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Full-Text Articles in Medicine and Health Sciences

The Rare C9 P167s Risk Variant For Age-Related Macular Degeneration Increases Polymerization Of The Terminal Component Of The Complement Cascade, O Mcmahon, A Java, J P Atkinson, Et Al. Jun 2021

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

2020-Current year OA Pubs

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


Dietary Fiber Intake, The Gut Microbiome, And Chronic Systemic Inflammation In A Cohort Of Adult Men, Wenjie Ma, Yin Cao, Et Al. Jun 2021

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

2020-Current year OA Pubs

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

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


Gps Driving: A Digital Biomarker For Preclinical Alzheimer Disease, Sayeh Bayat, Ganesh M Babulal, Suzanne E Schindler, Anne M Fagan, John C Morris, Alex Mihailidis, Catherine M Roe Jun 2021

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

2020-Current year OA Pubs

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


Inferring Tf Activities And Activity Regulators From Gene Expression Data With Constraints From Tf Perturbation Data, Cynthia Z Ma, Michael R Brent Jun 2021

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

2020-Current year OA Pubs

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

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


A Strong Effect Of Individual Compliance With Mass Drug Administration For Lymphatic Filariasis On Sustained Clearance Of Soil-Transmitted Helminth Infections, Jérémy T Campillo, Naomi P Awaca-Uvon, Jean-Paul Tambwe, Godefroy Kuyangisa-Simuna, Johnny Vlaminck, Gary J Weil, Michel Boussinesq, Cédric B Chesnais, Sébastien D S Pion Jun 2021

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

2020-Current year OA Pubs

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

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


Teaching Scripts Via Smartphone App Facilitate Resident-Led Teaching Of Medical Students, Nicholas R Zessis, Amanda R Dube, Arhanti Sadanand, Jordan J Cole, Christine M Hrach, Yasmeen N Daud Jun 2021

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

2020-Current year OA Pubs

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

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


Mitochondrial Genome Copy Number Measured By Dna Sequencing In Human Blood Is Strongly Associated With Metabolic Traits Via Cell-Type Composition Differences, Liron Ganel, Lei Chen, Ryan Christ, Erica Young, Indraniel Das, Krishna Kanchi, David Larson, Allison Regier, Haley Abel, Chul Joo Kang, Alexandra Scott, Adam Locke, Nathan O Stitziel, Ira M Hall, Et Al Jun 2021

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

2020-Current year OA Pubs

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

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


Destination Shapes Antibiotic Resistance Gene Acquisitions, Abundance Increases, And Diversity Changes In Dutch Travelers, Alaric W D'Souza, Manish Boolchandani, Sanket Patel, Gianluca Galazzo, Jarne M Van Hattem, Maris S Arcilla, Damian C Melles, Menno D De Jong, Constance Schultsz, Combat Consortium, Gautam Dantas, John Penders Jun 2021

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

2020-Current year OA Pubs

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

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


Sequence Determinants Of In Cell Condensate Morphology, Dynamics, And Oligomerization As Measured By Number And Brightness Analysis, Ryan J Emenecker, Alex S Holehouse, Lucia C Strader Jun 2021

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

2020-Current year OA Pubs

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

METHODS: In this study, we combined …


Malda, Accelerating Malaria Drug Discovery, Tuo Yang, Eva S. Istvan, Daniel E. Goldberg, Et Al. Jun 2021

Malda, Accelerating Malaria Drug Discovery, Tuo Yang, Eva S. Istvan, Daniel E. Goldberg, Et Al.

2020-Current year OA Pubs

The Malaria Drug Accelerator (MalDA) is a consortium of 15 leading scientific laboratories. The aim of MalDA is to improve and accelerate the early antimalarial drug discovery process by identifying new, essential, druggable targets. In addition, it seeks to produce early lead inhibitors that may be advanced into drug candidates suitable for preclinical development and subsequent clinical testing in humans. By sharing resources, including expertise, knowledge, materials, and reagents, the consortium strives to eliminate the structural barriers often encountered in the drug discovery process. Here we discuss the mission of the consortium and its scientific achievements, including the identification of …


Elevated Mrna Expression And Defective Processing Of Cathepsin D In Hela Cells Lacking The Mannose 6-Phosphate Pathway, Lin Liu, Balraj Doray Jun 2021

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

2020-Current year OA Pubs

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


Transfer Transcriptomic Signatures For Infectious Diseases, Julia Di Iulio, Istvan Bartha, Roberto Spreafico, Herbert W Virgin, Amalio Telenti Jun 2021

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

2020-Current year OA Pubs

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


Sars-Cov-2 Detection Among International Air Travellers To Ghana During Mandatory Quarantine, Bright Adu, Joseph K H Bonney, John K Odoom, Evelyn Y A Bonney, Evangeline Obodai, Ivy A Asante, James Aboagye, Mildred A Adusei-Poku, Lawrence Lartey, Ernest K Asiedu, William K Ampofo, George B Kyei Jun 2021

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

2020-Current year OA Pubs

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

DESIGN: A retrospective cross-sectional study.

SETTING: Air travellers to Ghana on 21

PARTICIPANTS: On 21

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

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

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


Evaluation Of Serum-Derived Bovine Immunoglobulin Protein Isolate In Subjects With Decompensated Cirrhosis With Ascites, Matthew J. Stotts, Amanda Cheung, Muhammad B. Hammami, David J. Westrich Jr., Eric Anderson, Lauren Counts, Alex S. Befeler, Adrian M. Di Bisceglie, Charlene Prather Jun 2021

Evaluation Of Serum-Derived Bovine Immunoglobulin Protein Isolate In Subjects With Decompensated Cirrhosis With Ascites, Matthew J. Stotts, Amanda Cheung, Muhammad B. Hammami, David J. Westrich Jr., Eric Anderson, Lauren Counts, Alex S. Befeler, Adrian M. Di Bisceglie, Charlene Prather

2020-Current year OA Pubs

Background Bacterial translocation plays a pivotal role in the natural course of cirrhosis and its complications. Serum-derived bovine immunoglobulin (SBI) is an oral medical food that has been shown to both reduce inflammation in the intestines and neutralize bacteria. It represents a unique intervention that has not been studied in this population. Methodology We conducted a prospective open-label trial with an eight-week treatment phase of SBI. Individuals were assessed using lactulose breath testing, serum markers for enterocyte damage and bacterial translocation, and the Chronic Liver Disease Questionnaire (CLDQ) prior to and after completion of the treatment phase. Results We evaluated …


Commonalities Across Computational Workflows For Uncovering Explanatory Variants In Undiagnosed Cases, Shilpa Nadimpalli Kobren, Dustin Baldridge, Daniel J Wegner, Alexander J Paul, Et Al. Jun 2021

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

2020-Current year OA Pubs

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

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


A Peptide-Based Checkpoint Immunomodulator Alleviates Immune Dysfunction In Murine Polymicrobial Sepsis, Timothy W Phares, Vinayaka Kotraiah, Chun-Shiang Chung, Jacqueline Unsinger, Monty Mazer, Kenneth E. Remy, Cecille D. Browne, Peter Buontempo, Marc Mansour, James Pannucci, Alfred Ayala, Richard S. Hotchkiss, Gabriel M. Gutierrez Jun 2021

A Peptide-Based Checkpoint Immunomodulator Alleviates Immune Dysfunction In Murine Polymicrobial Sepsis, Timothy W Phares, Vinayaka Kotraiah, Chun-Shiang Chung, Jacqueline Unsinger, Monty Mazer, Kenneth E. Remy, Cecille D. Browne, Peter Buontempo, Marc Mansour, James Pannucci, Alfred Ayala, Richard S. Hotchkiss, Gabriel M. Gutierrez

2020-Current year OA Pubs

Sepsis-induced immunosuppression involves both innate and adaptive immunity and is associated with the increased expression of checkpoint inhibitors, such as programmed cell-death protein 1 (PD-1). The expression of PD-1 is associated with poor outcomes in septic patients, and in models of sepsis, blocking PD-1 or its ligands with antibodies increased survival and alleviated immune suppression. While inhibitory antibodies are effective, they can lead to immune-related adverse events (irAEs), in part due to continual blockade of the PD-1 pathway, resulting in hyperactivation of the immune response. Peptide-based therapeutics are an alternative drug modality that provide a rapid pharmacokinetic profile, reducing the …


Addressing Cancer Survivors' Cardiovascular Health Using The Automated Heart Health Assessment (Ah-Ha) Ehr Tool: Initial Protocol And Modifications To Address Covid-19 Challenges, Randi E Foraker, Eleanor C Davidson, Emily V Dressler, Brian J Wells, Simon Craddock Lee, Heidi D Klepin, Karen M Winkfield, W Gregory Hundley, Philip R O Payne, Albert M Lai, Glenn J Lesser, Kathryn E Weaver Jun 2021

Addressing Cancer Survivors' Cardiovascular Health Using The Automated Heart Health Assessment (Ah-Ha) Ehr Tool: Initial Protocol And Modifications To Address Covid-19 Challenges, Randi E Foraker, Eleanor C Davidson, Emily V Dressler, Brian J Wells, Simon Craddock Lee, Heidi D Klepin, Karen M Winkfield, W Gregory Hundley, Philip R O Payne, Albert M Lai, Glenn J Lesser, Kathryn E Weaver

2020-Current year OA Pubs

BACKGROUND: The purpose of this paper is to describe the Automated Heart-Health Assessment (AH-HA) study protocol, which demonstrates an agile approach to cancer care delivery research. This study aims to assess the effect of a clinical decision support tool for cancer survivors on cardiovascular health (CVH) discussions, referrals, completed visits with primary care providers and cardiologists, and control of modifiable CVH factors and behaviors. The COVID-19 pandemic has caused widespread disruption to clinical trial accrual and operations. Studies conducted with potentially vulnerable populations, including cancer survivors, must shift towards virtual consent, data collection, and study visits to reduce risk for …


A Case Of Hepatic Cyst-Induced Internal Jugular Venous Thrombosis, Tuyen V Le, Thai Truong, Tam N M Ngo, Quoc Bui, Cassady Palmer, Vien T Truong, Duc H Nguyen Jun 2021

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

2020-Current year OA Pubs

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


Report Dose-To-Medium In Clinical Trials Where Available; A Consensus From The Global Harmonisation Group To Maximize Consistency, Stephen F Kry, Jeff Michalski, Et Al. Jun 2021

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

2020-Current year OA Pubs

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

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

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

CONCLUSIONS: Dose to medium in medium (D


Outcomes And Risk Factors Associated With Sars-Cov-2 Infection In A North American Registry Of Patients With Multiple Sclerosis, Amber Salter, Robert J Fox, Scott D Newsome, June Halper, David K B Li, Pamela Kanellis, Kathleen Costello, Bruce Bebo, Kottil Rammohan, Gary R Cutter, Anne H Cross Jun 2021

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

2020-Current year OA Pubs

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

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

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


Brain-Responsive Neurostimulation For The Treatment Of Adults With Epilepsy In Tuberous Sclerosis Complex: A Case Series, Danielle S Mcdermott, Emily A Mirro, Kirsten Fetrow, David E Burdette, Stephanie Chen, Jennifer Hopp, Todd Masel, Emily A Johnson, Felicia M K Elefant, Scheherazade Le, Sanjay E Patra, Mesha-Gay Brown, Zulfi Haneef Jun 2021

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

2020-Current year OA Pubs

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

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

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


Randomized Trial Of The Efficacy And Safety Of Berotralstat (Bcx7353) As An Oral Prophylactic Therapy For Hereditary Angioedema: Results Of Apex-2 Through 48 Weeks (Part 2), H James Wedner, Et Al. Jun 2021

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

2020-Current year OA Pubs

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

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

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


Association Of Clinical Factors And Recent Anticancer Therapy With Covid-19 Severity Among Patients With Cancer: A Report From The Covid-19 And Cancer Consortium, P Grivas, K E Stockerl-Goldstein, A Y Zhou, Et Al. Jun 2021

Association Of Clinical Factors And Recent Anticancer Therapy With Covid-19 Severity Among Patients With Cancer: A Report From The Covid-19 And Cancer Consortium, P Grivas, K E Stockerl-Goldstein, A Y Zhou, Et Al.

2020-Current year OA Pubs

BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.

PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). …


Effects Of Pathogen Reduction Technology And Storage Duration On The Ability Of Cryoprecipitate To Rescue Induced Coagulopathies In Vitro, Kimberly A Thomas, Susan M Shea, Philip C Spinella Jun 2021

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

2020-Current year OA Pubs

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

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


Clinical Epigenomics: Genome-Wide Dna Methylation Analysis For The Diagnosis Of Mendelian Disorders, Bekim Sadikovic, Jorge L Granadillo, Et Al. Jun 2021

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

2020-Current year OA Pubs

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

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


The Azithromycin To Prevent Wheezing Following Severe Rsv Bronchiolitis-Ii Clinical Trial: Rationale, Study Design, Methods, And Characteristics Of Study Population, Mythili Srinivasan, Leonard B Bacharier, Charles W Goss, Yanjiao Zhou, Jonathan Boomer, Sarah Bram, Dana Burgdorf, Carey-Ann Burnham, Timothy Casper, Mario Castro, Andrea Coverstone, Matthew Haslam, Watcharoot Kanchongkittiphon, Cadence Kuklinski, Qinghua Lian, Kenneth Schechtman, Gregory A Storch, Kelly True, Meghan A Wallace, Huiqing Yin-Declue, Elizabeth Ahrens, Jinli Wang, Avraham Beigelman Jun 2021

The Azithromycin To Prevent Wheezing Following Severe Rsv Bronchiolitis-Ii Clinical Trial: Rationale, Study Design, Methods, And Characteristics Of Study Population, Mythili Srinivasan, Leonard B Bacharier, Charles W Goss, Yanjiao Zhou, Jonathan Boomer, Sarah Bram, Dana Burgdorf, Carey-Ann Burnham, Timothy Casper, Mario Castro, Andrea Coverstone, Matthew Haslam, Watcharoot Kanchongkittiphon, Cadence Kuklinski, Qinghua Lian, Kenneth Schechtman, Gregory A Storch, Kelly True, Meghan A Wallace, Huiqing Yin-Declue, Elizabeth Ahrens, Jinli Wang, Avraham Beigelman

2020-Current year OA Pubs

Severe respiratory syncytial virus (RSV) bronchiolitis in early life is a significant risk factor for future recurrent wheeze (RW) and asthma. The goal of the Azithromycin to Prevent Wheezing following severe RSV bronchiolitis II (APW-RSV II) clinical trial is to evaluate if azithromycin treatment in infants hospitalized with RSV bronchiolitis reduces the occurrence of RW during the preschool years. The APW-RSV II clinical trial is a double-blind, placebo-controlled, parallel-group, randomized trial, including otherwise healthy participants, ages 30 days-18 months, who are hospitalized due to RSV bronchiolitis. The study includes an active randomized treatment phase with azithromycin or placebo for 2 …


Integration Of Immunotherapy Into Adjuvant Therapy For Resected Non-Small-Cell Lung Cancer: Alchemist Chemo-Io (Accio), Jacob M Sands, Ramaswamy Govindan, Jhanelle Gray, Et Al Jun 2021

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

2020-Current year OA Pubs

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


Multiparametric Early Detection And Prediction Of Cardiotoxicity Using Myocardial Strain, T1 And T2 Mapping, And Biochemical Markers: A Longitudinal Cardiac Resonance Imaging Study During 2 Years Of Follow-Up, Sorin Giusca, Grigorios Korosoglou, Moritz Montenbruck, Blaž Geršak, Arne Kristian Schwarz, Sebastian Esch, Sebastian Kelle, Pia Wülfing, Susan Dent, Daniel Lenihan, Henning Steen Jun 2021

Multiparametric Early Detection And Prediction Of Cardiotoxicity Using Myocardial Strain, T1 And T2 Mapping, And Biochemical Markers: A Longitudinal Cardiac Resonance Imaging Study During 2 Years Of Follow-Up, Sorin Giusca, Grigorios Korosoglou, Moritz Montenbruck, Blaž Geršak, Arne Kristian Schwarz, Sebastian Esch, Sebastian Kelle, Pia Wülfing, Susan Dent, Daniel Lenihan, Henning Steen

2020-Current year OA Pubs

BACKGROUND: Our goal was to evaluate the ability of cardiovascular magnetic resonance for detecting and predicting cardiac dysfunction in patients receiving cancer therapy. Left ventricular ejection fraction, global and regional strain utilizing fast-strain-encoded, T1 and T2 mapping, and cardiac biomarkers (troponin and BNP [brain natriuretic peptide]) were analyzed.

METHODS: Sixty-one patients (47 with breast cancer, 11 with non-Hodgkin lymphoma, and 3 with Hodgkin lymphoma) underwent cardiovascular magnetic resonance scans at baseline and at regular intervals during 2 years of follow-up. The percentage of all left ventricular myocardial segments with strain ≤-17% (normal myocardium [%]) was analyzed. Clinical cardiotoxicity (CTX) and …


Safety And Efficacy Of Umbilical Cord-Derived Wharton's Jelly Compared To Hyaluronic Acid And Saline For Knee Osteoarthritis: Study Protocol For A Randomized, Controlled, Single-Blind, Multi-Center Trial, Ashim Gupta, Nicola Maffulli, Hugo C Rodriguez, Eric W Carson, Randa A Bascharon, Kristin Delfino, Howard J Levy, Saadiq F El-Amin May 2021

Safety And Efficacy Of Umbilical Cord-Derived Wharton's Jelly Compared To Hyaluronic Acid And Saline For Knee Osteoarthritis: Study Protocol For A Randomized, Controlled, Single-Blind, Multi-Center Trial, Ashim Gupta, Nicola Maffulli, Hugo C Rodriguez, Eric W Carson, Randa A Bascharon, Kristin Delfino, Howard J Levy, Saadiq F El-Amin

2020-Current year OA Pubs

BACKGROUND: Osteoarthritis (OA) is the most common joint disorder in the United States of America (USA) with a fast-rising prevalence. Current treatment modalities are limited, and total knee replacement surgeries have shown disadvantages, especially for grade II/III OA. The interest in the use of biologics, including umbilical cord (UC)-derived Wharton's jelly (WJ), has grown in recent years. The results from a preliminary study demonstrated the presence of essential components of regenerative medicine, namely growth factors, cytokines, hyaluronic acid (HA), and extracellular vesicles, including exosomes, in WJ. The proposed study aims to evaluate the safety and efficacy of intra-articular injection of …


Hypergraph Models Of Biological Networks To Identify Genes Critical To Pathogenic Viral Response, Song Feng, Larissa B Thackray, Qing Tan, Michael S Diamond, Et Al May 2021

Hypergraph Models Of Biological Networks To Identify Genes Critical To Pathogenic Viral Response, Song Feng, Larissa B Thackray, Qing Tan, Michael S Diamond, Et Al

2020-Current year OA Pubs

BACKGROUND: Representing biological networks as graphs is a powerful approach to reveal underlying patterns, signatures, and critical components from high-throughput biomolecular data. However, graphs do not natively capture the multi-way relationships present among genes and proteins in biological systems. Hypergraphs are generalizations of graphs that naturally model multi-way relationships and have shown promise in modeling systems such as protein complexes and metabolic reactions. In this paper we seek to understand how hypergraphs can more faithfully identify, and potentially predict, important genes based on complex relationships inferred from genomic expression data sets.

RESULTS: We compiled a novel data set of transcriptional …