tbuckley/cabot-search huggingface dataset:
The End of an Era: Shall We Move Forward?
Authors: Chau Dang
Journal: Journal of Clinical Oncology (2011)

Systemic adjuvant chemotherapy is a critical means for eradicating occult micrometastatic disease after surgery and has had a significant public health impact.2] The next generation of randomized clinical trials evaluated paclitaxel and docetaxel.These agents were well established in the treatment of metastatic breast cancer and lacked cross-resistance with the anthracyclines, which supported their evaluation in the adjuvant setting. 3Using these studies, a metaanalysis showed that the addition of a taxane to an anthracyclinebased regimen improved DFS and OS in high-risk patients regardless of age, menopausal status, the number of nodes involved, hormonereceptor status, and the type of taxane. 4There are now several effective anthracycline-taxane combinations and anthracycline-based regimens used in patients with high-risk disease.[7][8][9][10][11][12][13][14][15] In the article that accompanies this editorial, Eiermann et al 16 reported the results of the large randomized study Breast Cancer International Research Group (BCIRG) 005. 16They enrolled more than 3,000 patients with invasive human epidermal growth factor receptor 2 (HER2) -normal breast carcinoma and at least one lymph node involved and randomly assigned them to one of two chemotherapy regimens.These included AC (60/600 mg/m 2 ) ϫ 4 3 docetaxel (100 mg/m 2 ) ϫ 4 or TAC (75/50/500 mg/m 2 ) ϫ 6, and all cycles were given every 3 weeks.Antibiotic prophylaxis was mandatory for those on TAC but not for patients treated with AC 3 docetaxel.At a median follow-up of 65 months, the efficacy seemed equal, with a DFS of 78.6% and 78.9% and OS of 88.9% and 88.1% for AC 3 docetaxel and TAC, respectively.In subgroups defined by hormone receptor status or the number of involved nodes, there were no differences observed with either DFS or OS.As expected, there were differences in toxicities according to the regimen.For example, TAC was associated with a higher febrile neutropenia (FN) rate (17.4% v 7.7%; P Ͻ .001),despite the mandatory use of prophylactic antibiotics and a higher usage of filgrastim (44% of patients on TAC and 28% of those on AC 3 docetaxel).There was more fluid retention, hand-foot skin reaction, myalgia, and sensory neuropathy in the group receiving AC 3 docetaxel, possibly as a result of the higher dose of docetaxel per treatment cycle.The authors conclude that both regimens are equal in efficacy and represent appropriate treatment options.For clinicians, it is reasonable to ask how this should influence practice when a range of other evidence-based regimens exist that have not been directly compared.To provide additional background, I will expand the discussion
Enhancement of periodontal tissue regeneration by locally controlled delivery of insulin-like growth factor-I from dextran–co-gelatin microspheres
Authors: Fa-ming Chen, Yi-min Zhao, Hong Wu, Zhi-hong Deng, Qin-tao Wang, Wei Zhou, Qing Liu, Guang-ying Dong, Kun Li, Zhi-fen Wu, Yan Jin
Journal: Journal of Controlled Release (2006)
Gliomagenesis Arising from Pten- and Ink4a/Arf-Deficient Neural Progenitor Cells Is Mediated by the p53-Fbxw7/Cdc4 Pathway, Which Controls c-Myc
Authors: Hong Sug Kim, Kevin Woolard, Chen Lai, Peter O. Bauer, Dragan Maric, Hua Song, Aiguo Li, Svetlana Kotliarova, Wei Zhang, Howard A. Fine
Journal: Cancer Research (2012)

Glioblastoma multiforme is the most common type of primary malignant brain tumor and may arise from a cell with neural stem-like properties. Deregulation of the retinoblastoma, phosphoinositide-3 kinase (PI3K), and p53 pathways are molecular hallmarks of this disease. Recent work has shown that p53(-/-)Pten(-/-) mice form gliomas in a c-Myc-dependent manner. To explore the role of the INK4A/ARF locus and Pten deletions in gliomagenesis, we generated Pten(-/-)Ink4a/Arf(-/-) mouse neural stem cells (mNSC) and such cells were highly proliferative, self-renewing, relatively refractory to differentiation, and induced both low- and high-grade glioma formation in vivo. In contrast to p53(-/-) Pten(-/-) mNSCs, however, Pten(-/-)Ink4a/Arf(-/-) mNSCs do not express appreciable levels of c-Myc in vitro, although glioma stem cells derived from thesecells did. Sequencing of Pten(-/-)Ink4a/Arf(-/-) mNSC-derived tumors revealed spontaneous mutations in Tp53 in vivo with subsequent downregulation of Fbxw7. Expression of p53 mutants in Pten(-/-)Ink4a/Arf(-/-) mNSC or knockdown of Fbxw7 resulted in reexpression of c-Myc with enhanced Pten(-/-)Ink4a/Arf(-/-) mNSC tumorigenecity. We propose that p53 mutations contribute to gliomagenesis by both allowing the overexpression of c-Myc through downregulation of Fbxw7 and by protecting against c-Myc-induced apoptosis.
Mechanisms of Mesothelioma Induction With Asbestos and Fibrous Glass
Authors: Mearl F. Stanton, Constance Wrench
Journal: JNCI Journal of the National Cancer Institute (1972)

Three types of asbestos in 7 forms, 6 types of fibrous glass, 2 types of silica, and 2 types of metal particles were applied on a fibrous glass vehicle to the pleura of rats. In 2 years, amosite, chrysotile, and 4 different specimens of crocidolite yielded equally high incidences of pleural mesotheliomas in the range of 58–75%. Hand-milled crocidolite fibers not exposed to extraneous oils or metallic milling yielded dose-related tumor responses comparable to those of a standard reference milled crocidolite. Standard crocidolite, inducing a high incidence of mesotheliomas, caused fewer mesotheliomas (20–32%) when reduced to submicroscopie fibrils by excessive milling. Pulverized fragments of the steel mill and nickel metal at doses exceeding potential contaminating levels did not induce tumors. Microspheres of noncrystalline silica resulted in a single mesothelioma among 48 rats. The intact fibrous glass vehicle did not yield tumors, nor did its absence alter the incidence of crocidolite-induced tumors. However, when the fibrous glass vehicle and 2 other types of fibrous glass, ranging in mean diameters from 5–10 μ, were reduced to short fibrous fragments and applied to the pleura, 4 mesotheliomas were induced among 91 rats. Two forms of an especially fine fibrous glass, ranging from 0.06–3 μ in diameter, further milled to approach the length of asbestos fibers, resulted in moderately high incidences of mesotheliomas in the range of 12–18%. Thus carcinogenicity of asbestos and fibrous glass seems primarily related to the structural shape of these materials rather than to physicochemical properties.
Lack of Specificity of Plasma Concentrations of Inhibin B and Follicle-Stimulating Hormone for Identification of Azoospermic Survivors of Childhood Cancer: A Report From the St Jude Lifetime Cohort Study
Authors: Daniel M. Green, Liang Zhu, Nan Zhang, Charles A. Sklar, Raymond W. Ke, William H. Kutteh, James L. Klosky, Sheri L. Spunt, Monika L. Metzger, Fariba Navid, DeoKumar Srivastava, Leslie L. Robison, Melissa M. Hudson
Journal: Journal of Clinical Oncology (2013)

Many male survivors of childhood cancer are at risk for azoospermia. Although both the levels of follicle-stimulating hormone (FSH) and inhibin B are correlated with sperm concentration, their ability to predict azoospermia in survivors of childhood cancer remains uncertain.Semen analysis was performed and serum levels of FSH and inhibin B were measured in 275 adult male survivors of childhood cancer who had received gonadotoxic therapy. Receiver operating characteristic (ROC) analysis was performed to determine the optimal inhibin B and FSH values for identifying patients with azoospermia. The patient sample was divided into a learning set and a validation set. Sensitivity, specificity, and positive and negative predictive value were calculated.Inhibin B was dichotomized as ≤ 31 ng/L or more than 31 ng/L and FSH was dichotomized as ≤ 11.5 mIU/mL or more than 11.5 mIU/mL based on results of the ROC analysis. Using these values, the specificity of the serum level of inhibin B for identifying azoospermic survivors was 45.0%, and the positive predictive value was 52.1%. The specificity for FSH was 74.1%, and the positive predictive value was 65.1%.Neither serum inhibin B nor FSH is a suitable surrogate for determination of sperm concentration in a semen sample. Young men and their physicians should be aware of the limitations of these measures for assessment of fertility potential.
CCDC88B is a novel regulator of maturation and effector functions of T cells during pathological inflammation
Authors: James M. Kennedy, Nassima Fodil, Sabrina Torre, Silayuv E. Bongfen, Jean-Frédéric Olivier, Vicki Leung, David Langlais, Charles Meunier, Joanne Berghout, Pinky Langat, Jeremy Schwartzentruber, Jacek Majewski, Mark Lathrop, Silvia M. Vidal, Philippe Gros
Journal: The Journal of Experimental Medicine (2014)

We used a genome-wide screen in mutagenized mice to identify genes which inactivation protects against lethal neuroinflammation during experimental cerebral malaria (ECM). We identified an ECM-protective mutation in coiled-coil domain containing protein 88b (Ccdc88b), a poorly annotated gene that is found expressed specifically in spleen, bone marrow, lymph nodes, and thymus. The CCDC88B protein is abundantly expressed in immune cells, including both CD4+ and CD8+ T lymphocytes, and in myeloid cells, and loss of CCDC88B protein expression has pleiotropic effects on T lymphocyte functions, including impaired maturation in vivo, significantly reduced activation, reduced cell division as well as impaired cytokine production (IFN-γ and TNF) in response to T cell receptor engagement, or to nonspecific stimuli in vitro, and during the course of P. berghei infection in vivo. This identifies CCDC88B as a novel and important regulator of T cell function. The human CCDC88B gene maps to the 11q13 locus that is associated with susceptibility to several inflammatory and auto-immune disorders. Our findings strongly suggest that CCDC88B is the morbid gene underlying the pleiotropic effect of the 11q13 locus on inflammation.
Medication Access and Continuity: The Experiences of Dual-Eligible Psychiatric Patients During the First 4 Months of the Medicare Prescription Drug Benefit
Authors: Joyce C. West, Joshua E. Wilk, Irvin L. Muszynski, Donald S. Rae, Maritza Rubio-Stipec, Carol L. Alter, William E. Narrow, Darrel A. Regier
Journal: American Journal of Psychiatry (2007)

This study attempted to systematically assess the experiences of Medicare and Medicaid "dual-eligible" psychiatric patients, including evaluating patients' access to medications and the administrative functioning of the program, during the first 4 months of the Medicare Part D prescription drug benefit.Psychiatrists (N=5,833) were randomly selected from the American Medical Association's Physicians Masterfile. After exclusion of those not practicing and with undeliverable addresses, 64% responded; 35% met study eligibility criteria of treating at least one dual-eligible patient during their last typical workweek and reported clinically detailed information on one systematically selected patient.A total of 53.4% had at least one medication access problem to report between Jan. 1 and April 30, 2006. Although 9.7% experienced improved medication access, 22.3% discontinued or temporarily stopped taking medication because of prescription drug coverage or management issues, and 18.3% were previously stable but were required to switch medications. Among those with medication access problems, 27.3% experienced a significant adverse clinical event; 19.8% had an emergency room visit. Most drug plan features studied, including preferred drug/formulary lists, prior authorization, medication dosing/number limits, "fail-first" protocols, and requirements to switch to generics, were associated with significantly higher rates of medication access problems.The findings indicate consequential medication access problems for psychiatric patients during the implementation of Medicare Part D. Although Centers for Medicare and Medicaid Services policies were enacted to ensure access to protected classes of psychopharmacologic medications, the high rates of medication access problems observed indicate further refinement of these policies is needed.
Colonoscopic Polypectomy and Long-Term Prevention of Colorectal-Cancer Deaths
Authors: Ann G. Zauber, Sidney J. Winawer, Michael J. O'Brien, Iris Lansdorp-Vogelaar, Marjolein van Ballegooijen, Benjamin F. Hankey, Weiji Shi, John H. Bond, Melvin Schapiro, Joel F. Panish, Edward T. Stewart, Jerome D. Waye
Journal: New England Journal of Medicine (2012)

In the National Polyp Study (NPS), colorectal cancer was prevented by colonoscopic removal of adenomatous polyps. We evaluated the long-term effect of colonoscopic polypectomy in a study on mortality from colorectal cancer.We included in this analysis all patients prospectively referred for initial colonoscopy (between 1980 and 1990) at NPS clinical centers who had polyps (adenomas and nonadenomas). The National Death Index was used to identify deaths and to determine the cause of death; follow-up time was as long as 23 years. Mortality from colorectal cancer among patients with adenomas removed was compared with the expected incidence-based mortality from colorectal cancer in the general population, as estimated from the Surveillance Epidemiology and End Results (SEER) Program, and with the observed mortality from colorectal cancer among patients with nonadenomatous polyps (internal control group).Among 2602 patients who had adenomas removed during participation in the study, after a median of 15.8 years, 1246 patients had died from any cause and 12 had died from colorectal cancer. Given an estimated 25.4 expected deaths from colorectal cancer in the general population, the standardized incidence-based mortality ratio was 0.47 (95% confidence interval [CI], 0.26 to 0.80) with colonoscopic polypectomy, suggesting a 53% reduction in mortality. Mortality from colorectal cancer was similar among patients with adenomas and those with nonadenomatous polyps during the first 10 years after polypectomy (relative risk, 1.2; 95% CI, 0.1 to 10.6).These findings support the hypothesis that colonoscopic removal of adenomatous polyps prevents death from colorectal cancer. (Funded by the National Cancer Institute and others.).
Geographical distribution of tuberculosis notifications in national surveys of England and Wales in 1988 and 1993: report of the Public Health Laboratory Service/British Thoracic Society/Department of Health Collaborative Group
Authors: L P Ormerod, A Charlett, C Gilham, J H Darbyshire, J M Watson
Journal: Thorax (1998)

<h3>Objective:</h3> The purpose of this study was to examine whether the degree of expression of the p16 protein in serous papillary endometrial cancer bears a prognostic significance. The secondary objective was to establish the value of p16 immunohistochemical staining as an adjunct to diagnosis. <h3>Study Design:</h3> Archived paraffin blocks holding specimens from the uteri of 31 serous papillary and 31 endometrioid endometrial carcinoma patients were recut and restained for p16 and p53. <h3>Results:</h3> Overexpression of p16 was found in 78% of the serous papillary patients versus 36% of the endometrioid patients. p16 was not found to be an independent prognostic factor in serous papillary endometrial carcinoma. <h3>Conclusions:</h3> Although p16 was not found to have prognostic significance in serous papillary endometrial carcinoma, it may be valuable as a diagnostic adjunct in histologically ambiguous tumors.
Serine 68 phosphorylation of phospholemman: acute isoform-specific activation of cardiac Na/K ATPase
Authors: B SILVERMAN, W FULLER, P EATON, J DENG, J MOORMAN, J CHEUNG, A JAMES, M SHATTOCK
Journal: Cardiovascular Research (2004)

The mechanism by which the cardiac Na/K ATPase (NKA) is regulated by phosphorylation is controversial. We have used the perforated-patch technique to limit cell dialysis and maintain conditions as near physiological as possible.NKA pump current (I(p)) was measured in isolated guinea pig ventricular myocytes, and its components (I(alpha 1) and I(alpha 2)) defined by their differing dihydroouabain sensitivities.Treatment with 1 micromol/l forskolin for 4 min at 35 degrees C caused a significant increase in I(alpha1) of 36+/-15% (P<0.05, n=6), but no change in I(alpha2). The presence of the PKA selective inhibitor H89 (50 micromol/l) throughout the protocol blocked the effect of the forskolin on I(alpha1). Treatment with H89 alone did not change I(alpha 1) or I(alpha 2). Isoelectric focusing gels of the NKA alpha1 subunit demonstrated six charge states, which were unaltered following treatment with forskolin. Western blots using an antibody specific for the PKA phosphorylation consensus site on the alpha1 subunit showed no change in the phosphorylation status of this residue following forskolin treatment. The sarcolemmal protein phospholemman (PLM) was found associated with NKA alpha 1 but not alpha 2 subunits by immunoprecipitation and immunofluorescence. PLM was phosphorylated at serine 68, but not 63, following treatment with forskolin.PKA-dependent, alpha 1-specific NKA activation may be mediated through phosphorylation of the accessory protein PLM, rather than direct alpha1 subunit phosphorylation.
Projecting Individualized Probabilities of Developing Bladder Cancer in White Individuals
Authors: Xifeng Wu, Jie Lin, H. Barton Grossman, Maosheng Huang, Jian Gu, Carol J. Etzel, Christopher I. Amos, Colin P. Dinney, Margaret R. Spitz
Journal: Journal of Clinical Oncology (2007)

Purpose There has been no risk assessment model for bladder cancer (BC). We developed the first model incorporating mutagen sensitivity and epidemiologic factors to predict BC risk. Patients and Methods We used epidemiologic and genetic data from a large case-control study to build the models and constructed receiver operating characteristic curves. The area under the curve (AUC) was used to evaluate model discriminatory ability. We also projected absolute risk of developing BC by taking into account competing causes of death. Results The study included 678 white BC patients and 678 controls. Significant risk factors in the epidemiologic model included pack-years smoked and exposures to diesel, aromatic amines, dry cleaning fluids, radioactive materials, and arsenic. This model yielded good discriminatory ability (AUC = 0.70; 95% CI, 0.67 to 0.73). When mutagen sensitivity data were incorporated, the AUC increased to 0.80 (95% CI, 0.72 to 0.82). The models showed excellent concordance in the internal validation. We also computed an easy to use ordinal risk score and provided examples for projecting absolute risk. Conclusion We have developed the first risk prediction model for BC. The enhanced model integrating the genetic factor exhibited excellent discriminatory ability. Our model only requires an individual to answer a few simple questions during a clinic visit to project individualized probability. This model may be used as a basis for developing a Web-based tool for BC risk assessment. Validation of our model in an external population is an essential next step towards practical use in the clinical setting.
The Deterioration of Vision During School Life
Authors: E. Sayer
Journal: BMJ (1904)

I418 Ba 1 HAEMOSOZIC PROPERTIES OF URINE.[Junq i8, 'go.seems not to,have-been.secondarytoany excessive haemolysis, but to have bben primary in the bone marrow, and I would regard it as a myelogenie form of splenic anaemia of adults, doubtless allied to what French authors" have termed an6mie spjoique myjloide.,"Therefore the case cannot b-e adduced as an example of pernicious anaemia being followed by or beciominf transformed into leukaemia, though it is probable that.similarcases have been erroneously supposed to illiustrAte such a course of events.It is also highly probable that similar cases, owing to enlargement of spleen and liver, have been clinically regarded (in spite' of the poikilocytosis) as ex- amples of Banti's disease.In the German cases, I believe, enlargement of haemo- lymph glands was not noted.It is very tempting to suggest that in the present case both the spleen (haemal gland) and the prevertebral haemolymph glanLds were actively engaged in supplementing the erythrocyte-forming functions of the diseased bone marrow, but I have no conclusive evidence to support such a supposition.From what has been lately written on the subject6 it seems that no really satisfactory evidence has been brought forward to show that in adults erythrocytes are produced in the spleen and haemolymph glands either in health or in disease.
Local corticosteroid injection in iliotibial band friction syndrome in runners: a randomised controlled trial
Authors: P Gunter, M P Schwellnus
Journal: British Journal of Sports Medicine (2004)

Objective: To establish whether a local injection of methylprednisolone acetate (40 mg) is effective in decreasing pain during running in runners with recent onset (less than two weeks) iliotibial band friction syndrome (ITBFS). Methods: Eighteen runners with at least grade 2 ITBFS underwent baseline investigations including a treadmill running test during which pain was recorded on a visual analogue scale every minute. The runners were then randomly assigned to either the experimental (EXP; nine) or a placebo control (CON; nine) group. The EXP group was infiltrated in the area where the iliotibial band crosses the lateral femoral condyle with 40 mg methylprednisolone acetate mixed with a short acting local anaesthetic, and the CON group with short acting local anaesthetic only. The same laboratory based running test was repeated after seven and 14 days. The main measure of outcome was total pain during running (calculated as the area under the pain versus time graph for each running test). Results: There was a tendency (p = 0.07) for a greater decrease in total pain (mean (SEM)) during the treadmill running in the EXP group than the CON group tests from day 0 (EXP = 222 (71), CON = 197 (31)) to day 7 (EXP = 140 (87), CON = 178 (76)), but there was a significant decrease in total pain during running (p = 0.01) from day 7 (EXP = 140 (87), CON = 178 (76)) to day 14 (EXP = 103 (89), CON = 157 (109)) in the EXP group compared with the CON group. Conclusion: Local corticosteroid infiltration effectively decreases pain during running in the first two weeks of treatment in patients with recent onset ITBFS.