tbuckley/cabot-search huggingface dataset:
Abstract P5-03-09: Breast cancer promotion by IL-6-mediated cross-talk between human preadipocyte and breast dutal carcinoma<i> in situ</i>
Authors: HS Kim, M Jung, SK Choi, WK Moon
Journal: Cancer Research (2018)

Abstract While the role of adipocyte, one of the major components of the breast microenvironment, has been well documented in breast cancer progression, the preadipocytes function to favor early-stage breast cancer progression at the molecular level is not fully elucidated. To delineate the role of human preadipocyte (hPreAd) on breast cancer progression, we investigated a cross-talk between human breast dutal carcinoma in situ (DCIS) and hPreAd in in vivo culture and in vivo tumor model. On Co-culture system with DCIS cell line MCF10DCIS.com and primary hPreAd, proliferation, migration and invasion of MCF10DCIS.com was promoted by hPreAd. Conditioned medium (CM) of hPreAd activated signaling molecules (AKT1, ERK1/2, mTOR, FAK and STAT3) in MCF10DCIS.com. hPreAd expressed fibroblast specific protein 1 (FSP1) and alpha-smooth muscle actin (α-SMC), and increased IL-6 secretion by co-culture or MCF10DCIS.com CM, whereas adipocyte differentiation of hPreAd was suppressed by co-culture. A neutralizing antibody (NAb) of IL-6 or IL-6 receptor suppressed the MCF10DCIS.com proliferation and migration enhanced by co-culture of hPreAd. In xenograft tumor model, tumor growth of MCF10DCIS.com was enhanced by co-injection with hPreAd. IL-6 NAb had minimal effect in xenografts with MCF10DCIS.com alone; however, in models co-administered with hPreAd, IL-6 NAb had more potent effects on tumor inhibition. Taken together, our study suggests that IL-6-mediated cross-talk between preadipocyte and breast DCIS can exert the breast cancer progression at early-stage. Deciphering the cellular and molecular mechanisms behind the preadipocyte-breast DCIS crosstalk might provide new targets for improving diagnosis/prognosis and for the design of innovative therapeutic strategies. Citation Format: Kim HS, Jung M, Choi SK, Moon WK. Breast cancer promotion by IL-6-mediated cross-talk between human preadipocyte and breast dutal carcinoma in situ [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 P5-03-09.
Abstract MP20: The Discriminatory Characteristics of Neighborhood Socioeconomic Status in Predicting Cardiovascular Disease in Electronic Health Record Based Studies Differs by Age
Authors: Nrupen A Bhavsar, Aijing Gao, Neha Pagidipati, Matthew Phelan, Benjamin Goldstein
Journal: Circulation (2018)

Introduction: Recent studies report an association between neighborhood residence and health outcomes. There is less information on the relative utility of neighborhood socioeconomic status (nSES) in models that predict future health outcomes and the impact that age may have on this. Objective: To quantify if nSES data alone or in concert with electronic health record (EHR) data can improve risk prediction for myocardial infarction (MI) and stroke beyond current models. Methods: Neighborhood SES was derived using the AHRQ SES index. Clinical and demographic data was obtained from the EHR of patients seen at the Duke University Health System from 2009-2015; it was split into a training set (2009-2012) and testing set (2012-2015). Age (in yrs) was categorized as young (18-44), middle age (45-64), and old (≥65). Logistic regression models were fit for each outcome over 6 time horizons (30, 90, &amp; 180 days; 1, 2, &amp; 3 years) using machine learning methods (least absolute shrinkage and selection operator [LASSO]) for model selection to determine if nSES improved discrimination, as measured by the c-statistic. Results: Of 106703 patients, 63% were female, 41% were Black, 2.6% had CVD, 12% had diabetes, and 29% had hypertension at baseline with mean age of 47 years. The majority of the correlation between EHR variables and nSES (r 2 =0.31) was explained by demographic information within the EHR (r 2 =0.29; p&lt;0.01). In LASSO models incorporating EHR and SES data, EHR variables (e.g., comorbidities) were frequently selected while nSES variables (e.g., AHRQ SES index) were rarely chosen. The c-statistic for predicting MI and stroke when using nSES data with and without EHR data was higher in middle aged and older patients as compared to younger patients (Figure). Conclusions: The added value of nSES was less than expected as much variability in nSES may be phenotyped through demographic information in the EHR. In discrete instances, nSES can improve risk prediction but varies by age, clinical outcome, and time horizon.
Emergency airway study day
Authors: Ananth Vijendren
Journal: BMJ (2012)

A “difficult airway” is defined as a clinical situation in which a trained medical practitioner has problems using a face mask on a patient and performing endotracheal ventilation.1 Its incidence during routine anaesthesia has been estimated at 3-18%, with higher figures reported in emergencies.2 Failure to recognise and intervene appropriately in a case of a patient with a difficult airway can have catastrophic repercussions. The Difficult Airway Society has therefore produced guidelines and algorithms that include recommending the creation of a surgical airway in such situations.3 However, this procedure lies outside the comfort zone of most trainees, being performed infrequently even by experienced clinicians.

In addition, postoperative airway management requires subspecialised knowledge and skills that doctors from other specialties who are providing cross cover …
Sumit R Majumdar: Clinician-researcher who aimed to improve patient care through knowledge transfer
Authors: Janice Hopkins Tanne
Journal: BMJ (2018)

Sumit R Majumdar (“Me2”) was born in in Tucson, Arizona, but spent most of his life and career in Alberta, Canada. As a professor in the University of Alberta’s department of medicine, he combined being a clinician, teacher, and researcher. “People in Boston couldn’t believe it was possible, but he did it,” said Robert Fletcher, one of his mentors at Harvard Medical School and later a colleague.

His other mentor at Harvard (where Majumdar was a visiting professor), Stephen B Soumerai, said, “I never knew anyone who was more of a gentleman than Me2. He never preached, but he was not afraid to tell you what he thought, and he was usually right. He never became angry, but he convinced you, as a consummate teacher, …
GLOBAL LONGITUDINAL STRAIN AND MECHANICAL DISPERSION IMPROVES RISK STRATIFICATION OF MALIGNANT VENTRICULAR ARRHYTHMIAS AND MAJOR ADVERSE CARDIAC EVENTS OVER EJECTION FRACTION ALONE
Authors: Rebecca Perry, Sanjana Patil, Matthew Horsfall, Christian Marx, Derek Chew, Majo Joseph, Anand Ganesan, Andrew McGavigan, Gaetano Nucifora, Joseph Selvanayagam
Journal: Journal of the American College of Cardiology (2018)
Separation and simultaneous quantitation of PGF2α and its epimer 8-iso-PGF2α using modifier-assisted differential mobility spectrometry tandem mass spectrometry
Authors: Chunsu Liang, Hui Sun, Xiangjun Meng, Lei Yin, J. Paul Fawcett, Huaidong Yu, Ting Liu, Jingkai Gu
Journal: Acta Pharmaceutica Sinica B (2018)

Because many therapeutic agents are contaminated by epimeric impurities or form epimers as a result of metabolism, analytical tools capable of determining epimers are increasingly in demand. This article is a proof-of-principle report of a novel DMS–MS/MS method to separate and simultaneously quantify epimers, taking PGF2α and its 8-epimer, 8-iso-PGF2α, as an example. Good accuracy and precision were achieved in the range of 10–500 ng/mL with a run time of only 1.5 min. Isopropanol as organic modifier facilitated a good combination of sensitivity and separation. The method is the first example of the quantitation of epimers without chromatographic separation.
Single-cell mass cytometry reveals distinct populations of brain myeloid cells in mouse neuroinflammation and neurodegeneration models
Authors: Bahareh Ajami, Nikolay Samusik, Peter Wieghofer, Peggy P. Ho, Andrea Crotti, Zach Bjornson, Marco Prinz, Wendy J. Fantl, Garry P. Nolan, Lawrence Steinman
Journal: Nature Neuroscience (2018)
UTILITY OF AN ADDITIVE FRAILTY TESTS SCORE FOR MORTALITY RISK ASSESSMENT FOLLOWING TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Ron Waksman, Kyle Buchanan, Arik Steinvil, Elizabeth Bond, M. Chadi Alraies, Micaela Iantorno, Deepakraj Gajanana, Toby Rogers, Linzhi Xu, Rebecca Torguson, Petros Okubagzi, Itsik Ben-Dor, Lowell Satler
Journal: Journal of the American College of Cardiology (2018)
Change in liver function as measured by change of Child Pugh Score to predict survival in patients with advanced hepatocellular carcinoma (HCC) during the treatment course.
Authors: Petra Prins, Titiksha Sharma, Kyung S Kim, Prarthna V Bhardwaj, Noah Collins, Emily Lu, Anna Bowie, Marcella Fegler, Kathrine Lee, Andrew Yang, Aiwu Ruth He
Journal: Journal of Clinical Oncology (2018)

310 Background: HCC is the sixth most common cancer and the second leading cause of cancer-related death worldwide. Most HCCs develop in severely damaged liver. Methods: The effect of multiple treatment options on liver function (LF) and disease outcome of patients (pts) with HCC (n = 380) were examined retrospectively. Pt LF (Child Pugh score [CPS]) was assessed at time of diagnosis (dx) and then after treatment. Kaplan Meier with log rank and Chi square test was used for comparisons. Results: Our cohort of 380 pts had the following demographics: 74% were male and 26% female; 42% were African American, 26% Caucasian, 13% Asian, and 8% undetermined. The mean age at dx was 62.7 yrs; 17% and 61% of pts were between 40-55 and 56-70 yrs, respectively. Only 2% were below 40 yrs, and 19.6% were above 70 yrs of age. About half of pts smoked (55%) or drank (54%). Regarding viral infection, 17% had Hep B, 52% Hep C, 3% both, and 26% neither. Risky behavior correlated with age of dx: pts aged 56-70 yrs of age had the highest of both (p &lt; 0.05). Cirrhosis and vascular invasion were seen in 66% and 40% of pts, respectively. Stage I/II HCC was seen in 38% and stage III/IV in 68% of pts. Median OS was significantly higher for stage I/II pts (p &lt; 0.001). Pts who had no change or improvement in LF had longer median OS vs. pts who had declining LF (p &lt; 0.001). Considering all treatment scenarios including local and systemic therapy, LF improved in 13%, did not change in 41%, and worsened in 46% of pts. LF decline in pts receiving various treatments was as follows: 53%, sorafenib (SFB); 39%, TACE; 53% radiation; 58% TACE/Y-90/SFB; and 32%, immunotherapy independent of prior treatment. However the degree in LF decline, as dictated by a ΔCPS of &gt; 4, 3 to 4, or 1 to 2 points, did not by itself correlate with significant changes in median OS. Conclusions: The outcome of pts with HCC depends on disease stage and LF. Most pts experience LF decline during treatment. The degree of LF decline is independent of median OS, but maintaining LF is significantly beneficial for OS. Balancing survival benefit with liver toxicities is critical to the successful treatment of pts with advanced HCC.
SEX DIFFERENCES AND ADENOSINE FREE CORONARY PRESSURE INDICES: A CONTRAST SUBSTUDY
Authors: Sonia Shah, Frederik M. Zimmermann, Nils Johnson, Takeshi Nishi, Yuhei Kobayashi, Nils Witt, Colin Berry, Allen Jeremias, Bon-Kwon Koo, Giovanni Esposito, Gilles Rioufol, Seung-Jung Park, Keith Oldroyd, Emanuele Barbato, Nico Pijls, Bernard De Bruyne, William Fearon
Journal: Journal of the American College of Cardiology (2018)
I will be taking the Professional and Linguistic Assessments Board test part 2 next summer. How should I prepare my CV for getting a clinical attachment?
Authors: John Adsett
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>
THE A-BODY-SHAPE-INDEX AND TYPE 2 DIABETES ARE MUTUALLY INDEPENDENT PREDICTORS OF CARDIOVASCULAR EVENTS RISK IN ANGIOGRAPHIED CORONARY PATIENTS
Authors: Alexander Vonbank, Christoph Saely, Christina Lins, Daniela Zanolin, Andreas Leiherer, Axel Muendlein, Heinz Drexel
Journal: Journal of the American College of Cardiology (2018)
Sodium bicarb vs sodium chloride, and acetylcysteine vs placebo, did not differ for adverse events after angiography
Authors: Anthony P. Carnicelli, Christopher B. Granger
Journal: Annals of Internal Medicine (2018)

Source Citation Weisbord SD, Gallagher M, Jneid H, et al.; PRESERVE Trial Group. Outcomes after angiography with sodium bicarbonate and acetylcysteine. N Engl J Med. 2017 Nov 12. [Epub ahead of print]. 29130810
Sex and degree of severity influence the prognostic impact of anemia in primary myelofibrosis: analysis based on 1109 consecutive patients
Authors: Maura Nicolosi, Mythri Mudireddy, Terra L. Lasho, Curtis A. Hanson, Rhett P. Ketterling, Naseema Gangat, Animesh Pardanani, Ayalew Tefferi
Journal: Leukemia (2018)
Erratum: Mutations in the protein tyrosine kinase gene, PTPN11, cause Noonan syndrome (Journal of Vascular Technology (2001) 29 (465-468))
Authors: M. Tartaglia, E. L. Mehler, R. Goldberg, G. Zampino, H. G. Brunner, H. Kremer, I. Van der Burgt, A. H. Crosby, A. Ion, S. Jeffery, K. Kalidas, M. A. Patton, R. S. Kucherlapati, B. Gelb
Journal: Nature Genetics (2001)
STRICT GLYCEMIC CONTROL ATTENUATES THE PROGRESSION OF CORONARY ARTERY CALCIFICATION IN ASYMPTOMATIC SUBJECTS WITH DIABETES MELLITUS
Authors: Ki-Bum Won, Su-Yeon Choi, Eun Ju Chun, Jidong Sung, Hae-Ok Jung, Hyuk-Jae Chang
Journal: Journal of the American College of Cardiology (2018)
The Current Landscape of 3D In Vitro Tumor Models: What Cancer Hallmarks Are Accessible for Drug Discovery?
Authors: Darren Rodenhizer, Teresa Dean, Elisa D'Arcangelo, Alison P. McGuigan
Journal: Advanced Healthcare Materials (2018)

Abstract Cancer prognosis remains a lottery dependent on cancer type, disease stage at diagnosis, and personal genetics. While investment in research is at an all‐time high, new drugs are more likely to fail in clinical trials today than in the 1970s. In this review, a summary of current survival statistics in North America is provided, followed by an overview of the modern drug discovery process, classes of models used throughout different stages, and challenges associated with drug development efficiency are highlighted. Then, an overview of the cancer hallmarks that drive clinical progression is provided, and the range of available clinical therapies within the context of these hallmarks is categorized. Specifically, it is found that historically, the development of therapies is limited to a subset of possible targets. This provides evidence for the opportunities offered by novel disease‐relevant in vitro models that enable identification of novel targets that facilitate interactions between the tumor cells and their surrounding microenvironment. Next, an overview of the models currently reported in literature is provided, and the cancer biology they have been used to explore is highlighted. Finally, four priority areas are suggested for the field to accelerate adoption of in vitro tumour models for cancer drug discovery.
BMA urges Hunt to lift imposition and resume talks
Authors: Abi Rimmer
Journal: BMJ (2016)

After the two days of full strike action by junior doctors this week, the BMA has written to England’s health secretary, Jeremy Hunt, offering to return to negotiations if the threat of imposition of the contract is lifted.

The letter from Johann Malawana, chair of the BMA’s Junior Doctors Committee, also highlighted the outstanding issues remaining in the contract.1

The letter was sent after the two days of strike action by junior …
How, where, and when
Authors: Tom Moberly
Journal: BMJ (2014)

Developments in technology, society, and medical practice have led to enormous changes in how doctors work, where they work, and also when they work. This week Adam Moreton looks at the history of efforts to reduce doctors’ working hours (http://careers.bmj.com/careers/advice/view-article.html?id=20019902). He shows that concessions to improve working conditions have not been given easily by the profession’s paymasters. Changes to doctors’ …
METABOLIC SYNDROME AS A PREDICTOR OF CARDIOVASCULAR MORTALITY IN THE CARMELA-CHILE STUDY: BETTER THAN THE ACC/AHA AND THE CHILEAN-MODIFIED FRAMINGHAM RISK SCORES
Authors: Monica Acevedo, Giovanna Valentino, Lorena Orellana, Marcela Adasme, Maria Jose Bustamante, Fernando Baraona, Carlos Navarrete
Journal: Journal of the American College of Cardiology (2018)
Phacomatosis pigmentokeratotica: a case of <i>HRAS</i> mosaicism causing rhabdomyosarcoma
Authors: M. Prieto-Barrios, R. Llamas-Martin, V. Velasco-Tamariz, A. Calleja-Algarra, Y. Ruano, P.L. Ortiz-Romero, J.L. Rodriguez-Peralto
Journal: British Journal of Dermatology (2018)

A 17‐year‐old male presented with a large sebaceous naevus (SN) comprising part of his right face and scalp and a speckled lentiginous naevus (SLN) on his left trunk, hip, neck and scalp with a checkerboard pattern. His right oral hemimucosa showed extensive papillomatous lesions, which were contiguous with the upper‐lip SN lesions. He also showed extracutaneous manifestations including cardiac, musculoskeletal and ocular alterations. Internally, he had developed two primary rhabdomyosarcomas. DNA samples of the SN, SLN, oral papillomatous hyperplasia and both rhabdomyosarcomas were analysed by Sanger sequencing. An HRAS c.37G>C mutation was detected in all of them. Skin and blood DNA were wild‐type. Phacomatosis pigmentokeratotica (PPK) is characterized by the association of an SN with a papular naevus spilus and extracutaneous manifestations. Until recently, the aetiopathogenetic hypothesis of didymosis was accepted. However, in 2013 Groesser et al. proved the existence of an activating HRAS mutation as the cause of this syndrome. A higher incidence of cancer has been observed in germline RASopathies. Furthermore, up to 30% of human cancers show dysregulation of the Ras–Raf–MEK–ERK pathways. In our patient, an HRAS mosaic mutation explains not only the cutaneous but also the extracutaneous manifestations. To our knowledge this is the first described case of PPK in which the existence of an HRAS mosaic mutation is the confirmed cause of rhabdomyosarcoma. Furthermore, the HRAS c.37G>C mutation has never been related to any type of rhabdomyosarcoma. Mosaicisms could be underdiagnosed causes of childhood tumours. As dermatologists we stand in a privileged position of being able to detect these alterations.
Abstract P3-06-09: Discovery of novel oridonin-derivatives for the treatment of metastatic breast cancer
Authors: D Li, Z Zhang, Y Ding, Z Zheng, J Dong, H Kim, J Xu, H Chen, J Zhou, Q Shen
Journal: Cancer Research (2018)

Abstract Metastasis to other organs is the major cause of death from breast cancer. The 5-year survival rate is approximately 99% for localized breast cancer, but sharply drops to approximately 26% for patients with distant metastasis. However, there are currently no effective, targeted therapies available for treating metastatic breast cancer. Oridonin, a complex ent-kaurane diterpenoid isolated from Chinese traditional herb Rabdosia rubescens, has demonstrated great potential in the treatment of various human cancers. However, relatively low aqueous solubility and bioavailability limited its development into clinical applications. Herein, a number of novel nitrogen-enriched heterocyclic oridonin derivatives and dienone analogs such as YD0514, CYD0618, and CYD0686 have been generated from oridonin. These derivative analogs showed improved anti-proliferation effects against breast cancer cells, compared to oridonin. YD0514, CYD0618, and CYD0686 also displayed significant suppression of migration and invasion in MDA-MB-231 cell, a highly metastatic triple-negative breast cancer cell line. Furthermore, YD0514, CYD0618 and CYD0686 also inhibited the endothelial adhesion of GI101 and its derived, highly metastatic sublines, to the endothelium. We next found that YD0514, CYD0618, and CYD0686 can significantly inhibit the expression and phosphorylation of FAK and block the expression of integrin family members in those highly metastatic breast cancer cell lines. Further pathway analysis demonstrated that YD0514, CYD0618, and CYD0686 inhibited cellular motility potentially by decreasing RHOA/ROCK signaling pathway. Our findings suggest that novel oridonin-derivatives, YD0514, CYD0618, and CYD0686 have the great potential to be developed as effective therapeutics for the treatment of metastatic breast cancer. This work was supported by Grants P50 CA097007, and P30DA028821 (JZ) from the NIH, CPRIT (JZ), John Sealy Memorial Endowment Fund (JZ), DFI Grants from MD Anderson Cancer Center (QS), and Holden Family Research Grant in BC Prevention (QS). Citation Format: Li D, Zhang Z, Ding Y, Zheng Z, Dong J, Kim H, Xu J, Chen H, Zhou J, Shen Q. Discovery of novel oridonin-derivatives for the treatment of metastatic 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 P3-06-09.
Treatment outcomes in newly diagnosed malignant glioma in elderly patients
Authors: Muhammad Dherijha, Likhith Alakandy, Chris Barrett
Journal: Neuro-Oncology (2018)

Treatment Outcomes in newly diagnosed malignant glioma in elderly patients - A 4years retrospective analysis M.S.A Dherijha1, Ali Rajabian2, C.Barrett2L.Alakandy21Salford Royal Hospital, Manchester 2Institute of Neuroscience, Queen Elizabeth University Hospital Glasgow Introduction: The number of GBMs discussed in MDT is increasing as the prevalence of GBM is known to increase with age and overall population is ageing. There are few evidence based established protocols of optimum management of such cases. We aimed to assess the outcome of various modalities of treatments and their combinations. MethodRetrospective analysis of GBM discussed in neurooncology MDT of Institute of Neuroscience Glasgow between 2011–2014 with prospective follow-up. Data included the performance status at presentation and modalities of treatment combinations offered. Outcomes measured by survival time and functional status after aggressive therapies.Inclusion criteria was age above 70.Results: 126 patients were followed M:F ratio 54:46. Median age was 77 (70–90). 35% (n=44) were offered best supportive care due to poor performance, 3% (n=4) had only palliative radiotherapy, 61%(n=78) were offered combined surgery and oncological therapies. That ranged between biopsy alone, debulking and adjuvant chemoradiotherapy. Median Survival rate for best supportive care was 3.2 months, whist for palliative radiotherapy alone was 6.1 months and for combined surgical and oncological treatmentwas 11.6 months. A further 12%(n=16) were not offered oncological therapy after rediscusson in MDT following their surgical intervention with survival of 4.4 months.Conclusion Combined modality treatment clearly has survival benefits even for patients above 70. It can be targeted better by taking into consideration their presenting performance status and other comorbidities in MDT settings.
MICROBIOLOGY OF ACUTE SEVERE AORTIC REGURGITATION COMPLICATING INFECTIVE ENDOCARDITIS
Authors: Andrew Higgins, Serge Harb, Bo Xu, Paul Cremer, Yuping Wu, Gosta Pettersson, Steve Gordon, Nabin Shrestha, Brian Griffin, Wael Jaber, Venu Menon
Journal: Journal of the American College of Cardiology (2018)