tbuckley/cabot-search huggingface dataset:
Caution Accompanies New MS Drug
Authors: Rebecca Voelker
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Injectable, long-acting PLGA formulations: Analyzing PLGA and understanding microparticle formation
Authors: Kinam Park, Sarah Skidmore, Justin Hadar, John Garner, Haesun Park, Andrew Otte, Bong Kwan Soh, Gwangheum Yoon, Dijia Yu, Yeonhee Yun, Byung Kook Lee, Xiaohui Jiang, Yan Wang
Journal: Journal of Controlled Release (2019)
Scotland increase minimum unit price of alcohol to increase to 50p
Authors: Tomasz Pierscionek
Journal: BMJ (2012)

A national bill to increase the minimum price of alcoholic beverages is being debated for the second time in the Scottish parliament. The Alcohol Minimum Pricing Bill, proposed by the Scottish National Party, would raise the minimum price of a unit of alcohol to 50p (€0.6; $0.8), an increase of 5p of current prices.

The proposed legislation announced …
Abstract P3-08-22: Oncotype Dx recurrence score risk groups according to Ki67, a predictor to be considered
Authors: F Namuche, R Ruiz, Z Morante, A Aguilar, H Gomez
Journal: Cancer Research (2019)

Abstract Background The gene expression profiling assay OncotypeDx (ODx) prognosticates the risk of estrogen receptor positive (ER+) breast cancer (BC) recurrence and assesses the likely benefit from adjuvant chemotherapy in addition to endocrine therapy. There have been several attempts to develop algorithms that provide similar outcome prediction to the ODx assay with the use of routine clinicopathological characteristics. Ki67 is frequently incorporated into these assessments, although there is no standard cut-off for its use. Methods We retrospectively reviewed the electronic medical records of 330 patients with early stage ER+ BC for whom ODx recurrence score (RS) was available. Patients were diagnosed and treated at two specialized cancer centers between 2014 and 2017. Our objective was to determine the ki67's median differences between ODx risk groups. We used Spearman rho for the correlation between Ki67 and ODx score and used Kruskal-Wallis test for compare medians, pairwaise comparison for the intergroup relations. Results Mean age at diagnosis was 57.42 years (range 28-89). Mean tumor diameter was 15.67 mm. 78.9% were intermediate histologic grade and 9.7% patients had lymph node involvement. Median expression of ER and PR were 90% (5-100) and 70% (0-100), respectively. We assessed the correlation between Ki67 and ODx score, with a pearson r:0.31, p&amp;lt;0.001. The data showed a directly proportional trend between Ki67 and ODx score. Median Ki67 was 20 (1-100). According to ODX RS, 61.5% of tumors were low risk, 30.3% were intermediate risk and, 8.2% were high risk. Median Ki67 within each category group is as follows: low: 15 (IQR:15), intermediate: 20 (IQR:18) and high: 40 (IQR:35), with a statistically significant difference between medians (p&amp;lt;0.001). In the Pairwise comparison intergroup the data showed: Low-Intermediate (p&amp;lt;0.05), Low-High (p&amp;lt;0.001), Intermediate-High (p&amp;lt;0.001). Conclusions The data showed directly proportional trend between Ki67 and ODx score. In our population there is a statistically significant difference between Ki67 medians according to ODx risk groups. Citation Format: Namuche F, Ruiz R, Morante Z, Aguilar A, Gomez H. Oncotype Dx recurrence score risk groups according to Ki67, a predictor to be considered [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-08-22.
Abstract P1-17-04: Long-term safety follow-up of patients with early stage breast cancer treated with scalp cooling on the Dignitana scalp cooling trial
Authors: HS Rugo, P Klein, SA Melin, SA Hurvitz, ME Melisko, A Moore, RB D'Agostino, A Deluca, T Cigler
Journal: Cancer Research (2019)

Abstract Background Scalp cooling has demonstrated efficacy in preventing hair loss in women with early stage breast cancer receiving neo/adjuvant chemotherapy. Data from 2 prospective trials (Rugo et al, and Nangia et al, JAMA 2017) led to FDA clearance of 2 automated scalp-cooling devices to prevent chemotherapy induced alopecia (CIA). Although scalp metastases from breast cancer are rare, historical concerns about scalp cooling included a theoretical increase in risk of recurrence in scalp due to reduced delivery of chemotherapy to the scalp. Methods We conducted a multicenter prospective trial evaluating the efficacy and safety of the DigniCap in women with stage I-II breast cancer receiving neo/adjuvant chemotherapy excluding sequential or combination anthracycline/taxanes with concurrent matched controls. The primary endpoint was unblinded patient self-assessment of 5 photographs using the Dean scale to estimate hair loss 4 weeks following the last dose of chemotherapy, with success defined as a Dean score of 0-2 (≤ 50% hair loss); additional endpoints included quality of life (QOL) and both short and long-term safety. Results 106 patients using the scalp cooling device and 16 concurrent controls were enrolled. As previously reported, the use of scalp cooling was associated with less alopecia and improvement in several measures of QOL (Rugo et al, JAMA 2017). 91 patients have follow-up (FU) out to 3 years; 73 with estrogen receptor (ER) positive and 18 with ER negative disease. 5 DigniCap patients have developed recurrent breast cancer in breast (n=1), liver (n=1), bone, liver and breast (n=1), bone, liver, lung, and nodes (1), and bone, breast, GI tract and bladder (n=1). Of 12 control patients with available FU, 1 developed metastases to liver. 2 patients have died of metastatic disease, one in the DigniCap arm and one in the control arm. No new safety signals have been detected. Conclusion Scalp cooling using the DigniCap system in patients with early stage breast cancer receiving taxane based neo/adjuvant chemotherapy is safe and effective. No scalp metastases have been reported 3 years following completion of study treatment. 4 year FU data will be presented. The study was funded by The Lazlo Tauber Family Foundation (UCSF), the Anne Moore Breast Cancer Research Fund (Weil Cornell), and the Friedman Family Foundation (Mount Sinai Beth Israel), as well as partially by Dignitana. Citation Format: Rugo HS, Klein P, Melin SA, Hurvitz SA, Melisko ME, Moore A, D'Agostino, Jr. RB, Deluca A, Cigler T. Long-term safety follow-up of patients with early stage breast cancer treated with scalp cooling on the Dignitana scalp cooling trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-17-04.
Expert consensus document: Reporting checklist for quantification of pulmonary congestion by lung ultrasound in heart failure
Authors: Elke Platz, Pardeep S. Jhund, Nicolas Girerd, Emanuele Pivetta, John J.V. McMurray, W. Frank Peacock, Josep Masip, Francisco Javier Martin‐Sanchez, Òscar Miró, Susanna Price, Louise Cullen, Alan S. Maisel, Christiaan Vrints, Martin R. Cowie, Salvatore DiSomma, Hector Bueno, Alexandre Mebazaa, Danielle M. Gualandro, Mucio Tavares, Marco Metra, Andrew J.S. Coats, Frank Ruschitzka, Petar M. Seferovic, Christian Mueller
Journal: European Journal of Heart Failure (2019)
Abstract SY13-02: Transcriptional control of tumor-induced myeloid-derived suppressor cells
Authors: Vincenzo Bronte
Journal: Cancer Research (2010)

Abstract We have generated myeloid-derived suppressor cells (MDSCs) from bone marrow precursors (BM-MDSCs) as a tool to investigate the molecular pathways involved in their immunosuppressive program. BM-MDSCs suppress in vitro both antigen-specific and unspecific CD8+ T cells. The tolerogenic properties of BM-MDSC were further confirmed in vivo following their adoptive transfer in a setting of allogeneic pancreatic insulae transplantation in pharmacologically-induced diabetic mice. The cytokines leading to generation of MDSCs are normally produced during an inflammatory response and act on a common transcription factor which is considered a master regulator of the emergency granulopoyesis. We investigated the effect of genetic knock out of this transcription factor in vivo by creating mice lacking it in myelomonocytic cells. In these mice tumor growth did not cause dysfunction in CD8+ T cells, suggesting that this transcription factor is crucial for their tolerogenic activity and a potential target for new approaches aimed at controlling tumor-induced tolerance. Citation Format: Vincenzo Bronte. Transcriptional control of tumor-induced myeloid-derived suppressor cells [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr SY13-02
Abstract 3696A: The detection and prediction of circulating tumor cells in breast cancer patients
Authors: Tim Molloy, Helgi H Helgason, Astrid Bosma, Laura J. van't Veer
Journal: Cancer Research (2008)

Abstract The detection of circulating tumor cells (CTC) in the blood of cancer patients is a promising tool for risk stratification, treatment tailoring, and monitoring of the disease state. The current study aims to develop a QPCR-based detection platform for the semi-quantitation of tumor cell load in the peripheral blood of breast cancer patients by combining gene expression data from 4 tumor marker genes into a single index-score. From a cohort of 131 individuals, CTC index-score positivity, indicating tumor cell presence, was observed in 14 out of 16 (88%) metastatic patients, 16 out of 87 (18%) non-metastatic stage I-III patients, and 0 out of 28 (0%) healthy female controls. A previous study demonstrated that CTC index-score positivity in metastatic patients correlated to a significantly shorter time to disease progression. This CTC detection platform demonstrates high specificity (100%) and sensitivity (88%), and can be an effective clinical tool providing valuable prognostic information. This CTC detection assay was subsequently compared to a CTC prediction assay developed using microarray expression data from the primary tumors of the patients from the same cohort. From 73 patients, a CTC predictive tumor profile was developed with the ability to distinguish those patients with a positive CTC QPCR index-score from those with a negative index-score with an average 83% internal cross-validation accuracy. When a small independent test set was assayed, those patients classified on the basis of their tumor gene expression as having a positive CTC QPCR score had a shorter interval to metastasis development (mean = 29.6 months) versus those predicted to have a negative score (mean = 51.4 months). When the QPCR-based and microarray-based CTC assays were compared directly, and each in combination with the “70-gene prognosis signature” for distant metastasis prediction, the CTC predictive microarray assay was superior to the CTC QPCR assay both alone and in combination with the 70-gene profile for time interval to metastasis. This study demonstrates that a microarray model predictive of tumor cell dissemination has prognostic value and seems independent of other metastasis-predictive microarray profiles.
DNA Hydrogels: Functionalized DNA Hydrogels Produced by Polymerase‐Catalyzed Incorporation of Non‐Natural Nucleotides as a Surface Coating for Cell Culture Applications (Adv. Healthcare Mater. 9/2019)
Authors: Alexander Finke, Ann‐Kathrin Schneider, Anna‐Sophie Spreng, Marcel Leist, Christof M. Niemeyer, Andreas Marx
Journal: Advanced Healthcare Materials (2019)

In article number 1900080 by Andreas Marx and co-workers, chemically cross-linked DNA hydrogels are generated by DNA polymerase I mediated incorporation of nucleotides carrying cell specific bait factors (shown as orange spheres). Using this technique different cells can specifically attach to this material. Furthermore channels were prepared and coated with modified DNA hydrogels which could be used to bind cells under flow conditions.
mRNA-to-protein translation in hypoxia
Authors: Nancy T. Chee, Ines Lohse, Shaun P. Brothers
Journal: Molecular Cancer (2019)

Cells respond to hypoxia by shifting cellular processes from general housekeeping functions to activating specialized hypoxia-response pathways. Oxygen plays an important role in generating ATP to maintain a productive rate of protein synthesis in normoxia. In hypoxia, the rate of the canonical protein synthesis pathway is significantly slowed and impaired due to limited ATP availability, necessitating an alternative mechanism to mediate protein synthesis and facilitate adaptation. Hypoxia adaptation is largely mediated by hypoxia-inducible factors (HIFs). While HIFs are well known for their transcriptional functions, they also play imperative roles in translation to mediate hypoxic protein synthesis. Such adaptations to hypoxia are often hyperactive in solid tumors, contributing to the expression of cancer hallmarks, including treatment resistance. The current literature on protein synthesis in hypoxia is reviewed here, inclusive of hypoxia-specific mRNA selection to translation termination. Current HIF targeting therapies are also discussed as are the opportunities involved with targeting hypoxia specific protein synthesis pathways.
Abstract P2-09-16: CD8 T cells induced by novel alphaviral vector predict improved progression free survival in advanced HER2+ breast cancer patients
Authors: EJ Crosby, WR Gwin, S Chang, HT Maecker, V Lubkov, JC Snyder, G Broadwater, T Hyslop, T Osada, AC Hobeika, ZC Hartman, MA Morse, HK Lyerly
Journal: Cancer Research (2019)

Abstract Background: Immune-based therapy for metastatic breast cancer has had limited success. Strategies to augment adaptive immunity include vaccines targeting genomic amplifications like Human Epidermal Growth Factor Type 2 (HER2), an established driver of malignancy. Using a novel alphaviral vector, we constructed a vaccine encoding a portion of HER2 (VRP-HER2). Methods: In preclinical studies, mice were immunized before or after implantation of hHER2+ tumor cells and HER2-specific immune responses and anti-tumor function were assessed. We then translated this vaccine into a phase I clinical trial in which subjects with advanced HER2-overexpressing breast cancers received VRP-HER2 every 2 weeks for a total of three doses (cohort 1). In cohort 2, subjects received the same dose of VRP-HER2 along with a standard HER2 targeted therapy. Results: VRP-HER2 induced HER2-specific T cell and antibody responses while controlling tumor growth in murine models. Vaccination with VRP-HER2 was well tolerated in both patient cohorts. PFS was modest, while median OS was 50.2 months in cohort 1 and 32.7 months in cohort 2. In cohort 2, there is one partial response and two patients with continued stable disease. Vaccine induced anti-HER2 antibodies and T cells were identified. Increased perforin expression by memory CD8 T cells post vaccination significantly correlated with improved PFS. Conclusions: VRP-HER2 led to an increase in perforin expressing HER2-specific memory CD8 T cells in preclinical and clinical studies, and had profound antitumor effects in murine models. The generation of HER2-specific memory CD8 T cells was significantly correlated with increased PFS in patients. Subsequent studies will seek to enhance T cell activity by combination with anti-PD-1/PD-L1 antibodies. Citation Format: Crosby EJ, Gwin WR, Chang S, Maecker HT, Lubkov V, Snyder JC, Broadwater G, Hyslop T, Osada T, Hobeika AC, Hartman ZC, Morse MA, Lyerly HK. CD8 T cells induced by novel alphaviral vector predict improved progression free survival in advanced HER2+ breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-09-16.
Abstract 13131: Hemodynamic Effects of Continuous Negative Extrathoracic Pressure in Fontan Physiology
Authors: David M Peng, Jeffrey D Zampi, Sue Smith, Nichole Rottach, Lori Q Riegger, Albert P Rocchini
Journal: Circulation (2018)

Introduction: Fontan physiology results in chronic systemic venous congestion with limited therapeutic options. We sought to evaluate the hemodynamic effects of continuous negative extrathoracic pr...
Climate change, health, and the NHS
Authors: Isobel Braithwaite
Journal: BMJ (2013)

I became interested in the links between climate change and health when I received an email publicising a student led pilot project on climate, health, and sustainable healthcare. Although I didn’t know much about it, it piqued my interest, and I thought it was worth applying. Over subsequent months I learnt things that were fascinating and worrying in equal measure.

The effects of climate change on health have the potential to be dramatic.1 We tend to think of obvious ones: heatwaves, changing patterns of infectious disease, and natural disasters, but my view is that climate change will affect health more through indirect pathways that are difficult to attribute to it. Science predicts a temperature rise of 4°C or more this century if current trends continue. Alongside population growth, resource scarcity, and rapid urbanisation, such a rise would contribute to economic instability, ecosystem collapse, migration on a large scale, and conflict.

Around the world, average carbon footprints range from under …
Abstract ES9-1: Optimizing treatment of early stage triple negative breast cancer: Clinical challenges and new scientific horizons
Authors: A DeMichele
Journal: Cancer Research (2019)

Abstract “Triple negative” breast cancer (TNBC) as defined by the lack of estrogen and progesterone receptors and absence of Her2-overexpression, is challenging due to its aggressive natural history and limited treatment options. However, significant progress has been made in the last decade in understanding the biological diversity of TNBC, its prognosis and approaches to successful treatment. For example, molecular classification by gene expression studies initially identified a basal molecular subtype enriched for TNBC, which was further refined to additional include 4 major subtypes: basal-like, mesenchymal, luminal androgen receptor and immune-enriched. In addition, clear associations between TNBC and mutations in DNA-repair-related genes, especially BRCA-1 and BRCA-2 have been elucidated. These findings have subsequently guided therapeutic development. The early-stage setting has been the focus of much of this work, as it is clear that patients who have tumors that respond vigorously to chemotherapy preoperatively have a reduced likelihood of later metastatic recurrence compared to those who have poorly-responsive disease. Capitalizing on this knowledge, trials in the neoadjuvant setting have defined the importance of pathologic complete response (pCR) as a surrogate endpoint, and have shed light on differential effects of standard therapy (such as platinums), development of new targeted therapies (such as PARP inhibitors) and the role of immunotherapy. The high rate of observed recurrence in patients who have high stage disease at diagnosis, or, in particular, residual disease after neoadjuvant therapy, has also led to the launch of clinical trials in the adjuvant and post-neoadjvuant setting designed to specifically address micrometastatic minimal residual disease and therapy resistance. The advantage of the post-neoadjvuant approach to trials amongst patients with residual disease is to decrease the size of adjuvant trials, and allow them to be focused within populations most at risk of recurrence, sparing those with good prognosis the need for additional, potentially toxic treatment. Despite this progress, there are still many unanswered questions regarding optimal therapy and potential to improve outcomes in TNBC. This session will review the state of the science with regard to biology, new treatment approaches, and the value of both the neoadjuvant and post-neoadjvuant settings in developing optimal approaches to tailor therapy on the basis of risk stratification, reduce recurrence, and improve outcomes for women presenting with triple negative breast cancer. Citation Format: DeMichele A. Optimizing treatment of early stage triple negative breast cancer: Clinical challenges and new scientific horizons [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES9-1.