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Ddr2 Expression In Cancer-Associated Fibroblasts Promotes Ovarian Cancer Tumor Invasion And Metastasis Through Periostin-Itgb1, Favour A Akinjiyan, Ritu M Dave, Emily Alpert, Gregory D Longmore, Katherine C Fuh

2020-Current year OA Pubs

Ovarian cancer has the highest mortality of all gynecologic malignancies. As such, there is a need to identify molecular mechanisms that underlie tumor metastasis in ovarian cancer. Increased expression of receptor tyrosine kinase, DDR2, has been associated with worse patient survival. Identifying downstream targets of DDR2 may allow specific modulation of ovarian cancer metastatic pathways. Additionally, stromal cells play a critical role in metastasis. The crosstalk between tumor and stromal cells can lead to tumor progression. We first identified that tumor cells co-cultured with DDR2-expressing fibroblasts had lower periostin expression when compared to tumor cells co-cultured with DDR2-depleted fibroblasts. We …

Clinical And Occupational Risk Factors For Coronavirus Disease 2019 (Covid-19) In Healthcare Personnel, Jennie H. Kwon, Philip J. Budge, Caroline A. O'Neil, Kate Peacock, Eva M. Aagaard, Victoria J. Fraser, Margaret A. Olsen, Hilary Babcock

2020-Current year OA Pubs

No abstract provided.

Α-Synuclein Conformational Plasticity: Physiologic States, Pathologic Strains, And Biotechnological Applications, Amanda Li, Cyrus Rastegar, Xiaobo Mao

2020-Current year OA Pubs

α-Synuclein (αS) is remarkable for both its extensive conformational plasticity and pathologic prion-like properties. Physiologically, αS may populate disordered monomeric, helically folded tetrameric, or membrane-bound oligomeric states. Pathologically, αS may assemble into toxic oligomers and subsequently fibrils, the prion-like transmission of which is implicated in a class of neurodegenerative disorders collectively termed α-synucleinopathies. Notably, αS does not adopt a single "amyloid fold", but rather exists as structurally distinct amyloid-like conformations referred to as "strains". The inoculation of animal models with different strains induces distinct pathologies, and emerging evidence suggests that the propagation of disease-specific strains underlies the differential pathologies observed …

Metrics To Evaluate Implementation Scientists In The Usa: What Matters Most?, Brenna B Maddox, Mary L Phan, Y Vivian Byeon, Courtney Benjamin Wolk, Rebecca E Stewart, Byron J Powell, Kelsie H Okamura, Melanie Pellecchia, Emily M Becker-Haimes, David A Asch, Rinad S Beidas

2020-Current year OA Pubs

BACKGROUND: Implementation science has grown rapidly as a discipline over the past two decades. An examination of how publication patterns and other scholarly activities of implementation scientists are weighted in the tenure and promotion process is needed given the unique and applied focus of the field.

METHODS: We surveyed implementation scientists (mostly from the USA) to understand their perspectives on the following matters: (1) factors weighted in tenure and promotion for implementation scientists, (2) how important these factors are for success as an implementation scientist, (3) how impact is defined for implementation scientists, (4) top journals in implementation science, and …

Single-Cell Transcriptional Regulation And Genetic Evolution Of Neuroendocrine Prostate Cancer, Ziwei Wang, Daofeng Li, Hyung Joo Lee, Et Al.

2020-Current year OA Pubs

Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer, with a 10% five-year survival rate. However, little is known about its origin and the mechanisms governing its emergence. Our study characterized ADPC and NEPC in prostate tumors from 7 patients using scRNA-seq. First, we identified two NEPC gene expression signatures representing different phases of

Cd11b Suppresses Tlr Activation Of Nonclassical Monocytes To Reduce Primary Graft Dysfunction After Lung Transplantation, Melissa Querrey, Stephen Chiu, Emilia Lecuona, Qiang Wu, Haiying Sun, Megan Anderson, Megan Kelly, Sowmya Ravi, Alexander V. Misharin, Daniel Kreisel, Ankit Bharat, G. R. Scott Budinger

2020-Current year OA Pubs

Primary graft dysfunction (PGD) is the leading cause of postoperative mortality in lung transplant recipients and the most important risk factor for development of chronic lung allograft dysfunction. The mechanistic basis for the variability in the incidence and severity of PGD between lung transplant recipients is not known. Using a murine orthotopic vascularized lung transplant model, we found that redundant activation of Toll-like receptors 2 and 4 (TLR2 and -4) on nonclassical monocytes activates MyD88, inducing the release of the neutrophil attractant chemokine CXCL2. Deletion of Itgam (encodes CD11b) in nonclassical monocytes enhanced their production of CXCL2 and worsened PGD, …

The Role Of Natural Products And Their Multitargeted Approach To Treat Solid Cancer, Naoshad Muhammad, Darksha Usmani, Mohammad Tarique, Huma Naz, Mohammad Ashraf, Ramesh Raliya, Shams Tabrez, Torki A Zughaibi, Ahdab Alsaieedi, Israa J Hakeem, Mohd Suhail

2020-Current year OA Pubs

Natural products play a critical role in the discovery and development of numerous drugs for the treatment of various types of cancer. These phytochemicals have demonstrated anti-carcinogenic properties by interfering with the initiation, development, and progression of cancer through altering various mechanisms such as cellular proliferation, differentiation, apoptosis, angiogenesis, and metastasis. Treating multifactorial diseases, such as cancer with agents targeting a single target, might lead to limited success and, in many cases, unsatisfactory outcomes. Various epidemiological studies have shown that the steady consumption of fruits and vegetables is intensely associated with a reduced risk of cancer. Since ancient period, plants, …

Post-Stroke Reorganization Of Transient Brain Activity Characterizes Deficits And Recovery Of Cognitive Functions, Elvira Pirondini, Nawal Kinany, Cécile Le Sueur, Joseph C Griffis, Gordon L Shulman, Maurizio Corbetta, Dimitri Van De Ville

2020-Current year OA Pubs

Functional magnetic resonance imaging (fMRI) has been widely employed to study stroke pathophysiology. In particular, analyses of fMRI signals at rest were directed at quantifying the impact of stroke on spatial features of brain networks. However, brain networks have intrinsic time features that were, so far, disregarded in these analyses. In consequence, standard fMRI analysis failed to capture temporal imbalance resulting from stroke lesions, hence restricting their ability to reveal the interdependent pathological changes in structural and temporal network features following stroke. Here, we longitudinally analyzed hemodynamic-informed transient activity in a large cohort of stroke patients (n = 103) to …

Factors Affecting Pathways To Care For Children And Adolescents With Complex Vascular Malformations: Parental Perspectives, Bryan A Sisk, Anna Kerr, Katherine A King

2020-Current year OA Pubs

BACKGROUND: Complex vascular malformations (VMs) are rare disorders that can cause pain, coagulopathy, disfigurement, asymmetric growth, and disability. Patients with complex VMs experience misdiagnosis, delayed diagnosis, delayed or inappropriate treatments, and worsened health. Given the potential consequences of delaying expert care, we must identify the factors that impede or facilitate this access to care.

RESULTS: We performed semi-structured interviews with 24 parents (21 mothers; 3 fathers; median age = 42.5 years) of children with complex VMs and overgrowth disorders living in the US, recruited through two patient advocacy groups - CLOVES Syndrome Community, and Klippel-Trenaunay Support Group. We performed thematic …

17q21.31 Sub-Haplotypes Underlying H1-Associated Risk For Parkinson's Disease Are Associated With Lrrc37a/2 Expression In Astrocytes, Kathryn R Bowles, Celeste M Karch, Et Al.

2020-Current year OA Pubs

BACKGROUND: Parkinson's disease (PD) is genetically associated with the H1 haplotype of the MAPT 17q.21.31 locus, although the causal gene and variants underlying this association have not been identified.

METHODS: To better understand the genetic contribution of this region to PD and to identify novel mechanisms conferring risk for the disease, we fine-mapped the 17q21.31 locus by constructing discrete haplotype blocks from genetic data. We used digital PCR to assess copy number variation associated with PD-associated blocks, and used human brain postmortem RNA-seq data to identify candidate genes that were then further investigated using in vitro models and human brain …

Slitrk2 Variants Associated With Neurodevelopmental Disorders Impair Excitatory Synaptic Function And Cognition In Mice, Salima El Chehadeh, Dorothy K Grange, Et Al

2020-Current year OA Pubs

SLITRK2 is a single-pass transmembrane protein expressed at postsynaptic neurons that regulates neurite outgrowth and excitatory synapse maintenance. In the present study, we report on rare variants (one nonsense and six missense variants) in SLITRK2 on the X chromosome identified by exome sequencing in individuals with neurodevelopmental disorders. Functional studies showed that some variants displayed impaired membrane transport and impaired excitatory synapse-promoting effects. Strikingly, these variations abolished the ability of SLITRK2 wild-type to reduce the levels of the receptor tyrosine kinase TrkB in neurons. Moreover, Slitrk2 conditional knockout mice exhibited impaired long-term memory and abnormal gait, recapitulating a subset of …

Hybrid-Control Arm Construction Using Historical Trial Data For An Early-Phase, Randomized Controlled Trial In Metastatic Colorectal Cancer, Chen Li, Katrina S Pedersen, Et Al

2020-Current year OA Pubs

Background: Treatment for metastatic colorectal cancer patients beyond the second line remains challenging, highlighting the need for early phase trials of combination therapies for patients who had disease progression during or following two prior lines of therapy. Leveraging hybrid control design in these trials may preserve the benefits of randomization while strengthening evidence by integrating historical trial data. Few examples have been established to assess the applicability of such design in supporting early phase metastatic colorectal cancer trials.

Methods: MORPHEUS-CRC is an umbrella, multicenter, open-label, phase Ib/II, randomized, controlled trial (NCT03555149), with active experimental arms ongoing. Patients enrolled were assigned …

Trial Of Erythropoietin For Hypoxic-Ischemic Encephalopathy In Newborns, Yvonne W Wu, Robert C Mckinstry, Rakesh Rao, Christopher D Smyser, Et Al.

2020-Current year OA Pubs

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy is an important cause of death as well as long-term disability in survivors. Erythropoietin has been hypothesized to have neuroprotective effects in infants with hypoxic-ischemic encephalopathy, but its effects on neurodevelopmental outcomes when given in conjunction with therapeutic hypothermia are unknown.

METHODS: In a multicenter, double-blind, randomized, placebo-controlled trial, we assigned 501 infants born at 36 weeks or more of gestation with moderate or severe hypoxic-ischemic encephalopathy to receive erythropoietin or placebo, in conjunction with standard therapeutic hypothermia. Erythropoietin (1000 U per kilogram of body weight) or saline placebo was administered intravenously within 26 hours after …

Long-Term Outcomes For Ibrutinib-Rituximab And Chemoimmunotherapy In Cll: Updated Results Of The E1912 Trial, Tait D Shanafelt, Amanda F Cashen, Et Al.

2020-Current year OA Pubs

Herein, we present the long-term follow-up of the randomized E1912 trial comparing the long-term efficacy of ibrutinib-rituximab (IR) therapy to fludarabine, cyclophosphamide, and rituximab (FCR) and describe the tolerability of continuous ibrutinib. The E1912 trial enrolled 529 treatment-naïve patients aged ≤70 years with chronic lymphocytic leukemia (CLL). Patients were randomly assigned (2:1 ratio) to receive IR or 6 cycles of FCR. With a median follow-up of 5.8 years, median progression-free survival (PFS) is superior for IR (hazard ratio [HR], 0.37; P < .001). IR improved PFS relative to FCR in patients with both immunoglobulin heavy chain variable region (IGHV) gene mutated CLL (HR: 0.27; P < .001) and IGHV unmutated CLL (HR: 0.27; P < .001). Among the 354 patients randomized to IR, 214 (60.5%) currently remain on ibrutinib. Among the 138 IR-treated patients who discontinued treatment, 37 (10.5% of patients who started IR) discontinued therapy due to disease progression or death, 77 (21.9% of patients who started IR) discontinued therapy for adverse events (AEs)/complications, and 24 (6.8% of patients who started IR) withdrew for other reasons. Progression was uncommon among patients able to remain on ibrutinib. The median time from ibrutinib discontinuation to disease progression or death among those who discontinued treatment for a reason other than progression was 25 months. Sustained improvement in overall survival (OS) was observed for patients in the IR arm (HR, 0.47; P = .018). In conclusion, IR therapy offers superior PFS relative to FCR in patients with IGHV mutated or unmutated CLL, as well as superior OS. Continuous ibrutinib therapy is tolerated beyond 5 years in the majority of CLL patients. This trial was registered at www.clinicaltrials.gov as #NCT02048813.

De Novo Variants Of Csnk2b Cause A New Intellectual Disability-Craniodigital Syndrome By Disrupting The Canonical Wnt Signaling Pathway, Maria Asif, Marwan Shinawi, Et Al.

2020-Current year OA Pubs

No abstract provided.

The Intrinsically Disordered Protein Tgist From Toxoplasma Gondii Inhibits Stat1 Signaling By Blocking Cofactor Recruitment, Zhou Huang, Hejun Liu, Jay Nix, Rui Xu, Catherine R Knoverek, Gregory R Bowman, Gaya K Amarasinghe, L David Sibley

2020-Current year OA Pubs

Signal transducer and activator of transcription (STAT) proteins communicate from cell-surface receptors to drive transcription of immune response genes. The parasite Toxoplasma gondii blocks STAT1-mediated gene expression by secreting the intrinsically disordered protein TgIST that traffics to the host nucleus, binds phosphorylated STAT1 dimers, and occupies nascent transcription sites that unexpectedly remain silenced. Here we define a core region within internal repeats of TgIST that is necessary and sufficient to block STAT1-mediated gene expression. Cellular, biochemical, mutational, and structural data demonstrate that the repeat region of TgIST adopts a helical conformation upon binding to STAT1 dimers. The binding interface is …

Surgery For Pituitary Tumor Apoplexy Is Associated With Rapid Headache And Cranial Nerve Improvement, Kevin A Cross, Rupen Desai, Ananth Vellimana, Yupeng Liu, Keith Rich, Gregory Zipfel, Ralph Dacey, Michael Chicoine, Cristine Klatt-Cromwell, Jonathan Mcjunkin, Patrik Pipkorn, John S Schneider, Julie Silverstein, Albert H Kim

2020-Current year OA Pubs

Pituitary tumor apoplexy (PTA) classically comprises sudden-onset headache, loss of vision, ophthalmoparesis, and decreased consciousness. It typically results from hemorrhage and/or infarction within a pituitary adenoma. Presentation is heterologous, and optimal management is debated. The time course of recovery of cranial nerve deficits (CNDs) and headaches is not well established. In this study, a retrospective series of consecutive patients with PTA managed at a single academic institution over a 22-year period is presented. Headaches at the time of surgery were more severe in the early and subacute surgical cohort and improved significantly within 72 h postoperatively (

Outcomes For Patients With Severe Chronic Neutropenia Treated With Granulocyte Colony-Stimulating Factor, David C Dale, Audrey Anna Bolyard, James A Shannon, James A Connelly, Daniel C Link, Mary Ann Bonilla, Peter E Newburger

2020-Current year OA Pubs

Severe chronic neutropenia (SCN), defined as blood neutrophils <0.5 × 109/L for >3 months, is an uncommon hematological condition associated with recurrent and severe bacterial infections. After short-term clinical trials showed the benefits of granulocyte colony-stimulating factor (G-CSF) treatment for SCN, SCNIR (Severe Chronic Neutropenia International Registry) opened to determine the long-term benefits and safety of this treatment. This report summarizes findings from more than 16 000 patient-years of prospective observations for patients with congenital and acquired SCN. We observed that adverse outcomes depend on the underlying etiology. Myelodysplasia (MDS) and acute myeloid leukemia (AML) occur infrequently and largely in patients with congenital neutropenias. …

Novel Implementation Strategy To Electronically Screen And Signpost Patients To Health Behavior Apps: Mixed Methods Implementation Study (Optimine Study), Zarnie Khadjesari, Tracey J Brown, Alex T Ramsey, Henry Goodfellow, Sherine El-Toukhy, Lorien C Abroms, Helena Jopling, Arden Dierker Viik, Michael S Amato

2020-Current year OA Pubs

BACKGROUND: Behavior change apps have the potential to provide individual support on a population scale at low cost, but they face numerous barriers to implementation. Electronic health records (EHRs) in acute care hospitals provide a valuable resource for identifying patients at risk, who may benefit from behavior change apps. A novel, emerging implementation strategy is to use digital technologies not only for providing support to help-seeking individuals but also for signposting patients at risk to support services (also called proactive referral in the United States).

OBJECTIVE: The OptiMine study aimed to increase the reach of behavior change apps by implementing …

Regulation Of Auxin Response Factor Condensation And Nucleo-Cytoplasmic Partitioning, Hongwei Jing, David A Korasick, Ryan J Emenecker, Nicholas Morffy, Edward G Wilkinson, Samantha K Powers, Lucia C Strader

2020-Current year OA Pubs

Auxin critically regulates plant growth and development. Auxin-driven transcriptional responses are mediated through the AUXIN RESPONSE FACTOR (ARF) family of transcription factors. ARF protein condensation attenuates ARF activity, resulting in dramatic shifts in the auxin transcriptional landscape. Here, we perform a forward genetics screen for ARF hypercondensation, identifying an F-box protein, which we named AUXIN RESPONSE FACTOR F-BOX1 (AFF1). Functional characterization of SCF

The Power Of Partnerships: State Public Health Department Multisector Collaborations In Major Chronic Disease Programme Areas In The United States, Edward Tsai, Peg Allen, Louise Farah Saliba, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Multisector collaboration between state public health departments (SHDs) and diverse community partners is increasingly recognized as important for promoting positive public health outcomes, addressing social determinants of health, and reducing health inequalities. This study investigates collaborations between SHDs in the United States and different types of organizations addressing chronic disease in and outside of the health sector.

METHODS: SHD employees were randomly selected from the National Association of Chronic Disease Directors membership list for participation in an online survey. Participants were asked about their primary chronic disease work unit (cancer, obesity, tobacco, diabetes, cardiovascular disease, and others), as well …

Relative Contributions Of Six Lifestyle- And Health-Related Exposures To Epigenetic Aging: The Coronary Artery Risk Development In Young Adults (Cardia) Study, Kyeezu Kim, Yinan Zheng, Brian T Joyce, Hongmei Jiang, Philip Greenland, David R Jacobs, Kai Zhang, Lei Liu, Norrina B Allen, John T Wilkins, Sarah N Forrester, Donald M Lloyd-Jones, Lifang Hou

2020-Current year OA Pubs

BACKGROUND: DNA methylation-based GrimAge acceleration (GrimAA) is associated with a wide range of age-related health outcomes including cardiovascular disease. Since DNA methylation is modifiable by external and behavioral exposures, it is important to identify which of these exposures may have the strongest contributions to differences in GrimAA, to help guide potential intervention strategies. Here, we assessed the relative contributions of lifestyle- and health-related components, as well as their collective association, to GrimAA.

RESULTS: We included 744 participants (391 men and 353 women) from the Coronary Artery Risk Development in Young Adults (CARDIA) study with blood DNA methylation information at CARDIA …

Lipid Absorption And Overall Intestinal Lymphatic Transport Are Impaired Following Partial Small Bowel Resection In Mice, Emily J Onufer, Rafael S Czepielewski, Yong-Hyun Han, Cathleen M Courtney, Stephanie Sutton, Anne Sescleifer, Gwendalyn J Randolph, Brad W Warner

2020-Current year OA Pubs

Short bowel syndrome (SBS) is associated with diminished levels of serum fats caused by unknown mechanisms. We have shown that mesenteric lymphatics remodel to a more primitive state one week after small bowel resection (SBR); therefore, this study focuses on the effect of chronic lymphatic remodeling and magnitude of resection on intestinal lipid uptake and transport. C57BL6 and Prox1 creER-Rosa26

Microbial Liberation Of N-Methylserotonin From Orange Fiber In Gnotobiotic Mice And Humans, Nathan D Han, Daniel Webber, Stacey Marion, Michael J Barratt, Andrew C Heath, Et Al.

2020-Current year OA Pubs

Plant fibers in byproduct streams produced by non-harsh food processing methods represent biorepositories of diverse, naturally occurring, and physiologically active biomolecules. To demonstrate one approach for their characterization, mass spectrometry of intestinal contents from gnotobiotic mice, plus in vitro studies, revealed liberation of N-methylserotonin from orange fibers by human gut microbiota members including Bacteroides ovatus. Functional genomic analyses of B. ovatus strains grown under permissive and non-permissive N-methylserotonin "mining" conditions revealed polysaccharide utilization loci that target pectins whose expression correlate with strain-specific liberation of this compound. N-methylserotonin, orally administered to germ-free mice, reduced adiposity, altered liver glycogenesis, shortened gut transit …

Hiv Cure Strategies: Which Ones Are Appropriate For Africa?, Christopher Zaab-Yen Abana, Helena Lamptey, Evelyn Y Bonney, George B Kyei

2020-Current year OA Pubs

Although combination antiretroviral therapy (ART) has reduced mortality and improved lifespan for people living with HIV, it does not provide a cure. Patients must be on ART for the rest of their lives and contend with side effects, unsustainable costs, and the development of drug resistance. A cure for HIV is, therefore, warranted to avoid the limitations of the current therapy and restore full health. However, this cure is difficult to find due to the persistence of latently infected HIV cellular reservoirs during suppressive ART. Approaches to HIV cure being investigated include boosting the host immune system, genetic approaches to …

Sickle Cell Transplantation Evaluation Of Long-Term And Late Effects Registry (Stellar) To Compare Long-Term Outcomes After Hematopoietic Cell Transplantation To Those In Siblings Without Sickle Cell Disease And In Nontransplanted Individuals With Sickle Cell Disease: Design And Feasibility Study, Lakshmanan Krishnamurti, Shalini Shenoy, Et Al

2020-Current year OA Pubs

BACKGROUND: There are sparse data on the long-term and late effects of hematopoietic cell transplantation (HCT) for sickle cell disease (SCD).

OBJECTIVE: This study aims to establish an international registry of long-term outcomes post-HCT for SCD and demonstrate the feasibility of recruitment at a single site in the United States.

METHODS: The Sickle Cell Transplantation Evaluation of Long-Term and Late Effects Registry (STELLAR) was designed to enroll patients with SCD ≥1 year post-HCT, their siblings without SCD, and nontransplanted controls with SCD to collect web-based participant self-reports of health status and practices by using the Bone Marrow Transplant Survivor Study …

South African University Staff And Students’ Perspectives, Preferences, And Drivers Of Hesitancy Regarding Covid-19 Vaccines: A Multi-Methods Study, Gavin George, Michael Strauss, Emma Lansdell, Nisha Nadesan-Reddy, Numfundo Moroe, Tarylee Reddy, Ingrid Eshun-Wilsonova, Mosa Moshabela

2020-Current year OA Pubs

No abstract provided.

Mapping The Single-Cell Transcriptomic Response Of Murine Diabetic Kidney Disease To Therapies, Haojia Wu, Romer Gonzalez Villalobos, Xiang Yao, Dermot Reilly, Tao Chen, Matthew Rankin, Eugene Myshkin, Matthew D. Breyer, Benjamin D. Humphreys

2020-Current year OA Pubs

Diabetic kidney disease (DKD) occurs in ∼40% of patients with diabetes and causes kidney failure, cardiovascular disease, and premature death. We analyzed the response of a murine DKD model to five treatment regimens using single-cell RNA sequencing (scRNA-seq). Our atlas of ∼1 million cells revealed a heterogeneous response of all kidney cell types both to DKD and its treatment. Both monotherapy and combination therapies targeted differing cell types and induced distinct and non-overlapping transcriptional changes. The early effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on the S1 segment of the proximal tubule suggest that this drug class induces fasting mimicry and …

Gene-Based Polygenic Risk Scores Analysis Of Alcohol Use Disorder In African Americans, Dongbing Lai, Arpana Agrawal, Et Al

2020-Current year OA Pubs

Genome-wide association studies (GWAS) in admixed populations such as African Americans (AA) have limited sample sizes, resulting in poor performance of polygenic risk scores (PRS). Based on the observations that many disease-causing genes are shared between AA and European ancestry (EA) populations, and some disease-causing variants are located within the boundaries of these genes, we proposed a novel gene-based PRS framework (PRS

Modeling The Prognostic Impact Of Circulating Tumor Cells Enumeration In Metastatic Breast Cancer For Clinical Trial Design Simulation, Lorenzo Gerratana, Andrew A Davis, Et Al.

2020-Current year OA Pubs

Despite the strong prognostic stratification of circulating tumor cells (CTCs) enumeration in metastatic breast cancer (MBC), current clinical trials usually do not include a baseline CTCs in their design. This study aimed to generate a classifier for CTCs prognostic simulation in existing datasets for hypothesis generation in patients with MBC. A K-nearest neighbor machine learning algorithm was trained on a pooled dataset comprising 2436 individual MBC patients from the European Pooled Analysis Consortium and the MD Anderson Cancer Center to identify patients likely to have CTCs ≥ 5/7 mL blood (StageIVaggressive vs StageIVindolent). The model had a 65.1% accuracy and …