tbuckley/cabot-search huggingface dataset:
Genomic Signatures of Domestication in a Fungus Obligately Farmed by Leafcutter Ants
Authors: Caio A Leal-Dutra, Joel Vizueta, Tobias Baril, Pepijn W Kooij, Asta Rødsgaard-Jørgensen, Benjamin H Conlon, Daniel Croll, Jonathan Z Shik
Journal: Molecular Biology and Evolution (2024)

Abstract The naturally selected fungal crop (Leucoagaricus gongylophorus) farmed by leafcutter ants shows striking parallels with artificially selected plant crops domesticated by humans (e.g., polyploidy, engorged nutritional rewards, dependence on cultivation). To date, poorly resolved L. gongylophorus genome assemblies based on short-read sequencing have constrained hypotheses about how millions of years under cultivation by ants shaped the fungal crop genome and potentially drove domestication. We use PacBio HiFi sequencing of L. gongylophorus from the leafcutter ant Atta colombica to identify 18 putatively novel biosynthetic gene clusters that likely cemented life as a cultivar (e.g., plant fragment degradation, ant-farmer communication, antimicrobial defense). Comparative analyses with cultivated and free-living fungi showed genomic signatures of stepwise domestication transitions: 1) free-living to ant-cultivated: loss of genes conferring stress response and detoxification, 2) hyphal food to engorged nutritional rewards: expansions of genes governing cellular homeostasis, carbohydrate metabolism, and siderophore biosynthesis, and 3) detrital provisioning to freshly cut plant fragments: gene expansions promoting cell wall biosynthesis, fatty acid metabolism, and DNA repair. Comparisons across L. gongylophorus fungi farmed by three leafcutter ant species highlight genomic signatures of exclusively vertical clonal propagation and widespread transposable element activity. These results show how natural selection can shape domesticated cultivar genomes towards long-term ecological resilience of farming systems that have thrived across millennia.
Functional characterization supports multiple evolutionary origins of pheromone receptors in bark beetles
Authors: Twinkle Biswas, Cassie Sims, Jothi Kumar Yuvaraj, Rebecca E Roberts, Christer Löfstedt, Martin N Andersson
Journal: Molecular Biology and Evolution (2024)

Abstract Chemical communication using pheromones is thought to have contributed to the diversification and speciation of insects. The species-specific pheromones are detected by specialized pheromone receptors. Whereas the evolution and function of pheromone receptors have been extensively studied in Lepidoptera, only a few pheromone receptors have been identified in beetles, which limits our understanding of their evolutionary histories and physiological functions. To shed light on these questions, we aimed to functionally characterize potential pheromone receptors in the spruce bark beetle Ips typographus (‘Ityp’) and explore their evolutionary origins and molecular interactions with ligands. Males of this species release an aggregation pheromone comprising 2-methyl-3-buten-2-ol and (4S)-cis-verbenol, which attracts both sexes to attacked trees. Using two systems for functional characterization, we show that the highly expressed odorant receptor (OR) ItypOR41 responds specifically to (4S)-cis-verbenol, with structurally similar compounds eliciting minor responses. We next targeted the closely related ItypOR40 and ItypOR45. Whereas ItypOR40 was unresponsive, ItypOR45 showed an overlapping response profile with ItypOR41, but a broader tuning. Our phylogenetic analysis shows that these ORs are present in a different OR clade as compared to all other known beetle pheromone receptors, suggesting multiple evolutionary origins of pheromone receptors in bark beetles. Next, using computational analyses and experimental validation, we reveal two amino acid residues (Gln179 and Trp310) that are important for ligand binding and pheromone specificity of ItypOR41 for (4S)-cis-verbenol, possibly via hydrogen bonding to Gln179. Collectively, our results shed new light on the origins, specificity, and ligand binding mechanisms of pheromone receptors in beetles.
Radial Egg White Hydrogel Releasing Extracellular Vesicles for Cell Fate Guidance and Accelerated Diabetic Skin Regeneration
Authors: Yuan Ma, Xinhui Wang, Xiaoqi Huang, Yu He, Ting Su, Xingtang Niu, Jianhua Gao, Feng Lu, Qiang Chang
Journal: Advanced Healthcare Materials (2024)

Abstract Topology and bioactive molecules are crucial for stimulating cellular and tissue functions. To regulate the chronic wound microenvironment, mono‐assembly technology is employed to fabricate a radial egg white hydrogel loaded with lyophilized adipose tissue‐extracellular vesicles (radial EWH@L‐EVs). The radial architecture not only significantly modified the gene expression of functional cells, but also achieved directional and controlled release kinetics of L‐EVs. Through the synergy of topographical and inherent bioactive cues, radial EWH@L‐EVs effectively reduced intracellular oxidative stress and promoted the polarization of macrophages toward an anti‐inflammatory phenotype during the inflammatory phase. Afterward, radial EWH@L‐EVs facilitated the centripetal migration and proliferation of fibroblasts and endothelial cells as the wound transitioned to the proliferative phase. During the latter remodeling phase, radial EWH@L‐EVs accelerated the regeneration of granulation tissue, angiogenesis, and collagen deposition, thereby promoting the reorganization chronic wound. Compared with the gold standard collagen scaffold, radial EWH@L‐EVs actively accommodated the microenvironment via various functions throughout all stages of diabetic wound healing. This can be attributed to the orientation of topological structures and bioactive molecules, which should be considered of utmost importance in tissue engineering.
Benefits and Harms of Hepatocellular Carcinoma Screening Outreach in Patients with Cirrhosis: A Multi-Center Randomized Clinical Trial
Authors: Amit G Singal, Darine Daher, Manasa Narasimman, Sruthi Yekkaluri, Yan Liu, Vanessa Cerda, Chaitra Banala, Aisha Khan, MinJae Lee, Karim Seif El Dahan, Caitlin C Murphy, Jennifer R Kramer, Ruben Hernaez
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background The value of hepatocellular carcinoma screening is defined by the balance of benefits from early tumor detection vs harms because of false-positive results. We evaluated the value of a mailed outreach strategy for hepatocellular carcinoma screening in patients with cirrhosis. Methods We conducted a multicenter pragmatic randomized clinical trial comparing mailed outreach for hepatocellular carcinoma screening (n = 1436) and usual care with visit-based screening (n = 1436) among patients with cirrhosis at 3 health systems from March 2018 to September 2021. Outcomes of interest were early stage hepatocellular carcinoma detection (ie, screening benefit) and diagnostic evaluation for false-positive or indeterminate results (ie, screening harm). Screening harm was categorized as mild, moderate, and severe based on number and type of diagnostic exams. All patients were included in intention-to-screen analyses. Results Of 125 patients diagnosed with hepatocellular carcinoma (67 outreach and 58 usual care), 71.2% were found at an early stage per the Milan criteria. Early tumor detection did not statistically significantly differ between the outreach and usual care arms (64.2% vs 79.3%; P = .06). The proportion of patients with physical harms also did not differ between the outreach and usual care arms (10.8% vs 10.7%; P = .95) with 5.9% in both arms having mild harms; 4.0% and 3.8%, respectively, with moderate harms; and 0.9% and 1.0%, respectively, with severe harms. Conclusion Most patients enrolled in hepatocellular carcinoma screening were detected at an early stage, and a minority experienced physical harms. A mailed outreach strategy did not increase early hepatocellular carcinoma detection or physical harms compared with usual care. Clinical trials number NCT02582918 and NCT03756051.
Patient Consent and The Right to Notice and Explanation of AI Systems Used in Health Care
Authors: Meghan E. Hurley, Benjamin H. Lang, Kristin Marie Kostick-Quenet, Jared N. Smith, Jennifer Blumenthal-Barby
Journal: The American Journal of Bioethics (2024)

Given the need for enforceable guardrails for artificial intelligence (AI) that protect the public and allow for innovation, the U.S. Government recently issued a Blueprint for an AI Bill of Rights which outlines five principles of safe AI design, use, and implementation. One in particular, the right to notice and explanation, requires accurately informing the public about the use of AI that impacts them in ways that are easy to understand. Yet, in the healthcare setting, it is unclear what goal the right to notice and explanation serves, and the moral importance of patient-level disclosure. We propose three normative functions of this right: (1) to notify patients about their care, (2) to educate patients and promote trust, and (3) to meet standards for informed consent. Additional clarity is needed to guide practices that respect the right to notice and explanation of AI in healthcare while providing meaningful benefits to patients.
Clonal Hematopoiesis and Clinical Outcomes in Metastatic Castration-Resistant Prostate Cancer Patients Given Androgen Receptor Pathway Inhibitors (Alliance A031201)
Authors: Jeffrey L. Jensen, Olivia Bobek, Irenaeus C. C. Chan, Brian C. Miller, David W. Hillman, Glenn Heller, Todd Druley, Andrew J. Armstrong, Michael J. Morris, Matthew I. Milowsky, Himisha Beltran, Kelly L. Bolton, Catherine C. Coombs
Journal: Clinical Cancer Research (2024)

Mutations in hematopoietic progenitor cells accumulate with age leading to clonal expansion, termed clonal hematopoiesis (CH). CH in the general population is associated with hematopoietic neoplasms and reduced overall survival (OS), predominantly through cardiovascular adverse events (CVAE). Because androgen receptor pathway inhibitors (ARPI) used in metastatic castration-resistant prostate cancer (mCRPC) are also associated with CVAEs and because CH negatively impacted survival in an advanced solid tumor cohort, we hypothesized that CH in mCRPC may be associated with increased CVAEs and inferior survival.
Therapeutic strategies and treatment sequencing in patients with chronic lymphocytic leukemia: An international study of ERIC, the European Research Initiative on CLL
Authors: Thomas Chatzikonstantinou, Lydia Scarfò, Eva Minga, Georgios Karakatsoulis, Dimitra Chamou, Jana Kotaskova, Gloria Iacoboni, Christos Demosthenous, Elisa Albi, Miguel Alcoceba, Salem Al‐Shemari, Thérèse Aurran‐Schleinitz, Francesca Bacchiarri, Sofia Chatzileontiadou, Rosa Collado, Zadie Davis, Marcos Daniel de Deus Santos, Maria Dimou, Elena Dmitrieva, David Donaldson, Gimena Dos Santos, Barbara Dreta, Maria Efstathopoulou, Shaimaa El‐Ashwah, Alicia Enrico, Andrzej Frygier, Sara Galimberti, Andrea Galitzia, Eva Gimeno, Valerio Guarente, Romain Guieze, Sean Harrop, Eleftheria Hatzimichael, Yair Herishanu, José‐Ángel Hernández‐Rivas, Ozren Jaksic, Elżbieta Kalicińska, Kamel Laribi, Volkan Karakus, Arnon P. Kater, Bonnie Kho, Maria Kislova, Εliana Konstantinou, Maya Koren‐Michowitz, Ioannis Kotsianidis, Zuzana Kubova, Jorge Labrador, Deepesh Lad, Luca Laurenti, Thomas Longval, Alberto Lopez‐Garcia, Juan Marquet, Stanislava Maslejova, Carlota Mayor‐Bastida, Biljana Mihaljevic, Ivana Milosevic, Fatima Miras, Riccardo Moia, Marta Morawska, Uttam K. Nath, Almudena Navarro‐Bailón, Jacopo Olivieri, Irina Panovska‐Stavridis, Maria Papaioannou, Cheyenne Pierie, Anna Puiggros, Gianluigi Reda, Gian M. Rigolin, Rosa Ruchlemer, Mattia Schipani, Annett Schiwitza, Yandong Shen, Tereza Shokralla, Martin Simkovic, Svetlana Smirnova, Dina S. A. Soliman, Stephan Stilgenbauer, Tamar Tadmor, Kristina Tomic, Eric Tse, Theodoros Vassilakopoulos, Andrea Visentin, Candida Vitale, George Vrachiolias, Vojin Vukovic, Renata Walewska, Zhenshu Xu, Munci Yagci, Lucrecia Yañez, Mohamed Yassin, Jana Zuchnicka, David Oscier, Alessandro Gozzetti, Panagiotis Panagiotidis, Francesc Bosch, Paolo Sportoletti, Blanca Espinet, Gerassimos A. Pangalis, Viola M. Popov, Stephen Mulligan, Maria Angelopoulou, Fatih Demirkan, Tomas Papajík, Bella Biderman, Roberta Murru, Marta Coscia, Constantine Tam, Antonio Cuneo, Gianluca Gaidano, Rainer Claus, Niki Stavroyianni, Livio Trentin, Darko Antic, Lukas Smolej, Olga B. Kalashnikova, Mark Catherwood, Martin Spacek, Sarka Pospisilova, Michael Doubek, Eugene Nikitin, Anastasia Chatzidimitriou, Paolo Ghia, Kostas Stamatopoulos
Journal: HemaSphere (2024)
Multiomics Profiling Distinguishes Sebaceous Carcinoma from Benign Sebaceous Neoplasms and Provides Insight into the Genetic Evolution of Sebaceous Carcinogenesis
Authors: Gabriel J. Starrett, Brittany C. Baikie, Benjamin K. Stoff, Hans E. Grossniklaus, Inga Van Buren, Elizabeth G. Berry, Roberto A. Novoa, Kerri E. Rieger, Kavita Y. Sarin, Charles F. Lynch, Michael C. Royer, Mary L. Piaskowski, Isaac Brownell, Emily Y. Chu, Rama Godse, Suephy C. Chen, Kelly J. Yu, Alisa M. Goldstein, Eric A. Engels, Michael R. Sargen
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Sebaceous carcinoma is the third most common nonkeratinocyte skin cancer in the United States with 1,000 cases per year. The clinicopathologic features of sebaceous carcinoma and benign sebaceous neoplasms (adenomas, sebaceomas) can overlap, highlighting the need for molecular biomarkers to improve classification. This study describes the genomic and transcriptomic landscape of sebaceous neoplasms in order to understand tumor etiology and biomarkers relevant for diagnosis and treatment. Experimental Design: We performed whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS) of sebaceous neoplasms from six academic and two federal healthcare facilities in the United States diagnosed between January 1, 1999, and December 31, 2021. Results: We evaluated 98 sebaceous neoplasms: 64 tumors (32 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 25 carcinomas) had sufficient material for WGS, 96 tumors (42 adenomas, 11 sebaceomas, 8 atypical sebaceous neoplasms, 35 carcinomas) had sufficient material for WTS, and 62 tumors (31 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 24 carcinomas) had sufficient material for combined WGS and WTS. Overall, we found decreased cholesterol biosynthesis and increased TP53 mutations, copy number gains (chromosome 6, 8q, and/or 18), and tumor mutation burden-high (&amp;gt;10 mutations/MB) in carcinomas compared to adenomas. Although diminished compared to adenomas, most carcinomas still had higher cholesterol biosynthesis than nonmalignant skin. Multiomics profiling also supported a precancerous model of tumor evolution with sebaceomas and atypical sebaceous neoplasms being likely intermediate lesions. Conclusions: The study findings highlight key diagnostic biomarkers for sebaceous carcinoma and suggest that immunotherapy and modulation of cholesterol biosynthesis could be effective treatment strategies.
Systemic Janus Kinase Inhibitor Treatment for Vitiligo: An Evidence-Based Review
Authors: Siddhartha Sood, Jaymie Varenbut, Ahmed Bagit, Jonah Perlmutter, Khalad Maliyar, Muskaan Sachdeva, Abrahim Abduelmula, Jorge R Georgakopoulos, Asfandyar Mufti, Vimal H Prajapati, Jensen Yeung
Journal: Journal of the American Academy of Dermatology (2024)
Liver cirrhosis: molecular mechanisms and therapeutic interventions
Authors: Zihe Dong, Yeying Wang, Weilin Jin
Journal: MedComm (2024)

Liver cirrhosis is the end-stage of chronic liver disease, characterized by inflammation, necrosis, advanced fibrosis, and regenerative nodule formation. Long-term inflammation can cause continuous damage to liver tissues and hepatocytes, along with increased vascular tone and portal hypertension. Among them, fibrosis is the necessary stage and essential feature of liver cirrhosis, and effective antifibrosis strategies are commonly considered the key to treating liver cirrhosis. Although different therapeutic strategies aimed at reversing or preventing fibrosis have been developed, the effects have not be more satisfactory. In this review, we discussed abnormal changes in the liver microenvironment that contribute to the progression of liver cirrhosis and highlighted the importance of recent therapeutic strategies, including lifestyle improvement, small molecular agents, traditional Chinese medicine, stem cells, extracellular vesicles, and gut remediation, that regulate liver fibrosis and liver cirrhosis. Meanwhile, therapeutic strategies for nanoparticles are discussed, as are their possible underlying broad application and prospects for ameliorating liver cirrhosis. Finally, we also reviewed the major challenges and opportunities of nanomedicine‒biological environment interactions. We hope this review will provide insights into the pathogenesis and molecular mechanisms of liver cirrhosis, thus facilitating new methods, drug discovery, and better treatment of liver cirrhosis.
CRISPR–Cas13d targeting suppresses repeat-associated non-AUG translation of C9orf72 hexanucleotide repeat RNA
Authors: Honghe Liu, Xiao-Feng Zhao, Yu-Ning Lu, Lindsey R Hayes, Jiou Wang
Journal: Journal of Clinical Investigation (2024)

A hexanucleotide GGGGCC repeat expansion in the non-coding region of C9orf72 gene is the most common genetic mutation identified in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The resulting repeat RNA and dipeptide repeat proteins from non-conventional repeat translation have been recognized as important markers associated with the diseases. CRISPR-Cas13d, a powerful RNA targeting tool, has faced challenges in effectively targeting RNA with stable secondary structures. Here we report that CRISPR-Cas13d can be optimized to specifically target GGGGCC repeat RNA. Our results demonstrate that the CRISPR-Cas13d system can be harnessed to significantly diminish the translation of poly-dipeptides originating from the GGGGCC repeat RNA. This efficacy has been validated in various cell types, including induced pluripotent stem cells and differentiated motor neurons originating from C9orf72-ALS patients, as well as in C9orf72 repeat transgenic mice. These findings demonstrate the application of CRISPR-Cas13d in targeting RNA with intricate higher-order structures and suggest a potential therapeutic approach for ALS and FTD.
Gut microbe–host interactions in post-COVID syndrome: a debilitating or restorative partnership?
Authors: Torsten P. M. Scheithauer, Roy C. Montijn, Arnout Mieremet
Journal: Gut Microbes (2024)

Post-COVID syndrome (PCS) patients have reported a wide range of symptoms, including fatigue, shortness of breath, and diarrhea. Particularly, the presence of gastrointestinal symptoms has led to the hypothesis that the gut microbiome is involved in the development and severity of PCS. The objective of this review is to provide an overview of the role of the gut microbiome in PCS by describing the microbial composition and microbial metabolites in COVID-19 and PCS. Moreover, host-microbe interactions via the microbiota-gut-brain (MGB) and the microbiota-gut-lung (MGL) axes are described. Furthermore, we explore the potential of therapeutically targeting the gut microbiome to support the recovery of PCS by reviewing preclinical model systems and clinical studies. Overall, current studies provide evidence that the gut microbiota is affected in PCS; however, diversity in symptoms and highly individual microbiota compositions suggest the need for personalized medicine. Gut-targeted therapies, including treatments with pre- and probiotics, have the potential to improve the quality of life of affected individuals.
Persistent menstruation in transgender people using testosterone gender-affirming hormone therapy
Authors: Sav Zwickl, Alex Fang Qi Wong, Laura Burchill, Shalem Y. Leemaqz, Teddy Cook, Lachlan M. Angus, Kalen Eshin, Charlotte V. Elder, Sonia R. Grover, Ada S. Cheung
Journal: International Journal of Transgender Health (2024)
Inter-organ cross-talk in human cancer cachexia revealed by spatial metabolomics
Authors: Na Sun, Tanja Krauss, Claudine Seeliger, Thomas Kunzke, Barbara Stöckl, Annette Feuchtinger, Chaoyang Zhang, Andreas Voss, Simone Heisz, Olga Prokopchuk, Marc E Martignoni, Klaus-Peter Janssen, Melina Claussnitzer, Hans Hauner, Axel Walch
Journal: Metabolism (2024)
Effect of diet on the gut mycobiome and potential implications in inflammatory bowel disease
Authors: J. Buttar, E. Kon, A. Lee, G. Kaur, G. Lunken
Journal: Gut Microbes (2024)

The gut microbiome is a complex, unique entity implicated in the prevention, pathogenesis, and progression of common gastrointestinal diseases. While largely dominated by bacterial populations, advanced sequencing techniques have identified co-inhabiting fungal communities, collectively referred to as the mycobiome. Early studies identified that gut inflammation is associated with altered microbial composition, known as gut dysbiosis. Altered microbial profiles are implicated in various pathological diseases, such as inflammatory bowel disease (IBD), though their role as a cause or consequence of systemic inflammation remains the subject of ongoing research. Diet plays a crucial role in the prevention and management of various diseases and is considered to be an essential regulator of systemic inflammation. This review compiles current literature on the impact of dietary modulation on the mycobiome, showing that dietary changes can alter the fungal architecture of the gut. Further research is required to understand the impact of diet on gut fungi, including the metabolic pathways and enzymes involved in fungal fermentation. Additionally, investigating whether dietary modulation of the gut mycobiome could be utilized as a therapy in IBD is essential.
Empowering probiotics with high xanthine transport for effective hyperuricemia management
Authors: Zhen-Ping Zou, Ju-Ling Li, Yi-Fan Zhang, Ying Zhou, Bang-Ce Ye
Journal: Gut Microbes (2024)

Hyperuricemia, a prevalent metabolic disorder, poses a susceptibility to various complications. The conventional pharmacotherapeutic approaches for hyperuricemia often entail notable adverse effects, posing substantial clinical challenges. Hence, the imperative lies in the development of novel, safe and effective strategies for preventing and treating hyperuricemia. Here, we developed a probiotic
ADP-heptose attenuates <i>Helicobacter pylori</i> -induced dendritic cell activation
Authors: Theresa Neuper, Tobias Frauenlob, Hieu-Hoa Dang, Peter W. Krenn, Gernot Posselt, Christof Regl, Nikolaus Fortelny, Veronika Schäpertöns, Michael S. Unger, Gunda Üblagger, Daniel Neureiter, Iris Mühlbacher, Michael Weitzendorfer, Franz Singhartinger, Klaus Emmanuel, Christian G. Huber, Silja Wessler, Fritz Aberger, Jutta Horejs-Hoeck
Journal: Gut Microbes (2024)

Sophisticated immune evasion strategies enable
Up‐dosing of reslizumab in severe asthmatics with persistent sputum eosinophilia: A feasibility study
Authors: Manali Mukherjee, Jaime Bernaola, Santi Nolasco, Melanie Kjarsgaard, Yinglan Xie, Katherine Radford, Bashayr Alotaibi, Carmen Venegas Garrido, Parameswaran Nair
Journal: Allergy (2024)
Management and outcomes of hidradenitis suppurativa in solid organ transplant recipients
Authors: Reese L Imhof, Christina Dai, Afsaneh Alavi, Olayemi Sokumbi
Journal: British Journal of Dermatology (2024)

This case series includes patients with hidradenitis suppurativa (HS) who underwent solid organ transplant with subsequent transplant-related immunosuppression. Most patients in this case series experienced improvement of their HS following the initiation of transplant immunosuppressive treatment, particularly with the majority on tacrolimus and mycophenolate mofetil.