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Performance Of The Lateral Flow Assay And The Latex Agglutination Serum Cryptococcal Antigen Test In Cryptococcal Disease In Patients With And Without Hiv, Matthew A Hevey, Ige A George, Adriana M Rauseo, Lindsey Larson, William Powderly, Andrej Spec

Open Access Publications

Cryptococcal epidemiology is shifting toward HIV-negative populations who have diverse presentations. Cryptococcal antigen (CrAg) testing is also changing, with development of the lateral flow assay (LFA) having reported increased sensitivity and specificity, but with minimal knowledge in the HIV-negative population. In this study, we evaluate the real-life performance of CrAg testing in patients with cryptococcal disease. We conducted a retrospective review of patients with cryptococcosis from 2002 to 2019 at Barnes-Jewish Hospital. Latex agglutination (LA) was used exclusively until April 2016, at which point LFA was used exclusively. Demographics, presentations, and testing outcomes were evaluated. Serum CrAg testing was completed …

Role Of Endothelial Nitric Oxide Synthase In Isoflurane Conditioning-Induced Neurovascular Protection In Subarachnoid Hemorrhage, Umeshkumar Athiraman, Keshav Jayaraman, Meizi Liu, Tusar Giri, Jane Yuan, Gregory J Zipfel

Open Access Publications

Background Delayed cerebral ischemia remains a common and profound risk factor for poor outcome after subarachnoid hemorrhage (SAH). The aim of our current study is to define the role of endothelial nitric oxide synthase (eNOS) in isoflurane conditioning-induced neurovascular protection after SAH. Methods and Results Ten- to 14-week-old male wild-type mice (C57BL/6) as controls and eNOS knockout male mice (strain # 002684) were obtained for the study. Animals underwent either sham surgery, SAH surgery, or SAH with isoflurane conditioning. Anesthetic post conditioning was performed with isoflurane 2% for 1 hour, 1 hour after SAH. Normothermia was maintained with the homeothermic …

Burst Mitofusin Activation Reverses Neuromuscular Dysfunction In Murine Cmt2a, Antonietta Franco, Xiawei Dang, Emily K. Walton, Joshua N. Ho, Barbara Zablocka, Cindy Ly, Timothy M. Miller, Robert H. Baloh, Michael E. Shy, Andrew S. Yoo, Gerald W. Dorn

Open Access Publications

Charcot-Marie-Tooth disease type 2A (CMT2A) is an untreatable childhood peripheral neuropathy caused by mutations of the mitochondrial fusion protein, mitofusin (MFN) 2. Here, pharmacological activation of endogenous normal mitofusins overcame dominant inhibitory effects of CMT2A mutants in reprogrammed human patient motor neurons, reversing hallmark mitochondrial stasis and fragmentation independent of causal

Walking School Bus Programs: Implementation Factors, Implementation Outcomes, And Student Outcomes, 2017-2018, Jordan A Carlson, Chelsea Steel, Carolina M Bejarano, Marshall T Beauchamp, Ann M Davis, James F Sallis, Jon Kerner, Ross Brownson, Sara Zimmerman

Open Access Publications

PURPOSE AND OBJECTIVES: Walking school bus programs increase children's physical activity through active travel to school; however, research to inform large-scale implementation of such programs is limited. We investigated contextual factors, implementation outcomes, and student outcomes in existing walking school bus programs in the United States and internationally.

INTERVENTION APPROACH: Walking school bus programs involve a group of children walking to school together with an adult leader. On the trip to school, these adults provide social support, address potential traffic and interpersonal safety, and serve as role models to the children while children increase their physical activity levels.

EVALUATION METHODS: …

Associations Between Multimodal Fitness Assessments And Rowing Ergometer Performance In Collegiate Female Athletes, Clifton J Holmes, Bjoern Hornikel, Katherine Sullivan, Michael V Fedewa

Open Access Publications

The purpose was to examine the association of critical power from a three-minute all-out row (CP

Zanubrutinib Monotherapy For Patients With Treatment Naïve Chronic Lymphocytic Leukemia And 17p Deletion, Constantine S. Tam, Brad S. Kahl, Et Al

Open Access Publications

Patients with chronic lymphocytic leukemia or small lymphocytic lymphoma whose tumors carry deletion of chromosome 17p13.1 [del(17p)] have an unfavorable prognosis and respond poorly to standard chemoimmunotherapy. Zanubrutinib is a selective next-generation Bruton tyrosine kinase inhibitor. We evaluated the safety and efficacy of zanubrutinib 160 mg twice daily in treatment-naïve patients with del(17p) disease enrolled in a dedicated, nonrandomized cohort (Arm C) of the phase 3 SEQUOIA trial. A total of 109 patients (median age, 70 years; range, 42 - 86) with centrally confirmed del(17p) were enrolled and treated. After a median of 18.2 months (range, 5.0 - 26.3), seven …

Acute Kidney Injury Pathology And Pathophysiology: A Retrospective Review, Joseph P. Gaut, Helen Liapis

Open Access Publications

Acute kidney injury (AKI) is the clinical term used for decline or loss of renal function. It is associated with chronic kidney disease (CKD) and high morbidity and mortality. However, not all causes of AKI lead to severe consequences and some are reversible. The underlying pathology can be a guide for treatment and assessment of prognosis. The Kidney Disease: Improving Global Outcomes guidelines recommend that the cause of AKI should be identified if possible. Renal biopsy can distinguish specific AKI entities and assist in patient management. This review aims to show the pathology of AKI, including glomerular and tubular diseases.

Argonaut: A Web Platform For Collaborative Multi-Omic Data Visualization And Exploration, Dain R Brademan, Ian J Miller, Nicholas W Kwiecien, David J Pagliarini, Michael S Westphall, Joshua J Coon, Evgenia Shishkova

Open Access Publications

Researchers now generate large multi-omic datasets using increasingly mature mass spectrometry techniques at an astounding pace, facing new challenges of "Big Data" dissemination, visualization, and exploration. Conveniently, web-based data portals accommodate the complexity of multi-omic experiments and the many experts involved. However, developing these tailored companion resources requires programming expertise and knowledge of web server architecture-a substantial burden for most. Here, we describe Argonaut, a simple, code-free, and user-friendly platform for creating customizable, interactive data-hosting websites. Argonaut carries out real-time statistical analyses of the data, which it organizes into easily sharable projects. Collaborating researchers worldwide can explore the results, visualized …

Proceedings From The Fourth International Symposium On Sigma-2 Receptors: Role In Health And Disease, Nicholas J Izzo, Martí Colom-Cadena, Aladdin A Riad, Jinbin Xu, Meharvan Singh, Carmen Abate, Michael A Cahill, Tara L Spires-Jones, Wayne D Bowen, Robert H Mach, Susan M Catalano

Open Access Publications

The sigma-2 receptor (S2R) complex has been implicated in central nervous system disorders ranging from anxiety and depression to neurodegenerative disorders such as Alzheimer's disease (AD). The proteins comprising the S2R complex impact processes including autophagy, cholesterol synthesis, progesterone signaling, lipid membrane-bound protein trafficking, and receptor stabilization at the cell surface. While there has been much progress in understanding the role of S2R in cellular processes and its potential therapeutic value, a great deal remains unknown. The

Delirium Prevention And Treatment In The Emergency Department (Ed): A Systematic Review Protocol, Elijah Blue Dahlstrom, Jin Ho Han, Heather Healy, Maura Kennedy, Glenn Arendts, Jacques Lee, Chris Carpenter, Sangil Lee

Open Access Publications

INTRODUCTION: Delirium is a dangerous syndrome of acute brain dysfunction that is common in the emergency department (ED), especially among the geriatric population. Most systematic reviews of interventions for delirium prevention and treatment have focused on inpatient settings. Best practices of effective delirium care in ED settings have not been established. The primary objective of this study is to identify pharmacologic and non-pharmacologic interventions as applied by physicians, nursing staff, pharmacists and other ED personnel to prevent incident delirium and to shorten the severity and duration of prevalent delirium in a geriatric population within the ED.

METHODS AND ANALYSIS: Searches …

Does The Presence Of Chondral Lesions Negatively Affect Patient-Determined Outcomes After Arthroscopic Rotator Cuff Repair?, Keith M Baumgarten, Peter S Chang, Will E Schweinle

Open Access Publications

Background: There are limited data available to guide patients to their prognosis when glenohumeral chondral lesions are found during arthroscopic rotator cuff repair.

Hypothesis: The primary hypothesis was that patients with glenohumeral chondral lesions will have inferior outcomes after arthroscopic rotator cuff repair compared with patients without chondral lesions. The secondary hypothesis was that patients with concomitant chondral lesions will have more severe preoperative symptoms compared with those without chondral lesions.

Study Design: Cohort study; Level of evidence, 3.

Methods: A retrospective analysis was performed of patients who underwent arthroscopic rotator cuff repair between 2008 and 2012. We examined the …

Classifying Complications: Assessing Adult Spinal Deformity 2-Year Surgical Outcomes, Eric O. Klineberg, Munish Chandra Gupta, Et Al.

Open Access Publications

STUDY DESIGN: Retrospective review of prospective database.

OBJECTIVE: Complication rates for adult spinal deformity (ASD) surgery vary widely because there is no accepted system for categorization. Our objective was to identify the impact of complication occurrence, minor-major complication, and Clavien-Dindo complication classification (Cc) on clinical variables and patient-reported outcomes.

METHODS: Complications in surgical ASD patients with complete baseline and 2-year data were considered intraoperatively, perioperatively (<6 weeks), and postoperatively (>6 weeks). Primary outcome measures were complication timing and severity according to 3 scales: complication presence (yes/no), minor-major, and Cc score. Secondary outcomes were surgical outcomes (estimated blood loss [EBL], length of stay [LOS], …

Spontaneous Restoration Of Functional Β-Cell Mass In Obese Sm/J Mice, Mario A Miranda, Caryn Carson, Celine L St Pierre, Juan F Macias-Velasco, Jing W Hughes, Marcus Kunzmann, Heather Schmidt, Jessica P Wayhart, Heather A Lawson

Open Access Publications

Maintenance of functional β-cell mass is critical to preventing diabetes, but the physiological mechanisms that cause β-cell populations to thrive or fail in the context of obesity are unknown. High fat-fed SM/J mice spontaneously transition from hyperglycemic-obese to normoglycemic-obese with age, providing a unique opportunity to study β-cell adaptation. Here, we characterize insulin homeostasis, islet morphology, and β-cell function during SM/J's diabetic remission. As they resolve hyperglycemia, obese SM/J mice dramatically increase circulating and pancreatic insulin levels while improving insulin sensitivity. Immunostaining of pancreatic sections reveals that obese SM/J mice selectively increase β-cell mass but not α-cell mass. Obese SM/J …

Upper Extremity Pain And Overuse Injuries In Fly-Fishing: A North American Cross-Sectional Survey And Implications For Injury Prevention, Andrew W Kuhn, John E Kuhn

Open Access Publications

Background: Fly-fishing requires rhythmic, coordinated movements to successfully cast a fly line. Previous studies have shown that the biomechanical demands of fly-casting may cause some individuals to develop upper extremity pain or injuries.

Purpose: To report the rates, trends, and contributing factors of upper extremity pain and overuse injuries in a sample of North American recreational fly-fishers.

Study Design: Descriptive epidemiology study.

Methods: Participants were reached via 3 popular online fly-fishing forums in April 2019. Each consenting North American participant over 18 years of age was given a link to a unique survey that recorded his or her demographic and …

Identifying And Validating Subtypes Within Major Psychiatric Disorders Based On Frontal-Posterior Functional Imbalance Via Deep Learning, Miao Chang, Fay Y Womer, Xiaohong Gong, Weixiong Zhang, Et Al

Open Access Publications

Converging evidence increasingly implicates shared etiologic and pathophysiological characteristics among major psychiatric disorders (MPDs), such as schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). Examining the neurobiology of the psychotic-affective spectrum may greatly advance biological determination of psychiatric diagnosis, which is critical for the development of more effective treatments. In this study, ensemble clustering was developed to identify subtypes within a trans-diagnostic sample of MPDs. Whole brain amplitude of low-frequency fluctuations (ALFF) was used to extract the low-dimensional features for clustering in a total of 944 participants: 581 psychiatric patients (193 with SZ, 171 with BD, and 217 …

Economic Evaluation Of The Specialized Donor Care Facility For Thoracic Organ Donor Management, Jason M. Gauthier, Maria B. Majella Doyle, William C. Chapman, Gary Marklin, Chad A. Witt, Elbert P. Trulock, Derek E. Byers, Ramsey R. Hachem, Michael K. Pasque, Bryan F. Meyers, G. Alexander Patterson, Ruben G. Nava, Benjamin D. Kozower, Daniel Kreisel, Su-Hsin Chang, Varun Puri

Open Access Publications

Background: Over the last decade two alternative models of donor care have emerged in the United States: the conventional model, whereby donors are managed at the hospital where brain death occurs, and the specialized donor care facility (SDCF), in which brain dead donors are transferred to a SDCF for medical optimization and organ procurement. Despite increasing use of the SDCF model, its cost-effectiveness in comparison to the conventional model remains unknown.

Methods: We performed an economic evaluation of the SDCF and conventional model of donor care from the perspective of U.S. transplant centers over a 2-year study period. In this …

Genetic Mutations In Young Nonsmoking Patients With Oral Cavity Cancer: A Systematic Review, Rohini R Bahethi, Katelyn O Stepan, Rachel Pinotti, Ryan Li, Nishant Agrawal, Sidharth V Puram, Brett A Miles, Brittany Barber

Open Access Publications

OBJECTIVE: This investigation aims to review the known genetic mutations associated with oral cavity squamous cell carcinoma (OCSCC) in young adults with limited environmental risk factors (YLERs).

DATA SOURCES: A comprehensive search strategy was designed to identify studies in MEDLINE (Ovid), Embase (Ovid), and Scopus from database inception to May 2017 that included adults ≤50 years of age with OCSCC and minimal tobacco use history (≤10 pack-years) who had their tumors genetically sequenced or mutational profiles analyzed.

REVIEW METHODS: Identified articles were screened by 2 reviewers. Quality of evidence was graded by the MINORS criteria for case-control studies; other studies …

Limb Lengthening In The Treatment Of Posteromedial Bowing Of The Tibia, J Eric Gordon, Perry L Schoenecker, Thomas R Lewis, Mark L Miller

Open Access Publications

PURPOSE: Posteromedial bowing of the tibia is an uncommon but recognized congenital lower extremity deformity in children that can lead to limb length discrepancy (LLD) and residual angulatory deformity. The purpose of this study is to report a series of children at a single institution with posteromedial bowing treated by lengthening.

METHODS: A retrospective review was carried out at our institution identifying 16 patients who were treated with limb lengthening for posteromedial bowing of the tibia and followed to skeletal maturity. Projected LLD was a mean of 7.7 cm (range 5.0 cm to 14.2 cm). Three patients were treated in …

Mechanisms Underlying Familial Aggregation Of Exceptional Health And Survival: A Three-Generation Cohort Study, Kaare Christensen, Mary K Wojczynski, Jacob K Pedersen, Lisbeth A Larsen, Susanne Kløjgaard, Axel Skytthe, Matt Mcgue, James W Vaupel, Michael A Province

Open Access Publications

The familial resemblance in length of adult life is very modest. Studies of parent-offspring and twins suggest that exceptional health and survival have a stronger genetic component than lifespan generally. To shed light on the underlying mechanisms, we collected information on Danish long-lived siblings (born 1886-1938) from 659 families, their 5379 offspring (born 1917-1982), and 10,398 grandchildren (born 1950-2010) and matched background population controls through the Danish 1916 Census, the Civil Registration System, the National Patient Register, and the Register of Causes of Death. Comparison with the background, population revealed consistently lower occurrence of almost all disease groups and causes …

High-Resolution Manometry Determinants Of Refractoriness Of Reflux Symptoms To Proton Pump Inhibitor Therapy, Mentore Ribolsi, Edoardo Savarino, Benjamin Rogers, Arvind Rengarajan, Marco Della Coletta, Matteo Ghisa, Michele Cicala, C Prakash Gyawali

Open Access Publications

Background/Aims: Impaired esophageal motility and disrupted esophagogastric junction (EGJ) on high-resolution manometry (HRM) have been associated with increased reflux severity in gastroesophageal reflux disease (GERD) patients. However, there are limited data evaluating HRM parameters in proton pump inhibitors (PPI) non-responders.

Methods: Clinical and endoscopic data, HRM and multichannel intraluminal impedance-pH studies performed of PPI therapy in patients with typical GERD symptoms were reviewed from 3 international centers. Frequency of GERD symptoms was assessed on and off PPI therapy in both non-responders (< 50% symptom improvement on PPI therapy) and responders. Rome IV definitions identified non-erosive reflux disease, reflux hypersensitivity, and functional heartburn. Univariate and multivariate analyses were performed to determine predictors of non-response.

Results: Of 204 patients, 105 were PPI non-responders and 99 were responders. Non-responders showed higher EGJ contractile integral …

Esophageal Baseline Impedance From High-Resolution Impedance Manometry Correlates With Mean Nocturnal Baseline Impedance From Ph-Impedance Monitoring, Anthony Horton, Brian Sullivan, Katie Charles, Thasha Mcintosh, Andrea Davis, Ziad Gellad, Rahul Shimpi, C Prakash Gyawali, Amit Patel

Open Access Publications

Background/Aims: Esophageal baseline impedance (BI) can be extracted from pH-impedance tracings as mean nocturnal baseline impedance (MNBI), and from high-resolution impedance manometry (HRIM), but it is unknown if values are similar between acquisition methods across HRIM manufacturers. We aim to assess correlations between MNBI and BI from HRIM (BI-HRIM) from 2 HRIM manufacturers in the setting of physiologic acid exposure time (AET).

Methods: HRIM and pH-impedance monitoring demonstrating physiologic AET (< 4%) off proton pump inhibitors were required. BI-HRIM was extracted as the average from 5 cm and 10 cm above the lower esophageal sphincter. Distal BI-HRIM (DBI-HRIM) was also extracted from the most distal channel (Medtronic studies). MNBI was extracted from 6 channels. Concordance between BI-HRIM across manufacturers with MNBI was analyzed.

Results: Thirty-six patients met the inclusion criteria (59.6 ± 1.7 years; 22% female; body mass index 30.5 ± 0.7; AET 1.6 ± 0.2%). Although MNBI was similar at all …

Adaptation Of Arginine Synthesis Among Uropathogenic Branches Of The Escherichia Coli Phylogeny Reveals Adjustment To The Urinary Tract Habitat, Michael E Hibbing, Karen W Dodson, Vasilios Kalas, Swaine L Chen, Scott J Hultgren

Open Access Publications

Urinary tract infections (UTIs) are predominantly caused by uropathogenic

Five Years Of Ocrelizumab In Relapsing Multiple Sclerosis: Opera Studies Open-Label Extension, Stephen L Hauser, Robert T Naismith, Et Al

Open Access Publications

OBJECTIVE: To assess over 3 years of follow-up the effects of maintaining or switching to ocrelizumab (OCR) therapy on clinical and MRI outcomes and safety measures in the open-label extension (OLE) phase of the pooled OPERA: I/II studies in relapsing multiple sclerosis.

METHODS: After 2 years of double-blind, controlled treatment, patients continued OCR (600 mg infusions every 24 weeks) or switched from interferon (IFN)-β-1a (44 μg 3 times weekly) to OCR when entering the OLE phase (3 years). Adjusted annualized relapse rate, time to onset of 24-week confirmed disability progression (CDP)/improvement (CDP), brain MRI activity (gadolinium-enhanced and new/enlarging T2 lesions), …

Integrase-Rna Interactions Underscore The Critical Role Of Integrase In Hiv-1 Virion Morphogenesis, Jennifer L. Elliott, Jenna E. Eschbach, Pratibha C. Koneru, Wen Li, Maritza Puray-Chavez, Dana Townsend, Dana Q. Lawson, Alan N. Engelman, Mamuka Kvaratskhelia, Sebla B. Kutluay

Open Access Publications

A large number of human immunodeficiency virus 1 (HIV-1) integrase (IN) alterations, referred to as class II substitutions, exhibit pleiotropic effects during virus replication. However, the underlying mechanism for the class II phenotype is not known. Here we demonstrate that all tested class II IN substitutions compromised IN-RNA binding in virions by one of the three distinct mechanisms: (i) markedly reducing IN levels thus precluding the formation of IN complexes with viral RNA; (ii) adversely affecting functional IN multimerization and consequently impairing IN binding to viral RNA; and (iii) directly compromising IN-RNA interactions without substantially affecting IN levels or functional …

Digenic Variants In The Fgf21 Signaling Pathway Associated With Severe Insulin Resistance And Pseudoacromegaly, Stephen I Stone, Daniel J Wegner, Jennifer A Wambach, F Sessions Cole, Fumihiko Urano, David M Ornitz

Open Access Publications

Insulin-mediated pseudoacromegaly (IMPA) is a rare disease of unknown etiology. Here we report a 12-year-old female with acanthosis nigricans, hirsutism, and acromegalic features characteristic of IMPA. The subject was noted to have normal growth hormone secretion, with extremely elevated insulin levels. Studies were undertaken to determine a potential genetic etiology for IMPA. The proband and her family members underwent whole exome sequencing. Functional studies were undertaken to validate the pathogenicity of candidate variant alleles. Whole exome sequencing identified monoallelic, predicted deleterious variants in genes that mediate fibroblast growth factor 21 (FGF21) signaling,

Incidence Of Uveitis And Macular Edema Among Patients Taking Fingolimod 0.5 Mg For Multiple Sclerosis., Scott Joseph Sonne, Bradley Thomas Smith

Open Access Publications

BACKGROUND: Patients with multiple sclerosis (MS) have a higher incidence of uveitis compared with the general population. Fingolimod, a first line disease modifying drug used in multiple sclerosis, may cause macular edema and thus requires ophthalmic examination. However, murine models and anecdotal reports suggest fingolimod may reduce the incidence of uveitis.

PURPOSE: To report the incidence of uveitis and macular edema among those on fingolimod 0.5 mg (Gilenya®) therapy for multiple sclerosis (MS).

METHODS: Retrospective review of patients on fingolimod who developed uveitis and/or macular edema.

RESULTS: No patients had an occurrence or history of uveitis. Four of the 188 …

Epidemiological Evidence For A Hereditary Contribution To Myasthenia Gravis: A Retrospective Cohort Study Of Patients From North America, Joshua D Green, Julaine Florence, Alan Pestronk, Charlie Wulf, Et Al

Open Access Publications

OBJECTIVES: To approximate the rate of familial myasthenia gravis and the coexistence of other autoimmune disorders in the patients and their families.

DESIGN: Retrospective cohort study.

SETTING: Clinics across North America.

PARTICIPANTS: The study included 1032 patients diagnosed with acetylcholine receptor antibody (AChR)-positive myasthenia gravis.

METHODS: Phenotype information of 1032 patients diagnosed with AChR-positive myasthenia gravis was obtained from clinics at 14 centres across North America between January 2010 and January 2011. A critical review of the epidemiological literature on the familial rate of myasthenia gravis was also performed.

RESULTS: Among 1032 patients, 58 (5.6%) reported a family history of …

Covid-19 Hyperinflammation And Post-Covid-19 Illness May Be Rooted In Mast Cell Activation Syndrome, Lawrence B Afrin, Leonard B Weinstock, Gerhard J Molderings

Open Access Publications

OBJECTIVES: One-fifth of Covid-19 patients suffer a severe course of Covid-19 infection; however, the specific causes remain unclear. Mast cells (MCs) are activated by SARS-CoV-2. Although only recently recognized, MC activation syndrome (MCAS), usually due to acquired MC clonality, is a chronic multisystem disorder with inflammatory and allergic themes, and an estimated prevalence of 17%. This paper describes a novel conjecture explaining how MCAS might cause a propensity for severe acute Covid-19 infection and chronic post-Covid-19 illnesses.

METHODS: Observations of Covid-19 illness in patients with/without MCAS were compared with extensive clinical experience with MCAS.

RESULTS: The prevalence of MCAS is …

Amygdalin Promotes Fracture Healing Through Tgf- Β/Smad Signaling In Mesenchymal Stem Cells, Jun Ying, Jie Shen, Et Al

Open Access Publications

No abstract provided.

Anti-Human Trem2 Induces Microglia Proliferation And Reduces Pathology In An Alzheimer's Disease Model, Shoutang Wang, Carla M. Yuede, Susan Gilfillan, Marco Colonna, Et Al

Open Access Publications

TREM2 is a receptor for lipids expressed in microglia. The R47H variant of human TREM2 impairs ligand binding and increases Alzheimer's disease (AD) risk. In mouse models of amyloid β (Aβ) accumulation, defective TREM2 function affects microglial response to Aβ plaques, exacerbating tissue damage, whereas TREM2 overexpression attenuates pathology. Thus, AD may benefit from TREM2 activation. Here, we examined the impact of an anti-human TREM2 agonistic mAb, AL002c, in a mouse AD model expressing either the common variant (CV) or the R47H variant of TREM2. Single-cell RNA-seq of microglia after acute systemic administration of AL002c showed induction of proliferation in …