Medicine and Health Sciences Commons^™

The Dusp Domain Of Pseudophosphatase Mk-Styx Interacts With G3bp1 To Decrease Stress Granules, Jonathan Smailys, Fei Jiang, Tatiana Prioleau, Kylan Kelley, Olivia Mitchell, Samah Nour, Lina Ali, William Buchser, Lynn Zavada, Shantá D Hinton

2020-Current year OA Pubs

Mitogen activated protein kinase phosphoserine/threonine/tyrosine-binding protein (MK-STYX) is a dual specificity (DUSP) member of the protein tyrosine phosphatase family. It is a pseudophosphatase, which lacks the essential amino acids histidine and cysteine in the catalytic active signature motif (HCX

Androgen Deprivation And Radiotherapy With Or Without Docetaxel For Localized High-Risk Prostate Cancer: Long-Term Follow-Up From The Randomized Nrg Oncology Rtog 0521 Trial, Oliver Sartor, Jeff M Michalski, Et Al.

2020-Current year OA Pubs

BACKGROUND: Intensification of therapy may improve outcomes for patients with high-risk localized prostate cancer.

OBJECTIVE: To provide long-term follow-up data from phase III RTOG 0521, which compared a combination of androgen deprivation therapy (ADT) + external beam radiation therapy (EBRT) + docetaxel with ADT + EBRT.

DESIGN, SETTING, AND PARTICIPANTS: High-risk localized prostate cancer patients (>50% of patients had Gleason 9-10 disease) were prospectively randomized to 2 yr of ADT + EBRT or ADT + EBRT + six cycles of docetaxel. A total of 612 patients were accrued, and 563 were eligible and included in the modified intent-to-treat analysis. …

Effects Of A Lpg Stove And Fuel Intervention On Adverse Maternal Outcomes: A Multi-Country Randomized Controlled Trial Conducted By The Household Air Pollution Intervention Network (Hapin), Ashley Younger, Ashley Toenjes, Lindsay Underhill, Et Al.

2020-Current year OA Pubs

Household air pollution from solid cooking fuel use during gestation has been associated with adverse pregnancy and birth outcomes. The Household Air Pollution Intervention Network (HAPIN) trial was a randomized controlled trial of free liquefied petroleum gas (LPG) stoves and fuel in Guatemala, Peru, India, and Rwanda. A primary outcome of the main trial was to report the effects of the intervention on infant birth weight. Here we evaluate the effects of a LPG stove and fuel intervention during pregnancy on spontaneous abortion, postpartum hemorrhage, hypertensive disorders of pregnancy, and maternal mortality compared to women who continued to use solid …

Induction Of Cancer Neoantigens Facilitates Development Of Clinically Relevant Models For The Study Of Pancreatic Cancer Immunobiology, Usman Y Panni, Michael Y Chen, Felicia Zhang, Darren R Cullinan, Lijin Li, C Alston James, Xiuli Zhang, S Rogers, A Alarcon, John M Baer, Daoxiang Zhang, Feng Gao, Christopher A Miller, Qingqing Gong, Kian-Huat Lim, David G Denardo, S Peter Goedegebuure, William E Gillanders, William G Hawkins

2020-Current year OA Pubs

Neoantigen burden and CD8 T cell infiltrate are associated with clinical outcome in pancreatic ductal adenocarcinoma (PDAC). A shortcoming of many genetic models of PDAC is the lack of neoantigen burden and limited T cell infiltrate. The goal of the present study was to develop clinically relevant models of PDAC by inducing cancer neoantigens in KP2, a cell line derived from the KPC model of PDAC. KP2 was treated with oxaliplatin and olaparib (OXPARPi), and a resistant cell line was subsequently cloned to generate multiple genetically distinct cell lines (KP2-OXPARPi clones). Clones A and E are sensitive to immune checkpoint …

Prescribing Patterns For Sodium-Glucose Cotransporter 2 Inhibitors: A Survey Of Nephrologists, Tripti Singh, Tingting Li, Didier Mandelbrot, Brad C Astor, Ali Poyan Mehr

2020-Current year OA Pubs

No abstract provided.

Loop-And-Let-Go Technique For The Management Of Symptomatic Large Colonic Lipoma, Syedreza Haider, Matthew Peller, Vladimir Lamm, Ahmad Najdat Bazarbashi

2020-Current year OA Pubs

Video 1We depict (1) identification of a large lipoma in the sigmoid colon; (2) radial echo endoscopy confirming diagnosis; (3) removal with the loop-and-let-go technique; (4) ex vivo demonstration of the technique; and (5) an interval follow-up demonstrating healing of the lesion.

Hgf/C-Met Pathway Inhibition Combined With Chemotherapy Increases Cytotoxic T-Cell Infiltration And Inhibits Pancreatic Tumour Growth And Metastasis, Alpha Raj Mekapogu, Zhihong Xu, Srinivasa Pothula, Chamini Perera, Tony Pang, S M Zahid Hosen, Vishnu Damalanka, James Janetka, David Goldstein, Romano Pirola, Jeremy Wilson, Minoti Apte

2020-Current year OA Pubs

Pancreatic cancer (PC) is a deadly cancer with a high mortality rate. The unique characteristics of PC, including desmoplasia and immunosuppression, have made it difficult to develop effective treatment strategies. Pancreatic stellate cells (PSCs) play a crucial role in the progression of the disease by interacting with cancer cells. One of the key mediators of PSC - cancer cell interactions is the hepatocyte growth factor (HGF)/c-MET pathway. Using an immunocompetent in vivo model of PC as well as in vitro experiments, this study has shown that a combined approach using HGF/c-MET inhibitors to target stromal-tumour interactions and chemotherapy (gemcitabine) to …

Shephard: A Modular And Extensible Software Architecture For Analyzing And Annotating Large Protein Datasets, Garrett M Ginell, Aidan J Flynn, Alex S Holehouse

2020-Current year OA Pubs

MOTIVATION: The emergence of high-throughput experiments and high-resolution computational predictions has led to an explosion in the quality and volume of protein sequence annotations at proteomic scales. Unfortunately, sanity checking, integrating, and analyzing complex sequence annotations remains logistically challenging and introduces a major barrier to entry for even superficial integrative bioinformatics.

RESULTS: To address this technical burden, we have developed SHEPHARD, a Python framework that trivializes large-scale integrative protein bioinformatics. SHEPHARD combines an object-oriented hierarchical data structure with database-like features, enabling programmatic annotation, integration, and analysis of complex datatypes. Importantly SHEPHARD is easy to use and enables a Pythonic interrogation …

Epigenetic Age Acceleration Mediates The Relationship Between Neighborhood Deprivation And Pain Severity In Adults With Or At Risk For Knee Osteoarthritis Pain, Pamela Jackson, Burel R Goodin, Et Al.

2020-Current year OA Pubs

An estimated 250 million people worldwide suffer from knee osteoarthritis (KOA), with older adults having greater risk. Like other age-related diseases, residents of high-deprivation neighborhoods experience worse KOA pain outcomes compared to their more affluent neighbors. The purpose of this study was to examine the relationship between neighborhood deprivation and pain severity in KOA and the influence of epigenetic age acceleration (EpAA) on that relationship. The sample of 128 participants was mostly female (60.9%), approximately half non-Hispanic Black (49.2%), and had a mean age of 58 years. Spearman bivariate correlations revealed that pain severity positively correlated with EpAA (ρ = …

Gel Stent Versus Trabeculectomy: The Randomized, Multicenter, Gold-Standard Pathway Study (Gps) Of Effectiveness And Safety At 12 Months, Arsham Sheybani, Vanessa Vera, Davinder S Grover, Steven D Vold, Frank Cotter, Sahar Bedrood, Gagan Sawhney, Scott D Piette, Susan Simonyi, Xuemin Gu, Mini Balaram, Mark J Gallardo

2020-Current year OA Pubs

PURPOSE: To compare effectiveness and safety of the gel stent to trabeculectomy in open-angle glaucoma (OAG).

DESIGN: Prospective, randomized, multicenter, noninferiority study.

METHODS: Patients with OAG and intraocular pressure (IOP) 15 to 44 mm Hg on topical IOP-lowering medication were randomized 2:1 to gel stent implantation or trabeculectomy. Primary end point (surgical success): percentage of patients at month 12 achieving ≥20% IOP reduction from baseline without medication increase, clinical hypotony, vision loss to counting fingers, or secondary surgical intervention (SSI) in a noninferiority test with 24% margins. Secondary end points (month 12) included mean IOP and medication count, postoperative intervention …

Long-Term Endothelial Safety Profile With Istent Inject In Patients With Open-Angle Glaucoma, Iqbal Ike K Ahmed, Arsham Sheybani, Ticiana De Francesco, Jonathan H Lass, Beth Ann Benetz, Thomas W Samuelson, Dale Usner, L Jay Katz

2020-Current year OA Pubs

PURPOSE: To report 5-year postoperative safety data of iStent inject, including overall stability, endothelial cell density (ECD), and endothelial cell loss (ECL) in patients with mild-to-moderate primary open-angle glaucoma (POAG).

DESIGN: 5-year follow-up safety study of the prospective, randomized, single-masked, concurrently controlled, multicenter iStent inject pivotal trial.

METHODS: In this 5-year follow-up safety study of the 2-year iStent inject pivotal randomized controlled trial, patients receiving iStent inject placement and phacoemulsification or phacoemulsification alone were studied for the incidence of clinically relevant complications associated with iStent inject placement and stability. Corneal endothelial endpoints were mean change in ECD from screening and …

Demographics And Baseline Disease Characteristics Of Black And Hispanic Patients With Multiple Sclerosis In The Open-Label, Single-Arm, Multicenter, Phase Iv Chimes Trial, Mitzi J Williams, Anne H Cross, Gregory F Wu, Et Al.

2020-Current year OA Pubs

BACKGROUND: Black/African American patients with multiple sclerosis (BpwMS) and Hispanic/Latino patients with multiple sclerosis (HpwMS), who historically have been underrepresented in multiple sclerosis (MS) clinical trials, exhibit greater disease severity and more rapid disease progression than White patients with MS (WpwMS). The lack of diversity and inclusion in clinical trials, which may be due to barriers at the system, patient and study levels, impacts the ability to effectively assess risks, benefits and treatment responses in a generalized patient population.

METHODS: CHIMES (Characterization of Ocrelizumab in Minorities With Multiple Sclerosis), an open-label, single-arm, multicenter, phase IV study of self-identified BpwMS and …

Perceived Utility Of Intracranial Pressure Monitoring In Traumatic Brain Injury: A Seattle International Brain Injury Consensus Conference Consensus-Based Analysis And Recommendations, Randall M. Chesnut, Michael Diringer, Et Al.

2020-Current year OA Pubs

BACKGROUND: Intracranial pressure (ICP) monitoring is widely practiced, but the indications are incompletely developed, and guidelines are poorly followed.

OBJECTIVE: To study the monitoring practices of an established expert panel (the clinical working group from the Seattle International Brain Injury Consensus Conference effort) to examine the match between monitoring guidelines and their clinical decision-making and offer guidance for clinicians considering monitor insertion.

METHODS: We polled the 42 Seattle International Brain Injury Consensus Conference panel members' ICP monitoring decisions for virtual patients, using matrices of presenting signs (Glasgow Coma Scale [GCS] total or GCS motor, pupillary examination, and computed tomography diagnosis). …

Genomic Risk For Post-Traumatic Stress Disorder In Families Densely Affected With Alcohol Use Disorders, Stacey Saenz De Viteri, Emma C Johnson, Vivia V Mccutcheon, Kathleen K Bucholz, Et Al.

2020-Current year OA Pubs

Recent genome-wide association studies (GWAS) have identified genetic markers of post-traumatic stress disorder (PTSD) in civilian and military populations. However, studies have yet to examine the genetics of PTSD while factoring in risk for alcohol dependence, which commonly co-occur. We examined genome-wide associations for DSM-IV PTSD among 4,978 trauma-exposed participants (31% with alcohol dependence, 50% female, 30% African ancestry) from the Collaborative Study on the Genetics of Alcoholism (COGA). We also examined associations of polygenic risk scores (PRS) derived from the Psychiatric Genomics Consortium (PGC)-PTSD Freeze 2 (N = 3533) and Million Veterans Program GWAS of PTSD (N = 5200) …

Courage-Als: A Randomized, Double-Blind Phase 3 Study Designed To Improve Participant Experience And Increase The Probability Of Success, Jeremy M Shefner, Timothy M Miller, Et Al.

2020-Current year OA Pubs

No abstract provided.

Music Can Be Reconstructed From Human Auditory Cortex Activity Using Nonlinear Decoding Models, Ludovic Bellier, Anaïs Llorens, Déborah Marciano, Aysegul Gunduz, Gerwin Schalk, Peter Brunner, Robert T. Knight

2020-Current year OA Pubs

Music is core to human experience, yet the precise neural dynamics underlying music perception remain unknown. We analyzed a unique intracranial electroencephalography (iEEG) dataset of 29 patients who listened to a Pink Floyd song and applied a stimulus reconstruction approach previously used in the speech domain. We successfully reconstructed a recognizable song from direct neural recordings and quantified the impact of different factors on decoding accuracy. Combining encoding and decoding analyses, we found a right-hemisphere dominance for music perception with a primary role of the superior temporal gyrus (STG), evidenced a new STG subregion tuned to musical rhythm, and defined …

Pharmacokinetics Of Moxidectin Combined With Albendazole Or Albendazole Plus Diethylcarbamazine For Bancroftian Filariasis, Yashpal S. Chhonker, Catherine Bjerum, Veenu Bala, Allassane F. Ouattara, Benjamin G. Koudou, Toki P. Gabo, Abdullah Alshehri, Abdoulaye Meïté, Peter U. Fischer, Gary J. Weil, Christopher L. King, Philip J. Budge, Daryl J. Murry

2020-Current year OA Pubs

Moxidectin (MOX) is a milbemycin endectocide recently approved by the U.S. FDA for the treatment of onchocerciasis in persons at least 12 years of age. MOX has been shown to have a good safety profile in recent clinical trials. The efficacy of MOX for the treatment of lymphatic filariasis (LF) and its potential use in mass drug administration protocols for the elimination of LF is currently under evaluation. In the context of a clinical trial, we investigated the pharmacokinetics and drug interactions of a combination of MOX plus albendazole (ALB) with or without diethylcarbamazine (DEC) compared to ivermectin (IVM) plus …

Scca1/Serpinb3 Suppresses Antitumor Immunity And Blunts Therapy-Induced T Cell Responses Via Stat-Dependent Chemokine Production, Liyun Chen, Victoria Shi, Songyan Wang, Lulu Sun, Rebecca Freeman, Jasmine Yang, Matthew J. Inkman, Subhajit Ghosh, Fiona Ruiz, Kay Jayachandran, Yi Huang, Jingqin Luo, Jin Zhang, Pippa Cosper, Clifford J Luke, Perry W. Grigsby, Julie K. Schwarz, Stephanie Markovina, Et Al.

2020-Current year OA Pubs

Patients with cancer who have high serum levels of squamous cell carcinoma antigen 1 (SCCA1, now referred to as SERPINB3) commonly experience treatment resistance and have a poor prognosis. Despite being a clinical biomarker, the modulation of SERPINB3 in tumor immunity is poorly understood. We found positive correlations of SERPINB3 with CXCL1, CXCL8 (CXCL8/9), S100A8, and S100A9 (S100A8/A9) myeloid cell infiltration through RNA-Seq analysis of human primary cervical tumors. Induction of SERPINB3 resulted in increased CXCL1/8 and S100A8/A9 expression, which promoted monocyte and myeloid-derived suppressor cell (MDSC) migration in vitro. In mouse models, Serpinb3a tumors showed increased MDSC and tumor-associated …

Spatial Epidemiologic Analysis And Risk Factors For Nontuberculous Mycobacteria Infections, Missouri, Usa, 2008-2019, Carlos Mejia-Chew, Miguel A Chavez, Min Lian, Angela Mckee, Leighton Garrett, Thomas C Bailey, Andrej Spec, Mansi Agarwal, George Turabelidze

2020-Current year OA Pubs

Nontuberculous mycobacteria (NTM) infections are caused by environmental exposure. We describe spatial distribution of NTM infections and associations with sociodemographic factors and flooding in Missouri, USA. Our retrospective analysis of mycobacterial cultures reported to the Missouri Department of Health and Social Services surveillance system during January 1, 2008-December 31, 2019, detected geographic clusters of infection. Multilevel Poisson regression quantified small-area geographic variations and identified characteristics associated with risk for infection. Median county-level NTM infection rate was 66.33 (interquartile range 51-91)/100,000 persons. Risk of clustering was significantly higher in rural areas (rate ratio 2.82, 95% CI 1.90-4.19) and in counties with …

Standardized Radiomics Analysis Of Clinical Myocardial Perfusion Stress Spect Images To Identify Coronary Artery Calcification, Saeed Ashrafinia, Pejman Dalaie, Thomas H. Schindler, Martin G. Pomper, Arman Rahmim

2020-Current year OA Pubs

PURPOSE: Myocardial perfusion (MP) stress single-photon emission computed tomography (SPECT) is an established diagnostic test for patients suspected of coronary artery disease (CAD). Meanwhile, coronary artery calcification (CAC) scoring obtained from diagnostic CT is a highly sensitive test, offering incremental diagnostic information in identifying patients with significant CAD yet normal MP stress SPECT (MPSS) scans. However, after decades of wide utilization of MPSS, CAC is not commonly reimbursed (e.g. by the CMS), nor widely deployed in community settings. We studied the potential of complementary information deduced from the radiomics analysis of normal MPSS scans in predicting the CAC score.

METHODS: …

The Stop Covid 2 Study: Fluvoxamine Vs Placebo For Outpatients With Symptomatic Covid-19, A Fully Remote Randomized Controlled Trial, Angela M Reiersen, Caline Mattar, J Philip Miller, William G Powderly, Michael W Rich, Julie Schweiger, Angela Stevens, Lei Yang, Michael Yingling, Torie R Gettinger, Charles F Zorumski, Eric J Lenze, Et Al.

2020-Current year OA Pubs

BACKGROUND: Prior randomized clinical trials have reported benefit of fluvoxamine ≥200 mg/d vs placebo for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

METHODS: This randomized, double-blind, placebo-controlled, fully remote multisite clinical trial evaluated whether fluvoxamine prevents clinical deterioration in higher-risk outpatients with acute coronavirus disease 2019 (COVID-19). Between December 2020 and May 2021, nonhospitalized US and Canadian participants with confirmed symptomatic infection received fluvoxamine (50 mg on day 1, 100 mg twice daily thereafter) or placebo for 15 days. The primary modified intent-to-treat (mITT) population included participants who started the intervention within 7 days of symptom onset …

Effect Of Fecal Microbiota, Live-Jslm (Rebyota [Rbl]) On Health-Related Quality Of Life In Patients With Recurrent Clostridioides Difficile Infection: Results From The Punch Cd3 Clinical Trial, Kevin W Garey, Erik R Dubberke, Amy Guo, Adam Harvey, Min Yang, Viviana García-Horton, Mirko Fillbrunn, Hongjue Wang, Glenn S Tillotson, Lindy L Bancke, Paul Feuerstadt

2020-Current year OA Pubs

BACKGROUND: Recurrence of

METHODS: This was a secondary analysis of a randomized, double-blind, placebo-controlled phase 3 study (PUNCH CD3). The disease-specific

RESULTS: Findings were analyzed in a total of 185 patients (RBL, n = 128 [69.2%]; placebo, n = 57 [30.8%]) with available Cdiff32 data. Patients from both arms showed significant improvements in Cdiff32 scores relative to baseline across all outcomes and at all time points (all

CONCLUSIONS: In a phase 3 double-blinded clinical trial, RBL-treated patients reported more substantial and sustained disease-specific HRQL improvements than placebo-treated patients.

CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT03244644 (https://clinicaltrials.gov/ct2/show/NCT03244644).

Association Of Soluble Markers Of Inflammation With Peri-Coronary Artery Inflammation In People With And Without Hiv Infection And Without Cardiovascular Disease, Michael L Freeman, Mian B Hossain, Shana A B Burrowes, Jean Jeudy, Ryan Bui, Daniela Moisi, Sarah E Mitchell, Mariam Khambaty, Robert G Weiss, Michael M Lederman, Shashwatee Bagchi

2020-Current year OA Pubs

BACKGROUND: Inflammation is linked to elevated cardiovascular disease (CVD) risk in people with HIV (PWH) on antiretroviral therapy (ART). Fat attenuation index (FAI) is a measure of peri-coronary inflammation that independently predicts CVD risk in HIV-uninfected persons. Whether FAI is associated with soluble inflammatory markers is unknown.

METHODS: Plasma levels of inflammatory markers were measured in 58 PWH and 16 controls without current symptoms or prior known CVD who underwent coronary computed tomography angiography and had FAI measurements. A cross-sectional analysis was performed, and associations of markers with FAI values of the right coronary artery (RCA) and left anterior descending …

Sars-Cov-2 Uses Cd4 To Infect T Helper Lymphocytes, Natalia S Brunetti, Louis-Marie Bloyet, Spencer Stumpf, Marjorie C Pontelli, Sean Whelan, Alessandro S Farias, Et Al.

2020-Current year OA Pubs

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4

Mettl1 Promotes Tumorigenesis Through Trna-Derived Fragment Biogenesis In Prostate Cancer, Raquel García-Vílchez, Sabine Dietmann, Et Al.

2020-Current year OA Pubs

Newly growing evidence highlights the essential role that epitranscriptomic marks play in the development of many cancers; however, little is known about the role and implications of altered epitranscriptome deposition in prostate cancer. Here, we show that the transfer RNA N

Using The Sociotechnical Model To Conduct A Focused Usability Assessment Of A Breast Reconstruction Decision Tool, Randi Foraker, Crystal Phommasathit, Kaleigh Clevenger, Clara Lee, Jessica Boateng, Napiera Shareef, Mary C Politi

2020-Current year OA Pubs

INTRODUCTION: BREASTChoice is a web-based breast reconstruction decision aid. The previous clinical trial-prior to the adaptation of this refined tool in which we explored usability-measured decision quality, quality of life, patient activation, shared decision making, and treatment choice. The current usability study was designed to elicit patients' and clinicians' perspectives on barriers and facilitators for implementing BREASTChoice into the clinical workflow.

METHODS: We conducted qualitative interviews with patients and clinicians from two Midwestern medical specialty centers from August 2020 to April 2021. Interviews were first double coded until coders achieved a kappa > 0.8 and percent agreement > 95%, then were coded …

Subunit Gating Resulting From Individual Protonation Events In Kir2 Channels, Grigory Maksaev, Michael Bründl-Jirout, Anna Stary-Weinzinger, Eva-Maria Zangerl-Plessl, Sun-Joo Lee, Colin G Nichols

2020-Current year OA Pubs

Inwardly rectifying potassium (Kir) channels open at the 'helix bundle crossing' (HBC), formed by the M2 helices at the cytoplasmic end of the transmembrane pore. Introduced negative charges at the HBC (G178D) in Kir2.2 channels forces opening, allowing pore wetting and free movement of permeant ions between the cytoplasm and the inner cavity. Single-channel recordings reveal striking, pH-dependent, subconductance behaviors in G178D (or G178E and equivalent Kir2.1[G177E]) mutant channels, with well-resolved non-cooperative subconductance levels. Decreasing cytoplasmic pH shifts the probability towards lower conductance levels. Molecular dynamics simulations show how protonation of Kir2.2[G178D], or the D173 pore-lining residues, changes solvation, K

Emerging Therapies For Antibody-Mediated Rejection In Kidney Transplantation, Farah Abuazzam, Casey Dubrawka, Tarek Abdulhadi, Gwendolyn Amurao, Louai Alrata, Dema Yaseen Alsabbagh, Omar Alomar, Tarek Alhamad

2020-Current year OA Pubs

Despite the advances in immunosuppressive medications, antibody-mediated rejection (AMR) continues to be a major cause of kidney allograft failure and remains a barrier to improving long-term allograft survival. Recently, there have been significant advances in the understanding of the pathophysiological process of AMR, along with the development of new therapeutic options. Additionally, surveillance protocols with donor-derived cell-free DNA and gene profile testing have been established, leading to the early detection of AMR. A multitude of clinical trials are ongoing, opening numerous opportunities for improving outcome in kidney transplant recipients. In this brief review, we discuss the emerging therapies for managing …

Accelerating Cryptic Pocket Discovery Using Alphafold, Artur Meller, Soumendranath Bhakat, Shahlo Solieva, Gregory R Bowman

2020-Current year OA Pubs

Cryptic pockets, or pockets absent in ligand-free, experimentally determined structures, hold great potential as drug targets. However, cryptic pocket openings are often beyond the reach of conventional biomolecular simulations because certain cryptic pocket openings involve slow motions. Here, we investigate whether AlphaFold can be used to accelerate cryptic pocket discovery either by generating structures with open pockets directly or generating structures with partially open pockets that can be used as starting points for simulations. We use AlphaFold to generate ensembles for 10 known cryptic pocket examples, including five that were deposited after AlphaFold's training data were extracted from the PDB. …

Utility Of Targeted Gene Sequencing To Differentiate Myeloid Malignancies From Other Cytopenic Conditions, Amy E Dezern, Robert S Fulton, Matthew J Walter, Et Al.

2020-Current year OA Pubs

The National Heart, Lung, and Blood Institute-funded National MDS Natural History Study (NCT02775383) is a prospective cohort study enrolling patients with cytopenia with suspected myelodysplastic syndromes (MDS) to evaluate factors associated with disease. Here, we sequenced 53 genes in bone marrow samples harvested from 1298 patients diagnosed with myeloid malignancy, including MDS and non-MDS myeloid malignancy or alternative marrow conditions with cytopenia based on concordance between independent histopathologic reviews (local, centralized, and tertiary to adjudicate disagreements when needed). We developed a novel 2-stage diagnostic classifier based on mutational profiles in 18 of 53 sequenced genes that were sufficient to best …