Medicine and Health Sciences Commons^™

Impact Of Prior Therapies And Subsequent Transplantation On Outcomes In Adult Patients With Relapsed Or Refractory B-Cell Acute Lymphoblastic Leukemia Treated With Brexucabtagene Autoleucel In Zuma-3, Bijal D Shah, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

BACKGROUND: Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the USA for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and in the European Union for patients ≥26 years with R/R B-ALL. After 2 years of follow-up in ZUMA-3, the overall complete remission (CR) rate (CR+CR with incomplete hematological recovery (CRi)) was 73%, and the median overall survival (OS) was 25.4 months in 78 Phase 1 and 2 patients with R/R B-ALL who received the pivotal dose of brexu-cel. Outcomes by prior therapies and subsequent allogeneic stem cell transplantation (alloSCT) …

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). …

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 …

Cation Leak Through The Atp1a3 Pump Causes Spasticity And Intellectual Disability, Daniel G Calame, Marwan Shinawi, Et Al.

2020-Current year OA Pubs

ATP1A3 encodes the α3 subunit of the sodium-potassium ATPase, one of two isoforms responsible for powering electrochemical gradients in neurons. Heterozygous pathogenic ATP1A3 variants produce several distinct neurological syndromes, yet the molecular basis for phenotypic variability is unclear. We report a novel recurrent variant, ATP1A3(NM_152296.5):c.2324C>T; p.(Pro775Leu), in nine individuals associated with the primary clinical features of progressive or non-progressive spasticity and developmental delay/intellectual disability. No patients fulfil diagnostic criteria for ATP1A3-associated syndromes, including alternating hemiplegia of childhood, rapid-onset dystonia-parkinsonism or cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss (CAPOS), and none were suspected of having an ATP1A3-related disorder. Uniquely among known …

Harm Reduction: A Missing Piece To The Holistic Care Of Patients Who Inject Drugs, Nathanial S Nolan, Sarah M Fracasso Francis, Laura R Marks, Susan E Beekmann, Philip M Polgreen, Stephen Y Liang, Michael J Durkin

2020-Current year OA Pubs

BACKGROUND: The rise in injection drug use (IDU) has led to an increase in drug-related infections. Harm reduction is an important strategy for preventing infections among people who inject drugs (PWID). We attempted to evaluate the harm reduction counseling that infectious diseases physicians provide to PWID presenting with infections.

METHODS: An electronic survey was distributed to physician members of the Emerging Infections Network to inquire about practices used when caring for patients with IDU-related infections.

RESULTS: In total, 534 ID physicians responded to the survey. Of those, 375 (70%) reported routinely caring for PWID. Most respondents report screening for human …

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.

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 …

Cerebrospinal Fluid Proteomics Define The Natural History Of Autosomal Dominant Alzheimer's Disease, Erik C B Johnson, Brian A Gordon, Eric Mcdade, Nicolas R Barthélemy, Celeste M Karch, Chengjie Xiong, Carlos Cruchaga, Richard J Perrin, John C Morris, Tammie L S Benzinger, Randall J Bateman, Anne M Fagan, Et Al.

2020-Current year OA Pubs

Alzheimer's disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes-aggregation of the amyloid-β (Aβ) peptide into plaques and the microtubule protein tau into neurofibrillary tangles (NFTs)-are hallmarks of the disease. However, other pathological brain processes are thought to be key disease mediators of Aβ plaque and NFT pathology. How these additional pathologies evolve over the course of the disease is currently unknown. Here we show that proteomic measurements in autosomal dominant AD cerebrospinal fluid (CSF) linked to brain protein coexpression can be used to characterize the evolution of AD pathology over a timescale spanning …

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 …

Management Of Acetaminophen Poisoning In The Us And Canada: A Consensus Statement, Richard C Dart, Michael E Mullins, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The US and Canada currently have no formal published nationwide guidelines for specialists in poison information or emergency departments for the management of acetaminophen poisoning, resulting in significant variability in management.

OBJECTIVE: To develop consensus guidelines for the management of acetaminophen poisoning in the US and Canada.

EVIDENCE REVIEW: Four clinical toxicology societies (America's Poison Centers, American Academy of Clinical Toxicology, American College of Medical Toxicology, and Canadian Association of Poison Control Centers) selected participants (n = 21). Led by a nonvoting chairperson using a modified Delphi method, the panel created a decision framework and determined the appropriate clinical …

Anesthesia Clinical Workload Estimated From Electronic Health Record Documentation Vs Billed Relative Value Units, Sunny S Lou, Laura R Baratta, Daphne Lew, Derek Harford, Michael S Avidan, Thomas Kannampallil

2020-Current year OA Pubs

IMPORTANCE: Accurate measurements of clinical workload are needed to inform health care policy. Existing methods for measuring clinical workload rely on surveys or time-motion studies, which are labor-intensive to collect and subject to biases.

OBJECTIVE: To compare anesthesia clinical workload estimated from electronic health record (EHR) audit log data vs billed relative value units.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study of anesthetic encounters occurring between August 26, 2019, and February 9, 2020, used data from 8 academic hospitals, community hospitals, and surgical centers across Missouri and Illinois. Clinicians who provided anesthetic services for at least 1 surgical encounter were …

Engaging Adolescents In Using Online Patient Portals, Bryan A Sisk, Alison L Antes, Christine Bereitschaft, Madi Enloe, Sunny Lin, Meghana Srinivas, Fabienne Bourgeois, James M Dubois

2020-Current year OA Pubs

IMPORTANCE: Many health care systems offer adolescents access to health information through online patient portals, but few studies have explored how to engage adolescents in using and benefiting from online portals.

OBJECTIVE: To determine how US children's hospitals have attempted to encourage adolescent portal use, barriers to engaging adolescents, and ideal future goals for engagement.

DESIGN, SETTING, AND PARTICIPANTS: This qualitative study performed structured qualitative interviews with informatics administrators from children's hospitals across the US between February and July 2022. Informatics administrators were employed by US health care systems that managed a children's hospital with at least 50 dedicated pediatrics …

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 …

Alcohol Consumption Among Adults With A Cancer Diagnosis In The All Of Us Research Program, Mengyao Shi, Chongliang Luo, Oluseye K Oduyale, Xiaoyu Zong, Noelle K Loconte, Yin Cao

2020-Current year OA Pubs

IMPORTANCE: Alcohol consumption is associated with adverse oncologic and treatment outcomes among individuals with a diagnosis of cancer. As a key modifiable behavioral factor, alcohol consumption patterns among cancer survivors, especially during treatment, remain underexplored in the United States.

OBJECTIVE: To comprehensively characterize alcohol consumption patterns among US cancer survivors.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from May 6, 2018, to January 1, 2022, from the National Institutes of Health All of Us Research Program, a diverse US cohort with electronic health record (EHR) linkage, and included 15 199 participants who reported a cancer diagnosis and 1839 …

Changing Faces: Factors Associated With The Intention To Pursue Plastic Surgery And Practice In Underserved Areas, Mytien Nguyen, Annette Kaminaka, Nicholas N. Brutus, Luis A. Gonzalez, Amit Ratanpal, Michael Alperovich, Donna B. Jeffe, Ashar Ata, Hyacinth R. C. Mason, Paris D. Butler

2020-Current year OA Pubs

UNLABELLED: Improving the number of plastic and reconstructive surgeons who provide care to patients in underserved communities is critical to achieving health equity. We aimed to identify factors associated with graduating medical students' intentions to pursue plastic surgery and practice in underserved areas.

METHODS: De-identified data for US medical school graduates were obtained from the Association of American Medical Colleges for students who matriculated in academic years 2007-2008 and 2011-2012. Data collected included self-reported demographic and future practice intentions. Multivariate analysis was conducted to determine indicators of students' interest in plastic surgery, and their intention to practice in underserved areas. …

Cardiovascular And Metabolic Health Is Associated With Functional Brain Connectivity In Middle-Aged And Older Adults: Results From The Human Connectome Project-Aging Study, Barnaly Rashid, Matthew F Glasser, Thomas Nichols, David Van Essen, Meher R Juttukonda, Nadine A Schwab, Douglas N Greve, Essa Yacoub, Allison Lovely, Melissa Terpstra, Michael P Harms, Susan Y Bookheimer, Beau M Ances, David H Salat, Steven E Arnold

2020-Current year OA Pubs

Several cardiovascular and metabolic indicators, such as cholesterol and blood pressure have been associated with altered neural and cognitive health as well as increased risk of dementia and Alzheimer's disease in later life. In this cross-sectional study, we examined how an aggregate index of cardiovascular and metabolic risk factor measures was associated with correlation-based estimates of resting-state functional connectivity (FC) across a broad adult age-span (36-90+ years) from 930 volunteers in the Human Connectome Project Aging (HCP-A). Increased (i.e., worse) aggregate cardiometabolic scores were associated with reduced FC globally, with especially strong effects in insular, medial frontal, medial parietal, and …

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 …

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 …

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 …

Refractory Mogamulizumab-Associated Rash Responding To An Oral Janus Kinase Inhibitor, Carine M Lama, Miguel A Hernandez-Rovira, Neha Mehta-Shah, Aaron Russell, Amy C M Musiek

2020-Current year OA Pubs

No abstract provided.

Location Of Pathogenic Variants In Psen1 Impacts Progression Of Cognitive, Clinical, And Neurodegenerative Measures In Autosomal-Dominant Alzheimer's Disease, Stephanie A Schultz, Eric Mcdade, Nicolas R Barthelemy, Nelly Joseph-Mathurin, Carlos Cruchaga, Charles D Chen, Tammie L S Benzinger, Anne M Fagan, Brian A Gordon, Jason J Hassenstab, Celeste M Karch, John C Morris, Richard J Perrin, Chengjie Xiong, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Although pathogenic variants in PSEN1 leading to autosomal-dominant Alzheimer disease (ADAD) are highly penetrant, substantial interindividual variability in the rates of cognitive decline and biomarker change are observed in ADAD. We hypothesized that this interindividual variability may be associated with the location of the pathogenic variant within PSEN1. PSEN1 pathogenic variant carriers participating in the Dominantly Inherited Alzheimer Network (DIAN) observational study were grouped based on whether the underlying variant affects a transmembrane (TM) or cytoplasmic (CY) protein domain within PSEN1. CY and TM carriers and variant non-carriers (NC) who completed clinical evaluation, multimodal neuroimaging, and lumbar puncture for collection …

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) …

Resolvin D1 Prevents Injurious Neutrophil Swarming In Transplanted Lungs, Wenjun Li, Hailey M Shepherd, Yuriko Terada, Ashley E Shay, Amit I Bery, Andrew E Gelman, Kory J Lavine, Charles N Serhan, Daniel Kreisel

2020-Current year OA Pubs

Neutrophils are the primary cell type involved in lung ischemia-reperfusion injury (IRI), which remains a frequent and morbid complication after organ transplantation. Endogenous lipid mediators that become activated during acute inflammation-resolution have gained increasing recognition for their protective role(s) in promoting the restoration of homeostasis, but their influence on early immune responses following transplantation remains to be uncovered. Resolvin D1, 7

Urine Biomarker Score Captures Response To Induction Therapy With Lupus Nephritis, Ellen M Cody, Scott E Wenderfer, Kathleen E Sullivan, Alfred H J Kim, Wesley Figg, Harneet Ghumman, Tingting Qiu, Bin Huang, Prasad Devarajan, Hermine I Brunner

2020-Current year OA Pubs

BACKGROUND: The Renal Activity Index for Lupus (RAIL) consists of urine protein assessment of neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, monocyte chemotactic protein 1, adiponectin, hemopexin, and ceruloplasmin, which non-invasively identifies lupus nephritis (LN). We aimed to delineate RAIL scores with inactive versus active LN and changes over time with response to LN induction therapy.

METHODS: There were 128 pediatric patients with systemic lupus erythematosus (SLE) and age-matched healthy controls recruited in a prospective case control study, with kidney biopsy confirmation of LN. Laboratory and clinical information was recorded and urine collected at diagnosis and end of induction and during …

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

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

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 …

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. …