tbuckley/cabot-search huggingface dataset:
Empagliflozin Inhibits Proximal Tubule NHE3 Activity, Preserves GFR, and Restores Euvolemia in Nondiabetic Rats with Induced Heart Failure
Authors: Flávio A. Borges-Júnior, Danúbia Silva dos Santos, Acaris Benetti, Juliano Z. Polidoro, Aline C.T. Wisnivesky, Renato O. Crajoinas, Ednei L. Antônio, Leonardo Jensen, Bruno Caramelli, Gerhard Malnic, Paulo J. Tucci, Adriana C.C. Girardi
Journal: Journal of the American Society of Nephrology (2021)

SGLT2 inhibitors reduce the risk of heart failure (HF) mortality and morbidity, regardless of the presence or absence of diabetes, but the mechanisms underlying this benefit remain unclear. Experiments with nondiabetic HF rats tested the hypothesis that the SGLT2 inhibitor empagliflozin (EMPA) inhibits proximal tubule (PT) NHE3 activity and improves renal salt and water handling.Male Wistar rats were subjected to myocardial infarction or sham operation. After 4 weeks, rats that developed HF and sham rats were treated with EMPA or untreated for an additional 4 weeks. Immunoblotting and quantitative RT-PCR evaluated SGLT2 and NHE3 expression. Stationary in vivo microperfusion measured PT NHE3 activity.EMPA-treated HF rats displayed lower serum B-type natriuretic peptide levels and lower right ventricle and lung weight to tibia length than untreated HF rats. Upon saline challenge, the diuretic and natriuretic responses of EMPA-treated HF rats were similar to those of sham rats and were higher than those of untreated HF rats. Additionally, EMPA treatment prevented GFR decline and renal atrophy in HF rats. PT NHE3 activity was higher in HF rats than in sham rats, whereas treatment with EMPA markedly reduced NHE3 activity. Unexpectedly, SGLT2 protein and mRNA abundance were upregulated in the PT of HF rats.Prevention of HF progression by EMPA is associated with reduced PT NHE3 activity, restoration of euvolemia, and preservation of renal mass. Moreover, dysregulation of PT SGLT2 may be involved in the pathophysiology of nondiabetic HF.
Hunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward autoactivation loop in mice
Authors: Luis Varela, Bernardo Stutz, Jae Eun Song, Jae Geun Kim, Zhong-Wu Liu, Xiao-Bing Gao, Tamas L. Horvath
Journal: Journal of Clinical Investigation (2021)

Hypothalamic feeding circuits have been identified as having innate synaptic plasticity, mediating adaption to the changing metabolic milieu by controlling responses to feeding and obesity. However, less is known about the regulatory principles underlying the dynamic changes in agouti-related protein (AgRP) perikarya, a region crucial for gating of neural excitation and, hence, feeding. Here we show that AgRP neurons activated by food deprivation, ghrelin administration, or chemogenetics decreased their own inhibitory tone while triggering mitochondrial adaptations in neighboring astrocytes. We found that it was the inhibitory neurotransmitter GABA released by AgRP neurons that evoked this astrocytic response; this in turn resulted in increased glial ensheetment of AgRP perikarya by glial processes and increased excitability of AgRP neurons. We also identified astrocyte-derived prostaglandin E2, which directly activated — via EP2 receptors — AgRP neurons. Taken together, these observations unmasked a feed-forward, self-exciting loop in AgRP neuronal control mediated by astrocytes, a mechanism directly relevant for hunger, feeding, and overfeeding.
Psychosocial Status in Chronic Illness
Authors: Barrie R. Cassileth, Edward J. Lusk, Thomas B. Strouse, David S. Miller, Lorraine L. Brown, Patricia A. Cross, Alan N. Tenaglia
Journal: New England Journal of Medicine (1984)

Abstract Assumptions that psychological attributes are specific to particular diagnoses characterize many investigations of chronically ill patients. We studied 758 patients, each of whom had one of six different chronic illnesses, to determine and compare their scores on the Mental Health Index. Five groups of physically ill patients (with arthritis, diabetes, cancer, renal disease, or dermatologic disorders) did not differ significantly from one another or from the general public, but all had significantly higher scores for psychological status when compared with the sixth group, patients under treatment for depression. There was a significant direct relation between higher mental-health scores and advancing age across all patient populations. Patients with recently diagnosed illness in all groups had poorer mental-health scores than did patients whose illness had been diagnosed more than four months previously. A direct relation between declining physical status and mental-health scores was observed. These results suggest that psychological adaptation among patients with chronic illnesses is remarkably effective and fundamentally independent of specific diagnosis. (N Engl J Med 1984; 311:506–11.)
Simultaneous Transcatheter Aortic Valve Replacement and Endovascular Aortic Aneurysm Repair
Authors: Halim Yammine, Charles S. Briggs, Quantel V. Rolle, Jocelyn K. Ballast, John R. Frederick, Eric Skipper, William Downey, Michael J. Rinaldi, Markus D. Scherer, Frank R. Arko
Journal: Journal of the American College of Cardiology (2021)
Reply to Dr. Bronswijk
Authors: Liselotte W. Zwager, Barbara A. J. Bastiaansen, Paul Fockens
Journal: Endoscopy (2021)

See also: Endoscopic full-thickness resection (eFTR) of colorectal lesions: results from the Dutch colorectal eFTR registryEndoscopy 2020; 52(11): 1014-1023DOI: 10.1055/a-1176-1107 See also: Endoscopic full-thickness resection and post-procedural appendicitis: every advantage has its disadvantageEndoscopy 2021; 53(05): 561-561DOI: 10.1055/a-1337-2523
A Biphasic Osteovascular Biomimetic Scaffold for Rapid and Self‐Sustained Endochondral Ossification
Authors: Hwan D. Kim, Xuechong Hong, Young‐Hyeon An, Mihn Jeong Park, Do‐Gyoon Kim, Arin K. Greene, Bonnie L. Padwa, Nathaniel S. Hwang, Ruei‐Zeng Lin, Juan M. Melero‐Martin
Journal: Advanced Healthcare Materials (2021)

Regeneration of large bones remains a challenge in surgery. Recent developmental engineering efforts aim to recapitulate endochondral ossification (EO), a critical step in bone formation. However, this process entails the condensation of mesenchymal stem cells (MSCs) into cartilaginous templates, which requires long-term cultures and is challenging to scale up. Here, a biomimetic scaffold is developed that allows rapid and self-sustained EO without initial hypertrophic chondrogenesis. The design comprises a porous chondroitin sulfate cryogel decorated with whitlockite calcium phosphate nanoparticles, and a soft hydrogel occupying the porous space. This composite scaffold enables human endothelial colony-forming cells (ECFCs) and MSCs to rapidly assemble into osteovascular niches in immunodeficient mice. These niches contain ECFC-lined blood vessels and perivascular MSCs that differentiate into RUNX2+ OSX+ pre-osteoblasts after one week in vivo. Subsequently, multiple ossification centers are formed, leading to de novo bone tissue formation by eight weeks, including mature human OCN+ OPN+ osteoblasts, collagen-rich mineralized extracellular matrix, hydroxyapatite, osteoclast activity, and gradual mechanical competence. The early establishment of blood vessels is essential, and grafts that do not contain ECFCs fail to produce osteovascular niches and ossification centers. The findings suggest a novel bioengineering approach to recapitulate EO in the context of human bone regeneration.
Abstract PO-071: Characterizing transcriptomic indicators of radiosensitivity in cancer and identifying sensitizing therapeutic agents
Authors: Ian Smith, Rachel Bell, Meghan Lambie, Benjamin Haibe-Kains, Scott Bratman
Journal: Clinical Cancer Research (2021)

Abstract While radiation therapy is an integral method for cancer treatment, clinical choices are not currently informed by the genetic and molecular profile of a patient’s tumor. Though it has been shown that genetic features implicate variability, the exact relationship between these features and radiosensitivity is poorly understood. Our work focuses on predicting radiosensitivity of squamous cell carcinoma from molecular features. First, we employ RadioGx, a computational platform for integrative analysis of radiogenomic datasets, to identify a gene expression signature predictive of radiosensitivity. To mitigate the high-dimensionality of gene expression data, we employ pathway-level transcriptomic modeling methods to identify cellular programs associated with radiation sensitivity. Our pancancer radiosensitivity model achieves a Pearson’s correlation of 0.47 with measured radiosensitivity from a radiogenomic dataset using only high level transcriptomic features. Second, we use that gene expression signature to query the Connectivity Map via the PharmacoGx resource and identify candidate radiosensitizers - compounds that may induce the radiosensitivity signature. Further validation is necessary to evaluate the efficacy of these compounds at improving radiosensitivity in both model systems and patient contexts. These results implicate cellular processes in radiosensitivity and advance an approach for identifying radiosensitizing agents through integration of large scale datasets. Citation Format: Ian Smith, Rachel Bell, Meghan Lambie, Benjamin Haibe-Kains, Scott Bratman. Characterizing transcriptomic indicators of radiosensitivity in cancer and identifying sensitizing therapeutic agents [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-071.
Association of Pre-diagnostic Antibody Responses to Escherichia coli and Bacteroides fragilis Toxin Proteins with Colorectal Cancer in a European Cohort
Authors: Julia Butt, Mazda Jenab, Jill Werner, Veronika Fedirko, Elisabete Weiderpass, Christina C. Dahm, Anne Tjønneland, Anja Olsen, Marie-Christine Boutron-Ruault, Joseph A. Rothwell, Gianluca Severi, Rudolf Kaaks, Renée Turzanski-Fortner, Krasimira Aleksandrova, Matthias Schulze, Domenico Palli, Valeria Pala, Salvatore Panico, Rosario Tumino, Carlotta Sacerdote, Bas Bueno-de-Mesquita, Carla H. Van Gils, Inger Torhild Gram, Marko Lukic, Núria Sala, María José Sánchez Pérez, Eva Ardanaz, María-Dolores Chirlaque, Richard Palmquist, Thyra Löwenmark, Ruth C Travis, Alicia Heath, Amanda J Cross, Heinz Freisling, Semi Zouiouich, Elom Aglago, Tim Waterboer, David J. Hughes
Journal: Gut Microbes (2021)

Experimental evidence has implicated genotoxic Escherichia coli (E. coli) and enterotoxigenic Bacteroides fragilis (ETBF) in the development of colorectal cancer (CRC). However, evidence from epidemiological studies is sparse. We therefore assessed the association of serological markers of E. coli and ETBF exposure with odds of developing CRC in the European Prospective Investigation into Nutrition and Cancer (EPIC) study.Serum samples of incident CRC cases and matched controls (n = 442 pairs) were analyzed for immunoglobulin (Ig) A and G antibody responses to seven E. coli proteins and two isoforms of the ETBF toxin via multiplex serology. Multivariable-adjusted conditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of sero-positivity to E. coli and ETBF with CRC.The IgA-positivity of any of the tested E. coli antigens was associated with higher odds of developing CRC (OR: 1.42; 95% CI: 1.05–1.91). Dual-positivity for both IgA and IgG to E. coli and ETBF was associated with >1.7-fold higher odds of developing CRC, with a significant association only for IgG (OR: 1.75; 95% CI: 1.04, 2.94). This association was more pronounced when restricted to the proximal colon cancers (OR: 2.62; 95% CI: 1.09, 6.29) compared to those of the distal colon (OR: 1.24; 95% CI: 0.51, 3.00) (pheterogeneity = 0.095). Sero-positivity to E. coli and ETBF was associated with CRC development, suggesting that co-infection of these bacterial species may contribute to colorectal carcinogenesis. These findings warrant further exploration in larger prospective studies and within different population groups.
Splanchnic nerve modulation in heart failure: mechanistic overview, initial clinical experience, and safety considerations
Authors: Marat Fudim, Piotr P. Ponikowski, Daniel Burkhoff, Mark E. Dunlap, Paul A. Sobotka, Jeroen Molinger, Manesh R. Patel, G. Michael Felker, Adrian F. Hernandez, Sheldon E. Litwin, Barry A. Borlaug, Anisha Bapna, Horst Sievert, Vivek Y. Reddy, Zoar J. Engelman, Sanjiv J. Shah
Journal: European Journal of Heart Failure (2021)

Volume recruitment from the splanchnic compartment is an important physiological response to stressors such as physical activity and blood loss. In the setting of heart failure (HF), excess fluid redistribution from this compartment leads to increased cardiac filling pressures with limitation in exercise capacity. Recent evidence suggests that blocking neural activity of the greater splanchnic nerve (GSN) could have significant benefits in some patients with HF by reducing cardiac filling pressures and improving exercise capacity. However, to date the long-term safety of splanchnic nerve modulation (SNM) in the setting of HF is unknown. SNM is currently used in clinical practice to alleviate some forms of chronic abdominal pain. A systematic review of the series where permanent SNM was used as a treatment for chronic abdominal pain indicates that permanent SNM is well tolerated, with side-effects limited to transient diarrhoea or abdominal colic and transient hypotension. The pathophysiological role of the GSN in volume redistribution, the encouraging findings of acute and chronic pilot SNM studies and the safety profile from permanent SNM for pain provides a strong basis for continued efforts to study this therapeutic target in HF.
Abstract 15756: The Administration of High-morbidity Group Box 1 Fragment Prevents Deterioration of Cardiac Performance by Enhancement of Bone-marrow Mesenchymal Stem Cells Homing in the Delta-sarcoglycan-deficient Hamster
Authors: Takashi Kido, Shigeru Miyagawa, Katsuto Tamai, Takayoshi Ueno, Koichi Toda, Toru Kuratani, Yoshiki Sawa
Journal: Circulation (2017)

Introduction: High-morbidity group box 1 (HMGB1) mobilizes bone-marrow mesenchymal stem cells (BMMSCs) into circulation and enhances the recruitment to damaged tissue. Hypothesis: We hypothesized w...
Surveillance for subsequent neoplasms of the CNS for childhood, adolescent, and young adult cancer survivors: a systematic review and recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group
Authors: Daniel C Bowers, Lisanne C Verbruggen, Leontien C M Kremer, Melissa M Hudson, Roderick Skinner, Louis S Constine, Noah D Sabin, Ranjeev Bhangoo, Riccardo Haupt, Mike M Hawkins, Helen Jenkinson, Raja B Khan, Paul Klimo, Pieter Pretorius, Antony Ng, Raoul C Reulen, Cécile M Ronckers, Zsila Sadighi, Katrin Scheinemann, Netteke Schouten-van Meeteren, Elaine Sugden, Jop C Teepen, Nicole J Ullrich, Andrew Walter, W Hamish Wallace, Kevin C Oeffinger, Gregory T Armstrong, Helena J H van der Pal, Renée L Mulder
Journal: The Lancet Oncology (2021)
Feasibility of Simplification From a Basal-Bolus Insulin Regimen to a Fixed-Ratio Formulation of Basal Insulin Plus a GLP-1RA or to Basal Insulin Plus an SGLT2 Inhibitor: BEYOND, a Randomized, Pragmatic Trial
Authors: Dario Giugliano, Miriam Longo, Paola Caruso, Rosa Di Fraia, Lorenzo Scappaticcio, Maurizio Gicchino, Michela Petrizzo, Giuseppe Bellastella, Maria Ida Maiorino, Katherine Esposito
Journal: Diabetes Care (2021)

OBJECTIVE BEYOND trial evaluated the feasibility of either basal insulin plus glucagon-like peptide 1 receptor agonist (GLP-1RA) or basal insulin plus sodium–glucose cotransporter 2 inhibitor (SGLT2i) to replace a full basal-bolus insulin (BBI) regimen in participants with type 2 diabetes and inadequate glycemic control. RESEARCH DESIGN AND METHODS Participants were randomized (1:1:1) to: 1) intensification of the BBI regimen (n = 101), 2) fixed ratio of basal insulin plus GLP-1RA (fixed-combo group; n = 102), and 3) combination of basal insulin plus SGLT2i (gliflo-combo group; n = 102). The primary efficacy outcome was change from baseline in HbA1c at 6 months. RESULTS Baseline characteristics were similar among the three groups (mean HbA1c was 8.6% [70 mmol/mol]). At 6 months, patients experienced similar reduction in HbA1c level (−0.6 ± 0.8, −0.6 ± 0.8, and −0.7 ± 0.9%, mean ± SD, respectively; noninferiority P &amp;lt; 0.001 vs. BBI), and the proportion of patients with HbA1c ≤7.5% was also similar (34%, 28%, and 27%, respectively; P = 0.489). Total insulin dose increased in the BBI group (62 units/day) and decreased both in the fixed-combo and gliflo-combo groups (27 units/day and 21 units/day, respectively; P &amp;lt; 0.01). The proportion of patients with hypoglycemia was 17.8%, 7.8%, and 5.9%, respectively (P = 0.015). There were 12 dropouts in the fixed-combo group, 9 in the gliflo-combo group, and none in the BBI group. CONCLUSIONS BEYOND provides evidence that it is possible and safe to switch from a BBI regimen to either a once-daily fixed-combo injection or once-daily gliflozin added to basal insulin, with similar glucose control, fewer insulin doses, fewer injections daily, and less hypoglycemia.
Abstract 10011: Liver Stiffness Assessed by Noninvasive Marker Fibrosis 4 Index is Associated With Right Ventricular Functionand Cardiovascular Prognosis in Patients With Heart Failure With Preseved Ejection Fraction
Authors: Mitsutaka Nakashima, Satoru Sakuragi
Journal: Circulation (2019)

Introduction: Liver stiffness is reported to be associated with right sided hemodynamics and worse prognosis of heart failure. Fibrosis-4 index (FIB4) (age (years) х aspartate aminotransferase (IU/...
A novel method to correct repolarization time estimation from unipolar electrograms distorted by standard filtering
Authors: Peter Langfield, Yingjing Feng, Laura R. Bear, Josselin Duchateau, Rafael Sebastian, Emma Abell, Remi Dubois, Louis Labrousse, Julien Rogier, Meleze Hocini, Michel Haissaguerre, Edward Vigmond
Journal: Medical Image Analysis (2021)

Reliable patient-specific ventricular repolarization times (RTs) can identify regions of functional block or afterdepolarizations, indicating arrhythmogenic cardiac tissue and the risk of sudden cardiac death. Unipolar electrograms (UEs) record electric potentials, and the Wyatt method has been shown to be accurate for estimating RT from a UE. High-pass filtering is an important step in processing UEs, however, it is known to distort the T-wave phase of the UE, which may compromise the accuracy of the Wyatt method. The aim of this study was to examine the effects of high-pass filtering, and improve RT estimates derived from filtered UEs. We first generated a comprehensive set of UEs, corresponding to early and late activation and repolarization, that were then high-pass filtered with settings that mimicked the CARTO filter. We trained a deep neural network (DNN) to output a probabilistic estimation of RT and a measure of confidence, using the filtered synthetic UEs and their true RTs. Unfiltered ex-vivo human UEs were also filtered and the trained DNN used to estimate RT. Even a modest 2 Hz high-pass filter imposes a significant error on RT estimation using the Wyatt method. The DNN outperformed the Wyatt method in 62.75% of cases, and produced a significantly lower absolute error (p=8.99E-13), with a median of 16.91 ms, on 102 ex-vivo UEs. We also applied the DNN to patient UEs from CARTO, from which an RT map was computed. In conclusion, DNNs trained on synthetic UEs improve the RT estimation from filtered UEs, which leads to more reliable repolarization maps that help to identify patient-specific repolarization abnormalities.
Hypothalamic bile acid-TGR5 signaling protects from obesity
Authors: Ashley Castellanos-Jankiewicz, Omar Guzmán-Quevedo, Valérie S. Fénelon, Philippe Zizzari, Carmelo Quarta, Luigi Bellocchio, Anne Tailleux, Julie Charton, Daniela Fernandois, Marcus Henricsson, Catherine Piveteau, Vincent Simon, Camille Allard, Sandrine Quemener, Valentine Guinot, Nathalie Hennuyer, Alessia Perino, Alexia Duveau, Marlène Maitre, Thierry Leste-Lasserre, Samantha Clark, Nathalie Dupuy, Astrid Cannich, Delphine Gonzales, Benoit Deprez, Gilles Mithieux, David Dombrowicz, Fredrik Bäckhed, Vincent Prevot, Giovanni Marsicano, Bart Staels, Kristina Schoonjans, Daniela Cota
Journal: Cell Metabolism (2021)
Clonal multi-omics reveals Bcor as a negative regulator of emergency dendritic cell development
Authors: Luyi Tian, Sara Tomei, Jaring Schreuder, Tom S. Weber, Daniela Amann-Zalcenstein, Dawn S. Lin, Jessica Tran, Cindy Audiger, Mathew Chu, Andrew Jarratt, Tracy Willson, Adrienne Hilton, Ee Shan Pang, Timothy Patton, Madison Kelly, Shian Su, Quentin Gouil, Peter Diakumis, Melanie Bahlo, Toby Sargeant, Lev M. Kats, Philip D. Hodgkin, Meredith O’Keeffe, Ashley P. Ng, Matthew E. Ritchie, Shalin H. Naik
Journal: Immunity (2021)
The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine
Authors: Deyang Yu, Nicole E. Richardson, Cara L. Green, Alexandra B. Spicer, Michaela E. Murphy, Victoria Flores, Cholsoon Jang, Ildiko Kasza, Maria Nikodemova, Matthew H. Wakai, Jay L. Tomasiewicz, Shany E. Yang, Blake R. Miller, Heidi H. Pak, Jacqueline A. Brinkman, Jennifer M. Rojas, William J. Quinn, Eunhae P. Cheng, Elizabeth N. Konon, Lexington R. Haider, Megan Finke, Michelle Sonsalla, Caroline M. Alexander, Joshua D. Rabinowitz, Joseph A. Baur, Kristen C. Malecki, Dudley W. Lamming
Journal: Cell Metabolism (2021)
Posters
Authors: Thierry Poynard, Olivier Deckmyn, Marika Rudler, Valentina Peta, Yen Ngo, Mathieu Vautier, Sepideh Akhavan, Vincent Calvez, Clemence Franc, Jean Marie Castille, Fabienne Drane, Mehdi Sakka, Dominique Bonnefont-Rousselot, Jean Marc Lacorte, David Saadoun, Yves Allenbach, Olivier Benveniste, Frederique Gandjbakhch, Julien Mayaux, Olivier Lucidarme, Bruno Fautrel, Vlad Ratziu, Chantal Housset, Dominique Thabut, Patrice Cacoub
Journal: Hepatology (2020)
日本におけるEhlers-Danlos症候群の血管型(vEDS,EDSIV)の遺伝的性質
Authors: Watanabe Atsushi, Kosho Tomoki, Wada Takahiro, Sakai Noriyasu, Fujimoto Mitsuo, Fukushima Yoshimitsu, Shimada Takashi
Journal: Circulation (2007)