Publications by authors named "Amy Williams"

238 Publications

Isha Yoga Practices and Participation in Samyama Program are Associated with Reduced HbA1C and Systemic Inflammation, Improved Lipid Profile, and Short-Term and Sustained Improvement in Mental Health: A Prospective Observational Study of Meditators.

Front Psychol 2021 19;12:659667. Epub 2021 May 19.

Department of Anesthesia, Critical Care and Pain Medicine, Sadhguru Center for a Conscious Planet, Beth Israel Deaconess Medical Center, Boston, MA, United States.

Meditation is gaining recognition as a tool to impact health and well-being. Samyama is an 8-day intensive residential meditation experience conducted by Isha Foundation requiring several months of extensive preparation and vegan diet. The health effects of Samyama have not been previously studied. The objective was to assess physical and emotional well-being before and after Samyama participation by evaluating psychological surveys and objective health biomarkers. This was an observational study of 632 adults before and after the Isha Samyama retreat. All participants were invited to complete surveys. Controls included household significant others. Surveys were completed at baseline (T1), just before Samyama (T2), immediately after Samyama (T3), and 3 months later (T4) to assess anxiety, depression, mindfulness, joy, vitality, and resilience through validated psychometric scales. Voluntary blood sampling for biomarker analysis was done to assess hemoglobin (Hb), HbA1c, lipid profile, and C-reactive protein (CRP). Primary outcomes were changes in psychometric scores, body weight, and blood biomarkers. Depression and anxiety scores decreased from T1 to T3, with the effect most pronounced in participants with baseline depression or anxiety. Scores at T4 remained below baseline for those with pre-existing depression or anxiety. Vitality, resilience, joy, and mindfulness increased from T1 to T3 (sustained at T4). Body weight decreased by 3% from T1 to T3. Triglycerides (TG) were lower from T2 to T3. Participants had lower HbA1c and HDL at T2, and lower CRP at all timepoints compared with controls. Participation in the Isha Samyama program led to multiple benefits. The 2-month preparation reduced anxiety, and participants maintained lower anxiety levels at 3 months post-retreat. Physical health improved over the course of the program as evidenced by weight loss and improved HbA1C and lipid profile. Practices associated with the Samyama preparation phase and the retreat may serve as an effective way to improve physical and mental health. Future studies may examine their use as an alternative therapy in patients with depression and/or anxiety. www.ClinicalTrials.gov, Identifier: 1801728792. Registered retrospectively on 4/17/2020.
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http://dx.doi.org/10.3389/fpsyg.2021.659667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170079PMC
May 2021

A review of the genotoxicity of the industrial chemical cumene.

Mutat Res 2021 Jan-Jun;787:108364. Epub 2021 Jan 5.

Exponent, Inc., Center for Health Sciences, 1800 Diagonal Road, Suite 500, Alexandria, VA, 22314, United States.

The purpose of this review is to evaluate the literature on the genotoxicity of cumene (CAS # 98-82-8) and to assess the role of mutagenicity, if any, in the mode of action for cumene-induced rodent tumors. The studies reviewed included microbial mutagenicity, DNA damage/ repair, cytogenetic effects, and gene mutations. In reviewing these studies, attention was paid to their conformance to applicable OECD test guidelines which are considered as internationally recognized standards for performing these assays. Cumene was not a bacterial mutagen and did not induce Hprt mutations in CHO cell cultures. In the primary rat hepatocyte cultures, cumene induced unscheduled DNA synthesis in one study but this response could not be reproduced in an independent study using a similar protocol. In a study that is not fully compliant to the current OECD guideline, no increase in chromosomal aberrations was observed in CHO cells treated with cumene. The weight of the evidence (WoE) from multiple in vivo studies indicates that cumene is not a clastogen or aneugen. The weak positive response in an in vivo comet assay in the rat liver and mouse lung tissues is of questionable significance due to several study deficiencies. The genotoxicity profile of cumene does not match that of a classic DNA-reactive molecule and the available data does not support a conclusion that cumene is an in vivo mutagen. As such, mutagenicity does not appear to be an early key event in cumene-induced rodent tumors and alternate hypothesized non-mutagenic modes-of-action are presented. Further data are necessary to rule in or rule out a particular MoA.
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http://dx.doi.org/10.1016/j.mrrev.2021.108364DOI Listing
January 2021

Quality Performance of a Transfer Center Reduces Interhospital Transfer and Direct Admission-Related ED Evaluations.

Am J Med Qual 2021 May 12. Epub 2021 May 12.

Department of Medicine, Division of Hospital Internal Medicine, Mayo Clinic, Rochester, MN Department of Health Sciences Research, Division of Biostatistics, Mayo Clinic, Rochester, MN Midwest Admission and Transfer Center, Mayo Clinic, Rochester, MN Department of Medicine, Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN Department of Medicine, Mayo Clinic, Phoenix, AZ Department of Medicine, Division of Nephrology, Mayo Clinic, Rochester, MN Executive Dean of Practice, Mayo Clinic, Rochester, MN.

Transfer centers play a vital role in the efficient triage of hospital admission requests that generate outside the emergency department (ED) of the given facility. This cohort study includes all the calls processed through the transfer center requesting an admission to Mayo Clinic, Rochester, from January 2016 to December 2018. More than 116,000 transfer request calls were processed. Of these, about 65% (75,000) were accepted for ED evaluation or direct admission. Of the 75,000 patients, >50% were accepted as direct admits. Among patients accepted for direct admission, a trend toward reduced utilization of ED reevaluation at the receiving facility was noted from 2016 to 2018. A temporal trend of overall reduced ED utilization reflects the adeptness of the transfer center. An effective transfer center promotes value-based care, optimizes the workflow in a hospital, and augments hospital administrative decisions to allocate resources.
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http://dx.doi.org/10.1097/01.JMQ.0000735520.04870.16DOI Listing
May 2021

Prevalence of SARS-CoV-2 Antibodies in a Multistate Academic Medical Center.

Mayo Clin Proc 2021 05 26;96(5):1165-1174. Epub 2021 Mar 26.

Mayo Clinic, Phoenix, AZ.

Objective: To estimate the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in health care personnel.

Methods: The Mayo Clinic Serology Screening Program was created to provide a voluntary, two-stage testing program for SARS-CoV-2 antibodies to health care personnel. The first stage used a dried blood spot screening test initiated on June 15, 2020. Those participants identified as reactive were advised to have confirmatory testing via a venipuncture. Venipuncture results through August 8, 2020, were considered. Consent and authorization for testing was required to participate in the screening program. This report, which was conducted under an institutional review board-approved protocol, only includes employees who have further authorized their records for use in research.

Results: A total of 81,113 health care personnel were eligible for the program, and of these 29,606 participated in the screening program. A total of 4284 (14.5%) of the dried blood spot test results were "reactive" and warranted confirmatory testing. Confirmatory testing was completed on 4094 (95.6%) of the screen reactive with an overall seroprevalence rate of 0.60% (95% CI, 0.52% to 0.69%). Significant variation in seroprevalence was observed by region of the country and age group.

Conclusion: The seroprevalence for SARS-CoV-2 antibodies through August 8, 2020, was found to be lower than previously reported in other health care organizations. There was an observation that seroprevalence may be associated with community disease burden.
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http://dx.doi.org/10.1016/j.mayocp.2021.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997730PMC
May 2021

A Blueprint to Control the SARS-CoV-2 Pandemic.

Mayo Clin Proc 2021 05 26;96(5):1128-1131. Epub 2021 Mar 26.

Department of Infectious Diseases, Mayo Clinic, Rochester, MN; Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN. Electronic address:

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http://dx.doi.org/10.1016/j.mayocp.2021.03.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997695PMC
May 2021

Keratinocyte-derived microvesicle particles mediate ultraviolet B radiation-induced systemic immunosuppression.

J Clin Invest 2021 May;131(10)

Department of Pharmacology and Toxicology.

A complete carcinogen, ultraviolet B (UVB) radiation (290-320 nm), is the major cause of skin cancer. UVB-induced systemic immunosuppression that contributes to photocarcinogenesis is due to the glycerophosphocholine-derived lipid mediator platelet-activating factor (PAF). A major question in photobiology is how UVB radiation, which only absorbs appreciably in the epidermal layers of skin, can generate systemic effects. UVB exposure and PAF receptor (PAFR) activation in keratinocytes induce the release of large numbers of microvesicle particles (MVPs; extracellular vesicles ranging from 100 to 1000 nm in size). MVPs released from skin keratinocytes in vitro in response to UVB (UVB-MVPs) are dependent on the keratinocyte PAFR. Here, we used both pharmacologic and genetic approaches in cells and mice to show that both the PAFR and enzyme acid sphingomyelinase (aSMase) were necessary for UVB-MVP generation. Our discovery that the calcium-sensing receptor is a keratinocyte-selective MVP marker allowed us to determine that UVB-MVPs leaving the keratinocyte can be found systemically in mice and humans following UVB exposure. Moreover, we found that UVB-MVPs contained bioactive contents including PAFR agonists that allowed them to serve as effectors for UVB downstream effects, in particular UVB-mediated systemic immunosuppression.
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http://dx.doi.org/10.1172/JCI144963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121517PMC
May 2021

Plasma IL-6 levels following corticosteroid therapy as an indicator of ICU length of stay in critically ill COVID-19 patients.

Cell Death Discov 2021 Mar 15;7(1):55. Epub 2021 Mar 15.

nference, Cambridge, MA, 02142, USA.

Intensive care unit (ICU) admissions and mortality in severe COVID-19 patients are driven by "cytokine storms" and acute respiratory distress syndrome (ARDS). Interim clinical trial results suggest that the corticosteroid dexamethasone displays better 28-day survival in severe COVID-19 patients requiring ventilation or oxygen. In this study, 10 out of 16 patients (62.5%) that had an average plasma IL-6 value over 10 pg/mL post administration of corticosteroids also had worse outcomes (i.e., ICU stay >15 days or death), compared to 8 out of 41 patients (19.5%) who did not receive corticosteroids (p-value = 0.0024). Given this potential association between post-corticosteroid IL-6 levels and COVID-19 severity, we hypothesized that the glucocorticoid receptor (GR or NR3C1) may be coupled to IL-6 expression in specific cell types that govern cytokine release syndrome (CRS). Examining single-cell RNA-seq data from BALF of severe COVID-19 patients and nearly 2 million cells from a pan-tissue scan shows that alveolar macrophages, smooth muscle cells, and endothelial cells co-express NR3C1 and IL-6, motivating future studies on the links between the regulation of NR3C1 function and IL-6 levels.
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http://dx.doi.org/10.1038/s41420-021-00429-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958587PMC
March 2021

Interprofessional Education: Current State in Psychology Training.

J Clin Psychol Med Settings 2021 Mar 10. Epub 2021 Mar 10.

College of Medicine, University of Arkansas for Medical Sciences, Little Rock, USA.

Healthcare reform has led to the consideration of interprofessional team-based, collaborative care as a way to provide comprehensive, high-quality care to patients and families. Interprofessional education is the mechanism by which the next generation health professional workforce is preparing for the future of health care-team-based, collaborative care. This literature review explored the extent and content of published studies documenting Interprofessional Education (IPE) activities with psychology trainees across learner level. A systematic review following PRISMA guidelines was conducted of studies describing IPE involving psychology learners. Electronic databases (MEDLINE, CINAHL, PsychINFO, and EMBASE) were searched for the following terms: inter/multi-professional education/practice, inter/multidisciplinary education/practice, and psychology/psychologists. Thirty-seven articles were identified that included psychology in clinical outcome studies or other reviews of interprofessional education initiatives. The review addresses the nature of current IPE learning activities, the impact of IPE activities on participating trainees, opportunities for, and challenges of, involving psychology trainees in IPE, and future directions for research. This review illuminates the relative paucity of the literature about IPE in psychology training. Given the trend toward increasing team-based collaborative care, the limited inclusion of psychology in the IPE literature is concerning. The next generation of health professional trainees is learning about, from, and with each other with the objective of building collaboration and teamwork. Given the few articles documenting psychology trainees' involvement in IPE, future health professionals quite possibly will have limited understanding of, and contact with, psychologists. Our findings are a call to action for greater psychology involvement in IPE.
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http://dx.doi.org/10.1007/s10880-021-09765-5DOI Listing
March 2021

Outcomes of COVID-19 With the Mayo Clinic Model of Care and Research.

Mayo Clin Proc 2021 03 26;96(3):601-618. Epub 2020 Dec 26.

Division of Infectious Diseases, Mayo Clinic, Rochester, MN.

Objective: To report the Mayo Clinic experience with coronavirus disease 2019 (COVID-19) related to patient outcomes.

Methods: We conducted a retrospective chart review of patients with COVID-19 diagnosed between March 1, 2020, and July 31, 2020, at any of the Mayo Clinic sites. We abstracted pertinent comorbid conditions such as age, sex, body mass index, Charlson Comorbidity Index variables, and treatments received. Factors associated with hospitalization and mortality were assessed in univariate and multivariate models.

Results: A total of 7891 patients with confirmed COVID-19 infection with research authorization on file received care across the Mayo Clinic sites during the study period. Of these, 7217 patients were adults 18 years or older who were analyzed further. A total of 897 (11.4%) patients required hospitalization, and 354 (4.9%) received care in the intensive care unit (ICU). All hospitalized patients were reviewed by a COVID-19 Treatment Review Panel, and 77.5% (695 of 897) of inpatients received a COVID-19-directed therapy. Overall mortality was 1.2% (94 of 7891), with 7.1% (64 of 897) mortality in hospitalized patients and 11.3% (40 of 354) in patients requiring ICU care.

Conclusion: Mayo Clinic outcomes of patients with COVID-19 infection in the ICU, hospital, and community compare favorably with those reported nationally. This likely reflects the impact of interprofessional multidisciplinary team evaluation, effective leveraging of clinical trials and available treatments, deployment of remote monitoring tools, and maintenance of adequate operating capacity to not require surge adjustments. These best practices can help guide other health care systems with the continuing response to the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.mayocp.2020.12.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831394PMC
March 2021

Does insurance type influence overall survival in patients with laryngeal squamous cell carcinoma?

Am J Otolaryngol 2021 Jul-Aug;42(4):102959. Epub 2021 Feb 27.

Department of Otolaryngology-Head and Neck Surgery, Henry Ford Hospital, Detroit, MI, USA. Electronic address:

Objective: Patients with head and neck cancer with Medicaid or no insurance present at a more advanced stage and have lower survival. This study is one of the first to examine the relationship between specific insurance types and overall survival for laryngeal squamous cell carcinoma patients.

Study Design: Retrospective chart review.

Setting: Henry Ford Cancer Institute.

Subjects And Methods: A retrospective database review was performed using the Henry Ford Virtual Data Warehouse Tumor Registry. Six hundred and fifty patients diagnosed with laryngeal squamous cell carcinoma were identified. Insurance groups analyzed were fee for service, health maintenance organization, Henry Ford Medical Group - a managed care type insurance, Medicare and Medicaid/uninsured. Cox proportional hazards and Kaplan-Meier curves were generated to analyze overall survival and display survival differences respectively.

Results: The uninsured group had the lowest median survival time of 29.8 months (95% CI: 20.3-44.8) and the highest HR of 1.85 (95% CI 1.16-2.93) as compared to the HMO group at p < 0.001. Patients with fee for service insurance had longer overall survival compared to the other insurance types. Patients with fee for service insurance also had a high proportion of patients with advanced stage disease, but a younger mean age. Henry Ford Medical Group had a higher mean age and no statistically significant difference in survival when compared to fee for service. (p = 0.999) After controlling for socioeconomic status, insurance type remains a significant predictor of overall survival.

Conclusions: Fee for service had the highest overall survival of the different insurance types, but it was only statistically significant when compared to the Medicaid/uninsured group.
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http://dx.doi.org/10.1016/j.amjoto.2021.102959DOI Listing
February 2021

Exploratory analysis of immunization records highlights decreased SARS-CoV-2 rates in individuals with recent non-COVID-19 vaccinations.

Sci Rep 2021 02 26;11(1):4741. Epub 2021 Feb 26.

Nference, Inc., One Main Street, Suite 400, East Arcade, Cambridge, MA, 02142, USA.

Clinical studies are ongoing to assess whether existing vaccines may afford protection against SARS-CoV-2 infection through trained immunity. In this exploratory study, we analyze immunization records from 137,037 individuals who received SARS-CoV-2 PCR tests. We find that polio, Haemophilus influenzae type-B (HIB), measles-mumps-rubella (MMR), Varicella, pneumococcal conjugate (PCV13), Geriatric Flu, and hepatitis A/hepatitis B (HepA-HepB) vaccines administered in the past 1, 2, and 5 years are associated with decreased SARS-CoV-2 infection rates, even after adjusting for geographic SARS-CoV-2 incidence and testing rates, demographics, comorbidities, and number of other vaccinations. Furthermore, age, race/ethnicity, and blood group stratified analyses reveal significantly lower SARS-CoV-2 rate among black individuals who have taken the PCV13 vaccine, with relative risk of 0.45 at the 5 year time horizon (n: 653, 95% CI (0.32, 0.64), p-value: 6.9e-05). Overall, this study identifies existing approved vaccines which can be promising candidates for pre-clinical research and Randomized Clinical Trials towards combating COVID-19.
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http://dx.doi.org/10.1038/s41598-021-83641-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910541PMC
February 2021

Socioeconomic Disparities in Patient Use of Telehealth During the Coronavirus Disease 2019 Surge.

JAMA Otolaryngol Head Neck Surg 2021 03;147(3):287-295

Department of Otolaryngology-Head & Neck Surgery, Henry Ford Hospital, Detroit, Michigan.

Importance: The coronavirus disease 2019 (COVID-19) pandemic required the rapid transition to telehealth with the aim of providing patients with medical access and supporting clinicians while abiding by the stay-at-home orders.

Objective: To assess demographic and socioeconomic factors associated with patient participation in telehealth during the COVID-19 pandemic.

Design, Setting, And Participants: This cohort study included all pediatric and adult patient encounters at the Department of Otolaryngology-Head & Neck Surgery in a tertiary care, academic, multisubspecialty, multisite practice located in an early hot spot for the COVID-19 pandemic from March 17 to May 1, 2020. Encounters included completed synchronous virtual, telephone, and in-person visits as well as visit no-shows.

Main Outcomes And Measures: Patient demographic characteristics, insurance status, and 2010 Census block level data as a proxy for socioeconomic status were extracted. Univariate and multivariate logistic regression models were created for patient-level comparisons.

Results: Of the 1162 patients (604 females [52.0%]; median age, 55 [range, 0-97] years) included, 990 completed visits; of these, 437 (44.1%) completed a virtual visit. After multivariate adjustment, females (odds ratio [OR], 1.71; 95% CI, 1.11-2.63) and patients with preferred provider organization insurance (OR, 2.70; 95% CI, 1.40-5.20) were more likely to complete a virtual visit compared with a telephone visit. Increasing age (OR per year, 0.98; 95% CI, 0.98-0.99) and being in the lowest median household income quartile (OR, 0.60; 95% CI, 0.42-0.86) were associated with lower odds of completing a virtual visit overall. Those patients within the second (OR, 0.53; 95% CI, 0.28-0.99) and lowest (OR, 0.33; 95% CI, 0.17-0.62) quartiles of median household income by census block and those with Medicaid, no insurance, or other public insurance (OR, 0.47; 95% CI, 0.23-0.94) were more likely to complete a telephone visit. Finally, being within the lower 2 quartiles of proportion being married (OR for third quartile, 0.49 [95% CI, 0.29-0.86]; OR for lowest quartile, 0.39 [95% CI, 0.23-0.67]) was associated with higher likelihood of a no-show visit.

Conclusions And Relevance: These findings suggest that age, sex, median household income, insurance status, and marital status are associated with patient participation in telehealth. These findings identify vulnerable patient populations who may not engage with telehealth, yet still require medical care in a changing health care delivery landscape.
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http://dx.doi.org/10.1001/jamaoto.2020.5161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809608PMC
March 2021

Service user and community clinician design of a partially virtual diabetic service improves access to care and education and reduces amputation incidence.

BMJ Open Diabetes Res Care 2021 Jan;9(1)

Integrated Diabetes Care, Northern Devon Healthcare NHS Trust, Barnstaple, Devon, UK

Introduction: Design of an integrated diabetes service based on needs of service users (persons living with diabetes) and community clinicians in a semirural low-income health district of the UK.

Research Design And Methods: One hundred and eighty-five service users engaged through public meetings, questionnaires and focus groups. General practice staff contributed views through workshops and questionnaires. Analysis of feedback indicated service user needs for better access to education, dietary advice and foot care. General practice staff endorsed these views and requested regular access to secondary care in the community. Seven hundred persons registered with diabetes attended eight well-being events in the community. From 2017 virtual practice multidisciplinary patient reviews, virtual referral of foot cases and non-face-to-face helplines were developed. A National Health Service (NHS) approved 'App' and web-based personalized education support for those recently diagnosed with diabetes was introduced.

Results: Engagement in education for those recently diagnosed with diabetes increased from 5% to 71%. Weight and hemoglobin A1c (HbA1c) levels before and 6 months after starting the program were 99.4±25 and 95.5±24.2 kg and 59.3±16 and 54.8±12.9 mmol/mol, respectively, p=0.00003 and 0.003. Of those engaging at well-being events, 44 had missed regular follow-up. One hundred and seventy-five cases were reviewed virtually with practice staff by the secondary care team avoiding referral to the hospital diabetic clinic. One hundred and seventy-six referrals were made to the virtual multidisciplinary diabetic foot team clinic. Major amputation incidence declined from 13 to 3 major procedures/10 000 per annum and minor amputation from 26 to 18/10 000. Percentage bed day occupancy by persons with diabetes fell significantly in the district general hospital.

Conclusions: Integrated community-based diabetes care delivery has been achieved with partially virtual reviews. Patient education, secondary care in the community, access to dietetic advice and foot care outcomes have all improved.
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http://dx.doi.org/10.1136/bmjdrc-2020-001657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802684PMC
January 2021

Distinguishing pedigree relationships via multi-way identity by descent sharing and sex-specific genetic maps.

Am J Hum Genet 2021 01 31;108(1):68-83. Epub 2020 Dec 31.

Department of Computational Biology, Cornell University, Ithaca, NY 14853, USA. Electronic address:

The proportion of samples with one or more close relatives in a genetic dataset increases rapidly with sample size, necessitating relatedness modeling and enabling pedigree-based analyses. Despite this, relatives are generally unreported and current inference methods typically detect only the degree of relatedness of sample pairs and not pedigree relationships. We developed CREST, an accurate and fast method that identifies the pedigree relationships of close relatives. CREST utilizes identity by descent (IBD) segments shared between a pair of samples and their mutual relatives, leveraging the fact that sharing rates among these individuals differ across pedigree configurations. Furthermore, CREST exploits the profound differences in sex-specific genetic maps to classify pairs as maternally or paternally related-e.g., paternal half-siblings-using the locations of autosomal IBD segments shared between the pair. In simulated data, CREST correctly classifies 91.5%-100% of grandparent-grandchild (GP) pairs, 80.0%-97.5% of avuncular (AV) pairs, and 75.5%-98.5% of half-siblings (HS) pairs compared to PADRE's rates of 38.5%-76.0% of GP, 60.5%-92.0% of AV, 73.0%-95.0% of HS pairs. Turning to the real 20,032 sample Generation Scotland (GS) dataset, CREST identified seven pedigrees with incorrect relationship types or maternal/paternal parent sexes, five of which we confirmed as mistakes, and two with uncertain relationships. After correcting these, CREST correctly determines relationship types for 93.5% of GP, 97.7% of AV, and 92.2% of HS pairs that have sufficient mutual relative data; the parent sex in 100% of HS and 99.6% of GP pairs; and it completes this analysis in 2.8 h including IBD detection in eight threads.
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http://dx.doi.org/10.1016/j.ajhg.2020.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820736PMC
January 2021

Influence of Calcium Perchlorate on the Search for Organics on Mars with Tetramethylammonium Hydroxide Thermochemolysis.

Astrobiology 2021 03 11;21(3):279-297. Epub 2020 Dec 11.

Space Science Exploration Division (Code 690), NASA Goddard Space Flight Center, Greenbelt, Maryland, USA.

The Mars Organic Molecule Analyzer (MOMA) and Sample Analysis at Mars (SAM) instruments onboard the Exomars 2022 and Mars Science Laboratory rovers, respectively, are capable of organic matter detection and differentiating potentially biogenic from abiotic organics in martian samples. To identify organics, both these instruments utilize pyrolysis-gas chromatography coupled to mass spectrometry, and the thermochemolysis agent tetramethylammonium hydroxide (TMAH) is also used to increase organic volatility. However, the reactivity and efficiency of TMAH thermochemolysis are affected by the presence of calcium perchlorate on the martian surface. In this study, we determined the products of TMAH pyrolysis in the presence and absence of calcium perchlorate at different heating rates (flash pyrolysis and SAM-like ramp pyrolysis with a 35°C·min heating rate). The decomposition mechanism of TMAH pyrolysis in the presence of calcium perchlorate was studied by using stepped pyrolysis. Moreover, the effect of calcium perchlorate (at Mars-relevant concentrations) on the recovery rate of fatty acids with TMAH thermochemolysis was studied. Results demonstrate that flash pyrolysis yields more diversity and greater abundances of TMAH thermochemolysis products than does the SAM-like ramp pyrolysis method. There is no obvious effect of calcium perchlorate on TMAH degradation when the [ClO] is lower than 10 weight percent (wt %). Most importantly, the presence of calcium perchlorate does not significantly impact the recovery rate of fatty acids with TMAH thermochemolysis under laboratory conditions, which is promising for the detection of fatty acids via TMAH thermochemolysis with the SAM and MOMA instruments on Mars.
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http://dx.doi.org/10.1089/ast.2020.2252DOI Listing
March 2021

Long-term SARS-CoV-2 RNA shedding and its temporal association to IgG seropositivity.

Cell Death Discov 2020 Dec 2;6(1):138. Epub 2020 Dec 2.

nference, inc., One Main Street, Suite 400, East Arcade, Cambridge, MA, 02142, USA.

Longitudinal characterization of SARS-CoV-2 PCR testing from COVID-19 patient's nasopharynx and its juxtaposition with blood-based IgG-seroconversion diagnostic assays is critical to understanding SARS-CoV-2 infection durations. Here, we retrospectively analyze 851 SARS-CoV-2-positive patients with at least two positive PCR tests and find that 99 of these patients remain SARS-CoV-2-positive after 4 weeks from their initial diagnosis date. For the 851-patient cohort, the mean lower bound of viral RNA shedding was 17.3 days (SD: 7.8), and the mean upper bound of viral RNA shedding from 668 patients transitioning to confirmed PCR-negative status was 22.7 days (SD: 11.8). Among 104 patients with an IgG test result, 90 patients were seropositive to date, with mean upper bound of time to seropositivity from initial diagnosis being 37.8 days (95% CI: 34.3-41.3). Our findings from juxtaposing IgG and PCR tests thus reveal that some SARS-CoV-2-positive patients are non-hospitalized and seropositive, yet actively shed viral RNA (14 of 90 patients). This study emphasizes the need for monitoring viral loads and neutralizing antibody titers in long-term non-hospitalized shedders as a means of characterizing the SARS-CoV-2 infection lifecycle.
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http://dx.doi.org/10.1038/s41420-020-00375-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709096PMC
December 2020

Race, not socioeconomic disparities, correlates with survival in human papillomavirus-negative oropharyngeal cancer: A retrospective study.

Am J Otolaryngol 2021 Jan - Feb;42(1):102816. Epub 2020 Oct 28.

Department of Otolaryngology-Head and Neck Surgery, K8, Henry Ford Hospital, 2799 W Grand Blvd., Detroit, MI 48202, USA. Electronic address:

Purpose: Investigate the impact of black versus white race, socioeconomic status (SES), and comorbidity burden on oropharyngeal cancer (OPC) survival.

Materials And Methods: This study retrospectively analyzed patients diagnosed between 1991 and 2012 at an urban tertiary care center with a high volume of head and neck cancer referrals. Data gathered included demographics, human papilloma virus (HPV) status, follow-up time, comorbidities, smoking history, and overall survival. SES was extrapolated from the 2000 and 2010 censuses. Analysis of variance, chi-square tests, multivariable Cox proportional hazards models, Cox proportional hazards regression, Kaplan Meier curves and the log-rank test were utilized.

Results: Of 208 charts reviewed, 192 patients met inclusion criteria. Black patients had significantly (p < 0.001) poorer survival at 1, 2, and 5 years than white patients (5-year survival: 32% vs 64%); this discrepancy persisted in only HPV-negative disease (20% vs 50%). In the HPV-negative subgroup, there was no racial difference in treatment modality received, Charlson Comorbidity Index, and proportion receiving inadequate, noncurative or no treatment. Univariate analysis identified significant differences in median household income, education level, and stage at presentation between black and white subgroups. Multivariate analysis identified white race and HPV-positive status as independent predictors of overall survival, but SES and stage at presentation were not.

Conclusion: SES did not explain the greater survival in HPV-negative white versus black patients. This indicates that race is an independent predictor of survival; future studies should examine more accurate indicators of SES and genetic differences in tumors of black and white patients.
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http://dx.doi.org/10.1016/j.amjoto.2020.102816DOI Listing
April 2021

Fatty Acid Preservation in Modern and Relict Hot-Spring Deposits in Iceland, with Implications for Organics Detection on Mars.

Astrobiology 2021 01 29;21(1):60-82. Epub 2020 Oct 29.

SETI Institute, Mountain View, California, USA.

Hydrothermal spring deposits host unique microbial ecosystems and have the capacity to preserve microbial communities as biosignatures within siliceous sinter layers. This quality makes terrestrial hot springs appealing natural laboratories to study the preservation of both organic and morphologic biosignatures. The discovery of hydrothermal deposits on Mars has called attention to these hot springs as Mars-analog environments, driving forward the study of biosignature preservation in these settings to help prepare future missions targeting the recovery of biosignatures from martian hot-spring deposits. This study quantifies the fatty acid load in three Icelandic hot-spring deposits ranging from modern and inactive to relict. Samples were collected from both the surface and 2-18 cm in depth to approximate the drilling capabilities of current and upcoming Mars rovers. To determine the preservation potential of organics in siliceous sinter deposits, fatty acid analyses were performed with pyrolysis-gas chromatography-mass spectrometry (GC-MS) utilizing thermochemolysis with tetramethylammonium hydroxide (TMAH). This technique is available on both current and upcoming Mars rovers. Results reveal that fatty acids are often degraded in the subsurface relative to surface samples but are preserved and detectable with the TMAH pyrolysis-GC-MS method. Hot-spring mid-to-distal aprons are often the best texturally and geomorphically definable feature in older, degraded terrestrial sinter systems and are therefore most readily detectable on Mars from orbital images. These findings have implications for the detection of organics in martian hydrothermal systems as they suggest that organics might be detectable on Mars in relatively recent hot-spring deposits, but preservation likely deteriorates over geological timescales. Rovers with thermochemolysis pyrolysis-GC-MS instrumentation may be able to detect fatty acids in hot-spring deposits if the organics are relatively young; therefore, martian landing site and sample selection are of paramount importance in the search for organics on Mars.
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http://dx.doi.org/10.1089/ast.2019.2115DOI Listing
January 2021

What's New in Pediatric Orthopaedic Tumor Surgery.

J Pediatr Orthop 2021 Feb;41(2):e174-e180

Department of Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadephia, PA.

Background: Pediatric Orthopaedic Oncology is a developing subspecialty within the field of Pediatric Orthopaedics. Traditionally, the field of Orthopaedic Oncology has been focused on the skeletally mature individual, and the research tends to be all encompassing rather than truly evaluating isolated populations. The purpose of this review is to summarize the most clinically relevant literature in the field of Pediatric Orthopaedic Oncology over the last 6 years.

Methods: We evaluated the PubMed database utilizing keywords for pediatric orthopaedic oncology: sarcoma, osteosarcoma, Ewing sarcoma, bone cyst. In additionally, we further broadened our search by searching for relevant articles in the contents sections of major orthopaedic surgery journals that routinely publish both pediatric and orthopaedic oncology literature. In keeping with "What's New," we selected the most clinically relevant articles published in the last 6 years from January 1, 2014 through February 2020. Basic science and systemic therapies literature was widely reviewed and the research and clinical trials most relevant to pediatric sarcoma and neoplastic processes found in the pediatric population were included.

Results: Our search yielded 60 articles that met general criteria, from which 14 were determined to be most relevant to the goals of this paper. Of the papers presented in this review, there were papers related to management of benign tumors/tumor-like conditions, bone cysts, limb salvage procedures, and amputation procedures. Ultimately included in the review were 5 studies related to limb salvage, 4 related to bone cysts, 1 related to multiple hereditary exostoses, 2 related to osteofibrous dysplasia, 1 related to chondroblastoma, and 1 discussing cementation in skeletally immature patients. They were level III, IV, and V studies. Basic science and systemic therapies literature was widely reviewed and the research and clinical trials most relevant to pediatric sarcoma and neoplastic processes found in the pediatric population were included. Our search of the basic science and systemic therapies literature yielded 19 sources were found to be pertinent to our aims and 18 of those sources were published between 2015 and 2020.

Conclusions: There are many, varied, and creative procedures in the realm of limb salvage, though there remains a lack of high-level evidence to support some of the more novel procedures. In regards to benign bone tumors, despite a more solid base of literature, there still does not seem to be consensus as to the best treatment. In particular, there continue to be many schools of thought on the treatment of benign bone cysts. Research in the basic science arena and systemic therapies are advancing in exciting ways in regards to pediatric sarcoma. Orthopaedic oncologic research specific to the pediatric population overall continues to be impeded by low sample sizes and inadequate levels of evidence, which limits the ability of surgeons to draw definitive conclusions from the literature.
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http://dx.doi.org/10.1097/BPO.0000000000001689DOI Listing
February 2021

Peer Support in the Treatment of Chronic Pain in Adolescents: A Review of the Literature and Available Resources.

Children (Basel) 2020 Sep 7;7(9). Epub 2020 Sep 7.

Department of Anesthesia, 1130 West Michigan St., Fesler Hall 204, Indianapolis, IN 46202, USA.

Peer support has found applications beyond the mental health field and is useful for managing several chronic disorders and supporting healthy lifestyle choices. Communication through telephone and the Internet allows for greater access to those who cannot meet in person. Adolescent chronic pain would seem ideally suited to benefit from online peer support groups. Research is lacking, however, to characterize benefit in terms of pain and function, despite a clear desire among adolescents for access to such programs. More rapid development of online applications is needed for peer support, and research into the associated outcomes will be necessary to optimally design such programs.
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http://dx.doi.org/10.3390/children7090129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552767PMC
September 2020

Introduction.

Mayo Clin Proc 2020 09 13;95(9S):S1-S2. Epub 2020 Jun 13.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1016/j.mayocp.2020.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293507PMC
September 2020

The Silver Lining for Health Care During and After the Pandemic.

Mayo Clin Proc 2020 09 20;95(9S):S69-S71. Epub 2020 Jun 20.

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1016/j.mayocp.2020.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305865PMC
September 2020

Inference from longitudinal laboratory tests characterizes temporal evolution of COVID-19-associated coagulopathy (CAC).

Elife 2020 08 17;9. Epub 2020 Aug 17.

nference, inc, Cambridge, United States.

Temporal inference from laboratory testing results and triangulation with clinical outcomes extracted from unstructured electronic health record (EHR) provider notes is integral to advancing precision medicine. Here, we studied 246 SARS-CoV-2 PCR-positive (COVID) patients and propensity-matched 2460 SARS-CoV-2 PCR-negative (COVID) patients subjected to around 700,000 lab tests cumulatively across 194 assays. Compared to COVID patients at the time of diagnostic testing, COVID patients tended to have higher plasma fibrinogen levels and lower platelet counts. However, as the infection evolves, COVID patients distinctively show declining fibrinogen, increasing platelet counts, and lower white blood cell counts. Augmented curation of EHRs suggests that only a minority of COVID patients develop thromboembolism, and rarely, disseminated intravascular coagulopathy (DIC), with patients generally not displaying platelet reductions typical of consumptive coagulopathies. These temporal trends provide fine-grained resolution into COVID-19 associated coagulopathy (CAC) and set the stage for personalizing thromboprophylaxis.
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http://dx.doi.org/10.7554/eLife.59209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473767PMC
August 2020

Mapping gene flow between ancient hominins through demography-aware inference of the ancestral recombination graph.

PLoS Genet 2020 08 6;16(8):e1008895. Epub 2020 Aug 6.

Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America.

The sequencing of Neanderthal and Denisovan genomes has yielded many new insights about interbreeding events between extinct hominins and the ancestors of modern humans. While much attention has been paid to the relatively recent gene flow from Neanderthals and Denisovans into modern humans, other instances of introgression leave more subtle genomic evidence and have received less attention. Here, we present a major extension of the ARGweaver algorithm, called ARGweaver-D, which can infer local genetic relationships under a user-defined demographic model that includes population splits and migration events. This Bayesian algorithm probabilistically samples ancestral recombination graphs (ARGs) that specify not only tree topologies and branch lengths along the genome, but also indicate migrant lineages. The sampled ARGs can therefore be parsed to produce probabilities of introgression along the genome. We show that this method is well powered to detect the archaic migration into modern humans, even with only a few samples. We then show that the method can also detect introgressed regions stemming from older migration events, or from unsampled populations. We apply it to human, Neanderthal, and Denisovan genomes, looking for signatures of older proposed migration events, including ancient humans into Neanderthal, and unknown archaic hominins into Denisovans. We identify 3% of the Neanderthal genome that is putatively introgressed from ancient humans, and estimate that the gene flow occurred between 200-300kya. We find no convincing evidence that negative selection acted against these regions. Finally, we predict that 1% of the Denisovan genome was introgressed from an unsequenced, but highly diverged, archaic hominin ancestor. About 15% of these "super-archaic" regions-comprising at least about 4Mb-were, in turn, introgressed into modern humans and continue to exist in the genomes of people alive today.
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http://dx.doi.org/10.1371/journal.pgen.1008895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410169PMC
August 2020

A Qualitative Analysis of Career Advice Given to Women Leaders in an Academic Medical Center.

JAMA Netw Open 2020 07 1;3(7):e2011292. Epub 2020 Jul 1.

Mayo Clinic, Rochester, Minnesota.

Importance: Women in academic medicine continue to face systemic obstacles on their paths to leadership. In addition to improving recruitment and advancement opportunities, academic medical centers must facilitate a cultural shift that ensures sustained leadership pathways for women.

Objective: To better understand, from the perspective of women leaders, the workplace and cultural changes that need to take place in academic medicine to increase inclusivity and gender equity.

Design, Setting, And Participants: This qualitative study of 40 women physicians and administrators with senior leadership roles at Mayo Clinic, a nonprofit academic medical center and research institution with campuses in Arizona, Florida, and Minnesota, examined participants' responses to a question regarding their paths to leadership. Replies were submitted between November and December 2018.

Main Outcomes And Measures: Women were asked to describe career advice (positive or negative) they had received that was the hardest to accept but, in retrospect, turned out to be valuable.

Results: Of 40 participants, 25 (63%) were physicians and 15 (37%) were administrators at Mayo Clinic; 27 (68%) had achieved the role of chair or the administrative equivalent. Career experience ranged from 6 to 40 years. Of the 40 women leaders queried, 38 (95%) provided written responses, which were separated into the 4 following categories: leadership styles are perceived as having gendered qualities, attaining leadership skills involves a strategic learning process, collisions between personal life and the workplace should not deter individuals from pursuing leadership roles, and leadership pathways for women involved hurdles. These categories represented a roadmap illuminating perceptions about the academic medical workplace.

Conclusions And Relevance: These findings link generalizable principles to help to drive new strategies for gender parity. Shifting the culture of academic medicine begins with fully understanding impediments to women's advancement. The advice women leaders recounted offered a roadmap as well as a glimpse of the extra effort required for women to succeed amid some of the system's limitations and obstacles. A more complete understanding of gender biases may help to shape future programs to expand inclusivity and establish sustained leadership paths for women.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.11292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376389PMC
July 2020

Pediatric Chondroblastoma and the Need for Lung Staging at Presentation.

J Pediatr Orthop 2020 Oct;40(9):e894-e897

Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.

Purpose: Chondroblastoma is a benign, but potentially locally aggressive, bone tumor with predilection for the epiphysis of long bones in growing children. Historically, there is a reported 2% risk of lung metastasis, however these cases are mostly in the form of isolated single reports and the vast majority in adults. The purpose of this study was to identify the "true" risk of lung metastases at presentation in skeletally immature patients with a benign chondroblastoma, and therefore revisit the need for routine chest staging.

Methods: This was a multi-institution, international retrospective study of children and adolescents diagnosed and treated for a benign chondroblastoma. We focused on the screening and diagnosis of lung metastasis, type of staging utilized and the incidence of local recurrence. Detailed review of the available literature was also performed for comparison.

Results: The final studied cohort included 130 children with an average age of 14.5 years (range: 6 to 18 y). There were 94 boys and 36 girls. Lesions more often involved the proximal humerus (32/130), proximal tibia (30/130), and proximal femur (28/130). At an average follow-up of 50 months, there were 15 local recurrences (11% rate) and no cases of lung metastasis. All patients underwent chest imaging at presentation. The overall reported lung metastases rate in the pulled literature review (larger series only) was 0.4% (7/1625), all patients were skeletally mature.

Conclusions: This is the largest cohort of pediatric-exclusive chondroblastoma in the literature. Despite minor differences in management between the centers included, the recurrence rate was similar and there was no evidence of lung metastasis (0 in 130). The incidence of distant involvement in a true benign chondroblastoma in children is much lower than the 2% previously reported in the literature, and the need for routine chest staging should be revisited.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1097/BPO.0000000000001631DOI Listing
October 2020

Teratogen update: Topical use and third-generation retinoids.

Birth Defects Res 2020 09 9;112(15):1105-1114. Epub 2020 Jul 9.

Exponent, Inc., Alexandria, Virginia, USA.

The first pharmaceutical retinoids approved by the U.S. Food and Drug Administration were given black-box warnings against their use in pregnancy due to potential teratogenic effects. These first- and second-generation retinoids were initially formulated for oral dosing and are structurally very similar to vitamin A, which has beneficial effects on skin as well as plays a vital role in driving healthy embryogenesis. Some of these early retinoids have since been reformulated for topical application, which has resulted in their diminished potential for systemic exposures. Additionally, rational drug design has been applied to create today's third-generation retinoids (adapalene, tazarotene, and bexarotene). These compounds include aromatic rings within their molecular cores to provide structural rigidity that contrasts with the flexible aliphatic backbone of vitamin A and the earlier generations of retinoids, and thus limits their off-target activity. As a result of these design features, the teratogenic potential in animals of the third-generation retinoids and those reformulated for topical use is generally less than seen with oral administration of earlier generations of retinoids. The available, but limited, epidemiologic data further show little-to-no teratogenic potential associated with real-life use of these compounds in humans. Given the paucity of epidemiologic data available at this time, however, it is recommended that the use of topical retinoids during pregnancy be avoided. However, in circumstances when inadvertent exposure in pregnancy may occur, the available data provide some reassurance that adverse pregnancy outcomes are unlikely.
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http://dx.doi.org/10.1002/bdr2.1745DOI Listing
September 2020

Augmented curation of clinical notes from a massive EHR system reveals symptoms of impending COVID-19 diagnosis.

Elife 2020 07 7;9. Epub 2020 Jul 7.

Mayo Clinic, Rochester, United States.

Understanding temporal dynamics of COVID-19 symptoms could provide fine-grained resolution to guide clinical decision-making. Here, we use deep neural networks over an institution-wide platform for the augmented curation of clinical notes from 77,167 patients subjected to COVID-19 PCR testing. By contrasting Electronic Health Record (EHR)-derived symptoms of COVID-19-positive (COVID; n = 2,317) versus COVID-19-negative (COVID; n = 74,850) patients for the week preceding the PCR testing date, we identify anosmia/dysgeusia (27.1-fold), fever/chills (2.6-fold), respiratory difficulty (2.2-fold), cough (2.2-fold), myalgia/arthralgia (2-fold), and diarrhea (1.4-fold) as significantly amplified in COVID over COVID patients. The combination of cough and fever/chills has 4.2-fold amplification in COVID patients during the week prior to PCR testing, in addition to anosmia/dysgeusia, constitutes the earliest EHR-derived signature of COVID-19. This study introduces an platform for the real-time synthesis of institutional biomedical knowledge. The platform holds tremendous potential for scaling up curation throughput, thus enabling EHR-powered early disease diagnosis.
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http://dx.doi.org/10.7554/eLife.58227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410498PMC
July 2020