tbuckley/cabot-search huggingface dataset:
LncRNA-encoded peptides in cancer
Authors: Yaguang Zhang
Journal: Journal of Hematology & Oncology (2024)

Long non-coding RNAs (lncRNAs), once considered transcriptional noise, have emerged as critical regulators of gene expression and key players in cancer biology. Recent breakthroughs have revealed that certain lncRNAs can encode small open reading frame (sORF)-derived peptides, which are now understood to contribute to the pathogenesis of various cancers. This review synthesizes current knowledge on the detection, functional roles, and clinical implications of lncRNA-encoded peptides in cancer. We discuss technological advancements in the detection and validation of sORFs, including ribosome profiling and mass spectrometry, which have facilitated the discovery of these peptides. The functional roles of lncRNA-encoded peptides in cancer processes such as gene transcription, translation regulation, signal transduction, and metabolic reprogramming are explored in various types of cancer. The clinical potential of these peptides is highlighted, with a focus on their utility as diagnostic biomarkers, prognostic indicators, and therapeutic targets. The challenges and future directions in translating these findings into clinical practice are also discussed, including the need for large-scale validation, development of sensitive detection methods, and optimization of peptide stability and delivery.
Abstract 2027: Validation of a Bleeding Risk Score for Acute Coronary Syndromes
Authors: Luis C Correia, Mário S Rocha, Marcelo Teixeira, Thais Cerqueira, Ana Vasconcelos, Saulo Merelles, Tiago Reis, J. Péricles Esteves
Journal: Circulation (2008)

Background: a number of prospective registries have identified independent predictors of bleeding during hospitalization for acute coronary syndromes (ACS). However, no score is validated to estimate individual risk of bleeding in ACS. Objectives and Methods: in order to create and validate a score for estimating risk of bleeding at admission of patients with ACS, independent predictors of bleeding reported in the GRACE registry ( Circulation 2007 ; 116 : 2793 –2801 ) were utilized according to the following rule: the presence of variables with odds ratio (OR) ≥ 2.5 in the GRACE registry added 3 points to the score, OR = 1.5–2.4 added 2 points and those with OR &lt; 1.5 added 1 point. Only information available at admission were considered: previous history of bleeding (3 points), creatinine clearance &lt; 30 ml/min (2 points), clearance = 30 – 60 ml/min (1 point), female gender (2 points), each 10 years of aging after 30 years old (1 point), ST-segment depression (1 point), peripheral artery disease (1 point), smoking (1 point). In order to validate the score, a sample of 383 consecutive individuals (66±12 yo, 58% males) admitted with ACS between 1999 and 2007 was studied. Inclusion criteria were defined as chest discomfort with at least one of the following: ST-segment elevation, ST-segment depression, T wave inversion, positive troponin or previous coronary artery disease. Major bleeding was defined as hematocrit fall ≥ 10%, blood transfusion of at least 2 units, intracerebral bleeding or fatal bleeding. Results: incidence of major bleeding was 3.1%. The bleeding score statistically predicted major bleeding (C-statistics=0.66; 95%IC = 0.52– 0.80). Patients in the first two quartiles of score distribution (1– 4 points) experienced the lowest risk of bleeding (1.6%), those in the third quartile (6 points) had intermediate risk (2.7%) and individuals in the fourth quartile (7–10 points) had the highest risk observed (6%, P=0.089). When sample population was dichotomized according to the best cut-off point in risk discrimination, those with a score ≥ 7 had 6% risk of bleeding, compared to individuals with a score &lt; 7 (1.9%, P=0.03). Conclusion: the tested score discriminates bleeding risk and is a potentially useful tool in clinical decision during acute coronary syndromes.
Abstract 544: Prognostic Implications of Left Ventricular Mass and Geometry Following a First ST-Elevation Acute Myocardial Infarction
Authors: Noriaki Iwahashi, Masami Kosuge, Jun Okuda, Kengo Tsukahara, Yoshio Tahara, KIyoshi Hibi, Toshiaki Ebina, Shinichi Sumita, Toshiaki Ishikawa, Kazuaki Uchino, Satoshi Umemura, Satoshi Umemura, Kazuo Kimura
Journal: Circulation (2009)

Left ventricular (LV) hypertrophy and alterations in LV geometry (Concentric LV hypertrophy and higher relative wall thickness: RWT) are associated with an increased risk of adverse events in a high risk acute myocardial infarction (AMI) from VALIANT echocardiography study ( JACC Img 2008 ; 1 : 582 ). However, the role of LV hypertrophy and RWT on a first ST-elevation AMI (STEMI) remains unclear. The aim of our study was to explore the impact of LV hypertrophy and geometry on a first reperfused STEMI exclusively involved. 278 consecutive STEMI patients (age = 64 ± 12years, male = 222, LMT = 5, LAD = 126, RCA = 115, LCx = 32) underwent echocardiography 2 weeks later and were followed for 36months. They underwent PCI successfully within 12 hours of onset. Patients with non-STEMI, A–C bypass, atrial fibrillation, and chronic renal failure on dialysis were excluded. LV mass index (LVMi) and RWT were calculated. Patients were classified into 4 mutually exclusive groups based on RWT and LVMi as follows: normal geometry (normal LVMi and normal RWT), concentric remodeling (normal LVMi and increased RWT), eccentric hypertrophy (increased LVMi and normal RWT), and concentric hypertrophy (increased LVMi and increased RWT). A cut-off value of LVMi was defined as 130g/m2 and RWT as 0.45. Primary end point was a major adverse cardiac/cerebrovascular event (MACCE: death from cardiovascular disease, ACS, readmission because of heart failure, stroke). MACCE was occurred in 49 patients within 36months (2 death, 21heart failure,18 ACS, 5 stroke, 3 arrhythmia). Eccentric hypertrophy was only an independent predictor of deterioration of renal function (eGFR decreased from baseline &gt;20%) (Odds ratio=4.12, 95%CI: 1.81–10.8, p&lt;0.01) and MACCE (Odds Ratio=2.99, 95% CI: 1.23 to 7.27, p&lt;0.01). This might be explained by the fact that eccentric hypertrophy stimulates renin-angiotensin-aldosterone system in LV remodeling strongly. RWT did not associate with deterioration of renal function or MACCE (Odds ratio=0.23, 0.31). Eccentric LV hypertrophy carries the greatest risk of MACCE among a first STEMI. RWT did not associate with an increased risk of cardiovascular complications among the patients with a first reperfused STEMI successfully.
Abstract 2667: Effects of Ranolazine in a Goat Model of Lone Atrial Fibrillation
Authors: Sander Verheule, Els Tuyls, Arne van Hunnik, Marion Kuiper, Wei-Qun Wang, Arvinder Dhalla, Luiz Belardinelli, Ulrich Schotten
Journal: Circulation (2009)

BACKGROUND: In MERLIN TIMI-36, ranolazine (RAN) reduced the indicidence of new onset AF ( Scirica et al, Circ 2007 ; 116 : 1647 ). At therapeutic concentrations, RAN inhibits the persistent sodium current. At higher concentrations, RAN also inhibits IKs, IKr and late ICaL. We investigated the effects RAN on cardiac electrophysiology in a goat model of AF. In this model, AF itself leads to a progressive shortening of the effective refractory period (ERP) and a gradual increase in AF stability. METHODS: Arrays of atrial epicardial electrodes were implanted in 7 Dutch milk goats. After recovery, experiments were performed at baseline and after 2 and 14 days of artificially maintained AF. At these time points, RAN was infused intravenously for 1 hour to result in plasma concentrations of 4, 8 and 16 uM. ECG parameters, ERP, conduction velocity (CV), AF cycle length (AFCL) and AF episode duration (AFdur) were determined. RESULTS: The main parameters are summarized in the table . At baseline and after 2 days of AF, 8 and 16 uM RAN significantly prolonged the PQ and RR intervals. After 2 days of AF, 8 and 16 uM RAN also significantly prolonged the QT interval and shortened the AFdur. After 14 days of AF, all goats were in persistent AF. At this time, 8 and 16 uM RAN significantly prolonged the AFCL, from 103±3 during solvent infusion to 109±3, 119±5* and 139±9* at 4, 8 and 16 uM RAN, respectively. However, only one out of 7 goats cardioverted during infusion of 16 uM RAN. CONCLUSION: The lowest concentration of ranolazine tested here, which mainly inhibits the late sodium current, did not significantly affect the atrial electrophysiological parameters assessed in this study. Higher doses of ranolazine significantly reduced CV, prolonged ERP and AFCL, and shortened AF episode duration. In the goat model of AF the antiarrhythmic effect appears to be due to action potential prolongation rather than due to late sodium current blockade.
Abstract P177: The Relationship between Out-of-Hospital Cardiac Arrest Due to cardiac Etiology and Medical History of Cardiovascular Disease
Authors: Kimio Kikushima, Ken Nagao, Tetsuya Sakamoto, Masaki Igarashi, Shinichi Ishimatsu, Akira Sato, Shingo Hori, Shigeru Kanesaka, Yuichi Hamabe, Nobuya Kitamura
Journal: Circulation (2008)

BACKGROUND Sudden cardiac arrest is a leading cause of death in the world. Although a strong chain of survival has improved outcomes, few data of medical history are available for patients with out-of-hospital cardiac arrest. METHODS We investigated the relationship between cardiovascular medical histories and incidence of out-of-hospital cardiac arrest due to cardiac etiology from the SOS-KANTO study ( Lancet 2007 ; 369 ). A total of 9,232 adult patients whose medical histories at the time of cardiac arrest were recorded were divided into 2 groups according to the Utstein style reporting guidelines (cardiac arrest due to cardiac etiology group vs. non-cardiac etiology group). RESULTS Of the 9,232 patients, 5,785 (63%) were caused by cardiac etiology. Of those 5,785 patients, 45% had the medical histories with cardiovascular disease including 17.4% hypertension, 14.9% diabetes, 12.4% ischemic heart disease, 8.7% cerebrovascular disease and 4.5% heart failure. The cardiac etiology group had significantly higher proportions of the total cardiovascular medical histories and each cardiovascular medical history without cerebrovascular disease than the non-cardiac etiology group. The adjusted hazard ratio for cardiac arrest due to cardiac etiology after heart failure was 5.1 (95%CI; 3.5 to 7.3), after ischemic heart disease; 5.0 (95%CI; 4.0 to 6.2), after diabetes; 2.1 (95%CI; 1.8 to 2.5), and after hypertension; 1.4 (95%CI; 1.3 to 1.6). Furthermore, the adjusted hazard ratio was after 1 cardiovascular medical history was 2.0 (95%CI; 1.8 to 2.2), after 2 histories; 2.9 (95%CI; 2.4 to 3.6), after 3 or more histories; 5.3 (95%CI; 3.2 to 9.1). Especially, incidence of cardiac arrest in patients with medical history of diabetes plus ischemic heart disease or heart failure was more than 10 times higher than that with no cardiovascular medical history. CONCLUSIONS Each cardiovascular medical history was associated with an increasing incidence of out-of-hospital cardiac arrest due to cardiac etiology, and the incidence increased in a stepwise fashion among patients in increasing number of cardiovascular medical histories. Especially, the overlaps of diabetes plus ischemic heart disease or heart failure were high risk factors of out-of-hospital cardiac arrest.
Development of Peptidomimetic Inhibitors of the ERG Gene Fusion Product in Prostate Cancer
Authors: Xiaoju Wang, Yuanyuan Qiao, Irfan A. Asangani, Bushra Ateeq, Anton Poliakov, Marcin Cieślik, Sethuramasundaram Pitchiaya, Balabhadrapatruni V.S.K. Chakravarthi, Xuhong Cao, Xiaojun Jing, Cynthia X. Wang, Ingrid J. Apel, Rui Wang, Jean Ching-Yi Tien, Kristin M. Juckette, Wei Yan, Hui Jiang, Shaomeng Wang, Sooryanarayana Varambally, Arul M. Chinnaiyan
Journal: Cancer Cell (2024)
Abstract 1629: Adrenal-Targeted GRK2 Gene Deletion Ameliorates Sympathetic Overstimulation and Improves Function of the Failing Heart
Authors: Anastasios Lymperopoulos, Giuseppe Rengo, Erhe Gao, Susan R Moraca, Steven N Ebert, Gerald W Dorn, Walter J Koch
Journal: Circulation (2008)

Chronic heart failure (HF) is characterized by sympathetic overactivity reflected by enhanced circulating catecholamines (CAs), which contribute to increased morbidity and mortality. We recently reported that adrenal G-protein coupled receptor kinase-2 (GRK2) is up-regulated in chronic HF, leading to enhanced CA release via desensitization/downregulation of the chromaffin cell a 2 -adrenergic receptors (a 2 ARs) that normally inhibit CA secretion. We also showed that adrenal GRK2 inhibition via adenoviral-mediated in vivo gene therapy acutely decreases circulating CAs and improves cardiac inotropic reserve and function ( Lymperopoulos, A. et al., Nat. Med. 13 : 315 –323, 2007 ). In the present study, we hypothesized that adrenal-targeted GRK2 gene deletion might be beneficial in chronic HF by means of normalizing sympathetic activity. Methods: To specifically delete GRK2 only in the chromaffin cells of the adrenal gland, we utilized the Cre/loxP technology, crossing PNMT-Cre mice, which express Cre recombinase under the gene promoter of phenylethanolamine N-methyl transferase (PNMT), a chromaffin cell-specific enzyme. We crossed these mice with floxGRK2 +/+ mice, which have the GRK2 gene flanked by loxP sites, thus targeted for deletion by Cre. At 2 months of age, offspring underwent surgical myocardial infarction (MI) to induce HF, and 4 weeks later, cardiac function, adrenal physiology and CA levels were assessed. Results: Genetic screening and western blotting in adrenal extracts confirmed a significant (54 ± 10 % vs. control, non-crossed floxGRK2 +/+ ) reduction of adrenal GRK2 protein levels in PNMTCre/floxGRK2 mice. Adrenal weight-to-body weight ratio was also significantly lower at 4 weeks post-MI, indicating prevention of post-MI adrenal hypertrophy. Additionally, plasma circulating CAs were reduced, and, importantly, cardiac ejection fraction of PNMTCre/floxGRK2 mice was markedly higher than that of floxGRK2 +/+ mice at 4-weeks post-MI (39.6 ± 1.0%, n = 9, vs. 30.9 ± 1.6%, n = 11, respectively, p = 0.0005). Moreover, contractile function and βAR signaling significantly improved. Conclusions: Adrenal-targeted GRK2 gene knockout decreases circulating CAs, leading to improved cardiac inotropic/adrenergic reserve in post-MI HF. This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania &amp; West Virginia).
Abstract 1470: A Circadian Periodicity in the Time of Onset of ST-segment Elevation Myocardial Infarction Disappears in Obese Subjects
Authors: Tomohiro Sakamoto, Naoko Takahashi, Takashi Fukunaga, Yoko Oe, Shinzo Miyamoto, Shinji Tayama, Koichi Nakao, Hisao Ogawa
Journal: Circulation (2009)

Background It is well known that the time of onset of ST-elevation myocardial infarction has a pronounced circadian periodicity, with peak incidence of events between 6AM and noon. The circadian rhythm of blood pressure, heart rate, vascular tonus, and prothrombotic factors could generate the peak incidence. Plasma type-1 plasminogen activator inhibitor (PAI-1) activity also has the diurnal variation and is thought to generate the prothrombotic circadian rhythm. Adipose tissue is one of the main sources of circulating PAI-1. Therefore, we hypothesized that obese subjects had more distinct periodicity than those of non-obesity do in the time of STEMI onset. Methods and Results We reviewed data from 2,644 acute myocardial infarction patients who admitted to our institute from January 1998 to April 2009. Of those, 1,962 cases showed ST elevation in their ECG on admission. After exclusion of the cases with ambiguous onset time and missing demographic data, 1,719 patients (female 28%, mean age 68.2y) were analyzed. Mean body mass index (BMI) was 23.7 kg/m 2 and obesity (BMI≥25) accounted for 23.0% of the total cases. There were strong circadian periodicity, with peak incidence of STEMI onset between 6AM and noon in all (chi-square 49.887, p&lt;0.0001; 19.1% in midnight-6AM, 30.7% in 6AM-noon, 26.8% in noon-6PM, 23.4% in 6PM-midnight) and non-obese (chi-square 59.201, p&lt;0.0001; 17.2% in midnight-6AM, 32.4% in 6AM-noon, 27.4% in noon-6PM, 23.0% in 6PM-midnight) cases. On the other hand, in obese cases, circadian rhythm in the time of onset of STEMI disappeared totally (chi-square 1.592, p&lt;0.6613; 23.2% in midnight-6AM, 26.9% in 6AM-noon, 25.6% in noon-6PM, 24.3% in 6PM-midnight). Conclusions and Discussion Contrary to our hypothesis, in obese cases, the onset time of STEMI dispersed evenly in a day. One possible explanation of this unexpected finding is that obesity is not a cause of loss of a circadian variation but could be one of results induced by preexistent circadian dysfunction, which affects diurnal rhythm of physiological and pathological conditions including STEMI onset time. Results from a recent molecular study, circadian Clock mutant mice are hyperphagic and obese, and develop a metabolic syndrome ( Science 2005 ; 308 : 1043 ), may support this speculation.
Abstract 4422: Initial Antihypertensive Drugs for Heart Failure Prevention: Network and Bayesian Meta-analyses of Clinical Trial Data
Authors: William J Elliott, Sanjib Basu, Peter M Meyer
Journal: Circulation (2008)

Heart failure continues to be the most common admitting diagnosis for Medicare beneficiaries, and is the only cardiovascular endpoint that has continuously increased in incidence in the USA since 1990. Early meta-analyses suggested that active antihypertensive drug therapy decreased heart failure incidence in hypertensives by about 50%. We therefore gathered data from existing clinical trials (minimum follow-up: 1 year) to compare the ability of the various antihypertensive drug classes regarding prevention of heart failure. Heart failure was reported in 53 clinical trials involving 281,626 patients. These data were subjected to both network ( Stat Med . 2002 ; 21 : 2313 –2324 ) and Bayesian ( Stat Comp . 2000 ; 10 : 325 –337 ) meta-analyses. The numbers of subjects with heart failure/number at risk were: Placebo (1264/43,142), Diuretic (1093/35,271), β-blocker (993/52,291), Calcium Channel Blocker (CCB: 2145/76,594), ACE-inhibitor (ACE-I: 1734/48,247), and Angiotensin Receptor Blocker (ARB: 1098/26,141). The incoherence for the network meta-analysis was very small (ω &lt; 0.000008), and the results (using diuretic as reference, 22 arms) were: These results were robust to many sensitivity analyses. After subdividing the trial results according to which diuretic was used initially (chlorthalidone, hydrochlorothiazide, or other), the incoherence was still very small (ω &lt; 0.000005), but HCTZ was significantly better than placebo (only), whereas chlorthalidone was also significantly better than all other non-diuretic drugs. These data indicate that an initial diuretic is superior to placebo and all other active antihypertensive drug classes in preventing heart failure, with chlorthalidone exhibiting somewhat better prevention than HCTZ.
Combined Surgical and Percutaneous Management of Circumflex Artery Occlusion After Minimally Invasive Mitral Valve Repair
Authors: Hristian Hinkov, Dustin Greve, Chong Bin Lee, Christoph Klein, Stephan Dreysse, Marian Kukucka, Serdar Akansel, Volkmar Falk, Markus Kofler, Jörg Kempfert
Journal: Journal of the American College of Cardiology (2024)

This report describes a hybrid intervention addressing left circumflex artery occlusion during minimally invasive mitral valve repair. By using a radiopaque Cor-Knot device (LSI Solutions), targeted removal of occluding sutures was achieved, circumventing sternotomy and coronary artery bypass. Real-time coronary angiography provided assessment of procedural success during surgical revision in a hybrid operating room.
SerpinA3N limits cartilage destruction in osteoarthritis by inhibiting macrophage-derived leucocyte elastase
Authors: Augustin Latourte, Sarah Jaulerry, Alice Combier, Chahrazad Cherifi, Yohan Jouan, Thierry Grange, Julien Daligault, Hang-Korng Ea, Martine Cohen-Solal, Eric Hay, Pascal Richette
Journal: Annals of the Rheumatic Diseases (2024)

Inflammatory mediators such as interleukin 6 (IL-6) are known to activate catabolic responses in chondrocytes during osteoarthritis (OA). This study aimed to investigate the role of a downstream target gene of IL-6, the serine protease inhibitor SerpinA3N, in the development of cartilage damage in OA.
Development, Progression, and Mortality of Suspected Interstitial Lung Disease in COPDGene
Authors: Jonathan A Rose, Ann-Marcia C. Tukpah, Claire Cutting, Noriaki Wada, Mizuki Nishino, Matthew Moll, Sean Kalra, Bina Choi, David A. Lynch, Benjamin A Raby, Ivan O. Rosas, Raúl San José Estépar, George R Washko, Edwin K Silverman, Michael H Cho, Hiroto Hatabu, Rachel K Putman, Gary M Hunninghake
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Rationale: Some with interstitial lung abnormalities (ILA) have suspected interstitial lung disease (ILD), a subgroup with adverse outcomes. Rates of development and progression of suspected ILD and their effect on mortality are unknown. Objectives: To determine rates of development and progression of suspected ILD and assess effects of individual ILD and progression criteria on mortality. Methods: Participants from COPDGene were included. ILD was defined as ILA and fibrosis and/or FVC <80% predicted. Prevalent ILD was assessed at enrollment, incident ILD and progression at 5-year follow-up. CT progression was assessed visually and FVC decline as relative change. Multivariable Cox regression tested associations between mortality and ILD groups. Results: Of 9,588 participants at enrollment, 267 (2.8%) had prevalent ILD. Those with prevalent ILD had 52% mortality after median 10.6 years, which was higher than ILA (33%; HR=2.0; p<0.001). The subgroup of prevalent ILD with fibrosis only had worse mortality (59%) than ILA (HR=2.2; p<0.001). 97 participants with prevalent ILD completed 5-year follow-up: 32% had stable CT and relative FVC decline <10%, 6% FVC decline ≥10% only, 39% CT progression only, and 22% both CT progression and FVC decline ≥10%. Mortality rates were 32%, 50%, 45%, and 46% respectively; those with CT progression only had worse mortality than ILA (HR=2.6; p=0.005). At 5-year follow-up, incident ILD occurred in 168/4,843 participants without prevalent ILD and had worse mortality than ILA (HR=2.5; p<0.001). Conclusion: Rates of mortality and progression are high among those with suspected ILD in COPDGene; fibrosis and radiologic progression are important predictors of mortality.
Hospitalizations for Multisystem Inflammatory Syndrome in Children (MIS-C) in US Children’s Hospitals in 2023 vs 2021
Authors: Anne K. Jackson, Patrick W. Brady, Matt Hall, Matthew J. Molloy, Katherine A. Auger
Journal: JAMA Pediatrics (2024)

This cross-sectional study evaluates hospitalizations for multisystem inflammatory syndrome in children in US pediatric hospitals in 2023 vs 2021.
Plant and Animal Fat Intake and Overall and Cardiovascular Disease Mortality
Authors: Bin Zhao, Lu Gan, Barry I. Graubard, Satu Männistö, Fang Fang, Stephanie J. Weinstein, Linda M. Liao, Rashmi Sinha, Xiang Chen, Demetrius Albanes, Jiaqi Huang
Journal: JAMA Internal Medicine (2024)

The impact of dietary fat intake on long-term human health has attracted substantial research interest, and the health effects of diverse dietary fats depend on available food sources. Yet there is a paucity of data elucidating the links between dietary fats from specific food sources and health.
Parkinsonism Following Chimeric Antigen Receptor T Cell Therapy
Authors: Jonas A. Gudera, Joachim M. Baehring, Philipp Karschnia
Journal: JAMA Neurology (2024)

This case report describes a 67-year-old woman who had received adoptive immunotherapy with chimeric antigen receptor T cells for multiple myeloma and was experiencing parkinsonism-like symptoms.