tbuckley/cabot-search huggingface dataset:
Acute changes in kidney function and outcomes following an acute myocardial infarction: Insights from <scp>PARADISE</scp>‐<scp>MI</scp>
Authors: Finnian R. Mc Causland, Martina M. McGrath, Brian L. Claggett, Ebrahim Barkoudah, Cara East, Alberto Fernandez, Karola S. Jering, Eldrin F. Lewis, John J.V. McMurray, Freny Vaghaiwalla Mody, Scott D. Solomon, Mariya Tokmakova, Peter van der Meer, Yinong Zhou, Marc A. Pfeffer
Journal: European Journal of Heart Failure (2024)
Increased SARS-CoV-2 reinfection frequency, attenuated severity, and risk factor analysis in patients with hematological malignancies
Authors: Jun Li, Yong Zhang, Zhanshu Liu, Zailiang Yang, Ling Liu, Guofa Xu, Zailin Yang, Yan Xiong, Jueyin Liu, Xiaomei Zhang, Ying Xiang, Qiying Li, Yingyu Nan, Jieping Li, Yongzhong Wu, Yao Liu
Journal: Journal of Infection (2024)
Advances in GPCR-targeted drug development in dermatology
Authors: Meng Wang, Tao Zan, Chengang Fan, Zhouxiao Li, Danru Wang, Qingfeng Li, Chao Zhang
Journal: Trends in Pharmacological Sciences (2024)

Achieving the efficacy and specificity of G-protein-coupled receptor (GPCR) targeting-drugs in the skin remains challenging. Understanding the molecular mechanism underlying GPCR dysfunction is crucial for developing targeted therapies. Recent advances in genetic, signal transduction, and structural studies have significantly improved our understanding of cutaneous GPCR functions in both normal and pathological states. In this review, we summarize recent discoveries of pathogenic GPCRs in dermal injuries, chronic inflammatory dermatoses, cutaneous malignancies, as well as the development of potent potential drugs. We also discuss targeting of cutaneous GPCR complexes via the transient receptor potential (TRP) channel and structure elucidation, which provide new opportunities for therapeutic targeting of GPCRs involved in skin disorders. These insights are expected to lead to more effective and specific treatments for various skin conditions.
Transcriptomic Profiling of Human Mesenchymal Stem Cells Using a Pulsed Electromagnetic-Wave Motion Bioreactor System for Enhanced Osteogenic Commitment and Therapeutic Potentials
Authors: Aayushi Randhawa, Keya Ganguly, Sayan Deb Dutta, Tejal V Patil, Ki-Taek Lim
Journal: Biomaterials (2024)
Platelet‐rich plasma and plasma rich in growth factors in extra‐oral wound care
Authors: Jeniffer Perussolo, Elena Calciolari, Xanthippi Dereka, Nikolaos Donos
Journal: Periodontology 2000 (2024)

Abstract This narrative review evaluates the existing literature on the clinical efficacy and safety of platelet‐rich plasma (PRP) and plasma rich in growth factors (PRGFs) in extra‐oral wound care, considering their potential benefits and drawbacks. The review specifically focuses on the impact of these treatments on patients' quality of life, pain management, treatment costs, recurrence rates, and potential complications. Given the extensive literature and diverse range of extra‐oral wound types in which these autologous platelet concentrates have been applied, this narrative review focuses on the most frequently described wound types, including diabetic foot ulcers, venous leg ulcers, pressure ulcers, surgical wounds, and burns. The use of PRP has been reported in various medical specialties, with a low risk of adverse events. While there is a growing interest in the use of PRGF with promising results, the available literature on this topic is still limited. Only a few studies evaluated patients' perception of the treatment and the relationship between treatment costs and clinical outcomes. Data on recurrence rates and complications also vary across studies. In conclusion, PRP and PRGF show promise as alternatives or as adjunctive therapies to conventional treatments for various extra‐oral wounds and ulcers, leading to reduced wound size and accelerated healing time but should be considered on a case‐by‐case basis, taking into account the type and severity of the wound.
Re: Chauhan et al.: Association of primary open-angle glaucoma with diabetic retinopathy among patients with type 1 and type 2 diabetes: a large global database study (Ophthalmology. 2024;131:827-835)
Authors: Wei-Hsuan Bai, Yi-Chiao Bai, James Cheng-Chung Wei
Journal: Ophthalmology (2024)
Activity limitations, use of assistive devices, and mortality and clinical events in 25 high-income, middle-income, and low-income countries: an analysis of the PURE study
Authors: Raed A Joundi, Bo Hu, Sumathy Rangarajan, Darryl P Leong, Shofiqul Islam, Eric E Smith, Erkin Mirrakhimov, Pamela Seron, Khalid F Alhabib, Batyrbek Assembekov, Jephat Chifamba, Rita Yusuf, Rasha Khatib, Camilo Felix, Afzalhussein Yusufali, Noushin Mohammadifard, Annika Rosengren, Aytekin Oguz, Romaina Iqbal, Karen Yeates, Alvaro Avezum, Iolanthé Kruger, Ranjit Anjana, Lakshmi Pvm, Rajeev Gupta, Katarzyna Zatońska, Olga Barbarash, Eugenia Pelliza, Kamala Rammohan, Mengya Li, Xiaocong Li, Rosnah Ismail, Patricio Lopez-Jaramillo, Marc Evans, Martin O'Donnell, Salim Yusuf
Journal: The Lancet (2024)
Towards eliminating hepatitis C as a public health threat: different speeds, different needs
Authors: Mojca Matičič, Maria Buti
Journal: Eurosurveillance (2024)

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Prevalence of chronic hepatitis C infection in the general population: results from a national survey, Romania, 2020 to 2023
Authors: Mira Hleyhel, Odette Popovici, Mihaela Leuștean, Suzanne Reed, Amal Sadou, Martina Furegato, Benjamin Bluemel, Erika Duffell, Otilia Mardh
Journal: Eurosurveillance (2024)

Introduction A national study from 2006 to 2008 showed a high antibody prevalence of 3.2% against hepatitis C virus (HCV) in Romania, but more recent epidemiological data on hepatitis C prevalence are lacking. Aim We aimed to estimate the current prevalence of HCV antibodies (anti-HCV) and chronic HCV infection in the general adult population in Romania, as a crucial element in monitoring progress towards eliminating hepatitis C. Methods We used anonymised leftover sera from a SARS-CoV-2 survey conducted between July and October 2020 (n = 2,100), supplemented with sera collected prospectively between July 2022 and March 2023 (n = 574). These included sera collected from adults visiting laboratories for routine medical check-ups. Sera were tested for anti-HCV and HCV core antigen and classified according to anti-HCV and chronic infection status. Results Of the total 2,674 specimens tested, 44 were anti-HCV-positive with a weighted anti-HCV prevalence of 1.4% (95% CI: 1.0–1.9), and 29 were HCV core antigen-positive with a weighted prevalence of chronic infection of 0.9% (95% CI: 0.5–1.2). The prevalence of chronic infection did not differ significantly between men and women. It was higher in persons 60 years and older (2.0%; 95% CI: 1.1–3.0) and in specimens from the North-East region (2.2%; 95% CI: 0.8–3.7). Conclusion Although the overall HCV prevalence in Romania is currently low, targeted screening, prevention measures and treatment scale-up are needed especially for the population 60 years and older and in the north-eastern part of the country to achieve the goal of ending the hepatitis C epidemic.
Vacation in Egypt associated with Shiga toxin-producing Escherichia coli infection in children and adolescents, northern Italy, 2023
Authors: Thomas Ria, Maria Cristina Mancuso, Laura Daprai, Maria Francesca Liporace, Alessandra Gazzola, Sara Arnaboldi, Federica Vianello, Mario Luini, Dario Consonni, Gianluigi Ardissino
Journal: Eurosurveillance (2024)

Background Haemolytic uremic syndrome (HUS) is a severe complication of infection with Shiga toxin-producing Escherichia coli (STEC). Although the reservoirs of STEC are known, the source of the infection of sporadic cases is often unknown. In 2023, we observed several cases of bloody diarrhoea with STEC infection in children and adolescents returning from vacations. Aim We aimed to explore the association between travel and bloody diarrhoea with STEC infection in children and adolescents. Methods We included all children and adolescents with bloody diarrhoea with STEC infection identified in 2023 by the ItalKid-HUS Network surveillance system in northern Italy. We interviewed children’s families and sent a questionnaire on recent travels abroad. The exposure time was between 3 days after arrival abroad and 5 days after return home. A self-controlled case series (SCCS) design was used in the analysis. Results Of the 43 cases, 11 developed HUS. Twenty-three cases did not travel abroad, while 20 had travelled to several destinations. The incidence rate ratio (IRR) associated with travel to Egypt was 88.6 (95% confidence interval (CI): 17.0–462). Serotype analysis excluded the possibility of a single strain causing the infections. We did not find the source of the infections. Conclusion There is an elevated risk of acquiring STEC infection with bloody diarrhoea and HUS associated with travel to Egypt. Specific investigations to identify the source are needed to implement effective preventive measures.
Early rise of West Nile fever in Israel, June 2024
Authors: Zohar Mor, Husein Omari, Victoria Indenbaum, Oscar D Kirstein, Oren Shatach Catabi, Shay Reicher, Yaniv Lustig, Maya Davidovich-Cohen, Ehud Kaliner, Rivka Sheffer, Shirly Elbaz, Or Kriger, Sharon Alroy-Preis
Journal: Eurosurveillance (2024)

This report describes an unusual surge of West Nile fever in Israel in June 2024, during which 125 cases were diagnosed, compared with 4 cases on average during June in previous years (2014–23). Of the cases, 64 (62.1%) had neuroinvasive disease and 12 (9.6%) died; the 2024 case fatality rate was not significantly elevated vs the average rate in 2014–23. The early rise could be related to a temperature increase in spring and early summer of 2024.
Prevalence of chronic hepatitis C infection in the general population: results from a national survey, Estonia, July to December 2022
Authors: Mira Hleyhel, Julia Geller, Amal Sadou, Paul Naaber, Tatiana Kuznetsova, Sigrid Vorobjov, Marleen Lõhmus, Martina Furegato, Suzanne Reed, Benjamin Bluemel, Erika Duffell, Kristi Rüütel
Journal: Eurosurveillance (2024)

Introduction Obtaining epidemiological data on chronic hepatitis C virus (HCV) infection is essential to monitor progress towards the hepatitis C elimination targets. Aim We aimed to estimate the prevalence of chronic HCV and the seroprevalence of HCV in the adult general population in Estonia. Methods This cross-sectional study, conducted between 12 July and 6 December 2022, included anonymised residual sera collected prospectively from patients 18 years and older visiting a general practitioner in all counties of Estonia. Specimens were considered HCV-seropositive if they tested positive for HCV antibodies by enzyme-linked immunoassay, confirmed by line-immunoblot assay. Chronic HCV infection was determined by positive RT-qPCR. Results We tested a total of 4,217 specimens. The estimated HCV seroprevalence and prevalence of chronic HCV infection were 1.8% (95% CI: 1.4–2.2) and 0.8% (95% CI: 0.5–1.1), respectively, with ca 8,100 persons estimated to have chronic HCV infection in the general adult population of Estonia. No statistically significant differences in the prevalence of chronic HCV infection were observed between sexes, counties or age groups, with the highest prevalence rates observed in men (sex ratio: 1.7), Ida-Virumaa County (1.8%; 95% CI: 0.8–3.6) and the age group 40–49 years (1.7%; 95% CI: 0.9–2.9). Conclusion This study found an overall low prevalence of chronic HCV infection in Estonia. Continued efforts should be made for the targeted screening, diagnosis and treatment of individuals with chronic HCV infection to achieve hepatitis elimination targets.
Strain-dependent variations in replication of European clade 2.3.4.4b influenza A(H5N1) viruses in bovine cells and thermal inactivation in semi-skimmed or whole milk
Authors: Diana I Palme, Juliane Lang, Dajana Helke, Maryna Kuryshko, Elsayed M Abdelwhab
Journal: Eurosurveillance (2024)

We investigated the thermostability of four European avian influenza A(H5N1) viruses in whole and semi-skimmed milk and their replication in bovine kidney and lung cells amid the current influenza A(H5N1) dairy cattle outbreak in the United States. Results showed strain-dependent differences in thermal inactivation, particularly in whole milk, and variable replication efficacy in lung cells. These findings support assessing the inactivation of European H5N1 viruses in milk and their replication in bovine cells, aiding biosafety protocols and public health measures.
Nanotherapeutic kidney cell-specific targeting to ameliorate acute kidney injury
Authors: Yoshio Funahashi, Seung Hun Park, Jessica F. Hebert, Mahaba B. Eiwaz, Adam C. Munhall, Tahnee Groat, Lingxue Zeng, Jonghan Kim, Hak Soo Choi, Michael P. Hutchens
Journal: Kidney International (2024)

Acute kidney injury (AKI) increases the risk of in-hospital death, adds to expense of care, and risk of early chronic kidney disease. AKI often follows an acute event such that timely treatment could ameliorate AKI and potentially reduce the risk of additional disease. Despite therapeutic success of dexamethasone in animal models, clinical trials have not demonstrated broad success. To improve the safety and efficacy of dexamethasone for AKI, we developed and characterized a novel, kidney-specific nanoparticle enabling specific within-kidney targeting to proximal tubular epithelial cells provided by the megalin ligand cilastatin. Cilastatin and dexamethasone were complexed to H-Dot nanoparticles, which were constructed from generally recognized as safe components. Cilastatin/Dexamethasone/H-Dot nanotherapeutics were found to be stable at plasma pH and demonstrated salutary release kinetics at urine pH. In vivo, they were specifically biodistributed to the kidney and bladder, with 75% recovery in the urine and with reduced systemic toxicity compared to native dexamethasone. Cilastatin complexation conferred proximal tubular epithelial cell specificity within the kidney in vivo and enabled dexamethasone delivery to the proximal tubular epithelial cell nucleus in vitro. The Cilastatin/Dexamethasone/H-Dot nanotherapeutic improved kidney function and reduced kidney cellular injury when administered to male C57BL/6 mice in two translational models of AKI (rhabdomyolysis and bilateral ischemia reperfusion). Thus, our design-based targeting and therapeutic loading of a kidney-specific nanoparticle resulted in preservation of the efficacy of dexamethasone, combined with reduced off-target disposition and toxic effects. Hence, our study illustrates a potential strategy to target AKI and other diseases of the kidney.
A TNIP1-driven systemic autoimmune disorder with elevated IgG4
Authors: Arti Medhavy, Vicki Athanasopoulos, Katharine Bassett, Yuke He, Maurice Stanley, Daniel Enosi Tuipulotu, Jean Cappello, Grant J. Brown, Paula Gonzalez-Figueroa, Cynthia Turnbull, Somasundhari Shanmuganandam, Padmaja Tummala, Gemma Hart, Tom Lea-Henry, Hao Wang, Sonia Nambadan, Qian Shen, Jonathan A. Roco, Gaetan Burgio, Phil Wu, Eun Cho, T. Daniel Andrews, Matt A. Field, Xiaoqian Wu, Huihua Ding, Qiang Guo, Nan Shen, Si Ming Man, Simon H. Jiang, Matthew C. Cook, Carola G. Vinuesa
Journal: Nature Immunology (2024)

Whole-exome sequencing of two unrelated kindreds with systemic autoimmune disease featuring antinuclear antibodies with IgG4 elevation uncovered an identical ultrarare heterozygous TNIP1
Competition shapes the landscape of X-chromosome-linked genetic diversity
Authors: Teresa Buenaventura, Hakan Bagci, Ilinca Patrascan, Joshua J. Graham, Kelsey D. Hipwell, Roel Oldenkamp, James W. D. King, Jesus Urtasun, George Young, Daniel Mouzo, David Gomez-Cabrero, Benjamin D. Rowland, Daniel Panne, Amanda G. Fisher, Matthias Merkenschlager
Journal: Nature Genetics (2024)

Abstract X chromosome inactivation (XCI) generates clonal heterogeneity within XX individuals. Combined with sequence variation between human X chromosomes, XCI gives rise to intra-individual clonal diversity, whereby two sets of clones express mutually exclusive sequence variants present on one or the other X chromosome. Here we ask whether such clones merely co-exist or potentially interact with each other to modulate the contribution of X-linked diversity to organismal development. Focusing on X-linked coding variation in the human STAG2 gene, we show that Stag2 variant clones contribute to most tissues at the expected frequencies but fail to form lymphocytes in Stag2 WT Stag2 variant mouse models. Unexpectedly, the absence of Stag2 variant clones from the lymphoid compartment is due not solely to cell-intrinsic defects but requires continuous competition by Stag2 WT clones. These findings show that interactions between epigenetically diverse clones can operate in an XX individual to shape the contribution of X-linked genetic diversity in a cell-type-specific manner.
SARS-CoV-2 correlates of protection from infection against variants of concern
Authors: Kaiyuan Sun, Jinal N. Bhiman, Stefano Tempia, Jackie Kleynhans, Vimbai Sharon Madzorera, Qiniso Mkhize, Haajira Kaldine, Meredith L. McMorrow, Nicole Wolter, Jocelyn Moyes, Maimuna Carrim, Neil A. Martinson, Kathleen Kahn, Limakatso Lebina, Jacques D. du Toit, Thulisa Mkhencele, Anne von Gottberg, Cécile Viboud, Penny L. Moore, Cheryl Cohen, Amelia Buys, Maimuna Carrim, Linda de Gouveia, Mignon du Plessis, Jacques du Toit, Francesc Xavier Gómez-Olivé, Kgaugelo Patricia Kgasago, Retshidisitswe Kotane, Meredith L. McMorrow, Tumelo Moloantoa, Stephen Tollman, Anne von Gottberg, Floidy Wafawanaka, Nicole Wolter
Journal: Nature Medicine (2024)
An intestinal TH17 cell-derived subset can initiate cancer
Authors: Olivier Fesneau, Valentin Thevin, Valérie Pinet, Chloe Goldsmith, Baptiste Vieille, Saïdi M’Homa Soudja, Rossano Lattanzio, Michael Hahne, Valérie Dardalhon, Hector Hernandez-Vargas, Nicolas Benech, Julien C. Marie
Journal: Nature Immunology (2024)

Approximately 25% of cancers are preceded by chronic inflammation that occurs at the site of tumor development. However, whether this multifactorial oncogenic process, which commonly occurs in the intestines, can be initiated by a specific immune cell population is unclear. Here, we show that an intestinal T cell subset, derived from interleukin-17 (IL-17)-producing helper T (T
RNA Helicase DDX5 Maintains Cardiac Function by Regulating <i>CamkIIδ</i> Alternative Splicing
Authors: Kangni Jia, Haomai Cheng, Wenqi Ma, Lingfang Zhuang, Hao Li, Zhigang Li, Ziyang Wang, Hang Sun, Yuke Cui, Hang Zhang, Hongyang Xie, Lei Yi, Zhiyong Chen, Motoaki Sano, Keiichi Fukuda, Lin Lu, Jun Pu, Yan Zhang, Ling Gao, Ruiyan Zhang, Xiaoxiang Yan
Journal: Circulation (2024)

BACKGROUND: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. RNA-binding proteins are identified as regulators of cardiac disease; DDX5 (dead-box helicase 5) is a master regulator of many RNA processes, although its function in heart physiology remains unclear. METHODS: We assessed DDX5 expression in human failing hearts and a mouse HF model. To study the function of DDX5 in heart, we engineered cardiomyocyte-specific Ddx5 knockout mice. We overexpressed DDX5 in cardiomyocytes using adeno-associated virus serotype 9 and performed transverse aortic constriction to establish the murine HF model. The mechanisms underlined were subsequently investigated using immunoprecipitation–mass spectrometry, RNA-sequencing, alternative splicing analysis, and RNA immunoprecipitation sequencing. RESULTS: We screened transcriptome databases of murine HF and human dilated cardiomyopathy samples and found that DDX5 was significantly downregulated in both. Cardiomyocyte-specific deletion of Ddx5 resulted in HF with reduced cardiac function, an enlarged heart chamber, and increased fibrosis in mice. DDX5 overexpression improved cardiac function and protected against adverse cardiac remodeling in mice with transverse aortic constriction–induced HF. Furthermore, proteomics revealed that DDX5 is involved in RNA splicing in cardiomyocytes. We found that DDX5 regulated the aberrant splicing of Ca 2+ /calmodulin-dependent protein kinase IIδ ( CamkIIδ ), thus preventing the production of CaMKIIδA, which phosphorylates L-type calcium channel by serine residues of Cacna1c, leading to impaired Ca 2+ homeostasis. In line with this, we found increased intracellular Ca 2+ transients and increased sarcoplasmic reticulum Ca 2+ content in DDX5-depleted cardiomyocytes. Using adeno-associated virus serotype 9 knockdown of CaMKIIδA partially rescued the cardiac dysfunction and HF in Ddx5 knockout mice. CONCLUSIONS: These findings reveal a role for DDX5 in maintaining calcium homeostasis and cardiac function by regulating alternative splicing in cardiomyocytes, identifying the DDX5 as a potential target for therapeutic intervention in HF.
Lysozyme 1 Inflamed CCR2 <sup>+</sup> Macrophages Promote Obesity-Induced Cardiac Dysfunction
Authors: Lai Zhang, Huian Han, Andi Xu, Adwait Sathe, Siying Fu, Jiaqi Zhao, Wenhan Cai, Yaqing Yang, Jinting Liu, Hui Bai, Jingjing Ben, Xudong Zhu, Xiaoyu Li, Qing Yang, Zidun Wang, Yayun Gu, Chao Xing, Gabriele G. Schiattarella, Steven Yan Cheng, Hanwen Zhang, Qi Chen
Journal: Circulation Research (2024)

BACKGROUND: Macrophages are key players in obesity-associated cardiovascular diseases, which are marked by inflammatory and immune alterations. However, the pathophysiological mechanisms underlying macrophage’s role in obesity-induced cardiac inflammation are incompletely understood. Our study aimed to identify the key macrophage population involved in obesity-induced cardiac dysfunction and investigate the molecular mechanism that contributes to the inflammatory response. METHODS: In this study, we used single-cell RNA-sequencing analysis of Cd45 + CD11b + F4/80 + cardiac macrophages to explore the heterogeneity of cardiac macrophages. The CCR2 + (C-C chemokine receptor 2) macrophages were specifically removed by a dual recombinase approach, and the macrophage CCR2 was deleted to investigate their functions. We also performed cleavage under target and tagmentation analysis, chromatin immunoprecipitation-polymerase chain reaction, luciferase assay, and macrophage-specific lentivirus transfection to define the impact of lysozyme C in macrophages on obesity-induced inflammation. RESULTS: We find that the Ccr2 cluster undergoes a functional transition from homeostatic maintenance to proinflammation. Our data highlight specific changes in macrophage behavior during cardiac dysfunction under metabolic challenge. Consistently, inducible ablation of CCR2 + CX3CR1 + macrophages or selective deletion of macrophage CCR2 prevents obesity-induced cardiac dysfunction. At the mechanistic level, we demonstrate that the obesity-induced functional shift of CCR2-expressing macrophages is mediated by the CCR2/activating transcription factor 3/lysozyme 1/NF-κB (nuclear factor kappa B) signaling. Finally, we uncover a noncanonical role for lysozyme 1 as a transcription activator, binding to the RelA promoter, driving NF-κB signaling, and strongly promoting inflammation and cardiac dysfunction in obesity. CONCLUSIONS: Our findings suggest that lysozyme 1 may represent a potential target for the diagnosis of obesity-induced inflammation and the treatment of obesity-induced heart disease.
PD‐L1 Immune Checkpoint Targeted Photoactivable Liposomes (iTPALs) Prime the Stroma of Pancreatic Tumors and Promote Self‐Delivery (Adv. Healthcare Mater. 19/2024)
Authors: Chanda Bhandari, Azophi Moffat, Nimit Shah, Adil Khan, Maxwell Quaye, John Fakhry, Siddharth Soma, Austin Nguyen, Menitte Eroy, Ashritha Malkoochi, Rolf Brekken, Tayyaba Hasan, Jacopo Ferruzzi, Girgis Obaid
Journal: Advanced Healthcare Materials (2024)