tbuckley/cabot-search huggingface dataset:
A proposal for an inclusive working definition of genetic discrimination to promote a more coherent debate
Authors: Beatrice Kaiser, Diya Uberoi, Maili C. Raven-Adams, Katherine Cheung, Andreas Bruns, Subhashini Chandrasekharan, Margaret Otlowski, Anya E. R. Prince, Jane Tiller, Arzoo Ahmed, Yvonne Bombard, Charles Dupras, Palmira Granados Moreno, Rosalyn Ryan, Augusto Valderrama-Aguirre, Yann Joly
Journal: Nature Genetics (2024)
RNA regulatory mechanisms controlling TGF-β signaling and EMT in cancer
Authors: Cameron P. Bracken, Gregory J. Goodall, Philip A. Gregory
Journal: Seminars in Cancer Biology (2024)

Epithelial-mesenchymal transition (EMT) is a major contributor to metastatic progression and is prominently regulated by TGF-β signalling. Both EMT and TGF-β pathway components are tightly controlled by non-coding RNAs - including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) - that collectively have major impacts on gene expression and resulting cellular states. While miRNAs are the best characterised regulators of EMT and TGF-β signaling and the miR-200-ZEB1/2 feedback loop plays a central role, important functions for lncRNAs and circRNAs are also now emerging. This review will summarise our current understanding of the roles of non-coding RNAs in EMT and TGF-β signaling with a focus on their functions in cancer progression.
Impact of a bundle of care (intravenous iron, erythropoietin and transfusion metabolic adjustment) on post-operative transfusion incidence in cardiac surgery: a single-centre, randomised, open-label, parallel-group controlled pilot trial
Authors: Marine Saour, Cinderella Blin, Norddine Zeroual, Marc Mourad, Maïlis Amico, Philippe Gaudard, Marie-Christine Picot, Pascal H. Colson
Journal: The Lancet Regional Health - Europe (2024)

SummaryBackgroundRed blood cell (RBC) transfusions are frequent in patients after cardiac surgery. This study assessed whether a bundle of care including pre-operative and post-operative administration of erythropoietin (EPO) with intravenous iron supplementation, and restrictive transfusion adjusted for ScvO2 could result in reduced postoperative transfusions.MethodsIn this single-centre, randomised, open-label, parallel-group controlled pilot study, patients undergoing elective cardiac surgery with high risk of transfusion in a University Hospital were enrolled by the investigator and the randomisation procedure using a central internet-based system was made by the clinical research assistant. Since the trial was open-label, no masking was used. Patients were assigned (1:1) to either the STOP group (40,000 IU subcutaneous EPO combined with 20 mg/kg intravenous ferric carboxymaltose if Hb < 13 g/dL the day before surgery or at ICU admission, and RBC transfusion if Hb ≤ 8 g/dL and ScvO2 ≤ 65%, or additional EPO dose if 8 < Hb < 13 g/dL) or to the control group (RBC transfusion if Hb ≤ 8 g/dL, or, if 8 < Hb < 13 g/dL, intravenous iron sucrose 200 mg or 300 mg according to weight). Primary outcome was the incidence of postoperative RBC transfusion up to hospital discharge or postoperative day 28. The trial is registered with ClinicalTrials.gov, NCT04141631.FindingsBetween Jan 20, 2020, and Sept 6, 2022, among 128 patients enrolled, 123 (male, 54.4%, 67/123) were included in the full analysis set: 62 in the STOP group and 61 in the control group. Nine patients (14.5%, 9/62) in the STOP group required RBC transfusion vs 19 (31.2%, 19/61) in the control group (odds ratio 0.37 [95% CI: 0.15–0.91], p = 0.03). The median length of follow up to transfusion was 2.6 days (1.5; 4.6) and 3.3 (1.6; 4.2) in control and STOP groups respectively (p = 0.61).InterpretationThe bundle of care may reduce postoperative RBC transfusion. The findings should be taken with caution due to the unblinded and exploratory nature of the study.FundingUniversity of Montpellier Hospital and Vifor Pharma.
Matrikines in the skin: Origin, effects, and therapeutic potential
Authors: Jonathan P. Sirois, Andrea Heinz
Journal: Pharmacology & Therapeutics (2024)

The extracellular matrix (ECM) represents a complex multi-component environment that has a decisive influence on the biomechanical properties of tissues and organs. Depending on the tissue, ECM components are subject to a homeostasis of synthesis and degradation, a subtle interplay that is influenced by external factors and the intrinsic aging process and is often disturbed in pathologies. Upon proteolytic cleavage of ECM proteins, small bioactive peptides termed matrikines can be formed. These bioactive peptides play a crucial role in cell signaling and contribute to the dynamic regulation of both physiological and pathological processes such as tissue remodeling and repair as well as inflammatory responses. In the skin, matrikines exert an influence for instance on cell adhesion, migration, and proliferation as well as vasodilation, angiogenesis and protein expression. Due to their manifold functions, matrikines represent promising leads for developing new therapeutic options for the treatment of skin diseases. This review article gives a comprehensive overview on matrikines in the skin, including their origin in the dermal ECM, their biological effects and therapeutic potential for the treatment of skin pathologies such as melanoma, chronic wounds and inflammatory skin diseases or for their use in anti-aging cosmeceuticals.
The impact of high‐IgE levels on metabolome and microbiome in experimental allergic enteritis
Authors: Elisa Zubeldia‐Varela, Frank Blanco‐Pérez, Tomás Clive Barker‐Tejeda, David Rojo, Alma Villaseñor, Jahidul Islam, Irene Gonzalez‐Menendez, Jonathan Laiño, Maren Krause, Hanna Steigerwald, Manuela Martella, Leticia Quintanilla‐Martinez, Philipp Yu, Coral Barbas, Stefan Vieths, Tomonori Nochi, Domingo Barber, Masako Toda, Marina Pérez‐Gordo
Journal: Allergy (2024)

Abstract Background The pathological mechanism of the gastrointestinal forms of food allergies is less understood in comparison to other clinical phenotypes, such as asthma and anaphylaxis Importantly, high‐IgE levels are a poor prognostic factor in gastrointestinal allergies. Methods This study investigated how high‐IgE levels influence the development of intestinal inflammation and the metabolome in allergic enteritis (AE), using IgE knock‐in (IgEki) mice expressing high levels of IgE. In addition, correlation of the altered metabolome with gut microbiome was analysed. Results Ovalbumin‐sensitized and egg‐white diet‐fed (OVA/EW) BALB/c WT mice developed moderate AE, whereas OVA/EW IgEki mice induced more aggravated intestinal inflammation with enhanced eosinophil accumulation. Untargeted metabolomics detected the increased levels of N‐tau‐methylhistamine and 2,3‐butanediol, and reduced levels of butyric acid in faeces and/or sera of OVA/EW IgEki mice, which was accompanied with reduced Clostridium and increased Lactobacillus at the genus level. Non‐sensitized and egg‐white diet‐fed (NC/EW) WT mice did not exhibit any signs of AE, whereas NC/EW IgEki mice developed marginal degrees of AE. Compared to NC/EW WT mice, enhanced levels of lysophospholipids, sphinganine and sphingosine were detected in serum and faecal samples of NC/EW IgEki mice. In addition, several associations of altered metabolome with gut microbiome—for example Akkermansia with lysophosphatidylserine—were detected. Conclusions Our results suggest that high‐IgE levels alter intestinal and systemic levels of endogenous and microbiota‐associated metabolites in experimental AE. This study contributes to deepening the knowledge of molecular mechanisms for the development of AE and provides clues to advance diagnostic and therapeutic strategies of allergic diseases.
“Find Me” and “Eat Me” signals: tools to drive phagocytic processes for modulating antitumor immunity
Authors: Lingjun Xiao, Louqian Zhang, Ciliang Guo, Qilei Xin, Xiaosong Gu, Chunping Jiang, Junhua Wu
Journal: Cancer Communications (2024)

Phagocytosis, a vital defense mechanism, involves the recognition and elimination of foreign substances by cells. Phagocytes, such as neutrophils and macrophages, rapidly respond to invaders; macrophages are especially important in later stages of the immune response. They detect "find me" signals to locate apoptotic cells and migrate toward them. Apoptotic cells then send "eat me" signals that are recognized by phagocytes via specific receptors. "Find me" and "eat me" signals can be strategically harnessed to modulate antitumor immunity in support of cancer therapy. These signals, such as calreticulin and phosphatidylserine, mediate potent pro-phagocytic effects, thereby promoting the engulfment of dying cells or their remnants by macrophages, neutrophils, and dendritic cells and inducing tumor cell death. This review summarizes the phagocytic "find me" and "eat me" signals, including their concepts, signaling mechanisms, involved ligands, and functions. Furthermore, we delineate the relationships between "find me" and "eat me" signaling molecules and tumors, especially the roles of these molecules in tumor initiation, progression, diagnosis, and patient prognosis. The interplay of these signals with tumor biology is elucidated, and specific approaches to modulate "find me" and "eat me" signals and enhance antitumor immunity are explored. Additionally, novel therapeutic strategies that combine "find me" and "eat me" signals to better bridge innate and adaptive immunity in the treatment of cancer patients are discussed.
Geographical variation in patient characteristics and outcomes in heart failure with mildly reduced and preserved ejection fraction
Authors: Mingming Yang, Toru Kondo, Pardeep S. Jhund, Marco Antonio Alcocer‐Gamba, C. Jan Willem Borleffs, Chern‐En Chiang, Josep Comin‐Colet, Akshay S. Desai, Dan Dobreanu, Jarosław Drożdż, Yaling Han, Stefan P. Janssens, Tzvetana Katova, Mikhail N. Kosiborod, Carolyn S.P. Lam, Béla Merkely, Vinh Nguyen Pham, Jorge Thierer, Muthiah Vaduganathan, Subodh Verma, Scott D. Solomon, John J.V. McMurray
Journal: European Journal of Heart Failure (2024)

Compared to heart failure (HF) with reduced ejection fraction, HF with preserved ejection fraction (HFpEF), and HF with mildly reduced ejection fraction (HFmrEF) are increasing in prevalence, yet little is known about the geographic variation in patient characteristics, treatments and outcomes among these two HF phenotypes. The aim of this study was to investigate geographic differences in HFpEF and HFmrEF.
<scp>OPTImal PHARMacological</scp> therapy for patients with heart failure: Rationale and design of the <scp>OPTIPHARM‐HF</scp> registry
Authors: Riccardo M. Inciardi, Muthiah Vaduganathan, Carlo M. Lombardi, Cristina Gussago, Piergiuseppe Agostoni, Pietro Ameri, Nadia Aspromonte, Leonardo Calò, Matteo Cameli, Erberto Carluccio, Stefano Carugo, Manlio Cipriani, Raffaele De Caterina, Gaetano M. De Ferrari, Michele Emdin, Alessandra Fornaro, Marco Guazzi, Massimo Iacoviello, Massimo Imazio, Maria Teresa La Rovere, Sergio Leonardi, Marta Maccallini, Daniele Masarone, Luigi Moschini, Alberto Palazzuoli, Giuseppe Patti, Roberto F.E. Pedretti, Pasquale Perrone Filardi, Massimo F. Piepoli, Luciano Potena, Andrea Salzano, Angela Sciacqua, Michele Senni, Gianfranco Sinagra, Claudia Specchia, Stefano Taddei, Dario Vizza, Gianluigi Savarese, Giuseppe Rosano, Maurizio Volterrani, Marco Metra
Journal: European Journal of Heart Failure (2024)

Aims Patients with heart failure (HF) remain often undertreated for multiple reasons, including treatment inertia, contraindications, and intolerance. The OPTIimal PHARMacological therapy for patients with Heart Failure (OPTIPHARM‐HF) registry is designed to evaluate the prevalence of evidence‐based medical treatment prescription and titration, as well as the causes of its underuse, in a broad real‐world population of consecutive patients with HF across the whole ejection fraction spectrum and among different clinical phenotypes. Methods The OPTIPHARM‐HF registry (NCT06192524) is a prospective, multicenter, observational, national study of adult patients with symptomatic HF, as defined by current international guidelines, regardless of ejection fraction. Both outpatients and inpatients with chronic and acute decompensated HF will be recruited. The study will enroll up to 2500 patients with chronic HF at approximately 35 Italian HF centres. Patients will be followed for a maximum duration of 24 months. The primary objective of the OPTIPHARM‐HF registry is to assess prescription and adherence to evidence‐based guideline‐directed medical therapy (GDMT) in patients with HF. The primary outcome is to describe the prevalence of GDMT use according to target guideline recommendation. Secondary objectives include implementation of comorbidity treatment, evaluation of sequence of treatment introduction and up‐titration, description of GDMT implementation in the specific HF population, main causes of GDMT underuse, and assessment of cumulative rate of cardiovascular events. Conclusion The OPTIPHARM‐HF registry will provide important implications for improving patient care and adoption of recommended medical therapy into clinical practice among HF patients.
Expansion of the National Amyloidosis Centre staging system to detect early mortality in transthyretin cardiac amyloidosis
Authors: Christian Nitsche, Adam Ioannou, Rishi K. Patel, Yousuf Razvi, Aldostefano Porcari, Muhammad U. Rauf, Francesco Bandera, Alberto Aimo, Michele Emdin, Ana Martinez‐Naharro, Lucia Venneri, Aviva Petrie, Ashutosh Wechalekar, Helen Lachmann, Philip N. Hawkins, Julian D. Gillmore, Marianna Fontana
Journal: European Journal of Heart Failure (2024)

Abstract Aims Transthyretin cardiac amyloidosis (ATTR‐CA) is stratified into prognostic categories using the National Amyloidosis Centre (NAC) staging system. The aims of this study were to further expand the existing NAC staging system to incorporate an additional disease stage that would identify patients at high risk of early mortality. Methods and results The traditional NAC staging system (stage 1: N‐terminal pro‐B‐type natriuretic peptide [NT‐proBNP] ≤3000 ng/L and estimated glomerular filtration rate [eGFR] ≥45 ml/min; stage 3: NT‐proBNP &gt;3000 ng/L and eGFR &lt;45 ml/min; stage 2: remainder) was expanded by the introduction of a new stage 4 (defined as NT‐proBNP ≥10 000 ng/L irrespective of eGFR) and studied in 2042 patients. The optimal NT‐proBNP cut‐point was established using time‐dependent receiver operating characteristic curves in the subgroup of patients with NAC stage 3 disease. Mortality at 1 year according to NAC stage was 2.3% ( n = 20/886) for stage 1, 8.8% ( n = 62/706) for stage 2, 10.4% ( n = 28/270) for stage 3, and 30.6% ( n = 55/180) for stage 4 (log‐rank p &lt; 0.001). After adjustment for age, mortality hazard for stage 4 was &gt;15‐fold higher than that of stage 1 (hazard ratio [HR] 15.5; 95% confidence interval [CI] 9.3–26.1) and &gt;3‐fold higher than that of stage 3 (HR 3.4; 95% CI 2.2–5.4). The increased risk of early mortality was consistent across the different genotypes and subclasses of patients based on the severity of heart failure symptoms and echocardiographic parameters. Conclusions The proposed modification of the NAC staging system identifies patients with ATTR‐CA at a high risk of early mortality, who may benefit from a more intensive treatment strategy, and who are most likely to experience an event early in the course of a clinical trial.
Incremental value of C‐reactive protein to the <scp>MEESSI</scp> acute heart failure risk score
Authors: Desiree Wussler, Maria Belkin, Samyut Shrestha, Hannah Wernicke, Androniki Papachristou, Albina Nowak, Fatima Aliyeva, Constantin Mork, Ivo Strebel, Gabrielle Valerie Francoi Huré, Dominic Weil, Eleni Michou, Nikola Kozhuharov, Danielle M. Gualandro, Christian Puelacher, Oscar Miró, Xavier Rossello, Francisco Javier Martín‐Sánchez, Stuart J. Pocock, Assen Goudev, Tobias Breidthardt, Christian Mueller
Journal: European Journal of Heart Failure (2024)

Abstract Aims We hypothesized that the current gold standard for risk stratification of patients with acute heart failure (AHF), the Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF (MEESSI‐AHF) risk score, can be further improved by adding systemic inflammation as quantified by C‐reactive protein (CRP). Methods and results In a prospective multicentre diagnostic study (BASEL V), AHF was centrally adjudicated by two independent cardiologists. The MEESSI‐AHF risk score was calculated using an established reduced and recalibrated model containing 12 independent risk factors. Model extension was performed by refitting and adding CRP in the logistic regression model with 30‐day mortality as binary outcome. Discrimination, calibration and clinical usefulness were used to assess the performance of the extended Multiple Estimation of risk based on the Emergency department Spanish Score In patients (MEESSI) model. Validation was performed in an independent, retrospective and single‐centre AHF cohort. Among 1208 AHF patients with complete data allowing calculation of the recalibrated MEESSI and the extended MEESSI models, the prognostic accuracy for 30‐day mortality of the extended MEESSI model (c‐statistic 0.83, 95% confidence interval [CI] 0.79–0.87) was significantly higher compared to the recalibrated model (c‐statistic 0.79, 95% CI 0.75–0.83, p = 0.013). The extended model allowed to stratify a higher percentage of patients into the lowest risk group compared to the recalibrated model (33.1% vs. 20.3%). Demonstrating a calibration plot's slope of 1.00 (95% CI 0.81–1.19) and an intercept of 0.0 (95% CI −0.22 to 0.22), the extended MEESSI model achieved excellent and improved calibration. Results were confirmed in the independent validation cohort ( n = 575). Conclusions Quantifying inflammation using CRP concentration provided incremental value in AHF risk stratification using the established MEESSI model.
Efficacy of Semaglutide by Sex in Obesity-Related Heart Failure With Preserved Ejection Fraction
Authors: Subodh Verma, Javed Butler, Barry A. Borlaug, Melanie Davies, Dalane W. Kitzman, Sanjiv J. Shah, Mark C. Petrie, Eric Barros, Cecilia Rönnbäck, Lene Sommer Vestergaard, Morten Schou, Justin A. Ezekowitz, Kavita Sharma, Shachi Patel, Khaja M. Chinnakondepalli, Mikhail N. Kosiborod
Journal: Journal of the American College of Cardiology (2024)

More women than men have heart failure with preserved ejection fraction (HFpEF).
Prognostic implications of ΔNp73/TAp73 expression ratio in core-binding factor acute myeloid leukemia
Authors: Maria L. Salustiano-Bandeira, Amanda Moreira-Aguiar, Diego A. Pereira-Martins, Juan L. Coelho-Silva, Isabel Weinhäuser, Pedro L. França-Neto, Aleide S. Lima, Ana S. Lima, Anemari R. Baccarin, Fernanda B. Silva, Manuela A. de Melo, Fernanda S. Niemann, Luciana Nardinelli, César A. Ortiz Rojas, Bruno K. Duarte, Aderson S. Araujo, Elisa A. Azevedo, Clarice N. Morais, Lorena L. Figueiredo-Pontes, Jan J. Schuringa, Gerwin Huls, Israel Bendit, Eduardo M. Rego, Sara T. Olalla Saad, Fabiola Traina, Marcos A. Bezerra, Antonio R. Lucena-Araujo
Journal: Blood Cancer Journal (2024)
A multiomic analysis to identify drivers of subclinical vascular disease in systemic lupus erythematosus
Authors: Christopher Oliveira, Yenealem Temesgen‐Oyelakin, Mohammad Naqi, Michael Davis, Faiza Naz, Stefania Dell'Orso, Stephen Brooks, Skyler Kuhn, Tom Hill, Xiaobai Li, Nidhi Patel, Philip Parel, Massimo Gadina, Sarthak Gupta, Nehal Mehta, Sarfaraz A. Hasni, Mariana J. Kaplan
Journal: Arthritis & Rheumatology (2024)

Systemic lupus erythematosus (SLE) increases cardiovascular disease (CVD) risk, and this is not explained by traditional risk factors. Characterization of blood immunologic signatures that associate with subclinical CVD and predict its progression has been challenging and may help identify subgroups at risk.
Effect of smoking on melanoma incidence: a systematic review with meta-analysis
Authors: Erica B Friedman, Gabrielle J Williams, Serigne N Lo, John F Thompson
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background There is a strong correlation between cigarette smoking and the development of many cancer types. It is therefore paradoxical that multiple reports have suggested a reduced incidence of melanoma in smokers. This study aimed to analyze all existing studies of melanoma incidence in smokers relative to nonsmokers. Methods Searches of MEDLINE and Embase were conducted for studies reporting data on melanoma in smokers and never-smokers. No study design limitations or language restrictions were applied. The outcome examined was the association between smoking status and melanoma. Analyses focused on risk of melanoma in smokers and never-smokers generated from multivariable analyses, and these analyses were pooled using a fixed-effects model. Risk of bias was assessed using the Newcastle-Ottawa tool. Results Forty-nine studies that included 59 429 patients with melanoma were identified. Pooled analyses showed statistically significant reduced risks of melanoma in male smokers (risk ratio [RR] = 0.60, 95% confidence interval [CI] = 0.56 to 0.65, P &amp;lt; .001) and female smokers (RR = 0.79, 95% CI = 0.73 to 0.86, P &amp;lt; .001). Male former smokers had a 16% reduction in melanoma risk compared with male never-smokers (RR = 0.84, 95% CI = 0.77 to 0.93, P &amp;lt; .001), but no risk reduction was observed in female former smokers (RR = 1.0, 95% CI = 0.92 to 1.08). Conclusions Current smokers have a statistically significant reduced risk of developing melanoma compared with never-smokers, with a reduction in melanoma risk of 40% in men and 21% in women.
Comparing characteristics of individuals screened for lung cancer with 2021 vs 2013 US Preventive Services Task Force recommendations
Authors: Louise M Henderson, Danielle D Durham, James Gruden, Michael Pritchard, Lindsay Lane, Jason Long, Christina Bellinger, M Patricia Rivera
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract We conducted a cross-sectional, multicenter study to compare the demographics, clinical characteristics, and lung cancer screening results among individuals eligible for lung cancer screening per 2013 vs 2021 US Preventive Services Task Force recommendations. Statistical tests are 2 sided, with P less than .05 considered statistically significant. Among 17 702 screened individuals (85.2% 2013 eligible, 14.8% 2021 newly eligible), a higher proportion of individuals screened per 2021 vs 2013 criteria were female (56.1% vs 48.1%, P &amp;lt; .001) and non-Hispanic Black (19.3% vs 13.4%, P &amp;lt; .001). The risk of developing and dying from lung cancer per 1000 people was statistically significantly higher among individuals eligible per 2013 vs 2021 criteria. A higher proportion of lung cancer screening exams had an increased suspicion of lung cancer in the 2013 vs 2021 criteria groups. Our data suggest that, as intended, updated 2021 US Preventive Services Task Force recommendations are leading to a higher proportion of lung cancer screening exams among non-Hispanic Black individuals and women.