tbuckley/cabot-search huggingface dataset:
Adaptive immune responses are larger and functionally preserved in a hypervaccinated individual
Authors: Katharina Kocher, Carolin Moosmann, Felix Drost, Christine Schülein, Pascal Irrgang, Philipp Steininger, Jahn Zhong, Johannes Träger, Bernd Spriewald, Christoph Bock, Dirk H Busch, Christian Bogdan, Benjamin Schubert, Thomas H Winkler, Matthias Tenbusch, Ev-Marie Schuster, Kilian Schober
Journal: The Lancet Infectious Diseases (2024)
Abstract P07: Identification of the unique preleukemic bone marrow niche in acute myeloid leukemia
Authors: Chinmayee Goda, Rohan Kulkarni, Alexander Rudich, Malith Karunasiri, Yaphet Bustos, Sadie Chidester, Ozlen Balcioglu, Elizabeth AR Garfinkle, Bethany Mundy-Bosse, Elaine R Mardis, Guido Marcucci, Ramiro Garzon, Katherine Miller, Adrienne M Dorrance
Journal: Blood Cancer Discovery (2024)

Abstract Preleukemic stem cells (LSCs) can remain dormant within the bone marrow (BM) for decades before disease onset, suggesting acquisition of mutations within hematopoietic stem/progenitor cells (HSPCs) alone is insufficient for acute myeloid leukemia (AML). It is likely that alterations within BM microenvironment (BMM) also occur due to dysregulated crosstalk with mutant HSCs thus favoring LSC growth over normal HSCs. Uncovering novel mechanisms by which preleukemic LSCs remodel the BMM is critical in understanding therapy resistance and to develop novel therapies targeting aberrant pathways in both the LSCs and cells within the BMM. To address this, we compared cells of the BMM of wildtype (WT) mice to our Mll-PTD;Flt3-ITD mouse model of AML, which has a distinct preleukemic phase. Using single cell RNA-sequencing we identified 17 stromal cell clusters and observed substantial changes in both cell numbers and transcriptional profiles of several key stromal cell subpopulations. Specifically, we found decreases in normal HSC regulatory populations such as LepR+ MSCs and Cdh5+ ECs (2 and 2.7-fold decreases, respectively) and increases in pericytes and fibroblasts in preleukemic BM compared to WT (2.7 and 3.5-fold increase, respectively). Unlike what is observed in full-blown AML, we found an increase in CD55+ fibroblasts resulting from increased proliferation (13% vs 6% cell cycling, P=0.0016). Importantly, co-culture assays found that CD55+ BM fibroblasts expanded LSCs at increased levels over normal HSCs (83+/-7.5 vs 57+/-10.1, P=0.0006). Downregulation of several collagen genes (Col1a1, Col1a2, Col3a1, Col4a1, and Col6a1, P&amp;lt; 0.05) was found in these preleukemic CD55+ fibroblasts, suggesting that remodeling of the extracellular matrix might be an important mechanism by which these CD55+ fibroblast remodel the normal BMM and promote leukemogenesis. Furthermore, sequencing of full-blown leukemic BM niche cells have identified several key differences in the BM architecture, suggesting that the preleukemic BM is indeed distinct from full-blown leukemic BM and is important for disease initiation and progression, and not disease maintenance. Citation Format: Chinmayee Goda, Rohan Kulkarni, Alexander Rudich, Malith Karunasiri, Yaphet Bustos, Sadie Chidester, Ozlen Balcioglu, Elizabeth AR Garfinkle, Bethany Mundy-Bosse, Elaine R Mardis, Guido Marcucci, Ramiro Garzon, Katherine Miller, Adrienne M Dorrance. Identification of the unique preleukemic bone marrow niche in acute myeloid leukemia [abstract]. In: Proceedings of the Blood Cancer Discovery Symposium; 2024 Mar 4-6; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(2_Suppl):Abstract nr P07.
Molecular Pathways Governing the Termination of Liver Regeneration
Authors: Lianne R. de Haan, Rowan F. van Golen, Michal Heger
Journal: Pharmacological Reviews (2024)

<h3>Abstract</h3> The liver has the unique capacity to regenerate, and up to 70% of the liver can be removed without detrimental consequences to the organism. Liver regeneration is a complex process involving multiple signaling networks and organs. Liver regeneration proceeds through three phases: the initiation phase, the growth phase, and the termination phase. Termination of liver regeneration occurs when the liver reaches a liver-to-body weight that is required for homeostasis, the so-called "hepatostat." The initiation and growth phases have been the subject of many studies. The molecular pathways that govern the termination phase, however, remain to be fully elucidated. This review summarizes the pathways and molecules that signal the cessation of liver regrowth after partial hepatectomy and answers the question, "What factors drive the hepatostat?" <h3>Significance Statement</h3> Unraveling the pathways underlying the cessation of liver regeneration enables the identification of druggable targets that will allow us to gain pharmacological control over liver regeneration. For these purposes, it would be useful to understand why the regenerative capacity of the liver is hampered under certain pathological circumstances so as to artificially modulate the regenerative processes (e.g., by blocking the cessation pathways) to improve clinical outcomes and safeguard the patient's life.
Long-Term Autoimmune Inflammatory Rheumatic Outcomes of COVID-19
Authors: Min Seo Kim, Hayeon Lee, Seung Won Lee, Rosie Kwon, Sang Youl Rhee, Jin A. Lee, Ai Koyanagi, Lee Smith, Guillaume Fond, Laurent Boyer, Jinseok Lee, Masoud Rahmati, Ju-Young Shin, Chanyang Min, Jae Il Shin, Dong Keon Yon
Journal: Annals of Internal Medicine (2024)

Background: Some data suggest a higher incidence of diagnosis of autoimmune inflammatory rheumatic diseases (AIRDs) among patients with a history of COVID-19 compared with uninfected patients. However, these studies had methodological shortcomings. Objective: To investigate the effect of COVID-19 on long-term risk for incident AIRD over various follow-up periods. Design: Binational, longitudinal, propensity-matched cohort study. Setting: Nationwide claims-based databases in South Korea (K-COV-N cohort) and Japan (JMDC cohort). Participants: 10 027 506 Korean and 12 218 680 Japanese patients aged 20 years or older, including those with COVID-19 between 1 January 2020 and 31 December 2021, matched to patients with influenza infection and to uninfected control patients. Measurements: The primary outcome was onset of AIRD (per appropriate codes from the International Classification of Diseases, 10th Revision) 1, 6, and 12 months after COVID-19 or influenza infection or the respective matched index date of uninfected control patients. Results: Between 2020 and 2021, among the 10 027 506 Korean participants (mean age, 48.4 years [SD, 13.4]; 50.1% men), 394 274 (3.9%) and 98 596 (0.98%) had a history of COVID-19 or influenza, respectively. After propensity score matching, beyond the first 30 days after infection, patients with COVID-19 were at increased risk for incident AIRD compared with uninfected patients (adjusted hazard ratio, 1.25 [95% CI, 1.18 to 1.31]) and influenza-infected control patients (adjusted hazard ratio, 1.30 [CI, 1.02 to 1.59]). The risk for incident AIRD was higher with more severe acute COVID-19. Similar patterns were observed in the Japanese cohort. Limitations: Referral bias due to the pandemic; residual confounding. Conclusion: SARS-CoV-2 infection was associated with increased risk for incident AIRD compared with matched patients without SARS-CoV-2 infection or with influenza infection. The risk for incident AIRD was higher with greater severity of acute COVID-19. Primary Funding Source: National Research Foundation of Korea.
In adults aged ≥80 y with NSTE-ACS, an invasive vs. conservative strategy improved outcomes at a median 5.3 y
Authors: Harman Yonis, Christopher B. Granger
Journal: Annals of Internal Medicine (2024)

Source CitationBerg ES, Tegn NK, Abdelnoor M, et al; After Eighty Study Investigators. Long-term outcomes of invasive vs conservative strategies for older patients with non-ST-segment elevation acute coronary syndromes. J Am Coll Cardiol. 2023;82:2021-2030. https://pubmed.ncbi.nlm.nih.gov/37968019/AbstractClinical Impact RatingsGIM/FP/GP: Cardiology: Geriatrics:
In subclinical AF, apixaban reduced stroke or systemic embolism but increased major bleeding vs. aspirin at 3.5 y
Authors: Ilya Y. Shadrin, L. Kristin Newby
Journal: Annals of Internal Medicine (2024)

ACP Journal Club5 March 2024In subclinical AF, apixaban reduced stroke or systemic embolism but increased major bleeding vs. aspirin at 3.5 yIlya Y. Shadrin, MD, PhD, L. Kristin Newby, MD, MHSIlya Y. Shadrin, MD, PhDDuke University School of Medicine, Durham, North Carolina, USA (I.Y.S., L.K.N.), L. Kristin Newby, MD, MHSDuke University School of Medicine, Durham, North Carolina, USA (I.Y.S., L.K.N.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/J24-0002 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationHealey JS, Lopes RD, Granger CB, et al; ARTESIA Investigators. Apixaban for stroke prevention in subclinical atrial fibrillation. N Engl J Med. 2024;390:107-117. https://pubmed.ncbi.nlm.nih.gov/37952132Clinical Impact RatingsGIM/FP/GP: Cardiology: References1. Kirchhof P, Toennis T, Goette A, et al; NOAH-AFNET 6 Investigators. Anticoagulation with edoxaban in patients with atrial high-rate episodes. N Engl J Med. 2023;389:1167-1179. [PMID: 37622677] Google Scholar2. Sabbag A, Berkovich A, Raanani E, et al. Subclinical postoperative atrial fibrillation: a randomized trial. Front Cardiovasc Med. 2023;10:1153275. [PMID: 37304958] Google Scholar3. Pepplinkhuizen S, Hoeksema WF, van der Stuijt W, et al. Accuracy and clinical relevance of the single-lead Apple Watch electrocardiogram to identify atrial fibrillation. Cardiovasc Digit Health J. 2022;3:S17-S22. [PMID: 36589758] Google Scholar4. Joglar JA, Chung MK, Armbruster AL, et al. 2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2024;149:e1-e156. [PMID: 38033089] Google Scholar Author, Article, and Disclosure InformationAuthors: Ilya Y. Shadrin, MD, PhD; L. Kristin Newby, MD, MHSAffiliations: Duke University School of Medicine, Durham, North Carolina, USA (I.Y.S., L.K.N.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J24-0002.This article was published at Annals.org on 5 March 2024.ACP Journal Club is editorially independent from Annals of Internal Medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics LatestKeywordsApixabanAspirinAtrial fibrillationClinical trialsEmbolismHemorrhageMedical risk factorsRandomized trialsStroke ePublished: 5 March 2024 Copyright & PermissionsCopyright © 2024 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The role of radiotherapy in immunotherapy strategies in the central nervous system
Authors: Matthew Gallitto, Peter C Pan, Michael D Chan, Michael T Milano, Tony J C Wang
Journal: Neuro-Oncology (2024)

Abstract The clinical efficacy and relative tolerability of adverse effects of immune checkpoint immunotherapy have led to its increasingly routine use in the management of multiple advanced solid malignancies. Radiation therapy (RT) is well-known to have both local and distant immunomodulatory effects, which has led to extensive investigation into the synergism of these 2 therapies. While the central nervous system (CNS) has historically been thought to be a sanctuary site, well-protected by the blood–brain barrier from the effects of immunotherapy, over the last several years studies have shown the benefits of these drugs, particularly in metastatic disease involving the CNS. This review explores current progress and the future of combination therapy with immune checkpoint inhibitors and RT.
Safety and efficacy of phage application in bacterial decolonisation: a systematic review
Authors: Qingqing Fang, Xin Yin, Yanling He, Yan Feng, Linwan Zhang, Huan Luo, Geng Yin, Alan McNally, Zhiyong Zong
Journal: The Lancet Microbe (2024)

Colonisation by bacterial pathogens typically precedes invasive infection and seeds transmission. Thus, effective decolonisation strategies are urgently needed. The literature reports attempts to use phages for decolonisation. To assess the in-vivo efficacy and safety of phages for bacterial decolonisation, we performed a systematic review by identifying relevant studies to assess the in-vivo efficacy and safety of phages for bacterial decolonisation. We searched PubMed, Embase (Ovid), MEDLINE (Ovid), Web of Science, and the Cochrane Library to identify relevant articles published between Jan 1, 1990, and May 12, 2023, without language restrictions. We included studies that assessed the efficacy of phage for bacterial decolonisation in humans or vertebrate animal models. This systematic review is registered with PROSPERO, CRD42023457637. We identified 6694 articles, of which 56 (51 animal studies and five clinical reports) met the predetermined selection criteria and were included in the final analysis. The gastrointestinal tract (n=49, 88%) was the most studied bacterial colonisation site, and other sites were central venous catheters, lung, nose, skin, and urinary tract. Of the 56 included studies, the bacterial load at the colonisation site was reported to decrease significantly in 45 (80%) studies, but only five described eradication of the target bacteria. 15 studies reported the safety of phages for decolonisation. No obvious adverse events were reported in both the short-term and long-term observation period. Given the increasing life-threatening risks posed by bacteria that are difficult to treat, phages could be an alternative option for bacterial decolonisation, although further optimisation is required before their application to meet clinical needs.
Impact of the Breast Cancer Index for Extended Endocrine Decision-Making: First Results of the Prospective BCI Registry Study
Authors: Tara B. Sanft, Jenna Wong, Brandon O’Neal, Natalia Siuliukina, Rachel C. Jankowitz, Mark D. Pegram, Jenny R. Fox, Yi Zhang, Kai Treuner, Joyce A. O’Shaughnessy
Journal: Journal of the National Comprehensive Cancer Network (2024)

The Breast Cancer Index (BCI) test assay provides an individualized risk of late distant recurrence (5-10 years) and predicts the likelihood of benefitting from extended endocrine therapy (EET) in hormone receptor-positive early-stage breast cancer. This analysis aimed to assess the impact of BCI on EET decision-making in current clinical practice.
In adults with stable angina, PCI vs. a placebo procedure reduced angina symptoms at 12 wk
Authors: Chirag Bavishi
Journal: Annals of Internal Medicine (2024)

Source Citation Rajkumar CA, Foley MJ, Ahmed-Jushuf F, et al; ORBITA-2 Investigators. A placebo-controlled trial of percutaneous coronary intervention for stable angina. N Engl J Med. 2023;389:2319-2330. 38015442
Abstract B089: Intratumoral expression analysis of mast cells in high grade serous ovarian cancer
Authors: Julia McAdams, Jasmine Ebott, Payton De La Cruz, Nicole E. James
Journal: Cancer Research (2024)

Abstract Objective: The goal of this study is to examine intratumoral expression and phenotypic changes in mast cells following neoadjuvant chemotherapy (NACT) exposure in high grade serous ovarian cancer (HGSOC). Methods: 37 HGSOC matched pre-and post-NACT patient tumors were stained with a commercially available mast cell hemotoxic-based kit and both intratumoral and stromal mast cells were quantified. Immunohistochemistry was employed to stain for histamine in 19 matched HGSOC patient tumors and mean intensity and integrated optical density was quantified using Image J. Kaplan Meier curve analysis was employed to determine the relationship between mast cells levels and progression-free survival (PFS). Immortalized human mast cells, LUVA were treated with carboplatin and paclitaxel and specific genomic changes were measured by quantitative PCR (qPCR). Results. Mast cells were more prominently expressed in intraepithelial regions compared to stromal cells, however both populations were significantly (p&amp;lt;0.05) increased following NACT. Total mast cells stratified by upper and lower quartile demonstrated that higher levels were significantly (p&amp;lt;0.05) associated with improved PFS. Furthermore, histamine, a marker of mast cell degranulation was significantly (p&amp;lt;0.05) increased in HGSOC tumors post-NACT and significantly correlated (r=0.553, p=0.013) with the change in total mast cells. Following chemotherapy treatment LUVA cells demonstrated an over 7-fold increase in amphiregulin (AREG) expression (p&amp;lt;0.01), a key marker of mast cell activation. Interestingly, angiogenic and pro-tumorigenic factors IL-10, IL-8, and VEGFA exhibited no significant differences in expression following chemotherapy exposure. Conclusions: Overall, our findings suggest a correlation in NACT exposure and intratumoral mast cell recruitment, degranulation, and activation. Further studies include investigating differences in specific tumorigenic genes and cell signaling pathways in mast cells pre- and post- NACT, as well as determining if mast cells can impact HGSOC chemotherapy response. Citation Format: Julia McAdams, Jasmine Ebott, Payton De La Cruz, Nicole E. James. Intratumoral expression analysis of mast cells in high grade serous ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B089.
Temporal Effects of Safflower Oil Diet-Based Linoleic Acid Supplementation on Barth Syndrome Cardiomyopathy
Authors: Siting Zhu, Jing Pang, Anh Nguyen, Changming Tan, Alexandria Tso, Tiana Huynh, Yusu Gu, Asa B. Gustafsson, Frédéric M. Vaz, Sylvia M. Evans, Xi Fang
Journal: Circulation (2024)
Why we should not mistake accuracy of medical AI for efficiency
Authors: Karin Rolanda Jongsma, Martin Sand, Megan Milota
Journal: npj Digital Medicine (2024)

In the medical literature, promising results regarding accuracy of medical AI are presented as claims for its potential to increase efficiency. This elision of concepts is misleading and incorrect. First, the promise that AI will reduce human workload rests on a too narrow assessment of what constitutes workload in the first place. Human operators need new skills and deal with new responsibilities, these systems need an elaborate infrastructure and support system that all contribute to an increased amount of human work and short-term efficiency wins may become sources of long-term inefficiency. Second, for the realization of increased efficiency, the human-side of technology implementation is determinate. Human knowledge, competencies and trust can foster or undermine efficiency. We conclude that is important to remain conscious and critical about how we talk about expected benefits of AI, especially when referring to systemic changes based on single studies.
Abstract B096: Targeting RNA splicing factor RBM39 improves therapy responses in ovarian high-grade serous carcinoma
Authors: Yuewei Xu, Sarah Spear, Yurui Ma, Marc Lorentzen, Michael Gruet, Flora McKinney, Yitao Xu, Chiharu Wickremesinghe, Iain McNeish, Hector Keun, Anke Nijhuis
Journal: Cancer Research (2024)

Abstract Ovarian high-grade serous carcinoma (HGSC) is the most common subtype of ovarian cancer with limited therapeutic options and poor prognosis. In recent years, PARP inhibitors have demonstrated significant clinical benefits, especially in patients with BRCA1/2 mutations. However, acquired drug resistance and relapse is a major challenge. Indisulam (E7070) has been identified as a molecular glue that brings together splicing factor RBM39 and DCAF15 E3 ubiquitin ligase resulting in polyubiquitination, degradation and subsequent RNA splicing defects. We demonstrate that RBM39 degradation results in large scale mis-splicing events that are enriched for DNA damage repair genes, including BRCA1, RAD51 and ATM. These events lead to a reduction of these targets at protein level, aberrant cell cycle progression and replication fork stalling. The treatment with indisulam leads to increased sensitivity to platinum and PARP inhibitors in-vitro as well as improved responses to olaparib in mice bearing PARP inhibitor-resistant tumors. In summary, our work demonstrates that combining RBM39 degrading molecular glues with PARP inhibitors is a promising therapeutic approach to improve PARP inhibitor response in ovarian HGSC. Citation Format: Yuewei Xu, Sarah Spear, Yurui Ma, Marc Lorentzen, Michael Gruet, Flora McKinney, Yitao Xu, Chiharu Wickremesinghe, Iain McNeish, Hector Keun, Anke Nijhuis. Targeting RNA splicing factor RBM39 improves therapy responses in ovarian high-grade serous carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B096.
Abstract B063: Vascular senescence associated cell migration inducing hyaluronidase-1 production promotes ovarian cancer migration and tumorigenesis
Authors: Asha Kumari, Peyton Clark, Mehri Monavarian, Liz Quintero Macias, Rebecca Arend, Camilla Margaroli, Mary Kathryn Sewell Loftin, Mythreye Karthikeyan
Journal: Cancer Research (2024)

Abstract Ovarian cancer is the most lethal gynecological cancer, typically diagnosed at advanced stages in post-menopausal women. The ovaries, which are a metastatic site of tumor growth for all ovarian cancers, are subjected to rapid changes in the vasculature upon the onset of menopause. Notably, we find that onset of menopause stimulates tumor growth in the ovaries, a key organ site involved in multiple ovarian cancers. In a corollary manner, vasculature is a primary therapeutic target for the management of advanced ovarian cancers indicating the significance of tumor angiogenesis in diseases progression and metastasis. Given the association between aging, endothelial senescence and angiogenesis, and our findings on the in vivo effect of menopause on tumor burden, we hypothesized that pre-existing senescent endothelial cells in ovaries as a result of follicle regression serve as a chemoattractant for tumor cells into the ovary leading to increased ovarian cancer cell migration and tumor growth. Using unbiased proteomics in conjunction with a novel 3D microphysiolological system along with studies using the ID8p53-/-ovarian cancer models we defined the effects of vascular senescence on ovarian tumor burden. We also identified cell migration inducing hyaluronidase 1 (CEMIP-1) as a vascular senescence factor. Notably, we observed that CEMIP is present in exosomes and regulates tumor cell migration and tumor burden changes in ovarian cancer models. Our findings demonstrate an active role for the changes in the ovarian vasculature with age, mediated potentially via cell migration inducing hyaluronidase 1 (CEMIP). Citation Format: Asha Kumari, Peyton Clark, Mehri Monavarian, Liz Quintero Macias, Rebecca Arend, Camilla Margaroli, Mary Kathryn Sewell Loftin, Mythreye Karthikeyan. Vascular senescence associated cell migration inducing hyaluronidase-1 production promotes ovarian cancer migration and tumorigenesis [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B063.