Medicine and Health Sciences Commons^™

Association Between Anticoagulant-Related Bleeding And Mortality In Patients With Hematological Malignancies And Cancer-Associated Venous Thromboembolism, Tzu-Fei Wang, Suhong Luo, Brian F Gage, Martin W Schoen, Amber Afzal, Kenneth Carson, Su-Hsin Chang, Amir Mahmoud, Kristen M Sanfilippo

2020-Current year OA Pubs

INTRODUCTION: Patients with hematological malignancies are at an increased risk of severe bleeding. Anticoagulant (AC) therapy further increases this risk. Mortality after these bleeds is unclear and may differ by bleeding site. Aim To evaluate the association between bleeding and mortality in patients with hematological malignancies prescribed AC therapy for cancer-associated venous thromboembolism (VTE).

METHODS: In a nationwide cohort of US Veterans (2012-2020), we identified patients with hematological malignancies and cancer-associated VTE prescribed AC therapy. Bleeding events were identified by a previously validated algorithm using hospitalization International Classification of Disease (ICD) codes. Within 12 months of AC therapy initiation, we …

Antibody Responses In Klebsiella Pneumoniae Bloodstream Infection: A Prospective Cohort Study, Wontae Hwang, Paeton L Wantuch, David A Rosen, Et Al.

2020-Current year OA Pubs

BACKGROUND: Klebsiella pneumoniae is a leading cause of infection-related deaths globally, yet little is known about human antibody responses to invasive K pneumoniae. We sought to determine whether the O-specific polysaccharide antigen is immunogenic in humans with K pneumoniae bloodstream infection. We also sought to define the cross-reactivity of human antibody responses among structurally related K pneumoniae O-specific polysaccharide subtypes and to assess the effect of capsule production on O-specific polysaccharide-targeted antibody binding and function.

METHODS: In this prospective cohort study, we compared plasma antibody responses to O-specific polysaccharide in a cohort of consecutively enrolled patients with K pneumoniae bloodstream …

The Ten Test And Sensory Evaluation Of Hand And Finger Injuries In The Emergency Department, Emilie H Lothet, Aaron J Lacy, Elizabeth B Odom

2020-Current year OA Pubs

BACKGROUND: Hand and finger injuries are a common presenting complaint to the emergency department (ED) and are associated with significant morbidity. Neurologic evaluation of these injuries is a crucial component of the patient assessment and can be done via a variety of testing methods.

DISCUSSION: Although most taught and cited in the ED literature, the two-point discrimination test for sensation has several drawbacks, including limited reproducibility and reliability. Although often utilized by hand surgical specialists, the Semmes-Weinstein monofilament test and the Weinstein Enhanced Sensory Test are not practical for the emergency physician due to the need for specialized equipment and …

Transcriptome Meta-Analysis Uncovers Cell-Specific Regulatory Relationships In Embryonic, Juvenile, Adult, And Aged Mouse Lens Epithelium And Fibers, Matthieu Duot, Sarah Y Coomson, Sanjaya K Shrestha, M V Murali Krishna Nagulla, Yann Audic, Ruteja A Barve, Hongzhan Huang, Carole Gautier-Courteille, Luc Paillard, Salil A Lachke

2020-Current year OA Pubs

PURPOSE: The lens transcriptome has been examined using microarrays and RNA-sequencing (RNA-seq). These omics data are the basis of the bioinformatics web-resource iSyTE that has identified new genes involved in lens development and cataract. The lens predominantly contains epithelial and fiber cells, and yet, presently, iSyTE is based on whole lens data. To gain cell-specific regulatory insights, we meta-analyzed isolated epithelium and fiber transcriptomes from embryonic/postnatal, adult and aged lenses.

METHODS: Mouse lens epithelium and fiber transcriptome public datasets at embryonic (E) and postnatal (P) stages E12.5, E14.5, E16.5, E18.5, P0.5, P0, P5, P13, and age one month, three months, …

Gene Expression Differences Associated With Alcohol Use Disorder In Human Brain, Caryn Willis, Julie D White, Melyssa S Minto, Bryan C Quach, Shizhong Han, Ran Tao, Joo Heon Shin, Amy Deep-Soboslay, Thomas M Hyde, R Dayne Mayfield, Bradley T Webb, Eric O Johnson, Joel E Kleinman, Laura J Bierut, Dana B Hancock

2020-Current year OA Pubs

Excessive alcohol consumption is a leading cause of preventable death worldwide. To improve understanding of neurobiological mechanisms associated with alcohol use disorder (AUD) in humans, we compared gene expression data from deceased individuals with and without AUD across two addiction-relevant brain regions: the nucleus accumbens (NAc) and dorsolateral prefrontal cortex (DLPFC). Bulk RNA-seq data from NAc and DLPFC (N ≥50 with AUD, ≥46 non-AUD) were analyzed for differential gene expression using modified negative binomial regression adjusting for technical and biological covariates. The region-level results were meta-analyzed with those from an independent dataset (N

Methylomic Signature Of Current Cannabis Use In Two First-Episode Psychosis Cohorts, Emma L Dempster, Emma C Johnson, Et Al.

2020-Current year OA Pubs

The rising prevalence and legalisation of cannabis worldwide have underscored the need for a comprehensive understanding of its biological impact, particularly on mental health. Epigenetic mechanisms, specifically DNA methylation, have gained increasing recognition as vital factors in the interplay between risk factors and mental health. This study aimed to explore the effects of current cannabis use and high-potency cannabis on DNA methylation in two independent cohorts of individuals experiencing first-episode psychosis (FEP) compared to control subjects. The combined sample consisted of 682 participants (188 current cannabis users and 494 never users). DNA methylation profiles were generated on blood-derived DNA samples …

Unleashing The Power Of Multiomics: Unraveling The Molecular Landscape Of Peripheral Neuropathy, Julie Choi, Zitian Tang, Wendy Dong, Jenna Ulibarri, Elvisa Mehinovic, Simone Thomas, Ahmet Höke, Sheng Chih Jin

2020-Current year OA Pubs

Peripheral neuropathies (PNs) affect over 20 million individuals in the United States, manifesting as a wide range of sensory, motor, and autonomic nerve symptoms. While various conditions such as diabetes, metabolic disorders, trauma, autoimmune disease, and chemotherapy-induced neurotoxicity have been linked to PN, approximately one-third of PN cases remain idiopathic, underscoring a critical gap in our understanding of these disorders. Over the years, considerable efforts have focused on unraveling the complex molecular pathways underlying PN to advance diagnosis and treatment. Traditional methods such as linkage analysis, fluorescence in situ hybridization, polymerase chain reaction, and Sanger sequencing identified initial genetic variants …

Hospital-Onset Bacteremia In The Neonatal Intensive Care Unit: Strategies For Risk Adjustment, Erica C Prochaska, Shaoming Xiao, Elizabeth Colantuoni, Nora Elhaissouni, Reese H Clark, Julia Johnson, Sagori Mukhopadhyay, Ibukunoluwa C Kalu, Danielle M Zerr, Patrick J Reich, Jessica Roberts, Dustin D Flannery, Aaron M Milstone, Cdc Prevention Epicenters Program

2020-Current year OA Pubs

OBJECTIVE: To quantify the impact of patient- and unit-level risk adjustment on infant hospital-onset bacteremia (HOB) standardized infection ratio (SIR) ranking.

DESIGN: A retrospective, multicenter cohort study.

SETTING AND PARTICIPANTS: Infants admitted to 284 neonatal intensive care units (NICUs) in the United States between 2016 and 2021.

METHODS: Expected HOB rates and SIRs were calculated using four adjustment strategies: birthweight (model 1), birthweight and postnatal age (model 2), birthweight and NICU complexity (model 3), and birthweight, postnatal age, and NICU complexity (model 4). Sites were ranked according to the unadjusted HOB rate, and these rankings were compared to rankings based …

Similarities And Differences In The Gene Expression Signatures Of Physiological Age Versus Future Lifespan, Matthew C Mosley, Holly E Kinser, Olivier M F Martin, Nicholas Stroustrup, Tim Schedl, Kerry Kornfeld, Zachary Pincus

2020-Current year OA Pubs

Across all taxa of life, individuals within a species exhibit variable lifespans. Differences in genotype or environment are not sufficient to explain this variance, as even isogenic Caenorhabditis elegans nematodes reared under uniform conditions show significant variability in lifespan. To investigate this phenomenon, we used lifespan-predictive biomarkers to isolate, at mid-adulthood, prospectively long- and short-lived individuals from an otherwise identical population. We selected two biomarkers which correlated positively with lifespan, lin-4p::GFP and mir-243p::GFP, and two which correlated negatively, mir-240/786p::GFP and autofluorescence. The gene-expression signature of long versus short future lifespan was strikingly similar across all four biomarkers tested. Since these …

Dorsal Root Ganglion Stimulation In Patients With Refractory Abdominal Pain: A Case Series, Zeshan R. Ali, Beker Karadaghy, Iqbal Khan, Geoffrey D. Panjeton, Hess Panjeton

2020-Current year OA Pubs

This case series highlights the use of dorsal root ganglion (DRG) stimulation for refractory chronic abdominal pain in three patients who failed to respond to conventional therapies. DRG stimulation modulates pain signals by targeting the sensory neurons present in the DRG. The three cases involved patients with chronic abdominal pain resulting from pancreatitis, endometriosis, and pancreatic cancer. DRG stimulation resulted in pain reductions of 100%, 90%, and 80%, respectively, accompanied by significant improvements in daily functionality and reduced analgesic use. These findings underscore the potential of DRG stimulation as a targeted, effective treatment for refractory abdominal pain. Further research with …

Femoral Nail And Cement Static Spacer Technique For The Treatment Of Chronic Periprosthetic Knee Infection, Katherine Mistretta, Caroline Granger, Joseph Kromka, Andrew M Schneider

2020-Current year OA Pubs

A 2-stage protocol is standard of care treatment in the United States for chronic periprosthetic joint infection of the knee. While many patients benefit from insertion of an articulating spacer, there are instances in which this is not feasible, and a static spacer is indicated. However, many static spacer techniques risk instability and lack durability. The ideal static spacer construct should provide immediate brace-free weight-bearing to maximize function during the spacer stage and, if needed, permit delayed reimplantation in the case of medically high-risk patients. Here, we describe our surgical technique for a femoral nail and cement static spacer in …

Single-Cell Transcriptomic Analysis Of Kaposi Sarcoma, Daniel A. Rauch, Paula Valiño Ramos, Mariam Khanfar, John Harding, Ancy Joseph, Anam Fahad, Paul Simonson, Isabel Risch, Obi Griffith, Malachi Griffith, Lee Ratner

2020-Current year OA Pubs

Kaposi Sarcoma (KS) is a complex tumor caused by KS-associated herpesvirus 8 (KSHV). Histological analysis reveals a mixture of "spindle cells", vascular-like spaces, extravasated erythrocytes, and immune cells. In order to elucidate the infected and uninfected cell types in KS tumors, we examined twenty-five skin and blood samples from sixteen subjects by single cell RNA sequence analyses. Two populations of KSHV-infected cells were identified, one of which represented a CD34-negative proliferative fraction of endothelial cells, and the second representing CD34-positive cells expressing endothelial genes found in a variety of cell types including high endothelial venules, fenestrated capillaries, and endothelial tip …

Dynein Light Chains 1 And 2 Are Auxiliary Proteins Of Ph-Sensitive Kir4.1 Channels, Sun-Joo Lee, Jian Gao, Ellen Thompson, Jonathan Mount, Colin G Nichols

2020-Current year OA Pubs

Inward rectifier Kir4.1 potassium channels are abundantly expressed in cells that are important for electrolyte homeostasis. Dysregulation of Kir4.1 underlies various neurological disorders. Here, through biochemical and structural studies of full-length Kir4.1, we show that dynein light chain 1 and 2 proteins, also as known as LC8, copurify with Kir4.1 at stoichiometric levels. Direct interaction between Kir4.1 and LC8 is supported by in vitro binding assays and reiterated with native Kir4.1 proteins from mouse brain. Notably, we identify a LC8 binding motif in the unstructured N terminus of Kir4.1. Among Kir subtypes, the motif is unique to Kir4.1 and is …

Applying Results Of Extended Genotyping To Management Of Positive Cervicovaginal Human Papillomavirus Test Results: Enduring Guidelines, L. Stewart Massad, Megan A. Clarke, Rebecca B. Perkins, Francisco Garcia, David Chelmow, Li C. Cheung, Teresa M. Darragh, Didem Egemen, Thomas S. Lorey, Ritu Nayar, Morgan Newman, Carolann Risley, Robert A. Smith, Nicolas Wentzensen, Enduring Consensus Cervical Cancer Screening And Management Guidelines Committee

2020-Current year OA Pubs

OBJECTIVE: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for the use of extended genotyping results in cervical cancer prevention programs.

METHODS: Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated using data obtained with the Onclarity HPV Assay from large cohorts. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Risk estimates were reviewed in relation to clinical action thresholds and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through …

Self-Collected Vaginal Specimens For Hpv Testing: Recommendations From The Enduring Consensus Cervical Cancer Screening And Management Guidelines Committee, Nicolas Wentzensen, L. Stewart Massad, Megan A. Clarke, Francisco Garcia, Robert Smith, Jeanne Murphy, Richard Guido, Ana Reyes, Sarah Phillips, Nancy Berman, Jeffrey Quinlan, Eileen Lind, Rebecca B. Perkins, Enduring Consensus Cervical Cancer Screening And Management Guidelines Committee

2020-Current year OA Pubs

OBJECTIVE: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for the use of self-collected vaginal specimens for human papillomavirus (HPV) testing in health care settings.

METHODS: A comprehensive literature search was performed, external systematic reviews were evaluated, and HPV genotype agreement between self-collected vaginal and clinician-collected cervical specimens was summarized. Recommendations considered available data, public comments, and expert consensus. Recommendations were ratified through a vote by the Consensus Stakeholder Group.

RESULTS: Clinician-collected cervical specimens are preferred and self-collected vaginal specimens are acceptable for primary HPV screening of asymptomatic average-risk individuals. Repeat testing in 3 years is …

The Role Of Androgens On Experimental Pain Sensitivity: A Systemic Review And Meta-Analysis, Elizabeth Wu-Chen, Gourav Banerjee, Elise Requadt, Benjamin Hunter, Thomas J. Baranski, Whitney Trotter Ross, Hadas Nahman-Averbuch

2020-Current year OA Pubs

Animal studies have shown androgens, especially testosterone, may have an analgesic effect on nociceptive behavior. However, it is unclear if this effect is present in humans. This review and meta-analysis aim to summarize and synthesize the role of androgens on experimental pain sensitivity in humans. Studies were included if they examined the (1) relationships between androgens and experimental pain sensitivity, (2) group differences in androgen or pain levels, and (3) the effect of androgen interventions on experimental pain sensitivity. After a comprehensive search, 31 papers were identified. When possible, meta-analyses were performed. Most studies examined the impact of testosterone on …

Subgroup Evaluation To Understand Performance Gaps In Deep Learning-Based Classification Of Regions Of Interest On Mammography, Minjae Woo, Linglin Zhang, Beatrice Brown-Mulry, Inchan Hwang, Judy Wawira Gichoya, Aimilia Gastounioti, Imon Banerjee, Laleh Seyyed-Kalantari, Hari Trivedi

2020-Current year OA Pubs

This study evaluates a deep learning model for classifying normal versus potentially abnormal regions of interest (ROIs) on mammography, aiming to identify imaging, pathologic, and demographic characteristics that may induce suboptimal model performance in certain patient subgroups. We utilized the EMory BrEast imaging Dataset (EMBED), containing 3.4 million mammographic images from 115,931 patients. Full-field digital mammograms from women aged 18 years or older were used to create positive and negative patches with the patches matched based on size, location, patient demographics, and imaging features. Several convolutional neural network (CNN) architectures were tested, with ResNet152V2 demonstrating the best performance. The dataset …

Systemic Inflammation Is Associated With Worse Outcomes From Sars-Cov-2 Infection But Not Neutralizing Antibody, Christopher W Farnsworth, Brittany Roemmich, John Prostko, Gerard Davis, Gillian Murtagh, Laurel Jackson, Christopher Jacobson, Nicolette Jeanblanc, Timothy Griffiths, Edwin Frias, David J Daghfal

2020-Current year OA Pubs

Systemic inflammation is associated with COVID-19 mortality rates, but the impact of inflammation on neutralizing antibodies to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and on outcomes is poorly understood. This study aimed to determine the association between neutralizing antibody responses, inflammation, and clinical outcomes in hospitalized patients with COVID-19. Two hundred and eight patients presenting to the ED with symptomatic SARS-CoV-2 were included. Neutralization was assessed using the architect angiotensin-converting enzyme-2 (ACE2) binding inhibition assay, and inflammation was assessed using C reactive protein (CRP) and interleukin 6 (IL-6). Medical records were examined for 30-day mortality and 10-day intubation. Correlation …

Severe Aortic Stenosis And Chronic Myeloid Leukemia: Considerations For Valve Management, Rebecca Cunningham, Sang Gune K Yoo, Alexander A Brescia, Karolyn A Oetjen, Iskra Pusic, Joshua D Mitchell

2020-Current year OA Pubs

No abstract provided.

Management Aspects Of Medical Therapy In Graves Disease, Rutu Shah, Samantha E Adamson, Sina Jasim

2020-Current year OA Pubs

OBJECTIVE: Graves disease (GD) is the most common cause of hyperthyroidism. Treatment options include antithyroid drugs (ATDs), radioactive iodine, and surgery. In this review, we focus on the medical aspects of managing GD.

METHODS: The authors conducted a literature review of PubMed to include studies and review articles on GD management, ATDs, long-term safety of antithyroid drugs, hyperthyroidism in pregnancy, Graves ophthalmopathy, and special circumstances related to hyperthyroidism.

RESULTS: In adjunction to ATDs, medical management for GD also includes beta-blockers, glucocorticoids, and iodine containing agents. ATDs are currently the preferred option for initial management of GD, reflecting a shift in …

Biliary Metaplasia And Macrophage Activation Define The Cellular Landscape Of Cardiogenic Liver Disease, Arick C Park, Christina F Fu, Adeesh Parvathaneni, Bin Q Yang, Mandy M Chan, Kathleen Byrnes, Joel D Schilling

2020-Current year OA Pubs

Right heart failure significantly impacts liver remodeling and function, a process referred to as cardiogenic liver disease. Although recognized as a risk factor for adverse outcomes, little is understood about the cellular and molecular players that contribute to liver disease in heart failure. Using human liver biopsy samples from patients with heart failure and a mouse model of liver congestion, we unraveled a nexus of macrophages, hepatic stellate cells, and biliary metaplastic cells that shape the pathologic environment of cardiogenic liver disease.

The Cognitive Profile Of Older Adults With Treatment-Resistant Depression: An Analysis Of The Optimum Randomized Controlled Trial, Nicholas J Ainsworth, Hanadi Oughli, Helen Lavretsky, Daniel M Blumberger, Patrick J Brown, Meryl A Butters, Jordan F Karp, Emily Lenard, Eric J Lenze, Mary Pat Mcandrews, J Philip Miller, Bruce G Pollock, Charles F Reynolds, Benoit H Mulsant

2020-Current year OA Pubs

OBJECTIVE: Major depressive disorder in older adults (late-life depression; LLD) is frequently associated with cognitive impairment, and some deficits (e.g., executive function) have been associated with a higher level of treatment resistance. However, the cognitive profile of treatment-resistant LLD (TR-LLD) has not been characterized. We hypothesized that patients with TR-LLD would show deficits in cognitive function, especially executive function, and that executive function deficits would predict poorer response to pharmacotherapy.

DESIGN: Secondary analysis of baseline cognitive data from OPTIMUM, a multicenter RCT evaluating pharmacotherapy strategies for TR-LLD.

SETTING: Five outpatient academic medical centers (4 US, 1 Canada).

PARTICIPANTS: About 369 …

Sexually Dimorphic Cardiovascular Impacts Of Prenatal Exposure To A Real-Life Environmental Chemical Mixture In Adult Offspring, Noor Muhammad Khan, Victoria Scott, Mohammad Ghasemzadeh-Hasankolaei, Vasantha Padmanabhan, Arpita Vyas, Neil P Evans, Michelle Bellingham

2020-Current year OA Pubs

Cardiovascular disease (CVD) is a leading cause of death that is sexually dimorphic. This study used an ovine model to investigate whether maternal exposure to an environmental chemical (EC) mixture (biosolids) prior to and throughout pregnancy, affected offspring cardiovascular (CV) structure and function in adulthood. CV function of male and female offspring from ewes grazed on either conventionally fertilised (control, C) or biosolids-treated pasture (B) was assessed. Males exhibited higher blood pressure compared to females with no significant effect of EC exposure. Heart rate variability in females suggested reduced autonomic regulation in the B group. EC-exposed males, but not females, …

Long-Term Results Of Bone-Patellar Tendon-Bone Versus Hamstring Tendon Autograft For Primary Anterior Cruciate Ligament Reconstruction: A Meta-Analysis Of Randomized Controlled Trials, Varun Gopinatth, Sina Tartibi, Matthew V Smith, Matthew J Matava, Robert H Brophy, Derrick M Knapik

2020-Current year OA Pubs

BACKGROUND: Bone-patellar tendon-bone (BTB) and hamstring tendon (HT) autografts are the most commonly utilized grafts for primary anterior cruciate ligament reconstruction (ACLR). While previous studies have compared outcomes using BTB and HT grafts for ACLR at short- and mid-term follow-ups, outcomes at long-term follow-ups remain unclear.

PURPOSE: To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating BTB versus HT autografts for primary ACLR at a minimum 10-year follow-up.

STUDY DESIGN: Systematic review; Level of evidence, 2.

METHODS: A systematic review was performed in accordance with the 2020 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) …

Neuroimmune Mechanisms Of Type 2 Inflammation In The Skin And Lung, Masato Tamari, Aaron M Ver Heul

2020-Current year OA Pubs

Type 2 inflammation has a major role in barrier tissues such as the skin and airways and underlies common conditions including atopic dermatitis (AD) and asthma. Cytokines including interleukin 4 (IL-4), IL-5, and IL-13 are key immune signatures of type 2 inflammation and are the targets of multiple specific therapeutics for allergic diseases. Despite shared core immune mechanisms, the distinct structures and functions of the skin and airways lead to unique therapeutic responses. It is increasingly recognized that the nervous system has a major role in sensing and directing inflammatory processes. Indeed, crosstalk between type 2 immune activation and somatosensory …

Enhancing Human Nk Cell Antitumor Function By Knocking Out Smad4 To Counteract Tgfβ And Activin A Suppression, Anna Rea, Bishan Bhattarai, Marco Colonna, Et Al.

2020-Current year OA Pubs

Transforming growth factor beta (TGFβ) and activin A suppress natural killer (NK) cell function and proliferation, limiting the efficacy of adoptive NK cell therapies. Inspired by the partial resistance to TGFβ of NK cells with SMAD4 haploinsufficiency, we used CRISPR-Cas9 for knockout of SMAD4 in human NK cells. Here we show that SMAD4

Tenapanor Improves Abdominal Symptoms Irrespective Of Changes In Complete Spontaneous Bowel Movement Frequency In Adults With Irritable Bowel Syndrome With Constipation, Darren M Brenner, Gregory S Sayuk, Brooks D Cash, Lucinda A Harris, Nitin K Ahuja, Jill K Deutsch, Yang Yang, Suling Zhao, David P Rosenbaum, Anthony J Lembo

2020-Current year OA Pubs

INTRODUCTION: Tenapanor is a first-in-class, minimally absorbed intestinal sodium/hydrogen exchanger isoform 3 inhibitor approved by the US Food and Drug Administration for adults with irritable bowel syndrome with constipation (IBS-C). Pooled data from the phase 2b (NCT01923428) and phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies examined the effects of tenapanor on abdominal symptoms independent of tenapanor's effect on complete spontaneous bowel movement (CSBM) frequency in adults with IBS-C.

METHODS: This post hoc analysis was performed for patients with no CSBMs in ≥6 of the first 12 weeks of treatment (no-CSBM subgroup). The three-item abdominal score (AS3; the average of …

First-In-Human Phase I Study Of A Cd16a Bispecific Innate Cell Engager, Afm24, Targeting Egfr-Expressing Solid Tumors, Anthony El-Khoueiry, Todd A Fehniger, Mark Foster, Melissa M Berrien-Elliott, Et Al.

2020-Current year OA Pubs

PURPOSE: Innate immune cell-based therapies have shown promising antitumor activity against solid and hematologic malignancies. AFM24, a bispecific innate cell engager, binds CD16A on NK cells/macrophages and EGFR on tumor cells, redirecting antitumor activity toward tumors. The safety and tolerability of AFM24 were evaluated in this phase I/IIa dose-escalation/dose-expansion study in patients with recurrent or persistent, advanced solid tumors known to express EGFR.

PATIENTS AND METHODS: The main objective in phase I was to determine the MTD and/or recommended phase II dose. The primary endpoint was the incidence of dose-limiting toxicities during the observation period. Secondary endpoints included the incidence …

Genomic Analysis Of 11,555 Probands Identifies 60 Dominant Congenital Heart Disease Genes, Michael C Sierant, Sheng Chih Jin, Et Al.

2020-Current year OA Pubs

Congenital heart disease (CHD) is a leading cause of infant mortality. We analyzed de novo mutations (DNMs) and very rare transmitted/unphased damaging variants in 248 prespecified genes in 11,555 CHD probands. The results identified 60 genes with a significant burden of heterozygous damaging variants. Variants in these genes accounted for CHD in 10.1% of probands with similar contributions from de novo and transmitted variants in parent-offspring trios that showed incomplete penetrance. DNMs in these genes accounted for 58% of the signal from DNMs. Thirty-three genes were linked to a single CHD subtype while 12 genes were associated with 2 to …

Acute Trem2 Inhibition Depletes Mafb-High Microglia And Hinders Remyelination, Jinchao Hou, Roberta Magliozzi, Yun Chen, Junjie Wu, John Wulf Ii, Gregory Strout, Xiangming Fang, Marco Colonna

2020-Current year OA Pubs

We investigated the role of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) in myelin regeneration in the brain. TREM2 is a receptor that activates microglia, which are crucial for clearing myelin debris and promoting remyelination. Previous studies in a mouse model of demyelination induced by the copper-chelating agent Cuprizone (CPZ) have shown that stimulation of TREM2 with a monoclonal antibody reduces demyelination, while deleting the