tbuckley/cabot-search huggingface dataset:
Comparative Genome Microsynteny Illuminates the Fast Evolution of Nuclear Mitochondrial Segments (NUMTs) in Mammals
Authors: Marek Uvizl, Sebastien J Puechmaille, Sarahjane Power, Martin Pippel, Samuel Carthy, Wilfried Haerty, Eugene W Myers, Emma C Teeling, Zixia Huang
Journal: Molecular Biology and Evolution (2023)

The escape of DNA from mitochondria into the nuclear genome (nuclear mitochondrial DNA, NUMT) is an ongoing process. Although pervasively observed in eukaryotic genomes, their evolutionary trajectories in a mammal-wide context are poorly understood. The main challenge lies in the orthology assignment of NUMTs across species due to their fast evolution and chromosomal rearrangements over the past 200 million years. To address this issue, we systematically investigated the characteristics of NUMT insertions in 45 mammalian genomes and established a novel, synteny-based method to accurately predict orthologous NUMTs and ascertain their evolution across mammals. With a series of comparative analyses across taxa, we revealed that NUMTs may originate from nonrandom regions in mtDNA, are likely found in transposon-rich and intergenic regions, and unlikely code for functional proteins. Using our synteny-based approach, we leveraged 630 pairwise comparisons of genome-wide microsynteny and predicted the NUMT orthology relationships across 36 mammals. With the phylogenetic patterns of NUMT presence-and-absence across taxa, we constructed the ancestral state of NUMTs given the mammal tree using a coalescent method. We found support on the ancestral node of Fereuungulata within Laurasiatheria, whose subordinal relationships are still controversial. This study broadens our knowledge on NUMT insertion and evolution in mammalian genomes and highlights the merit of NUMTs as alternative genetic markers in phylogenetic inference.
Independent prognostic importance of blood urea nitrogen to creatinine ratio in heart failure
Authors: Paolo Tolomeo, Jawad H. Butt, Toru Kondo, Gianluca Campo, Akshay S. Desai, Pardeep S. Jhund, Lars Køber, Martin P. Lefkowitz, Jean L. Rouleau, Scott D. Solomon, Karl Swedberg, Muthiah Vaduganathan, Michael R. Zile, Milton Packer, John J.V. McMurray
Journal: European Journal of Heart Failure (2023)
Prognostic value of gut <scp>microbe‐generated</scp> metabolite phenylacetylglutamine in patients with heart failure
Authors: W.H. Wilson Tang, Ina Nemet, Xinmin S. Li, Yuping Wu, Arash Haghikia, Marco Witkowski, Robert A. Koeth, Ilja Demuth, Maximilian König, Elisabeth Steinhagen‐Thiessen, Fredrik Bäckhed, Michael A. Fischbach, Arjun Deb, Ulf Landmesser, Stanley L. Hazen
Journal: European Journal of Heart Failure (2023)

Phenylacetylglutamine (PAGln) is a phenylalanine-derived metabolite produced by gut microbiota with mechanistic links to heart failure (HF)-relevant phenotypes. We sought to investigate the prognostic value of PAGln in patients with stable HF.
Vasodilators in congestive heart failure: The perfect weapon aiming just off the target? Letter regarding the article ‘Impact of vasodilators on diuretic response in patients with congestive heart failure: A mechanistic trial of cimlanod (BMS‐986231)’
Authors: Pier Paolo Bocchino, Guglielmo Gallone, Simone Frea, Gaetano Maria De Ferrari
Journal: European Journal of Heart Failure (2023)
Lymphopenia confers poorer prognosis in Myelodysplastic Syndromes with very low and low IPSS-M
Authors: David Fandrei, Tony Huynh, Marie Sébert, Lorea Aguinaga, Valeria Bisio, Rathana Kim, Emmanuelle Clappier, Marion Espéli, Karl Balabanian, Hélène Moins-Teisserenc, Antoine Toubert, Nicolas Dulphy, Pierre Fenaux, Lionel Adès, Lin-Pierre Zhao
Journal: Blood Cancer Journal (2023)
Effect of paced heart rate on quality of life and natriuretic peptides for stage B or C heart failure with preserved ejection fraction: A secondary analysis of the <scp>myPACE</scp> trial
Authors: Rafael de la Espriella, Kramer J. Wahlberg, Margaret Infeld, Patricia Palau, Eduardo Núñez, Juan Sanchis, Markus Meyer, Julio Núñez
Journal: European Journal of Heart Failure (2023)
<i>Fusobacterium nucleatum</i> promotes inflammatory and anti-apoptotic responses in colorectal cancer cells via ADP-heptose release and ALPK1/TIFA axis activation
Authors: Camille Martin-Gallausiaux, Laurène Salesse, Diego Garcia-Weber, Ludovica Marinelli, Fabienne Beguet-Crespel, Vincent Brochard, Camille Le Gléau, Alexandre Jamet, Joël Doré, Hervé M. Blottière, Cécile Arrieumerlou, Nicolas Lapaque
Journal: Gut Microbes (2023)

The anaerobic bacterium Fusobacterium nucleatum is significantly associated with human colorectal cancer (CRC) and is considered a significant contributor to the disease. The mechanisms underlying the promotion of intestinal tumor formation by F. nucleatum have only been partially uncovered. Here, we showed that F. nucleatum releases a metabolite into the microenvironment that strongly activates NF-κB in intestinal epithelial cells via the ALPK1/TIFA/TRAF6 pathway. Furthermore, we showed that the released molecule had the biological characteristics of ADP-heptose. We observed that F. nucleatum induction of this pathway increased the expression of the inflammatory cytokine IL-8 and two anti-apoptotic genes known to be implicated in CRC, BIRC3 and TNFAIP3. Finally, it promoted the survival of CRC cells and reduced 5-fluorouracil chemosensitivity in vitro. Taken together, our results emphasize the importance of the ALPK1/TIFA pathway in Fusobacterium induced-CRC pathogenesis, and identify the role of ADP-H in this process.
Induced Endothelial Cell Cycle Arrest Prevents Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia
Authors: Gael Genet, Nafiisha Genet, Umadevi Paila, Shelby R. Cain, Aleksandra Cwiek, Nicholas W. Chavkin, Vlad Serbulea, Agnès Figueras, Pau Cerdà, Stephanie P. McDonnell, Danya Sankaranarayanan, Mahalia Huba, Elizabeth A. Nelson, Antoni Riera-Mestre, Karen K. Hirschi
Journal: Circulation (2023)

Distinct endothelial cell cycle states (early G1 versus late G1) provide different "windows of opportunity" to enable the differential expression of genes that regulate venous versus arterial specification, respectively. Endothelial cell cycle control and arteriovenous identities are disrupted in vascular malformations including arteriovenous shunts, the hallmark of hereditary hemorrhagic telangiectasia (HHT). To date, the mechanistic link between endothelial cell cycle regulation and the development of arteriovenous malformations (AVMs) in HHT is not known.
A commentary on ‘Long-term health-related quality of life in patients with gastric cancer after total or distal gastrectomy: a propensity score-matched cohort study’
Authors: Zhiheng Chen, Haiqiang Li, Honggang Jiang, Jiaming Wu, Yuping Peng
Journal: International Journal of Surgery (2023)

Chen, Zhiheng; Li, Haiqiang; Jiang, Honggang; Wu, Jiaming; Peng, Yuping Author Information
Benchmarking splice variant prediction algorithms using massively parallel splicing assays
Authors: Cathy Smith, Jacob O. Kitzman
Journal: Genome biology (2023)

Variants that disrupt mRNA splicing account for a sizable fraction of the pathogenic burden in many genetic disorders, but identifying splice-disruptive variants (SDVs) beyond the essential splice site dinucleotides remains difficult. Computational predictors are often discordant, compounding the challenge of variant interpretation. Because they are primarily validated using clinical variant sets heavily biased to known canonical splice site mutations, it remains unclear how well their performance generalizes.
Assessing the survival advantage of deferred cytoreductive nephrectomy using a prediction interval
Authors: Kuo-Chuan Hung, I-Ting Tsai, Cheuk-Kwan Sun
Journal: International Journal of Surgery (2023)

aDepartment of Anesthesiology, Chi Mei Medical Center, Tainan City, Taiwan bDepartment of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan cSchool of Medicine, College of Medicine, I-Shou University, Kaohsiung City, Taiwan dDepartment of Emergency Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung City, Taiwan Short title: Survival advantage from deferred cytoreductive nephrectomy Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding Author. Address: Department of Emergency Medicine, E-Da Dachang Hospital, I-Shou University, No. 305, Dachang 1st Road, Sanmin District, Kaohsiung City, Taiwan. Tel: +886-7-6150011 ext 1007; Mobile: +886-975106203. Fax: +886-7-6150915. E-mail address: [email protected]; [email protected] (C-K. Sun). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
Drugs/agents for the treatment of ischemic stroke: Advances and perspectives
Authors: Jian Jia, Weijie Jiao, Guan Wang, Jianbing Wu, Zhangjian Huang, Yihua Zhang
Journal: Medicinal Research Reviews (2023)

Ischemic stroke (IS) poses a significant threat to global human health and life. In recent decades, we have witnessed unprecedented progresses against IS, including thrombolysis, thrombectomy, and a few medicines that can assist in reopening the blocked brain vessels or serve as standalone treatments for patients who are not eligible for thrombolysis/thrombectomy therapies. However, the narrow time windows of thrombolysis/thrombectomy, coupled with the risk of hemorrhagic transformation, as well as the lack of highly effective and safe medications, continue to present big challenges in the acute treatment and long-term recovery of IS. In the past 3 years, several excellent articles have reviewed pathophysiology of IS and therapeutic medicines for the treatment of IS based on the pathophysiology. Regretfully, there is no comprehensive overview to summarize all categories of anti-IS drugs/agents designed and synthesized based on molecular mechanisms of IS pathophysiology. From medicinal chemistry view of point, this article reviews a multitude of anti-IS drugs/agents, including small molecule compounds, natural products, peptides, and others, which have been developed based on the molecular mechanism of IS pathophysiology, such as excitotoxicity, oxidative/nitrosative stresses, cell death pathways, and neuroinflammation, and so forth. In addition, several emerging medicines and strategies, including nanomedicines, stem cell therapy and noncoding RNAs, which recently appeared for the treatment of IS, are shortly introduced. Finally, the perspectives on the associated challenges and future directions of anti-IS drugs/agents are briefly provided to move the field forward.
Single-Cell RNA Sequencing Reveals Metabolic Stress-Dependent Activation of Cardiac Macrophages in a Model of Dyslipidemia-Induced Diastolic Dysfunction
Authors: Cristina Panico, Arianna Felicetta, Paolo Kunderfranco, Marco Cremonesi, Nicolò Salvarani, Pierluigi Carullo, Federico Colombo, Alessandra Idini, Mauro Passaretti, Riccardo Doro, Marcello Rubino, Alessandro Villaschi, Giorgio Da Rin, Clelia Peano, Marinos Kallikourdis, Carolina M. Greco, Gianluigi Condorelli
Journal: Circulation (2023)

BACKGROUND: Metabolic distress is often associated with heart failure with preserved ejection fraction (HFpEF) and represents a therapeutic challenge. Metabolism-induced systemic inflammation links comorbidities with HFpEF. How metabolic changes affect myocardial inflammation in the context of HFpEF is not known. METHODS: We found that ApoE knockout mice fed a Western diet recapitulate many features of HFpEF. Single-cell RNA sequencing was used for expression analysis of CD45 + cardiac cells to evaluate the involvement of inflammation in diastolic dysfunction. We focused bioinformatics analysis on macrophages, obtaining high-resolution identification of subsets of these cells in the heart, enabling us to study the outcomes of metabolic distress on the cardiac macrophage infiltrate and to identify a macrophage-to-cardiomyocyte regulatory axis. To test whether a clinically relevant sodium glucose cotransporter-2 inhibitor could ameliorate the cardiac immune infiltrate profile in our model, mice were randomized to receive the sodium glucose cotransporter-2 inhibitor dapagliflozin or vehicle for 8 weeks. RESULTS: ApoE knockout mice fed a Western diet presented with reduced diastolic function, reduced exercise tolerance, and increased pulmonary congestion associated with cardiac lipid overload and reduced polyunsaturated fatty acids. The main immune cell types infiltrating the heart included 4 subpopulations of resident and monocyte-derived macrophages, determining a proinflammatory profile exclusively in ApoE knockout-Western diet mice. Lipid overload had a direct effect on inflammatory gene activation in macrophages, mediated through endoplasmic reticulum stress pathways. Investigation of the macrophage-to-cardiomyocyte regulatory axis revealed the potential effects on cardiomyocytes of multiple inflammatory cytokines secreted by macrophages, affecting pathways such as hypertrophy, fibrosis, and autophagy. Finally, we describe an anti-inflammatory effect of sodium glucose cotransporter-2 inhibition in this model. CONCLUSIONS: Using single-cell RNA sequencing in a model of diastolic dysfunction driven by hyperlipidemia, we have determined the effects of metabolic distress on cardiac inflammatory cells, in particular on macrophages, and suggest sodium glucose cotransporter-2 inhibitors as potential therapeutic agents for the targeting of a specific phenotype of HFpEF.
A commentary on ‘Intelligent cataract surgery supervision and evaluation via deep learning’
Authors: Xiaoli Wang, Yunxia Gao, Fangrong Cai, Ming Zhang
Journal: International Journal of Surgery (2023)

aDepartment of Ophthalmology, West China Hospital, Sichuan University, Sichuan, 610041, China bDepartment of Ophthalmology, the People's Hospital of Jianyang City, Sichuan, 641400, China Fund: Project of Sichuan Medical Association (S22058); National Key R&D Project (2018YFC1106103) Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article Published online ■ ■ *Corresponding author. Address: West China hospital, CHINA. E-mail address: [email protected] (M. Zhang). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Concerns over prognosis prediction for non-small cell lung cancers using major pathological response
Authors: Kuo-Chuan Hung, I-Wen Chen, Cheuk-Kwan Sun
Journal: International Journal of Surgery (2023)

aDepartment of Anesthesiology, Chi Mei Medical Center, Tainan city, Taiwan bDepartment of Anesthesiology, Chi Mei Medical Center, Liouying, Tainan city, Taiwan cDepartment of Emergency Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung City, Taiwan dSchool of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung City, Taiwan Short title: Major pathological response for non-small cell lung cancers Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article Published online ■ ■ *Corresponding author. Address: Department of Emergency Medicine, E-Da Dachang Hospital, I-Shou University, No. 305, Dachang 1st Road, Sanmin District, Kaohsiung City, Taiwan, Tel: +886-7-6150011 ext 1007; Mobile: +886-975106203, Fax: +886-7-6150915. E-mail address: [email protected], [email protected] (C-K. Sun). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
Allogeneic hematopoietic cell transplantation for patients with acute myeloid leukemia not in remission
Authors: Masamitsu Yanada, Satoshi Yamasaki, Tadakazu Kondo, Takahito Kawata, Kaito Harada, Naoyuki Uchida, Noriko Doki, Satoshi Yoshihara, Yuta Katayama, Tetsuya Eto, Masatsugu Tanaka, Satoru Takada, Toshiro Kawakita, Tetsuya Nishida, Shuichi Ota, Kentaro Serizawa, Makoto Onizuka, Yoshinobu Kanda, Takahiro Fukuda, Yoshiko Atsuta, Takaaki Konuma
Journal: Leukemia (2023)
Whole-Brain Radiotherapy Alone vs Preceded by Bevacizumab, Etoposide, and Cisplatin for Untreated Brain Metastases From Breast Cancer
Authors: Tom Wei-Wu Chen, Ming-Shen Dai, Ling-Ming Tseng, Shin-Cheh Chen, Tsu-Yi Chao, Ta-Chung Chao, Yuan-Ching Chang, Chang-Fang Chiu, Chien-Ting Liu, Ching-Hung Lin, Chun-Yu Liu, Ya-Fang Chen, Dwan-Ying Chang, Jyh-Cherng Yu, Kun-Ming Rau, Yao-Yu Hsieh, Shih-Che Shen, Shu-Min Huang, Ann-Lii Cheng, Yen-Shen Lu
Journal: JAMA Oncology (2023)

The incidence of brain metastasis is increasing in patients with metastatic breast cancer. Treatments to extend the control of brain metastasis are urgently required.
Methods for Estimating Personal Disease Risk and Phylogenetic Diversity of Hematopoietic Stem Cells
Authors: Jack M Craig, Glenn S Gerhard, Sudip Sharma, Anastasia Yankovskiy, Sayaka Miura, Sudhir Kumar
Journal: Molecular Biology and Evolution (2023)

Abstract An individual's chronological age does not always correspond to the health of different tissues in their body, especially in cases of disease. Therefore, estimating and contrasting the physiological age of tissues with an individual's chronological age may be a useful tool to diagnose disease and its progression. In this study, we present novel metrics to quantify the loss of phylogenetic diversity in hematopoietic stem cells (HSCs), which are precursors to most blood cell types and are associated with many blood-related diseases. These metrics showed an excellent correspondence with an age-related increase in blood cancer incidence, enabling a model to estimate the phylogeny-derived age (phyloAge) of HSCs present in an individual. The HSC phyloAge was generally older than the chronological age of patients suffering from myeloproliferative neoplasms (MPNs). We present a model that relates excess HSC aging with increased MPN risk. It predicted an over 200 times greater risk based on the HSC phylogenies of the youngest MPN patients analyzed. Our new metrics are designed to be robust to sampling biases and do not rely on prior knowledge of driver mutations or physiological assessments. Consequently, they complement conventional biomarker-based methods to estimate physiological age and disease risk.
Online Purchase Attempts of Flavored E-Cigarettes to Minors in California Before and After Senate Bill 793
Authors: Scott I. Donaldson, Trista A. Beard, Rafael Colonna, Elizabeth Andersen-Rodgers, Heather L. Wipfli, Kurt M. Ribisl, Jon-Patrick Allem
Journal: JAMA Network Open (2023)

This survey study assesses whether the online purchase attempt completion rate of e-cigarettes changed after passage of California Senate Bill 793.
Error in Byline and Corresponding Author Contact Information
Journal: JAMA Network Open (2023)

Chen He, MD; Yi Li, MD; Xi Jiang, MD; Meng-Ni Jiang, MD; Xian-Xian Zhao, MD; Shu-Ren Ma, MD; Dan Bao, MD; Miao-Han Qiu, MD; Jie Deng, MD; Jin-Hai Wang, MD; Peng Qu, MD; Chun-Meng Jiang, MD; Shao-Bin Jia, MD; Shao-Qi Yang, MD; Lei-Sheng Ru, MD; Jia Feng, MD; Wei Gao, MD; Yong-Hui Huang, MD; Ling Tao, MD; Ying Han, MD; Kan Yang, MD; Xiao-Yan Wang, MD; Wen-Juan Zhang, MD; Bang-Mao Wang, MD; Yue Li, MD; You-Lin Yang, MD; Jun-Xia Li, MD; Jian-Qiu Sheng, MD; Yi-Tong Ma, MD; Min Cui, MD; Si-Cong Ma, MD; Xiao-Zeng Wang, MD; Zhao-Shen Li, MD; Zhuan Liao, MD; Ya-Ling Han, MD; Gregg W. Stone, MD
Objective Analysis and Clinical Significance of the Spatial Tumor-Infiltrating Lymphocyte Patterns in Non–Small Cell Lung Cancer
Authors: Miguel Lopez De Rodas, Yvonne Wang, Gang Peng, Jianlei Gu, Mari Mino-Kenudson, Jonathan W. Riess, Vamsidhar Velcheti, Matthew Hellmann, Justin F. Gainor, Hongyu Zhao, Kurt A. Schalper
Journal: Clinical Cancer Research (2023)

Abstract Purpose: The spatial arrangement of lymphocytes in the tumor bed (e.g., immune infiltrated, immune excluded, immune desert) is expected to reflect distinct immune evasion mechanisms and to associate with immunotherapy outcomes. However, data supporting these associations are scant and limited by the lack of a clear definition for lymphocyte infiltration patterns and the subjective nature of pathology-based approaches. Experimental Design: We used multiplexed immunofluorescence to study major tumor-infiltrating lymphocyte (TIL) subsets with single-cell resolution in baseline whole-tissue section samples from NSCLC patients treated with immune checkpoint inhibitors (ICI). The spatial TIL patterns were analyzed using a qualitative pathologist-based approach, and an objective analysis of TIL density ratios in tumor/stromal tissues. The association of spatial patterns with outcomes was studied for different TIL markers. Results: The analysis of CD8+ TIL patterns using qualitative assessment identified prominent limitations including the presence of a broad spectrum of phenotypes within most tumors and limited association with outcomes. The utilization of an objective method to classify NSCLCs showed the existence of at least three subgroups with partial overlap with those defined using visual patterns. Using this strategy, a subset of cases with “immune excluded-like” tumors showed prominently worse outcomes, suggesting reduced sensitivity to ICI; however, these results need to be validated. The analysis for other TIL subsets showed different results, underscoring the relevance of the marker selected for spatial TIL pattern evaluation and opportunities for market integration. Conclusions: Our results identified major challenges associated with the qualitative spatial TIL pattern evaluation. We devised a novel objective strategy to overcome some of these limitations that has strong biomarker potential.