tbuckley/cabot-search huggingface dataset:
Abstract P3-15-04: Signalling pathways targeted by the <i>YangZheng Xiaoji</i> extract and the therapeutic implications in human breast cancer
Authors: WG Jiang, L Ye, S Owen, F Ruge, TA Martin, AJ Sanders, G Gao, C Wei, Y Wu, E Davies
Journal: Cancer Research (2018)

Abstract Background. Yangzheng Xiaoji is a formulation of Chinese medicine and has been used in the treatment of solid cancer as an adjuvant to chemotherapy by reducing the side effects to the patient. There has been evidence to show that the medicine has a direct biological role in cancer cells. In the present study, we sought to investigate the potential effects of the medicine on breast cancer cells and in particular aimed to identify the key targets and molecular pathways contributing to the anti-cancer effect of the medicine. Methods. Human breast cancer cell lines (BT549, BT20, MDA MB-231, MCF-7 and ZR 75-1) with varying invasiveness and receptor status were used. The soluble extract of Yangzheng Xiaoji, namely DME25 was used in the study. The effects of DME25 on the growth, toxicity and cellular migration were assessed. Signalling kinase changes were screened using kinase antibody array based array technologies. Kinases were also validated using phosphorylation based protein blotting. Results. Of the five breast cancer cell lines tested, Yangzheng Xiaoji extract DME25 showed little cytotoxicity over a broad range of concentrations. However, DME25 were able to markedly reduce the migration of the panel of breast cancer tested, without being toxic. Triple negative cells responded in a similar fashion with other cells. It was also noted that the adhesion of these cells were also inhibited by DME25. Using a protein kinase array, it was shown that a number of kinase complexes were inhibited by the medicine, notable ones including EGFR family kinases (reduced by 35%), Janus protein kinases (JAK) (by 57%), and Ras-related C3 botulinum toxin substrate (Rac1 or CDC42 GTPase) (by 49%) and Ribosomal protein S6 kinases (RSKs) (by 52%). Given the clinical significance of RSKs in human breast cancer, we further evaluated the role of RSK and RSK inhibitors in DME mediated cell functions and have demonstrated that both in triple negative breast cancer cells and receptor positive breast cancer cell lines, DME25 was able to synergistically enhance the effect of RSK2 inhibitor, SL1010-1, on the both the cellular migration and cell growth. Conclusion. Yangzheng Xiaoji has a broad and direct effect on the migration of breast cancer, an effect unrelated to hormone receptor status and independent of cytotoxicity. The medicine appears to target kinase pathway, particularly for the RSK kinases, suggesting an important clinical implication in the treatment of breast cancer. Citation Format: Jiang WG, Ye L, Owen S, Ruge F, Martin TA, Sanders AJ, Gao G, Wei C, Wu Y, Davies E. Signalling pathways targeted by the YangZheng Xiaoji extract and the therapeutic implications in human breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-15-04.
The sociocultural functions of episodic memory
Authors: Robyn Fivush
Journal: Behavioral and Brain Sciences (2018)

Abstract The functional use of episodic memories to claim epistemic truth must be placed within sociocultural contexts in which certain truths are privileged. Episodic memories are shared, evaluated, and understood within sociocultural interactions, creating both individual and group identities. These negotiated identities provide the foundation from which epistemic claims to truth can be made.
18F-NaF PET/CT Finding in a Patient With Abdominal Discomfort After Schistosomiasis
Authors: Wei Zhang, Li Chen, Qiang Wan, Yue Chen
Journal: Clinical Nuclear Medicine (2018)

A 77-year-old man with back pain and abdominal distention underwent F-NaF PET/CT examination to evaluate potential bone lesions. Multiple foci of increased activity were noted in the chest, which corresponded to bilateral ribs and suggested possible occult fractures. Surprisingly, increased F-NaF uptake was observed in the region of pelvis, which corresponded to calcification along the colon wall, a sequela of intestinal Japanese schistosomiasis that the patient experienced 30 years ago.
Peptide mimic for influenza vaccination using nonnatural combinatorial chemistry
Authors: John J. Miles, Mai Ping Tan, Garry Dolton, Emily S.J. Edwards, Sarah A.E. Galloway, Bruno Laugel, Mathew Clement, Julia Makinde, Kristin Ladell, Katherine K. Matthews, Thomas S. Watkins, Katie Tungatt, Yide Wong, Han Siean Lee, Richard J. Clark, Johanne M. Pentier, Meriem Attaf, Anya Lissina, Ann Ager, Awen Gallimore, Pierre J. Rizkallah, Stephanie Gras, Jamie Rossjohn, Scott R. Burrows, David K. Cole, David A. Price, Andrew K. Sewell
Journal: Journal of Clinical Investigation (2018)

Polypeptide vaccines effectively activate human T cells but suffer from poor biological stability, which confines both transport logistics and in vivo therapeutic activity. Synthetic biology has the potential to address these limitations through the generation of highly stable antigenic "mimics" using subunits that do not exist in the natural world. We developed a platform based on D–amino acid combinatorial chemistry and used this platform to reverse engineer a fully artificial CD8+ T cell agonist that mirrored the immunogenicity profile of a native epitope blueprint from influenza virus. This nonnatural peptide was highly stable in human serum and gastric acid, reflecting an intrinsic resistance to physical and enzymatic degradation. In vitro, the synthetic agonist stimulated and expanded an archetypal repertoire of polyfunctional human influenza virus–specific CD8+ T cells. In vivo, specific responses were elicited in naive humanized mice by subcutaneous vaccination, conferring protection from subsequent lethal influenza challenge. Moreover, the synthetic agonist was immunogenic after oral administration. This proof-of-concept study highlights the power of synthetic biology to expand the horizons of vaccine design and therapeutic delivery.
PROCEDURAL OUTCOMES OF MULTIPLE CTO INTERVENTION CARRIED OUT IN THE SAME PROCEDURE: INSIGHT FROM A MULTICENTER CTO REGISTRY
Authors: Peter Tajti, Dimitrios I. Karmpaliotis, Khaldoon Alaswad, Farouc Jaffer, Robert Yeh, Mitul Patel, Ehtisham Mahmud, James Choi, M. Nicholas Burke, Anthony Doing, Catalin Toma, Barry Uretsky, Elizabeth Holper, David Kandzari, Nicholas Lembo, Santiago Garcia, Oleg Krestyaninov, Dmitrii Khelimskii, Michalis Koutouzis, Jeffrey Moses, Ajay Kirtane, Ziad Ali, Bavana Rangan, Subhash Banerjee, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2018)
Correction: Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease
Authors: Stefan Uderhardt, Jochen A. Ackermann, Tobias Fillep, Victoria J. Hammond, Johann Willeit, Peter Santer, Manuel Mayr, Markus Biburger, Meike Miller, Katie R. Zellner, Konstantin Stark, Alexander Zarbock, Jan Rossaint, Irene Schubert, Dirk Mielenz, Barbara Dietel, Dorette Raaz-Schrauder, Cihan Ay, Thomas Gremmel, Johannes Thaler, Christian Heim, Martin Herrmann, Peter W. Collins, Gernot Schabbauer, Nigel Mackman, David Voehringer, Jerry L. Nadler, James J. Lee, Steffen Massberg, Manfred Rauh, Stefan Kiechl, Georg Schett, Valerie B. O’Donnell, Gerhard Krönke
Journal: The Journal of Experimental Medicine (2018)
Abstract OT1-05-01: A phase I/II, single arm, non-randomized study of ribociclib (LEE011), a CDK 4/6 inhibitor, in combination with bicalutamide, an androgen receptor (AR) inhibitor, in advanced AR+ triple-negative breast cancer
Authors: CA Santa-Maria, M Rampurwala, K Wisinski, D Toppmeyer, R O'Regan
Journal: Cancer Research (2018)

Abstract Background: Triple negative breast cancer (TNBC) is a heterogeneous disease encompassing distinct intrinsic molecular subtypes, including a luminal androgen receptor (AR) subtype, characteristically dependent on AR signaling. The AR is expressed in more than 50% of TNBCs. Bicalutamide is an oral, non-steroidal, AR antagonist, which has been studied in metastatic TNBC with a clinical benefit rate of 19% at 24 weeks. In preclinical models, cyclin dependant kinase (CDK) 4/6 inhibition has been shown to restore sensitivity to AR inhibition, and may thus be an important resistance mechanism. Ribociclib is an orally bioavailable, highly specific CDK4/6 inhibitor that induces cell cycle arrest, already approved in endocrine receptor positive breast cancers. We hypothesize that inhibition of CDK inhibition can enhance the activity of anti-androgen therapy in TNBC that express AR. Methods: We designed a phase I/II, single arm, non-randomized, open label study of the combination of bicalutamide with ribociclib in women with advanced AR-positive TNBC. The primary objective of the phase I component is to determine the maximum tolerated dose of the combination, and of the phase II component to assess the clinical benefit rate at 16 weeks. Secondary objectives include progression free and overall survival, objective response rates, and safety and tolerability. Exploratory objectives will be to assess AR quantification, localization and splice variants in circulating tumor cells, as well as quantification of pan and phospho proteins of Rb. Eligible patients must have measurable metastatic or unresectable AR-positive TNBC and have had no more than 1 line of systemic therapy for metastatic disease. The phase I study will be conducted using a 3+3 dose escalation schema, 12 to 18 patients are expected to enroll. The phase II component will utilize a Simon's two stage design, enrolling 24 patients for the first stage. At least 5 subjects must have clinical benefit by 16 weeks to proceed onto the second stage, which would enroll an additional 22 subjects for a total of 46 patients. The study will be powered to detect a clinical benefit rate of 40% with a power of 80% and a type I error rate of 10%. Contact dmusapatika@hoosiercancer.org for more information about the study. Citation Format: Santa-Maria CA, Rampurwala M, Wisinski K, Toppmeyer D, O'Regan R. A phase I/II, single arm, non-randomized study of ribociclib (LEE011), a CDK 4/6 inhibitor, in combination with bicalutamide, an androgen receptor (AR) inhibitor, in advanced AR+ triple-negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-05-01.
Junior doctors are set to take strike action, says BMA
Authors: Abi Rimmer
Journal: BMJ (2016)

Junior doctors are set to take three days of industrial action after negotiations between the association and the government over the terms of the junior doctor contract broke down on Monday 4 January, the BMA has said.

The association announced that the action would take place in January and February, after the government failed to meet junior doctors’ concerns over changes to the contract. It said that the government did not recognise the need for robust contractual safeguards …
Challenges in Pulmonary Hypertension: Controversies in Treating the Tip of the Iceberg. A Joint National Institutes of Health Clinical Center and Pulmonary Hypertension Association Symposium Report
Authors: Jason M. Elinoff, Richa Agarwal, Christopher F. Barnett, Raymond L. Benza, Michael J. Cuttica, Ahmed M. Gharib, Michael P. Gray, Paul M. Hassoun, Anna R. Hemnes, Marc Humbert, Todd M. Kolb, Tim Lahm, Jane A. Leopold, Stephen C. Mathai, Vallerie V. McLaughlin, Ioana R. Preston, Erika B. Rosenzweig, Oksana A. Shlobin, Virginia D. Steen, Roham T. Zamanian, Michael A. Solomon
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
T1 MAPPING PREDICTS ADVERSE CLINICAL OUTCOME IN MYOCARDITIS
Authors: Chirag Agarwal, Mario Rivera Rodriguez, Basera Sabharwal, Bing Yue, Eelin Wilson, Shuyang Fang, Allen Weiss, Rebecca Smoller, Jagat Narula, Valentin Fuster, Juan Badimon, Javier Sanz
Journal: Journal of the American College of Cardiology (2018)
IMPACT OF CHRONIC KIDNEY DISEASE AMONG DIABETIC PATIENTS WITH STABLE CORONARY DISEASE UNDERGOING SURGERY, ANGIOPLASTY OR MEDICAL TREATMENT IN A 10 YEAR FOLLOW-UP
Authors: Daniel Valente Batista, Whady Hueb, Jaime Linhares Filho, Eduardo Lima, Paulo Rezende, Diogo Azevedo, Eduardo Martins, Alexandre Hueb, Expedito Silva, Jose Ramires, Roberto Kalil Filho
Journal: Journal of the American College of Cardiology (2018)
Emergency management of severe burns
Authors: Cynthia Tsang
Journal: BMJ (2012)

The one day course in emergency management of severe burns is run centrally by the British Burns Association but can be done at a number of hospitals nationwide, including Birmingham, Swansea, and Nottingham. It aims to train you in the emergency assessment, resuscitation, and transfer of patients with severe burns.

The course is aimed at medical and nursing healthcare staff involved in the field of burn care, from members of burns units to staff working in isolated rural areas. The session I attended had a good mix of candidates, including foundation year 2 doctors, core surgical trainees and specialist registrars planning a career in plastic surgery, and senior clinical nurses from various burns units.

The experience of referring to and receiving patients at a …
Dutch to start presumed consent for organ donation in 2020
Authors: Tony Sheldon
Journal: BMJ (2018)

The Netherlands will introduce presumed consent for organ donation in July 2020, after a private member’s bill passed the Dutch Senate by just two votes, ending decades of debate.

The Dutch Society of Intensive Care (NVIC) was “delighted” with the Active Donor Registration Law, claiming that it would place less of a burden on next of kin. The Kidney Patients’ Association described it as a “milestone” that would save lives.

Under the new law all 18 year olds will …
Junior doctors’ strike is “totemic” of a system that undermines staff, says McNeil
Authors: Tom Moberly
Journal: BMJ (2016)

The junior doctors’ ongoing industrial action over contract changes is “totemic” of a system that undermines staff efforts to improve healthcare, the former chief executive of Addenbrooke’s Hospital has said.

Keith McNeil believes that the future leaders of the health service are being demoralised. “We’re getting them while they’re young and we’re disillusioning them, disengaging them, and disempowering them,” he told BMJ Careers .

McNeil left his job as chief executive of Cambridge University Hospitals NHS Foundation Trust, which runs Addenbrooke’s Hospital and the Rosie maternity hospital, last year. He made the …
Foundation allocation error affects thousands of medical students
Authors: Tom Moberly
Journal: BMJ (2013)

Final year medical students have been left confused and distressed after learning a day after they had received their foundation school allocation that the offers may be withdrawn.

Over 7200 medical students are having their situational judgment test (SJT) scores rechecked after an error in the marking of these papers was discovered.1 Students received details of their foundation school allocations on 25 February and were told about the error on 26 February.

Scores on the SJT, a multiple choice examination that requires candidates to rank clinical scenarios, are combined with an educational performance score to decide foundation school allocation. Students will be given new SJT scores and foundation school allocations at 9 am on Friday 8 March.

Clare Smyth, a final year medical student at the University of Glasgow, said that there had …
Extra funding is agreed for GP practices affected by MPIG changes
Authors: Abi Rimmer
Journal: BMJ (2014)

GP practices that have been affected by recent funding changes to the GP contract will receive extra financial support, NHS England has said.

The London office of NHS England said that a small number of practices across London that were most affected by the funding changes would receive additional financial support for 2014-15 and 2015-16. This support will be equal to the funding they would have received before the recent changes. A spokeswoman for NHS England said that the offer was specifically for London but that other area teams across the country would be making the same offer to practices that met the criteria. 

In 2013, as part of the agreement on the GP contract …
WHAT FACTORS INFLUENCE THE CHOICE OF APIXABAN, RIVAROXABAN, OR DABIGATRAN FOR STROKE PREVENTION AMONG ATRIAL FIBRILLATION PATIENTS IN REAL-WORLD CLINICAL PRACTICE? INSIGHTS FROM THE PROSPECTIVE SPRINT-AF REGISTRY
Authors: Andrew C.T. Ha, Christopher Labos, Mahesh Kajil, Michelle Tsigoulis, Jafna Cox, G.B. John Mancini, Paul Dorian, David Gladstone, Evan Lockwood, Ashfaq Shuaib, William Chan, Narendra Singh, Milan Gupta
Journal: Journal of the American College of Cardiology (2018)
EV-201 Study: A single-arm, open-label, multicenter study of enfortumab vedotin for treatment of patients with locally advanced or metastatic urothelial cancer who previously received immune checkpoint inhibitor therapy.
Authors: Jonathan E. Rosenberg, Elisabeth I. Heath, Peter H. O'Donnell, Noah M. Hahn, Arjun Vasant Balar, Elaina M. Gartner, Amal Melhem-Bertrandt, Daniel Peter Petrylak
Journal: Journal of Clinical Oncology (2018)

TPS4590 Background: Most patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC) treated with checkpoint inhibitor immunotherapy (CPI) will fail to achieve a durable response regardless of treatment setting (post-platinum or first-line cisplatin-ineligible). Enfortumab vedotin (EV), an antibody-drug conjugate, delivers the microtubule-disrupting agent monomethyl auristatin E to tumors expressing Nectin-4, which is overexpressed in mUC. Preliminary results from an ongoing phase 1 study of EV (Petrylak ASCO-GU 2018) showed that EV (1.25 mg/kg) was well-tolerated in pts with CPI-treated mUC (n = 67). Fatigue (55%), nausea (48%), and decreased appetite (45%) were the most commonly reported treatment-related AEs. Hyponatremia (n = 4, 6%) was the only AE grade ≥3 (regardless of attribution) in > 5% of the cohort; vomiting (n = 2, 3%) was the only treatment-related AE grade ≥3 occurring in ≥2 pts. Hyperglycemia, a new safety finding, emerged post-database cutoff; the protocol was revised. EV showed a confirmed objective response rate (ORR) of 31% in 55 of 67 evaluable pts (23.5% in pts with baseline liver metastases, n = 17) with most responses ongoing as of 02-Oct-2017. Nine pts with unconfirmed PR are pending response assessment. These encouraging results warrant further investigation in this population. Methods: This single-arm, open-label, multicenter phase 2 study (NCT03219333) evaluates the antitumor activity and safety of EV monotherapy in ~120 pts with la/mUC. Pts must have previously received a CPI and either have received prior platinum or be cisplatin-ineligible. Pts must have histologically or cytologically documented transitional cell carcinoma of the urothelium that progressed during or following receipt of most recent therapy. The primary objective is to determine antitumor activity as measured by ORR. Secondary objectives include assessment of duration of response, disease control rate, PFS, OS, and safety/tolerability. Pts must have tumor tissue available for exploratory analyses. Response is assessed per RECIST v1.1. Study enrollment began in Sep 2017. Clinical trial information: NCT03219333.
Rhizospheric microbial communities are driven by Panax ginseng at different growth stages and biocontrol bacteria alleviates replanting mortality
Authors: Linlin Dong, Jiang Xu, Lianjuan Zhang, Ruiyang Cheng, Guangfei Wei, He Su, Juan Yang, Jun Qian, Ran Xu, Shilin Chen
Journal: Acta Pharmaceutica Sinica B (2018)

The cultivation of Panax plants is hindered by replanting problems, which may be caused by plant-driven changes in the soil microbial community. Inoculation with microbial antagonists may efficiently alleviate replanting issues. Through high-throughput sequencing, this study revealed that bacterial diversity decreased, whereas fungal diversity increased, in the rhizosphere soils of adult ginseng plants at the root growth stage under different ages. Few microbial community, such as Luteolibacter, Cytophagaceae, Luteibacter, Sphingomonas, Sphingomonadaceae, and Zygomycota, were observed; the relative abundance of microorganisms, namely, Brevundimonas, Enterobacteriaceae, Pandoraea, Cantharellales, Dendryphion, Fusarium, and Chytridiomycota, increased in the soils of adult ginseng plants compared with those in the soils of 2-year-old seedlings. Bacillus subtilis 50-1, a microbial antagonist against the pathogenic Fusarium oxysporum, was isolated through a dual culture technique. These bacteria acted with a biocontrol efficacy of 67.8%. The ginseng death rate and Fusarium abundance decreased by 63.3% and 46.1%, respectively, after inoculation with B. subtilis 50-1. Data revealed that microecological degradation could result from ginseng-driven changes in rhizospheric microbial communities; these changes are associated with the different ages and developmental stages of ginseng plants. Biocontrol using microbial antagonists alleviated the replanting problem.
What is expected from a clinical attaché and how can one make the most of a clinical attachment?
Authors: Shaaz Mahboob
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>
GMC increases annual retention fees by 8%
Authors: Abi Rimmer
Journal: BMJ (2014)

The General Medical Council’s annual retention fees will rise by 8% in 2015.

From April 2015 the fee for registration with a licence will increase from £390 to £420, restoring the fee to the level it was at in 2010, the GMC has said. The provisional registration fee will remain at £90, and the low income threshold will remain at £32 000. Doctors whose income …
Doctors’ leaders brand new scoring system for GPs as “too crude”
Authors: Adrian O’Dowd
Journal: BMJ (2012)

GPs and their practices are to be scored out of 10 for patient experience under new data being published in England for the first time. Doctors’ leaders, however, have described the data as too simplistic, lacking detail, and creating a risk of overwhelming patients with information.

Data on more than 8000 GP practices will be used to form a new measure of patient experience for each surgery based on several areas including convenience in securing an appointment; length of time patients have to spend waiting in reception; opening hours; and skill of doctors and nurses at explaining things and listening to patients.

Each …
My GP registrar year
Authors: Emma Hawkins
Journal: BMJ (2005)

I have recently finished my GP registrar training. It has been the best experience of my professional career so far and I feel I have found my niche in general practice after years of floundering within the NHS. But my training was not without its hitches—one of which left me unable to work for five months. Let me explain.

“I always advise new registrars to send in their paperwork at the start of the job”. This was the advice I received four months after finishing my training. I had naively waited until all my paperwork was complete at the end of my training to submit it to the deanery and then on to the JCTGP (Joint Committee on Training in General Practice). Nothing prepared …
Antibiotic Prophylaxis and Recurrent Urinary Tract Infection in Children (vol 361, pg 1748, 2009)
Authors: J. C. Craig, J. M. Simpson, G. J. Williams, A. Lowe, G. J. Reynolds, S. J. McTaggart, E. M. Hodson, J. R. Carapetis, N. E. Cranswick, G. Smith, L. M. Irwig, P. H. Y. Caldwell, S. Hamilton, L. P. Roy
Journal: New England Journal of Medicine (2010)