Medicine and Health Sciences Commons^™

Brain Deficit Patterns Of Metabolic Illnesses Overlap With Those For Major Depressive Disorder: A New Metric Of Brain Metabolic Disease, Kathryn S Hatch, Si Gao, Yizhou Ma, Alessandro Russo, Neda Jahanshad, Paul M Thompson, Bhim M Adhikari, Heather Bruce, Andrew Van Der Vaart, Aristeidis Sotiras, Mark D Kvarta, Thomas E Nichols, Lianne Schmaal, L Elliot Hong, Peter Kochunov

2020-Current year OA Pubs

Metabolic illnesses (MET) are detrimental to brain integrity and are common comorbidities in patients with mental illnesses, including major depressive disorder (MDD). We quantified effects of MET on standard regional brain morphometric measures from 3D brain MRI as well as diffusion MRI in a large sample of UK BioBank participants. The pattern of regional effect sizes of MET in non-psychiatric UKBB subjects was significantly correlated with the spatial profile of regional effects reported by the largest meta-analyses in MDD but not in bipolar disorder, schizophrenia or Alzheimer's disease. We used a regional vulnerability index (RVI) for MET (RVI-MET) to measure …

A Peptide-Centric Quantitative Proteomics Dataset For The Phenotypic Assessment Of Alzheimer's Disease, Gennifer E Merrihew, Randall Bateman, Richard J Perrin, Et Al.

2020-Current year OA Pubs

Alzheimer's disease (AD) is a looming public health disaster with limited interventions. Alzheimer's is a complex disease that can present with or without causative mutations and can be accompanied by a range of age-related comorbidities. This diverse presentation makes it difficult to study molecular changes specific to AD. To better understand the molecular signatures of disease we constructed a unique human brain sample cohort inclusive of autosomal dominant AD dementia (ADD), sporadic ADD, and those without dementia but with high AD histopathologic burden, and cognitively normal individuals with no/minimal AD histopathologic burden. All samples are clinically well characterized, and brain …

A Systematic Review Of Multimodal Brain Age Studies: Uncovering A Divergence Between Model Accuracy And Utility, Robert J Jirsaraie, Aaron J Gorelik, Martins M Gatavins, Denis A Engemann, Ryan Bogdan, Deanna M Barch, Aristeidis Sotiras

2020-Current year OA Pubs

Brain aging is a complex, multifaceted process that can be challenging to model in ways that are accurate and clinically useful. One of the most common approaches has been to apply machine learning to neuroimaging data with the goal of predicting age in a data-driven manner. Building on initial brain age studies that were derived solely from T1-weighted scans (i.e., unimodal), recent studies have incorporated features across multiple imaging modalities (i.e., "multimodal"). In this systematic review, we show that unimodal and multimodal models have distinct advantages. Multimodal models are the most accurate and sensitive to differences in chronic brain disorders. …

Single-Cell Discovery And Multiomic Characterization Of Therapeutic Targets In Multiple Myeloma, Lijun Yao, Julia T Wang, Reyka G Jayasinghe, Julie O'Neal, Chia-Feng Tsai, Michael P Rettig, Yizhe Song, Ruiyang Liu, Yanyan Zhao, Omar M Ibrahim, Mark A Fiala, Julie M Fortier, Siqi Chen, Leah Gehrs, Fernanda Martins Rodrigues, Michael C Wendl, Daniel Kohnen, Andrew Shinkle, Song Cao, Steven M Foltz, Daniel Cui Zhou, Erik Storrs, Matthew A Wyczalkowski, Smrithi Mani, Scott R Goldsmith, Feng Chen, Ravi Vij, Li Ding, John F Dipersio, Et Al.

2020-Current year OA Pubs

UNLABELLED: Multiple myeloma (MM) is a highly refractory hematologic cancer. Targeted immunotherapy has shown promise in MM but remains hindered by the challenge of identifying specific yet broadly representative tumor markers. We analyzed 53 bone marrow (BM) aspirates from 41 MM patients using an unbiased, high-throughput pipeline for therapeutic target discovery via single-cell transcriptomic profiling, yielding 38 MM marker genes encoding cell-surface proteins and 15 encoding intracellular proteins. Of these, 20 candidate genes were highlighted that are not yet under clinical study, 11 of which were previously uncharacterized as therapeutic targets. The findings were cross-validated using bulk RNA sequencing, flow …

Mek Inhibition Synergizes With Tyk2 Inhibitors In Nf1-Associated Malignant Peripheral Nerve Sheath Tumors, Dana C Borcherding, Neha V Amin, Kevin He, Xiaochun Zhang, Yang Lyu, Carina Dehner, Himanshi Bhatia, Angad Gothra, Layla Daud, Peter Ruminski, Christine A Pratilas, Kai Pollard, Taylor Sundby, Brigitte C Widemann, Angela C Hirbe

2020-Current year OA Pubs

PURPOSE: Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas with limited treatment options and poor survival rates. About half of MPNST cases are associated with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome. Overexpression of TYK2 occurs in the majority of MPNST, implicating TYK2 as a therapeutic target.

EXPERIMENTAL DESIGN: The effects of pharmacologic TYK2 inhibition on MPNST cell proliferation and survival were examined using IncuCyte live cell assays in vitro, and downstream actions were analyzed using RNA-sequencing (RNA-seq), qPCR arrays, and validation of protein changes with the WES automated Western system. Inhibition of TYK2 alone and in combination …

Integrated Model Of The Vertebrate Augmin Complex, Sophie M Travis, Brian P Mahon, Wei Huang, Meisheng Ma, Michael J Rale, Jodi Kraus, Derek J Taylor, Rui Zhang, Sabine Petry

2020-Current year OA Pubs

Accurate segregation of chromosomes is required to maintain genome integrity during cell division. This feat is accomplished by the microtubule-based spindle. To build a spindle rapidly and with high fidelity, cells take advantage of branching microtubule nucleation, which rapidly amplifies microtubules during cell division. Branching microtubule nucleation relies on the hetero-octameric augmin complex, but lack of structure information about augmin has hindered understanding how it promotes branching. In this work, we combine cryo-electron microscopy, protein structural prediction, and visualization of fused bulky tags via negative stain electron microscopy to identify the location and orientation of each subunit within the augmin …

Cancer Neuroscience: State Of The Field, Emerging Directions, Frank Winkler, David H Gutmann, Et Al.

2020-Current year OA Pubs

The nervous system governs both ontogeny and oncology. Regulating organogenesis during development, maintaining homeostasis, and promoting plasticity throughout life, the nervous system plays parallel roles in the regulation of cancers. Foundational discoveries have elucidated direct paracrine and electrochemical communication between neurons and cancer cells, as well as indirect interactions through neural effects on the immune system and stromal cells in the tumor microenvironment in a wide range of malignancies. Nervous system-cancer interactions can regulate oncogenesis, growth, invasion and metastatic spread, treatment resistance, stimulation of tumor-promoting inflammation, and impairment of anti-cancer immunity. Progress in cancer neuroscience may create an important new …

Cultivating Anti-Racism Allies In Academic Medicine, Cassandra D L Fritz, Shirlene Obuobi, Monica E Peek, Monica B Vela

2020-Current year OA Pubs

Racial microaggressions, racially based remarks, or actions that negatively impact marginalized physicians of color (Black, Latino/a/x, and American Indian/Alaskan Natives) often go unaddressed. This article provides four strategies for how individuals and institutions can engage in anti-racism allyship: (1) be an upstander during microaggressions, (2) be a sponsor and advocate for physicians of color, (3) acknowledge academic titles and accomplishments, and (4) challenge the idea of a "standard fit" for academic faculty and research. Skills in academic allyship should be taught to

Isoflurane Conditioning Provides Protection Against Subarachnoid Hemorrhage Induced Delayed Cerebral Ischemia Through Nf-Kb Inhibition, Meizi Liu, Keshav Jayaraman, Jogender Mehla, Deepti Diwan, James W Nelson, Ahmed E Hussein, Ananth K Vellimana, Yousef Abu-Amer, Gregory J Zipfel, Umeshkumar Athiraman

2020-Current year OA Pubs

Delayed cerebral ischemia (DCI) is the largest treatable cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Nuclear Factor Kappa-light-chain-enhancer of Activated B cells (NF-kB), a transcription factor known to function as a pivotal mediator of inflammation, is upregulated in SAH and is pathologically associated with vasospasm. We previously showed that a brief exposure to isoflurane, an inhalational anesthetic, provided multifaceted protection against DCI after SAH. The aim of our current study is to investigate the role of NF-kB in isoflurane-conditioning-induced neurovascular protection against SAH-induced DCI. Twelve-week-old wild type male mice (C57BL/6) were divided into five groups: sham, SAH, SAH …

Sleep-Wake Patterns Are Altered With Age, Prdm13 Signaling In The Dmh, And Diet Restriction In Mice, Shogo Tsuji, Cynthia S Brace, Nicholas Rensing, Michael Wong, Shin-Ichiro Imai, Et Al.

2020-Current year OA Pubs

Old animals display significant alterations in sleep-wake patterns such as increases in sleep fragmentation and sleep propensity. Here, we demonstrated that PR-domain containing protein 13 (Prdm13)+ neurons in the dorsomedial hypothalamus (DMH) are activated during sleep deprivation (SD) in young mice but not in old mice. Chemogenetic inhibition of Prdm13+ neurons in the DMH in young mice promotes increase in sleep attempts during SD, suggesting its involvement in sleep control. Furthermore, DMH-specific

"Helicase" Activity Promoted Through Dynamic Interactions Between A Ssdna Translocase And A Diffusing Ssb Protein, Kacey N Mersch, Joshua E Sokoloski, Binh Nguyen, Roberto Galletto, Timothy M Lohman

2020-Current year OA Pubs

Replication protein A (RPA) is a eukaryotic single-stranded (ss) DNA-binding (SSB) protein that is essential for all aspects of genome maintenance. RPA binds ssDNA with high affinity but can also diffuse along ssDNA. By itself, RPA is capable of transiently disrupting short regions of duplex DNA by diffusing from a ssDNA that flanks the duplex DNA. Using single-molecule total internal reflection fluorescence and optical trapping combined with fluorescence approaches, we show that

Sting-Dependent Interferon Signatures Restrict Osteoclast Differentiation And Bone Loss In Mice, Susan Maclauchlan, Priyanka Kushwaha, Albert Tai, Sijia Chen, Catherine Manning, Gaurav Swarnkar, Yousef Abu-Amer, Katherine A Fitzgerald, Shruti Sharma, Ellen M Gravallese

2020-Current year OA Pubs

Stimulator of interferon genes (STING) is a key mediator of type-I interferon (IFN-I) signaling in response to a variety of stimuli, but the contribution of STING to homeostatic processes is not fully characterized. Previous studies showed that ligand activation of STING limits osteoclast differentiation in vitro through the induction of IFNβ and IFN-I interferon-stimulated genes (ISGs). In a disease model (SAVI) driven by the V154M gain-of-function mutation in STING, fewer osteoclasts form from SAVI precursors in response to receptor activator of NF-kappaB ligand (RANKL) in an IFN-I-dependent manner. Due to the described role of STING-mediated regulation of osteoclastogenesis in activation …

Changing Trends In Demographics, Risk Factors, And Clinical Features Of Patients With Infective Endocarditis-Related Stroke, 2005-2015, Mohamed Ridha, Opeolu Adeoye, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: There is a rising incidence of infective endocarditis-related stroke (IERS) in the United States attributed to the opioid epidemic. A contemporary epidemiologic description is necessary to understand the impact of the opioid epidemic on clinical characteristics of IERS. We describe and analyze trends in the demographics, risk factors, and clinical features of IERS.

METHODS: This is a retrospective cohort study within a biracial population of 1.3 million in the Greater Cincinnati/Northern Kentucky region. All hospitalized patients with hemorrhagic or ischemic stroke were identified and physician verified from the 2005, 2010, and 2015 calendar years using ICD-9 and …

Neuronal Birthdate Reveals Topography In A Vestibular Brainstem Circuit For Gaze Stabilization, Dena Goldblatt, Stephanie Huang, Marie R Greaney, Kyla R Hamling, Venkatakaushik Voleti, Citlali Perez-Campos, Kripa B Patel, Wenze Li, Elizabeth M C Hillman, Martha W Bagnall, David Schoppik

2020-Current year OA Pubs

Across the nervous system, neurons with similar attributes are topographically organized. This topography reflects developmental pressures. Oddly, vestibular (balance) nuclei are thought to be disorganized. By measuring activity in birthdated neurons, we revealed a functional map within the central vestibular projection nucleus that stabilizes gaze in the larval zebrafish. We first discovered that both somatic position and stimulus selectivity follow projection neuron birthdate. Next, with electron microscopy and loss-of-function assays, we found that patterns of peripheral innervation to projection neurons were similarly organized by birthdate. Finally, birthdate revealed spatial patterns of axonal arborization and synapse formation to projection neuron outputs. …

Uropathogenic Escherichia Coli Infection-Induced Epithelial Trained Immunity Impacts Urinary Tract Disease Outcome, Seongmi K Russell, Jessica K Harrison, Benjamin S Olson, Hyung Joo Lee, Valerie P O'Brien, Xiaoyun Xing, Lu Yu, Elisha D O Roberson, Rajdeep Bomjan, Changxu Fan, Marina Sha, Marco Colonna, Ting Wang, Thomas J Hannan, Scott J Hultgren, Et Al.

2020-Current year OA Pubs

Previous urinary tract infections (UTIs) can predispose one to future infections; however, the underlying mechanisms affecting recurrence are poorly understood. We previously found that UTIs in mice cause differential bladder epithelial (urothelial) remodelling, depending on disease outcome, that impacts susceptibility to recurrent UTI. Here we compared urothelial stem cell (USC) lines isolated from mice with a history of either resolved or chronic uropathogenic Escherichia coli (UPEC) infection, elucidating evidence of molecular imprinting that involved epigenetic changes, including differences in chromatin accessibility, DNA methylation and histone modification. Epigenetic marks in USCs from chronically infected mice enhanced caspase-1-mediated cell death upon UPEC …

Il-15 Enhances Hiv-1 Infection By Promoting Survival And Proliferation Of Ccr5+Cd4+ T Cells, Yuhao Li, Hongbo Gao, Kolin M. Clark, Liang Shan

2020-Current year OA Pubs

HIV-1 usually utilizes CCR5 as its coreceptor and rarely switches to a CXCR4-tropic virus until the late stage of infection. CCR5+CD4+ T cells are the major virus-producing cells in viremic individuals as well as SIV-infected nonhuman primates. The differentiation of CCR5+CD4+ T cells is associated with the availability of IL-15, which increases during acute HIV-1 infection. Here, we report that CCR5 was expressed by CD4+ T cells exhibiting effector or effector memory phenotypes with high expression levels of the IL-2/IL-15 receptor common β and γ chains. IL-15, but not IL-7, improved the survival of CCR5+CD4+ T cells, drove their expansion, …

Increased Clonal Hematopoiesis Involving Dna Damage Response Genes In Patients Undergoing Lung Transplantation, Laneshia K Tague, Karolyn A. Oetjen, Anirudh Mahadev, Matthew J. Walter, Hephzibah Anthony, Daniel Kreisel, Daniel C. Link, Andrew E Gelman

2020-Current year OA Pubs

BACKGROUNDCellular stressors influence the development of clonal hematopoiesis (CH). We hypothesized that environmental, inflammatory, and genotoxic stresses drive the emergence of CH in lung transplant recipients. METHODSWe performed a cross-sectional cohort study of 85 lung transplant recipients to characterize CH prevalence. We evaluated somatic variants using duplex error-corrected sequencing and germline variants using whole exome sequencing. We evaluated CH frequency and burden using χ2 and Poisson regression, and we evaluated associations with clinical and demographic variables and clinical outcomes using χ2, logistic regression, and Cox regression. RESULTSCH in DNA damage response (DDR) genes TP53, PPM1D, and ATM was increased in …

The Co-Morbidity Of Dsm-V Gambling With Dsm-V Mental Disorders And Substance Abuse In A Kenyan Context Of High Risk Schizophrenia, David M Ndetei, Victoria Mutiso, Reinpeter Momanyi, Pascalyne Nyamai, Christine Musyimi, Daniel Mamah

2020-Current year OA Pubs

INTRODUCTION: There is evidence that gambling disorder shares similarities with other types of addictive behavior, such as occurs in substance abuse. In addition, co-morbidity of gambling with mental disorders has been established in school-going students.

AIM: This study aimed at determining the comorbidity of DSM-V gambling disorder with DSM-V mental disorders and substance abuse in high school, college and university students in Kenya.

METHODS: This was a cross-sectional study among 536 high school, college and university students. We collected data on socio-demographic characteristics, economic indicators, DSM-V diagnosis including DSM-V gambling disorder and substance use disorders using the WHO ASSIST tool. …

Automatic Detection Of Circulating Tumor Cells And Cancer Associated Fibroblasts Using Deep Learning, Cheng Shen, Siddarth Rawal, Rebecca Brown, Haowen Zhou, Ashutosh Agarwal, Mark A Watson, Richard J Cote, Changhuei Yang

2020-Current year OA Pubs

Circulating tumor cells (CTCs) and cancer-associated fibroblasts (CAFs) from whole blood are emerging as important biomarkers that potentially aid in cancer diagnosis and prognosis. The microfilter technology provides an efficient capture platform for them but is confounded by two challenges. First, uneven microfilter surfaces makes it hard for commercial scanners to obtain images with all cells in-focus. Second, current analysis is labor-intensive with long turnaround time and user-to-user variability. Here we addressed the first challenge through developing a customized imaging system and data pre-processing algorithms. Utilizing cultured cancer and CAF cells captured by microfilters, we showed that images from our …

Factor Xa Cleaves Sars-Cov-2 Spike Protein To Block Viral Entry And Infection, Wenjuan Dong, Sean P J Whelan, Et Al.

2020-Current year OA Pubs

Serine proteases (SP), including furin, trypsin, and TMPRSS2 cleave the SARS-CoV-2 spike (S) protein, enabling the virus to enter cells. Here, we show that factor (F) Xa, an SP involved in blood coagulation, is upregulated in COVID-19 patients. In contrast to other SPs, FXa exerts antiviral activity. Mechanistically, FXa cleaves S protein, preventing its binding to ACE2, and thus blocking viral entry and infection. However, FXa is less effective against variants carrying the D614G mutation common in all pandemic variants. The anticoagulant rivaroxaban, a direct FXa inhibitor, inhibits FXa-mediated S protein cleavage and facilitates viral entry, whereas the indirect FXa …

Sphingomyelin 16:0 Is A Therapeutic Target For Neuronal Death In Acid Sphingomyelinase Deficiency, Ángel Gaudioso, Xuntian Jiang, Josefina Casas, Edward H Schuchman, María Dolores Ledesma

2020-Current year OA Pubs

Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disorder caused by mutations in the SMPD1 gene encoding for the acid sphingomyelinase (ASM). While intravenous infusion of recombinant ASM is an effective treatment for the peripheral disease, the neurological complications of ASMD remain unaddressed. It has been shown that aberrantly high level of total brain sphingomyelin (SM) is a key pathological event leading to neurodegeneration. Using mice lacking ASM (ASMko), which mimic the disease, we here demonstrate that among the SM species, SM16:0 shows the highest accumulation and toxicity in ASMko neurons. By targeting lysosomes, SM16:0 causes permeabilization and exocytosis of …

Extended Dna Threading Through A Dual-Engine Motor Module Of The Activating Signal Co-Integrator 1 Complex, Junqiao Jia, Tarek Hilal, Katherine E Bohnsack, Aleksandar Chernev, Ning Tsao, Juliane Bethmann, Aruna Arumugam, Lane Parmely, Nicole Holton, Bernhard Loll, Nima Mosammaparast, Markus T Bohnsack, Henning Urlaub, Markus C Wahl

2020-Current year OA Pubs

Activating signal co-integrator 1 complex (ASCC) subunit 3 (ASCC3) supports diverse genome maintenance and gene expression processes, and contains tandem Ski2-like NTPase/helicase cassettes crucial for these functions. Presently, the molecular mechanisms underlying ASCC3 helicase activity and regulation remain unresolved. We present cryogenic electron microscopy, DNA-protein cross-linking/mass spectrometry as well as in vitro and cellular functional analyses of the ASCC3-TRIP4 sub-module of ASCC. Unlike the related spliceosomal SNRNP200 RNA helicase, ASCC3 can thread substrates through both helicase cassettes. TRIP4 docks on ASCC3 via a zinc finger domain and stimulates the helicase by positioning an ASC-1 homology domain next to the C-terminal …

The F-Pilus Biomechanical Adaptability Accelerates Conjugative Dissemination Of Antimicrobial Resistance And Biofilm Formation, Jonasz B Patkowski, Tobias Dahlberg, Himani Amin, Dharmender K Gahlot, Sukhithasri Vijayrajratnam, Joseph P Vogel, Matthew S Francis, Joseph L Baker, Magnus Andersson, Tiago R D Costa

2020-Current year OA Pubs

Conjugation is used by bacteria to propagate antimicrobial resistance (AMR) in the environment. Central to this process are widespread conjugative F-pili that establish the connection between donor and recipient cells, thereby facilitating the spread of IncF plasmids among enteropathogenic bacteria. Here, we show that the F-pilus is highly flexible but robust at the same time, properties that increase its resistance to thermochemical and mechanical stresses. By a combination of biophysical and molecular dynamics methods, we establish that the presence of phosphatidylglycerol molecules in the F-pilus contributes to the structural stability of the polymer. Moreover, this structural stability is important for …

Cross-Sectional Study To Assess Depression Among Healthcare Workers In Lusaka, Zambia During The Covid-19 Pandemic, Sandra Simbeza, Jacob Mutale, Musunge Mulabe, Lazarus Jere, Chama Bukankala, Kombatende Sikombe, Izukanji Sikazwe, Carolyn Bolton-Moore, Aaloke Mody, Elvin H. Geng, Anjali Sharma, Laura K. Beres, Jake M. Pry

2020-Current year OA Pubs

OBJECTIVES: We sought to assess depression among healthcare workers (HCWs) in the context of COVID-19 in Lusaka Province, Zambia.

DESIGN: This cross-sectional study is nested within a larger study, the Person-Centred Public Health for HIV Treatment in Zambia (PCPH), a cluster-randomised trial to assess HIV care and outcomes.

SETTING: The research was conducted in 24 government-run health facilities from 11 August to 15 October 2020 during the first wave of the COVID-19 pandemic in Lusaka, Zambia.

PARTICIPANTS: We used convenience sampling to recruit HCW participants who were previously enrolled in the PCPH study, had more than 6 months' experience working …

A Dna Damage-Induced Phosphorylation Circuit Enhances Mec1atr Ddc2atrip Recruitment To Replication Protein A, Luke A Yates, Elias A Tannous, R Marc Morgan, Peter M Burgers, Xiaodong Zhang

2020-Current year OA Pubs

The cell cycle checkpoint kinase Mec1

Statins Enhance The Efficacy Of Her2-Targeting Radioligand Therapy In Drug-Resistant Gastric Cancers, Yi Rao, Zachary Samuels, Lukas M Carter, Sebastien Monette, Sandeep Surendra Panikar, Patricia M R Pereira, Jason S Lewis

2020-Current year OA Pubs

Human epidermal growth factor receptor 2 (HER2) is overexpressed in various cancer types. HER2-targeting trastuzumab plus chemotherapy is used as first-line therapy for HER2-positive recurrent or primary metastatic gastric cancer, but intrinsic and acquired trastuzumab resistance inevitably develop over time. To overcome gastric cancer resistance to HER2-targeted therapies, we have conjugated trastuzumab with a beta-emitting therapeutic isotope, lutetium-177, to deliver radiation locally to gastric tumors with minimal toxicity. Because trastuzumab-based targeted radioligand therapy (RLT) requires only the extramembrane domain binding of membrane-bound HER2 receptors, HER2-targeting RLT can bypass any resistance mechanisms that occur downstream of HER2 binding. Leveraging our previous …

Association Of Radiotherapy Duration With Clinical Outcomes In Patients With Esophageal Cancer Treated In Nrg Oncology Trials: A Secondary Analysis Of Nrg Oncology Randomized Clinical Trials, Christopher L Hallemeier, Hyun Kim, Et Al.

2020-Current year OA Pubs

IMPORTANCE: For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes.

OBJECTIVE: To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT).

DESIGN, SETTING, AND PARTICIPANTS: This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology …

Associations Of Combined Physical Activity And Body Mass Index Groups With Colorectal Cancer Survival Outcomes, Caroline Himbert, Matthew G Mutch, Corey Bernadt, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

BACKGROUND: Physical activity and BMI have been individually associated with cancer survivorship but have not yet been studied in combinations in colorectal cancer patients. Here, we investigate individual and combined associations of physical activity and BMI groups with colorectal cancer survival outcomes.

METHODS: Self-reported physical activity levels (MET hrs/wk) were assessed using an adapted version of the International Physical Activity Questionnaire (IPAQ) at baseline in 931 patients with stage I-III colorectal cancer and classified into 'highly active' and'not-highly active'(≥ / < 18 MET hrs/wk). BMI (kg/m

RESULTS: 'Not-highly active' compared to 'highly active' and 'overweight'/ 'obese' compared to 'normal weight' patients had a 40-50% increased risk …

Monocyte Depletion Enhances Neutrophil Influx And Proneural To Mesenchymal Transition In Glioblastoma, Zhihong Chen, David H Gutmann, Et Al.

2020-Current year OA Pubs

Myeloid cells comprise the majority of immune cells in tumors, contributing to tumor growth and therapeutic resistance. Incomplete understanding of myeloid cells response to tumor driver mutation and therapeutic intervention impedes effective therapeutic design. Here, by leveraging CRISPR/Cas9-based genome editing, we generate a mouse model that is deficient of all monocyte chemoattractant proteins. Using this strain, we effectively abolish monocyte infiltration in genetically engineered murine models of de novo glioblastoma (GBM) and hepatocellular carcinoma (HCC), which show differential enrichment patterns for monocytes and neutrophils. Eliminating monocyte chemoattraction in monocyte enriched PDGFB-driven GBM invokes a compensatory neutrophil influx, while having no …

Evaluation Of Birth By Cesarean Delivery And Development Of Early-Onset Colorectal Cancer, Yin Cao, Long H Nguyen, Stefani Tica, Ebunoluwa Otegbeye, Xiaoyu Zong, Bjorn Roelstraete, Andrew T Chan, Barbara B Warner, Olof Stephansson, Jonas F Ludvigsson

2020-Current year OA Pubs

IMPORTANCE: The incidence of early-onset colorectal cancer (CRC), diagnosed younger than 50 years of age, has increased worldwide. Gut dysbiosis throughout the life course is hypothesized as a leading mechanism, yet epidemiologic data are limited.

OBJECTIVE: To prospectively examine the association between birth by cesarean delivery and early-onset CRC among offspring.

DESIGN, SETTING, AND PARTICIPANTS: In this population-based, nationwide case-control study in Sweden, adults diagnosed with CRC between 18 and 49 years of age from 1991 to 2017 were identified through the Epidemiology Strengthened by Histopathology Reports in Sweden (ESPRESSO) cohort. Up to 5 general population control individuals without CRC …