tbuckley/cabot-search huggingface dataset:
Molecular characterization of SETD2, a histone methyltransferase, in clear cell renal cell carcinoma (ccRCC).
Authors: Thai Huu Ho, Federico A. Monzon, Anh Hoang, Pheroze Tamboli, Kyle A. Furge, Karl Dykema, David Petillo, Bin Tean Teh, Nizar M. Tannir, Mien-Chie Hung, Eric Jonasch
Journal: Journal of Clinical Oncology (2012)

4624 Background: Although the von Hippel-Lindau (VHL) tumor suppressor is mutated in 60% of ccRCC, deletion of VHL in mice is insufficient for tumorigenesis. Sequencing of ccRCC tumors identified mutations in SETD2, a histone H3 lysine 36 (H3K36) trimethyltransferase. We hypothesize that loss of SETD2 methyltransferase activity decreases H3K36 trimethylation (H3K36Me3) in ccRCC, and contributes to the cancer phenotype. Methods: H3K36Me3 immunohistochemical (IHC) staining was quantitated in wild-type and mutant SETD2 nephrectomy tissue. To establish frequency of SETD2 loss of heterozygosity (LOH), genomic DNA was isolated from 51 VHL deficient ccRCC specimens and analyzed with Affymetrix single-nucleotide polymorphism (SNP) arrays. To evaluate alterations of histone modifications in advanced ccRCC, H3K36Me3 IHC was quantitated on tissue microarrays (TMAs) representing 28 paired ccRCC specimens with unaffected kidney parenchyma and 40 metastases. To identify kidney-specific H3K36Me3 binding sites, chromatin immunoprecipitation (ChIP) sequencing was performed on nephrectomy specimens. Results: Nephrectomy specimens with SETD2 truncating mutations have decreased H3K36Me3 (&gt;50%) compared to uninvolved kidney tissue. Using SNP arrays, LOH at chromosome 3p (location of VHL and SETD2 genes) was detected in &gt;90% of the tested tumors. IHC reveals a 27.4% and 52.0% decrease in H3K36Me3 positive nuclei in primary ccRCC and metastases, respectively, when compared to matched adjacent unaffected kidney tissue (p &lt;0.0001). Using ChIP sequencing, 421 and 1,718 genomic regions were upregulated in the tumor and unaffected kidney tissue. Conclusions: SETD2 truncating mutations in patient-derived tissue have decreased H3K36Me3 indicating that SETD2 is a non-redundant H3K36 methyltransferase. LOH of VHL and SETD2 occurs in &gt;90% of tested ccRCC tumors. Genomic regions enriched for H3K36Me3 binding are being validated in additional patient-derived tissues. H3K36Me3 is decreased in primary ccRCC and even more in metastases, suggesting that SETD2 methyltransferase activity is progressively misregulated in RCC. Loss of SETD2 activity may cooperate with VHL silencing to promote tumorigenesis.
Skin Disease as Art
Authors: Neha Jariwala, Jules B. Lipoff
Journal: JAMA Dermatology (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 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
The Outcome of Patients with Primary Refractory or Relapsed Peripheral T-Cell Lymphoma: Analysis of 1020 Cases Registered in the Prospective T-Cell Project
Authors: Monica Bellei, Francine M Foss, Steven M Horwitz, Luigi Marcheselli, Won Seong Kim, Maria Elena Cabrera, Ivan Dlouhy, Arnon Nagler, Ranjana H Advani, Emanuela Pesce, Young Hyeh Ko, Virginia Martinez, Silvia Montoto, Carlos Chiattone, Alison J. Moskowitz, Michele Spina, Marina Cesaretti, Irene Biasoli, Massimo Federico
Journal: Blood (2016)
Farnesoid-X Receptor single nucleotide polymorphism rs35724 is potentially associated with patients’ outcome in decompensated liver cirrhosis
Authors: N.F. Mueller, J. Fischer, S. Krohn, A. Böhlig, T. Herta, C. Domeratius, A. Herber, T. Berg, C. Engelmann
Journal: Journal of Hepatology (2017)
IKKalpha regulates G2/M cell cycle checkpoint through 14-3-3sigma independently of p53 in response to DNA damage
Authors: Feng Zhu, Yinling Hu
Journal: Cancer Research (2007)

4261   A large proportion of the aggressive squamous cell carcinomas of humans and mice have been reported to express markedly reduced IKKα, implying that IKKα is involved in maintaining genomic stability in keratinocytes. However, whether IKKα loss increases genomic instability is unknown. In present study, we found that the level of 14-3-3σ was markedly lower in  Ikk  α   -/-   than in wild-type (WT) primary cultured keratinocytes, which was not caused by a defect in terminal differentiation in  Ikk  α   -/-   keratinocytes. Importantly,  Ikk  α   -/-   primary cultured keratinocytes showed a defect in the G2/M cell cycle arrest in response to DNA damage. Enforced expression of IKKα, but not IKKβ, restored 14-3-3σ expression, and rescued the defect in the G2/M cell cycle arrest in response to DNA damage in  Ikk  α   -/-   keratinocytes. Doxorubicin, a DNA damage reagent, induced the expression of p53 and p21 in both WT and  Ikk  α   -/-   keratinocytes, however, 14-3-3σ was only slightly induced in  Ikk  α   -/-   keratinocytes. These results indicate that downregulation of 14-3-3σ does not require the involvement of p53 in  Ikk  α   -/-   keratonocytes. Futhermore, we identified and discussed how IKKα regulates 14-3-3σ expression independently of p53 at transcriptional level. Taken together, our findings reveal a novel function of IKKα in cell cycle control through regulating 14-3-3σ expression in a p53-independent manner.
Multicenter Retrospective Observational Study to Assess the Clinical Characteristics and the Outcome of Patients with Relapsed or Refractory Mantle Cell Non-Hodgkin's Lymphoma Treated in Italy According to the Ibrutinib Named Patient Program
Authors: Vittorio Stefoni, Federico Sottotetti, Manuel Gotti, Michele Spina, Stefano Volpetti, Simone Ferrero, Francesco Spina, Francesco Pisani, Michele Merli, Carlo Visco, Rossella Paolini, Vittorio Ruggero Zilioli, Luca Baldini, Nicola Di Renzo, Patrizia Tosi, Nicola Cascavilla, Stefano Molica, Lisa Argnani, Pier Luigi Zinzani
Journal: Blood (2016)
Injecting risk behaviours among people with a history of injecting drug use in an Australian prison setting, 2005–2014: the HITS-p study
Authors: E.B. Cunningham, B. Hajarizadeh, J. Amin, N.A. Bretana, F. Luciani, L. Degenhardt, S. Larney, G.J. Dore, A.R. Lloyd, J. Grebely
Journal: Journal of Hepatology (2017)
VIDEO ANALYSIS OF CONTACT TECHNIQUE DURING HEAD COLLISIONS IN RUGBY UNION
Authors: Sharief Hendricks, Demi Davidow, Wayne Viljoen, Nicholas Burger, Mike Lambert, Clint Readhead, James Brown, Ben Jones, Ken Quarrie
Journal: British Journal of Sports Medicine (2017)

Background Rugby union is characterised by frequent and dynamic collisions. Players typically aim to avoid direct contact to the head due to its potential for serious head injury. However, head collisions still occur – possibly due to players either being unaware of the impending contact, or executing poor technique during, or prior to contact. Objective Video analysis of contact technique and head collisions in rugby union. Design Retrospective video analysis. Setting Professional rugby union players. Participants Video footage of 211 contact events. Assessment of Risk Factors Contact characteristics and contact technique for attackers and defenders during head collisions. Attackers and defenders were categorized into higher and lower risk roles depending on which had the higher potential for injury. Main Outcome Measurements Contact descriptors and contact proficiency scores Results Eighty-four percent of head collisions occurred during the tackle, followed by aerial collisions (10%), and rucks (6%). Eighty-two percent of collisions occurred with an opponent. Higher risk players were aware of the impending contact 70% of the time. Mean contact proficiency score (arbitrary units; AU) in front-on tackled ball-carriers was 6.4±3.2 and 8.2±3.2 AU for ball carriers at higher and lower injury risk, respectively (p≤0.01, effect size=0.6, moderate). The mean contact proficiency score in front-on tackle tacklers was 9.8±3.7 and 9.2±3.5 AU for tacklers at higher and lower injury risk, respectively (p&gt;0.05, ES=0.2, small). Conclusions The tackle event accounted for most head collisions. Most players were aware of the impending contact. Higher injury risk ball-carriers in front-on tackles scored relatively low in proficiency compared to lower injury risk ball-carriers. For contact proficiency score, each technical criterion was equally weighted. Failure to execute specific criteria (e.g. head up and forward) may increase the risk of head collisions compared to other criteria (e.g. fending). Future studies on contact techniques should weight technical criteria more appropriately.
Challenges of Using NT-Probnp for Response Assessment in Systemic AL Amyloidosis - Analysis of a Prospective Study
Authors: Ashutosh Wechalekar, Darren Foard, Carol Whelan, Mariana Fontana, Thirusha Lane, Candida Quarta, Shameem Mahmood, Helen Lachmann, Julian D Gillmore, Philip N Hawkins
Journal: Blood (2016)
Temporal trends in etiology of liver disease, tumor characteristics, and long-term survival of patients with hepatocellular carcinoma: results of a single-center U.S. cohort from 1997–2016
Authors: N.G. Kim, P. Nguyen, M. Ladenheim, Z. Rosenthal, H. Nguyen, G. Garcia, M. Nguyen
Journal: Journal of Hepatology (2017)
British Thoracic Society guidelines on respiratory aspects of fitness for diving
Journal: Thorax (2003)

### Need for recommendations on respiratory aspects of fitness to dive Diving has long been performed for commercial and military purposes but it has undergone a dramatic increase in popularity as a leisure pursuit over the past 30 years. It is estimated that, in the United Kingdom, 100 000 individuals participate in diving activities. In addition, diving technology has evolved rapidly, allowing divers to descend to greater depths and to dive in places which would previously have been impossible. As a sport, diving can be physically and emotionally demanding, and is associated with some specific risks. Medical practitioners are increasingly likely to be faced with requests to comment on fitness to undertake diving. Many of these requests relate to respiratory aspects of fitness. A number of existing guidelines or discussion papers on respiratory aspects of fitness to dive are in existence.1–3 However, the advice given in these is not consistent and these documents may not be readily available to the practising physician or general practitioner. The British Thoracic Society (BTS) Standards of Care Committee therefore established a Working Party to formulate national recommendations for assessing respiratory fitness to dive. This guideline is intended to provide respiratory physicians and physicians interested in diving medicine with a practical framework on which to base advice. The UK Sport Medical Diving Committee advises the British Sub Aqua Club, the Sub Aqua Association, and the Scottish Sub Aqua Club on aspects of fitness to dive. It has recently introduced a questionnaire-based declaration of fitness for prospective members of these organisations and advises that medical examination is required only when positive responses to the questionnaire are obtained. Commercial and military diving are subject to additional specific regulations. ### Purpose of recommendations
Hepatitis C virus-RNA decay with direct acting antivirals in human immunodeficiency virus/hepatitis C virus coinfected patients
Authors: D. Barbanotti, L. Marinaro, A. Barco, M. Merli, G. Vendemiati, E. Messina, C.U. Foppa, S. Bonora, G. Di Perri, A. Lazzarin, H. Hasson
Journal: Journal of Hepatology (2017)
Treatment with anti-TNFa reduces neuroinflammation and restores neurotransmission, learning and motor coordination in rats with hepatic encephalopathy
Authors: S. Dadsetan, T. Balzano, J. Forteza, A. Cabrera-Pastor, L. Taoro-Gonzalez, V. Hernandez-Rabaza, A. Agusti, C. Montoliu, M. Llansola, V. Felipo
Journal: Journal of Hepatology (2017)
Lesson of the Week: Methadone maintenance and tuberculosis treatment
Authors: D. Raistrick, A. Hay, K. Wolff
Journal: BMJ (1996)

Rifampicin is a potent inducer of hepatic microsomal enzymes. It increases drug clearance and reduces the half life of a wide range of drugs, including barbiturates, oral contraceptives, propranolol, sulphonylureas, and methadone.1 Without a concomitant increase in methadone dose, patients also taking rifampicin are likely to experience opiate withdrawal symptoms and may stop their antituberculosis drugs or supplement their methadone prescription with illicitly obtained opiates. Failure to comply with antituberculosis treatment compromises recovery and increases the risk of secondary resistance.2 The symptoms of methadone withdrawal usually occur only when intake is reduced and are not expected by a user starting rifampicin. Notifications of tuberculosis in the United Kingdom rose from a plateau of some 5100 in 1987 to over 5700 in 1994. Drug misusers account for only a small number of cases, but they share nationally identified risk factors3; thus high rates of tuberculosis can be expected …
A standardized CT estimation of liver volume is associated to the severity of cirrhosis and predicts the risk of decompensation
Authors: M. Romero, A. Clemente, E. Ramón, I. Peligros, E. Rodriguez, M. Salcedo, A. Matilla, L. Ibáñez, R. García, G. Clemente, D. Rincón, R. Bañares
Journal: Journal of Hepatology (2017)
Abstract A46: Wnt5a signals through DVL1 to repress ribosomal DNA transcription by RNA polymerase I
Authors: Randall Dass, Aishe Sarshad, Brittany Carson, Jennifer Feenstra, Amanpreet Kaur, Ales Obrdlik, Matthew Parks, Varsha Prakash, Damon Love, Kristian Pietras, Rosa Serra, Scott Blanchard, Piergiorgio Percipalle, Anthony Brown, Clara Theresa Vincent
Journal: Cancer Research (2017)

Abstract Ribosome biogenesis is essential for cell growth and proliferation and is commonly elevated in cancer. Accordingly, numerous oncogene and tumor suppressor signaling pathways target rRNA synthesis. In breast cancer, non-canonical Wnt signaling by Wnt5a has been reported to antagonize tumor growth. Here, we show that Wnt5a rapidly represses rDNA gene transcription in breast cancer cells and generates a chromatin state with reduced transcription of rDNA by RNA polymerase I (Pol I). These effects were specifically dependent on Dishevelled1 (DVL1), which accumulates in nucleolar organizer regions (NORs) and binds to rDNA regions of the chromosome. Upon DVL1 binding, the Pol I transcription activator and deacetylase Sirtuin 7 (SIRT7) releases from rDNA loci, concomitant with disassembly of Pol I transcription machinery at the rDNA promoter. These findings reveal that Wnt5a signals through DVL1 to suppress rRNA transcription. This provides a novel mechanism for how Wnt5a exerts tumor suppressive effects and why disruption of Wnt5a signaling enhances mammary tumor growth in vivo. Note: This abstract was not presented at the conference. Citation Format: Randall Dass, Aishe Sarshad, Brittany Carson, Jennifer Feenstra, Amanpreet Kaur, Ales Obrdlik, Matthew Parks, Varsha Prakash, Damon Love, Kristian Pietras, Rosa Serra, Scott Blanchard, Piergiorgio Percipalle, Anthony Brown, Clara Theresa Vincent. Wnt5a signals through DVL1 to repress ribosomal DNA transcription by RNA polymerase I. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr A46.
CT measurement of prevertebral soft tissue (PVST) and epiglottis as a predictor of swallowing dysfunction in head and neck cancer (HNC).
Authors: Elizabeth Marie Wulff-Burchfield, Sheila H. Ridner, Mary S. Dietrich, Joseph M. Aulino, Barbara A. Murphy
Journal: Journal of Clinical Oncology (2015)

e17061 Background: Surgery & radiation cause soft tissue damage resulting in lymphedema and fibrosis (LEF). LEF of Dysphagia/Aspiration Related Structures (DARS) may result in late swallowing abnormalities. Currently there are no objective screening measures for LEF involving DARS. Surveillance CTs are routinely used in HNC patients post-treatment. We developed a measurement tool to assess LEF using data from routine CT scans (CT-LEF Assessment Tool). Using this tool, we prospectively assessed PVST & epigolottic thickness, then correlated measurements with self-reported swallowing & voice abnormalities. Methods: 90 pts with stage 3 or 4 HNC were enrolled in a prospective study assessing the incidence, severity, & functional implications of LEF in post treatment HNC patients (1R01 CA149113-01A1). 58 were included in this analysis. Pts completed swallow solids (SS), swallow liquids (SL), & voice subscales of the Vanderbilt Head & Neck Symptom Survey at baseline, end-of-treatment, and 6, 12, 18, 24, 36, 42, 60, & 72 wks as well as CT scans at baseline & every 3 months post treatment. CTs were graded with the CT-LEF Assessment Tool. Subscale scores were correlated with PVST & epiglottic thickness at the respective assessment points. Results: Median PVST and epiglottic thickness ↑ from baseline to 6-18 wks (2.6 mm to 5.65 mm, p < 0.001 and 2 mm to 4.6 mm, p < 0.001 respectively). Measures ↓ over time, but never returned to baseline, the difference remaining statistically significantly at all post-treatment time points (p < 0.001). Correlations were observed between: 1) PPW thickness and the SS subscale at 24-36 wks (rs = 0.35, p = 0.009); 2) median epiglottic thickness and the SS subscale at 24-36 & 42-60 wks (rs = 0.31, p = 0.034 and 0.42, p = 0.001, respectively); 3) median epiglottic thickness & the SL subscale at 24-36 & 42-60 wks (rs= 0.39, p = 0.008 and 0.39, p = 0.004, respectively). Neither measurement correlated with voice scores. Conclusions: PVST & epiglottic thickness as measured by the CT-LEF Assessment tool correlate with swallowing dysfunction. Although confirmatory data is needed, this tool may serve as an objective measure for identification of patients requiring swallowing assessment.
NACSELD acute-on-chronic liver failure (NACSELD-ACLF) predicts 30-day mortality in admitted cirrhotic patients
Authors: J.G. O’leary, K.R. Reddy, P. Tanson, P.S. Kamath, F. Wong, G. Garcia-Tsao, J. Lai, S. Biggins, M.B. Fallon, R. Subramanian, P. Thuluvath, B. Maliakkal, L. Thacker, J.S. Bajaj
Journal: Journal of Hepatology (2017)
Institutional experiences with panitumumab monotherapy in metastatic colorectal cancer (mCRC) patients (pts) intolerant to cetuximab
Authors: A. D. Langerak, E. Mitchell, P. Cheema, G. L. River, M. Shing
Journal: Journal of Clinical Oncology (2007)

14579 Background: Two monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor are approved for the treatment (tx) of advanced mCRC - panitumumab (Vectibix™), a fully human mAb, and cetuximab (Erbitux®), a chimeric mAb. Potential for cross-reactivity between these two mAbs with regard to infusion reactions (IR) has not been fully explored. Given the lack of sequence homology between the 2 agents and the fully human nature of panitumumab, it is hypothesized that pts intolerant to cetuximab due to IR could be tolerant to panitumumab. Methods: Single pt tx IND applications to administer panitumumab monotherapy in pts with advanced mCRC were approved by the FDA and local institutions as part of the Panitumumab Compassionate Use program. Eligibility also included previous tx with standard chemotherapy and intolerability to cetuximab, ie. CTCAE v3.0 grade 3 (severe) or grade 4 (life-threatening) IR. Results: Upon informed consent, 4 pts (2M/ 2F) were enrolled in 4 centers. Median (range) age was 62.5 (52, 64) years. 3 pts had colon cancer and 1 pt had rectal cancer. All had surgery and received prior 5-fluorouracil, leucovorin, irinotecan, oxaliplatin, bevacizumab, and cetuximab. One pt had a CTC grade 3 IR and 3 pts had a CTC grade 4 IR to cetuximab. IR symptoms included fever, wheezing, dyspnea, chest/back/abdominal pain, anxiety, hypotension, flushing, tachycardia, and tachypnea. Two IRs occurred within 10 minutes of the first cetuximab infusion. Cetuximab was discontinued and IR symptoms were treated with bronchodilators, diphenhydramine, epinephrine, methylprednisolone, oxygen, intravenous saline, and hospitalization. All pts received panitumumab. Data for pts 1, 2, and 3 are available: pt 1 received 1 infusion of panitumumab at 5 mg/kg Q2W with premedication (diphenhydramine and methylprednisolone); pts 2 and 3 received 7 and 2 panitumumab infusions, respectively, at 6 mg/kg Q2W without premedication. No pt had an IR to panitumumab. Pt 2 had stable disease; pts 1 and 3 died due to disease progression. Conclusions: Panitumumab monotherapy was tolerated without incidence of an IR in these cases of mCRC pts who are intolerant to cetuximab due to a severe or life-threatening IR. Additional data will be presented. No significant financial relationships to disclose.
Von Willebrand factor antigen predicts portal hypertensive bleeding, infections, and survival, independently of portal hypertension severity
Authors: M. Mandorfer, P. Schwabl, T. Bucsics, R. Paternostro, K. Pomej, J. Thaler C. Ay, P. Quehenberger, M. Trauner, M. Peck-Radosavljevic, T. Reiberger, A. Ferlitsch
Journal: Journal of Hepatology (2017)
Cold polypectomy for duodenal adenomas: a prospective clinical trial
Authors: Daisuke Maruoka, Tomoaki Matsumura, Shingo Kasamatsu, Hideaki Ishigami, Takashi Taida, Kenichiro Okimoto, Tomoo Nakagawa, Tatsuro Katsuno, Makoto Arai
Journal: Endoscopy (2017)

Abstract Background and study aims Endoscopic resection is effective in treating nonampullary duodenal adenomas but has a high incidence of complications. Cold polypectomy, including cold forceps polypectomy (CFP) and cold snare polypectomy (CSP), is safe and effective in treating colorectal polyps. However, its utility in sporadic nonampullary duodenal adenomas has not been investigated. The purpose of this prospective study was to examine the safety and efficacy of cold polypectomy for sporadic nonampullary duodenal adenomas. Patients and methods Between March 2015 and June 2016, patients who were endoscopically diagnosed with sporadic nonampullary duodenal adenomas up to 6 mm underwent cold polypectomy. Patients with pathologically confirmed adenomas underwent endoscopic biopsy 3 months after resection. The main outcomes of interest were incomplete resection and complications. Results Overall, 39 lesions in 30 patients were removed via cold polypectomy (CFP, 9 lesions in 8 patients; CSP, 30 lesions in 22 patients). Seven of 9 (77.8 %) and 29 of 30 (96.7 %) lesions were removed en bloc via CFP and CSP, respectively. Pathologically, 34 of the 39 lesions (87.2 %) were confirmed as adenomas, and their mean size was 3.9 ± 1.2 mm (range 2 – 6 mm). Of the 34 adenomas, 20 (58.8 %) were R0 resection lesions, of which 3 of 9 (33.3 %) and 17 of 25 (68.0 %) had undergone CFP and CSP, respectively. No delayed bleeding or intraprocedural/delayed perforation was observed. All 30 patients with the 34 pathologically confirmed adenomas underwent upper gastrointestinal endoscopy 3 months after cold polypectomy, and no morphological or pathological recurrence was identified. Conclusions In this small study, cold polypectomy appeared to be safe and effective in treating diminutive and small sporadic nonampullary duodenal adenomas. (Clinical trial registration number: UMIN000016829)