tbuckley/cabot-search huggingface dataset:
Benefits of In Situ Foamed and Printed Porous Scaffolds in Wound Healing
Authors: Amir Seyedsalehi, Farnoosh Saeedinejad, Steven Toro, Fatemeh Alipanah, Jacob Quint, Tannin A. Schmidt, Mohamadmahdi Samandari, Ali Tamayol
Journal: Advanced Healthcare Materials (2024)

Abstract Macroporous hydrogels have shown significant promise in biomedical applications, particularly regenerative medicine, due to their enhanced nutrient and waste permeability, improved cell permissibility, and minimal immunogenicity. However, traditional methods of generating porous hydrogels require secondary post‐processing steps or harmful reagents making simultaneous fabrication with bioactive factors and cells impossible. Therefore, a handheld printer is engineered for facile and continuous generation and deposition of hydrogel foams directly within the skin defect to form defect‐specific macroporous scaffolds. Within the handheld system, a temperature‐controlled microfluidic homogenizer is coupled with miniaturized liquid and air pumps to mix sterile air with gelatin methacryloyl (GelMA) at the desired ratio. An integrated photocrosslinking unit is then utilized to crosslink the printed foam in situ to form scaffolds with controlled porosity. The system is optimized to form reliable and uniform GelMA foams. The resulting foam scaffolds demonstrate mechanical properties with excellent flexibility making them suitable for wound healing applications. The results of in vitro cell culture on the scaffolds demonstrate significantly increased cellular activity compared to the solid hydrogel. The in vivo printed foam scaffolds enhanced the rate and quality of wound healing in mice with full‐thickness wound without the use of biological materials.
From Nanozymes to Multi‐Purpose Nanomaterials: The Potential of Metal–Organic Frameworks for Proteomics Applications
Authors: Siene Swinnen, Francisco de Azambuja, Tatjana N. Parac‐Vogt
Journal: Advanced Healthcare Materials (2024)

Abstract Metal‐organic frameworks (MOFs) have the potential to revolutionize the biotechnological and medical landscapes due to their easily tunable crystalline porous structure. Herein, the study presents MOFs' potential impact on proteomics, unveiling the diverse roles MOFs can play to boost it. Although MOFs are excellent catalysts in other scientific disciplines, their role as catalysts in proteomics applications remains largely underexplored, despite protein cleavage being of crucial importance in proteomics protocols. Additionally, the study discusses evolving MOF materials that are tailored for proteomics, showcasing their structural diversity and functional advantages compared to other types of materials used for similar applications. MOFs can be developed to seamlessly integrate into proteomics workflows due to their tunable features, contributing to protein separation, peptide enrichment, and ionization for mass spectrometry. This review is meant as a guide to help bridge the gap between material scientists, engineers, and MOF chemists and on the other side researchers in biology or bioinformatics working in proteomics.
Respiratory syncytial virus vaccination and immunoprophylaxis: realising the potential for protection of young children
Authors: Clint Pecenka, Erin Sparrow, Daniel R Feikin, Padmini Srikantiah, Delese Mimi Darko, Eric Karikari-Boateng, Ranju Baral, Carla Vizzotti, Analia Rearte, Rose Jalang'o, Jessica A Fleming, Federico Martinón-Torres, Ruth A Karron
Journal: The Lancet (2024)
Role of N6‐methyladenosine RNA modification in cancer
Authors: Yi Qu, Nannan Gao, Shengwei Zhang, Limin Gao, Bing He, Chao Wang, Chunli Gong, Qiuyue Shi, Zhibin Li, Shiming Yang, Yufeng Xiao
Journal: MedComm (2024)

Abstract N6‐methyladenosine (m6A) is the most abundant modification of RNA in eukaryotic cells. Previous studies have shown that m6A is pivotal in diverse diseases especially cancer. m6A corelates with the initiation, progression, resistance, invasion, and metastasis of cancer. However, despite these insights, a comprehensive understanding of its specific roles and mechanisms within the complex landscape of cancer is still elusive. This review begins by outlining the key regulatory proteins of m6A modification and their posttranslational modifications (PTMs), as well as the role in chromatin accessibility and transcriptional activity within cancer cells. Additionally, it highlights that m6A modifications impact cancer progression by modulating programmed cell death mechanisms and affecting the tumor microenvironment through various cancer‐associated immune cells. Furthermore, the review discusses how microorganisms can induce enduring epigenetic changes and oncogenic effect in microorganism‐associated cancers by altering m6A modifications. Last, it delves into the role of m6A modification in cancer immunotherapy, encompassing RNA therapy, immune checkpoint blockade, cytokine therapy, adoptive cell transfer therapy, and direct targeting of m6A regulators. Overall, this review clarifies the multifaceted role of m6A modification in cancer and explores targeted therapies aimed at manipulating m6A modification, aiming to advance cancer research and improve patient outcomes.
Tunable Hybrid Hydrogels of Alginate and Cell‐Derived dECM to Study the Impact of Matrix Alterations on Epithelial‐to‐Mesenchymal Transition
Authors: P. Barros da Silva, Xiaoyu Zhao, Sílvia J. Bidarra, Diana S. Nascimento, Vernon LaLone, Bianca N. Lourenço, Joana Paredes, Molly M. Stevens, C. C. Barrias
Journal: Advanced Healthcare Materials (2024)

Abstract Epithelial‐to‐mesenchymal transition (EMT) is crucial for tumor progression, being linked to alterations in the extracellular matrix (ECM). Understanding the ECM's role in EMT can uncover new therapeutic targets, yet replicating these interactions in vitro remains challenging. It is shown that hybrid hydrogels of alginate (ALG) and cell‐derived decellularized ECM (dECM), with independently tunable composition and stiffness, are useful 3D‐models to explore the impact of the breast tumor matrix on EMT. Soft RGD‐ALG hydrogels (200 Pa), used as neutral bulk material, supported mammary epithelial cells morphogenesis without spontaneous EMT, allowing to define the gene, protein, and biochemical profiles of cells at different TGFβ1‐induced EMT states. To mimic the breast tumor composition, dECM from TGFβ1‐activated fibroblasts (adECM) are generated, which shows upregulation of tumor‐associated proteins compared to ndECM from normal fibroblasts. Using hybrid adECM‐ALG hydrogels, it is shown that the presence of adECM induces partial EMT in normal epithelial cells, and amplifes TGF‐β1 effects compared to ALG and ndECM‐ALG. Increasing the hydrogel stiffness to tumor‐like levels (2.5 kPa) have a synergistic effect, promoting a more evident EMT. These findings shed light on the complex interplay between matrix composition and stiffness in EMT, underscoring the utility of dECM‐ALG hydrogels as a valuable in vitro platform for cancer research.
Radiogenomics: bridging the gap between imaging and genomics for precision oncology
Authors: Wenle He, Wenhui Huang, Lu Zhang, Xuewei Wu, Shuixing Zhang, Bin Zhang
Journal: MedComm (2024)

Abstract Genomics allows the tracing of origin and evolution of cancer at molecular scale and underpin modern cancer diagnosis and treatment systems. Yet, molecular biomarker‐guided clinical decision‐making encounters major challenges in the realm of individualized medicine, consisting of the invasiveness of procedures and the sampling errors due to high tumor heterogeneity. By contrast, medical imaging enables noninvasive and global characterization of tumors at a low cost. In recent years, radiomics has overcomes the limitations of human visual evaluation by high‐throughput quantitative analysis, enabling the comprehensive utilization of the vast amount of information underlying radiological images. The cross‐scale integration of radiomics and genomics (hereafter radiogenomics) has the enormous potential to enhance cancer decoding and act as a catalyst for digital precision medicine. Herein, we provide a comprehensive overview of the current framework and potential clinical applications of radiogenomics in patient care. We also highlight recent research advances to illustrate how radiogenomics can address common clinical problems in solid tumors such as breast cancer, lung cancer, and glioma. Finally, we analyze existing literature to outline challenges and propose solutions, while also identifying future research pathways. We believe that the perspectives shared in this survey will provide a valuable guide for researchers in the realm of radiogenomics aiming to advance precision oncology.
Leveraging single‐cell RNA‐seq for uncovering naïve B cells associated with better prognosis of hepatocellular carcinoma
Authors: Qingjia Sun, Rui Gao, Yingxin Lin, Xianchao Zhou, Tao Wang, Jian He
Journal: MedComm (2024)

Abstract Hepatocellular carcinoma (HCC) is a typical highly heterogeneous solid tumor with high morbidity and mortality worldwide, especially in China; however, the immune microenvironment of HCC has not been clarified so far. Here, we employed single‐cell RNA sequencing (scRNA‐seq) on diethylnitrosamine (DEN)‐induced mouse HCC model to dissect the immune cell dynamics during tumorigenesis. Our findings reveal distinct immune profiles in both precancerous and cancerous lesions, indicating early tumor‐associated immunological alterations. Notably, specific T and B cell subpopulations are preferentially enriched in the HCC tumor microenvironment (TME). Furthermore, we identified a subpopulation of naïve B cells with high CD83 expression, correlating with improved prognosis in human HCC. These signature genes were validated in The Cancer Genome Atlas HCC RNA‐seq dataset. Moreover, cell interaction analysis revealed that subpopulations of B cells in both mouse and human samples are activated and may potentially contribute to oncogenic processes. In summary, our study provides insights into the dynamic immune microenvironment and cellular networks in HCC pathogenesis, with a specific emphasis on naïve B cells. These findings emphasize the significance of targeting TME in HCC patients to prevent HCC pathological progression, which may give a new perspective on the therapeutics for HCC.
Emapalumab Use in Patients With Rheumatologic Disease–Associated Hemophagocytic Lymphohistiocytosis in the United States: the <scp>REAL</scp>‐<scp>HLH</scp> Study
Authors: Shanmuganathan Chandrakasan, Carl E. Allen, Deepika Bhatla, John Carter, May Chien, Robert Cooper, Lauren Draper, Olive S. Eckstein, Rabi Hanna, J. Allyson Hays, Michelle L. Hermiston, Ashley P. Hinson, Patricia M. Hobday, Michael S. Isakoff, Michael B. Jordan, Jennifer W. Leiding, Renee Modica, Taizo A. Nakano, Abiola Oladapo, Sachit A. Patel, Priti Pednekar, Mona Riskalla, Susmita N. Sarangi, Prakash Satwani, Anand Tandra, Kelly J. Walkovich, John D. Yee, Adi Zoref‐Lorenz, Edward M. Behrens
Journal: Arthritis & Rheumatology (2024)

Rheumatologic disease-associated hemophagocytic lymphohistiocytosis (HLH), a rare, life-threatening, systemic hyperinflammatory syndrome, occurs as a complication of underlying rheumatologic disease. Real-world evidence is lacking on emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon-γ, approved for treating patients with primary HLH.
Long-Term survival across breslow thickness categories: Findings from a Population-Based study of 210,042 Australian melanoma patients
Authors: Serigne N Lo, Gabrielle J Williams, Anne E Cust, Alexander H R Varey, Sydney Ch’ng, Richard A Scolyer, John F Thompson
Journal: JNCI Journal of the National Cancer Institute (2024)

The prognosis of a patient with a primary cutaneous melanoma is known to be related to the Breslow thickness of their tumor. This study sought to determine long-term (30-year) survival rates for the four AJCC 8th Edition T-categories by analyzing Australian registry data for 210,042 melanoma patients diagnosed from 1982-2014. The 30-year incidence rates of death due to melanoma and non-melanoma causes (with 95% confidence intervals) were 7.1% (CI 6.9-7.3%) and 32.8% (CI 32.3-33.3%), respectively. For T2 melanomas, the corresponding rates were 21.6% (CI 21.0-22.3%) and 35.6% (CI 34.7-36.6%), for T3 melanomas 34.2% (CI 33.4-35.1%) and 39.6% (CI 38.5-40.8%), and for T4 melanomas 44.3% (CI 43.2-45.3%) and 39.6% (CI 38.3-41.0%). A plateau in melanoma-related deaths occurred in T4 patients after 20 years but there were ongoing melanoma-related deaths for the other T-categories beyond 30 years. A progressive rise in the risk of death from other causes occurred across all T-categories.
An integrated long-acting implant of clinical safe cells, drug and biomaterials effectively promotes spinal cord repair and restores motor functions
Authors: Liming Li, Jiafu Mu, Jiachen Chen, Tianchen Huang, Yu Zhang, Youzhi Cai, Tianyuan Zhang, Xianglei Kong, Jihong Sun, Xinchi Jiang, Jiahe Wu, Jian Cao, Xunqi Zhang, Fei Huang, Shiqing Feng, Jianqing Gao
Journal: Journal of Controlled Release (2024)
Predictors of long-term clinical outcomes after TIPS: An ALTA group study
Authors: Yael R. Nobel, Justin R. Boike, Nikhilesh R. Mazumder, Bartley Thornburg, Rachel Hoffman, K. Pallav Kolli, Michael Fallon, Jennifer C. Lai, Giuseppi Morelli, Erin K. Spengler, Adnan Said, Archita P. Desai, Sonali Paul, Aparna Goel, Kelly Hu, Catherine Frenette, Dyanna Gregory, Cynthia Padilla, Yuan Zhang, Lisa B. VanWagner, Elizabeth C. Verna
Journal: Hepatology (2024)

Background and Aims: While TIPS is traditionally considered a bridge to liver transplant (LT), some patients achieve long-term transplant-free survival (TFS) with TIPS alone. Prognosis and need for LT should not only be assessed at time of procedure, but also re-evaluated in patients with favorable early outcomes. Approach and Results: Adult recipients of TIPS in the multicenter advancing liver therapeutic approaches retrospective cohort study were included (N=1127 patients; 2040 person-years follow-up). Adjusted competing risk regressions were used to assess factors associated with long-term post-TIPS clinical outcomes at the time of procedure and 6 months post-TIPS. MELD-Na at TIPS was significantly associated with post-TIPS mortality (subdistribution hazards ratio of death 1.1 [ p =0.42], 1.3 [ p =0.04], and 1.7 [ p &lt;0.01] for MELD-Na 15–19, 20–24, and ≥25 relative to MELD-Na &lt;15, respectively). MELD 3.0 was also associated with post-TIPS outcomes. Among the 694 (62%) patients who achieved early (6 mo) post-TIPS TFS, rates of long-term TFS were 88% at 1 year and 57% at 3 years post-TIPS. Additionally, a within-individual increase in MELD-Na score of &gt;3 points from TIPS to 6 months post-TIPS was significantly associated with long-term mortality, regardless of initial MELD-Na score (subdistribution hazards ratio of death 1.8, p &lt;0.01). For patients with long-term post-TIPS TFS, rates of complications of the TIPS or portal hypertension were low. Conclusions: Among patients with early post-TIPS TFS, prognosis and need for LT should be reassessed, informed by postprocedure changes in MELD-Na and clinical status. For selected patients, “destination TIPS” without LT may offer long-term survival with freedom from portal hypertensive complications.
ArboTracker: a multipathogen dashboard and data platform for arbovirus seroprevalence studies
Authors: Mairead G Whelan, Harriet Ware, Himanshu Ranka, Sean Kenny, Sabah Shaikh, Yannik Roell, Shaila Akter, Anabel Selemon, Emilie Toews, May Chu, Niklas Bobrovitz, Rahul K Arora, Thomas Jaenisch
Journal: The Lancet Infectious Diseases (2024)
[89Zr]Zr-girentuximab for PET–CT imaging of clear-cell renal cell carcinoma: a prospective, open-label, multicentre, phase 3 trial
Authors: Brian Shuch, Allan J Pantuck, Jean-Christophe Bernhard, Michael A Morris, Viraj Master, Andrew M Scott, Charles van Praet, Clement Bailly, Bülent Önal, Tamer Aksoy, Robin Merkx, David M Schuster, Sze Ting Lee, Neeta Pandit-Taskar, Alice C Fan, Phillip Allman, Karl Schmidt, Libuse Tauchmanova, Michael Wheatcroft, Christian Behrenbruch, Colin R W Hayward, Peter Mulders
Journal: The Lancet Oncology (2024)
Trends in Racial/Ethnic Disparities in Early Glycemic Control Among Veterans Receiving Care in the Veterans Health Administration, 2008–2019
Authors: Simin Hua, Rania Kanchi, Rebecca Anthopolos, Mark D. Schwartz, Jay Pendse, Andrea R. Titus, Lorna E. Thorpe
Journal: Diabetes Care (2024)

OBJECTIVE Racial/ethnic disparities in glycemic control among non-Hispanic Black (NHB) and non-Hispanic White (NHW) veterans with type 2 diabetes (T2D) have been reported. This study examined trends in early glycemic control by race/ethnicity to understand how disparities soon after T2D diagnosis have changed between 2008 and 2019 among cohorts of U.S. veterans with newly diagnosed T2D. RESEARCH DESIGN AND METHODS We estimated the annual percentage of early glycemic control (average A1C &amp;lt;7%) in the first 5 years after diagnosis among 837,023 veterans (95% male) with newly diagnosed T2D in primary care. We compared early glycemic control by racial/ethnic group among cohorts defined by diagnosis year (2008–2010, 2011–2013, 2014–2016, and 2017–2018) using mixed-effects models with random intercepts. We estimated odds ratios of early glycemic control comparing racial/ethnic groups with NHW, adjusting for age, sex, and years since diagnosis. RESULTS The average annual percentage of veterans who achieved early glycemic control during follow-up was 73%, 72%, 72%, and 76% across the four cohorts, respectively. All racial/ethnic groups were less likely to achieve early glycemic control compared with NHW veterans in the 2008–2010 cohort. In later cohorts, NHB and Hispanic veterans were more likely to achieve early glycemic control; however, Hispanic veterans were also more likely to have an A1C ≥9% within 5 years in all cohorts. Early glycemic control disparities for non-Hispanic Asian, Native Hawaiian/Pacific Islander, and American Indian/Alaska Native veterans persisted in cohorts until the 2017–2018 cohort. CONCLUSIONS Overall early glycemic control trends among veterans with newly diagnosed T2D have been stable since 2008, but trends differed by racial/ethnic groups and disparities in very poor glycemic control were still observed. Efforts should continue to minimize disparities among racial/ethnic groups.
Final Overall Survival Analysis of S1500: A Randomized, Phase II Study Comparing Sunitinib With Cabozantinib, Crizotinib, and Savolitinib in Advanced Papillary Renal Cell Carcinoma
Authors: Pedro Barata, Catherine Tangen, Melissa Plets, Ian M. Thompson, Vivek Narayan, Daniel J. George, Daniel Y.C. Heng, Brian Shuch, Mark Stein, Shuchi Gulati, Maria Tretiakova, Abhishek Tripathi, Georg A. Bjarnason, Peter Humphrey, Adebowale Adeniran, Ulka Vaishampayan, Ajjai Alva, Tian Zhang, Scott Cole, Primo N. Lara, Seth P. Lerner, Naomi Balzer-Haas, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2024)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Mesenchymal-epithelial transition (MET) signaling pathway plays a role in the pathogenesis of selected patients with papillary renal cell carcinoma (PRCC). In the phase II PAPMET trial (ClinicalTrials.gov identifier: NCT02761057 ), cabozantinib significantly prolonged progression-free survival and improved objective response rate compared with sunitinib in patients with advanced PRCC. Here, we present the final overall survival (OS) analysis. In this multicenter, randomized phase II, open-label trial, 147 patients with advanced PRCC who have received up to one previous therapy (excluding vascular endothelial growth factor–directed agents) were assigned to sunitinib, cabozantinib, crizotinib, or savolitinib. Ultimately, savolitinib and crizotinib arms were closed because of futility. With a median follow-up of 17.5 months, the median OS was 21.5 months (95% CI, 12.0 to 28.1) with cabozantinib and 17.3 months (95% CI, 12.8 to 21.8) with sunitinib (hazard ratio, 0.83; 95% CI, 0.51 to 1.36; P = .46). The OS landmark estimates for cabozantinib and sunitinib were 50% versus 39% at 24 months and 32% versus 28% at 36 months. In conclusion, we observed no significant difference in OS across treatment arms. Although cabozantinib represents a well-supported option for advanced PRCC, the lack of survival benefit underscores the need to develop novel therapies for this disease.
Selective targeting of mutated calreticulin by the monoclonal antibody INCA033989 inhibits oncogenic function of MPN
Authors: Edimara Reis, Rebecca Buonpane, Hamza Celik, Caroline Marty, Angela Lei, Fatoumata Jobe, Mark Rupar, Yue Zhang, Darlise DiMatteo, Rahel Awdew, Bianca L Ferreira, Lynn Leffet, Lu Lu, Elodie Rosa, Maxime Evrard, Gaurang Trivedi, Brittney Wass, April Horsey, Xin He, Maryanne B Covington, Alla Volgina, Florence Pasquier, Laurence Legros, Guillemette Fouquet, William Vainchenker, Yan-ou Yang, Breann Barker, Jing Zhou, Shaun Stewart, Ian S Hitchcock, Dashyant Dhanak, Ricardo Macarron, Isabelle Plo, Horacio G Nastri, Patrick A Mayes
Journal: Blood (2024)

Mutations in calreticulin (mutCALR) are the second most common drivers of myeloproliferative neoplasms (MPNs) and yet, the current therapeutic landscape lacks a selective agent for mutCALR-expressing MPNs. Here we show that the monoclonal antibody INCA033989 selectively targets mutCALR-positive cells. INCA033989 antagonized mutCALR-driven signaling and proliferation in engineered cell lines and primary CD34+ cells from patients with MPN. No antibody binding or functional activity was observed in cells lacking mutCALR. In a mouse model of mutCALR-driven MPN, treatment with a INCA033989 mouse surrogate antibody effectively prevented the development of thrombocytosis and accumulation of megakaryocytes in the bone marrow. INCA033989 reduced the pathogenic self-renewal of mutCALR-positive disease-initiating cells in both primary and secondary transplantations, illustrating its disease-modifying potential. In summary, we describe a novel mutCALR-targeted therapy for MPNs, a monoclonal antibody that selectively inhibits the oncogenic function of MPN cells without interfering with normal hematopoiesis.
Multicohort Epigenome-Wide Association Study of All-Cause Cardiovascular Disease and Cancer Incidence
Authors: Arce Domingo-Relloso, Angela L Riffo-Campos, Naisi Zhao, Guillermo Ayala, Karin Haack, Carlos Manterola, Dorothy A Rhoades, Jason G Umans, M Daniele Fallin, Miguel Herreros-Martinez, Marina Pollan, Eric Boerwinkle, Elizabeth A Platz, Miranda R Jones, Jan Bressler, Roby Joehanes, Calen P Ryan, Juan R Gonzalez, Daniel Levy, Daniel W Belsky, Shelley A Cole, Dominique S Michaud, Ana Navas-Acien, Maria Tellez-Plaza
Journal: JACC CardioOncology (2024)
Diverse mechanisms of leukemogenesis associated with PAX5 germline mutation
Authors: Laura Rachele Bettini, Grazia Fazio, Claudia Saitta, Rocco Piazza, Sonia Palamini, Chiara Buracchi, Stefano Rebellato, Nicola Santoro, Cristiano Simone, Andrea Biondi, Giovanni Cazzaniga
Journal: Leukemia (2024)
Are measurable residual disease results after consolidation therapy useful in children with acute lymphoblastic leukemia?
Authors: Janine Stutterheim, Rachella van der Waarden, Hester A de Groot-Kruseman, Edwin Sonneveld, Valérie de Haas, Rana Dandis, C Ellen van der Schoot, Vincent H J van der Velden, Rob Pieters
Journal: Leukemia (2024)