Digital Commons Network^™

Sillyputty: Improved Clustering By Optimizing The Silhouette Width, Polina Bombina, Dwayne Tally, Zachary B. Abrams, Kevin R. Coombes

2020-Current year OA Pubs

Clustering is an important task in biomedical science, and it is widely believed that different data sets are best clustered using different algorithms. When choosing between clustering algorithms on the same data set, reseachers typically rely on global measures of quality, such as the mean silhouette width, and overlook the fine details of clustering. However, the silhouette width actually computes scores that describe how well each individual element is clustered. Inspired by this observation, we developed a novel clustering method, called SillyPutty. Unlike existing methods, SillyPutty uses the silhouette width for individual elements as a tool to optimize the mean …

Buffered Lugol's Iodine Preserves Dna Fragment Lengths, P M Gignac, D Valdez, A C Morhardt, L M Lynch

2020-Current year OA Pubs

Museum collections play a pivotal role in the advancement of biological science by preserving phenotypic and genotypic history and variation. Recently, contrast-enhanced X-ray computed tomography (CT) has aided these advances by allowing improved visualization of internal soft tissues. However, vouchered specimens could be at risk if staining techniques are destructive. For instance, the pH of unbuffered Lugol's iodine (I

Stat1 Employs Myeloid Cell-Extrinsic Mechanisms To Regulate The Neutrophil Response And Provide Protection Against Invasive Klebsiella Pneumoniae Lung Infection, Shekina Gonzalez-Ferrer, Zeyu Xiong, Atish Gheware, Janet S Lee, Et Al.

2020-Current year OA Pubs

Klebsiella pneumoniae (KP) is an extracellular Gram-negative bacterium that causes infections in the lower respiratory and urinary tracts and the bloodstream. STAT1 is a master transcription factor that acts to maintain T cell quiescence under homeostatic conditions. Although STAT1 helps defend against systemic spread of acute KP intrapulmonary infection, whether STAT1 regulation of T cell homeostasis impacts pulmonary host defense during acute bacterial infection and injury is less clear. Using a clinical KP respiratory isolate and a pneumonia mouse model, we found that STAT1 deficiency led to an early neutrophil-dominant transcriptional profile and neutrophil recruitment in the lung preceding widespread …

Cep120 Is Essential For Kidney Stromal Progenitor Cell Growth And Differentiation, Ewa Langner, Tao Cheng, Eirini Kefaloyianni, Charles Gluck, Baolin Wang, Moe R Mahjoub

2020-Current year OA Pubs

Mutations in genes that disrupt centrosome structure or function can cause congenital kidney developmental defects and lead to fibrocystic pathologies. Yet, it is unclear how defective centrosome biogenesis impacts renal progenitor cell physiology. Here, we examined the consequences of impaired centrosome duplication on kidney stromal progenitor cell growth, differentiation, and fate. Conditional deletion of the ciliopathy gene Cep120, which is essential for centrosome duplication, in the stromal mesenchyme resulted in reduced abundance of interstitial lineages including pericytes, fibroblasts and mesangial cells. These phenotypes were caused by a combination of delayed mitosis, activation of the mitotic surveillance pathway leading to apoptosis, …

Phosphorylation Regulates Viral Biomolecular Condensates To Promote Infectious Progeny Production, Nicholas Grams, Matthew Charman, Edwin Halko, Richard Lauman, Benjamin A Garcia, Matthew D Weitzman

2020-Current year OA Pubs

Biomolecular condensates (BMCs) play important roles in diverse biological processes. Many viruses form BMCs which have been implicated in various functions critical for the productive infection of host cells. The adenovirus L1-52/55 kilodalton protein (52K) was recently shown to form viral BMCs that coordinate viral genome packaging and capsid assembly. Although critical for packaging, we do not know how viral condensates are regulated during adenovirus infection. Here we show that phosphorylation of serine residues 28 and 75 within the N-terminal intrinsically disordered region of 52K modulates viral condensates in vitro and in cells, promoting liquid-like properties. Furthermore, we demonstrate that …

Characterization And Individual-Level Prediction Of Cognitive State In The First Year After 'Mild' Stroke, Juan Pablo Saa, Tamara Tse, Gerald Choon-Huat Koh, Philip Yap, Carolyn M. Baum, David E. Uribe-Rivera, Saras M. Windecker, Henry Ma, Stephen M. Davis, Geoffrey A. Donnan, Leeanne M. Carey

2020-Current year OA Pubs

BACKGROUND: Mild stroke affects more than half the stroke population, yet there is limited evidence characterizing cognition over time in this population, especially with predictive approaches applicable at the individual-level. We aimed to identify patterns of recovery and the best combination of demographic, clinical, and lifestyle factors predicting individual-level cognitive state at 3- and 12-months after mild stroke.

METHODS: In this prospective cohort study, the Montreal Cognitive Assessment (MoCA) was administered at 3-7 days, 3- and 12-months post-stroke. Raw changes in MoCA and impairment rates (defined as MoCA<24 points) were compared between assessment time-points. Trajectory clusters were identified using variations of ≥1 point in MoCA scores. To further compare clusters, additional assessments administered at 3- and 12-months were included. Gamma and Quantile mixed-effects regression were used to predict individual MoCA scores over time, using baseline clinical and demographic variables. Model predictions were fitted for each stroke survivor and evaluated using model cross-validation to identify the overall best predictors of cognitive recovery.

RESULTS: Participants' (n = 119) MoCA scores improved from baseline to 3-months …

Trauma Patients Have Reduced Ex Vivo Flow-Dependent Platelet Hemostatic Capacity In A Microfluidic Model Of Vessel Injury, Kimberly A. Thomas, Rassam M. G. Rassam, Ronit Kar, Devin M. Dishong, Katelin C. Rahn, Ricardo Fonseca, Melissa Canas, Jose Aldana, Hussain Afzal, Kelly Bochicchio, Matthew D. Neal, Grant V. Bochicchio, Philip C. Spinella, Susan M. Shea

2020-Current year OA Pubs

Trauma is the leading cause of death in individuals up to 45 years of age. Alterations in platelet function are a critical component of trauma-induced coagulopathy (TIC), yet these changes and the potential resulting dysfunction is incompletely understood. The lack of clinical assays available to explore platelet function in this patient population has hindered detailed understanding of the role of platelets in TIC. The objective of this study was to assess trauma patient ex vivo flow-dependent platelet hemostatic capacity in a microfluidic model. We hypothesized that trauma patients would have flow-regime dependent alterations in platelet function. Blood was collected from …

Neurocognitive Outcome In Children With Sickle Cell Disease After Myeloimmunoablative Conditioning And Haploidentical Hematopoietic Stem Cell Transplantation: A Non-Randomized Clinical Trial, Suzanne Braniecki, Shalini Shenoy, Robert C Mckinstry, Et Al.

2020-Current year OA Pubs

BACKGROUND: Due to the risk of cerebral vascular injury, children and adolescents with high-risk sickle cell disease (SCD) experience neurocognitive decline over time. Haploidentical stem cell transplantation (HISCT) from human leukocyte antigen-matched sibling donors may slow or stop progression of neurocognitive changes.

OBJECTIVES: The study is to determine if HISCT can ameliorate SCD-associated neurocognitive changes and prevent neurocognitive progression, determine which specific areas of neurocognitive functioning are particularly vulnerable to SCD, and determine if there are age-related differences in neurocognitive functioning over time.

METHODS: We performed neurocognitive and neuroimaging in SCD recipients following HISCT. Children and adolescents with high-risk SCD …

Negligence In Biomedical Research: An Anti-Racist Approach For Substance Use Researchers, Jonathan Lehman, Danniella Balangoy, Angie P Mejia, Carlos Cardenas-Iniguez, Scott Marek, Anita C Randolph

2020-Current year OA Pubs

Racism is embedded in the fabric of society at structural, disciplinary, hegemonic, and interpersonal levels, working as a mechanism that drives health disparities. In particular, stigmatized views of substance use get entangled with racialization, serving as a tool to uphold oppressive systems. While national health institutions have made commitments to dismantle these systems in the United States, anti-racism has not been integrated into biomedical research practice. The ways in which substance use researchers use and interpret race data-without engaging in structural racism as a mechanism of health inequity-can only be described as inadequate. Drawing upon concepts from the Public Health …

Systematic Computer-Aided Disulfide Design As A General Strategy To Stabilize Prefusion Class I Fusion Proteins, Karen J Gonzalez, Kevin C Yim, Jorge C G Blanco, Marina S Boukhvalova, Eva-Maria Strauch

2020-Current year OA Pubs

Numerous enveloped viruses, such as coronaviruses, influenza, and respiratory syncytial virus (RSV), utilize class I fusion proteins for cell entry. During this process, the proteins transition from a prefusion to a postfusion state, undergoing substantial and irreversible conformational changes. The prefusion conformation has repeatedly shown significant potential in vaccine development. However, the instability of this state poses challenges for its practical application in vaccines. While non-native disulfides have been effective in maintaining the prefusion structure, identifying stabilizing disulfide bonds remains an intricate task. Here, we present a general computational approach to systematically identify prefusion-stabilizing disulfides. Our method assesses the geometric …

Unmet Patient Needs In Monocarboxylate Transporter 8 (Mct8) Deficiency: A Review, Andrew J Bauer, Bethany Auble, Amy L Clark, Tina Y Hu, Amber Isaza, Kyle P Mcnerney, Daniel L Metzger, Lindsey Nicol, Samuel R Pierce, Richard Sidlow

2020-Current year OA Pubs

Monocarboxylate transporter 8 (MCT8) deficiency is a rare, X-linked disorder arising from mutations in the

A Global Scoping Review Of Adaptations In Nurturing Care Interventions During The Covid-19 Pandemic, Lidia Godoi, Simone Schenkman, Ana A Baumann, Aylene Bousquat, Gabriela Buccini

2020-Current year OA Pubs

BACKGROUND: During the COVID-19 pandemic, children faced a disproportionate burden of malnutrition and poor health outcomes. Nurturing care interventions (NCIs) including actions toward good health, adequate nutrition, responsive care, opportunities for early learning, and security and safety are critical for promoting equity. Due to the need for evidence-based responses and preparedness, we analyzed adaptations in NCIs' implementation strategies during COVID-19 according to the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS).

METHOD: We conducted a global scoping review including peer-reviewed and non-peer-reviewed literature. The databases searched were PubMed, Embase, Scopus, BVS, Scielo, and Web of Science. This …

Sexual Dimorphism In Hepatic Ppar Alpha And Cyp4a12a Expression Is Associated With Reduced Development Of Drug-Induced Non-Alcoholic Steatohepatitis In Female Il-33-/- Mice, Chloe Thomas, Dolores B Njoku

2020-Current year OA Pubs

Males are at higher risk for developing metabolic dysfunction-associated steatohepatitis (MASH) than females; however, mechanisms mediating sexual dimorphism in MASH development are not completely understood. Nutrition-based mouse models suggest that dysregulated fatty acid biosynthesis promotes MASH. Drugs recapitulate MASH without diet variabilities. This brief report investigates associations of sexual dimorphism with male susceptibility to MASH utilizing a drug-induced MASH model and focuses on very-long-chain fatty acid biosynthesis pathways. We assessed male and female mouse livers at 5 and 15 weeks following MASH induction by immunizations and age-matched un-immunized controls utilizing Western blot. Our results suggest that PPAR alpha and CYP4a12a …

Recarving The Future: Bridging Car T-Cell Therapy Gaps With Synthetic Biology, Engineering, And Economic Insights, Alaa Ali, John F Dipersio

2020-Current year OA Pubs

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematologic malignancies, offering remarkable remission rates in otherwise refractory conditions. However, its expansion into broader oncological applications faces significant hurdles, including limited efficacy in solid tumors, safety concerns related to toxicity, and logistical challenges in manufacturing and scalability. This review critically examines the latest advancements aimed at overcoming these obstacles, highlighting innovations in CAR T-cell engineering, novel antigen targeting strategies, and improvements in delivery and persistence within the tumor microenvironment. We also discuss the development of allogeneic CAR T cells as off-the-shelf therapies, strategies to mitigate adverse effects, and …

Molecular Characterization Of Gliomas And Glioneuronal Tumors Amid Noonan Syndrome: Cancer Predisposition Examined, Margaret Shatara, Mohamed S Abdelbaki, Et Al

2020-Current year OA Pubs

INTRODUCTION: In the setting of pediatric and adolescent young adult cancer, increased access to genomic profiling has enhanced the detection of genetic variation associated with cancer predisposition, including germline syndromic conditions. Noonan syndrome (NS) is associated with the germline RAS pathway activating alterations and increased risk of cancer. Herein, we describe our comprehensive molecular profiling approach, the association of NS with glioma and glioneuronal tumors, and the clinical and histopathologic characteristics associated with the disease.

METHODS: Within an institutional pediatric cancer cohort (n = 314), molecular profiling comprised of paired somatic disease-germline comparator exome analysis, RNA sequencing, and tumor classification …

Protocol For A Pilot Clinical Trial Of The Senolytic Drug Combination Dasatinib Plus Quercetin To Mitigate Age-Related Health And Cognitive Decline In Mental Disorders [Version 2; Peer Review: 1 Approved, 2 Approved With Reservations], Abigail Schweiger, Breno Diniz, Ginger Nicol, Julie Schweiger, Andes E Dasklakis-Perez, Eric J Lenze

2020-Current year OA Pubs

BACKGROUND: Major depressive disorder (MDD) and schizophrenia are linked to accelerated aging leading to reduced lifespan, health span and cognitive decline. Cellular senescence, in which cells lose proliferative capacity and develop a senescence-associated secretory phenotype (SASP), plays a role in this process. Emerging research suggests that the senolytic regimen of dasatinib+quercetin (D+Q) reduces senescent cells, potentially mitigating age-related health and cognitive decline. This pilot study aims to assess the feasibility and safety of D+Q in older adults with schizophrenia, schizoaffective disorder, and treatment-resistant depression (TRD).

METHODS: This single-center study will recruit 30 participants total aged 50 years or older with …

Sirtuin3 Ensures The Metabolic Plasticity Of Neurotransmission During Glucose Deprivation, Anupama Tiwari, Arsalan Hashemiaghdam, Marissa A Laramie, Dario Maschi, Tristaan Haddad, Marion I Stunault, Carmen Bergom, Ali Javaheri, Vitaly Klyachko, Ghazaleh Ashrafi

2020-Current year OA Pubs

Neurotransmission is an energetically expensive process that underlies cognition. During intense electrical activity or dietary restrictions, the glucose level in the brain plummets, forcing neurons to utilize alternative fuels. However, the molecular mechanisms of neuronal metabolic plasticity remain poorly understood. Here, we demonstrate that glucose-deprived neurons activate the CREB and PGC1α transcriptional program, which induces expression of the mitochondrial deacetylase Sirtuin 3 (Sirt3) both in vitro and in vivo. We show that Sirt3 localizes to axonal mitochondria and stimulates mitochondrial oxidative capacity in hippocampal nerve terminals. Sirt3 plays an essential role in sustaining synaptic transmission in the absence of glucose …

Everything But The Kitchen Sink: An Analysis Of Bacterial And Chemical Contaminants Found In Syringe Residue From People Who Inject Drugs, John A Wildenthal, Drew J Schwartz, Nathanial S Nolan, Lingxia Zhao, John I Robinson, Erin Jones, Raagini Jawa, Jeffrey P Henderson, Laura R Marks

2020-Current year OA Pubs

BACKGROUND: People who inject drugs (PWID) are at high risk of severe wounds, invasive infections, and overdoses. To date, there are few data on the bacterial and chemical contaminants PWID are exposed to when using illicitly manufactured fentanyls and stimulants.

METHODS: Previously used injection drug use equipment was recovered in St Louis, Missouri, by harm reduction organizations over a 12-month period. Syringe residue was analyzed for bacterial contaminants by routine culturing followed by whole genome sequencing of single bacterial isolates. Chemical adulterants in syringe residue were identified by liquid chromatography-mass spectrometry.

RESULTS: Bacteria were cultured from 58.75% of 160 syringes …

Cryptosporidium Infection Of Human Small Intestinal Epithelial Cells Induces Type Iii Interferon And Impairs Infectivity Of Rotavirus, Valentin Greigert, Iti Saraav, Juhee Son, Yinxing Zhu, Denise Dayao, Avan Antia, Saul Tzipori, William H Witola, Thaddeus S Stappenbeck, Siyuan Ding, L David Sibley

2020-Current year OA Pubs

Cryptosporidiosis is a major cause of severe diarrheal disease in infants from resource poor settings. The majority of infections are caused by the human-specific pathogen

Hyperbaric Oxygen Augments Susceptibility To C. Difficile Infection By Impairing Gut Microbiota Ability To Stimulate The Hif-1Α-Il-22 Axis In Ilc3, José L Fachi, Laís P Pral, Helder C Assis, Sarah Oliveira, Vinícius R Rodovalho, Jefferson A C Dos Santos, Mariane F Fernandes, Valquíria A Matheus, Renata Sesti-Costa, Paulo J Basso, Marina Flóro E Silva, Niels O S Câmara, Selma Giorgio, Marco Colonna, Marco A R Vinolo

2020-Current year OA Pubs

Hyperbaric oxygen (HBO) therapy is a well-established method for improving tissue oxygenation and is typically used for the treatment of various inflammatory conditions, including infectious diseases. However, its effect on the intestinal mucosa, a microenvironment known to be physiologically hypoxic, remains unclear. Here, we demonstrated that daily treatment with hyperbaric oxygen affects gut microbiome composition, worsening antibiotic-induced dysbiosis. Accordingly, HBO-treated mice were more susceptible to

Biology Of Childhood Hepatoblastoma And The Search For Novel Treatments, Marjut Pihlajoki, Katja Eloranta, Ruth Nousiainen, Ville Väyrynen, Tea Soini, Antti Kyrönlahti, Seppo Parkkila, Jukka Kanerva, David B. Wilson, Mikko P. Pakarinen, Markku Heikinheimo

2020-Current year OA Pubs

No abstract provided.

Bioactive Glycans In A Microbiome-Directed Food For Children With Malnutrition, Matthew C Hibberd, Daniel M Webber, Suzanne Henrissat, Robert Y Chen, Cyrus Zhou, Hannah M Lynn, Yi Wang, Hao-Wei Chang, Evan M Lee, Janaki Lelwala-Guruge, Ye Chen, Ishita Mostafa, Subhasish Das, Mustafa Mahfuz, Michael J Barratt, Tahmeed Ahmed, Jeffrey I Gordon, Et Al.

2020-Current year OA Pubs

Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition

The Response Of Dual-Leucine Zipper Kinase (Dlk) To Nocodazole: Evidence For A Homeostatic Cytoskeletal Repair Mechanism, Laura Devault, Chase Mateusiak, John Palucki, Michael Brent, Jeffrey Milbrandt, Aaron Diantonio

2020-Current year OA Pubs

Genetic and pharmacological perturbation of the cytoskeleton enhances the regenerative potential of neurons. This response requires Dual-leucine Zipper Kinase (DLK), a neuronal stress sensor that is a central regulator of axon regeneration and degeneration. The damage and repair aspects of this response are reminiscent of other cellular homeostatic systems, suggesting that a cytoskeletal homeostatic response exists. In this study, we propose a framework for understanding DLK mediated neuronal cytoskeletal homeostasis. We demonstrate that low dose nocodazole treatment activates DLK signaling. Activation of DLK signaling results in a DLK-dependent transcriptional signature, which we identify through RNA-seq. This signature includes genes likely …

Arid1a Loss Is Associated With Increased Nrf2 Signaling In Human Head And Neck Squamous Cell Carcinomas, Vinh Nguyen, Travis P. Schrank, Michael B. Major, Bernard E. Weissman

2020-Current year OA Pubs

Prior to the next generation sequencing and characterization of the tumor genome landscape, mutations in the SWI/SNF chromatin remodeling complex and the KEAP1-NRF2 signaling pathway were underappreciated. While these two classes of mutations appeared to independently contribute to tumor development, recent reports have demonstrated a mechanistic link between these two regulatory mechanisms in specific cancer types and cell models. In this work, we expand upon these data by exploring the relationship between mutations in BAF and PBAF subunits of the SWI/SNF complex and activation of NRF2 signal transduction across many cancer types. ARID1A/B mutations were strongly associated with NRF2 transcriptional …

Biopsychosocial Factors Associated With Pain And Pain-Related Outcomes In Adults And Children With Sickle Cell Disease: A Multivariable Analysis Of The Grndad Multicenter Registry, Martha O Kenney, Sana Saif Ur Rehman, Et Al.

2020-Current year OA Pubs

Pain is the primary symptomatic manifestation of sickle cell disease (SCD), an inherited hemoglobinopathy. The characteristics that influence pain experiences and outcomes in SCD are not fully understood. The primary objective of this study was to use multivariable modeling to examine associations of biopsychosocial variables with a disease-specific measure of pain interference known as pain impact. We conducted a secondary analysis of data from the Global Research Network for Data and Discovery national SCD registry. A total of 657 children and adults with SCD were included in the analysis. This sample was 60% female with a median age of 34 …

Beta Cell Primary Cilia Mediate Somatostatin Responsiveness Via Sstr3, Samantha E Adamson, Zipeng A Li, Jing W Hughes

2020-Current year OA Pubs

Somatostatin is a paracrine modulator of insulin secretion and beta cell function with pleotropic effects on glucose homeostasis. The mechanism of somatostatin-mediated communication between delta and beta cells is not well-understood, which we address in this study via the ciliary somatostatin receptor 3 (SSTR3). Primary cilia are membrane organelles that act as signaling hubs in islets by virtue of their subcellular location and enrichment in signaling proteins such as G-protein coupled receptors (GPCRs). We show that SSTR3, a ciliary GPCR, mediates somatostatin suppression of insulin secretion in mouse islets. Quantitative analysis of calcium flux using a mouse model of genetically …

Using Long-Read Cage Sequencing To Profile Cryptic-Promoter-Derived Transcripts And Their Contribution To The Immunopeptidome, Ju Heon Maeng, H Josh Jang, Alan Y Du, Shin-Cheng Tzeng, Ting Wang

2020-Current year OA Pubs

Recent studies have shown that the noncoding genome can produce unannotated proteins as antigens that induce immune response. One major source of this activity is the aberrant epigenetic reactivation of transposable elements (TEs). In tumors, TEs often provide cryptic or alternate promoters, which can generate transcripts that encode tumor-specific unannotated proteins. Thus, TE-derived transcripts (TE transcripts) have the potential to produce tumor-specific, but recurrent, antigens shared among many tumors. Identification of TE-derived tumor antigens holds the promise to improve cancer immunotherapy approaches; however, current genomics and computational tools are not optimized for their detection. Here we combined CAGE technology with …

Single-Pulse Electrical Stimulation Artifact Removal Using The Novel Matching Pursuit-Based Artifact Reconstruction And Removal Method (Mparrm), Tao Xie, Thomas J Foutz, Markus Adamek, James R Swift, Cory S Inman, Joseph R Manns, Eric C Leuthardt, Jon T Willie, Peter Brunner

2020-Current year OA Pubs

No abstract provided.

A Distinct Human Cell Type Expressing Mhcii And Rorγt With Dual Characteristics Of Dendritic Cells And Type 3 Innate Lymphoid Cells, Alina Ulezko Antonova, Changxu Fan, Natalia Jaeger, Patrick Fernandes Rodrigues, Simone Brioschi, Tihana Trsan, José L Fachi, Khai M Nguyen, Ryan M Nunley, Ting Wang, Marina Cella, William Vermi, Marco Colonna, Et Al.

2020-Current year OA Pubs

Recent studies have characterized various mouse antigen-presenting cells (APCs) expressing the lymphoid-lineage transcription factor RORγt (Retinoid-related orphan receptor gamma t), which exhibit distinct phenotypic features and are implicated in the induction of peripheral regulatory T cells (Tregs) and immune tolerance to microbiota and self-antigens. These APCs encompass Janus cells and Thetis cell subsets, some of which express the AutoImmune REgulator (AIRE). RORγt

Genomic Loci Influence Patterns Of Structural Covariance In The Human Brain, Junhao Wen, Aristeidis Sotiras, Daniel S Marcus, Pamela Lamontagne, John C Morris, Et Al.

2020-Current year OA Pubs

Normal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to patterns of structural covariance (PSC) across brain regions and individuals during brain aging and diseases. The genetic underpinnings of these patterns remain largely unknown. We apply a stochastic multivariate factorization method to a diverse population of 50,699 individuals (12 studies and 130 sites) and derive data-driven, multi-scale PSCs of regional brain size. PSCs were significantly correlated with 915 genomic loci in the discovery set, 617 of which are newly identified, and 72% were independently replicated. Key pathways influencing PSCs involve reelin signaling, apoptosis, neurogenesis, and …