tbuckley/cabot-search huggingface dataset:
GC-01 * ELUCIDATION OF PATHOGENESIS IN INTRACRANIAL GERM CELL TUMORS BASED ON A GENOME-WIDE METHYLATION STUDY
Authors: S. Fukushima, S. Yamashita, H. Takami, K. Fukuoka, Y. Narita, T. Ushijima, M. Matsutani, R. Nishikawa, K. Ichimura
Journal: Neuro-Oncology (2015)

OBJECTIVE: Although “germ cell theory” that primordial germ cells (PGCs) might be a cell of origin of intracranial germ cell tumors (iGCTs) is now widely accepted, the nature of this heterogeneous tumor remains largely unknown. To elucidate the pathogenesis of iGCT, we are currently conducting a comprehensive methylation analysis. METHODS: Bisulfite-modified DNA of 58 iGCTs from frozen tissues (20 germinomas, and 38 NGGCTs), and 4 mixed-GCTs from FFPE tissues after microdissection (germinoma and the other histological component) were subjected to a genome-wide methylation analysis using HumanMethylation450 BeadChip, which were subclassified by an unsupervised hierarchical clustering. The DNA methylation levels of iGCTs were compared to those of mice PGCs in the published data. In mixed-GCTs after microdissection, mutation status of each component was analyzed by Sanger sequencing. RESULTS: According to the methylation profiles, iGCTs were subclassified into the following 3 groups; global lower methylation (GLM), partial lower methylation (PLM) and higher methylation (HM). Pure germinomas showed a prominent hypomethylation pattern clustered to GLM, which is a unique epigenomic feature distinguishable from NGGCTs. DNA methylation profiles in pure germinoma are similar to those in mice PGCs at E10.5. Mixed-GCTs show different methylation, but common mutation profiles between germinoma and the other histological component. CONCLUSION: We conclude that intracranial germinoma might originate from the migration phase of PGC, but the other subtypes of GCTs might not. We further propose that mutation is earlier event than methylation in the pathogenesis of iGCTs.
Myocardial Induction of Nucleostemin in Response to Postnatal Growth and Pathological Challenge
Authors: Sailay Siddiqi, Natalie Gude, Toru Hosoda, John Muraski, Marta Rubio, Gregory Emmanuel, Jenna Fransioli, Serena Vitale, Carola Parolin, Domenico D'Amario, Erik Schaefer, Jan Kajstura, Annarosa Leri, Piero Anversa, Mark A. Sussman
Journal: Circulation Research (2008)

Stem cell-specific proteins and regulatory pathways that determine self-renewal and differentiation have become of fundamental importance in understanding regenerative and reparative processes in the myocardium. One such regulatory protein, named nucleostemin, has been studied in the context of stem cells and several cancer cell lines, where expression is associated with proliferation and maintenance of a primitive cellular phenotype. We find nucleostemin is present in young myocardium and is also induced following cardiomyopathic injury. Nucleostemin expression in cardiomyocytes is induced by fibroblast growth factor-2 and accumulates in response to Pim-1 kinase activity. Cardiac stem cells also express nucleostemin that is diminished in response to commitment to a differentiated phenotype. Overexpression of nucleostemin in cultured cardiac stem cells increases proliferation while preserving telomere length, providing a mechanistic basis for potential actions of nucleostemin in promotion of cell survival and proliferation as seen in other cell types.
The association between hyperoxia and patient outcomes after cardiac arrest: analysis of a high-resolution database
Authors: Jonathan Elmer, Michael Scutella, Raghevesh Pullalarevu, Bo Wang, Nishit Vaghasia, Stephen Trzeciak, Bedda L. Rosario-Rivera, Francis X. Guyette, Jon C. Rittenberger, Cameron Dezfulian
Journal: Intensive Care Medicine (2014)
Abstract 4688: A relationship between environmental tobacco smoke (ETS) and epidermal growth factor receptor (EGFR) mutations in never smoker patients with non-small cell lung cancer
Authors: Young Joo Lee, Byoung Chul Cho, Hye Jin Choi, Jin Gu Lee, Joo-Hang Kim
Journal: Cancer Research (2010)

Abstract Purpose The etiology of EGFR-mutant lung cancer remains unknown. The high incidence of EGFR mutations are observed in life-time never smokers. We investigated whether the risk factors of lung cancer in never smoker may be associated with a mutant-EGFR dependent carcinogenesis. Especially, we focused on the effect of ETS on EGFR-mutant lung cancer. Patients and Methods We enrolled 179 consecutive never smokers who were newly diagnosed with NSCLC. The history of ETS exposure was obtained with a standardized questionnaire that included exposure period, place, and duration. The nucleotide sequences of exons 18-21 on EGFR gene were determined using nested PCR amplification. Those patients with an exon 19 deletion and exon 21 point mutations were selected as a subgroup with activating mutations for further analysis. Results The median total smoker-year of patients with ETS exposure was higher than that of those without (25 years vs. 15 years; P = 0.002). The incidence of EGFR mutations was significantly lower in patients with ETS exposure than in those without (38.5% vs. 61.4%; P = 0.008). The proportion of exon 19 mutation was lower in patients with ETS exposure (59.6% vs. 81.5%; P = 0.050). In a logistic regression model that adjusted for gender and histology, an adjusted odds ratio (AOR) for the risk of EGFR mutations with exposure to ETS was 0.40 (95% confidential interval [CI], 0.20-0.81; P = 0.011). In quartile groups based on total smoker-year, the AORs for the lowest- to highest-quartile groups were 0.59 (95% CI, 0.23-1.49), 0.50 (0.17-1.50), 0.48 (0.20-1.18), and 0.22 (0.08-0.62) (Ptrend = 0.028). The period and place of ETS exposure had no different effect on the incidence of EGFR mutations. Patients with ETS exposure showed a lower response rate to EGFR tyrosine kinase inhibitors than did patients without ETS exposure (24.6% vs. 44.8%; P = 0.053). Conclusions Exposure to ETS is negatively associated with the incidence of EGFR mutations in lung cancer in never smokers. There was an inverse trend between the cumulative dose of ETS exposure and the frequency of EGFR mutations. A mutant-EGFR-dependent carcinogenesis may be different from a tobacco-smoke-associated carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4688.
PNEUMONIC FEVER; ITS SYMPTOMATOLOGY.
Authors: EDWARD F. WELLS
Journal: JAMA (1894)

NERVOUS SYSTEM. Headache of more or less prominence is encountered in almost every case. In my experience it has not seemed to differ in character from that met with in other febrile disorders. It is a symptom of the early periods of the attack, in adults usually diminishing or ceasing after a few days. In children it is often a most distressing symptom, continuing throughout the attack and possibly overshadowing all others. Severe frontal headache is so constant and prominent in senile pneumonic fever that its occurrence in an aged person should lead to an examination of the lungs. The headache is greatly aggravated by efforts at coughing and vomiting. Juergensen has met with two cases of pneumonic fever following exposure of the bared head to the hot sun, in which the seizure began with lancinating pains in the head and the symptoms of insolation. It has been thought that
Abstract 3027: Dishevelled proteins are highly upregulated in chronic lymphocytic leukemia
Authors: Abdul Salam Khan, Anders Österborg, Ali Moshfegh, Håkan Mellstedt
Journal: Cancer Research (2012)

Abstract Chronic Lymphocytic Leukemia (CLL) is the most common adult leukemia and is characterized by the progressive accumulation of CD5+ B cells. An important signaling pathway in CLL cells might be Wnt signaling pathways. Wnt signaling pathways include the Wnt/ β-catenin pathway and the non-canonical Wnt pathways. Dishevelled proteins (DVL1, DVL2, and DVL3) are important mediators in Wnt signaling and have been shown in to be expressed many cancer types but their precise role is not clear. The aim of the study was to characterize the expression of DVL1, DVL2 and DVL3 proteins in indolent and progressive CLL and compare to normal white blood cells (PBMC) as well as to assess the expression of other important proteins of the canonical pathway as β-catenin and the non-canonical pathways as GSK-3β, PKC, ERK and AKT respectively. Leukemic cells from indolent (n=9) and progressive (n=9) CLL patients were isolated by Ficoll gradient centrifugation as well as PBMC from healthy donors (n=9). Six cell lines including four CLL cell lines EHEH, CII, I83, 232 B4, and the Jurkat and Lucas cell lines were also used. DVL 1, DVL 2, DVL 3 were analyzed by Western blot and densitometric calculations as well as PKC, GSK-3β, AKT and ERK using antibodies against the total protein and the phosphorylated protein respectively. Overexpression of DVL1, DVL 2, and DVL3 was seen in all indolent and progressive CLL patients and the six cell lines. There was a significantly higher expression of DVL 1 and DVL 3 in indolent compared to progressive CLL patients (p&amp;lt;0.01 and p&amp;lt;0.01 respectively). In contrast to DVL 1 and DVL 3, DVL 2 was highly expressed in indolent as compared to progressive CLL patients. ≤ -catenin followed the same expression pattern as DVL2 being highly expressed in indolent CLL as compared to progressive CLL patients (p&amp;lt;0.001). There was no significant difference in the degree phosphorylation of PKC and GSK-3β between indolent CLL, progressive CLL and healthy donors.The degree of AKT and ERK phosphorylation was significantly higher in indolent than in progressive CLL patients (p&amp;lt;0.001 and p&amp;lt;0.01 respectively). In summary DVL1, DVL2 and DVL3 are highly expressed in CLL patients and CLL cell lines but their expression in normal PBMC is almost negligible but expression of other canonical and non-canonical pathways proteins are seen both in CLL and healthy donors. DVL1, DVL2 and DVL3 may have a key role in the transduction of Wnt mediated signals in CLL. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3027. doi:1538-7445.AM2012-3027
THE CHANGE IN LOWER LIMB KINEMATIC AND EMG ACTIVITY OF SPRINTING AFTER SOCCER-SPECIFIC FATIGUE AMONG FEMALE SOCCER PLAYERS
Authors: CK Chan, SH Yung, MW Liu, KM Chan
Journal: British Journal of Sports Medicine (2014)

Background Hamstring strain during sprinting is one of the dominant injuries among soccer players, which constitutes 12–16% of all injury. Fatigue is claimed to alter the lower limb mechanism during sprinting, which trigger hamstring strain injury. Objective The purpose of this study was to find out the changes in electromyography and kinematic profile of the lower limb muscles during sprinting after fatigue among female soccer players, hence, to suggest injury prevention strategies. It is hypothesized that the EMG activity of BF and ST decrease after fatigue. Design Prospective observational study. Setting Kinematic and electromyographic analysis of sprinting before and after soccer-specific fatigue intervention were measured in an indoor setting. Participants 9 semi-professional female soccer players were recruited from 1 st division club teams. Risk factor assessment Each subject completed the SAFT90 soccer-specific fatigue protocol that simulates the movement pattern of soccer game. Main outcome measurements 20 metres sprint test were done on each subject before and after the SAFT90. EMG activity of biceps femoris (BF), semitendinosus (ST), rectus femoris (RF), vastus lateralis (VL) and vastus medialis (VM) and lower limb kinematic in sagittal plane were measured between 10 m–20 m during the sprints. Results The sprint time across the pre-test and post-test increased. Significant reduction in stride length and maximum combined hip flexion and knee extension angle were observed in the post-test. The EMG amplitude of BF decreased by 14.3%, and the EMG amplitude of ST increased by 10% in late swing phase across pre-test and post-test. Conclusions The reduction in maximum combined hip flexion and knee extension angle indicated that the length of hamstring muscle is shortened after fatigue. The alternation in muscle activation of ST and BF could be a mechanism to reduce the risk of muscle strain of BF during the late swing phase of sprinting after fatigue.
Association Between Newborn Birth Weight and the Risk of Postpartum Maternal Venous Thromboembolism
Authors: Marc Blondon, Bradley S. Quon, Laura B. Harrington, Henri Bounameaux, Nicholas L. Smith
Journal: Circulation (2015)

Postpartum venous thromboembolism (VTE) is a potentially fatal and preventable event leading to substantial short- and long-term morbidity. We sought to evaluate whether the delivery of term newborns of low or high birth weight was associated with greater risks of VTE.In a population-based case-control study conducted in Washington State from 1987 through 2011, cases of hospitalized VTE within 3 months of delivery were identified by using selected International Classification of Diseases, Ninth Revision, Clinical Modification codes. Controls were randomly selected postpartum women without VTE, matched on birth year. Birth weight and other maternal and pregnancy characteristics were extracted from birth certificate data. Among term live singleton deliveries, we compared the risk of VTE for mothers of newborns of low and high birth weights (<2500 g and >4000 g, respectively) versus mothers of newborns of normal birth weight (2500-4000 g). Logistic regression models were adjusted for maternal age, race, education, body mass index, parity, delivery methods, gestational length, smoking, gestational diabetes mellitus, and preeclampsia. Patients with VTE (n=547) were older, had a higher body mass index, and experienced more pregnancy-related complications than controls (n=9482). In comparison with mothers of newborns with normal birth weight, mothers of newborns with low birth weight had a 3-fold increased risk of VTE, which persisted after multivariable adjustment (odds ratio, 2.98; 95% confidence interval, 1.80-4.93). Mothers of newborns with high birth weight had only a slightly increased risk of VTE, which was attenuated after multivariable adjustment (odds ratio, 1.26; 95% confidence interval, 0.99-1.61).The delivery of a newborn with low birth weight is associated with a 3-fold increased risk of maternal postpartum VTE. This should be considered when assessing VTE risk at delivery.
Ending "forensic blind man's buff".
Authors: C Dyer
Journal: BMJ (1987)

A decision of the Court of Appeal last month1 could pave the way for more settlements in medical negligence cases and shorter (and therefore cheaper) trials for those cases that do go to court. The ruling, ordering advance mutual disclosure of experts' reports in four claims against health authorities, comes at a time when the whole system of civil justice is under review, with far reaching proposals to cut costs and delays. Though there has been a steady move towards more openness, the parties in the English legal system have traditionally kept many of their cards close to their chest, showing their full hands only at the trial. The drawbacks of this game of forensic blind man's bluff (Lord Justice MustilPs words) were starkly illustrated in a case which went to the Court of Appeal last year, Wilsher v Essex Area Health Authority.2 In that case, in which a premature baby's blindness was alleged to have been caused by the administration of excessive amounts of oxygen, the Master of the Rolls, Sir John Donaldson, described the result of non-disclosure as total disaster.
The Invisible Hospital and the Secret Garden: An Insider's Commentary on the NHS Reforms
Authors: P. Draper
Journal: BMJ (1995)

John Spiers Radcliffe Medical Press, pounds sterling18.50, pp 211 ISBN 1 85775 126 4

Do people who chair health boards need experience of organising health services or does the outsider bring a fresh and valuable perspective? John Spiers's book mainly consists of his sparingly revised speeches and articles from nearly four years of chairing first Brighton District Health Authority and then its hospitals trust. It provides plenty of ammunition for both sides of the argument despite what he calls his “premature discharge into the community by Brighton doctors” in 1994.

The Invisible Hospital and the Secret Garden omits Spiers's version …
The Virtue of Mobile and Free Money for the Future
Authors: Lester J. Evans
Journal: JAMA (1962)

ALTHOUGH I was asked to speak today because of a reasonably long experience as a foundation executive concerned with a broad spectrum of health activities, more particularly medical education in the last 15 years, there was no indication that my task is to defend, or extol, private foundations or voluntary giving. Rather, it was said that my experience, as well as my present university responsibility, might have led to certain observations which would be helpful at this moment when there is unprecedented public and professional interest in health. As a result of the opportunity to observe and, hopefully, to learn from the purposes for which money was given and the manner in which it was received, I have formed certain opinions which I hope are not too far afield. As more money has become available from all sources for varied activities and services, particularly research, in medical schools and their
The Global Fight against the Stigma of Schizophrenia
Authors: Nadia Kadri, Norman Sartorius
Journal: PLoS Medicine (2005)

The stigma attached to mental illness is the greatest obstacle to the improvement of the lives of people with mental illness and their families [1]. Such stigma results in (1) a lower priority for mental health services, (2) difficulty getting staff of good quality to work in these services, (3) continuing problems in finding employment and housing for people who have had an episode of mental disorder, (4) the social isolation of people who suffer from mental illness and their families, and (5) poorer quality of care for physical illnesses occurring in people diagnosed as having had psychiatric illnesses [1]. These effects of stigma are true for all mental disorders, and in particular, for schizophrenia.

The history of the stigmatisation of mental illness is long, but it is probable that intolerance to mental abnormality (and the rejection of people who had it) has become stronger in the past two centuries because of urbanisation and the growing demands for skills and qualifications in almost all sectors of employment. This, however, is only part of the story: mental illness is also linked to stigmatisation, discrimination, and intolerance in rural settings and in all countries, regardless of their level of industrialisation and sophistication of labour. Recent studies carried out in developing countries confirm that this stigma is universal [1]—indeed it is fair to say that stigma is attached to mental illness in different socio-cultural settings throughout the world, and that it is growing in strength and in its negative consequences.
Study of IgE antibody specificity to penicillin after a boosting process in patients allergic to betalactams
Authors: M. Blanca, C. Moya, J.L. Rodriguez-Bada, M.J. Torres, J.A. Cornejo-Garcia, C. Antunez, A.G. Romano, C. Mayorga
Journal: Journal of Allergy and Clinical Immunology (2003)
Routine hepatitis B virus DNA testing in patients with human immunodeficiency virus
Authors: Akif Altinbas, Fuat Ekiz, Osman Yuksel
Journal: Hepatology (2010)

We read the article by Núñez with great interest.1 In the literature, three cases who were positive for human immunodeficiency virus (HIV) were described with hepatitis B reactivation after withdrawal of hepatitis B virus (HBV)-active drug due to the virologic failure of HIV. All three of the patients were positive for antibody to hepatitis B core antigen (anti-HBc).2, 3 The HBV reactivations could be controlled by highly active antiretroviral therapy regimens including lamivudine and tenofovir in the first patient,2 tenofovir/emtricitabine in the second patient,3 and without any HBV-active drug in the third patient.2 The author's concerns were mostly based on economics. However, without knowing the HBV DNA presence, we should get some different recommendations for clinicians, such as choosing an HBV-active drug in all anti-HBc–positive patients with HIV. Moreover, some authors also suggest hat the follow-up should be based on HBV DNA levels in only anti-HBc–positive patients with HIV.2 Akif Altinbas M.D.*, Fuat Ekiz M.D.*, Osman Yuksel M.D. Assoc. Prof*, * Department of Gastroenterology, Dıskapı Yıldırım Beyazıt Education and Research Hospital Ankara, Turkey.
Tolerability-Adapted Imatinib 800 mg/d Versus 400 mg/d Versus 400 mg/d Plus Interferon-α in Newly Diagnosed Chronic Myeloid Leukemia
Authors: Rüdiger Hehlmann, Michael Lauseker, Susanne Jung-Munkwitz, Armin Leitner, Martin C. Müller, Nadine Pletsch, Ulrike Proetel, Claudia Haferlach, Brigitte Schlegelberger, Leopold Balleisen, Mathias Hänel, Markus Pfirrmann, Stefan W. Krause, Christoph Nerl, Hans Pralle, Alois Gratwohl, Dieter K. Hossfeld, Joerg Hasford, Andreas Hochhaus, Susanne Saußele
Journal: Journal of Clinical Oncology (2011)

Treatment of chronic-phase (CP) chronic myeloid leukemia (CML) with imatinib 400 mg/d can be unsatisfactory. Optimization of treatment is warranted.In all, 1,014 newly diagnosed CP-CML patients were randomly assigned to imatinib 800 mg/d (n = 338), imatinib 400 mg/d (n = 325), or imatinib 400 mg/d plus interferon alfa (IFN-α; n = 351). Dose adaptation to avoid higher-grade toxicity was recommended. First primary end point was major molecular remission (MMR) at 12 months.A higher rate of MMR at 12 months occurred with tolerability-adapted imatinib 800 mg/d than with imatinib 400 mg/d (59% [95% CI, 53% to 65%] v 44% [95% CI, 37% to 50%]; P < .001) or imatinib 400 mg/d plus IFN-α (59% v 46% [95% CI, 40% to 52%]; P = .002). Median dose in the 800-mg/d arm was 628 mg/d with a maximum dose of 737 mg/d during months 4 to 6 and a maintenance dose of 600 mg/d. All three treatment approaches were well tolerated with similar grade 3 and 4 adverse events. Independent of treatment approach, MMR at 12 months showed better progression-free survival (99% v 94%; P = .0023) and overall survival (99% v 93%; P = .0011) at 3 years when compared with > 1% on the international scale or no MMR but showed no difference in 0.1% to < 1% on the international scale, which closely correlates with complete cytogenetic remission.Treatment of early-phase CML with imatinib can be optimized. Early high-dose therapy followed by rapid adaptation to good tolerability increases the rate of MMR at 12 months. Achievement of MMR by month 12 is directly associated with improved survival.
Points: Late mortality after vagotomy and drainage for duodenal ulcer
Authors: C Caygill
Journal: BMJ (1984)

known inhibitors of the enzyme-for example, isoniazide.Isoniazide interferes with the ALA- synthase coenzyme, pyridoxal phosphate, and, chronically administered, has a potent inhibitory effect on the hepatic enzyme in guinea pigS.2 3 I know of no trial concerning the effect of the drug in acute porphyria, either clinical or experimental.