tbuckley/cabot-search huggingface dataset:
Predisposal of Interferon Regulatory Factor 1 Deficiency to Accumulate <scp>DNA</scp> Damage and Promote Osteoarthritis Development in Cartilage
Authors: Yongsik Cho, Hyeonkyeong Kim, Geunho Yook, Sangmin Yong, Soy Kim, Narae Lee, Yi‐Jun Kim, Jin‐Hee Kim, Tae Woo Kim, Moon Jong Chang, Kyoung Min Lee, Chong Bum Chang, Seung‐Baik Kang, Jin‐Hong Kim
Journal: Arthritis & Rheumatology (2024)

Interferon regulatory factor 1 (IRF1) is a transcriptional regulator conventionally associated with immunomodulation. Recent molecular analyses mapping DNA binding sites of IRF1 have suggested its potential function in DNA repair. However, the physiologic significance of this noncanonical function remains unexplored. Here, we investigated the role of IRF1 in osteoarthritis (OA), a condition marked by senescence and chronic joint inflammation.
Impact of hemodilution on flow cytometry based measurable residual disease assessment in acute myeloid leukemia
Authors: Jesse M. Tettero, Maaike E. Heidinga, Tim R. Mocking, Glenn Fransen, Angèle Kelder, Willemijn J. Scholten, Alexander N. Snel, Lok Lam Ngai, Costa Bachas, Arjan A. van de Loosdrecht, Gert J. Ossenkoppele, David C. de Leeuw, Jacqueline Cloos, Jeroen J. W. M. Janssen
Journal: Leukemia (2024)

Measurable residual disease (MRD) measured in the bone marrow (BM) of acute myeloid leukemia (AML) patients after induction chemotherapy is an established prognostic factor. Hemodilution, stemming from peripheral blood (PB) mixing within BM during aspiration, can yield false-negative MRD results. We prospectively examined hemodilution by measuring MRD in BM aspirates obtained from three consecutive 2 mL pulls, along with PB samples. Our results demonstrated a significant decrease in MRD percentages between the first and second pulls (P = 0.025) and between the second and third pulls (P = 0.025), highlighting the impact of hemodilution. Initially, 39% of MRD levels (18/46 leukemia-associated immunophenotypes) exceeded the 0.1% cut-off, decreasing to 30% (14/46) in the third pull. Additionally, we assessed the performance of six published methods and parameters for distinguishing BM from PB samples, addressing or compensating for hemodilution. The most promising results relied on the percentages of CD16dim granulocytic population (scarce in BM) and CD117
Alterations in chromosome 1q in multiple myeloma randomized clinical trials: a systematic review
Authors: Karun Neupane, Gliceida Galarza Fortuna, Riyasha Dahal, Timothy Schmidt, Rafael Fonseca, Rajshekhar Chakraborty, Kelly Ann Koehn, Meera Mohan, Hira Mian, Luciano J. Costa, Douglas Sborov, Ghulam Rehman Mohyuddin
Journal: Blood Cancer Journal (2024)

Abstract Extra copies of chromosome 1q21 (+1q: gain = 3 copies, amp &gt;= 4 copies) are associated with worse outcomes in multiple myeloma (MM). This systematic review assesses the current reporting trends of +1q, the efficacy of existing regimens on +1q, and its prognostic implications in MM randomized controlled trials (RCTs). Pubmed, Embase and Cochrane Registry of RCTs were searched from January 2012 to December 2022. Only MM RCTs were included. A total of 124 RCTs were included, of which 29 (23%) studies reported on +1q. Among them, 10% defined thresholds for +1q, 14% reported survival data separately for gain and amp, and 79% considered +1q a high-risk cytogenetic abnormality. Amongst RCTs that met the primary endpoint showing improvement in progression free survival (PFS), lenalidomide maintenance (Myeloma XI), selinexor (BOSTON), and isatuximab (IKEMA and ICARIA) were shown to improve PFS for patients with evidence of +1q. Some additional RCT’s such as Myeloma XI+ (carfilzomib), ELOQUENT-3 (elotuzumab), and HOVON-65/GMMG-HD4 (bortezomib) met their endpoint showing improvement in PFS and also showed improvement in PFS in the +1q cohort, although the confidence interval crossed 1. All six studies that reported HR for +1q patients vs. without (across both arms) showed worse OS and PFS for +1q. There is considerable heterogeneity in the reporting of +1q. All interventions that have shown to be successful in RCTs and have clearly reported on the +1q subgroup have shown concordant direction of results and benefit of the applied intervention. A more standardized approach to reporting this abnormality is needed.
Collagen in the central nervous system: contributions to neurodegeneration and promise as a therapeutic target
Authors: Lauren K. Wareham, Robert O. Baratta, Brian J. Del Buono, Eric Schlumpf, David J. Calkins
Journal: Molecular Neurodegeneration (2024)

Abstract The extracellular matrix is a richly bioactive composition of substrates that provides biophysical stability, facilitates intercellular signaling, and both reflects and governs the physiological status of the local microenvironment. The matrix in the central nervous system (CNS) is far from simply an inert scaffold for mechanical support, instead conducting an active role in homeostasis and providing broad capacity for adaptation and remodeling in response to stress that otherwise would challenge equilibrium between neuronal, glial, and vascular elements. A major constituent is collagen, whose characteristic triple helical structure renders mechanical and biochemical stability to enable bidirectional crosstalk between matrix and resident cells. Multiple members of the collagen superfamily are critical to neuronal maturation and circuit formation, axon guidance, and synaptogenesis in the brain. In mature tissue, collagen interacts with other fibrous proteins and glycoproteins to sustain a three-dimensional medium through which complex networks of cells can communicate. While critical for matrix scaffolding, collagen in the CNS is also highly dynamic, with multiple binding sites for partnering matrix proteins, cell-surface receptors, and other ligands. These interactions are emerging as critical mediators of CNS disease and injury, particularly regarding changes in matrix stiffness, astrocyte recruitment and reactivity, and pro-inflammatory signaling in local microenvironments. Changes in the structure and/or deposition of collagen impact cellular signaling and tissue biomechanics in the brain, which in turn can alter cellular responses including antigenicity, angiogenesis, gliosis, and recruitment of immune-related cells. These factors, each involving matrix collagen, contribute to the limited capacity for regeneration of CNS tissue. Emerging therapeutics that attempt to rebuild the matrix using peptide fragments, including collagen-enriched scaffolds and mimetics, hold great potential to promote neural repair and regeneration. Recent evidence from our group and others indicates that repairing protease-degraded collagen helices with mimetic peptides helps restore CNS tissue and promote neuronal survival in a broad spectrum of degenerative conditions. Restoration likely involves bolstering matrix stiffness to reduce the potential for astrocyte reactivity and local inflammation as well as repairing inhibitory binding sites for immune-signaling ligands. Facilitating repair rather than endogenous replacement of collagen degraded by disease or injury may represent the next frontier in developing therapies based on protection, repair, and regeneration of neurons in the central nervous system.
Bi- and Tri-specific antibodies in non-Hodgkin lymphoma: current data and perspectives
Authors: Iman Abou Dalle, Remy Dulery, Nour Moukalled, Laure Ricard, Nicolas Stocker, Jean El-Cheikh, Mohamad Mohty, Ali Bazarbachi
Journal: Blood Cancer Journal (2024)

Abstract Bispecific antibodies (BsAbs) are a new group of targeted therapies that are revolutionizing the treatment landscape of B-cell non-Hodgkin’s lymphoma (B-NHL). In the relapsed/refractory setting, salvage chemotherapy and autologous stem cell transplantation are capable of curing 50% of patients, whereas the other half will have a dismal outcome with a median overall survival of less than 12 months. This unmet need reinforced the importance of innovative therapies like the BsAbs and CAR-T cell therapies. In this review, we delve into BsAbs in B-NHL from the preclinical development to clinical data in both refractory and frontline settings, and then discuss future perspectives.
Genetics and pathologic landscape of lineage switch of acute leukemia during therapy
Authors: Ting Zhou, Choladda V. Curry, Mahsa Khanlari, Min Shi, Wei Cui, Deniz Peker, Weina Chen, Endi Wang, Juehua Gao, Qi Shen, Wei Xie, Fatima Z. Jelloul, Rebecca L. King, Ji Yuan, Xiaoqiong Wang, Chen Zhao, Ifeyinwa E. Obiorah, Elizabeth L. Courville, Eric Nomura, Sindhu Cherian, Mina L. Xu, W. Richard Burack, Hong-xing Liu, Elias J. Jabbour, Koichi Takahashi, Wei Wang, Sa A. Wang, Joseph D. Khoury, L. Jeffrey Medeiros, Shimin Hu
Journal: Blood Cancer Journal (2024)

Table 1.Clinicopathologic features of patients with lineage-switching leukemia.Case # Sex Age at acute #1 Dx of acute #1 Tx of acute #1 Dz status of acute #1 at dx of acute #2 Dx of acute #2 Interval from acute #1 to #2 Tx of acute #2 Pt status at last F/U Dz status of acute #1 at last F/U Dz status of acute #2 at last F/U identify patients for whom the benefits outweigh the side effects Table 1.
Enhancement of Omicron-specific immune responses following bivalent COVID-19 booster vaccination in patients with chronic lymphocytic leukaemia
Authors: Thomas Roberts, Grace Uwenedi, Rachel Bruton, Graham McIlroy, Sarah Damery, Panagiota Sylla, Nicola Logan, Sam Scott, May Lau, Ahmed Elzaidi, Siobhan Plass, Soumyajit Mallick, Katie Spencer, Christine Stephens, Christopher Bentley, Guy Pratt, Jianmin Zuo, Shankara Paneesha, Brian Willett, Paul Moss, Helen Parry
Journal: Blood Cancer Journal (2024)
Beneath the radar: immune-evasive cell sources for stroke therapy
Authors: Beatriz Achón Buil, Nora H. Rentsch, Rebecca Z. Weber, Chiara Rickenbach, Stefanie J. Halliday, Akitsu Hotta, Christian Tackenberg, Ruslan Rust
Journal: Trends in Molecular Medicine (2024)

Stem cell therapy is an emerging treatment paradigm for stroke patients with remaining neurological deficits. While allogeneic cell transplants overcome the manufacturing constraints of autologous grafts, they can be rejected by the recipient's immune system, which identifies foreign cells through the human leukocyte antigen (HLA) system. The heterogeneity of HLA molecules in the human population would require a very high number of cell lines, which may still be inadequate for patients with rare genetic HLAs. Here, we outline key progress in genetic HLA engineering in pluripotent stem and derived cells to evade the host's immune system, reducing the number of allogeneic cell lines required, and examine safety measures explored in both preclinical studies and upcoming clinical trials.
Nickel’s carcinogenicity: the need of more studies to progress
Authors: Consolato M. Sergi
Journal: Military Medical Research (2024)

On March 8-15, 2022, a board of international scientists assembled in Lyon to evaluate the carcinogenicity of cobalt metal, cobalt(II) salts, antimony trioxide, and weapons-grade tungsten alloy harboring nickel and cobalt [1].The 131st International Agency for Research on Cancer (IARC) Monograph is the result of a 6-9month work of perusing the literature, slide evaluation, data interpretation, and interim meetings.The assessment of cobalt, antimony, and nickel-containing alloys will have tremendous consequences for the industry, health, and defense departments [1].Armor-penetrating projectiles utilize tungsten alloys of weapons-grade quality, consisting of 91-93% tungsten, 2-4% cobalt, and 3-5% nickel.Inhalation of hazardous substances can occur because of occupational exposure in weapons production.Both military personnel and civilians may encounter nickel-containing metal aerosols that are generated during the firing or impact of weapons.Long-term exposure to residual embedded fragments from munitions can pose significant hazards.The available exposure data were limited, nevertheless, the
A Laparoscopically Compatible Rapid‐Adhesion Bioadhesive for Asymmetric Adhesion, Non‐Pressing Hemostasis, and Seamless Seal
Authors: Yueying Yang, Jiaxin Wang, Jiashen Yang, Xiaoyu Wu, Ye Tian, Hanchuan Tang, Na Li, Xurui Liu, Mengyuan Zhou, Jihong Liu, Qing Ling, Jianfeng Zang
Journal: Advanced Healthcare Materials (2024)

Abstract Bioadhesive hydrogels offer unprecedented opportunities in hemostatic agents and tissue sealing; however, the application of existing bioadhesive hydrogels through narrow spaces to achieve strong adhesion in fluid‐rich physiological environments is challenged either by undesired indiscriminate adhesion or weak wet tissue adhesion. Here, a laparoscopically compatible asymmetric adhesive hydrogel (aAH) composed of sprayable adhesive hydrogel powders and injectable anti‐adhesive glue is proposed for hemostasis and to seal the bloody tissues in a non‐pressing way, allowing for preventing postoperative adhesion. The powders can seed on the irregular bloody wound to rapidly absorb interfacial fluid, crosslink, and form an adhesive hydrogel to hemostatic seal (blood clotting time and tissue sealing in 10 s, ≈200 mm Hg of burst pressure in sealed porcine tissues). The aAH can be simply formed by crosslinking the upper powder with injectable glue to prevent postoperative adhesion (adhesive strength as low as 1 kPa). The aAH outperforms commercial hemostatic agents and sealants in the sealing of bleeding organs in live rats, demonstrating superior anti‐adhesive efficiency. Further, the hemostatic seamless sealing by aAH succeeds in shortening the time of warm ischemia, decreasing the blood loss, and reducing the possibility of rebleeding in the porcine laparoscopic partial nephrectomy model.
Plasma Matrix Metalloproteinase Concentrations and Risk of Interstitial Lung Disease in a Prospective Rheumatoid Arthritis Cohort
Authors: Brent A. Luedders, Austin M. Wheeler, Dana P. Ascherman, Joshua F. Baker, Michael J. Duryee, Yangyuna Yang, Punyasha Roul, Katherine D. Wysham, Paul Monach, Andreas Reimold, Gail S. Kerr, Gary Kunkel, Grant W. Cannon, Jill A. Poole, Geoffrey M. Thiele, Ted R. Mikuls, Bryant R. England
Journal: Arthritis & Rheumatology (2024)

Objective To evaluate the associations of plasma matrix metalloproteinases (MMPs) with prevalent and incident interstitial lung disease (ILD) in people with rheumatoid arthritis (RA). Methods Within a multicenter, prospective cohort of US veterans with RA, we performed a cross‐sectional study of prevalent ILD and cohort study of incident ILD. ILD diagnoses were validated by medical record review of provider diagnoses and chest imaging and/or pathology reports. MMP‐1, 3, 7, and 9 concentrations were measured in plasma samples, then standardized and categorized into quartiles. The associations of MMPs with prevalent and incident ILD were assessed with logistic (prevalent) and Cox (incident) regression models adjusted for RA‐ILD risk factors. Results Among 2,312 participants (88.9% male; mean age 63.8 years), 96 had prevalent ILD. Incident ILD developed in 130 participants over 17,378 person‐years of follow‐up (crude incidence rate 7.5/1,000 person‐years). Participants with the highest quartile of MMP‐7 concentrations had a nearly four‐fold increased odds of prevalent ILD (adjusted odds ratio 3.78 [95% confidence interval (95% CI) 1.86–7.65]) and over two‐fold increased risk of incident ILD (adjusted hazard ratio 2.33 [95% CI 1.35–4.02]). Higher MMP‐9 concentrations were also associated with prevalent and incident ILD, as well as negatively correlated with forced vital capacity among those with prevalent ILD ( r = −0.30, P = 0.005). Conclusion MMP‐7 and MMP‐9 were strongly associated with both prevalent and incident ILD in this large, multicenter RA cohort after adjustment for other RA‐ILD risk factors. These population‐level findings further support a potential pathogenic role for MMPs in RA‐ILD and suggest that their measurement could facilitate RA‐ILD risk stratification.
<scp>CCL19</scp>‐Positive Lymph Node Stromal Cells Govern the Onset of Inflammatory Arthritis via Tropomyosin Receptor Kinase
Authors: Fabian Schälter, Vugar Azizov, Michael Frech, Kerstin Dürholz, Eva Schmid, Anna Hendel, Ilann Sarfati, Yuichi Maeda, Maria Sokolova, Ippei Miyagawa, Kristin Focke, Kerstin Sarter, Lisa G. M. van Baarsen, Stefan Krautwald, Georg Schett, Mario M. Zaiss
Journal: Arthritis & Rheumatology (2024)

The study objective was to assess the role of CCL19
Integration of implantable device therapy in patients with heart failure. A clinical consensus statement from the <scp>Heart Failure Association</scp> (<scp>HFA</scp>) and <scp>European Heart Rhythm Association</scp> (<scp>EHRA</scp>) of the <scp>European Society of Cardiology</scp> (<scp>ESC</scp>)
Authors: Wilfried Mullens, Jeroen Dauw, Finn Gustafsson, Alexandre Mebazaa, Jan Steffel, Klaus K. Witte, Victoria Delgado, Cecilia Linde, Kevin Vernooy, Stefan D. Anker, Ovidiu Chioncel, Davor Milicic, Gerd Hasenfuß, Piotr Ponikowski, Ralph Stephan von Bardeleben, Friedrich Koehler, Frank Ruschitzka, Kevin Damman, Ehud Schwammenthal, Jeffrey M. Testani, Faiez Zannad, Michael Böhm, Martin R. Cowie, Kenneth Dickstein, Tiny Jaarsma, Gerasimos Filippatos, Maurizio Volterrani, Thomas Thum, Stamatis Adamopoulos, Alain Cohen‐Solal, Brenda Moura, Amina Rakisheva, Arsen Ristic, Antoni Bayes‐Genis, Sophie Van Linthout, Carlo Gabriele Tocchetti, Gianluigi Savarese, Hadi Skouri, Marianna Adamo, Offer Amir, Mehmet Birhan Yilmaz, Maggie Simpson, Mariya Tokmakova, Arantxa González, Massimo Piepoli, Petar Seferovic, Marco Metra, Andrew J.S. Coats, Giuseppe M.C. Rosano
Journal: European Journal of Heart Failure (2024)
Efficacy and safety of <scp>CDR132L</scp> in patients with reduced left ventricular ejection fraction after myocardial infarction: Rationale and design of the <scp>HF‐REVERT</scp> trial
Authors: Johann Bauersachs, Scott D. Solomon, Stefan D. Anker, Isabel Antorrena‐Miranda, Sandor Batkai, Janika Viereck, Steffen Rump, Gerasimos Filippatos, Ulrich Granzer, Piotr Ponikowski, Rudolf A. de Boer, Orly Vardeny, Wilfried Hauke, Thomas Thum
Journal: European Journal of Heart Failure (2024)

Aim Inhibition of microRNA (miR)‐132 effectively prevents and reverses adverse cardiac remodelling, making it an attractive heart failure (HF) target. CDR132L, a synthetic antisense oligonucleotide selectively blocking pathologically elevated miR‐132, demonstrated beneficial effects on left ventricular (LV) structure and function in relevant preclinical models, and was safe and well tolerated in a Phase 1b study in stable chronic HF patients. Patients with acute myocardial infarction (MI) and subsequent LV dysfunction and remodelling have limited therapeutic options, and may profit from early CDR132L treatment. Methods The HF‐REVERT (Phase 2, multicenter, randomized, parallel, 3‐arm, placebo‐controlled Study to Assess Efficacy and Safety of CDR132L in Patients with Reduced Left Ventricular Ejection Fraction after Myocardial Infarction) evaluates the efficacy and safety of CDR132L in HF patients post‐acute MI ( n = 280), comparing the effect of 5 and 10 mg/kg CDR132L, administered as three single intravenous doses 28 days apart, in addition to standard of care. Key inclusion criteria are the diagnosis of acute MI, the development of systolic dysfunction (LV ejection fraction ≤45%) and elevated N‐terminal pro‐B‐type natriuretic peptide. The study consists of a 6‐month double‐blinded treatment period with the primary endpoint LV end‐systolic volume index and relevant secondary endpoints, followed by a 6‐month open‐label observation period. Conclusion The HF‐REVERT trial may underpin the concept of miR‐132 inhibition to prevent or reverse cardiac remodelling in post‐MI HF. The results will inform the design of subsequent outcome trials to test CDR132L in HF.
Adoptive cellular therapy after hematopoietic stem cell transplantation
Authors: Pongthep Vittayawacharin, Piyanuch Kongtim, Yaya Chu, Carl H. June, Catherine M. Bollard, Stefan O. Ciurea
Journal: American Journal of Hematology (2024)

Effective cellular therapy using CD19 chimeric antigen receptor T-cells for the treatment of advanced B-cell malignancies raises the question of whether the administration of adoptive cellular therapy (ACT) posttransplant could reduce relapse and improve survival. Moreover, several early phase clinical studies have shown the potential beneficial effects of administration of tumor-associated antigen-specific T-cells and natural killer cells posttransplant for high-risk patients, aiming to decrease relapse and possibly improve survival. In this article, we present an in-depth review of ACT after transplantation, which has the potential to significantly improve the efficacy of this procedure and revolutionize this field.
C5 inhibition with eculizumab prevents thrombotic microangiopathy in a case series of pig-to-human kidney xenotransplantation
Authors: Maggie E. Jones-Carr, Huma Fatima, Vineeta Kumar, Douglas J. Anderson, Julie Houp, Jackson C. Perry, Gavin A. Baker, Leigh McManus, Andrew J. Shunk, Paige M. Porrett, Jayme E. Locke
Journal: Journal of Clinical Investigation (2024)
<i>B. thetaiotaomicron</i> -derived acetic acid modulate immune microenvironment and tumor growth in hepatocellular carcinoma
Authors: Hongbin Ma, Liang Yang, Yingchao Liang, Fenghua Liu, Jinxiang Hu, Rui Zhang, Yong Li, Lei Yuan, Feiling Feng
Journal: Gut Microbes (2024)

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, and emerging evidence suggests that the gut microbiota may play a role in its development and progression. In this study, the association between B. thetaiotaomicron, a gut microbiota species, and HCC recurrence, as well as patient clinical outcomes, was investigated. It was observed that B. thetaiotaomicron-derived acetic acid has the potential to modulate the polarization of pro-pro-inflammatory macrophagess, which promotes the function of cytotoxic CD8+ T cells. The increased biosynthesis of fatty acids was implicated in the modulation of pro-inflammatory macrophages polarization by B. thetaiotaomicron-derived acetic acid. Furthermore, B. thetaiotaomicron-derived acetic acid was found to facilitate the transcription of ACC1, a key enzyme involved in fatty acid biosynthesis, through histone acetylation modification in the ACC1 promoter region. Curcumin, an acetylation modification inhibitor, significantly blocked the inhibitory effects of B. thetaiotaomicron and acetic acid on HCC tumor growth. These findings highlight the potential role of gut microbiota-derived acetic acid in HCC recurrence and patient clinical outcomes, and suggest a complex interplay between gut microbiota, immune modulation, fatty acid metabolism, and epigenetic regulation in the context of HCC development. Further research in this area may provide insights into novel strategies for HCC prevention and treatment by targeting the gut microbiota and its metabolites.