Digital Commons Network^™

Preparing To Implement Shared Decision Making In Anaesthesia For Hip Fracture Surgery: A Qualitative Interview Study, Eliana C Goldstein, Mark D Neuman, Viktoria Vonder Haar, Aaron C Li, Carlos E Guerra-Londono, Glyn Elwyn, Stacie G Deiner, Adnan Hussain, Joshua W Sappenfield, Christopher J Edwards, Sabry Ayad, James H Baraldi, Karah Whatley, Mary C Politi

2020-Current year OA Pubs

BACKGROUND: Shared decision making is rarely used in anaesthesia consultations. Because either spinal or general anaesthesia can be appropriate for many patients undergoing surgery to repair a hip fracture, this is an appropriate context to implement and test shared decision making and associated resources for anaesthesia decisions. Conversation aids can facilitate shared decision making between clinicians, patients, and caregivers about treatment choices.

METHODS: We conducted semi-structured qualitative interviews at seven sites from April to September 2024 to prepare for implementation of a conversation aid about anaesthesia choices for hip fracture surgery. Interviews elicited feedback on shared decision making and a …

Methylomic Signature Of Current Cannabis Use In Two First-Episode Psychosis Cohorts, Emma L Dempster, Emma C Johnson, Et Al.

2020-Current year OA Pubs

The rising prevalence and legalisation of cannabis worldwide have underscored the need for a comprehensive understanding of its biological impact, particularly on mental health. Epigenetic mechanisms, specifically DNA methylation, have gained increasing recognition as vital factors in the interplay between risk factors and mental health. This study aimed to explore the effects of current cannabis use and high-potency cannabis on DNA methylation in two independent cohorts of individuals experiencing first-episode psychosis (FEP) compared to control subjects. The combined sample consisted of 682 participants (188 current cannabis users and 494 never users). DNA methylation profiles were generated on blood-derived DNA samples …

A Scoping Review Of Interventions To Address Financial Toxicity In Pediatric And Adult Patients And Survivors Of Cancer, Christina Ping, D Carolina Andrade, Ashley Housten, Michelle Doering, Eliana Goldstein, Mary C Politi

2020-Current year OA Pubs

BACKGROUND: Financial toxicity (FT) is a common and significant challenge for people with cancer, impacting immediate clinical outcomes such as treatment adherence, as well as long-term outcomes such as quality of life and mortality. Multiple studies have tested interventions to address FT and develop recommendations for their implementation.

METHODS: In this scoping review, we analyzed thirty-six studies across 35,405 participants examining institution-based interventions for FT in both pediatric and adult patients and survivors of cancer in the U.S.

RESULTS: Common interventions included: financial navigation (n = 15), direct financial/medical assistance (n = 8), financial counseling or coaching (n = 5), …

Diverse Case Series Of Granulomatous Peritonitis Mimicking Advanced Ovarian Cancer, Rachel L Furuya, Bobbie J Rimel, Richard Tsai, Rebecca Ann Brooks, L Stewart Massad, Premal H Thaker, John D Pfeifer

2020-Current year OA Pubs

BACKGROUND: Epithelial ovarian cancer commonly presents with vague symptoms that delay diagnosis until disease is advanced. Granulomatous peritonitis is a term used to describe granulomatous inflammation within the peritoneal cavity and mimics advanced stage ovarian cancer clinically and on imaging. The goal of this study was to examine the frequency and characteristics of cases of granulomatous peritonitis mimicking ovarian cancer at a single institution and to describe the etiology in this population.

METHODS: Eight cases were identified with pathology conformation of granulomatous disease and absence of cancer. The etiologies include pelvic tuberculosis, ruptured dermoid cyst, ruptured hemorrhagic corpus luteum, prior …

Thrombotic Microangiopathy After Kidney Transplantation: Insights Into Genetic Etiology And Clinical Outcomes, Massini Merzkani, Nyein Chann Wai Lynn, Karen Flores, Gaurav Rajashekar, Kristin Progar, Rowena Delos Santos, John P Atkinson, Daniel C Brennan, Anuja Java

2020-Current year OA Pubs

INTRODUCTION: Thrombotic microangiopathy (TMA), characterized by small-vessel thrombosis caused by endothelial injury, presents significant diagnostic and treatment challenges in kidney transplantation.

METHODS: To investigate the factors associated with posttransplant TMA, we conducted a retrospective study of 3535 kidney transplant recipients at our center from 2008 to 2023.

RESULTS: Sixty-eight patients were diagnosed with TMA, and 93% (63 of 68) underwent genetic testing. Patients were categorized into 3 groups based on the TMA etiology. Group 1 (

CONCLUSION: Our findings underscore the need for comprehensive pre and posttransplantation genetic testing to predict and manage the risk of TMA and prevent graft …

Saludo: A Randomized Phase Iib/Iii Study Of Lurbinectedin Plus Doxorubicin As First-Line Treatment In Leiomyosarcoma, Gregory M Cote, Mia C Weiss, Et Al.

2020-Current year OA Pubs

Previous phase I/II trials indicate promising activity of lurbinectedin plus doxorubicin (DOX) in leiomyosarcoma (LMS). We describe here the rationale and design of SaLuDo, an open label, randomized, multicenter, seamless phase IIb/III study to evaluate the antitumor activity and safety of lurbinectedin plus DOX

First-In-Human Phase I Study Of A Cd16a Bispecific Innate Cell Engager, Afm24, Targeting Egfr-Expressing Solid Tumors, Anthony El-Khoueiry, Todd A Fehniger, Mark Foster, Melissa M Berrien-Elliott, Et Al.

2020-Current year OA Pubs

PURPOSE: Innate immune cell-based therapies have shown promising antitumor activity against solid and hematologic malignancies. AFM24, a bispecific innate cell engager, binds CD16A on NK cells/macrophages and EGFR on tumor cells, redirecting antitumor activity toward tumors. The safety and tolerability of AFM24 were evaluated in this phase I/IIa dose-escalation/dose-expansion study in patients with recurrent or persistent, advanced solid tumors known to express EGFR.

PATIENTS AND METHODS: The main objective in phase I was to determine the MTD and/or recommended phase II dose. The primary endpoint was the incidence of dose-limiting toxicities during the observation period. Secondary endpoints included the incidence …

Genomic Analysis Of 11,555 Probands Identifies 60 Dominant Congenital Heart Disease Genes, Michael C Sierant, Sheng Chih Jin, Et Al.

2020-Current year OA Pubs

Congenital heart disease (CHD) is a leading cause of infant mortality. We analyzed de novo mutations (DNMs) and very rare transmitted/unphased damaging variants in 248 prespecified genes in 11,555 CHD probands. The results identified 60 genes with a significant burden of heterozygous damaging variants. Variants in these genes accounted for CHD in 10.1% of probands with similar contributions from de novo and transmitted variants in parent-offspring trios that showed incomplete penetrance. DNMs in these genes accounted for 58% of the signal from DNMs. Thirty-three genes were linked to a single CHD subtype while 12 genes were associated with 2 to …

Acute Trem2 Inhibition Depletes Mafb-High Microglia And Hinders Remyelination, Jinchao Hou, Roberta Magliozzi, Yun Chen, Junjie Wu, John Wulf Ii, Gregory Strout, Xiangming Fang, Marco Colonna

2020-Current year OA Pubs

We investigated the role of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) in myelin regeneration in the brain. TREM2 is a receptor that activates microglia, which are crucial for clearing myelin debris and promoting remyelination. Previous studies in a mouse model of demyelination induced by the copper-chelating agent Cuprizone (CPZ) have shown that stimulation of TREM2 with a monoclonal antibody reduces demyelination, while deleting the

Bcl-Xl Protects Ass1-Deficient Cancers From Arginine Starvation-Induced Apoptosis, Prashanta Kumar Panda, Ana Carolina Paschoalini Mafra, Alliny C S Bastos, Li Cao, Maria Serra Bonet, Caitlyn B Brashears, Ethan Yang Chen, Heather M Benedict-Hamilton, William Ehrhardt, John Bomalaski, Carina Dehner, Leonard C Rogers, Toshinao Oyama, Brian A Van Tine

2020-Current year OA Pubs

PURPOSE: Argininosuccinate synthetase 1 (ASS1) silencing in carcinomas and sarcomas leads to a dependence on extracellular arginine for survival. Arginine deprivation therapies, such as PEGylated arginine deiminase (ADI-PEG20), have shown limited effectiveness, which may be due to underlying mechanisms that inhibit apoptosis.

EXPERIMENTAL DESIGN: The effects of ADI-PEG20 on cell-cycle regulation, apoptosis, and BCL-XL-mediated survival pathways in ASS1-deficient cancer cells were determined. The mechanism of cell death protection was determined by assessing caspase and PARP cleavage, CDK2 activity, MCL1 expression, and the interactions among BCL-XL, BAX, and BAK. In vitro synergy was determined, and in vivo efficacy was modeled.

RESULTS: …

Patient- And Community-Level Characteristics Associated With Respiratory Syncytial Virus Vaccination, Diya Surie, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

IMPORTANCE: In 2023, the first respiratory syncytial virus (RSV) vaccines were recommended for US adults 60 years or older, but few data are available about which patients were most likely to receive vaccine to inform future RSV vaccine outreach efforts.

OBJECTIVE: To assess patient- and community-level characteristics associated with RSV vaccine receipt and patient knowledge and attitudes related to RSV disease and RSV vaccines.

DESIGN, SETTING, AND PARTICIPANTS: During the first season of RSV vaccine use from October 1, 2023, to April 30, 2024, adults 60 years or older hospitalized with RSV-negative acute respiratory illness were enrolled in this cross-sectional …

Patients' Attitudes To Magnetic Resonance Imaging In Perianal Fistulizing Crohn's Disease: A Global Survey, Easan Anand, Jalpa Devi, Anna Antoniou, Shivani Joshi, Jaap Stoker, Phillip Lung, Ailsa Hart, Phil Tozer, David H Ballard, Parakkal Deepak

2020-Current year OA Pubs

BACKGROUND: There is limited patient involvement in radiological research for perianal fistulizing Crohn's disease (pfCD), despite magnetic resonance imaging (MRI)'s critical role in diagnosis and management. Patient and public involvement is essential for aligning research with patient priorities. This study aimed to gather patient perspectives on the use of MRI in pfCD.

METHODS: A mixed-methods approach was used, following Guidance for Reporting Involvement of Patients and the Public (GRIPP2) guidelines. An online survey, co-developed with a patient representative, included open and closed questions on MRI experiences, advantages, challenges, and the potential for Artificial Intelligence (AI)-generated reports. This was followed by …

Hypertension Diagnosis And Management In Bamako, Mali, Issiaka Camara, Mohamed Traore, Mamoudou Maiga, Dike Ojji, Jane Holl, Souleymane Coulibaly, Mark D Huffman

2020-Current year OA Pubs

PROBLEM: The capacity and site readiness for delivering hypertension management services in Mali were unknown, hindering the effective implementation of the World Health Organization (WHO) HEARTS technical package for cardiovascular disease management.

APPROACH: We selected one tertiary and two secondary hospitals to be assessed. From December 2021 to January 2022, hospital cardiologists collected data on indicators of capacity and site readiness using an adapted version of the WHO service availability and readiness assessment questionnaire. The study team verified the collected data through site inspection and review of administrative documents.

LOCAL SETTING: Mali, a low-income country with a population of 22 …

Dynamic Femoral Head Coverage Following Periacetabular Osteotomy For Developmental Dysplasia Of The Hip, Christina A Bourantas, Emma C Behrman, Molly C Shepherd, Keith R Lohse, John C Clohisy, Michael D Harris

2020-Current year OA Pubs

BACKGROUND: Developmental dysplasia of the hip reduces hip stability due to insufficient femoral head coverage. Periacetabular osteotomy surgery aims to increase this coverage. Typically measured using radiographs, most coverage assessments are limited to static hip positions and cannot capture 3D anatomy. This study quantified how dynamic 3D femoral coverage changes during gait and squat after periacetabular osteotomy surgery and compared dynamic coverage to static measures.

METHODS: Pre- and post-surgery CT scans from 38 patients with hip dysplasia were used to reconstruct 3D femur and pelvis bones with which gait and squat were simulated. Models of 38 control subjects were also …

Factors Associated With Shock At Presentation In Kawasaki Disease Versus Multisystem Inflammatory Syndrome In Children Associated With Covid-19, Supriya S Jain, William B Orr, Et Al.

2020-Current year OA Pubs

BACKGROUND: While clinical overlap between Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) has been evident, information regarding those presenting with shock has been limited. We sought to determine associations with shock within and between diagnosis groups.

METHODS: The International KD Registry enrolled contemporaneous patients with either KD or MIS-C from 39 sites in 7 countries from January 1, 2020, to January 1, 2023. Demographics, clinical features and presentation, management, laboratory values, and outcomes were compared between the diagnosis and shock groups.

RESULTS: Shock at presentation was noted for 19 of 672 KD patients (2.8%) and 653 of …

Quantitative And Visual Benefits Of Data-Driven Motion Correction On Oncologic Pet/Ct: A Prospective Cross-Sectional Study, Semra Ince, M Allan Thomas, Malak Itani, Christopher Swingle, Richard Laforest, Adeel Haq, Genevieve Muñoz, Saeed Ashrafinia, Paul Schleyer, Richard L Wahl, Tyler J Fraum

2020-Current year OA Pubs

RATIONALE AND OBJECTIVE: Conventional positron emission tomography (PET) respiratory gating utilizes a fraction of acquired PET counts (i.e., optimal gate [OG]), whereas elastic motion correction with deblurring (EMCD) utilizes all PET counts to reconstruct motion-corrected images without increasing image noise. Our aim was to assess the quantitative and visual impacts of EMCD-based motion correction on FDG-PET and DOTATATE-PET images relative to OG and ungated (UG) images.

MATERIALS AND METHODS: This prospective, single-center study enrolled adults undergoing FDG or DOTATATE oncologic PET/CT between June 2020 and October 2022. Subjects underwent a standard-of-care (SOC) PET acquisition while wearing a respiratory gating belt. …

Statistical Properties Of Functional Connectivity Mri Enrichment Analysis In School-Age Autism Research, Austin S Ferguson, Tomoyuki Nishino, Natasha Marrus, John R Pruett Jr, Alexandre A Todorov, Et Al.

2020-Current year OA Pubs

Mass univariate testing on functional connectivity MRI (fcMRI) data is limited by difficulties achieving experiment-wide significance. Recent work addressing this problem has used enrichment analysis, which aggregates univariate screening statistics for a set of variables into a single enrichment statistic. There have been promising results using this method to explore fcMRI-behavior associations. However, there has not yet been a rigorous examination of the statistical properties of enrichment analysis when applied to fcMRI data. Establishing power for fcMRI enrichment analysis will be important for future neuropsychiatric and cognitive neuroscience study designs that plan to include this method. Here, we use realistic …

Single-Cell Transcriptomic Analysis Of Kaposi Sarcoma, Daniel A. Rauch, Paula Valiño Ramos, Mariam Khanfar, John Harding, Ancy Joseph, Anam Fahad, Paul Simonson, Isabel Risch, Obi Griffith, Malachi Griffith, Lee Ratner

2020-Current year OA Pubs

Kaposi Sarcoma (KS) is a complex tumor caused by KS-associated herpesvirus 8 (KSHV). Histological analysis reveals a mixture of "spindle cells", vascular-like spaces, extravasated erythrocytes, and immune cells. In order to elucidate the infected and uninfected cell types in KS tumors, we examined twenty-five skin and blood samples from sixteen subjects by single cell RNA sequence analyses. Two populations of KSHV-infected cells were identified, one of which represented a CD34-negative proliferative fraction of endothelial cells, and the second representing CD34-positive cells expressing endothelial genes found in a variety of cell types including high endothelial venules, fenestrated capillaries, and endothelial tip …

Dynein Light Chains 1 And 2 Are Auxiliary Proteins Of Ph-Sensitive Kir4.1 Channels, Sun-Joo Lee, Jian Gao, Ellen Thompson, Jonathan Mount, Colin G Nichols

2020-Current year OA Pubs

Inward rectifier Kir4.1 potassium channels are abundantly expressed in cells that are important for electrolyte homeostasis. Dysregulation of Kir4.1 underlies various neurological disorders. Here, through biochemical and structural studies of full-length Kir4.1, we show that dynein light chain 1 and 2 proteins, also as known as LC8, copurify with Kir4.1 at stoichiometric levels. Direct interaction between Kir4.1 and LC8 is supported by in vitro binding assays and reiterated with native Kir4.1 proteins from mouse brain. Notably, we identify a LC8 binding motif in the unstructured N terminus of Kir4.1. Among Kir subtypes, the motif is unique to Kir4.1 and is …

Self-Collected Vaginal Specimens For Hpv Testing: Recommendations From The Enduring Consensus Cervical Cancer Screening And Management Guidelines Committee, Nicolas Wentzensen, L. Stewart Massad, Megan A. Clarke, Francisco Garcia, Robert Smith, Jeanne Murphy, Richard Guido, Ana Reyes, Sarah Phillips, Nancy Berman, Jeffrey Quinlan, Eileen Lind, Rebecca B. Perkins, Enduring Consensus Cervical Cancer Screening And Management Guidelines Committee

2020-Current year OA Pubs

OBJECTIVE: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for the use of self-collected vaginal specimens for human papillomavirus (HPV) testing in health care settings.

METHODS: A comprehensive literature search was performed, external systematic reviews were evaluated, and HPV genotype agreement between self-collected vaginal and clinician-collected cervical specimens was summarized. Recommendations considered available data, public comments, and expert consensus. Recommendations were ratified through a vote by the Consensus Stakeholder Group.

RESULTS: Clinician-collected cervical specimens are preferred and self-collected vaginal specimens are acceptable for primary HPV screening of asymptomatic average-risk individuals. Repeat testing in 3 years is …

The Role Of Androgens On Experimental Pain Sensitivity: A Systemic Review And Meta-Analysis, Elizabeth Wu-Chen, Gourav Banerjee, Elise Requadt, Benjamin Hunter, Thomas J. Baranski, Whitney Trotter Ross, Hadas Nahman-Averbuch

2020-Current year OA Pubs

Animal studies have shown androgens, especially testosterone, may have an analgesic effect on nociceptive behavior. However, it is unclear if this effect is present in humans. This review and meta-analysis aim to summarize and synthesize the role of androgens on experimental pain sensitivity in humans. Studies were included if they examined the (1) relationships between androgens and experimental pain sensitivity, (2) group differences in androgen or pain levels, and (3) the effect of androgen interventions on experimental pain sensitivity. After a comprehensive search, 31 papers were identified. When possible, meta-analyses were performed. Most studies examined the impact of testosterone on …

Subgroup Evaluation To Understand Performance Gaps In Deep Learning-Based Classification Of Regions Of Interest On Mammography, Minjae Woo, Linglin Zhang, Beatrice Brown-Mulry, Inchan Hwang, Judy Wawira Gichoya, Aimilia Gastounioti, Imon Banerjee, Laleh Seyyed-Kalantari, Hari Trivedi

2020-Current year OA Pubs

This study evaluates a deep learning model for classifying normal versus potentially abnormal regions of interest (ROIs) on mammography, aiming to identify imaging, pathologic, and demographic characteristics that may induce suboptimal model performance in certain patient subgroups. We utilized the EMory BrEast imaging Dataset (EMBED), containing 3.4 million mammographic images from 115,931 patients. Full-field digital mammograms from women aged 18 years or older were used to create positive and negative patches with the patches matched based on size, location, patient demographics, and imaging features. Several convolutional neural network (CNN) architectures were tested, with ResNet152V2 demonstrating the best performance. The dataset …

Systemic Inflammation Is Associated With Worse Outcomes From Sars-Cov-2 Infection But Not Neutralizing Antibody, Christopher W Farnsworth, Brittany Roemmich, John Prostko, Gerard Davis, Gillian Murtagh, Laurel Jackson, Christopher Jacobson, Nicolette Jeanblanc, Timothy Griffiths, Edwin Frias, David J Daghfal

2020-Current year OA Pubs

Systemic inflammation is associated with COVID-19 mortality rates, but the impact of inflammation on neutralizing antibodies to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and on outcomes is poorly understood. This study aimed to determine the association between neutralizing antibody responses, inflammation, and clinical outcomes in hospitalized patients with COVID-19. Two hundred and eight patients presenting to the ED with symptomatic SARS-CoV-2 were included. Neutralization was assessed using the architect angiotensin-converting enzyme-2 (ACE2) binding inhibition assay, and inflammation was assessed using C reactive protein (CRP) and interleukin 6 (IL-6). Medical records were examined for 30-day mortality and 10-day intubation. Correlation …

Severe Aortic Stenosis And Chronic Myeloid Leukemia: Considerations For Valve Management, Rebecca Cunningham, Sang Gune K Yoo, Alexander A Brescia, Karolyn A Oetjen, Iskra Pusic, Joshua D Mitchell

2020-Current year OA Pubs

No abstract provided.

Management Aspects Of Medical Therapy In Graves Disease, Rutu Shah, Samantha E Adamson, Sina Jasim

2020-Current year OA Pubs

OBJECTIVE: Graves disease (GD) is the most common cause of hyperthyroidism. Treatment options include antithyroid drugs (ATDs), radioactive iodine, and surgery. In this review, we focus on the medical aspects of managing GD.

METHODS: The authors conducted a literature review of PubMed to include studies and review articles on GD management, ATDs, long-term safety of antithyroid drugs, hyperthyroidism in pregnancy, Graves ophthalmopathy, and special circumstances related to hyperthyroidism.

RESULTS: In adjunction to ATDs, medical management for GD also includes beta-blockers, glucocorticoids, and iodine containing agents. ATDs are currently the preferred option for initial management of GD, reflecting a shift in …

Biliary Metaplasia And Macrophage Activation Define The Cellular Landscape Of Cardiogenic Liver Disease, Arick C Park, Christina F Fu, Adeesh Parvathaneni, Bin Q Yang, Mandy M Chan, Kathleen Byrnes, Joel D Schilling

2020-Current year OA Pubs

Right heart failure significantly impacts liver remodeling and function, a process referred to as cardiogenic liver disease. Although recognized as a risk factor for adverse outcomes, little is understood about the cellular and molecular players that contribute to liver disease in heart failure. Using human liver biopsy samples from patients with heart failure and a mouse model of liver congestion, we unraveled a nexus of macrophages, hepatic stellate cells, and biliary metaplastic cells that shape the pathologic environment of cardiogenic liver disease.

Neuroimmune Mechanisms Of Type 2 Inflammation In The Skin And Lung, Masato Tamari, Aaron M Ver Heul

2020-Current year OA Pubs

Type 2 inflammation has a major role in barrier tissues such as the skin and airways and underlies common conditions including atopic dermatitis (AD) and asthma. Cytokines including interleukin 4 (IL-4), IL-5, and IL-13 are key immune signatures of type 2 inflammation and are the targets of multiple specific therapeutics for allergic diseases. Despite shared core immune mechanisms, the distinct structures and functions of the skin and airways lead to unique therapeutic responses. It is increasingly recognized that the nervous system has a major role in sensing and directing inflammatory processes. Indeed, crosstalk between type 2 immune activation and somatosensory …

Enhancing Human Nk Cell Antitumor Function By Knocking Out Smad4 To Counteract Tgfβ And Activin A Suppression, Anna Rea, Bishan Bhattarai, Marco Colonna, Et Al.

2020-Current year OA Pubs

Transforming growth factor beta (TGFβ) and activin A suppress natural killer (NK) cell function and proliferation, limiting the efficacy of adoptive NK cell therapies. Inspired by the partial resistance to TGFβ of NK cells with SMAD4 haploinsufficiency, we used CRISPR-Cas9 for knockout of SMAD4 in human NK cells. Here we show that SMAD4

The Ten Test And Sensory Evaluation Of Hand And Finger Injuries In The Emergency Department, Emilie H Lothet, Aaron J Lacy, Elizabeth B Odom

2020-Current year OA Pubs

BACKGROUND: Hand and finger injuries are a common presenting complaint to the emergency department (ED) and are associated with significant morbidity. Neurologic evaluation of these injuries is a crucial component of the patient assessment and can be done via a variety of testing methods.

DISCUSSION: Although most taught and cited in the ED literature, the two-point discrimination test for sensation has several drawbacks, including limited reproducibility and reliability. Although often utilized by hand surgical specialists, the Semmes-Weinstein monofilament test and the Weinstein Enhanced Sensory Test are not practical for the emergency physician due to the need for specialized equipment and …

In Vivo Manipulation Of Human Gut Bacteroides Fitness By Abiotic Oligosaccharides, Darryl A Wesener, Zachary W Beller, Megan F Hill, Han Yuan, David B Belanger, Cheryl Frankfater, Nicolas Terrapon, Bernard Henrissat, Dmitry A Rodionov, Semen A Leyn, Andrei Osterman, Johan E T Van Hylckama Vlieg, Jeffrey I Gordon

2020-Current year OA Pubs

Synthetic glycans (SGs) containing glycosidic linkages and structures not identified in nature offer a means for deliberately altering microbial community properties. Here pools of SG oligosaccharides were generated via polymerization of monosaccharides and screened for their ability to increase saccharolytic Bacteroides in ex vivo cultures of human fecal samples. A lead SG preparation was orally administered to gnotobiotic mice harboring a consortium of 56 cultured, phylogenetically diverse human gut bacteria and fed a Western diet. The abundances of 3 of 15 Bacteroides strains increased, most prominently B. intestinalis. Underlying mechanisms were characterized by analyzing in vivo expression of the carbohydrate …