tbuckley/cabot-search huggingface dataset:
Machine learning based on biomarker profiles identifies distinct subgroups of heart failure with preserved ejection fraction
Authors: Rebecca J. Woolley, Daan Ceelen, Wouter Ouwerkerk, Jasper Tromp, Sylwia M. Figarska, Stefan D. Anker, Kenneth Dickstein, Gerasimos Filippatos, Faiez Zannad, Marco Metra, Leong Ng, Nilesh Samani, Dirk J van Veldhuisen, Chim Lang, Carolyn S. Lam, Adriaan A. Voors
Journal: European Journal of Heart Failure (2021)

Abstract Aims The lack of effective therapies for patients with heart failure with preserved ejection fraction (HFpEF) is often ascribed to the heterogeneity of patients with HFpEF. We aimed to identify distinct pathophysiologic clusters of HFpEF based on circulating biomarkers. Methods and results We performed an unsupervised cluster analysis using 363 biomarkers from 429 patients with HFpEF. Relative differences in expression profiles of the biomarkers between clusters were assessed and used for pathway over‐representation analyses. We identified four distinct patient subgroups based on their biomarker profiles: cluster 1 with the highest prevalence of diabetes mellitus and renal disease; cluster 2 with oldest age and frequent age‐related comorbidities; cluster 3 with youngest age, largest body size, least symptoms and lowest N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) levels; and cluster 4 with highest prevalence of ischaemic aetiology, smoking and chronic lung disease, most symptoms, as well as highest NT‐proBNP and troponin levels. Over a median follow‐up of 21 months, the occurrence of death or heart failure hospitalization was highest in clusters 1 and 4 (62.1% and 62.8%, respectively) and lowest in cluster 3 (25.6%). Pathway over‐representation analyses revealed that the biomarker profile of patients in cluster 1 was associated with activation of inflammatory pathways while the biomarker profile of patients in cluster 4 was specifically associated with pathways implicated in cell proliferation regulation and cell survival. Conclusion Unsupervised cluster analysis based on biomarker profiles identified mutually exclusive subgroups of patients with HFpEF with distinct biomarker profiles, clinical characteristics and outcomes, suggesting different underlying pathophysiological pathways.
Change in neutrophil to lymphocyte ratio (NLR) as a predictor of treatment failure in renal cell carcinoma patients: Analysis of the IROC (Investigating RCC Outcomes) cohort.
Authors: Arnab Basu, Audrey Phone, Tristan Bice, Patrick Sweeney, Luna Acharya, Yash Suri, Abigail Sy Chan, Lakshminarayanan Nandagopal, Rohan Garje, Yousef Zakharia, Deepak Kilari, Vadim S Koshkin, Mollie R. De Shazo, Pedro C. Barata, Arpita Desai
Journal: Journal of Clinical Oncology (2021)

344 Background: IROC is an expanding multi-institution collaborative database which includes socioeconomic, genomic, pathologic, clinical and laboratory data in metastatic RCC patients (pts), primarily in the modern setting. Elevated baseline NLR is now an established poor prognostic factor in renal cell carcinoma (RCC) but currently has limited practical use. We hypothesized that an increase in NLR of 3 or more (NLR Failure) at 2 months on therapy could be a predictor of eventual treatment failure and shorter overall survival and thus augment the utility of this marker. Methods: Patients with complete data on NLR at time = 0 and +2 months of therapy were analyzed. Information on comorbidities, previous therapy, demographics were collected for adjusted analysis. NLR failure was defined as an increase of 3 or more compared to baseline NLR. Cox proportional hazard models were used to analyze the risk of progression and death with NLR failure at 2 months (+/- 2 weeks). Kaplan Meier graphs were constructed to trace survival functions for PFS and OS by NLR. Results: Among 165 pts; 121 were eligible (Table). NLR failure at 2 months was associated with a highly statistically significant increase in the risk of death in &lt; 1 year (HR 6.82, 95% CI [3.16-14.70], p&lt;0.001). In a model adjusted for NLR change, the value of baseline NLR to predict OS &lt;1 year was non-significant (HR 1.02, p = 0.65). Similarly, NLR failure increased the risk of treatment failure in less than 6 months (HR 4.83 95% CI [ 2.29-10 .19], p&lt;0.001), while baseline NLR did not predict it (HR 1.03, p = 0.34). These findings were unaffected by immunotherapy vs TKI therapy. NLR failure at 2 months had a 78% (11/14) positive predictive value for survival &lt;1 year and 86% (12/14) [p=.0001] for treatment failure in 6 months. Conclusions: In this multi-institutional cohort of RCC pts; an increase in NLR of 3 or more at 2 months following therapy start predicts for an increasing risk of death and impending treatment failure with a high PPV. The prognostic value of baseline NLR is non-significant when adjusting for NLR change. NLR failure should be validated in prospective studies and could have clinical utility in management of RCC pts. [Table: see text]
Therapeutic applications of the cancer immunoediting hypothesis
Authors: Rupen Desai, Andrew T. Coxon, Gavin P. Dunn
Journal: Seminars in Cancer Biology (2021)

Since the late 19th century, the immune system has increasingly garnered interest as a novel avenue for cancer therapy, particularly given scientific breakthroughs in recent decades delineating the fundamental role of the immune system in tumorigenesis. The immunoediting hypothesis has articulated this role, describing three phases of the tumor-immune system interaction: Elimination, Equilibrium, and Escape wherein tumors progress from active immunologic surveillance and destruction through dynamic immunologic stasis to unfettered growth. The primary goals of immunotherapy are to restrict and revert progression through these phases, thereby improving the immune system's ability to control tumor growth. In this review, we detail the development and foundation of the cancer immunoediting hypothesis and apply this hypothesis to the dynamic immunotherapy field that includes checkpoint blockade, vaccine therapy, and adoptive cell transfer.
Ticagrelor vs Clopidogrel for Patients With Acute Coronary Syndrome Undergoing Percutaneous Intervention—Reply
Authors: Seng Chan You, Aakriti Gupta, Harlan M. Krumholz
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
CD99 favours the malignant potential of Ewing’s sarcoma cells.
Authors: Katia Scotlandi, Stefania Benini, Anna Rocchi, Giordano Nicoletti, Pier-Luigi Lollini
Journal: Cancer Research (2006)

5134  Purpose of this study was to gain new insights in the biological role of CD99, a 32kDa surface glycoprotein, in Ewing’s sarcoma. Despite the high expression of CD99 in this tumor has been widely used for differential diagnosis of Ewing’s sarcoma, no information is available on the putative role/s of this molecule in the pathogenesis or progression of the neoplasm. We investigated functional effects of CD99 molecules on proliferation, migration and metastatic potential of Ewing’s sarcoma cells after silencing CD99 expression by using small interfering RNAs (siRNA) approach. A CD99 siRNA expressing vector was transfected in the Ewing’s sarcoma cell line TC-71. Stable clones with low if any expression of CD99 grew poorly in soft agar, showed limited migratory ability and did not develop metastases after being xenotransplanted in athymic mice. Therefore, we first report a functional role for CD99 in the malignancy of Ewing’s sarcoma, suggesting that high expression of the molecule is necessary for the metastasis repertoire of Ewing’s sarcoma cells. The study gives new clues in the explanation of Ewing’s sarcoma pathogenesis, indicating how the molecule is not a simple remembrance of the cell of origin of Ewing’ sarcoma but rather represents a requirement for the malignant behaviour of the neoplasm.
Genome-Wide 5-Hydroxymethylcytosine Profiling Analysis Identifies MAP7D1 as A Novel Regulator of Lymph Node Metastasis in Breast Cancer
Authors: Shuang-Ling Wu, Xiaoyi Zhang, Mengqi Chang, Changcai Huang, Jun Qian, Qing Li, Fang Yuan, Lihong Sun, Xinmiao Yu, Xinmiao Cui, Jiayi Jiang, Mengyao Cui, Ye Liu, Huan-Wen Wu, Zhi-Yong Liang, Xiaoyue Wang, Yamei Niu, Wei-Min Tong, Feng Jin
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract Although DNA 5-hydroxymethylcytosine (5hmC) is recognized as an important epigenetic mark in cancer, its precise role in lymph node metastasis remains elusive. In this study, we investigated how 5hmC associates with lymph node metastasis in breast cancer. Accompanying with high expression of TET1 and TET2 proteins, large numbers of genes in the metastasis-positive primary tumors exhibit higher 5hmC levels than those in the metastasis-negative primary tumors. In contrast, the TET protein expression and DNA 5hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors. Through genome-wide analysis of 8 sets of primary tumors, we identified 100 high-confidence metastasis-associated 5hmC signatures, and it is found that increased levels of DNA 5hmC and gene expression of MAP7D1 associate with high risk of lymph node metastasis. Furthermore, we demonstrate that MAP7D1, regulated by TET1, promotes tumor growth and metastasis. In conclusion, the dynamic 5hmC profiles during lymph node metastasis suggest a link between DNA 5hmC and lymph node metastasis. Meanwhile, the role of MAP7D1 in breast cancer progression suggests that the metastasis-associated 5hmC signatures are potential biomarkers to predict the risk for lymph node metastasis, which may serve as diagnostic and therapeutic targets for metastatic breast cancer.
MIR503HG Loss Promotes Endothelial-to-Mesenchymal Transition in Vascular Disease
Authors: João P. Monteiro, Julie Rodor, Axelle Caudrillier, Jessica P. Scanlon, Ana-Mishel Spiroski, Tatiana Dudnakova, Beatrice Pflüger-Müller, Alena Shmakova, Alex von Kriegsheim, Lin Deng, Richard S. Taylor, John R. Wilson-Kanamori, Shiau-Haln Chen, Kevin Stewart, Adrian Thomson, Tijana Mitić, John D. McClure, Jean Iynikkel, Patrick W.F. Hadoke, Laura Denby, Angela C. Bradshaw, Paola Caruso, Nicholas W. Morrell, Jason C. Kovacic, Igor Ulitsky, Neil C. Henderson, Andrea Caporali, Matthias S. Leisegang, Ralf P. Brandes, Andrew H. Baker
Journal: Circulation Research (2021)

Rationale: Endothelial-to-mesenchymal transition (EndMT) is a dynamic biological process involved in pathological vascular remodeling. However, the molecular mechanisms that govern this transition remain largely unknown, including the contribution of long noncoding RNAs (lncRNAs). Objectives: To investigate the role of lncRNAs in EndMT and their relevance to vascular remodeling. Methods and Results: To study EndMT in vitro, primary endothelial cells were treated with transforming growth factor-β2 and interleukin-1β. Single-cell and bulk RNA-seq (RNA-sequencing) were performed to investigate the transcriptional architecture of EndMT and identify regulated lncRNAs. The functional contribution of seven lncRNAs during EndMT was investigated based on a DsiRNA (dicer-substrate short interfering RNAs) screening assay. The loss of lncRNA MIR503HG was identified as a common signature across multiple human endothelial cell types undergoing EndMT in vitro. MIR503HG depletion induced a spontaneous EndMT phenotype, while its overexpression repressed hallmark EndMT changes, regulating 29% of its transcriptome signature. Importantly, the phenotypic changes induced by MIR503HG were independent of miR-424 and miR-503, which overlap the lncRNA locus. The pathological relevance of MIR503HG downregulation was confirmed in vivo using sugen/hypoxia–induced pulmonary hypertension in mice, as well as in human clinical samples, in lung sections and blood outgrowth endothelial cells from pulmonary arterial hypertension patients. Overexpression of human MIR503HG in sugen/hypoxia mice led to reduced mesenchymal marker expression, suggesting MIR503HG therapeutic potential. We also revealed that MIR503HG interacts with the PTBP1 (polypyrimidine tract binding protein 1) and regulates its protein level. PTBP1 regulation of EndMT markers suggests that the role of MIR503HG in EndMT might be mediated in part by PTBP1. Conclusions: This study reports a novel lncRNA transcriptional profile associated with EndMT and reveals the crucial role of the loss of MIR503HG in EndMT and its relevance to pulmonary hypertension.
Post-injury immunosuppression and secondary infections are caused by an AIM2 inflammasome-driven signaling cascade
Authors: Stefan Roth, Jiayu Cao, Vikramjeet Singh, Steffen Tiedt, Gabriel Hundeshagen, Ting Li, Julia D. Boehme, Dhruv Chauhan, Jie Zhu, Alessio Ricci, Oliver Gorka, Yaw Asare, Jun Yang, Mary S. Lopez, Markus Rehberg, Dunja Bruder, Shengxiang Zhang, Olaf Groß, Martin Dichgans, Veit Hornung, Arthur Liesz
Journal: Immunity (2021)
Quantitative Secretome Analysis Reveals Clinical Values of Carbonic Anhydrase II in Hepatocellular Carcinoma
Authors: Xiaohua Xing, Hui Yuan, Hongzhi Liu, Xionghong Tan, Bixing Zhao, Yingchao Wang, Jiahe Ouyang, Minjie Lin, Xiaolong Liu, Aimin Huang
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract Early detection and intervention are key strategies to reduce mortality, increase long-term survival, and improve the therapeutic effects of hepatocellular carcinoma (HCC) patients. Herein, the isobaric tag for relative and absolute quantitation (iTRAQ)-based quantitative proteomic strategy was used to study the secretomes in conditioned media from HCC cancerous tissues, surrounding noncancerous tissues, and distal noncancerous tissues to identify diagnostic and prognostic biomarkers for HCC. In total, 22 and 49 dysregulated secretory proteins were identified in the cancerous and surrounding noncancerous tissues, respectively, compared with the distal noncancerous tissues. Among these proteins, carbonic anhydrase II (CA2) was identified to be significantly upregulated in the secretome of cancerous tissues; correspondingly, the serum concentrations of CA2 were remarkably increased in HCC patients compared with that in normal populations. Interestingly, a significant increase of serum CA2 in recurrent HCC patients after radical resection was also confirmed compared with HCC patients without recurrence, and the serum level of CA2 could act as an independent prognostic factor for time to recurrence and overall survival. Regarding the mechanism, the secreted CA2 enhances the migration and invasion of HCC cells by activating the epithelial mesenchymal transition pathway. Taken together, this study identified a novel biomarker for HCC diagnosis and prognosis, and provided a valuable resource of HCC secretome for investigating serological biomarkers.
Prognostic biomarkers of systemic inflammation in patients on active surveillance for metastatic renal cell carcinoma (mRCC): A biobank analysis.
Authors: Vishwani Chauhan, Jahangeer Malik, Aravindhan Sundaramurthy, Stefan N. Symeonides, Mark Stares
Journal: Journal of Clinical Oncology (2021)

348 Background: A subset of patients with metastatic renal cell carcinoma (mRCC) follow an indolent disease course. Given the toxicity and non-curative nature associated with systemic anti-cancer therapy (SACT), some patients may benefit from initial active surveillance (AS). However, selecting patients suitable for this approach is challenging. Biomarkers of systemic inflammation predict survival in mRCC, both independently and as part of the International Metastatic Database Consortium (IMDC) risk score. We sought to use these biomarkers to characterise the time to initiation of SACT (tSACT) in mRCC patients on AS. Methods: 126 mRCC patients clinically assessed and commenced on AS prior to any systemic therapy were retrospectively identified from a regional mRCC clinical database. Patients who underwent metastasectomy for oligometastatic disease at any time were excluded. The primary endpoint, tSACT, was defined as the time from radiological diagnosis of mRCC until SACT initiation, or death, or censorship if continuing AS at follow-up date. Inflammatory biomarkers from routine blood tests (haemoglobin, white cell count, neutrophil count, platelets, C-reactive protein (CRP), albumin) and the IMDC score, measured at the time of diagnosis of mRCC, were recorded. The relationship between these and tSACT was examined using Kaplan-Meier and Cox-regression methods. Results: 66 (52%) patients had commenced SACT. 17 (13.5%) had died without commencing SACT (median survival of the 17 was 40.4 months, range 9.1-130.2 months, and comorbidities may have affected fitness for starting therapy or led to all-cause mortality). 43 patients remained on AS, with minimum and median follow-up of 12.6 months and 39.6 months respectively. The median tSACT was 17.2 months (IQR 8.8-34.8 months). On univariate analysis, CRP and albumin were predictive of time on AS ( p= 0.01 and p= 0.049 respectively). On multivariate analysis, only CRP was independently associated with tSACT ( p= 0.035), stratifying tSACT from 9.1 months (CRP &gt; 10) to 20.9 months (CRP≤10) ( p= 0.009). 111 (88.1%) patients were IMDC 0-1, while 12 (9.5%) and 3 (2.4%) were IMDC 2 or 3 and may have had comorbidities that influenced the initial AS decision. In our cohort the IMDC risk score did not predict time on AS. Conclusions: These results highlight that some patients with mRCC may undergo active surveillance for a marked time period before SACT initiation. We identify routine biomarkers of the systemic inflammatory response that predict time to systemic therapy. In particular CRP, a simple measure of inflammation, stratifies the time to initiation of SACT across a clinically significant time period. This simple, widely available test may help to objectively inform clinical decisions about AS in patients in mRCC. Additional experience is necessary to further define the risks and benefits of this approach.
Abstract 15077: Remote Pulmonary Artery Hemodynamic Monitoring System Progressively Reduces Hospital Re-Admissions in Heart Failure Patients: 2-Year Real World Data Outcomes
Authors: Smitha Narayana Gowda, Udit B Bhatnagar, Adam Stys, Tom Stys, Marian S Petrasko, Naveen Rajpurohit, Valerie Bares, Orvar Jonsson
Journal: Circulation (2019)

Introduction: Remote pulmonary artery(PA) hemodynamic monitoring (CardioMEMS device) has shown to reduce Heart failure (HF) readmissions post-implantation. However, there is a paucity of data regar...
Blood-brain barrier resealing in neuromyelitis optica occurs independently of astrocyte regeneration
Authors: Anne Winkler, Claudia Wrzos, Michael Haberl, Marie-Theres Weil, Ming Gao, Wiebke Möbius, Francesca Odoardi, Dietmar R. Thal, Mayland Chang, Ghislain Opdenakker, Jeffrey L. Bennett, Stefan Nessler, Christine Stadelmann
Journal: Journal of Clinical Investigation (2021)

Approximately 80% of neuromyelitis optica spectrum disorder (NMOSD) patients harbor serum anti-aquaporin-4 autoantibodies targeting astrocytes in the CNS. Crucial for NMOSD lesion initiation is disruption of the blood-brain barrier (BBB), which allows the entrance of Abs and serum complement into the CNS and which is a target for new NMOSD therapies. Astrocytes have important functions in BBB maintenance; however, the influence of their loss and the role of immune cell infiltration on BBB permeability in NMOSD have not yet been investigated. Using an experimental model of targeted NMOSD lesions in rats, we demonstrate that astrocyte destruction coincides with a transient disruption of the BBB and a selective loss of occludin from tight junctions. It is noteworthy that BBB integrity is reestablished before astrocytes repopulate. Rather than persistent astrocyte loss, polymorphonuclear leukocytes (PMNs) are the main mediators of BBB disruption, and their depletion preserves BBB integrity and prevents astrocyte loss. Inhibition of PMN chemoattraction, activation, and proteolytic function reduces lesion size. In summary, our data support a crucial role for PMNs in BBB disruption and NMOSD lesion development, rendering their recruitment and activation promising therapeutic targets.
Status of Cancer Care at Network Sites of the Nation’s Academic Cancer Centers
Authors: Stanton L. Gerson, Kate Shaw, Louis B. Harrison, Randall F. Holcombe, Laura Hutchins, Carrie B. Lee, Patrick J. Loehrer, Daniel Mulkerin, W. Thomas Purcell, Lois Teston, Louis M. Weiner, George J. Weiner
Journal: Journal of the National Comprehensive Cancer Network (2021)

Background: Cancer care coordination across major academic medical centers and their networks is evolving rapidly, but the spectrum of organizational efforts has not been described. We conducted a mixed-methods survey of leading cancer centers and their networks to document care coordination and identify opportunities to improve geographically dispersed care. Methods: A mixed-methods survey was sent to 91 cancer centers in the United States and Canada. We analyzed the number and locations of network sites; access to electronic medical records (EMRs); clinical research support and participation at networks; use of patient navigators, care paths, and quality measures; and physician workforce. Responses were collected via Qualtrics software between September 2017 and December 2018. Results: Of the 69 responding cancer centers, 74% were NCI-designated. Eighty-seven percent of respondents were part of a matrix health system, and 13% were freestanding. Fifty-six reported having network sites. Forty-three respondents use navigators for disease-specific populations, and 24 use them for all patients. Thirty-five respondents use ≥1 types of care path. Fifty-seven percent of networks had complete, integrated access to their main center’s EMRs. Thirty-nine respondents said the main center provides funding for clinical research at networks, with 22 reporting the main center provides all funding. Thirty-five said the main center provided pharmacy support at the networks, with 15 indicating the main center provides 100% pharmacy support. Certification program participation varied extensively across networks. Conclusions: The data show academic cancer centers have extensive involvement in network cancer care, often extending into rural communities. Coordinating care through improved clinical trial access and greater use of patient navigation, care paths, coordinated EMRs, and quality measures is likely to improve patient outcomes. Although it is premature to draw firm conclusions, the survey results are appropriate for mapping next steps and data queries.