tbuckley/cabot-search huggingface dataset:
Comprehensive sequential genetic analysis delineating frequency, patterns, and prognostic impact of genomic dynamics in a real‐world cohort of patients with lower‐risk MDS
Authors: Paolo Mazzeo, Christina Ganster, John Wiedenhöft, Katayoon Shirneshan, Katharina Rittscher, Elzbieta B. Brzuszkiewicz, Doris Steinemann, Maximilian Schieck, Catharina Müller‐Thomas, Hannes Treiber, Friederike Braulke, Ulrich Germing, Katja Sockel, Ekaterina Balaian, Julie Schanz, Uwe Platzbecker, Katharina S. Götze, Detlef Haase
Journal: HemaSphere (2024)

The acquisition of subsequent genetic lesions (clonal evolution, CE) and/or the expansion of existing clones (CEXP) contributes to clonal dynamics (CD) in myelodysplastic syndromes (MDS). Although CD plays an important role in high-risk patients in disease progression and transformation into acute myeloid leukemia (AML), knowledge about CD in lower-risk MDS (LR-MDS) patients is limited due to lack of robust longitudinal data considering the long clinically stable courses of the disease. In this retrospective analysis, we delineate the frequency and the prognostic impact of CD in an unselected real-world cohort of LR-MDS patients. We screened 68 patients with a median follow-up of 40.5 months and a median of 7.5 (range: 2-22) timepoints for CE and CEXP detected by chromosomal banding analysis, fluorescence in situ hybridization, sequencing, and molecular karyotyping. In 30/68 patients, 47 CE events and a CD rate of 1 event per 4 years were documented. Of note, patients with at least 1 CE event had an increased probability for subsequent treatment. Unexpectedly, CE did not correlate with inferior outcomes, which could be reasonably explained by CD detection triggering the subsequent start of a disease-modifying therapy.
Interatrial Shunt Treatment for Heart Failure: The Randomized RELIEVE-HF Trial
Authors: Gregg W. Stone, JoAnn Lindenfeld, Josep Rodés-Cabau, Stefan D. Anker, Michael R. Zile, Saibal Kar, Richard Holcomb, Michael P. Pfeiffer, Antoni Bayes-Genis, Jeroen J. Bax, Alan J. Bank, Maria Rosa Costanzo, Stefan Verheye, Ariel Roguin, Gerasimos Filippatos, Julio Núñez, Elizabeth C. Lee, Michal Laufer-Perl, Gil Moravsky, Sheldon E. Litwin, Edgard Prihadi, Hemal Gada, Eugene S. Chung, Matthew J. Price, Vinay Thohan, Dimitry Schewel, Sachin Kumar, Stephan Kische, Kevin S. Shah, Daniel J. Donovan, Yiran Zhang, Neal L. Eigler, William T. Abraham, John Gorcsan, Marrick Kukin, Kunjan Bhatt, David Shavelle, Liviu Klein, Alicia Romero, Garrie Haas, Vijay Swarup, Elizabeth Volz, Fareed Collado, Amit Badiye, Luanda Grazette, Michelle Hamilton, Tom McRae, Sumant Lamba, Steven Krueger, Timothy Byrne, Leslie Miller, Youssef Al-Saghir, Robin Chand, David Shavelle, Saeb Khoury, Ira Dauber, Sula Mazimba, Suneet Mittal, Steven Driver, Stanislav Weiner, Samir Kapadia, Priyanka Gosain, Rajeev Singh, Zvonimir Krejcer, Lynn Punnoose, Stuart Russell, Maria Karas, Gautam Kumar, Ajith Nair, Robert Widmer, Ramesh Kundur, Nabil Dib, Ugochukwu Egolum, Miguel Alvarez Villela, John Boehmer, George Petrossian, Jeffrey Teuteberg, Peter Bittenbender, Ignacio Amat Santos, Ana Garcia, Maria del Trigo, Sònia Pérez Mirabet, Luis Nombela, Domingo Pascual Figal, Israel Gotsman, Wadi Kinany, Sorel Goland, Dov Freimark, Tal Hasin, Oren Caspi, Eli Lev, Hilmi Alnsasra, Burkhard Sievers, Mohammad Sherif, Karl Fengler, Rolf Wachter, Ince Hüseyin, Jörg Hausleiter, Ralf Stephan Von Bardeleben, Ince Hüseyin, Reda Ibrahim, Eric Horlick, Bartosz Krakowiak, Adam Witkowski, Wojciech Wojakowski, Jan Van Der Heyden, Nicholas Van Mieghem, Martijn Post, Carmine DePasquale, Frank Ruschitzka, Richard Troughton
Journal: Circulation (2024)

An interatrial shunt may provide an autoregulatory mechanism to decrease left atrial pressure and improve heart failure (HF) symptoms and prognosis.
DNA Methylation Age Mediates Effect of Metabolic Profile on Cardiovascular and General Aging
Authors: Jiahui Si, Yu Ma, Canqing Yu, Dianjianyi Sun, Yuanjie Pang, Pei Pei, Ling Yang, Iona Y. Millwood, Robin G. Walters, Yiping Chen, Huaidong Du, Xiaoyan Zheng, Daniel Avery, Junshi Chen, Zhengming Chen, Liming Liang, Liming Li, Jun Lv, Rory Collins, Richard Peto, Ruth Boxall, Derrick Bennett, Yumei Chang, Robert Clarke, Simon Gilbert, Alex Hacker, Michael Holmes, Andri Iona, Christiana Kartsonaki, Rene Kerosi, Ling Kong, Om Kurmi, Garry Lancaster, Sarah Lewington, Kuang Lin, John McDonnell, Winnie Mei, Qunhua Nie, Jayakrishnan Radhakrishnan, Sajjad Rafiq, Paul Ryder, Sam Sansome, Dan Schmidt, Paul Sherliker, Rajani Sohoni, Iain Turnbull, Jenny Wang, Lin Wang, Xiaoming Yang, Zheng Bian, Ge Chen, Yu Guo, Can Hou, Jun Lv, Shuzhen Qu, Yunlong Tan, Canqing Yu, Zengchang Pang, Ruqin Gao, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Liang Cheng, Xiaocao Tian, Hua Zhang, Silu Lv, Junzheng Wang, Wei Hou, Jiyuan Yin, Ge Jiang, Xue Zhou, Liqiu Yang, Hui He, Bo Yu, Yanjie Li, Huaiyi Mu, Qinai Xu, Meiling Dou, Jiaojiao Ren, Shanqing Wang, Ximin Hu, Hongmei Wang, Jinyan Chen, Yan Fu, Zhenwang Fu, Xiaohuan Wang, Min Weng, Xiangyang Zheng, Yilei Li, Huimei Li, Yanjun Wang, Ming Wu, Jinyi Zhou, Ran Tao, Jie Yang, Chuanming Ni, Jun Zhang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Shuo Zhang, Jianrong Jin, Jingchao Liu, Zhenzhu Tang, Naying Chen, Ying Huang, Mingqiang Li, Jinhuai Meng, Rong Pan, Qilian Jiang, Weiyuan Zhang, Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen, Hairong Guan, Xianping Wu, Ningmei Zhang, Xiaofang Chen, Xuefeng Tang, Guojin Luo, Jianguo Li, Xiaofang Chen, Xunfu Zhong, Jiaqiu Liu, Qiang Sun, Pengfei Ge, Xiaolan Ren, Caixia Dong, Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi Zhang, Ding Zhang, Gang Zhou, Shixian Feng, Liang Chang, Lei Fan, Yulian Gao, Tianyou He, Huarong Sun, Pan He, Chen Hu, Qiannan Lv, Xukui Zhang, Min Yu, Ruying Hu, Hao Wang, Yijian Qian, Chunmei Wang, Kaixue Xie, Lingli Chen, Yidan Zhang, Dongxia Pan, Yuelong Huang, Biyun Chen, Li Yin, Donghui Jin, Huilin Liu, Zhongxi Fu, Qiaohua Xu, Xin Xu, Hao Zhang, Youping Xiong, Huajun Long, Xianzhi Li, Libo Zhang, Zhe Qiu
Journal: Circulation Research (2024)

Alterations in lipid metabolism and DNA methylation are 2 hallmarks of aging. Connecting metabolomic, epigenomic, and aging outcomes help unravel the complex mechanisms underlying aging. We aimed to assess whether DNA methylation clocks mediate the association of circulating metabolites with incident atherosclerotic cardiovascular disease (ASCVD) and frailty.
Nanomaterials: Recent Advances in Knee Osteoarthritis Treatment
Authors: Yufeng Peng, Ying Wang, Ru Bai, Kejian Shi, Huige Zhou, Chunying Chen
Journal: Advanced Healthcare Materials (2024)

Osteoarthritis (OA) of the knee is the most prevalent degenerative joint condition that places a substantial financial and medical burden on society. However, due to drawbacks such as inefficiency, adverse effects, and brief duration of action, the clinical efficacy of the current major therapies for knee OA is largely restricted. Therefore, novel medication development is highly required to address these issues. Numerous studies in recent years have established that nanomaterials can be a potential and highly effective way to overcome these challenges. In this review, the anatomical distinctions between healthy and OA knee joints, as well as novel advances in the field of nanomaterials for the treatment of knee OA are summarized. The limits of the present therapeutic strategies for treating knee OA are also highlighted, as well as the potential prospects of nanomaterials in the future.
Hypoxia-responsive zinc finger E-box-binding homeobox 2 (ZEB2) regulates a network of calcium-handling genes in the injured heart
Authors: Monika M Gladka, Arwa Kohela, Anne E de Leeuw, Bas Molenaar, Danielle Versteeg, Lieneke Kooijman, Mariska van Geldorp, Willem B van Ham, Rocco Caliandro, Jody J Haigh, Toon A B van Veen, Eva van Rooij
Journal: Cardiovascular Research (2024)

Intracellular calcium (Ca2+) overload is known to play a critical role in the development of cardiac dysfunction. Despite the remarkable improvement in managing the progression of heart disease, developing effective therapies for heart failure (HF) remains a challenge. A better understanding of molecular mechanisms that maintain proper Ca2+ levels and contractility in the injured heart could be of therapeutic value.
A non-genetic model of vascular shunts informs on the cellular mechanisms of formation and resolution of arteriovenous malformations
Authors: Marie Ouarné, Andreia Pena, Daniela Ramalho, Nadine V Conchinha, Tiago Costa, Romain Enjalbert, Ana M Figueiredo, Marta Pimentel Saraiva, Yulia Carvalho, Miguel O Bernabeu, Lenka Henao Misikova, S Paul Oh, Cláudio A Franco
Journal: Cardiovascular Research (2024)

Arteriovenous malformations (AVMs), a disorder characterized by direct shunts between arteries and veins, are associated with genetic mutations. However, the mechanisms leading to AV shunt formation and how shunts can be reverted are poorly understood.
Renin-Angiotensin-Aldosterone System Modulators in Adults with Hypertension: A Network Meta-Analysis of Randomized Controlled Trials
Authors: Xiaoyan Yi, Shumin Yang, Jun Yang, Xiangjun Chen, Aipin Zhang, Qinglian Zeng, Wenjin Luo, Qifu Li, Jinbo Hu
Journal: Drugs (2024)
Impact of COVID-19 on 2021 cancer incidence rates and potential rebound from 2020 decline
Authors: Nadia Howlader, Huann-Sheng Chen, Anne-Michelle Noone, Daniel Miller, Jeffry Byrne, Serban Negoita, Kathleen A Cronin, Angela B Mariotto
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract The COVID-19 pandemic led to substantial declines in cancer incidence rates in 2020, likely because of disruptions in screening and diagnostic services. This study aimed to assess the impact of the pandemic on cancer incidence rates in the United States using 2021 incidence data from the Surveillance, Epidemiology, and End Results program. The analysis compared observed 2021 cancer incidence rates with expected prepandemic trends, evaluating changes by individual cancer site and stage. Although incidence overall and in many cancer sites the rates were close to prepandemic levels, they did not exhibit a recovery that incorporated the delayed diagnoses from 2020. There were exceptions, however, such as metastatic breast cancer, which showed significantly higher observed rates than expected (rate ratio = 1.09, 95% confidence interval = 1.04 to 1.13). Ongoing monitoring and targeted interventions are needed to address the long-term consequences of the COVID-19 pandemic on cancer care and outcomes.
Cell membrane-coated mRNA nanoparticles for enhanced delivery to dendritic cells and immunotherapy
Authors: Qiaoyun Li, Junho Byun, Dongyoon Kim, Yina Wu, Jaiwoo Lee, Yu-Kyoung Oh
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Cationic polymers such as polyethylenimine have been considered promising carriers for mRNA vaccines. However, their application is hindered by their inherent toxicity and a lack of targeted delivery capability. These issues need to be addressed to develop effective cancer vaccines. In this study, we investigated whether dendritic cell membrane-coated polyethylenimine/mRNA nanoparticles (DPN) could effectively deliver mRNA to dendritic cells and induce immune responses. For comparison, we employed red blood cell membrane-coated polyethylenimine/mRNA (RPN) and plain polyethylenimine/mRNA polyplex (PN). The dendritic cell membrane coating altered the zeta potential values and surface protein patterns of PN. DPN demonstrated significantly higher uptake in dendritic cells compared to PN and RPN, and it also showed greater mRNA expression within these cells. DPN, carrying mRNA encoding luciferase, enhanced green fluorescent protein, or ovalbumin (OVA), exhibited higher protein expression in dendritic cells than the other groups. Additionally, DPN exhibited favorable mRNA escape from lysosomes post-internalization into dendritic cells. In mice, subcutaneous administration of DPN containing ovalbumin mRNA (DPN
Semi-quantitative elemental imaging of corrosion products from bioabsorbable Mg vascular implants in vivo
Authors: Weilue He, Keith W MacRenaris, Adam Griebel, Maria P Kwesiga, Erico Freitas, Amani Gillette, Jeremy Schaffer, Thomas V O'Halloran, Roger J Guillory Ii
Journal: Bioactive Materials (2024)
Efficacy and Safety of Upadacitinib for Perianal Fistulizing Crohn’s Disease: A Post Hoc Analysis of 3 Phase 3 Trials
Authors: Jean-Frédéric Colombel, Ana P Lacerda, Peter M Irving, Remo Panaccione, Walter Reinisch, Florian Rieder, Adam Steinlauf, David Schwartz, Tian Feng, Elena Dubcenco, Samuel I Anyanwu, F Stephen Laroux, Colla Cunneen, Nick Powell
Journal: Clinical Gastroenterology and Hepatology (2024)
Comparison of short- and long-term humoral immune responses to pneumococcal polysaccharide and glycoconjugate vaccines in an HIV-infected population
Authors: Siân E Faustini, James Hodson, Jane Birtwistle, Alison Whitelegg, Sindiso Masuka, Mebie Singo, Joyful Chigiga, Adrian Shields, Timothy Plant, Mark T Drayson, Kaveh Manavi, Calman A MacLennan, Alex G Richter
Journal: Journal of Infection (2024)

Immunisation is recommended internationally to protect against pneumococcal infections in HIV-infected adults. However, vaccination schedule designs are mostly based on studies of initial rather than long-term antibody responses. This UK observational study investigated the short- and long-term antibody responses to polysaccharide and glycoconjugate pneumococcal vaccines in an adult HIV-infected cohort.
Aberrant pre-mRNA processing in cancer
Authors: Jeetayu Biswas, Leora Boussi, Eytan Stein, Omar Abdel-Wahab
Journal: The Journal of Experimental Medicine (2024)

Dysregulation of the flow of information from genomic DNA to RNA to protein occurs within all cancer types. In this review, we described the current state of understanding of how RNA processing is dysregulated in cancer with a focus on mutations in the RNA splicing factor machinery that are highly prevalent in hematologic malignancies. We discuss the downstream effects of these mutations highlighting both individual genes as well as common pathways that they perturb. We highlight examples of how alterations in RNA processing have been harnessed for therapeutic intent as well as to promote the selective toxicity of cancer cells.
Retraction Note: High replicability of newly discovered social-behavioural findings is achievable
Authors: John Protzko, Jon Krosnick, Leif Nelson, Brian A Nosek, Jordan Axt, Matt Berent, Nicholas Buttrick, Matthew DeBell, Charles R Ebersole, Sebastian Lundmark, Bo MacInnis, Michael O'Donnell, Hannah Perfecto, James E Pustejovsky, Scott S Roeder, Jan Walleczek, Jonathan W Schooler
Journal: Nature Human Behaviour (2024)
Modeling primary microcephaly with human brain organoids reveals fundamental roles of CIT kinase activity
Authors: Gianmarco Pallavicini, Amanda Moccia, Giorgia Iegiani, Roberta Parolisi, Emily R Peirent, Gaia Elena Berto, Martina Lorenzati, Rami Y Tshuva, Alessia Ferraro, Fiorella Balzac, Emilia Turco, Shachi U Salvi, Hedvig F Myklebust, Sophia Wang, Julia Eisenberg, Maushmi Chitale, Navjit S Girgla, Enrica Boda, Orly Reiner, Annalisa Buffo, Ferdinando Di Cunto, Stephanie L Bielas
Journal: Journal of Clinical Investigation (2024)

Brain size and cellular heterogeneity are tightly regulated by species-specific proliferation and differentiation of multipotent neural progenitor cells (NPCs). Errors in this process are among the mechanisms of primary hereditary microcephaly (MCPH), a group of disorders characterized by reduced brain size and intellectual disability. Biallelic CIT missense variants that disrupt kinase function (CITKI/KI) and frameshift loss-of-function variants (CITFS/FS) are the genetic basis for MCPH17; however, the function of CIT catalytic activity in brain development and NPC cytokinesis is unknown. Therefore, we created the CitKI/KI mouse model and found that it does not phenocopy human microcephaly, unlike biallelic CitFS/FS animals. Nevertheless, both Cit models exhibited binucleation, DNA damage, and apoptosis. To investigate human-specific mechanisms of CIT microcephaly, we generated CITKI/KI and CITFS/FS human forebrain organoids. We found that CITKI/KI and CITFS/FS organoids lose cytoarchitectural complexity, transitioning from pseudostratified to simple neuroepithelium. This change was associated with defects that disrupt polarity of NPC cytokinesis, in addition to elevating apoptosis. Together, our results indicate that both CIT catalytic and scaffolding functions in NPC cytokinesis are critical for human corticogenesis. Species differences in corticogenesis and the dynamic 3D features of NPC mitosis underscore the utility of human forebrain organoid models for understanding human microcephaly.
Stimulation of an entorhinal-hippocampal extinction circuit facilitates fear extinction in a post-traumatic stress disorder model
Authors: Ze-Jie Lin, Xue Gu, Wan-Kun Gong, Mo Wang, Yan-Jiao Wu, Qi Wang, Xin-Rong Wu, Xin-Yu Zhao, Michael X Zhu, Lu-Yang Wang, Quanying Liu, Ti-Fei Yuan, Wei-Guang Li, Tian-Le Xu
Journal: Journal of Clinical Investigation (2024)

Effective psychotherapy of post-traumatic stress disorder (PTSD) remains challenging due to the fragile nature of fear extinction, for which ventral hippocampal CA1 (vCA1) region is considered as a central hub. However, neither the core pathway nor the cellular mechanisms involved in implementing extinction are known. Here, we unveil a direct pathway, where layer 2a fan cells in the lateral entorhinal cortex (LEC) target parvalbumin-expressing interneurons (PV-INs) in the vCA1 region to propel low gamma-band synchronization of the LEC-vCA1 activity during extinction learning. Bidirectional manipulations of either hippocampal PV-INs or LEC fan cells sufficed fear extinction. Gamma entrainment of vCA1 by deep brain stimulation (DBS) or noninvasive transcranial alternating current stimulation (tACS) of LEC persistently enhanced the PV-IN activity in vCA1, thereby promoting fear extinction. These results demonstrate that the LEC-vCA1 pathway forms a top-down motif to empower low gamma-band oscillations that facilitate fear extinction. Finally, application of low gamma DBS and tACS to a mouse model with persistent PTSD showed potent efficacy, suggesting that the dedicated LEC-vCA1 pathway can be stimulated for therapy to remove traumatic memory trace.
Proteogenomic analysis integrated with electronic health records data reveals disease-associated variants in Black Americans
Authors: Usman A Tahir, Jacob L Barber, Daniel E Cruz, Meltem Ece Kars, Shuliang Deng, Bjoernar Tuftin, Madeline G Gillman, Mark D Benson, Jeremy M Robbins, Zsu-Zsu Chen, Prashant Rao, Daniel H Katz, Laurie Farrell, Tamar Sofer, Michael E Hall, Lynette Ekunwe, Russell P Tracy, Peter Durda, Kent D Taylor, Yongmei Liu, W Craig Johnson, Xiuqing Guo, Yii-Der Ida Chen, Ani W Manichaikul, Deepti Jain, Thomas J Wang, Alex P Reiner, Pradeep Natarajan, Yuval Itan, Stephen S Rich, Jerome I Rotter, James G Wilson, Laura M Raffield, Robert E Gerszten
Journal: Journal of Clinical Investigation (2024)

BACKGROUNDMost GWAS of plasma proteomics have focused on White individuals of European ancestry, limiting biological insight from other ancestry-enriched protein quantitative loci (pQTL).METHODSWe conducted a discovery GWAS of approximately 3,000 plasma proteins measured by the antibody-based Olink platform in 1,054 Black adults from the Jackson Heart Study (JHS) and validated our findings in the Multi-Ethnic Study of Atherosclerosis (MESA). The genetic architecture of identified pQTLs was further explored through fine mapping and admixture association analysis. Finally, using our pQTL findings, we performed a phenome-wide association study (PheWAS) across 2 large multiethnic electronic health record (EHR) systems in All of Us and BioMe.RESULTSWe identified 1,002 pQTLs for 925 protein assays. Fine mapping and admixture analyses suggested allelic heterogeneity of the plasma proteome across diverse populations. We identified associations for variants enriched in African ancestry, many in diseases that lack precise biomarkers, including cis-pQTLs for cathepsin L (CTSL) and Siglec-9, which were linked with sarcoidosis and non-Hodgkin's lymphoma, respectively. We found concordant associations across clinical diagnoses and laboratory measurements, elucidating disease pathways, including a cis-pQTL associated with circulating CD58, WBC count, and multiple sclerosis.CONCLUSIONSOur findings emphasize the value of leveraging diverse populations to enhance biological insights from proteomics GWAS, and we have made this resource readily available as an interactive web portal.FUNDINGNIH K08 HL161445-01A1; 5T32HL160522-03; HHSN268201600034I; HL133870.
Innate immune cell activation by adjuvant AS01 in human lymph node explants is age-independent
Authors: Vicki V Stylianou, Kirstie M Bertram, Van Anh Vo, Elizabeth B Dunn, Heeva Baharlou, Darcii J Terre, James Elhindi, Elisabeth Elder, James French, Farid Meybodi, Stéphane T Temmerman, Arnaud M Didierlaurent, Margherita Coccia, Kerrie J Sandgren, Anthony L Cunningham
Journal: Journal of Clinical Investigation (2024)

Vaccine adjuvants are thought to work by stimulating innate immunity in the draining lymph node (LN), although this has not been proven in humans. To bridge the data obtained in animals to humans, we have developed an in situ human LN explant model to investigate how adjuvants initiate immunity. Slices of explanted LNs were exposed to vaccine adjuvants and revealed responses that were not detectable in LN cell suspensions. We used this model to compare the liposome-based AS01 with its components, monophosphoryl lipid A (MPL) and QS-21, and TLR ligands. Liposomes were predominantly taken up by subcapsular sinus-lining macrophages, monocytes, and DCs. AS01 induced DC maturation and a strong proinflammatory cytokine response in intact LN slices but not in dissociated cell cultures, in contrast to R848. This suggests that the onset of the immune response to AS01 required a coordinated activation of LN cells in time and space. Consistent with the robust immune response observed in older adults with AS01-adjuvanted vaccines, the AS01 response in human LNs was independent of age, unlike the response to R848. This human LN explant model is a valuable tool for studying the mechanism of action of adjuvants in humans and for screening new formulations to streamline vaccine development.