tbuckley/cabot-search huggingface dataset:
Single-neuron projectomes of mouse paraventricular hypothalamic nucleus oxytocin neurons reveal mutually exclusive projection patterns
Authors: Humingzhu Li, Tao Jiang, Sile An, Mingrui Xu, Lingfeng Gou, Biyu Ren, Xiaoxue Shi, Xiaofei Wang, Jun Yan, Jing Yuan, Xiaohong Xu, Qing-Feng Wu, Qingming Luo, Hui Gong, Wen-Jie Bian, Anan Li, Xiang Yu
Journal: Neuron (2024)
Targeting EMSY-mediated methionine metabolism is a potential therapeutic strategy for triple-negative breast cancer
Authors: Cui-Cui Liu, Lie Chen, Yu-Wen Cai, Yu-Fei Chen, Yi-Ming Liu, Yu-Jie Zhou, Zhi-Ming Shao, Ke-Da Yu
Journal: Cell Reports Medicine (2024)

Cancer stem cells (CSCs) are the most intractable subpopulation of triple-negative breast cancer (TNBC) cells, which have been associated with a high risk of relapse and poor prognosis. However, eradication of CSCs continues to be difficult. Here, we integrate the multiomics data of a TNBC cohort (n = 360) to identify vital markers of CSCs. We discover that EMSY, inducing a BRCAness phenotype, is preferentially expressed in breast CSCs, promotes ALDH+ cells enrichment, and is positively correlated with poor relapse-free survival. Mechanistically, EMSY competitively binds to the Jmjc domain, which is critical for KDM5B enzyme activity, to reshape methionine metabolism, and to promote CSC self-renewal and tumorigenesis in an H3K4 methylation-dependent manner. Moreover, EMSY accumulation in TNBC cells sensitizes them to PARP inhibitors against bulk cells and methionine deprivation against CSCs. These findings indicate that clinically relevant eradication of CSCs could be achieved with a strategy that targets CSC-specific vulnerabilities in amino acid metabolism.
Avoiding conflicts of interest and reputational risks associated with population research on food and nutrition: the Food Research risK (FoRK) guidance and toolkit for researchers
Authors: Katherine Cullerton, Jean Adams, Nita G Forouhi, Oliver Francis, Martin White
Journal: BMJ (2024)

Researchers wishing to interact with the food industry can be subject to conflicts of interest and reputational risks, but new guidance from Cullerton and colleagues should help researchers navigate this tricky territory, make informed decisions, and minimise adverse outcomes.
Physical and functional convergence of the autism risk genes Scn2a and Ank2 in neocortical pyramidal cell dendrites
Authors: Andrew D. Nelson, Amanda M. Catalfio, Julie P. Gupta, Lia Min, René N. Caballero-Florán, Kendall P. Dean, Carina C. Elvira, Kimberly D. Derderian, Henry Kyoung, Atehsa Sahagun, Stephan J. Sanders, Kevin J. Bender, Paul M. Jenkins
Journal: Neuron (2024)
EML4-ALK fusions drive lung adeno-to-squamous transition through JAK-STAT activation
Authors: Zhen Qin, Meiting Yue, Shijie Tang, Fengying Wu, Honghua Sun, Yuan Li, Yongchang Zhang, Hiroki Izumi, Hsinyi Huang, Wanying Wang, Yun Xue, Xinyuan Tong, Shunta Mori, Tetsuro Taki, Koichi Goto, Yujuan Jin, Fei Li, Fu-Ming Li, Yijun Gao, Zhaoyuan Fang, Yisheng Fang, Liang Hu, Xiumin Yan, Guoliang Xu, Haiquan Chen, Susumu S. Kobayashi, Andrea Ventura, Kwok-Kin Wong, Xueliang Zhu, Liang Chen, Shengxiang Ren, Luo-Nan Chen, Hongbin Ji
Journal: The Journal of Experimental Medicine (2024)

Human lung adenosquamous cell carcinoma (LUAS), containing both adenomatous and squamous pathologies, exhibits strong cancer plasticity. We find that ALK rearrangement is detectable in 5.1–7.5% of human LUAS, and transgenic expression of EML4-ALK drives lung adenocarcinoma (LUAD) formation initially and squamous transition at late stage. We identify club cells as the main cell-of-origin for squamous transition. Through recapitulating lineage transition in organoid system, we identify JAK-STAT signaling, activated by EML4-ALK phase separation, significantly promotes squamous transition. Integrative study with scRNA-seq and immunostaining identify a plastic cell subpopulation in ALK-rearranged human LUAD showing squamous biomarker expression. Moreover, those relapsed ALK-rearranged LUAD show notable upregulation of squamous biomarkers. Consistently, mouse squamous tumors or LUAD with squamous signature display certain resistance to ALK inhibitor, which can be overcome by combined JAK1/2 inhibitor treatment. This study uncovers strong plasticity of ALK-rearranged tumors in orchestrating phenotypic transition and drug resistance and proposes a potentially effective therapeutic strategy.
Antibiotic-induced gut dysbiosis elicits gut-brain axis relevant multi-omic signatures and behavioral and neuroendocrine changes in a nonhuman primate model
Authors: Shivdeep S. Hayer, Mackenzie Conrin, Jeffrey A. French, Andrew K. Benson, Sophie Alvarez, Kathryn Cooper, Anne Fischer, Zahraa Wajih Alsafwani, William Gasper, Mallory J. Suhr Van Haute, Haley R. Hassenstab, Shayda Azadmanesh, Missy Briardy, Skyler Gerbers, Aliyah Jabenis, Jennifer L. Thompson, Jonathan B. Clayton
Journal: Gut Microbes (2024)

Emerging evidence indicates that antibiotic-induced dysbiosis can play an etiological role in the pathogenesis of neuropsychiatric disorders. However, most of this evidence comes from rodent models. The objective of this study was to evaluate if antibiotic-induced gut dysbiosis can elicit changes in gut metabolites and behavior indicative of gut-brain axis disruption in common marmosets (Callithrix jacchus) – a nonhuman primate model often used to study sociability and stress. We were able to successfully induce dysbiosis in marmosets using a custom antibiotic cocktail (vancomycin, enrofloxacin and neomycin) administered orally for 28 days. This gut dysbiosis altered gut metabolite profiles, behavior, and stress reactivity. Increase in gut Fusobacterium spp. post-antibiotic administration was a novel dysbiotic response and has not been observed in any rodent or human studies to date. There were significant changes in concentrations of several gut metabolites which are either neurotransmitters (e.g., GABA and serotonin) or have been found to be moderators of gut-brain axis communication in rodent models (e.g., short-chain fatty acids and bile acids). There was an increase in affiliative behavior and sociability in antibiotic-administered marmosets, which might be a coping mechanism in response to gut dysbiosis-induced stress. Increase in urinary cortisol levels after multiple stressors provides more definitive proof that this model of dysbiosis may cause disrupted communication between gut and brain in common marmosets. This study is a first attempt to establish common marmosets as a novel model to study the impact of severe gut dysbiosis on gut-brain axis cross-talk and behavior.
The Role of 5-Hydroxymethylcytosine as a Potential Epigenetic Biomarker in a Large Series of Thyroid Neoplasms
Authors: Sule Canberk, João Gonçalves, Elisabete Rios, Antónia A. Povoa, Ebru Tastekin, Manuel Sobrinho-Simões, Aysun Uguz, Ozlem Aydin, Umit Ince, Paula Soares, Valdemar Máximo
Journal: Endocrine Pathology (2024)

Abstract Cytosine modifications at the 5-carbon position play a critical role in gene expression regulation and have been implicated in cancer development. 5-Hydroxymethylcytosine (5hmC), arising from 5-methylcytosine (5-mC) oxidation, has shown promise as a potential malignancy marker due to its depletion in various human cancers. However, its significance in thyroid tumors remains underexplored, primarily due to limited data. In our study, we evaluated 5hmC expression levels by immunohistochemistry in a cohort of 318 thyroid tumors. Our analysis revealed significant correlations between 5hmC staining extension scores and nodule size, vascular invasion, and oncocytic morphology. Nuclear 5hmC staining intensity demonstrated associations with focality, capsule status, extrathyroidal extension, vascular invasion, and oncocytic morphology. Follicular/oncocytic adenomas exhibited higher 5hmC expression than uncertain malignant potential (UMP) or noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), as well as malignant neoplasms, including papillary thyroid carcinomas (PTCs), oncocytic carcinomas (OCAs), follicular thyroid carcinomas (FTCs), and invasive encapsulated follicular variants of PTC (IEFV-PTC). TERT promoter mutation cases showed notably lower values for the 5hmC expression, while RAS ( H , N , or K ) mutations, particularly HRAS mutations, were associated with higher 5hmC expression. Additionally, we identified, for the first time, a significant link between 5hmC expression and oncocytic morphology. However, despite the merits of these discoveries, we acknowledge that 5hmC currently cannot segregate minimally invasive from widely invasive tumors, although 5hmC levels were lower in wi-FPTCs. Further research is needed to explore the potential clinical implications of 5hmC in thyroid tumors.
Prospective observational study on biomarkers of response in pancreatic ductal adenocarcinoma
Authors: Lingxi Jiang, Jiejie Qin, Yuting Dai, Shulin Zhao, Qian Zhan, Peng Cui, Lingjie Ren, Xuelong Wang, Ruihong Zhang, Chenxu Gao, Yanting Zhou, Shangli Cai, Guoqiang Wang, Wenchuan Xie, Xiaomei Tang, Minmin Shi, Fangfang Ma, Jia Liu, Ting Wang, Chaofu Wang, Magali Svrcek, Armelle Bardier-Dupas, Jean Francois Emile, Louis de Mestier, Jean-Baptiste Bachet, Remy Nicolle, Jerome Cros, Pierre Laurent-Puig, Miaoyan Wei, Bin Song, Wei Jing, Shiwei Guo, Kailian Zheng, Hui Jiang, Huan Wang, Xiaxing Deng, Hao Chen, Qiang Tian, Shengyue Wang, Si Shi, Gang Jin, Tong Yin, Hai Fang, Saijuan Chen, Baiyong Shen
Journal: Nature Medicine (2024)
Loss of Pip4k2c confers liver-metastatic organotropism through insulin-dependent PI3K-AKT pathway activation
Authors: Meri Rogava, Tyler J. Aprati, Wei-Yu Chi, Johannes C. Melms, Clemens Hug, Stephanie H. Davis, Ethan M. Earlie, Charlie Chung, Sachin K. Deshmukh, Sharon Wu, George Sledge, Stephen Tang, Patricia Ho, Amit Dipak Amin, Lindsay Caprio, Carino Gurjao, Somnath Tagore, Bryan Ngo, Michael J. Lee, Giorgia Zanetti, Yiping Wang, Sean Chen, William Ge, Luiza Martins Nascentes Melo, Gabriele Allies, Jonas Rösler, Goeffrey T. Gibney, Oliver J. Schmitz, Megan Sykes, Rémi J. Creusot, Thomas Tüting, Dirk Schadendorf, Martin Röcken, Thomas K. Eigentler, Andrei Molotkov, Akiva Mintz, Samuel F. Bakhoum, Semir Beyaz, Lewis C. Cantley, Peter K. Sorger, Sven W. Meckelmann, Alpaslan Tasdogan, David Liu, Ashley M. Laughney, Benjamin Izar
Journal: Nature Cancer (2024)
Employing toehold-mediated DNA strand displacement reactions for biomedical applications
Authors: Keziah Jacob Souza, Deepak K. Agrawal
Journal: Med-X (2024)

Abstract Dynamic DNA nanotechnology belongs to a larger umbrella of DNA nanotechnology that primarily uses DNA as a nanoscopic material to build mobile structures and cascaded reaction networks powered by DNA oligonucleotides. A widely used mechanism to construct a dynamic DNA system is toehold-mediated strand displacement reactions (TMSDRs). TMSDRs are easy to engineer because of the known base-pairing rules that follow the Watson–Crick model of DNA, sequence-dependent binding rates, and energies of DNAs, whose secondary structure is predictable. Due to these attributes, TMSDRs have been used to develop enzyme-free isothermal reaction networks with remarkable applications in diagnostics, therapeutics and DNA computing. In this review, we briefly introduce the working principle of TMSDRs, in silico design considerations, and diverse input and output signals that can be processed through TMSDRs. We then summarize recent applications where TMSDRs are successfully employed in detecting clinically relevant targets such as single nucleotide polymorphisms and variants, microRNAs and whole cells and to develop programmable drug delivery vehicles and regulation therapies including transcriptional and protein regulations. We also discuss TMSDRs driven biomedical applications of DNA hydrogels and DNA computing. Finally, we discuss the challenges in each of these applications and the prospects of TMSDRs in biomedical engineering.
Trajectories of Sleep Over Midlife and Incident Cardiovascular Disease Events in the Study of Women’s Health Across the Nation
Authors: Rebecca C. Thurston, Yuefang Chang, Christopher E. Kline, Leslie M. Swanson, Samar R. El Khoudary, Elizabeth A. Jackson, Carol A. Derby
Journal: Circulation (2024)

Up to 50% of women report sleep problems in midlife, and cardiovascular disease (CVD) is the leading cause of death in women. How chronic poor sleep exposure over decades of midlife is related to CVD risk in women is poorly understood. We tested whether trajectories of insomnia symptoms or sleep duration over midlife were related to subsequent CVD events among SWAN (Study of Women's Health Across the Nation) participants, whose sleep was assessed up to 16 times over 22 years.
Anti-GM-CSF autoantibodies predict outcome of cryptococcal meningitis in patients not infected with HIV: a cohort study
Authors: Ying-Kui Jiang, Ling-Hong Zhou, Jia-Hui Cheng, Jun-Hao Zhu, Yu Luo, Li Li, Min Zhu, Rong-Sheng Zhu, Wen-Jia Qiu, Hua-Zhen Zhao, Xuan Wang, Jun-Tian Huang, Oliver A. Cornely, Wen-Hong Zhang, Li-Ping Zhu
Journal: Clinical Microbiology and Infection (2024)

ObjectivesTo explore the seroprevalence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies in non-HIV cryptococcal meningitis (CM) and assess its predictive value for survival.MethodsThis is a retrospective study of 12 years of non-HIV CM. We detected serum anti-GM-CSF autoantibodies, evaluated the clinical features and outcomes, together with the exploration of prognostic factors for 2-week and 1-year survival.ResultsA total of 584 non-HIV CM cases were included. 301 of 584 patients (51.5%) were phenotypically healthy. 264 Cryptococcus isolates were obtained from cerebrospinal fluid (CSF) culture, of which 251 were identified as C. neoformans species complex and 13 as C. gattii species complex. 37 of 455 patients (8.1%) tested positive for serum anti-GM-CSF autoantibodies. Patients with anti-GM-CSF autoantibodies were more susceptible to C. gattii species complex infection (66.7% vs. 6.3%, p < 0.001) and more likely to develop pulmonary mass lesions with a diameter > 3 centimetres (42.9% vs. 6.5%, p 0.001). Of 584 patients 16 (2.7%) died within 2 weeks, 77 of 563 patients (13.7%) died at 1 year, and 93 of 486 patients (19.1%) lived with disabilities at 1 year. Univariant Cox regression analysis found that anti-GM-CSF autoantibodies were associated with lower 1-year survival (HR 2.66, 95% CI 1.34–5.27, p 0.005). Multivariable Cox proportional hazards modelling revealed that CSF cryptococcal antigen titres ≥ 1:1280 were associated with both, reduced 2-week and 1-year survival rates (HR 5.44, 95% CI 1.23–24.10, p 0.026 and HR 5.09, 95% CI 1.95–13.26, p 0.001).ConclusionsPresence of serum anti-GM-CSF autoantibodies is predictive of poor outcomes, regardless of host immune status and the causative Cryptococcus species complex.
Ficonalkib (SY-3505) in Advanced ALK-Positive NSCLC: A Multicenter, Open-Label, Single-Arm, Phase 1/2 Study
Authors: Yuankai Shi, Xingsheng Hu, Xingya Li, Caifeng Gong, Ke Wang, Yongsheng Li, Shucai Zhang, Yongzhong Luo, Pingli Wang, Liyan Jiang, Xiangjiao Meng, Xiaorong Dong, Huijuan Wang, Runxiang Yang, Qi Mei, Baogang Liu, Limin Yang, Yinghui Sun
Journal: Journal of Thoracic Oncology (2024)
LAT1-dependent placental methionine uptake is a key player in fetal programming of metabolic disease
Authors: Mariana Schroeder, Barbara Fuenzalida, Nan Yi, Saira Shahnawaz, Jürg Gertsch, Daniele Pellegata, Edgar Ontsouka, Andrea Leiva, Jaime Gutiérrez, Martin Müller, Marcela A. Brocco, Christiane Albrecht
Journal: Metabolism (2024)

The Developmental Origins of Health and Disease hypothesis sustains that exposure to different stressors during prenatal development prepares the offspring for the challenges to be encountered after birth. We studied the gestational period as a particularly vulnerable window where different stressors can have strong implications for fetal programming of the offspring's life-long metabolic status via alterations of specific placentally expressed nutrient transporters. To study this mechanism, we used a murine prenatal stress model, human preeclampsia, early miscarriage, and healthy placental tissue samples, in addition to in vitro models of placental cells. In stressed mice, placental overexpression of L-type amino acid transporter 1 (Lat1) and subsequent global placental DNA hypermethylation was accompanied by fetal and adult hypothalamic dysregulation in global DNA methylation and gene expression as well as long-term metabolic abnormalities exclusively in female offspring. In human preeclampsia, early miscarriage, and under hypoxic conditions, placental LAT1 was significantly upregulated, leading to increased methionine uptake and global DNA hypermethylation. Remarkably, subgroups of healthy term placentas with high expression of stress-related genes presented increased levels of placental LAT1 mRNA and protein, DNA and RNA hypermethylation, increased methionine uptake capacity, one-carbon metabolic pathway disruption, higher methionine concentration in the placenta and transport to the fetus specifically in females. Since LAT1 mediates the intracellular accumulation of methionine, global DNA methylation, and one-carbon metabolism in the placenta, our findings hint at a major sex-specific global response to a variety of prenatal stressors affecting placental function, epigenetic programming, and life-long metabolic disease and provide a much-needed insight into early-life factors predisposing females/women to metabolic disorders.
Prior exposure to fumaric acid esters does not impact on subsequent treatment response to guselkumab
Authors: Niamh Kearney, Brian Kirby
Journal: British Journal of Dermatology (2024)

Journal Article Corrected proof Prior exposure to fumaric acid esters does not impact on subsequent treatment response to guselkumab Get access Niamh Kearney, Niamh Kearney Writing - original draft, Writing - review & editing Department of Dermatology, Ulster Hospital Dundonald, South Eastern Health and Social Care Trust, UK Correspondence: Niamh Kearney. Email: nkearne@tcd.ie https://orcid.org/0000-0002-6469-3462 Search for other works by this author on: Oxford Academic Google Scholar Brian Kirby Brian Kirby Writing - review & editing Department of Dermatology, St. Vincent's University Hospital Dublin, IrelandCharles Institute of Dermatology, University College Dublin, Ireland https://orcid.org/0000-0001-7596-892X Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae036, https://doi.org/10.1093/bjd/ljae036 Published: 29 January 2024 Article history Received: 22 January 2024 Accepted: 23 January 2024 Published: 29 January 2024 Corrected and typeset: 04 March 2024
Significant survival disparity in Black patients with cutaneous lymphoma: a retrospective cohort study
Authors: Nicholas A Trum, Lu Chen, Jasmine Zain, Steven T Rosen, Christiane Querfeld
Journal: British Journal of Dermatology (2024)

The prognosis for Black patients with classical cutaneous T-cell lymphoma (CTCL) [mycosis fungoides (MF) and Sézary syndrome (SS)] is known to be worse than that of other ethnicities, but there is a paucity of data on which demographic factors or disease characteristics may contribute to this disparity. In our retrospective cohort study of 229 patients, Black patients experienced poorer overall survival adjusted for confounding variables including demographics and key disease characteristics (P = 0.01), and suffered a significantly higher rate of large-cell transformation when compared with White patients (P = 0.012). Our study suggests that Black patients with MF/SS experience poorer overall survival that cannot be explained by sex, age or CTCL disease characteristics.
Expert consensus guidelines: Intravenous iron uses, formulations, administration, and management of reactions
Authors: Layla Van Doren, Marlene Steinheiser, Kristen Boykin, Kristine J. Taylor, Monica Menendez, Michael Auerbach
Journal: American Journal of Hematology (2024)

Intravenous iron has become an essential component for the treatment of iron deficiency and iron deficiency anemia. Individuals administering Intravenous iron should have knowledge in intravenous iron administration, including a pre-infusion assessment to evaluate infusion reaction risks, pre- and post-infusion monitoring, identification of and management of infusion reactions, accurate documentation of these reactions, laboratory monitoring and recognition and management of treatment-emergent hypophosphatemia. This comprehensive consensus provides step-by-step guidance and tools for practitioners to promote safe delivery of intravenous iron, recognition, and management of infusion reactions and treatment-emergent hypophosphatemia.
Identifying candidates for early intervention in hidradenitis suppurativa
Authors: Carlo Alberto Maronese, Angelo V Marzano
Journal: British Journal of Dermatology (2024)

Journal Article Corrected proof Identifying candidates for early intervention in hidradenitis suppurativa Get access Carlo Alberto Maronese, Carlo Alberto Maronese Conceptualization, Writing - original draft, Writing - review & editing Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy https://orcid.org/0000-0002-9449-849X Search for other works by this author on: Oxford Academic Google Scholar Angelo V Marzano Angelo V Marzano Conceptualization, Supervision, Writing - original draft, Writing - review & editing Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy Correspondence: Angelo V. Marzano. Email: angelo.marzano@unimi.it https://orcid.org/0000-0002-8160-4169 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae034, https://doi.org/10.1093/bjd/ljae034 Published: 29 January 2024 Article history Received: 17 January 2024 Accepted: 18 January 2024 Published: 29 January 2024 Corrected and typeset: 20 February 2024
Improving cancer stem cells killing in malignant melanoma
Authors: Daniele Bergamaschi
Journal: British Journal of Dermatology (2024)

Journal Article Corrected proof Improving cancer stem cells killing in malignant melanoma Get access Daniele Bergamaschi Daniele Bergamaschi Conceptualization, Writing - original draft, Writing - review & editing Centre for Cell Biology and Cutaneous Research, Blizard Institute, Faculty of Medicine & Dentistry, Queen Mary University of London, London, UK Correspondence: Daniele Bergamaschi. Email: d.bergamaschi@qmul.ac.uk https://orcid.org/0000-0002-3955-1091 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae035, https://doi.org/10.1093/bjd/ljae035 Published: 29 January 2024 Article history Received: 16 January 2024 Accepted: 18 January 2024 Published: 29 January 2024 Corrected and typeset: 04 March 2024
The Exposome: What Is It, Really, and Does it Help to Understand Environmental Influences on Human Health and Rheumatic Disease?
Authors: Christine G. Parks, Karen H. Costenbader
Journal: Arthritis & Rheumatology (2024)

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