tbuckley/cabot-search huggingface dataset:
Deubiquitinase JOSD2 alleviates colitis by inhibiting inflammation via deubiquitination of IMPDH2 in macrophages
Authors: Xin Liu, Yi Fang, Mincong Huang, Shiliang Tu, Boan Zheng, Hang Yuan, Peng Yu, Mengyao Lan, Wu Luo, Yongqiang Zhou, Guorong Chen, Zhe Shen, Yi Wang, Guang Liang
Journal: Acta Pharmaceutica Sinica B (2024)

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.
Free fatty acid receptor-4 regulates T-cell-mediated allogeneic reaction through activating an aryl hydrocarbon receptor pathway
Authors: Maxwell Duah, Fei Zheng, Jingyi Shen, Yan Xu, Shuo Cao, Zhiling Yan, Qiu Lan, Ying Wang, Kailin Xu, Bin Pan
Journal: Acta Pharmaceutica Sinica B (2024)

Targeting T-cell is a strategy to control allogeneic response disorders, such as acute graft-versus-host disease (GVHD) which is an important cause of therapy-failure after allogeneic hematopoietic cell transplants. Free fatty acid receptor-4 (FFAR4) is a regulator of obesity but its role in T-cell and allogeneic reactions is unknown. Here, we found knockout of Ffar4 in donor T-cells in a mouse allograft model increased acute GVHD whereas the natural FFAR4 ligands and the synthetic FFAR4 agonists decreased it. FFAR4 agonist-mediated anti-acute GVHD effects depended on FFAR4-expression in donor T-cells. The FFAR4 agonist CpdA suppressed donor T-cell-mediated alloreaction by activating an aryl hydrocarbon receptor (AhR) pathway. CpdA recruited β-Arrestin2 to FFAR4 which facilitated nuclear translocation of AhR and upregulation of IL-22. The CpdA-mediated anti-acute GVHD effect was absent in mice receiving Ahr-knockout or Il22-knockout T-cells. Recipient-expressing Ffar4 was also important for the anti-acute GVHD effect of CpdA which inhibited activation of antigen presenting cells. Importantly, CpdA decreased acute GVHD in obese mice, an effect also depended on Ffar4-expression in donor T-cells and recipients. Our study shows the immunoregulatory effect of FFAR4 in T-cell, and targeting FFAR4 might be a relative option for controlling allogeneic reactions in obese patients.
Decoding the Clinical and Molecular Signatures of EGFR Common, Compound, and Uncommon Mutations in Non-Small Cell Lung Cancer.
Authors: Daniele Tavernari, Maxime Borgeaud, Ximeng Liu, Kaushal Parikh, Xiuning Le, Giovanni Ciriello, Alfredo Addeo
Journal: Journal of Thoracic Oncology (2024)
The landscape of primary mismatch repair deficient gliomas in children, adolescents, and young adults: a multi-cohort study
Authors: Logine Negm, Jiil Chung, Liana Nobre, Julie Bennett, Nicholas R Fernandez, Nuno Miguel Nunes, Zhihui Amy Liu, Martin Komosa, Melyssa Aronson, Cindy Zhang, Lucie Stengs, Vanessa Bianchi, Melissa Edwards, Sheradan Doherty, Ayse Bahar Ercan, Maria F Cardenas, Michael Macias, Matthew R Lueder, Michelle Ku, Monique Johnson, Yuan Chang, Jose Rafael Dimayacyac, Adam A Kraya, Yiran Guo, Stav Naky, Julia Keith, Andrew F Gao, David G Munoz, Lananh Nguyen, Derek S Tsang, Mary Jane Lim-Fat, Sunit Das, Adam Shlien, Vijay Ramaswamy, Annie Huang, David Malkin, Anita Villani, Birgit Ertl-Wagner, Adrian Levine, Giles W Robinson, Brad H Pollock, Logan G Spector, Shizuko Sei, Peter B Dirks, Gad Getz, Kim E Nichols, Adam C Resnick, David A Wheeler, Anirban Das, Yosef E Maruvka, Cynthia Hawkins, Uri Tabori
Journal: The Lancet Oncology (2024)
The costs and benefits of a dynamic host microbiome
Authors: Mark A F Gillingham, Hanna Prüter, B Karina Montero, Bart Kempenaers
Journal: Trends in Ecology & Evolution (2024)

All species host a rich community of microbes. This microbiome is dynamic, and displays seasonal, daily, and even hourly changes, but also needs to be resilient to fulfill important roles for the host. In evolutionary ecology, the focus of microbiome dynamism has been on how it can facilitate host adaptation to novel environments. However, an hitherto largely overlooked issue is that the host needs to keep its microbiome in check, which is costly and leads to trade-offs with investing in other fitness-related traits. Investigating these trade-offs in natural vertebrate systems by collecting longitudinal data will lead to deeper insight into the evolutionary mechanisms that shape host-microbiome interactions.
Mitochondrial-derived microproteins: from discovery to function
Authors: Kelvin Yen, Brendan Miller, Hiroshi Kumagai, Ana Silverstein, Pinchas Cohen
Journal: Trends in Genetics (2024)

Given the uniqueness of the mitochondria, and the fact that they have their own genome, mitochondrial-derived microproteins (MDPs) are similar to, but different from, nuclear-encoded microproteins. The discovery of an increasing number of microproteins from this organelle and the importance of mitochondria to cellular and organismal health make it a priority to study this novel class of proteins in search of possible therapeutic targets and cures. In this review, we discuss the history of MDP discovery, describe the function of each MDP, and conclude with future goals and techniques to help discover more MDPs.
The changing global landscape of national cancer control plans
Authors: Yannick Romero, Zuzanna Tittenbrun, Dario Trapani, Leslie Given, Karin Hohman, Mishka Kohli Cira, Kalina Duncan, Andre Ilbawi, Lisa M Stevens, Abeer Al-Battashi, Khalil Albiroty, Maha Alghafry, Sana Al-Sukhun, Nicoleta Antone, Shen Aomei, Hyo Sook Bae, Karen Bedirian, Justyna Bochenek-Cibor, Anna Cabanes, Tanja Cufer, Urania Dafni, Anita Das, Csaba Degi, Le Cong Dinh, Pham Anh Duc, Catherine Duggan, Naillid Felipe, Jamila Fonseca, Lewis Foxhall, Allison Frank, Julia Gage, Elise Garton, Ophira Ginsburg, Freddy Gnangnon, Mary Gospodarowicz, Anna Grigoryan, Nazik Hammad, Leshia Hansen, Laura Haskins, Ernie Hawk, Fatou Jallow, Dalana Johnson, Sonali Johnson, Arsen Juric, Lisa Kennedy Sheldon, Wui Jin Koh, Somesh Kumar, Catherine Lam, Søren Gray Worsøe Laursen, Seohyun Lee, Jing Li, John D. Murphy, Marianna Nobile, Andrew Oar, Dennis Orkoulas-Razis, Neal Palafox, Douglas Puricelli Perin, Evangelia Razis, Andrea Reed, Felipe Roitberg, Louisa Salemi, Melanie Samson, Amalya Sargsyan, Yelena Shnayder, Sarah Slater, Winnie So, Igor Stojkovski, Carolyn Taylor, Julie Torode, Adrian Udrea, Vahur Valvere, Nguyen Thi Hong Van, Igor Veljkovikj, Horia Vulpe, Ena Wanliss, Katy Winckworth-Prejsnar, Mei Ling Yap, Abdulhafiz Zakieh
Journal: The Lancet Oncology (2024)
Effectiveness of ceftazidime–avibactam versus ceftolozane–tazobactam for multidrug-resistant Pseudomonas aeruginosa infections in the USA (CACTUS): a multicentre, retrospective, observational study
Authors: Ryan K Shields, Lilian M Abbo, Renee Ackley, Samuel L Aitken, Benjamin Albrecht, Ahmed Babiker, Rachel Burgoon, Renzo Cifuentes, Kimberly C Claeys, Brooke N Curry, Kathryn E DeSear, Jason C Gallagher, Esther Y Golnabi, Alan E Gross, Jonathan Hand, Emily L Heil, Krutika M Hornback, Keith S Kaye, Trieu-Vi Khuu, Megan E Klatt, Ellen G Kline, Ryan C Kubat, Wesley D Kufel, Jae Hyoung Lee, Alexander J Lepak, Ahmi Lim, Justin M Ludwig, Conan Macdougall, Anjali Majumdar, Amy J Mathers, Erin K McCreary, William R Miller, Marguerite L Monogue, W Justin Moore, Shannon Olson, Jessica Oxer, Jeffrey C Pearson, Christine Pham, Paulette Pinargote, Christopher Polk, Michael J Satlin, Sarah W Satola, Sunish Shah, Pranita D Tamma, Truc T Tran, David van Duin, Mollie VanNatta, Ana Vega, Veena Venugopalan, Michael P Veve, Walaiporn Wangchinda, Lucy S Witt, Janet Y Wu, Jason M Pogue
Journal: The Lancet Infectious Diseases (2024)
Hybrid closed-loop insulin therapy and risk of severe hypoglycaemia and diabetic ketoacidosis in young people (aged 2–20 years) with type 1 diabetes: a population-based study
Authors: Beate Karges, Joachim Rosenbauer, Anna Stahl-Pehe, Monika Flury, Torben Biester, Martin Tauschmann, Eggert Lilienthal, Johannes Hamann, Angela Galler, Reinhard W Holl
Journal: The Lancet Diabetes & Endocrinology (2024)
Reply to Cheng and Wei: Limitations in the Study of Vitamin D Supplementation and Severe Asthma Exacerbations
Authors: Franziska J. Rosser, Yueh-Ying Han, Juan C. Celedón
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Reply to Cheng and Wei: Limitations in the Study of Vitamin D Supplementation and Severe Asthma Exacerbations." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Editorial Position of the American Thoracic Society Journal Family on the Evolving Role of Artificial Intelligence in Scientific Research and Review
Authors: Nitin Seam, Sanjay H Chotirmall, Fernando J. Martinez, Andrew J. Halayko, Michael O Harhay, Stephanie D. Davis, Paul T Schumacker, Robert M Tighe, Kristin M. Burkart, Colin Cooke
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Editorial Position of the American Thoracic Society Journal Family on the Evolving Role of Artificial Intelligence in Scientific Research and Review." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Prevalence and Clinical Correlates of Radiologically Detected Coronary Artery Disease in COPD: A Cross-Sectional Observational Study
Authors: Mairi A. MacLeod, Kristopher D Knott, James P. Allinson, Lydia J. Finney, Dexter J. Wiseman, Andrew I Ritchie, Aaron Braddy-Green, Sam Barlett-Pestell, Ralph Lopez, Logan Sun, Philippa Webb, Paras Dalal, Michael Rubens, Simon Davies, Dorian O Haskard, Anand Devaraj, Gavin C Donaldson, Ramzi Y Khamis, Edward D Nicol, Jadwiga A. Wedzicha
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Unrecognised coronary artery disease (CAD) may contribute to adverse outcomes in chronic obstructive pulmonary disease (COPD). Improved identification of at-risk groups could inform better preventative care. We aimed to evaluate the burden and relationships of radiologically detectable CAD in COPD, establish frequency of occult disease, and examine potential cardiovascular screening methods. Using CT coronary angiogram (CTCA), we prospectively evaluated CAD in 50 patients with COPD compared to age, sex-matched controls. In those with COPD, the relationship of CAD to cardiac symptoms (chest pain, dyspnoea), functional capacity (six-minute walk), exacerbations and inflammation was assessed. The performance of screening tests (cardiovascular risk scores, biomarkers and CT thorax-derived coronary artery calcium score (CACS-Tx)) were evaluated using receiver operator curves. CAD was present in 88% of patients with COPD (42% had obstructive (≥50% stenosis of any vessel) and 28% severe obstructive (≥70%) disease). Rates of obstructive (OR 3·1 (95%CI 1·1-8·9) P=0·037) and severe obstructive CAD (OR 10·1(95%CI 1·9-52·7) P=0·006) were higher in COPD than controls. In the COPD group, those with CAD had greater functional impairments but not dyspnoea scores, and 75% reported no chest pain or prior IHD. CAD was more extensive in those with increased systemic inflammation (fibrinogen, c-reactive protein, leucocyte, and neutrophil count), bronchial wall thickening, and sputum bacterial growth but bore no relation to exacerbation frequency. CACS-Tx was an effective screening tool, with an area under the curve for CAD of 0·98 (95%CI 0·95-1·00) and obstructive CAD of 0·89 (95%CI 0·79-1·00). CTCA-detected CAD is common in patients with COPD, correlating poorly with symptoms and risk scores. Radiological screening, using CT thorax, might improve detection and outcomes in this patient group.
Hyaluronic acid conjugates with controlled oleic acid substitution as new nanomaterials for improving ocular co-delivery of cyclosporine A and oleic acid
Authors: Hai V Ngo, Hy D Nguyen, Beom-Jin Lee
Journal: Asian Journal of Pharmaceutical Sciences (2024)

A structural conjugate (HOC) of polysaccharide, hyaluronic acid (HA) with different ratios of oleic acid (OA) via cystamine (CYS) linker as a new ocular biomaterial was developed. The HOCs with controlled degrees of substitution of OA (4.6 %, 8.3 % and 12.2 %) were synthesized to form self-assembled HA-CYS-OA nanoparticles (HONs, HON1, HON2, HON3). A poorly water-soluble cyclosporine A (CsA) to be used for the treatment of multifactorial dry eye disease (DED) was chosen as model drug. CsA-loaded HONs exhibited improved solution transparency via solubilizing capacity of HON, and increased in vitro drug permeation compared to Restasis®. The physicochemical properties of CsA-loaded HONs such as nano behaviors, solution transparency, drug release, drug permeation and ocular cytocompatibility were highly variable according to the ratios of OA substitution. Interestingly, this CsA-loaded HON1 as optimal ocular nanoformulation showed markedly augmented macrophage polarization into the M2 phenotype, downregulated the expression of proinflammatory cytokines levels in LPS-induced M1 macrophage, and effectively inhibited VEGF-induced endothelial cell proliferation and capillary-like tube formation by the synergistic effect of CsA and HON1 containing OA at the same time. Collectively, the current fatty acid conjugated to HA, named fattigation platform, providing the roles and physicochemical properties via structural features of HA could be a promising co-delivery strategy of drug and fatty acid for DED and other ophthalmic disease treatments.
Endosomal disruption by co-encapsulating gentamicin in lipid nanoparticles for efficient siRNA delivery and cancer therapy
Authors: Ning Yang, Qi Sun, Yaoqi Wang, Dong Mei, Xiaoling Wang, Jie Zhang, Danni Liu, Ran Huo, Yang Tian, Yan Su, Shuang Zhang, Chunying Cui
Journal: Asian Journal of Pharmaceutical Sciences (2024)
Beyond the Algorithm: Ethical Challenges in AI-Driven Skin Cancer Diagnosis
Authors: Magnus Lynch
Journal: British Journal of Dermatology (2024)

Journal Article Accepted manuscript Beyond the Algorithm: Ethical Challenges in AI-Driven Skin Cancer Diagnosis Get access Magnus Lynch Magnus Lynch St John's Institute of Dermatology, London, UK Email:[email protected] Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae490, https://doi.org/10.1093/bjd/ljae490 Published: 16 December 2024 Article history Received: 09 December 2024 Accepted: 15 December 2024 Published: 16 December 2024
Single-cell RNA sequencing of chronic idiopathic erythroderma defines disease-specific markers
Authors: Sumanth Chennareddy, Katharina Rindler, Shannon Meledathu, Malini P Naidu, Natalia Alkon, John R Ruggiero, Lisa Szmolyan, Wolfgang Weninger, Wolfgang M Bauer, Johannes Griss, Constanze Jonak, Patrick M Brunner
Journal: Journal of Allergy and Clinical Immunology (2024)

Chronic erythroderma is a potentially life-threatening condition that can be caused by a variety of diseases, but approximately 30% of cases remain idiopathic, often with insufficient treatment options.
Acute MeCP2 loss in adult mice reveals transcriptional and chromatin changes that precede neurological dysfunction and inform pathogenesis
Authors: Sameer S Bajikar, Jian Zhou, Ryan O'Hara, Harini P Tirumala, Mark A Durham, Alexander J Trostle, Michelle Dias, Yingyao Shao, Hu Chen, Wei Wang, Hari Krishna Yalamanchili, Ying-Wooi Wan, Laura A Banaszynski, Zhandong Liu, Huda Y Zoghbi
Journal: Neuron (2024)

Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene cause Rett syndrome, a severe childhood neurological disorder. MeCP2 is a well-established transcriptional repressor, yet upon its loss, hundreds of genes are dysregulated in both directions. To understand what drives such dysregulation, we deleted Mecp2 in adult mice, circumventing developmental contributions and secondary pathogenesis. We performed time series transcriptional, chromatin, and phenotypic analyses of the hippocampus to determine the immediate consequences of MeCP2 loss and the cascade of pathogenesis. We find that loss of MeCP2 causes immediate and bidirectional progressive dysregulation of the transcriptome. To understand what drives gene downregulation, we profiled genome-wide histone modifications and found that a decrease in histone H3 acetylation (ac) at downregulated genes is among the earliest molecular changes occurring well before any measurable deficiencies in electrophysiology and neurological function. These data reveal a molecular cascade that drives disease independent of any developmental contributions or secondary pathogenesis.
Evaluation of a point-of-care immunochromatographic assay for enteric fever in Dhaka, Bangladesh: a prospective diagnostic accuracy study
Authors: Sira J Munira, Nahidul Islam, Nowshin T Prithe, Anik Sarkar, Javan Esfandiari, Dhammika Gunasekera, Shuborno Islam, Tanjila Akter, Denise O Garrett, Samir K Saha, Jason R Andrews, Senjuti Saha, Richelle C Charles
Journal: The Lancet Microbe (2024)

There is a shortage of rapid, accurate, and low-cost assays for diagnosing enteric fever. The dual-path platform for typhoid (DPPT) assay had high accuracy in retrospective studies with banked plasma samples. We aimed to evaluate the diagnostic accuracy of the DPPT assay in a prospective study using fingerstick capillary blood.
Abnormalities in gut virome signatures linked with cognitive impairment in older adults
Authors: Adewale S. James, Noorul A. Adil, Dayna Goltz, Divyani Tangudu, Diptaraj S. Chaudhari, Rohit Shukla, Vivek Kumar, Ambuj Kumar, Michal M. Masternak, Peter Holland, Corinne Labyak, Adam Golden, Mariana Dangiolo, Andrea Y. Arikawa, Judyta Kociolek, Amoy Fraser, Cynthia Williams, Marc Agronin, Mariolga Aymat, Shalini Jain, Hariom Yadav
Journal: Gut Microbes (2024)

Multiple emerging lines of evidence indicate that the microbiome contributes to aging and cognitive health. However, the roles of distinct microbial components, such as viruses (virome) and their interactions with bacteria (bacteriome), as well as their metabolic pathways (metabolome) in relation to aging and cognitive function, remain poorly understood. Here, we present proof-of-concept results from a pilot study using datasets (n = 176) from the Microbiome in Aging Gut and Brain (MiaGB) consortium, demonstrating that the human virome signature significantly differs across the aging continuum (60s vs. 70s vs. 80+ years of age) in older adults. We observed that the predominant virome signature was enriched with bacteriophages, which change considerably with aging continuum. Analyses of interactions between phages and the host bacteriome suggest that lytic or temperate relationships change distinctly across the aging continuum, as well as cognitive impairment. Interestingly, the phage-bacteriome-metabolome interactions develop unique patterns that are distinctly linked to aging and cognitive dysfunction in older adults. The phage-bacteriome interactions affect bacterial metabolic pathways, potentially impacting older adults' health, including the risk of cognitive decline and dementia. Further comprehension of these studies could provide opportunities to target the microbiome by developing phage therapies to improve aging and brain health in older adults.
NCCN Guidelines® Insights: Survivorship, Version 2.2024
Authors: Tara Sanft, Andrew T. Day, Mindy Goldman, Shannon Ansbaugh, Saro Armenian, K. Scott Baker, Tarah J. Ballinger, Wendy Demark-Wahnefried, Nathan Paul Fairman, Josephine Feliciano, Tessa Faye Flores, Debra L. Friedman, Nicolette Gabel, Christine Hill-Kayser, Divya Koura, Kimberley Lee, Nita Lee, Allison L. McDonough, Michelle Melisko, Kathi Mooney, Halle C.F. Moore, Natalie Moryl, Heather Neuman, Linda Overholser, Chirayu Patel, Lindsay Peterson, William Pirl, Andrea Porpiglia, Lidia Schapira, Anna Schwartz, Sophia Smith, Amye Tevaarwerk, Diane Von Ah, Robert Wake, Eric Yang, Phyllis Zee, Nicole McMillian, Deborah Freedman-Cass
Journal: Journal of the National Comprehensive Cancer Network (2024)

The NCCN Guidelines for Survivorship include recommendations for screening, evaluation, and treatment of psychosocial and physical problems resulting from adult-onset cancer and its treatment. They also include recommendations to promote healthy behaviors and immunizations in survivors and provide a framework for care coordination. These NCCN Guidelines Insights summarize the panel’s current recommendations regarding sexual health and fertility.
ctDNA/MRD Testing for Colon Cancer: A Work in Progress or Ready for Prime-Time Standard of Care?
Authors: Bennett A. Caughey, Aparna R. Parikh
Journal: Journal of the National Comprehensive Cancer Network (2024)

In patients with surgically resectable colon cancer (CC), clinicopathologic characteristics translate into cancer staging and predict recurrence risk. Adjuvant chemotherapy reduces the risk of recurrence and is offered to high-risk patients. However, some patients are inevitably overtreated or undertreated; better risk stratification is necessary to improve outcomes after surgery. Circulating tumor DNA (ctDNA)–based minimum residual disease (MRD) assays sequence plasma cell-free DNA for tumor DNA to predict the presence of otherwise subclinical malignancy. Studies have demonstrated that detectable ctDNA after surgery for CC predicts a high rate of recurrence and improves prognostication. Recent clinical trials show promise for using ctDNA to guide therapy, in particular standard-risk stage II CC. Large, randomized studies evaluating ctDNA-guided adjuvant chemotherapy versus standard of care in stage III CC are ongoing. Current data are insufficient to recommend routine use of ctDNA to guide adjuvant chemotherapy in resectable stage III CC.