Digital Commons Network^™

Machine Learning For Modeling The Progression Of Alzheimer Disease Dementia Using Clinical Data: A Systematic Literature Review, Sayantan Kumar, Inez Oh, Suzanne Schindler, Albert M Lai, Philip R O Payne, Aditi Gupta

2020-Current year OA Pubs

OBJECTIVE: Alzheimer disease (AD) is the most common cause of dementia, a syndrome characterized by cognitive impairment severe enough to interfere with activities of daily life. We aimed to conduct a systematic literature review (SLR) of studies that applied machine learning (ML) methods to clinical data derived from electronic health records in order to model risk for progression of AD dementia.

MATERIALS AND METHODS: We searched for articles published between January 1, 2010, and May 31, 2020, in PubMed, Scopus, ScienceDirect, IEEE Explore Digital Library, Association for Computing Machinery Digital Library, and arXiv. We used predefined criteria to select relevant …

Comparison Of Early Warning Scores For Sepsis Early Identification And Prediction In The General Ward Setting, Sean C Yu, Nirmala Shivakumar, Kevin Betthauser, Aditi Gupta, Albert M Lai, Marin H Kollef, Philip R O Payne, Andrew P Michelson

2020-Current year OA Pubs

The objective of this study was to directly compare the ability of commonly used early warning scores (EWS) for early identification and prediction of sepsis in the general ward setting. For general ward patients at a large, academic medical center between early-2012 and mid-2018, common EWS and patient acuity scoring systems were calculated from electronic health records (EHR) data for patients that both met and did not meet Sepsis-3 criteria. For identification of sepsis at index time, National Early Warning Score 2 (NEWS 2) had the highest performance (area under the receiver operating characteristic curve: 0.803 [95% confidence interval [CI]: …

Renal Mucosa-Associated Lymphoid Tissue (Malt) Associated End-Stage Renal Disease In A Patient Presenting With Diarrhea, Faran S. Polani, Fawwad Zaidi

2020-Current year OA Pubs

Extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT) is most commonly found in the GI tract. Other less common anatomical sites for MALT include the skin, intestine, salivary glands, lungs, and ocular adnexa. Isolated MALT of the kidney has only been sporadically reported. Most of the reported cases in the literature present with underlying renal mass and are generally diagnosed post nephrectomy. We present a case of a 73-year-old gentleman with biopsy-proven primary MALT of the kidney who presented with acute kidney injury (AKI) in the background of

Riociguat: Clinical Research And Evolving Role In Therapy, James R Klinger, Murali M Chakinala, David Langleben, Stephan Rosenkranz, Olivier Sitbon

2020-Current year OA Pubs

Riociguat is a first-in-class soluble guanylate cyclase stimulator, approved for the treatment of adults with pulmonary arterial hypertension (PAH), inoperable chronic thromboembolic pulmonary hypertension (CTEPH), or persistent or recurrent CTEPH after pulmonary endarterectomy. Approval was based on the results of the phase III PATENT-1 (PAH) and CHEST-1 (CTEPH) studies, with significant improvements in the primary endpoint of 6-minute walk distance vs placebo of +36 m and +46 m, respectively, as well as improvements in secondary endpoints such as pulmonary vascular resistance and World Health Organization functional class. Riociguat acts as a stimulator of cyclic guanosine monophosphate synthesis rather than as …

Cost Talk: Protocol For A Stepped-Wedge Cluster Randomized Trial Of An Intervention Helping Patients And Urologic Surgeons Discuss Costs Of Care For Slow-Growing Prostate Cancer During Shared Decision-Making, Mary C Politi, Rachel C Forcino, Katelyn Parrish, Marie-Anne Durand, A James O'Malley, Glyn Elwyn

2020-Current year OA Pubs

BACKGROUND: Costs of care are important to patients making cancer treatment decisions, but clinicians often do not feel prepared to discuss treatment costs. We aim to (1) assess the impact of a conversation-based decision aid (Option Grid) containing cost information about slow-growing prostate cancer management options, combined with urologic surgeon training, on the frequency and quality of patient-urologic surgeon cost conversations, and (2) examine the impact of the decision aid and surgeon training on decision quality.

METHODS: We will conduct a stepped-wedge cluster randomized trial in outpatient urology practices affiliated with a large academic medical center in the USA. We …

A Systematic Review Of School Health Policy Measurement Tools: Implementation Determinants And Outcomes, Gabriella M Mcloughlin, Peg Allen, Callie Walsh-Bailey, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Governments in some countries or states/provinces mandate school-based policies intended to improve the health and well-being of primary and secondary students and in some cases the health of school staff. Examples include mandating a minimum time spent per week in programmed physical activity, mandating provision of healthy foods and limiting fat content of school meals, and banning tobacco products or use on school campuses. Although school health researchers have studied whether schools, districts, or states/provinces are meeting requirements, it is unclear to what extent implementation processes and determinants are assessed. The purposes of the present systematic review of quantitative …

Directed Evolution Of An Enhanced Pou Reprogramming Factor For Cell Fate Engineering, Daisylyn Senna Tan, Gary D Stormo, Et Al.

2020-Current year OA Pubs

Transcription factor-driven cell fate engineering in pluripotency induction, transdifferentiation, and forward reprogramming requires efficiency, speed, and maturity for widespread adoption and clinical translation. Here, we used Oct4, Sox2, Klf4, and c-Myc driven pluripotency reprogramming to evaluate methods for enhancing and tailoring cell fate transitions, through directed evolution with iterative screening of pooled mutant libraries and phenotypic selection. We identified an artificially evolved and enhanced POU factor (ePOU) that substantially outperforms wild-type Oct4 in terms of reprogramming speed and efficiency. In contrast to Oct4, not only can ePOU induce pluripotency with Sox2 alone, but it can also do so in the …

A Case Of Intermittent Left Bundle Branch Block, Syed M. Saad, Faran S. Polani, Paul Lelorier

2020-Current year OA Pubs

An 82-year-old woman with uncontrolled hypertension and occasional exertional dyspnea was found to be in intermittent left bundle branch block (LBBB). Her laboratory results, echocardiogram, and ischemic workup were unremarkable. This case highlights that intermittent LBBB is not always associated with coronary ischemia, vasospasm, blunt cardiac injury, drugs, and high catecholaminergic or inflammatory states.

Advanced Cognitive Impairment Among Older Nursing Home Residents, Tadeja Gracner, Patricia W Stone, Mansi Agarwal, Mark Sorbero, Susan L Mitchell, Andrew W Dick

2020-Current year OA Pubs

BACKGROUND: Though work has been done studying nursing home (NH) residents with either advanced Alzheimer's disease (AD) or Alzheimer's disease related dementia (ADRD), none have distinguished between them; even though their clinical features affecting survival are different. In this study, we compared mortality risk factors and survival between NH residents with advanced AD and those with advanced ADRD.

METHODS: This is a retrospective observational study, in which we examined a sample of 34,493 U.S. NH residents aged 65 and over in the Minimum Data Set (2011-2013). Incident assessment of advanced disease was defined as the first MDS assessment with severe …

The Rare C9 P167s Risk Variant For Age-Related Macular Degeneration Increases Polymerization Of The Terminal Component Of The Complement Cascade, O Mcmahon, A Java, J P Atkinson, Et Al.

2020-Current year OA Pubs

Age-related macular degeneration (AMD) is a complex neurodegenerative eye disease with behavioral and genetic etiology and is the leading cause of irreversible vision loss among elderly Caucasians. Functionally significant genetic variants in the alternative pathway of complement have been strongly linked to disease. More recently, a rare variant in the terminal pathway of complement has been associated with increased risk, Complement component 9 (C9) P167S. To assess the functional consequence of this variant, C9 levels were measured in two independent cohorts of AMD patients. In both cohorts, it was demonstrated that the P167S variant was associated with low C9 plasma …

Dietary Fiber Intake, The Gut Microbiome, And Chronic Systemic Inflammation In A Cohort Of Adult Men, Wenjie Ma, Yin Cao, Et Al.

2020-Current year OA Pubs

BACKGROUND: A higher intake of dietary fiber is associated with a decreased risk of chronic inflammatory diseases such as cardiovascular disease and inflammatory bowel disease. This may function in part due to abrogation of chronic systemic inflammation induced by factors such as dysbiotic gut communities. Data regarding the detailed influences of long-term and recent intake of differing dietary fiber sources on the human gut microbiome are lacking.

METHODS: In a cohort of 307 generally healthy men, we examined gut microbiomes, profiled by shotgun metagenomic and metatranscriptomic sequencing, and long-term and recent dietary fiber intake in relation to plasma levels of …

Gps Driving: A Digital Biomarker For Preclinical Alzheimer Disease, Sayeh Bayat, Ganesh M Babulal, Suzanne E Schindler, Anne M Fagan, John C Morris, Alex Mihailidis, Catherine M Roe

2020-Current year OA Pubs

BACKGROUND: Alzheimer disease (AD) is the most common cause of dementia. Preclinical AD is the period during which early AD brain changes are present but cognitive symptoms have not yet manifest. The presence of AD brain changes can be ascertained by molecular biomarkers obtained via imaging and lumbar puncture. However, the use of these methods is limited by cost, acceptability, and availability. The preclinical stage of AD may have a subtle functional signature, which can impact complex behaviours such as driving. The objective of the present study was to evaluate the ability of in-vehicle GPS data loggers to distinguish cognitively …

Inferring Tf Activities And Activity Regulators From Gene Expression Data With Constraints From Tf Perturbation Data, Cynthia Z Ma, Michael R Brent

2020-Current year OA Pubs

MOTIVATION: The activity of a transcription factor (TF) in a sample of cells is the extent to which it is exerting its regulatory potential. Many methods of inferring TF activity from gene expression data have been described, but due to the lack of appropriate large-scale datasets, systematic and objective validation has not been possible until now.

RESULTS: We systematically evaluate and optimize the approach to TF activity inference in which a gene expression matrix is factored into a condition-independent matrix of control strengths and a condition-dependent matrix of TF activity levels. We find that expression data in which the activities …

A Strong Effect Of Individual Compliance With Mass Drug Administration For Lymphatic Filariasis On Sustained Clearance Of Soil-Transmitted Helminth Infections, Jérémy T Campillo, Naomi P Awaca-Uvon, Jean-Paul Tambwe, Godefroy Kuyangisa-Simuna, Johnny Vlaminck, Gary J Weil, Michel Boussinesq, Cédric B Chesnais, Sébastien D S Pion

2020-Current year OA Pubs

BACKGROUND: The impact of semiannual mass drug administration (MDA) with albendazole (ALB; 400 mg) alone on lymphatic filariasis (LF) and soil-transmitted helminth (STH) infections was assessed during two trials conducted from 2012 to 2018 in the Republic of Congo and the Democratic Republic of Congo. The collected data were analyzed to evaluate the effect of compliance with ALB treatment on STH infections.

METHODS: STH infections were diagnosed with duplicate Kato-Katz thick smears and the results are reported as eggs per gram of stool. All subjects with at least two STH infection assessments were included in the analyses. We used parametric …

Teaching Scripts Via Smartphone App Facilitate Resident-Led Teaching Of Medical Students, Nicholas R Zessis, Amanda R Dube, Arhanti Sadanand, Jordan J Cole, Christine M Hrach, Yasmeen N Daud

2020-Current year OA Pubs

BACKGROUND: Previous studies have suggested that resident physicians are the most meaningful teachers during the clinical clerkships of third-year medical students (MS3s). Unfortunately, residents often feel unprepared for this crucial role. The pediatrics clerkship at our institution identified a paucity in the frequency of resident-led teaching with MS3s. Lack of confidence, suboptimal teaching space, and insufficient time were cited as the most significant barriers. To enhance resident-led teaching of MS3s, we created teaching scripts of general pediatrics topics accessible via a smartphone application (app).

METHODS: Prior to the implementation of the app, MS3s and pediatric residents were surveyed on clerkship …

Destination Shapes Antibiotic Resistance Gene Acquisitions, Abundance Increases, And Diversity Changes In Dutch Travelers, Alaric W D'Souza, Manish Boolchandani, Sanket Patel, Gianluca Galazzo, Jarne M Van Hattem, Maris S Arcilla, Damian C Melles, Menno D De Jong, Constance Schultsz, Combat Consortium, Gautam Dantas, John Penders

2020-Current year OA Pubs

BACKGROUND: Antimicrobial-resistant bacteria and their antimicrobial resistance (AMR) genes can spread by hitchhiking in human guts. International travel can exacerbate this public health threat when travelers acquire AMR genes endemic to their destinations and bring them back to their home countries. Prior studies have demonstrated travel-related acquisition of specific opportunistic pathogens and AMR genes, but the extent and magnitude of travel's effects on the gut resistome remain largely unknown.

METHODS: Using whole metagenomic shotgun sequencing, functional metagenomics, and Dirichlet multinomial mixture models, we investigated the abundance, diversity, function, resistome architecture, and context of AMR genes in the fecal microbiomes of …

Mitochondrial Genome Copy Number Measured By Dna Sequencing In Human Blood Is Strongly Associated With Metabolic Traits Via Cell-Type Composition Differences, Liron Ganel, Lei Chen, Ryan Christ, Erica Young, Indraniel Das, Krishna Kanchi, David Larson, Allison Regier, Haley Abel, Chul Joo Kang, Alexandra Scott, Adam Locke, Nathan O Stitziel, Ira M Hall, Et Al

2020-Current year OA Pubs

BACKGROUND: Mitochondrial genome copy number (MT-CN) varies among humans and across tissues and is highly heritable, but its causes and consequences are not well understood. When measured by bulk DNA sequencing in blood, MT-CN may reflect a combination of the number of mitochondria per cell and cell-type composition. Here, we studied MT-CN variation in blood-derived DNA from 19184 Finnish individuals using a combination of genome (N = 4163) and exome sequencing (N = 19034) data as well as imputed genotypes (N = 17718).

RESULTS: We identified two loci significantly associated with MT-CN variation: a common variant at the MYB-HBS1L locus …

Sequence Determinants Of In Cell Condensate Morphology, Dynamics, And Oligomerization As Measured By Number And Brightness Analysis, Ryan J Emenecker, Alex S Holehouse, Lucia C Strader

2020-Current year OA Pubs

BACKGROUND: Biomolecular condensates are non-stoichiometric assemblies that are characterized by their capacity to spatially concentrate biomolecules and play a key role in cellular organization. Proteins that drive the formation of biomolecular condensates frequently contain oligomerization domains and intrinsically disordered regions (IDRs), both of which can contribute multivalent interactions that drive higher-order assembly. Our understanding of the relative and temporal contribution of oligomerization domains and IDRs to the material properties of in vivo biomolecular condensates is limited. Similarly, the spatial and temporal dependence of protein oligomeric state inside condensates has been largely unexplored in vivo.

METHODS: In this study, we combined …

Sars-Cov-2 Detection Among International Air Travellers To Ghana During Mandatory Quarantine, Bright Adu, Joseph K H Bonney, John K Odoom, Evelyn Y A Bonney, Evangeline Obodai, Ivy A Asante, James Aboagye, Mildred A Adusei-Poku, Lawrence Lartey, Ernest K Asiedu, William K Ampofo, George B Kyei

2020-Current year OA Pubs

OBJECTIVES: To determine the prevalence of SARS-CoV-2 detection among international travellers to Ghana during mandatory quarantine.

DESIGN: A retrospective cross-sectional study.

SETTING: Air travellers to Ghana on 21

PARTICIPANTS: On 21

MAIN OUTCOME MEASURE: Positivity for SARS-CoV-2 by polymerase chain reaction.

RESULTS: The initial testing at the beginning of quarantine found 79 (7.7%) individuals to be positive for SARS-CoV-2. In the exit screening after 12 to 13 days of quarantine, it was discovered that 26 of those who tested negative for SARS-CoV-2 in the initial screening subsequently tested positive.

CONCLUSIONS: Ghana likely averted an early community spread of COVID-19 through …

Outcomes And Risk Factors Associated With Sars-Cov-2 Infection In A North American Registry Of Patients With Multiple Sclerosis, Amber Salter, Robert J Fox, Scott D Newsome, June Halper, David K B Li, Pamela Kanellis, Kathleen Costello, Bruce Bebo, Kottil Rammohan, Gary R Cutter, Anne H Cross

2020-Current year OA Pubs

Importance: Emergence of SARS-CoV-2 causing COVID-19 prompted the need to gather information on clinical outcomes and risk factors associated with morbidity and mortality in patients with multiple sclerosis (MS) and concomitant SARS-CoV-2 infections.

Objective: To examine outcomes and risk factors associated with COVID-19 clinical severity in a large, diverse cohort of North American patients with MS.

Design, Setting, and Participants: This analysis used deidentified, cross-sectional data on patients with MS and SARS-CoV-2 infection reported by health care professionals in North American academic and community practices between April 1, 2020, and December 12, 2020, in the COVID-19 Infections in MS Registry. …

Transfer Transcriptomic Signatures For Infectious Diseases, Julia Di Iulio, Istvan Bartha, Roberto Spreafico, Herbert W Virgin, Amalio Telenti

2020-Current year OA Pubs

The modulation of the transcriptome is among the earliest responses to infection. However, defining the transcriptomic signatures of disease is challenging because logistic, technical, and cost factors limit the size and representativeness of samples in clinical studies. These limitations lead to a poor performance of signatures when applied to new datasets. Although the study focuses on infection, the central hypothesis of the work is the generalization of sets of signatures across diseases. We use a machine learning approach to identify common elements in datasets and then test empirically whether they are informative about a second dataset from a disease or …

Brain-Responsive Neurostimulation For The Treatment Of Adults With Epilepsy In Tuberous Sclerosis Complex: A Case Series, Danielle S Mcdermott, Emily A Mirro, Kirsten Fetrow, David E Burdette, Stephanie Chen, Jennifer Hopp, Todd Masel, Emily A Johnson, Felicia M K Elefant, Scheherazade Le, Sanjay E Patra, Mesha-Gay Brown, Zulfi Haneef

2020-Current year OA Pubs

OBJECTIVE: Tuberous sclerosis complex (TSC) is a genetic disorder primarily characterized by the development of multisystem benign tumors. Epilepsy is the most common neurologic manifestation, affecting 80%-90% of TSC patients. The diffuse structural brain abnormalities and the multifocal nature of epilepsy in TSC pose diagnostic challenges when evaluating patients for epilepsy surgery.

METHODS: We retrospectively reviewed the safety experience and efficacy outcomes of five adult TSC patients who were treated with direct brain-responsive neurostimulation (RNS System, NeuroPace, Inc).

RESULTS: The average follow-up duration was 20 months. All five patients were responders (≥50% disabling seizure reduction) at last follow-up. The median …

Elevated Mrna Expression And Defective Processing Of Cathepsin D In Hela Cells Lacking The Mannose 6-Phosphate Pathway, Lin Liu, Balraj Doray

2020-Current year OA Pubs

Disruption of the mannose 6-phosphate (M-6-P) pathway in HeLa cells by inactivation of the GNPTAB gene, which encodes the α/β subunits of GlcNAc-1-phosphotransferase, results in missorting of newly synthesized lysosomal acid hydrolases to the cell culture media instead of transport to the endolysosomal system. We previously demonstrated that the majority of the lysosomal aspartyl protease, cathepsin D, is secreted in these GNPTAB

A Case Of Hepatic Cyst-Induced Internal Jugular Venous Thrombosis, Tuyen V Le, Thai Truong, Tam N M Ngo, Quoc Bui, Cassady Palmer, Vien T Truong, Duc H Nguyen

2020-Current year OA Pubs

• Echocardiography can demonstrate hepatic cyst–induced right atrial compression. • Hepatic cyst–induced blood flow stasis can cause internal jugular venous thrombus. • Laparoscopic deroofing of hepatic cysts is a safe and effective treatment.

Report Dose-To-Medium In Clinical Trials Where Available; A Consensus From The Global Harmonisation Group To Maximize Consistency, Stephen F Kry, Jeff Michalski, Et Al.

2020-Current year OA Pubs

PURPOSE: To promote consistency in clinical trials by recommending a uniform framework as it relates to radiation transport and dose calculation in water versus in medium.

METHODS: The Global Quality Assurance of Radiation Therapy Clinical Trials Harmonisation Group (GHG; www.rtqaharmonization.org) compared the differences between dose to water in water (D

RESULTS: No framework was found to be ideal or perfect given the history, complexity, and current status of radiation therapy. Nevertheless, based on the evidence available, the GHG established a recommendation preferring dose to medium in medium (D

CONCLUSIONS: Dose to medium in medium (D

Effects Of Pathogen Reduction Technology And Storage Duration On The Ability Of Cryoprecipitate To Rescue Induced Coagulopathies In Vitro, Kimberly A Thomas, Susan M Shea, Philip C Spinella

2020-Current year OA Pubs

BACKGROUND: Fibrinogen concentrates and cryoprecipitate are currently used for fibrinogen supplementation in bleeding patients with dysfibrinogenemia. Both products provide an abundant source of fibrinogen but take greater than 10 min to prepare for administration. Fibrinogen concentrates lack coagulation factors (i.e., factor VIII [FVIII], factor XIII [FXIII], von Willebrand factor [VWF]) important for robust hemostatic function. Cryoprecipitate products contain these factors but have short shelf lives (<6 h). Pathogen reduction (PR) of cryoprecipitate would provide a shelf-stable immediately available adjunct containing factors important for rescuing hemostatic dysfunction.

STUDY DESIGN AND METHODS: Hemostatic adjunct study products were psoralen-treated PR-cryoprecipitated fibrinogen complex (PR-Cryo FC), cryoprecipitate (Cryo), and fibrinogen concentrates (FibCon). PR-Cryo FC and Cryo were stored for 10 days at 20-24°C. Adjuncts were …

Clinical Epigenomics: Genome-Wide Dna Methylation Analysis For The Diagnosis Of Mendelian Disorders, Bekim Sadikovic, Jorge L Granadillo, Et Al.

2020-Current year OA Pubs

PURPOSE: We describe the clinical implementation of genome-wide DNA methylation analysis in rare disorders across the EpiSign diagnostic laboratory network and the assessment of results and clinical impact in the first subjects tested.

METHODS: We outline the logistics and data flow between an integrated network of clinical diagnostics laboratories in Europe, the United States, and Canada. We describe the clinical validation of EpiSign using 211 specimens and assess the test performance and diagnostic yield in the first 207 subjects tested involving two patient subgroups: the targeted cohort (subjects with previous ambiguous/inconclusive genetic findings including genetic variants of unknown clinical significance) …

Randomized Trial Of The Efficacy And Safety Of Berotralstat (Bcx7353) As An Oral Prophylactic Therapy For Hereditary Angioedema: Results Of Apex-2 Through 48 Weeks (Part 2), H James Wedner, Et Al.

2020-Current year OA Pubs

BACKGROUND: Berotralstat (BCX7353) is a recently approved, oral, once-daily kallikrein inhibitor for hereditary angioedema (HAE) prophylaxis. In the APeX-2 trial, berotralstat reduced HAE attack rates over 24 weeks, with a favorable safety and tolerability profile.

OBJECTIVE: Evaluate berotralstat safety, tolerability, and effectiveness over 48 weeks.

METHODS: APeX-2 is a phase 3, parallel-group, multicenter trial (NCT03485911) in patients with HAE due to C1 esterase inhibitor deficiency. Part 1 was double-blind and placebo-controlled, with patients randomized to 24 weeks of berotralstat 150 mg, 110 mg, or placebo. In part 2, patients continued berotralstat the same dose or, if initially randomized to placebo, …

Commonalities Across Computational Workflows For Uncovering Explanatory Variants In Undiagnosed Cases, Shilpa Nadimpalli Kobren, Dustin Baldridge, Daniel J Wegner, Alexander J Paul, Et Al.

2020-Current year OA Pubs

PURPOSE: Genomic sequencing has become an increasingly powerful and relevant tool to be leveraged for the discovery of genetic aberrations underlying rare, Mendelian conditions. Although the computational tools incorporated into diagnostic workflows for this task are continually evolving and improving, we nevertheless sought to investigate commonalities across sequencing processing workflows to reveal consensus and standard practice tools and highlight exploratory analyses where technical and theoretical method improvements would be most impactful.

METHODS: We collected details regarding the computational approaches used by a genetic testing laboratory and 11 clinical research sites in the United States participating in the Undiagnosed Diseases Network …

Integration Of Immunotherapy Into Adjuvant Therapy For Resected Non-Small-Cell Lung Cancer: Alchemist Chemo-Io (Accio), Jacob M Sands, Ramaswamy Govindan, Jhanelle Gray, Et Al

2020-Current year OA Pubs

Non-small-cell lung cancer (NSCLC) causes significant mortality each year. After successful resection of disease stage IB (>4 cm) to IIIA (per AJCC 7), adjuvant platinum-based chemotherapy improves median overall survival and is the standard of care, but many patients still experience recurrence of disease. An adjuvant regimen with greater efficacy could substantially improve outcomes. Pembrolizumab, a programmed cell death-1 inhibitor, has become an important option in the treatment of metastatic NSCLC. ALCHEMIST is a clinical trial platform of the National Cancer Institute that includes biomarker analysis for resected NSCLC and supports therapeutic trials including A081801 (ACCIO), a three-arm study …