tbuckley/cabot-search huggingface dataset:
Importance of <scp>SREBP</scp> signaling in controlling lipid metabolism and homeostasis in B cells for future vaccine design
Authors: Zsófia Unger, Alina Kuklinski, Cristina Gomez‐Casado
Journal: Allergy (2024)

The authors declare that they do not have any conflict of interest to declare. Data sharing is not applicable to this article as no new data were generated in this study.
D3S-001, a KRAS G12C Inhibitor with Rapid Target Engagement Kinetics, Overcomes Nucleotide Cycling, and Demonstrates Robust Preclinical and Clinical Activities
Authors: Jing Zhang, Sun Min Lim, Mi Ra Yu, Cheng Chen, Jia Wang, Wenqian Wang, Haopeng Rui, Jingtao Lu, Shun Lu, Tony Mok, Zhi Jian Chen, Byoung Chul Cho
Journal: Cancer Discovery (2024)

First-generation KRAS G12C inhibitors, such as sotorasib and adagrasib, are limited by the depth and duration of clinical responses. One potential explanation for their modest clinical activity is the dynamic "cycling" of KRAS between its guanosine diphosphate (GDP)- and guanosine triphosphate (GTP)-bound states, raising controversy about whether targeting the GDP-bound form can fully block this oncogenic driver. We herein report that D3S-001, a next-generation GDP-bound G12C inhibitor with faster target engagement (TE) kinetics, depletes cellular active KRAS G12C at nanomolar concentrations. In the presence of growth factors, such as epithelial growth factor and hepatocyte growth factor, the ability of sotorasib and adagrasib to inhibit KRAS was compromised whereas the TE kinetics of D3S-001 was nearly unaffected, a unique feature differentiating D3S-001 from other GDP-bound G12C inhibitors. Furthermore, the high covalent potency and cellular TE efficiency of D3S-001 contributed to robust antitumor activity preclinically and translated into promising clinical efficacy in an ongoing phase 1 trial (NCT05410145). Significance: The kinetic study presented in this work unveils, for the first time, that a GDP-bound conformation-selective KRAS G12C inhibitor can potentially deplete cellular active KRAS in the presence of growth factors and offers new insights into the critical features that drive preclinical and clinical efficacy for this class of drugs.
Metabolome-associated psychological comorbidities improvement in irritable bowel syndrome patients receiving a probiotic
Authors: Francois-Pierre Martin, Ornella Cominetti, Bernard Berger, Séverine Combremont, Julien Marquis, Guoxiang Xie, Wei Jia, Maria Inés Pinto-Sanchez, Premysl Bercik, Gabriela Bergonzelli
Journal: Gut Microbes (2024)

Our recent randomized, placebo-controlled study in Irritable Bowel Syndrome (IBS) patients with diarrhea or alternating bowel habits showed that the probiotic Bifidobacterium longum (BL) NCC3001 improves depression scores and decreases brain emotional reactivity. However, the involved metabolic pathways remain unclear. This analysis aimed to investigate the biochemical pathways underlying the beneficial effects of BL NCC3001 using metabolomic profiling. Patients received probiotic (1x 1010CFU, n=16) or placebo (n=19) daily for 6 weeks. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale. Brain activity in response to negative emotional stimuli was assessed by functional Magnetic Resonance Imaging. Probiotic fecal abundance was quantified by qPCR. Quantitative measurement of specific panels of plasma host-microbial metabolites was performed by mass spectrometry-based metabolomics. Probiotic abundance in feces was associated with improvements in anxiety and depression scores, and a decrease in amygdala activation. The probiotic treatment increased the levels of butyric acid, tryptophan, N-acetyl tryptophan, glycine-conjugated bile acids, and free fatty acids. Butyric acid concentration correlated with lower anxiety and depression scores, and decreased amygdala activation. Furthermore, butyric acid concentration correlated with the probiotic abundance in feces. In patients with non-constipation IBS, improvements in psychological comorbidities and brain emotional reactivity were associated with an increased abundance of BL NCC3001 in feces and specific plasma metabolites, mainly butyric acid. These findings suggest the importance of a probiotic to thrive in the gut and highlight butyric acid as a potential biochemical marker linking microbial metabolism with beneficial effects on the gut-brain axis.
Single-Cell Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis
Authors: Avraham Unterman, Amy Y. Zhao, Nir Neumark, Jonas C. Schupp, Farida Ahangari, Carlos Cosme, Prapti Sharma, Jasper Flint, Yan Stein, Changwan Ryu, Genta Ishikawa, Tomokazu S. Sumida, Jose L. Gomez, Jose D. Herazo-Maya, Charles S. Dela Cruz, Erica L. Herzog, Naftali Kaminski
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Changes in peripheral blood cell populations have been observed, but not detailed, at single-cell resolution in idiopathic pulmonary fibrosis (IPF).
Neuroecological links of the exposome and One Health
Authors: Agustin Ibanez, Lucia Melloni, Paweł Świeboda, William Hynes, Burcin Ikiz, Rym Ayadi, Massamba Thioye, Consuelo Walss-Bass, Bahar Güntekin, Jyoti Mishra, Mohamed Salama, Sarah Dunlop, Claudia Duran-Aniotz, Harris A. Eyre
Journal: Neuron (2024)
Chemoradiotherapy-induced ACKR2+ tumor cells drive CD8+ T cell senescence and cervical cancer recurrence
Authors: Dongfang Dai, Yifei Pei, Biqing Zhu, Deqiang Wang, Siyu Pei, Huan Huang, Qingchen Zhu, Xiuyu Deng, Jialin Ye, Jing Xu, Xiaoxiang Chen, Mingzhu Huang, Yichuan Xiao
Journal: Cell Reports Medicine (2024)

Tumor recurrence after chemoradiotherapy is challenging to overcome, and approaches to predict the recurrence remain elusive. Here, human cervical cancer tissues before and after concurrent chemoradiotherapy (CCRT) analyzed by single-cell RNA sequencing reveal that CCRT specifically promotes CD8
New methods to unveil host-microbe interaction mechanisms along the microbiota-gut-brain-axis
Authors: Habibullah Moradian, Tristan Gabriel, Mathilde Barrau, Xavier Roblin, Stéphane Paul
Journal: Gut Microbes (2024)

Links between the gut microbiota and human health have been supported throughout numerous studies, such as the development of neurological disease disorders. This link is referred to as the "microbiota-gut-brain axis" and is the focus of an emerging field of research. Microbial-derived metabolites and gut and neuro-immunological metabolites regulate this axis in health and many diseases. Indeed, assessing these signals, whether induced by microbial metabolites or neuro-immune mediators, could significantly increase our knowledge of the microbiota-gut-brain axis. However, this will require the development of appropriate techniques and potential models. Methods for studying the induced signals originating from the microbiota remain crucial in this field. This review discusses the methods and techniques available for studies of microbiota-gut-brain interactions. We highlight several much-debated elements of these methodologies, including the widely used
Collaborative Care for Injured Older Adults
Authors: Ben L. Zarzaur, Emma Holler, Damaris Ortiz, Anthony Perkins, Sue Lasiter, Sujuan Gao, Dustin D. French, Babar Khan, Malaz Boustani
Journal: JAMA Surgery (2024)

Older adults with recent injuries can have impaired long-term biopsychosocial function and may benefit from interventions adapted to their needs.
Preexisting Diabetes and Breast Cancer Treatment Among Low-Income Women
Authors: Bayu Begashaw Bekele, Min Lian, Chester Schmaltz, Tracy Greever-Rice, Pratibha Shrestha, Ying Liu
Journal: JAMA Network Open (2024)

IMPORTANCE Diabetes is associated with poorer prognosis of patients with breast cancer. The association between diabetes and adjuvant therapies for breast cancer remains uncertain. OBJECTIVE To comprehensively examine the associations of preexisting diabetes with radiotherapy, chemotherapy, and endocrine therapy in low-income women with breast cancer. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study included women younger than 65 years diagnosed with nonmetastatic breast cancer from 2007 through 2015, followed up through 2016, continuously enrolled in Medicaid, and identified from the linked Missouri Cancer Registry and Medicaid claims data set. Data were analyzed from January 2022 to October 2023. EXPOSURE Preexisting diabetes. MAIN OUTCOMES AND MEASURES Logistic regression was used to estimate odds ratios (ORs) of utilization (yes/no), timely initiation (≤90 days postsurgery), and completion of radiotherapy and chemotherapy, as well as adherence (medication possession ratio ≥80%) and persistence (&amp;amp;lt;90–consecutive day gap) of endocrine therapy in the first year of treatment for women with diabetes compared with women without diabetes. Analyses were adjusted for sociodemographic and tumor factors. RESULTS Among 3704 women undergoing definitive surgery, the mean (SD) age was 51.4 (8.6) years, 1038 (28.1%) were non-Hispanic Black, 2598 (70.1%) were non-Hispanic White, 765 (20.7%) had a diabetes history, 2369 (64.0%) received radiotherapy, 2237 (60.4%) had chemotherapy, and 2505 (67.6%) took endocrine therapy. Compared with women without diabetes, women with diabetes were less likely to utilize radiotherapy (OR, 0.67; 95% CI, 0.53-0.86), receive chemotherapy (OR, 0.67; 95% CI, 0.48-0.93), complete chemotherapy (OR, 0.71; 95% CI, 0.50-0.99), and be adherent to endocrine therapy (OR, 0.71; 95% CI, 0.56-0.91). There were no significant associations of diabetes with utilization (OR, 0.95; 95% CI, 0.71-1.28) and persistence (OR, 1.09; 95% CI, 0.88-1.36) of endocrine therapy, timely initiation of radiotherapy (OR, 1.09; 95% CI, 0.86-1.38) and chemotherapy (OR, 1.09; 95% CI, 0.77-1.55), or completion of radiotherapy (OR, 1.25; 95% CI, 0.91-1.71). CONCLUSIONS AND RELEVANCE In this cohort study, preexisting diabetes was associated with subpar adjuvant therapies for breast cancer among low-income women. Improving diabetes management during cancer treatment is particularly important for low-income women with breast cancer who may have been disproportionately affected by diabetes and are likely to experience disparities in cancer treatment and outcomes.
Thomas, Unsainted
Authors: William R. Clarke
Journal: JAMA (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Surgical Competency Assessment Using Entrustable Professional Activities
Authors: Stephanie L. Nitzschke, Stanley W. Ashley, Gilbert R. Upchurch
Journal: JAMA Surgery (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
The landscape of cancer-rewired GPCR signaling axes
Authors: Chakit Arora, Marin Matic, Luisa Bisceglia, Pierluigi Di Chiaro, Natalia De Oliveira Rosa, Francesco Carli, Lauren Clubb, Lorenzo Amir Nemati Fard, Giorgos Kargas, Giuseppe R. Diaferia, Ranka Vukotic, Luana Licata, Guanming Wu, Gioacchino Natoli, J. Silvio Gutkind, Francesco Raimondi
Journal: Cell Genomics (2024)

We explored the dysregulation of G-protein-coupled receptor (GPCR) ligand systems in cancer transcriptomics datasets to uncover new therapeutics opportunities in oncology. We derived an interaction network of receptors with ligands and their biosynthetic enzymes. Multiple GPCRs are differentially regulated together with their upstream partners across cancer subtypes and are associated to specific transcriptional programs and to patient survival patterns. The expression of both receptor-ligand (or enzymes) partners improved patient stratification, suggesting a synergistic role for the activation of GPCR networks in modulating cancer phenotypes. Remarkably, we identified many such axes across several cancer molecular subtypes, including many involving receptor-biosynthetic enzymes for neurotransmitters. We found that GPCRs from these actionable axes, including, e.g., muscarinic, adenosine, 5-hydroxytryptamine, and chemokine receptors, are the targets of multiple drugs displaying anti-growth effects in large-scale, cancer cell drug screens, which we further validated. We have made the results generated in this study freely available through a webapp (gpcrcanceraxes.bioinfolab.sns.it).
Role of Inflammation in Short Sleep Duration Across Childhood and Psychosis in Young Adulthood
Authors: Isabel Morales-Muñoz, Steven Marwaha, Rachel Upthegrove, Vanessa Cropley
Journal: JAMA Psychiatry (2024)

Short sleep duration over a prolonged period in childhood could have a detrimental impact on long-term mental health, including the development of psychosis. Further, potential underlying mechanisms of these associations remain unknown.
Characterization of Biologic Discontinuation Among Pediatric Patients with Crohn’s Disease
Authors: Sabina Ali, Brad Pasternak, Jonathan Moses, David L. Suskind, Charles Samson, Jess Kaplan, Jana Creps, Lauren Manning, Michaella Baker, Dianne Singer, Perseus Patel, Becca Trombler, Archana Anandakrishnan, Camila Khorrami, Maya Feldman, Molly McGoldrick, Jeremy Adler
Journal: Clinical Gastroenterology and Hepatology (2024)
Interleukin-17 blockade by secukinumab was not effective in controlling lichen planus in a randomized controlled clinical trial
Authors: Claudia Günther
Journal: British Journal of Dermatology (2024)

Journal Article Accepted manuscript IL-17 blockade by secukinumab was not effective in controlling lichen planus in a randomized controlled clinical trial Get access Claudia Günther Claudia Günther Department of Dermatology, University Medical Center Hospital, TU Dresden Email:Claudia.Guenther@ukdd.de https://orcid.org/0000-0002-4330-1861 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae186, https://doi.org/10.1093/bjd/ljae186 Published: 08 May 2024 Article history Received: 26 April 2024 Accepted: 06 May 2024 Published: 08 May 2024
Advanced Immunomodulatory Biomaterials for Therapeutic Applications
Authors: Ji‐Eun Park, Dong‐Hwee Kim
Journal: Advanced Healthcare Materials (2024)

The multifaceted biological defense system modulating complex immune responses against pathogens and foreign materials plays a critical role in tissue homeostasis and disease progression. Recently developed biomaterials that can specifically regulate immune responses, nanoparticles, graphene, and functional hydrogels have contributed to the advancement of tissue engineering as well as disease treatment. The interaction between innate and adaptive immunity, collectively determining immune responses, can be regulated by mechanobiological recognition and adaptation of immune cells to the extracellular microenvironment. Therefore, applying immunomodulation to tissue regeneration and cancer therapy involves manipulating the properties of biomaterials by tailoring their composition in the context of the immune system. This review provides a comprehensive overview of how the physicochemical attributes of biomaterials determine immune responses, focusing on the physical properties that influence innate and adaptive immunity. This review also underscores the critical aspect of biomaterial-based immune engineering for the development of novel therapeutics and emphasizes the importance of understanding the biomaterials-mediated immunological mechanisms and their role in modulating the immune system.
SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes
Authors: Joan Sabadell-Basallote, Brenno Astiarraga, Carlos Castaño, Miriam Ejarque, Maria Repollés-de-Dalmau, Ivan Quesada, Jordi Blanco, Catalina Núñez-Roa, M-Mar Rodríguez-Peña, Laia Martínez, Dario F. De Jesus, Laura Marroquí, Ramon Bosch, Eduard Montanya, Francesc X. Sureda, Andrea Tura, Andrea Mari, Rohit N. Kulkarni, Joan Vendrell, Sonia Fernández-Veledo
Journal: Journal of Clinical Investigation (2024)

Pancreatic β-cell dysfunction is a key feature of type 2 diabetes, and novel regulators of insulin secretion are desirable. Here we report that the succinate receptor (SUCNR1) is expressed in β-cells and is up-regulated in hyperglycemic states in mice and humans. We found that succinate acts as a hormone-like metabolite and stimulates insulin secretion via a SUCNR1-Gq-PKC-dependent mechanism in human β-cells. Mice with β-cell-specific Sucnr1 deficiency exhibit impaired glucose tolerance and insulin secretion on a high-fat diet, indicating that SUCNR1 is essential for preserving insulin secretion in diet-induced insulin resistance. Patients with impaired glucose tolerance show an enhanced nutritional-related succinate response, which correlates with the potentiation of insulin secretion during intravenous glucose administration. These data demonstrate that the succinate/SUCNR1 axis is activated by high glucose and identify a GPCR-mediated amplifying pathway for insulin secretion relevant to the hyperinsulinemia of prediabetic states.
Meta-analysis identifying gut microbial biomarkers of Qinghai-Tibet Plateau populations and the functionality of microbiota-derived butyrate in high-altitude adaptation
Authors: Hongwen Zhao, Longjie Sun, Jiali Liu, Bin Shi, Yaopeng Zhang, Ci-Ren Qu-Zong, Tsechoe Dorji, Tieyu Wang, Hongli Yuan, Jinshui Yang
Journal: Gut Microbes (2024)

The extreme environmental conditions of a plateau seriously threaten human health. The relationship between gut microbiota and human health at high altitudes has been extensively investigated. However, no universal gut microbiota biomarkers have been identified in the plateau population, limiting research into gut microbiota and high-altitude adaptation. 668 16s rRNA samples were analyzed using meta-analysis to reduce batch effects and uncover microbiota biomarkers in the plateau population. Furthermore, the robustness of these biomarkers was validated. Mendelian randomization (MR) results indicated that Tibetan gut microbiota may mediate a reduced erythropoietic response. Functional analysis and qPCR revealed that butyrate may be a functional metabolite in high-altitude adaptation. A high-altitude rat model showed that butyrate reduced intestinal damage caused by high altitudes. According to cell experiments, butyrate may downregulate hypoxia-inducible factor-1α (HIF-1α) expression and blunt cellular responses to hypoxic stress. Our research found universally applicable biomarkers and investigated their potential roles in promoting human health at high altitudes.
A mitochondrial surveillance mechanism activated by SRSF2 mutations in hematologic malignancies
Authors: Xiaolei Liu, Sudhish A. Devadiga, Robert F. Stanley, Ryan M. Morrow, Kevin A. Janssen, Mathieu Quesnel-Vallières, Oz Pomp, Adam A. Moverley, Chenchen Li, Nicolas Skuli, Martin Carroll, Jian Huang, Douglas C. Wallace, Kristen W. Lynch, Omar Abdel-Wahab, Peter S. Klein
Journal: Journal of Clinical Investigation (2024)

Splicing factor mutations are common in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but how they alter cellular functions is unclear. We show that the pathogenic SRSF2P95H/+ mutation disrupts the splicing of mitochondrial mRNAs, impairs mitochondrial complex I function, and robustly increases mitophagy. We also identified a mitochondrial surveillance mechanism by which mitochondrial dysfunction modifies splicing of the mitophagy activator PINK1 to remove a poison intron, increasing the stability and abundance of PINK1 mRNA and protein. SRSF2P95H-induced mitochondrial dysfunction increased PINK1 expression through this mechanism, which is essential for survival of SRSF2P95H/+ cells. Inhibition of splicing with a glycogen synthase kinase 3 inhibitor promoted retention of the poison intron, impairing mitophagy and activating apoptosis in SRSF2P95H/+ cells. These data reveal a homeostatic mechanism for sensing mitochondrial stress through PINK1 splicing and identify increased mitophagy as a disease marker and a therapeutic vulnerability in SRSF2P95H mutant MDS and AML.