Digital Commons Network^™

Quantification Of Enteric Dysfunction In Cystic Fibrosis: Inter- And Intraindividual Variability, Laura A Duckworth, Kimberly A Sutton, Nurmohammad Shaikh, Jinli Wang, Carla Hall-Moore, Lori R Holtz, Phillip I Tarr, Ronald C Rubenstein

2020-Current year OA Pubs

OBJECTIVES: To test the utility of various biomarkers as indicators of gut dysfunction in cystic fibrosis (CF) and determine whether intraindividual variations in these measures are repeatable over short intervals and whether interindividual variations correlate with clinical outcomes.

STUDY DESIGN: We performed a cross-sectional, limited longitudinal study of children with CF aged 1-21 years who provided blood and stool samples at 2 or 3 visits, 2 weeks and 3 months apart, which were assayed for markers of intestinal inflammation (fecal calprotectin [fCal], lipocalin-2 [fLcn2], neopterin), and permeability (plasma lipopolysaccharide [LPS] antibodies, LPS-binding protein) by enzyme immunoassays. Control specimens were obtained …

Assessment Of Bovine Cortical Bone Fracture Behavior Using Impact Microindentation As A Surrogate Of Fracture Toughness, Babak Jahani, Rachana Vaidya, James M Jin, Donald A Aboytes, Kaitlyn S Broz, Siva Krothapalli, Bhanuteja Pujari, Walee M Baig, Simon Y Tang

2020-Current year OA Pubs

The fracture behavior of bone is critically important for evaluating its mechanical competence and ability to resist fractures. Fracture toughness is an intrinsic material property that quantifies a material's ability to withstand crack propagation under controlled conditions. However, properly conducting fracture toughness testing requires the access to calibrated mechanical load frames and the destructive testing of bone samples, and therefore fracture toughness tests are clinically impractical. Impact microindentation mimicks certain aspects of fracture toughness measurements, but its relationship with fracture toughness remains unknown. In this study, we aimed to compare measurements of notched fracture toughness and impact microindentation in fresh …

Bintrafusp Alfa With Ccrt Followed By Bintrafusp Alfa Versus Placebo With Ccrt Followed By Durvalumab In Patients With Unresectable Stage Iii Nsclc: A Phase 2 Randomized Study, Everett E Vokes, Clifford G Robinson, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Preclinical evaluation of bintrafusp alfa (BA) combined with radiotherapy revealed greater antitumor effects than BA or radiotherapy alone. In a phase 1 study, BA exhibited encouraging clinical activity in patients with stage IIIB or IV NSCLC who had received previous treatment.

METHODS: This multicenter, double-blind, controlled phase 2 study (NCT03840902) evaluated the safety and efficacy of BA with concurrent chemoradiotherapy (cCRT) followed by BA (BA group) versus placebo with cCRT followed by durvalumab (durvalumab group) in patients with unresectable stage III NSCLC. The primary end point was progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 …

Control Intervention Design For Preclinical And Clinical Trials: Consensus-Based Core Recommendations From The Third Stroke Recovery And Rehabilitation Roundtable, Kathryn S Hayward, Emily J Dalton, Jessica Barth, Marian Brady, Leora R Cherney, Leonid Churilov, Andrew N Clarkson, Jesse Dawson, Sean P Dukelow, Peter Feys, Maree Hackett, Steve R Zeiler, Catherine E Lang

2020-Current year OA Pubs

Control comparator selection is a critical trial design issue. Preclinical and clinical investigators who are doing trials of stroke recovery and rehabilitation interventions must carefully consider the appropriateness and relevance of their chosen control comparator as the benefit of an experimental intervention is established relative to a comparator. Establishing a strong rationale for a selected comparator improves the integrity of the trial and validity of its findings. This Stroke Recovery and Rehabilitation Roundtable (SRRR) taskforce used a graph theory voting system to rank the importance and ease of addressing challenges during control comparator design. "Identifying appropriate type of control" was …

Integrative Analysis Of Pathogenic Variants In Glucose-6-Phosphatase Based On An Alphafold2 Model, Matt Sinclair, Richard A Stein, Jonathan H Sheehan, Emily M Hawes, Richard M O'Brien, Emad Tajkhorshid, Derek P Claxton

2020-Current year OA Pubs

Mediating the terminal reaction of gluconeogenesis and glycogenolysis, the integral membrane protein glucose-6-phosphate catalytic subunit 1 (G6PC1) regulates hepatic glucose production by catalyzing hydrolysis of glucose-6-phosphate (G6P) within the lumen of the endoplasmic reticulum. Consistent with its vital contribution to glucose homeostasis, inactivating mutations in G6PC1 causes glycogen storage disease (GSD) type 1a characterized by hepatomegaly and severe hypoglycemia. Despite its physiological importance, the structural basis of G6P binding to G6PC1 and the molecular disruptions induced by missense mutations within the active site that give rise to GSD type 1a are unknown. In this study, we determine the atomic interactions …

Machine Learning-Derived Baseline Visual Field Patterns Predict Future Glaucoma Onset In The Ocular Hypertension Treatment Study, Rishabh K Singh, Sophie Smith, John Fingert, Mae Gordon, Michael Kass, Todd Scheetz, Ayellet V Segrè, Janey Wiggs, Tobias Elze, Nazlee Zebardast

2020-Current year OA Pubs

PURPOSE: The Ocular Hypertension Treatment Study (OHTS) identified risk factors for primary open-angle glaucoma (POAG) in patients with ocular hypertension, including pattern standard deviation (PSD). Archetypal analysis, an unsupervised machine learning method, may offer a more interpretable approach to risk stratification by identifying patterns in baseline visual fields (VFs).

METHODS: There were 3272 eyes available in the OHTS. Archetypal analysis was applied using 24-2 baseline VFs, and model selection was performed with cross-validation. Decomposition coefficients for archetypes (ATs) were calculated. A penalized Cox proportional hazards model was implemented to select discriminative ATs. The AT model was compared to the OHTS …

Disease Characteristics, Treatments, And Outcomes Of Patients With Pulmonary Arterial Hypertension Treated With Selexipag In Real-World Settings From The Sphere Registry (Selexipag: The Users Drug Registry), Vallerie Mclaughlin, Harrison W Farber, Kristin B Highland, Anna R Hemnes, Murali M Chakinala, Kelly M Chin, Michelle Han, Michelle Cho, Tobore Tobore, Mohammad Rahman, Nick H Kim

2020-Current year OA Pubs

BACKGROUND: Selexipag is an oral prostacyclin receptor agonist, indicated for pulmonary arterial hypertension to delay disease progression and reduce the risk of pulmonary arterial hypertension-related hospitalization. SelexiPag: tHe usErs dRug rEgistry (NCT03278002) was a US-based, prospective, real-world registry of selexipag-treated patients.

METHODS: Adults with pulmonary hypertension (enrolled 2016-2020) prescribed selexipag were followed for ≤18 months, with data collected at routine clinic visits. Patients were defined as newly or previously initiated if they had started selexipag ≤60 days or >60 days, respectively, before enrollment.

RESULTS: The registry included 829 patients (430 newly initiated, 399 previously initiated; 759 with pulmonary arterial hypertension), …

The Bethesda Ercp Skills Assessment Tool (Besat) Can Reliably Differentiate Endoscopists Of Different Experience Levels, Kevin Liu, Vladimir Kushnir, Et Al.

2020-Current year OA Pubs

No abstract provided.

Creation Of A National Emergency Medicine Medical Education Journal Club, Jessica Pelletier, James Ahn, Andrew Golden, Caroline Astemborski, Michelle D. Lall, Albert Kim, Sara Dimeo

2020-Current year OA Pubs

Background There are a relatively limited number of emergency medicine (EM) medical education (MedEd) fellowships with few trainees at each program, creating barriers to local collaboration and networking. While best practices for developing MedEd journal clubs exist, there has not been an established national EM MedEd journal club. To address this need, we created a national journal club, the Council of Residency Directors (CORD) MedEd Journal Club (MEJC), to facilitate collaboration and networking opportunities by providing a synchronous online journal club. Objectives Our primary objective was to create a network for collaboration across geographical barriers to form a virtual community …

Spatial And Amplitude Dynamics Of Neurostimulation: Insights From The Acute Intrahippocampal Kainate Seizure Mouse Model, Thomas J Foutz, Nicholas Rensing, Lirong Han, Dominique M Durand, Michael Wong

2020-Current year OA Pubs

OBJECTIVE: Neurostimulation is an emerging treatment for patients with drug-resistant epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even after years of empirical optimization. The objective of this study is to determine optimal spatial and amplitude properties of neurostimulation in inhibiting epileptiform activity in an acute hippocampal seizure model.

METHODS: We performed high-throughput testing of high-frequency focal brain stimulation in the acute intrahippocampal kainic acid mouse model of status epilepticus. We evaluated combinations of six anatomic targets and three stimulus amplitudes.

RESULTS: …

Cardiovascular Health Assessment In Routine Cancer Follow-Up In Community Settings: Survivor Risk Awareness And Perspectives, Kathryn E Weaver, Emily V Dressler, Sydney Smith, Chandylen L Nightingale, Heidi D Klepin, Simon Craddock Lee, Brian J Wells, W Gregory Hundley, Joseph A Demari, Sarah N Price, Randi E Foraker

2020-Current year OA Pubs

BACKGROUND: Guidelines recommend cardiovascular risk assessment and counseling for cancer survivors. For effective implementation, it is critical to understand survivor cardiovascular health (CVH) profiles and perspectives in community settings. We aimed to (1) Assess survivor CVH profiles, (2) compare self-reported and EHR-based categorization of CVH factors, and (3) describe perceptions regarding addressing CVH during oncology encounters.

METHODS: This cross-sectional analysis utilized data from an ongoing NCI Community Oncology Research Program trial of an EHR heart health tool for cancer survivors (WF-1804CD). Survivors presenting for routine care after potentially curative treatment recruited from 8 oncology practices completed a pre-visit survey, including …

Basis Of Executive Functions In Fine-Grained Architecture Of Cortical And Subcortical Human Brain Networks, Moataz Assem, Sneha Shashidhara, Matthew F Glasser, John Duncan

2020-Current year OA Pubs

Theoretical models suggest that executive functions rely on both domain-general and domain-specific processes. Supporting this view, prior brain imaging studies have revealed that executive activations converge and diverge within broadly characterized brain networks. However, the lack of precise anatomical mappings has impeded our understanding of the interplay between domain-general and domain-specific processes. To address this challenge, we used the high-resolution multimodal magnetic resonance imaging approach of the Human Connectome Project to scan participants performing 3 canonical executive tasks: n-back, rule switching, and stop signal. The results reveal that, at the individual level, different executive activations converge within 9 domain-general territories …

Reaction Hijacking Inhibition Of Plasmodium Falciparum Asparagine Trna Synthetase, Stanley C Xie, Eva S Istvan, Daniel E Goldberg, Et Al.

2020-Current year OA Pubs

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein …

A Cataract-Causing Mutation In The Trpm3 Cation Channel Disrupts Calcium Dynamics In The Lens, Yuefang Zhou, Thomas M Bennett, Philip A Ruzycki, Zhaohua Guo, Yu-Qing Cao, Mohammad Shahidullah, Nicholas A Delamere, Alan Shiels

2020-Current year OA Pubs

TRPM3 belongs to the melastatin sub-family of transient receptor potential (TRPM) cation channels and has been shown to function as a steroid-activated, heat-sensitive calcium ion (Ca

Enhancing Antibody Responses By Multivalent Antigen Display On Thymus-Independent Dna Origami Scaffolds, Eike-Christian Wamhoff, James Brett Case, Shilpa Sanapala, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Protein-based virus-like particles (P-VLPs) are commonly used to spatially organize antigens and enhance humoral immunity through multivalent antigen display. However, P-VLPs are thymus-dependent antigens that are themselves immunogenic and can induce B cell responses that may neutralize the platform. Here, we investigate thymus-independent DNA origami as an alternative material for multivalent antigen display using the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, the primary target of neutralizing antibody responses. Sequential immunization of mice with DNA-based VLPs (DNA-VLPs) elicits protective neutralizing antibodies to SARS-CoV-2 in a manner that depends on the valency of the antigen displayed and on T …

Complement Receptor 1 Is The Human Erythrocyte Receptor For Plasmodium Vivax Erythrocyte Binding Protein, Seong-Kyun Lee, Cécile Crosnier, Paola Carolina Valenzuela-Leon, Brian L P Dizon, John P Atkinson, Jianbing Mu, Gavin J Wright, Eric Calvo, Karthigayan Gunalan, Louis H Miller

2020-Current year OA Pubs

The discovery that Africans were resistant to infection by

A Quick Recap: Discovering Cryptococcus Neoformans Capsule Mutants, Daphne Boodwa-Ko, Tamara L Doering

2020-Current year OA Pubs

No abstract provided.

Inter- And Intra-Observer Variability Of Radial-Endobronchial Ultrasound Image Interpretation For Peripheral Pulmonary Lesions, Nathaniel Moulton, Daniel B. Abbasi, Danish Ahmad, Nikki E. Burks, Praveen Chenna, Kevin Haas, Andrea Loiselle, Essam Mekhaiel, Mayank R. Pilli, Ali Sadoughi, Brandt Lydon, Tej Patel, Alexander C. Chen

2020-Current year OA Pubs

BACKGROUND: Radial probe endobronchial ultrasound (R-EBUS) is often utilized in guided bronchoscopy for the diagnosis of peripheral pulmonary lesions. R-EBUS probe positioning has been shown to correlate with diagnostic yield, but overall diagnostic yield with this technology has been inconsistent across the published literature. Currently there is no standardization for R-EBUS image interpretation, which may result in variability in grading concentricity of lesions and subsequently procedure performance. This was a survey-based study evaluating variability among practicing pulmonologists in R-EBUS image interpretation.

METHODS: R-EBUS images from peripheral bronchoscopy cases were sent to 10 practicing Interventional Pulmonologists at two different time points …

Clinical Situations For Which 3d Printing Is Considered An Appropriate Representation Or Extension Of Data Contained In A Medical Imaging Examination: Pediatric Congenital Heart Disease Conditions, Justin R Ryan, David Ballard, Et Al.

2020-Current year OA Pubs

BACKGROUND: The use of medical 3D printing (focusing on anatomical modeling) has continued to grow since the Radiological Society of North America's (RSNA) 3D Printing Special Interest Group (3DPSIG) released its initial guideline and appropriateness rating document in 2018. The 3DPSIG formed a focused writing group to provide updated appropriateness ratings for 3D printing anatomical models across a variety of congenital heart disease. Evidence-based- (where available) and expert-consensus-driven appropriateness ratings are provided for twenty-eight congenital heart lesion categories.

METHODS: A structured literature search was conducted to identify all relevant articles using 3D printing technology associated with pediatric congenital heart disease …

Analysis Of Anemia And Iron Supplementation Among Glioblastoma Patients Reveals Sex-Biased Association Between Anemia And Survival, Ganesh Shenoy, Becky Slagle-Webb, Chachrit Khunsriraksakul, Bhavyata Pandya Shesh, Jingqin Luo, Vladimir Khristov, Nataliya Smith, Alireza Mansouri, Brad E Zacharia, Sheldon Holder, Justin D Lathia, Jill S Barnholtz-Sloan, James R Connor

2020-Current year OA Pubs

The association between anemia and outcomes in glioblastoma patients is unclear. We analyzed data from 1346 histologically confirmed adult glioblastoma patients in the TriNetX Research Network. Median hemoglobin and hematocrit levels were quantified for 6 months following diagnosis and used to classify patients as anemic or non-anemic. Associations of anemia and iron supplementation of anemic patients with median overall survival (median-OS) were then studied. Among 1346 glioblastoma patients, 35.9% of male and 40.5% of female patients were classified as anemic using hemoglobin-based WHO guidelines. Among males, anemia was associated with reduced median-OS compared to matched non-anemic males using hemoglobin (HR …

Dorsal Hippocampus To Nucleus Accumbens Projections Drive Reinforcement Via Activation Of Accumbal Dynorphin Neurons, Khairunisa Mohamad Ibrahim, Nicolas Massaly, Hye-Jean Yoon, Rossana Sandoval, Allie J Widman, Robert J Heuermann, Sidney Williams, William Post, Sulan Pathiranage, Tania Lintz, Azra Zec, Ashley Park, Robert W Gereau 4th, Jose A Morón, Et Al.

2020-Current year OA Pubs

The hippocampus is pivotal in integrating emotional processing, learning, memory, and reward-related behaviors. The dorsal hippocampus (dHPC) is particularly crucial for episodic, spatial, and associative memory, and has been shown to be necessary for context- and cue-associated reward behaviors. The nucleus accumbens (NAc), a central structure in the mesolimbic reward pathway, integrates the salience of aversive and rewarding stimuli. Despite extensive research on dHPC→NAc direct projections, their sufficiency in driving reinforcement and reward-related behavior remains to be determined. Our study establishes that activating excitatory neurons in the dHPC is sufficient to induce reinforcing behaviors through its direct projections to the …

Mosaic Loss Of Y Chromosome Is Associated With Aging And Epithelial Injury In Chronic Kidney Disease, Parker C Wilson, Amit Verma, Yasuhiro Yoshimura, Yoshiharu Muto, Haikuo Li, Nicole P Malvin, Eryn E Dixon, Benjamin D Humphreys

2020-Current year OA Pubs

BACKGROUND: Mosaic loss of Y chromosome (LOY) is the most common chromosomal alteration in aging men. Here, we use single-cell RNA and ATAC sequencing to show that LOY is present in the kidney and increases with age and chronic kidney disease.

RESULTS: The likelihood of a cell having LOY varies depending on its location in the nephron. Cortical epithelial cell types have a greater proportion of LOY than medullary or glomerular cell types, which may reflect their proliferative history. Proximal tubule cells are the most abundant cell type in the cortex and are susceptible to hypoxic injury. A subset of …

Venovenous Extracorporeal Membrane Oxygenation After Cardiac Arrest For Acute Respiratory Distress Syndrome Caused By Legionella: A Case Report, John C Grotberg, Linda Schulte, Erin Schumer, Mary Sullivan, Kunal Kotkar, Mohammad F Masood, Amit Pawale

2020-Current year OA Pubs

BACKGROUND: Legionella remains underdiagnosed in the intensive care unit and can progress to acute respiratory distress syndrome (ARDS), multiorgan failure and death. In severe cases, venovenous extracorporeal membrane oxygenation (VV-ECMO) allows time for resolution of disease with Legionella-targeted therapy. VV-ECMO outcomes for Legionella are favorable with reported survival greater than 70%. Rapid molecular polymerase chain reaction (PCR) testing of the lower respiratory tract aids in diagnosing Legionella with high sensitivity and specificity. We present a unique case of a patient with a positive COVID-19 test and ARDS who suffered a cardiac arrest. The patient was subsequently cannulated for VV-ECMO, and …

Reviewing The Clostridioides Difficile Mouse Model: Insights Into Infection Mechanisms, José L Fachi, Marco A R Vinolo, Marco Colonna

2020-Current year OA Pubs

No abstract provided.

Association Of Genetic Variation In Col11a1 With Adolescent Idiopathic Scoliosis, Hao Yu, Lilian Antunes, Christina A Gurnett, Et Al.

2020-Current year OA Pubs

Adolescent idiopathic scoliosis (AIS) is a common and progressive spinal deformity in children that exhibits striking sexual dimorphism, with girls at more than fivefold greater risk of severe disease compared to boys. Despite its medical impact, the molecular mechanisms that drive AIS are largely unknown. We previously defined a female-specific AIS genetic risk locus in an enhancer near the

Tempo And Mode Of Gene Expression Evolution In The Brain Across Primates, Katherine Rickelton, Trisha M Zintel, Jason Pizzollo, Emily Miller, John J Ely, Mary Ann Raghanti, William D Hopkins, Patrick R Hof, Chet C Sherwood, Amy L Bauernfeind, Courtney C Babbitt

2020-Current year OA Pubs

Primate evolution has led to a remarkable diversity of behavioral specializations and pronounced brain size variation among species (Barton, 2012; DeCasien and Higham, 2019; Powell et al., 2017). Gene expression provides a promising opportunity for studying the molecular basis of brain evolution, but it has been explored in very few primate species to date (e.g. Khaitovich et al., 2005; Khrameeva et al., 2020; Ma et al., 2022; Somel et al., 2009). To understand the landscape of gene expression evolution across the primate lineage, we generated and analyzed RNA-seq data from four brain regions in an unprecedented eighteen species. Here, we …

Gliopredictor: A Deep Learning Model For Identification Of High-Risk Adult Idh-Mutant Glioma Towards Adjuvant Treatment Planning, Shuhua Zheng, Nikhil Rammohan, Timothy Sita, P Troy Teo, Yilin Wu, Maciej Lesniak, Sean Sachdev, Tarita O Thomas

2020-Current year OA Pubs

Identification of isocitrate dehydrogenase (IDH)-mutant glioma patients at high risk of early progression is critical for radiotherapy treatment planning. Currently tools to stratify risk of early progression are lacking. We sought to identify a combination of molecular markers that could be used to identify patients who may have a greater need for adjuvant radiation therapy machine learning technology. 507 WHO Grade 2 and 3 glioma cases from The Cancer Genome Atlas, and 1309 cases from AACR GENIE v13.0 datasets were studied for genetic disparities between IDH1-wildtype and IDH1-mutant cohorts, and between different age groups. Genetic features such as mutations and …

Comparative And Integrative Single Cell Analysis Reveals New Insights Into The Transcriptional Immaturity Of Stem Cell-Derived Β Cells, Mason D Schmidt, Matthew Ishahak, Punn Augsornworawat, Jeffrey R Millman

2020-Current year OA Pubs

Diabetes cell replacement therapy has the potential to be transformed by human pluripotent stem cell-derived β cells (SC-β cells). However, the precise identity of SC-β cells in relationship to primary fetal and adult β-cells remains unclear. Here, we used single-cell sequencing datasets to characterize the transcriptional identity of islets from in vitro differentiation, fetal islets, and adult islets. Our analysis revealed that SC-β cells share a core β-cell transcriptional identity with human adult and fetal β-cells, however SC-β cells possess a unique transcriptional profile characterized by the persistent expression and activation of progenitor and neural-biased gene networks. These networks are …

Neuronal Deletion Of The Circadian Clock Gene Bmal1 Induces Cell-Autonomous Dopaminergic Neurodegeneration, Michael K. Kanan, Patrick W. Sheehan, Jessica N. Haines, Pedro G. Gomez, Adya Dhuler, Collin J. Nadarajah, Zachary M. Wargel, Brittany M. Freeberg, Hemanth R. Nelvagal, Mariko Izumo, Joseph S. Takahashi, Jonathan D. Cooper, Albert A. Davis, Erik S. Musiek

2020-Current year OA Pubs

Circadian rhythm dysfunction is a hallmark of Parkinson disease (PD), and diminished expression of the core clock gene Bmal1 has been described in patients with PD. BMAL1 is required for core circadian clock function but also serves nonrhythmic functions. Germline Bmal1 deletion can cause brain oxidative stress and synapse loss in mice, and it can exacerbate dopaminergic neurodegeneration in response to the toxin MPTP. Here we examined the effect of cell type-specific Bmal1 deletion on dopaminergic neuron viability in vivo. We observed that global, postnatal deletion of Bmal1 caused spontaneous loss of tyrosine hydroxylase+ (TH+) dopaminergic neurons in the substantia …

Targeting Efferocytosis In Inflammaging, Ivan K H Poon, Kodi S Ravichandran

2020-Current year OA Pubs

Rapid removal of apoptotic cells by phagocytes, a process known as efferocytosis, is key for the maintenance of tissue homeostasis, the resolution of inflammation, and tissue repair. However, impaired efferocytosis can result in the accumulation of apoptotic cells, subsequently triggering sterile inflammation through the release of endogenous factors such as DNA and nuclear proteins from membrane permeabilized dying cells. Here, we review the molecular basis of the three key phases of efferocytosis, that is, the detection, uptake, and degradation of apoptotic materials by phagocytes. We also discuss how defects in efferocytosis due to the alteration of phagocytes and dying cells …