tbuckley/cabot-search huggingface dataset:
Author Correction: Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B
Authors: Martina Musella, Andrea Guarracino, Nicoletta Manduca, Claudia Galassi, Eliana Ruggiero, Alessia Potenza, Ester Maccafeo, Gwenola Manic, Luca Mattiello, Sara Soliman Abdel Rehim, Michele Signore, Marco Pietrosanto, Manuela Helmer-Citterich, Matteo Pallocca, Maurizio Fanciulli, Tiziana Bruno, Francesca De Nicola, Giacomo Corleone, Anna Di Benedetto, Cristiana Ercolani, Edoardo Pescarmona, Laura Pizzuti, Francesco Guidi, Francesca Sperati, Sara Vitale, Daniele Macchia, Massimo Spada, Giovanna Schiavoni, Fabrizio Mattei, Adele De Ninno, Luca Businaro, Valeria Lucarini, Laura Bracci, Eleonora Aricò, Giovanna Ziccheddu, Francesco Facchiano, Stefania Rossi, Massimo Sanchez, Alessandra Boe, Mauro Biffoni, Ruggero De Maria, Ilio Vitale, Antonella Sistigu
Journal: Nature Immunology (2024)
A drug mix and dose decision algorithm for individualized type 2 diabetes management
Authors: Mila Nambiar, Yong Mong Bee, Yu En Chan, Ivan Ho Mien, Feri Guretno, David Carmody, Phong Ching Lee, Sing Yi Chia, Nur Nasyitah Mohamed Salim, Pavitra Krishnaswamy
Journal: npj Digital Medicine (2024)
Vascular heterogeneity of tight junction Claudins guides organotropic metastasis
Authors: Xunian Zhou, Valerie S LeBleu, Eliot Fletcher-Sananikone, Jiha Kim, Jianli Dai, Bingrui Li, Chia-Chin Wu, Hikaru Sugimoto, Toru Miyake, Lisa M Becker, Olga V Volpert, Erica Lawson, Cristina Espinosa Da Silva, Sarah I Patel, Akane Kizu, Ehsan A Ehsanipour, Di Sha, Jose Antonio Karam, Kathleen M McAndrews, Raghu Kalluri
Journal: Nature Cancer (2024)
Correction: Chronic myeloid leukemia diagnosed in pregnancy: management and outcome of 87 patients reported to the European LeukemiaNet international registry
Authors: Ekaterina Chelysheva, Jane Apperley, Anna Turkina, Mohamed A Yassin, Delphine Rea, Franck E Nicolini, Daniela Barraco, Khamida Kazakbaeva, Sukhrob Saliev, Adi Shacham Abulafia, Salam Al-Kindi, Jennifer Byrne, Harry F Robertson, Marco Cerrano, Roman Shmakov, Evgenia Polushkina, Paolo de Fabritiis, Malgorzata Monika Trawinska, Elisabetta Abruzzese
Journal: Leukemia (2024)
Relationship between post-ablation fever and prognosis in initial hepatocellular carcinoma: A 15-year multicenter, retrospective cohort study
Authors: Qian Cai, Chuan Pang, Zhen Wang, Jianming Li, Yuqing Dai, Fang-ying Fan, Zhong-qi Wang, Xin Hu, Lijuan Li, Xu-wei Chen, Ran Ji, Qian Mei, Chao Zhang, Ping Liang, Xiaoling Yu, Fang-yi Liu, Zhigang Cheng, Jie Yu
Journal: International Journal of Surgery (2024)
Multi‐Chambered Core/Shell Supraparticles for Real‐Time, Full‐Time Diagnosis and Treatment Integration of Tumors
Authors: Degang Kong, Xiaotong Zheng, Kai Ding, Run Zhong, Zhao Zhang, Qingyi Wang, Chunxiu Dong, Zhiwen Zheng, Xiaohong Li, Jie Weng, Shaobing Zhou
Journal: Advanced Healthcare Materials (2024)

Abstract To a certain extent, theranostic nanoplatforms promote tumor treatment efficiency. However, timely monitoring of the critical stages and signal sustainability of the entire process is challenging. In this study, multi‐chambered core/shell magnetic nanoparticles (MC‐MNPs) as drug and imaging agent multi‐loaded nanocarriers with a synergistic release function are reported. Supraparticles with stable chambers are formed by the supercooling self‐assembly of several core/shell magnetic nanoparticles composed of amphiphilic copolymers as the core and hydrophilic magnetic iron oxide nanoparticles as the shell. Desalinized doxorubicin and coumarin 6 are stored in different cavities of nanocarriers, and chitosan is used as an outer encapsulation layer. Based on their construction properties, MC‐MNPs can exhibit gradient‐degraded and steady‐released controllability in the tumor environment. Furthermore, real‐time accumulation situations and full‐time diagnostic signals of nanocarriers are thoroughly demonstrated using fluorescence imaging and T 2 ‐weighted magnetic resonance imaging before and after magnetic hyperthermia in targeted tumors under an alternating magnetic field. Thus, MC‐MNPs as theranostic nanocarriers exhibit great potential for the timely monitoring and full‐time guidance of tumor treatment.
Corrigendum to “Quantitative scoring of progression in transplant glomerulopathy using digital pathology may be superior to Banff cg scoring.” Kidney International 2023;103:365–377
Authors: Željko Kikić, Benjamin A Adam, Anna Buxeda, Carmen Lefaucheur, Alexandre Loupy, Heinz Regele, Daniel Cejka, Mark Haas, Robert B Colvin, Michael Mengel
Journal: Kidney International (2024)
Drug-drug interactions of simnotrelvir/ritonavir: an open-lable, fixed-sequence, two-period clinical trial
Authors: Pan-Pan Ye, Bu-Fan Yao, Yang Yang, Xin-Mei Yang, Qian Li, Lin-Lin Song, Ke-Guang Chen, Hai-Yan Zhou, Jin-Yi Shi, Ye-Hui Zhang, Fu-Rong Zhao, Zi-Jia Guo, Shan-Sen Xu, Jia Chen, Aik Han Goh, Shun-Wei Zhu, Yi Zheng, Wei Zhao
Journal: Clinical Microbiology and Infection (2024)
Preventing Site-Specific Calpain Proteolysis of Junctophilin-2 Protects Against Stress-Induced Excitation-Contraction Uncoupling and Heart Failure Development
Authors: Jinxi Wang, Biyi Chen, Qian Shi, Grace Ciampa, Weiyang Zhao, Guangqin Zhang, Robert M. Weiss, Tianqing Peng, Duane D. Hall, Long-Sheng Song
Journal: Circulation (2024)

BACKGROUND: Excitation-contraction (E-C) coupling processes become disrupted in heart failure (HF), resulting in abnormal Ca 2+ homeostasis, maladaptive structural and transcriptional remodeling, and cardiac dysfunction. Junctophilin-2 (JP2) is an essential component of the E-C coupling apparatus but becomes site-specifically cleaved by calpain, leading to disruption of E-C coupling, plasmalemmal transverse tubule degeneration, abnormal Ca 2+ homeostasis, and HF. However, it is not clear whether preventing site-specific calpain cleavage of JP2 is sufficient to protect the heart against stress-induced pathological cardiac remodeling in vivo. METHODS: Calpain-resistant JP2 knock-in mice (JP2 CR ) were generated by deleting the primary JP2 calpain cleavage site. Stress-dependent JP2 cleavage was assessed through in vitro cleavage assays and in isolated cardiomyocytes treated with 1 μmol/L isoproterenol by immunofluorescence. Cardiac outcomes were assessed in wild-type and JP2 CR mice 5 weeks after transverse aortic constriction compared with sham surgery using echocardiography, histology, and RNA-sequencing methods. E-C coupling efficiency was measured by in situ confocal microscopy. E-C coupling proteins were evaluated by calpain assays and Western blotting. The effectiveness of adeno-associated virus gene therapy with JP2 CR , JP2, or green fluorescent protein to slow HF progression was evaluated in mice with established cardiac dysfunction. RESULTS: JP2 proteolysis by calpain and in response to transverse aortic constriction and isoproterenol was blocked in JP2 CR cardiomyocytes. JP2 CR hearts are more resistant to pressure-overload stress, having significantly improved Ca 2+ homeostasis and transverse tubule organization with significantly attenuated cardiac dysfunction, hypertrophy, lung edema, fibrosis, and gene expression changes relative to wild-type mice. JP2 CR preserves the integrity of calpain-sensitive E-C coupling–related proteins, including ryanodine receptor 2, Ca V 1.2, and sarcoplasmic reticulum calcium ATPase 2a, by attenuating transverse aortic constriction–induced increases in calpain activity. Furthermore, JP2 CR gene therapy after the onset of cardiac dysfunction was found to be effective at slowing the progression of HF and superior to wild-type JP2. CONCLUSIONS: The data presented here demonstrate that preserving JP2-dependent E-C coupling by prohibiting the site-specific calpain cleavage of JP2 offers multifaceted beneficial effects, conferring cardiac protection against stress-induced proteolysis, hypertrophy, and HF. Our data also indicate that specifically targeting the primary calpain cleavage site of JP2 by gene therapy approaches holds great therapeutic potential as a novel precision medicine for treating HF.
Serum Cytokine Panels in Pediatric Clinical Practice
Authors: Paul M Gallo, Jihwan Kim, Kevin O McNerney, Caroline Diorio, Caelin Foley, Laura Kagami, Kristina Wagner, Whitney L Petrosa, Hana Conlon, Kandace L Gollomp, Scott W Canna, Alix E Seif, Maire A Conrad, Judith R Kelsen, Neil Romberg, Hamid Bassiri, Kathleen E Sullivan, David T Teachey, Michele E Paessler, Edward M Behrens, Michele P Lambert
Journal: Journal of Allergy and Clinical Immunology (2024)
ASSOCIATION BETWEEN PULSE WAVE VELOCITY AND WHITE MATTER HYPERINTENSITIES AMONG OLDER ADULTS: A META-ANALYSIS OF CROSS-SECTIONAL AND LONGITUDINAL STUDIES.
Authors: Celia Álvarez-Bueno, María Medrano, Maribel Lucerón-Lucas-Torres, Iris Otero-Luis, Samuel López-López, Carla Geovanna Lever-Megina, Iván Cavero-Redondo
Journal: Ageing Research Reviews (2024)
Tertiary lymphoid structure formation induced by LIGHT-engineered and photosensitive nanoparticles-decorated bacteria enhances immune response against colorectal cancer
Authors: Lijun Hu, Tan Li, Shaohui Deng, Honglin Gao, Yujie Jiang, Qiu Chen, Hui Chen, Zecong Xiao, Xintao Shuai, Zhongzhen Su
Journal: Biomaterials (2024)
Rna-loaded nanoparticles for the treatment of hematological cancers
Authors: Elisa Garbayo, Souhaila H El Moukhtari, Carlos Rodríguez-Nogales, Xabier Agirre, Juan R Rodriguez-Madoz, Paula Rodriguez-Marquez, Felipe Prósper, Patrick Couvreur, María J Blanco-Prieto
Journal: Advanced Drug Delivery Reviews (2024)
UnTWISTing intestinal fibrosis: single-cell transcriptomics deciphers fibroblast heterogeneity, uncovers molecular pathways, and identifies therapeutic targets
Authors: Giovanni Santacroce, Antonio Di Sabatino
Journal: Journal of Clinical Investigation (2024)

Intestinal fibrosis is a severe complication of Crohn's disease, often requiring surgical intervention. Despite extensive research efforts, an effective treatment to prevent or reverse intestinal fibrosis remains elusive. In this issue of the JCI, Zhang, Wang, and colleagues employed single-cell RNA sequencing to uncover mechanisms of the fibrotic process. They identified a key fibroblast subset of TWIST1+FAP+ cells that interacts with CXCL9+ macrophages. TWIST1 emerged as a central regulator of the fibrotic microenvironment, representing a promising therapeutic target for effectively treating intestinal fibrosis.
Targeting aryl hydrocarbon receptor functionally restores tolerogenic dendritic cells derived from patients with multiple sclerosis
Authors: Federico Fondelli, Jana Willemyns, Roger Domenech-Garcia, Maria José Mansilla, Gerard Godoy-Tena, Anna G Ferreté-Bonastre, Alex Agúndez-Moreno, Silvia Presas-Rodriguez, Cristina Ramo-Tello, Esteban Ballestar, Eva Martínez-Cáceres
Journal: Journal of Clinical Investigation (2024)

Multiple sclerosis (MS) is a chronic disease characterized by dysregulated self-reactive immune responses that damage the neurons' myelin sheath, leading to progressive disability. The primary therapeutic option, immunosuppressants, inhibits pathogenic anti-myelin responses but depresses the immune system. Antigen-specific monocyte-derived autologous tolerogenic dendritic cells (tolDCs) offer alternative therapeutic approaches to restore tolerance to autoantigens without causing generalized immunosuppression. However, immune dysregulation in MS could impact the properties of the monocytes used as starting material for this cell therapy. Here, we characterized CD14+ monocytes, mature dendritic cells, and vitamin D3-tolDCs (VitD3-tolDCs) from active, treatment-naive MS patients and healthy donors (HDs). Using multiomics, we identified a switch in these cell types toward proinflammatory features characterized by alterations in the aryl hydrocarbon receptor (AhR) and NF-κB pathways. MS patient-derived VitD3-tolDCs showed reduced tolerogenic properties compared with those from HDs, which were fully restored through direct AhR agonism and by use of in vivo or in vitro dimethyl fumarate (DMF) supplementation. Additionally, in the experimental autoimmune encephalomyelitis mouse model, combined therapy of DMF and VitD3-tolDCs was more efficient than monotherapies in reducing the clinical score of mice. We propose that a combined therapy with DMF and VitD3-tolDCs offers enhanced therapeutic potential in treating MS.
Fibrosis uncovered: ADAMTS12 cuts to the core of extracellular matrix drama
Authors: Bernhard Dumoulin, Katalin Susztak
Journal: Journal of Clinical Investigation (2024)

Fibrosis is a common manifestation of most progressive and degenerative diseases, with myofibroblast activation and matrix accumulation playing a key role. In this issue of the JCI, Hoeft et al. identify the important role of ADAMTS12 in fibroblast activation. ADAMTS12, a secreted protein, is involved in extracellular matrix (ECM) remodeling, cell signaling, and inflammation. ADAMTS12 facilitates proteolysis by cleaving various substrates such as ECM components, which are vital for cellular signaling and remodeling. Additionally, it modulates cell-matrix interactions, influencing cell adhesion and migration, and plays an important role in the inflammatory processes. Understanding the role of ADAMTS12 offers potential therapeutic insights for targeting fibrosis in progressive diseases.
Connecting the dots: sex, depression, and musculoskeletal health
Authors: Mackenzie Newman, Henry J Donahue, Gretchen N Neigh
Journal: Journal of Clinical Investigation (2024)

Depression and multiple musculoskeletal disorders are overrepresented in women compared with men. Given that depression is a modifiable risk factor and improvement of depressive symptoms increases positive outcomes following orthopedic intervention, efforts to improve clinical recognition of depressive symptoms and increased action toward ameliorating depressive symptoms among orthopedic patients are positioned to reduce complications and positively affect patient-reported outcomes. Although psychosocial factors play a role in the manifestation and remittance of depression, it is also well appreciated that primary biochemical changes are capable of causing and perpetuating depression. Unique insight for novel treatments of depression may be facilitated by query of the bidirectional relationship between musculoskeletal health and depression. This Review aims to synthesize the diverse literature on sex, depression, and orthopedics and emphasize the potential for common underlying biological substrates. Given the overrepresentation of depression and musculoskeletal disorders among women, increased emphasis on the biological drivers of the co-occurrence of these disorders is positioned to improve women's health.
ADAMTS12 promotes fibrosis by restructuring extracellular matrix to enable activation of injury-responsive fibroblasts
Authors: Konrad Hoeft, Lars Koch, Susanne Ziegler, Ling Zhang, Steffen Luetke, Maria C Tanzer, Debashish Mohanta, David Schumacher, Felix Schreibing, Qingqing Long, Hyojin Kim, Barbara M Klinkhammer, Carla Schikarski, Sidrah Maryam, Mathijs Baens, Juliane Hermann, Sarah Krieg, Fabian Peisker, Laura De Laporte, Gideon Jl Schaefer, Sylvia Menzel, Joachim Jankowski, Benjamin D Humphreys, Adam Wahida, Rebekka K Schneider, Matthias Versele, Peter Boor, Matthias Mann, Gerhard Sengle, Sikander Hayat, Rafael Kramann
Journal: Journal of Clinical Investigation (2024)

Fibrosis represents the uncontrolled replacement of parenchymal tissue with extracellular matrix (ECM) produced by myofibroblasts. While genetic fate-tracing and single-cell RNA-Seq technologies have helped elucidate fibroblast heterogeneity and ontogeny beyond fibroblast to myofibroblast differentiation, newly identified fibroblast populations remain ill defined, with respect to both the molecular cues driving their differentiation and their subsequent role in fibrosis. Using an unbiased approach, we identified the metalloprotease ADAMTS12 as a fibroblast-specific gene that is strongly upregulated during active fibrogenesis in humans and mice. Functional in vivo KO studies in mice confirmed that Adamts12 was critical during fibrogenesis in both heart and kidney. Mechanistically, using a combination of spatial transcriptomics and expression of catalytically active or inactive ADAMTS12, we demonstrated that the active protease of ADAMTS12 shaped ECM composition and cleaved hemicentin 1 (HMCN1) to enable the activation and migration of a distinct injury-responsive fibroblast subset defined by aberrant high JAK/STAT signaling.
<scp>FDA IDE</scp> validation of multiple myeloma <scp>MRD</scp> test by flow cytometry
Authors: Dragan Jevremovic, Min Shi, Pedro Horna, Gregory E. Otteson, Michael M. Timm, Shannon A. Bennett, Linda B. Baughn, Patricia T. Greipp, Wilson I. Gonsalves, Prashant Kapoor, Morie A. Gertz, Moritz Binder, Francis K. Buadi, Angela Dispenzieri, Taxiarchis Kourelis, Eli Muchtar, Jiehao Zhou, S. Vincent Rajkumar, Shaji K. Kumar, Horatiu Olteanu
Journal: American Journal of Hematology (2024)
Survival of men with metastatic hormone-sensitive prostate cancer and adrenal-permissive HSD3B1 inheritance
Authors: Nima Sharifi, Robert Diaz, Hui-Ming Lin, Evan Roberts, Lisa G Horvath, Andrew Martin, Martin R Stockler, Sonia Yip, Vinod V Subhash, Neil Portman, Ian D Davis, Christopher J Sweeney
Journal: Journal of Clinical Investigation (2024)

BACKGROUNDMetastatic hormone-sensitive prostate cancer (mHSPC) is androgen dependent, and its treatment includes androgen deprivation therapy (ADT) with gonadal testosterone suppression. Since 2014, overall survival (OS) has been prolonged with addition of other systemic therapies, such as adrenal androgen synthesis blockers, potent androgen receptor blockers, or docetaxel, to ADT. HSD3B1 encodes the rate-limiting enzyme for nongonadal androgen synthesis, 3β-hydroxysteroid dehydrogenase-1, and has a common adrenal-permissive missense-encoding variant that confers increased synthesis of potent androgens from nongonadal precursor steroids and poorer prostate cancer outcomes.METHODSOur prespecified hypothesis was that poor outcome associated with inheritance of the adrenal-permissive HSD3B1 allele with ADT alone is reversed in patients with low-volume (LV) mHSPC with up-front ADT plus addition of androgen receptor (AR) antagonists to inhibit the effect of adrenal androgens. HSD3B1 genotype was obtained in 287 patients with LV disease treated with ADT + AR antagonist only in the phase III Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer (ENZAMET) trial and was associated with clinical outcomes.RESULTSPatients who inherited the adrenal-permissive HSD3B1 allele had more favorable 5-year clinical progression-free survival and OS when treated with ADT plus enzalutamide or ADT plus nonsteroidal antiandrogen compared with their counterparts who did not have adrenal-permissive HSD3B1 inheritance. HSD3B1 was also associated with OS after accounting for known clinical variables. Patients with both genotypes benefited from early enzalutamide.CONCLUSIONThese data demonstrated an inherited physiologic driver of prostate cancer mortality is associated with clinical outcomes and is potentially pharmacologically reversible.FUNDINGNational Cancer Institute, NIH; Department of Defense; Prostate Cancer Foundation, Australian National Health and Medical Research Council.
Mechanisms underlying sex differences in autoimmunity
Authors: DeLisa Fairweather, Danielle J Beetler, Elizabeth J McCabe, Scott M Lieberman
Journal: Journal of Clinical Investigation (2024)

Autoimmune diseases are a leading cause of disability worldwide. Most autoimmune diseases occur more often in women than men, with rheumatic autoimmune diseases being among those most highly expressed in women. Several key factors, identified mainly in animal models and cell culture experiments, are important in increasing autoimmune disease in females. These include sex hormones, immune genes including those found on the X chromosome, sex-specific epigenetic effects on genes by estrogen and the environment, and regulation of genes and messenger RNA by microRNAs found in extracellular vesicles. Evidence is also emerging that viruses as well as drugs or toxins that damage mitochondria may contribute to increased levels of autoantibodies against nuclear and mitochondrial antigens, which are common in many autoimmune diseases. The purpose of this Review is to summarize our current understanding of mechanisms that may determine sex differences in autoimmune disease.
Functional and dynamic profiling of transcript isoforms reveals essential roles of alternative splicing in interferon response
Authors: Mahoko Takahashi Ueda, Jun Inamo, Fuyuki Miya, Mihoko Shimada, Kensuke Yamaguchi, Yuta Kochi
Journal: Cell Genomics (2024)

Type I interferon (IFN-I) plays an important role in the innate immune response through inducing IFN-I-stimulated genes (ISGs). However, how alternative splicing (AS) events, especially over time, affect their function remains poorly understood. We generated an annotation (113,843 transcripts) for IFN-I-stimulated human B cells called isoISG using high-accuracy long-read sequencing data from PacBio Sequel II/IIe. Transcript isoform profiling using isoISG revealed that isoform switching occurred in the early response to IFN-I so that ISGs would gain functional domains (e.g., C4B) or higher protein production (e.g., IRF3). Conversely, isoforms lacking functional domains increased during the late phase of IFN-I response, mainly due to intron retention events. This suggests that isoform switching both triggers and terminates IFN-I responses at the translation and protein levels. Furthermore, genetic variants influencing the isoform ratio of ISGs were associated with immunological and infectious diseases. AS has essential roles in regulating innate immune response and associated diseases.
Subcutaneous adipose tissue and skeletal muscle mitochondria following weight loss
Authors: Birgitta W van der Kolk, Eija Pirinen, Rachel Nicoll, Kirsi H Pietiläinen, Sini Heinonen
Journal: Trends in Endocrinology and Metabolism (2024)

Obesity is a major global health issue with various metabolic complications. Both bariatric surgery and dieting achieve weight loss and improve whole-body metabolism, but vary in their ability to maintain these improvements over time. Adipose tissue and skeletal muscle metabolism are crucial in weight regulation, and obesity is linked to mitochondrial dysfunction in both tissues. The impact of bariatric surgery versus dieting on adipose tissue and skeletal muscle mitochondrial metabolism remains to be elucidated. Understanding the molecular pathways that modulate tissue metabolism following weight loss holds potential for identifying novel therapeutic targets in obesity management. This narrative review summarizes current knowledge on mitochondrial metabolism following bariatric surgery and diet-induced weight loss in adipose tissue and skeletal muscle, and sheds light on their respective effects.