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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 Aug 2023

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).


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. Aug 2023

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 …


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 Aug 2023

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 …


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 Aug 2023

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 Aug 2023

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. …


The Flipped Classroom Approach In A Pediatric Anesthesiology Fellowship Curriculum, Rachel Moquin, Megan Dewey, Ashley Weinhold, Ottavia Green, Anna Rebecca Young Aug 2023

The Flipped Classroom Approach In A Pediatric Anesthesiology Fellowship Curriculum, Rachel Moquin, Megan Dewey, Ashley Weinhold, Ottavia Green, Anna Rebecca Young

2020-Current year OA Pubs

Background The flipped classroom approach is well documented to enhance medical education outcomes. Additionally, both the need for online learning materials and the increased demand for medical professionals during the COVID-19 pandemic has made this approach more relevant. The pediatric anesthesiology fellowship curriculum at one institution transitioned from a traditional classroom model to a flipped classroom approach to optimize the educational experience and support learner well-being. Approach Utilizing the American Board of Anesthesiology (ABA) and Accreditation Council for Graduate Medical Education (ACGME) content outlines, a novel, comprehensive curriculum was developed focusing on core clinical material and board review with the …


Delayed-Onset Angioedema Following A Snakebite In A Patient On Ace Inhibitors: A Case Report, Christopher Scott Sampson, Evan Schwarz Aug 2023

Delayed-Onset Angioedema Following A Snakebite In A Patient On Ace Inhibitors: A Case Report, Christopher Scott Sampson, Evan Schwarz

2020-Current year OA Pubs

INTRODUCTION: Angiotensin converting enzyme inhibitors (ACEI) are a common class of medications prescribed to patients for hypertension. Anti-hypertensive use is not normally considered an important factor when treating patients with crotalid envenomations; however, in combination with the venom in this patient, it may have resulted in angioedema.

CASE REPORT: A 65-year-old male on ACEI presented to his community emergency department following a snake envenomation to his thumb. Six vials of Crotalidae polyvalent immune fab were administered, and he was transferred to a referral center. Approximately 18 hours after the envenomation, the patient complained of tongue swelling and difficulty speaking. There …


Symbiotic Bacteria, Immune-Like Sentinel Cells, And The Response To Pathogens In A Social Amoeba, Trey J. Scott, Tyler J. Larsen, Debra A. Brock, So Yeon Stacey Uhm, David C. Queller, Joan E. Strassmann Aug 2023

Symbiotic Bacteria, Immune-Like Sentinel Cells, And The Response To Pathogens In A Social Amoeba, Trey J. Scott, Tyler J. Larsen, Debra A. Brock, So Yeon Stacey Uhm, David C. Queller, Joan E. Strassmann

2020-Current year OA Pubs

Some endosymbionts living within a host must modulate their hosts' immune systems in order to infect and persist. We studied the effect of a bacterial endosymbiont on a facultatively multicellular social amoeba host. Aggregates of the amoeba


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. Aug 2023

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. Aug 2023

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 …


Shephard: A Modular And Extensible Software Architecture For Analyzing And Annotating Large Protein Datasets, Garrett M Ginell, Aidan J Flynn, Alex S Holehouse Aug 2023

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 …


Increased Incidence And Risk Of Septicemia And Urinary Tract Infection After Clostridioides Difficile Infection, Margaret A Olsen, Matthew R Keller, Dustin Stwalley, Holly Yu, Erik R Dubberke Aug 2023

Increased Incidence And Risk Of Septicemia And Urinary Tract Infection After Clostridioides Difficile Infection, Margaret A Olsen, Matthew R Keller, Dustin Stwalley, Holly Yu, Erik R Dubberke

2020-Current year OA Pubs

BACKGROUND: Although increased occurrence of septicemia in persons with

METHODS: The first episode of CDI was identified using 2011-2017 MarketScan and CMS Medicare data and CDI cases categorized by standard surveillance definitions. Uninfected persons were frequency matched 4:1 to cases by the CDI case surveillance definition. Multivariable Cox proportional hazards models were used to identify risk factors for septicemia and UTI within 90 days of CDI onset, accounting for the competing risk of death in the Medicare population.

RESULTS: The incidence of septicemia was highest after hospital-onset CDI in the Medicare, younger commercial, and younger Medicaid populations (25.5%, 15.7%, and …


Pact: A Pipeline For Analysis Of Circulating Tumor Dna, Jace Webster, Ha X Dang, Pradeep S Chauhan, Wenjia Feng, Alex Shiang, Peter K Harris, Russell K Pachynski, Aadel A Chaudhuri, Christopher A Maher Aug 2023

Pact: A Pipeline For Analysis Of Circulating Tumor Dna, Jace Webster, Ha X Dang, Pradeep S Chauhan, Wenjia Feng, Alex Shiang, Peter K Harris, Russell K Pachynski, Aadel A Chaudhuri, Christopher A Maher

2020-Current year OA Pubs

MOTIVATION: Detection of genomic alterations in circulating tumor DNA (ctDNA) is currently used for active clinical monitoring of cancer progression and treatment response. While methods for analysis of small mutations are more developed, strategies for detecting structural variants (SVs) in ctDNA are limited. Additionally, reproducibly calling small-scale mutations, copy number alterations, and SVs in ctDNA is challenging due to the lack to unified tools for these different classes of variants.

RESULTS: We developed a unified pipeline for the analysis of ctDNA [Pipeline for the Analysis of ctDNA (PACT)] that accurately detects SVs and consistently outperformed similar tools when applied to …


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 Aug 2023

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. Aug 2023

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.


Proteomics Of Adjacent-To-Tumor Samples Uncovers Clinically Relevant Biological Events In Hepatocellular Carcinoma, Hongwen Zhu, Li Ding, Et Al. Aug 2023

Proteomics Of Adjacent-To-Tumor Samples Uncovers Clinically Relevant Biological Events In Hepatocellular Carcinoma, Hongwen Zhu, Li Ding, Et Al.

2020-Current year OA Pubs

Normal adjacent tissues (NATs) of hepatocellular carcinoma (HCC) differ from healthy liver tissues and their heterogeneity may contain biological information associated with disease occurrence and clinical outcome that has yet to be fully evaluated at the proteomic level. This study provides a detailed description of the heterogeneity of NATs and the differences between NATs and healthy livers and revealed that molecular features of tumor subgroups in HCC were partially reflected in their respective NATs. Proteomic data classified HCC NATs into two subtypes (Subtypes 1 and 2), and Subtype 2 was associated with poor prognosis and high-risk recurrence. The pathway and …


Impact Of Donor Age And Relationship On Outcomes Of Peripheral Blood Haploidentical Hematopoietic Cell Transplantation, Aaron Pruitt, Feng Gao, Elisa De Togni, Hunter Cochran, Sonia Godbole, Michael Slade, Ramzi Abboud Aug 2023

Impact Of Donor Age And Relationship On Outcomes Of Peripheral Blood Haploidentical Hematopoietic Cell Transplantation, Aaron Pruitt, Feng Gao, Elisa De Togni, Hunter Cochran, Sonia Godbole, Michael Slade, Ramzi Abboud

2020-Current year OA Pubs

Here we describe a retrospective analysis of outcomes in 299 patients who underwent peripheral blood haplo-HCT with PTCy from July 2009 through May 2021 and their association with donor characteristics. Patients had mostly acute leukemias and high or very high DRI. Multivariate analyses were conducted examining OS, NRM, relapse, cytokine release syndrome, acute and chronic GVHD. Donor characteristics included age, sex, relationship, ABO status, CMV status, and HLA match grade. Our analysis revealed increasing donor age was associated with higher NRM (compared to age <30; age 30-44 HR, 1.65; P = 0.110, age >44 HR, 1.80; P = 0.056) but lower relapse risk (compared to age <30; age 30-44 HR, 0.61; P = 0.034, age > 44 HR, 0.71; …


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 Aug 2023

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 …


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 Aug 2023

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 …


Csf Mtbr-Tau243 Is A Specific Biomarker Of Tau Tangle Pathology In Alzheimer's Disease, Kanta Horie, Nicolas R Barthélemy, Yan Li, Yingxin He, Benjamin Saef, Charles D Chen, Hong Jiang, Chihiro Sato, Brian A Gordon, Tammie L S Benzinger, David M Holtzman, John C Morris, Suzanne E Schindler, Randall J Bateman, Et Al. Aug 2023

Csf Mtbr-Tau243 Is A Specific Biomarker Of Tau Tangle Pathology In Alzheimer's Disease, Kanta Horie, Nicolas R Barthélemy, Yan Li, Yingxin He, Benjamin Saef, Charles D Chen, Hong Jiang, Chihiro Sato, Brian A Gordon, Tammie L S Benzinger, David M Holtzman, John C Morris, Suzanne E Schindler, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Aggregated insoluble tau is one of two defining features of Alzheimer's disease. Because clinical symptoms are strongly correlated with tau aggregates, drug development and clinical diagnosis need cost-effective and accessible specific fluid biomarkers of tau aggregates; however, recent studies suggest that the fluid biomarkers currently available cannot specifically track tau aggregates. We show that the microtubule-binding region (MTBR) of tau containing the residue 243 (MTBR-tau243) is a new cerebrospinal fluid (CSF) biomarker specific for insoluble tau aggregates and compared it to multiple other phosphorylated tau measures (p-tau181, p-tau205, p-tau217 and p-tau231) in two independent cohorts (BioFINDER-2, n = 448; and …


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. Aug 2023

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 …


A High-Performance Speech Neuroprosthesis, Francis R Willett, Erin M Kunz, Chaofei Fan, Donald T Avansino, Guy H Wilson, Eun Young Choi, Foram Kamdar, Matthew F Glasser, Leigh R Hochberg, Shaul Druckmann, Krishna V Shenoy, Jaimie M Henderson Aug 2023

A High-Performance Speech Neuroprosthesis, Francis R Willett, Erin M Kunz, Chaofei Fan, Donald T Avansino, Guy H Wilson, Eun Young Choi, Foram Kamdar, Matthew F Glasser, Leigh R Hochberg, Shaul Druckmann, Krishna V Shenoy, Jaimie M Henderson

2020-Current year OA Pubs

Speech brain-computer interfaces (BCIs) have the potential to restore rapid communication to people with paralysis by decoding neural activity evoked by attempted speech into text


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 Aug 2023

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 …


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. Aug 2023

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) …


The Covid-19 Pandemic And Associated Inequities In Acute Myocardial Infarction Treatment And Outcomes, Laurent G Glance, Karen E Joynt Maddox, Jingjing Shang, Patricia W Stone, Stewart J Lustik, Peter W Knight, Andrew W Dick Aug 2023

The Covid-19 Pandemic And Associated Inequities In Acute Myocardial Infarction Treatment And Outcomes, Laurent G Glance, Karen E Joynt Maddox, Jingjing Shang, Patricia W Stone, Stewart J Lustik, Peter W Knight, Andrew W Dick

2020-Current year OA Pubs

IMPORTANCE: The COVID-19 pandemic disrupted usual care for emergent conditions, such as acute myocardial infarction (AMI). Understanding whether Black and Hispanic individuals experiencing AMI had greater increases in poor outcomes compared with White individuals during the pandemic has important equity implications.

OBJECTIVE: To investigate whether the COVID-19 pandemic was associated with increased disparities in treatment and outcomes among Medicare patients hospitalized with AMI.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used Medicare data for patients hospitalized with AMI between January 2016 and November 2020. Patients were categorized as Hispanic, non-Hispanic Black, and non-Hispanic White. The association between race and ethnicity …


Prospective Role Of Cefiderocol In The Management Of Carbapenem-Resistant Acinetobacter Baumannii Infections: Review Of The Evidence, Marin Kollef, Herve Dupont, David E Greenberg, Pierluigi Viale, Roger Echols, Yoshinori Yamano, David P Nicolau Aug 2023

Prospective Role Of Cefiderocol In The Management Of Carbapenem-Resistant Acinetobacter Baumannii Infections: Review Of The Evidence, Marin Kollef, Herve Dupont, David E Greenberg, Pierluigi Viale, Roger Echols, Yoshinori Yamano, David P Nicolau

2020-Current year OA Pubs

Carbapenem-resistant Acinetobacter baumannii (CRAB) has been classified by the World Health Organization as being in the critical category of pathogens requiring urgent new antibiotic treatment options. Cefiderocol, the first approved siderophore cephalosporin, was designed for the treatment of carbapenem-resistant Gram-negative pathogens, particularly the non-fermenting species A. baumannii and Pseudomonas aeruginosa. Cefiderocol is mostly stable against hydrolysis by serine β-lactamases and metallo-β-lactamases, which are leading causes of carbapenem resistance. This review collates the available evidence on the in vitro activity, pharmacokinetics/pharmacodynamics, and efficacy and safety of cefiderocol, and outlines its current role in the management of CRAB infections. In vitro surveillance …


Exploring Hand And Upper Limb Function In Patients With Inclusion Body Myositis (Ibm), Stephanie Hunn, Lindsay Alfano, Michelle Seiffert, Conrad C Weihl Aug 2023

Exploring Hand And Upper Limb Function In Patients With Inclusion Body Myositis (Ibm), Stephanie Hunn, Lindsay Alfano, Michelle Seiffert, Conrad C Weihl

2020-Current year OA Pubs

Inclusion body myositis (IBM) is an inflammatory myopathy characterized by progressive weakness of knee extensors and finger flexors. Many patients lose independence with fine motor tasks; however, a gap remains as to how these deficits correlate with performance on functional outcome measures. We describe functional hand impairments as measured by performance-based outcome measures in a cross-sectional sample of 74 patients with IBM. Subjects completed a series of outcome measures (Functional Dexterity Test (FDT), Performance of the Upper Limb (PUL), and Sollerman Hand Function Test (SHFT)) alongside a collection of patient reported outcomes (PROs). Assessments were compared to standard IBM measurements, …


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. Aug 2023

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 …


Use Of A Mixed Reality System For Navigational Mapping During Cardiac Electrophysiological Testing Does Not Prolong Case Duration: A Subanalysis From The Cardiac Augmented Reality Study, David Bloom, David Catherall, Nathan Miller, Michael K Southworth, Andrew C Glatz, Jonathan R Silva, Jennifer N Avari Silva Aug 2023

Use Of A Mixed Reality System For Navigational Mapping During Cardiac Electrophysiological Testing Does Not Prolong Case Duration: A Subanalysis From The Cardiac Augmented Reality Study, David Bloom, David Catherall, Nathan Miller, Michael K Southworth, Andrew C Glatz, Jonathan R Silva, Jennifer N Avari Silva

2020-Current year OA Pubs

BACKGROUND: CommandEP™ is a mixed reality (MXR) system for cardiac electrophysiological (EP) procedures that provides a real-time 3-dimensional digital image of cardiac geometry and catheter locations. In a previous study, physicians using the system demonstrated improved navigational accuracy. This study investigated the impact of the CommandEP system on EP procedural times compared to the standard-of-care electroanatomic mapping system (EAMS) display.

OBJECTIVE: The purpose of this retrospective case-controlled analysis was to evaluate the impact of a novel MXR interface on EP procedural times compared to a case-matched cohort.

METHODS: Cases from the Cardiac Augmented REality (CARE) study were matched for diagnosis …


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. Aug 2023

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 = …