tbuckley/cabot-search huggingface dataset:
Yes-Associated Protein Targets the Transforming Growth Factor β Pathway to Mediate High-Fat/High-Sucrose Diet-induced Arterial Stiffness
Authors: Yanan Liu, Mengke Li, Xue Lv, Kaiwen Bao, Xiao Yu Tian, Lei He, Lei Shi, Yi Zhu, Ding Ai
Journal: Circulation Research (2022)

Background: Metabolic syndrome is related to cardiovascular diseases, which is attributed in part, to arterial stiffness; however, the mechanisms remain unclear. The present study aimed to investigate the molecular mechanisms of metabolic syndrome–induced arterial stiffness and to identify new therapeutic targets. Methods: Arterial stiffness was induced by high-fat/high-sucrose diet in mice, which was quantified by Doppler ultrasound. Four-dimensional label-free quantitative proteomic analysis, affinity purification and mass spectrometry, and immunoprecipitation and GST (glutathione S-transferase) pull-down experiments were performed to explore the mechanism of YAP (Yes-associated protein)-mediated TGF (transforming growth factor) β pathway activation. Results: YAP protein was upregulated in the aortic tunica media of mice fed a high-fat/high-sucrose diet for 2 weeks and precedes arterial stiffness. Smooth muscle cell–specific YAP knockdown attenuated high-fat/high-sucrose diet–induced arterial stiffness and activation of TGFβ-Smad2/3 signaling pathway in arteries. By contrast, Myh11Cre ERT2 -Yap Tg mice exhibited exacerbated high-fat/high-sucrose diet–induced arterial stiffness and enhanced TGFβ-activated Smad2/3 phosphorylation in arteries. PPM1B (protein phosphatase, Mg 2+ /Mn 2+ -dependent 1B) was identified as a YAP-bound phosphatase that translocates into the nucleus to dephosphorylate Smads (mothers against decapentaplegic homologs) in response to TGFβ. This process was inhibited by YAP through removal of the K63-linked ubiquitin chain of PPM1B at K326. Conclusions: This study provides a new mechanism by which smooth muscle cell YAP regulates the TGFβ pathway and a potential therapeutic target in metabolic syndrome–associated arterial stiffness.
An imaging-based artificial intelligence model for non-invasive grading of hepatic venous pressure gradient in cirrhotic portal hypertension
Authors: Qian Yu, Yifei Huang, Xiaoguo Li, Michael Pavlides, Dengxiang Liu, Hongwu Luo, Huiguo Ding, Weimin An, Fuquan Liu, Changzeng Zuo, Chunqiang Lu, Tianyu Tang, Yuancheng Wang, Shan Huang, Chuan Liu, Tianlei Zheng, Ning Kang, Changchun Liu, Jitao Wang, Seray Akçalar, Emrecan Çelebioğlu, Evren Üstüner, Sadık Bilgiç, Qu Fang, Chi-Cheng Fu, Ruiping Zhang, Chengyan Wang, Jingwei Wei, Jie Tian, Necati Örmeci, Zeynep Ellik, Özgün Ömer Asiller, Shenghong Ju, Xiaolong Qi
Journal: Cell Reports Medicine (2022)
Re: Karin Welén, Ebba Rosendal, Magnus Gisslén, et al. A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome: No Evidence of Benefit, Supported by Epidemiology and In Vitro Data. Eur Urol. 2022;81:285–93
Authors: Carlos G. Wambier, Gerard J. Nau
Journal: European Urology (2022)
Thulium Fibre Laser versus Holmium:YAG for Ureteroscopic Lithotripsy: Outcomes from a Prospective Randomised Clinical Trial
Authors: Øyvind Ulvik, Mathias Sørstrand Æsøy, Patrick Juliebø-Jones, Peder Gjengstø, Christian Beisland
Journal: European Urology (2022)

Holmium:yttrium-aluminium-garnet (Ho:YAG) laser is the gold standard for ureterorenoscopic (URS) lithotripsy. Thulium fibre laser (TFL) has recently been introduced as a new technology and may challenge Ho:YAG as the preferred laser owing to favourable properties as demonstrated in preclinical studies.To evaluate and compare outcomes after URS lithotripsy with Ho:YAG and TFL.In a prospective randomised trial, patients aged ≥18 yr with ureteral and/or renal stones (≥5 mm) scheduled to undergo day-case URS lithotripsy were invited to participate. In total, 120 consecutively admitted patients with signed consent were included for randomisation.URS lithotripsy with Ho:YAG or TFL.The primary outcome was the stone-free rate (SFR) assessed on noncontrast computed tomography at 3-mo follow-up. Secondary outcomes were the operative time and complications. Outcomes were compared between the groups using the t test and χ2 test.After a single session, the SFR was 67% in the Ho:YAG group and 92% in the TFL group, p = 0.001. For ureteral stones, the SFR was 100% in both groups, and for renal stones; 49% (Ho:YAG) and 86% (TFL), p = 0.001. Operative time was shorter using TFL (49 min) compared to Ho:YAG (57 min), p = 0.008. Bleeding that impaired the endoscopic view was the most frequent intraoperative adverse event and occurred in 13 patients (22%) in the Ho:YAG group and three (5%) in the TFL group, p = 0.014.In this study, significantly more patients with renal stones achieved stone-free status and fewer experienced intraoperative complications using TFL compared to Ho:YAG. TFL is the emerging laser of choice for stone lithotripsy.We compared outcomes after ureterorenoscopic treatment of kidney and ureteral stones using two different lasers. Our results show that the new thulium fibre laser technology is superior to the current standard laser (holmium:YAG) in clearing kidney stones and reducing operative complications.
PREDICTIVE VALUE OF CTA-DERIVED SEPTAL EXTRACELLULAR VOLUME FRACTION FOR PACEMAKER IMPLANTATION POST TAVR IN PATIENTS WITH LOW-FLOW, LOW GRADIENT AORTIC STENOSIS
Authors: Billy Chen, Donghee Han, Heidi Gransar, John Friedman, Balaji Tamarappoo, Raj Makkar, Daniel S. Berman
Journal: Journal of the American College of Cardiology (2022)
Host immune response mediates changes in <i>cagA</i> copy number and virulence potential of <i>Helicobacter pylori</i>
Authors: Sungil Jang, Lori M. Hansen, Hanfu Su, Jay V. Solnick, Jeong-Heon Cha
Journal: Gut Microbes (2022)

Helicobacter pylori is the major risk factor for gastric cancer. H. pylori harboring the type IV secretion system (T4SS) and its effector CagA encoded on the cag pathogenicity Island (cagPAI) increases the risk. H. pylori PMSS1 has a multi-cagA genotype, modulating cagA copy number dynamically from zero to four copies. To examine the effect of the immune response on cagA copy number change, we utilized a mouse model with different immune status. PMSS1 recovered from Rag1−/− mice, lacking functional T or B cells, retained more cagA copies. PMSS1 recovered from Il10−/− mice, showing intense inflammation, had fewer cagA copies compared to those recovered from wild-type mice. Moreover, cagA copy number of PMSS1 recovered from wild-type and Il10−/− mice was positively correlated with the capacity to induce IL-8 secretion at four weeks of infection. Since recombination in cagY influences T4SS function, including CagA translocation and IL-8 induction, we constructed a multiple linear regression model to predict H. pylori-induced IL-8 expression based on cagA copy number and cagY recombination status; H. pylori induces more IL-8 secretion when the strain has more cagA copies and intact cagY. This study shows that H. pylori PMSS1 in mice with less intense immune response possess higher cagA copy number than those infected in mice with more intense immune response and thus the multi-cagA genotype, along with cagY recombination, functions as an immune-sensitive regulator of H. pylori virulence.
PREDICTION OF METABOLIC SYNDROME USING REGIONAL BODY VOLUMES MEASURED USING A MULTISENSORY WHITE-LIGHT 3-D SCANNER
Authors: Betsy J. Medina Inojosa, Virend K. Somers, Jose Medina-Inojosa, Lynne A. Johnson, Francisco Lopez-Jimenez
Journal: Journal of the American College of Cardiology (2022)
LONGITUDINAL OUTPATIENT FOLLOW-UP OF CARDIAC BIOMARKERS AND ECHOCARDIOGRAPHIC FINDINGS IN CHILDREN AND ADOLESCENTS WITH MULTI INFLAMMATORY SYNDROME IN CHILDREN (MIS-C) ASSOCIATED WITH COVID-19
Authors: Abhishek Chakraborty, Jason N. Johnson, Jonathan Spagnoli, Nomisha Amin, Mia McCoy, Nithya Swaminathan, Thomas M. Yohannan, Ranjit Philip
Journal: Journal of the American College of Cardiology (2022)
IMPACT OF EXTRAVALVULAR CARDIAC DAMAGE ON MID-TERM CLINICAL OUTCOME FOLLOWING TRANSCATHETER AORTIC VALVE REPLACEMENT IN PATIENTS WITH SEVERE AORTIC STENOSIS
Authors: Costanza Pellegrini, Amelie Berg, Tobias Andreas Rheude, Hector A. Alvarez-Covarrubias, Teresa Trenkwalder, N.Patrick Mayr, Philipp Nicol, Erion Xhepa, Michael Joner
Journal: Journal of the American College of Cardiology (2022)
Strong and consistent associations of precedent chronic rhinosinusitis with risk of non–cystic fibrosis bronchiectasis
Authors: Brian S. Schwartz, Saba A. Al-Sayouri, Jonathan S. Pollak, Annemarie G. Hirsch, Robert Kern, Bruce Tan, Atsushi Kato, Robert P. Schleimer, Anju T. Peters
Journal: Journal of Allergy and Clinical Immunology (2022)
DGAT2 Inhibition Potentiates Lipid Droplet Formation To Reduce Cytotoxicity in APOL1 Kidney Risk Variants
Authors: Justin Chun, Cristian V. Riella, Hyunjae Chung, Shrijal S. Shah, Minxian Wang, Jose M. Magraner, Guilherme T. Ribas, Hennrique T. Ribas, Jia-Yue Zhang, Seth. L. Alper, David J. Friedman, Martin R. Pollak
Journal: Journal of the American Society of Nephrology (2022)

Two variants in the gene encoding apolipoprotein L1 (APOL1) that are highly associated with African ancestry are major contributors to the large racial disparity in rates of human kidney disease. We previously demonstrated that recruitment of APOL1 risk variants G1 and G2 from the endoplasmic reticulum to lipid droplets leads to reduced APOL1-mediated cytotoxicity in human podocytes.We used CRISPR-Cas9 gene editing of induced pluripotent stem cells to develop human-derived APOL1G0/G0 and APOL1G2/G2 kidney organoids on an isogenic background, and performed bulk RNA sequencing of organoids before and after treatment with IFN-γ. We examined the number and distribution of lipid droplets in response to treatment with inhibitors of diacylglycerol O-acyltransferases 1 and 2 (DGAT1 and DGAT2) in kidney cells and organoids.APOL1 was highly upregulated in response to IFN-γ in human kidney organoids, with greater increases in organoids of high-risk G1 and G2 genotypes compared with wild-type (G0) organoids. RNA sequencing of organoids revealed that high-risk APOL1G2/G2 organoids exhibited downregulation of a number of genes involved in lipogenesis and lipid droplet biogenesis, as well as upregulation of genes involved in fatty acid oxidation. There were fewer lipid droplets in unstimulated high-risk APOL1G2/G2 kidney organoids than in wild-type APOL1G0/G0 organoids. Whereas DGAT1 inhibition reduced kidney organoid lipid droplet number, DGAT2 inhibition unexpectedly increased organoid lipid droplet number. DGAT2 inhibition promoted the recruitment of APOL1 to lipid droplets, with associated reduction in cytotoxicity.Lipogenesis and lipid droplet formation are important modulators of APOL1-associated cytotoxicity. Inhibition of DGAT2 may offer a potential therapeutic strategy to attenuate cytotoxic effects of APOL1 risk variants.
Paleozoic Protein Fossils Illuminate the Evolution of Vertebrate Genomes and Transposable Elements
Authors: Martin C. Frith
Journal: Molecular Biology and Evolution (2022)

Genomes hold a treasure trove of protein fossils: Fragments of formerly protein-coding DNA, which mainly come from transposable elements (TEs) or host genes. These fossils reveal ancient evolution of TEs and genomes, and many fossils have been exapted to perform diverse functions important for the host's fitness. However, old and highly degraded fossils are hard to identify, standard methods (e.g. BLAST) are not optimized for this task, and few Paleozoic protein fossils have been found. Here, a recently optimized method is used to find protein fossils in vertebrate genomes. It finds Paleozoic fossils predating the amphibian/amniote divergence from most major TE categories, including virus-related Polinton and Gypsy elements. It finds 10 fossils in the human genome (eight from TEs and two from host genes) that predate the last common ancestor of all jawed vertebrates, probably from the Ordovician period. It also finds types of transposon and retrotransposon not found in human before. These fossils have extreme sequence conservation, indicating exaptation: some have evidence of gene-regulatory function, and they tend to lie nearest to developmental genes. Some ancient fossils suggest "genome tectonics," where two fragments of one TE have drifted apart by up to megabases, possibly explaining gene deserts and large introns. This paints a picture of great TE diversity in our aquatic ancestors, with patchy TE inheritance by later vertebrates, producing new genes and regulatory elements on the way. Host-gene fossils too have contributed anciently conserved DNA segments. This paves the way to further studies of ancient protein fossils.
THE UTILIZATION OF TRANSESOPHAGEAL ECHOCARDIOGRAM IN A CASE OF A LARGE ATRIAL SEPTAL DEFECT: TO CLOSE OR NOT TO CLOSE?
Authors: Janet Cai, Joanna Rock, Fady Ibrahim, Abhigyan Mukherjee, Andrew Aboyme, Chunguang Chen, Ashok Chaudhary
Journal: Journal of the American College of Cardiology (2022)
Brain-wide electrical dynamics encode individual appetitive social behavior
Authors: Stephen D. Mague, Austin Talbot, Cameron Blount, Kathryn K. Walder-Christensen, Lara J. Duffney, Elise Adamson, Alexandra L. Bey, Nkemdilim Ndubuizu, Gwenaëlle E. Thomas, Dalton N. Hughes, Yael Grossman, Rainbo Hultman, Saurabh Sinha, Alexandra M. Fink, Neil M. Gallagher, Rachel L. Fisher, Yong-Hui Jiang, David E. Carlson, Kafui Dzirasa
Journal: Neuron (2022)
WDR82-binding long noncoding RNA <i>lncEry</i> controls mouse erythroid differentiation and maturation
Authors: Shangda Yang, Guohuan Sun, Peng Wu, Cong Chen, Yijin Kuang, Ling Liu, Zhaofeng Zheng, Yicheng He, Quan Gu, Ting Lu, Caiying Zhu, Fengjiao Wang, Fanglin Gou, Zining Yang, Xiangnan Zhao, Shiru Yuan, Liu Yang, Shihong Lu, Yapu Li, Xue Lv, Fang Dong, Yanni Ma, Jia Yu, Lai Guan Ng, Lihong Shi, Jing Liu, Lei Shi, Tao Cheng, Hui Cheng
Journal: The Journal of Experimental Medicine (2022)

Hematopoietic differentiation is controlled by both genetic and epigenetic regulators. Long noncoding RNAs (lncRNAs) have been demonstrated to be important for normal hematopoiesis, but their function in erythropoiesis needs to be further explored. We profiled the transcriptomes of 16 murine hematopoietic cell populations by deep RNA sequencing and identified a novel lncRNA, Gm15915, that was highly expressed in erythroid-related progenitors and erythrocytes. For this reason, we named it lncEry. We also identified a novel lncEry isoform, which was the principal transcript that has not been reported before. lncEry depletion impaired erythropoiesis, indicating the important role of the lncRNA in regulating erythroid differentiation and maturation. Mechanistically, we found that lncEry interacted with WD repeat-containing protein 82 (WDR82) to promote the transcription of Klf1 and globin genes and thus control the early and late stages of erythropoiesis, respectively. These findings identified lncEry as an important player in the transcriptional regulation of erythropoiesis.
Comparison of Child Undernutrition Anthropometric Indicators Across 56 Low- and Middle-Income Countries
Authors: Jewel Gausman, Rockli Kim, Zhihui Li, Lucia Tu, Sunil Rajpal, William Joe, S. V. Subramanian
Journal: JAMA Network Open (2022)

The United Nations' Sustainable Development Goal Target 2.2 seeks to end all forms of malnutrition by 2030 by meeting targets, including the elimination of stunting and wasting in all children younger than 5 years. Such indicators are used to monitor childhood undernutrition but may not provide a complete picture at a population level.To compare global estimates of the prevalence of undernutrition using conventional indicators of anthropometric failure (AF; stunting, underweight, and wasting); the Composite Index of Anthropometric Failure (CIAF); and a proposed classification system called Categories of Anthropometric Failure (CAF) as well as to investigate the association of the conventional indicators, CIAF, and CAF with diarrheal disease as an assessment of the validity of each measure.Cross-sectional study of the prevalence of undernutrition among children in 56 low- and middle-income countries using data from the nationally representative Demographic and Health Surveys. The study included 530 906 children younger than 5 years. Data were collected from June 2005 to December 2018 and analyzed from September 27, 2020, to February 4, 2021.Undernutrition identified according to conventional indicators (stunting, underweight, and wasting), the CIAF, and the proposed CAF classification system was estimated and compared. Six logistic regression models were used to examine the association between different classifications of anthropometric failure (AF) and morbidity.A total of 530 906 children (mean [SD] age, 29.0 [17.2] months; 272 355 [51.3%] boys and 258 551 [48.7%] girls) from 56 low- and middle-income countries were included in the analysis. Estimates of undernutrition generated using the conventional indicators of stunting, underweight, and wasting were lower than estimates generated using the CIAF in all countries. The CAF classification system pointed to considerable variation across countries in children with multiple AFs, which does not correspond to the overall prevalence of undernutrition. For example, 7.5% of children in Niger and 7.1% of children in Timor-Leste were stunted, underweight, and wasted, while 56.0% of children in Niger and 71.1% of children in Timor-Leste were undernourished according to the CIAF. In addition, children who had stunting, underweight, and wasting had 1.52 (95% CI, 1.45-1.61) times the odds of diarrhea compared with children who exhibited no AFs.The results of this study highlight the importance of using different approaches to aid understanding of the entire spectrum of AF with regard to research and development of policies and programs to address AF. The use of the CIAF and the CAF classification system may be useful for treatment to prevent AFs and could accelerate progress in meeting targets for the Sustainable Development Goal.
Long-read genome sequencing of bread wheat facilitates disease resistance gene cloning
Authors: Naveenkumar Athiyannan, Michael Abrouk, Willem H. P. Boshoff, Stéphane Cauet, Nathalie Rodde, David Kudrna, Nahed Mohammed, Jan Bettgenhaeuser, Kirsty S. Botha, Shannon S. Derman, Rod A. Wing, Renée Prins, Simon G. Krattinger
Journal: Nature Genetics (2022)

Abstract The cloning of agronomically important genes from large, complex crop genomes remains challenging. Here we generate a 14.7 gigabase chromosome-scale assembly of the South African bread wheat ( Triticum aestivum ) cultivar Kariega by combining high-fidelity long reads, optical mapping and chromosome conformation capture. The resulting assembly is an order of magnitude more contiguous than previous wheat assemblies. Kariega shows durable resistance to the devastating fungal stripe rust disease 1 . We identified the race-specific disease resistance gene Yr27 , which encodes an intracellular immune receptor, to be a major contributor to this resistance. Yr27 is allelic to the leaf rust resistance gene Lr13 ; the Yr27 and Lr13 proteins show 97% sequence identity 2,3 . Our results demonstrate the feasibility of generating chromosome-scale wheat assemblies to clone genes, and exemplify that highly similar alleles of a single-copy gene can confer resistance to different pathogens, which might provide a basis for engineering Yr27 alleles with multiple recognition specificities in the future.
Oligodendrocyte precursor cells sculpt the visual system by regulating axonal remodeling
Authors: Yan Xiao, Luigi Petrucco, Laura J. Hoodless, Ruben Portugues, Tim Czopka
Journal: Nature Neuroscience (2022)

Abstract Many oligodendrocyte precursor cells (OPCs) do not differentiate to form myelin, suggesting additional roles of this cell population. The zebrafish optic tectum contains OPCs in regions devoid of myelin. Elimination of these OPCs impaired precise control of retinal ganglion cell axon arbor size during formation and maturation of retinotectal connectivity and degraded functional processing of visual stimuli. Therefore, OPCs fine-tune neural circuits independently of their canonical role to make myelin.
Global variations in barriers to exercise for individuals with intellectual and developmental disability
Authors: Irene Chern, Laura Tosi
Journal: The Lancet Global Health (2022)

Intellectual and developmental disabilities (IDD) comprise lifelong limitations of intellectual, physical, or emotional development. Individuals with IDD face a mean reduction in lifespan of 12·7 years, a 5-times increase in the rate of type 2 diabetes, and a 2-times increase in the rate of cardiovascular disease versus the general public. Exercise can alleviate morbidity and mortality faced by individuals with IDD; however, the barriers to exercise for this population are not well elucidated. We aimed to understand the global variations in barriers to exercise for individuals with IDD.This retrospective review examined data collected by the Special Olympics Healthy Athletes Program across 193 countries, separated into seven regions, between February, 2007, and January, 2020. We included 5135 participants (aged 0-80 years) with IDD who reported having no regular activity programme. The primary outcome was which of nine barriers to exercise participants reported, totaling 6368 responses. χ2 tests were used to test significance, at p<0·0001. Participants and guardians provided written informed consent and the study was approved by the author's institutional review board.5135 participants were enrolled, with a mean age of 22·9 years (SD 12·9); 1998 (38·9%) were female. 672 participants lived in Africa, 985 in Asia Pacific, 269 in east Asia, 1135 in Europe and Eurasia, 859 in Latin America, 83 in the Middle East and north Africa, and 1132 in North America. The primary outcome had 6368 responses. For each region except the Middle East and north Africa (p=0·002), there was statistically significant variation in the frequency of reported barriers (all p<0·0001). In east Asia, Europe and Eurasia, and North America, the most frequently cited barrier to exercise was no interest (48·3%, 44·6%, and 56·4% respectively; all p<0·0001). By contrast, no exercise facilities was the most frequently cited barrier in Africa, Asia Pacific, and Latin America (25·1%, 74·9%, and 26·0% respectively; all p<0·0001). For all nine barriers there was regional variation in the frequency each barrier was cited (all p<0·0001). No interest was most often cited as a barrier in North America (56·4%), no exercise person to help in east Asia (11·8%), no equipment or clothes in Africa (5·2%), no person to exercise with in east Asia (9·2%), no transportation in Africa (22·1%), no money in Africa (23·5%), no exercise facilities in Asia Pacific (74·9%), and not safe in Latin America (3·6%).Barriers to exercise for individuals with IDD vary depending on the region of the world. Although there are limitations to self-reported data and retrospective review, to our knowledge this is the largest study examining barriers to exercise for individuals with IDD to date. This analysis could help to inform health policy and target interventions to the needs of specific IDD communities to mitigate the effects of their disabilities on chronic conditions and mortality.None.
CHARACTERISTICS AND OUTCOMES OF PATIENTS UNDERGOING ENDOVASCULAR REMOVAL OF TRICUSPID VALVE VEGETATIONS VS. CATHETER-RELATED MASSES USING THE ANGIOVAC SYSTEM
Authors: Sheng Fu, Tanveer Mian, Srikanth Radhakrishnan, Namita R. Joseph, Adnan Khalif, Rachel Hughes-Doichev, David Lasorda, Mithun Chakravarthy, Anita Umayal Radhakrishnan, Amresh Raina
Journal: Journal of the American College of Cardiology (2022)
COVID-19 RELATED OUTCOMES IN PATIENTS WITH PREEXISTING CARDIOVASCULAR DISEASES, WITH OR WITHOUT CANCER
Authors: Brijesh D. Patel, Scott Chapman, Aayush Visaria, Stephanie Hong, Makwana Priyal, Maryam Khodaverdi, Sijin Wen, Jasvinder Singh, Oluwabunmi Ogungbe, Jake Neumann, Sula Mazimba, Wesley Kimble, George Sokos
Journal: Journal of the American College of Cardiology (2022)