tbuckley/cabot-search huggingface dataset:
Altered gut bacterial and metabolic signatures and their interaction in gestational diabetes mellitus
Authors: Xing Wang, Hongli Liu, Yifan Li, Shuai Huang, Lan Zhang, Chiying Cao, Philip N. Baker, Chao Tong, Peng Zheng, Hongbo Qi
Journal: Gut Microbes (2020)

Emerging evidence indicates that the gut microbiome can modulate metabolic homeostasis, and thus may influence the development of gestational diabetes mellitus (GDM). However, whether and how the gut microbiome and its correlated metabolites change in GDM is uncertain. Herein we compare the gut microbial compositions, and fecal and urine metabolomes, of 59 patients with GDM versus 48 pregnant healthy controls (HCs). We showed that the microbial and metabolic signatures of GDM patients were significantly different from those of HCs. Compared to HCs, the GDM subjects were characterized by enriched bacterial operational taxonomic units (OTUs) of the family Lachnospiraceae, and depleted OTUs of the families Enterobacteriaceae and Ruminococcaceae. Some altered gut microbes were significantly correlated with glucose values and fetal ultrasonography indexes. Moreover, we identified four fecal and 15 urine metabolites that discriminate GDM from HC. These differential metabolites are mainly involved in carbohydrate and amino acid metabolism. Significantly, co-occurrence network analysis revealed that Lachnospiraceae and Enterobacteriaceae bacterial OTUs formed strong co-occurring relationships with metabolites involved in carbohydrate and amino acid metabolism, suggesting that disturbed gut microbiome may mediate GDM. Furthermore, we identified a novel combinatorial marker panel that could distinguish GDM from HC subjects with high accuracy. Together our findings demonstrate that altered microbial composition and metabolic function may be relevant to the pathogenesis and pathophysiology of GDM.
D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization
Authors: Drew Weissman, Mohamad-Gabriel Alameh, Thushan de Silva, Paul Collini, Hailey Hornsby, Rebecca Brown, Celia C. LaBranche, Robert J. Edwards, Laura Sutherland, Sampa Santra, Katayoun Mansouri, Sophie Gobeil, Charlene McDanal, Norbert Pardi, Nick Hengartner, Paulo J.C. Lin, Ying Tam, Pamela A. Shaw, Mark G. Lewis, Carsten Boesler, Uğur Şahin, Priyamvada Acharya, Barton F. Haynes, Bette Korber, David C. Montefiori
Journal: Cell Host & Microbe (2020)
Constitutive androstane receptor induced-hepatomegaly and liver regeneration is partially via yes-associated protein activation
Authors: Yue Gao, Shicheng Fan, Hua Li, Yiming Jiang, Xinpeng Yao, Shuguang Zhu, Xiao Yang, Ruimin Wang, Jianing Tian, Frank J. Gonzalez, Min Huang, Huichang Bi
Journal: Acta Pharmaceutica Sinica B (2020)

The constitutive androstane receptor (CAR, NR3I1) belongs to nuclear receptor superfamily. It was reported that CAR agonist TCPOBOP induces hepatomegaly but the underlying mechanism remains largely unknown. Yes-associated protein (YAP) is a potent regulator of organ size. The aim of this study is to explore the role of YAP in CAR activation-induced hepatomegaly and liver regeneration. TCPOBOP-induced CAR activation on hepatomegaly and liver regeneration was evaluated in wild-type (WT) mice, liver-specific YAP-deficient mice, and partial hepatectomy (PHx) mice. The results demonstrate that TCPOBOP can increase the liver-to-body weight ratio in wild-type mice and PHx mice. Hepatocytes enlargement around central vein (CV) area was observed, meanwhile hepatocytes proliferation was promoted as evidenced by the increased number of KI67+ cells around portal vein (PV) area. The protein levels of YAP and its downstream targets were upregulated in TCPOBOP-treated mice and YAP translocation can be induced by CAR activation. Co-immunoprecipitation results suggested a potential protein–protein interaction of CAR and YAP. However, CAR activation-induced hepatomegaly can still be observed in liver-specific YAP-deficient (Yap–/–) mice. In summary, CAR activation promotes hepatomegaly and liver regeneration partially by inducing YAP translocation and interaction with YAP signaling pathway, which provides new insights to further understand the physiological functions of CAR.
Cardiovascular Magnetic Resonance Imaging: Is Only One Shop Worth the Stop?⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: W. Gregory Hundley, Jagat Narula
Journal: JACC. Cardiovascular imaging (2009)
Single-cell profiling reveals the trajectories of natural killer cell differentiation in bone marrow and a stress signature induced by acute myeloid leukemia
Authors: Adeline Crinier, Pierre-Yves Dumas, Bertrand Escalière, Christelle Piperoglou, Laurine Gil, Arnaud Villacreces, Frédéric Vély, Zoran Ivanovic, Pierre Milpied, Émilie Narni-Mancinelli, Éric Vivier
Journal: Cellular and Molecular Immunology (2020)

Natural killer (NK) cells are innate cytotoxic lymphoid cells (ILCs) involved in the killing of infected and tumor cells. Among human and mouse NK cells from the spleen and blood, we previously identified by single-cell RNA sequencing (scRNAseq) two similar major subsets, NK1 and NK2. Using the same technology, we report here the identification, by single-cell RNA sequencing (scRNAseq), of three NK cell subpopulations in human bone marrow. Pseudotime analysis identified a subset of resident CD56bright NK cells, NK0 cells, as the precursor of both circulating CD56dim NK1-like NK cells and CD56bright NK2-like NK cells in human bone marrow and spleen under physiological conditions. Transcriptomic profiles of bone marrow NK cells from patients with acute myeloid leukemia (AML) exhibited stress-induced repression of NK cell effector functions, highlighting the profound impact of this disease on NK cell heterogeneity. Bone marrow NK cells from AML patients exhibited reduced levels of CD160, but the CD160high group had a significantly higher survival rate.
Usefulness of the S-O clip in balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography
Authors: Kotaro Takeshita, Satoshi Asai, Naoki Fujimoto, Hitomi Jimbo, Takumi Ichinona, Eisuke Akamine
Journal: Endoscopy (2020)

A 77-year-old woman with a history of total gastrectomy with Roux-en-Y anastomosis was admitted with acute gallstone cholangitis ([Fig. 1]). We attempted endoscopic stone removal with a double-balloon enteroscope (DBE) (EI-580BT; Fujifilm, Osaka, Japan).
Dual delivery of IL-10 and AT-RvD1 from PEG hydrogels polarize immune cells towards pro-regenerative phenotypes
Authors: Mary Caitlin P. Sok, Nusaiba Baker, Claire McClain, Hong Seo Lim, Thomas Turner, Lauren Hymel, Molly Ogle, Claire Olingy, Joshua I. Palacios, José R. Garcia, Krithik Srithar, Andrés J. García, Peng Qiu, Edward A. Botchwey
Journal: Biomaterials (2020)
MDR M. tuberculosis outbreak clone in Eswatini missed by Xpert has elevated bedaquiline resistance dated to the pre-treatment era
Authors: Patrick Beckert, Elisabeth Sanchez-Padilla, Matthias Merker, Viola Dreyer, Thomas A. Kohl, Christian Utpatel, Claudio U. Köser, Ivan Barilar, Nazir Ismail, Shaheed Vally Omar, Marisa Klopper, Robin M. Warren, Harald Hoffmann, Gugu Maphalala, Elisa Ardizzoni, Bouke C. de Jong, Bernhard Kerschberger, Birgit Schramm, Sönke Andres, Katharina Kranzer, Florian P. Maurer, Maryline Bonnet, Stefan Niemann
Journal: Genome Medicine (2020)

Multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains not detected by commercial molecular drug susceptibility testing (mDST) assays due to the RpoB I491F resistance mutation are threatening the control of MDR tuberculosis (MDR-TB) in Eswatini.We investigate the evolution and spread of MDR strains in Eswatini with a focus on bedaquiline (BDQ) and clofazimine (CFZ) resistance using whole-genome sequencing in two collections ((1) national drug resistance survey, 2009-2010; (2) MDR strains from the Nhlangano region, 2014-2017).MDR strains in collection 1 had a high cluster rate (95%, 117/123 MDR strains) with 55% grouped into the two largest clusters (gCL3, n = 28; gCL10, n = 40). All gCL10 isolates, which likely emerged around 1993 (95% highest posterior density 1987-1998), carried the mutation RpoB I491F that is missed by commercial mDST assays. In addition, 21 (53%) gCL10 isolates shared a Rv0678 M146T mutation that correlated with elevated minimum inhibitory concentrations (MICs) to BDQ and CFZ compared to wild type isolates. gCL10 isolates with the Rv0678 M146T mutation were also detected in collection 2.The high clustering rate suggests that transmission has been driving the MDR-TB epidemic in Eswatini for three decades. The presence of MDR strains in Eswatini that are not detected by commercial mDST assays and have elevated MICs to BDQ and CFZ potentially jeopardizes the successful implementation of new MDR-TB treatment guidelines. Measures to limit the spread of these outbreak isolates need to be implemented urgently.
Physics-informed neural networks for myocardial perfusion MRI quantification
Authors: Rudolf L.M. van Herten, Amedeo Chiribiri, Marcel Breeuwer, Mitko Veta, Cian M. Scannell
Journal: Medical Image Analysis (2022)

Tracer-kinetic models allow for the quantification of kinetic parameters such as blood flow from dynamic contrast-enhanced magnetic resonance (MR) images. Fitting the observed data with multi-compartment exchange models is desirable, as they are physiologically plausible and resolve directly for blood flow and microvascular function. However, the reliability of model fitting is limited by the low signal-to-noise ratio, temporal resolution, and acquisition length. This may result in inaccurate parameter estimates. This study introduces physics-informed neural networks (PINNs) as a means to perform myocardial perfusion MR quantification, which provides a versatile scheme for the inference of kinetic parameters. These neural networks can be trained to fit the observed perfusion MR data while respecting the underlying physical conservation laws described by a multi-compartment exchange model. Here, we provide a framework for the implementation of PINNs in myocardial perfusion MR. The approach is validated both in silico and in vivo. In the in silico study, an overall decrease in mean-squared error with the ground-truth parameters was observed compared to a standard non-linear least squares fitting approach. The in vivo study demonstrates that the method produces parameter values comparable to those previously found in literature, as well as providing parameter maps which match the clinical diagnosis of patients.
16822 Effect of commonly antiseptics used in clinic in an artificial autologous skin model based on hyaluronic acid biomaterial
Authors: Ana Fernández-González, MarÃ­a I. Quiñones-Vico, Elena Pérez-Castejón, Antonio M. Lizana-Moreno, Jorge Guerrero Calvo, Natividad Fernández-Porcel, Antonio Ruiz-Garcia, Álvaro Sierra-Sánchez, Salvador Arias-Santiago, Alexandra Ordoñez-Luque, Olga Espinosa-Ibañez
Journal: Journal of the American Academy of Dermatology (2020)
Human “Nuclear” Mitochondrial Cardiomyopathy: A Novel Mouse Model Characterizes the Disease⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Eloisa Arbustini, Maurizia Grasso
Journal: JACC. Cardiovascular imaging (2011)
Non–Small Cell Lung Cancer
Authors: David S. Ettinger, Wallace Akerley, Gerold Bepler, Matthew G. Blum, Andrew Chang, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D'Amico, Todd L. Demmy, Apar Kishor P. Ganti, Ramaswamy Govindan, Frederic W. Grannis, Thierry Jahan, Mohammad Jahanzeb, David H. Johnson, Anne Kessinger, Ritsuko Komaki, Feng-Ming Kong, Mark G. Kris, Lee M. Krug, Quynh-Thu Le, Inga T. Lennes, Renato Martins, Janis O'Malley, Raymond U. Osarogiagbon, Gregory A. Otterson, Jyoti D. Patel, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Eric Rohren, George R. Simon, Scott J. Swanson, Douglas E. Wood, Stephen C. Yang
Journal: Journal of the National Comprehensive Cancer Network (2010)

deaths (88,900 men; 70,490 women) occurred from the disease. 1 Only 15% of all lung cancer patients are alive 5 years or more after diagnosis (http://seer.cancer.gov/statfacts/html/lungb.html).
348P Anti-VEGF inhibitors and renal safety in onco-nephrology consortium: Urinary protein/creatinine ratio (VERSiON UP study)
Authors: M. Nakamura, T. Funakoshi, S. Kataoka, T. Horimatsu, Y. Nishikawa, T. Matsubara, T. Mizukami, T. Goto, K. Tsuchihashi, E. Baba, T. Tsumura, Y. Mihara, T. Hamaguchi, M. Muto, M. Yanagita
Journal: Annals of Oncology (2020)
15280 Characterization of super responders to guselkumab treatment in moderate to severe psoriasis: Results from the VOYAGE 1 and 2 clinical trials
Authors: Kristian Reich, Bruce Strober, Richard Langley, Michael Song, Yaung-Kaung Shen, Yin You, Peter Foley, Andrew Blauvelt
Journal: Journal of the American Academy of Dermatology (2020)
Glycemic Control and Risk of Cellulitis
Authors: Galia Zacay, Fabienne Hershkowitz Sikron, Anthony D. Heymann
Journal: Diabetes Care (2020)

OBJECTIVE We know that diabetes predisposes to common infections, such as cellulitis and pneumonia. However, the correlation between the level of glycemic control and the rate of infection is unknown. RESEARCH DESIGN AND METHODS We examined the association between glycemic control in patients with diabetes and the incidence of infection in the entire population of patients with diabetes in a large HMO. During the study period, we first selected an HbA1c test for each patient and then searched for an infection diagnosis in the 60 days that followed the test. A multivariate logistic regression analysis was performed to determine the independent effect of HbA1c on the likelihood of being diagnosed with an infection. We were able to control for many confounders, such as other chronic illness, time since the diagnosis of diabetes, and use of steroids before the infection. RESULTS We identified 407 cases of cellulitis. Multivariate logistic regressions for cellulitis showed a 1.4-fold increased risk among patients with HbA1c &amp;gt;7.5% (58 mmol/mol). Factors such as obesity, Parkinson’s disease, peripheral vascular disease, and prior treatment with prednisone predisposed to cellulitis. There was an increase of 12% in the odds of cellulitis for every 1% (11 mmol/mol) elevation in HbA1c (odds ratio [OR] 1.12; CI 1.05–1.19). A similar analysis showed a trend toward an increased risk of pneumonia in patients with HbA1c &amp;gt;7.5% (58 mmol/mol) (OR 1.1; CI 0.9–1.4). CONCLUSIONS Poor glycemic control was associated in this study with the development of cellulitis. The study also suggests that exposure to oral prednisolone increases the risk of cellulitis, pneumonia, and upper respiratory infection.
Quantification of Myocardial Flow Reserve Using Positron Emission Imaging: The Journey to Clinical Use⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Rob S.B. Beanlands, Maria Cecilia Ziadi, Kathryn Williams
Journal: Journal of the American College of Cardiology (2009)
Abstract IA23: The role of EZH2 gain-of-function mutations in lymphoma
Authors: Wendy Béguelin
Journal: Blood Cancer Discovery (2020)

Abstract Follicular lymphomas (FLs) are slow-growing, indolent tumors containing extensive follicular dendritic cell (FDC) networks and recurrent EZH2 gain-of-function mutations. Paradoxically, FLs originate from highly proliferative germinal center (GC) B cells with proliferation strictly dependent on interactions with T follicular helper cells. Herein, we show that EZH2 mutations initiate FL by attenuating GC B-cell requirement for T-cell help and driving slow expansion of GC centrocytes that become enmeshed with and dependent on FDCs. By impairing T-cell help, mutant EZH2 prevents induction of proliferative MYC programs. Thus, EZH2 mutation fosters malignant transformation by epigenetically reprograming B cells to form an aberrant immunologic niche that reflects characteristic features of human FLs, explaining how indolent tumors arise from GC B cells. Citation Format: Wendy Béguelin. The role of EZH2 gain-of-function mutations in lymphoma [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr IA23.
Increase in Hospital-Acquired Carbapenem-Resistant <i>Acinetobacter baumannii</i> Infection and Colonization in an Acute Care Hospital During a Surge in COVID-19 Admissions — New Jersey, February–July 2020
Authors: Stephen Perez, Gabriel K. Innes, Maroya Spalding Walters, Jason Mehr, Jessica Arias, Rebecca Greeley, Debra Chew
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Carbapenem-resistant Acinetobacter baumannii (CRAB), an opportunistic pathogen primarily associated with hospital-acquired infections, is an urgent public health threat (1). In health care facilities, CRAB readily contaminates the patient care environment and health care providers' hands, survives for extended periods on dry surfaces, and can be spread by asymptomatically colonized persons; these factors make CRAB outbreaks in acute care hospitals difficult to control (2,3). On May 28, 2020, a New Jersey hospital (hospital A) reported a cluster of CRAB infections during a surge in patients hospitalized with coronavirus disease 2019 (COVID-19). Hospital A and the New Jersey Department of Health (NJDOH) conducted an investigation, and identified 34 patients with hospital-acquired multidrug-resistant CRAB infection or colonization during February-July 2020, including 21 (62%) who were admitted to two intensive care units (ICUs) dedicated to caring for COVID-19 patients. In late March, increasing COVID-19-related hospitalizations led to shortages in personnel, personal protective equipment (PPE), and medical equipment, resulting in changes to conventional infection prevention and control (IPC) practices. In late May, hospital A resumed normal operations, including standard IPC measures, as COVID-19 hospitalizations decreased, lessening the impact of personnel and supply chain shortages on hospital functions. CRAB cases subsequently returned to a pre-COVID-19 baseline of none to two cases monthly. The occurrence of this cluster underscores the potential for multidrug-resistant organisms (MDROs) to spread during events when standard hospital practices might be disrupted; conventional IPC strategies should be reinstated as soon as capacity and resources allow.
False-Positive 18F–Prostate-Specific Membrane Antigen–1007 PET/CT Caused by Hepatic Multifocal Inflammatory Foci
Authors: David Ladrón-de-Guevara, Alejando Canelo, Antonio Piottante, Carlos Regonesi
Journal: Clinical Nuclear Medicine (2020)

Abstract A 68-year-old man with history of treated prostate cancer was referred to 68 Ga–prostate-specific membrane antigen (PSMA)–11 PET/CT imaging. Moderate bone involvement was observed, with a normal liver tracer uptake. Bone biopsy confirmed metastases of prostate cancer. After therapy adjustment, a follow-up 18 F-PSMA-1007 PET/CT revealed good response in bone lesions, although it showed 3 new rounded liver intense uptake foci. Concurrent PSA was 0.6 ng/mL. Liver function tests were normal. PET/CT-guided hepatic biopsy demonstrated no malignant cells, focal inflammation, and steatosis, being possibly the inflammation the cause of false-positive multifocal uptake of 18 F-PSMA-1007. Following PET/CT, controls showed a normal liver.
15287 Comparisons of symptom-free and sign-free status among patients with moderate to severe plaque psoriasis treated with guselkumab or adalimumab: Results from VOYAGE 1
Authors: Christopher E.M. Griffiths, Sandra Philipp, Jerry Bagel, Chenglong Han, Michael Song, Yu-Huei Huang, David N. Adam, Tina Bhutani, Andrew Blauvelt
Journal: Journal of the American Academy of Dermatology (2020)
DDRE-21. PNOC015: PHASE 1 STUDY OF MTX110 DELIVERED BY CONVECTION ENHANCED DELIVERY (CED) IN CHILDREN WITH NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) PREVIOUSLY TREATED WITH RADIATION THERAPY
Authors: Sabine Mueller, Cassie Kline, Javier Villanueva-Meyer, Carly Hoffman, Shannon Raber, Erin R Bonner, Javad Nazarian, Shannon Lundy, Annette Molinaro, Michael Prados, Mariella Filbin, Nalin Gupta
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE To determine safety and distribution of MTX110 delivered by CED in newly diagnosed DIPG patients. METHODS DIPG patients (3–21 years) were enrolled after radiation. CED of MTX110 combined with gadoteridol was completed based on dose levels (DL) (30–90 µM with volumes ranging from 3 cc (single dose) to 2 consecutive doses of 6 cc; total number of DL=7). Catheter position was chosen to maximize tumor coverage. Distribution of infusate was monitored with real-time MR imaging. Repeat CED was performed every 4–8 weeks if tolerated. Quality of life (QOL) assessments using PedsQL Generic Core and Brain Tumor modules were obtained at baseline (n=5), 3-months (n=3), and end of therapy (n=2). Single-cell RNA sequencing and analysis of histone modifications was performed to assess pharmacodynamic effects on DIPG cells. RESULTS Between May 2018-Dec 2019, 6 patients were enrolled (median age 8 years, range 5–21). Dose limiting toxicities included: grade 3 gait disturbance (DL7; cycle 1); grade 3 muscle weakness/vagus nerve disorder (DL5; cycle 4) and grade 2 intolerable dysphagia (DL7; cycle 4). Twelve CED procedures were completed at DL7 and repeated cycles ranged from 2 to 7. Infusion to distribution volume ratio was approximately 1:3.5. There were no significant changes in self-reported QOL. Parent ratings of patients’ worry (p = 0.04) and overall QOL (p = 0.03) significantly decreased at 3-months. CONCLUSION Repeat CED of MTX110 at the highest dose is tolerable. Tissue concentrations are likely to be substantially higher compared to oral dosing. Pharmacodynamic effects will be presented.
Diagnostic approach to the evaluation of myeloid malignancies following CAR T-cell therapy in B-cell acute lymphoblastic leukemia
Authors: George Mo, Hao-Wei Wang, Aimee C Talleur, Shilpa A Shahani, Bonnie Yates, Haneen Shalabi, Michael G Douvas, Katherine R Calvo, Jack F Shern, Sridhar Chaganti, Katharine Patrick, Young Song, Terry J Fry, Xiaolin Wu, Brandon M Triplett, Javed Khan, Rebecca A Gardner, Nirali N Shah
Journal: Journal for ImmunoTherapy of Cancer (2020)

Immunotherapeutic strategies targeting B-cell acute lymphoblastic leukemia (B-ALL) effectively induce remission; however, disease recurrence remains a challenge. Due to the potential for antigen loss, antigen diminution, lineage switch or development of a secondary or treatment-related malignancy, the phenotype and manifestation of subsequent leukemia may be elusive. We report on two patients with multiply relapsed/refractory B-ALL who, following chimeric antigen receptor T-cell therapy, developed myeloid malignancies. In the first case, a myeloid sarcoma developed in a patient with a history of myelodysplastic syndrome. In the second case, two distinct events occurred. The first event represented a donor-derived myelodysplastic syndrome with monosomy 7 in a patient with a prior hematopoietic stem cell transplantation. This patient went on to present with lineage switch of her original B-ALL to ambiguous lineage T/myeloid acute leukemia. With the rapidly evolving field of novel immunotherapeutic strategies, evaluation of relapse and/or subsequent neoplasms is becoming increasingly more complex. By virtue of these uniquely complex cases, we provide a framework for the evaluation of relapse or evolution of a subsequent malignancy following antigen-targeted immunotherapy.
Pneumomediastinum in Acute Respiratory Distress Syndrome from COVID-19
Authors: Matthew F. Mart, Stephanie G. Norfolk, Lisa N. Flemmons, John W. Stokes, Matthew D. Bacchetta, Anil J. Trindade, Jonathan D. Casey, Matthew W. Semler, E. Wesley Ely, Michael J. Noto
Journal: American Journal of Respiratory and Critical Care Medicine (2020)