tbuckley/cabot-search huggingface dataset:
Mettl14 Is Essential for Epitranscriptomic Regulation of Striatal Function and Learning
Authors: Jessica L. Koranda, Lou Dore, Hailing Shi, Meera J. Patel, Lee O. Vaasjo, Meghana N. Rao, Kai Chen, Zhike Lu, Yangtian Yi, Wanhao Chi, Chuan He, Xiaoxi Zhuang
Journal: Neuron (2018)
Michael Rosen: anaesthetist who championed patients’ rights to pain relief
Authors: Matthew Limb
Journal: BMJ (2018)

Michael Rosen was a pioneering anaesthetist who championed patients’ rights to pain relief and fought for his profession to receive proper recognition. Determined to show that “anaesthetists work with, and not for, surgeons” in an equal capacity, he raised both their standing and the cause of clinical safety through his practice, research, and advocacy.

Rosen developed patient controlled analgesia (PCA), substantially advanced maternal safety, and did much to drive the modern concept of the perioperative physician.

Towards the end of a 32 year career as a consultant anaesthetist in Cardiff—first at the Cardiff Royal Infirmary and then at University Hospital of Wales—he was awarded the CBE for his medical contributions to Wales and as first president of the College of Anaesthetists.

“He was the most outstanding anaesthetist in the last half of the twentieth century in the UK,” says Ralph Vaughan, who first worked with Rosen in the 1960s.

Rosen was a pioneer of individualised postsurgical pain relief. He believed that “there’s no excuse for someone being in pain and we should never deny appropriate relief.” But in the 1960s and 1970s patients were routinely suffering. Pain relief was poorly managed, leading to pathological consequences such as chest infections, prolonged hospital stays, thromboembolism, and the development of crippling chronic pain syndromes.

David Bogod, consultant anaesthetist and past vice president of the Association of Anaesthetists of Great Britain and Ireland, says, “Rosen realised that patients themselves were best placed to determine how often they needed doses of morphine, the requirements for which were otherwise very variable and unpredictable.”1

Funded by a Medical …
Self-expandable covered metallic stent as a conduit for pancreatic stone extraction
Authors: Heather Branstetter, Umangi Patel, Prashant Kedia, Paul Tarnasky
Journal: Endoscopy (2018)

A 50-year-old man was referred for evaluation of alcohol-related chronic relapsing pancreatitis. Initial endoscopic retrograde cholangiopancreatography (ERCP) revealed a dilated pancreatic duct with a stone proximal to a distal stricture. The stricture was dilated to 6 mm using a balloon, and an 8.5-Fr plastic stent was placed to ensure drainage. ERCP 2 months later showed no improvement in the stricture and a 10-Fr stent was placed.
Moving From Hope to Hard Work in Data Sharing
Authors: C. Michael Gibson
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Abstract 1084: TRAF4-mediated NGF receptor TrkA ubiquitination regulates prostate cancer metastasis
Authors: Ramesh Singh, Dileep Karri, Jiangyong Shao, Subhamoy Dasgupta, Shixia Huang, Dean P. Edwards, Bert W. O'Malley, Ping Yi
Journal: Cancer Research (2018)

Abstract Receptor tyrosine kinases (RTKs) are important drivers of cancers. In addition to genomic alterations, aberrant activation of wild type RTKs play an important role in driving cancer progression. However, the underlying mechanisms of how RTKs drive prostate cancer remains incompletely characterized. Here we show that non-proteolytic ubiquitination of RTK regulates its kinase activity and contributes to RTK-mediated prostate cancer metastasis. TRAF4, a RING domain E3 ubiquitin ligase, is highly expressed in metastatic prostate cancer. We demonstrated here that it is a key player in regulating RTK mediated prostate cancer metastasis. We further identified TrkA, a neurotrophin receptor tyrosine kinase, as a TRAF4-targeted ubiquitination substrate that promotes cancer cell invasion and genetic ablation of TrkA abolished TRAF4-dependent cell invasion. TRAF4 promoted atypical K27 and K29-linked ubiquitination at the TrkA kinase domain and increased its kinase activity. Mutation of TRAF4-targeted ubiquitination sites abolished TrkA tyrosine auto-phosphorylation and its interaction with downstream effector proteins. TRAF4 knockdown also suppressed nerve growth factor-stimulated TrkA downstream p38 MAPK activation and subsequent invasion-associated gene expression. Furthermore, elevated TRAF4 levels significantly correlated with increased NGF-stimulated invasion-associated gene expression in prostate cancer patients, indicating this signaling axis is significantly activated during oncogenesis. Our results revealed a post-translational modification mechanism contributing to aberrant non-mutated receptor tyrosine kinase activation in cancer cells. Citation Format: Ramesh Singh, Dileep Karri, Jiangyong Shao, Subhamoy Dasgupta, Shixia Huang, Dean P. Edwards, Bert W. O'Malley, Ping Yi. TRAF4-mediated NGF receptor TrkA ubiquitination regulates prostate cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1084.
Epidemiology of injuries in outdoor and indoor hockey players over one season: a prospective cohort study
Authors: Karsten Hollander, Kai Wellmann, Christine zu Eulenburg, Klaus-Michael Braumann, Astrid Junge, Astrid Zech
Journal: British Journal of Sports Medicine (2018)

Objectives To determine the incidence and characteristics of hockey (‘field hockey’) injuries over the course of one outdoor and indoor season. Comparisons of female versus male players, outdoor versus indoor season and match versus practice were performed. Methods Female and male teams of the first, second, third, regional and youth divisions were recruited among a local hockey association in Northern Germany, and followed over an indoor and an outdoor season. Exposure times and location, type, severity and cause of injuries during practice and matches were documented by the coaches or medical staff and collected weekly. Prevalence and incidence rates were calculated. Results Of the 232 players (mean±SD age 20.7±4.7 years, 68.1% male, 31.9% first division), 84 players (36.2%) suffered 108 new injuries during the season. The overall incidence rate was 3.7 injuries per 1000 player hours (95% CI 3.0 to 4.4). The injury incidence was lower in practice (2.7 per 1000 player practice hours, 95% CI 2.0 to 3.3) than in matches (9.7 per 1000 player match hours, 95% CI 6.8 to 12.7), and was similar for female and male players as well as during the outdoor and the indoor season. Most injuries affected the lower limb (thigh, knee and ankle) and occurred without contact (58.3%). Severe injuries (n=34; 31.5%) were predominantly located at the knee and hand/finger. Conclusion Hockey players have a high prevalence and incidence of injuries, especially at the lower limb.
Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: ASCO Clinical Practice Guideline Update
Authors: Sharon H. Giordano, Sarah Temin, Sarat Chandarlapaty, Jennie R. Crews, Francisco J. Esteva, Jeffrey J. Kirshner, Ian E. Krop, Jennifer Levinson, Nancy U. Lin, Shanu Modi, Debra A. Patt, Jane Perlmutter, Naren Ramakrishna, Eric P. Winer, Nancy E. Davidson
Journal: Journal of Clinical Oncology (2018)

Purpose To update evidence-based guideline recommendations for practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer to 2018. Methods An Expert Panel conducted a targeted systematic literature review (for both systemic treatment and CNS metastases) and identified 622 articles. Outcomes of interest included overall survival, progression-free survival, and adverse events. Results Of the 622 publications identified and reviewed, no additional evidence was identified that would warrant a change to the 2014 recommendations. Recommendations HER2-targeted therapy is recommended for patients with HER2-positive advanced breast cancer, except for those with clinical congestive heart failure or significantly compromised left ventricular ejection fraction, who should be evaluated on a case-by-case basis. Trastuzumab, pertuzumab, and taxane for first-line treatment and trastuzumab emtansine for second-line treatment are recommended. In the third-line setting, clinicians should offer other HER2-targeted therapy combinations or trastuzumab emtansine (if not previously administered) and may offer pertuzumab if the patient has not previously received it. Optimal duration of chemotherapy is at least 4 to 6 months or until maximum response, depending on toxicity and in the absence of progression. HER2-targeted therapy can continue until time of progression or unacceptable toxicities. For patients with HER2-positive and estrogen receptor-positive/progesterone receptor-positive breast cancer, clinicians may recommend either standard first-line therapy or, for selected patients, endocrine therapy plus HER2-targeted therapy or endocrine therapy alone. Additional information is available at www.asco.org/breast-cancer-guidelines .
SET1A-Mediated Mono-Methylation at K342 Regulates YAP Activation by Blocking Its Nuclear Export and Promotes Tumorigenesis
Authors: Lan Fang, Hongqi Teng, Yilin Wang, Guanghong Liao, Linjun Weng, Yaxu Li, Xinbo Wang, Jiali Jin, Chenchen Jiao, Lei Chen, Xiaoping Peng, Jiayu Chen, Yongzhi Yang, Houqin Fang, Dongyan Han, Cheng Li, Xueling Jin, Shihao Zhang, Zhongchen Liu, Min Liu, Qing Wei, Lujian Liao, Xin Ge, Bin Zhao, Dawang Zhou, Huan-Long Qin, Jun Zhou, Ping Wang
Journal: Cancer Cell (2018)
Biological effects of radiation on cancer cells
Authors: Jin-song Wang, Hai-juan Wang, Hai-li Qian
Journal: Military Medical Research (2018)

With the development of radiotherapeutic oncology, computer technology and medical imaging technology, radiation therapy has made great progress. Research on the impact and the specific mechanism of radiation on tumors has become a central topic in cancer therapy. According to the traditional view, radiation can directly affect the structure of the DNA double helix, which in turn activates DNA damage sensors to induce apoptosis, necrosis, and aging or affects normal mitosis events and ultimately rewires various biological characteristics of neoplasm cells. In addition, irradiation damages subcellular structures, such as the cytoplasmic membrane, endoplasmic reticulum, ribosome, mitochondria, and lysosome of cancer cells to regulate various biological activities of tumor cells. Recent studies have shown that radiation can also change the tumor cell phenotype, immunogenicity and microenvironment, thereby globally altering the biological behavior of cancer cells. In this review, we focus on the effects of therapeutic radiation on the biological features of tumor cells to provide a theoretical basis for combinational therapy and inaugurate a new era in oncology.
Photopatch and patch testing in 63 patients with frontal fibrosing alopecia: a case series
Authors: V.B. Rocha, A. Donati, L.A. Contin, P. Kakizaki, C.J. Machado, F.F. Brito, D. Claudino, P. Moraes, J. Guerra, M.C. Pires
Journal: British Journal of Dermatology (2018)

Fund for Dermatology of Sao Paulo - Sebastiao Sampaio (FUNADERSP) from the Brazilian Society of Dermatology - Region of Sao Paulo State
Abstract 1664: 4-Bromophenylhydrazinyl benzenesulfonylphenylureas inhibit indoleamine 2,3-dioxygenase in vitro and in vivo
Authors: Shau-Hua Ueng, Ching-Chuan Kuo, Shu-Yu Lin, Teng-Kuang Yeh, Jen-Shin Song, Ming-Shiu Hung, Chiung-Tong Chen
Journal: Cancer Research (2018)

Abstract Indoleamine 2,3-dioxygenase has been considered as a promising anti-cancer drug target. Several pharmaceutical companies, including Pfizer, Merck, and Bristol-Myers Squibb, are known to be in pursuit of IDO inhibitors, and Incyte recently reported good results in the phase II clinical trial of the IDO inhibitor Epacadostat. In previous work, we developed a series of IDO inhibitors based on a high-throughput screening core structure, sulfonylhydrazide. Further, we developed the 4-bromophenylhydrazinyl benzenesulfonylphenylurea, as a potent IDO inhibitor with an IC50 value within 100 nM in inhibiting IDO in vitro. This compound demonstrated a 30% reduction in tumor weight in a murine CT26 syngeneic model on day 18 with 100 mg/kg oral administration twice daily, indicating that the 4-bromophenylhydrazinyl benzenesulfonylphenylurea may have potential for further investigation in the development of anti-tumor drugs. Citation Format: Shau-Hua Ueng, Ching-Chuan Kuo, Shu-Yu Lin, Teng-Kuang Yeh, Jen-Shin Song, Ming-Shiu Hung, Chiung-Tong Chen. 4-Bromophenylhydrazinyl benzenesulfonylphenylureas inhibit indoleamine 2,3-dioxygenase in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1664.
Abstract 11996: Nicotine Promotes Foam Cell Formation and Atherosclerosis by Receptor-mediated Activation of Cd36
Authors: Ming-sheng Zhou, Kiranmai Chadipiralla, Armando J Mendez, Edgar Jaimes, Roy L Silverstein, Keith A Webster, Leopoldo Raij
Journal: Circulation (2012)

In the USA smoking is associated with 175,000 annual deaths due to cardiovascular disease and 30% of all deaths caused by heart attack. The pathogenic roles of stable compounds in the gas phase of ...
Abstract 3893: Quantitative contribution of rs75017182 to dihydropyrimidine dehydrogenase mRNA splicing and enzyme activity
Authors: Qian Nie, Shikshya Shrestha, Erin E. Tapper, Colbren S. Trogstad-Isaacson, Kelly J. Bouchonville, Steven M. Offer, Robert B. Diasio
Journal: Cancer Research (2018)

Abstract 5-Fluorouracil (5-FU) has remained a widely prescribed anti-cancer drug for decades. However, 5-FU–based treatments show inter-individual variability, with up to 34% of 5-FU–treated patients developing severe (grade 3+) adverse toxicity. Dihydropyrimidine dehydrogenase (DPD; DPYD gene) is the rate-limiting enzyme of 5-FU catabolism and converts 80–85% of 5-FU into its inactive metabolites. Three deleterious genetic variations in DPYD are well-established predictors of severe 5-FU toxicity (i.e., *2A, p. I560S, and p. D949V); however, these variants only explain 30–35% of adverse cases. Recently, an intronic variant (rs75017182) has been suggested to contribute to 5-FU–related toxicity by promoting the alternative splicing of DPYD. However, clinical studies are conflicting as to the degree to which rs75017182 affects DPD enzyme function, and the true contribution of the rs75017182 variant towards DPD function and 5-FU toxicity remains unclear and inconclusive. In the present study, we directly examined the effect of the intronic SNP rs75017182 on DPYD mRNA splicing, DPYD expression, and DPD enzyme function. We genotyped 3950 healthy Caucasian volunteers from the Mayo Clinic Biobank to identify the rs75017182, *2A, p.I560S, and p.D949V variants. From the initial cohort, 204 volunteers who were rs75017182 heterozygous carriers were recruited as our study population. Alternative splicing and DPD activity in rs75017182 carriers were measured. The findings were confirmed using a novel mini-gene reporter system in vitro. A moderate, but significant, reduction (30%) was detected in canonically spliced DPYD expression in rs75017182 carriers compared to non-carriers. A correlative reduction (35%) in DPD enzyme activity was observed in those carriers, which was similar to that of D949V carriers (31%). The results demonstrated an association of this deep intronic variant with decreased DPD activity and suggested that rs75017182 may be a predictor of 5-FU toxicity similar to D949V. Citation Format: Qian Nie, Shikshya Shrestha, Erin E. Tapper, Colbren S. Trogstad-Isaacson, Kelly J. Bouchonville, Steven M. Offer, Robert B. Diasio. Quantitative contribution of rs75017182 to dihydropyrimidine dehydrogenase mRNA splicing and enzyme activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3893.
Abstract 2167: Efficacy assessment of BTK inhibitor ibrutinib in de novo and viral-induced B cell lymphoma
Authors: Jessie Jingjing Wang, Meiling Zheng, Xuesong Huang, Yanrui Song, Wubin Qian, Likun Zhang, Jie Cai, Sheng Guo, Henry Qixiang Li, Davy Xuesong Ouyang
Journal: Cancer Research (2018)

Abstract Bruton's tyrosine kinase (BTK) is crucial for B cell maturation. Its activation has also been considered as a major oncogenic driver for various B cell-derived lymphoid cancers. A BTK inhibitor, Ibrutinib, has been approved for mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenström's macroglobulinemia, a form of non-Hodgkin's lymphoma (NHL). Ibrutinib has also shown encouraging efficacies in defuse large B cell lymphoma (DLBCL), specifically in activated B cell-like (ABC) subtype, but not in germinal center B cell-like (GCB) subtype. We have established a series of patient derived xenograft (PDX) models, recapitulating diverse genotypes of de novo DLBCL patients, including two MYD88L265P/CD79BY197N double mutants (LY2298, LY2264), one MYD88L265P single mutant (LY0257), and a variety of wild-types (LY2214, LY3604, and LY6934, etc.). This cohort of PDX models serve as perfect preclinical tools to investigate Ibrutinib responses in different genotypes. Our studies demonstrated a moderate to robust efficacies of Ibrutinib in the MYD88/CD79B double mutants, suggesting that CD79B mutation is the predictive biomarker for chronic activation of B cell receptor (BCR) signaling, as well as generally good responses to BTK inhibitor. Interestingly, the MYD88 single mutant model LY0257, where the disease is likely driven by constitutive activation of MYD88 signaling, also showed response to Ibrutinib when dosed in drinking water. In the wild type PDXs, two of seven models tested so far are either partially responsive or sensitive to Ibrutinib, while the others are resistant to the treatment. It seems that Ibrutinib response does not always require CD79B mutation, and BCR pathway addiction may occur by other means in DLBCL, even when MYD88 signaling is constitutively active. Notably, all 5 wild type DLBCL PDXs that are non-responsive to Ibrutinib are EBV positive verified by RNAseq. These EBV-transformed B lymphoma PDX models, which share the similar histopathology as de novo DLBCL, but have distinct molecular pathology signatures and different pathogenesis. In efficacy studies, none of the transformed B lymphoma PDXs showed response to Ibrutinib. Taken together, our DLBCL and EBV-induced lymphoma PDX models provide a valuable preclinical platform for evaluating BTK inhibitors, as well as future drug discovery efforts on other targets in the BCR and MYD88 pathways, such as PI3K, SYK, and IRAK4. Citation Format: Jessie Jingjing Wang, Meiling Zheng, Xuesong Huang, Yanrui Song, Wubin Qian, Likun Zhang, Jie Cai, Sheng Guo, Henry Qixiang Li, Davy Xuesong Ouyang. Efficacy assessment of BTK inhibitor ibrutinib in de novo and viral-induced B cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2167.
Doctors call for public inquiry into GMC’s handling of Bawa-Garba case
Authors: Zosia Kmietowicz
Journal: BMJ (2018)

Doctors have declared that they have no confidence in the General Medical Council and have called for a public inquiry into the regulator’s conduct in the case of trainee paediatrician Hadiza Bawa-Garba.

A motion declaring no confidence in the GMC was passed by 89% to 11% at the BMA annual representative meeting in Brighton on 27 June. Representatives also backed calls for the GMC to apologise over its handling of the Bawa-Garba case. But calls for the GMC’s chief executive and its chairman to resign over the case were rejected by 51%, as were demands for the government …
Abstract LB-394: Profiling of endogenous circular RNA molecules in formalin-fixed paraffin-embedded tissues from patients with B-cell malignancies using an enzyme-free digital counting method
Authors: Lasse Sommer Kristensen, Mette Dahl, Maria S. Andersen, Iben Daugaard, Thomas B. Hansen, Kirsten Grønbæk, Jørgen Kjems
Journal: Cancer Research (2018)

Abstract Circular RNAs (circRNAs) are covalently closed endogenous RNA molecules with tissue- and disease specific expression patterns, which have potential as diagnostic and prognostic biomarkers in cancer. The landscape of circRNA expression has not been characterized in B-cell malignancies, and current methods for circRNA quantification have several limitations that prevent development of clinically applicable assays. Based on high-throughput RNA sequencing (RNA-seq) data, we designed assays for analyzing 52 unique circRNAs simultaneously, using a digital, enzyme-free technology termed NanoString, in cell lines and paired fresh frozen and formalin-fixed, paraffin-embedded (FFPE) patient samples (including mantle cell lymphoma, multiple myeloma, follicular lymphoma, diffuse large B-cell lymphoma, Burkitt lymphoma and chronic lymphocytic leukemia). The data obtained using NanoString were compared to RNA-seq and reverse transcription-qPCR (RT-qPCR) data obtained on the same samples. RNA-seq profiling revealed a high expression of circRNAs in B-cell malignancies and the NanoString circRNA expression profiles were able to distinguish different B-cell malignancies. We detected circRNAs known to be deregulated in other cancers, including ciRS-7, circHIPK3 circCCDC66, circCDYL, circZKSCAN1 and circFBXW7, and identified a novel circRNA from the IKZF3 oncogene. NanoString data were more reproducible and quantitatively accurate than RNA-seq data and the technology works in particular well for low quality RNA samples. Together, we demonstrate that the NanoString technology enables specific, sensitive and accurate quantification of circRNAs in FFPE samples and provide a map of circRNA expression in B-cell malignancies. Citation Format: Lasse Sommer Kristensen, Mette Dahl, Maria S. Andersen, Iben Daugaard, Thomas B. Hansen, Kirsten Grønbæk, Jørgen Kjems. Profiling of endogenous circular RNA molecules in formalin-fixed paraffin-embedded tissues from patients with B-cell malignancies using an enzyme-free digital counting method [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-394.