tbuckley/cabot-search huggingface dataset:
Biomarkers for a less invasive strategy to predict children with eosinophilic esophagitis
Authors: Helena Thulin, Ladan Mansouri, Maria Altman, Simon Kebede Merid, Joachim Lundahl, Caroline Nilsson, Jesper Säfholm
Journal: Allergy (2024)

Abstract Background Noninvasive biomarkers for diagnosing and monitoring eosinophilic esophagitis (EoE) are currently lacking. This study evaluates 20 biomarkers in serum and saliva, aiming to assess their diagnostic potential in pediatric EoE patients and healthy individuals. Methods Blood and saliva from children undergoing upper endoscopy were analyzed for biomarkers, including absolute eosinophil count (AEC), eosinophil‐derived neurotoxin (EDN), total and specific IgG 4 ‐antibodies (sIgG 4 ), specific IgE‐antibodies (sIgE) and 15‐hydroxyeicosatetraenoic acid (15(S)‐HETE). Some patients participated twice, forming a longitudinal cohort. The ability to use the biomarkers to predict the EoE diagnosis was evaluated. Results Analysis from 105 children divided into active EoE, remission, and healthy, revealed elevated levels of serum biomarkers (AEC, EDN, 15(S)‐HETE, sIgG 4 , and sIgE) in active EoE compared to healthy individuals. A combination of biomarkers (AEC, EDN, sIgE to egg white and wheat) and symptoms showed an AUC of 0.92 in distinguishing between the three groups. We further showed that optimal cutoff values for these biomarkers could discriminate between active EoE and healthy with a sensitivity of 88% and a specificity of 100% in distinguishing EoE (active and in remission) from healthy. Longitudinally, levels of EDN, sIgG 4 to Bos d 4, Bos d 5, Bos d 8, gliadin, and birch, and sIgE to milk decreased in patients progressing from active EoE to remission ( p &lt;.05). Conclusions This study identified novel biomarkers associated with EoE and proposes a panel, together with symptoms, for effective discrimination between active EoE, EoE in remission, and healthy individuals. The findings may contribute to a less invasive diagnostic method and may be a potential surveillance tool for pediatric EoE patients.
Antisense Oligonucleotide Therapy for Calmodulinopathy
Authors: Raul H. Bortolin, Farina Nawar, Chaehyoung Park, Michael A. Trembley, Maksymilian Prondzynski, Mason E. Sweat, Peizhe Wang, Jiehui Chen, Fujian Lu, Carter Liou, Paul Berkson, Erin M. Keating, Daisuke Yoshinaga, Nikoleta Pavlaki, Thomas Samenuk, Cecilia B. Cavazzoni, Peter T. Sage, Qing Ma, Robert D. Whitehill, Dominic J. Abrams, Chrystalle Katte Carreon, Juan Putra, Sanda Alexandrescu, Shuai Guo, Wen-Chin Tsai, Michael Rubart, Dieter A. Kubli, Adam E. Mullick, Vassilios J. Bezzerides, William T. Pu
Journal: Circulation (2024)

BACKGROUND: Calmodulinopathies are rare inherited arrhythmia syndromes caused by dominant heterozygous variants in CALM1 , CALM2 , or CALM3 , which each encode the identical CaM (calmodulin) protein. We hypothesized that antisense oligonucleotide (ASO)–mediated depletion of an affected calmodulin gene would ameliorate disease manifestations, whereas the other 2 calmodulin genes would preserve CaM level and function. METHODS: We tested this hypothesis using human induced pluripotent stem cell–derived cardiomyocyte and mouse models of CALM1 pathogenic variants. RESULTS: Human CALM1 F142L/+ induced pluripotent stem cell–derived cardiomyocytes exhibited prolonged action potentials, modeling congenital long QT syndrome. CALM1 knockout or CALM1-depleting ASOs did not alter CaM protein level and normalized repolarization duration of CALM1 F142L/+ induced pluripotent stem cell–derived cardiomyocytes. Similarly, an ASO targeting murine Calm1 depleted Calm1 transcript without affecting CaM protein level. This ASO alleviated drug-induced bidirectional ventricular tachycardia in Calm1 N98S/+ mice without a deleterious effect on cardiac electrical or contractile function. CONCLUSIONS: These results provide proof of concept that ASOs targeting individual calmodulin genes are potentially effective and safe therapies for calmodulinopathies.
Effect of early administration of tetracosactide on mortality and host response in critically ill patients requiring rescue surgery: a sensitivity analysis of the STOPSHOCK phase 3 randomized controlled trial
Authors: Giorgio Noera, Alfio Bertolini, Laura Calzà, Mercedes Gori, Annalisa Pitino, Graziella D’Arrigo, Colin Gerard Egan, Giovanni Tripepi
Journal: Military Medical Research (2024)

Undifferentiated shock is recognized as a criticality state that is transitional in immune-mediated topology for casual risk of lethal microcirculatory dysfunction. This was a sensitivity analysis of a drug (tetracosactide; TCS10) targeting melanocortin receptors (MCRs) in a phase 3 randomized controlled trial to improve cardiovascular surgical rescue outcome by reversing mortality and hemostatic disorders.
Genomic characterization of AML with aberrations of chromosome 7: a multinational cohort of 519 patients
Authors: Adriane Halik, Marlon Tilgner, Patricia Silva, Natalia Estrada, Robert Altwasser, Ekaterina Jahn, Michael Heuser, Hsin-An Hou, Marta Pratcorona, Robert K. Hills, Klaus H. Metzeler, Laurene Fenwarth, Anna Dolnik, Christine Terre, Klara Kopp, Olga Blau, Martin Szyska, Friederike Christen, Jan Krönke, Loïc Vasseur, Bob Löwenberg, Jordi Esteve, Peter J. M. Valk, Matthieu Duchmann, Wen-Chien Chou, David C. Linch, Hartmut Döhner, Rosemary E. Gale, Konstanze Döhner, Lars Bullinger, Kenichi Yoshida, Frederik Damm
Journal: Journal of Hematology & Oncology (2024)

Deletions and partial losses of chromosome 7 (chr7) are frequent in acute myeloid leukemia (AML) and are linked to dismal outcome. However, the genomic landscape and prognostic impact of concomitant genetic aberrations remain incompletely understood.
The dual role of cellular senescence in human tumor progression and therapy
Authors: Liang Ma, Jie Yu, Yidian Fu, Xiaoyu He, Shengfang Ge, Renbing Jia, Ai Zhuang, Zhi Yang, Xianqun Fan
Journal: MedComm (2024)

Cellular senescence, one of the hallmarks of cancer, is characterized by cell cycle arrest and the loss of most normal cellular functions while acquiring a hypersecretory, proinflammatory phenotype. The function of senescent cells in cancer cells varies depending on the cellular conditions. Before the occurrence of cancer, senescent cells act as a barrier to prevent its development. But once cancer has occurred, senescent cells play a procancer role. However, few of the current studies have adequately explained the diversity of cellular senescence across cancers. Herein, we concluded the latest intrinsic mechanisms of cellular senescence in detail and emphasized the senescence-associated secretory phenotype as a key contributor to heterogeneity of senescent cells in tumor. We also discussed five kinds of inducers of cellular senescence and the advancement of senolytics in cancer, which are drugs that tend to clear senescent cells. Finally, we summarized the various effects of senescent cells in different cancers and manifested that their functions may be diametrically opposed under different circumstances. In short, this paper contributes to the understanding of the diversity of cellular senescence in cancers and provides novel insight for tumor therapy.
Anthropometric measures and long‐term mortality in non‐ischaemic heart failure with reduced ejection fraction: Questioning the obesity paradox
Authors: Jawad H. Butt, Jens Jakob Thune, Jens C. Nielsen, Jens Haarbo, Lars Videbæk, Finn Gustafsson, Søren L. Kristensen, Niels E. Bruun, Hans Eiskjær, Axel Brandes, Christian Hassager, Jesper H. Svendsen, Dan E. Høfsten, Christian Torp‐Pedersen, Morten Schou, Steen Pehrson, Milton Packer, John J.V. McMurray, Lars Køber
Journal: European Journal of Heart Failure (2024)

Abstract Aims Although body mass index (BMI) is the most commonly used anthropometric measure to assess adiposity, alternative indices such as the waist‐to‐height ratio may better reflect the location and amount of ectopic fat as well as the weight of the skeleton. Methods and results The prognostic value of several alternative anthropometric measures was compared with that of BMI in 1116 patients with non‐ischaemic heart failure with reduced ejection fraction (HFrEF) enrolled in DANISH. The association between anthropometric measures and all‐cause death was adjusted for prognostic variables, including natriuretic peptides. Median follow‐up was 9.5 years (25th–75th percentile, 7.9–10.9). Compared to patients with a BMI 18.5–24.9 kg/m 2 ( n = 363), those with a BMI ≥25 kg/m 2 had a higher risk of all‐cause and cardiovascular death, although this association was only statistically significant for a BMI ≥35 kg/m 2 ( n = 91) (all‐cause death: hazard ratio [HR] 1.78, 95% confidence interval [CI] 1.28–2.48; cardiovascular death: HR 2.46, 95% CI 1.69–3.58). Compared to a BMI 18.5–24.9 kg/m 2 , a BMI &lt;18.5 kg/m 2 ( n = 24) was associated with a numerically, but not a significantly, higher risk of all‐cause and cardiovascular death. Greater waist‐to‐height ratio (as an exemplar of indices not incorporating weight) was also associated with a higher risk of all‐cause and cardiovascular death (HR for the highest vs. the lowest quintile: all‐cause death: HR 2.11, 95% CI 1.53–2.92; cardiovascular death: HR 2.17, 95% CI 1.49–3.15). Conclusion In patients with non‐ischaemic HFrEF, there was a clear association between greater adiposity and higher long‐term mortality. Clinical Trial Registration: ClinicalTrials.gov NCT00542945.
Empagliflozin and glucagon‐like peptide‐1 receptor agonists: The brothers for heart failure? Letter regarding the article ‘Time from admission to randomization and the effect of empagliflozin in acute heart failure: A post‐hoc analysis from EMPULSE’
Authors: Yue Hu, Zheng Li, Yingzi Zhang
Journal: European Journal of Heart Failure (2024)
Dual alarmin-receptor-specific targeting peptide systems for treatment of sepsis
Authors: Seok-Jun Mun, Euni Cho, Woo Jin Gil, Seong Jae Kim, Hyo Keun Kim, Yu Seong Ham, Chul-Su Yang
Journal: Acta Pharmaceutica Sinica B (2024)

The pathophysiology of sepsis is characterized by a systemic inflammatory response to infection; however, the cytokine blockade that targets a specific early inflammatory mediator, such as tumor necrosis factor, has shown disappointing results in clinical trials. During sepsis, excessive endotoxins are internalized into the cytoplasm of immune cells, resulting in dysregulated pyroptotic cell death, which induces the leakage of late mediator alarmins such as HMGB1 and PTX3. As late mediators of lethal sepsis, overwhelming amounts of alarmins bind to high-affinity TLR4/MD2 and low-affinity RAGE receptors, thereby amplifying inflammation during early-stage sepsis. In this study, we developed a novel alarmin/receptor-targeting system using a TLR4/MD2/RAGE-blocking peptide (TMR peptide) derived from the HMGB1/PTX3-receptors interacting motifs. The TMR peptide successfully attenuated HMGB1/PTX3- and LPS-mediated inflammatory cytokine production by impairing its interactions with TLR4 and RAGE. Moreover, we developed TMR peptide-conjugated liposomes (TMR-Lipo) to improve the peptide pharmacokinetics. In combination therapy, moderately antibiotic-loaded TMR-Lipo demonstrated a significant therapeutic effect in a mouse model of cecal ligation- and puncture-induced sepsis. The identification of these peptides will pave the way for the development of novel pharmacological tools for sepsis therapy.
Risk and protective factors of youth crime: An umbrella review of systematic reviews and meta-analyses
Authors: Getinet Ayano, Rosanna Rooney, Christina M Pollard, Jaya A R Dantas, Roanna Lobo, Zakia Jeemi, Sharyn Burns, Robert Cunningham, Stephen Monterosso, Lynne Millar, Sharinaz Hassan, Sender Dovchin, Rhonda Oliver, Kael Coleman, Rosa Alati
Journal: Clinical Psychology Review (2024)

Several systematic reviews and meta-analyses have been conducted on the risk and protective factors of youth crime. This study aims to consolidate this evidence using an umbrella review methodology.
Epidemiology of Metabolic Dysfunction Associated Steatotic Liver Disease
Authors: Zobair M. Younossi, Markos Kalligeros, Linda Henry
Journal: Clinical and Molecular Hepatology (2024)

As the rates of obesity and type 2 diabetes (T2D) continue to increase globally, so does the prevalence of metabolic dysfunction associated steatotic liver disease (MASLD). Currently, 38% of all adults and 7-14% of children and adolescents have MASLD. By 2040, the MASLD prevalence rate for adults is projected to increase to over 55%. Although many with MASLD will not develop progressive liver disease, given the vast number of patients with MASLD, it has now become the top indication for liver transplant in the United States for those with hepatocellular carcinoma (HCC) and women. However, the most common cause of mortality among patients with MASLD remains death cardiovascular diseases. In addition to liver outcomes (cirrhosis and HCC), MASLD is associated with increased risk for the developing de-novo T2D, chronic kidney disease, sarcopenia and extrahepatic cancers. Furthermore, MASLD is associated with decreased health related quality of life, decreased work productivity, fatigue and increased healthcare resource utilization and substantial economic burden. Similar to other metabolic disease, lifestyle interventions with heathy diet and increased physical activity remain the cornerstone of managing these patients. Although a number of obesity and T2D drugs are available to treat co-morbid disease, Resmetirom is the only MASH-targeted medication that was recently approved by the Federal Drug Administration for use in the United States for those with stage 2-3 fibrosis. The following review provides an overview of MASLD epidemiology, its related risk factors and outcomes and demonstrates that without further global initiatives, MASLD may continue to increase.
Criteria and prognostic models for patients with hepatocellular carcinoma undergoing liver transplantation
Authors: Meng Sha, Jun Wang, Jie Cao, Zhi-Hui Zou, Xiao-ye Qu, Zhi-feng Xi, Chuan Shen, Ying Tong, Jian-jun Zhang, Seogsong Jeong, Qiang Xia
Journal: Clinical and Molecular Hepatology (2024)

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.
KASL Clinical Practice Guidelines for Noninvasive Tests to Assess Liver Fibrosis in Chronic Liver Disease
Authors: Mi Na Kim, Ji Won Han, Jihyun An, Beom Kyung Kim, Young-Joo Jin, Seung-Seob Kim, Minjong Lee, Han Ah Lee, Yuri Cho, Hee Yeon Kim, Yu Rim Shin, Jung Hwan Yu, Moon Young Kim, YoungRok Choi, Young Eun Chon, Eun Ju Cho, Eun Joo Lee, Sang Gyune Kim, Won Kim, Dae Won Jun, Seung Up Kim
Journal: Clinical and Molecular Hepatology (2024)
Stealth mRNA nanovaccines to control lymph node trafficking
Authors: Coral García-Fernández, Tommaso Virgilio, Irene Latino, Marta Guerra-Rebollo, Santiago F Gonzalez, Salvador Borrós, Cristina Fornaguera
Journal: Journal of Controlled Release (2024)

mRNA-based vaccines symbolize a new paradigm shift in personalized medicine for the treatment of infectious and non-infectious diseases. However, the reactogenicity associated with the currently approved formulations limits their applicability in autoinflammatory disorders, such as tumour therapeutics. In this study, we present a delivery system showing controlled immunogenicity and minimal non-specific inflammation, allowing for selective delivery of mRNA to antigen presenting cells (APCs) within the medullary region of the lymph nodes. Our platform offers precise control over the trafficking of nanoparticles within the lymph nodes by optimizing stealth and targeting properties, as well as the subsequent opsonization process. By targeting specific cells, we observed a potent adaptive and humoral immune response, which holds promise for preventive and therapeutic anti-tumoral vaccines. Through spatial programming of nanoparticle distribution, we can promote robust immunization, thus improving and expanding the utilization of mRNA vaccines. This innovative approach signifies a remarkable step forward in the field of targeted nanomedicine.
C-type natriuretic peptide (CNP): The cardiovascular system and beyond
Authors: Yasmin A Dickinson, Amie J Moyes, Adrian J Hobbs
Journal: Pharmacology & Therapeutics (2024)

C-type natriuretic peptide (CNP) represents the 'local' member of the natriuretic peptide family, functioning in an autocrine or paracrine capacity to modulate a hugely diverse portfolio of physiological processes. Whilst the best-characterised of these regulatory roles are in the cardiovascular system, akin to its predominantly endocrine siblings atrial (ANP) and brain (BNP) natriuretic peptides, CNP governs many additional, unrelated mechanisms including bone growth, gamete maturation, auditory processing, and neuronal integrity. Furthermore, there is currently great interest in mimicking the biological activity of CNP for therapeutic gain in many of these disparate organ systems. Herein, we provide an overview of the physiology, pathophysiology and pharmacology of CNP in both cardiovascular and non-cardiovascular settings.
Engineered lipid nanoparticles enable therapeutic gene silencing of GTSE1 for the treatment of liver fibrosis
Authors: Michaela Jeong, Sumin Shin, Gyeongseok Lee, Yeji Lee, Seo Bhin Park, Jisoo Kang, Young-Sun Lee, Wonhyo Seo, Hyukjin Lee
Journal: Journal of Controlled Release (2024)
Utility of epitope-specific IgE, IgG4, and IgG1 antibodies for the diagnosis of wheat allergy
Authors: Witchaya Srisuwatchari, Mayte Suárez-Fariñas, Andrew D Delgado, Galina Grishina, Maria Suprun, Ashley Sang Eun Lee, Pakit Vichyanond, Punchama Pacharn, Hugh A Sampson
Journal: Journal of Allergy and Clinical Immunology (2024)
Survival of patients with classical Hodgkin lymphoma in Finland: a national population-based analysis
Authors: Noora Hannuksela, Anu Partanen, Anna Anttalainen, Liisa Ukkola-Vuoti, Iiro Toppila, Johanna Vikkula, Katja Marin, Hanne Kuitunen, Tatu Miettinen, Outi Kuittinen, Aino Rönkä
Journal: Blood Cancer Journal (2024)
Haplotype analysis identifies functional elements in monoclonal gammopathy of unknown significance
Authors: Hauke Thomsen, Subhayan Chattopadhyay, Niels Weinhold, Pavel Vodicka, Ludmila Vodickova, Per Hoffmann, Markus M. Nöthen, Karl-Heinz Jöckel, Börge Schmidt, Roman Hajek, Göran Hallmans, Ulrika Pettersson-Kymmer, Florentin Späth, Hartmut Goldschmidt, Kari Hemminki, Asta Försti
Journal: Blood Cancer Journal (2024)

Genome-wide association studies (GWASs) based on common single nucleotide polymorphisms (SNPs) have identified several loci associated with the risk of monoclonal gammopathy of unknown significance (MGUS), a precursor condition for multiple myeloma (MM). We hypothesized that analyzing haplotypes might be more useful than analyzing individual SNPs, as it could identify functional chromosomal units that collectively contribute to MGUS risk. To test this hypothesis, we used data from our previous GWAS on 992 MGUS cases and 2910 controls from three European populations. We identified 23 haplotypes that were associated with the risk of MGUS at the genome-wide significance level (p < 5 × 10
Audacity of Gene Therapy
Authors: Marketa Dimitrov, Christen L Ebens, Jakub Tolar
Journal: British Journal of Dermatology (2024)

Since the identification of DNA as the hereditary material, therapeutic advances have focused on gene therapy and allogeneic haematopoietic cell transplants for inherited diseases. Despite successes in treating conditions like β-thalassaemia and sickle cell disease, challenges such as insertional oncogenesis and immunogenicity persist. Future efforts must prioritize improving vector safety, refining manufacturing processes and expanding access to gene therapy, to fully realize its potential.
The muscle tissue transcriptome of idiopathic inflammatory myopathy reflects the muscle damage process by monocytes and presence of skin lesions
Authors: Shinji Izuka, Natsuka Umezawa, Toshihiko Komai, Yusuke Sugimori, Naoki Kimura, Fumitaka Mizoguchi, Yuichiro Fujieda, Keita Ninagawa, Takeshi Iwasaki, Katsuya Suzuki, Tsutomu Takeuchi, Koichiro Ohmura, Tsuneyo Mimori, Tatsuya Atsumi, Eiryo Kawakami, Akari Suzuki, Yuta Kochi, Kazuhiko Yamamoto, Shinsuke Yasuda, Tomohisa Okamura, Mineto Ota, Keishi Fujio
Journal: Arthritis & Rheumatology (2024)

We aim to investigate transcriptomic and immunophenotypic features of muscle specimens from patients with idiopathic inflammatory myopathy (IIM).
Randomized Crossover Trial of 2-Week Ketone Ester Treatment in Patients With Type 2 Diabetes and Heart Failure With Preserved Ejection Fraction
Authors: Nigopan Gopalasingam, Kristoffer Berg-Hansen, Kristian Hylleberg Christensen, Bertil T. Ladefoged, Steen Hvitfeldt Poulsen, Mads Jønsson Andersen, Barry Borlaug, Roni Nielsen, Niels Møller, Henrik Wiggers
Journal: Circulation (2024)

Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality in patients with type 2 diabetes (T2DM). Acute increases in circulating levels of ketone body 3-hydroxybutyrate have beneficial acute hemodynamic effects in patients without T2DM with chronic heart failure with reduced ejection fraction. However, the cardiovascular effects of prolonged oral ketone ester (KE) treatment in patients with T2DM and HFpEF remain unknown.
Sacubitril-Valsartan in Patients Requiring Hemodialysis
Authors: Dustin Le, Morgan E. Grams, Josef Coresh, Jung-Im Shin
Journal: JAMA Network Open (2024)

Randomized clinical trials have shown that sacubitril-valsartan reduces the risks of mortality and hospitalization in patients with heart failure with reduced ejection fraction (HFrEF), but patients with kidney failure requiring dialysis were excluded.