tbuckley/cabot-search huggingface dataset:
Biologically active adrenomedullin as a marker for residual congestion and early rehospitalization in patients hospitalized for acute heart failure: Data from <scp>STRONG</scp>‐<scp>HF</scp>
Authors: Geert Voordes, Beth Davison, Jan Biegus, Christopher Edwards, Kevin Damman, Jozine ter Maaten, Alexandre Mebazaa, Koji Takagi, Marianna Adamo, Andrew P. Ambrosy, Mattia Arrigo, Marianela Barros, Jelena Celutkiene, Kamilė Čerlinskaitė‐Bajorė, Ovidiu Chioncel, Alain Cohen‐Solal, Albertino Damasceno, Benjamin Deniau, Rafael Diaz, Gerasimos Filippatos, Etienne Gayat, Antoine Kimmoun, Carolyn S.P. Lam, Marco Metra, Maria Novosadova, Matteo Pagnesi, Peter Pang, Piotr Ponikowski, Hadiza Saidu, Karen Sliwa, Daniela Tomasoni, Gad Cotter, Adriaan A. Voors
Journal: European Journal of Heart Failure (2024)

Aims Biologically active adrenomedullin (bio‐ADM) is a promising marker of residual congestion. The STRONG‐HF trial showed that high‐intensity care (HIC) of guideline‐directed medical therapy (GDMT) improved congestion and clinical outcomes in heart failure (HF) patients. The association between bio‐ADM, decongestion, outcomes and the effect size of HIC of GDMT remains to be elucidated. Methods and results We measured plasma bio‐ADM concentrations in 1005 patients within 2 days prior to anticipated discharge (baseline) and 90 days later. Bio‐ADM correlated with most signs of congestion, with the exception of rales. Changes in bio‐ADM were strongly correlated with change in congestion status from baseline to day 90 (gamma −0.24; p = 0.0001). Patients in the highest tertile of baseline bio‐ADM concentrations were at greater risk than patients in the lowest tertile for the primary outcome of 180‐day all‐cause mortality or HF rehospitalization (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.42–3.22) and 180‐day HF rehospitalization (HR 2.33, 95% CI 1.38–3.94). Areas under the receiver‐operating characteristic curves were 0.5977 (95% CI 0.5561–0.6393), 0.5800 (95% CI 0.5356–0.6243), and 0.6159 (95% CI 0.5711–0.6607) for bio‐ADM, N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and their combination, respectively, suggesting that both bio‐ADM and NT‐proBNP provided similarly modest discrimination for this outcome. A trend towards better discrimination by combined bio‐ADM and NT‐proBNP than NT‐proBNP alone was found ( p = 0.059). HIC improved the primary outcome, irrespective of baseline bio‐ADM concentration (interaction p = 0.37). In contrast to NT‐proBNP, the 90‐day change in bio‐ADM did not differ significantly between HIC and usual care. Conclusions Bio‐ADM is a marker of congestion and predicts congestion at 3 months after a HF hospitalization. Higher bio‐ADM was modestly associated with a higher risk of death and early hospital readmission and may have added value when combined with NT‐proBNP.
Myocardial infarction accelerates the progression of MASH by triggering immunoinflammatory response and induction of periostin
Authors: Wei Xie, Jing Gan, Xiaodong Zhou, Huiying Tian, Xingchao Pan, Wenyue Liu, Xiaokun Li, Jie Du, Aimin Xu, Minghua Zheng, Fan Wu, Yulin Li, Zhuofeng Lin
Journal: Cell Metabolism (2024)
Hepatitis E virus infections in German blood donors: results of 8 years of screening, 2015 to 2022
Authors: Ricarda Plümers, Jens Dreier, Cornelius Knabbe, André Gömer, Eike Steinmann, Daniel Todt, Tanja Vollmer
Journal: Eurosurveillance (2024)

Background Awareness of transfusion-transmitted hepatitis E raised in recent years led to the mandatory testing of blood donations in some European countries for hepatitis E virus (HEV) RNA. However, little is known about the epidemiology of HEV infections. Aim To and describe and analyse the epidemiology of HEV infections in blood donors in Germany. Methods Data from routine testing of therapeutic blood products donated between January 2015 and December 2022 at the Uni.Blutspendedienst OWL were analysed at the Institute of Laboratory and Transfusion Medicine, Heart and Diabetes Centre North Rhine-Westphalia. A total of 731,630 allogenic blood donations from 119,610 individual blood donors were tested for HEV RNA in minipools of 96 samples. The HEV RNA-positive donations were analysed for the presence of anti-HEV IgM and IgG. The HEV strains were genotyped and various clinical liver-specific parameters were determined. Results A total of 497 HEV-positive blood donations were identified, resulting in a yearly incidence of 1:1,474, from which 78.4% of the donations were RNA-only positive. Increased alanine aminotransferase activity was determined in 26.6% of HEV RNA-positive donors and was associated with the detection of IgG antibodies (1.2% anti-HEV IgM-positive, 11.9% anti-HEV IgM- and IgG-positive and 8.5% anti-HEV IgG-positive). An average incidence of 0.084–0.083% HEV RNA-positive donations in June and July in all years was observed, and a higher proportion of HEV RNA-positive men compared with women. All isolated HEV sequences corresponded to genotype 3. Conclusion Our results underline the necessity of HEV RNA screening in blood donations.
Detection of carbapenemase producing Acinetobacter baumannii ST19 from Georgia and Ukraine carrying blaOXA-23, blaOXA-72, and/or blaNDM-5, December 2019 to June 2023
Authors: Ting L Luo, Melissa J Martin, Valentyn Kovalchuk, Viacheslav Kondratiuk, Nino Trapaidze, Magda Metreveli, Christine E Hulseberg, Henry D Dao, Yoon I Kwak, Rosslyn Maybank, Thomas A Musich, Matthew R Scherer, Jason W Bennett, Patrick T Mc Gann, Francois Lebreton
Journal: Eurosurveillance (2024)

In 2003−2023, amid 5,436 Acinetobacter baumannii isolates collected globally through the Multidrug-Resistant Organism Repository and Surveillance Network, 97 were ST19 PAS , 34 of which carbapenem-resistant. Strains (n = 32) sampled after 2019 harboured either bla OXA-23 , bla OXA-72 , and/or bla NDM-5 . Phylogenetic analysis of the 97 isolates and 11 publicly available ST19 genomes revealed three sub-lineages of carbapenemase-producing isolates from mainly Ukraine and Georgia, including an epidemic clone carrying all three carbapenemase genes. Infection control and global surveillance of carbapenem-resistant A. baumannii remain important.
Increase of pertussis cases in the Vallès region, Catalonia, Spain, September 2023 to April 2024
Authors: Violeta Poltorak, Alba Cabré-Riera, Ferran Martínez-Botías, Eva Borràs López, Laura Clotet Romero, Maria Rosa Sala Farré, Mireia Jané Checa
Journal: Eurosurveillance (2024)

We describe a pertussis outbreak in the Vallès region of Catalonia, from September 2023 to April 2024. Incidence was high in children aged 10–14 years compared with previous outbreaks. Limited impact in newborns could be explained by the high vaccination coverage during pregnancy and at 11 months of age in 2022, at 85% and 94.1 %, respectively. A third booster vaccine dose during preadolescence should be considered and vaccination coverage in pregnant women be improved to control future outbreaks.
The impact of living conditions and health interventions on tuberculosis, Denmark, 1876 to 2022
Authors: Anne Christine Nordholm, Anja Joergensen, Louise Hedevang Holm, Aase Bengaard Andersen, Anders Koch, Peter Henrik Andersen, Troels Lillebaek
Journal: Eurosurveillance (2024)

Background Denmark possesses an exceptional historical data collection on tuberculosis (TB) from 1876 to the present, providing a unique opportunity to assess TB epidemiology over 147 years in Denmark. Aim Our aim was to describe the TB disease burden in Denmark in relation to historical events, living conditions and health interventions during the past 147 years. Methods We performed a nationwide register-based ecological study including all persons with TB in Denmark from 1876 through 2022, correlating the TB incidence to social, economic and health indicators. Results In Denmark, the overall TB incidence and mortality declined markedly over the past 147 years, only marginally influenced by specific TB interventions such as sanatoria, Bacillus Calmette-Guèrin (BCG) vaccination, mass screenings and antibiotics. Parallel to this decline, the country experienced improved living conditions, as illustrated by decreased infant mortality and increased life expectancy and wealth. In 1978, Denmark became a low-incidence country for TB with risk groups predominantly affected, and with a continuous change in demographics towards fewer Danish-born cases and relatively more migrant cases. Conclusions The decline over time in TB incidence and mortality in Denmark preceded specific TB interventions and can, first of all, be attributed to improved living conditions. TB has now become a rare disease in Denmark, predominantly occurring in particular risk groups. Future elimination of TB will require a combination of specific health interventions in these risk groups combined with a continued focus on improving socioeconomic status and living conditions.
Refugees from Ukraine receiving antiretroviral therapy in destination countries and territories of the World Health Organization European Region, including EU/EEA countries, February 2022 to March 2023
Authors: Giorgi Kuchukhidze, Machiko Otani, Stela Bivol, Teymur Noori
Journal: Eurosurveillance (2024)

Between the start of the Russian Federation’s invasion of Ukraine on 24 February 2022 and May 2023, more than 8 million individuals have been displaced from Ukraine. Ukraine has the second-largest HIV epidemic in the World Health Organization (WHO) European Region. From a humanitarian and public health perspective it is critical that Ukrainian refugees living with or at risk of HIV have access to testing, treatment and healthcare in their destination country. To gain better insight on the number of refugees from Ukraine receiving antiretroviral therapy (ART) in destination countries, the WHO Regional Office for Europe and the European Centre for Disease Prevention and Control conducted three surveys in July 2022, November 2022 and March 2023. Among 39 countries that responded to at least one survey, 31 had information on the number of refugees from Ukraine receiving ART in their country. A total of 6,519 refugees (1.5 per 1,000 refugees) received ART, lower than previous estimates by WHO, ECDC and partners of between 0.16% and 1.0%. This discrepancy may suggest a substantial number of undiagnosed and/or diagnosed but untreated HIV infections. Improving access to healthcare for people living with HIV among refugees from Ukraine is vital to ensure quality care.
Epidemic of parvovirus B19 and disease severity in pregnant people, Denmark, January to March 2024
Authors: Anne Christine Nordholm, Frederik Trier Møller, Signe Fischer Ravn, Lotte Flink Sørensen, Anja Moltke-Prehn, Jacob Elskær Mollerup, Tjede Funk, Lene Sperling, Ulisa Jeyaratnam, Kristina Træholt Franck, Karina Hjort-Pedersen, Christina Hjørnet Kamper, Rikke Thoft Nielsen, Pikka Jokelainen, Maria Wessman
Journal: Eurosurveillance (2024)

We report an epidemic of parvovirus B19 infections in Denmark during the first quarter of 2024, with a peak incidence 3.5 times higher than during the most recent epidemic in 2017. In total, 20.1% (130/648) of laboratory-confirmed cases were pregnant. Severe adverse outcomes were observed among 12.3% (16/130) of pregnant people and included foetal anaemia, foetal hydrops and miscarriage. Parvovirus B19 infection is not systematically monitored, but a national laboratory-based surveillance system is currently being established in Denmark.
Concurrent loss of LKB1 and KEAP1 enhances SHMT-mediated antioxidant defence in KRAS-mutant lung cancer
Authors: Hyun Min Lee, Nefertiti Muhammad, Elizabeth L. Lieu, Feng Cai, Jiawei Mu, Yun-Sok Ha, Guoshen Cao, Chamey Suchors, Kenneth Joves, Constantinos Chronis, Kailong Li, Gregory S. Ducker, Kellen Olszewski, Ling Cai, Derek B. Allison, Sara E. Bachert, William R. Ewing, Harvey Wong, Hyosun Seo, Isaac Y. Kim, Brandon Faubert, James Kim, Jiyeon Kim
Journal: Nature Metabolism (2024)
Genetic and environmental interactions contribute to immune variation in rewilded mice
Authors: Oyebola Oyesola, Alexander E. Downie, Nina Howard, Ramya S. Barre, Kasalina Kiwanuka, Kimberly Zaldana, Ying-Han Chen, Arthur Menezes, Soo Ching Lee, Joseph Devlin, Octavio Mondragón-Palomino, Camila Oliveira Silva Souza, Christin Herrmann, Sergei B. Koralov, Ken Cadwell, Andrea L. Graham, P’ng Loke
Journal: Nature Immunology (2024)

Abstract The relative and synergistic contributions of genetics and environment to interindividual immune response variation remain unclear, despite implications in evolutionary biology and medicine. Here we quantify interactive effects of genotype and environment on immune traits by investigating C57BL/6, 129S1 and PWK/PhJ inbred mice, rewilded in an outdoor enclosure and infected with the parasite Trichuris muris . Whereas cellular composition was shaped by interactions between genotype and environment, cytokine response heterogeneity including IFNγ concentrations was primarily driven by genotype with consequence on worm burden. In addition, we show that other traits, such as expression of CD44, were explained mostly by genetics on T cells, whereas expression of CD44 on B cells was explained more by environment across all strains. Notably, genetic differences under laboratory conditions were decreased following rewilding. These results indicate that nonheritable influences interact with genetic factors to shape immune variation and parasite burden.
Ultrasensitive plasma-based monitoring of tumor burden using machine-learning-guided signal enrichment
Authors: Adam J. Widman, Minita Shah, Amanda Frydendahl, Daniel Halmos, Cole C. Khamnei, Nadia Øgaard, Srinivas Rajagopalan, Anushri Arora, Aditya Deshpande, William F. Hooper, Jean Quentin, Jake Bass, Mingxuan Zhang, Theophile Langanay, Laura Andersen, Zoe Steinsnyder, Will Liao, Mads Heilskov Rasmussen, Tenna Vesterman Henriksen, Sarah Østrup Jensen, Jesper Nors, Christina Therkildsen, Jesus Sotelo, Ryan Brand, Joshua S. Schiffman, Ronak H. Shah, Alexandre Pellan Cheng, Colleen Maher, Lavinia Spain, Kate Krause, Dennie T. Frederick, Wendie den Brok, Caroline Lohrisch, Tamara Shenkier, Christine Simmons, Diego Villa, Andrew J. Mungall, Richard Moore, Elena Zaikova, Viviana Cerda, Esther Kong, Daniel Lai, Murtaza S. Malbari, Melissa Marton, Dina Manaa, Lara Winterkorn, Karen Gelmon, Margaret K. Callahan, Genevieve Boland, Catherine Potenski, Jedd D. Wolchok, Ashish Saxena, Samra Turajlic, Marcin Imielinski, Michael F. Berger, Sam Aparicio, Nasser K. Altorki, Michael A. Postow, Nicolas Robine, Claus Lindbjerg Andersen, Dan A. Landau
Journal: Nature Medicine (2024)
Comparing experience- and description-based economic preferences across 11 countries
Authors: Hernán Anlló, Sophie Bavard, FatimaEzzahra Benmarrakchi, Darla Bonagura, Fabien Cerrotti, Mirona Cicue, Maelle Gueguen, Eugenio José Guzmán, Dzerassa Kadieva, Maiko Kobayashi, Gafari Lukumon, Marco Sartorio, Jiong Yang, Oksana Zinchenko, Bahador Bahrami, Jaime Silva Concha, Uri Hertz, Anna B. Konova, Jian Li, Cathal O’Madagain, Joaquin Navajas, Gabriel Reyes, Atiye Sarabi-Jamab, Anna Shestakova, Bhasi Sukumaran, Katsumi Watanabe, Stefano Palminteri
Journal: Nature Human Behaviour (2024)
Randomized Trial for Evaluation in Secondary Prevention Efficacy of Combination Therapy–Statin and Eicosapentaenoic Acid (RESPECT-EPA)
Authors: Katsumi Miyauchi, Hiroshi Iwata, Yuji Nishizaki, Teruo Inoue, Atsushi Hirayama, Kazuo Kimura, Yukio Ozaki, Toyoaki Murohara, Kenji Ueshima, Yoshihiro Kuwabara, Sachiko Tanaka-Mizuno, Naotake Yanagisawa, Tosiya Sato, Hiroyuki Daida
Journal: Circulation (2024)

BACKGROUND: Low plasma levels of eicosapentaenoic acid (EPA) are associated with cardiovascular events. This trial aimed to assess the clinical benefits of icosapent ethyl in patients with coronary artery disease, a low EPA/arachidonic acid (AA) ratio, and statin treatment. METHODS: In this prospective, multicenter, randomized, open-label, blinded end-point study, patients with stable coronary artery disease and a low EPA/AA ratio (&lt;0.4) were randomized to EPA (1800 of icosapent ethyl administered daily) or control group. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, unstable angina pectoris, and coronary revascularization. The secondary composite end points of coronary events included sudden cardiac death, fatal and nonfatal myocardial infarction, unstable angina requiring emergency hospitalization and coronary revascularization, or coronary revascularization. RESULTS: Overall, 3884 patients were enrolled at 95 sites in Japan. Among them, 2506 patients had a low EPA/AA ratio, and 1249 and 1257 patients were randomized to the EPA and control group, respectively. The median EPA/AA ratio was 0.243 (interquartile range, 0.180–0.314) and 0.235 (interquartile range, 0.163–0.310) in the EPA and control group, respectively. Over a median period of 5 years, the primary end point occurred in 112 of 1225 patients (9.1%) and 155 of 1235 patients (12.6%) in the EPA and control group, respectively (hazard ratio, 0.79 [95% CI, 0.62–1.00]; P =0.055). Meanwhile, the secondary composite end point of coronary events in the EPA group was significantly lower (81/1225 [6.6%] versus 120/1235 [9.7%] patients; hazard ratio, 0.73 [95% CI, 0.55–0.97]). Adverse events did not differ between the groups, but the rate of new-onset atrial fibrillation was significantly higher in the EPA group (3.1% versus 1.6%; P =0.017). CONCLUSIONS: Icosapent ethyl treatment resulted in a numerically lower risk of cardiovascular events that did not reach statistical significance in patients with chronic coronary artery disease, a low EPA/AA ratio, and statin treatment. REGISTRATION: URL: https://www.umin.ac.jp/ctr/ ; Unique identifier: UMIN000012069.
Endothelial Heterogeneity in the Response to Autophagy Drives Small Vessel Muscularization in Pulmonary Hypertension
Authors: Qi Zhang, Nobuhiro Yaoita, Arata Tabuchi, Shaofei Liu, Shiau-Haln Chen, Qiuhua Li, Niklas Hegemann, Caihong Li, Julie Rodor, Sara Timm, Hebatullah Laban, Toren Finkel, Troy Stevens, Diego F. Alvarez, Lasti Erfinanda, Marc de Perrot, Mariya M. Kucherenko, Christoph Knosalla, Matthias Ochs, Stefanie Dimmeler, Thomas Korff, Subodh Verma, Andrew H. Baker, Wolfgang M. Kuebler
Journal: Circulation (2024)

Endothelial cell (EC) apoptosis and proliferation of apoptosis-resistant cells is a hallmark of pulmonary hypertension (PH). Yet, why some ECs die and others proliferate and how this contributes to vascular remodeling is unclear. We hypothesized that this differential response may: (1) relate to different EC subsets, namely pulmonary artery (PAECs) versus microvascular ECs (MVECs); (2) be attributable to autophagic activation in both EC subtypes; and (3) cause replacement of MVECs by PAECs with subsequent distal vessel muscularization.
The Ubiquitin Ligase RBX2/SAG Regulates Mitochondrial Ubiquitination and Mitophagy
Authors: Wenjuan Wang, Ermin Li, Jianqiu Zou, Chen Qu, Juan Ayala, Yuan Wen, Md Sadikul Islam, Neal L. Weintraub, David J.R. Fulton, Qiangrong Liang, Jiliang Zhou, Jinbao Liu, Jie Li, Yi Sun, Huabo Su
Journal: Circulation Research (2024)

Clearance of damaged mitochondria via mitophagy is crucial for cellular homeostasis. Apart from Parkin, little is known about additional Ub (ubiquitin) ligases that mediate mitochondrial ubiquitination and turnover, particularly in highly metabolically active organs such as the heart.
Germline <i>CDH1</i> Variants and Lifetime Cancer Risk
Authors: Carrie E. Ryan, Grace-Ann Fasaye, Amber F. Gallanis, Lauren A. Gamble, Paul H. McClelland, Anna Duemler, Sarah G. Samaranayake, Andrew M. Blakely, Christine M. Drogan, Kerry Kingham, Devanshi Patel, Linda Rodgers-Fouche, Ava Siegel, Sonia S. Kupfer, James M. Ford, Daniel C. Chung, James G. Dowty, Joshua Sampson, Jeremy L. Davis
Journal: JAMA (2024)

Approximately 1% to 3% of gastric cancers and 5% of lobular breast cancers are hereditary. Loss of function CDH1 gene variants are the most common gene variants associated with hereditary diffuse gastric cancer and lobular breast cancer. Previously, the lifetime risk of gastric cancer was estimated to be approximately 25% to 83% and for breast cancer it was estimated to be approximately 39% to 55% in individuals with loss of function CDH1 gene variants.
Lipopolysaccharide released from gut activates pyroptosis of macrophages via Caspase 11‐Gasdermin D pathway in systemic lupus erythematosus
Authors: Yue Xin, Changxing Gao, Lai Wang, Qianmei Liu, Qianjin Lu
Journal: MedComm (2024)

Abstract Noncanonical pyroptosis is triggered by Caspase 4/5/11, which cleaves Gasdermin D (GSDMD), leading to cell lysis. While GSDMD has been studied previously in systemic lupus erythematosus (SLE), the role of pyroptosis in SLE pathogenesis remains unclear and contentious, with limited understanding of Caspase 11‐mediated pyroptosis in this condition. In this study, we explored the level of Caspase 11‐mediated pyroptosis in SLE, identifying both the upstream pathways and the interaction between pyroptosis and adaptive immune responses. We observed increased Caspase 5/11 and GSDMD‐dependent pyroptosis in the macrophages/monocytes of both lupus patients and mice. We identified serum lipopolysaccharide (LPS), released from the gut due to a compromised gut barrier, as the signal that triggers Caspase 11 activation in MRL/lpr mice. We further discovered that pyroptotic macrophages promote the differentiation of mature B cells independently of T cells. Additionally, inhibiting Caspase 11 and preventing LPS leakage proved effective in improving lupus symptoms in MRL/lpr mice. These findings suggest that elevated serum LPS, resulting from a damaged gut barrier, induces Caspase 11/GSDMD‐mediated pyroptosis, which in turn promotes B cell differentiation and enhances autoimmune responses in SLE. Thus, targeting Caspase 11 could be a viable therapeutic strategy for SLE.
CircMALAT1 promotes cancer stem‐like properties and chemoresistance via regulating Musashi‐2/c‐Myc axis in esophageal squamous cell carcinoma
Authors: Zitong Zhao, Yingni Deng, Jing Han, Liying Ma, Yumeng Zhu, Hua Zhang, Zhixu He, Yongmei Song
Journal: MedComm (2024)

Abstract The primary challenge in treating esophageal squamous cell carcinoma (ESCC) is resistance to chemotherapy. Cancer stem cell (CSC) is the root cause of tumor drug resistance. Therefore, targeting CSCs has been considered promising therapeutic strategy for tumor treatment. Here, we report that circMALAT1 was significantly upregulated in ESCC CSC‐like cells and primary tumors from ESCC patients. Clinically, there was a positive correlation between circMALAT1 expression and ESCC stage and lymph node metastasis, as well as poor prognosis for ESCC patients. In vitro and in vivo functional studies revealed that circMALAT1 promoted CSC‐like cells expansion, tumor growth, lung metastasis and drug resistance of ESCC. Mechanistically, circMALAT1 directly interacted with CSC‐functional protein Musashi RNA Binding Protein 2 (MSI2). CircMALAT1 inhibited MSI2 ubiquitination by preventing it from interacting with β‐transducin repeat containing protein (BTRC) E3 ubiquitin ligase. Also, circMALAT1 knockdown inhibited the expression of MSI2‐regulating CSC‐markers c‐Myc in ESCC. Collectively, circMALAT1 modulated the ubiquitination and degradation of the MSI2 protein signaling with ESCC CSCs and accelerated malignant progression of ESCC. CircMALAT1 has the potential to serve as a biomarker for drug resistance and as a target for therapy in CSCs within ESCC.