Medicine and Health Sciences Commons^™

Coronary Artery Calcium On Lung Cancer Radiation Planning Ct Aids Cardiovascular Risk Assessment, Matthew Lui, Noah Kim, Raja Zaghlol, Pouya Joolharzadeh, Elena Deych, Clifford Robinson, Shahed Badiyan, Pamela K Woodard, Joshua D Mitchell

2020-Current year OA Pubs

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) undergoing thoracic radiation are at high cardiovascular risk. Semiquantitative assessment of coronary artery calcification (CAC) on baseline planning non-gated chest computed tomography (CT) scans may help further risk stratify patients.

OBJECTIVES: This study aimed to characterize the association between CAC and major adverse cardiovascular events (MACE; myocardial infarction or stroke) and assess the utility of semiquantitative assessment of CAC.

METHODS: Patients with NSCLC with non-contrast planning chest CT scans were evaluated for CAC. Planning scans were visually graded using the CAC-DRS method, stratifying patients into no, mild, moderate, and severe CAC groups. …

Collaboration Strategies Affecting Implementation Of A Cross-Systems Intervention For Child Welfare And Substance Use Treatment: A Mixed Methods Analysis, Emmeline Chuang, Byron J Powell, Et Al.

2020-Current year OA Pubs

BACKGROUND: Collaboration strategies refer to policies and practices used to align operations and services across organizations or systems. These strategies can influence implementation of cross-system interventions focused on improving integration of care, but remain under-specified and under-examined. This study identifies collaboration strategies and the conditions under which they affected implementation of Sobriety Treatment and Recovery Teams (START), an evidence-based intervention focused on integrating child welfare and behavioral health services for families involved with both systems.

METHODS: Our study sample included 17 county child welfare agencies that implemented START. Data on collaboration strategies and organizational context were obtained from key informant …

Impact Of Socioeconomic Deprivation On Care Quality And Surgical Outcomes For Early-Stage Non-Small Cell Lung Cancer In United States Veterans, Steven Tohmasi, Brendan T Heiden, Nikki E Rossetti, Ana A Baumann, Theodore S Thomas, Su-Hsin Chang, Nahom Seyoum, Yan Yan, Whitney S Brandt, Bryan F Meyers, Benjamin D Kozower, Varun Puri, Et Al.

2020-Current year OA Pubs

No abstract provided.

Regulatory T Cells Require Peripheral Ccl2-Ccr2 Signaling To Facilitate The Resolution Of Medication Overuse Headache-Related Behavioral Sensitization, Sun Ryu, Jintao Zhang, Roli Simoes, Xuemei Liu, Zhaohua Guo, Li Feng, Jacqueline Unsinger, Richard S Hotchkiss, Yu-Qing Cao

2020-Current year OA Pubs

BACKGROUND: Medication overuse headache (MOH) is the most common secondary headache disorder, resulting from chronic and excessive use of medication to treat headaches, for example, sumatriptan. In a recent study, we have shown that the peripheral C-C motif ligand 2 (CCL2), C-C motif chemokine receptor 2 (CCR2) and calcitonin-gene-related peptide (CGRP) signaling pathways interact with each other and play critical roles in the development of chronic migraine-related behavioral and cellular sensitization. In the present study, we investigated whether CCL2-CCR2 and CGRP signaling pathways play a role in the development of sumatriptan overuse-induced sensitization, and whether they are involved in its …

Length Of Hospital And Intensive Care Unit Stay In Patients With Invasive Candidiasis And/Or Candidemia Treated With Rezafungin: A Pooled Analysis Of Two Randomised Controlled Trials, Patrick M Honoré, Matteo Bassetti, Oliver A Cornely, Herve Dupont, Jesús Fortún, Marin H Kollef, Peter Pappas, John Pullman, Jose Vazquez, Inga Bielicka, Sara Dickerson, Nick Manamley, Taylor Sandison, George R Thompson

2020-Current year OA Pubs

BACKGROUND: Invasive candidiasis/candidemia (IC/C) is associated with a substantial health economic burden driven primarily by prolonged hospital stay. The once-weekly IV echinocandin, rezafungin acetate, has demonstrated non-inferiority to caspofungin in the treatment of IC/C. This paper reports a post hoc pooled exploratory analysis of length of stay (LoS) for hospital and intensive care unit (ICU) stays in two previously published clinical trials (ReSTORE [NCT03667690] and STRIVE [NCT02734862], that compared rezafungin with daily IV caspofungin (stable patients in the caspofungin group who met relevant criteria could step down to fluconazole after 3 days or more).

METHODS: LoS outcomes were analysed descriptively …

Addressing Hypertension And Diabetes Through Community-Engaged Systems (Andes) In Puno, Peru: Rationale And Study Protocol For A Hybrid Type 2 Effectiveness And Implementation Randomized Controlled Trial, Lindsay J Underhill, Lisa De Las Fuentes, Mark D Huffman, Kenneth B Schechtman, Abigail Barker, Aaloke Mody, Elvin H Geng, Victor G Dávila-Román, Et Al.

2020-Current year OA Pubs

BACKGROUND: Hypertension is the most common cardiovascular disease in Peru despite the availability of cost-effective, evidence-based treatment. Here we describe the rationale and study design for a hybrid type 2 randomized controlled trial to test the implementation and effectiveness of a community health worker (CHW)-led hypertension control program within the national primary care system in Puno, Peru.

METHODS: We will recruit 1068 adult participants with hypertension aged ≥ 18 years in Puno, Peru, via facility-based enrollment and community health fairs. Participants will be individually randomized (1:1) to either continue with usual care or participate in a 12-month CHW-led home-based hypertension …

Sacituzumab-Govitecan-Induced Severe Acute Tubulointerstitial Nephritis Requiring Hemodialysis, Geneva Guarin, Audrey Netzel, Karen Marie Flores, Arun Cumpelik, Ron Bose

2020-Current year OA Pubs

BACKGROUND: Sacituzumab govitecan is an antibody-drug conjugate that is FDA approved for refractory metastatic triple-negative breast cancer. It targets the human trophoblastic cell-surface antigen 2 (Trop-2) with SN-38, a topoisomerase I inhibitor, attached to the antibody [1]. SN-38 breaks DNA strands and induces tumor apoptosis [2]. Acute kidney injury (AKI) is one of its adverse effects mainly prerenal due to gastrointestinal toxicity, but it has not been reported to cause acute tubulointerstitial nephritis (ATIN).

CASE PRESENTATION: This report describes a rare adverse effect of sacituzumab govitecan, the approach to diagnosing the etiology of the patient's AKI, and the mechanism by …

Microglia Drive Diurnal Variation In Susceptibility To Inflammatory Blood-Brain Barrier Breakdown, Jennifer H. Lawrence, Asha Patel, Melvin W. King, Collin J. Nadarajah, Richard Daneman, Erik S. Musiek

2020-Current year OA Pubs

The blood-brain barrier (BBB) is critical for maintaining brain homeostasis but is susceptible to inflammatory dysfunction. While transporter-dependent efflux of some lipophilic substrates across the BBB shows circadian variation due to rhythmic transporter expression, basal transporter-independent permeability and leakage is nonrhythmic. Whether daily timing influences BBB permeability in response to inflammation is unknown. Here, we induced systemic inflammation through repeated LPS injections either in the morning (ZT1) or evening (ZT13) under standard lighting conditions; we then examined BBB permeability to a polar molecule that is not a transporter substrate, sodium fluorescein. We observed clear diurnal variation in inflammatory BBB permeability, …

Hurp Facilitates Spindle Assembly By Stabilizing Microtubules And Working Synergistically With Tpx2, Venecia Alexandria Valdez, Meisheng Ma, Bernardo Gouveia, Rui Zhang, Sabine Petry

2020-Current year OA Pubs

In vertebrate spindles, most microtubules are formed via branching microtubule nucleation, whereby microtubules nucleate along the side of pre-existing microtubules. Hepatoma up-regulated protein (HURP) is a microtubule-associated protein that has been implicated in spindle assembly, but its mode of action is yet to be defined. In this study, we show that HURP is necessary for RanGTP-induced branching microtubule nucleation in Xenopus egg extract. Specifically, HURP stabilizes the microtubule lattice to promote microtubule formation from γ-TuRC. This function is shifted to promote branching microtubule nucleation through enhanced localization to TPX2 condensates, which form the core of the branch site on microtubules. …

Polygenic Risk For Alcohol Use Disorder Affects Cellular Responses To Ethanol Exposure In A Human Microglial Cell Model, Xindi Li, Arpana Agrawal, Et Al.

2020-Current year OA Pubs

Polygenic risk scores (PRSs) assess genetic susceptibility to alcohol use disorder (AUD), yet their molecular implications remain underexplored. Neuroimmune interactions, particularly in microglia, are recognized as notable contributors to AUD pathophysiology. We investigated the interplay between AUD PRS and ethanol in human microglia derived from iPSCs from individuals with AUD high-PRS (diagnosed with AUD) or low-PRS (unaffected). Ethanol exposure induced elevated CD68 expression and morphological changes in microglia, with differential responses between high-PRS and low-PRS microglial cells. Transcriptomic analysis revealed expression differences in MHCII complex and phagocytosis-related genes following ethanol exposure; high-PRS microglial cells displayed enhanced phagocytosis and increased

Association Of Neighborhood-Level Disadvantage Beyond Individual Sociodemographic Factors In Patients With Or At Risk Of Knee Osteoarthritis, Jessica Peoples, Jared J Tanner, Emily J Bartley, Lisa H Domenico, Cesar E Gonzalez, Josue S Cardoso, Catalina Lopez-Quintero, Elizabeth A Reynolds Losin, Roland Staud, Burel R Goodin, Roger B Fillingim, Ellen L Terry

2020-Current year OA Pubs

OBJECTIVE: Lower socioeconomic status (SES) is a risk factor for poorer pain-related outcomes. Further, the neighborhood environments of disadvantaged communities can create a milieu of increased stress and deprivation that adversely affects pain-related and other health outcomes. Socioenvironmental variables such as the Area Deprivation Index, which ranks neighborhoods based on socioeconomic factors could be used to capture environmental aspects associated with poor pain outcomes. However, it is unclear whether the ADI could be used as a risk assessment tool in addition to individual-level SES.

METHODS: The current study investigated whether neighborhood-level disadvantage impacts knee pain-related outcomes above sociodemographic measures. Participants …

Brain Metastases In Sarcomas: A Multicenter Retrospective Cohort Study, Ellen Zhang, Sheima Farag, Hilary Dietz, Daniel Wang, Angela Hirbe, Kristen Ganjoo, Brian Van Tine, Shane Zaid, Aisha Miah, Vicki Keedy, Elizabeth Davis, Nam Bui

2020-Current year OA Pubs

PURPOSE: Brain metastases (BM) in sarcomas occur rarely and are associated with poor prognosis. This study is a large retrospective cohort describing the demographic and clinical characteristics of these patients, treatment strategies, and survival outcomes.

METHODS: In total, 81 patients with BM from sarcomas were identified across five sarcoma centers. Demographic data, clinical presentation, and treatment modalities were analyzed.

RESULTS: The most common histologies were leiomyosarcoma (12.3%) and undifferentiated pleomorphic sarcoma (12.3%). The median time from sarcoma diagnosis to brain metastases was 1.9 years. Upon presentation, 88.9% of patients with BM from sarcomas were symptomatic with the most common presenting …

Racial Disparity In Mortality From Tuberculosis In The Us Between States With And Without A History Of Jim-Crow Laws: An Analysis Of The Global Burden Of Disease (Gbd) And Risk Factors Study, 1990 To 2019, Philimon N Gona, Lorena M Estrada-Martinez, Lingling Zhang, Clara M Gona, Aaloke Mody, Sowmya R Rao, Joseph Cooper, Kibibi Mack-Shelton, Ping Chen, Suzanne G Leveille, Ali H Mokdad, G. B. D. 2019 T. B. Racial Disparity

2020-Current year OA Pubs

BACKGROUND: While TB-related mortality in the US declined four-fold from 1990 to 2019, country-level estimates of TB burden obscure within-state racial heterogeneity and changes in TB burden over time. In sixteen US Southern States and Washington DC, the effects of health inequities engendered by Jim-Crow laws enacted from the late 1800s to the 1960s have not been evaluated for TB-related mortality. We, therefore, sought to compare TB mortality rates and annualized rate of change (AROC) between 1990 and 2019 in former Jim-Crow vs. non-Jim-Crow states to help guide response efforts and inform resource prioritization to improve racial equity.

METHODS: We …

Crispr/Cas9 Screens Identify Key Host Factors That Enhance Rotavirus Reverse Genetics Efficacy And Vaccine Production, Yinxing Zhu, Meagan E Sullender, Danielle E Campbell, Leran Wang, Sanghyun Lee, Takahiro Kawagishi, Gaopeng Hou, Alen Dizdarevic, Philippe H Jais, Megan T Baldridge, Siyuan Ding

2020-Current year OA Pubs

Rotaviruses pose a significant threat to young children. To identify novel pro- and anti-rotavirus host factors, we performed genome-wide CRISPR/Cas9 screens using rhesus rotavirus and African green monkey cells. Genetic deletion of either SERPINB1 or TMEM236, the top two antiviral factors, in MA104 cells increased virus titers in a rotavirus strain independent manner. Using this information, we optimized the existing rotavirus reverse genetics systems by combining SERPINB1 knockout MA104 cells with a C3P3-G3 helper plasmid. We improved the recovery efficiency and rescued several low-titer rotavirus reporter and mutant strains that prove difficult to rescue otherwise. Furthermore, we demonstrate that TMEM236 …

Volumetric Body Composition Analysis Of The Cancer Genome Atlas Reveals Novel Body Composition Traits And Molecular Markers Associated With Renal Carcinoma Outcomes, Olesya Mironchuk, Andrew L Chang, Farzaneh Rahmani, Kaitlyn Portell, Elena Nunez, Zack Nigogosyan, Da Ma, Karteek Popuri, Vincent Tze Yang Chow, Mirza Faisal Beg, Jingqin Luo, Joseph E Ippolito

2020-Current year OA Pubs

Clinically, the body mass index remains the most frequently used metric of overall obesity, although it is flawed by its inability to account for different adipose (i.e., visceral, subcutaneous, and inter/intramuscular) compartments, as well as muscle mass. Numerous prior studies have demonstrated linkages between specific adipose or muscle compartments to outcomes of multiple diseases. Although there are no universally accepted standards for body composition measurement, many studies use a single slice at the L3 vertebral level. In this study, we use computed tomography (CT) studies from patients in The Cancer Genome Atlas (TCGA) to compare current L3-based techniques with volumetric …

Induction Of A Distinct Macrophage Population And Protection From Lung Injury And Fibrosis By Notch2 Blockade, Mayra Cruz Tleugabulova, Meizi Liu, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Macrophages are pleiotropic and diverse cells that populate all tissues of the body. Besides tissue-specific resident macrophages such as alveolar macrophages, Kupffer cells, and microglia, multiple organs harbor at least two subtypes of other resident macrophages at steady state. During certain circumstances, like tissue insult, additional subtypes of macrophages are recruited to the tissue from the monocyte pool. Previously, a recruited macrophage population marked by expression of Spp1, Cd9, Gpnmb, Fabp5, and Trem2, has been described in several models of organ injury and cancer, and has been linked to fibrosis in mice and humans. Here, we show that Notch2 blockade, …

Failure In A Population: Tauopathy Disrupts Homeostatic Set-Points In Emergent Dynamics Despite Stability In The Constituent Neurons, James N Mcgregor, Clayton A Farris, Sahara Ensley, Aidan Schneider, Leandro J Fosque, Chao Wang, Elizabeth I Tilden, Yuqi Liu, Jianhong Tu, Halla Elmore, Keenan D Ronayne, Ralf Wessel, Kiran Bhaskaran-Nair, David M Holtzman, Keith B Hengen, Et Al.

2020-Current year OA Pubs

Homeostatic regulation of neuronal activity is essential for robust computation; set-points, such as firing rate, are actively stabilized to compensate for perturbations. The disruption of brain function central to neurodegenerative disease likely arises from impairments of computationally essential set-points. Here, we systematically investigated the effects of tau-mediated neurodegeneration on all known set-points in neuronal activity. We continuously tracked hippocampal neuronal activity across the lifetime of a mouse model of tauopathy. We were unable to detect effects of disease in measures of single-neuron firing activity. By contrast, as tauopathy progressed, there was disruption of network-level neuronal activity, quantified by measuring neuronal …

Engineered Self-Regulating Macrophages For Targeted Anti-Inflammatory Drug Delivery, Molly Klimak, Amanda Cimino, Kristin L Lenz, Luke E Springer, Kelsey H Collins, Natalia S Harasymowicz, Nathan Xu, Christine T N Pham, Farshid Guilak

2020-Current year OA Pubs

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by increased levels of inflammation that primarily manifests in the joints. Macrophages act as key drivers for the progression of RA, contributing to the perpetuation of chronic inflammation and dysregulation of pro-inflammatory cytokines such as interleukin 1 (IL-1). The goal of this study was to develop a macrophage-based cell therapy for biologic drug delivery in an autoregulated manner.

METHODS: For proof-of-concept, we developed "smart" macrophages to mitigate the effects of IL-1 by delivering its inhibitor, IL-1 receptor antagonist (IL-1Ra). Bone marrow-derived macrophages were lentivirally transduced with a synthetic gene circuit …

Facilitating And Restraining Virus Infection Using Cell-Attachable Soluble Viral Receptors, Heng Zhang, Zhengli Wang, Huong T T Nguyen, Marjorie Cornejo Pontelli, Wanrong Qi, Liem Rao, Zhuoming Liu, Sean P J Whelan, Jieqing Zhu

2020-Current year OA Pubs

SARS-CoV-2 uses the receptor binding domain (RBD) of its spike protein to recognize and infect host cells by binding to the cell surface receptor angiotensin converting enzyme 2 (ACE2). The ACE2 receptor is composed of peptidase domain (PD), collectrin-like domain, transmembrane domain, and short cytoplasmic domain, and may exist as a dimer on cell surface. The RBD binding site is located atop of the ACE2 PD, but the involvement of other domains in virus infection is uncertain. We found that the ACE2 PD alone, whether anchored to cell membrane via a glycosylphosphatidylinositol anchor or attached to another surface protein, is …

Nkp46+ Ilc3s Promote Early Neutrophil Defense Against Clostridioides Difficile Infection Through Gm-Csf Secretion, José L Fachi, Sarah De Oliveira, Susan Gilfillan, Alina Ulezko Antonova, Jinchao Hou, Marco A R Vinolo, Marco Colonna

2020-Current year OA Pubs

No abstract provided.

Extending The Translational Science Benefits Model To Implementation Science For Cancer Prevention And Control, Karen M Emmons, Ross C Brownson, Douglas A Luke

2020-Current year OA Pubs

INTRODUCTION: There is increasing pressure on the federal research budget and shifting public opinions about the value of the academic enterprise. We must develop and apply metrics that demonstrate the broad benefits of research for health and society. The Translational Science Benefits Model (TSBM) measures the impact of large-scale translational science initiatives, such as the National Cancer Institute's Cancer Moonshot. TSBM provides the scaffolding to illustrate how science has real-world health impacts. We propose an expansion of the TSBM to explicitly include implementation-focused outcomes.

METHODS: TSBM includes four categories of benefits, including (1) clinical and medical, (2) community and public …

Mitral Annular Disjunction In Heritable Thoracic Aortic Disease: Insights From The Montalcino Aortic Consortium, Kishan L Asokan, Alan Braverman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Mitral annular disjunction (MAD), posterior displacement of the mitral valve leaflet hinge point, predisposes to arrhythmias or sudden cardiac death. We evaluated the burden of MAD, mitral valve prolapse (MVP), and mitral regurgitation (MR) by heritable thoracic aortic disease gene in a cross-sectional analysis of 2014-2023 data in the Montalcino Aortic Consortium registry.

METHODS AND RESULTS: MAD was determined by direct measurement of echocardiographic images. MR and MVP were defined according to current clinical guidelines. Associations were evaluated using χ

CONCLUSIONS: Pathological mitral valve phenotypes are more prevalent in individuals with PV in transforming growth factor-β pathway genes, particularly

The Upfront Project: Tailored Implementation And Evaluation Of A Patient Decision Aid To Support Shared Decision-Making About Management Of Symptomatic Uterine Fibroids, Rachel C Forcino, Mary Politi, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To evaluate implementation of a patient decision aid for symptomatic uterine fibroid management to improve shared decision-making at five clinical settings across the United States.

METHODS: We used a type 3 hybrid effectiveness-implementation stepped-wedge design and the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) planning and evaluation framework. We conducted clinician training, monthly reach tracking with feedback to site clinical leads, patient and clinician surveys, and visit audio-recordings. Implementation strategies included assessment of organizational readiness for shared decision-making, synchronous clinician training, audit and feedback of decision aid reach, and access to multiple decision aid formats. Outcomes and analyses included patient-level …

Improving Risk Stratification For 2022 European Leukemianet Favorable-Risk Patients With Acute Myeloid Leukemia, Kellie J Archer, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

Assignment of patients diagnosed with acute myeloid leukemia (AML) to the 2022 European LeukemiaNet (ELN) favorable genetic risk group has important clinical implications, as allogeneic stem cell transplantation in first complete remission (CR) is not advised due to a relatively good outcome of patients receiving chemotherapy alone and transplant-associated mortality. However, not all favorable genetic risk patients experience long-term relapse-free survival (RFS), making recognition of patients who would most likely be cured of high importance. We analyzed 297 patients aged < 60 years with

Quality Of Publicly Available Information About Urinary Tract Infections, Viktoria Schmitz, Zoe Troubh, Michael Durkin, Kevin Hsueh, Katheryn Ney, Brian D Carpenter, Shinbee Waldron, Mary C Politi, Cdc Prevention Epicenters Program

2020-Current year OA Pubs

No abstract provided.

Actionable Structural Variant Detection Via Rns-Ngs And Dna-Ngs In Patients With Advanced Non-Small Cell Lung Cancer, Dwight Owen, Daniel Morgensztern, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The National Comprehensive Cancer Network (NCCN) guidelines for non-small cell lung cancer suggest that RNA next-generation sequencing (NGS) may improve the detection of fusions and splicing variants compared with DNA-NGS alone. However, there is limited adoption of RNA-NGS in routine oncology clinical care today.

OBJECTIVE: To analyze clinical evidence from a diverse cohort of patients with advanced lung adenocarcinoma and compare the detection of NCCN-recommended actionable structural variants (aSVs; fusions and splicing variants) via concurrent DNA and RNA-NGS vs DNA-NGS alone.

DESIGN, SETTING, AND PARTICIPANTS: This multisite, retrospective cohort study examined patients sequenced between February 2021 and October 2023 …

Performance Of Risk Models For Antimicrobial Resistance In Adult Patients With Sepsis, M Cristina Vazquez Guillamet, Hanyang Liu, Andrew Atkinson, Victoria J Fraser, Chenyang Lu, Marin H Kollef

2020-Current year OA Pubs

IMPORTANCE: The results of prediction models that stratify patients with sepsis and risk of resistant gram-negative bacilli (GNB) infections inform treatment guidelines. However, these models do not extrapolate well across hospitals.

OBJECTIVE: To assess whether patient case mix and local prevalence rates of resistance contributed to the variable performance of a general risk stratification GNB sepsis model for community-onset and hospital-onset sepsis across hospitals.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study conducted from January 2016 and October 2021. Adult patients with sepsis at 10 acute-care hospitals in rural and urban areas across Missouri and Illinois were included. …

Multicenter Validation Of An Rna-Based Assay To Predict Anti-Pd-1 Disease Control In Patients With Recurrent Or Metastatic Head And Neck Squamous Cell Carcinoma: The Predapt Study, Kevin C Flanagan, Jessica Ley, Douglas Adkins, Eric J Duncavage, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite advances in cancer care and detection, >65% of patients with squamous cell cancer of the head and neck (HNSCC) will develop recurrent and/or metastatic disease. The prognosis for these patients is poor with a 5-year overall survival of 39%. Recent treatment advances in immunotherapy, including immune checkpoint inhibitors like pembrolizumab and nivolumab, have resulted in clinical benefit in a subset of patients. There is a critical clinical need to identify patients who benefit from these antiprogrammed cell death protein 1 (anti-PD-1) immune checkpoint inhibitors.

METHODS: Here, we report findings from a multicenter observational study, PREDicting immunotherapy efficacy from …

Distinct Escherichia Coli Transcriptional Profiles In The Guts Of Recurrent Uti Sufferers Revealed By Pangenome Hybrid Selection, Mark G Young, Jesús Bazan Villicana, Philippe Azimzadeh, Andrew Kau, Karen W Dodson, Henry L Schreiber 4th, Scott J Hultgren, Et Al.

2020-Current year OA Pubs

Low-abundance members of microbial communities are difficult to study in their native habitats, including Escherichia coli, a minor but common inhabitant of the gastrointestinal tract, and key opportunistic pathogen of the urinary tract. While multi-omic analyses have detailed interactions between uropathogenic Escherichia coli (UPEC) and the bladder mediating urinary tract infection (UTI), little is known about UPEC in its pre-infection reservoir, the gastrointestinal tract, partly due to its low relative abundance (<1%). To sensitively explore the genomes and transcriptomes of diverse gut E. coli, we develop E. coli PanSelect, which uses probes designed to specifically capture E. coli's broad pangenome. We demonstrate its ability to enrich diverse E. coli by orders of magnitude, in a mock community and in human stool from a study investigating recurrent UTI (rUTI). Comparisons of transcriptomes between gut E. coli of women with and without history of rUTI suggest rUTI gut E. coli are responding to increased oxygen and nitrate, suggestive of mucosal inflammation, which may have implications for recurrent disease. E. coli PanSelect is well suited for investigations of in vivo E. coli biology in other low-abundance environments, and the framework described here has broad applicability to other diverse, low-abundance organisms.

Fusobacterium Nucleatum Abundance Is Associated With Cachexia In Colorectal Cancer Patients: The Colocare Study, Mmadili N Ilozumba, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

BACKGROUND: Cachexia accounts for about 20% of all cancer-related deaths and indicates poor prognosis. The impact of Fusobacterium nucleatum (Fn), a microbial risk factor for colorectal cancer (CRC), on the development of cachexia in CRC has not been established.

METHODS: We evaluated the association between Fn abundance in pre-surgical stool samples and onset of cachexia at 6 months post-surgery in n = 87 patients with stages I-III CRC in the ColoCare Study.

RESULTS: High fecal Fn abundance compared to negative/low fecal Fn abundance was associated with 4-fold increased risk of cachexia onset at 6 months post-surgery (OR = 4.82, 95% …