Digital Commons Network^™

Timing Of Medicaid Enrollment, Late-Stage Breast Cancer Diagnosis, Treatment Delays, And Mortality, Evaline Xie, Graham A Colditz, Min Lian, Tracy Greever-Rice, Chester Schmaltz, Jill Lucht, Ying Liu

2020-Current year OA Pubs

BACKGROUND: Disrupted and delayed Medicaid coverage has been consistently associated with lower rates of cancer screening and early-stage cancer diagnosis compared with continuous coverage. However, the relationships between Medicaid coverage timing, breast cancer treatment delays, and survival are less clear.

METHODS: Using the linked Missouri Cancer Registry-Medicaid claims data, we identified 4583 women diagnosed with breast cancer between 2007 and 2016. We used logistic regression to estimate odds ratios (ORs) of late-stage diagnosis and treatment delays for prediagnosis (>30 days, >90 days, and >1 year before diagnosis) vs peridiagnosis enrollment. Cox proportional hazards models were used to estimate the …

A Novel Methodological Approach To Simultaneously Extract High-Quality Total Rna And Proteins From Cortical And Trabecular Bone, Martina Faraldi, Laura Mangiavini, Caterina Conte, Giuseppe Banfi, Nicola Napoli, Giovanni Lombardi

Open Access Publications

Molecular differences between cortical and trabecular bone, of relevance to understanding the pathophysiological basis of bone diseases, can be determined only through effective isolation methods for RNA and proteins. Here we present a TRIzol-based method, which combines bone pulverization and homogenization to extract simultaneously total RNA and proteins from human cortical and trabecular bone from the same carrot. RNA integrity and purity were determined as the 260/280 nm and 260/230 nm absorbance ratios and the 28S/18S rRNA ratio. Protein integrity and quality were evaluated by Coomassie blue staining. Reverse transcription quantitative polymerase chain reaction and immunoblotting for bone-specific genes and …

H3k36 Dimethylation Shapes The Epigenetic Interaction Landscape By Directing Repressive Chromatin Modifications In Embryonic Stem Cells, Haifen Chen, Bo Hu, Cynthia Horth, Eric Bareke, Phillip Rosenbaum, Sin Young Kwon, Jacinthe Sirois, Daniel N Weinberg, Faith M Robison, Benjamin A Garcia, Chao Lu, William A Pastor, Jacek Majewski

Open Access Publications

Epigenetic modifications on the chromatin do not occur in isolation. Chromatin-associated proteins and their modification products form a highly interconnected network, and disturbing one component may rearrange the entire system. We see this increasingly clearly in epigenetically dysregulated cancers. It is important to understand the rules governing epigenetic interactions. Here, we use the mouse embryonic stem cell (mESC) model to describe in detail the relationships within the H3K27-H3K36-DNA methylation subnetwork. In particular, we focus on the major epigenetic reorganization caused by deletion of the histone 3 lysine 36 methyltransferase NSD1, which in mESCs deposits nearly all of the intergenic H3K36me2. …

Sars-Cov-2 Infection And Covid-19 Outcomes In Rheumatic Diseases: A Systematic Literature Review And Meta-Analysis, Richard Conway, Alfred H J Kim, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The relative risk of SARS-CoV-2 infection and COVID-19 disease severity among people with rheumatic and musculoskeletal diseases (RMDs) compared to those without RMDs is unclear. This study was undertaken to quantify the risk of SARS-CoV-2 infection in those with RMDs and describe clinical outcomes of COVID-19 in these patients.

METHODS: We conducted a systematic literature review using 14 databases from January 1, 2019 to February 13, 2021. We included observational studies and experimental trials in RMD patients that described comparative rates of SARS-CoV-2 infection, hospitalization, oxygen supplementation/intensive care unit (ICU) admission/mechanical ventilation, or death attributed to COVID-19. Methodologic quality …

The Clinical Cell-Cycle Risk (Ccr) Score Is Associated With Metastasis After Radiation Therapy And Provides Guidance On When To Forgo Combined Androgen Deprivation Therapy With Dose-Escalated Radiation, Jonathan Tward, Hiram A. Gay, Jeff Michalski, Et Al.

2020-Current year OA Pubs

PURPOSE: The clinical cell-cycle risk (CCR) score, which combines the University of California, San Francisco's Cancer of the Prostate Risk Assessment (CAPRA) and the cell cycle progression (CCP) molecular score, has been validated to be prognostic of disease progression for men with prostate cancer. This study evaluated the ability of the CCR score to prognosticate the risk of metastasis in men receiving dose-escalated radiation therapy (RT) with or without androgen deprivation therapy (ADT).

METHODS AND MATERIALS: This retrospective, multi-institutional cohort study included men with localized National Comprehensive Cancer Network (NCCN) intermediate-, high-, and very high-risk prostate cancer (N = 741). …

Bisphenol A Exposure Induces Sensory Processing Deficits In Larval Zebrafish During Neurodevelopment, Courtney Scaramella, Joseph B Alzagatiti, Christopher Creighton, Samandeep Mankatala, Fernando Licea, Gabriel M Winter, Jasmine Emtage, Joseph R Wisnieski, Luis Salazar, Anjum Hussain, Faith M Lee, Asma Mammootty, Niyaza Mammootty, Andrew Aldujaili, Kristine A Runnberg, Daniela Hernandez, Trevor Zimmerman-Thompson, Rikhil Makwana, Julien Rouvere, Zahra Tahmasebi, Gohar Zavradyan, Christopher S Campbell, Meghna Komaranchath, Javier Carmona, Jennifer Trevitt, David Glanzman, Adam C Roberts

2020-Current year OA Pubs

Because of their

Effect Of Active And Passive Function Of The Posterosuperior Rotator Cuff On Compensatory Muscle Loads In The Shoulder, Philipp Moroder, Aaron Chamberlain, Stefan M Gabriel, Marc C Jacofsky, Mehmet Z Sengun, David B Spenciner, John M Tokish, Lucca Lacheta

Open Access Publications

Background: Irreparable posterosuperior rotator cuff (PSRC) tears have been shown to result in shoulder pain and loss of function.

Purpose/Hypothesis: The purpose of this study was to determine the effect of the loss of active or passive function of the PSRC on compensatory muscle loads in the deltoid and the remaining rotator cuff. It was hypothesized that both deactivation and resection of the PSRC would result in load increases in the remaining muscles and that resection of the PSRC would result in even higher required compensatory forces than would mere deactivation.

Study Design: Controlled laboratory study.

Methods: A total of …

Immunotherapy-Induced Auto-Splenectomy In A Patient Of Malignant Melanoma, Syed Ehsanullah, Azharuddin Muhammad, Syed Hasan, John M. Richart

Open Access Publications

Immune checkpoint inhibitors like programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are biological agents that help in boosting the immune system of the body to fight against cancer cells. These checkpoint inhibitors are now being approved by the Food and Drug Administration (FDA) to treat various malignancies due to remarkable response. Here, we present a rare immune-related adverse event in a 77-year-old female with metastatic melanoma treated with ipilimumab and nivolumab, later presented with auto-splenectomy.

Veliparib Plus Carboplatin And Paclitaxel Versus Investigator's Choice Of Standard Chemotherapy In Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer, Ramaswamy Govindan, Et Al

2020-Current year OA Pubs

BACKGROUND: This open-label Phase III trial (NCT02264990) evaluated the PARP inhibitor, veliparib, combined with carboplatin/paclitaxel versus chemotherapy alone for first-line treatment of patients with advanced non-squamous non-small cell lung cancers (NSCLC). A 52-gene expression classifier (LP52) previously shown to identify patients more likely to respond to veliparib was evaluated as a planned correlative analysis.

MATERIALS AND METHODS: Adult current or former smokers with advanced non-squamous NSCLC were randomized 1:1 to veliparib (120 mg daily for 7 days/cycle) with carboplatin and paclitaxel or to investigators' choice of platinum doublet chemotherapy (up to 6, 21-day cycles), with optional pemetrexed maintenance. Prospective analysis …

The Heritage Family Study: A Review Of The Effects Of Exercise Training On Cardiometabolic Health, With Insights Into Molecular Transducers, Mark A Sarzynski, Treva K Rice, D C Rao, Et Al

2020-Current year OA Pubs

The aim of the HERITAGE Family Study was to investigate individual differences in response to a standardized endurance exercise program, the role of familial aggregation, and the genetics of response levels of cardiorespiratory fitness and cardiovascular disease and diabetes risk factors. Here we summarize the findings and their potential implications for cardiometabolic health and cardiorespiratory fitness. It begins with overviews of background and planning, recruitment, testing and exercise program protocol, quality control measures, and other relevant organizational issues. A summary of findings is then provided on cardiorespiratory fitness, exercise hemodynamics, insulin and glucose metabolism, lipid and lipoprotein profiles, adiposity and …

Bone Metastases In Non-Small Cell Lung Cancer: A Narrative Review, Brendan J. Knapp, Siddhartha Devarakonda, Ramaswamy Govindan

2020-Current year OA Pubs

Background and Objective: Bone metastases are common in patients with non-small cell lung cancer (NSCLC) and remain a significant source of morbidity, mortality, and diminished quality of life, despite the considerable progress made in the overall management of patients with metastatic NSCLC over the last decade. Understanding the molecular pathogenesis of bone metastases is critical to improving survival, preserving function, and managing symptoms in this patient population. The objective of our review is to provide a comprehensive review of the pathophysiology, clinical presentation, management, and factors predicting the development and prognosis of patients with NSCLC with bone metastases.

Methods: An …

Hold That Pose: Capturing Cervical Dystonia's Head Deviation Severity From Video, Zheng Zhang, Joel S Perlmutter, Et Al

2020-Current year OA Pubs

OBJECTIVE: Deviated head posture is a defining characteristic of cervical dystonia (CD). Head posture severity is typically quantified with clinical rating scales such as the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Because clinical rating scales are inherently subjective, they are susceptible to variability that reduces their sensitivity as outcome measures. The variability could be circumvented with methods to measure CD head posture objectively. However, previously used objective methods require specialized equipment and have been limited to studies with a small number of cases. The objective of this study was to evaluate a novel software system-the Computational Motor Objective Rater …

Physician-Scientists In The United States At 2020: Trends And Concerns, Howard H Garrison, Timothy J Ley

2020-Current year OA Pubs

Physician-scientists comprise a unique and valuable part of the biomedical workforce, but for decades there has been concern about the number of physicians actively engaged in research. Reports have outlined the challenges facing physician-scientists, and programs have been initiated to encourage and facilitate research careers for medically trained scientists. Many of these initiatives have demonstrated successful outcomes, but there has not been a recent summary of the impact of the past decade of effort. This report compiles available data from surveys of medical education and physician research participation to assess changes in the physician-scientist workforce from 2011-2020. Several trends are …

Characteristics, Treatment, And Control Of Hypertension In Public Primary Healthcare Centers In Nigeria: Baseline Results From The Hypertension Treatment In Nigeria Program, Dike B Ojji, Mark D Huffman, Et Al

2020-Current year OA Pubs

BACKGROUND: There are limited data on large-scale, multilevel implementation research studies to improve hypertension diagnosis, treatment, and control rates at the primary healthcare (PHC) level in Africa. We describe the characteristics, treatment, and control rates of patients with hypertension in public PHC centers in the Hypertension Treatment in Nigeria Program.

METHODS: Data were collected from adults at least 18 years at 60 public PHC centers between January 2020 and November 2020. Hypertension treatment rates were calculated at registration and upon completion of the initial visit. Hypertension control rates were calculated based on SBP and DBPs less than 140/90 mmHg. Regression …

Functional Analysis Of A Novel De Novo Variant In Ppp5c Associated With Microcephaly, Seizures, And Developmental Delay, Sara M Fielder, Jill A Rosenfeld, Lindsay C Burrage, Lisa Emrick, Seema Lalani, Ruben Attali, Joshua N Bembenek, Hieu Hoang, Dustin Baldridge, Gary A Silverman, Undiagnosed Diseases Network, Tim Schedl, Stephen C Pak

2020-Current year OA Pubs

We describe a proband evaluated through the Undiagnosed Diseases Network (UDN) who presented with microcephaly, developmental delay, and refractory epilepsy with a de novo p.Ala47Thr missense variant in the protein phosphatase gene, PPP5C. This gene has not previously been associated with a Mendelian disease, and based on the population database, gnomAD, the gene has a low tolerance for loss-of-function variants (pLI = 1, o/e = 0.07). We functionally evaluated the PPP5C variant in C. elegans by knocking the variant into the orthologous gene, pph-5, at the corresponding residue, Ala48Thr. We employed assays in three different biological processes where pph-5 was …

Anxiety Symptoms Among Patients With Systemic Lupus Erythematosus Persist Over Time And Are Independent Of Sle Disease Activity, Daphne Lew, Xinliang Huang, Sara R Kellahan, Hong Xian, Seth Eisen, Alfred H J Kim

2020-Current year OA Pubs

OBJECTIVE: The objectives of this study are to identify patterns of anxiety symptomology over time among patients with systemic lupus erythematosus (SLE) and to assess the longitudinal relationship between SLE disease activity and anxiety symptomology.

METHODS: Longitudinal data from 139 patients with American College of Rheumatology or Systemic Lupus International Collborating Clinic (SLICC)-classified SLE were analyzed. Anxiety symptomology was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Emotional Distress: Anxiety Short Form 8a. SLE disease activity was measured using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2000 (S2K) and S2K Responder Index 50 (S2K RI-50). Group-based trajectory modeling (GBTM) …

Targeted Treatment For High-Risk Early-Stage Triple-Negative Breast Cancer: Spotlight On Pembrolizumab, Nusayba A Bagegni, Andrew A Davis, Katherine K Clifton, Foluso O Ademuyiwa

Open Access Publications

Triple-negative breast cancer (TNBC) is a biologically aggressive yet heterogeneous disease that disproportionately affects younger women and women of color compared to other breast cancer subtypes. The paucity of effective targeted therapies and the prevalence of chemotherapeutic resistance in high-risk, early-stage TNBC pose significant clinical challenges. Deeper insights into the genomic and immune landscape have revealed key features of TNBC, including intrinsic genomic instability, DNA repair deficiency, and potentially an immunogenic tumor microenvironment. These advances led to landmark trials with immune checkpoint inhibitors in the advanced-stage setting, which subsequently translated into immunotherapy-based clinical trials in the early-stage setting and recent …

Risk Factors For Severe Covid-19 Differ By Age For Hospitalized Adults, Sevda Molani, Patricia V Hernandez, Ryan T Roper, Venkata R Duvvuri, Andrew M Baumgartner, Jason D Goldman, Nilüfer Ertekin-Taner, Cory C Funk, Nathan D Price, Noa Rappaport, Jennifer J Hadlock

Open Access Publications

Risk stratification for hospitalized adults with COVID-19 is essential to inform decisions about individual patients and allocation of resources. So far, risk models for severe COVID outcomes have included age but have not been optimized to best serve the needs of either older or younger adults. Models also need to be updated to reflect improvements in COVID-19 treatments. This retrospective study analyzed data from 6906 hospitalized adults with COVID-19 from a community health system across five states in the western United States. Risk models were developed to predict mechanical ventilation illness or death across one to 56 days of hospitalization, …

Thermodynamically Coupled Biosensors For Detecting Neutralizing Antibodies Against Sars-Cov-2 Variants, Jason Z Zhang, Laura A Vanblargan, Michael S Diamond, Et Al.

2020-Current year OA Pubs

We designed a protein biosensor that uses thermodynamic coupling for sensitive and rapid detection of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in serum. The biosensor is a switchable, caged luciferase-receptor-binding domain (RBD) construct that detects serum-antibody interference with the binding of virus RBD to angiotensin-converting enzyme 2 (ACE-2) as a proxy for neutralization. Our coupling approach does not require target modification and can better distinguish sample-to-sample differences in analyte binding affinity and abundance than traditional competition-based assays.

A Cryptic Pocket In Ebola Vp35 Allosterically Controls Rna Binding, Matthew A Cruz, Thomas E Frederick, Upasana L Mallimadugula, Sukrit Singh, Neha Vithani, Maxwell I Zimmerman, Justin R Porter, Katelyn E Moeder, Gaya K Amarasinghe, Gregory R Bowman

Open Access Publications

Protein-protein and protein-nucleic acid interactions are often considered difficult drug targets because the surfaces involved lack obvious druggable pockets. Cryptic pockets could present opportunities for targeting these interactions, but identifying and exploiting these pockets remains challenging. Here, we apply a general pipeline for identifying cryptic pockets to the interferon inhibitory domain (IID) of Ebola virus viral protein 35 (VP35). VP35 plays multiple essential roles in Ebola's replication cycle but lacks pockets that present obvious utility for drug design. Using adaptive sampling simulations and machine learning algorithms, we predict VP35 harbors a cryptic pocket that is allosterically coupled to a key …

Circadian Pacemaker Neurons Display Cophasic Rhythms In Basal Calcium Level And In Fast Calcium Fluctuations, Xitong Liang, Timothy E Holy, Paul H Taghert

Open Access Publications

SignificanceDaily rhythms in the molecular clock, in calcium, and in electrical activity all interact to support the functions of circadian pacemaker neurons. However, the regulatory mechanisms that unify these properties are not defined. Here, we utilize the cellular resolution of the

Oncogenic Kras-Mediated Cytokine Ccl15 Regulates Pancreatic Cancer Cell Migration And Invasion Through Ros, Justin K Messex, Kiyah L A Adams, William G Hawkins, David Denardo, Nabeel Bardeesy, Daniel D Billadeau, Geou-Yarh Liou

Open Access Publications

Pancreatic ductal adenocarcinoma (PDAC) is well known for its high death rate due to prompt cancer metastasis caused by cancer cell migration and invasion within the early stages of its development. Here, we reveal a new function of cytokine CCL15, namely the upregulation of PDAC cell migration and invasion. We showed increased levels of CCL15 transcripts and protein expressions in human PDAC tissue samples, as well as in cultured cell lines. Furthermore, PDAC cells also expressed CCL15 receptors, including CCR1 and CCR3. Murine PDAC cell lines and tissues strengthened this finding. The manipulation of CCL15 in metastatic Panc-1 cells through …

Combining Plasma Extracellular Vesicle Let-7b-5p, Mir-184 And Circulating Mir-22-3p Levels For Nsclc Diagnosis And Drug Resistance Prediction, G P Vadla, B Daghat, N Patterson, V Ahmad, G Perez, A Garcia, Y Manjunath, J T Kaifi, G Li, C Y Chabu

Open Access Publications

Low-dose computed tomography (LDCT) Non-Small Cell Lung (NSCLC) screening is associated with high false-positive rates, leading to unnecessary expensive and invasive follow ups. There is a need for minimally invasive approaches to improve the accuracy of NSCLC diagnosis. In addition, NSCLC patients harboring sensitizing mutations in epidermal growth factor receptor EGFR (T790M, L578R) are treated with Osimertinib, a potent tyrosine kinase inhibitor (TKI). However, nearly all patients develop TKI resistance. The underlying mechanisms are not fully understood. Plasma extracellular vesicle (EV) and circulating microRNA (miRNA) have been proposed as biomarkers for cancer screening and to inform treatment decisions. However, the …

A Somatic Mutation In Moesin Drives Progression Into Acute Myeloid Leukemia, Ouyang Yuan, Jeffrey A Magee, Et Al.

Open Access Publications

Acute myeloid leukemia (AML) arises when leukemia-initiating cells, defined by a primary genetic lesion, acquire subsequent molecular changes whose cumulative effects bypass tumor suppression. The changes that underlie AML pathogenesis not only provide insights into the biology of transformation but also reveal novel therapeutic opportunities. However, backtracking these events in transformed human AML samples is challenging, if at all possible. Here, we approached this question using a murine in vivo model with an MLL-ENL fusion protein as a primary molecular event. Upon clonal transformation, we identified and extensively verified a recurrent codon-changing mutation (Arg

Cisplatin Resistance Can Be Curtailed By Blunting Bnip3-Mediated Mitochondrial Autophagy, Caterina Vianello, Gerald W Dorn 2nd, Et Al

Open Access Publications

Cisplatin (CDDP) is commonly used to treat a multitude of tumors including sarcomas, ovarian and cervical cancers. Despite recent investigations allowed to improve chemotherapy effectiveness, the molecular mechanisms underlying the development of CDDP resistance remain a major goal in cancer research. Here, we show that mitochondrial morphology and autophagy are altered in different CDDP resistant cancer cell lines. In CDDP resistant osteosarcoma and ovarian carcinoma, mitochondria are fragmented and closely juxtaposed to the endoplasmic reticulum; rates of mitophagy are also increased. Specifically, levels of the mitophagy receptor BNIP3 are higher both in resistant cells and in ovarian cancer patient samples …

The Geriatric Emergency Care Applied Research (Gear) Network Approach: A Protocol To Advance Stakeholder Consensus And Research Priorities In Geriatrics And Dementia Care In The Emergency Department, Ula Hwang, Christopher Carpenter, Scott Dresden, Jeffrey Dussetschleger, Angela Gifford, Ly Hoang, Jesseca Leggett, Armin Nowroozpoor, Zachary Taylor, Manish Shah, The Gear And Gear 2.0 Networks

Open Access Publications

INTRODUCTION: Increasingly, older adults are turning to emergency departments (EDs) to address healthcare needs. To achieve these research demands, infrastructure is needed to both generate evidence of intervention impact and advance the development of implementation science, pragmatic trials evaluation and dissemination of findings from studies addressing the emergency care needs of older adults. The Geriatric Emergency Care Applied Research Network (https://gearnetwork.org) has been created in response to these scientific needs-to build a transdisciplinary infrastructure to support the research that will optimise emergency care for older adults and persons living with dementia.

METHODS AND ANALYSIS: In this paper, we describe our …

Development And Validation Of A Novel Anaerobic Carbapenem Inactivation Method (Ana-Cim) For The Detection Of Carbapenemase Production In Bacteroides Fragilis, Allison R Eberly, Meghan A Wallace, Samantha Shannon, Angela K Heitman, Audrey N Schuetz, Carey-Ann D Burnham, Sophonie Jean

Open Access Publications

Antibiotic resistance, particularly to carbapenems, is of increasing concern in Bacteroides fragilis. Carbapenem resistance in B. fragilis is most often mediated by the activation of chromosomally encoded metallo-β-lactamase

A Proposed Role For Interactions Between Argonautes, Mirisc, And Rna Binding Proteins In The Regulation Of Local Translation In Neurons And Glia, Sarah K Koester, Joseph D Dougherty

2020-Current year OA Pubs

The first evidence of local translation in the CNS appeared nearly 40 years ago, when electron microscopic studies showed polyribosomes localized to the base of dendritic spines. Since then, local translation has been established as an important regulatory mechanism for gene expression in polarized or functionally compartmentalized cells. While much attention has been placed on characterizing the local transcriptome and regulatory "grammar" directing mRNA localization in neurons and glia, less is understood about how these cells subsequently de-repress mRNA translation in their peripheral processes to produce a rapid translational response to stimuli. MicroRNA-mediated translation regulation offers a possible solution to …

Calgb 40603 (Alliance): Long-Term Outcomes And Genomic Correlates Of Response And Survival After Neoadjuvant Chemotherapy With Or Without Carboplatin And Bevacizumab In Triple-Negative Breast Cancer, Jonathan H Shepherd, Cynthia Ma, Et Al.

2020-Current year OA Pubs

PURPOSE: CALGB 40603 (NCT00861705), a 2 × 2 randomized phase II trial, demonstrated that adding carboplatin or bevacizumab to weekly paclitaxel (wP) followed by doxorubicin and cyclophosphamide significantly increased the pathologic complete response (pCR) rate in stage II-III triple-negative breast cancer. We now report long-term outcomes (LTOs) and correlative science end points.

PATIENTS AND METHODS: The Kaplan-Meier method was used to estimate LTOs in 443 patients who initiated study treatment. Log-rank tests and Cox proportional hazards models evaluated the impact of clinical characteristics, pathologic response, calculated residual cancer burden (RCB) in patients with residual disease (RD), treatment assignment, and dose …

Integrin-Mediated Adhesion Promotes Centrosome Separation In Early Mitosis, Siamak A Kamranvar, Deepesh Kumar Gupta, Anishia Wasberg, Liangwen Liu, Joan Roig, Staffan Johansson

Open Access Publications

Integrin-mediated adhesion to the extracellular matrix is a key regulator of the cell cycle, as demonstrated for the passage of the G1/S checkpoint and the completion of cytokinetic abscission. Here, integrin-dependent regulation of the cell cycle in G2 and early M phases was investigated. The progression through the G2 and M phases was monitored by live-cell imaging and immunofluorescence staining in adherent and non-adherent fibroblast cells. Non-adherent cells, as well as adherent cells lacking FAK activity due to suppressed expression or pharmacological inhibition, exhibited a prolonged G2 phase and severely defect centrosome separation, resulting in delayed progress through the early …