tbuckley/cabot-search huggingface dataset:
Abstract ES3-1: Targeted approach to breast cancer surveillance in high risk women: update of the newest technologies and how to use them
Authors: M Jochelson
Journal: Cancer Research (2020)

Abstract In multiple prospective randomized trials, screening mammography alone has been demonstrated to reduce breast cancer mortality by approximately 30%. These studies did not account for differences in breast cancer risk. With increasing knowledge of factors that increase breast cancer risk including pathologic mutations, thoracic radiation at a young age, strong family history and incidence of some high-risk lesions, it has become clear that supplemental breast imaging might be necessary to improve early breast cancer detection and outcomes in women at increased risk. Additionally, it has become clear that different high-risk categories are associated with different types and presentations of breast cancer and that these differences might also translate into different imaging strategies. This presentation will address the standard breast cancer imaging tools such as Digital Mammography and Ultrasound and compare them with the newest imaging techniques in breast cancer imaging including Digital Breast Tomosynthesis, and physiologic imaging with a relatively new technology for screening: Contrast Enhanced Digital Mammography and Contrast Enhanced Breast MRI to include the most recent data on Abbreviated Breast MRI. There will be a discussion of fine-tuning the screening strategies based on the specific risk factors which will address the ideal frequency of screening, when screening should start and end and the utility of mammography and ultrasound in women undergoing breast MRI. Citation Format: M Jochelson. Targeted approach to breast cancer surveillance in high risk women: update of the newest technologies and how to use them [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES3-1.
Utilizing cell penetrating peptides to enhance the potency of a thermally responsive c-Myc inhibitory polypeptide
Authors: Gene Bidwell, Aisha Davis, Drazen Raucher
Journal: Cancer Research (2008)

5600  Current cancer therapy is limited by the extreme toxicity of chemotherapeutic drugs, which can cause extensive damage to non-cancerous tissues when used in doses required to eradicate cancer cells. The side effect profile and the efficacy of chemotherapeutics can be improved by two mechanisms: 1) developing drugs which are specifically toxic to the cancer cells and 2) developing methods to deliver drugs to the tumor site. In an attempt to combine these approaches, we developed a thermally responsive polypeptide inhibitor of the c-Myc oncogene. This polypeptide is based on the thermally responsive Elastin-like polypeptide (ELP). When injected systemically, ELP-fused drugs will aggregate and accumulate at the tumor site where local hyperthermia is applied. For this study, ELP was fused to a peptide which blocks c-Myc / Max dimerization (H1), thereby inhibiting transcription activation by c-Myc. In a previous study, the H1 peptide was fused to ELP and the penetratin peptide (Pen-ELP-H1), and it was shown that Pen-ELP-H1 was capable of entering MCF-7 breast cancer cells, binding and sequestering c-Myc to the cytoplasm, preventing expression of c-Myc target genes, and inhibiting cell proliferation. Here, the ELP-H1 polypeptide is fused to two different cell penetrating peptides (CPPs), the Tat peptide from HIV-1 and the Bac peptide from the antimicrobial bactenecin 7 peptide. Both CPPs improved cellular uptake relative to ELP-H1 alone, but neither produced intracellular levels equivalent to those seen with Pen-ELP-H1. However, Bac-ELP-H1 was a more potent inhibitor of MCF-7 cell proliferation than Pen-ELP-H1. Bac-ELP-H1 localized to the nucleus in a percentage of the cells, and the nuclear targeting was proportional to increases in both polypeptide concentration and time after treatment. Although more Pen-ELP-H1 entered the cell, it functioned through a mechanism of binding and sequestering newly translated c-Myc to the cytoplasm. The improved potency of Bac-ELP-H1 is likely due to its ability to deliver the H1 peptide to the nucleus, where the c-Myc / Max interaction naturally occurs. The potency of Bac-ELP-H1 was also tested against four cell lines with varying c-Myc expression levels. Bac-ELP-H1 was most potent in the cancer cell lines with high c-Myc expression, HeLa and MCF-7, and less potent in the low c-Myc expressing non-cancerous cell lines MCF-10A and WI-38. This data demonstrates that ELP can be targeted to the desired cellular compartment simply by choice of the CPP used. Also, when targeted to the nucleus by Bac, the c-Myc inhibitor was most potent in the cell lines with the highest c-Myc expression levels. The ELP-based c-Myc inhibitor employs both design strategies described above, creating a therapeutic molecule with two levels of target specificity. The polypeptide can be targeted to the tumor site using focused hyperthermia, and the polypeptide is most toxic to the cancerous cells.
Management of Acute Asthma in Adults in 2020
Authors: Mohammed F. Zaidan, Bill T. Ameredes, William J. Calhoun
Journal: JAMA (2020)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Blinatumomab for infant acute lymphoblastic leukemia
Authors: Katherine Clesham, Vasudha Rao, Jack Bartram, Philip Ancliff, Sara Ghorashian, David O’Connor, Vesna Pavasovic, Anupama Rao, Sujith Samarasinghe, Michelle Cummins, Andrea Malone, Katharine Patrick, Denise Bonney, Beki James, Brenda Gibson, Ajay Vora
Journal: Blood (2020)
STING Pathway Expression Identifies NSCLC With an Immune-Responsive Phenotype
Authors: Carminia M. Della Corte, Triparna Sen, Carl M. Gay, Kavya Ramkumar, Lixia Diao, Robert J. Cardnell, Bertha Leticia Rodriguez, C. Allison Stewart, Vassiliki A. Papadimitrakopoulou, Laura Gibson, Jared J. Fradette, Qi Wang, Youhong Fan, David H. Peng, Marcelo V. Negrao, Ignacio I. Wistuba, Junya Fujimoto, Luisa M. Solis Soto, Carmen Behrens, Ferdinandos Skoulidis, John V. Heymach, Jing Wang, Don L. Gibbons, Lauren A. Byers
Journal: Journal of Thoracic Oncology (2020)
Calming Down about Sedation in Critically Ill Patients
Authors: Claude Guérin
Journal: New England Journal of Medicine (2020)

Invasive mechanical ventilation after tracheal intubation is among the most frequently performed procedures in adult patients admitted to the intensive care unit (ICU). Sedation and analgesia are provided at the time of intubation and may be maintained for hours or days. The aim of sedation is to minimize oxygen consumption and facilitate a patient's ability to remain comfortably connected to a ventilator. The current status of the use of sedation for mechanical ventilation is most easily understood by reviewing the sequence of developments in the field. Over the past two decades, it has been recognized that prolonged and deep sedation . . .
Celebrating sports physiotherapy specialist: kudos Jacinta Horan (SEPNZ)
Authors: Blair Jarratt
Journal: British Journal of Sports Medicine (2020)

> Specialisation - the process of becoming an expert in a particular area of work, study or business; the fact of spending more time on one area of work. Oxford dictionary

For the field of sports medicine, 2019 will stand in the history of New Zealand (NZ) physiotherapy. When the NZ Board of Physiotherapy first released the areas of specialisation, the category ‘sports’ was left off the list. Some argued that sports should sit under the musculoskeletal specialisation area and there would be no need for a stand-alone category.

At that time, the leaders of Sport and Exercise New Zealand (SEPNZ) stood up for all sports practitioners and argued that in its own right it …
Routine-Dose and High-Dose Icotinib in Patients with Advanced Non–Small Cell Lung Cancer Harboring EGFR Exon 21-L858R Mutation: the Randomized, Phase II, INCREASE Trial
Authors: Xi Li, Li Zhang, Da Jiang, Yan Wang, Aimin Zang, Cuimin Ding, Min Zhao, Wuyun Su, Yan Zhang, Diansheng Zhong, Jin Wu, Cuiying Zhang, Guangyu An, Xingsheng Hu, Gang Cheng, Huaqing Wang, Yongqun Li, Xiaohui He, Junli Liu, Li Liang, Lieming Ding, Li Mao, Shucai Zhang
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Our primary purpose is to explore safety and efficacy of high-dose icotinib in comparison with routine-dose icotinib in patients with non–small cell lung cancer (NSCLC) harboring 21-L858R mutation. Patients and Methods: Patients with treatment-naïve, EGFR-mutant (21-L858R or exon 19 deletion at 2:1) NSCLC were enrolled. Patients with 21-L858R mutation were randomized to receive routine-dose icotinib (125 mg, thrice daily; L858R-RD) or high-dose icotinib (250 mg, thrice daily; L858R-HD), whereas patients with exon 19 deletion received only routine-dose icotinib (19-Del-RD) until progression, death, or unacceptable toxicity. The primary endpoint was median progression-free survival (mPFS), assessed by an independent review committee. Results: From May 2015 to November 2017, 253 patients (86 in L858R-RD; 90 in L858R-HD; and 77 in 19-Del-RD) were enrolled. The mPFS in L858R-HD group was similar to that in 19-Del-RD group (12.9 months and 12.5 months, respectively) and was significantly longer than that in L858R-RD group [12.9 months vs. 9.2 months, hazard ratio (HR): 0.75; 95% confidence interval (CI), 0.53–1.05]. A longer but statistically nonsignificant mPFS was observed between 19-Del-RD and L858R-RD groups (12.5 months vs. 9.2 months, HR: 0.80; 95% CI, 0.57–1.13). A higher objective response rate (ORR) was observed in L858R-HD group compared with L858R-RD group (73% vs. 48%), also between 19-Del-RD and L858R-RD groups (75% vs. 48%). Similar incidences of grade 3/4 toxicities were observed among the three treatment groups. Conclusions: High-dose icotinib improved mPFS and ORR in patients with NSCLC harboring 21-L858R mutation with acceptable tolerability, which could be a new therapeutic option for this patient population.
21-gene RT-PCR assay in lymph node negative (LN-), estrogen receptor positive (ER+) breast cancer: An economic analysis including prognostic and predictive information
Authors: L. E. Cosler, N. M. Kuderer, J. Hornberger, G. H. Lyman
Journal: Journal of Clinical Oncology (2006)

6024 Background: The prognostic accuracy of a 21-gene RT-PCR assay has undergone validation in 668 evaluable LN-, ER+ early stage breast cancer patients receiving tamoxifen on NSABP B-14 (Paik, NEJM 2004) and its economic evaluation (Hornberger, Am J Man Care 2005). Assay predictive accuracy for response to chemotherapy or tamoxifen has also undergone recent validation in 651 patients on NSABP B-20 and 645 patients on NSABP B-14 (Paik, SABCS 2004). Methods: Based on the model recurrence score (RS), women with LN−, ER+ breast cancer with and without adjuvant chemotherapy (C) or tamoxifen (T) were classified as high (RS ≥31), intermediate (RS 18–30) or low (RS &lt;18) risk of distant recurrence at 10 years. Incremental costs ($), life-years (LYs), quality-adjusted LYs (QALYs) and cost-effectiveness (C/E; cost per LY gained) were estimated for: RS-guided treatment (RSGT) with T for low and intermediate risk patients and C+T for high-risk patients, compared to either T alone or C+T for all patients. Results: Under base case assumptions, no significant difference in life expectancy at 10 years is estimated between the RSGT and C+T strategies whereas RSGT is associated with a gain in individual life expectancy of 2.7 LYs compared to T alone. RSGT is estimated to yield a net cost savings of $4,502 compared to C+T with an incremental C/E of $1,059 per LY saved compared to T alone. At a utility of 90% associated with adjuvant chemotherapy, RSGT is associated with a gain in individual QALYs of 1.82 compared to T alone at a cost utility of $1,573/QALY and a gain in 3.21 QALYs compared to C+T. RSGT is associated with lower expected cost than C+T for total chemotherapy costs above $3,998. The gain in LYs with RSGT compared to T alone increases with healthy age-specific life expectancy (years) while the cost per LY gained decreases. Conclusions: Treatment based on the RSGT compared to T alone is associated with acceptable C/E ratios and substantially lower toxicity and cost compared to C+T. [Table: see text] [Table: see text]
Surgery in General Practice
Authors: L R P Marshall
Journal: BMJ (1926)

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 Journals 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 2024 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
Epigenetic Marks Repressing Gluconeogenesis in Liver and Kidney Cancer
Authors: Katharina Leithner
Journal: Cancer Research (2020)

Gluconeogenesis is frequently suppressed in tumors arising in gluconeogenic organs and reexpression of a gluconeogenesis enzyme, fructose-1,6-bisphosphatase (FBP1), was found to inhibit tumor growth. In this issue of Cancer Research, Liao and colleagues show that histone H3 trimethylation on lysine 27, induced by polycomb repressive complex 2 (PRC2), is responsible for downregulating FBP1 in liver and kidney cancer cells. Moreover, they identified FBP1 repression as an important downstream mechanism of PRC2-mediated carcinogenesis. FBP1 inhibits glycolysis but also directly interferes with PRC2 function, thus FBP1 and PRC2 are part of a novel negative feedback loop that is deregulated in liver and kidney cancer.See related article by Liao et al., p. 675.
Myocardial Evaluation of Post-Preeclamptic Women by CMR
Authors: Anna Birukov, Stephanie Wiesemann, Michaela Golic, Andras Balogh, Lajos Marko, Natalia Rakova, Nicola Wilck, Edyta Blaszczyk, Carolin Lim, Sara Weiss, Kristin Kräker, Nadine Haase, Alina Frolova, Jan Stener Jørgensen, Steffen Daub, Dominik N. Müller, Florian Herse, Jeanette Schulz-Menger, Ralf Dechend
Journal: JACC. Cardiovascular imaging (2020)
Eosinophils, basophils and type 2 immune microenvironments in COPD-affected lung tissue
Authors: Prajakta Jogdand, Premkumar Siddhuraj, Michiko Mori, Caroline Sanden, Jimmie Jönsson, Andrew F. Walls, Jennifer Kearley, Alison A. Humbles, Roland Kolbeck, Leif Bjermer, Paul Newbold, Jonas S. Erjefält
Journal: European Respiratory Journal (2020)

Although elevated blood or sputum eosinophils are present in many patients with COPD, uncertainties remain regarding the anatomical distribution pattern of lung-infiltrating eosinophils. Basophils have remained virtually unexplored in COPD. This study mapped tissue-infiltrating eosinophils, basophils and eosinophil-promoting immune mechanisms in COPD-affected lungs. Surgical lung tissue and biopsies from major anatomical compartments were obtained from COPD patients with severity grades Global Initiative for Chronic Obstructive Lung Disease stages I–IV; never-smokers/smokers served as controls. Automated immunohistochemistry and in situ hybridisation identified immune cells, the type 2 immunity marker GATA3 and eotaxins (CCL11, CCL24). Eosinophils and basophils were present in all anatomical compartments of COPD-affected lungs and increased significantly in very severe COPD. The eosinophilia was strikingly patchy, and focal eosinophil-rich microenvironments were spatially linked with GATA3 + cells, including type 2 helper T-cell lymphocytes and type 2 innate lymphoid cells. A similarly localised and interleukin-33/ST2-dependent eosinophilia was demonstrated in influenza-infected mice. Both mice and patients displayed spatially confined eotaxin signatures with CCL11 + fibroblasts and CCL24 + macrophages. In addition to identifying tissue basophilia as a novel feature of advanced COPD, the identification of spatially confined eosinophil-rich type 2 microenvironments represents a novel type of heterogeneity in the immunopathology of COPD that is likely to have implications for personalised treatment.
White doctors are still over-represented in top NHS jobs, study finds
Authors: Abi Rimmer
Journal: BMJ (2020)

The NHS favours white candidates when hiring for its most prestigious and highly paid positions, researchers have found.

The study, published in the online journal BMJ Open ,1 found that 46% of white doctors were consultants, compared with 33.4% of Chinese doctors and 30.6% of black doctors. This was despite a much larger proportion of Chinese people employed by the NHS being doctors than white employees.

The researchers also found similar results among nurses and health visitors, as white people were over-represented in the higher pay bands of these professions.

The results were based on data from NHS Digital’s 2017 workforce statistics on NHS hospital and community health service staff groups working in trusts …
Modernizing Scope-of-Practice Regulations — Time to Prioritize Patients
Authors: Bianca K. Frogner, Erin P. Fraher, Joanne Spetz, Patricia Pittman, Jean Moore, Angela J. Beck, David Armstrong, Peter I. Buerhaus
Journal: New England Journal of Medicine (2020)

Interview with Dr. Bianca Frogner on scope-of-practice regulations and how they can be redesigned to better serve the needs of patients. (10:23)Download Many health care organizations are experimenting with new ways of unleashing their workforce’s potential. Such approaches require reconfiguring of provider roles, but states and organizations often place restrictions on health professionals’ scope of practice.
Blood eosinophil count in the general population: typical values and potential confounders
Authors: Sylvia Hartl, Marie-Kathrin Breyer, Otto C. Burghuber, Alina Ofenheimer, Andrea Schrott, Matthias H. Urban, Alvar Agusti, Michael Studnicka, Emiel F.M. Wouters, Robab Breyer-Kohansal
Journal: European Respiratory Journal (2020)

There is growing interest in blood eosinophil counts in the management of chronic respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD). Despite this, typical blood eosinophil levels in the general population, and the impact of potential confounders on these levels have not been clearly defined. We measured blood eosinophil counts in a random sample of 11 042 subjects recruited from the general population in Austria. We then: 1) identified factors associated with high blood eosinophil counts (&gt;75th percentile); and 2) excluded subjects with these factors to estimate median blood eosinophil counts in a “healthy” sub-population (n=3641). We found that: 1) in the entire cohort, age ≤18 years (OR 2.41), asthma (OR 2.05), current smoking (OR 1.72), positive skin prick test (OR 1.64), COPD (OR 1.56), metabolic syndrome (OR 1.41), male sex (OR 1.36) and obesity (OR 1.16) were significantly (p&lt;0.05) associated with high blood eosinophil counts (binary multivariable logistic regression analysis), and had an additive effect; and 2) after excluding these factors, in those older than 18 years, blood eosinophil counts were higher in males than in females (median 120 (5%–95% CI: 30–330) versus 100 (30–310) cells·µL −1 , respectively) and did not change with age. Median blood eosinophil counts in adults are considerably lower than those currently regarded as normal, do not change with age beyond puberty, but are significantly influenced by a variety of factors which have an additive effect. These observations will contribute to the interpretation of blood eosinophil levels in clinical practice.
Decreasing Dose and Duration of Dexamethasone Therapy for Low-Risk Childhood Acute Lymphoblastic Leukemia Aiming to Avoid Serious Viral Infections Results in Significant Increase in Isolated CNS Relapse: A Prospective Study
Authors: Khaled M Ghanem, Miguel R Abboud, Nidale Tarek, Raya Saab, Hani Tamim, Hassan El-Solh, Samar A. Muwakkit
Journal: Blood (2017)