Digital Commons Network^™

How I Prescribe Prolonged Intermittent Renal Replacement Therapy, Edward G Clark, Anitha Vijayan

2020-Current year OA Pubs

Prolonged Intermittent Renal Replacement Therapy (PIRRT) is the term used to define 'hybrid' forms of renal replacement therapy. PIRRT can be provided using an intermittent hemodialysis machine or a continuous renal replacement therapy (CRRT) machine. Treatments are provided for a longer duration than typical intermittent hemodialysis treatments (6-12 h vs. 3-4 h, respectively) but not 24 h per day as is done for continuous renal replacement therapy (CRRT). Usually, PIRRT treatments are provided 4 to 7 times per week. PIRRT is a cost-effective and flexible modality with which to safely provide RRT for critically ill patients. We present a brief …

Molnupiravir And Risk Of Hospital Admission Or Death In Adults With Covid-19: Emulation Of A Randomized Target Trial Using Electronic Health Records, Yan Xie, Benjamin Bowe, Ziyad Al-Aly

2020-Current year OA Pubs

OBJECTIVE: To emulate a randomized target trial to estimate the association between the antiviral drug molnupiravir and hospital admission or death in adults with SARS-CoV-2 infection in the community during the omicron predominant era who were at high risk of progression to severe covid-19.

DESIGN: Emulation of a randomized target trial using electronic health records.

SETTING: US Department of Veterans Affairs.

PARTICIPANTS: 85 998 adults with SARS-CoV-2 infection between 5 January and 30 September 2022 and at least one risk factor for progression to severe covid-19: 7818 participants were eligible for and treated with molnupiravir and 78 180 received no …

Long-Term Gastrointestinal Outcomes Of Covid-19, Evan Xu, Yan Xie, Ziyad Al-Aly

2020-Current year OA Pubs

A comprehensive evaluation of the risks and 1-year burdens of gastrointestinal disorders in the post-acute phase of COVID-19 is needed but is not yet available. Here we use the US Department of Veterans Affairs national health care databases to build a cohort of 154,068 people with COVID-19, 5,638,795 contemporary controls, and 5,859,621 historical controls to estimate the risks and 1-year burdens of a set of pre-specified incident gastrointestinal outcomes. We show that beyond the first 30 days of infection, people with COVID-19 exhibited increased risks and 1-year burdens of incident gastrointestinal disorders spanning several disease categories including motility disorders, acid …

Social Determinants, Cardiovascular Disease, And Health Care Cost: A Nationwide Study In The United States Using Machine Learning, Feinuo Sun, Jie Yao, Shichao Du, Feng Qian, Allison A Appleton, Cui Tao, Hua Xu, Lei Liu, Qi Dai, Brian T Joyce, Drew R Nannini, Lifang Hou, Kai Zhang

2020-Current year OA Pubs

Background Existing studies on cardiovascular diseases (CVDs) often focus on individual-level behavioral risk factors, but research examining social determinants is limited. This study applies a novel machine learning approach to identify the key predictors of county-level care costs and prevalence of CVDs (including atrial fibrillation, acute myocardial infarction, congestive heart failure, and ischemic heart disease). Methods and Results We applied the extreme gradient boosting machine learning approach to a total of 3137 counties. Data are from the

The Implementation Playbook: Study Protocol For The Development And Feasibility Evaluation Of A Digital Tool For Effective Implementation Of Evidence-Based Innovations, Melanie Barwick, Jacquie Brown, Kadia Petricca, Bonnie Stevens, Byron J Powell, Alexia Jaouich, Jill Shakespeare, Emily Seto

2020-Current year OA Pubs

BACKGROUND: Evidence-based innovations can improve health outcomes, but only if successfully implemented. Implementation can be complex, highly susceptible to failure, costly and resource intensive. Internationally, there is an urgent need to improve the implementation of effective innovations. Successful implementation is best guided by implementation science, but organizations lack implementation know-how and have difficulty applying it. Implementation support is typically shared in static, non-interactive, overly academic guides and is rarely evaluated. In-person implementation facilitation is often soft-funded, costly, and scarce. This study seeks to improve effective implementation by (1) developing a first-in-kind digital tool to guide pragmatic, empirically based and self-directed …

Rethinking The Difficult Patient: Formative Qualitative Study Using Participatory Theater To Improve Physician-Patient Communication In Rheumatology, Jerik Leung, Avira Som, Lily Mcmorrow, Lisa Zickuhr, John Wolbers, Karen Bain, Julia Flood, Elizabeth A Baker

2020-Current year OA Pubs

BACKGROUND: Effective physician-patient communication is crucial for positive health outcomes for patients with chronic diseases. However, current methods of physician education in communication are often insufficient to help physicians understand how patients' actions are influenced by the contexts within which they live. An arts-based participatory theater approach can provide the necessary health equity framing to address this deficiency.

OBJECTIVE: The aim of this study was to develop, pilot, and conduct a formative evaluation of an interactive arts-based communication skills intervention for graduate-level medical trainees grounded in a narrative representative of the experience of patients with systemic lupus erythematosus.

METHODS: We …

Charge-Voltage Curves Of Shaker Potassium Channel Are Not Hysteretic At Steady State, John Cowgill, Baron Chanda

2020-Current year OA Pubs

Charge-voltage curves of many voltage-gated ion channels exhibit hysteresis but such curves are also a direct measure of free energy of channel gating and, hence, should be path-independent. Here, we identify conditions to measure steady-state charge-voltage curves and show that these are curves are not hysteretic. Charged residues in transmembrane segments of voltage-gated ion channels (VGICs) sense and respond to changes in the electric field. The movement of these gating charges underpins voltage-dependent activation and is also a direct metric of the net free-energy of channel activation. However, for most voltage-gated ion channels, the charge-voltage (Q-V) curves appear to be …

Application Of Artificial Intelligence In Measuring Novel Ph-Impedance Metrics For Optimal Diagnosis Of Gerd, Ming-Wun Wong, Benjamin D Rogers, Min-Xiang Liu, Wei-Yi Lei, Tso-Tsai Liu, Chih-Hsun Yi, Jui-Sheng Hung, Shu-Wei Liang, Chiu-Wang Tseng, Jen-Hung Wang, Ping-An Wu, Chien-Lin Chen

2020-Current year OA Pubs

Novel metrics extracted from pH-impedance monitoring can augment the diagnosis of gastroesophageal reflux disease (GERD). Artificial intelligence (AI) is being widely used to improve the diagnostic capabilities of various diseases. In this review, we update the current literature regarding applications of artificial intelligence in measuring novel pH-impedance metrics. AI demonstrates high performance in the measurement of impedance metrics, including numbers of reflux episodes and post-reflux swallow-induced peristaltic wave index and, furthermore, extracts baseline impedance from the entire pH-impedance study. AI is expected to play a reliable role in facilitating measuring novel impedance metrics in patients with GERD in the near …

Association Between Community-Level Social Risk And Spending Among Medicare Beneficiaries: Implications For Social Risk Adjustment And Health Equity, Brian W Powers, Jose F Figueroa, Melanie Canterberry, Suhas Gondi, Stephanie M Franklin, William H Shrank, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: Payers are increasingly using approaches to risk adjustment that incorporate community-level measures of social risk with the goal of better aligning value-based payment models with improvements in health equity.

OBJECTIVE: To examine the association between community-level social risk and health care spending and explore how incorporating community-level social risk influences risk adjustment for Medicare beneficiaries.

DESIGN, SETTING, AND PARTICIPANTS: Using data from a Medicare Advantage plan linked with survey data on self-reported social needs, this cross-sectional study estimated health care spending health care spending was estimated as a function of demographics and clinical characteristics, with and without the inclusion …

Appeal Of Tobacco Quitline Services Among Low-Income Smokers, Lauren M Grimes, Rachel Garg, Olivia Weng, Jennifer M Wolff, Amy Mcqueen, Kelly M Carpenter, Matthew W Kreuter

2020-Current year OA Pubs

INTRODUCTION: State tobacco quitlines are delivering cessation assistance through an increasingly diverse range of channels. However, offerings vary from state to state, many smokers are unaware of what is available, and it is not yet clear how much demand exists for different types of assistance. In particular, the demand for online and digital cessation interventions among low-income smokers, who bear a disproportionate burden of tobacco-related disease, is not well understood.

METHODS: We examined interest in using 13 tobacco quitline services in a racially diverse sample of 1,605 low-income smokers in 9 states who had called a 2-1-1 helpline and participated …

Insights Into Pulmonary Phosphate Homeostasis And Osteoclastogenesis Emerge From The Study Of Pulmonary Alveolar Microlithiasis, Yasuaki Uehara, Steven L Teitelbaum, Et Al.

2020-Current year OA Pubs

Pulmonary alveolar microlithiasis is an autosomal recessive lung disease caused by a deficiency in the pulmonary epithelial Npt2b sodium-phosphate co-transporter that results in accumulation of phosphate and formation of hydroxyapatite microliths in the alveolar space. The single cell transcriptomic analysis of a pulmonary alveolar microlithiasis lung explant showing a robust osteoclast gene signature in alveolar monocytes and the finding that calcium phosphate microliths contain a rich protein and lipid matrix that includes bone resorbing osteoclast enzymes and other proteins suggested a role for osteoclast-like cells in the host response to microliths. While investigating the mechanisms of microlith clearance, we found …

A Trpv4-Dependent Neuroimmune Axis In The Spinal Cord Promotes Neuropathic Pain, Xueming Hu, Lixia Du, Shenbin Liu, Zhou Lan, Kaikai Zang, Jing Feng, Yonghui Zhao, Xingliang Yang, Zili Xie, Peter L. Wang, Aaron M. Ver Heul, Lvyi Chen, Vijay K. Samineni, Yan-Qing Wang, Kory J. Lavine, Robert W. Gereau, Gregory F. Wu, Hongzhen Hu

2020-Current year OA Pubs

Microglia, resident macrophages of the CNS, are essential to brain development, homeostasis, and disease. Microglial activation and proliferation are hallmarks of many CNS diseases, including neuropathic pain. However, molecular mechanisms that govern the spinal neuroimmune axis in the setting of neuropathic pain remain incompletely understood. Here, we show that genetic ablation or pharmacological blockade of transient receptor potential vanilloid type 4 (TRPV4) markedly attenuated neuropathic pain-like behaviors in a mouse model of spared nerve injury. Mechanistically, microglia-expressed TRPV4 mediated microglial activation and proliferation and promoted functional and structural plasticity of excitatory spinal neurons through release of lipocalin-2. Our results suggest …

Nitric Oxide-Driven Modifications Of Lipoic Arm Inhibit Α-Ketoacid Dehydrogenases, Gretchen L Seim, Steven V John, Nicholas L Arp, Zixiang Fang, David J Pagliarini, Jing Fan

2020-Current year OA Pubs

Pyruvate dehydrogenase complex (PDHC) and oxoglutarate dehydrogenase complex (OGDC), which belong to the mitochondrial α-ketoacid dehydrogenase family, play crucial roles in cellular metabolism. These multi-subunit enzyme complexes use lipoic arms covalently attached to their E2 subunits to transfer an acyl group to coenzyme A (CoA). Here, we report a novel mechanism capable of substantially inhibiting PDHC and OGDC: reactive nitrogen species (RNS) can covalently modify the thiols on their lipoic arms, generating a series of adducts that block catalytic activity. S-Nitroso-CoA, a product between RNS and the E2 subunit's natural substrate, CoA, can efficiently deliver these modifications onto the lipoic …

Society For Immunotherapy Of Cancer (Sitc) Consensus Definitions For Resistance To Combinations Of Immune Checkpoint Inhibitors With Chemotherapy, Naiyer Rizvi, Foluso O. Ademuyiwa, Z Alexander Cao, Helen X. Chen, Robert L. Ferris, Sarah B. Goldberg, Matthew D. Hellmann, Ranee Mehra, Ina Rhee, Jong Chul Park, Harriet Kluger, Hussein Tawbi, Ryan J. Sullivan

2020-Current year OA Pubs

Although immunotherapy can offer profound clinical benefit for patients with a variety of difficult-to-treat cancers, many tumors either do not respond to upfront treatment with immune checkpoint inhibitors (ICIs) or progressive/recurrent disease occurs after an interval of initial control. Improved response rates have been demonstrated with the addition of ICIs to cytotoxic therapies, leading to approvals from the US Food and Drug Administration and regulatory agencies in other countries for ICI-chemotherapy combinations in a number of solid tumor indications, including breast, head and neck, gastric, and lung cancer. Designing trials for patients with tumors that do not respond or stop …

Clinical Pattern Of Tolvaptan-Associated Liver Injury In Trial Participants With Autosomal Dominant Polycystic Kidney Disease (Adpkd): An Analysis Of Pivotal Clinical Trials, David H Alpers, James H Lewis, Christine M Hunt, James W Freston, Vicente E Torres, Hui Li, Wenchyi Wang, Molly E Hoke, Sharin E Roth, Lucas Westcott-Baker, Alvin Estilo

2020-Current year OA Pubs

RATIONALE & OBJECTIVE: Tolvaptan is associated with risk of drug-induced liver injury when used to treat autosomal dominant polycystic kidney disease (ADPKD). After this risk was described based on the clinical trials TEMPO 3:4 and TEMPO 4:4, additional data from the REPRISE trial and a long-term extension of TEMPO 4:4, REPRISE, and other tolvaptan trials in ADPKD have become available. To further characterize the hepatic safety profile of tolvaptan, an analysis of the expanded dataset was conducted.

STUDY DESIGN: Analysis of safety data from prospective clinical trials of tolvaptan.

SETTING & PARTICIPANTS: Multicenter clinical trials including more than 2,900 tolvaptan-treated …

Cnih3 Deletion Dysregulates Dorsal Hippocampal Transcription Across The Estrous Cycle, Bernard Mulvey, Hannah E. Frye, Tania Lintz, Stuart Fass, Eric Tycksen, Elliot C. Nelson, Jose A. Morón, Joseph D. Dougherty

2020-Current year OA Pubs

In females, the hippocampus, a critical brain region for coordination of learning, memory, and behavior, displays altered physiology and behavioral output across the estrous or menstrual cycle. However, the molecular effectors and cell types underlying these observed cyclic changes have only been partially characterized to date. Recently, profiling of mice null for the AMPA receptor trafficking gene

Venographic Classification And Long-Term Surgical Treatment Outcomes For Axillary-Subclavian Vein Thrombosis Due To Venous Thoracic Outlet Syndrome (Paget-Schroetter Syndrome), Esmaeel Reza Dadashzadeh, J. Westley Ohman, Pavan K. Kavali, Karen M. Henderson, Danita M. Goestenkors, Robert W. Thompson

2020-Current year OA Pubs

OBJECTIVE: We assessed the clinical presentation, operative findings, and surgical treatment outcomes for axillary-subclavian vein (AxSCV) thrombosis due to venous thoracic outlet syndrome (VTOS).

METHODS: We performed a retrospective, single-center review of 266 patients who had undergone primary surgical treatment of VTOS between 2016 and 2022. The clinical outcomes were compared between the patients in four treatment groups determined by intraoperative venography.

RESULTS: Of the 266 patients, 132 were male and 134 were female. All patients had a history of spontaneous arm swelling and idiopathic AxSCV thrombosis, including 25 (9%) with proven pulmonary embolism, at a mean age of 32.1 …

Design Of Serena-6, A Phase Iii Switching Trial Of Camizestrant In Esr1-Mutant Breast Cancer During First-Line Treatment, Nicholas Turner, Cynthia Huang-Bartlett, Kevin Kalinsky, Massimo Cristofanilli, Giampaolo Bianchini, Stephen Chia, Hiroji Iwata, Wolfgang Janni, Cynthia X Ma, Erica L Mayer, Yeon Hee Park, Steven Fox, Xiaochun Liu, Sasha Mcclain, Francois-Clement Bidard

2020-Current year OA Pubs

No abstract provided.

Reduction Of Surgical Site Infection After Trauma Laparotomy Through Use Of A Specific Protocol For Antibiotic Prophylaxis, John E Mazuski, William J Symons, Stephen Jarman, Bryan Sato, William Carroll, Grant V Bochicchio, John P Kirby, Douglas J Schuerer

2020-Current year OA Pubs

No abstract provided.

Building The Foundation For A Community-Generated National Research Blueprint For Inherited Bleeding Disorders: Research Priorities For Mucocutaneous Bleeding Disorders, Robert F Sidonio Jr, Jorge Di Paola, Et Al.

2020-Current year OA Pubs

BACKGROUND: Excessive or abnormal mucocutaneous bleeding (MCB) may impact all aspects of the physical and psychosocial wellbeing of those who live with it (PWMCB). The evidence base for the optimal diagnosis and management of disorders such as inherited platelet disorders, hereditary hemorrhagic telangiectasia (HHT), hypermobility spectrum disorders (HSD), Ehlers-Danlos syndromes (EDS), and von Willebrand disease (VWD) remains thin with enormous potential for targeted research.

RESEARCH DESIGN AND METHODS: National Hemophilia Foundation and American Thrombosis and Hemostasis Network initiated the development of a National Research Blueprint for Inherited Bleeding Disorders with extensive all-stakeholder consultations to identify the priorities of people with …

Frequent First-Trimester Pregnancy Loss In Rhesus Macaques Infected With African-Lineage Zika Virus, Jenna R. Rosinski, Kevin K. Noguchi, Et Al.

2020-Current year OA Pubs

In the 2016 Zika virus (ZIKV) pandemic, a previously unrecognized risk of birth defects surfaced in babies whose mothers were infected with Asian-lineage ZIKV during pregnancy. Less is known about the impacts of gestational African-lineage ZIKV infections. Given high human immunodeficiency virus (HIV) burdens in regions where African-lineage ZIKV circulates, we evaluated whether pregnant rhesus macaques infected with simian immunodeficiency virus (SIV) have a higher risk of African-lineage ZIKV-associated birth defects. Remarkably, in both SIV+ and SIV- animals, ZIKV infection early in the first trimester caused a high incidence (78%) of spontaneous pregnancy loss within 20 days. These findings suggest …

Selective Dorsal Rhizotomy For Treatment Of Spasticity After Hemispherectomy In Children: A Case Report, Ts Park, Susan Joh, Matthew D. Smyth, Nicole L. Meyer, Deanna M. Walter

2020-Current year OA Pubs

Performing a hemispherotomy or hemispherectomy is known to treat medically intractable epilepsy successfully, yet contralateral hemiparesis and increased muscle tone follow the epilepsy surgery. Spasticity and coexisting dystonia presumably cause the increased muscle tone in the lower extremity on the opposite side of epilepsy surgery. However, the extent of the role of spasticity and dystonia in high muscle tone is unknown. A selective dorsal rhizotomy is performed to reduce spasticity. If a selective dorsal rhizotomy is performed in the affected patient and muscle tone is reduced, the high muscle tone is not due to dystonia. Two children, who previously underwent …

Aberrant Right Gastric Vein Mimicking Hepatic Spread Of Prostate Cancer On Psma-Pet/Ct, Genevieve C Muñoz, Tyler J Fraum

2020-Current year OA Pubs

Hepatic vasculature can exhibit a wide variety of variants, some of which may resemble pathologic findings. In this case, a 53-year-old man presenting for staging of biochemically recurrent prostatic adenocarcinoma was found to have focally increased prostate-specific membrane antigen (PSMA) tracer uptake on positron emission tomography (PET) imaging in hepatic segment IV. This finding was initially concerning for hepatic metastasis of the patient's primary prostate adenocarcinoma. However, the area of radiotracer uptake was not associated with a discrete lesion on CT, and the geographic morphology of the uptake raised the possibility of a vascular etiology. Magnetic resonance imaging (MRI) of …

Harmonization And Standardization Of Nucleus Pulposus Cell Extraction And Culture Methods, Shaghayegh Basatvat, Liufang Jing, Lori Setton, Xiaohong Tan, Et Al.

2020-Current year OA Pubs

BACKGROUND: In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab-to-lab variability jeopardizes the much-needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources.

METHODS: The most commonly applied methods for NP cell extraction, expansion, and re-differentiation were identified using a questionnaire to research groups worldwide. NP cell extraction methods from rat, rabbit, pig, dog, …

Clinical Outcomes After Reverse Shoulder Arthroplasty In Patients 60 Years Old And Younger; Medium-Term Results, Aaron M Chamberlain, Alexander W Aleem, Julianne A Sefko, Karen Steger-May, Jay D Keener

2020-Current year OA Pubs

BACKGROUND: Reverse total shoulder arthroplasty (RTSA) has been well-described as a surgical solution to manage rotator cuff tear arthropathy in elderly, low demand paitents. As experience has increased along with improvements in technique and implant design, RTSA has become increasingly used to manage more varied pathologic conditions of the shoulder in younger, more active patients. This study evaluates outcomes in a consecutive series of patients aged 60 years old and younger after undergoing RTSA.

METHODS: There were 94 shoulders in 89 patients enrolled. Mean age of the cohort was 54.8 (range 18-60 years). Surgical indications included rotator cuff tear arthropathy, …

Aim18p And Aim46p Are Chalcone Isomerase Domain-Containing Mitochondrial Hemoproteins In Saccharomyces Cerevisiae, Jonathan M Schmitz, John F Wolters, Nathan H Murray, Rachel M Guerra, Craig A Bingman, Chris Todd Hittinger, David J Pagliarini

2020-Current year OA Pubs

Chalcone isomerases (CHIs) have well-established roles in the biosynthesis of plant flavonoid metabolites. Saccharomyces cerevisiae possesses two predicted CHI-like proteins, Aim18p (encoded by YHR198C) and Aim46p (YHR199C), but it lacks other enzymes of the flavonoid pathway, suggesting that Aim18p and Aim46p employ the CHI fold for distinct purposes. Here, we demonstrate using proteinase K protection assays, sodium carbonate extractions, and crystallography that Aim18p and Aim46p reside on the mitochondrial inner membrane and adopt CHI folds, but they lack select active site residues and possess an extra fungal-specific loop. Consistent with these differences, Aim18p and Aim46p lack CHI activity and also …

Apolipoprotein M Attenuates Anthracycline Cardiotoxicity And Lysosomal Injury, Zhen Guo, Carla Valenzuela Ripoll, Antonino Picataggi, David R Rawnsley, Mualla Ozcan, Ezhilarasi Chendamarai, Amanda Girardi, Terrence Riehl, Hosannah Evie, Ahmed Diab, Attila Kovacs, Krzysztof Hyrc, Xiucui Ma, Lauren N Pedersen, Carmen Bergom, Nathan O Stitziel, Michael P Rettig, John F Dipersio, Abhinav Diwan, Ali Javaheri, Et Al.

2020-Current year OA Pubs

Apolipoprotein M (ApoM) binds sphingosine-1-phosphate (S1P) and is inversely associated with mortality in human heart failure (HF). Here, we show that anthracyclines such as doxorubicin (Dox) reduce circulating ApoM in mice and humans, that ApoM is inversely associated with mortality in patients with anthracycline-induced heart failure, and ApoM heterozygosity in mice increases Dox-induced mortality. In the setting of Dox stress, our studies suggest ApoM can help sustain myocardial autophagic flux in a post-transcriptional manner, attenuate Dox cardiotoxicity, and prevent lysosomal injury.

Prospective Associations Between Accelerometry-Derived Physical Activity And Sedentary Behaviors And Mortality Among Cancer Survivors, Elizabeth A Salerno, Pedro F Saint-Maurice, Fei Wan, Lindsay L Peterson, Yikyung Park, Yin Cao, Ryan P Duncan, Richard P Troiano, Charles E Matthews

2020-Current year OA Pubs

BACKGROUND: Survival benefits of self-reported recreational physical activity (PA) during cancer survivorship are well-documented in common cancer types, yet there are limited data on the associations between accelerometer-derived PA of all domains, sedentary behavior, and mortality in large, diverse cohorts of cancer survivors.

METHODS: Participants included adults who reported a cancer diagnosis in the National Health and Nutrition Examination Survey and wore an accelerometer for up to 7 days in 2003-2006. Participants were followed for subsequent mortality through 2015. We examined the association of light PA, moderate to vigorous PA, total PA, and sedentary behavior, with all-cause mortality. Cox proportional …

Effect Of Fecal Microbial Transplantation On Clostridioides Difficile Infection: Dysbiosis, Metabolites And Health Related Quality Of Life, Kevin W Garey, Paul Feuerstadt, Erik R Dubberke, Amy Guo, Glenn S Tillotson

2020-Current year OA Pubs

No abstract provided.

Predicting Locations Of Cryptic Pockets From Single Protein Structures Using The Pocketminer Graph Neural Network, Artur Meller, Michael Ward, Jonathan Borowsky, Meghana Kshirsagar, Jeffrey M Lotthammer, Felipe Oviedo, Juan Lavista Ferres, Gregory R Bowman

2020-Current year OA Pubs

Cryptic pockets expand the scope of drug discovery by enabling targeting of proteins currently considered undruggable because they lack pockets in their ground state structures. However, identifying cryptic pockets is labor-intensive and slow. The ability to accurately and rapidly predict if and where cryptic pockets are likely to form from a structure would greatly accelerate the search for druggable pockets. Here, we present PocketMiner, a graph neural network trained to predict where pockets are likely to open in molecular dynamics simulations. Applying PocketMiner to single structures from a newly curated dataset of 39 experimentally confirmed cryptic pockets demonstrates that it …