tbuckley/cabot-search huggingface dataset:
Intestinal Barrier, Immunity and Microbiome: Partners in the Depression Crime
Authors: Eva M. Medina-Rodríguez, José Martínez-Raga, Yolanda Sanz
Journal: Pharmacological Reviews (2024)

Depression is a highly prevalent disorder and a leading cause of disability worldwide. It has a major impact on the affected individual and on society as a whole. Regrettably, current available treatments for this condition are insufficient in many patients. In recent years, the gut microbiome has emerged as a promising alternative target for treating and preventing depressive disorders. However, the microbes that form this ecosystem do not act alone but are part of a complicated network connecting the gut and the brain that influences our mood. Host cells that are in intimate contact with gut microbes, such as the epithelial cells forming the gut barrier and the immune cells in their vicinity, play a key role in the process. These cells continuously shape immune responses to maintain healthy communication between gut microbes and the host. In this article, we review how the interplay among epithelial cells, the immune system, and gut microbes mediates gut-brain communication to influence mood. We also discuss how advances in our knowledge of the mechanisms underlying the gut-brain axis could contribute to addressing depression. <h3>Significance Statement</h3> This review does not aim to systematically describe intestinal microbes that might be beneficial or detrimental for depression. We have adopted a novel point of view by focusing on potential mechanisms underlying the crosstalk between gut microbes and their intestinal environment to control mood. These pathways could be targeted by well defined and individually tailored dietary interventions, microbes, or microbial metabolites to ameliorate depression and decrease its important social and economic impact.
Meta-analysis identifies common gut microbiota associated with multiple sclerosis
Authors: Qingqi Lin, Yair Dorsett, Ali Mirza, Helen Tremlett, Laura Piccio, Erin E. Longbrake, Siobhan Ni Choileain, David A. Hafler, Laura M. Cox, Howard L. Weiner, Takashi Yamamura, Kun Chen, Yufeng Wu, Yanjiao Zhou
Journal: Genome Medicine (2024)

Previous studies have identified a diverse group of microbial taxa that differ between patients with multiple sclerosis (MS) and the healthy population. However, interpreting findings on MS-associated microbiota is challenging, as there is no true consensus. It is unclear whether there is gut microbiota commonly altered in MS across studies. To answer this, we performed a meta-analysis based on the 16S rRNA gene sequencing data from seven geographically and technically diverse studies comprising a total of 524 adult subjects (257 MS and 267 healthy controls). Analysis was conducted for each individual study after reprocessing the data and also by combining all data together. The blocked Wilcoxon rank-sum test and linear mixed-effects regression were used to identify differences in microbial composition and diversity between MS and healthy controls. Network analysis was conducted to identify bacterial correlations. A leave-one-out sensitivity analysis was performed to ensure the robustness of the findings. The microbiome community structure was significantly different between studies. Re-analysis of data from individual studies revealed a lower relative abundance of Prevotella in MS across studies, compared to controls. Meta-analysis found that although alpha and beta diversity did not differ between MS and controls, a higher abundance of Actinomyces and a lower abundance of Faecalibacterium were reproducibly associated with MS. Additionally, network analysis revealed that the recognized negative Bacteroides-Prevotella correlation in controls was disrupted in patients with MS. Our meta-analysis identified common gut microbiota associated with MS across geographically and technically diverse studies.
Relationship Between Early-Pregnancy Glycemia and Adverse Outcomes: Findings From the TOBOGM Study
Authors: Arianne Sweeting, Joanne Enticott, Jincy Immanuel, William M. Hague, Helena Teede, Christopher J. Nolan, Michael J. Peek, Jeff R. Flack, Mark McLean, Vincent W. Wong, Emily J. Hibbert, Alexandra Kautzky-Willer, Jürgen Harreiter, Helena Backman, Emily Gianatti, Viswanathan Mohan, N. Wah Cheung, David Simmons, David Simmons, N. Wah Cheung, Jincy Immanuel, William M. Hague, Helena Teede, Christopher J. Nolan, Michael J. Peek, Jeff R. Flack, Mark McLean, Vincent Wong, Emily J. Hibbert, Emily Gianatti, Arianne Sweeting, Suzette Coat, Raiyomand Dalal, Georgia Soldatos, Suja Padmanabhan, Rohit Rajagopal, Victoria Rudland, Jürgen Harreiter, Alexandra Kautzky-Willer, Herbert Kiss, Helena Backman, Erik Schwarcz, Glynis Ross, Viswanathan Mohan, Ranjit Mohan Anjana, Uma Ram
Journal: Diabetes Care (2024)

OBJECTIVE We evaluated associations between early-pregnancy oral glucose tolerance test (OGTT) glucose and complications in the Treatment of Booking Gestational Diabetes Mellitus (TOBOGM) cohort to inform prognostic OGTT thresholds. RESEARCH DESIGN AND METHODS Individuals with risk factors for hyperglycemia were recruited for an international, multicenter, randomized controlled gestational diabetes mellitus (GDM) (World Health Organization 2013 criteria) treatment trial. A 2-h 75-g OGTT was performed at &amp;lt;20 weeks’ gestation. Individuals with early treated hyperglycemia in pregnancy were excluded from the primary analysis. Early OGTT glucose concentrations were analyzed continuously and in glycemic categories (normal, low band, and high band). RESULTS Overall, 3,645 individuals had an OGTT at (mean ± SD) 15.6 ± 2.5 weeks. For each 1-SD increase in fasting, 1-h, and 2-h glucose values, there were continuous positive associations with late GDM: adjusted odds ratio (aOR) 2.04 (95% CI 1.82–2.27), 3.05 (2.72–3.43), and 2.21 (1.99–2.45), respectively. There were continuous positive associations between 1-h and 2-h glucose and the perinatal composite (birth &amp;lt;37 + 0 weeks, birth trauma, birth weight ≥4,500 g, respiratory distress, phototherapy requirement, stillbirth/neonatal death, and shoulder dystocia), with aOR 1.15 (95% CI 1.04–1.26) and 1.14 (1.04–1.25), respectively, and with large-for-gestational-age offspring, with aOR 1.18 (1.06–1.31) and 1.26 (1.01–1.25), respectively. Significant associations were also observed between 1-h glucose and cesarean section and between fasting and 2-h glucose and neonatal hypoglycemia. In categorical analysis, only the high-band 1-h glucose (≥10.6 mmol/L [191 mg/dL]) predicted the perinatal composite. CONCLUSIONS There is a continuous positive association between early-pregnancy OGTT glucose and complications. In individuals with hyperglycemia risk factors, only the high-glycemic-band 1-h glucose corresponded to increased risk of major perinatal complications.
History of the Diabetes Control and Complications Trial and Its Follow-up Epidemiology of Diabetes Interventions and Complications Study: Studies That Changed the Treatment of Type 1 Diabetes
Authors: David M. Nathan, John M. Lachin
Journal: Diabetes Care (2024)

DCCT/EDIC 40th Anniversary Collection| July 31 2024 History of the Diabetes Control and Complications Trial and Its Follow-up Epidemiology of Diabetes Interventions and Complications Study: Studies That Changed the Treatment of Type 1 Diabetes In Special Collection: DCCT-EDIC 40th Anniversary Collection David M. Nathan 0000-0003-2503-2650 ; David M. Nathan 1Diabetes Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA Corresponding author: David M. Nathan, dnathan@mgh.harvard.edu Search for other works by this author on: This Site PubMed Google Scholar John M. Lachin 0000-0001-9838-2841 John M. Lachin 2Biostatistics Center, The George Washington University, Rockville, MD Search for other works by this author on: This Site PubMed Google Scholar Corresponding author: David M. Nathan, dnathan@mgh.harvard.edu Diabetes Care 2024;47(9):1511–1517 https://doi.org/10.2337/dci24-0063 Article history Received: June 18 2024 Accepted: June 19 2024 PubMed: 39083683 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation David M. Nathan, John M. Lachin; History of the Diabetes Control and Complications Trial and Its Follow-up Epidemiology of Diabetes Interventions and Complications Study: Studies That Changed the Treatment of Type 1 Diabetes. Diabetes Care 27 August 2024; 47 (9): 1511–1517. https://doi.org/10.2337/dci24-0063 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsDiabetes Care Search Advanced Search This article is part of a special article collection available at diabetesjournals.org/collection/2296/DCCT-EDIC-40th-Anniversary-Collection. This article is featured in a podcast available at diabetesjournals.org/care/pages/diabetes_care_on_air. This article is part of a special article collection available at diabetesjournals.org/collection/2296/DCCT-EDIC-40th-Anniversary-Collection. This article is featured in a podcast available at diabetesjournals.org/care/pages/diabetes_care_on_air. © 2024 by the American Diabetes Association2024Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/journals/pages/license. © 2024 by the American Diabetes Association2024Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/journals/pages/license. You do not currently have access to this content.
Tackling unhealthy food and obesity: how far will the new Labour government go?
Authors: Adam Briggs, Grace Everest
Journal: BMJ (2024)

The King's speech confirmed Labour's manifesto commitments to "restrict the advertising of junk food to children along with the sale of high caffeine energy drinks to children." 1 2 It's a welcome signal that Labour is taking childhood obesity seriously.Although it will be rightly applauded, more still needs to be done to reverse persistently high obesity rates
Obesity and Weight Loss Strategies for Patients With Heart Failure
Authors: Amanda R. Vest, Philip R. Schauer, Jo E. Rodgers, Emily Sanderson, Courtney L. LaChute, Jessica Seltz, Carl J. Lavie, Stacy A. Mandras, W.H. Wilson Tang, Adrian daSilva-deAbreu
Journal: JACC Heart Failure (2024)
Continuum of Preshock to Classic Cardiogenic Shock in the Critical Care Cardiology Trials Network Registry
Authors: Siddharth M Patel, David D Berg, Erin A Bohula, Vivian M Baird-Zars, Jeong-Gun Park, Christopher F Barnett, Lori B Daniels, Christopher B Fordyce, Shahab Ghafghazi, Michael J Goldfarb, Kari Gorder, Younghoon Kwon, Evan Leibner, Venu Menon, Brian J Potter, Rajnish Prasad, Michael A Solomon, Jeffrey J Teuteberg, Andrea D Thompson, Sammy Zakaria, Jason N Katz, Sean van Diepen, David A Morrow
Journal: JACC Heart Failure (2024)
Evaluating Patient-Oriented Echocardiogram Reports Augmented by Artificial Intelligence
Authors: Jacob A. Martin, Theodore Hill, Muhamed Saric, Alan F. Vainrib, Daniel Bamira, Samuel Bernard, Richard Ro, Hao Zhang, Jonathan S. Austrian, Yindalon Aphinyanaphongs, Vidya Koesmahargyo, Mathew R. Williams, Larry A. Chinitz, Lior Jankelson
Journal: JACC. Cardiovascular imaging (2024)
GPR126 is a specifier of blood-brain barrier formation in the mouse central nervous system
Authors: Nikolaos Kakogiannos, Anna Agata Scalise, Emanuele Martini, Claudio Maderna, Andrea Francesco Benvenuto, Michele D’Antonio, Laura Carmignani, Serena Magni, Giorgia Serena Gullotta, Maria Grazia Lampugnani, Fabio Iannelli, Galina V. Beznoussenko, Alexander A. Mironov, Camilla Cerutti, Katie Bentley, Andrew Philippides, Federica Zanardi, Marco Bacigaluppi, Sara Sigismund, Claudia Bassani, Cinthia Farina, Gianvito Martino, Marco De Giovanni, Elisabetta Dejana, Matteo Iannacone, Donato Inverso, Monica Giannotta
Journal: Journal of Clinical Investigation (2024)

The blood-brain barrier (BBB) acquires unique properties to regulate neuronal function during development. The formation of the BBB, which occurs in tandem with angiogenesis, is directed by the Wnt/β-catenin signaling pathway. Yet the exact molecular interplay remains elusive. Our study reveals the G protein–coupled receptor GPR126 as a critical target of canonical Wnt signaling, essential for the development of the BBB's distinctive vascular characteristics and its functional integrity. Endothelial cell–specific deletion of the Gpr126 gene in mice induced aberrant vascular morphogenesis, resulting in disrupted BBB organization. Simultaneously, heightened transcytosis in vitro compromised barrier integrity, resulting in enhanced vascular permeability. Mechanistically, GPR126 enhanced endothelial cell migration, pivotal for angiogenesis, acting through an interaction between LRP1 and β1 integrin, thereby balancing the levels of β1 integrin activation and recycling. Overall, we identified GPR126 as a specifier of an organotypic vascular structure, which sustained angiogenesis and guaranteed the acquisition of the BBB properties during development.
A prM mutation that attenuates dengue virus replication in human cells enhances midgut infection in mosquitoes
Authors: Allyson N. X. Choi, Tanamas Siriphanitchakorn, Milly M. Choy, Justin S. G. Ooi, Menchie Manuel, Hwee Cheng Tan, Lowell Z. Lin, Xin Yap, Duane J. Gubler, Eng Eong Ooi
Journal: Science Translational Medicine (2024)

Dengue viruses (DENVs), like all viruses, evolve to perpetuate transmission of their species in their hosts. However, how DENV genetics influences dengue disease outbreaks remains poorly understood. Here, we examined isolates of the South Pacific dengue virus type 2 (DENV-2) that emerged in the 1970s and caused major dengue outbreaks in islands in this region until it reached Tonga, where only a few mild cases were reported. Phylogenetically, the DENV-2 strain isolated in Tonga segregated into a clade different from those clades infecting populations in other South Pacific islands. We found that this epidemiological observation could be explained by a single histidine-to-arginine substitution in position 86 of the premembrane (prM) protein of the Tonga DENV-2 strain. This mutation attenuated viral protein translation in mammalian cells but not in midgut cells of the mosquito vector Aedes aegypti . In mammalian cells, the prM mutation resulted in reduced translation of the viral genome and subsequent reduced virus replication. In contrast, in mosquito midgut cells, the prM mutation conferred a selective infection advantage, possibly because of the positively charged arginine residue introduced by the mutation. These findings provide molecular insights into the year-long silent transmission of attenuated DENV-2 in Tonga during the 1970s dengue outbreak in the South Pacific.
Functional and epigenetic changes in monocytes from adults immunized with an AS01-adjuvanted vaccine
Authors: Viviane Bechtold, Kinga K. Smolen, Wivine Burny, Simone P. de Angelis, Simon Delandre, Ahmed Essaghir, Arnaud Marchant, Cheikh Ndour, Martin Taton, Robbert van der Most, Fabienne Willems, Arnaud M. Didierlaurent
Journal: Science Translational Medicine (2024)

The adjuvant AS01 plays a key role in the immunogenicity of several approved human vaccines with demonstrated high efficacy. Its adjuvant effect relies on activation of the innate immune system. However, specific effects of AS01-adjuvanted vaccines on innate cell function and epigenetic remodeling, as described for Bacille Calmette-Guérin (BCG) and influenza vaccines, are still unknown. We assessed the long-term functional and epigenetic changes in circulating monocytes and dendritic cells induced by a model vaccine containing hepatitis B surface antigen and AS01 in healthy adults (NCT01777295). The AS01-adjuvanted vaccine, but not an Alum-adjuvanted vaccine, increased the number of circulating monocytes and their expression of human leukocyte antigen (HLA)–DR, which correlated with the magnitude of the memory CD4 + T cell response. Single-cell analyses revealed epigenetic alterations in monocyte and dendritic cell subsets, affecting accessibility of transcription factors involved in cell functions including activator protein-1 ( AP-1 ), GATA , C/EBP , and interferon regulatory factor. The functional changes were characterized by a reduced proinflammatory response to Toll-like receptor activation and an improved response to interferon-γ, a cytokine critical for the adjuvant’s mode of action. Epigenetic changes were most evident shortly after the second vaccine dose in CD14 + monocytes, for which accessibility differences of some transcription factors could persist for up to 6 months postvaccination. Together, we show that reprogramming of monocyte subsets occurs after vaccination with an AS01-adjuvanted vaccine, an effect that may contribute to the impact of vaccination beyond antigen-specific protection.
Human milk antibodies to global pathogens reveal geographic and interindividual variations in IgA and IgG
Authors: Joseph J. Campo, Antti E. Seppo, Arlo Z. Randall, Jozelyn Pablo, Chris Hung, Andy Teng, Adam D. Shandling, Johnathon Truong, Amit Oberai, James Miller, Najeeha Talat Iqbal, Pablo Peñataro Yori, Anna Kaarina Kukkonen, Mikael Kuitunen, L. Beryl Guterman, Shaun K. Morris, Lisa G. Pell, Abdullah Al Mahmud, Girija Ramakrishan, Eva Heinz, Beth D. Kirkpatrick, Abu S.G. Faruque, Rashidul Haque, R. John Looney, Margaret N. Kosek, Erkki Savilahti, Saad B. Omer, Daniel E. Roth, William A. Petri, Kirsi M. Järvinen
Journal: Journal of Clinical Investigation (2024)

BACKGROUND. The use of high-throughput technologies has enabled rapid advancement in the knowledge of host immune responses to pathogens. Our objective was to compare the repertoire, protection, and maternal factors associated with human milk antibodies to infectious pathogens in different economic and geographic locations.
Super-relaxed myosins contribute to respiratory muscle hibernation in mechanically ventilated patients
Authors: Marloes van den Berg, Zhonghua Shi, Wout J. Claassen, Pleuni Hooijman, Christopher T. A. Lewis, Jesper L. Andersen, Robbert J. van der Pijl, Sylvia J. P. Bogaards, Stefan Conijn, Eva L. Peters, Leon P. L. Begthel, Bas Uijterwijk, Johan Lindqvist, Paul R. Langlais, Armand R. J. Girbes, Sandra Stapel, Henk Granzier, Kenneth S. Campbell, Weikang Ma, Thomas Irving, Darren T. Hwee, James J. Hartman, Fady I. Malik, Marinus Paul, Albertus Beishuizen, Julien Ochala, Leo Heunks, Coen A. C. Ottenheijm
Journal: Science Translational Medicine (2024)

Patients receiving mechanical ventilation in the intensive care unit (ICU) frequently develop contractile weakness of the diaphragm. Consequently, they may experience difficulty weaning from mechanical ventilation, which increases mortality and poses a high economic burden. Because of a lack of knowledge regarding the molecular changes in the diaphragm, no treatment is currently available to improve diaphragm contractility. We compared diaphragm biopsies from ventilated ICU patients (
<i>MGA</i> deletion leads to Richter’s transformation by modulating mitochondrial OXPHOS
Authors: Prajish Iyer, Bo Zhang, Tingting Liu, Meiling Jin, Kevyn Hart, Jibin Zhang, Viola Siegert, Marianne Remke, Xuesong Wang, Lei Yu, Joo Song, Girish Venkataraman, Wing C. Chan, Zhenyu Jia, Maike Buchner, Tanya Siddiqi, Steven T. Rosen, Alexey Danilov, Lili Wang
Journal: Science Translational Medicine (2024)

Richter’s transformation (RT) is a progression of chronic lymphocytic leukemia (CLL) to aggressive lymphoma. MGA ( Max gene associated ), a functional MYC suppressor, is mutated at 3% in CLL and 36% in RT. However, genetic models and molecular mechanisms of MGA deletion that drive CLL to RT remain elusive. We established an RT mouse model by knockout of Mga in the Sf3b1 / Mdr CLL model using CRISPR-Cas9 to determine the role of Mga in RT. Murine RT cells exhibited mitochondrial aberrations with elevated oxidative phosphorylation (OXPHOS). Through RNA sequencing and functional characterization, we identified Nme1 (nucleoside diphosphate kinase) as an Mga target, which drives RT by modulating OXPHOS. Given that NME1 is also a known MYC target without targetable compounds, we found that concurrent inhibition of MYC and electron transport chain complex II substantially prolongs the survival of RT mice in vivo. Our results suggest that the Mga-Nme1 axis drives murine CLL-to-RT transition via modulating OXPHOS, highlighting a potential therapeutic avenue for RT.
Neural landscape is associated with functional outcomes in irradiated patients with oropharyngeal squamous cell carcinoma
Authors: Shajedul Islam, Frederico O. Gleber-Netto, Collin F. Mulcahy, Mica D. E. Glaun, Snigdha Srivastava, Patrick J. Hunt, Michelle D. Williams, Carly E. Barbon, Michael Spiotto, Weilu Zhao, Adewale Adebayo, Shamima Akhter, Tongxin Xie, Kala Chand Debnath, Hinduja Naidu Sathishkumar, Blake Myers, Sahana Lothumalla, Ismail Yaman, Jared K. Burks, Javier Gomez, Xiayu Rao, Jing Wang, Karin Woodman, Jobran Mansour, Benjamin Arenkiel, Kate L. Osman, Chandler Haxton, Teresa E. Lever, Katherine A. Hutcheson, Moran Amit
Journal: Science Translational Medicine (2024)

The incidence of human papilloma virus–mediated oropharyngeal squamous cell carcinoma (OPSCC) has increased over the past 40 years, particularly among young individuals with a favorable prognosis; however, current therapy often leads to unfortunate side effects, such as dysphagia. Despite the emphasis on dysphagia in previous studies, there is an important research gap in understanding the correlation between neuronal changes and patient-reported and functional outcomes in patients with OPSCC. To address this issue, we examined pathologic tissue samples from patients with OPSCC using multiplex immunofluorescence staining and machine learning to correlate tumor-associated neuronal changes with prospectively collected patient-reported and functional outcomes. We found that tumor enrichment of adrenergic (TH + ) and CGRP + sensory–afferent nerves correlated with poorer swallowing outcomes. Functional electromyography recordings showed correlations between growing (GAP43 + ) and immature cholinergic (ChAT + DCX + ) nerves and denervation patterns in survivors of OPSCC. A murine model of radiation-induced dysphagia further confirmed that immature cholinergic and CGRP + nerves were correlated with impaired swallowing. Preclinical interventional studies also supported the independent contributions of CGRP + and cholinergic (ChAT + ) nerves to dysphagia in treated mouse models of OPSCC. Our results suggest that CGRP + and ChAT + neuronal signaling play distinct roles in tumor- and radiation-induced dysphagia in OPSCC and offer a comprehensive dataset on the neural landscape of OPSCC. These insights may guide early interventions for swallow preservation and the repurposing of neurology-related drugs, such as CGRP blockers, in clinical oncology and survivorship.
Epigenetics enters the stage in vascular malformations
Authors: Salim Abdelilah-Seyfried
Journal: Journal of Clinical Investigation (2024)

Cerebral arteriovenous malformations represent the most common form of vascular malformations and can cause recurrent bleeding and hemorrhagic stroke. The current issue of the JCI features an article by Zhao et al. describing a mouse model of cerebral arteriovenous malformations. Endothelial cells lacking matrix Gla protein, a BMP inhibitor, underwent epigenetic changes characteristic of an endothelial-to-mesenchymal fate transition. The authors uncovered a two-step process for this transition controlled by the epigenetic regulator histone deacetylase 2 (HDAC2), which controls endothelial cell differentiation, and by enhancer of zeste homolog 1 (EZH1), which suppressed mesenchymal fate. This discovery provides a promising entry point for preventive pharmacological interventions.