tbuckley/cabot-search huggingface dataset:
COVID-19 vaccination coverage for half a million non-EU migrants and refugees in England
Authors: Rachel Burns, Sacha Wyke, Max T. Eyre, Yamina Boukari, Tina B. Sørensen, Camille Tsang, Colin N. J. Campbell, Sarah Beale, Dominik Zenner, Sally Hargreaves, Ines Campos-Matos, Katie Harron, Robert W. Aldridge
Journal: Nature Human Behaviour (2023)

Abstract Despite evidence suggesting that some migrants are at risk of under-immunization and have experienced severe health inequities during the pandemic, data are limited on migrants’ COVID-19 vaccine coverage globally. Here we linked data from non-European Union migrants and resettled refugees to the national COVID-19 vaccination dataset in England. We estimated patterns in second and third dose delays and overdue doses between 12 December 2020 and 20 April 2022 by age, visa type and ethnicity. Of the 465,470 linked records, 91.8% (427,073/465,470) of migrants received a second dose and 51.3% (238,721/465,470) received a third. Refugees had the highest risk of delayed second (adjusted odds ratio 1.66; 95% confidence interval 1.55–1.79) and third dose (1.55; 1.43–1.69). Black migrants were twice as likely to have a second dose delayed (2.37; 2.23–2.54) than white migrants, but this trend reversed for the third dose. Older migrants (&gt;65 years) were four times less likely to have received their second or third dose compared with the general population in England aged &gt;65 or older. Policymakers, researchers and practitioners should work to understand and address personal and structural barriers to vaccination for diverse migrant populations.
Cytokine-responsive T- and NK-cells portray SARS-CoV-2 vaccine-responders and infection in multiple myeloma patients
Authors: Julius C. Enssle, Julia Campe, Alina Moter, Isabel Voit, Alec Gessner, Weijia Yu, Sebastian Wolf, Björn Steffen, Hubert Serve, Melanie Bremm, Sabine Huenecke, Michael Lohoff, Maria Vehreschild, Holger F. Rabenau, Marek Widera, Sandra Ciesek, Thomas Oellerich, Katharina Imkeller, Michael A. Rieger, Ivana von Metzler, Evelyn Ullrich
Journal: Leukemia (2023)

Patients with multiple myeloma (MM) routinely receive mRNA-based vaccines to reduce COVID-19-related mortality. However, whether disease- and therapy-related alterations in immune cells and cytokine-responsiveness contribute to the observed heterogeneous vaccination responses is unclear. Thus, we analyzed peripheral blood mononuclear cells from patients with MM during and after SARS-CoV-2 vaccination and breakthrough infection (BTI) using combined whole-transcriptome and surface proteome single-cell profiling with functional serological and T-cell validation in 58 MM patients. Our results demonstrate that vaccine-responders showed a significant overrepresentation of cytotoxic CD4+ T- and mature CD38+ NK-cells expressing FAS+/TIM3+ with a robust cytokine-responsiveness, such as type-I-interferon-, IL-12- and TNF-α-mediated signaling. Patients with MM experiencing BTI developed strong serological and cellular responses and exhibited similar cytokine-responsive immune cell patterns as vaccine-responders. This study can expand our understanding of molecular and cellular patterns associated with immunization responses and may benefit the design of improved vaccination strategies in immunocompromised patients.
The BAF chromatin remodeler synergizes with RNA polymerase II and transcription factors to evict nucleosomes
Authors: Sandipan Brahma, Steven Henikoff
Journal: Nature Genetics (2023)

Abstract Chromatin accessibility is a hallmark of active transcription and entails ATP-dependent nucleosome remodeling, which is carried out by complexes such as Brahma-associated factor (BAF). However, the mechanistic links between transcription, nucleosome remodeling and chromatin accessibility are unclear. Here, we used a chemical–genetic approach coupled with time-resolved chromatin profiling to dissect the interplay between RNA Polymerase II (RNAPII), BAF and DNA-sequence-specific transcription factors in mouse embryonic stem cells. We show that BAF dynamically unwraps and evicts nucleosomes at accessible chromatin regions, while RNAPII promoter-proximal pausing stabilizes BAF chromatin occupancy and enhances ATP-dependent nucleosome eviction by BAF. We find that although RNAPII and BAF dynamically probe both transcriptionally active and Polycomb-repressed genomic regions, pluripotency transcription factor chromatin binding confers locus specificity for productive chromatin remodeling and nucleosome eviction by BAF. Our study suggests a paradigm for how functional synergy between dynamically acting chromatin factors regulates locus-specific nucleosome organization and chromatin accessibility.
Noncoding mutations cause super-enhancer retargeting resulting in protein synthesis dysregulation during B cell lymphoma progression
Authors: Rebecca J. Leeman-Neill, Dong Song, Jonathan Bizarro, Ludivine Wacheul, Gerson Rothschild, Sameer Singh, Yang Yang, Aditya Y. Sarode, Kishore Gollapalli, Lijing Wu, Wanwei Zhang, Yiyun Chen, Max C. Lauring, D. Eric Whisenant, Shweta Bhavsar, Junghyun Lim, Steven H. Swerdlow, Govind Bhagat, Qian Zhao, Luke E. Berchowitz, Denis L. J. Lafontaine, Jiguang Wang, Uttiya Basu
Journal: Nature Genetics (2023)

Abstract Whole-genome sequencing of longitudinal tumor pairs representing transformation of follicular lymphoma to high-grade B cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma) identified coding and noncoding genomic alterations acquired during lymphoma progression. Many of these transformation-associated alterations recurrently and focally occur at topologically associating domain resident regulatory DNA elements, including H3K4me3 promoter marks located within H3K27ac super-enhancer clusters in B cell non-Hodgkin lymphoma. One region found to undergo recurrent alteration upon transformation overlaps a super-enhancer affecting the expression of the PAX5 / ZCCHC7 gene pair. ZCCHC7 encodes a subunit of the Trf4/5-Air1/2-Mtr4 polyadenylation-like complex and demonstrated copy number gain, chromosomal translocation and enhancer retargeting-mediated transcriptional upregulation upon lymphoma transformation. Consequently, lymphoma cells demonstrate nucleolar dysregulation via altered noncoding 5.8S ribosomal RNA processing. We find that a noncoding mutation acquired during lymphoma progression affects noncoding rRNA processing, thereby rewiring protein synthesis leading to oncogenic changes in the lymphoma proteome.
A Comparative Inflammation‐on‐a‐Chip with a Complete 3D Interface: Pharmacological Applications in COPD‐Induced Neutrophil Migration (Adv. Healthcare Mater. 30/2023)
Authors: Soohyun Kim, Sung Kyun Lee, Ahryeong Son, Jong‐Hwan Lee, Hong Gi Kim
Journal: Advanced Healthcare Materials (2023)

3D Printing In article 2301673 by Hong Gi Kim and co-workers, a comparative inflammation-on-a-chip (IoC), not having fixed structures such as micropillar and phaseguide structures, is newly developed with two comparative channels. This is the first study to evaluate inhibitors of CXCR2-dependent neutrophil transendothelial migration (NETM) in this IoC model that mimics the physiological 3D microenvironment, consisting of an endothelial barrier, extracellular compartment, and COPD-induced inflammatory conditions.
Biomimetic Fibers Based on Equidistant Micropillar Arrays Determines Chondrocyte Fate via Mechanoadaptability (Adv. Healthcare Mater. 30/2023)
Authors: Chenchen Zhou, Yueyi Yang, Mengmeng Duan, Cheng Chen, Caixia Pi, Demao Zhang, Xiaoheng Liu, Jing Xie
Journal: Advanced Healthcare Materials (2023)

Micropillar Substrates In article 2301685, Xiaoheng Liu, Jing Xie and co-workers report a biomimetic fiber fabricated by polydimethylsiloxane (PDMS) that simulates the microenvironment matrix of cartilage and brings it closer to the tissue texture. This biomimetic fiber provides a novel interaction between cell and interface and allows one to observe chondrocyte behaviors from physiological to pathological changes closer to the tissue level.
Gut microbiome-associated predictors as biomarkers of response to advanced therapies in inflammatory bowel disease: a systematic review
Authors: Susanna Meade, Jeremy Liu Chen Kiow, Cristian Massaro, Gurpreet Kaur, Elizabeth Squirell, Brian Bressler, Genelle Lunken
Journal: Gut Microbes (2023)

Loss of response to therapy in inflammatory bowel disease (IBD) has led to a surge in research focusing on precision medicine. Three systematic reviews have been published investigating the associations between gut microbiota and disease activity or IBD therapy. We performed a systematic review to investigate the microbiome predictors of response to advanced therapy in IBD. Unlike previous studies, our review focused on predictors of response to therapy; so the included studies assessed microbiome predictors before the proposed time of response or remission. We also provide an update of the available data on mycobiomes and viromes. We highlight key themes in the literature that may serve as future biomarkers of treatment response: the abundance of fecal SCFA-producing bacteria and opportunistic bacteria, metabolic pathways related to butyrate synthesis, and non-butyrate metabolomic predictors, including bile acids (BAs), amino acids, and lipids, as well as mycobiome predictors of response.
Inhibiting tau-induced elevated nSMase2 activity and ceramides is therapeutic in an Alzheimer’s disease mouse model
Authors: Carolyn Tallon, Benjamin J. Bell, Medhinee M. Malvankar, Pragney Deme, Carlos Nogueras-Ortiz, Erden Eren, Ajit G. Thomas, Kristen R. Hollinger, Arindom Pal, Maja Mustapic, Meixiang Huang, Kaleem Coleman, Tawnjerae R. Joe, Rana Rais, Norman J. Haughey, Dimitrios Kapogiannis, Barbara S. Slusher
Journal: Translational Neurodegeneration (2023)

Abstract Background Cognitive decline in Alzheimer’s disease (AD) is associated with hyperphosphorylated tau (pTau) propagation between neurons along synaptically connected networks, in part via extracellular vesicles (EVs). EV biogenesis is triggered by ceramide enrichment at the plasma membrane from neutral sphingomyelinase2 (nSMase2)-mediated cleavage of sphingomyelin. We report, for the first time, that human tau expression elevates brain ceramides and nSMase2 activity. Methods To determine the therapeutic benefit of inhibiting this elevation, we evaluated PDDC, the first potent, selective, orally bioavailable, and brain-penetrable nSMase2 inhibitor in the transgenic PS19 AD mouse model. Additionally, we directly evaluated the effect of PDDC on tau propagation in a mouse model where an adeno-associated virus (AAV) encoding P301L/S320F double mutant human tau was stereotaxically-injected unilaterally into the hippocampus. The contralateral transfer of the double mutant human tau to the dentate gyrus was monitored. We examined ceramide levels, histopathological changes, and pTau content within EVs isolated from the mouse plasma. Results Similar to human AD, the PS19 mice exhibited increased brain ceramide levels and nSMase2 activity; both were completely normalized by PDDC treatment. The PS19 mice also exhibited elevated tau immunostaining, thinning of hippocampal neuronal cell layers, increased mossy fiber synaptophysin immunostaining, and glial activation, all of which were pathologic features of human AD. PDDC treatment reduced these changes. The plasma of PDDC-treated PS19 mice had reduced levels of neuronal- and microglial-derived EVs, the former carrying lower pTau levels, compared to untreated mice. In the tau propagation model, PDDC normalized the tau-induced increase in brain ceramides and significantly reduced the amount of tau propagation to the contralateral side. Conclusions PDDC is a first-in-class therapeutic candidate that normalizes elevated brain ceramides and nSMase2 activity, leading to the slowing of tau spread in AD mice.
2D Ultrathin Iron Doped Bismuth Oxychloride Nanosheets with Rich Oxygen Vacancies for Enhanced Sonodynamic Therapy (Adv. Healthcare Mater. 30/2023)
Authors: Miaomiao Wu, Jiaxi Yong, Huayue Zhang, Zhiliang Wang, Zhi Ping Xu, Run Zhang
Journal: Advanced Healthcare Materials (2023)
Drug‐Eluting Porous Embolic Microspheres for Trans‐Arterial Delivery of Dual Synergistic Anticancer Therapy for the Treatment of Liver Cancer (Adv. Healthcare Mater. 30/2023)
Authors: Benzion Amoyav, Allan I. Bloom, Yoel Goldstein, Rafael Miller, Mariana Sharam, Arnon Fluksman, Ofra Benny
Journal: Advanced Healthcare Materials (2023)

Embolization Article 2301548 by Ofra Benny and co-workers describes a novel drug eluting agent combining dual therapy of both cytotoxic and hypoxia-activated-prodrug in unique porous morphology administered trans-arterially for treating liver cancer. Porous particles show advantages over nonporous particles, suggesting that morphology may affect the treatment outcomes. This study combines multiple research disciplines, among others microfluidics, 3D printing methods, versatile cell culture assays and an advanced rat tumor-bearing in vivo model.
Four‐Arm Polymer‐Guided Formation of Curcumin‐Loaded Flower‐Like Porous Microspheres as Injectable Cell Carriers for Diabetic Wound Healing (Adv. Healthcare Mater. 30/2023)
Authors: Xiaohuan Yuan, Wei Yang, Yingying Fu, Ziwei Tao, Lan Xiao, Qinzhou Zheng, Dan Wu, Mengya Zhang, Luxin Li, Zhengmao Lu, Yan Wu, Jie Gao, Yulin Li
Journal: Advanced Healthcare Materials (2023)
Glioma-derived ANXA1 suppresses the immune response to TLR3 ligands by promoting an anti-inflammatory tumor microenvironment
Authors: Yu Zheng, Haihui Jiang, Naixue Yang, Shaoping Shen, Daosheng Huang, Lemei Jia, Jing Ling, Longchen Xu, Mingxiao Li, Kefu Yu, Xiaohui Ren, Yong Cui, Xun Lan, Song Lin, Xin Lin
Journal: Cellular and Molecular Immunology (2023)
Immunoproteasome function maintains oncogenic gene expression in KMT2A-complex driven leukemia
Authors: Nuria Tubío-Santamaría, Ashok Kumar Jayavelu, Tina M. Schnoeder, Theresa Eifert, Chen-Jen Hsu, Florian Perner, Qirui Zhang, Daniela V. Wenge, Fynn M. Hansen, Joanna M. Kirkpatrick, Nidhi Jyotsana, Steven W. Lane, Björn von Eyss, Aniruddha J. Deshpande, Michael W. M. Kühn, Juerg Schwaller, Clemens Cammann, Ulrike Seifert, Frédéric Ebstein, Elke Krüger, Andreas Hochhaus, Michael Heuser, Alessandro Ori, Matthias Mann, Scott A. Armstrong, Florian H. Heidel
Journal: Molecular Cancer (2023)

Abstract Pharmacologic targeting of chromatin-associated protein complexes has shown significant responses in KMT2A -rearranged ( KMT2A-r ) acute myeloid leukemia (AML) but resistance frequently develops to single agents. This points to a need for therapeutic combinations that target multiple mechanisms. To enhance our understanding of functional dependencies in KMT2A-r AML, we have used a proteomic approach to identify the catalytic immunoproteasome subunit PSMB8 as a specific vulnerability. Genetic and pharmacologic inactivation of PSMB8 results in impaired proliferation of murine and human leukemic cells while normal hematopoietic cells remain unaffected. Disruption of immunoproteasome function drives an increase in transcription factor BASP1 which in turn represses KMT2A-fusion protein target genes. Pharmacologic targeting of PSMB8 improves efficacy of Menin-inhibitors, synergistically reduces leukemia in human xenografts and shows preserved activity against Menin-inhibitor resistance mutations. This identifies and validates a cell-intrinsic mechanism whereby selective disruption of proteostasis results in altered transcription factor abundance and repression of oncogene-specific transcriptional networks. These data demonstrate that the immunoproteasome is a relevant therapeutic target in AML and that targeting the immunoproteasome in combination with Menin-inhibition could be a novel approach for treatment of KMT2A-r AML.
Update on Cardiovascular Implantable Electronic Device Infections and Their Prevention, Diagnosis, and Management: A Scientific Statement From the American Heart Association
Authors: Larry M. Baddour, Zerelda Esquer Garrigos, M. Rizwan Sohail, Eva Havers-Borgersen, Andrew D. Krahn, Vivian H. Chu, Connie S. Radke, Jennifer Avari-Silva, Mikhael F. El-Chami, Jose M. Miro, Daniel C. DeSimone
Journal: Circulation (2023)

The American Heart Association sponsored the first iteration of a scientific statement that addressed all aspects of cardiovascular implantable electronic device infection in 2010. Major advances in the prevention, diagnosis, and management of these infections have occurred since then, necessitating a scientific statement update. An 11-member writing group was identified and included recognized experts in cardiology and infectious diseases, with a career focus on cardiovascular infections. The group initially met in October 2022 to develop a scientific statement that was drafted with front-line clinicians in mind and focused on providing updated clinical information to enhance outcomes of patients with cardiovascular implantable electronic device infection. The current scientific statement highlights recent advances in prevention, diagnosis, and management, and how they may be incorporated in the complex care of patients with cardiovascular implantable electronic device infection.
Lack of Effectiveness of Computer Aided Detection for Colorectal Neoplasia: A Systematic Review and Meta-Analysis of Nonrandomized Studies
Authors: Harsh K. Patel, Yuichi Mori, Cesare Hassan, Tommy Rizkala, Dhruvil K. Radadiya, Piyush Nathani, Sachin Srinivasan, Masashi Misawa, Roberta Maselli, Giulio Antonelli, Marco Spadaccini, Antonio Facciorusso, Kareem Khalaf, Davide Lanza, Giacomo Bonanno, Douglas K. Rex, Alessandro Repici, Prateek Sharma
Journal: Clinical Gastroenterology and Hepatology (2023)
Infant gut microbiota contributes to cognitive performance in mice
Authors: Tomás Cerdó, Alicia Ruiz-Rodríguez, Inmaculada Acuña, Francisco José Torres-Espínola, Sergio Menchén-Márquez, Fernando Gámiz, Milagros Gallo, Nico Jehmlich, Sven-Bastiaan Haange, Martin von Bergen, Cristina Campoy, Antonio Suárez
Journal: Cell Host & Microbe (2023)
TROP2 Is Associated with Primary Resistance to Immune Checkpoint Inhibition in Patients with Advanced Non–Small Cell Lung Cancer
Authors: Alban Bessede, Florent Peyraud, Benjamin Besse, Sophie Cousin, Mathilde Cabart, François Chomy, Christophe Rey, Oren Lara, Ophélie Odin, Imane Nafia, Lucile Vanhersecke, Fabrice Barlesi, Jean-Philippe Guégan, Antoine Italiano
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Mechanisms of primary resistance to inhibitors of the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling axis in non–small cell lung cancer (NSCLC) are still poorly understood. While some studies suggest the involvement of trophoblast cell surface antigen 2 (TROP2) in modulating tumor cell resistance to therapeutic drugs, its specific role in the context of PD-1/PD-L1 axis blockade is not definitively established. Experimental Design: We performed high-throughput analysis of transcriptomic data from 891 NSCLC tumors from patients treated with either the PD-L1 inhibitor atezolizumab or chemotherapy in two large randomized clinical trials. To confirm our results at the protein level, we complemented this transcriptional approach by performing a multiplex immunofluorescence analysis of tumor tissue samples as well as a proteomic profiling of plasma. Results: We observed a significant association of TROP2 overexpression with worse progression-free survival and overall survival on PD-L1 blockade, independent of other prognostic factors. Importantly, we found increased TROP2 expression to be predictive of survival in patients treated with atezolizumab but not chemotherapy. TROP2 overexpression was associated with decreased T-cell infiltration. We confirmed these results at the proteomic level both on tumor tissue and in plasma. Conclusions: Our results suggest an important contribution of TROP2 expression to the primary resistance to PD-L1 blockade in NSCLC. TROP2-biomarker–based strategy may be relevant in selecting patients with NSCLC who are more likely to benefit from a combination of immunotherapy and an anti-TROP2 agent.
Reliability and Responsiveness of Histologic Indices for the Assessment of Crohn’s Disease Activity
Authors: Virginia Solitano, David F. Schaeffer, Malcolm Hogan, Niels Vande Casteele, Rish K. Pai, Guangyong Zou, Reetesh K. Pai, Claire E. Parker, Julie Rémillard, Britt Christensen, Silvio Danese, Laurent Peyrin-Biroulet, Remo Panaccione, Bruce E. Sands, Geert D’Haens, Brian G. Feagan, Christopher Ma, Vipul Jairath
Journal: Clinical Gastroenterology and Hepatology (2023)
FK506 bypasses the effect of erythroferrone in cancer cachexia skeletal muscle atrophy
Authors: Erica Mina, Elisabeth Wyart, Roberta Sartori, Elia Angelino, Ivan Zaggia, Valentina Rausch, Mara Maldotti, Alessia Pagani, Myriam Y. Hsu, Alberto Friziero, Cosimo Sperti, Alessio Menga, Andrea Graziani, Emilio Hirsch, Salvatore Oliviero, Marco Sandri, Laura Conti, Léon Kautz, Laura Silvestri, Paolo E. Porporato
Journal: Cell Reports Medicine (2023)

Skeletal muscle atrophy is a hallmark of cachexia, a wasting condition typical of chronic pathologies, that still represents an unmet medical need. Bone morphogenetic protein (BMP)-Smad1/5/8 signaling alterations are emerging drivers of muscle catabolism, hence, characterizing these perturbations is pivotal to develop therapeutic approaches. We identified two promoters of "BMP resistance" in cancer cachexia, specifically the BMP scavenger erythroferrone (ERFE) and the intracellular inhibitor FKBP12. ERFE is upregulated in cachectic cancer patients' muscle biopsies and in murine cachexia models, where its expression is driven by STAT3. Moreover, the knock down of Erfe or Fkbp12 reduces muscle wasting in cachectic mice. To bypass the BMP resistance mediated by ERFE and release the brake on the signaling, we targeted FKBP12 with low-dose FK506. FK506 restores BMP-Smad1/5/8 signaling, rescuing myotube atrophy by inducing protein synthesis. In cachectic tumor-bearing mice, FK506 prevents muscle and body weight loss and protects from neuromuscular junction alteration, suggesting therapeutic potential for targeting the ERFE-FKBP12 axis.
Evaluation of Regional Ventilation Distributions in Newborns with Congenital Diaphragmatic Hernia
Authors: Lukas Schroeder, Florian Kipfmueller, Benjamin Hentze, Christian Putensen, Soyhan Bagci, Till Dresbach, Hemmen Sabir, Andreas Mueller, Thomas Muders
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Evaluation of Regional Ventilation Distributions in Newborns with Congenital Diaphragmatic Hernia." American Journal of Respiratory and Critical Care Medicine, 209(5), pp. 601–606
Association between Noise and Cardiovascular Disease in a Nationwide U.S. Prospective Cohort Study of Women Followed from 1988 to 2018
Authors: Charlotte Roscoe, Stephanie T. Grady, Jaime E. Hart, Hari S. Iyer, JoAnn E. Manson, Kathryn M. Rexrode, Eric B. Rimm, Francine Laden, Peter James
Journal: Environmental Health Perspectives (2023)

Long-term noise exposure is associated with cardiovascular disease (CVD), including acute cardiovascular events such as myocardial infarction and stroke. However, longitudinal cohort studies in the U.S. of long-term noise and CVD are almost exclusively from Europe and few modeled nighttime noise, when an individual is likely at home or asleep, separately from daytime noise. We aimed to examine the prospective association of outdoor long-term nighttime and daytime noise from anthropogenic sources with incident CVD using a U.S.-based, nationwide cohort of women.