tbuckley/cabot-search huggingface dataset:
IL-17-receptor-associated adaptor Act1 directly stabilizes mRNAs to mediate IL-17 inflammatory signaling
Authors: Tomasz Herjan, Lingzi Hong, Jodi Bubenik, Katarzyna Bulek, Wen Qian, Caini Liu, Xiao Li, Xing Chen, Hui Yang, Suidong Ouyang, Hao Zhou, Junjie Zhao, Kommireddy Vasu, Eric Cockman, Mark Aronica, Kewal Asosingh, Donny D. Licatalosi, Jun Qin, Paul L. Fox, Thomas A. Hamilton, Donna Driscoll, Xiaoxia Li
Journal: Nature Immunology (2018)
Future surgeons: critical care
Authors: Joanna Mennie
Journal: BMJ (2011)

“Future surgeons: critical care” is a new course run by the Royal College of Surgeons of Edinburgh. It is an intensive one day course led by consultant general surgeons and consultant anaesthetists and is designed to develop skills in recognising and managing the critically ill surgical patient.

The course is targeted at foundation doctors who have an interest in pursuing a career in surgery. It would also be appropriate for those wishing to pursue a career in anaesthetics and intensive care medicine.

The course is held at the Royal College of Surgeons of Edinburgh. It costs £125 (£105 for affiliates) and includes lunch. The course will be held each year in January. …
Ronald Fieve: lithium researcher and psychiatrist to Hollywood moguls and Wall Street tycoons
Authors: Ned Stafford
Journal: BMJ (2018)

During the 1980s, Ronald Fieve’s psychiatric practice in New York City was thriving. At the time, Fieve was arguably the most famous of the psychiatrists in the US who were championing the use of lithium to treat bipolar disorder. The result was that many of his patients were “manic depressive” as well as rich and famous.

The actress Patty Duke, in her 1992 book about her battle with bipolar disorder, described Fieve’s practice in Manhattan’s Upper East Side as “crammed with Wall Street tycoons and Hollywood producers who often arrive at his office in long, black limousines.”1

Fieve is quoted in the book, saying: “When they come to me for treatment, they have usually come down from a manic state and are into severe depression. Often they are desperate and suicidal.” In most cases, Fieve’s treatment included lithium and was successful.

Fieve had helped pioneer lithium research in the US in the late 1950s, and by the 1960s he was convinced that it was the most effective treatment for bipolar disorder. Although other psychiatrists also voiced strong support, Fieve was probably the most effective at educating the general public about bipolar disorder and its treatment with lithium, a natural medication that seemed almost magical to him. “Few experiences in psychiatry,” Fieve said in Patty Duke’s book, “are as dramatic as watching lithium carbonate in one to two weeks utterly transform a manic depressive personality.”

During the 1970s his efforts to promote lithium turned into …
I start as a plastics specialist registrar in April 2006. Meanwhile I want to help (as a surgeon) in an area of the world that has been affected by natural disaster. Can anyone offer advice?
Authors: Mark Wilson
Journal: BMJ (2005)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
Novel Adipokine, FAM19A5, Inhibits Neointima Formation After Injury Through Sphingosine-1-Phosphate Receptor 2
Authors: Yingbao Wang, Dixin Chen, Yan Zhang, Pingzhang Wang, Can Zheng, Songyang Zhang, Bing Yu, Lu Zhang, Guizhen Zhao, Baihui Ma, Zeyu Cai, Nan Xie, Shiyang Huang, Ziyi Liu, Xiaoning Mo, Youfei Guan, Xian Wang, Yi Fu, Dalong Ma, Ying Wang, Wei Kong
Journal: Circulation (2018)

Background: Obesity plays crucial roles in the development of cardiovascular diseases. However, the mechanisms that link obesity and cardiovascular diseases remain elusive. Compelling evidence indicates that adipokines play an important role in obesity-related cardiovascular diseases. Here, we found a new adipokine-named family with sequence similarity 19, member A5 (FAM19A5), a protein with unknown function that was predicted to be distantly related to the CC-chemokine family. We aimed to test whether adipose-derived FAM19A5 regulates vascular pathology on injury. Methods: DNA cloning, protein expression, purification, and N-terminal sequencing were applied to characterize FAM19A5. Adenovirus infection and siRNA transfection were performed to regulate FAM19A5 expression. Balloon and wire injury were performed in vivo on the rat carotid arteries and mouse femoral arteries, respectively. Bioinformatics analysis, radioactive ligand-receptor binding assays, receptor internalization, and calcium mobilization assays were used to identify the functional receptor for FAM19A5. Results: We first characterized FAM19A5 as a secreted protein, and the first 43 N-terminal amino acids were the signal peptides. Both FAM19A5 mRNA and protein were abundantly expressed in the adipose tissue but were downregulated in obese mice. Overexpression of FAM19A5 markedly inhibited vascular smooth muscle cell proliferation and migration and neointima formation in the carotid arteries of balloon-injured rats. Accordingly, FAM19A5 silencing in adipocytes significantly promoted vascular smooth muscle cell activation. Adipose-specific FAM19A5 transgenic mice showed greater attenuation of neointima formation compared with wild-type littermates fed with or without Western-style diet. We further revealed that sphingosine-1-phosphate receptor 2 was the functional receptor for FAM19A5, with a dissociation constant ( K d ) of 0.634 nmol/L. Inhibition of sphingosine-1-phosphate receptor 2 or its downstream G12/13-RhoA signaling circumvented the suppressive effects of FAM19A5 on vascular smooth muscle cell proliferation and migration. Conclusions: We revealed that a novel adipokine, FAM19A5, was capable of inhibiting postinjury neointima formation via sphingosine-1-phosphate receptor 2-G12/13-RhoA signaling. Downregulation of FAM19A5 during obesity may trigger cardiometabolic diseases.
A&amp;E radiology survival course for doctors
Authors: Aarti Shah
Journal: BMJ (2010)

The A&E radiology survival course for doctors is run by a group of doctors from Addenbrooke’s Hospital and the London Hospital. It is held at various times throughout the year at Northwick Park Hospital. The course has been running for 10 years and is now the largest radiology teaching course in the United Kingdom, with more than 800 participants a year.

The course is targeted towards doctors who are interested in developing their radiograph interpretation skills within the emergency department. It is ideally suited to junior doctors, who are currently in or due to …
Reaction of Immune Complexes With Hodgkin's Disease Tissue Cultures
Authors: J C Long, A M Dvorak, S C Quay, C Stamatos
Journal: JNCI Journal of the National Cancer Institute (1981)

Reaction of Immune Complexes With Hodgkin's Disease Tissue Cultures Get access John C. Long, John C. Long Search for other works by this author on: Oxford Academic PubMed Google Scholar Ann M. Dvorak, Ann M. Dvorak Search for other works by this author on: Oxford Academic PubMed Google Scholar Steven C. Quay, Steven C. Quay Search for other works by this author on: Oxford Academic PubMed Google Scholar Cathyrn Stamatos, Cathyrn Stamatos Search for other works by this author on: Oxford Academic PubMed Google Scholar Shu-Yuan Chi Shu-Yuan Chi Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 67, Issue 1, July 1981, Page 3, https://doi.org/10.1093/jnci/67.1.3 Published: 01 July 1981
Genomic Changes Associated with the Evolutionary Transitions of Nostoc to a Plant Symbiont
Authors: Denis Warshan, Anton Liaimer, Eric Pederson, Sea-Yong Kim, Nicole Shapiro, Tanja Woyke, Bjørn Altermark, Katharina Pawlowski, Philip D Weyman, Christopher L Dupont, Ulla Rasmussen
Journal: Molecular Biology and Evolution (2018)

Cyanobacteria belonging to the genus Nostoc comprise free-living strains and also facultative plant symbionts. Symbiotic strains can enter into symbiosis with taxonomically diverse range of host plants. Little is known about genomic changes associated with evolutionary transition of Nostoc from free-living to plant symbiont. Here, we compared the genomes derived from 11 symbiotic Nostoc strains isolated from different host plants and infer phylogenetic relationships between strains. Phylogenetic reconstructions of 89 Nostocales showed that symbiotic Nostoc strains with a broad host range, entering epiphytic and intracellular or extracellular endophytic interactions, form a monophyletic clade indicating a common evolutionary history. A polyphyletic origin was found for Nostoc strains which enter only extracellular symbioses, and inference of transfer events implied that this trait was likely acquired several times in the evolution of the Nostocales. Symbiotic Nostoc strains showed enriched functions in transport and metabolism of organic sulfur, chemotaxis and motility, as well as the uptake of phosphate, branched-chain amino acids, and ammonium. The genomes of the intracellular clade differ from that of other Nostoc strains, with a gain/enrichment of genes encoding proteins to generate l-methionine from sulfite and pathways for the degradation of the plant metabolites vanillin and vanillate, and of the macromolecule xylan present in plant cell walls. These compounds could function as C-sources for members of the intracellular clade. Molecular clock analysis indicated that the intracellular clade emerged ca. 600 Ma, suggesting that intracellular Nostoc symbioses predate the origin of land plants and the emergence of their extant hosts.
How to miss meetings
Authors: Mark Griffiths
Journal: BMJ (2006)

Meetings are a fact of working life but there is nothing more infuriating than sitting in a meeting for two hours and then realising it was a complete waste of your time—especially if you had to travel a couple of hours there and back just to attend. So how do you know which meetings not to attend, or simply how to get out of meetings in the first place? Here are a few tips.
Efficacy and safety of CetuGEX in recurrent/metastatic squamous cell carcinoma of the head and neck (RM-HNSCC): Results from the randomized phase II RESGEX study.
Authors: Ulrich Keilholz, Andrzej Kawecki, Andreas Dietz, Bogdan Zurawski, Michael Schenker, Bozena Kukielka-Budny, Philippe Schafhausen, Anca C. Mihailov, Sebastian Ochenduszko, Ilaria Imarisio, Simona Mihutiu, Cristina-Marinela Oprean, Gunnar Folprecht, Alina Turcu, Sylvie Rottey, Philippe Debourdeau, Javier Lavernia, Bruno Dietrich, Alfredo Zurlo, Jerome Fayette
Journal: Journal of Clinical Oncology (2018)

59 Background: Standard treatment for RM-HNSCC is a combination of cisplatin (P), 5-FU (F), and the epidermal growth factor receptor (EGFR) blocking monoclonal antibody cetuximab. CetuGEX is a new monoclonal antibody sharing the identical EGFR-binding domain with cetuximab, but a modified Fc part by a proprietary glycosylation method to optimize antibody dependent cellular cytotoxicity (ADCC). Methods: Patients with RM-HNSCC without relevant comorbidities were randomized to receive up to 6 cycles of P 100 mg/m 2 , F 4 x 1000 mg/m 2 /24hrs and CetuGEX vs. cetuximab. Initial dose of cetuximab was 400mg/m 2 , followed by weekly 250 mg/m 2 . CetuGEX was given as 990 mg, followed by weekly 720 mg. After end of combination treatment, patients received single agent antibody maintenance until disease progression or intolerable toxicity. Stratification factors included FcγRIIIa status, primary tumor site, EGFR pretreatment vs. naïve, and recurrent vs. metastatic disease. Primary endpoint was progression-free survival (PFS) by immune related response criteria (irRC). Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR) and overall survival (OS) as well as safety and QoL. Results: During Jan 2014 and Feb 2016, 240 patients were accrued in 34 European centers, of which 123 received cetuximab and 117 CetuGEX. The median follow-up was 15 month until May 2017. No difference was observed for the primary endpoint of PFS by irRC [median 27.7 (CetuGEX) and 26.4 (cetuximab) weeks; HR 1.003; 95%-CI 0.738 – 1.363; p = 0.98]. No advantage of CetuGEX over cetuximab was observed for all other secondary efficacy endpoints and subgroup analyses by stratification factors. Infusion related reactions (IRR) were higher for CetuGEX (38.8%) than for cetuximab (5.7%) (Pearson chi 2 = 37.08; p &lt; 0.0001), but without sequelae. Conclusions: The RESGEX study is the first head-to-head comparison of an ADCC-optimized to a conventional EGFR-directed antibody. The study failed to show superior efficacy of CetuGEX over cetuximab. Both compounds appear to have the same efficacy and a similar safety profile. Glycosylation changes in the Fc part induced more IRRs. Clinical trial information: NCT02052960.
Episodic memory is as much about communicating as it is about relating to others
Authors: Alin Coman
Journal: Behavioral and Brain Sciences (2018)

Abstract Mahr &amp; Csibra (M&amp;C) provide extensive evidence for the communicative function of episodic memory, suggesting that the malleability of human memory is in large part due to its communicative dimension. I argue that emphasizing the relational motivations involved in communication provides a more proximal explanation for why our memories are as malleable.
NHS must champion women as leaders in CCGs, experts say
Authors: Matthew Limb
Journal: BMJ (2015)

The NHS needs to champion women as leaders and boost their numbers in clinical commissioning groups, their membership body NHS Clinical Commissioners has said.

The organisation said that women were under-represented on CCGs and that the lack of balance was unfair and weakened CCGs’ performance. CCGs should develop a talent management programme to identify, support, and nurture women who had the potential to be clinical leaders, it said. NHS England should also appoint a champion for women in clinical leadership and regularly publish data on representation of women, it argued. 

NHS Clinical Commissioners represents 90% of CCGs in England. Julie Wood, its chief executive, said, “I strongly believe that if everyone takes action …
Soluble urokinase plasminogen activator receptor (suPAR) as a novel serum biomarker for patients undergoing resection of colorectal liver metastases.
Authors: Sven H Loosen, Marcel Binneboesel, Christian Klink, Tom Florian Ulmer, Thomas Longerich, Christian Trautwein, Christoph Roderburg, Tom Luedde, Ulf Peter Neumann
Journal: Journal of Clinical Oncology (2018)

309 Background: In colorectal cancer (CRC), the liver is the most common site of metastasis. Surgical resection represents the standard potentially curative therapy for patients with colorectal liver metastases (CRLM). However, 5-year survival rates after resection do not exceed 50%, and despite existing preoperative stratification algorithms it is still not fully understood which patients benefit most from surgery. The soluble urokinase plasminogen activator receptor (suPAR) has recently evolved as a promising biomarker for distinct clinical conditions. Here, we examined a potential role of circulating suPAR as a biomarker in patients undergoing resection of CRLM. Methods: Expression levels of uPAR, the membrane-bound source of circulating suPAR, were analysed in tissue samples of CRLM using RT-PCR and IHC. SuPAR serum levels were measured by ELISA in 104 patients undergoing surgical resection of CRLM as well as 50 healthy controls. Results were correlated with clinical data. Results: In line with an upregulation of uPAR in the CRLM tissue, serum levels of suPAR were significantly elevated in patients with CRLM compared to healthy controls. Patients with preoperative suPAR serum levels above our defined ideal cut-off value of 4.83 ng/ml showed a strikingly reduced overall survival after resection of CRLM, which could be confirmed for right- and left-sided primary CRC. Importantly, none of these patients reached long-term survival compared to patients with preoperative suPAR serum concentrations below the cut-off value. Moreover, multivariate Cox-regression analysis revealed preoperative suPAR serum levels as an independent prognostic factor in this setting. Additionally, elevated preoperative suPAR but not creatinine levels were a predictor of acute kidney injury after CRLM resection, correlating with a longer postoperative hospitalization. Conclusions: Serum levels of suPAR represent a promising novel biomarker in patients with resectable CRLM that might help to guide preoperative treatment decisions with regards to patients’ outcome and the identification of patients particularly susceptible to postoperative acute kidney injury.
Therapeutic Nucleic Acids: Advances in Stimulus‐Responsive Polymeric Materials for Systemic Delivery of Nucleic Acids (Adv. Healthcare Mater. 4/2018)
Authors: Minjie Sun, Kaikai Wang, David Oupický
Journal: Advanced Healthcare Materials (2018)

Polymeric materials responsive to endogenous and exogenous stimuli promise to overcome multitude of barriers faced during systemic delivery of therapeutic nucleic acids. In article number 1701070, David Oupický and co-workers survey successful examples of enhanced nucleic acid delivery using polymers that respond to changes in pH, redox state, enzyme levels, hypoxia, reactive oxygen species, light, ultrasound, and hyperthermia.
Visualization of Breast Cancer Metabolism Using Multimodal Nonlinear Optical Microscopy of Cellular Lipids and Redox State
Authors: Jue Hou, Joshua Williams, Elliot L. Botvinick, Eric O. Potma, Bruce J. Tromberg
Journal: Cancer Research (2018)

Abstract Label-free nonlinear optical microscopy (NLOM) based on two-photon excited fluorescence (TPEF) from cofactors nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD+) is widely used for high-resolution cellular redox imaging. In this work, we combined three label-free NLOM imaging methods to quantitatively characterize breast cancer cells and their relative invasive potential: (i) TPEF optical redox ratio (ORR = FAD+/NADH + FAD+), (ii) coherent Raman scattering of cellular lipids, and (iii) second harmonic generation of extracellular matrix (ECM) collagen. 3D spheroid models of primary mammary epithelial (PME) cells and breast cancer cell lines (T47D and MDA-MB-231) were characterized based on their unique ORR and lipid volume fraction signatures. Treatment with 17β-estradiol (E2) increased glycolysis in both PME and T47D ER+ breast cancer acini. However, PME cells displayed increased lipid content with no effect on ECM, while T47D cells had decreased lipid storage (P &amp;lt; 0.001) and significant reorganization of collagen. By measuring deuterated lipids synthesized from exogenously administered deuterium-labeled glucose, treatment of T47D cells with E2 increased both lipid synthesis and consumption rates. These results confirm that glucose is a significant source for the cellular synthesis of lipid in glycolytic breast cancer cells, and that the combination of cellular redox and lipid fraction imaging endpoints is a powerful approach with new and complementary information content. Significance: These findings provide unique insight into metabolic processes, revealing correlations between cancer metastasis and cellular redox state, lipid metabolism, and extracellular matrix. Cancer Res; 78(10); 2503–12. ©2018 AACR.
RIGHT VENTRICULAR MECHANICAL DISPERSION BY STRAIN ECHOCARDIOGRAPHY IMPACTS PROGNOSIS IN SIGNIFICANT TRICUSPID REGURGITATION
Authors: Edgard Alexander Prihadi, Omar Pappalardo, Pieter van der Bijl, Rachid Abou, Elise Vollema, Nina Marsan, Victoria Delgado, Jeroen J. Bax
Journal: Journal of the American College of Cardiology (2018)
IMPLICATIONS OF LEFT VENTRICULAR ANEURYSM IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION: AN ANALYSIS FROM NATIONAL INPATIENT SAMPLE DATABASE
Authors: Bhaskar Bhardwaj, Varun Kumar, Nileshkumar Patel, Obai Abdullah, Sudarshan Balla, Martin Alpert, Albert Chan, Arun Kumar
Journal: Journal of the American College of Cardiology (2018)
Dosimetric analysis of distal esophageal adenocarcinoma patients treated by intensity-modulated proton therapy with small spot size.
Authors: Chenbin Liu, Terence Tai Weng Sio, Ronik S Bhangoo, William G. Rule, Helen J. Ross, Harshita Paripati, Dawn E. Jaroszewski, Staci Beamer, David Fleischer, Francisco Ramirez, Xiaoning Ding, Martin Bues, Jonathan Ben Ashman, Wei Liu
Journal: Journal of Clinical Oncology (2018)

159 Background: Intensity-modulated proton therapy (IMPT) with small spot size has the potential to reduce dose to normal tissues but also introduces new confounding factors such as setup uncertainty, range uncertainty, and interplay effects due to breathing motion. We investigated plan quality and robustness of IMPT with small spot size for distal esophageal adenocarcinoma (DEA). Methods: 19 patients with DEA treated by IMPT were retrospectively evaluated. Spot sizes ranged from 2 to 6mm, with spot spacing of 5mm. All plans were generated using a commercial treatment planning system. In-house-developed dose-evaluation software modeled time-dependent spot delivery to incorporate interplay effects. Dose-volume-histogram (DVH) indices were used to evaluate plan quality and robustness was evaluated using the DVH band method. Results: For plan quality, median values of clinical target volume D 95% and D 5% -D 95% (normalized to the prescribed doses), total lung mean dose, heart mean dose, and cord D max were 1.014, 0.035, 3.82Gy[RBE], 7.73Gy[RBE], 39.16Gy[RBE], respectively. For plan robustness, median band widths of the aforementioned DVH indices were 0.018, 0.048, 0.60Gy[RBE], 4.17Gy[RBE], and 2.36Gy[RBE], respectively. For interplay effects, median values of the aforementioned DVH indices were 0.99, 0.061, 4.07Gy[RBE], 7.87Gy[RBE], and 39.66Gy[RBE], respectively. Seven patients underwent esophagectomy after neoadjuvant chemoradiation, and five, three, and one of them achieved downstaging, near complete response, and pathologic complete response, respectively; R0 resection was achieved in all cases. For all patients, acute side effects were mostly limited to grades 1-2 only. The only grade 3 adverse events were related to feeding tube placement (8 patients); there were no RT-induced pneumonitis or other lung-related toxicities. Conclusions: IMPT plans with small spot size for DEA have good target dose coverage, homogeneity and normal tissue protection. Treatment plans are also robust to uncertainties and interplay effects. Early clinical results demonstrate low acute toxicity and encouraging clinical and pathologic response.