tbuckley/cabot-search huggingface dataset:
Influence of solvent mixtures on HPMCAS-celecoxib microparticles prepared by electrospraying
Authors: Adam Bohr, Yingya Wang, Moritz Beck-Broichsitter, Mingshi Yang
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Hypromellose acetate succinate (HPMCAS) microparticles containing the poorly-water soluble drug celecoxib (CEL) were prepared by electrospraying intended for oral drug delivery. Various solvent mixtures with different solubility for CEL and HPMCAS were used to induce changes in the polymer structural conformation of the microparticles. The performance of the prepared microparticles was evaluated by studying the solid state from, particle size and morphology, radial drug distribution and drug release. CEL was amorphous in all electrosprayed HPMCAS microparticles. The particle size and morphology was dependent on the solubility of HPMCAS in the solvent mixture used with poorer solvents resulting in smaller microparticles with rougher appearance. The CEL distribution on the particles surface was relatively homogeneous and similar for all microparticles. Drug release from the microparticles was observed at a higher rate depending on the solubility of HPMCAS in the solvent used for electrospraying, and in all cases an at least 4-fold higher rate was observed compared with the crystalline drug. Drug precipitation from the supersaturated solution was inhibited by HPMCAS for all microparticles based on its parachute effect while crystalline CEL did not reach supersaturation. This study demonstrated that electrospraying can be used to produce microparticles with tailored properties for pharmaceutical application by adjusting solvent selection.
SHORT AND LONG TERM RISK OF CONGESTIVE HEART FAILURE IN BREAST CANCER AND LYMPHOMA PATIENTS COMPARED TO CONTROLS: AN EPIDEMIOLOGIC STUDY
Authors: Carolyn Larsen, Harika Dasari, Maria C. Arciniegas Calle, Juan Rico Mesa, Christopher Scott, Carrie A. Thompson, James Cerhan, Tufia C. Haddad, Matthew P. Goetz, Joerg Herrmann
Journal: Journal of the American College of Cardiology (2018)
Abstract P3-03-02: ER dependent breast cancer phenotype in <i>BRCA</i> <i> 1/2</i> carriers
Authors: TY Peretz, A Zick, K Luna, A Grinshpun, A Sonneblick, B Iziely, TG Hamburger, S Cohen, AM Granit, M Dvir, S Rosenberg
Journal: Cancer Research (2018)

Abstract Background: Hereditary breast cancer (HBC) comprises more than 10% of all breast cancers (BC). Mutations in the BRCA1/2 genes are found in approximately half of HBC patients. The majority of BRCA1 associated tumors are ER, PR and HER2 negative with basal-like expression pattern. BRCA2 associated tumors are mostly ER positive (ER+). In the present study we aim to further explore clinical and molecular characteristics of BRCA associated BC in 3 different cohorts. Methods: Three different BC databases (DB) were evaluated: (i) Hadassah oncogenetic BC DB (n=4429); (ii) Nick-Zainal et al. BC DB (n=560), and (iii) METABRIC BC DB (n= 1980). We tested for differences in age at diagnosis between BRCA positive (BRCA+) and BRCA negative (BRCA-) patients with either ER+ or ER negative (ER-) tumors. Point mutation analysis was performed in cohorts ii &amp; iii and mRNA differential expression (DEA) and pathway analysis were performed in cohort iii, using Ingenuity Pathway Analysis (IPA). Results: Age (years) at diagnosis for cohorts i, ii,&amp;iii respectively, for ER+ PT:BRCA1-44, NA, 60; for BRCA2-49, 48, 64; for BN – 53, 56, 63. For ER-: BRCA1-42, 42, 47; for BRCA2-48, 52, 49; for BN-49, 54, 56. For cohorts ii&amp;iii, higher frequencies of TP53 and PIK3Ca mutations were found among BRCA+&amp;BRCA-, respectively. DEA was performed between BRCA+&amp;BRCA- in ER- tumors: the major activated pathways involved cancer related processes and were highly significant (up to p=1e-7.5, FDR=1e-4.5). Surprisingly - the most significant pathway was Estrogen Mediated S-phase Entry and the most activated upstream regulator was ERBB2. Similar evaluation in ER+ showed mostly differences in immune related pathways (differences not statistically significant). Conclusions: Younger age at presentation was observed in BRCA1 vs. BRCA2 patients. No age differences were observed between ER+&amp;ER- PT in cohort i&amp;ii, in cohort iii ER- BRCA+ Patients were younger than ER+ BRCA+ (similar age as ER+ BRCA-). BRCA+ show different mutational profile than BRCA-. ER+ BRCA+ and BRCA- show similar genomic characteristics. By contrast, for ER- BRCA+ differs markedly from BRCA-. This might imply that BRCA+ associated tumors consist of two genomically distinct subtypes: (i) ER-, and (ii) ER+. The results may shed light on possible somatic factors which affect the development of BC BRCA+ and carry preventive and therapeutic implications. Citation Format: Peretz TY, Zick A, Luna K, Grinshpun A, Sonneblick A, Iziely B, Hamburger TG, Cohen S, Granit AM, Dvir M, Rosenberg S. ER dependent breast cancer phenotype in BRCA 1/2 carriers [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 P3-03-02.
Discharge Destination and Disparities in Postoperative Care
Authors: Robert E. Burke, Said A. Ibrahim
Journal: JAMA (2018)

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I am a medical doctor from Greece and I am interested in doing paediatrics. I have worked for a year as a rural doctor and for seven months in adult intensive care medicine. I have no previous experience in paediatrics and currently I am working on my thesis. Which is the best position to start from in the United Kingdom?
Authors: Elitham B Turya
Journal: BMJ (2004)

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 (www.bmjcareers.com/advicezone) 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.
Planning an “F3” year: opportunities and considerations for aspiring surgeons
Authors: Matthew John Fell, Matthew Robert Frederick Jaring, Kenneth Russell MacKenzie
Journal: BMJ (2013)

Often termed an “F3,” a year away from the UK training pathway after the second year of foundation training is an increasingly popular option for doctors in training. <b>Matthew Fell and colleagues</b> look at the options available and discuss what aspiring surgeons should consider
Sixty seconds on . . . malnutrition
Authors: Susan Mayor
Journal: BMJ (2018)

No, much closer to home—in UK hospitals, in fact. The Telegraph ’s recent headline summed things up: “Record numbers of patients are dying malnourished in NHS hospitals with almost one case a day.” Charities slammed the latest figures as “shocking,” urging hospitals to do more to ensure that vulnerable elderly patients receive help with eating and drinking.

Malnutrition was the underlying cause or a contributory factor in 351 deaths in NHS …
Letter by Koh Regarding Article, “Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors)”
Authors: Kwang Kon Koh
Journal: Circulation (2018)
Reply to: “Pitfalls in the non-invasive assessment of liver fibrosis with eLIFT-FM VCTE algorithm” and to “Application of the new eLIFT test for the non-invasive diagnosis of advanced liver fibrosis in people with type 2 diabetes”
Authors: Jérôme Boursier, Victor de Ledinghen, Vincent Leroy, Paul Calès
Journal: Journal of Hepatology (2017)
APABETALONE (RVX-208) MODULATES EPIGENETIC PROCESSES IN MONOCYTES AND ENDOTHELIAL CELLS AFFECTED BY DIABETES MELLITUS AND DIET THAT ENHANCE RISK OF CARDIOVASCULAR DISEASE (CVD)
Authors: Christopher Halliday, Laura Tsujikawa, Ewelina Kulikowski, Cyrus Calosing, Sylwia Wasiak, Dean Gilham, Jan Johansson, Mike Sweeney, Norman Wong
Journal: Journal of the American College of Cardiology (2018)
IS SPONTANEOUS PRETERM DELIVERY ASSOCIATED WITH IMPAIRED VASCULAR FUNCTION?
Authors: Margo B. Minissian, Sarah Kilpatrick, JoAnn Eastwood, Kathryn J. Sharma, Chrisandra Shufelt, Michael Luu, Janet Wei, Lynn Doering, C. Noel Bairey Merz
Journal: Journal of the American College of Cardiology (2018)
HEMODYNAMIC PROFILE AND ECHOCARDIOGRAPHIC OUTCOMES AT 1 YEAR OF THE LOTUS TRANSCATHETER AORTIC VALVE IN HIGH AND EXTREME SURGICAL RISK PATIENTS: AN ANALYSIS FROM THE REPRISE III RANDOMIZED CONTROLLED TRIAL
Authors: Federico M. Asch, Mani Vannan, Siddharth Singh, Bijoy Khandheria, Stephen Little, Dominic Allocco, Ian Meredith, Ted Feldman, Michael Reardon, Neil Weissman
Journal: Journal of the American College of Cardiology (2018)
CXCR4 antagonist (BL-8040) to enhance antitumor effects by increasing tumor infiltration of antigen-specific effector T-cells.
Authors: Pankaj Gaur, Vivek Verma, Seema Gupta, Ella Sorani, Abi Vainstein Haras, Galia Oberkovitz, Amnon Peled, Samir Khleif
Journal: Journal of Clinical Oncology (2018)

73 Background: C-X-C chemokine receptor type 4 (CXCR4) helps to retain the hematopoietic stem cells (HSC) in the bone marrow (BM). CXCR4 binds to its ligand CXCL12/SDF1 which is constitutively expressed in the BM thereby inhibiting the mobilization of CXCR4 expressing immune progenitor cells. Moreover, increased numbers of effector cells in the tumor microenvironment (TME) are directly correlated to enhanced immunotherapeutic efficacy. Therefore, we hypothesized that CXCR4 antagonism will result in movement of immune progenitor cells from BM to periphery leading to increased availability of T-cells in the periphery and better infiltration of effector cells into the TME. Methods: In TC-1 mouse tumor-model, we tested the effects of CXCR4 antagonist (BL-8040; 4 doses; 24 h apart; 20 mg/kg) on the tumor growth and mice survival in the presence of tumor-specific antigen priming using E7 peptide vaccine (3 doses, one week apart). Anti-tumor immune responses were determined in the tumor tissues obtained 3-4 days after the second vaccination using flow cytometry. Results: We found that BL-8040 given with specific antigenic stimulation results in significantly enhanced anti-tumor immune response, leading to a decrease in tumor growth (p≤0.001 at day 21) and prolonged mice survival. At day 35 after tumor implantation, 80% of mice survived in the BL-8040 + vaccine treatment group compared to 0% survival following BL-8040 or vaccine treatments. Interestingly, we also found that BL-8040 leads to a significant increase in the numbers of antigen-specific CD8 + T-cells in the TME. We also found that starting BL-8040 prior to or together with the priming of the mice did not affect the outcome, suggesting that the scheduling of BL-8040 does not affect the therapeutic outcomes. Conclusions: These results suggest that BL-8040 treatment enhances anti-tumor immune response by potentially increasing the immune progenitor cells in the periphery leading to a better immune response. These results also suggest that BL-8040, a CXCR4 antagonist, is a promising immune-modulatory agent with potent anti-tumor effects.
Creation of a tissue expression biomarker-augmented prognostic model for patients with metastatic renal cell carcinoma.
Authors: Bimal Bhindi, Christine M. Lohse, John C. Cheville, Ross Mason, Matthew K. Tollefson, Susan Harrington, Haidong Dong, Alexander S. Parker, Stephen A. Boorjian, Robert Houston Thompson, Bradley C. Leibovich
Journal: Journal of Clinical Oncology (2018)

703 Background: Clinical and pathologic factors alone have limited prognostic ability in patients with metastatic clear cell renal cell carcinoma (ccRCC). We sought to determine if tissue biomarkers, along with our previously reported clinical metastases score, can be used to predict cancer specific survival (CSS) in patients with metastatic ccRCC. Methods: Patients with metastatic ccRCC who underwent nephrectomy between 1990-2004 were identified using the Mayo Clinic Nephrectomy Registry. Sections from paraffin-embedded primary tumor tissue blocks were used for immunohistochemistry staining for PD-1, B7-H1 (PD-L1), B7-H3, Bim (downstream pro-apoptotic signaling molecule in PD-1 pathway), CA-IX, IMP3, Ki67, and survivin. CSS was the primary outcome. Biomarkers that were significantly associated with CSS after adjusting for the metastases score were used to develop a biomarker-specific multivariable model using a bootstrap resampling approach and forward selection. Predictive ability was summarized using a bootstrap-corrected c-index. Results: The cohort included 602 patients, 192 (32%) with metastases at diagnosis and 410 (68%) who developed metastases after nephrectomy. Median follow-up among survivors was 9.6 years (IQR 4.2,12.8) and 504 patients died of RCC. Bim, IMP3, Ki67, and survivin expression were significantly associated with CSS after adjusting for the metastases score and were used to develop a biomarker-specific model. High Bim (HR 1.44; 95%CI 1.16-1.78; p &lt; 0.001), high survivin (HR 1.35; 95%CI 1.08-1.68; p = 0.008), and the metastases score (HR 1.13 per one point; 95%CI 1.10-1.16; p &lt; 0.001) were retained as independent predictors in the final multivariable model (c-index 0.69). Conclusions: We created a prognostic model combining the clinical metastases score and two primary tissue expression biomarkers, Bim and survivin, for patients with metastatic RCC who underwent nephrectomy. External validation will be required prior to clinical use.
Ginsenoside Re Protects Rhinovirus-Induced Disruption Of Tight Junction Through Inhibition Of ROS-Mediated Phosphatases Inactivation In Human Nasal Epithelial Cells
Authors: Kyeong Ah Kim, Joo Hyun Jung, Yun Sook Choi, Seon Tae Kim
Journal: Journal of Allergy and Clinical Immunology (2018)
INCREASED BILATERAL CAROTID INFLAMMATION IS ASSOCIATED WITH INCREASED CEREBROVASCULAR EVENT RATE
Authors: Georgios Benetos, Konstantinos Toutouzas, George Oikonomou, Iosif Koutagiar, Fotini Mitropoulou, Nikolaos Barampoutis, Periklis Davlouros, Andreas Synetos, Elias Siores, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2018)
INCIDENCE OF LUNG CANCER AMONG SOLITARY PULMONARY NODULES INCIDENTALLY DETECTED ON CARDIAC COMPUTED TOMOGRAPHY ANGIOGRAM IN A MULTIETHNIC POPULATION: DO WE INCORPORATE FLEISCHNER GUIDELINES 2017 INTO LOCAL PRACTICE?
Authors: Hong Jie Gabriel Tan, Jien Sze Ho, Yet Yen Yan, Haja Mohideen Salahudeen Mohamed, Lohendran Baskaran, Weng Kit Lye, Foong Koon Cheah, Terrance Chua, Swee Yaw Tan
Journal: Journal of the American College of Cardiology (2018)
Pyruvate Dehydrogenase PDH-E1β Controls Tumor Progression by Altering the Metabolic Status of Cancer Cells
Authors: Ryo Yonashiro, Kayoko Eguchi, Masaki Wake, Norihiko Takeda, Koh Nakayama
Journal: Cancer Research (2018)

Abstract Downregulation of pyruvate dehydrogenase (PDH) is critical for the aberrant preferential activation of glycolysis in cancer cells under normoxic conditions. Phosphorylation-dependent inhibition of PDH is a relevant event in this process, but it is not durable as it relies on PDH kinases that are activated ordinarily under hypoxic conditions. Thus, it remains unclear how PDH is durably downregulated in cancer cells that are not hypoxic. Building on evidence that PDH activity depends on the stability of a multi-protein PDH complex, we found that the PDH-E1β subunit of the PDH complex is downregulated to inhibit PDH activity under conditions of prolonged hypoxia. After restoration of normoxic conditions, reduced expression of PDH-E1β was sustained such that glycolysis remained highly activated. Notably, PDH-E1β silencing in cancer cells produced a metabolic state strongly resembling the Warburg effect, but inhibited tumor growth. Conversely, enforced exogenous expression of PDH-E1β durably increased PDH activity and promoted the malignant growth of breast cancer cells in vivo. Taken together, our results establish the specific mechanism through which PDH acts as an oncogenic factor by tuning glycolytic metabolism in cancer cells. Significance: This seminal study offers a mechanistic explanation for why glycolysis is aberrantly activated in normoxic cancer cells, offering insights into this long-standing hallmark of cancer termed the Warburg effect. Cancer Res; 78(7); 1592–603. ©2018 AACR.
I'm a medical student and am interested in maxillofacial surgery. I understand that most people who do maxillofacial surgery initially train as dentists and then do a medical degree. Is it possible to do it the other way round?
Authors: James A McCaul
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>
Correlates and Outcomes of Physician Burnout Within a Large Academic Medical Center
Authors: Amy K. Windover, Kathryn Martinez, Mary Beth Mercer, Katie Neuendorf, Adrienne Boissy, Michael B. Rothberg
Journal: JAMA Internal Medicine (2018)

and 2014, compared with 25.1% (89 of 354) and 39.5% (879 of 2225) for general payments, respectively.Receipt of research payments was associated with increased prescribing for mRCC but not CML.Similarly, when treating payments as a continuous variable, increasing amounts of general payments were associated with increased prescribing.Considering individual drugs, we found increased prescribing when receiving vs not receiving general payments for sunitinib (50.5% vs 34.4%, P = .01),dasatinib (13.8% vs 11.4%, P = .02),and nilotinib (15.4% vs 12.5%, P = .01)(Figure) but found decreased prescribing of imatinib (72.4% vs 75.5%, P = .02).Differences for sorafenib and pazopanib were not statistically significant.Research payments were not associated with statistically significant differences in prescribing for any individual drug.Results were similar when including payments specifically attributed to the drug of interest rather than all payments from the corresponding manufacturer and when changing the exposure to receipt of payments in both 2013 and 2014 (vs 2013 without respect to 2014).Our study had some limitations.These include the observational design precluding causal assessment, potential inaccuracies with Open Payments data, 5 lack of generalizability to other cancers, absence of information about the indications for the drugs, and small sample sizes for comparisons in the research payments analysis, notably for physicians receiving CML research payments.Conclusions | For 3 of the 6 cancer drugs studied, physicians who received general payments were more likely to prescribe the drug marketed by the company that made the payments.Imatinib was a notable exception; this may reflect a strategy by the manufacturer of imatinib (which also produces nilotinib) to promote switching to nilotinib before the patent expiration of imatinib in 2015.
PATIENT-PROVIDER RACIAL CONCORDANCE AND PATIENT REPORTED HEALTHCARE EXPERIENCE, AMONG ADULTS WITH ATHEROSCLEROTIC CARDIOVASCULAR DISEASE: INSIGHTS FROM MEDICAL EXPENDITURE PANEL SURVEY, 2010-2013
Authors: Victor Okunrintemi, Erica Spatz, Rohan Khera, Joseph Salami, Javier Valero-Elizondo, Oluseye Ogunmoroti, Hakeem Ayinde, Benjamin Patrick, Salim Virani, Michael Blaha, Ron Blankstein, Khurram Nasir
Journal: Journal of the American College of Cardiology (2018)
CHANGES IN CHARACTERISTICS, TREATMENT STRATEGIES, AND OUTCOMES OF CORONARY BIFURCATION LESIONS OVER TIME
Authors: Duk-Woo Park, Se Hun Kang, Jung-Min Ahn, Jung-Bok Lee, Cheol Hyun Lee, Do-Yoon Kang, Pil Hyung Lee, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2018)
SGLT2 Inhibitor–Associated Euglycemic Diabetic Ketoacidosis: A South Australian Clinical Case Series and Australian Spontaneous Adverse Event Notifications
Authors: Emily J. Meyer, Genevieve Gabb, David Jesudason
Journal: Diabetes Care (2018)

Sodium–glucose cotransporter 2 (SGLT2) inhibitors have been linked with diabetic ketoacidosis (DKA) (1–4). However, characteristics of “at-risk” patients are less well described.

Clinical cases were collected from South Australia between December 2015 and March 2017. The audit was approved by the Royal Adelaide Hospital Human Research Ethics Committee (HREC reference no. HREC/17/RAH/185).

The Therapeutic Goods Administration (TGA) of the Australian Government Department of Health was contacted, and a search of the Database of Adverse Event Notifications (medicines) for all reports of SGLT2 inhibitor–associated DKA was requested up until April 2017 using the search terms ketoacidosis, diabetic ketoacidosis, and generic and brand drug names. Full case line listings for each notification were provided by the TGA.

Autoantibodies against glutamic acid decarboxylase (GAD) and insulinoma-associated antigen 2 (tyrosine phosphatase IA-2) were quantitated using commercial ELISA test kits (Euroimmun AG, Lubeck, Germany). These assays are calibrated in international units (IU) using the first World Health Organization reference reagent for islet cell antibodies (1999, reagent 97/550; National Institute for Biological Standards and Control, Hertfordshire, U.K.), which contains 100 IU of anti-GAD and 100 IU of anti–IA-2 per ampoule by definition.

We identified thirteen cases of SGLT2 inhibitor–associated DKA occurring in South Australia between December 2015 and March 2017 (Table 1). Eight case subjects had type 2 diabetes (T2D) and five had …
Combination Cancer Immunotherapy in Hepatocellular Carcinoma
Authors: Masatoshi Kudo
Journal: Liver Cancer (2018)

Combination cancer immunotherapy is becoming a major topic in cancer therapy research including in hepatocellular carcinoma (HCC). Well-known combinations include two types of immune checkpoint inhibitors (anti-PD-1/PD-L1 and anti-CTLA-4 antibodies), anti-PD-1/PD-L1 antibody with a molecular targeted agent, and anti-PD-1/PD-L1 or -CTLA-4 antibody with existing locoregional therapies (Fig. ​(Fig.11).






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Fig. 1


Treatment strategy using immune checkpoint inhibitors. Future direction: combination therapy. RFA, radiofrequency ablation; TACE, transarterial chemoembolization; HAIC, hepatic arterial infusion chemotherapy; TKIs, tyrosine kinase inhibitors.
TRENDS OF ACUTE MYOCARDIAL INFARCTION IN PATIENTS WITH COCAINE AND AMPHETAMINE ABUSE
Authors: Nirali Patel, Sopan Lahewala, Prashant Patel, Shilpkumar Arora, Byomesh Tripathi, Abhishek Deshmukh, Apurva Badheka
Journal: Journal of the American College of Cardiology (2018)