tbuckley/cabot-search huggingface dataset:
Nasopharyngeal brushing: a convenient and feasible sampling method for nucleic acid‐based nasopharyngeal carcinoma research
Authors: Pei‐Fen Zhang, Xiao‐Hui Zheng, Xi‐Zhao Li, Tian Tian, Shao‐Dan Zhang, Ye‐Zhu Hu, Wei‐Hua Jia
Journal: Cancer Communications (2018)

Tissue specimens for nasopharyngeal carcinoma (NPC) research are scarce because of sampling difficulties. Previous studies have suggested non-invasive nasopharyngeal brushing as an effective sampling method for NPC diagnosis. The present study aimed to evaluate the feasibility of nasopharyngeal brushing in the acquisition of NPC nucleic acids for research.Nasopharyngeal brushing samples were acquired from 24 healthy individuals and 48 NPC patients. Tissues from 48 NPC and 18 nasopharyngitis patients were collected by endoscopic biopsy. The expression levels of tumor suppressor genes (TSGs) and Epstein-Barr virus (EBV)-encoded microRNAs as well as EBV DNA copy number were measured by quantitative polymerase chain reaction in both types of samples.Among six TSGs examined, the expression levels of two genes were significantly decreased in nasopharyngeal brushing and tissue samples from NPC patients as compared with those from healthy/nasopharyngitis individuals. Four EBV-encoded microRNAs, mir-bart1-5p, mir-bart5, mir-bart6-5p, and mir-bart17-5p, were significantly up-regulated in both NPC brushing and tissue samples compared with those from healthy/nasopharyngitis controls (P < 0.001). EBV DNA was significantly increased in both nasopharyngeal brushing samples (P < 0.001) and tissue samples (P < 0.001) from NPC patients in comparison with those from healthy controls.Nasopharyngeal brushing can obtain sufficient tumoral materials for the analysis of viral nucleic acid, including EBV-encoded microRNAs and EBV DNA. For the detection of TSG expression, nasopharyngeal brushings was feasible but inferior to tissue samples. This study confirms nasopharyngeal brushing as an applicable sampling method that can aid in nucleic acid-based NPC research.
Magnetic compression anastomosis for biliary obstruction after partial hepatectomy
Authors: Xue-Mei Jiang, Kenjiro Yamamoto, Takayoshi Tsuchiya, Atsushi Sofuni, Shuntaro Mukai, Yuichi Nagakawa, Takao Itoi
Journal: Endoscopy (2018)

Magnetic compression anastomosis (MCA) is a revolutionary method of performing choledochocholedochostomy without surgery in patients with biliary obstruction [1] [2] [3] [4] [5]. Herein, we report the successful treatment, using MCA, of a case of complete biliary obstruction after partial hepatectomy.
Clarifying the roles of patients in research
Authors: Kristin Liabo, Kate Boddy, Helen Burchmore, Emma Cockcroft, Nicky Britten
Journal: BMJ (2018)

The term ‘patient’ no longer denotes a passive recipient of healthcare. Patients have demanded, and are increasingly given, the opportunity to influence health services and policies.1 Similarly, in health research patients are sought as partners in study design and governance.2 This is reflected in The BMJ ’s patient partnership initiative (www.bmj.com/campaign/patient-partnership),3 the Patient-Centred Outcomes Research Institute (PCORI) in the US,4 and the National Institute for Health Research (NIHR) in the UK.5 

Because of the history of (un)ethical conduct in research, including patients as partners in research studies requires clarity about what the role includes. Patients’ roles must be defined so that we achieve meaningful patient partnership and well conducted, ethical research.

‘The patient’ is a construct that assumes an inherent imbalance of power and includes expectations of compliance by those inhabiting it.6 That it has taken so long to acknowledge the value patients bring to healthcare and research emphasises just how difficult it can be to broaden their role beyond passively receiving treatment.

Many …
TLR9 triggering/STAT3 inhibition to reprogram leukemic cells into antigen-presenting cells and trigger T-cell responses.
Authors: Priyanka Dutta Gupta, Brandon Lu, Haiqing Li, Zhou Li, Xingli Zhao, Ya-Huei Kuo, Marcin Kortylewski
Journal: Journal of Clinical Oncology (2017)

118 Background: Clinical studies demonstrated potential of cancer immunotherapies while underscoring the need to block immune checkpoints shielding tumors from immune attack. We recently generated a strategy to target STAT3 transcription factor, critical immune checkpoint regulator, using TLR9-targeted delivery of STAT3 decoy inhibitor (CpG-STAT3dODN) targeting TLR9+ immune cells and all subsets of leukemic cells, including leukemic progenitor/stem cells in vitro and in vivo experiments in murine and human AML cells. Methods: Studies were conducted using mouse Cbfb/MYH11/Mpl and C1498 models of AML and acombination of flow cytometry, electron microscopy, and sequencing techniques were used to define changes in the AML cells after CpG-STAT3dODN treatment. Results: Intravenous injections of CpG-STAT3dODN into engrafted mice, led to significant changes in CD11b/CD11c expression, cell morphology, mitochondrial shape and number within the first 5 days of treatment. RNA-sequencing studies indicated increased expression of genes regulating differentiation and antigen presentation such as IRF8, GADD45A, CIITA, IL-12A, IFNγ. These effects associated with increased number of activated T cells in the leukemic microenvironment, thereby resulting in regression of AML in majority of treated mice. Two week CpG-STAT3dODN treatment was sufficient to generate protective antitumor immunity as demonstrated in rechallenge experiments. Conclusions: Our studies suggested that concurrent TLR9-stimulation and STAT3 inhibition trigger potent immunogenicity of AML cells sufficient to drive effector and memory T cell responses. We hypothesize that STAT3-inhibition can unleash immune-stimulation downstream of TLR9 signaling transforming leukemic cells into antigen-presenting cells Our further studies will dissect role of STAT3 and TLR9-induced signaling mediators (IRF, NF-κB) in regulation of the process.This information should support the design of new therapeutic regimens for AML immunotherapy using CpG-STAT3dODN alone or in combination with T cell-based therapies.
Selenoprotein P Promotes the Development of Pulmonary Arterial Hypertension
Authors: Nobuhiro Kikuchi, Kimio Satoh, Ryo Kurosawa, Nobuhiro Yaoita, Md. Elias-Al-Mamun, Mohammad Abdul Hai Siddique, Junichi Omura, Taijyu Satoh, Masamichi Nogi, Shinichiro Sunamura, Satoshi Miyata, Yoshiro Saito, Yasushi Hoshikawa, Yoshinori Okada, Hiroaki Shimokawa
Journal: Circulation (2018)

Background: Excessive proliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) are key mechanisms of pulmonary arterial hypertension (PAH). Despite the multiple combination therapy, a considerable number of patients develop severe pulmonary hypertension (PH) because of the lack of diagnostic biomarker and antiproliferative therapies for PASMCs. Methods: Microarray analyses were used to identify a novel therapeutic target for PAH. In vitro experiments, including lung and serum samples from patients with PAH, cultured PAH-PASMCs, and high-throughput screening of 3336 low-molecular-weight compounds, were used for mechanistic study and exploring a novel therapeutic agent. Five genetically modified mouse strains, including PASMC-specific selenoprotein P (SeP) knockout mice and PH model rats, were used to study the role of SeP and therapeutic capacity of the compounds for the development of PH in vivo. Results: Microarray analysis revealed a 32-fold increase in SeP in PAH-PASMCs compared with control PASMCs. SeP is a widely expressed extracellular protein maintaining cellular metabolism. Immunoreactivity of SeP was enhanced in the thickened media of pulmonary arteries in PAH. Serum SeP levels were also elevated in patients with PH compared with controls, and high serum SeP predicted poor outcome. SeP-knockout mice ( SeP –/– ) exposed to chronic hypoxia showed significantly reduced right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary artery remodeling compared with controls. In contrast, systemic SeP-overexpressing mice showed exacerbation of hypoxia-induced PH. Furthermore, PASMC-specific SeP –/– mice showed reduced hypoxia-induced PH compared with controls, whereas neither liver-specific SeP knockout nor liver-specific SeP-overexpressing mice showed significant differences with controls. Altogether, protein levels of SeP in the lungs were associated with the development of PH. Mechanistic experiments demonstrated that SeP promotes PASMC proliferation and resistance to apoptosis through increased oxidative stress and mitochondrial dysfunction, which were associated with activated hypoxia-inducible factor-1α and dysregulated glutathione metabolism. It is important to note that the high-throughput screening of 3336 compounds identified that sanguinarine, a plant alkaloid with antiproliferative effects, reduced SeP expression and proliferation in PASMCs and ameliorated PH in mice and rats. Conclusions: These results indicate that SeP promotes the development of PH, suggesting that it is a novel biomarker and therapeutic target of the disorder.
59P Circulating microRNAs as novel predictive markers of afatinib efficacy in squamous cell lung cancer (SCC): An exploratory sub-analysis of the LUX-Lung 8 trial
Authors: Y. Gaston Mathé, P. Fogel, S. Martin-Lannerée, C. Marcaillou, E. Lallet, N. Krämer, N. Gibson, F. Solca, E. Ehrnrooth, J. Cadranel
Journal: Journal of Thoracic Oncology (2018)
Retrospective study comparing survival when ipilimimab used with and without radiotherapy in patients with advanced melanoma.
Authors: Dominique Siobhan Parslow, Toby Laurence James Talbot
Journal: Journal of Clinical Oncology (2017)

83 Background: Ipilimumab, a monoclonal antibody targeting CTLA-4, has increased median survival in patients with advanced melanoma from 6.4 to 10 months, with 20% of patients showing a sustained response. Preclinical and clinical studies have shown possible synergistic and abscopal effects between ipilimumab and radiotherapy. The aim of this study was to compare survival curves of patients who have received ipilimumab with and without radiotherapy, and also look at other potential prognostic indicators for patients with advanced melanoma. Methods: Data was collected retrospectively from patients with advanced melanoma treated with ipilimumab at Royal Cornwall Hospital (RCH), United Kingdom. The data collection proforma included: demographic details, BRAF status, treatments prior to and since ipilimumab, whether and when radiotherapy given, response, autoimmune phenomena documented, overall survival, and survival time since ipilimumab. Results: 43 patients (20 men and 23 women) have received ipilimumab for metastatic melanoma at RCH between 2011 and 2015. Age range 27-88 years, with a median age of 60 years. 13 were BRAF mutated, 28 were BRAF wild-type and 2 were unknown. 33% of patients who received ipilimumab had some response to it, with 21% achieving a complete response. 25% of patient who displayed autoimmune phenomena clinically responded to ipilimumab; only 15% of those who did not display autoimmune phenomena clinically responded. 20 patients received radiotherapy and 23 did not; there was no significant survival difference related to radiotherapy usage. Patients with the BRAF mutation had a shorter median survival than those who were BRAF wild-type. Conclusions: Although this study was retrospective and not randomised, it appears to show an increased likelihood of a response to ipilimumab in patients who also had autoimmune side effects from treatment. Patients with a BRAF mutation had a shorter median survival than those who were BRAF wild type. The addition of radiotherapy to ipilimumab did not appear to impact on survival or response, although, as the patients were not randomised as to whether they received radiotherapy it is difficult to draw firm conclusions from this.
Finding a Treatment for ALS — Will Gene Editing Cut It?
Authors: Ammar Al-Chalabi, Robert H. Brown
Journal: New England Journal of Medicine (2018)

Gaj et al. used the CRISPR-Cas9 complex to diminish levels of mutant SOD1 in a mouse model of amyotrophic lateral sclerosis (the mouse is transgenic for mutated human SOD1) and found delayed disease onset and improved survival.
HER2 Overexpression Triggers an IL1α Proinflammatory Circuit to Drive Tumorigenesis and Promote Chemotherapy Resistance
Authors: Shou Liu, Ji Shin Lee, Chunfa Jie, Min Ho Park, Yoichiro Iwakura, Yogin Patel, Mithil Soni, David Reisman, Hexin Chen
Journal: Cancer Research (2018)

Abstract Systemic inflammation in breast cancer correlates with poor prognosis, but the molecular underpinnings of this connection are not well understood. In this study, we explored the relationship between HER2 overexpression, inflammation, and expansion of the mammary stem/progenitor and cancer stem–like cell (CSC) population in breast cancer. HER2-positive epithelial cells initiated and sustained an inflammatory milieu needed to promote tumorigenesis. HER2 induced a feedforward activation loop of IL1α and IL6 that stimulated NFκB and STAT3 pathways for generation and maintenance of breast CSC. In mice, Il1a genetic deficiency delayed MMTV-Her2–induced tumorigenesis and reduced inflammatory cytokine expression as well as CSC in primary tumors. In clinical specimens of human breast tumor tissues, tissue microarray analysis revealed a strong positive correlation between IL1α/IL6 expression and CSC-positive phenotype. Pharmacologic blockade of IL1α signaling reduced the CSC population and improved chemotherapeutic efficacy. Our findings suggest new therapeutic or prevention strategies for HER2-positive breast cancers. Significance: IL1α signaling driven by HER2 promotes chronic inflammation needed to support cancer stem-like cell maintenance in HER2-positive breast cancers. Cancer Res; 78(8); 2040–51. ©2018 AACR.
Letter by Chertoff et al Regarding Article, “The Effects of Public Access Defibrillation on Survival After Out-of-Hospital Cardiac Arrest: A Systematic Review of Observational Studies”
Authors: Jason Chertoff, Mohammad Khalid Mojadidi, Daniel Urbine
Journal: Circulation (2018)

Recently in Circulation, Baekgaard et al 1 reported encouraging results highlighting the benefits that a public access defibrillation program has on long-term survival after out-of-hospital cardiac arrest.However, the authors do not clearly specify the order in which cardiopulmonary resuscitation and defibrillation were performed in the studies that they analyzed in their systematic review.As you are certainly aware, the updated adult basic life support and cardiopulmonary resuscitation guidelines recommend chest compressions before defibrillation for out-of-hospital cardiac arrest despite numerous studies failing to show any significant difference. 2-5A recent review of 3090 patients could not conclusively state whether initial therapy with immediate defibrillation or chest compressions led to superior outcomes. 2Given this uncertainty, I implore the authors to revisit their data and, if possible, analyze whether any of their outcomes depended on the initial intervention (chest compressions versus defibrillation).As presented by Baekgaard et al, 1 cardiopulmonary resuscitation and defibrillation have significant long-term benefits for patients with cardiac arrest, but the order in which they should be performed remains ambiguous.It is prudent that we cast light on this uncertainty to ensure optimal basic life support training and cardiac arrest outcomes.
216PD Should radical surgery be performed in non-epithelioid malignant pleural mesothelioma?
Authors: L. Lang-Lazdunski, N. Tokaca, K.R. Lal, J. Steele, T. Newsom-Davis, D. Landau, J. Spicer, S. Popat
Journal: Journal of Thoracic Oncology (2018)
Diagnosing Acute Mountain Sickness
Authors: Franziska Macholz, Mahdi Sareban, Marc Moritz Berger
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Feasibility of miR-9, miR-21, and miR-155 as alternative biomarkers in both HPV-positive and HPV-negative cervical cancers.
Authors: Dawn Chung, Sunyoung Park, Kiyoon Eom, Kwang Hwa Park, Hyeyoung Lee
Journal: Journal of Clinical Oncology (2017)

52 Background: Cervical cancer is the second leading cause of death among female patients with cancer in the world. High risk human papillomavirus has causal roles in cervical cancer initiation and progression by deregulating several cellular processes. However, HPV infection is not sufficient for cervical carcinoma development. Therefore, other genetic and epigenetic factors may be involved in this complex disease, and the identification of which may lead to better diagnosis and treatment. Our aim was to analyze the expression of microRNAs in cervical cancer cases positive or negative for HPV E6/E7 mRNA, and to assess their diagnostic usefulness and relevance. Methods: The expression of three different microRNAs (miR-9, miR-21, and miR-155) in 52 formalin-fixed paraffin-embedded (FFPE) primary cervical cancer tissue samples and 50 FFPE normal cervical tissue samples were evaluated. Results: MiR-9, miR-21, and miR-155 were significantly overexpressed in cervical cancer tissues compared to normal tissues ( P &lt; 0.001). MiR-9, miR-21, and miR-155 expression combined with the HPV E6/E7 mRNA assay showed sensitivities of 82.7 %, 92.3 %, and 84.6 % respectively, demonstrating their potential as diagnostic tools. Moreover, miR-21 and miR-155 were predictors showing a 7 fold and 10.3 fold higher risk for HPV E6/E7 negative patients with cervical cancer ( P = 0.024 and P = 0.017, respectively) while miR-155 was a predictor showing a 27.9 fold higher risk for HPV E6/E7 positive patients with cervical cancer ( P &lt; 0.0001). Conclusions: There is a strong demand for additional, alternative molecular biomarkers for diagnosis and management of precancer patients. MiR-9, miR-21, and miR-155 may be helpful in the prediction of both HPV positive and HPV negative cases of cervical cancer.
Hulusi Behçet—A Life of Passion and Endeavor in Dermatology
Authors: Aria Shakeri
Journal: JAMA Dermatology (2018)

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 Dermatology 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 Dermatology journal
Abstract 13509: A Prospective Randomized Study on the Prevalence, Characteristics, and Predictors of Pulmonary Vein Reconnections and the Clinical Outcomes Between Contact Force-Guided and Conventional Circumferential Pulmonary Vein Isolation of Atrial Fibrillation
Authors: Kohki Nakamura, Shigeto Naito, Takehito Sasaki, Kentaro Minami, Eri Goto, Masahiro Nakano, Koji Kumagai, Nobusada Funabashi, Yoshio Kobayashi, Shigeru Oshima
Journal: Circulation (2015)

Purpose: To prospectively investigate the differences in pulmonary vein reconnections (PVRs) and clinical outcomes between contact force (CF)-guided and conventional circumferential PV isolation (CPVI) of atrial fibrillation (AF). Methods: A total of 120 consecutive AF patients (63±10 years; 88 males) undergoing an initial CPVI were randomized to ablation with a target CF of 20g (CF-group; n=60) or that with operators blinded to the CF information (Blind-group; n=60). The right and left CPVI lines were each divided into 12 segments, and the occurrence of PVRs and CF-related parameters were evaluated in each segment. Time-dependent and adenosine-dependent PVRs were assessed twice during the procedure, just after completing the CPVI and at the end of the procedure. Results: The CF-group had significantly fewer PVRs (0.67±0.91/patient vs. 1.16±1.16/patient; P=0.007), a higher percentage of adenosine-dependent transient PVRs (60.5% vs. 28.8%; P=0.001), and lower percentage of persistent PVRs than the Blind-group. The mean CF was higher in the CF-group than in the Blind-group (Median, 18.0g vs. 16.1g; P&lt;0.001), with the most significant difference observed along the posterior right-sided PVs (P-RPVs) and anterior left-sided PVs (A-LPVs). In multiple logistic regression models, the mean CF was a negative predictor of PVRs along the P-RPVs and A-LPVs in the Blind-group (odds ratios, 0.728 and 0.786; P&lt;0.001 and 0.007), while no significant predictor was identified in the CF-group or along the anterior RPVs and posterior LPVs in the Blind-group. In the Kaplan-Meier analysis, the arrhythmia-free survival rate at 12 months was 91.2% in the CF-group (29.8% with antiarrhythmic drugs [AADs]) and 89.4% in the Blind-group (21.1% with AADs), respectively (P=0.596). Conclusions: CF-guided CPVI can reduce PVRs and result in a higher percentage of adenosine-dependent transient PVRs, and may be particularly beneficial along regions where a relatively low CF tends to be applied: the P-RPVs and A-LPVs. The comparable clinical outcomes may be due to (1) the learning curve effect obtained by the CF-guided technique, which improved the ablation electrode-tissue contact in the Blind-group, and (2) repeated provocation and elimination of dormant PV conduction.
Erratum: Corrigendum: Sex-specific transcriptional signatures in human depression
Authors: Benoit Labonté, Olivia Engmann, Immanuel Purushothaman, Caroline Menard, Junshi Wang, Chunfeng Tan, Joseph R Scarpa, Gregory Moy, Yong-Hwee E Loh, Michael Cahill, Zachary S Lorsch, Peter J Hamilton, Erin S Calipari, Georgia E Hodes, Orna Issler, Hope Kronman, Madeline Pfau, Aleksandar L J Obradovic, Yan Dong, Rachael L Neve, Scott Russo, Andrew Kasarskis, Carol Tamminga, Naguib Mechawar, Gustavo Turecki, Bin Zhang, Li Shen, Eric J Nestler
Journal: Nature Medicine (2018)