tbuckley/cabot-search huggingface dataset:
Once-Daily Tiotropium Respimat® Add-on to at Least Ics Maintenance Therapy Demonstrates Improved Lung Function in Patients with Symptomatic Asthma, Independent of Serum IgE or Blood Eosinophil Levels
Authors: Donald P. Tashkin, Ronald Dahl, Johann Christian Virchow, Michael Engel, Petra Moroni-Zentgraf, Liliana Zaremba-Pechmann, Huib A.M. Kerstjens
Journal: Journal of Allergy and Clinical Immunology (2016)
Commentary: Disagreements are not substantial
Authors: M R Law, N J Wald
Journal: BMJ (1994)

George Davey Smith and Matthias Egger agree with the conclusions and recommendations in our cholesterol papers*RF 1-3* and also with our recommendation against mass cholesterol testing.4 They disagree with us on two aspects but these are both minor. One relates to the methods and the other to interpretation. Neither affects the importance of serum cholesterol concentration in the aetiology and prevention of ischaemic heart disease, but both raise issues of general epidemiological application.

It is well recognised that cohort studies underestimate the dose-response relation between an imprecisely measured risk factor (here serum cholesterol) and its effect (here mortality from ischaemic heart disease).5 The statistical procedure to adjust for this regression dilution bias is simple, accurate, and corroborated by direct measurement.

Davey Smith and Egger do not give the correct reason for taking account of the second source of underestimation, the surrogate dilution effect. It is not that low density lipoprotein cholesterol measures an effect closer to the target site than total cholesterol. It is because it permits the quantitative reconciliation of data from observational studies with data from randomised trials. In the trials the reduction in total serum cholesterol concentration is almost entirely due to reduction in low density lipoprotein cholesterol because the interventions are relatively specific for this cholesterol subfraction. In the observational studies the variation in total serum cholesterol concentration is not due to low density lipoprotein cholesterol alone. This difference needs to be adjusted for if the two types of studies are to be quantitatively compared.

The adjustment is small, changing the estimated decrease in mortality from 24% to 27% for a 0.6 mmol/l decrease in cholesterol concentration.1 Davey Smith and Egger acknowledge that the association with ischaemic heart disease must be greater for low density lipoprotein …
Experiential sampling in the study of multiple personality disorder
Authors: R J Loewenstein, J Hamilton, S Alagna, N Reid, M deVries
Journal: American Journal of Psychiatry (1987)

The authors describe the application of experiential sampling, a new time-sampling method, to the assessment of rapid state changes in a woman with multiple personality disorder. She was signaled at random intervals during study periods and asked to provide information on alternate personality switches, amnesia, and mood state. The alternates displayed some characteristics that were as different as those occurring between separate individuals studied previously with this method. There were notable discrepancies between the self-report study data and information reported during therapy hours. The authors conclude that the phenomenology of multiple personality disorder is frequently more complex than is suspected early in the course of treatment.
Era 223—A Phase 3 Trial of Radium-223 Dichloride (Ra-223) in Combination with Abiraterone Acetate (Aa) and Prednisone in the Treatment of Asymptomatic or Mildly Symptomatic Chemotherapy-Naïve Patients with Bone-Predominant Metastatic Castration-Resistant Prostate Cancer (Crpc)
Authors: M.R. Smith, C. Parker, B. Tombal, K. Miller, F. Saad, F. Fang, A. Zhang, M. Kornacker, C. Higano
Journal: Annals of Oncology (2014)
Patterns of orodental injury and mouthguard use in Dutch field hockey
Authors: Strahinja Vucic, Rosalin W Drost, Arjen J van Wijk, Paul R Wesselink, Eppo B Wolvius
Journal: British Journal of Sports Medicine (2016)

Orodental injuries in field hockey are a growing cause of concern that requires attention.The objective of this cross-sectional study was to investigate the patterns of orodental injury, and the use of mouthguards in Dutch national field hockey.In the period from 1 May to 31 July 2014, a 33-item questionnaire about orodental injury and mouthguard use was sent to 7 field hockey clubs in the Netherlands. Data were analysed using 2 multivariable logistic (non-)linear regression per outcome measurement: (1) orodental injury and (2) type of mouthguard.Out of 6585 players, 1299 (20%) responded sufficiently and were eligible for the study. In total, 214 hockey players (16%) experienced at least 1 orodental injury in their career. The injuries were less severe in athletes who wore a mouthguard during an accident than in those who did not, OR=2.1 to 3.3, p≤0.05. Players without mouthguard sustained broken and knocked out teeth more frequently, while players with a mouthguard had more lip cuts (p≤0.05). Players complained less about custom-made than about mouth-moulded mouthguards (p≤0.05). Also, males were more at risk for an orodental injury, OR=1.4 (95% CI 1.0 to 1.9), and were less likely to have a custom-made mouthguard, OR=0.7 (95% CI 0.6 to 0.9), than females.A substantial number of field hockey players suffers from orodental injury. Mouthguards should be included in prevention strategies as they are associated with less severe injuries and patterns of injury are to be taken into account when targeting specific groups.
Proliferation of Tracheal Epithelial Cells in Normal and Vitamin A-Deficient Syrian Golden Hamsters2
Authors: Curtis C. Harris, Toby Silverman, Joseph M. Smith, Frank Jackson, Hollis G. Boren
Journal: JNCI Journal of the National Cancer Institute (1973)

The Syrian golden hamster is relatively insensitive to mitotic arrest caused by colchicine when compared to other animal species. Before measuring the mitotic index in vitamin A-deficient hamsters, we determined the dose of colchicine, which arrested the maximal number of mitotic cells in metaphase. This dose of colchicine was 10 mg/kg in the esophageal epithelium, 100 mg/kg in the duodenal epithelium, and 500 mg/kg in the regenerating epithelium of the trachea. The sensitivity to colchicine was, therefore, organ dependent. The number of mitotic cells arrested by colchicine was increased in the tracheal epithelium of vitamin A- deficient hamsters. Incorporation of3H-thymidine into mucous and basal cells was also augmented and measured by autoradiography.
An Ethical Framework for Allocating Scarce Life-Saving Chemotherapy and Supportive Care Drugs for Childhood Cancer
Authors: Yoram Unguru, Conrad V. Fernandez, Brooke Bernhardt, Stacey Berg, Kim Pyke-Grimm, Catherine Woodman, Steven Joffe
Journal: JNCI Journal of the National Cancer Institute (2016)

Shortages of life-saving chemotherapy and supportive care agents for children with cancer are frequent. These shortages directly affect patients' lives, compromise both standard of care therapies and clinical research, and create substantial ethical challenges. Efforts to prevent drug shortages have yet to gain traction, and existing prioritization frameworks lack concrete guidance clinicians need when faced with difficult prioritization decisions among equally deserving children with cancer. The ethical framework proposed in this Commentary is based upon multidisciplinary expert opinion, further strengthened by an independent panel of peer consultants. The two-step allocation process includes strategies to mitigate existing shortages by minimizing waste and addresses actual prioritization across and within diseases according to a modified utilitarian model that maximizes total benefit while respecting limited constraints on differential treatment of individuals. The framework provides reasoning for explicit decision-making in the face of an actual drug shortage. Moreover, it minimizes bias that might occur when individual clinicians or institutions are forced to make bedside rationing and prioritization decisions and addresses the challenge that individual clinicians face when confronted with bedside decisions regarding allocation. Whenever possible, allocation decisions should be supported by evidence-based recommendations. "Curability," prognosis, and the incremental importance of a particular drug to a given patient's outcome are the critical factors to consider when deciding how to allocate scarce life-saving cancer drugs.
Treatment compliance in patients with metastatic renal cell carcinoma.
Authors: C. Chen, G. P. Hess, J. W. Hill, Z. Liu, S. S. Agarwala
Journal: Journal of Clinical Oncology (2010)

e16560 Background: Treatment for metastatic renal cell carcinoma (mRCC) includes surgery, immunotherapy, and/or targeted therapy: kinase inhibitors (including mTOR) and anti-VEGF agents. Little is known about real-world compliance to these emerging treatments. This analysis utilizes recent data to provide insight into compliance, an important component of effectiveness. Methods: A retrospective observational study using SDI Health's claims data was conducted. The study period encompassed 1/1/2005 to 9/30/2009. Qualifying patients were adults diagnosed with RCC, and then diagnosed with a secondary neoplasm (n = 179) or treated with IL-2, IFN, sunitinib, sorafenib, temsirolimus, everolimus or bevacizumab (n = 470) during the study period. A 90-day gap in therapy defined the start and end of therapy. Compliance was measured as the medication possession ratio (MPR). For oral therapies, the MPR was calculated as (the number of days of supply dispensed/the number of days the patient was on therapy). For infused therapies, the MPR was defined as (the administration day plus the duration of clinical benefit (DCB)/the number of days the patient was on therapy). The DCB was based on the recommended frequency of administration in the label and regimen guidelines. Results: The study sample of 649 newly treated mRCC patients had a median age of 63 years. Male patients were more than double females (68.1 vs. 31.9%). Patients were generally very compliant across the entire range of mRCC regimens; the majority (i.e., 86.5% of patients) had an MPR ≥ 80%: the literature's threshold for high compliance. First line and second line patients had similar compliance (mean MPR 91.8% vs. 89.3%, p = 0.34). Within first line, oral therapy had a statistically higher MPR than infused therapy (0.94 vs. 0.89, p < 0.0001) but no difference was observed in second line (0.91 vs. 0.87, p=0.19). Conclusions: The observed compliance was similar across all treatment regimens and administration routes (oral vs. IV) for mRCC patients. Similar rates of compliance likely reflect varying combinations of contributing factors including safety, efficacy, and access to therapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis
Determination of Specificity in Natural Cell-Mediated Cytotoxicity by Natural Antibodies 2
Authors: Yukio Koide, Mitsuo Takasugi
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Determination of Specificity in Natural Cell-Mediated Cytotoxicity by Natural Antibodies Get access Yukio Koide, Yukio Koide 3Department of Surgery, School of Medicine, University of California, Los Angeles, Calif. 90024. Search for other works by this author on: Oxford Academic PubMed Google Scholar Mitsuo Takasugi Mitsuo Takasugi 4 3Department of Surgery, School of Medicine, University of California, Los Angeles, Calif. 90024. 5We thank Minarni Hardiwidjaja, Mary Langford, and Suzan Johnston for expert technical assistance, and Veronica Whalen, Lynn Babbitt, Nanette Covier, and Rita Loew for preparation of the manuscript. 4Address reprint requests to Dr. Takasugi. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 4, October 1977, Pages 1099–1105, https://doi.org/10.1093/jnci/59.4.1099 Published: 01 October 1977 Article history Received: 06 December 1976 Accepted: 25 April 1977 Published: 01 October 1977
Sprouty 2, an inhibitor of MAPK signalling is down-regulated I hepatocellular carcinoma
Authors: Wai, Fong, C, M-S Chua, AB McKie, Shm Ling, Mason, R Li, P Yusoff, Ling, Lo, T, HY Leung, Sks So, GR Guy
Journal: Cancer Research (2006)
Continuities between psychiatric disorders in adolescents and personality disorders in young adults
Authors: J M Rey, A Morris-Yates, M Singh, G Andrews, G W Stewart
Journal: American Journal of Psychiatry (1995)

Personality disorders are a major mental health problem, but little information about their etiology and natural history is available. This study examined continuities between axis I disorders in adolescents and personality disorders in young adults.The authors interviewed 145 young adults (mean age, 19.6 years) who had been diagnosed with a variety of DSM-III emotional and disruptive disorders during adolescence (mean age, 13.7 years). The Personality Disorder Examination was used to establish whether the subjects currently suffered from personality disorders.Subjects who had had disruptive disorders during adolescence showed high rates of all types of personality disorders (40% had a personality disorder at follow-up), while subjects who had had emotional disorders had a lower rate of personality disorders (12%). Men were more likely to have cluster A personality disorders, and women were more likely to have cluster C personality disorders. Disruptive diagnoses were associated with cluster B personality disorders, but emotional disorders did not show an association with cluster C personality disorders. Oppositional disorder did not increase the likelihood of passive-aggressive personality disorder. There was an association between attention deficit disorder with hyperactivity and borderline personality disorder.The rate of personality disorders was lower among young adults who had had emotional disorders during adolescence than among those who had had disruptive disorders, suggesting either that treatment for emotional disorders is more effective or that the personality psychopathology in these adolescents is not as severe as that in adolescents with disruptive disorders.
Position of the Carcinoembryonic Antigen of the Human Digestive System in Ultrastructure of Tumor Cell Surface&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Phil Gold, John Krupey, Harriett Ansari
Journal: JNCI Journal of the National Cancer Institute (1970)

A monospecific antibody preparation directed against the carcinoembryonic antigen (CEA) of the human digestive system was con jugated to ferritin. Many different specimens of viable colonic cancer tissue were incubated with the ferritin-anti-CEA conjugate and studied, by electron microscopy, for localization of the ferritin label. These studies revealed that CEA is, to a large extent, in the glycocalyx of the colonic cancer cell surface.
ATPS-19POLO LIKE KINASE INHIBITOR VOLASERTIB SYNERGISTICALLY IMPROVE RADIATION EFFICACY IN GLIOBLASTOMA
Authors: Jianwen Dong, Nghi Nguyen, Ravesanker Ezhilarasan, Shaofang Wu, Verlene Henry, Yuji Piao, Soon Young Park, Ningyi Tiao, Clifford Stephan, Erik Sulman, John de Groot
Journal: Neuro-Oncology (2015)

Despite the availability of hundreds of drugs, there is little data on the efficacy of these agents in the extremely heterogeneous populations of tumor cells observed in glioblastoma. In this study, a high-throughput compound-screening (HTS) assay was used to identify drug sensitivities in a panel of 15 glioblastoma stem cell (GSC) lines, which are representative of the classic cancer genome atlas (TCGA) molecular subtypes, to 21 compounds in Published Protein Kinase Inhibitor Set (PKSI, GSK). This HTS screen identified sensitivity of GSCs to inhibitors of polo like kinase-1 (PLK-1), a key regulator of mitosis. Given that PLK-1 is often overexpressed in a broad spectrum of cancers, and with highest expression levels being correlated with poor prognosis in several cancer types, we further verified the HTS result with the second-generation PLK1 inhibitor volasertib as a single agent or in combination with ionizing radiation. Efficacy of volasertib was analyzed by Cell-Titer Glo 5 days after treatment. Molecular and cellular changes were approached by immunoblotting and flow cytometry. In vitro studies showed that volasertib inhibited cell viability with an IC50 ranging from 8.2nM to 4.36 µM. Volasertib induced G2/M arrest accompanied by high levels of PLK-1, Aurora B and phospho-histone 3 and prominent cleaved poly ADP ribose polymerase (PARP) in a dose- and time-dependent manner. Colony formation assay demonstrated that volasertib plus ionizing radiation had synergistic effects on colony formation inhibition, suggesting that GSCs arrested in M phase by volasertib are more sensitive to ironizing radiation. Intracranial xenograft models showed that the combination of volasertib (10mg/Kg) and 10Gy radiation significantly inhibited GSC tumor growth and prolonged median survival when compared with radiation alone. Taken together, our results reinforce the potential therapeutic efficacy of volasertib in combination with radiation therapy for the treatment of glioblastoma.
Effect of Methylmercury Chloride on Transplacental Tumors Induced by Sodium Nitrite and Ethylurea in Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: J E Nixon, L D Koller, J H Exon
Journal: JNCI Journal of the National Cancer Institute (1979)

Pregnant W rats fed 10 ppm methylmercury chloride (MeHg) from weaning were administered increasing concentrations of sodium nitrite and ethylurea (EU) either in the diet or by gavage, and then progeny were observed for induction of neurogenic tumors. Progeny from the group treated with the highest dose of sodium nitrite-EU in the diet did not survive to weanling age. The mean survival times of the postweanling progeny from the group given MeHg plus the highest dose of sodium nitrite-EU by gavage (50 mg sodium nitrite and 100 mg EU/kg body wt) and of the postweanling progeny from the group given MeHg plus the intermediate dose of sodium nitrite-EU in the diet (1 g sodium nitrite/liter drinking water and 0.318% EU in the diet) were 51 and 57%, respectively, of that of the progeny from sodium nitrite-EU control treatments. Tumors developed earlier for these two treatments, and the mean latency period was 45 and 28% shorter, respectively, than that for the sodium nitrite-EU-treated controls. Furthermore, treatment with the highest dose of sodium nitrite-EU by gavage plus MeHg resulted in a 67% incidence of neural tumors before the first neural tumor occurred in the control progeny from rats given sodium nitrite-EU; in addition, it shortened the minimum latency period by 5 weeks. Ependymomas were found only in progeny from rats given MeHg plus sodium nitrite-EU, and the incidences of schwannomas of the cranial nerves were consistently higher in progeny from rats given MeHg plus sodium nitrite-EU than in the sodium nitrite-EU-treated controls. MeHg did not appear to affect incidences or latency periods of other neural tumors induced by the lowest doses of sodium nitrite-EU.
Alzheimer's disease and depression: neuropsychological impairment and progression of the illness
Authors: O L Lopez, F Boller, J T Becker, M Miller, C F Reynolds
Journal: American Journal of Psychiatry (1990)

The authors longitudinally evaluated the cognitive functions of patients with probable Alzheimer's disease who also met criteria for major depression and compared them with matched patients with Alzheimer's disease who were not depressed. They found no significant difference in the pattern of neuropsychological deficits between the two groups; composite scores on attention, language, memory, learning, and visuospatial functions did not differentiate the two groups at baseline or at 1-year follow-up. The results of this preliminary report suggest that depression does not modify the neuropsychological features and the rate of progression of Alzheimer's disease.
Peak in deaths in 2015 is not a complete mystery
Authors: John N Newton, Richard Pebody, Justine Fitzpatrick
Journal: BMJ (2016)

In his otherwise balanced article on the rise in death registrations in 2015, Hawkes overstates the case when he says that “public health experts are left grasping for answers.”1

Numbers of deaths fluctuate from year to year and have done for decades.2 They also vary markedly during the year owing …
Cancer outcomes will not improve without more funding, say GPs
Authors: Matthew Limb
Journal: BMJ (2015)

More general practitioners and diagnostic resources are needed in primary care to realise ambitions for improving cancer survival rates, doctors have warned.

Richard Roope, clinical lead for cancer at the Royal College of General Practitioners, said, “We really do need to spend money now to save money later and to save misery later.” He said that national cancer strategy recommendations for England must be backed up with resources, “or we’re facing a complete Armageddon in terms of funding in the future.”

Roope spoke at a seminar titled Next Steps for Cancer Care: Access, Integration and Policy Priorities, hosted in …
Neoadjuvant Therapy in Advanced Ovarian Cancer Patients: Efficiency of Screening By Laparoscopy for Clinical Trial Recruitment
Authors: R. Rouzier, E. Chereau, A. Floquet, F. Selle, V. Fourchotte, C. Pomel, P. Follana, S. Martin-Françoise, R. Fauvet, P. Colombo, E. Kalbacher, A. Lesoin, F. Lécuru, P.H. Cottu, F. Joly Lobbedez, V. Menguy, Y. Ghazi, P. Morice
Journal: Annals of Oncology (2014)
Therapeutic Trial of Pyrazole Derivative KB-92 in Patients with Rheumatoid Arthritis
Authors: G E PRICE, D K FORD
Journal: JAMA (1963)

A phenylbutazone-like pyrazole derivative, Sandoz KB-95, claimed to have antiserotonin, anti-inflammatory and analgesic properties, was tested on patients with rheumatoid arthritis. A double-blind study on 17 patients with definite or classical rheumatoid arthritis was performed for two-week periods on both KB-95 and placebo. Grip strength, the time to walk 50 feet, the number of other analgesic tablets taken daily, the erythrocyte sedimentation rate and a subjective rating of pain were the parameters of measurement. KB-95 failed to produce significantly more improvement than the placebo in this trial and was therefore considered not to be a useful drug for the treatment of rheumatoid arthritis. No acute toxic effects were observed to this dose of 300 mg. given three times daily.