Medicine and Health Sciences Commons^™

Quantitative Single-Cell Analysis Of Leishmania Major Amastigote Differentiation Demonstrates Variably Extended Expression Of The Lipophosphoglycan (Lpg) Virulence Factor In Different Host Cell Types, Michael A. Mandell, Wandy L. Beatty, Stephen M. Beverley

2020-Current year OA Pubs

Immediately following their deposition into the mammalian host by an infected sand fly vector, Leishmania parasites encounter and are engulfed by a variety of cell types. From there, parasites may transit to other cell types, primarily macrophages or dendritic cells, where they replicate and induce pathology. During this time, Leishmania cells undergo a dramatic transformation from the motile non-replicating metacyclic stage to the non-motile replicative amastigote stage, a differentiative process that can be termed amastigogenesis. To follow this at the single cell level, we identified a suite of experimental 'landmarks' delineating different stages of amastigogenesis qualitatively or quantitatively, including new …

The Inner Nuclear Membrane Protein Nemp1 Supports Nuclear Envelope Openings And Enucleation Of Erythroblasts, Didier Hodzic, Jun Wu, Karen Krchma, Andrea Jurisicova, Yonit Tsatskis, Yijie Liu, Peng Ji, Kyunghee Choi, Helen Mcneill

2020-Current year OA Pubs

Nuclear envelope membrane proteins (NEMPs) are a conserved family of nuclear envelope (NE) proteins that reside within the inner nuclear membrane (INM). Even though Nemp1 knockout (KO) mice are overtly normal, they display a pronounced splenomegaly. This phenotype and recent reports describing a requirement for NE openings during erythroblasts terminal maturation led us to examine a potential role for Nemp1 in erythropoiesis. Here, we report that Nemp1 KO mice show peripheral blood defects, anemia in neonates, ineffective erythropoiesis, splenomegaly, and stress erythropoiesis. The erythroid lineage of Nemp1 KO mice is overrepresented until the pronounced apoptosis of polychromatophilic erythroblasts. We show …

Choline, Dha, And Diarrheal Disease Associated With Growth Faltering In A Case-Control Study, Jenna N Diaz, Sherlie Jean Louis Dulience, Noah Wolthausen, Xuntian Jiang, Emmanuel Gyimah, Francesca J Marhône Pierre, F Matthew Kuhlmann, Lora L Iannotti

2020-Current year OA Pubs

BACKGROUND: Children with recurrent infectious diarrhea are susceptible to growth faltering. DHA and choline may play a role in this relationship due to their involvement in lipid metabolism, gut immunity, and inflammatory pathways.

OBJECTIVES: This study aimed to characterize the contributions made by DHA and choline status and enteric damage in young children in the association between diarrheal illness and child growth.

METHODS: A longitudinal case-control study was conducted among children aged 6-36 mo (

RESULTS: At baseline, mean plasma DHA concentrations (1.03 µg/mL; 95% CI: 0.91, 1.15) were not significantly different between cases and controls, nor was there a …

Impact Of Updated Clinical Practice Guidelines On Outpatient Treatment For Clostridioides Difficile Infection And Associated Clinical Outcomes, Erik R Dubberke, Justin T Puckett, Engels N Obi, Sachin Kamal-Bahl, Kaushal Desai, Bruce Stuart, Jalpa A Doshi

2020-Current year OA Pubs

BACKGROUND: The 2017 Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA)

METHODS: A pre-post study design was employed using Medicare data. CDI treatment utilization and clinical outcomes (4- and 8-week sustained response, CDI recurrence) were compared between patients indexed from April-September 2017 (preguideline period) and those indexed from April-September 2018 (postguideline period). Clinical outcomes associated with fidaxomicin versus vancomycin were compared using propensity score-matched analyses.

RESULTS: From the pre- to postguideline period, metronidazole use decreased (initial CDI: 81.2% to 53.5%; recurrent CDI: 49.7% to 27.6%) while vancomycin (initial CDI: 17.9% to 44.9%; recurrent CDI: 48.1% to 66.4%) …

Health-Related Quality Of Life In Older Patients With Heart Failure From Before To Early After Advanced Surgical Therapies: Findings From The Sustain-It Study, Kathleen L. Grady, Justin Hartupee, Et Al.

2020-Current year OA Pubs

BACKGROUND: Restoring health-related quality of life (HRQOL) is a therapeutic goal for older patients with advanced heart failure. We aimed to describe change in HRQOL in older patients (60-80 years) awaiting heart transplantation (HT) with or without pretransplant mechanical circulatory support (MCS) or scheduled for long-term MCS, if ineligible for HT, from before to 6 months after these surgeries and identify factors associated with change.

METHODS: Patients from 13 US sites completed the EuroQol 5-dimension 3L questionnaire and Kansas City Cardiomyopathy Questionnaire-12 at baseline and 3 and 6 months after HT or long-term MCS. Analyses included univariate comparisons and multivariable …

Peristaltic Pumps Adapted For Laminar Flow Experiments Enhance In Vitro Modeling Of Vascular Cell Behavior, Javier Abello, Shreya Raghavan, Yvette Y. Yien, Amber N. Stratman

2020-Current year OA Pubs

Endothelial cells (ECs) are the primary cellular constituent of blood vessels that are in direct contact with hemodynamic forces over their lifetime. Throughout the body, vessels experience different blood flow patterns and rates that alter vascular architecture and cellular behavior. Because of the complexities of studying blood flow in an intact organism, particularly during development, the field has increasingly relied on in vitro modeling of blood flow as a powerful technique for studying hemodynamic-dependent signaling mechanisms in ECs. While commercial flow systems that recirculate fluids exist, many commercially available pumps are peristaltic and best model pulsatile flow conditions. However, there …

Gynecologic Oncology Patient Perspectives And Knowledge On Advance Care Planning: A Quality Improvement Intervention, Sarah P. Huepenbecker, Sophia Lewis, Mark C. Valentine, Marguerite L. Palisoul, Premal H. Thaker, Andrea R. Hagemann, Carolyn K. Mccourt, Katherine C. Fuh, Matthew A. Powell, David G. Mutch, Lindsay M. Kuroki

2020-Current year OA Pubs

OBJECTIVES: Assess and improve advance care planning (ACP) awareness and uptake among gynecologic oncology patients.

METHODS: Using a quality improvement Plan-Do-Check-Act framework, we completed a single institution needs assessment and intervention. The needs assessment was a 26-question survey assessing baseline ACP knowledge and preferences of gynecologic oncology patients. We used this survey to implement an outpatient intervention in which patients were offered ACP resources (pamphlet, discussion with their gynecologic oncologist, and/or social work referral). We conducted a post-intervention survey among patients who had and had not received ACP resource(s) to assess whether our intervention increased ACP knowledge, discussions, or uptake. …

Neuroinflammation And Covid-19, Abigail Vanderheiden, Robyn S. Klein

2020-Current year OA Pubs

Coronavirus disease 2019 (COVID-19) has caused a historic pandemic of respiratory disease. COVID-19 also causes acute and post-acute neurological symptoms, which range from mild, such as headaches, to severe, including hemorrhages. Current evidence suggests that there is no widespread infection of the central nervous system (CNS) by SARS-CoV-2, thus what is causing COVID-19 neurological disease? Here, we review potential immunological mechanisms driving neurological disease in COVID-19 patients. We begin by discussing the implications of imbalanced peripheral immunity on CNS function. Next, we examine the evidence for dysregulation of the blood-brain barrier during SARS-CoV-2 infection. Last, we discuss the role myeloid …

Stress Radiography Is A Reliable Method To Quantify Posterior Cruciate Ligament Insufficiency: A Systematic Review, J. Jared Guth, Robert H. Brophy, Matthew J. Matava, R. Garrett Steinmetz, Matthew V. Smith

2020-Current year OA Pubs

PURPOSE: To perform a systematic review of posterior tibial stress radiography techniques and radiographic measurement methods to compare their accuracy and efficacy to aid clinicians in quantifying posterior cruciate ligament laxity.

METHODS: Electronic databases, including PubMed, MEDLINE, Embase.com 1947- , Ovid Medline 1946- , Scopus 1823- , Cochrane Central Register of Controlled Trials (CENTRAL), and Clinicaltrials.gov 1997- were queried in December 2020. The abstracts of articles were reviewed by 2 authors for published studies comparing posterior tibial stress radiography techniques, describing, and comparing radiographic measurement methods, and comparing stress radiographs with instrumented knee testing.

RESULTS: The systematic review included 13 …

Margetuximab With Retifanlimab As First-Line Therapy In Her2+/Pd-L1+ Unresectable Or Metastatic Gastroesophageal Adenocarcinoma: Mahogany Cohort A, D. V. T. Catenacci, H. Park, Et Al.

2020-Current year OA Pubs

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric and gastroesophageal adenocarcinoma (GEA) is globally treated with chemotherapy plus trastuzumab. Novel therapeutic strategies strive to not only optimize efficacy, but also limit toxicities. In MAHOGANY cohort A, margetuximab, an Fc-engineered, anti-HER2 monoclonal antibody (mAb) was combined with retifanlimab, an anti-programmed cell death protein 1 mAb, in the first-line HER2-positive/programmed death-ligand 1 (PD-L1)-positive GEA.

PATIENTS AND METHODS: MAHOGANY cohort A part 1 is a single-arm trial to evaluate margetuximab plus retifanlimab in patients with HER2 immunohistochemistry 3+, PD-L1-positive (combined positive score ≥1%), and non-microsatellite instability-high tumors. Primary objectives for cohort …

Telomere Biology Disorders: Time For Moving Towards The Clinic?, Luis F Z Batista, Inderjeet Dokal, Roy Parker

2020-Current year OA Pubs

Telomere biology disorders (TBDs) are a group of rare diseases caused by mutations that impair telomere maintenance. Mutations that cause reduced levels of TERC/hTR, the telomerase RNA component, are found in most TBD patients and include loss-of-function mutations in hTR itself, in hTR-binding proteins [NOP10, NHP2, NAF1, ZCCHC8, and dyskerin (DKC1)], and in proteins required for hTR processing (PARN). These patients show diverse clinical presentations that most commonly include bone marrow failure (BMF)/aplastic anemia (AA), pulmonary fibrosis, and liver cirrhosis. There are no curative therapies for TBD patients. An understanding of hTR biogenesis, maturation, and degradation has identified pathways and …

Treatment Of Stage I Lung Cancer Detected By Computed Tomography Screening, David S. Gierada, Yun Zhu Bai, Matthew B. Spraker, Anne Stilinovic, Ruben G. Nava

2020-Current year OA Pubs

INTRODUCTION: Reducing lung cancer deaths through early detection by computed tomography (CT) screening requires delivery of effective treatment. We performed this retrospective study to determine the types of treatment used for screen-detected stage I lung cancer at our academic center and to compare the demographic and clinical characteristics of patients by type of treatment.

METHODS: All persons screened in the lung cancer screening program at our institution through June 16, 2021, were included. Those with screening CT findings needing follow-up were managed through a thoracic surgery clinic. Demographic and clinical characteristics of patients diagnosed with having stage I lung cancer …

Evaluating Brain Damage In Multiple Sclerosis With Simultaneous Multi-Angular-Relaxometry Of Tissue, Biao Xiang, Jie Wen, Robert E Schmidt, Alexander L Sukstanskii, Daniel Mamah, Dmitriy A Yablonskiy, Anne H Cross

2020-Current year OA Pubs

OBJECTIVE: Multiple sclerosis (MS) is a common demyelinating central nervous system disease. MRI methods that can quantify myelin loss are needed for trials of putative remyelinating agents. Quantitative magnetization transfer MRI introduced the macromolecule proton fraction (MPF), which correlates with myelin concentration. We developed an alternative approach, Simultaneous-Multi-Angular-Relaxometry-of-Tissue (SMART) MRI, to generate MPF. Our objective was to test SMART-derived MPF metric as a potential imaging biomarker of demyelination.

METHODS: Twenty healthy control (HC), 11 relapsing-remitting MS (RRMS), 22 progressive MS (PMS), and one subject with a biopsied tumefactive demyelinating lesion were scanned at 3T using SMART MRI. SMART-derived MPF metric …

Multi-Modulated Frequency Domain High Density Diffuse Optical Tomography, Guy A. Perkins, Adam T. Eggebrecht, Hamid Dehghani

2020-Current year OA Pubs

No abstract provided.

Calciphylaxis Arising Following Bariatric Surgery: A Case Series, Bethany Cucka, Bianca Biglione, Lauren Ko, Emily D Nguyen, Charbel C Khoury, Sagar U Nigwekar, Malcolm K Robinson, Daniela Kroshinsky

2020-Current year OA Pubs

No abstract provided.

Semiautomated Analysis Of An Optical Atp Indicator In Neurons, Taher Dehkharghanian, Arsalan Hashemiaghdam, Ghazaleh Ashrafi

2020-Current year OA Pubs

No abstract provided.

Early Preclinical Experience Of A Mixed Reality Ultrasound System With Active Guidance For Needle-Based Interventions: The Guide Study, David Bloom, Jamie N Colombo, Nathan Miller, Michael K Southworth, Christopher Andrews, Alexander Henry, William B Orr, Jonathan R Silva, Jennifer N Avari Silva

2020-Current year OA Pubs

BACKGROUND: Use of ultrasound (US) to facilitate vascular access has increased compared to landmark-based procedures despite ergonomic challenges and need for extrapolation of 2-dimensional images to understand needle position. The MantUS™ system (Sentiar, Inc.,) uses a mixed reality (MxR) interface to display US images and integrate real-time needle tracking.

OBJECTIVE: The purpose of this prospective preclinical study was to evaluate the feasibility and usability of MantUS in a simulated environment.

METHODS: Participants were recruited from pediatric cardiology and critical care. Access was obtained in 2 vascular access training models: a femoral access model and a head and neck model for …

A Saturated Map Of Common Genetic Variants Associated With Human Height, Loïc Yengo, E Warwick Daw, Lihua Wang, Mary F. Feitosa, Michael A. Province, Dabeeru C. Rao, Adam E. Locke, Et Al.

2020-Current year OA Pubs

No abstract provided.

Sweat Icu-An Observational Study Of Physician Workload And The Association Of Physician Outcomes In Academic Icus, Ankita Agarwal, Patrick G. Lyons, Et Al.

2020-Current year OA Pubs

UNLABELLED: The optimal staffing model for physicians in the ICU is unknown. Patient-to-intensivist ratios may offer a simple measure of workload and be associated with patient mortality and physician burnout. To evaluate the association of physician workload, as measured by the patient-to-intensivist ratio, with physician burnout and patient mortality.

DESIGN: Cross-sectional observational study.

SETTING: Fourteen academic centers in the United States from August 2020 to July 2021.

SUBJECTS: We enrolled ICU physicians and collected data on adult ICU patients under the physician's care on the single physician-selected study day for each physician.

MEASUREMENTS AND MAIN RESULTS: The primary exposure was …

Response To Brentuximab Vedotin By Cd30 Expression In Non-Hodgkin Lymphoma, Deepa Jagadeesh, Steve Horwitz, Nancy L Bartlett, Youn Kim, Eric Jacobsen, Madeleine Duvic, Meredith Little, William Trepicchio, Keenan Fenton, Matthew Onsum, Julie Lisano, Ranjana Advani

2020-Current year OA Pubs

BACKGROUND: The safety and efficacy of brentuximab vedotin (BV), an antibody-drug conjugate directed to the CD30 antigen, has been assessed in several trials in patients with peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), or B-cell non-Hodgkin lymphoma (NHL). The objective of this research was to examine the relationship between CD30 expression level and clinical response to BV.

PATIENTS AND METHODS: We analyzed response in patients treated with BV monotherapy in 5 prospective clinical studies in relapsed or refractory PTCL, CTCL, or B-cell NHL. CD30 expression was assessed by immunohistochemistry (IHC) using the Ber H2 antibody for 275 patients.

RESULTS: …

High Polygenic Risk Scores Are Associated With Early Age Of Onset Of Alcohol Use Disorder In Adolescents And Young Adults At Risk, John I Nurnberger Jr, Kathleen Bucholz, Laura Bierut, Vivia Mccutcheon, Andrey P Anokhin, Et Al.

2020-Current year OA Pubs

BACKGROUND: Genome-wide association studies have been conducted in alcohol use disorder (AUD), and they permit the use of polygenic risk scores (PRSs), in combination with clinical variables, to predict the onset of AUD in vulnerable populations.

METHODS: A total of 2794 adolescent/young adult subjects from the Collaborative Study on the Genetics of Alcoholism were followed, with clinical assessments every 2 years. Subjects were genotyped using a genome-wide chip. Separate PRS analyses were performed for subjects of European ancestry and African ancestry. Age of onset of DSM-5 AUD was evaluated using the Cox proportional hazard model. Predictive power was assessed using …

Variability In Energy Expenditure Is Much Greater In Males Than Females, Lewis G Halsey, Susan B Racette, Et Al.

2020-Current year OA Pubs

In mammals, trait variation is often reported to be greater among males than females. However, to date, mainly only morphological traits have been studied. Energy expenditure represents the metabolic costs of multiple physical, physiological, and behavioral traits. Energy expenditure could exhibit particularly high greater male variation through a cumulative effect if those traits mostly exhibit greater male variation, or a lack of greater male variation if many of them do not. Sex differences in energy expenditure variation have been little explored. We analyzed a large database on energy expenditure in adult humans (1494 males and 3108 females) to investigate whether …

Comprehensive Characterization Of The Multiple Myeloma Immune Microenvironment Using Integrated Scrna-Seq, Cytof, And Cite-Seq Analysis, Lijun Yao, Reyka G Jayasinghe, Mark A Fiala, Michael C Wendl, Stephen T Oh, John F Dipersio, Ravi Vij, Li Ding

2020-Current year OA Pubs

UNLABELLED: As part of the Multiple Myeloma Research Foundation (MMRF) immune atlas pilot project, we compared immune cells of multiple myeloma bone marrow samples from 18 patients assessed by single-cell RNA sequencing (scRNA-seq), mass cytometry (CyTOF), and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to understand the concordance of measurements among single-cell techniques. Cell type abundances are relatively consistent across the three approaches, while variations are observed in T cells, macrophages, and monocytes. Concordance and correlation analysis of cell type marker gene expression across different modalities highlighted the importance of choosing cell type marker genes best suited to …

Six-Year Results From Relevance: Lenalidomide Plus Rituximab (R2) Versus Rituximab-Chemotherapy Followed By Rituximab Maintenance In Untreated Advanced Follicular Lymphoma, Franck Morschhauser, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

No abstract provided.

Tnfr1 Contributes To Activation-Induced Cell Death Of Pathological Cd4+ T Lymphocytes During Ischemic Heart Failure, Vinay Kumar, Rachel Rosenzweig, Suman Asalla, Sarita Nehra, Sumanth D Prabhu, Shyam S Bansal

2020-Current year OA Pubs

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Neoadjuvant Atezolizumab For Resectable Non-Small Cell Lung Cancer: An Open-Label, Single-Arm Phase Ii Trial, Jamie E Chaft, G Alexander Patterson, Saiama N Waqar, Et Al.

2020-Current year OA Pubs

In an ongoing, open-label, single-arm phase II study ( NCT02927301 ), 181 patients with untreated, resectable, stage IB-IIIB non-small cell lung cancer received two doses of neoadjuvant atezolizumab monotherapy. The primary end point was major pathological response (MPR; ≤10% viable malignant cells) in resected tumors without EGFR or ALK alterations. Of the 143 patients in the primary end point analysis, the MPR was 20% (95% confidence interval, 14-28%). With a minimum duration of follow-up of 3 years, the 3-year survival rate of 80% was encouraging. The most common adverse events during the neoadjuvant phase were fatigue (39%, 71 of 181) …

The Gut Microbial Metabolic Capacity Of Microbiome-Humanized Vs. Wild Type Rodents Reveals A Likely Dual Role Of Intestinal Bacteria In Hepato-Intestinal Schistosomiasis, Alba Cortés, John Martin, Bruce A. Rosa, Klara A. Stark, Simon Clare, Catherine Mccarthy, Katherine Harcourt, Cordelia Brandt, Charlotte Tolley, Trevor D. Lawley, Makedonka Mitreva, Matthew Berriman, Gabriel Rinaldi, Cinzia Cantacessi

2020-Current year OA Pubs

Increasing evidence shows that the host gut microbiota might be involved in the immunological cascade that culminates with the formation of tissue granulomas underlying the pathophysiology of hepato-intestinal schistosomiasis. In this study, we investigated the impact of Schistosoma mansoni infection on the gut microbial composition and functional potential of both wild type and microbiome-humanized mice. In spite of substantial differences in microbiome composition at baseline, selected pathways were consistently affected by parasite infection. The gut microbiomes of infected mice of both lines displayed, amongst other features, enhanced capacity for tryptophan and butyrate production, which might be linked to the activation …

Newborn Mid-Upper Arm Circumference Identifies Low-Birth Weight And Vulnerable Infants: A Secondary Analysis, D Taylor Hendrixson, Patrick N Lasowski, Aminata Shamit Koroma, Mark J Manary

2020-Current year OA Pubs

BACKGROUND: Low birth weight (LBW) infants are at increased risk of morbidity and mortality. Identification of LBW may not occur in settings where access to reliable scales is limited. Mid-upper arm circumference (MUAC) may be an accessible, low-cost measure to identify LBW and vulnerable infants.

OBJECTIVES: We explored the validity of newborn MUAC in identifying LBW and vulnerable newborns in rural Sierra Leone.

METHODS: This study was a secondary analysis of infant data from a randomized controlled clinical trial of supplementary food and anti-infective therapies compared with standard care for undernourished pregnant women. Data for singleton liveborn infants with birth …

Antimicrobial Stewardship For Sepsis In The Intensive Care Unit: Survey Of Critical Care And Infectious Diseases Physicians, M Cristina Vazquez Guillamet, Jason P Burnham, Maria Pérez, Marin H Kollef, Constantine A Manthous, Donna B Jeffe

2020-Current year OA Pubs

OBJECTIVE: To evaluate the attitudes of infectious diseases (ID) and critical care physicians toward antimicrobial stewardship in the intensive care unit (ICU).

DESIGN: Anonymous, cross-sectional, web-based surveys.

SETTING: Surveys were completed in March-November 2017, and data were analyzed from December 2017 to December 2019.

PARTICIPANTS: ID and critical care fellows and attending physicians.

METHODS: We included 10 demographic and 17 newly developed, 5-point, Likert-scaled items measuring attitudes toward ICU antimicrobial stewardship and transdisciplinary collaboration. Exploratory principal components analysis (PCA) was used for data reduction. Multivariable linear regression models explored demographic and attitudinal variables.

RESULTS: Of 372 respondents, 315 physicians had …

Clinical Use Of Mean Nocturnal Baseline Impedance And Post-Reflux Swallow-Induced Peristaltic Wave Index For The Diagnosis Of Gastro-Esophageal Reflux Disease, Pierfrancesco Visaggi, Lucia Mariani, Federica Baiano Svizzero, Luca Tarducci, Andrea Sostilio, Marzio Frazzoni, Salvatore Tolone, Roberto Penagini, Leonardo Frazzoni, Linda Ceccarelli, Vincenzo Savarino, Massimo Bellini, Prakash C Gyawali, Edoardo V Savarino, Nicola De Bortoli

2020-Current year OA Pubs

The clinical diagnosis of gastro-esophageal reflux disease (GERD) is based on the presence of typical esophageal troublesome symptoms. In clinical practice, heartburn relief following a proton pump inhibitor (PPI) trial or endoscopy can confirm a diagnosis of GERD. In cases of diagnostic uncertainty or before anti-reflux interventions, combined impedance-pH monitoring (MII-pH) provides a comprehensive assessment of both physical and chemical properties of the refluxate, allowing to achieve a conclusive diagnosis of GERD. Recently, the Lyon Consensus proposed the use of mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave index (PSPW-I) as novel MII-pH metrics to support the diagnosis …