tbuckley/cabot-search huggingface dataset:
Highlights from Recent Cancer Literature
Journal: Cancer Research (2022)

Dendritic cells (DC) prime T-cell responses to cancer.CD8 þ T-cell priming against tumor antigens is due to cross-presentation of tumorderived antigens on type 1 conventional DC (DC1) major histocompatibility complex (MHC) molecules.Duong and colleagues revealed a new DC differentiated state that allows type 2-like DCs (DC2) to pick up intact MHC antigen from tumor cells (called "dressing") and prime CD8 þ T-cell responses.A robust interferon-stimulated gene signature (ISG) distinguishes these ISG þ DCs from DC2s.Importantly, when ISG þ DCs were present, antigen presentation and activation of CD8 þ T cells occurred in the absence of DC1s.Type I IFN produced by tumors induced the ISG þ DC phenotype.Therapeutic delivery of IFNb to tumors could generate ISG þ DCs that promoted CD8 þ T-cell responses in the absence of DC1s.
33P A literature review of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) caused by immune checkpoint inhibitors (ICIs), epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and multikinase inhibitors (MKIs)
Authors: Z. Hu, H. Dong, Y. Zhai, H. Cui, C. Li, J. Li, C. Xue, X. Lu, Y. Yu
Journal: Annals of Oncology (2022)
Moving Beyond Race-Based Medicine
Authors: David S. Jones
Journal: Annals of Internal Medicine (2022)

LettersMarch 2022Moving Beyond Race-Based MedicineDavid S. Jones, MD, PhDDavid S. Jones, MD, PhDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L21-0779 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE: The divisiveness of race in the United States is reflected in these 2 comments on my editorial. We agree about the need to heal the wounds of racism but not about first steps.Dr. Daftary highlights 1 problem: How should race-based medicine manage him? As an Asian Indian, he does not fit into U.S. race taxonomies. When should a South Asian woman begin screening mammography? Chapman and others are silent, presumably because the U.S. health care system has not collected the data needed to answer this question. Persons from North Africa, South Asia, and the Middle East experience ...References1. Lauderdale DS. Birth outcomes for Arabic-named women in California before and after September 11. Demography. 2006;43:185-201. [PMID: 16579214] CrossrefMedlineGoogle Scholar2. Bakhtiari E. Health effects of Muslim racialization: evidence from birth outcomes in California before and after September 11, 2001. SSM Popul Health. 2020;12:100703. [PMID: 33313375] doi:10.1016/j.ssmph.2020.100703 CrossrefMedlineGoogle Scholar3. Bassett MT, Galea S. Reparations as a public health priority—a strategy for ending black-white health disparities. N Engl J Med. 2020;383:2101-3. [PMID: 33031653] doi:10.1056/NEJMp2026170 CrossrefMedlineGoogle Scholar4. Richardson ET, Malik MM, Darity WA, et al. Reparations for Black American descendants of persons enslaved in the U.S. and their potential impact on SARS-CoV-2 transmission. Soc Sci Med. 2021;276:113741. [PMID: 33640157] doi:10.1016/j.socscimed.2021.113741 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Disclosures: The author has reported no disclosures of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M21-3804. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMoving Beyond Race-Based Medicine David S. Jones Moving Beyond Race-Based Medicine Mack Roach III Moving Beyond Race-Based Medicine Ashok V. Daftary Metrics March 2022Volume 175, Issue 3Page: W20-W21KeywordsMammographyRacial and ethnic issuesRacismResearch designStructural racism ePublished: 15 March 2022 Issue Published: March 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
New Horizons in the Treatment of Osteosarcoma
Authors: Paul S. Meltzer, Lee J. Helman
Journal: New England Journal of Medicine (2021)

Osteosarcoma, which is most common in people 10 to 30 years of age, is generally treated with resection and adjuvant chemotherapy. Detection of gene rearrangements, copy-number variations, and targeted disruption of tumor suppressors by whole-genome sequencing has not yet led to improved treatment.
REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19
Authors: David M Weinreich, Sumathi Sivapalasingam, Thomas Norton, Shazia Ali, Haitao Gao, Rafia Bhore, Jing Xiao, Andrea T Hooper, Jennifer D Hamilton, Bret J Musser, Diana Rofail, Mohamed Hussein, Joseph Im, Dominique Y Atmodjo, Christina Perry, Cynthia Pan, Adnan Mahmood, Romana Hosain, John D Davis, Kenneth C Turner, Alina Baum, Christos A Kyratsous, Yunji Kim, Amanda Cook, Wendy Kampman, Lilia Roque-Guerrero, Gerard Acloque, Hessam Aazami, Kevin Cannon, J Abraham Simón-Campos, Joseph A Bocchini, Bari Kowal, A Thomas DiCioccio, Yuhwen Soo, Gregory P Geba, Neil Stahl, Leah Lipsich, Ned Braunstein, Gary Herman, George D Yancopoulos
Journal: New England Journal of Medicine (2021)

In the phase 1-2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (Covid-19). REGEN-COV has activity in vitro against current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. In the phase 3 portion of an adaptive trial, we randomly assigned outpatients with Covid-19 and risk factors for severe disease to receive various doses of intravenous REGEN-COV or placebo. Patients were followed through day 29. A prespecified hierarchical analysis was used to assess the end points of hospitalization or death and the time to resolution of symptoms. Safety was also evaluated. Covid-19-related hospitalization or death from any cause occurred in 18 of 1355 patients in the REGEN-COV 2400-mg group (1.3%) and in 62 of 1341 patients in the placebo group who underwent randomization concurrently (4.6%) (relative risk reduction [1 minus the relative risk], 71.3%; P<0.001); these outcomes occurred in 7 of 736 patients in the REGEN-COV 1200-mg group (1.0%) and in 24 of 748 patients in the placebo group who underwent randomization concurrently (3.2%) (relative risk reduction, 70.4%; P = 0.002). The median time to resolution of symptoms was 4 days shorter with each REGEN-COV dose than with placebo (10 days vs. 14 days; P<0.001 for both comparisons). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody-positive at baseline. Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was -0.71 log10 copies per milliliter (95% confidence interval [CI], -0.90 to -0.53) in the 1200-mg group and -0.86 log10 copies per milliliter (95% CI, -1.00 to -0.72) in the 2400-mg group. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%); infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups. REGEN-COV reduced the risk of Covid-19-related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04425629.).
Amplatzer Amulet Left Atrial Appendage Occluder Versus Watchman Device for Stroke Prophylaxis (Amulet IDE): A Randomized, Controlled Trial
Authors: Dhanunjaya Lakkireddy, David Thaler, Christopher R. Ellis, Vijendra Swarup, Lars Sondergaard, John Carroll, Michael R. Gold, James Hermiller, Hans-Christoph Diener, Boris Schmidt, Lee MacDonald, Moussa Mansour, Brijeshwar Maini, Laura O’Brien, Stephan Windecker
Journal: Circulation (2021)

Percutaneous closure of the left atrial appendage (LAA) is an alternative to chronic oral anticoagulation to reduce stroke risk in patients with nonvalvular atrial fibrillation. The Amulet IDE trial (Amplatzer Amulet Left Atrial Appendage Occluder IDE Trial) was designed to evaluate the safety and effectiveness of the dual-seal mechanism of the Amulet LAA occluder compared with the Watchman device. Patients with nonvalvular atrial fibrillation at increased risk of stroke were randomly assigned (1:1) to undergo percutaneous implantation of a LAA occluder with the Amulet occluder or Watchman device. The primary end points included safety (composite of procedure-related complications, all-cause death, or major bleeding at 12 months), effectiveness (composite of ischemic stroke or systemic embolism at 18 months), and the rate of LAA occlusion at 45 days. Prespecified secondary end points included a composite of all stroke, systemic embolism, or cardiovascular/unexplained death at 18 months, major bleeding at 18 months, and superiority test of the 3 primary end points. A total of 1878 patients were enrolled. The Amulet occluder was noninferior to the Watchman device for the primary safety end point (14.5% versus 14.7%; difference=-0.14 [95% CI, -3.42 to 3.13]; P<0.001 for noninferiority). Major bleeding and all-cause death were similar between groups (10.6% versus 10.0% and 3.9% versus 5.1%, respectively). Procedure-related complications were higher for the Amulet occluder (4.5% versus 2.5%), largely related to more frequent pericardial effusion and device embolization. The Amulet occluder was noninferior to the Watchman device for the primary effectiveness end point (2.8% versus 2.8%; difference=0.00 [95% CI, -1.55 to 1.55]; P<0.001 for noninferiority), and the composite of stroke, systemic embolism, or cardiovascular/unexplained death (5.6% versus 7.7%, difference=-2.12 [95% CI, -4.45 to 0.21]; P<0.001 for noninferiority). The rate of major bleeding was similar between groups (11.6% versus 12.3%; difference=-0.71 [95% CI, -3.72 to 2.31]; P=0.32 for superiority). LAA occlusion was higher for the Amulet occluder than for the Watchman device (98.9% versus 96.8%; difference=2.03 [95% CI, 0.41-3.66]; P<0.001 for noninferiority; P=0.003 for superiority). The Amulet occluder was noninferior for safety and effectiveness of stroke prevention for nonvalvular atrial fibrillation compared with the Watchman device and superior for LAA occlusion. Procedure-related complications were higher with the Amulet occluder and decreased with operator experience. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02879448.
Erratum. The Women’s Leadership Gap in Diabetes: A Call for Equity and Excellence. Diabetes Care 2021;44:1734–1743
Authors: Jessica L. Dunne, Jennifer L. Maizel, Amanda L. Posgai, Mark A. Atkinson, Linda A. DiMeglio
Journal: Diabetes Care (2022)

In the Results and Fig. 2B of article cited above, the percentage of female American Diabetes Association (ADA) Presidents of Medicine and Science was given as 9%; the correct percentage is 11%. This work undercounted one female individual serving in this leadership capacity. This miscalculation occurred as the specialized program (https://gender-api.com/) utilized to determine the most probable gender of each name provided an errant assignment. As noted in the methods, manual quality control was performed for names with accuracy scores &amp;lt;95. The software provided male gender for the individual in question, with an accuracy score of 97 that did not hit the threshold for further verification. Therefore, the article Results section, second paragraph in closing, should have stated: “Since the 1970s, 83% of persons appointed as ADA President of Health Care and Education have been women (Fig. 2A), but only 11% of those appointed as ADA President of Medicine and Science have been female (Fig. 2B).” The authors apologize for the error. The online version of the article (https://doi.org/10.2337/dci21-0015) has been updated to correct the error in the text and figure.
Evaluation of Early Biomarkers of Atherosclerosis Associated with Polychlorinated Biphenyl Exposure: An <i>in Vitro</i> and <i>in Vivo</i> Study
Authors: Bingwei Yang, Zhishuai Ye, Yawen Wang, Hongzhou Guo, Hans-Joachim Lehmler, Rongchong Huang, Erqun Song, Yang Song
Journal: Environmental Health Perspectives (2022)

Background: Miscellaneous cardiovascular risk factors have been defined, but the contribution of environmental pollutants exposure on cardiovascular disease (CVD) remains underappreciated. Objective: We investigated the potential impact of typical environmental pollutant exposure on atherogenesis and its underlying mechanisms. Methods: We used human umbilical vein endothelial cells (HUVECs) and apolipoprotein E knockout (ApoE−/−) mice to investigate how 2,3,5-trichloro-6-phenyl-[1,4]-benzoquinone (PCB29-pQ, a toxic polychlorinated biphenyl metabolite) affects atherogenesis and identified early biomarkers of CVD associated with PCB29-pQ exposures. Then, we used long noncoding RNAs (lncRNAs) HDAC7-AS1–overexpressing ApoE−/− mice and apolipoprotein E/caveolin 1 double-knockout (ApoE−/−/CAV1−/−) mice to address the role of these early biomarkers in PCB29-pQ–induced atherogenesis. Plasma samples from patients with coronary heart disease (CHD) were also used to confirm our findings. Results: Our data indicate that lncRNA HDAC7-AS1 bound to MIR-7-5p via argonaute 2 in PCB29-pQ–challenged HUVECs. Our mRNA sequencing assay identified transforming growth factor-β2 (TGF-β2) as a possible target gene of MIR-7-5p; HDAC7-AS1 sponged MIR-7-5p and inhibited the binding of TGF-β2 to MIR-7-5p. The effect of PCB29-pQ–induced endothelial injury, vascular inflammation, development of plaques, and atherogenesis in ApoE−/− mice was greater with MIR-7-5p–mediated TGF-β2 inhibition, whereas HDAC7-AS1–overexpressing ApoE−/− mice and ApoE−/−/CAV1−/− mice showed the opposite effect. Consistently, plasma levels of HDAC7-AS1 and MIR-7-5p were found to be significantly associated individuals diagnosed with CHD. Discussions: These findings demonstrated that a mechanism-based, integrated-omics approach enabled the identification of potentially clinically relevant diagnostic indicators and therapeutic targets of CHD mediated by environmental contaminants using in vitro and in vivo models of HUVECs and ApoE−/− and ApoE−/−/CAV1−/− mice. https://doi.org/10.1289/EHP9833
SETD2 Haploinsufficiency Enhances Germinal Center–Associated AICDA Somatic Hypermutation to Drive B-cell Lymphomagenesis
Authors: Wilfred Leung, Matt Teater, Ceyda Durmaz, Cem Meydan, Alexandra G. Chivu, Amy Chadburn, Edward J. Rice, Ashlesha Muley, Jeannie M. Camarillo, Jaison Arivalagan, Ziyi Li, Christopher R. Flowers, Neil L. Kelleher, Charles G. Danko, Marcin Imielinski, Sandeep S. Dave, Scott A. Armstrong, Christopher E. Mason, Ari M. Melnick
Journal: Cancer Discovery (2022)

SETD2 is the sole histone methyltransferase responsible for H3K36me3, with roles in splicing, transcription initiation, and DNA damage response. Homozygous disruption of SETD2 yields a tumor suppressor effect in various cancers. However, SETD2 mutation is typically heterozygous in diffuse large B-cell lymphomas. Here we show that heterozygous Setd2 deficiency results in germinal center (GC) hyperplasia and increased competitive fitness, with reduced DNA damage checkpoint activity and apoptosis, resulting in accelerated lymphomagenesis. Impaired DNA damage sensing in Setd2-haploinsufficient germinal center B (GCB) and lymphoma cells associated with increased AICDA-induced somatic hypermutation, complex structural variants, and increased translocations including those activating MYC. DNA damage was selectively increased on the nontemplate strand, and H3K36me3 loss was associated with greater RNAPII processivity and mutational burden, suggesting that SETD2-mediated H3K36me3 is required for proper sensing of cytosine deamination. Hence, Setd2 haploinsufficiency delineates a novel GCB context-specific oncogenic pathway involving defective epigenetic surveillance of AICDA-mediated effects on transcribed genes. Our findings define a B cell-specific oncogenic effect of SETD2 heterozygous mutation, which unleashes AICDA mutagenesis of nontemplate strand DNA in the GC reaction, resulting in lymphomas with heavy mutational burden. GC-derived lymphomas did not tolerate SETD2 homozygous deletion, pointing to a novel context-specific therapeutic vulnerability. This article is highlighted in the In This Issue feature, p. 1599.
ARRY-382 in Combination with Pembrolizumab in Patients with Advanced Solid Tumors: Results from a Phase 1b/2 Study
Authors: Melissa Johnson, Arkadiusz Z. Dudek, Ammar Sukari, Justin Call, Paul R. Kunk, Karl Lewis, Justin F. Gainor, John Sarantopoulos, Patrice Lee, Adele Golden, Allison Harney, S. Michael Rothenberg, Yuanyuan Zhang, Jonathan W. Goldman
Journal: Clinical Cancer Research (2022)

Abstract Purpose: ARRY-382 (PF-07265804) is a selective inhibitor of colony-stimulating factor-1 receptor. We evaluated the safety and preliminary efficacy of ARRY-382 plus pembrolizumab in patients with advanced solid tumors. Patients and Methods: This was an open-label, multicenter, Phase 1b/2 study (NCT02880371) performed over September 1, 2016 to October 24, 2019. In the Phase 1b dose-escalation, patients with selected advanced solid tumors received ARRY-382 [starting dose 200 mg once daily (QD) orally] plus pembrolizumab [2 mg/kg intravenously (IV) every 3 weeks (Q3W)]. Phase 2 patients had: Pancreatic ductal adenocarcinoma (PDA); programmed cell death protein-1 (PD-1)/PD-ligand 1 (PD-L1) inhibitor-refractory (PD-1/PD-L1 IR) advanced solid tumors; or platinum-resistant ovarian cancer (prOVCA). Patients received ARRY-382 at the maximum tolerated dose (MTD) of 300 mg QD plus pembrolizumab 200 mg IV Q3W. Results: Primary endpoints of dose-limiting toxicities (DLT; Phase 1b) and objective response rate (Phase 2) were met. In Phase 1b, 19 patients received ARRY-382 200–400 mg. Three patients reported DLTs. The MTD of ARRY-382 (plus pembrolizumab) was 300 mg QD. In Phase 1b, 2 patients (10.5%) had confirmed partial response (PR): 1 with PDA and 1 with ovarian cancer, lasting 29.2 and 3.1 months, respectively. In Phase 2, there were 27, 19, and 11 patients in the PDA, PD-1/PD-L1 IR, and prOVCA cohorts, respectively. One patient (3.7%) with PDA had a PR lasting 2.4 months. The most frequent ARRY-382–related adverse events were increased transaminases (10.5%–83.3%) and increased creatine phosphokinase (18.2%–50.0%). Conclusions: Although limited clinical benefit was observed, ARRY-382 plus pembrolizumab was well tolerated.
60P Machine learning based on blood biomarkers predicts fast progression in advanced NSCLC patients treated with immunotherapy
Authors: J-G. Zhou, J. Yang, H. Wang, A.H-H. Wong, F. Tan, X. Chen, S. He, G. Shen, Y-J. Wang, B. Frey, R. Fietkau, M. Hecht, H. Ma, U.S. Gaipl
Journal: Annals of Oncology (2022)
Race, Genetic Ancestry, and Estimating Kidney Function in CKD
Authors: Chi-yuan Hsu, Wei Yang, Rishi V. Parikh, Amanda H. Anderson, Teresa K. Chen, Debbie L. Cohen, Jiang He, Madhumita J. Mohanty, James P. Lash, Katherine T. Mills, Anthony N. Muiru, Afshin Parsa, Milda R. Saunders, Tariq Shafi, Raymond R. Townsend, Sushrut S. Waikar, Jianqiao Wang, Myles Wolf, Thida C. Tan, Harold I. Feldman, Alan S. Go
Journal: New England Journal of Medicine (2021)

The inclusion of race in equations to estimate the glomerular filtration rate (GFR) has become controversial. Alternative equations that can be used to achieve similar accuracy without the use of race are needed.
Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes: a multicentre, randomised, double-blind, parallel-arm, phase 1 clinical trial
Authors: Tim Heise, Andrea Mari, J Hans DeVries, Shweta Urva, Jing Li, Edward John Pratt, Tamer Coskun, Melissa K Thomas, Kieren J Mather, Axel Haupt, Zvonko Milicevic
Journal: The Lancet Diabetes & Endocrinology (2022)
Abstract 11733: Gender Differences in Statin Prescriptions for Secondary Prevention in Ambulatory Settings
Authors: Anthony Mufarreh, Amit J Shah, Viola Vaccarino, Ambar Kulshreshtha
Journal: Circulation (2021)

Introduction: The American College of Cardiology and American Heart Association (ACC/AHA) 2013 guidelines recommend statin medications and lifestyle counselling for patients with a history of atherosclerotic cardiovascular disease (ASCVD). There is limited data regarding statin prescriptions and lifestyle counselling for secondary prevention in ambulatory settings. We aimed to examine temporal trends in primary care usage of recommended secondary prevention strategies among men and women with ASCVD in a nationally representative, ambulatory care database. Methods: The National Ambulatory Medical Care Survey (NAMCS) provides measures of ambulatory medical care services used in the United States. The study sample consisted of adults with ASCVD seen in ambulatory care clinics from 2006-2016. We analyzed the proportion of patients receiving secondary prevention strategies, statin medications or lifestyle counseling (including weight reduction, diet, and exercise) and examined differences by gender. Patient sample weights were applied to enable nationally representative estimates. Results: From 2006-2016, there were 7263 total outpatient visits (representing 179.9 million visits) for adults with a history of ASCVD. Average age was 63 (SD, 10), 37% were women. Statin prescriptions ranged from 44% (2006) to 46% (2016). Lifestyle counselling was also recommended very infrequently (16-34% range). Women were less likely than men to receive statins. For example, in 2016 men received statins 49% of the time compared with only 41 % in women. Following 2013 AHA/ACC guidelines, men had a 9% increase in statin prescriptions while for women it increased only 5%. Lifestyle counseling decreased from 25% to 23% post-2013, men decreasing by 6% and women increasing by 5%. Nutrition and exercise counseling was done only in 21% and 13% of the visits in 2016. Conclusion: Despite the ACC/AHA guidelines emphasis on statin use and lifestyle recommendations for secondary prevention in high risk ASCVD patients, the overall rates in ambulatory care remain low. Women were less likely to receive these preventive measures.
Benchmarking challenging small variants with linked and long reads
Authors: Justin Wagner, Nathan D. Olson, Lindsay Harris, Ziad Khan, Jesse Farek, Medhat Mahmoud, Ana Stankovic, Vladimir Kovacevic, Byunggil Yoo, Neil Miller, Jeffrey A. Rosenfeld, Bohan Ni, Samantha Zarate, Melanie Kirsche, Sergey Aganezov, Michael C. Schatz, Giuseppe Narzisi, Marta Byrska-Bishop, Wayne Clarke, Uday S. Evani, Charles Markello, Kishwar Shafin, Xin Zhou, Arend Sidow, Vikas Bansal, Peter Ebert, Tobias Marschall, Peter Lansdorp, Vincent Hanlon, Carl-Adam Mattsson, Alvaro Martinez Barrio, Ian T. Fiddes, Chunlin Xiao, Arkarachai Fungtammasan, Chen-Shan Chin, Aaron M. Wenger, William J. Rowell, Fritz J. Sedlazeck, Andrew Carroll, Marc Salit, Justin M. Zook
Journal: Cell Genomics (2022)

Genome in a Bottle benchmarks are widely used to help validate clinical sequencing pipelines and develop variant calling and sequencing methods. Here we use accurate linked and long reads to expand benchmarks in 7 samples to include difficult-to-map regions and segmental duplications that are challenging for short reads. These benchmarks add more than 300,000 SNVs and 50,000 insertions or deletions (indels) and include 16% more exonic variants, many in challenging, clinically relevant genes not covered previously, such as PMS2. For HG002, we include 92% of the autosomal GRCh38 assembly while excluding regions problematic for benchmarking small variants, such as copy number variants, that should not have been in the previous version, which included 85% of GRCh38. It identifies eight times more false negatives in a short read variant call set relative to our previous benchmark. We demonstrate that this benchmark reliably identifies false positives and false negatives across technologies, enabling ongoing methods development.