tbuckley/cabot-search huggingface dataset:
Radiation Exposure From Diagnostic Imaging in Patients with Lymphoma - The Cost Of The Cure?
Authors: Maeve P Crowley, Siobhan B O'Neill, Damien C O'Neill, Joesph A Eustace, Brian R Healey Bird, Mary R Cahill, Michael M Maher, Kevin N O' Regan, Derville M O'Shea
Journal: Blood (2013)
Potassium in heart failure.
Authors: A Caniggia
Journal: BMJ (1977)

best provoked by inhalation,30 while dietary manipulation is currently the most effective way of evincing food allergy.3'The solution to many of these problems lies in the introduction of pure, carefully characterised allergens for both skin testing and assays of specific IgE antibody.32 33"Allergy" has been a subject of confusion in the past and will not be clarified even now without rigorous standardisation.A good example of the perils of allergic controversy was the recent suggestion that milk allergy contributes to myocardial infarction; this was firmly refuted by prompt recourse to the RAST test.34
Abstract 44: Building patient-specific predictors of drug responses from cell line genomics
Authors: Christopher W. Szeto, Stephen Benz, Charlies Vaske
Journal: Clinical Cancer Research (2016)

Abstract Hundreds of model cancer cell lines from diverse tissues have now been comprehensively assayed using several different genome-scale technologies. Additionally, many of these model lines have been challenged with dozens of clinically available oncotherapies. Here we present a set of high-throughput technologies suitable for turning these diverse datasources into actionable, patient-specific diagnostic predictors of response. First, we computationally integrate diverse -omics data from the DNA, mRNA and protein levels into a pathway model of the cellular state. Next, parallel compute clusters are used to develop and evaluate accurate predictive models upon these pathway activity levels. Finally, these predictive models are used to suggest therapies in a patient-specific manner. Here we show results from applying these technologies to learning a simple 50-gene signature for response to the the tyrosine kinase inhibitor Dasatinib. This signature utilizes features from the TP53/FOXM1, FOS/JUN &amp; MYC pathways. We note that the exceptional responders to Dasatinib are enriched for nervous-system cancer cell lines. We applied our predictive signature to glioblastoma multiforme samples to correctly indicate which specific GBM patients may have respond to Dasatinib. Citation Format: Christopher W. Szeto, Stephen Benz, Charlies Vaske. Building patient-specific predictors of drug responses from cell line genomics. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr 44.
Progress against Cancer?
Authors: H J Berkel
Journal: New England Journal of Medicine (1986)

Data from the population based cancer registry in Alberta, Canada as well as from the National Canadian Cancer registry were used to evaluate the outcome of oncologic treatment over the past 25 years. Age standardized incidence rates for all cancers combined, and for most individual cancer sites separately, show a continuous increase over time. Overall, the mortality rates have been increasing as well. Age specific trends in incidence and mortality show that, despite an increase in incidence rate, only in childhood cancers does a decrease in mortality exist. However, in patients aged 50 years or more at the time of the cancer diagnosis an increase in mortality was noted which actually exceeded the increase in incidence. Site specific analysis showed a decreasing trend in mortality for Hodgkin's disease, testicular cancer, stomach cancer, and melanoma (in females). A disturbingly increasing trend, specifically in women, existed for lung cancer mortality. It is projected that in women in Alberta mortality from lung cancer will surpass breast cancer mortality to become the number one cancer killer in women within the next few years. The overall 1-year, 2-year, and 5-year relative survival for all cancers combined remained constant over the 25-year period covered in this study. In conclusion, when analyzing the three indicators (incidence, mortality, and survival rates) of success in the fight against cancer no objective signs of progress could be found. Exceptions are the childhood cancers and relatively infrequent tumors such as Hodgkin's disease and testicular cancer. A plea is made for a shift in funding towards an increased emphasis on applied prevention programs and research.
Hemorrhagic Stroke
Authors: Janet M. Torpy
Journal: JAMA (2010)

Hemorrhagic StrokeA stroke occurs when brain tissue is damaged because there is not enough blood flow or oxygen delivery to the brain' s cells.Ischemic strokes are a result of lack of blood flow.Different types of ischemic stroke may be due to blockage in the arteries that supply blood to the brain (such as in carotid artery disease), a clot in the smaller arteries in the brain itself (thrombotic stroke), a blood clot from the heart that travels to the brain (embolic stroke), or poor flow to the brain because of heart failure.Damage caused by bleeding into or around the brain is called a hemorrhagic stroke.Hemorrhagic strokes are less common than ischemic strokes but cause a significant number of deaths worldwide.Hemorrhagic strokes are also responsible for severe, nonfatal damage to brain tissue that can leave individuals paralyzed or weak, with difficulty speaking, swallowing, thinking properly, or doing activities of daily living.The June 9, 2010, issue of JAMA contains an article about hemorrhagic stroke.
John Mark Hinton
Authors: Kimberley Jensen
Journal: BMJ (2016)

John Mark Hinton was a pivotal figure in psychiatry and palliative care. He attended school at Christ’s Hospital, Horsham, and qualified at King’s College Hospital in 1949. During his houseman year at King’s, he met a ward sister, Pat, whom he married in 1950. After national service with the Royal Army Medical Corps in Sierra Leone, he returned to London, and, after a period of general medicine and neurology, he chose a psychiatric career path, making a career defining move to the Maudsley Hospital in 1955. While there he discovered that little research had been done to …
Mortality in Children and Adolescents, 1990-2013
Authors: Laurie Marczak, Kevin O’Rourke, Dawn Shepard
Journal: JAMA (2016)

This Visualizing Health Metrics infographic, based on the Global Burden of Disease Study 2013, provides information on mortality for children and adolescents from four age groups, including both sexes, from 1990 to 2013. The top causes of death in developed versus developing countries, as well as mortality rates by World Health Organization (WHO) region, are illustrated. In developed countries in 2013, the top cause of death for children under 1 was congenital anomalies, while in developing countries it was preterm birth complications. Sudden infant death syndrome was the fifth-highest cause of death for children under 1 in developed countries. In contrast, road injuries ranked highly across several age groups in both developed and developing countries. From 1990- 2013, mortality rates for children and adolescents declined in every WHO region. However, disparities in mortality rates persisted across WHO regions. Notably, mortality rates in the African region remained the highest relative to all other regions for every year from 1990 to 2013.
Abstract B21: Integrated genomic and functional analyses of histone demethylases identify oncogenic KDM2A isoform in breast cancer
Authors: Zeng-Quan Yang
Journal: Cancer Research (2016)

Abstract Histone lysine demethylases (KDMs) comprise a large class of enzymes that catalyze site-specific demethylation of lysine residues on histones and other proteins. They play critical roles in controlling transcription, chromatin architecture, and cellular differentiation. However, the genomic landscape and clinical significance of KDMs in breast cancer remain poorly characterized. Here, we conducted a meta-analysis of 24 KDMs in breast cancer and identified associations among recurrent copy number alterations, gene expression, breast cancer subtypes, and clinical outcome. Two KDMs, KDM2A and KDM5B, had the highest frequency of genetic amplification and overexpression. Furthermore, among the 24 KDM genes, KDM2A had the highest correlation between copy number and mRNA expression, and high mRNA levels of KDM2A were significantly associated with shorter survival of breast cancer patients. KDM2A has two isoforms: the long isoform is comprised of a JmjC domain, CXXC-zinc finger, PHD zinc finger, F-box, and the AMN1 protein domain; whereas the short isoform of KDM2A lacks the N-terminal JmjC domain but contains all other motifs. Detailed characterization of KDM2A in breast cancer revealed that the short isoform of KDM2A is more abundant than the long isoform at DNA, mRNA, and protein levels in a subset of breast cancers. Furthermore, our data indicate that the short isoform of KDM2A has oncogenic potential and functions as an oncogenic isoform in a subset of breast cancers. Taken together, our findings suggest that amplification and overexpression of the KDM2A short isoform is critical in breast cancer progression. Citation Format: Zeng-Quan Yang. Integrated genomic and functional analyses of histone demethylases identify oncogenic KDM2A isoform in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr B21.
Abstract P6-10-19: Clinicopathologic features of breast cancers that develop in women with previous benign breast disease
Authors: DW Visscher, MH Frost, LC Hartmanan, RD Frank, RA Vierkant, AE McCullough, SJ Winham, C Vachon, K Ghosh, KR Brandt, AM Farrell, Y Tarabishy, TJ Hieken, TC Haddad, RA Kraft, DC Radisky, AC Degnim
Journal: Cancer Research (2016)

Abstract Background Women with benign breast disease (BBD) have an increased risk for breast cancer (BC). Almost 30% of all BCs develop in women with prior BBD. Information about the features of the expected BCs after BBD would enable individualized surveillance and prevention strategies for these women. We sought to characterize BCs developing in a large cohort of women with BBD. Methods Our cohort includes 13,485 women who underwent breast biopsy for mammographic or palpable concern between 1967-2001. Biopsy slides were reviewed and classified as nonproliferative (NP), proliferative disease without atypia (PDWA), or atypical hyperplasia (AH). BCs were identified by follow-up questionnaires, medical records, and Tumor Registry data. BC tissues were obtained and reviewed. Results With a median follow-up of 15.8 years, 1273 women developed BC. Most BCs were invasive (81%), among which 61% were ductal, 13% mixed ductal/lobular, and 14% lobular. Two thirds were intermediate or high-grade, and 29% were node positive. Cancer characteristics were similar across the three histologic categories of BBD, with similar frequency of DCIS and invasive disease, tumor size, time to invasive BC, histologic type of BC, nodal positivity and HER2 positivity. Women with AH had a higher frequency of ER+ BC (91%) vs women with PD (80%) or NP (85%), p=0.02. Conclusion A substantial proportion of all BCs develop in women with prior BBD. We show that the majority of BCs after BBD are invasive tumors of ductal type, with a substantial proportion node positive. 84% of cancers were ER-positive. Chemoprevention should be strongly encouraged in higher-risk women with BBD. Citation Format: Visscher DW, Frost MH, Hartmanan LC, Frank RD, Vierkant RA, McCullough AE, Winham SJ, Vachon C, Ghosh K, Brandt KR, Farrell AM, Tarabishy Y, Hieken TJ, Haddad TC, Kraft RA, Radisky DC, Degnim AC. Clinicopathologic features of breast cancers that develop in women with previous benign breast disease. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-10-19.
Abstract IA08: Prostate cancer tumor dormancy and the development of metastases
Authors: Colm Morrissey
Journal: Cancer Research (2016)

Abstract Cancer dormancy refers to the prolonged clinical disease-free time between removal of the primary tumor and recurrence, which is common in prostate cancer (PCa). PCa disseminated tumor cells (DTC) can be detected in the bone marrow of patients with no evidence of disease (NED) and advanced disease (ADV). However, the molecular and cellular nature of DTC is unknown. Single cell transcriptomic analyses comparing DTC in NED versus ADV PCa patients identified a molecular signature associated with the p38 stress activated kinase pathway and dormancy. Understanding the mechanism by which dormant tumor cells are triggered to proliferate may provide new targets for therapy. We have demonstrated that LuCaP PCa xenografts, which appear dormant in vitro, can be induced to proliferate through contact with each other and bone marrow stroma. Constitutive activation of myosin light chain kinase (MLCK), a downstream effector of integrin-β1 and TGFβ2, in non-proliferating cells promoted cell proliferation. Additionally, gene expression analyses and in vitro data support a role for TGFβ2 in suppressing proliferation. Taken together, these data point to a potential mechanism by which PCa cells are released from dormancy to form lethal metastases. The early dissemination of cells from the primary to other sites most likely involves epithelial-mesenchymal transition (EMT)-like behavior. It has been proposed that further dissemination can occur where a metastasis can seed further metastases. TGFβ is a known driver of EMT which is associated with tumor aggressiveness and metastasis. We assessed the natural history of tumor dissemination and EMT-related markers TGFβ, Twist, Slug, and Zeb1 in bone and visceral metastases from castration resistant PCa (CRPC) patients. Importantly, nuclear Twist, Slug, and Zeb1 were only present in a subset of epithelial cells that had an EMT-like phenotype, suggesting only a subset of cells display an EMT-like behavior in any given CRPC metastasis. These studies highlight the biological relevance of dormancy, cell-contact and EMT-like behavior in the seeding and establishment of CRPC metastases. Citation Format: Colm Morrissey. Prostate cancer tumor dormancy and the development of metastases. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr IA08.
Effect Of The JAK1/2 Inhibitor GS-0387 (momelotinib) On The Anemia Associated With a Preclinical Murine Model Of Human Primary Myelofibrosis
Authors: Jean-Luc Villeval, Claudine Moratal, Franck Debeurme, Catherine Lacout, Eric Solary, William Vainchenker, Christopher J Burns, Gregg Smith
Journal: Blood (2013)
Abstract IA02: Human ES cells for modeling brain cancer
Authors: Viviane Tabar
Journal: Cancer Research (2016)

Abstract Diffuse Intrinsic Pontine Gliomas (DIPG) are a highly aggressive tumor of the brainstem occurring primarily in children. The outlook of patients with this disease is particularly dire due to the tumor's inaccessible location and its lethal course over one or two years. Recent sequencing data identified, for the first time in human cancer, heterozygous mutations in the histone H3 that create a lysine to methionine amino acid substitution. Using a human ES-based platform, we demonstrate the exquisitely cell-context specific oncogenic role of the H3K27M mutation. The model recapitulated the histological features and in vivo progression of the human tumor, as well as its transcriptomal and epigenetic profile. Genome wide analyses indicate a resetting of the transformed precursors to a developmentally more primitive state, with evidence of major modifications of histone marks at master regulatory genes. Drug screens in the ES model identified a compound that targets menin, a protein with multiple partners the mixed leukemia lineage protein MLL. The compounds have been validated in patient derived DIPG cell lines and are undergoing intense preclinical assessments. The ES model, coupled with more recent gene editing technology, provides a very powerful platform for the dissection of the requirements of neoplastic transformation in specific tumors, the specification of cells of origin, as well insight into the downstream effectors of individual and combined mutations. Human pluripotent stem cells have an excellent potential as platform for modeling cancer. Work to extend these findings to additional mutations and tumor types is ongoing. Ref. Funato et al. Science. 2014 Dec 19;346 (6216) Citation Format: Viviane Tabar. Human ES cells for modeling brain cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr IA02.
The Forgotten People: Survey of the Chronic Younger Sick in Welsh Hospitals
Authors: J M Swithinbank, N Beswick, J F Mayberry
Journal: Journal of the Royal Society of Medicine (1984)

In a survey of Welsh hospitals, 96 patients were identified who had been continuously resident for between 4 months and 20 years; they were aged between 15 and 65 years on admission. The commonest causes for such admissions were cerebrovascular accidents, trauma and diabetes. Suitable facilities for the long-term care and rehabilitation of such severely disabled young people are very limited in Wales, and in an era when rehabilitation should be possible they have been forgotten.
Explaining the increased arrest rate among mental patients: the changing clientele of state hospitals
Authors: H J Steadman, J J Cocozza, M E Melick
Journal: American Journal of Psychiatry (1978)

The arrest rates of nearly 2,000 psychiatric patients released from psychiatric centers in 1968 and those of nearly 2,000 patients released in 1975 were compared with the arrest rates of a group of 5,000 patients studied 25 years earlier. In general, arrest rates among the two recent samples were considerably higher than general population rates, primarily because of the large proportion of patients previously arrested. Other characteristics related to subsequent arrest were age and admitting diagnosis. One additional finding was that the number of patients with prior arrests had increased markedly over the years.
Estrogen Use in Postmenopausal Women
Authors: A M Kaunitz
Journal: New England Journal of Medicine (1980)

It is unfortunate that Weinstein's report in the August 7 issue on the cost effectiveness of estrogen use during menopause fails to discuss progestogens. The Journal has published a series of retrospective studies linking endometrial cancer with estrogen treatment. None of the patients with endometrial cancer in these studies received appropriate progestogen therapy (described by Quigley and Hammond as 7-10 days of progestogen use each month). Indeed, British experts on menopause have labelled American neglect of progestogens as "bizarre." To bemoan the risks of endometrial cancer associated with therapy with estrogen alone is out of date. That progestogen therapy markedly reduces and apparently even eliminates the risk of endometrial neoplasia associated with estrogen use in menopausal women has now been well established by both British and American prospective studies. Initial enthusiastic and inappropriate use of estrogen in this country hass now been followed by a marked drop in estrogen prescribing, reflecting professional and lay reaction to the cancer risk inherent in such therapy. If American medicine is willing to embrace a more enlightened approach toward the use of sex steroids during menopause, the current cost effectiveness of menopausal estrogen can be adjusted in a most desirable direction.
Antitumor activity of alectinib (CH5424802/RO5424802) for ALK-rearranged NSCLC with or without prior crizotinib treatment in bioequivalence study.
Authors: Kazuhiko Nakagawa, Toyoaki Hida, Takashi Seto, Miyako Satouchi, Makoto Nishio, Katsuyuki Hotta, Haruyasu Murakami, Yuichiro Ohe, Koji Takeda, Masahiro Tatsuno, Naoki Yoshikawa, Tomohiro Tanaka, Tomohide Tamura
Journal: Journal of Clinical Oncology (2014)

8103 Background: Alectinib, a potent highly selective ALK inhibitor, shows good efficacy and safety for crizotinib-naïve and -resistant patients (pts) with ALK-rearranged non-small cell lung cancer (NSCLC). However, each dose required 8 capsules (caps). Thus, a higher strength formulation was developed. Methods: This 2-arm crossover study (JP28927) evaluated the bioequivalence of alectinib 300 mg b.i.d. with 20 and 40 mg caps vs. 150 mg caps at steady state in ALK-rearranged NSCLC pts. Primary objectives were to evaluate bioequivalence between drug formulations and food effect with 150 mg caps; secondary objectives were to evaluate efficacy and safety. Arm 1 of Cycle 1 (30 d) consisted of 300 mg b.i.d. with 20/40 mg caps for 10 d, 150 mg caps for the next 10 d, and 150 mg caps after meals for the last 10 d. The order was different in arm 2: 150 mg caps for 10 d, 20/40 mg caps for the next 10 d, and 150 mg caps after meals for the last 10 d. After Cycle 1, to evaluate bioequivalence, pts continued alectinib 300 mg b.i.d. with 150 mg caps until the investigator determined lack of clinical benefit. Tumors were assessed on Day 31 and 59, and then every 56 d. Results: As of Dec 16, 2013, 35 ALK-rearranged NSCLC pts were enrolled. The exposure between formulations was similar, and no food effect was seen with 150 mg caps. Safety (median follow-up period, 4 months) was acceptable: no pt discontinued treatment due to AEs; AEs were mostly Grade 1 or 2. Preliminary efficacy was observed with 63.3% partial response (PR) (including 9 unconfirmed PR) by investigator's assessment in the 30 pts with target lesions. Among 20 crizotinib-resistant pts with target lesions (median duration from last dose of crizotinib, 18.5 d [15–361]), response rate was 60.0% (including 5 unconfirmed PR) and median time to response was 36 d (29–119). In 2 pts, non-irradiated brain metastases over 10 mm had complete response at first assessment (Day 34 and 36). Conclusions: The exposure of 20/40 mg and 150 mg caps was similar, and no food effect was seen with 150 mg caps. Alectinib in 150 mg caps was efficacious for ALK-rearranged NSCLC pts regardless of crizotinib treatment history, with quick and high efficacy and good safety. Clinical trial information: JapicCTI-132186.