tbuckley/cabot-search huggingface dataset:
Humanism in global oncology curricula: An emerging priority.
Authors: Meredith Elana Giuliani, Maria Athina (Tina) Martimianakis, Janet Papadakos, Michaela Broadhurst, Erik Driessen, Janneke Frambach
Journal: Journal of Clinical Oncology (2019)

10505 Background: Training in humanism provides the skills to achieve shared decision making with patients and their families, to navigate systems level challenges and to function positively within the healthcare team. However, there is potentially a lack of attention to humanistic competencies in global oncology curricula due to the dominance of the biomedical model in curriculum design, the challenge of assessing humanistic competencies and global cultural considerations. The aims of this study were to explore to what extent humanistic competencies are included in global oncology curricula and the nature of the humanistic competencies included. Methods: Sixteen global oncology curricula identified in a prior systematic review were analysed. The curricula were coded using the Gold Foundation’s I.E.C.A.R.E.S (Integrity, Excellence, Collaboration &amp; compassion, Altruism, Respect &amp; Resilience, Empathy and Service) humanistic competency framework and the CanMEDS framework. Descriptive statistics were used to describe the proportion of items attributed to each aspect of the framework. Results: 7733 curricular items were identified in the 16 curricula and 729 (9%) aligned with the I.E.C.A.R.E.S framework. The proportion of humanistic items in individual curricula ranged from 2% to 26%. The proportion of humanistic items has been increasing from the curricula published in 1980-1989 (3%) to the curricula published in 2010-2017 with a mean of 11% (4 to 25%). There was a higher proportion of humanistic competencies in curricula from the European region (9%) than in other regions. Of the humanistic items 35% were under respect, 31% under compassion, 24% under empathy, 5% were under integrity, 2% under excellence, 1% under altruism, and 1% under service. The majority of the humanistic items also aligned with the professional (35%), medical expert (31%) or communicator (26%) CanMEDS domains. Conclusions: The proportion of humanistic competencies has been increasing in global oncology curricula over time however the overall proportion remains low. Humanism is largely represented by competencies of respect, compassion and empathy and there exists a conflation between humanism and professionalism. Future global curricular efforts may benefit from attention to incorporating all aspects of humanistic competencies.
The clinicopathological and socioeconomic features of patients with gastric cancer in Turkey (Turkish Oncology Group)
Authors: B. Yalcin, F. Aydin, N. Zengin, M. Ilhan, A. Isikdogan, F. Aykan, G. Demir, I. Celik, S. Turhal, F. Icli, H. Akbulut
Journal: Journal of Clinical Oncology (2006)

20098 Background: The incidence of gastric cancer has declined dramatically in western countries. However it is the second most common cancer in Turkey, and its mortality rate is still high. The aim of this study was to evaluate the clinicopathological and socioeconomic features of patients with gastric cancer in Turkey. Methods: A questionnaire including the clinicopathological and socioeconomic features of gastric cancer patients diagnosed in 2004, was used in this retrospective multicentre study. The characteristic of patients in economically developed Western Turkey (WT) was compared to those in less developed Eastern Turkey (ET). Results: From sixteen centers, 971 patients with gastric cancer during the year 2004 were included in the study. Male-female ratio was 2/1. Mean age was 57 ± 12.9 years. Of patients, 75.3% had low socioeconomic status. Distal and middle gastric cancers were the most common locations (distal 39%, middle 36.5% vs upper 24.5%). The R0 resectability rate was 54.1% in all patients. There was no statistically significant difference in gender, age, smoking rate, anemia, the location of tumor and the frequency of atrophic gastritis between WT and ET. The rate of cancer resectability was lower in Eastern Turkey (ET) than Western Turkey (WT) (31.6% vs. 63.4%, p = 0.0001). Also, socioeconomic status of patients was lower in ET than those in WT (53.6% vs. 32.3%, p = 0.0001). H. pylori associated gastritis and intestinal metaplasia were more common in ET when compared with WT (75.0% vs. 40.5%, P = 0.003, and 68.4% vs. 18.1%, respectively, P = 0.0001). Conclusions: Lower socioeconomic status and lower resectability rate of gastric cancer in ET is considerable. Further epidemiological study of gastric cancer is warranted in Turkey. No significant financial relationships to disclose.
Preclinical development of a novel inhibitor of oncogenic B-Raf
Authors: K. Nolop, W. B. Jones, J. Tsai, H. Cho, R. Bremer, P. Ibrahim, D. R. Artis, P. Hirth, G. Bollag
Journal: Journal of Clinical Oncology (2006)

13056 Background: The discovery of oncogenic B-Raf mutations in a majority of patients with metastatic melanoma, and in many tumors from patients with colorectal cancer and other cancers, presents the opportunity to develop oncogene-selective inhibitors with a favorable safety profile. Methods: Guided by co-crystallography, a novel chemical scaffold has been developed into a series of potent inhibitors of oncogenic B-Raf with selectivity versus wild-type B-Raf. From this series, a potent inhibitor has been chosen as a candidate for development. Results: Consistent with the structure-guided approach, this compound shows pronounced selectivity versus a wide array of over 70 other kinases covering all branches of the kinome. This selectivity translates to a wide cellular therapeutic index: inhibition of proliferation of a panel of cell lines bearing the V600E oncogenic B-Raf mutation occurs at IC50s ranging from 40–400 nM while inhibition of cell lines lacking oncogenic B-Raf occurs at IC50s greater than 6500 nM. This cell-based selectivity for the oncogenic B-Raf is greater than the selectivity shown in biochemical assays, supporting that tumor cells bearing the oncogenic B-Raf protein are more dependent on the MAP kinase pathway. Combination experiments with a series of cytotoxic and targeted clinical anti-cancer agents reveal multiple examples of synergistic inhibition of proliferation in vitro, and this synergy generally appears selectively in oncogenic B-Raf-bearing cells. The good oral bioavailability (F &gt; 70%) allows for prolonged exposure in both rodents and non-rodents. Robust efficacy is evident in a murine COLO205 tumor xenograft model, with once-daily oral dosing at 20 mg/kg over 14 days resulting in &gt; 80% inhibition of tumor growth with no effect on body weight. Conclusions: Since this compound is highly selective and targets a B-Raf variant that is absent in all non-transformed cells, it may have a broad therapeutic index, alone or in combination, for the treatment of patients with V600E oncogenic B-Raf tumors. [Table: see text]
Internal Versus External Electrical Cardioversion of Atrial Arrhythmia in Patients With Implantable Cardioverter-Defibrillator
Authors: Jakob Lüker, Kathrin Kuhr, Arian Sultan, Georg Nölker, Hazem Omran, Stephan Willems, René Andrié, Jan W. Schrickel, Stefan Winter, Dirk Vollmann, Roland R. Tilz, Alexander Jobs, Christian-H. Heeger, Andreas Metzner, Sven Meyer, Karl Mischke, Andreas Napp, Andreas Fahrig, Susanne Steinhauser, Johannes Brachmann, Stephan Baldus, Rajiv Mahajan, Prashanthan Sanders, Daniel Steven
Journal: Circulation (2019)

Background: Atrial arrhythmias are common in patients with implantable cardioverter-defibrillator (ICD). External shocks and internal cardioversion through commanded ICD shock for electrical cardioversion are used for rhythm-control. However, there is a paucity of data on efficacy of external versus internal cardioversion and on the risk of lead and device malfunction. We hypothesized that external cardioversion is noninferior to internal cardioversion for safety, and superior for successful restoration of sinus rhythm. Methods: Consecutive patients with ICD undergoing elective cardioversion for atrial arrhythmias at 13 centers were randomized in 1:1 fashion to either internal or external cardioversion. The primary safety end point was a composite of surrogate events of lead or device malfunction. Conversion of atrial arrhythmia to sinus rhythm was the primary efficacy end point. Myocardial damage was studied by measuring troponin release in both groups. Results: N=230 patients were randomized. Shock efficacy was 93% in the external cardioversion group and 65% in the internal cardioversion group ( P &lt;0.001). Clinically relevant adverse events caused by external or internal cardioversion were not observed. Three cases of pre-existing silent lead malfunction were unmasked by internal shock, resulting in lead failure. Troponin release did not differ between groups. Conclusions: This is the first randomized trial on external vs internal cardioversion in patients with ICDs. External cardioversion was superior for the restoration of sinus rhythm. The unmasking of silent lead malfunction in the internal cardioversion group suggests that an internal shock attempt may be reasonable in selected ICD patients presenting for electrical cardioversion. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03247738.
A Practical Treatise on the Diseases of Women.
Journal: JAMA (1891)

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
Non-coding RNAs in cardiovascular cell biology and atherosclerosis
Authors: Francesca Fasolo, Karina Di Gregoli, Lars Maegdefessel, Jason L Johnson
Journal: Cardiovascular Research (2019)

Atherosclerosis underlies the predominant number of cardiovascular diseases and remains a leading cause of morbidity and mortality worldwide. The development, progression and formation of clinically relevant atherosclerotic plaques involves the interaction of distinct and over-lapping mechanisms which dictate the roles and actions of multiple resident and recruited cell types including endothelial cells, vascular smooth muscle cells, and monocyte/macrophages. The discovery of non-coding RNAs (ncRNAs) including microRNAs, long non-coding RNAs, and circular RNAs, and their identification as key mechanistic regulators of mRNA and protein expression has piqued interest in their potential contribution to atherosclerosis. Accruing evidence has revealed ncRNAs regulate pivotal cellular and molecular processes during all stages of atherosclerosis including cell invasion, growth, and survival; cellular uptake and efflux of lipids, expression and release of pro- and anti-inflammatory intermediaries, and proteolytic balance. The expression profile of ncRNAs within atherosclerotic lesions and the circulation have been determined with the aim of identifying individual or clusters of ncRNAs which may be viable therapeutic targets alongside deployment as biomarkers of atherosclerotic plaque progression. Consequently, numerous in vivo studies have been convened to determine the effects of moderating the function or expression of select ncRNAs in well-characterized animal models of atherosclerosis. Together, clinicopathological findings and studies in animal models have elucidated the multifaceted and frequently divergent effects ncRNAs impose both directly and indirectly on the formation and progression of atherosclerosis. From these findings' potential novel therapeutic targets and strategies have been discovered which may pave the way for further translational studies and possibly taken forward for clinical application.
Paediatric severe asthma: a need for novel innate molecular phenotypes
Authors: Kristina Laubhahn, Bianca Schaub
Journal: European Respiratory Journal (2019)

Asthma is a heterogeneous chronic inflammatory disease of the airways with variety of different phenotypes and is most frequently classified according to clinical phenotypes into allergic and non-allergic asthma [1] or according to severity into intermittent, mild, moderate or severe asthma [2]. Asthma affects around 14% of children worldwide and different immune cells and inflammatory mediators play a role, leading to typical asthma pathophysiology [3]. Severe asthma is associated with high mortality, morbidity and healthcare expense [4]. Molecular phenotyping and mainstay treatment of children with severe asthma is a great challenge and requires further in depth studies <http://bit.ly/2ME9GQP>
Homeobox B9 integrates bone morphogenic protein 4 with inflammation at atheroprone sites
Authors: Celine Souilhol, Ismael Gauci, Shuang Feng, Blanca Tardajos Ayllon, Marwa Mahmoud, Lindsay Canham, Maria Fragiadaki, Jovana Serbanovic-Canic, Victoria Ridger, Paul Charles Evans
Journal: Cardiovascular Research (2019)

Atherosclerosis develops near branches and bends of arteries that are exposed to disturbed blood flow which exerts low wall shear stress (WSS). These mechanical conditions alter endothelial cells (EC) by priming them for inflammation and by inducing turnover. Homeobox (Hox) genes are developmental genes involved in the patterning of embryos along their anterior-posterior and proximal-distal axes. Here we identified Hox genes that are regulated by WSS and investigated their functions in adult arteries.EC were isolated from inner (low WSS) and outer (high WSS) regions of the porcine aorta and the expression of Hox genes was analysed by quantitative real-time PCR. Several Hox genes (HoxA10, HoxB4, HoxB7, HoxB9, HoxD8, HoxD9) were significantly enriched at the low WSS compared to the high WSS region. Similarly, studies of cultured human umbilical vein EC (HUVEC) or porcine aortic EC revealed that the expression of multiple Hox genes (HoxA10, HoxB9, HoxD8, HoxD9) was enhanced under low (4 dyn/cm2) compared to high (13 dyn/cm2) WSS conditions. Gene silencing studies identified Hox genes (HoxB9, HoxD8, HoxD9) that are positive regulators of inflammatory molecule expression in EC exposed to low WSS, and others (HoxB9, HoxB7, HoxB4) that regulated EC turnover. We subsequently focused on HoxB9 because it was strongly up-regulated by low WSS and, uniquely, was a driver of both inflammation and proliferation. At a mechanistic level, we demonstrate using cultured EC and murine models that bone morphogenic protein 4 (BMP4) is an upstream regulator of HoxB9 which elicits inflammation via induction of numerous inflammatory mediators including TNF and downstream NF-κB activation. Moreover, the BMP4-HoxB9-TNF pathway was potentiated by hypercholesterolaemic conditions.Low WSS induces multiple Hox genes that control the activation state and turnover of EC. Notably, low WSS activates a BMP4-HoxB9-TNF signalling pathway to initiate focal arterial inflammation, thereby demonstrating integration of the BMP and Hox systems in vascular pathophysiology.
Best practices for bioinformatic characterization of neoantigens for clinical utility
Authors: Megan M. Richters, Huiming Xia, Katie M. Campbell, William E. Gillanders, Obi L. Griffith, Malachi Griffith
Journal: Genome Medicine (2019)

Neoantigens are newly formed peptides created from somatic mutations that are capable of inducing tumor-specific T cell recognition. Recently, researchers and clinicians have leveraged next generation sequencing technologies to identify neoantigens and to create personalized immunotherapies for cancer treatment. To create a personalized cancer vaccine, neoantigens must be computationally predicted from matched tumor-normal sequencing data, and then ranked according to their predicted capability in stimulating a T cell response. This candidate neoantigen prediction process involves multiple steps, including somatic mutation identification, HLA typing, peptide processing, and peptide-MHC binding prediction. The general workflow has been utilized for many preclinical and clinical trials, but there is no current consensus approach and few established best practices. In this article, we review recent discoveries, summarize the available computational tools, and provide analysis considerations for each step, including neoantigen prediction, prioritization, delivery, and validation methods. In addition to reviewing the current state of neoantigen analysis, we provide practical guidance, specific recommendations, and extensive discussion of critical concepts and points of confusion in the practice of neoantigen characterization for clinical use. Finally, we outline necessary areas of development, including the need to improve HLA class II typing accuracy, to expand software support for diverse neoantigen sources, and to incorporate clinical response data to improve neoantigen prediction algorithms. The ultimate goal of neoantigen characterization workflows is to create personalized vaccines that improve patient outcomes in diverse cancer types.
Systemic Therapy for Locally Advanced and Metastatic Non–Small Cell Lung Cancer
Authors: Kathryn C. Arbour, Gregory J. Riely
Journal: JAMA (2019)

<h3>Importance</h3> Non–small cell lung cancer remains the leading cause of cancer death in the United States. Until the last decade, the 5-year overall survival rate for patients with metastatic non–small cell lung cancer was less than 5%. Improved understanding of the biology of lung cancer has resulted in the development of new biomarker–targeted therapies and led to improvements in overall survival for patients with advanced or metastatic disease. <h3>Observations</h3> Systemic therapy for metastatic non–small cell lung cancer is selected according to the presence of specific biomarkers. Therefore, all patients with metastatic non–small cell lung cancer should undergo molecular testing for relevant mutations and expression of the protein PD-L1 (programmed death ligand 1). Molecular alterations that predict response to treatment (eg,<i>EGFR</i>mutations,<i>ALK</i>rearrangements,<i>ROS1</i>rearrangements, and<i>BRAF</i>V600E mutations) are present in approximately 30% of patients with non–small cell lung cancer. Targeted therapy for these alterations improves progression-free survival compared with cytotoxic chemotherapy. For example, somatic activating mutations in the<i>EGFR</i>gene are present in approximately 20% of patients with advanced non–small cell lung cancer. Tyrosine kinase inhibitors such as gefitinib, erlotinib, and afatinib improve progression-free survival in patients with susceptible<i>EGFR</i>mutations. In patients with overexpression of ALK protein, the response rate was significantly better with crizotinib (a tyrosine kinase inhibitor) than with the combination of pemetrexed and either cisplatin or carboplatin (platinum-based chemotherapy) (74% vs 45%, respectively;<i>P</i> &lt; .001) and progression-free survival (median, 10.9 months vs 7.0 months;<i>P</i> &lt; .001). Subsequent generations of tyrosine kinase inhibitors have improved these agents. For patients without biomarkers indicating susceptibility to specific targeted treatments, immune checkpoint inhibitor–containing regimens either as monotherapy or in combination with chemotherapy are superior vs chemotherapy alone. These advances in biomarker-directed therapy have led to improvements in overall survival. For example, the 5-year overall survival rate currently exceeds 25% among patients whose tumors have high PD-L1 expression (tumor proportion score of ≥50%) and 40% among patients with<i>ALK</i>-positive tumors. <h3>Conclusions and Relevance</h3> Improved understanding of the biology and molecular subtypes of non–small cell lung cancer have led to more biomarker-directed therapies for patients with metastatic disease. These biomarker-directed therapies and newer empirical treatment regimens have improved overall survival for patients with metastatic non–small cell lung cancer.
The Creative Home.
Journal: JAMA (1931)

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
Divide and conquer: two stem cell populations in squamous epithelia, reserves and the active duty forces
Authors: Spencer Dunaway, Alexandra Rothaus, Yuhang Zhang, Ana Luisa Kadekaro, Thomas Andl, Claudia D. Andl
Journal: International Journal of Oral Science (2019)

Stem cells are of great interest to the scientific community due to their potential role in regenerative and rejuvenative medicine. However, their role in the aging process and carcinogenesis remains unclear. Because DNA replication in stem cells may contribute to the background mutation rate and thereby to cancer, reducing proliferation and establishing a relatively quiescent stem cell compartment has been hypothesized to limit DNA replication-associated mutagenesis. On the other hand, as the main function of stem cells is to provide daughter cells to build and maintain tissues, the idea of a quiescent stem cell compartment appears counterintuitive. Intriguing observations in mice have led to the idea of separated stem cell compartments that consist of cells with different proliferative activity. Some epithelia of short-lived rodents appear to lack quiescent stem cells. Comparing stem cells of different species and different organs (comparative stem cell biology) may allow us to elucidate the evolutionary pressures such as the balance between cancer and longevity that govern stem cell biology (evolutionary stem cell biology). The oral mucosa and its stem cells are an exciting model system to explore the characteristics of quiescent stem cells that have eluded biologists for decades.