Open Access. Powered by Scholars. Published by Universities.®

Medicine and Health Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 4921 - 4950 of 5035

Full-Text Articles in Medicine and Health Sciences

A Phase 1-2 Study Of Rovalpituzumab Tesirine In Combination With Nivolumab Plus Or Minus Ipilimumab In Patients With Previously Treated Extensive-Stage Sclc, Jyoti Malhotra, Daniel Morgensztern, Et Al. Sep 2021

A Phase 1-2 Study Of Rovalpituzumab Tesirine In Combination With Nivolumab Plus Or Minus Ipilimumab In Patients With Previously Treated Extensive-Stage Sclc, Jyoti Malhotra, Daniel Morgensztern, Et Al.

2020-Current year OA Pubs

INTRODUCTION: This open-label, phase 1-2 study evaluated the safety and efficacy of rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate targeting DLL3, plus immune checkpoint inhibitors nivolumab plus or minus ipilimumab in previously treated extensive-stage SCLC (ES SCLC).

METHODS: Patients with histologically or cytologically confirmed, previously treated (two or more lines of therapy) ES SCLC were enrolled into two cohorts. Cohort 1 received 0.3 mg/kg Rova-T (once every 6 wk for two cycles) plus 360 mg nivolumab (two 3-wk cycles beginning on week 4). Cohort 2 received the same dosage of Rova-T as cohort 1 plus 1 mg/kg nivolumab (four 3-wk cycles) …


Initial Antimicrobial Management Of Sepsis, Michael S Niederman, Rebecca M Baron, Lila Bouadma, Thierry Calandra, Nick Daneman, Jan Dewaele, Marin H Kollef, Jeffrey Lipman, Girish B Nair Aug 2021

Initial Antimicrobial Management Of Sepsis, Michael S Niederman, Rebecca M Baron, Lila Bouadma, Thierry Calandra, Nick Daneman, Jan Dewaele, Marin H Kollef, Jeffrey Lipman, Girish B Nair

2020-Current year OA Pubs

Sepsis is a common consequence of infection, associated with a mortality rate > 25%. Although community-acquired sepsis is more common, hospital-acquired infection is more lethal. The most common site of infection is the lung, followed by abdominal infection, catheter-associated blood steam infection and urinary tract infection. Gram-negative sepsis is more common than gram-positive infection, but sepsis can also be due to fungal and viral pathogens. To reduce mortality, it is necessary to give immediate, empiric, broad-spectrum therapy to those with severe sepsis and/or shock, but this approach can drive antimicrobial overuse and resistance and should be accompanied by a commitment to …


Improved Integration Of Single-Cell Transcriptome And Surface Protein Expression By Linq-View, Lei Li, Christopher Nelson, Daved H Fremont, Et Al. Aug 2021

Improved Integration Of Single-Cell Transcriptome And Surface Protein Expression By Linq-View, Lei Li, Christopher Nelson, Daved H Fremont, Et Al.

2020-Current year OA Pubs

Multimodal advances in single-cell sequencing have enabled the simultaneous quantification of cell surface protein expression alongside unbiased transcriptional profiling. Here, we present LinQ-View, a toolkit designed for multimodal single-cell data visualization and analysis. LinQ-View integrates transcriptional and cell surface protein expression profiling data to reveal more accurate cell heterogeneity and proposes a quantitative metric for cluster purity assessment. Through comparison with existing multimodal methods on multiple public CITE-seq datasets, we demonstrate that LinQ-View efficiently generates accurate cell clusters, especially in CITE-seq data with routine numbers of surface protein features, by preventing variations in a single surface protein feature from affecting …


Differential Classification Of States Of Consciousness Using Envelope- And Phase-Based Functional Connectivity, Catherine Duclos, Michael S Avidan, Et Al. Aug 2021

Differential Classification Of States Of Consciousness Using Envelope- And Phase-Based Functional Connectivity, Catherine Duclos, Michael S Avidan, Et Al.

2020-Current year OA Pubs

The development of sophisticated computational tools to quantify changes in the brain's oscillatory dynamics across states of consciousness have included both envelope- and phase-based measures of functional connectivity (FC), but there are very few direct comparisons of these techniques using the same dataset. The goal of this study was to compare an envelope-based (i.e. Amplitude Envelope Correlation, AEC) and a phase-based (i.e. weighted Phase Lag Index, wPLI) measure of FC in their classification of states of consciousness. Nine healthy participants underwent a three-hour experimental anesthetic protocol with propofol induction and isoflurane maintenance, in which five minutes of 128-channel electroencephalography were …


Extracorporeal Photopheresis To Attenuate Decline In Lung Function Due To Refractory Obstructive Allograft Dysfunction, Epi Study Group, Chadi A Hage, Suresh Vedantham, Mary Clare Derfler, Paul Commean, Ed Spitznagel, Jeff Atkinson, George Despotis, Et Al. Aug 2021

Extracorporeal Photopheresis To Attenuate Decline In Lung Function Due To Refractory Obstructive Allograft Dysfunction, Epi Study Group, Chadi A Hage, Suresh Vedantham, Mary Clare Derfler, Paul Commean, Ed Spitznagel, Jeff Atkinson, George Despotis, Et Al.

2020-Current year OA Pubs

BACKGROUND: This study was designed to prospectively evaluate the efficacy of extracorporeal photopheresis (ECP) to attenuate the rate of decline of FEV

STUDY DESIGN AND METHODS: Subjects from 10 lung transplant centres were assigned to ECP treatment or to observation based on spirometric criteria, with potential crossover for those under observation. The primary endpoint of this study was to assess response to ECP (i.e., greater than a 50% decrease in the rate of FEV

RESULTS: Of 44 enrolled subjects, 31 were assigned to ECP treatment while 13 were initially assigned to observation on a non-random basis using specific spirometric inclusion …


Use Of Convalescent Plasma In Covid-19 Patients With Immunosuppression, Jonathon W Senefeld, Jeffrey P Henderson, Et Al. Aug 2021

Use Of Convalescent Plasma In Covid-19 Patients With Immunosuppression, Jonathon W Senefeld, Jeffrey P Henderson, Et Al.

2020-Current year OA Pubs

In the absence of effective countermeasures, human convalescent plasma has been widely used to treat severe acute respiratory syndrome coronavirus 2, the causative agent of novel coronavirus disease 19 (COVID-19), including among patients with innate or acquired immunosuppression. However, the association between COVID-19-associated mortality in patients with immunosuppression and therapeutic use of convalescent plasma is unknown. We review 75 reports, including one large matched-control registry study of 143 COVID-19 patients with hematological malignancies, and 51 case reports and 23 case series representing 238 COVID-19 patients with immunosuppression. We review clinical features and treatment protocols of COVID-19 patients with immunosuppression after …


Alliance Foundation Trial 09: A Randomized, Multicenter, Phase 2 Trial Evaluating Two Sequences Of Pembrolizumab And Standard Platinum-Based Chemotherapy In Patients With Metastatic Nsclc, Thomas A Hensing, Xiaofei Wang, Thomas E Stinchcombe, Junheng Gao, Michael V Knopp, Mark Watson, Arkadiusz Z Dudek, Stephen L Graziano, Jyoti D Patel, Bryan A Faller, Konstantin H Dragnev, David Kozono, Everett E Vokes Aug 2021

Alliance Foundation Trial 09: A Randomized, Multicenter, Phase 2 Trial Evaluating Two Sequences Of Pembrolizumab And Standard Platinum-Based Chemotherapy In Patients With Metastatic Nsclc, Thomas A Hensing, Xiaofei Wang, Thomas E Stinchcombe, Junheng Gao, Michael V Knopp, Mark Watson, Arkadiusz Z Dudek, Stephen L Graziano, Jyoti D Patel, Bryan A Faller, Konstantin H Dragnev, David Kozono, Everett E Vokes

2020-Current year OA Pubs

INTRODUCTION: The sequence of chemotherapy and pembrolizumab may affect antitumor immune response and efficacy of immunotherapy.

METHODS: This multicenter, randomized, phase 2 trial was designed to evaluate the efficacy of two sequences of chemotherapy and pembrolizumab in patients with stage 4 NSCLC. Both arms were considered investigational, and the study used a "pick a winner" design. The primary end point was objective response rate by independent radiologic review after eight cycles (24 wk). Patients were randomized 1:1 to arm A (chemotherapy for four cycles followed by pembrolizumab for four cycles) or arm B (pembrolizumab for four cycles followed by chemotherapy …


Tumor-On-Chip Modeling Of Organ-Specific Cancer And Metastasis, Nuala Del Piccolo, Venktesh S Shirure, Ye Bi, S Peter Goedegebuure, Sepideh Gholami, Christopher C W Hughes, Ryan C Fields, Steven C George Aug 2021

Tumor-On-Chip Modeling Of Organ-Specific Cancer And Metastasis, Nuala Del Piccolo, Venktesh S Shirure, Ye Bi, S Peter Goedegebuure, Sepideh Gholami, Christopher C W Hughes, Ryan C Fields, Steven C George

2020-Current year OA Pubs

Every year, cancer claims millions of lives around the globe. Unfortunately, model systems that accurately mimic human oncology - a requirement for the development of more effective therapies for these patients - remain elusive. Tumor development is an organ-specific process that involves modification of existing tissue features, recruitment of other cell types, and eventual metastasis to distant organs. Recently, tissue engineered microfluidic devices have emerged as a powerful in vitro tool to model human physiology and pathology with organ-specificity. These organ-on-chip platforms consist of cells cultured in 3D hydrogels and offer precise control over geometry, biological components, and physiochemical properties. …


Comparative Effectiveness Of Sodium-Glucose Cotransporter 2 Inhibitors Vs Sulfonylureas In Patients With Type 2 Diabetes, Yan Xie, Benjamin Bowe, Andrew K Gibson, Janet B Mcgill, Geetha Maddukuri, Ziyad Al-Aly Aug 2021

Comparative Effectiveness Of Sodium-Glucose Cotransporter 2 Inhibitors Vs Sulfonylureas In Patients With Type 2 Diabetes, Yan Xie, Benjamin Bowe, Andrew K Gibson, Janet B Mcgill, Geetha Maddukuri, Ziyad Al-Aly

2020-Current year OA Pubs

IMPORTANCE: In the treatment of type 2 diabetes, evidence of the comparative effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors vs sulfonylureas-the second most widely used antihyperglycemic class after metformin-is lacking.

OBJECTIVE: To evaluate the comparative effectiveness of SGLT2 inhibitors and sulfonylureas associated with the risk of all-cause mortality among patients with type 2 diabetes using metformin.

DESIGN, SETTING, AND PARTICIPANTS: A cohort study used data from the US Department of Veterans Affairs compared the use of SGLT2 inhibitors vs sulfonylureas in individuals receiving metformin for treatment of type 2 diabetes. A total of 23 870 individuals with new use of …


Effects Of A Dvd-Delivered Randomized Controlled Physical Activity Intervention On Functional Health In Cancer Survivors, Elizabeth A Salerno, Neha P Gothe, Jason Fanning, Lindsay L Peterson, Graham A Colditz, Edward Mcauley Jul 2021

Effects Of A Dvd-Delivered Randomized Controlled Physical Activity Intervention On Functional Health In Cancer Survivors, Elizabeth A Salerno, Neha P Gothe, Jason Fanning, Lindsay L Peterson, Graham A Colditz, Edward Mcauley

2020-Current year OA Pubs

BACKGROUND: Supervised physical activity interventions improve functional health during cancer survivorship, but remain costly and inaccessible for many. We previously reported on the benefits of a DVD-delivered physical activity program (FlexToBa™) in older adults. This is a secondary analysis of the intervention effects among cancer survivors in the original sample.

METHODS: Low active, older adults who self-reported a history of cancer (N = 46; M time since diagnosis = 10.7 ± 9.4 years) participated in a 6-month, home-based physical activity intervention. Participants were randomized to either the DVD-delivered physical activity program focused on flexibility, toning, and balance (FlexToBa™; n = …


Altered Neuronal Physiology, Development, And Function Associated With A Common Chromosome 15 Duplication Involving Chrna7, Kesavan Meganathan, Ramachandran Prakasam, Dustin Baldridge, Paul Gontarz, Bo Zhang, Fumihiko Urano, Azad Bonni, Susan E Maloney, Tychele N Turner, James E Huettner, John N Constantino, Kristen L Kroll Jul 2021

Altered Neuronal Physiology, Development, And Function Associated With A Common Chromosome 15 Duplication Involving Chrna7, Kesavan Meganathan, Ramachandran Prakasam, Dustin Baldridge, Paul Gontarz, Bo Zhang, Fumihiko Urano, Azad Bonni, Susan E Maloney, Tychele N Turner, James E Huettner, John N Constantino, Kristen L Kroll

2020-Current year OA Pubs

BACKGROUND: Copy number variants (CNVs) linked to genes involved in nervous system development or function are often associated with neuropsychiatric disease. While CNVs involving deletions generally cause severe and highly penetrant patient phenotypes, CNVs leading to duplications tend instead to exhibit widely variable and less penetrant phenotypic expressivity among affected individuals. CNVs located on chromosome 15q13.3 affecting the alpha-7 nicotinic acetylcholine receptor subunit (CHRNA7) gene contribute to multiple neuropsychiatric disorders with highly variable penetrance. However, the basis of such differential penetrance remains uncharacterized. Here, we generated induced pluripotent stem cell (iPSC) models from first-degree relatives with a 15q13.3 duplication and …


The Informed Road Map To Prevention Of Alzheimer Disease: A Call To Arms, Eric Mcdade, Jorge J Llibre-Guerra, David M Holtzman, John C Morris, Randall J Bateman Jul 2021

The Informed Road Map To Prevention Of Alzheimer Disease: A Call To Arms, Eric Mcdade, Jorge J Llibre-Guerra, David M Holtzman, John C Morris, Randall J Bateman

2020-Current year OA Pubs

Alzheimer disease (AD) prevention trials hold the promise to delay or prevent cognitive decline and dementia onset by intervening before significant neuronal damage occurs. In recent years, the first AD prevention trials have launched and are yielding important findings on the biology of targeting asymptomatic AD pathology. However, there are limitations that impact the design of these prevention trials, including the translation of animal models that recapitulate key stages and multiple pathological aspects of the human disease, missing target validation in asymptomatic disease, uncertain causality of the association of pathophysiologic changes with cognitive and clinical symptoms, and limited biomarker validation …


A Single Intranasal Or Intramuscular Immunization With Chimpanzee Adenovirus-Vectored Sars-Cov-2 Vaccine Protects Against Pneumonia In Hamsters, Traci L. Bricker, Tamarand L. Darling, Ahmed O. Hassan, Houda H. Harastani, Allison Soung, Xiaoping Jiang, Ya-Nan Dai, Haiyan Zhao, Lucas J. Adams, Michael J. Holtzman, Adam L. Bailey, James Brett Case, Daved H. Fremont, Robyn Klein, Michael S. Diamond, Adrianus C. M. Boon Jul 2021

A Single Intranasal Or Intramuscular Immunization With Chimpanzee Adenovirus-Vectored Sars-Cov-2 Vaccine Protects Against Pneumonia In Hamsters, Traci L. Bricker, Tamarand L. Darling, Ahmed O. Hassan, Houda H. Harastani, Allison Soung, Xiaoping Jiang, Ya-Nan Dai, Haiyan Zhao, Lucas J. Adams, Michael J. Holtzman, Adam L. Bailey, James Brett Case, Daved H. Fremont, Robyn Klein, Michael S. Diamond, Adrianus C. M. Boon

2020-Current year OA Pubs

The development of an effective vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), is a global priority. Here, we compare the protective capacity of intranasal and intramuscular delivery of a chimpanzee adenovirus-vectored vaccine encoding a prefusion stabilized spike protein (chimpanzee adenovirus [ChAd]-SARS-CoV-2-S) in Golden Syrian hamsters. Although immunization with ChAd-SARS-CoV-2-S induces robust spike-protein-specific antibodies capable of neutralizing the virus, antibody levels in serum are higher in hamsters vaccinated by an intranasal compared to intramuscular route. Accordingly, against challenge with SARS-CoV-2, ChAd-SARS-CoV-2-S-immunized hamsters are protected against less weight loss and have reduced …


Coding And Noncoding Variants In Ebf3 Are Involved In Hadds And Simplex Autism, Evin M Padhi, Jeffrey K Ng, Elvisa Mehinovic, Tychele N Turner, Et Al. Jul 2021

Coding And Noncoding Variants In Ebf3 Are Involved In Hadds And Simplex Autism, Evin M Padhi, Jeffrey K Ng, Elvisa Mehinovic, Tychele N Turner, Et Al.

2020-Current year OA Pubs

BACKGROUND: Previous research in autism and other neurodevelopmental disorders (NDDs) has indicated an important contribution of protein-coding (coding) de novo variants (DNVs) within specific genes. The role of de novo noncoding variation has been observable as a general increase in genetic burden but has yet to be resolved to individual functional elements. In this study, we assessed whole-genome sequencing data in 2671 families with autism (discovery cohort of 516 families, replication cohort of 2155 families). We focused on DNVs in enhancers with characterized in vivo activity in the brain and identified an excess of DNVs in an enhancer named hs737. …


Quality-Adjusted Time Without Symptoms Of Disease Or Toxicity (Q-Twist) Analysis Of Cpx-351 Versus 7 + 3 In Older Adults With Newly Diagnosed High-Risk/Secondary Aml, Jorge E Cortes, Tara L Lin, Geoffrey L Uy, Robert J Ryan, Stefan Faderl, Jeffrey E Lancet Jul 2021

Quality-Adjusted Time Without Symptoms Of Disease Or Toxicity (Q-Twist) Analysis Of Cpx-351 Versus 7 + 3 In Older Adults With Newly Diagnosed High-Risk/Secondary Aml, Jorge E Cortes, Tara L Lin, Geoffrey L Uy, Robert J Ryan, Stefan Faderl, Jeffrey E Lancet

2020-Current year OA Pubs

BACKGROUND: CPX-351 (United States: Vyxeos

METHODS: Patients were randomized 1:1 between December 20, 2012 and November 11, 2014 to receive induction with CPX-351 or 7 + 3. Survival time for each patient was partitioned into 3 health states: TOX (time with any grade 3 or 4 toxicity or prior to remission), TWiST (time in remission without relapse or grade 3 or 4 toxicity), and REL (time after relapse). Within each treatment arm, Q-TWiST was calculated by adding the mean time spent in each health state weighted by its respective quality-of-life, represented by health utility. The relative Q-TWiST gain, calculated as …


The New (Version 9) American Joint Committee On Cancer Tumor, Node, Metastasis Staging For Cervical Cancer, Alexander B Olawaiye, Thomas P Baker, M Kay Washington, David G Mutch Jul 2021

The New (Version 9) American Joint Committee On Cancer Tumor, Node, Metastasis Staging For Cervical Cancer, Alexander B Olawaiye, Thomas P Baker, M Kay Washington, David G Mutch

2020-Current year OA Pubs

The American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging for all cancer sites has been periodically updated as a published manual for many years. The last update, the eighth edition AJCC Cancer Staging Manual went into use on January 1, 2018. The AJCC has since restructured and updated its processes, and all AJCC staging-related data are now housed on its new application programming interface. Consequently, the next AJCC TNM staging update, AJCC version 9 TNM staging, will be published electronically and will be released chapter by chapter. The first chapter of version 9 AJCC TNM staging is …


Sonothermogenetics For Noninvasive And Cell-Type Specific Deep Brain Neuromodulation, Yaoheng Yang, Christopher Pham Pacia, Dezhuang Ye, Lifei Zhu, Hongchae Baek, Yimei Yue, Jinyun Yuan, Mark J Miller, Jianmin Cui, Joseph P Culver, Michael R Bruchas, Hong Chen Jul 2021

Sonothermogenetics For Noninvasive And Cell-Type Specific Deep Brain Neuromodulation, Yaoheng Yang, Christopher Pham Pacia, Dezhuang Ye, Lifei Zhu, Hongchae Baek, Yimei Yue, Jinyun Yuan, Mark J Miller, Jianmin Cui, Joseph P Culver, Michael R Bruchas, Hong Chen

2020-Current year OA Pubs

BACKGROUND: Critical advances in the investigation of brain functions and treatment of brain disorders are hindered by our inability to selectively target neurons in a noninvasive manner in the deep brain.

OBJECTIVE: This study aimed to develop sonothermogenetics for noninvasive, deep-penetrating, and cell-type-specific neuromodulation by combining a thermosensitive ion channel TRPV1 with focused ultrasound (FUS)-induced brief, non-noxious thermal effect.

METHODS: The sensitivity of TRPV1 to FUS sonication was evaluated in vitro. It was followed by in vivo assessment of sonothermogenetics in the activation of genetically defined neurons in the mouse brain by two-photon calcium imaging. Behavioral response evoked by sonothermogenetic …


Riociguat: Clinical Research And Evolving Role In Therapy, James R Klinger, Murali M Chakinala, David Langleben, Stephan Rosenkranz, Olivier Sitbon Jul 2021

Riociguat: Clinical Research And Evolving Role In Therapy, James R Klinger, Murali M Chakinala, David Langleben, Stephan Rosenkranz, Olivier Sitbon

2020-Current year OA Pubs

Riociguat is a first-in-class soluble guanylate cyclase stimulator, approved for the treatment of adults with pulmonary arterial hypertension (PAH), inoperable chronic thromboembolic pulmonary hypertension (CTEPH), or persistent or recurrent CTEPH after pulmonary endarterectomy. Approval was based on the results of the phase III PATENT-1 (PAH) and CHEST-1 (CTEPH) studies, with significant improvements in the primary endpoint of 6-minute walk distance vs placebo of +36 m and +46 m, respectively, as well as improvements in secondary endpoints such as pulmonary vascular resistance and World Health Organization functional class. Riociguat acts as a stimulator of cyclic guanosine monophosphate synthesis rather than as …


Oral Once-Daily Berotralstat For The Prevention Of Hereditary Angioedema Attacks: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial, Bruce Zuraw, H James Wedner, Et Al. Jul 2021

Oral Once-Daily Berotralstat For The Prevention Of Hereditary Angioedema Attacks: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial, Bruce Zuraw, H James Wedner, Et Al.

2020-Current year OA Pubs

BACKGROUND: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks.

OBJECTIVE: Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial).

METHODS: APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 …


Cystic Fibrosis Foundation Consensus Statements For The Care Of Cystic Fibrosis Lung Transplant Recipients, Pali Shah, Marina Litvin, Ramsey R Hachem, Et Al. Jul 2021

Cystic Fibrosis Foundation Consensus Statements For The Care Of Cystic Fibrosis Lung Transplant Recipients, Pali Shah, Marina Litvin, Ramsey R Hachem, Et Al.

2020-Current year OA Pubs

Cystic fibrosis (CF) is the indication for transplantation in approximately 15% of recipients worldwide, and Cystic Fibrosis Lung Transplant Recipients (CFLTRs) have excellent long-term outcomes. Yet, CFLTRs have unique comorbidities that require specialized care. The objective of this document is to provide recommendations to CF and lung transplant clinicians for the management of perioperative and underlying comorbidities of CFLTRs and the impact of transplantation on these comorbidities. The Cystic Fibrosis Foundation (CFF) organized a multidisciplinary committee to develop CF Lung Transplant Clinical Care Recommendations. Three workgroups were formed to develop focused questions. Following a literature search, consensus recommendations were developed …


Epigenetic Regulation During Human Cortical Development: Seq-Ing Answers From The Brain To The Organoid, Emily M A Lewis, Komal Kaushik, Luke A Sandoval, Irene Antony, Sabine Dietmann, Kristen L Kroll Jul 2021

Epigenetic Regulation During Human Cortical Development: Seq-Ing Answers From The Brain To The Organoid, Emily M A Lewis, Komal Kaushik, Luke A Sandoval, Irene Antony, Sabine Dietmann, Kristen L Kroll

2020-Current year OA Pubs

Epigenetic regulation plays an important role in controlling gene expression during complex processes, such as development of the human brain. Mutations in genes encoding chromatin modifying proteins and in the non-protein coding sequences of the genome can potentially alter transcription factor binding or chromatin accessibility. Such mutations can frequently cause neurodevelopmental disorders, therefore understanding how epigenetic regulation shapes brain development is of particular interest. While epigenetic regulation of neural development has been extensively studied in murine models, significant species-specific differences in both the genome sequence and in brain development necessitate human models. However, access to human fetal material is limited …


Bintrafusp Alfa, A Bifunctional Fusion Protein Targeting Tgf-Β And Pd-L1, In Patients With Esophageal Adenocarcinoma: Results From A Phase 1 Cohort, Benjamin Tan, Adnan Khattak, Enriqueta Felip, Karen Kelly, Patricia Rich, Ding Wang, Christoph Helwig, Isabelle Dussault, Laureen S Ojalvo, Nicolas Isambert Jul 2021

Bintrafusp Alfa, A Bifunctional Fusion Protein Targeting Tgf-Β And Pd-L1, In Patients With Esophageal Adenocarcinoma: Results From A Phase 1 Cohort, Benjamin Tan, Adnan Khattak, Enriqueta Felip, Karen Kelly, Patricia Rich, Ding Wang, Christoph Helwig, Isabelle Dussault, Laureen S Ojalvo, Nicolas Isambert

2020-Current year OA Pubs

BACKGROUND: Esophageal adenocarcinoma patients have limited treatment options. TGF-β can be upregulated in esophageal adenocarcinoma, and blocking this pathway may enhance clinical response to PD-(L)1 inhibitors. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β "trap") fused to a human IgG1 mAb blocking PD-L1.

OBJECTIVE: The objective of this study was to investigate the efficacy and safety of bintrafusp alfa in patients with advanced, post-platinum esophageal adenocarcinoma, unselected for PD-L1 expression.

PATIENTS AND METHODS: In this phase 1 study, patients with post-platinum, PD-L1-unselected esophageal adenocarcinoma received bintrafusp alfa 1200 mg …


Active Surveillance Of Metastatic Renal Cell Carcinoma: Results From A Prospective Observational Study (Marcc), Michael R Harrison, Russell K Pachynski, Et Al. Jul 2021

Active Surveillance Of Metastatic Renal Cell Carcinoma: Results From A Prospective Observational Study (Marcc), Michael R Harrison, Russell K Pachynski, Et Al.

2020-Current year OA Pubs

BACKGROUND: Systemic therapy (ST) can be deferred in patients who have metastatic renal cell carcinoma (mRCC) and slow-growing metastases. Currently, this subset of patients managed with active surveillance (AS) is not well described in the literature.

METHODS: This was a prospective observational study of patients with mRCC across 46 US community and academic centers. The objective was to describe baseline characteristics and demographics of patients with mRCC initially managed by AS, reasons for AS, and patient outcomes. Descriptive statistics were used to characterize demographics, baseline characteristics, and patient-related outcomes. Wilcoxon 2-sample rank-sum tests and χ

RESULTS: Of 504 patients, mRCC …


A Systematic Review Of School Health Policy Measurement Tools: Implementation Determinants And Outcomes, Gabriella M Mcloughlin, Peg Allen, Callie Walsh-Bailey, Ross C Brownson Jun 2021

A Systematic Review Of School Health Policy Measurement Tools: Implementation Determinants And Outcomes, Gabriella M Mcloughlin, Peg Allen, Callie Walsh-Bailey, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Governments in some countries or states/provinces mandate school-based policies intended to improve the health and well-being of primary and secondary students and in some cases the health of school staff. Examples include mandating a minimum time spent per week in programmed physical activity, mandating provision of healthy foods and limiting fat content of school meals, and banning tobacco products or use on school campuses. Although school health researchers have studied whether schools, districts, or states/provinces are meeting requirements, it is unclear to what extent implementation processes and determinants are assessed. The purposes of the present systematic review of quantitative …


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 …


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 …


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 …


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 …


Implementation And Sustainability Factors Of Two Early-Stage Breast Cancer Conversation Aids In Diverse Practices, Danielle Schubbe, Mary C Politi, Julie Margenthaler, Courtney Goodwin, Et Al May 2021

Implementation And Sustainability Factors Of Two Early-Stage Breast Cancer Conversation Aids In Diverse Practices, Danielle Schubbe, Mary C Politi, Julie Margenthaler, Courtney Goodwin, Et Al

2020-Current year OA Pubs

BACKGROUND: Conversation aids can facilitate shared decision-making and improve patient-centered outcomes. However, few examples exist of sustained use of conversation aids in routine care due to numerous barriers at clinical and organizational levels. We explored factors that will promote the sustained use of two early-stage breast cancer conversation aids. We examined differences in opinions between the two conversation aids and across socioeconomic strata.

METHODS: We nested this study within a randomized controlled trial that demonstrated the effectiveness of two early-stage breast cancer surgery conversation aids, one text-based and one picture-based. These conversation aids facilitated more shared decision-making and improved the …


Endoscopic Retrieval Of A Proximally Migrated Biliary Stent Using Extracorporeal Shockwave Lithotripsy, Electrohydraulic Lithotripsy, And Cholangioscopy With Minisnare, Michael J Weaver, Vladimir M Kushnir May 2021

Endoscopic Retrieval Of A Proximally Migrated Biliary Stent Using Extracorporeal Shockwave Lithotripsy, Electrohydraulic Lithotripsy, And Cholangioscopy With Minisnare, Michael J Weaver, Vladimir M Kushnir

2020-Current year OA Pubs

Video 1ERCP was notable for a proximally migrated biliary stent. Cholangiogram demonstrated multiple filling defects consistent with choledocholithiasis surrounding the proximally migrated biliary stent. Retrieval of the stent was successful using cholangioscopy-directed electrohydraulic lithotripsy, extracorporeal shockwave lithotripsy, mechanical lithotripsy, and minisnare over the course of 2 ERCPs. Complete duct clearance of stones was accomplished with balloon sweeps.