tbuckley/cabot-search huggingface dataset:
International survey of androgen deprivation therapy (ADT) for non-metastatic prostate cancer in 19 countries.
Authors: Alexander Liede, David Hallett, Kirsty Hope, Alex Graham, Jorge Arellano, Vahakn B. Shahinian
Journal: Journal of Clinical Oncology (2015)

248 Background: ADT is commonly used for non-metastatic (M0) prostate cancer (PC) patients as primary therapy for high risk disease, adjuvant therapy together with radiation, or for recurrence after initial local therapy. Intermittent androgen deprivation (IAD) is a more recently developed alternative strategy for providing ADT that is thought to potentially reduce adverse effects, but little is known about practice patterns relating to it. We aimed to describe factors related to physicians' ADT use and modality for M0 PC patients. Methods: A 45-minute online survey was completed by urologists and oncologists from 19 countries with high or increasing prevalence of M0 PC. Respondents were responsible for treatment decisions for M0 PC, and had ≥10 patients on ADT. ADT comprises gonadotropin agonist (GnRH) treatment or bilateral orchiectomy. Results: 441 physicians completed the survey representing 98,689 PC patients under their care, of which 76,386 (77%) had M0 PC. Of M0-PC patients, 38% received ADT (37% GnRH, 2% orchiectomy); among patients on GnRH, 48% received continuous ADT (≥6 months [mos]), 25% IAD, and 26% &lt;6 mos (table). Highest rates of ADT were reported among oncologists (62%) and in Eastern Europe (68%). PSA levels (65%), Gleason score (52%), and treatment guidelines (48%) were the most common reasons for continuous ADT whereas PSA levels (54%), patient request (48%), and patient age (38%) were cited most frequently as the reason for IAD. Conclusions: This international comparison showed that ADT modalities are commonly used in the treatment of M0 PC patients, and that the decision to use ADT is influenced by high risk criteria (PSA and Gleason) and treatment guidelines. IAD use is prevalent and often driven by patient choice and PSA levels. [Table: see text]
Long-term Impact of Lanadelumab on Patients with Hereditary Angioedema (HAE) Type 1/2: Patient Reported Outcome (PRO) Findings from the HELP Open-label Extension Study (OLE)
Authors: Maureen Watt, Marcus Maurer, Giovanna Devercelli, Kim Paes, Antoine Regnault, Julliette Meunier, Laurine Bunod, Marc Riedl, William Lumry
Journal: Journal of Allergy and Clinical Immunology (2021)
Abstract #1342: Loss of FHIT expression due to epigenetic silencing is a frequent event in African American (AA) patients with colorectal cancer (CRC)
Authors: Ajay Goel, Thuy-Phuong Nguyen, Alexander Link, Takeshi Nagasaka, Minoru Koi, Wen Sui, Xiang Jun Shen, Norman Sharpless, Cheng Fan, Joseph Galanko, Robert Sandler, Temitope Keku, C. Richard Boland
Journal: Cancer Research (2009)

Introduction: CRC incidence and mortality are higher in AA patients compared to Caucasians, and colorectal polyps develop at younger ages in AA patients. Prior studies have failed to identify genetic markers that account for the poorer CRC prognosis in AA with CRC. We hypothesized that aberrant epigenetic silencing of tumor suppressor genes (TSG), perhaps influenced by dietary and lifestyle factors, may provide an explanation for this. Aim: We compared gene expression profiles in CRC tissues from AA and Caucasian patients to identify potential epigenetic TSG targets in AA patients. Methods: Samples were drawn from 486 CRC patients (218 AA and 286 Caucasians) enrolled in the population-based North Carolina Colon Cancer Study (NCCCS). Microarray-based gene expression profiling of ~45,000 mRNA transcripts was performed on a subset of 42 patients (19 AA and 23 Caucasian) from whom fresh frozen tissue was available. Data were analyzed using SAM, Cluster, TreeView and hierarchical clustering algorithms to identify significantly down-regulated genes in AA vs Caucasian subjects. Microsatellite instability (MSI) was determined using 5 mononucleotide markers. Methylation-specific PCR (MSP) and bisulfite sequencing analyses were used to analyze promoter methylation. Results: Gene expression analysis identified a subset of 94 genes that were significantly under-expressed in AA patients compared to Caucasians, including fragile histidine triad (FHIT), claudin 3 (CLDN3), BRCA1 associated protein 1 (BAP1), CDK1 associated protein 2 (CDK1AP2) and nuclear transcription factor Y-alpha (NFYA), all of which are TSG targets of methylation-induced silencing in various human cancers. MSP analysis of the FHIT promoter in a randomly selected subset of 126 CRCs (61 AA and 65 Caucasian) revealed a significantly higher frequency of FHIT methylation in AA compared to Caucasian subjects (39% vs 22%; P  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1342.
Abstract 16442: Cardiac Mitochondrial Dynamic-related LncRNA (CMDL)-1 Protects Cardiomyocytes Against Apoptosis in Doxorubicin-induced Cardiotoxicity
Authors: Lynn-Htet-Htet Aung, Xiatian Chen, Ziqian Liu, Zhe Li, Peifeng Li
Journal: Circulation (2020)

Introduction: With the rapid development of sequencing technologies, several long non-coding RNAs (lncRNAs) have been identified; among which many are significant players in cardiac physiology and pathology. Doxorubicin (Dox), a commonly used anticancer agent, in the long-term can induce cardiotoxicity, limiting its clinical use. Despite the multiple signaling pathways involved in Dox cardiotoxicity, most of them ultimately lead to the activation of apoptosis, contributing to the progressive cardiomyocyte loss, and hence ensuring heart failure. Methods and Results: Microarray analysis showed that multiple lncRNAs were differentially expressed between control and doxorubicin-treated groups, denoting that lncRNAs may play a critical role in Dox cardiotoxicity. Functional enrichment analysis displayed that the differentially expressed genes are annotated to MAPK signaling and cardiac hypertrophic pathways. CMDL-1 is first characterized in rat cardiomyocytes and is the most significantly downregulated lncRNA after doxorubicin exposure. CMDL-1 is located upstream to the transient receptor potential cation channel, subfamily M, member 7 (Trpm-7), which can function as a kinase by phosphorylating itself or other substrates. Mechanistic analysis indicated that lentiviral overexpression of CMDL-1 decreased Dox-induced mitochondrial fission (MitoTracker Red CMXRos) and apoptosis (TUNEL and flow cytometry) in cardiomyocytes. Bioinformatic and experimental data showed that CMDL-1 could bind to Drp1. Overexpression of CMDL-1 promoted its association with Drp1, as well as with phosphorylated (p)-Drp1, evidenced by RNA immunoprecipitation analysis. However, overexpression of CMDL-1 couldn’t effectively reduce mitochondrial fission if Drp1 was minimally expressed by siDrp1. These findings suggest that CMDL-1 could prevent mitochondrial fission and apoptosis by impairing Drp1 phosphorylation. Conclusions: Collectively, we demonstrated that a novel lncRNA CMDL-1 could play a protective role in cardiac injury and could be a potential therapeutic target in Dox cardiotoxicity. Our study is additional evidence of the less appreciated mechanism of lncRNAs, modulating the phosphorylation status of its interacting proteins.
Association of Metabolic Phenotypes With Coronary Artery Disease and Cardiovascular Events in Patients With Stable Chest Pain
Authors: Andreas A. Kammerlander, Thomas Mayrhofer, Maros Ferencik, Neha J. Pagidipati, Julia Karady, Geoffrey S. Ginsburg, Michael T. Lu, Daniel O. Bittner, Stefan B. Puchner, Nathan A. Bihlmeyer, Nandini M. Meyersohn, Hamed Emami, Svati H. Shah, Pamela S. Douglas, Udo Hoffmann
Journal: Diabetes Care (2021)

Obesity and metabolic syndrome are associated with major adverse cardiovascular events (MACE). However, whether distinct metabolic phenotypes differ in risk for coronary artery disease (CAD) and MACE is unknown. We sought to determine the association of distinct metabolic phenotypes with CAD and MACE.
Quantification of fibroblast growth factor 23 and N-terminal pro-B-type natriuretic peptide to identify patients with atrial fibrillation using a high-throughput platform: A validation study
Authors: Winnie Chua, Jonathan P. Law, Victor R. Cardoso, Yanish Purmah, Georgiana Neculau, Muhammad Jawad-Ul-Qamar, Kalisha Russell, Ashley Turner, Samantha P. Tull, Frantisek Nehaj, Paul Brady, Peter Kastner, André Ziegler, Georgios V. Gkoutos, Davor Pavlovic, Charles J. Ferro, Paulus Kirchhof, Larissa Fabritz
Journal: PLoS Medicine (2021)

Background Large-scale screening for atrial fibrillation (AF) requires reliable methods to identify at-risk populations. Using an experimental semi-quantitative biomarker assay, B-type natriuretic peptide (BNP) and fibroblast growth factor 23 (FGF23) were recently identified as the most suitable biomarkers for detecting AF in combination with simple morphometric parameters (age, sex, and body mass index [BMI]). In this study, we validated the AF model using standardised, high-throughput, high-sensitivity biomarker assays. Methods and findings For this study, 1,625 consecutive patients with either (1) diagnosed AF or (2) sinus rhythm with CHA 2 DS 2 -VASc score of 2 or more were recruited from a large teaching hospital in Birmingham, West Midlands, UK, between September 2014 and February 2018. Seven-day ambulatory ECG monitoring excluded silent AF. Patients with tachyarrhythmias apart from AF and incomplete cases were excluded. AF was diagnosed according to current clinical guidelines and confirmed by ECG. We developed a high-throughput, high-sensitivity assay for FGF23, quantified plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and FGF23, and compared results to the previously used multibiomarker research assay. Data were fitted to the previously derived model, adjusting for differences in measurement platforms and known confounders (heart failure and chronic kidney disease). In 1,084 patients (46% with AF; median [Q1, Q3] age 70 [60, 78] years, median [Q1, Q3] BMI 28.8 [25.1, 32.8] kg/m 2 , 59% males), patients with AF had higher concentrations of NT-proBNP (median [Q1, Q3] per 100 pg/ml: with AF 12.00 [4.19, 30.15], without AF 4.25 [1.17, 15.70]; p &lt; 0.001) and FGF23 (median [Q1, Q3] per 100 pg/ml: with AF 1.93 [1.30, 4.16], without AF 1.55 [1.04, 2.62]; p &lt; 0.001). Univariate associations remained after adjusting for heart failure and estimated glomerular filtration rate, known confounders of NT-proBNP and FGF23. The fitted model yielded a C-statistic of 0.688 (95% CI 0.656, 0.719), almost identical to that of the derived model (C-statistic 0.691; 95% CI 0.638, 0.744). The key limitation is that this validation was performed in a cohort that is very similar demographically to the one used in model development, calling for further external validation. Conclusions Age, sex, and BMI combined with elevated NT-proBNP and elevated FGF23, quantified on a high-throughput platform, reliably identify patients with AF. Trial registration Registry IRAS ID 97753 Health Research Authority (HRA), United Kingdom
Physicians’ Electrocardiogram Interpretations—Reply
Authors: David A. Cook, Martin V. Pusic
Journal: JAMA Internal Medicine (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Nanopore sequencing from liquid biopsy: analysis of copy number variations from cell-free DNA of lung cancer patients
Authors: Filippo Martignano, Uday Munagala, Stefania Crucitta, Alessandra Mingrino, Roberto Semeraro, Marzia Del Re, Iacopo Petrini, Alberto Magi, Silvestro G. Conticello
Journal: Molecular Cancer (2021)

Abstract In the “precision oncology” era the characterization of tumor genetic features is a pivotal step in cancer patients’ management. Liquid biopsy approaches, such as analysis of cell-free DNA from plasma, represent a powerful and noninvasive strategy to obtain information about the genomic status of the tumor. Sequencing-based analyses of cell-free DNA, currently performed with second generation sequencers, are extremely powerful but poorly scalable and not always accessible also due to instrumentation costs. Third generation sequencing platforms, such as Nanopore sequencers, aim at overcoming these obstacles but, unfortunately, are not designed for cell-free DNA analysis. Here we present a customized workflow to exploit low-coverage Nanopore sequencing for the detection of copy number variations from plasma of cancer patients. Whole genome molecular karyotypes of 6 lung cancer patients and 4 healthy subjects were successfully produced with as few as 2 million reads, and common lung-related copy number alterations were readily detected. This is the first successful use of Nanopore sequencing for copy number profiling from plasma DNA. In this context, Nanopore represents a reliable alternative to Illumina sequencing, with the advantages of minute instrumentation costs and extremely short analysis time. The availability of protocols for Nanopore-based cell-free DNA analysis will make this analysis finally accessible, exploiting the full potential of liquid biopsy both for research and clinical purposes.
Role of 3D volume growth rate for drug activity evaluation in meningioma clinical trials: the example of the CEVOREM study
Authors: Thomas Graillon, Loic Ferrer, Jason Siffre, Marc Sanson, Matthieu Peyre, Hadrien Peyrière, Grégory Mougel, Didier Autran, Emeline Tabouret, Dominique Figarella-Branger, Anne Barlier, Michel Kalamarides, Henry Dufour, Thierry Colin, Olivier Chinot
Journal: Neuro-Oncology (2021)

We aimed to improve the assessment of the drug activity in meningioma clinical trials based on the study of the 3D volume growth rate (3DVGR) in a series of aggressive meningiomas. We secondarily aimed to correlate 3DVGR study with patient outcome.
Feed-forward regulation between cellular senescence and immunosuppression promotes the aging process and age-related diseases
Authors: Antero Salminen
Journal: Ageing Research Reviews (2021)

Aging is a progressive degenerative process involving a chronic low-grade inflammation and the accumulation of senescent cells. One major issue is to reveal the mechanisms which promote the deposition of pro-inflammatory senescent cells within tissues. The accumulation involves mechanisms which increase cellular senescence as well as those inhibiting the clearance of senescent cells from tissues. It is known that a persistent inflammatory state evokes a compensatory immunosuppression which inhibits pro-inflammatory processes by impairing the functions of effector immune cells, e.g., macrophages, T cells and natural killer (NK) cells. Unfortunately, these cells are indispensable for immune surveillance and the subsequent clearance of senescent cells, i.e., the inflammation-induced counteracting immunosuppression prevents the cleansing of host tissues. Moreover, senescent cells can also repress their own clearance by expressing inhibitors of immune surveillance and releasing the ligands of NKG2D receptors which impair their surveillance by NK and cytotoxic CD8+ T cells. It seems that cellular senescence and immunosuppression establish a feed-forward process which promotes the aging process and age-related diseases. I will examine in detail the immunosuppressive mechanisms which impair the surveillance and clearance of pro-inflammatory senescent cells with aging. In addition, I will discuss several therapeutic strategies to halt the degenerative feed-forward circuit associated with the aging process and age-related diseases.
Androgen-deprivation therapy and SARS-CoV-2 in men with prostate cancer: findings from the University of California Health System registry
Authors: D.H. Kwon, R. Vashisht, H.T. Borno, R.R. Aggarwal, E.J. Small, A.J. Butte, F.W. Huang
Journal: Annals of Oncology (2021)
Effect of redundant clinical trials from mainland China evaluating statins in patients with coronary artery disease: cross sectional study
Authors: Yuanxi Jia, Jiajun Wen, Riaz Qureshi, Stephan Ehrhardt, David D Celentano, Xin Wei, Lori Rosman, Yumeng Wen, Karen A Robinson
Journal: BMJ (2021)

Abstract Objective To identify redundant clinical trials evaluating statin treatment in patients with coronary artery disease from mainland China, and to estimate the number of extra major adverse cardiac events (MACEs) experienced by participants not treated with statins in those trials. Design Cross sectional study. Setting 2577 randomized clinical trials comparing statin treatment with placebo or no treatment in patients with coronary artery disease from mainland China, searched from bibliographic databases to December 2019. Participants 250 810 patients with any type of coronary artery disease who were enrolled in the 2577 randomized clinical trials. Main outcome measures Redundant clinical trials were defined as randomized clinical trials that initiated or continued recruiting after 2008 (ie, one year after statin treatment was strongly recommended by clinical practice guidelines). The primary outcome is the number of extra MACEs that were attributable to the deprivation of statins among patients in the control groups of redundant clinical trials—that is, the number of extra MACEs that could have been prevented if patients were given statins. Cumulative meta-analyses were also conducted to establish the time points when statins were shown to have a statistically significant effect on coronary artery disease. Results 2045 redundant clinical trials were identified published between 2008 and 2019, comprising 101 486 patients in the control groups not treated with statins for 24 638 person years. 3470 (95% confidence interval 3230 to 3619) extra MACEs were reported, including 559 (95% confidence interval 506 to 612) deaths, 973 (95% confidence interval 897 to 1052) patients with new or recurrent myocardial infarction, 161 (132 to 190) patients with stroke, 83 (58 to 105) patients requiring revascularization, 398 (352 to 448) patients with heart failure, 1197 (1110 to 1282) patients with recurrent or deteriorated angina pectoris, and 99 (95% confidence interval 69 to 129) unspecified MACEs. Conclusions Of more than 2000 redundant clinical trials on statins in patients with coronary artery disease identified from mainland China, an extra 3000 MACEs, including nearly 600 deaths, were experienced by participants not treated with statins in these trials. The scale of redundancy necessitates urgent reform to protect patients.
Abstract 5128: Polyethnic-1000: Advancing cancer genomics by studying ethnically diverse, underserved patient populations in New York
Authors: Fieke E. Froeling, Nicolas Robine, Benjamin Hubert, Michael Zody, Dayna Oschwald, Harold E. Varmus, Charles L. Sawyers, David A. Tuveson
Journal: Cancer Research (2019)

Abstract Background and aims Recent advances in DNA sequencing technologies have revolutionized approaches to the prevention, risk assessment, early detection, diagnosis, and treatment of cancers. However, many ethnic groups, especially non-European populations, have been significantly under-represented in cancer research, including clinical trials, and have not received equal benefits in clinical practice. As a result, our current knowledge about tumor biology, cancer risk, and response to treatment has primarily been derived from patients of European descent. These inequities limit our understanding of the many types of cancer and may exacerbate health disparities in the United States. This multi-institutional study, named Polyethnic-1000, aims to address both the scientific and social issues by creating a dynamic research platform within the ethnically diverse greater New York City area. Methods and results Polyethnic-1000 is a collaborative effort organized by the New York Genome Center (NYGC), involving staff and patients at academic centers and partnering hospitals in the New York City region. The genomics and informatics capabilities of the NYGC will be used to determine how inherited and somatically acquired genetic variations affect the behavior of cancers occurring in ethnically diverse populations. In a first, retrospective stage we are establishing the necessary infrastructure and workflow from sample acquisition to whole-exome and RNA sequencing, data analysis and data sharing within the consortium. Then we will start a prospective study enabling the formation of cohorts of interest for particular cancer types and particular ethnicities, with uniform consent allowing germline and somatic sequencing with broad data sharing of the somatic variants identified. Conclusion By establishing a collaborative network, Polyethnic-1000 will deepen our understanding of the contributions that ethnicities make to the incidence and biology of cancers, potentially improving outcomes for patients who currently lack access to the most recent advances in medical science. Citation Format: Fieke E. Froeling, Nicolas Robine, Benjamin Hubert, Michael Zody, Dayna Oschwald, Harold E. Varmus, Charles L. Sawyers, David A. Tuveson, On behalf of the NYGC P1000 Consortium. Polyethnic-1000: Advancing cancer genomics by studying ethnically diverse, underserved patient populations in New York [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5128.