tbuckley/cabot-search huggingface dataset:
Targeting of Low‐Immunogenic Poly(ethylene glycol) Nanoparticles for Photothermal‐Enhanced Immunotherapy
Authors: Mengqi Li, Zhiliang Gao, Ning Wang, Kanaparedu P. C. Sekhar, Jingcheng Hao, Jiwei Cui
Journal: Advanced Healthcare Materials (2024)

Abstract The assembly of low‐immunogenic poly(ethylene glycol) nanoparticles (PEG NPs) for targeted delivery of therapeutics (i.e., mitoxantrone and imidazoquinoline) and improved photothermal‐immunotherapy is reported. The targeted PEG NPs incorporating targeting molecules of hyaluronic acid are engineered via the templating of metal–organic frameworks, which can circumvent accelerated blood clearance and exhibit prolonged circulation time as well as improved accumulation of therapeutics at tumor sites. The targeted delivery of mitoxantrone under laser radiation induces immunogenic cell death of tumor cells, which is combined with toll‐like receptor 7/8 agonists of imidazoquinoline to trigger immune responses of cytotoxic T lymphocytes for the eradication of tumor cells. Furthermore, the treatment can induce tumor‐specific immune responses that inhibit metastatic lung tumor growth. This reported targeted PEG NPs provide a rational design for cancer immunotherapy.
Capillary leak phenotype as a major cause of death in patients with POEMS syndrome
Authors: Kenzie Lee, Taxiarchis Kourelis, Marcella Tschautscher, Rahma Warsame, Francis Buadi, Morie Gertz, Eli Muchtar, David Dingli, Suzanne Hayman, Ronald Go, Lisa Hwa, Amie Fonder, Wilson Gonsalves, Miriam Hobbs, Robert Kyle, Prashant Kapoor, Nelson Leung, Moritz Binder, Joselle Cook, Yi Lin, Michelle Rogers, S. Vincent Rajkumar, Shaji Kumar, Angela Dispenzieri
Journal: Leukemia (2024)

Cause of death (COD) in POEMS (polyneuropathy, organomegaly, endocrinopathies, monoclonal protein and skin changes) syndrome is not well described. We investigated COD in patients with POEMS syndrome treated at Mayo Clinic between 2000 and 2022. Of the 89 deaths, 49 patients had known COD and were the subject of this study. Seventeen patients died of unrelated causes, while 32 patients (65%) died from causes related to POEMS syndrome including secondary malignancies like myelodysplastic syndrome and acute leukemia (n = 5) and complications from active therapy (n = 5). Notably, 19 patients died with a stereotypic syndrome we termed capillary leak phenotype (CLP), which was characterized by refractory ascites, effusions and/or anasarca that ultimately resulted in hypotension, renal failure and cardiopulmonary arrest. Alternate causes for these symptoms, such as cardiac and hepatic etiologies, were excluded. CLP as a COD was an earlier event with a median time from diagnosis to death of 2.5 years compared to 12.0 years for all other deceased patients (p = <0.0001). By definition, treatment of terminal CLP was unsuccessful with median survival of only 4 months after CLP onset. The driver of CLP is unknown, but recognition as an entity should allow for systematic study.
Radiation‐Resistant Bacteria <i>Deinococcus radiodurans</i>‐Derived Extracellular Vesicles as Potential Radioprotectors
Authors: Jeong Moo Han, Godfrey Mwiti, Seo‐Joon Yeom, Jaeyoon Lim, Woo Sik Kim, Sangyong Lim, Seung‐Taik Lim, Eui‐Baek Byun
Journal: Advanced Healthcare Materials (2024)

The increasing use of radiation presents a risk of radiation exposure, making the development of radioprotectors necessary. In the previous study, it is investigated that Deinococcus radiodurans (R1-EVs) exert the antioxidative properties. However, the radioprotective activity of R1-EVs remains unclear. In the present study, the protective effects of R1-EVs against total body irradiation (TBI)-induced acute radiation syndrome (ARS) are investigated. To assess R1-EVs' radioprotective efficacy, ARS is induced in mice with 8 Gy of TBI, and protection against hematopoietic (H)- and gastrointestinal (GI)-ARS is evaluated. The survival rate of irradiated mice group decreases substantially after irradiation. In contrast, pretreatment with R1-EVs increases the survival rates of the mice. The administration of R1-EVs provides effective protection against radiation-induced death of bone marrow cells and splenocytes by scavenging reactive oxygen species (ROS). Additionally, R1-EVs protect both intestinal stem and epithelial cells from radiation-induced apoptosis. R1-EVs stimulate the production of short-chain fatty acids in the gastrointestinal tract, suppress proinflammatory cytokines, and increase regulatory T cells in pretreated mice versus the irradiation-only group. Proteomic analysis shows that the R1-EV proteome is significantly enriched with proteins involved in oxidative stress response. These findings highlight R1-EVs as potent radioprotectors with applications against radiation damage and ROS-mediated diseases.
The mycobiome as integral part of the gut microbiome: crucial role of symbiotic fungi in health and disease
Authors: Hui Huang, Qiurong Wang, Ying Yang, Wei Zhong, Feng He, Jun Li
Journal: Gut Microbes (2024)

The gut mycobiome significantly affects host health and immunity. However, most studies have focused on symbiotic bacteria in the gut microbiome, whereas less attention has been given to symbiotic fungi. Although fungi constitute only 0.01%–0.1% of the gut microbiome, their larger size and unique immunoregulatory functions make them significant. Factors like diet, antimicrobials use, and age can disrupt the fungal community, leading to dysbiosis. Fungal-bacterial-host immune interactions are critical in maintaining gut homeostasis, with fungi playing a role in mediating immune responses such as Th17 cell activation. This review highlights methods for studying gut fungi, the composition and influencing factors of the gut mycobiome, and its potential in therapeutic interventions for intestinal and hepatic diseases. We aim to provide new insights into the underexplored role of gut fungi in human health.
Neonatal gut microbiota and risk of developing food sensitization and allergy
Authors: Ryohei Shibata, Yumiko Nakanishi, Wataru Suda, Taiji Nakano, Noriko Sato, Yosuke Inaba, Yohei Kawasaki, Masahira Hattori, Naoki Shimojo, Hiroshi Ohno
Journal: Journal of Allergy and Clinical Immunology (2024)

Food sensitization (FS) develops in early infancy and is a risk factor for subsequent food allergy (FA). Recent evidence suggests relationships of gut microbiota with FS and FA. However, little is known about the role of neonatal gut microbiota in the pathobiology of these manifestations.
Genomic and transmission dynamics of the 2024 Marburg Virus Outbreak in Rwanda
Authors: Yvan Butera, Leon Mutesa, Edyth Parker, Raissa Muvunyi, Esperance Umumararungu, Alisen Ayitewala, Jean Pierre Musabyimana, Alhaji Olono, Placide Sesonga, Olusola Ogunsanya, Emmanuel Kabalisa, Oluwatobi Adedokun, Nelson Gahima, Laetitia Irankunda, Chantal Mutezemariya, Richard Niyonkuru, Arlene Uwituze, Ithiel Uwizera, James Kagame, Arlette Umugwaneza, John Rwabuhihi, Fidele Umwanankabandi, Valens Mbonitegeka, Edouard Ntagwabira, Etienne Kayigi, Gerard Izuwayo, Herve Murenzi, Therese Mukankwiro, Nasson Tuyiringire, Jean Marie Vianney Uwimana, Agnes Gasengayire, Reuben Sindayiheba, Glory-Ugochi Onyeugo, Merawi Aragaw, Lenny Gitundu, Radjabu Bigirimana, Mosoka Fallah, Adaora Ejikeme, Senga Sembuche, Alice Kabanda, Jean Claude Mugisha, Emmanuel Edwar Siddig Francis, Pierre Gashema, Jerome Ndayisenga, Alexis Rugamba, Faustin Kanyabwisha, Gad Murenzi, Anise Happi, Jean Claude Semuto Ngabonziza, Misbah Gashegu, Ayman Ahmed, Noella Bigirimana, Edson Rwagasore, Muhammed Semakula, Jean Paul Rwabihama, Clarisse Musanabaganwa, Eric Seruyange, Menelas Nkeshimana, Theogene Twagirumugabe, David Turatsinze, Eric Remera, Noel Gahamanyi, Sofonias Kifle Tessema, Isabelle Mukagatare, Sabin Nsanzimana, Christian Happi, Claude Mambo Muvunyi
Journal: Nature Medicine (2024)
Cross‐Phenotype Genome‐Wide Association Study Supports Shared Genetic Susceptibility to Systemic Sclerosis and Primary Biliary Cholangitis
Authors: Yiming Luo, Atlas Khan, Lili Liu, Cue Hyunkyu Lee, Gabriel J Perreault, Sydney F Pomenti, Pravitt Gourh, Krzysztof Kiryluk, Elana J Bernstein
Journal: Arthritis & Rheumatology (2024)

Objective An increased risk of primary biliary cholangitis (PBC) has been reported in patients with systemic sclerosis (SSc). Our study aims to investigate the shared genetic susceptibility between the two disorders and to define candidate causal genes using cross‐phenotype GWAS meta‐analysis. Methods We performed cross‐phenotype GWAS meta‐analysis and Bayesian colocalization analysis for SSc and PBC. We performed both genome‐wide and locus‐based analysis, including tissue and pathway enrichment analyses, fine‐mapping, Bayesian colocalization analyses with expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) datasets, and phenome‐wide association studies (PheWAS). Finally, we used an integrative approach to prioritize candidate causal genes from the novel loci. Results We detected a strong genetic correlation between SSc and PBC (rg = 0.84, p = 1.7 x 10 ‐6 ). In the cross‐phenotype GWAS meta‐analysis, we identified 44 non‐HLA loci that reached genome‐wide significance (p &lt; 5 x 10 ‐8 ). Evidence of shared causal variants between SSc and PBC was found for nine loci, five of which were novel. Integrating multiple sources of evidence, we prioritized CD40 , ERAP1 , PLD4 , SPPL3, and CCDC113 as novel candidate causal genes. The CD40 risk locus colocalized with trans‐pQTLs of multiple plasma proteins involved in B cell function. Conclusion Our study supports a strong shared genetic susceptibility between SSc and PBC. Through cross‐phenotype analyses, we have prioritized several novel candidate causal genes and pathways for these disorders.
TIGIT and PD-L1 co-blockade promotes clonal expansion of multipotent, non-exhausted antitumor T cells by facilitating co-stimulation
Authors: Katherine Nutsch, Karl L. Banta, Thomas D. Wu, Charles W. Tran, Stephanie Mittman, Ellen Duong, Barzin Y. Nabet, Yan Qu, Katherine Williams, Sören Müller, Namrata S. Patil, Eugene Y. Chiang, Ira Mellman
Journal: Nature Cancer (2024)

Blockade of immune checkpoints PD-1 and TIGIT has demonstrated activity in mouse tumor models and human patients with cancer. Although these coinhibitory receptors can restrict signaling in CD8+ T cells by regulating their associated co-stimulatory receptors CD28 and CD226, the functional consequences of combining PD-1 and TIGIT blockade remain poorly characterized. In mouse tumor models, we show that combination blockade elicited CD226-driven clonal expansion of tumor antigen-specific CD8+ T cells. The expanded clones emerged from a population of stem-like cells in draining lymph nodes, entering the blood as a previously unidentified single-phenotype, multiclonal population. Upon reaching the tumor, these transiting cells expanded further and differentiated into effector or exhausted T cells, with combination blockade restricting entry into the exhaustion pathway by favoring co-stimulation. Thus, PD-1 and TIGIT inhibition helps shape the repertoire of tumor-reactive CD8+ T cells in draining lymph nodes and determines their immunological fate in the tumor to enhance therapeutic benefit. Analysis of clinical trial samples suggests a similar mechanism may also occur in patients with cancer. Mellman and colleagues present a multiomic single-cell analysis of the effects of combined anti-TIGIT and anti-PD-1 blockade on T cell populations trafficking from the draining lymph node to the blood and tumor.
Delivery of FBXO6 with highly branched poly(β-amino ester)s to modulate the inflammatory environment for the treatment of osteoarthritis
Authors: Yongxiang Shi, Shuying Shen, Dongdong Huang, Kamuran Yilamu, Zhengju Chen, Kefan Wang, Pengyu Chen, Nan Pan, Zhanping Jin, Lei Guo, Wenbin Xu, Xing Zhao
Journal: Journal of Controlled Release (2024)
Author Correction: Opportunities and challenges of single-cell and spatially resolved genomics methods for neuroscience discovery
Authors: Boyan Bonev, Gonçalo Castelo-Branco, Fei Chen, Simone Codeluppi, M. Ryan Corces, Jean Fan, Myriam Heiman, Kenneth Harris, Fumitaka Inoue, Manolis Kellis, Ariel Levine, Mo Lotfollahi, Chongyuan Luo, Kristen R. Maynard, Mor Nitzan, Vijay Ramani, Rahul Satijia, Lucas Schirmer, Yin Shen, Na Sun, Gilad S. Green, Fabian Theis, Xiao Wang, Joshua D. Welch, Ozgun Gokce, Genevieve Konopka, Shane Liddelow, Evan Macosko, Omer Ali Bayraktar, Naomi Habib, Tomasz J. Nowakowski
Journal: Nature Neuroscience (2024)
Therapeutic potential of <i>Parabacteroides distasonis</i> in gastrointestinal and hepatic disease
Authors: Jinyi Duan, Qinmei Li, Yan Cheng, Weifeng Zhu, Hongning Liu, Fei Li
Journal: MedComm (2024)

Abstract Increasing evidences indicate that the gut microbiota is involved in the development and therapy of gastrointestinal and hepatic disease. Imbalance of gut microbiota occurs in the early stages of diseases, and maintaining the balance of the gut microbiota provides a new strategy for the treatment of diseases. It has been reported that Parabacteroides distasonis is associated with multiple diseases. As the next‐generation probiotics, several studies have demonstrated its positive regulation on the gastrointestinal and hepatic disease, including inflammatory bowel disease, colorectal cancer, hepatic fibrosis, and fatty liver. The function of P. distasonis and its metabolites mainly affect host immune system, intestinal barrier function, and metabolic networks. Manipulation of P. distasonis with natural components lead to the protective effect on enterohepatic disease. In this review, the metabolic pathways regulated by P. distasonis are summarized to illustrate its active metabolites and their impact on host metabolism, the role and action mechanism in gastrointestinal and hepatic disease are discussed. More importantly, the natural components can be used to manipulate P. distasonis as treatment strategies, and the challenges and perspectives of P. distasonis in clinical applications are discussed.
Meta‐analyses uncover the genetic architecture of Idiopathic Inflammatory Myopathies
Authors: Catherine Zhu, Younghun Han, Jinyoung Byun, Xiangjun Xiao, Simon Rothwell, Frederick W. Miller, Ingrid E. Lundberg, Peter K. Gregersen, Jiri Vencovsky, Vikram R. Shaw, Neil McHugh, Vidya Limaye, Albert Selva‐O'Callaghan, Michael G. Hanna, Pedro M. Machado, Lauren M. Pachman, Ann M. Reed, Lisa G. Rider, Øyvind Molberg, Olivier Benveniste, Timothy Radstake, Andrea Doria, Jan L. De Bleecker, Boel De Paepe, Britta Maurer, William E. Ollier, Leonid Padyukov, Lucy R. Wedderburn, Hector Chinoy, Janine A. Lamb, Christopher I. Amos
Journal: Arthritis & Rheumatology (2024)

Objective Idiopathic inflammatory myopathies (myositis, IIMs) are rare, systemic autoimmune disorders that lead to muscle inflammation, weakness, and extra‐muscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome‐wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome‐wide myositis studies and analyzed the largest myositis dataset to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes. Methods We performed association analyses on 14,903 individuals (3,206 cases and 11,697 controls) with genotypes and imputed data from the Trans‐Omics for Precision Medicine (TOPMed) reference panel. Fine‐mapping and expression quantitative trait locus co‐localization analyses in myositis‐relevant tissues indicated potential causal variants. Functional annotation and network analyses using the random walk with restart (RWR) algorithm explored underlying genetic networks and drug repurposing opportunities. Results Our analyses identified novel risk loci and susceptibility genes, such as FCRLA, NFKB1 , IRF4 , DCAKD , and ATXN2 in overall IIMs; NEMP2 in polymyositis; ACBC11 in dermatomyositis; and PSD3 in myositis with anti‐histidyl‐tRNA synthetase autoantibodies (anti‐Jo1). We also characterized effects of HLA region variants and the role of C4 . Colocalization analyses suggested putative causal variants in DCAKD in skin and muscle, HCP5 in lung, and IRF4 in EBV‐transformed lymphocytes, lung, and whole blood. RWR further prioritized additional candidate genes, including APP, CD74 , CIITA, NR1H4, and TXNIP , for future investigation. Conclusion Our study uncovers novel genetic regions contributing to IIMs, advancing our understanding of myositis pathogenesis and offering new insights for future research.
Drink less, be your best
Authors: Hendrien Kuipers
Journal: Hepatology (2024)

Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA Abbreviations: aHR, adjusted hazard ratio; MASLD, metabolic dysfunction–associated steatotic liver disease; MetALD, metabolic dysfunction- and alcohol-associated liver disease; NHANES III, Third National Health and Nutrition Examination Survey. Correspondence Hendrien Kuipers, Department of Surgery, Mayo Clinic, Rochester, MN, 55905 USA. Email: [email protected]
The clot and the complicated consult
Authors: Daniel D. Penrice, Sumera I. Ilyas
Journal: Hepatology (2024)

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA Abbreviation: EHPVO, extrahepatic portal vein obstruction. Correspondence Sumera I. Ilyas, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. Email: [email protected]
Unraveling bile acid dynamics in severe obesity
Authors: Francisco Idalsoaga, Juan Pablo Arab
Journal: Hepatology (2024)

1Department of Medicine, Division of Gastroenterology, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada 2Department of Gastroenterology, School of Medicine, Pontifical Catholic University of Chile, Santiago, Chile 3Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA Abbreviation: BA, bile acid. Correspondence Juan Pablo Arab, Stravitz-Sanyal Institute of Liver Disease and Metabolic Health, Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23284, USA. Email: [email protected]
Putting mean arterial pressure on the map as an AKI biomarker in cirrhosis
Authors: Robert M. Wilechansky
Journal: Hepatology (2024)

Department of Medicine, Division of Gastroenterology, Oregon Health & Science University, Portland, Oregon, USA Abbreviations: AKI, acute kidney injury; HRS, hepatorenal syndrome; MAP, mean arterial pressure; sCr, serum creatinine. Correspondence Robert M. Wilechansky, Division of Gastroenterology and Hepatology, Department of Medicine, Oregon Health & Science University, 3161 SW Pavilion Loop, Mail Code: L461, Portland, 97239 OR, USA Email: [email protected]
The Landscape of Circulating Tumor DNA (ctDNA) in Appendiceal Adenocarcinoma
Authors: Michael G. White, Mohammad A. Zeineddine, Eleanor A. Fallon, Fadl A. Zeineddine, Julia Dansby, Saikat Chowdhury, Nicholas Hornstein, Abdelrahman Yousef, Mahmoud Yousef, Neal Bhutiani, Yue Gu, Bryan Kee, Arvind Dasari, Michael J. Overman, Kanwal Raghav, Scott Kopetz, Abhineet Uppal, Melissa Taggart, Timothy Newhook, Keith Fournier, Beth Helmink, Leylah M. Drusbosky, John Paul Shen
Journal: Clinical Cancer Research (2024)

Appendiceal adenocarcinoma is a rare malignancy with distinct histopathologic subtypes and a natural history with metastasis primarily limited to the peritoneum. Little is known about the molecular pathogenesis of appendiceal adenocarcinoma relative to common tumors. We analyzed molecular data for patients within the Guardant Health database with appendix cancer (n = 718). We then identified patients with appendiceal adenocarcinoma at our institution (from October 2004-September 2022) for whom ctDNA mutation profiling (liquid biopsy) was performed (n = 168) and extracted clinicopathologic and outcomes data. Of these 168 patients, 57 also had tissue-based tumor mutational profiling, allowing for evaluation of concordance between liquid and tissue assays. The mutational landscape of ctDNA in appendiceal adenocarcinoma is distinct from tissue-based sequencing, with TP53 being the most frequently mutated (46%). Relative to other tumors, appendiceal adenocarcinoma seems less likely to shed ctDNA, with only 38% of patients with metastatic appendiceal adenocarcinoma having detectable ctDNA (OR = 0.26; P < 0.0001 relative to colorectal cancer). When detectable, the median variant allele frequency was significantly lower in appendiceal adenocarcinoma (0.4% vs. 1.3% for colorectal cancer; P ≤ 0.001). High-grade, signet ring, or colonic-type histology, metastatic spread beyond the peritoneum, and TP53 mutation were associated with detectable ctDNA. With respect to clinical translation, patients with detectable ctDNA had worse overall survival (HR = 2.32; P = 0.048). In the Guardant Health cohort, actionable mutations were found in 93 patients (13.0%). Although metastatic appendiceal adenocarcinoma tumors are less likely to shed tumor DNA into the blood relative to colorectal cancer, ctDNA profiling in appendiceal adenocarcinoma has clinical utility.
HMGA2 Expression Predicts Subtype, Survival, and Treatment Outcome in Pancreatic Ductal Adenocarcinoma
Authors: Naomi Yamamoto, Stephanie Dobersch, Ian Loveless, Annie N. Samraj, Gun Ho Jang, Miki Haraguchi, Liang-I Kang, Marianna B. Ruzinova, Kiran R. Vij, Jacqueline L. Mudd, Thomas Walsh, Rachael A. Safyan, E. Gabriela Chiorean, Sunil R. Hingorani, Nathan M. Bolton, Li Li, Ryan C. Fields, David G. DeNardo, Faiyaz Notta, Howard C. Crawford, Nina G. Steele, Sita Kugel
Journal: Clinical Cancer Research (2024)

Abstract Purpose: To establish HMGA2 as a marker of basal-like disease in pancreatic ductal adenocarcinoma (PDAC) and explore its use as a biomarker for prognosis and treatment resistance. Experimental Design: We identified high expression of HMGA2 in basal PDAC cells in a scRNAseq Atlas of 172 patient samples. We then analyzed HMGA2 expression, along with expression of the classical marker GATA6, in a cohort of 580 PDAC samples with multiplex immunohistochemistry. We further supplemented these data with an additional 30 diverse patient samples and multiple independent single-cell RNAseq databases. Results: We found that expression of HMGA2, but not previously described basal markers CK5 or CK17, predicted overall survival in our cohort. Combining HMGA2 and GATA6 status allowed for identification of two key study groups: an HMGA2+/GATA6- cohort with worse survival, low tumor-infiltrating CD8+ T cells, increased FAP+ fibroblasts, and poorer response to gemcitabine-based chemotherapies (n=94, median survival=11.2 months post-surgery); and an HMGA2-/GATA6+ cohort with improved survival, increased CD8+ T-cell infiltrate, decreased FAP+ fibroblasts, and improved survival with gemcitabine-based chemotherapy (n=198, median survival=21.7 months post-surgery). HMGA2 was also prognostic for overall survival in RNA sequencing from an independent cohort. Conclusions: IHC stratification of primary tumors by HMGA2 and GATA6 status in pancreatic cancer is associated with differential outcomes, survival following chemotherapy, and tumor microenvironments. As a nuclear marker for basal disease, HMGA2 complements GATA6 to identify disease subtypes in PDAC.