=103). We used t-tests to compare timeliness and chi-square tests to compare the proportion of guideline-concordant workups. We used multivariable linear and logistic models to control for demographic factors.

Results: FNAs preceded by endocrinology e-consult had more timely workups compared to those preceded by endocrinology face-to-face visits in terms of days elapsed between referral and FNA biopsy [geometric mean [95% confidence interval]: 44.7 [37.2, 53.7] days vs. 61.7 [52.5, 72.4] days, t(195)=2.55, P=0.01]. The difference in the summary measure of guideline concordance across groups was not statistically significant (P=0.38).

Conclusion: E-consults were faster than face-to-face consults and similar guideline concordant as compared to both face-to-face consults and no endocrinology input for workups resulting in FNA. Decisions about appropriate use of e-consults for thyroid nodules should account for these data while also considering potential benefits of direct patient-endocrinologist interaction for complex situations.
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http://dx.doi.org/10.1016/j.eprac.2021.03.008DOI Listing
March 2021

Unnecessary ordering of magnetic resonance imaging of the knee: A retrospective chart review of referrals to orthopedic surgeons.

PLoS One 2020 2;15(11):e0241645. Epub 2020 Nov 2.

eHealth Centre of Excellence, Kitchener, Ontario, Canada.

There is a noticeable increase in the unnecessary ordering of Magnetic Resonance Imaging (MRI) of the knee in older patients. This quality improvement study assessed the frequency of unnecessary pre-consultation knee MRIs and investigated the effect on the outcome of the patients' consultation with the orthopedic surgeon. 650 medical charts of patients aged 55 years or older referred to an orthopedic clinic with knee complaints were reviewed. Patients arriving with a pre-consultation MRI were identified, and the usefulness of the MRI was evaluated using the appropriateness criteria developed to support this study. Of the 650 patient charts reviewed, 225 patients presented with a pre-consultation MRI, 76% of which were not useful for the orthopedic surgeon. The ordered knee MRI scans were considered not useful because they were requested for confirmed meniscal tear for patients ≥55 years, suspected degenerative disorder and ligament/tendon injury, or for patients with severe osteoarthritis without locking or extension. These MRI scans were done despite the absence of signs of effusion, tenderness, soft tissue swelling, decreased range of motion, or difficulty of weight-bearing, a lack of persistent knee joint pain at the time of assessment, or with no x-ray before ordering MRI. Half of the patients with a pre-consult MRI did not present with plain radiographs of their knee, however, 35% of those still required an x-ray to be ordered at the time of the surgical consult. A logistic regression analysis on post-consult disposition found that patients with pre-consult MRI were less likely to be considered for total knee arthroplasty (TKA) (OR 0.424, CI 0.258-0.698, p = 0.001). Patients assessed by an advanced practice physiotherapist prior to referral for surgical consult were 4.47 more likely to have TKA (CI 2.844-7.039, p< 0.000). Most of the pre-consult knee MRIs were deemed as unnecessary for the orthopedic surgeon's clinical decision-making. This study highlights the potential benefits of following a comprehensive model of care within the referral process to reduce the unnecessary high orders of pre-consult MRI scans.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241645PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605700PMC
December 2020

Epidemiological study of dogs with diabetes mellitus attending primary care veterinary clinics in Australia.

Vet Rec 2020 08 12;187(3):e22. Epub 2020 Feb 12.

Sydney School of Veterinary Science, New South Wales, Sydney, Australia

Background: The objectives of this study were to establish the prevalence, risk factors and comorbidities/sequelae for diabetes mellitus (DM) in Australian dogs presented to first-opinion veterinary practices.

Methods: Electronic patient records of dogs (n=134,329) attending 152 veterinary clinics during 2017 were sourced through VetCompass Australia. They included 418 dogs with DM; a prevalence of 0.36 per cent (95 per cent CI 0.33 per cent to 0.39 per cent) in Australian dogs attending these veterinary clinics. By comparing with the reference group of rarer breeds and unidentified crossbreeds, multivariable modelling was used to reveal breeds (and their crosses) with significantly higher odds of having DM.

Results: The results revealed that breeds (and their crosses) with significantly higher odds of having DM were Australian terriers (ORs=7.93 (95 per cent CI 2.83 to 22.27)), Siberian huskies (OR=6.24 (95 per cent CI 2.51 to 15.54)), English springer spaniels (OR=5.37 (95 per cent CI 1.48 to 19.53)), West Highland white terriers (OR=4.85 (95 per cent CI 2.55 to 9.25)), miniature schnauzers (OR=3.47 (95 per cent CI 1.16 to 10.35)), all types of poodles (OR=3.41 (95 per cent CI 2.07 to 5.61)), bichon frises (OR=3.41 (95 per cent CI 1.65 to 7.01)), schnauzers (OR=3.18 (95 per cent CI 1.42 to 7.11)) and cavalier King Charles spaniels (CKCS; OR=1.84 (95 per cent CI 1.08 to 3.13)). Breeds with lower risk were German shepherd dogs (OR=0.11 (95 per cent CI 0.01 to 0.84)), golden retrievers (OR=0.09 (95 per cent CI 0.01 to 0.68)) and boxers (no cases identified). Fisher's exact tests showed that labradoodles were diagnosed significantly more often than purebred Labradors (P=0.04) and did not differ significantly from poodles (P=0.81). Cavoodles did not differ significantly from either CKCS (p~1.00) or poodles (P=0.12). Spoodles were significantly less diagnosed than poodles (P=0.003) but did not differ from cocker spaniels (P=0.66). Desexed male dogs had a higher odds of DM than entire male (OR=0.62 (95 per cent CI 0.39 to 0.98)) and desexed female dogs (OR=0.76 (95 per cent CI 0.61 to 0.96)). Comorbidities/sequelae associated with canine DM included suspected pancreatitis (OR 10.58 (95 per cent CI 5.17 to 22.78)), cataracts (OR 9.80 (95 per cent CI 5.65 to 17.35)), hyperadrenocorticism (OR 6.21 (95 per cent CI 3.29 to 11.88)), urinary tract infection (OR 5.09 (95 per cent CI 1.97 to 13.41)) and hypothyroidism (OR 4.10 (95 per cent CI 1.08 to 15.58)).

Conclusions: Breeds at most risk included Australian terriers and Siberian huskies as previously reported, as well as, for the first time, English springer spaniels. In contrast to other populations where there is female predisposition for DM, desexed male dogs in Australia were at increased risk for DM compared with both entire males and desexed females. This predisposition for desexed males to develop DM warrants further investigation.
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http://dx.doi.org/10.1136/vr.105467DOI Listing
August 2020

Complete resolution of postbariatric surgery associated hepatic steatosis after nutrition support.

Surg Obes Relat Dis 2020 Jan 10;16(1):165-167. Epub 2019 Oct 10.

Boston University School of Medicine, Boston, Massachusetts. Electronic address:

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http://dx.doi.org/10.1016/j.soard.2019.10.001DOI Listing
January 2020

Spatial phenotyping of the endocardial endothelium as a function of intracardiac hemodynamic shear stress.

J Biomech 2017 01 16;50:11-19. Epub 2016 Nov 16.

Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Despite substantial evidence for the central role of hemodynamic shear stress in the functional integrity of vascular endothelial cells, hemodynamic and molecular regulation of the endocardial endothelium lining the heart chambers remains understudied. We propose that regional differences in intracardiac hemodynamics influence differential endocardial gene expression leading to phenotypic heterogeneity of this cell layer. Measurement of intracardiac hemodynamics was performed using 4-dimensional flow MRI in healthy humans (n=8) and pigs (n=5). Local wall shear stress (WSS) and oscillatory shear indices (OSI) were calculated in three distinct regions of the LV - base, mid-ventricle (midV), and apex. In both the humans and pigs, WSS values were significantly lower in the apex and midV relative to the base. Additionally, both the apex and midV had greater oscillatory shear indices (OSI) than the base. To investigate regional phenotype, endocardial endothelial cells (EEC) were isolated from an additional 8 pigs and RNA sequencing was performed. A false discovery rate of 0.10 identified 1051 differentially expressed genes between the base and apex, and 321 between base and midV. Pathway analyses revealed apical upregulation of genes associated with translation initiation. Furthermore, tissue factor pathway inhibitor (TFPI; mean 50-fold) and prostacyclin synthase (PTGIS; 5-fold), genes prominently associated with antithrombotic protection, were consistently upregulated in LV apex. These spatio-temporal WSS values in defined regions of the left ventricle link local hemodynamics to regional heterogeneity in endocardial gene expression.
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http://dx.doi.org/10.1016/j.jbiomech.2016.11.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513694PMC
January 2017

The Effect of Noseband Tightening on Horses' Behavior, Eye Temperature, and Cardiac Responses.

PLoS One 2016 3;11(5):e0154179. Epub 2016 May 3.

Faculty of Veterinary Science, The University of Sydney, Camperdown, Sydney, New South Wales, Australia.

Restrictive nosebands are common in equestrian sport. This is concerning, as recent evidence suggests that very tight nosebands can cause a physiological stress response, and may compromise welfare. The objective of the current study was to investigate relationships that noseband tightness has with oral behavior and with physiological changes that indicate a stress response, such as increases in eye temperature (measured with infrared thermography) and heart rate and decreases in heart rate variability (HRV). Horses (n = 12) wearing a double bridle and crank noseband, as is common in dressage at elite levels, were randomly assigned to four treatments: unfastened noseband (UN), conventional area under noseband (CAUN) with two fingers of space available under the noseband, half conventional area under noseband (HCAUN) with one finger of space under the noseband, and no area under the noseband (NAUN). During the tightest treatment (NAUN), horse heart rate increased (P = 0.003), HRV decreased (P < 0.001), and eye temperature increased (P = 0.011) compared with baseline readings, indicating a physiological stress response. The behavioral results suggest some effects from bits alone but the chief findings are the physiological readings that reflect responses to the nosebands at their tightest. Chewing decreased during the HCAUN (P < 0.001) and NAUN (P < 0.001) treatments. Yawning rates were negligible in all treatments. Similarly, licking was eliminated by the NAUN treatment. Following the removal of the noseband and double bridle during the recovery session, yawning (P = 0.015), swallowing (P = 0.003), and licking (P < 0.001) significantly increased compared with baseline, indicating a post-inhibitory rebound response. This suggests a rise in motivation to perform these behaviors and implies that their inhibition may place horses in a state of deprivation. It is evident that a very tight noseband can cause physiological stress responses and inhibit the expression of oral behaviors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0154179PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854461PMC
July 2017

Gender-specific genital and subjective sexual arousal to prepotent sexual features in heterosexual women and men.

Biol Psychol 2014 Oct 21;102:1-9. Epub 2014 Jul 21.

Department of Psychology, Queen's University, 354 Humphrey Hall, 62 Arch Street, Kingston, ON, Canada K7L 3N6. Electronic address:

Heterosexual women respond genitally to stimuli featuring both their preferred and nonpreferred genders, whereas men's genital responses are gender-specific, suggesting that gender cues are less relevant to women's sexual response. Instead, prepotent sexual features (exposed and sexually aroused genitals), ubiquitous in audiovisual sexual stimuli, may elicit automatic genital responses, thereby leading to a nonspecific sexual arousal pattern in women. To examine the role of stimulus potency in women's sexual response, we assessed heterosexual women's and men's genital and subjective sexual arousal to slideshows of prepotent stimuli (erect penises and aroused vulvas), non-prepotent stimuli (flaccid penises and female pubic triangles), and sexually neutral stimuli. Contrary to our hypotheses, both women and men demonstrated gender-specific genital and subjective sexual arousal, such that sexual arousal was greatest to prepotent male and female stimuli, respectively. This is the first study to demonstrate gender-specific genital responding in heterosexual women.
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http://dx.doi.org/10.1016/j.biopsycho.2014.07.008DOI Listing
October 2014

Assessment of contemporary stent deployment using intravascular ultrasound.

Catheter Cardiovasc Interv 2002 Oct;57(2):150-4

University of Maryland School of Medicine, Baltimore, Maryland, USA.

Four second- and third-generation coronary stents were evaluated using QCA and intravascular ultrasound for adequacy of stent expansion, the influence of disease burden on adequacy of deployment, and postdeployment structural effects on the artery. Despite satisfactory stent deployment rates on angiography of 92 %, adequate stent deployment by IVUS ranged from 38% to 55%. There was no significant difference in deployment success across the four stent types. Lesions with significant plaque burden were associated with a lower rate of deployment success (P = 0.04). Twenty-one edge dissections were demonstrated by IVUS; only six were detected by angiography. Observations made on first-generation stents regarding adequacy of deployment still hold true for newer-generation stents. Significant plaque burden is an independent negative predictor of stent deployment success. The presence of IVUS-detected edge dissections indicates that the extent of injury during PCI extends beyond the physical length of the stent.
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http://dx.doi.org/10.1002/ccd.10311DOI Listing
October 2002