tbuckley/cabot-search huggingface dataset:
Prevalence, recurrence, and cost burden of locally advanced basal cell carcinoma (BCC) not amenable to surgery or radiotherapy in the UK.
Authors: John Lear, Rafal Jakubanis, Mark Silvey, James Piercy, Tim Holbrook, Alina Charter, Eirini Palaka, Jo Annah Jensen, Robert Wood
Journal: Journal of Clinical Oncology (2016)

e18247 Background: Most BCCs, accounting for ≈75% of skin cancers in the UK, are treated effectively with surgery and/or radiotherapy. Limited data exist on the prevalence and burden of BCCs that become locally advanced (laBCC) and potentially not amenable to surgery or radiotherapy (NATSOR). In this analysis, the burden of laBCC(NATSOR) was evaluated based on UK population, patterns of recurrence, and per-patient cost. Methods: Linked records from primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care UK databases were used to extract demographic, medical history, prescription, and cost data for patients with BCC. In the absence of unique laBCC diagnosis codes, an exclusion-based patient identification algorithm was developed in collaboration with UK experts. Patients first treated for laBCC between Jan 2007-Dec 2012 with ≥ 2 years’ follow-up were indexed. Non-laBCC controls were propensity matched on year of birth and BCC diagnosis, sex, and comorbidities. Pairs in which controls had BCC-related events ≤ 2 years before case indexing were excluded. Results: Of the 64,126 patients with BCC with linked records assessed, 159 patients (0.25%) were identified as having laBCC(NATSOR). In 29 control-matched cases, recurrence rates at 1, 2, 3, and 4 years post indexing were 21%, 41%, 62%, and 76%, respectively. Patients with laBCC(NATSOR) used significantly more healthcare resources (range, £301-5,743) than controls (range, £18-4,491), with a difference in overall annualized burden per patient of £1,242 (P= .0002). Conclusions: Identification of patients with laBCC(NATSOR) is challenging, and their treatment can be costly. In this UK-based analysis, only 0.25% of patients with BCC with linked records were identified as having laBCC(NATSOR). Recurrence rates in this population were high and likely contributed to the increased per-patient cost compared with patients without laBCC(NATSOR). Given the stringent exclusion algorithm and limitations of the analysis (lack of laBCC diagnosis codes and missing data [resource use, cancer drug therapy/radiotherapy]), the burden of laBCC(NATSOR) in the UK estimated in this analysis is conservative.
SETDB1 prevents TET2-dependent activation of IAP retroelements in naïve embryonic stem cells
Authors: Özgen Deniz, Lorenzo de la Rica, Kevin C. L. Cheng, Dominik Spensberger, Miguel R. Branco
Journal: Genome biology (2018)

Endogenous retroviruses (ERVs), which are responsible for 10% of spontaneous mouse mutations, are kept under control via several epigenetic mechanisms. The H3K9 histone methyltransferase SETDB1 is essential for ERV repression in embryonic stem cells (ESCs), with DNA methylation also playing an important role. It has been suggested that SETDB1 protects ERVs from TET-dependent DNA demethylation, but the relevance of this mechanism for ERV expression remains unclear. Moreover, previous studies have been performed in primed ESCs, which are not epigenetically or transcriptionally representative of preimplantation embryos.We use naïve ESCs to investigate the role of SETDB1 in ERV regulation and its relationship with TET-mediated DNA demethylation. Naïve ESCs show an increased dependency on SETDB1 for ERV silencing when compared to primed ESCs, including at the highly mutagenic intracisternal A particles (IAPs). We find that in the absence of SETDB1, TET2 activates IAP elements in a catalytic-dependent manner. Surprisingly, TET2 does not drive changes in DNA methylation levels at IAPs, suggesting that it regulates these retrotransposons indirectly. Instead, SETDB1 depletion leads to a TET2-dependent loss of H4R3me2s, which is indispensable for IAP silencing during epigenetic reprogramming.Our results demonstrate a novel and unexpected role for SETDB1 in protecting IAPs from TET2-dependent histone arginine demethylation.
Delayed Adjuvant Chemotherapy and Survival After Lung Cancer Surgery—Reply
Authors: Daniel Joseph Boffa
Journal: JAMA Oncology (2017)

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 Oncology 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 Oncology journal
Induction of Hepatomas in Mice by Repeated Oral Administration of Chloroform, with Observations on Sex Differences
Authors: Eschenbrenner, Allen B., Miller, Eliza
Journal: JNCI Journal of the National Cancer Institute (1945)

Journal Article Induction of Hepatomas in Mice by Repeated Oral Administration of Chloroform, with Observations on Sex Differences Get access Allen B. Eschenbrenner, Allen B. Eschenbrenner passed assistant surgeon National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Eliza Miller Eliza Miller National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 5, Issue 4, February 1945, Pages 251–255, https://doi.org/10.1093/jnci/5.4.251 Published: 01 February 1945
Chronic liver injury alters driver mutation profiles in hepatocellular carcinoma in mice
Authors: Jesse D. Riordan, Charlotte R. Feddersen, Barbara R. Tschida, Pauline J. Beckmann, Vincent W. Keng, Michael A. Linden, Khalid Amin, Christopher S. Stipp, David A. Largaespada, Adam J. Dupuy
Journal: Hepatology (2017)

Most hepatocellular carcinomas (HCCs) develop in a chronically injured liver, yet the extent to which this microenvironment promotes neoplastic transformation or influences selective pressures for genetic drivers of HCC remains unclear. We sought to determine the impact of hepatic injury in an established mouse model of HCC induced by Sleeping Beauty transposon mutagenesis. Chemically induced chronic liver injury dramatically increased tumor penetrance and significantly altered driver mutation profiles, likely reflecting distinct selective pressures. In addition to established human HCC genes and pathways, we identified several injury‐associated candidates that represent promising loci for further study. Among them, we found that FIGN is overexpressed in human HCC and promotes hepatocyte invasion. We also validated Gli2 's oncogenic potential in vivo , providing direct evidence that Hedgehog signaling can drive liver tumorigenesis in the context of chronic injury. Finally, we show that a subset of injury‐associated candidate genes identifies two distinct classes of human HCCs. Further analysis of these two subclasses revealed significant trends among common molecular classification schemes of HCC. The genes and mechanisms identified here provide functional insights into the origin of HCC in a chronic liver damage environment. Conclusion : A chronically damaged liver microenvironment influences the genetic mechanisms that drive hepatocarcinogenesis. (H epatology 2018;67:924–939)
Protein Phosphatase Inhibitor-1 Gene Therapy in a Swine Model of Nonischemic Heart Failure
Authors: Shin Watanabe, Kiyotake Ishikawa, Kenneth Fish, Jae Gyun Oh, Lukas J. Motloch, Erik Kohlbrenner, Philyoung Lee, Chaoqin Xie, Ahyoung Lee, Lifan Liang, Changwon Kho, Lauren Leonardson, Maritza McIntyre, Scott Wilson, R. Jude Samulski, Evangelia G. Kranias, Thomas Weber, Fadi G. Akar, Roger J. Hajjar
Journal: Journal of the American College of Cardiology (2017)
Gene-environment interaction between an IL4R variant and school endotoxin exposure contributes to asthma symptoms in inner-city children
Authors: Peggy S. Lai, Amir H. Massoud, Mingcan Xia, Carter R. Petty, Amparito Cunningham, Talal A. Chatila, Wanda Phipatanakul
Journal: Journal of Allergy and Clinical Immunology (2017)
INTERMACS Analysis of Stroke During Support With Continuous-Flow Left Ventricular Assist Devices
Authors: Deepak Acharya, Renzo Loyaga-Rendon, Charity J. Morgan, Kara A. Sands, Salpy V. Pamboukian, Indranee Rajapreyar, William L. Holman, James K. Kirklin, José A. Tallaj
Journal: JACC Heart Failure (2017)
Resting and exercise haemodynamics in relation to six‐minute walk test in patients with heart failure and preserved ejection fraction
Authors: Emil Wolsk, David Kaye, Barry A. Borlaug, Daniel Burkhoff, Dalane W. Kitzman, Jan Komtebedde, Carolyn S.P. Lam, Piotr Ponikowski, Sanjiv J. Shah, Finn Gustafsson
Journal: European Journal of Heart Failure (2017)
Induction of abnormal proliferation by non-myelinating Schwann cells triggers neurofibroma formation
Authors: Huarui Zheng, Lou Chang, Neha Patel, Jiong Yang, Lori Lowe, Dennis Burns, Yuan Zhu
Journal: Cancer Research (2008)

2955  Recent evidence suggests that alterations in the self-renewal program of stem/progenitor cells can lead to tumorigenesis. Identification of stem cell-like cells or cancer stem cells raises the possibility that human cancers likely arise from the stem or progenitor cells possessing self-renewal capabilities. However, the nature of the cell(s)-of-origin of central and peripheral nervous system tumors remains largely unknown. Neurofibromatosis type 1 (NF1) is a common inherited neurological disease, which affects 1 in 3500 newborns worldwide. The hallmark feature of NF1 is the development of benign peripheral nerve sheath tumors or neurofibromas in the peripheral nervous system. Individuals afflicted with this disease carry germline loss-of -function mutations in NF1 gene. The protein product of NF1 gene (neurofibromin) is a tumor suppressor that negatively regulates Ras signaling pathway. Plexiform neurofibroma is the only neurofibroma subtype with potential for malignant transformation and is often observed during early childhood. These clinical observations raise the possibility that this tumor arises from the transformation of fetal stem/progenitor cells during nerve development. By utilizing genetically engineered mouse models of NF1, we demonstrated that plexiform neurofibroma, results from NF1 deficiency in fetal stem/progenitor cells of peripheral nerves. Surprisingly, this did not cause hyperproliferation or tumorigenesis in early postnatal period. Instead, peripheral nerve development appeared largely normal in the absence of NF1 except for a subset of abnormally differentiated Remak bundles, the non-myelinated axon-Schwann cell unit, identified in postnatal mutant nerves. Subsequent degeneration of the abnormal Remak bundles was accompanied by initial expansion of fully differentiated non-myelinating Schwann cells. These results suggest that the abnormally differentiated glia in peripheral nerves can give rise to plexiform neurofibroma. Furthermore, Our study demonstrated that an expansion of non-myelinating Schwann cells was identified in a microenvironment characterized by degeneration of normal unmyelinated axon/Schwann cell relationships and mast cell infiltration in the early stages of tumor formation. These observations suggest potential future therapies for preventing neurofibroma formation by stabilizing axon-Schwann cell interactions and reducing mast cell infiltration.
ACE gene I/D polymorphism and pulmonary disease severity in UKand Czech sarcoidosis populations
Authors: Deirdre McGrath, Patrick J Foley, Martin Petrek, Lydie IzakovičováHollá, Vítězslav Kolek, Srihari Veeraraghavan, Penelope A Lympany, Panagiotis Pantelidis, Anna Vašků, Athol U Wells, Kenneth I Welsh, Roland M du Bois
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Previous studies of the Insertion/Deletion (I/D) polymorphism
of the Angiotensin-Converting Enzyme (ACE) gene in sarcoidosis
have revealed both ethnic heterogeneity of I/D frequencies and
controversy surrounding the association between the
polymorphism and severity of disease. The objective of this
study was, therefore, to clarify the role of the ACE I/D
polymorphism in, 1) disease susceptibility, 2) pulmonary
disease severity (with particular reference to pulmonary
fibrosis) and 3) pulmonary disease progression, in two distinct
European sarcoidosis populations.
RAS testing of liquid biopsy correlates with the outcome of metastatic colorectal cancer patients treated with first-line FOLFIRI plus cetuximab in the CAPRI-GOIM trial
Authors: N. Normanno, R. Esposito Abate, M. Lambiase, L. Forgione, C. Cardone, A. Iannaccone, A. Sacco, A.M. Rachiglio, E. Martinelli, D. Rizzi, S. Pisconti, M. Biglietto, R. Bordonaro, T. Troiani, T.P. Latiano, F. Giuliani, S. Leo, A. Rinaldi, E. Maiello, F. Ciardiello
Journal: Annals of Oncology (2017)

Liquid biopsy is an alternative to tissue for RAS testing in metastatic colorectal carcinoma (mCRC) patients. Little information is available on the predictive role of liquid biopsy RAS testing in patients treated with first-line anti-EGFR monoclonal antibody-based therapy.In the CAPRI-GOIM trial, 340 KRAS exon-2 wild-type mCRC patients received first-line cetuximab plus FOLFIRI. Tumor samples were retrospectively assessed by next generation sequencing (NGS). Baseline plasma samples were analyzed for KRAS and NRAS mutations using beads, emulsion, amplification, and magnetics digital PCR (BEAMing). Discordant cases were solved by droplet digital PCR (ddPCR) or deep-sequencing.A subgroup of 92 patients with available both NGS data on tumor samples and baseline plasma samples were included in this study. Both NGS analysis of tumor tissue and plasma testing with BEAMing identified RAS mutations in 33/92 patients (35.9%). However, 10 cases were RAS tissue mutant and plasma wild-type, and additional 10 cases were tissue wild-type and plasma mutant, resulting in a concordance rate of 78.3%. Analysis of plasma samples with ddPCR detected RAS mutations in 2/10 tissue mutant, plasma wild-type patients. In contrast, in all tissue wild-type and plasma mutant cases, ddPCR or deep-sequencing analysis of tumor tissue confirmed the presence of RAS mutations at allelic frequencies ranging between 0.15% and 1.15%. The median progression-free survival of RAS mutant and wild-type patients according to tissue (7.9 versus 12.6 months; P = 0.004) and liquid biopsy testing (7.8 versus 13.8 moths; P < 0.001) were comparable. Similar findings were observed for the median overall survival of RAS mutant and wild-type patients based on tissue (22.1 versus 35.8 months; P = 0.016) and plasma (19.9 versus 35.8 months; P = 0.013) analysis.This study indicates that RAS testing of liquid biopsy results in a similar outcome when compared with tissue testing in mCRC patients receiving first-line anti-EGFR monoclonal antibodies.
Erratum: Corrigendum: Hormonal gain control of a medial preoptic area social reward circuit
Authors: Jenna A McHenry, James M Otis, Mark A Rossi, J Elliott Robinson, Oksana Kosyk, Noah W Miller, Zoe A McElligott, Evgeny A Budygin, David R Rubinow, Garret D Stuber
Journal: Nature Neuroscience (2017)
Exercise is effective for patellofemoral pain, but what type, who benefits most and by how much remain unknown
Authors: Michael J Callaghan
Journal: British Journal of Sports Medicine (2017)

Exercise is a core component in the treatment of patellofemoral pain (PFP).1 Esculier et al 2 compared three rehabilitation programmes, one of which was education plus a personalised graduated exercise regimen consistent with the recommendations from the most recent consensus statement on PFP.3 Their aim was to improve symptoms, quadriceps strength and running mechanics. The personalised programme of four phases over 2 weeks was gradually progressed through higher difficulty under a physiotherapist’s guidance. Three to four exercises were performed three times per week (maximum 20 min/session), and one exercise (lower limb dynamic control) was performed daily.

As might be expected, the education+exercise group (the only group with specific strengthening exercises) showed a significant increase in isometric strength of the quadriceps and hip abductor muscles. Despite the improvement in strength, there were no greater improvements in symptoms and no alteration in running mechanics compared with the other two groups. This pattern of results …
Genotoxicity of 4-trifluoromethylaniline in vitro and in vivo: Evaluation of DNA adducts, DNA strand breaks and/or mutations
Authors: M. Vijayaraj Reddy, George M. Laws, John E. Barnum, Sean Gill, Caron L. Cunningham, Gwendolyn J. Ward, Katherine K. McGettigan, Richard D. Storer, Sheila M. Galloway
Journal: Cancer Research (2005)

2115  We evaluated the potential genotoxicity risk of 4-trifluoromethylaniline (TFMA), a material used in the synthesis of pharmaceutical drugs and a known structural component and metabolite of a marketed drug, in various short-term in vitro and in vivo test systems. TFMA increased mutations 5.4- to 14-fold (maximum) over background levels at 1000 or 3000 μg/plate in Salmonella typhimurium strains TA100 and TA1535 and in an E. Coli strain WP2 uvrA pKM101, both with and without S9 activation in a plate incorporation assay. In a pre-incubation assay in TA100, 2.1- to 3.7-fold increases in mutation were seen and DNA adducts were found at 100 to 1000 μg/plate (equivalent to 0.9 to 8.9 mM) both with and without S9 activation. Adducts were measured by the 32P-postlabeling assay, using nuclease P1 and butanol for enhancement with HPLC and TLC for separation. Both mutagenic and adduct signals were slightly ( 90%) and some minor adducts were seen, which were chromatographically similar in bacteria, hepatocytes, and calf thymus DNA with and without S9. The numbers of adducts per 106 nucleotides were in the range 0.01 to 0.2 in bacteria and hepatocytes and 3 to 9 in calf thymus DNA at the concentrations tested. On a per mM basis, the order of adduct response was bacteria
Letter by Kosiuk et al Regarding Article, “Effect of Aggressive Blood Pressure Control on the Recurrence of Atrial Fibrillation After Catheter Ablation: A Randomized, Open Label Clinical Trial (SMAC-AF [Substrate Modification With Aggressive Blood Pressure Control])”
Authors: Jedrzej Kosiuk, Dominik Linz, Gerhard Hindricks
Journal: Circulation (2017)
Stroke Imaging
Authors: Bruce C. V. Campbell
Journal: JAMA Neurology (2017)

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 Neurology 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 Neurology journal
Recent advances in nanocarrier-loaded gels: Which drug delivery technologies against which diseases?
Authors: Marion Pitorre, Henri Gondé, Clotilde Haury, Marwa Messous, Jérémie Poilane, David Boudaud, Erdem Kanber, Glenn Alexis Rossemond Ndombina, Jean-Pierre Benoit, Guillaume Bastiat
Journal: Journal of Controlled Release (2017)
CheckMate 436: A phase 1-2 study to evaluate safety and efficacy of nivolumab plus brentuximab vedotin in patients with CD30-expressing relapsed/refractory non-Hodgkin lymphomas.
Authors: Paul M. Barr, Kenneth Robert Carson, Joshua Brody, Andrei R. Shustov, Alison J. Moskowitz, Justin Paul Kline, Kerry J. Savage, John Kuruvilla, Mary S. Campbell, Pier Luigi Zinzani, Gilles A. Salles, Aisha Masood, Stephen Maxted Ansell
Journal: Journal of Clinical Oncology (2017)

TPS7577 Background: Nivolumab (nivo) is a PD-1 immune checkpoint inhibitor that augments T-cell activation and host anti-tumor responses. PD-1 blockade has shown promise in B- and T-cell non-Hodgkin lymphoma (NHL), 1 but many patients (pts) with NHL do not respond or progress after response. Combination therapy using anti-tumor agents with complementary mechanisms of action and low immunosuppressive impact may result in more frequent and durable responses. Brentuximab vedotin (BV) is an anti-CD30 antibodydrug conjugate that induces cell cycle arrest and apoptosis, with activity in a range of NHL tumors. 2,3 Tumor cells undergoing BV-induced apoptosis have shown subsequent immune-mediated anti-tumor cytotoxicity. 4 Therefore, nivo and BV may synergize if combined for relapsed/refractory (RR) NHL. Methods: CheckMate 436 (NCT02581631) is a phase 12, open-label, international, single-arm study evaluating nivo + BV for CD30-expressing RR NHL (study start: Dec 2015) in pts with RR diffuse large B-cell lymphoma, peripheral T-cell lymphoma (excluding anaplastic large cell lymphoma), and cutaneous T-cell lymphoma (mycosis fungoides/Sézary syndrome); cohorts with primary mediastinal B-cell lymphoma (PMBL) and mediastinal gray zone lymphoma were made eligible in Sept 2016. Pts with PMBL must be aged ≥15 y (≥18 y for other histologies). All pts must have CD30-expressing disease, defined by CD30 on ≥1% of tumor cells or tumor-infiltrating lymphocytes by immunohistochemistry. In the phase 1 component, 6 pts will receive nivo and BV until disease progression or unacceptable toxicity. In the phase 2 component, ~130 more pts across the 5 histologies will be enrolled and treated at the recommended dose. Primary endpoints: safety, tolerability, and investigator-assessed objective response rate; secondary endpoints: duration of response and complete response (CR), CR rate, and progression-free and overall survival. Accrual is ongoing. References: 1. Lesokhin A et al. JCO 2016;34:2698704 2. Jacobsen E et al. Blood 2015;125:1394402 3. Horwitz S et al. Blood 2014;123:3095100 4. Gardai S et al. Cancer Res 2015;75(15 Suppl):2469 [abstract]. Clinical trial information: NCT02581631.