tbuckley/cabot-search huggingface dataset:
Caregiver burden due to long-term breathlessness: a hypothesis-generating study
Authors: Slavica Kochovska, Diana Ferreira, Sungwon Chang, Tim Luckett, Jessica Roydhouse, Magnus Ekström, David C. Currow
Journal: European Respiratory Journal (2024)

<h3>Shareable abstract</h3> Higher caregiver burden in the context of long-term breathlessness is associated with both caregiver and patient factors. A more nuanced delineation of caregiver burden can help the design of tailored support interventions to be evaluated in future studies.
A synbiotic of Anaerostipes caccae and lactulose prevents and treats food allergy in mice
Authors: Lauren A. Hesser, Armando A. Puente, Jack Arnold, Edward Ionescu, Anjali Mirmira, Nidhi Talasani, Jacqueline Lopez, Lisa Maccio-Maretto, Mark Mimee, Cathryn R. Nagler
Journal: Cell Host & Microbe (2024)
Global herpes zoster burden in adults with asthma: a systematic review and meta-analysis
Authors: Kevin J. Mortimer, Alvaro A. Cruz, Ingrid T. Sepúlveda-Pachón, Anamaria Jorga, Hilde Vroling, Charles Williams
Journal: European Respiratory Journal (2024)

Asthma is a common respiratory disease, which may be associated with an increased risk of herpes zoster (HZ), often a debilitating disease associated with severe pain. This is the first systematic review with the objective of summarising evidence on HZ burden in adults with asthma.
Epigenomic partitioning of a polygenic risk score for asthma reveals distinct genetically driven disease pathways
Authors: Bernard Stikker, Lianne Trap, Bahar Sedaghati-Khayat, Marjolein J.W. de Bruijn, Wilfred F.J. van Ijcken, Emmely de Roos, Arfan Ikram, Rudi W. Hendriks, Guy Brusselle, Jeroen van Rooij, Ralph Stadhouders
Journal: European Respiratory Journal (2024)

Individual differences in susceptibility to developing asthma, a heterogeneous chronic inflammatory lung disease, are poorly understood. Whether genetics can predict asthma risk and how genetic variants modulate the complex pathophysiology of asthma are still debated.
IRF4 requires ARID1A to establish plasma cell identity in multiple myeloma
Authors: Arnold Bolomsky, Michele Ceribelli, Sebastian Scheich, Kristina Rinaldi, Da Wei Huang, Papiya Chakraborty, Lisette Pham, George W. Wright, Tony Hsiao, Vivian Morris, Jaewoo Choi, James D. Phelan, Ronald J. Holewinski, Thorkell Andresson, Jan Wisniewski, Deanna Riley, Stefania Pittaluga, Elizabeth Hill, Craig J. Thomas, Jagan Muppidi, Ryan M. Young
Journal: Cancer Cell (2024)
Impact of elexacaftor/tezacaftor/ivacaftor therapy on lung clearance index and magnetic resonance imaging in children with cystic fibrosis and one or two<i>F508del</i>alleles
Authors: Mirjam Stahl, Martha Dohna, Simon Y. Graeber, Olaf Sommerburg, Diane M. Renz, Sophia T. Pallenberg, Andreas Voskrebenzev, Katharina Schütz, Gesine Hansen, Felix Doellinger, Eva Steinke, Stephanie Thee, Jobst Röhmel, Sandra Barth, Claudia Rückes-Nilges, Julian Berges, Susanne Hämmerling, Mark O. Wielpütz, Lutz Naehrlich, Jens Vogel-Claussen, Burkhard Tümmler, Marcus A. Mall, Anna-Maria Dittrich
Journal: European Respiratory Journal (2024)

Background We recently demonstrated that elexacaftor/tezacaftor/ivacaftor (ETI) improves the lung clearance index (LCI) and abnormalities in lung morphology detected by magnetic resonance imaging (MRI) in adolescent and adult patients with cystic fibrosis (CF). However, real-world data on the effect of ETI on these sensitive outcomes of lung structure and function in school-age children with CF have not been reported. The aim of this study was therefore to examine the effect of ETI on the LCI and the lung MRI score in children aged 6–11 years with CF and one or two F508del alleles. Methods This prospective, observational, multicentre, post-approval study assessed the longitudinal LCI up to 12 months and the lung MRI score before and 3 months after initiation of ETI. Results A total of 107 children with CF including 40 heterozygous for F508del and a minimal function mutation (F/MF) and 67 homozygous for F508del (F/F) were enrolled in this study. Treatment with ETI improved the median (interquartile range (IQR)) LCI in F/MF (−1.0 (−2.0– −0.1); p&lt;0.01) and F/F children (−0.8 (−1.9– −0.2); p&lt;0.001) from 3 months onwards. Further, ETI improved the median (IQR) MRI global score in F/MF (−4.0 (−9.0–0.0); p&lt;0.01) and F/F children (−3.5 (−7.3– −0.8); p&lt;0.001). Conclusions ETI improves early abnormalities in lung ventilation and morphology in school-age children with CF and at least one F508del allele in a real-world setting. Our results support early initiation of ETI to reduce or even prevent lung disease progression in school-age children with CF.
Astrocytic LRP1 enables mitochondria transfer to neurons and mitigates brain ischemic stroke by suppressing ARF1 lactylation
Authors: Jian Zhou, Lifang Zhang, Jianhua Peng, Xianhui Zhang, Fan Zhang, Yuanyuan Wu, An Huang, Fengling Du, Yuyan Liao, Yijing He, Yuke Xie, Long Gu, Chenghao Kuang, Wei Ou, Maodi Xie, Tianqi Tu, Jinwei Pang, Dingkun Zhang, Kecheng Guo, Yue Feng, Shigang Yin, Yang Cao, Tao Li, Yong Jiang
Journal: Cell Metabolism (2024)
Advances and prospects of biomarkers for immune checkpoint inhibitors
Authors: Hirohito Yamaguchi, Jung-Mao Hsu, Linlin Sun, Shao-Chun Wang, Mien-Chie Hung
Journal: Cell Reports Medicine (2024)

Immune checkpoint inhibitors (ICIs) activate anti-cancer immunity by blocking T cell checkpoint molecules such as programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Although ICIs induce some durable responses in various cancer patients, they also have disadvantages, including low response rates, the potential for severe side effects, and high treatment costs. Therefore, selection of patients who can benefit from ICI treatment is critical, and identification of biomarkers is essential to improve the efficiency of ICIs. In this review, we provide updated information on established predictive biomarkers (tumor programmed death-ligand 1 [PD-L1] expression, DNA mismatch repair deficiency, microsatellite instability high, and tumor mutational burden) and potential biomarkers currently under investigation such as tumor-infiltrated and peripheral lymphocytes, gut microbiome, and signaling pathways related to DNA damage and antigen presentation. In particular, this review aims to summarize the current knowledge of biomarkers, discuss issues, and further explore future biomarkers.
CREB1 promotes expression of immune checkpoint HLA-E leading to immune escape in multiple myeloma
Authors: Aya Ismael, Allen J. Robinette, Laila Huric, Jamie Schuetz, Kameron Dona, Don Benson, Emanuele Cocucci, Francesca Cottini
Journal: Leukemia (2024)

Multiple myeloma (MM) cells effectively escape anti-tumoral immunity to survive in the tumor microenvironment (TME). Herein, we identify non-classical major histocompatibility complex (MHC) class I molecule HLA-E as a major contributing factor in immune escape. Clinically, HLA-E expression correlates with aggressive disease features such as t(4;14) and CD56 expression and is induced by IFN-gamma (IFN-γ) in the TME. We discovered that HLA-E is regulated by cAMP responsive element binding protein 1 (CREB1) transcription factor by direct promoter binding; genomic and pharmacological inhibition of CREB1 reduced HLA-E levels even in the presence of IFN-γ or IFN-γ activating agents, such as immunomodulatory drugs and panobinostat. HLA-E binds to natural killer group 2A (NKG2A), delivering an inhibitor signal to natural killer (NK) cells. Treatment with a CREB1 inhibitor was able to restore NK cell-mediated cytotoxicity against MM cell lines and patient samples. In conclusion, our results strongly demonstrate that CREB1 inhibition promotes anti-tumoral immunity in MM by limiting HLA-E expression and enhancing the activity of NK cells.
CD28 Costimulation Augments CAR Signaling in NK Cells via the LCK/CD3ζ/ZAP70 Signaling Axis
Authors: Sunil Acharya, Rafet Basar, May Daher, Hind Rafei, Ping Li, Nadima Uprety, Emily Ensley, Mayra Shanley, Bijender Kumar, Pinaki P. Banerjee, Luciana Melo Garcia, Paul Lin, Vakul Mohanty, Kun H. Kim, Xianli Jiang, Yuchen Pan, Ye Li, Bin Liu, Ana K. Nunez Cortes, Chenyu Zhang, Mohsen Fathi, Ali Rezvan, Melisa J. Montalvo, Sophia L. Cha, Francia Reyes-Silva, Rejeena Shrestha, Xingliang Guo, Kiran Kundu, Alexander Biederstädt, Luis Muniz-Feliciano, Gary M. Deyter, Mecit Kaplan, Xin R. Jiang, Enli Liu, Antrix Jain, Janos Roszik, Natalie W. Fowlkes, Luisa M. Solis Soto, Maria G. Raso, Joseph D. Khoury, Pei Lin, Francisco Vega, Navin Varadarajan, Ken Chen, David Marin, Elizabeth J. Shpall, Katayoun Rezvani
Journal: Cancer Discovery (2024)

Multiple factors in the design of a chimeric antigen receptor (CAR) influence CAR T-cell activity, with costimulatory signals being a key component. Yet, the impact of costimulatory domains on the downstream signaling and subsequent functionality of CAR-engineered natural killer (NK) cells remains largely unexplored. Here, we evaluated the impact of various costimulatory domains on CAR-NK cell activity, using a CD70-targeting CAR. We found that CD28, a costimulatory molecule not inherently present in mature NK cells, significantly enhanced the antitumor efficacy and long-term cytotoxicity of CAR-NK cells both in vitro and in multiple xenograft models of hematologic and solid tumors. Mechanistically, we showed that CD28 linked to CD3ζ creates a platform that recruits critical kinases, such as lymphocyte-specific protein tyrosine kinase (LCK) and zeta-chain-associated protein kinase 70 (ZAP70), initiating a signaling cascade that enhances CAR-NK cell function. Our study provides insights into how CD28 costimulation enhances CAR-NK cell function and supports its incorporation in NK-based CARs for cancer immunotherapy. Significance: We demonstrated that incorporation of the T-cell-centric costimulatory molecule CD28, which is normally absent in mature natural killer (NK) cells, into the chimeric antigen receptor (CAR) construct recruits key kinases including lymphocyte-specific protein tyrosine kinase and zeta-chain-associated protein kinase 70 and results in enhanced CAR-NK cell persistence and sustained antitumor cytotoxicity.
Ibrutinib in Combination with R-GemOx in Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma of Nongerminal Center B-cell–like Type: Phase II Clinical Trial of the Spanish GELTAMO Group
Authors: Beatriz Rey Búa, Carlos Grande, Jose Javier Sánchez Blanco, Pau Abrisqueta, Antonio Gutiérrez, Ángel Ramírez Páyer, Eva Giné, Izaskun Zeberio Etxetxipia, Maria Jose Terol, Fátima de la Cruz Vicente, Rafael Andreu, María José Ramírez, Adolfo de la Fuente, María Cruz Viguria, María Jesus Peñarrubia, Ana Jiménez-Ubieto, Santiago Montes-Moreno, Armando Lopez-Guillermo, María Dolores Caballero, Alejandro Martín García-Sancho
Journal: Clinical Cancer Research (2024)

This phase II clinical trial evaluated the combination of ibrutinib with rituximab, gemcitabine, and oxaliplatin (R-GemOx) in patients with nongerminal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL).
Identification of Therapy-Induced Clonal Evolution and Resistance Pathways in Minimal Residual Clones in Multiple Myeloma through Single-Cell Sequencing
Authors: Jian Cui, Xiaoyun Li, Shuhui Deng, Chenxing Du, Huishou Fan, Wenqiang Yan, Jingyu Xu, Xiaoqing Li, Tengteng Yu, Shuaishuai Zhang, Rui Lv, Weiwei Sui, Mu Hao, Xin Du, Yan Xu, Shuhua Yi, Dehui Zou, Tao Cheng, Lugui Qiu, Xin Gao, Gang An
Journal: Clinical Cancer Research (2024)

Abstract Purpose: In multiple myeloma (MM), therapy-induced clonal evolution is associated with treatment resistance and is one of the most important hindrances toward a cure for MM. To further understand the molecular mechanisms controlling the clonal evolution of MM, we applied single-cell RNA sequencing (scRNA-seq) to paired diagnostic and posttreatment bone marrow (BM) samples. Experimental Design: scRNA-seq was performed on 38 BM samples from patients with monoclonal gammopathy of undetermined significance (n = 1), MM patients at diagnosis (n = 19), MM posttreatment (n = 17), and one healthy donor (HD). The single-cell transcriptome data of malignant plasma cells (PC) and the surrounding immune microenvironment were analyzed. Results: Profiling by scRNA-seq data revealed three primary trajectories of transcriptional evolution after treatment: clonal elimination in patients with undetectable minimal residual disease (MRD−) and clonal stabilization and clonal selection in detectable MRD (MRD+) patients. We noted a metabolic shift toward fatty acid oxidation in cycling-resistant PCs, whereas selective PCs favored the NF-κB pathway. Intriguingly, when comparing the genetic and transcriptional dynamics, we found a significant correlation between genetic and nongenetic factors in driving the clonal evolution. Furthermore, we identified variations in cellular interactions between malignant PCs and the tumor microenvironment. Selective PCs showed the most robust cellular interactions with the tumor microenvironment. Conclusions: These data suggest that MM cells could rapidly adapt to induction treatment through transcriptional adaptation, metabolic adaptation, and specialized immune evasion. Targeting therapy-induced resistance mechanisms may help to avert refractory disease in MM.
Valproic Acid Confers Functional Pluripotency to Human Amniotic Fluid Stem Cells in a Transgene-free Approach
Authors: Dafni Moschidou, Sayandip Mukherjee, Michael P. Blundell, Katharina Drews, Gemma N. Jones, Hassan Abdulrazzak, Beata Nowakowska, Anju Phoolchund, Kenneth Lay, T Selvee Ramasamy, Mara Cananzi, Daniel Nettersheim, Mark Sullivan, Jennifer Frost, Gudrun Moore, Joris R. Vermeesch, Nicholas M. Fisk, Adrian J. Thrasher, Anthony Atala, James Adjaye, Hubert Schorle, Paolo De Coppi, Pascale V. Guillot
Journal: Molecular Therapy (2024)
Dual-aptamer-engineered M1 macrophage with enhanced specific targeting and checkpoint blocking for solid-tumor immunotherapy
Authors: Husun Qian, Yixin Fu, Minkang Guo, Yu Chen, Dian Zhang, Yu Wei, Fangfang Jin, Qian Zeng, Yange Wang, Chengsen Chai, Shijia Ding, Wei Cheng, Tingmei Chen
Journal: Molecular Therapy (2024)
Heterologous expression and antimicrobial potential of class II bacteriocins
Authors: Carola Elisa Heesemann Rosenkilde, Ditte Olsen Lützhøft, Ruben Vazquez-Uribe, Morten Otto Alexander Sommer
Journal: Gut Microbes (2024)

Gut bacteria are known to produce bacteriocins to inhibit the growth of other bacteria. Consequently, bacteriocins have attracted increased attention as potential microbiome-editing tools. In this study we examine the inhibitory spectrum of 75 class II bacteriocins against 48 representative gut microbiota species. The bacteriocins were heterologously expressed in Escherichia coli and evaluated in vitro, ex vivo and in vivo. In vitro assays revealed 22 bacteriocins to inhibit at least one species and showed selective inhibition patterns against species implicated in certain disorders and diseases. Three bacteriocins were selected for ex vivo assessment on mouse feces. Based on 16S rRNA sequencing of the cultivated feces we showed that the two bacteriocins: Actifencin (#13) and Bacteroidetocin A (#22) selectively inhibited the growth of Lactobacillus and Bacteroides, respectively. The probiotic: E. coli Nissle 1917 was engineered to express these two bacteriocins in mice. However, the selective inhibitory patterns found in the in vitro and ex vivo experiments could not be observed in vivo. Our study describes a methodology for heterologous high throughput bacteriocin expression and screening and elucidates the inhibitory patterns of class II bacteriocins on the gut microbiota.
Clinical features and outcomes in primary nervous system histiocytic neoplasms
Authors: Nabeela Nathoo, Joon H. Uhm, Alyx B. Porter, Julie Hammack, Kurt A. Jaeckle, Maciej M. Mrugala, Brian A. Crum, Eoin P. Flanagan, Sean J. Pittock, Gaurav Goyal, Jason R. Young, Matthew J. Koster, Robert Vassallo, Jay H. Ryu, Caroline J. Davidge-Pitts, Corrie Bach, Aishwarya Ravindran, Julio C. Sartori Valinotti, N. Nora Bennani, Jithma P. Abeykoon, Mithun V. Shah, C. Christopher Hook, Karen L. Rech, Ronald S. Go, W. Oliver Tobin, Lucinda M. Gruber
Journal: Blood Cancer Journal (2024)
Multiomic analysis identifies a high-risk signature that predicts early clinical failure in DLBCL
Authors: Kerstin Wenzl, Matthew E. Stokes, Joseph P. Novak, Allison M. Bock, Sana Khan, Melissa A. Hopper, Jordan E. Krull, Abigail R. Dropik, Janek S. Walker, Vivekananda Sarangi, Raphael Mwangi, Maria Ortiz, Nicholas Stong, C. Chris Huang, Matthew J. Maurer, Lisa Rimsza, Brian K. Link, Susan L. Slager, Yan Asmann, Patrizia Mondello, Ryan Morin, Stephen M. Ansell, Thomas M. Habermann, Thomas E. Witzig, Andrew L. Feldman, Rebecca L. King, Grzegorz Nowakowski, James R. Cerhan, Anita K. Gandhi, Anne J. Novak
Journal: Blood Cancer Journal (2024)

Abstract Recent genetic and molecular classification of DLBCL has advanced our knowledge of disease biology, yet were not designed to predict early events and guide anticipatory selection of novel therapies. To address this unmet need, we used an integrative multiomic approach to identify a signature at diagnosis that will identify DLBCL at high risk of early clinical failure. Tumor biopsies from 444 newly diagnosed DLBCL were analyzed by WES and RNAseq. A combination of weighted gene correlation network analysis and differential gene expression analysis was used to identify a signature associated with high risk of early clinical failure independent of IPI and COO. Further analysis revealed the signature was associated with metabolic reprogramming and identified cases with a depleted immune microenvironment. Finally, WES data was integrated into the signature and we found that inclusion of ARID1A mutations resulted in identification of 45% of cases with an early clinical failure which was validated in external DLBCL cohorts. This novel and integrative approach is the first to identify a signature at diagnosis, in a real-world cohort of DLBCL, that identifies patients at high risk for early clinical failure and may have significant implications for design of therapeutic options.
The role of RNA methylation in tumor immunity and its potential in immunotherapy
Authors: Yan Li, Haoer Jin, Qingling Li, Liangrong Shi, Yitao Mao, Luqing Zhao
Journal: Molecular Cancer (2024)

Abstract RNA methylation, a prevalent post-transcriptional modification, has garnered considerable attention in research circles. It exerts regulatory control over diverse biological functions by modulating RNA splicing, translation, transport, and stability. Notably, studies have illuminated the substantial impact of RNA methylation on tumor immunity. The primary types of RNA methylation encompass N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), and N7-methylguanosine (m7G), and 3-methylcytidine (m3C). Compelling evidence underscores the involvement of RNA methylation in regulating the tumor microenvironment (TME). By affecting RNA translation and stability through the "writers", "erasers" and "readers", RNA methylation exerts influence over the dysregulation of immune cells and immune factors. Consequently, RNA methylation plays a pivotal role in modulating tumor immunity and mediating various biological behaviors, encompassing proliferation, invasion, metastasis, etc. In this review, we discussed the mechanisms and functions of several RNA methylations, providing a comprehensive overview of their biological roles and underlying mechanisms within the tumor microenvironment and among immunocytes. By exploring how these RNA modifications mediate tumor immune evasion, we also examine their potential applications in immunotherapy. This review aims to provide novel insights and strategies for identifying novel targets in RNA methylation and advancing cancer immunotherapy efficacy.
Physician‐directed patient self‐management in heart failure using left atrial pressure: Interim insights from the <scp>VECTOR</scp>‐<scp>HF</scp> I and <scp>IIa</scp> studies
Authors: David Meerkin, Leor Perl, Tal Hasin, Shalva Petriashvili, Levan Kurashvili, Mikheil Metreveli, Hüseyin Ince, Sebastian Feickert, Manhal Habib, Oren Caspi, Michael Jonas, Ignacio J. Amat‐Santos, Antoni Bayes‐Genis, Pau Codina, Oran Koren, Shir Frydman, Rachel M. Pachino, Stefan D. Anker, William T. Abraham
Journal: European Journal of Heart Failure (2024)

Aims Haemodynamic monitoring using implantable pressure sensors reduces the risk of heart failure (HF) hospitalizations. Patient self‐management (PSM) of haemodynamics in HF has the potential to personalize treatment, increase adherence, and reduce the risk of worsening HF, while lowering clinicians' burden. Methods and results The VECTOR‐HF I and IIa studies are prospective, single‐arm, open‐label clinical trials assessing safety, usability and performance of left atrial pressure (LAP)‐guided HF management using PSM in New York Heart Association class II and III HF patients. Physician‐prescribed LAP thresholds trigger patient self‐adjustment of diuretics. Primary endpoints include the ability to perform LAP measurements and transmit data to the healthcare provider (HCP) interface and the patient guidance application, and safety outcomes. This is an interim analysis of 13 patients using the PSM approach. Over 12 months, no procedure‐ or device‐related major adverse cardiovascular or neurological events were observed, and there were no failures to obtain measurements from the sensor and transmit the data to the HCP interface and the patient guidance application. Patient adherence was 91.4%. Using PSM, annualized HF hospitalization rate significantly decreased compared to a similar period prior to PSM utilization (0 admissions vs. 0.69 admissions over 11.84 months, p = 0.004). At 6 months, 6‐min walk test distance and the Kansas City Cardiomyopathy Questionnaire overall summary score demonstrated significant improvement. Conclusions Interim findings suggest that PSM using a LAP monitoring system is feasible and safe. PSM is associated with high patient adherence, potentially improving HF patients' functional status, quality of life, and limiting HF hospitalizations.
A miniaturized mesoscope for the large-scale single-neuron-resolved imaging of neuronal activity in freely behaving mice
Authors: Yuanlong Zhang, Lekang Yuan, Qiyu Zhu, Jiamin Wu, Tobias Nöbauer, Rujin Zhang, Guihua Xiao, Mingrui Wang, Hao Xie, Zengcai Guo, Qionghai Dai, Alipasha Vaziri
Journal: Nature Biomedical Engineering (2024)