tbuckley/cabot-search huggingface dataset:
Odronextamab monotherapy in R/R DLBCL after progression with CAR T-cell therapy: Primary analysis of the ELM-1 study
Authors: Max S. Topp, Matthew J. Matasar, John N. Allan, Stephen M. Ansell, Jeffrey A. Barnes, Jon E. Arnason, Jean-Marie Michot, Neta Goldschmidt, Susan M. O'Brien, Uri Abadi, Irit Avivi, Yuan Cheng, Dina M. Flink, Min Zhu, Jurriaan Brouwer-Visser, Aafia Chaudhry, Hesham Mohamed, Srikanth Ambati, Jennifer L. Crombie
Journal: Blood (2024)

Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) progressing after chimeric antigen receptor T-cell therapy (CAR T) have dismal outcomes. The prespecified post-CAR T expansion cohort of the ELM-1 study investigated the efficacy and safety of odronextamab, a CD20×CD3 bispecific antibody, in patients with disease progression after CAR T. Sixty patients received IV odronextamab weekly for 4 cycles followed by maintenance until progression. The primary endpoint was objective response rate (ORR) by independent central review. The median number of prior lines of therapy was 3 (range 2-9), 71.7% were refractory to CAR T, and 48.3% relapsed within 90 days of CAR T. After a median follow-up of 16.2 months, ORR and complete response (CR) rate were 48.3% and 31.7%, respectively. Responses were similar across prior CAR T products and time to relapse on CAR T. Median duration of response was 14.8 months and median duration of CR was not reached. Median progression-free survival and overall survival were 4.8 months and 10.2 months, respectively. The most common treatment-emergent adverse event was cytokine release syndrome (48.3%; no Grade ≥3 events). No cases of immune effector cell-associated neurotoxicity syndrome were reported. Grade ≥3 infections occurred in 12 patients (20.0%), two of which were COVID-19. Odronextamab monotherapy demonstrated encouraging efficacy and generally manageable safety, supporting its potential as an off-the-shelf option for post-CAR T patients. This trial was registered at www.clinicaltrials.gov as #NCT02290951.
Inflammation and mechanical force‐induced bone remodeling
Authors: Hyeran Helen Jeon, Xin Huang, Leticia Rojas Cortez, Puttipong Sripinun, Jung‐me Lee, Julie J. Hong, Dana T. Graves
Journal: Periodontology 2000 (2024)

Periodontitis arises from imbalanced host-microbe interactions, leading to dysbiosis and destructive inflammation. The host's innate and adaptive immune responses produce pro-inflammatory mediators that stimulate destructive events, which cause loss of alveolar bone and connective tissue attachment. There is no consensus on the factors that lead to a conversion from gingivitis to periodontitis, but one possibility is the proximity of the inflammation to the bone, which promotes bone resorption and inhibits subsequent bone formation during coupled bone formation. Conversely, orthodontic tooth movement is triggered by the mechanical force applied to the tooth, resulting in bone resorption on the compression side and new bone formation on the tension side. However, the environment around orthodontic brackets readily retains dental plaque and may contribute to inflammation and bone remodeling. The immune, epithelial, stromal, endothelial and bone cells of the host play an important role in setting the stage for bone remodeling that occurs in both periodontitis and orthodontic tooth movement. Recent advancements in single-cell RNA sequencing have provided new insights into the roles and interactions of different cell types in response to challenges. In this review, we meticulously examine the functions of key cell types such as keratinocytes, leukocytes, stromal cells, osteocytes, osteoblasts, and osteoclasts involved in inflammation- and mechanical force-driven bone remodeling. Moreover, we explore the combined effects of these two conditions: mechanical force-induced bone remodeling combined with periodontal disease (chronic inflammation) and periodontally accelerated osteogenic orthodontics (acute transient inflammation). This comprehensive review enhances our understanding of inflammation- and mechanical force-induced bone remodeling.
Iron, lipid peroxidation and ferroptosis play pathogenic roles in atherosclerosis
Authors: Swetha Jinson, Ziyang Zhang, Graeme I Lancaster, Andrew J Murphy, Pooranee K Morgan
Journal: Cardiovascular Research (2024)

Oxidation of lipids, excessive cell death and iron deposition are prominent features of human atherosclerotic plaques. While extensive research has established the detrimental roles of lipid oxidation and apoptosis in atherosclerosis development, the involvement of iron in atherogenesis is not yet fully understood. With the emergence of an iron-dependent form of cell death termed ferroptosis, new attention has been brought to the complex interplay among iron, ferroptosis and atherosclerosis. Mechanistically, ferroptosis is caused by the lethal accumulation of iron-mediated lipid peroxides. Emerging studies have underscored ferroptosis as a contributor to worsened atherosclerosis. Herein, we review the evidence that oxidative damage and iron overload in the context of atherosclerosis may promote ferroptosis within plaques. Furthermore, we summarize recent findings of lipid peroxidation, thereby potentially ferroptosis, in various plaque cell types-such as endothelial cells, macrophages, dendritic cells, T cells, and vascular smooth muscle cells-across different stages of atherosclerosis. Understanding how these processes influence atherosclerotic plaque progression may permit targeting stage-dependent ferroptosis in each cell population and could provide a rationale for developing cell type-specific intervention strategies to mitigate atherogenic ferroptosis effectively.
Ellagic acid-protein nano-complex inhibits tumor growth by reducing the intratumor bacteria and inhibiting histamine production
Authors: Bingbing Wu, Chenlu Yao, Heng Wang, Huaxing Dai, Bo Tian, Dongxiao Li, Jialu Xu, Haibo Cheng, Fang Xu, Dongdong Sun, Chao Wang
Journal: Biomaterials (2024)
How I Manage Patients with Unexplained Cytopenia
Authors: Luca Malcovati, Mario Cazzola
Journal: Blood (2024)

The term "unexplained cytopenia" is used to describe a condition characterized by peripheral blood (PB) cytopenia that cannot be attributed to identifiable causes using conventional tests or to any concomitant diseases. Unexplained cytopenia requires clinical attention and further investigation to identify individuals at risk of developing a hematologic neoplasm. The available evidence suggests that somatic mutation analysis may effectively complement the diagnostic work-up and clinical management of unexplained cytopenia. Indeed, the presence or absence of somatic mutation(s) in myeloid genes shows high positive and negative predictive values for myeloid neoplasms (MN). Mutation analysis is also crucial for identifying patients with clonal cytopenia of undetermined significance (CCUS), a condition at increased risk of developing a MN. Recently, clinical/molecular prognostic models have been developed, providing valuable tools for the personalization of clinical and molecular surveillance. Most patients with CCUS show mild cytopenia and do not require therapeutic intervention. Currently, there is no treatment approved for CCUS, and transfusion therapy is the sole therapeutic option for patients with severe symptomatic cytopenia. However, this field has been emerging as a domain of active clinical investigation. This article presents four case studies of patients with unexplained cytopenia, which hematologists may encounter in their clinical practice.
Core-shell vector-mediated co-delivery of CRISPR/Cas9 system and hydrophobic drugs against triple-negative breast cancer stem cells
Authors: Tong Wang, Tianyi Chen, Dazhao Li, Xiaoxing Hang, Shuangshuang Zhang, Han Yi, Tianyue Jiang, Dawei Ding, Xuenong Zhang
Journal: Journal of Controlled Release (2025)
Interpretation and classification of FBN1 variants associated with Marfan syndrome: consensus recommendations from the Clinical Genome Resource’s FBN1 variant curation expert panel
Authors: A. Drackley, C. Somerville, P. Arnaud, L. M. Baudhuin, N. Hanna, M. L. Kluge, K. Kotzer, C. Boileau, L. Bronicki, B. Callewaert, A. Cecchi, H. Dietz, D. Guo, S. Harris, O. Jarinova, M. Lindsay, L. Little, B. Loeys, G. MacCarrick, J. Meester, D. Milewicz, T. Morisaki, H. Morisaki, D. Murdock, M. Renard, J. Richer, L. Robert, M. Ouzounian, L. Van Laer, J. De Backer, L. Muiño-Mosquera
Journal: Genome Medicine (2024)
Triple Combination of MEK, BET, and CDK Inhibitors Significantly Reduces Human Malignant Peripheral Nerve Sheath Tumors in Mouse Models
Authors: Sara Ortega-Bertran, Juana Fernández-Rodríguez, Miriam Magallón-Lorenz, Xiaohu Zhang, Edgar Creus-Bachiller, Adriana Paola Diazgranados, Itziar Uriarte-Arrazola, Helena Mazuelas, Ignacio Blanco, Claudia Valverde, Meritxell Carrió, Alberto Villanueva, Thomas De Raedt, Cleofé Romagosa, Bernat Gel, Héctor Salvador, Marc Ferrer, Conxi Lázaro, Eduard Serra
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive soft tissue sarcoma that develops sporadically or in Neurofibromatosis type 1 patients. Its development is marked by the inactivation of specific tumor suppressor genes (TSGs): NF1, CDKN2A and SUZ12EED (Polycomb Repressor Complex 2). Each TSG loss can be targeted by particular drug inhibitors and we aimed to systematically combine these inhibitors, guided by TSG inactivation status, to test their precision medicine potential for MPNSTs. Experimental Design: We performed a high-throughput screening in three MPNST cell lines testing 14 MEK (MEKi), 11 CDK4/6 (CDKi) and 3 bromodomain (BETi) inhibitors as single agents and 147 pair-wise co-treatments. Best combinations were validated in 9 MPNST cell lines and three were tested in one sporadic and one NF1-associated patient-derived orthotopic xenograft (PDOX) MPNST mouse models. A final combination of the three inhibitor classes was tested in the same PDOX models. Results: A high degree of redundancy was observed in the effect of compounds of the same inhibitory class, individually or in combination, and responses matched with TSG inactivation status. The MEKi-BETi (Arry-162+I-BET151) co-treatment triggered reduction of half of the NF1-related MPNST-PDOXs, and all the sporadic tumors, reaching 65% reduction in tumor volume in the latter. Remarkably, this reduction was further increased in both models combining the three inhibitor classes, reaching 85% shrinkage on average in the sporadic MPNST. Conclusions: Our results strongly support precision therapies for MPNSTs guided by TSG inactivation status. MEKi-BETi-CDKi triple treatment elicits a significant reduction of human MPNST PDOX.
Activity and safety of avelumab in high-grade neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas progressive after chemotherapy (AveNEC trial)
Authors: Christian Fottner, Leonidas Apostolidis, Sebastian Krug, Anja Rinke, Barbara Grün, Patrick Michl, Thomas M. Gress, Daniel-Christoph Wagner, Wilfried Roth, Esther Mettler, Jana Topsch, Christian Ruckes, Peter R. Galle, Mathias M. Weber
Journal: Clinical Cancer Research (2024)

Abstract Background: Neuroendocrine neoplasias grade 3 (NEN G3) are rare tumors with poor prognosis and no established second-line therapy. The role of immune checkpoint blockade in these aggressive tumors remains unclear. Methods: The phase II AVENEC study evaluated the effect of avelumab (AVE, 10 mg/kg IV Q2W) in 60 patients with well-differentiated high-grade neuroendocrine tumors (NET G3, N=22) or poorly differentiated neuroendocrine carcinomas (NEC, N=38) progressing after ≥ one prior chemotherapy (excluding Merkel cell and small-cell lung cancer). Results: The best overall response according to iRECIST was partial response (PR) in 3 (5%) and stable disease (SD) in 9 (15%) patients, with a disease control rate at 16 weeks of 15% (3 PR, 6 SD), and a median duration of response of 4.3 months. Six patients (10%) achieved SD or PR for &amp;gt; 6 months and two for &amp;gt; one year. Response rates were similar regardless of differentiation, Ki67 expression, or primary localization. The median progression-free survival (PFS) was 1.9 months and overall survival (OS) was 6.6 months. After a median follow-up of 3.6 years, only four (7%) patients were still alive. One- and two-year survival rates were 33% and 17%, respectively. Responders had significantly longer OS of 30.2 months compared to 4.8 months in non-responders. AVE was well tolerated, with few treatment-related grade 3/4 adverse events, and quality of life remained stable during treatment. Conclusions: In patients with progressive high-grade NEN G3, avelumab was well tolerated and provided disease control with significant clinical benefit in 15% of heavily pretreated patients.
Prognostic and therapeutic implications of measurable residual disease levels during remission induction of childhood ALL
Authors: Weina Zhang, Jiaoyang Cai, Xiang Wang, Yani Ma, Xiaofan Zhu, Jie Yu, Peifang Xiao, Ju Gao, Yongjun Fang, Changda Liang, Xue Li, Fen Zhou, Xiaowen Zhai, Xiaoxiao Xu, Xin Tian, Aiguo Liu, Ningling Wang, Jiashi Zhu, Lingzhen Wang, Frankie Wai Tsoi Cheng, Liangchun Yang, Ge Zhang, Cheng Cheng, Jun J. Yang, Shuhong Shen, Chi-kong Li, Benshang Li, Hua Jiang, Ching-Hon Pui
Journal: Blood (2024)
Targeting Enterobacter cloacae attenuates osteolysis by reducing ammonium in multiple myeloma
Authors: Qin Yang, Yinghong Zhu, Xingxing Jian, Yi Qiu, Yan Zhu, Lia Zhao, Yanjuan He, Gang An, Lugui Qiu, Jiaojiao Guo, Nihan He, Huerxidan Abudumijiti, Cong Hu, Xun Chen, Siqing Huang, Xiangling Feng, Xin Li, Jing Liu, Yajing Xu, Wen Zhou
Journal: Blood (2024)

Multiple myeloma (MM)-induced bone disease affects not only patients' quality of life but also their overall survival. Our previous work demonstrated that the gut microbiome plays a crucial role in MM progression and drug resistance. However, the role of altered gut microbiota in MM bone disease remains unclear. In this study, we show that intestinal E. cloacae is significantly enriched in MM patients with osteolysis. Through fecal microbial transplantation and single bacterial colonization experiments in a 5TGM1 MM mouse model, we found that intestinal colonization of E. cloacae promotes osteolysis by increasing circulating ammonium levels. Elevated ammonium promotes osteoclastogenesis by increasing Trap protein levels in osteoclast precursors and by acetylating and stabilizing CCL3 protein in MM cells. Inhibition of ammonium synthesis, using E. cloacae with a deleted dcd gene, along with probiotic supplementation, alleviated osteolysis in MM. Overall, our work suggests that E. cloacae promotes osteolysis in MM by synthesizing ammonium. This establishes a novel mechanism and potential intervention strategy for managing MM with osteolysis.
A field resource for the glioma cerebrospinal fluid proteome: impacts of resection and location on biomarker discovery
Authors: Cecile Riviere-Cazaux, Christopher J Graser, Arthur E Warrington, Matthew D Hoplin, Katherine M Andersen, Noor Malik, Elizabeth A Palmer, Lucas P Carlstrom, Surendra Dasari, Amanda Munoz-Casabella, Samar Ikram, Keyvan Ghadimi, Benjamin T Himes, Ignacio Jusue-Torres, Jann N Sarkaria, Fredric B Meyer, Jamie J Van Gompel, Sani H Kizilbash, Ugur Sener, Franziska Michor, Jian L Campian, Ian F Parney, Terry C Burns
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND While serial sampling of glioma tissue is rarely performed prior to recurrence, cerebrospinal fluid (CSF) is an underutilized longitudinal source of candidate glioma biomarkers for understanding therapeutic impacts. However, the impact of key variables to consider in longitudinal CSF samples for monitoring biomarker discovery, including anatomical location and post-surgical changes, remains unknown. METHODS Aptamer-based proteomics was performed on 147 CSF samples from 74 patients, 71 of whom had grade 2-4 astrocytomas or grade 2-3 oligodendrogliomas. This included pre- versus post-resection intracranial CSF samples obtained at early (1-16 days; n=20 patients) or delayed (86-153 days; n=11 patients) timepoints for patients with glioma. Paired lumbar-versus-intracranial glioma CSF samples were also obtained (n=14 patients). RESULTS Significant differences were identified in the CSF proteome between lumbar, subarachnoid, and ventricular CSF from patients with gliomas. Importantly, we found that resection had a significant, evolving longitudinal impact on the CSF proteome, with distinct sets of proteins present at different timepoints since resection. Our analysis of serial intracranial CSF samples suggests the early potential for disease monitoring and evaluation of pharmacodynamic impact of targeted therapies, such as bevacizumab and immunotherapies. CONCLUSIONS The intracranial glioma CSF proteome serves as a rich and dynamic reservoir of potential biomarkers that can be used to evaluate the effects of resection and other therapies over time. All data within this study, including detailed individual clinical annotations, are shared as a resource for the neuro-oncology community to collectively address these unanswered questions and further understand glioma biology through CSF proteomics.
A Hitchhiker’s Guide Toward CSF Biomarkers for Neuro-Oncology
Authors: Cecile Riviere-Cazaux, Michael B Keough, Jeffrey A Zuccato, Rahul Kumar, Sebastian Schulz, Arthur E Warrington, Michael W Ruff, Benjamin M Ellingson, Nader Sanai, Jian L Campian, Sani H Kizilbash, Ian F Parney, Gelareh Zadeh, Mustafa Khasraw, Tobias Kessler, Ugur Sener, Daniel P Cahill, Alireza Mansouri, Terry C Burns
Journal: Neuro-Oncology (2024)

Cerebrospinal fluid (CSF) has emerged as a valuable liquid biopsy source for glioma biomarker discovery and validation. CSF produced within the ventricles circulates through the subarachnoid space, where the composition of glioma-derived analytes is influenced by the proximity and anatomical location of sampling relative to tumor, in addition to underlying tumor biology. The substantial gradients observed between lumbar and intracranial CSF compartments for tumor-derived analytes underscore the importance of sampling site selection. Moreover, radiographic features, such as tumor-CSF contact and blood-brain barrier (BBB) disruption, are critical covariates that may affect biomarker detectability and the abundance of plasma-derived analytes in CSF, respectively. Longitudinal intracranial CSF sampling, enabled by access devices like Ommaya reservoirs, may offer a window into treatment response and disease progression, though variability in analyte yield, sample volumes, and the dynamic effects of surgical resection pose challenges. This review critically evaluates the anatomic, radiographic, and longitudinal factors that impact glioma CSF biomarker abundance. Practical considerations for longitudinal CSF biobanking, including access device placement and collection, are also reviewed. Key takeaways and recommendations for CSF glioma biomarker discovery and validation are provided based on our collective experience, along with resources for investigators aiming to develop CSF biobanking at their institutions.
A simulation based digital twin approach to assessing the organization of response to emergency calls
Authors: Yann Penverne, Clea Martinez, Nicolas Cellier, Canan Pehlivan, Joel Jenvrin, Dominique Savary, Valerie Debierre, Florence Deciron, Anis Bichri, Quentin Lebastard, Emmanuel Montassier, Brice Leclere, Franck Fontanili
Journal: npj Digital Medicine (2024)

In emergency situations, timely contact with emergency medical communication centers (EMCCs) is critical for patient outcomes. Increasing call volumes and economic constraints are challenging many countries, necessitating organizational changes in EMCCs. This study uses a simulation-based digital twin approach, creating a virtual model of EMCC operations to assess the impact of different organizational scenarios on accessibility. Specifically, we explore two decompartmentalized scenarios where traditionally isolated call centers are reorganized to enable more flexible call distribution. The primary measure of accessibility was service quality within 30 s of call reception. Our results show that decompartmentalization improves service quality by 17% to 21%. This study demonstrates that reducing regional isolation in EMCCs can enhance performance and accessibility with a simulation-based digital twin approach providing a clear and objective method to quantify the benefits."
The direct and indirect inhibition of proinflammatory adipose tissue macrophages by acarbose in diet-induced obesity
Authors: Xiaohui Li, Shimeng Zheng, Haozhe Xu, Zihan Zhang, Xiaotong Han, Yunxiong Wei, Hua Jin, Xiaonan Du, Hufeng Xu, Mengyi Li, Zhongtao Zhang, Songlin Wang, Guangyong Sun, Dong Zhang
Journal: Cell Reports Medicine (2024)

Inflammation is critical for obesity and obesity-induced insulin resistance (IR). In this study, we reveal the function and mechanism of acarbose on adipose tissue macrophage (ATM)-mediated inflammation in obesity and obesity-induced IR. First, acarbose enhances the abundance of propionic acid-producing Parasutterella, therefore indirectly inhibiting the survival and proinflammatory function of M1-like ATMs via GPR43. Most interestingly, acarbose can directly inhibit M1-like ATM-mediated inflammation through GPR120. Diet-induced obese mice exhibit nitrobenzoxadiazoles (NBD) fluorescence-labeled ATMs, but lean mice that also orally received NBD fluorescence-labeled acarbose do not exhibit NBD fluorescence-labeled ATMs. This direct inhibition of macrophages by acarbose is validated in mouse and human macrophages in vitro. In conclusion, our study reveals that acarbose directly and indirectly inhibits proinflammatory macrophage phenotype, which contributes to the improvement of obesity and obesity-induced IR. The understanding of the immune regulatory effects of acarbose may extend its potential for further therapeutic applications.
The Case | A patient with chronic kidney disease and new-onset heart failure
Authors: Shun Watanabe, Naoki Sawa, Rikako Hiramatsu, Yuki Oba, Hiroki Mizuno, Shigekazu Kurihara, Noriko Inoue, Akinari Sekine, Kiho Tanaka, Masayuki Yamanouchi, Eiko Hasegawa, Tatsuya Suwabe, Takehiko Wada, Izumi Sugimoto, Yoshifumi Ubara
Journal: Kidney International (2024)