tbuckley/cabot-search huggingface dataset:
Effects of Early Life Exposures to the Aryl Hydrocarbon Receptor Ligand TCDF on Gut Microbiota and Host Metabolic Homeostasis in C57BL/6J Mice
Authors: Yuan Tian, Bipin Rimal, Jordan E. Bisanz, Wei Gui, Trenton M. Wolfe, Imhoi Koo, Iain A. Murray, Shaneice K. Nettleford, Shigetoshi Yokoyama, Fangcong Dong, Sergei Koshkin, K. Sandeep Prabhu, Peter J. Turnbaugh, Seth T. Walk, Gary H. Perdew, Andrew D. Patterson
Journal: Environmental Health Perspectives (2024)

Exposure to persistent organic pollutants (POPs) and disruptions in the gastrointestinal microbiota have been positively correlated with a predisposition to factors such as obesity, metabolic syndrome, and type 2 diabetes; however, it is unclear how the microbiome contributes to this relationship.
Cobalt ions-derived nanoenzyme array for endosseous neural network reconstruction and osseointegration
Authors: Xinmei Cai, Meng Yu, Bo Li, Yingang Zhang, Yong Han
Journal: Bioactive Materials (2024)

Interactions between bone cells and neurocytes are crucial for endosseous nerve and ensuing bone regeneration. However, absence of neural stem cells in bone makes the innervation of implant osseointegration a major challenge. Herein, a nanorod-like array of sodium hydrogen titanate (ST) co-doped with Co
Parabrachial neurons promote nociplastic pain
Authors: Richard D Palmiter
Journal: Trends in Neurosciences (2024)

The parabrachial nucleus (PBN) in the dorsal pons responds to bodily threats and transmits alarm signals to the forebrain. Parabrachial neuron activity is enhanced during chronic pain, and inactivation of PBN neurons in mice prevents the establishment of neuropathic, chronic pain symptoms. Chemogenetic or optogenetic activation of all glutamatergic neurons in the PBN, or just the subpopulation that expresses the Calca gene, is sufficient to establish pain phenotypes, including long-lasting tactile allodynia, that scale with the extent of stimulation, thereby promoting nociplastic pain, defined as diffuse pain without tissue inflammation or nerve injury. This review focuses on the role(s) of molecularly defined PBN neurons and the downstream nodes in the brain that contribute to establishing nociplastic pain.
Comprehensive network modeling approaches unravel dynamic enhancer-promoter interactions across neural differentiation
Authors: William DeGroat, Fumitaka Inoue, Tal Ashuach, Nir Yosef, Nadav Ahituv, Anat Kreimer
Journal: Genome biology (2024)

Increasing evidence suggests that a substantial proportion of disease-associated mutations occur in enhancers, regions of non-coding DNA essential to gene regulation. Understanding the structures and mechanisms of the regulatory programs this variation affects can shed light on the apparatuses of human diseases.
Advances in euglenoid genomics: unravelling the fascinating biology of a complex clade
Authors: Oskar Fields, Michael J Hammond, Xiao Xu, Ellis C O'Neill
Journal: Trends in Genetics (2024)

Euglenids have long been studied due to their unique physiology and versatile metabolism, providing underpinnings for much of our understanding of photosynthesis and biochemistry, and a growing opportunity in biotechnology. Until recently there has been a lack of genetic studies due to their large and complex genomes, but recently new technologies have begun to unveil their genetic capabilities. Whilst much research has focused on the model organism Euglena gracilis, other members of the euglenids have now started to receive due attention. Currently only poor nuclear genome assemblies of E. gracilis and Rhabdomonas costata are available, but there are many more plastid genome sequences and an increasing number of transcriptomes. As more assemblies become available, there are great opportunities to understand the fundamental biology of these organisms and to exploit them for biotechnology.
Restoring Atrial T-Tubules Augments Systolic Ca Upon Recovery From Heart Failure
Authors: Jessica L. Caldwell, Jessica D. Clarke, Charlotte E.R. Smith, Christian Pinali, Callum J. Quinn, Charles M. Pearman, Aiste Adomaviciene, Emma J. Radcliffe, Amy Watkins, Margaux A Horn, Elizabeth F. Bode, George W.P. Madders, Mark Eisner, David A. Eisner, Andrew W. Trafford, Katharine M. Dibb
Journal: Circulation Research (2024)

BACKGROUND: Transverse (t)-tubules drive the rapid and synchronous Ca 2+ rise in cardiac myocytes. The virtual complete atrial t-tubule loss in heart failure (HF) decreases Ca 2+ release. It is unknown if or how atrial t-tubules can be restored and how this affects systolic Ca 2+ . METHODS: HF was induced in sheep by rapid ventricular pacing and recovered following termination of rapid pacing. Serial block-face scanning electron microscopy and confocal imaging were used to study t-tubule ultrastructure. Function was assessed using patch clamp, Ca 2+ , and confocal imaging. Candidate proteins involved in atrial t-tubule recovery were identified by western blot and expressed in rat neonatal ventricular myocytes to determine if they altered t-tubule structure. RESULTS: Atrial t-tubules were lost in HF but reappeared following recovery from HF. Recovered t-tubules were disordered, adopting distinct morphologies with increased t-tubule length and branching. T-tubule disorder was associated with mitochondrial disorder. Recovered t-tubules were functional, triggering Ca 2+ release in the cell interior. Systolic Ca 2+ , I Ca-L , sarcoplasmic reticulum Ca 2+ content, and sarcoendoplasmic reticulum Ca 2+ ATPase function were restored following recovery from HF. Confocal microscopy showed fragmentation of ryanodine receptor staining and movement away from the z-line in HF, which was reversed following recovery from HF. Acute detubulation, to remove recovered t-tubules, confirmed their key role in restoration of the systolic Ca 2+ transient, the rate of Ca 2+ removal, and the peak L-type Ca 2+ current. The abundance of telethonin and myotubularin decreased during HF and increased during recovery. Transfection with these proteins altered the density and structure of tubules in neonatal myocytes. Myotubularin had a greater effect, increasing tubule length and branching, replicating that seen in the recovery atria. CONCLUSIONS: We show that recovery from HF restores atrial t-tubules, and this promotes recovery of I Ca-L , sarcoplasmic reticulum Ca 2+ content, and systolic Ca 2+ . We demonstrate an important role for myotubularin in t-tubule restoration. Our findings reveal a new and viable therapeutic strategy.
Empowering Hospitalized Patients With Diabetes: Implementation of a Hospital-wide CGM Policy With EHR-Integrated Validation for Dosing Insulin
Authors: Ming Yeh Lee, Susan M. Seav, Loice Ongwela, Julie J. Lee, Rachel Aubyrn, Fang Y. Cao, Anna Kalinsky, Olivia Aparicio Ramos, Yunzi Gu, Kailee Kingston, Maja Ivanovic, Bruce A. Buckingham, Dimpi Desai, Rayhan A. Lal, Marilyn Tan, Marina Basina, Michael S. Hughes
Journal: Diabetes Care (2024)

OBJECTIVE We aimed to assess the feasibility, clinical accuracy, and acceptance of a hospital-wide continuous glucose monitoring (CGM) policy with electronic health record (EHR)–integrated validation for insulin dosing. RESEARCH DESIGN AND METHODS A hospital policy was developed and implemented at Stanford Health Care for using personal CGMs in lieu of fingerstick blood glucose (FSBG) monitoring. It included requirements specific to each CGM, accuracy monitoring protocols, and EHR integration. User experience surveys were conducted among a subset of patients and nurses. RESULTS From November 2022 to August 2023, 135 patients used the CGM protocol in 185 inpatient encounters. This group included 27% with type 1 diabetes and 24% with automated insulin delivery systems. The most-used CGMs were Dexcom G6 (44%) and FreeStyle Libre 2 (43%). Of 1,506 CGM validation attempts, 87.8% met the 20% or 20 mg/dL (%20/20) criterion for CGM-based insulin dosing and 99.3% fell within Clarke zones A or B. User experience surveys were completed by 27 nurses and 46 patients. Most nurses found glucose management under the protocol effective (74%), easy to use (67%), and efficient (63%); 80% of nurses preferred inpatient CGM to FSBG. Most patients liked the CGM protocol (63%), reported positive CGM interactions with nursing staff (63%), and felt no significant interruptions to their diabetes management (63%). CONCLUSIONS Implementation of a hospital-wide inpatient CGM policy supporting multiple CGM types with real-time accuracy monitoring and integration into the EHR is feasible. Initial feedback from nurses and patients was favorable, and further investigation toward broader use and sustainability is needed.
Frontiers in CAR-T cell therapy for autoimmune diseases
Authors: Yan-Ruide Li, Zibai Lyu, Yuning Chen, Ying Fang, Lili Yang
Journal: Trends in Pharmacological Sciences (2024)

Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy has demonstrated significant success in treating cancers. The potential of CAR-T cells is now being explored in the context of autoimmune diseases. Recent clinical trials have shown sustained and profound elimination of autoreactive B cells by CAR-T cells, leading to promising autoimmune disease control with minimal safety concerns. These encouraging results have inspired further investigation into CAR-T cell applications for a broader range of autoimmune diseases and the development of advanced cell products with improved efficacy and safety. In this review, we discuss the mechanisms by which CAR-T cells target autoimmune conditions, summarize current preclinical models, and highlight ongoing clinical trials, including CAR-T therapy design, clinical outcomes, and challenges. Additionally, we discuss the limitations and future directions of CAR-T therapy in the treatment of autoimmune diseases.
Associating transcription factors to single-cell trajectories with DREAMIT
Authors: Nathan D. Maulding, Lucas Seninge, Joshua M. Stuart
Journal: Genome biology (2024)

Abstract Inferring gene regulatory networks from single-cell RNA-sequencing trajectories has been an active area of research yet methods are still needed to identify regulators governing cell transitions. We developed DREAMIT (Dynamic Regulation of Expression Across Modules in Inferred Trajectories) to annotate transcription-factor activity along single-cell trajectory branches, using ensembles of relations to target genes. Using a benchmark representing several different tissues, as well as external validation with ATAC-Seq and Perturb-Seq data on hematopoietic cells, the method was found to have higher tissue-specific sensitivity and specificity over competing approaches.
Arid1a-dependent canonical BAF complex suppresses inflammatory programs to drive efficient germinal center B cell responses
Authors: Ajay Abraham, Daniela Samaniego-Castruita, Isabella Han, Prathyaya Ramesh, Mi Thao Tran, Jillian Paladino, Heather Kligfeld, Roxroy C. Morgan, Rebecca L. Schmitz, Rebecca M. Southern, Ashima Shukla, Vipul Shukla
Journal: Nature Immunology (2024)
Nurse‐led diuretic titration via a point‐of‐care urinary sodium sensor in patients with acute decompensated heart failure (<scp>EASY</scp>‐<scp>HF</scp>): A single‐centre, randomized, open‐label study
Authors: Evelyne Meekers, Pieter Martens, Jeroen Dauw, Henri Gruwez, Sebastiaan Dhont, Petra Nijst, Frederik H. Verbrugge, Koen Ameloot, David Verhaert, Matthias Dupont, Jorien Stassen, Marleen Opdenacker, Stefan Janssens, Wilfried Mullens
Journal: European Journal of Heart Failure (2024)
S-acylation of ATGL is required for lipid droplet homoeostasis in hepatocytes
Authors: Yuping Zheng, Jishun Chen, Vinitha Macwan, Charneal L. Dixon, Xinran Li, Shengjie Liu, Yuyun Yu, Pinglong Xu, Qiming Sun, Qi Hu, Wei Liu, Brian Raught, Gregory D. Fairn, Dante Neculai
Journal: Nature Metabolism (2024)
Nonlinear dynamics of multi-omics profiles during human aging
Authors: Xiaotao Shen, Chuchu Wang, Xin Zhou, Wenyu Zhou, Daniel Hornburg, Si Wu, Michael P. Snyder
Journal: Nature Aging (2024)

Aging is a complex process associated with nearly all diseases. Understanding the molecular changes underlying aging and identifying therapeutic targets for aging-related diseases are crucial for increasing healthspan. Although many studies have explored linear changes during aging, the prevalence of aging-related diseases and mortality risk accelerates after specific time points, indicating the importance of studying nonlinear molecular changes. In this study, we performed comprehensive multi-omics profiling on a longitudinal human cohort of 108 participants, aged between 25 years and 75 years. The participants resided in California, United States, and were tracked for a median period of 1.7 years, with a maximum follow-up duration of 6.8 years. The analysis revealed consistent nonlinear patterns in molecular markers of aging, with substantial dysregulation occurring at two major periods occurring at approximately 44 years and 60 years of chronological age. Distinct molecules and functional pathways associated with these periods were also identified, such as immune regulation and carbohydrate metabolism that shifted during the 60-year transition and cardiovascular disease, lipid and alcohol metabolism changes at the 40-year transition. Overall, this research demonstrates that functions and risks of aging-related diseases change nonlinearly across the human lifespan and provides insights into the molecular and biological pathways involved in these changes.
Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline
Authors: Michael R. Duggan, Zhongsheng Peng, Pyry N. Sipilä, Joni V. Lindbohm, Jingsha Chen, Yifei Lu, Christos Davatzikos, Guray Erus, Timothy J. Hohman, Shea J. Andrews, Julián Candia, Toshiko Tanaka, Cassandra M. Joynes, Chelsea X. Alvarado, Mike A. Nalls, Jenifer Cordon, Gulzar N. Daya, Yang An, Alexandria Lewis, Abhay Moghekar, Priya Palta, Josef Coresh, Luigi Ferrucci, Mika Kivimäki, Keenan A. Walker
Journal: Nature Aging (2024)

Abstract Infections have been associated with the incidence of Alzheimer disease and related dementias, but the mechanisms responsible for these associations remain unclear. Using a multicohort approach, we found that influenza, viral, respiratory, and skin and subcutaneous infections were associated with increased long-term dementia risk. These infections were also associated with region-specific brain volume loss, most commonly in the temporal lobe. We identified 260 out of 942 immunologically relevant proteins in plasma that were differentially expressed in individuals with an infection history. Of the infection-related proteins, 35 predicted volumetric changes in brain regions vulnerable to infection-specific atrophy. Several of these proteins, including PIK3CG, PACSIN2, and PRKCB, were related to cognitive decline and plasma biomarkers of dementia (Aβ 42/40 , GFAP, NfL, pTau-181). Genetic variants that influenced expression of immunologically relevant infection-related proteins, including ITGB6 and TLR5, predicted brain volume loss. Our findings support the role of infections in dementia risk and identify molecular mediators by which infections may contribute to neurodegeneration.
Essential Oil Components Incorporated Emulsion Hydrogels for Eradicating Dermatophytosis Caused by Pathogenic Fungi <i>Trichophyton mentagrophytes</i> and <i>Microsporum canis</i>
Authors: Namitha K. Preman, Nikhitha Amin, Sandesh G. Sanjeeva, Suprith Surya, Sukesh Kumar B, Manjunath M. Shenoy, Rajesh P. Shastry, Renjith P. Johnson
Journal: Advanced Healthcare Materials (2024)

Dermatophytosis is a prevalent fungal infection and public health burden, majorly caused by the attack of zoophilic fungi genera of Trichophyton and Microsporum. Among them, T. mentagrophytes and M. canis are the dominating pathogens that cause dermatophytosis in humans. Though anti-fungal treatments are available, the widespread drug resistance and minimal efficacy of conventional therapies cause recurring infections. In addition, prolonged anti-fungal medications induce several systemic side effects, including hepatotoxicity and leucopenia. The anti-dermatophytic formulation of biocompatible essential oil components (EOCs) is attractive due to their highly potent anti-dermatophytic action. Herein, two EOCs, Eugenol (EU) and Isoeugenol (IU), incorporated emulsion hydrogel (EOCs-EHG) synthesized from hydroxypropylmethyl cellulose and poly(ethylene glycol) methyl ether methacrylate. The cytocompatibility of the hydrogels is confirmed by treating them with fibroblast and keratinocyte cell lines. The EOCs-EHG demonstrated pH and temperature-responsive sustained release of entrapped EOCs and inhibited fungal spore germination. T. mentagrophytes and M. canis biofilms are eradicated at a minimal inhibitory concentration of 2 µg mL
Nanozyme‐Enabled Biomedical Diagnosis: Advances, Trends, and Challenges
Authors: Qingzhen Tian, Shu Li, Zheng Tang, Ziyu Zhang, Dan Du, Xiao Zhang, Xiangheng Niu, Yuehe Lin
Journal: Advanced Healthcare Materials (2024)

Abstract As nanoscale materials with the function of catalyzing substrates through enzymatic kinetics, nanozymes are regarded as potential alternatives to natural enzymes. Compared to protein‐based enzymes, nanozymes exhibit attractive characteristics of low preparation cost, robust activity, flexible performance adjustment, and versatile functionalization. These advantages endow them with wide use from biochemical sensing and environmental remediation to medical theranostics. Especially in biomedical diagnosis, the feature of catalytic signal amplification provided by nanozymes makes them function as emerging labels for the detection of biomarkers and diseases, with rapid developments observed in recent years. To provide a comprehensive overview of recent progress made in this dynamic field, here an overview of biomedical diagnosis enabled by nanozymes is provided. This review first summarizes the synthesis of nanozyme materials and then discusses the main strategies applied to enhance their catalytic activity and specificity. Subsequently, representative utilization of nanozymes combined with biological elements in disease diagnosis is reviewed, including the detection of biomarkers related to metabolic, cardiovascular, nervous, and digestive diseases as well as cancers. Finally, some development trends in nanozyme‐enabled biomedical diagnosis are highlighted, and corresponding challenges are also pointed out, aiming to inspire future efforts to further advance this promising field.
Targeting TNFRSF25 by agonistic antibodies and multimeric TL1A proteins co-stimulated CD8<sup>+</sup>T cells and inhibited tumor growth
Authors: Xueyuan Lyu, Linlin Zhao, Sijia Chen, Yulu Li, Yajing Yang, Huisi Liu, Fang Yang, Wenhui Li, Jianhua Sui
Journal: Journal for ImmunoTherapy of Cancer (2024)

Tumor necrosis factor receptor superfamily 25 (TNFRSF25) is a T-cell co-stimulatory receptor. Expression of its ligand, TNF-like cytokine 1A (TL1A), on mouse tumor cells has been shown to promote tumor regression. This study aimed to develop TNFRSF25 agonists (both antibodies (Abs) and TL1A proteins) and to investigate their potential antitumor effects.
Case report of fatal immune-mediated myocarditis following treatment with davoceticept (ALPN-202), a PD-L1-dependent CD28 costimulator and dual PD-L1/CTLA-4 checkpoint inhibitor, in combination with pembrolizumab
Authors: Ludimila Cavalcante, Sreenivasa Chandana, Nehal Lakhani, Amanda Enstrom, Heidi LeBlanc, Joseph Schmalz, Krisztina Lengyel, Frank Schneider, Heather Thomas, Michael J Chisamore, Stanford L Peng, Allison Naumovski, Diwakar Davar
Journal: Journal for ImmunoTherapy of Cancer (2024)

Engagement of programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) can interfere with the CD28 signaling requisite for T-cell activation. While immune checkpoint inhibitors (ICIs) can relieve this suppression, they are unable to drive CD28 costimulation that may mechanistically contribute to ICI resistance. Thus, CD28 costimulation in the context of checkpoint inhibition may activate immunosuppressed T-cells in the tumor microenvironment. Davoceticept (ALPN-202) is an Fc fusion of a CD80 variant immunoglobulin domain (vIgD) designed to mediate PD-L1-dependent CD28 costimulation while inhibiting the PD-L1 and CTLA-4 checkpoints. PD-L1-restriction of davoceticept’s CD28 costimulatory activity may minimize systemic T-cell activation and avoid untoward systemic toxicities. At the same time, preclinical studies have suggested that treatment with davoceticept during PD-1 inhibition may enhance antitumor activity by upregulating PD-L1, potentially synergizing with davoceticept’s PD-L1-dependent costimulatory mechanism. This report details two cases of fatal cardiac events following treatment with davoceticept in combination with pembrolizumab (anti-PD-1) in the phase 1 study, NEON-2. Both events occurred in females in their 60s; one with choroidal melanoma and prior immunotherapy, the other with ICI-naïve microsatellite stable colorectal cancer. The clinical courses were fulminant with symptom onset at 2 weeks, followed by rapid decline. Cardiac autopsy from one patient confirmed immune-related myocarditis, and immunosequencing revealed expansion of a single T-cell clone that was not present in the pretreatment tumor. These cases highlight the importance of understanding risk factors that may contribute to immune-related myocarditis and other severe immune-related adverse events when CD28 agonism is targeted in the context of checkpoint inhibition.Trial registration number: NEON-2 ( NCT04920383 ).
Targeting Cyclophilin A in the Cardiac Microenvironment Preserves Heart Function and Structure in Failing Hearts
Authors: Manuel Sigle, Anne-Katrin Rohlfing, Melanie Cruz Santos, Timo Kopp, Konstantin Krutzke, Vincent Gidlund, Ferdinand Kollotzek, Julia Marzi, Saskia von Ungern-Sternberg, Antti Poso, Mathias Heikenwälder, Katja Schenke-Layland, Peter Seizer, Julia Möllmann, Nikolaus Marx, Robert Feil, Susanne Feil, Robert Lukowski, Oliver Borst, Tilman E. Schäffer, Karin Anne Lydia Müller, Meinrad P. Gawaz, David Heinzmann
Journal: Circulation Research (2024)

Cardiac hypertrophy is characterized by remodeling of the myocardium, which involves alterations in the ECM (extracellular matrix) and cardiomyocyte structure. These alterations critically contribute to impaired contractility and relaxation, ultimately leading to heart failure. Emerging evidence implicates that extracellular signaling molecules are critically involved in the pathogenesis of cardiac hypertrophy and remodeling. The immunophilin CyPA (cyclophilin A) has been identified as a potential culprit. In this study, we aimed to unravel the interplay between eCyPA (extracellular CyPA) and myocardial dysfunction and evaluate the therapeutic potential of inhibiting its extracellular accumulation to improve heart function.