tbuckley/cabot-search huggingface dataset:
Proteogenomic analysis reveals cytoplasmic sequestration of RUNX1 by the acute myeloid leukemia–initiating CBFB::MYH11 oncofusion protein
Authors: Ryan B. Day, Julia A. Hickman, Ziheng Xu, Casey D.S. Katerndahl, Francesca Ferraro, Sai Mukund Ramakrishnan, Petra Erdmann-Gilmore, Robert W. Sprung, Yiling Mi, R. Reid Townsend, Christopher A. Miller, Timothy J. Ley
Journal: Journal of Clinical Investigation (2023)

Several canonical translocations produce oncofusion genes that can initiate Acute Myeloid Leukemia (AML). Although each translocation is associated with unique features, the mechanisms responsible remain unclear. While proteins interacting with each oncofusion are known to be relevant for how they act, these interactions have not yet been systematically defined. To address this issue in an unbiased fashion, we fused a promiscuous biotin ligase ("TurboID") in-frame with three favorable-risk acute myeloid leukemia (AML) oncofusion cDNAs (PML::RARA, RUNX1::RUNX1T1, and CBFB::MYH11), and identified their interacting proteins in primary murine hematopoietic cells. The PML::RARA- and RUNX1::RUNX1T1-TurboID fusion proteins labeled common and unique nuclear repressor complexes, implying their nuclear localization. However, CBFB::MYH11-TurboID interacting proteins were largely cytoplasmic, probably due to an interaction of the MYH11 domain with several cytoplasmic myosin-related proteins. Using a variety of methods, we showed that the CBFB domain of CBFB::MYH11 sequesters RUNX1 in cytoplasmic aggregates; these findings were confirmed in primary human AML cells. Paradoxically, CBFB::MYH11 expression was associated with increased RUNX1/2 expression, suggesting the presence of a sensor for reduced functional RUNX1 protein, and a feedback loop that that may attempt to compensate by increasing RUNX1/2 transcription. These findings may have broad implications for AML pathogenesis.
Protein-centric omics analysis reveals circulating complements linked to non-viral liver diseases as potential therapeutic targets
Authors: Yingzhou Shi, Hang Dong, Shiwei Sun, Xiaoqin Wu, Jiansong Fang, Jianbo Zhao, Junming Han, Zongyue Li, Huixiao Wu, Luna Liu, Wanhong Wu, Yang Tian, Guandou Yuan, Xiude Fan, Chao Xu
Journal: Clinical and Molecular Hepatology (2023)

Background/Aims: To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets.Methods: We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases. A complement-centric protein interaction network was constructed to explore biological functions and identify potential therapeutic options.Results: In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 1.018–1.244), while complement factor H-related protein 5 (CFHR5) was positively associated with the risk of primary sclerosing cholangitis (PSC;1.193, 1.048– 1.357). On the other hand, CFHR1 (0.621, 0.497–0.776) and CFHR2 (0.824, 0.703–0.965) were inversely associated with the risk of alcohol-related cirrhosis. There were also significant inverse associations between C8 gamma chain (C8G) and PSC (0.832, 0.707–0.979), as well as the risk of metabolic dysfunction-associated steatotic liver disease (1.167, 1.036–1.314). Additionally, C1S (0.111, 0.018–0.672), C7 (1.631, 1.190–2.236), and CFHR2 (1.279, 1.059–1.546) were significantly associated with the risk of hepatocellular carcinoma. Proteins from the complement regulatory networks and various liver diseaserelated proteins share common biological processes. Furthermore, potential therapeutic drugs for various liver diseases were identified through drug repurposing based on the complement regulatory network.Conclusions: Our study suggests that certain complement components, including C1S, C1QC, CFHR1, CFHR2, CFHR5, C7, and C8G, might play a role in non-viral liver diseases and could be potential targets for drug development.
The Arylamine N-Acetyltransferases as Therapeutic Targets in Metabolic Diseases Associated with Mitochondrial Dysfunction
Authors: Chandra Choudhury, Melinder K. Gill, Courtney E. McAleese, Neville J. Butcher, Shyuan T. Ngo, Frederik J. Steyn, Rodney F. Minchin
Journal: Pharmacological Reviews (2023)

In humans, there are two arylamine N-acetyltransferase genes that encode functional enzymes (<i>NAT1</i> and <i>NAT2</i>) as well as one pseudogene, all of which are located together on chromosome 8. While they were first identified by their role in the acetylation of drugs and other xenobiotics, recent studies have shown strong associations for both enzymes in a variety of diseases including cancer, cardiovascular disease, and diabetes. There is growing evidence that this association may be causal. Consistently, NAT1 and NAT2 are shown to be required for healthy mitochondrial. This review discusses the current literature on the role of both NAT1 and NAT2 in mitochondrial bioenergetics. It will attempt to relate our understanding of the evolution of the two genes with biological function and then present evidence that several major metabolic diseases are influenced by NAT1 and NAT2. Finally, it will discuss current and future approaches to inhibit or enhance NAT1 and NAT2 activity/expression using small molecule drugs. <b>Significance Statement</b> The arylamine N-acetyltransferases, NAT1 and NAT2, share common features in their associations with mitochondrial bioenergetics. Together, they are potential drug targets for diseases where mitochondrial dysfunction is a hallmark of onset and progression.
PATH-HHT, a Double-Blind, Randomized, Placebo-Controlled Trial in Hereditary Hemorrhagic Telangiectasia Demonstrates That Pomalidomide Reduces Epistaxis and Improves Quality of Life
Authors: Hanny Al-Samkari, Raj S. Kasthuri, Vivek Iyer, Allyson M Pishko, Jake E Decker, Kevin J Whitehead, Miles B Conrad, Clifford Weiss, Joseph Parambil, Marc Stuart Zumberg, Jenny Y Zhou, Holly C Boyer, Vernon R Sutton, Marshall Mazepa, Lauren Bradley, Marianne S. Clancy, Lisa Wisniewski, Benjamin Carper, Diane Catellier, Sonia M Thomas, Keith R. McCrae
Journal: Blood (2023)
Reduced Intensity Haploidentical Bone Marrow Transplantation in Adults with Severe Sickle Cell Disease: BMT CTN 1507
Authors: Adetola A. Kassim, Mark C. Walters, Mary Eapen, Nicole Ritzau, Madoc Smith, Melhem M. Solh, Christopher McKinney, Michael Nieder, Maureen Ross, Michael Kent, Ghada Abusin, Kanwaldeep K. Mallhi, Jorge Galvez Silva, Paul Shaughnessy, Julie Kanter, Hilary Haines, Rafic J Farah, Yasser Khaled, Allistair Abraham, Catherine M. Bollard, Kenneth R. Cooke, Josu de La Fuente, Rabi Hanna, Mary M. Horowitz, Lori C Jordan, Lakshmanan Krishnamurti, Eric Leifere, Kris Michael Mahadeo, Shalini Shenoy, Nicole M. Ritzau, Michael R. DeBaun, Robert A. Brodsky
Journal: Blood (2023)
Revumenib Monotherapy in Patients with Relapsed/Refractory <i>KMT2Ar</i> Acute Leukemia: Topline Efficacy and Safety Results from the Pivotal Augment-101 Phase 2 Study
Authors: Ibrahim Aldoss, Ghayas C. Issa, Michael Thirman, John DiPersio, Martha Arellano, James S. Blachly, Gabriel N. Mannis, Alexander Perl, David S. Dickens, Christine M. McMahon, Elie Traer, C. Michel Zwaan, Carolyn Grove, Richard Stone, Paul J. Shami, Ioannis Mantzaris, Matthew Greenwood, Neerav Shukla, Branko Cuglievan, Yu Gu, Rebecca G. Bagley, Kate Madigan, Soujanya Sunkaraneni, Huy Van Nguyen, Nicole McNeer, Eytan M. Stein
Journal: Blood (2023)
Phase 3 Randomized Study of Daratumumab (DARA) + Bortezomib, Lenalidomide, and Dexamethasone (VRd) Versus Vrd Alone in Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) Who Are Eligible for Autologous Stem Cell Transplantation (ASCT): Primary Results of the Perseus Trial
Authors: Pieter Sonneveld, Meletios A. Dimopoulos, Mario Boccadoro, Hang Quach, P. Joy Ho, Meral Beksac, Cyrille Hulin, Elisabetta Antonioli, Xavier Leleu, Silvia Mangiacavalli, Aurore Perrot, Michele Cavo, Angelo Belotti, Annemiek Broijl, Francesca Gay, Roberto Mina, Inger S. Nijhof, Niels W.C.J van de Donk, Eirini Katodritou, Fredrik Schjesvold, Anna Sureda Balari, Laura Rosiñol, Michel Delforge, Wilfried Roeloffzen, Tobias Silzle, Annette Vangsted, Hermann Einsele, Andrew Spencer, Roman Hajek, Artur Jurczyszyn, Sarah Lonergan, Tahamtan Ahmadi, Yanfang Liu, Jianping Wang, Diego Vieyra, Emilie M.J. van Brummelen, Veronique Vanquickelberghe, Anna Sitthi-Amorn, Carla J. de Boer, Robin Carson, Paula Rodríguez Otero, Joan Bladé, Philippe Moreau
Journal: Blood (2023)
ERG Is a New Predisposition Gene for Bone Marrow Failure and Hematological Malignancy
Authors: Hamish S Scott, Jiarna Zerella, Claire Homan, Peer Arts, Steve Lin, Sam J Spinelli, Milena Babic, Peter J Brautigan, Lynda Truong, Luis Arriola-Martinez, Parvathy Venugopal, Simone K Feurstein, Lise Larcher, Flore Sicre De Fontbrune, Serwet Demirdas, Sonja De Munnik, Hélène Poirel, Benedicte Brichard, Sara Dobbins, Pim Mutsaers, Desiree S DeMille, Josue Flores-Daboub, Michael W Drazer, Alison Crawford, Julie McCarrier, Donald G Basel, Kerry Phillips, Nicola K Poplawski, Graeme Birdsey, Daniela Pirri, Pia Ostergaard, Annet Simons, Lucy Godley, David M. Ross, Devendra Hiwase, Jean Soulier, Anna Brown, Catherine Carmichael, Christopher N. Hahn
Journal: Blood (2023)
Ibrutinib Combined with Venetoclax in Patients with Relapsed/Refractory Mantle Cell Lymphoma: Primary Analysis Results from the Randomized Phase 3 Sympatico Study
Authors: Michael Wang, Wojciech Jurczak, Marek Trněný, David Belada, Tomasz Wrobel, Nilanjan Ghosh, Mary-Margaret Keating, Tom van Meerten, Ruben Fernandez Alvarez, Gottfried von Keudell, Catherine Thieblemont, Frederic Peyrade, Marc Andre, Marc Hoffmann, Edith Szafer Glusman, Jennifer Lin, James P. Dean, Jutta K. Neuenburg, Constantine S. Tam
Journal: Blood (2023)
Postoperative Radiation Therapy for Thymic Carcinoma: An Analysis of the International Thymic Malignancy Interest Group/European Society of Thoracic Surgeons Database
Authors: Andreas Rimner, Usman Ahmad, Stephanie M. Lobaugh, Zhigang Zhang, Annemarie F. Shepherd, James Huang, Alberto Antonicelli, Nicolas Girard, Bernhard Moser, Pierluigi Filosso, Marco Lucchi, Edith M. Marom, Anja Roden, Frank Detterbeck, Enrico Ruffini, Charles B. Simone
Journal: Journal of Thoracic Oncology (2023)

R0 resection and radiation therapy have been associated with improved overall survival (OS) in patients with thymic carcinoma (TC). Here, we analyzed which subgroups of patients derive the greatest benefit from postoperative radiation therapy (PORT).
Sketch-based semantic retrieval of medical images
Authors: Kazuma Kobayashi, Lin Gu, Ryuichiro Hataya, Takaaki Mizuno, Mototaka Miyake, Hirokazu Watanabe, Masamichi Takahashi, Yasuyuki Takamizawa, Yukihiro Yoshida, Satoshi Nakamura, Nobuji Kouno, Amina Bolatkan, Yusuke Kurose, Tatsuya Harada, Ryuji Hamamoto
Journal: Medical Image Analysis (2023)

The volume of medical images stored in hospitals is rapidly increasing; however, the utilization of these accumulated medical images remains limited. Existing content-based medical image retrieval (CBMIR) systems typically require example images, leading to practical limitations, such as the lack of customizable, fine-grained image retrieval, the inability to search without example images, and difficulty in retrieving rare cases. In this paper, we introduce a sketch-based medical image retrieval (SBMIR) system that enables users to find images of interest without the need for example images. The key concept is feature decomposition of medical images, which allows the entire feature of a medical image to be decomposed into and reconstructed from normal and abnormal features. Building on this concept, our SBMIR system provides an easy-to-use two-step graphical user interface: users first select a template image to specify a normal feature and then draw a semantic sketch of the disease on the template image to represent an abnormal feature. The system integrates both types of input to construct a query vector and retrieves reference images. For evaluation, ten healthcare professionals participated in a user test using two datasets. Consequently, our SBMIR system enabled users to overcome previous challenges, including image retrieval based on fine-grained image characteristics, image retrieval without example images, and image retrieval for rare cases. Our SBMIR system provides on-demand, customizable medical image retrieval, thereby expanding the utility of medical image databases.
Telehealth Mindfulness-Oriented Recovery Enhancement vs Usual Care in Individuals With Opioid Use Disorder and Pain
Authors: Nina A. Cooperman, Shou-En Lu, Adam W. Hanley, Thanusha Puvananayagam, Patricia Dooley-Budsock, Anna Kline, Eric L. Garland
Journal: JAMA Psychiatry (2023)

Methadone treatment (MT) fails to address the emotion dysregulation, pain, and reward processing deficits that often drive opioid use disorder (OUD). New interventions are needed to address these factors.
A multicenter single‐arm trial of neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2‐positive breast cancer
Authors: Qiyun Shi, Xiaowei Qi, Peng Tang, Linjun Fan, Li Chen, Shushu Wang, Yan Liang, Ying Hu, Minghao Wang, Lin Ren, Guozhi Zhang, Xuanni Tan, Long Yuan, Junze Du, Xiujuan Wu, Mengyuan Wang, Hongying Che, Pengwei Lv, Dejie Chen, Jinhui Hu, Qiuyun Li, Yanwu Zhang, Kunxian Yang, Yuan Zhong, Chuang Chen, Zemin Zhou, Liyuan Qian, Jingwei Zhang, Mingde Ma, Yi Sun, Yi Zhang, Jun Jiang
Journal: MedComm (2023)

Abstract The objective of this multicenter, single‐arm trial (ChiCTR1900022293) was to explore the efficacy and safety of neoadjuvant therapy with epirubicin, cyclophosphamide, and pyrotinib followed by docetaxel, trastuzumab, and pyrotinib (ECPy‐THPy) in the treatment of patients with stage II–III HER2‐positive breast cancer. The present study enrolled patients with stage II–III HER2‐positive breast cancer. Epirubicin and cyclophosphamide were administrated for four 21‐day cycles, followed by four cycles of docetaxel and trastuzumab. Pyrotinib was taken orally once per day throughout the treatment period. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0) rate in the modified intention‐to‐treat (mITT) population. In total, 175 patients were included. The tpCR rate was 68.6% (95% CI, 60.7–75.8%), while the objective response rate was 89.1%. In the post‐hoc subgroup analysis, no association between clinical characteristics and the tpCR rate was observed. The most common grade ≥3 adverse events were diarrhea (54.3%), followed by white blood cell count decreased (5.1%), and neutrophil count decreased (4.6%). In conclusion, the neoadjuvant regimen with ECPy‐THPy showed promising pathological response and clinical benefits with an acceptable safety profile in patients with stage II–III HER2‐positive breast cancer.
Receptor tyrosine kinases: biological functions and anticancer targeted therapy
Authors: Nan Zhang, Yongsheng Li
Journal: MedComm (2023)

Abstract Receptor tyrosine kinases (RTKs) are a class of protein kinases that play crucial roles in various cellular processes, including cell migration, morphological differentiation, cell growth, and angiogenesis. In humans, 58 RTKs have been identified and categorized into 20 distinct families based on the composition of their extracellular regions. RTKs are primarily activated by specific ligands that bind to their extracellular region. They not only regulate tumor transformation, proliferation, metastasis, drug resistance, and angiogenesis, but also initiate and maintain the self‐renewal and cloning ability of cancer stem cells. Accurate diagnosis and grading of tumors with dysregulated RTKs are essential in clinical practice. There is a growing body of evidence supporting the benefits of RTKs‐targeted therapies for cancer patients, and researchers are actively exploring new targets and developing targeted agents. However, further optimization of RTK inhibitors is necessary to effectively target the diverse RTK alterations observed in human cancers. This review provides insights into the classification, structure, activation mechanisms, and expression of RTKs in tumors. It also highlights the research advances in RTKs targeted anticancer therapy and emphasizes their significance in optimizing cancer diagnosis and treatment strategies.
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration
Authors: Honglin Xiang, Weikang Zhao, Ke Jiang, Jiangtao He, Lu Chen, Wenguo Cui, Yuling Li
Journal: Bioactive Materials (2023)

Intervertebral disc degeneration (IVDD) is rising worldwide and leading to significant health issues and financial strain for patients. Traditional treatments for IVDD can alleviate pain but do not reverse disease progression, and surgical removal of the damaged disc may be required for advanced disease. The inflammatory microenvironment is a key driver in the development of disc degeneration. Suitable anti-inflammatory substances are critical for controlling inflammation in IVDD. Several treatment options, including glucocorticoids, non-steroidal anti-inflammatory drugs, and biotherapy, are being studied for their potential to reduce inflammation. However, anti-inflammatories often have a short half-life when applied directly and are quickly excreted, thus limiting their therapeutic effects. Biomaterial-based platforms are being explored as anti-inflammation therapeutic strategies for IVDD treatment. This review introduces the pathophysiology of IVDD and discusses anti-inflammatory therapeutics and the components of these unique biomaterial platforms as comprehensive treatment systems. We discuss the strengths, shortcomings, and development prospects for various biomaterials platforms used to modulate the inflammatory microenvironment, thus providing guidance for future breakthroughs in IVDD treatment.
Nrf2/PHB2 alleviates mitochondrial damage and protects against <i>Staphylococcus aureus</i>‐induced acute lung injury
Authors: Si‐Hao Jin, Jiao‐Jiao Sun, Gang Liu, Li‐Juan Shen, Yuan Weng, Jin‐You Li, Min Chen, Ying‐Ying Wang, Zhi‐Qi Gao, Feng‐Juan Jiang, Sheng‐Peng Li, Dan Chen, Qing‐Feng Pang, Ya‐Xian Wu, Zhi‐Qiang Wang
Journal: MedComm (2023)

(SA) is a major cause of sepsis, leading to acute lung injury (ALI) characterized by inflammation and oxidative stress. However, the role of the Nrf2/PHB2 pathway in SA-induced ALI (SA-ALI) remains unclear. In this study, serum samples were collected from SA-sepsis patients, and a SA-ALI mouse model was established by grouping WT and Nrf2
T Follicular Helper Cell Heterogeneity
Authors: Wenzhi Song, Joe Craft
Journal: Annual Review of Immunology (2023)

T follicular helper (Tfh) cells specialize in helping B cells and are therefore critical contributors to the generation of humoral immunity. Tfh cells aid immunoglobulin class-switch recombination and support the germinal center response, thereby promoting immunoglobulin affinity maturation and the generation of humoral immune memory. Although their primary function is to promote B cell responses, Tfh cells also display phenotypic and functional diversity determined by the immunological and spatial contexts from which they emerge. We review recent advances in understanding the heterogeneity within Tfh cell subsets along with their differentiation and migratory trajectory, the phenotypes they adopt, their ontological relationships with one another, and their function in their respective environments.
The next step in hyperhidrosis evaluation: Hyperhidrosis Quality of Life Index (HidroQol©) scores
Authors: Flora Balieva
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof The next step in hyperhidrosis evaluation: Hyperhidrosis Quality of Life Index (HidroQol©) scores Get access Flora Balieva Flora Balieva Conceptualization, Resources, Writing - original draft, Writing - review & editing Department of Dermatology, Helse Stavanger HF, Stavanger, NorwayDepartment of Public Health, University of Stavanger, Stavanger, Norway Email: floranicol@gmail.com https://orcid.org/0000-0002-1939-2142 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad485, https://doi.org/10.1093/bjd/ljad485 Published: 08 December 2023 Article history Received: 25 November 2023 Accepted: 27 November 2023 Published: 08 December 2023 Corrected and typeset: 23 January 2024
Genomic characterisation of respiratory syncytial virus: a novel system for whole genome sequencing and full-length G and F gene sequences
Authors: María Iglesias-Caballero, Sara Camarero-Serrano, Sarai Varona, Vicente Mas, Cristina Calvo, María Luz García, Juan García-Costa, Sonia Vázquez-Morón, Sara Monzón, Albert Campoy, Isabel Cuesta, Francisco Pozo, Inmaculada Casas
Journal: Eurosurveillance (2023)

To advance our understanding of respiratory syncytial virus (RSV) impact through genomic surveillance, we describe two PCR-based sequencing systems, (i) RSVAB-WGS for generic whole-genome sequencing and (ii) RSVAB-GF, which targets major viral antigens, G and F, and is used as a complement for challenging cases with low viral load. These methods monitor RSV genetic diversity to inform molecular epidemiology, vaccine effectiveness and treatment strategies, contributing also to the standardisation of surveillance in a new era of vaccines.