tbuckley/cabot-search huggingface dataset:
Analysis of blood methylation quantitative trait loci in East Asians reveals ancestry-specific impacts on complex traits
Authors: Qianqian Peng, Xinxuan Liu, Wenran Li, Han Jing, Jiarui Li, Xingjian Gao, Qi Luo, Charles E. Breeze, Siyu Pan, Qiwen Zheng, Guochao Li, Jiaqiang Qian, Liyun Yuan, Na Yuan, Chenglong You, Siyuan Du, Yuanting Zheng, Ziyu Yuan, Jingze Tan, Peilin Jia, Jiucun Wang, Guoqing Zhang, Xianping Lu, Leming Shi, Shicheng Guo, Yun Liu, Ting Ni, Bo Wen, Changqing Zeng, Li Jin, Andrew E. Teschendorff, Fan Liu, Sijia Wang
Journal: Nature Genetics (2024)
GLI1+ Cells Contribute to Vascular Remodeling in Pulmonary Hypertension
Authors: Xuran Chu, Vahid Kheirollahi, Arun Lingampally, Prakash Chelladurai, Chanil Valasarajan, Ana Ivonne Vazquez-Armendariz, Stefan Hadzic, Ali Khadim, Oleg Pak, Stefano Rivetti, Jochen Wilhelm, Marek Bartkuhn, Slaven Crnkovic, Alena Moiseenko, Monika Heiner, Simone Kraut, Leila Sotoodeh Atefi, Janine Koepke, Guilherme Valente, Clemens Ruppert, Thomas Braun, Christos Samakovlis, Ioannis Alexopoulos, Mario Looso, Cho-Ming Chao, Susanne Herold, Werner Seeger, Grazyna Kwapiszewska, Xiaoying Huang, Jin-San Zhang, Soni Savai Pullamsetti, Norbert Weissmann, Xiaokun Li, Elie El Agha, Saverio Bellusci
Journal: Circulation Research (2024)

The precise origin of newly formed ACTA2+ (alpha smooth muscle actin-positive) cells appearing in nonmuscularized vessels in the context of pulmonary hypertension is still debatable although it is believed that they predominantly derive from preexisting vascular smooth muscle cells (VSMCs).
Mitochondrial CypD Acetylation Promotes Endothelial Dysfunction and Hypertension
Authors: Anna Dikalova, Daniel Fehrenbach, Vladimir Mayorov, Alexander Panov, Mingfang Ao, Louise Lantier, Venkataraman Amarnath, Marcos G. Lopez, Frederic T. Billings, Michael N. Sack, Sergey Dikalov
Journal: Circulation Research (2024)

Nearly half of adults have hypertension, a major risk factor for cardiovascular disease. Mitochondrial hyperacetylation is linked to hypertension, but the role of acetylation of specific proteins is not clear. We hypothesized that acetylation of mitochondrial CypD (cyclophilin D) at K166 contributes to endothelial dysfunction and hypertension.
Heterogeneous Uptake of 68Ga-DOTATATE and 18F-FDG in Initial Diagnosed Neuroendocrine Tumors Patients
Authors: Yi Zhou, Li Li, Hui Wang, He-xiao Huang, Dan Cao, Neng-wen Ke, Ming-gang Su, Rong Tian
Journal: Clinical Nuclear Medicine (2024)

Purpose This study was designed to assess the uptake heterogeneity in neuroendocrine tumor (NET) patients at initial diagnosis with dual-tracer PET imaging and the staging changes and prognostic value it brings to explore the indication of the use of dual-tracer PET. Methods Fifty-one newly diagnosed patients with pathologically confirmed NET who underwent 18 F-FDG and 68 Ga-DOTATATE PET imaging between January 2020 and September 2022 were enrolled. Dual-tracer uptake patterns were classified into 3 groups: A. 68 Ga-DOTATATE positive and 18 F-FDG negative, B. 68 Ga-DOTATATE positive and 18 F-FDG positive, and C. 68 Ga-DOTATATE negative and 18 F-FDG positive. Descriptive statistics were used to evaluate the heterogeneity of dual-tracer uptake patterns among different grading (G) groups, between primary and metastatic lesions, and staging changes. Moreover, dual-tracer uptake patterns, grade, age, sex, and stage were compared with progression-free survival (PFS) by Cox regression. Results In the different G groups, none of the patients with dual-tracer uptake pattern A had grade 3 histology, but 57% of patients with grade 1 disease had FDG avidity (25% of them resulting in dual-tracer uptake pattern C). Patients with no metastasis were well differentiated, but one of them presented with dual-tracer uptake pattern C. Different uptake patterns were also observed between primary and metastatic lesions, particularly 44% of patients with dual-tracer uptake pattern A of primary with FDG avidity of metastases. Moreover, 9 (17.6%) had new lesions detected by additional 18 F-FDG PET imaging, and 3 of them (5.9%) had clinical stage changed accordingly. The Cox regression test showed that the dual-tracer uptake patterns were significantly correlated with PFS by univariate and multivariate analyses ( P = 0.026 and 0.039, respectively), whereas the grade and stage did not correlate with survival (all P &gt;0.05). Conclusion The current study has proven the uptake heterogeneity of the NET at initial diagnosis and demonstrated the staging and prognostic value of dual-tracer PET imaging. Our preliminary results have confirmed the importance of dual-tracer imaging modalities and concluded that dual-tracer PET imaging could be considered as prognostic tool for all patients with an initial diagnosis of NET.
Radiomic signatures associated with tumor immune heterogeneity predict survival in locally recurrent nasopharyngeal carcinoma
Authors: Da-Feng Lin, Hai-Lin Li, Ting Liu, Xiao-Fei Lv, Chuan-Miao Xie, Xiao-Min Ou, Jian Guan, Ye Zhang, Wen-Bin Yan, Mei-Lin He, Meng-Yuan Mao, Xun Zhao, Lian-Zhen Zhong, Wen-Hui Chen, Qiu-Yan Chen, Hai-Qiang Mai, Rou-Jun Peng, Jie Tian, Lin-Quan Tang, Di Dong
Journal: JNCI Journal of the National Cancer Institute (2024)

The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma is limited because of their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in locally recurrent nasopharyngeal carcinoma.
Stimuli‐Mediated Macrophage Switching, Unraveling the Dynamics at the Nanoplatforms–Macrophage Interface
Authors: Keya Ganguly, Rachmi Luthfikasari, Aayushi Randhawa, Sayan Deb Dutta, Tejal V. Patil, Rumi Acharya, Ki‐Taek Lim
Journal: Advanced Healthcare Materials (2024)

Abstract Macrophages play an essential role in immunotherapy and tissue regeneration owing to their remarkable plasticity and diverse functions. Recent bioengineering developments have focused on using external physical stimuli such as electric and magnetic fields, temperature, and compressive stress, among others, on micro/nanostructures to induce macrophage polarization, thereby increasing their therapeutic potential. However, it is difficult to find a concise review of the interaction between physical stimuli, advanced micro/nanostructures, and macrophage polarization. This review examines the present research on physical stimuli‐induced macrophage polarization on micro/nanoplatforms, emphasizing the synergistic role of fabricated structure and stimulation for advanced immunotherapy and tissue regeneration. A concise overview of the research advancements investigating the impact of physical stimuli, including electric fields, magnetic fields, compressive forces, fluid shear stress, photothermal stimuli, and multiple stimulations on the polarization of macrophages within complex engineered structures, is provided. The prospective implications of these strategies in regenerative medicine and immunotherapeutic approaches are highlighted. This review will aid in creating stimuli‐responsive platforms for immunomodulation and tissue regeneration.
Measuring, visualizing, and diagnosing reference bias with biastools
Authors: Mao-Jan Lin, Sheila Iyer, Nae-Chyun Chen, Ben Langmead
Journal: Genome biology (2024)

Abstract Many bioinformatics methods seek to reduce reference bias, but no methods exist to comprehensively measure it. analyzes and categorizes instances of reference bias. It works in various scenarios: when the donor’s variants are known and reads are simulated; when donor variants are known and reads are real; and when variants are unknown and reads are real. Using , we observe that more inclusive graph genomes result in fewer biased sites. We find that end-to-end alignment reduces bias at indels relative to local aligners. Finally, we use to characterize how T2T references improve large-scale bias.
spVC for the detection and interpretation of spatial gene expression variation
Authors: Shan Yu, Wei Vivian Li
Journal: Genome biology (2024)

Abstract Spatially resolved transcriptomics technologies have opened new avenues for understanding gene expression heterogeneity in spatial contexts. However, existing methods for identifying spatially variable genes often focus solely on statistical significance, limiting their ability to capture continuous expression patterns and integrate spot-level covariates. To address these challenges, we introduce spVC, a statistical method based on a generalized Poisson model. spVC seamlessly integrates constant and spatially varying effects of covariates, facilitating comprehensive exploration of gene expression variability and enhancing interpretability. Simulation and real data applications confirm spVC’s accuracy in these tasks, highlighting its versatility in spatial transcriptomics analysis.
Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy
Authors: Pei-Chien Tsai, Chung-Feng Huang, Ming-Lun Yeh, Meng-Hsuan Hsieh, Hsing-Tao Kuo, Chao-Hung Hung, Kuo-Chih Tseng, Hsueh-Chou Lai, Cheng-Yuan Peng, Jing-Houng Wang, Jyh-Jou Chen, Pei-Lun Lee, Rong-Nan Chien, Chi-Chieh Yang, Gin-Ho Lo, Jia-Horng Kao, Chun-Jen Liu, Chen-Hua Liu, Sheng-Lei Yan, Chun-Yen Lin, Wei-Wen Su, Cheng-Hsin Chu, Chih-Jen Chen, Shui-Yi Tung, Chi‐Ming Tai, Chih-Wen Lin, Ching-Chu Lo, Pin-Nan Cheng, Yen-Cheng Chiu, Chia-Chi Wang, Jin-Shiung Cheng, Wei-Lun Tsai, Han-Chieh Lin, Yi-Hsiang Huang, Chi-Yi Chen, Jee-Fu Huang, Chia-Yen Dai, Wan-Long Chung, Ming-Jong Bair, Ming-Lung Yu
Journal: Clinical and Molecular Hepatology (2024)

Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan's cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray's cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.
A roadmap for therapeutic discovery in pulmonary hypertension associated with left heart failure. A scientific statement of the Heart Failure Association (<scp>HFA</scp>) of the <scp>ESC</scp> and the <scp>ESC</scp> Working Group on Pulmonary Circulation &amp; Right Ventricular Function
Authors: Pietro Ameri, Valentina Mercurio, Piero Pollesello, Markus S. Anker, Johannes Backs, Antoni Bayes‐Genis, Barry A. Borlaug, Daniel Burkhoff, Sergio Caravita, Stephen Y. Chan, Frances de Man, George Giannakoulas, Aránzazu González, Marco Guazzi, Paul M. Hassoun, Anna R. Hemnes, Cristoph Maack, Brendan Madden, Vojtech Melenovsky, Oliver J. Müller, Zoltan Papp, Soni Savai Pullamsetti, Peter P. Rainer, Margaret M. Redfield, Stuart Rich, Gabriele G. Schiattarella, Hall Skaara, Kostantinos Stellos, Ryan J. Tedford, Thomas Thum, Jean Luc Vachiery, Peter van der Meer, Sophie Van Linthout, Piotr Pruszczyk, Petar Seferovic, Andrew J.S. Coats, Marco Metra, Giuseppe Rosano, Stephan Rosenkranz, Carlo Gabriele Tocchetti
Journal: European Journal of Heart Failure (2024)

Pulmonary hypertension (PH) associated with left heart failure (LHF) (PH‐LHF) is one of the most common causes of PH. It directly contributes to symptoms and reduced functional capacity and negatively affects right heart function, ultimately leading to a poor prognosis. There are no specific treatments for PH‐LHF, despite the high number of drugs tested so far. This scientific document addresses the main knowledge gaps in PH‐LHF with emphasis on pathophysiology and clinical trials. Key identified issues include better understanding of the role of pulmonary venous versus arteriolar remodelling, multidimensional phenotyping to recognize patient subgroups positioned to respond to different therapies, and conduct of rigorous pre‐clinical studies combining small and large animal models. Advancements in these areas are expected to better inform the design of clinical trials and extend treatment options beyond those effective in pulmonary arterial hypertension. Enrichment strategies, endpoint assessments, and thorough haemodynamic studies, both at rest and during exercise, are proposed to play primary roles to optimize early‐stage development of candidate therapies for PH‐LHF.
Synthetic cationic helical polypeptides for the stimulation of antitumour innate immune pathways in antigen-presenting cells
Authors: DaeYong Lee, Kristin Huntoon, Yifan Wang, Minjeong Kang, Yifei Lu, Seong Dong Jeong, Todd M. Link, Thomas D. Gallup, Yaqing Qie, Xuefeng Li, Shiyan Dong, Benjamin R. Schrank, Adam J. Grippin, Abin Antony, JongHoon Ha, Mengyu Chang, Yi An, Liang Wang, Dadi Jiang, Jing Li, Albert C. Koong, John A. Tainer, Wen Jiang, Betty Y. S. Kim
Journal: Nature Biomedical Engineering (2024)
Increased reports of measles in the Metropolitan City of Milan, northern Italy, September 2023 to March 2024
Authors: Maria Gori, Clara Fappani, Silvia Bianchi, Sabrina Senatore, Daniela Colzani, Priscilla Pasutto, Melissa Baggieri, Silvia Gioacchini, Antonella Marchi, Paola Bucci, Emilio D’Ugo, Marino Faccini, Danilo Cereda, Luigi Vezzosi, Elisabetta Tanzi, Fabio Magurano, Antonella Amendola
Journal: Eurosurveillance (2024)

Since late 2023, the Metropolitan City of Milan and surrounding areas (northern Italy) have been experiencing a resurgence of measles, with most cases detected starting from January 2024. During this brief period, we observed measles in travellers from endemic areas, participants in international events, vaccinees and healthcare workers. Indigenous cases have also been identified. Even though we have not yet identified large and disruptive outbreaks, strengthening surveillance and vaccination activities is pivotal to help limit the impact of measles spread.
Lkb1 orchestrates γδ T-cell metabolic and functional fitness to control IL-17-mediated autoimmune hepatitis
Authors: Zhiqiang Xiao, Shanshan Wang, Liang Luo, Wenkai Lv, Peiran Feng, Yadong Sun, Quanli Yang, Jun He, Guangchao Cao, Zhinan Yin, Meixiang Yang
Journal: Cellular and Molecular Immunology (2024)
Single-Cell Gene-Regulatory Networks of Advanced Symptomatic Atherosclerosis
Authors: Giuseppe Mocci, Katyayani Sukhavasi, Tiit Örd, Sean Bankier, Prosanta Singha, Uma Thanigai Arasu, Olayinka Oluwasegun Agbabiaje, Petri Mäkinen, Lijiang Ma, Chani J. Hodonsky, Redouane Aherrahrou, Lars Muhl, Jianping Liu, Sonja Gustafsson, Byambajav Byandelger, Ying Wang, Simon Koplev, Urban Lendahl, Gary K. Owens, Nicholas J. Leeper, Gerard Pasterkamp, Michael Vanlandewijck, Tom Michoel, Arno Ruusalepp, Ke Hao, Seppo Ylä-Herttuala, Marika Väli, Heli Järve, Michal Mokry, Mete Civelek, Clint J. Miller, Jason C. Kovacic, Minna U. Kaikkonen, Christer Betsholtz, Johan L.M. Björkegren
Journal: Circulation Research (2024)

While our understanding of the single-cell gene expression patterns underlying the transformation of vascular cell types during the progression of atherosclerosis is rapidly improving, the clinical and pathophysiological relevance of these changes remains poorly understood.
<i>Ncf1</i> knockout in smooth muscle cells exacerbates angiotensin II–induced aortic aneurysm and dissection by activating the STING pathway
Authors: Hao Liu, Peiwen Yang, Shu Chen, Shilin Wang, Lang Jiang, Xiaoyue Xiao, Sheng Le, Shanshan Chen, Xinzhong Chen, Ping Ye, Jiahong Xia
Journal: Cardiovascular Research (2024)

Abstract Aims Aortic aneurysm and dissection (AAD) is caused by the progressive loss of aortic smooth muscle cells (SMCs) and is associated with a high mortality rate. Identifying the mechanisms underlying SMC apoptosis is crucial for preventing AAD. Neutrophil cytoplasmic factor 1 (Ncf1) is essential in reactive oxygen species production and SMC apoptosis; Ncf1 absence leads to autoimmune diseases and chronic inflammation. Here, the role of Ncf1 in angiotensin II (Ang II)–induced AAD was investigated. Methods and results Ncf1 expression increased in injured SMCs. Bioinformatic analysis identified Ncf1 as a mediator of AAD-associated SMC damage. Ncf1 expression is positively correlated with DNA replication and repair in SMCs of AAD aortas. AAD incidence increased in Ang II–challenged Sm22CreNcf1fl mice. Transcriptomics showed that Ncf1 knockout activated the stimulator of interferon genes (STING) and cell death pathways. The effects of Ncf1 on SMC death and the STING pathway in vitro were examined. Ncf1 regulated the hydrogen peroxide–mediated activation of the STING pathway and inhibited SMC apoptosis. Mechanistically, Ncf1 knockout promoted the ubiquitination of nuclear factor erythroid 2-related factor 2 (NRF2), thereby inhibiting the negative regulatory effect of NRF2 on the stability of STING mRNA and ultimately promoting STING expression. Additionally, the pharmacological inhibition of STING activation prevented AAD progression. Conclusion Ncf1 deficiency in SMCs exacerbated Ang II–induced AAD by promoting NRF2 ubiquitination and degradation and activating the STING pathway. These data suggest that Ncf1 may be a potential therapeutic target for AAD treatment.
Potential and pitfalls of repurposing the CAR-T cell regimen for the treatment of autoimmune disease
Authors: Andrea R Daamen, Peter E Lipsky
Journal: Annals of the Rheumatic Diseases (2024)

Chimeric antigen receptors (CARs) are synthetic proteins designed to direct an immune response toward a specific target and have been used in immunotherapeutic applications through the adoptive transfer of T cells genetically engineered to express CARs. This technology received early attention in oncology with particular success in treatment of B cell malignancies leading to the launch of numerous successful clinical trials and the US Food and Drug Administration approval of several CAR-T-based therapies. Many CAR-T constructs have been employed, but have always been administered following a lymphodepletion regimen. The success of CAR-T cell treatment in targeting malignant B cells has led many to consider the potential for using these regimens to delete pathogenic B cells in autoimmune diseases. Preliminary results have suggested efficacy, but the sample size remains small, controlled trials have not been done, the role of immunodepletion has not been established, the most effective CAR-T constructs have not been identified and the most appropriate patient subsets for treatment have not been established.
An autoantibody signature predictive for multiple sclerosis
Authors: Colin R. Zamecnik, Gavin M. Sowa, Ahmed Abdelhak, Ravi Dandekar, Rebecca D. Bair, Kristen J. Wade, Christopher M. Bartley, Kerry Kizer, Danillo G. Augusto, Asritha Tubati, Refujia Gomez, Camille Fouassier, Chloe Gerungan, Colette M. Caspar, Jessica Alexander, Anne E. Wapniarski, Rita P. Loudermilk, Erica L. Eggers, Kelsey C. Zorn, Kirtana Ananth, Nora Jabassini, Sabrina A. Mann, Nicholas R. Ragan, Adam Santaniello, Roland G. Henry, Sergio E. Baranzini, Scott S. Zamvil, Joseph J. Sabatino, Riley M. Bove, Chu-Yueh Guo, Jeffrey M. Gelfand, Richard Cuneo, H.-Christian von Büdingen, Jorge R. Oksenberg, Bruce A. C. Cree, Jill A. Hollenbach, Ari J. Green, Stephen L. Hauser, Mitchell T. Wallin, Joseph L. DeRisi, Michael R. Wilson
Journal: Nature Medicine (2024)
Emergence of OXA-48-producing Klebsiella pneumoniae in Lithuania, 2023: a multi-cluster, multi-hospital outbreak
Authors: Paulius Greičius, Marius Linkevicius, Jelena Razmuk, Jekaterina Sinotova, Erik Alm, Olov Svartström, Valeria Bortolaia, Eglė Kudirkienė, Louise Roer, Rene S Hendriksen, Gabija Tamoliūnaitė, Daniel Palm, Dominique L Monnet, Anke Kohlenberg, Algirdas Griškevičius
Journal: Eurosurveillance (2024)

In 2023, an increase of OXA-48-producing
Postpartum Breast Cancer and Survival in Women With Germline <i>BRCA</i> Pathogenic Variants
Authors: Zhenzhen Zhang, Shangyuan Ye, Sarah M. Bernhardt, Heidi D. Nelson, Ellen M. Velie, Virginia F. Borges, Emma R. Woodward, D. Gareth R. Evans, Pepper J. Schedin
Journal: JAMA Network Open (2024)

In young-onset breast cancer (YOBC), a diagnosis within 5 to 10 years of childbirth is associated with increased mortality. Women with germline BRCA1/2 pathogenic variants (PVs) are more likely to be diagnosed with BC at younger ages, but the impact of childbirth on mortality is unknown.
Harnessing the Electronic Health Record to Improve Empiric Antibiotic Prescribing
Authors: Anurag N. Malani, Preeti N. Malani
Journal: JAMA (2024)

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