tbuckley/cabot-search huggingface dataset:
Role of INSL4 Signaling in Sustaining the Growth and Viability of LKB1-Inactivated Lung Cancer
Authors: Rongqiang Yang, Steven W Li, Zirong Chen, Xin Zhou, Wei Ni, Dongtao A Fu, Jianrong Lu, Frederic J Kaye, Lizi Wu
Journal: JNCI Journal of the National Cancer Institute (2018)

The LKB1 tumor suppressor gene is commonly inactivated in non-small cell lung carcinomas (NSCLC), a major form of lung cancer. Targeted therapies for LKB1-inactivated lung cancer are currently unavailable. Identification of critical signaling components downstream of LKB1 inactivation has the potential to uncover rational therapeutic targets. Here we investigated the role of INSL4, a member of the insulin/IGF/relaxin superfamily, in LKB1-inactivated NSCLCs.INSL4 expression was analyzed using global transcriptome profiling, quantitative reverse transcription PCR, western blotting, enzyme-linked immunosorbent assay, and RNA in situ hybridization in human NSCLC cell lines and tumor specimens. INSL4 gene expression and clinical data from The Cancer Genome Atlas lung adenocarcinomas (n = 515) were analyzed using log-rank and Fisher exact tests. INSL4 functions were studied using short hairpin RNA (shRNA) knockdown, overexpression, transcriptome profiling, cell growth, and survival assays in vitro and in vivo. All statistical tests were two-sided.INSL4 was identified as a novel downstream target of LKB1 deficiency and its expression was induced through aberrant CRTC-CREB activation. INSL4 was highly induced in LKB1-deficient NSCLC cells (up to 543-fold) and 9 of 41 primary tumors, although undetectable in all normal tissues except the placenta. Lung adenocarcinomas from The Cancer Genome Atlas with high and low INSL4 expression (with the top 10th percentile as cutoff) showed statistically significant differences for advanced tumor stage (P < .001), lymph node metastasis (P = .001), and tumor size (P = .01). The INSL4-high group showed worse survival than the INSL4-low group (P < .001). Sustained INSL4 expression was required for the growth and viability of LKB1-inactivated NSCLC cells in vitro and in a mouse xenograft model (n = 5 mice per group). Expression profiling revealed INSL4 as a critical regulator of cell cycle, growth, and survival.LKB1 deficiency induces an autocrine INSL4 signaling that critically supports the growth and survival of lung cancer cells. Therefore, aberrant INSL4 signaling is a promising therapeutic target for LKB1-deficient lung cancers.
Proportion of Violent Injuries Unreported to Law Enforcement
Authors: Daniel T. Wu, Jasmine C. Moore, Daniel A. Bowen, Laura M. Mercer Kollar, Elizabeth W. Mays, Thomas R. Simon, Steven A. Sumner
Journal: JAMA Internal Medicine (2018)

This analysis of data collected in a metropolitan area emergency department and from 2 local police departments compares the report of violent injury and estimates the proportion of violent injury that is unreported to police.
Abstract 18387: Comparison of Application of the 2013 ACC/AHA Guidelines and Adult Treatment Panel III Guidelines for Cardiovascular Disease Prevention in Asian Population: Result From Korean Health Cohort
Authors: Sanghoon Shin, Hyunsun Lim, Dong Woon Jeon
Journal: Circulation (2016)

Introduction: The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines for cholesterol management defined new eligibility criteria for statin therapy. Implications of...
What members of the public think about taking part in medical research during an influenza pandemic: an international cross-sectional survey across eight OECD countries
Authors: Nina Gobat, Christopher C Butler, Victoria Harris, Micaela Gal, Nicholas A Francis, Jill Mollison, John-Paul Byrne, Angela Watkins, Kerenza Hood, Ronald Moore, Prasanth Sukumar, Steve A R Webb, Alistair Nichol
Journal: The Lancet (2018)
Odds Ratios vs Risk Ratios
Authors: Jeffrey Sonis
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 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
Incomplete Data in Cutaneous Squamous Cell Carcinoma Staging System Analysis
Authors: Anokhi Jambusaria-Pahlajani, Pritesh S. Karia, Chrysalyne D. Schmults
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 16668: Long-term Outcomes After Endo-epicardial Catheter Ablation of Ventricular Tachycardia in Nonischemic Cardiomyopathy
Authors: Erica S Zado, Pasquale Santangeli, Francis E Marchlinski
Journal: Circulation (2015)

Introduction: Endo-epicardial catheter ablation of ventricular tachycardia (VT) in patients (pts) with nonischemic cardiomyopathy (NICM) has been reported to have satisfactory results at the short- and mid-term follow-up. We sought to determine the outcomes at the long-term follow-up of endo-epicardial ablation of VT in NICM. Hypothesis: Catheter ablation provides satisfactory long term outcome Methods: We prospectively enrolled 128 pts (age 59±13 years, 116 [91%] males) with NICM who underwent endo-epicardial radiofrequency catheter ablation at our Institution. After substrate mapping, all critical sites for the clinical or induced VT(s), identified with activation, entrainment or pace-mapping, together with late, split and fractionated potentials were targeted with focal and/or linear ablation. The procedural endpoint was noninducibility of sustained monomorphic VT. Pts were followed with ICD interrogation. Results: A total of 108 (73%) pts had idiopathic dilated NICM. The remaining 20 (14%) pts had hypertrophic CM (n=11), suspected inflammatory CM (n=6), or valvular CM (n=3). The mean LV ejection fraction was 33±15%. After a mean follow-up of 19 months (max 97 months), a total of 36 (28%) pts died and 17 (13%) underwent heart transplant. Cumulative survival free from any recurrent VT was 53% (68/128 patients) (Figure A). In the remaining 60 (47%) patients with VT recurrences, catheter ablation still resulted in a significant beneficial clinical impact on VT burden, with 25/60 (42%) having only isolated (1-2) VT episodes over follow-up, and a striking reduction of VT storm in the remaining pts (Figure B). Conclusions: In patients with NICM and VT, endo-epicardial substrate-based ablation is effective in achieving long-term freedom from any VT in 53% of patients, with a substantial improvement in VT burden in many of the remaining patients.
Biologic and Immunotherapy Developments in Advanced Hepatocellular Carcinoma
Authors: Mohammad Telfah, Mohammed Al-Jumayli, Anwaar Saeed
Journal: Liver Cancer (2018)

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver, and the second leading cause of cancer-related mortality worldwide with a very poor 5-year survival. Treatment for HCC includes surgery, liver-directed therapies and systemic therapies. Until 2008, no effective systemic therapy was available for advanced HCC. Sorafenib is the first drug to show improvement in overall survival among patients with advanced HCC in comparison to placebo, and it is approved by U.S. Food and Drug Administration (FDA) as a first-line treatment of advanced HCC. After sorafenib approval, several targeted and immune therapies were tested and showed efficacy in advanced HCC. Lenvatinib has been shown to be non-inferior to sorafenib as first-line treatment. Both nivolumab and regorafenib showed improvement in overall survival among patients with advanced HCC as a second line treatment after progression on sorafenib, and both are FDA approved for this indication. There is a limited role for cytotoxic agents in the treatment of advanced HCC.
FAF1 Regulates Antiviral Immunity by Inhibiting MAVS but Is Antagonized by Phosphorylation upon Viral Infection
Authors: Tong Dai, Liming Wu, Shuai Wang, Jing Wang, Feng Xie, Zhengkui Zhang, Xiuwu Fang, Jingxian Li, Pengfei Fang, Fang Li, Ke Jin, Jianfeng Dai, Bing Yang, Fangfang Zhou, Hans van Dam, Dachuan Cai, Huizhe Huang, Long Zhang
Journal: Cell Host & Microbe (2018)
Ciprofloxacin Prophylaxis Does Not Affect Incidence of Clostridium Difficile Infection in Autologous Stem Cell Transplant Patients
Authors: Kyle Grose, Karen K. Ballen, Tamila L Kindwall-Keller, Kathlene DeGregory, Gina Petroni, Gerald R. Donowitz, Brian Wispelwey, Costi Sifri, Leonid Volodin
Journal: Blood (2018)
Prophylaxis of Trimethoprim-Sulfamethoxazole for Pneumocystis Pneumonia in Diffuse Large B-Cell Lymphoma Treated with R-CHOP Therapy: A Single Center Experience
Authors: Joo Young Ha, Kyoungmin Lee, Jung Yong Hong, Dok Hyun Yoon, Sung-Han Kim, Seongsoo Jang, Chan-Sik Park, Jooryung Huh, Jin-Sook Ryu, Sang-wook Lee, Cheolwon Suh
Journal: Blood (2018)
Pharmacokinetics of NC-6004, a novel micellar formulation of cisplatin, in a Phase I trial
Authors: Alan Boddy, Melanie Griffin, Jullieann Sludden, E Plummer, A Calvert, Rebecca Perrett, Richard Wilson, Rebecca Gallagher, Martin Eatock, Y Matsumura, T Hayashi, T Shimuzu, D Pearson, Chris Otley, Michael Tilby
Journal: Cancer Research (2008)

208  NC-6004 is a novel micellar formulation of cisplatin. The micelles (M Wt 660,000) are composed of cisplatin residues conjugated to polyethylene glycol poly(L-glutamate) block co-polymers (M Wt 22,500). Promising preclinical activity has led to a Phase I trial of NC-6004, with doses ranging from 10-120 mg/m2 cisplatin equivalent. In order to characterize the pharmacokinetics of NC-6004 in patients, a combination of separation methods and analytical approaches was used. The total concentration of platinum species in plasma was measured by atomic absorption spectrometry (AAS). The micellar component of the platinum species in plasma was separated by gel-filtration, with a cut-off of 100,000 Da, and the concentration measured by AAS. Plasma ultrafiltrates were prepared and the concentration of free, small molecular weight platinum species, including cisplatin, was measured using inductively-coupled plasma mass spectrometry (ICPMS). For total plasma Pt, the half-life ranged from 20.4 up to 169 hours, with a volume of distribution less than 15 litres in most patients. Clearance was only 44 to186 ml/hr. For the micellar component, half life was shorter (13.1-126 hours) than that for total plasma Pt. AUC for the micellar component was 26 to 73% of the AUC for total Pt. In the ultrafiltrate fraction, there was delayed (tmax = 24 hr) and prolonged (half-life 68 to 580 hours) detection of small molecular weight platinum species. The mean AUC of UF Pt at 90mg/m2 was 12.4 μg/ml.hr, compared to values of 2 to 5 μg/ml.hr for similar doses of cisplatin. The AUC for total Pt at 90mg/m2 was 3000 mg/ml.hr, compared to typical AUC of 40 mg/ml.hr for equivalent cisplatin doses.  NC-6004 provides a sustained and prolonged release of potentially-active platinum species. Using gel-filtration, we have been able to separate the Pt present in the original formulation from other Pt species in the plasma. The Phase I study is continuing to recruit patients.
Abstract 94: Diagnostic value of D-dimer and fibrinogen degradation products In Kawasaki disease
Authors: Hideki Motomura, Hirofumi Fukunaga, Mari Nakagaki, Kunio Hashimoto, Tomoyuki Hasuwa, Hiroyuki Moriuchi
Journal: Circulation (2015)

Background: Echocardiography remains the cornerstone of diagnosis of cardiac complications in patients with Kawasaki disease (KD), and is also useful for the diagnosis of incomplete KD (i-KD). Since echocardiographic evaluation is based on somewhat subjective assessment by pediatric cardiologists, objective diagnostic measures by which general pediatricians can screen high-risk patients or make diagnosis of i-KD are desired. Objective: To assess D-dimer and fibrinogen degradation products (FDP) as possible markers of coronary vascular damage in KD patients. Design/Methods: Between June 2008 and March 2014, we recruited 121 KD patients: 86 with complete KD (c-KD) treated with intravenous immunoglobulin (IVIG), 10 with c-KD treated only with aspirin (a-KD), 16 with i-KD fulfilling four major criteria, and seven with severe refractory KD (s-KD). Control patients included five with Henoch-Schonlein purpura (HSP), 15 with fibrile convulsion (FC), and 39 with pneumonia. We retrospectively checked their medical records, echocardiography, and blood test results on admission and after IVIG therapy. Results: Peak D-dimer values (normal range &lt; 1.0 μg/ml) were significantly higher in c-KD (2.9±2.4) than in a-KD (1.1±0.7), FC (0.8±0.4) and pneumonia (1.3±1.1) groups (p &lt; 0.05). Peak FDP value in the c-KD group was 6.8±4.7 μg/ml (&lt; 5.0). Peak D-dimer and FDP values were the highest in the HSP group, followed by the s-KD group, and were comparable between the i-KD and c-KD groups. D-dimer values (2.9±1.4) at post IVIG were higher than those on admission (1.8±1.1) (p &lt; 0.0001), while there was no significant change in FDP values. There was no significant difference in D-dimer or FDP values between KD with cardiac finding(s) and without. WBC and CRP values had no correlation with those of FDP or D-dimer. Receiver operating characteristic analysis determined a cut-off value of 1.1 μg/ml for D-dimer for c-KD, with the area under the curve (AUC) 0.85, sensitivity 0.95, specificity 0.59 and probability 0.44. Similarly, a cut-off value for FDP was determined as 2.5 μg/ml with AUC 0.90, sensitivity 0.89, specificity 0.70 and probability 0.40. Conclusions: Elevated D-dimer and FDP values help assist diagnosis of i-KD, but cannot predict cardiac complications in KD patients.
Ribociclib (RIB) + non-steroidal aromatase inhibitor (NSAI) + goserelin in premenopausal Asian women with hormone-receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC): Results from the randomized phase III MONALEESA-7 study
Authors: S.-A. Im, J. Sohn, D. Tripathy, L. Chow, K.S. Lee, K.H. Jung, G. Babu, Y.-H. Im, N. El Saghir, M.-C. Liu, I. Diaz-Padilla, J. Alam, O. Kong, M. Miller, Y.-S. Lu
Journal: Annals of Oncology (2018)
Rare, Pathogenic Germline Variants in <i>Fanconi Anemia</i> Genes Increase Risk for Squamous Lung Cancer
Authors: Myvizhi Esai Selvan, Robert J. Klein, Zeynep H. Gümüş
Journal: Clinical Cancer Research (2018)

Lung cancer is the leading cause of cancer deaths worldwide, with substantially better prognosis in early-stage as opposed to late-stage disease. Identifying genetic factors for lung squamous cell carcinoma (SqCC) risk will enable their use in risk stratification, and personalized intensive surveillance, early detection, and prevention strategies for high-risk individuals.We analyzed whole-exome sequencing datasets of 318 cases and 814 controls (discovery cohort) and then validated our findings in an independent cohort of 444 patients and 3,479 controls (validation cohort), all of European descent. We also combined all the samples from both cohorts, which, after principal component analysis (PCA) and population stratification, included 765 cases and 4,344 controls (combined cohort). We focused on rare, pathogenic variants found in the ClinVar database and used penalized logistic regression to identify genes in which such variants are enriched in cases. All statistical tests were two-sided.We observed an overall enrichment of rare, deleterious germline variants in Fanconi anemia genes in cases with SqCC [joint analysis odds ratio (OR) = 3.08; P = 1.4e-09; 95% confidence interval (CI), 2.2-4.3]. Consistent with previous studies, BRCA2 in particular exhibited an increased overall burden of rare, deleterious variants (joint OR = 3.2; P = 8.7e-08; 95% CI, 2.1-4.7). More importantly, rare, deleterious germline variants were enriched in Fanconi anemia genes even without the BRCA2 rs11571833 variant that is strongly enriched in lung SqCC cases (joint OR = 2.76; P = 7.0e-04; 95% CI, 1.6-4.7).These findings can be used toward the development of a genetic diagnostic test in the clinic to identify SqCC high-risk individuals, who can benefit from personalized programs, improving prognosis.
Differences in prognosis and efficacy of chemotherapy by p53 expression in triple negative breast cancer
Authors: S.Y. Bae, S.P. Jung, K.B.C.S. Korean Breast Cancer Society, S.J. Nam, Y. Jung, B.W. Park, W. Lim, S.H. Jung, H.K. Kim, J.-Y. You, S.B. Lee
Journal: Annals of Oncology (2018)
Study Protocol for the DETECTIVE Study: An International Collaborative Study To Develop Consensus Statements for Deferred Treatment with Curative Intent for Localised Prostate Cancer
Authors: Thomas B.L. Lam, Steven MacLennan, Karin Plass, Peter-Paul M. Willemse, Malcolm D. Mason, Philip Cornford, James Donaldson, Niall F. Davis, Paolo Dell’Oglio, Christian Fankhauser, Nikos Grivas, Alexandre Ingels, Michael Lardas, Matthew Liew, Karl H. Pang, Catherine Paterson, Muhammad I. Omar, Fabio Zattoni, Karel T. Buddingh, Thomas Van den Broeck, Marcus G. Cumberbatch, Nicola Fossati, Tobias Gross, Lisa Moris, Ivo G. Schoots, Roderick C.N. van den Bergh, Erik Briers, Stefano Fanti, Maria De Santis, Silke Gillessen, Jeremy P. Grummet, Ann M. Henry, Henk G. van der Poel, Theodorus H. van der Kwast, Olivier Rouvière, Derya Tilki, Thomas Wiegel, James N’Dow, Hendrik Van Poppel, Nicolas Mottet
Journal: European Urology (2018)
Abstract 16045: Is Low Dose Beta Blocker Equivalent to High Dose for Reducing Major Adverse Cardiovascular Events?
Authors: Jason E Allen, Stacey Knight, Raymond O McCubrey, Joseph B Muhlestein, Donald L Lappé, Jeffrey J Goldberger, Jeffrey L Anderson
Journal: Circulation (2015)

Introduction: Beta-blockers (BB) are a fundamental component of care for patients (pts) with coronary artery disease (CAD) and acute coronary syndromes (ACS). BB therapy based on decades-old trials generally targets high doses (HD). Yet, whether better-tolerated low-dose (LD) BB is as effective in the current era of medical and interventional therapy has not been tested. Hypothesis: LD BB is equivalent to HD BB for major adverse cardiovascular events (MACE), i.e., all-cause death, myocardial infarction, and stroke, in patients (pts) with symptomatic CAD. Methods: Intermountain Healthcare pts with CAD documented at coronary angiography (n=12,882; 60.9% with ACS) were studied. BB use and dose were determined at discharge and 6 mo. LD was defined as ≤25% and HD as ≥50% of the equivalent of 200 mg metoprolol. Univariate testing of associations between BB usage and clinical characteristics was performed using chi-square and Wilcoxon tests. Significant factors were entered into logistic regressions to calculate propensity scores. Equivalence testing was done using time until MACE for 0 to 6 mo, 7 to 24 mo, and combined periods using the Wellek method based on Cox proportional hazards and an assumed risk function within 0.15. Results: 7158 (55.6%) of pts were discharged on BB: 6078 (85.0%) on LD and 974 (13.6%) on HD. Within 6 mo, 263 (4.3%) of LD compared to 47 (4.8%) of HD pts had a MACE. After adjusting for propensity score, MACE on LD versus HD BB was equivalent (p=0.036) but not superior (HR= 0.92; 95% CI: 0.67, 1.28). For 7 to 24 mo, of the 7090 pts without a prior MACE, 5868 (82.8%) were on LD and 1145 (16.1%) on HD BB, and 433 (7.4%) of LD versus 109 (9.5%) of HD pts had a MACE. After adjusting for propensity score, LD again was equivalent to HD (p&lt;0.005) but not superior (HR=0.98; CI: 0.76, 1.26). Outcome for pts on LD versus HD over the entire 0-24 mo period was equivalent (p=0.002) and nearly superior (HR=0.86; CI: 0.71-1.05). ACS pts also showed dose equivalence (p=0.02) and near LD superiority (HR=0.82; CI: 0.64-1.04). Conclusions: In the modern era of advanced medical and interventional therapy for symptomatic CAD and ACS, LD BB is associated with at least equivalent cardiovascular protection as HD and should be encouraged when HD BB is not tolerated or contraindicated.
Low Frequency of Lymph Node Metastases in Patients in the United States With Early-stage Gastric Cancers That Fulfill Japanese Endoscopic Resection Criteria
Authors: Yuri Hanada, Alyssa Y. Choi, Joo Ha Hwang, Peter V. Draganov, Lauren Khanna, Amrita Sethi, Michael J. Bartel, Neha Goel, Seiichiro Abe, Rabia A. De Latour, Kenneth Park, Marcovalerio Melis, Elliot Newman, Ioannis Hatzaras, Sanjay S. Reddy, Jeffrey M. Farma, Xiuli Liu, Alexander Schlachterman, Jesse Kresak, Garrick Trapp, Nadia Ansari, Beth Schrope, Jong Yeul Lee, Deepti Dhall, Simon Lo, Laith H. Jamil, Miguel Burch, Srinivas Gaddam, Yulan Gong, Armando Del Portillo, Yutaka Tomizawa, Camtu D. Truong, Olaya I. Brewer Gutierrez, Elizabeth Montgomery, Fabian M. Johnston, Mark Duncan, Marcia Canto, Nita Ahuja, Anne Marie Lennon, Saowanee Ngamruengphong
Journal: Clinical Gastroenterology and Hepatology (2018)
Referring patients with suspected oral cancer to dentists may delay diagnosis, say GPs
Authors: Jacqui Wise
Journal: BMJ (2018)

National Institute of Health and Care Excellence (NICE) guidance that GPs should refer patients suspected of having oral cancer to a dentist may delay diagnosis, researchers have warned.1

The guidelines state that patients with a lump on their lip or in their oral cavity or who have a red or red and white patch in their oral cavity should be sent for assessment for possible oral cancer by a dentist within two weeks of seeing their GP.2

If GPs follow the guidance then the emphasis …