tbuckley/cabot-search huggingface dataset:
Vincristine, Actinomycin, and Cyclophosphamide Compared With Vincristine, Actinomycin, and Cyclophosphamide Alternating With Vincristine, Topotecan, and Cyclophosphamide for Intermediate-Risk Rhabdomyosarcoma: Children's Oncology Group Study D9803
Authors: Carola A.S. Arndt, Julie A. Stoner, Douglas S. Hawkins, David A. Rodeberg, Andrea A. Hayes-Jordan, Charles N. Paidas, David M. Parham, Lisa A. Teot, Moody D. Wharam, John C. Breneman, Sarah S. Donaldson, James R. Anderson, William H. Meyer
Journal: Journal of Clinical Oncology (2009)

Purpose The purpose of this study was to compare the outcome of patients with intermediate-risk rhabdomyosarcoma (RMS) treated with standard VAC (vincristine, dactinomycin, and cyclophosphamide) chemotherapy to that of patients treated with VAC alternating with vincristine, topotecan, and cyclophosphamide (VAC/VTC). Patients and Methods Patients were randomly assigned to 39 weeks of VAC versus VAC/VTC; local therapy began after week 12. Patients with parameningeal RMS with intracranial extension (PME) were treated with VAC and immediate x-ray therapy. The primary study end point was failure-free survival (FFS). The study was designed with 80% power (5% two-sided α level) to detect an increase in 5-year FFS from 64% to 75% with VAC/VTC. Results A total of 617 eligible patients were entered onto the study: 264 were randomly assigned to VAC and 252 to VAC/VTC; 101 PME patients were nonrandomly treated with VAC. Treatment strata were embryonal RMS, stage 2/3, group III (33%); embryonal RMS, group IV, less than age 10 years (7%); alveolar RMS or undifferentiated sarcoma (UDS), stage 1 or group I (17%); alveolar RMS/UDS (27%); and PME (16%). At a median follow-up of 4.3 years, 4-year FFS was 73% with VAC and 68% with VAC/VTC (P = .3). There was no difference in effect of VAC versus VAC/VTC across risk groups. The frequency of second malignancies was similar between the two treatment groups. Conclusion For intermediate-risk RMS, VAC/VTC does not significantly improve FFS compared with VAC.
Activity of Sorafenib in Recurrent Ovarian Cancer and Primary Peritoneal Carcinomatosis: A Gynecologic Oncology Group Trial
Authors: Daniela Matei, Michael W. Sill, Heather A. Lankes, Koen DeGeest, Robert E. Bristow, David Mutch, S. Diane Yamada, David Cohn, Valerie Calvert, John Farley, Emanuel F. Petricoin, Michael J. Birrer
Journal: Journal of Clinical Oncology (2010)

PURPOSE Sorafenib is a kinase inhibitor targeting Raf and other kinases (ie, vascular endothelial growth factor receptor [VEGFR], platelet-derived growth factor receptor [PDGFR], Flt3, and c-KIT). This study assessed its activity and tolerability in patients with recurrent ovarian cancer (OC) or primary peritoneal carcinomatosis (PPC). METHODS This open-label, multi-institutional, phase II study used a two-stage design. Eligible patients had persistent or recurrent OC/PPC after one to two prior cytotoxic regimens, and they experienced progression within 12 months of platinum-based therapy. Treatment consisted of sorafenib 400 mg orally twice per day. Primary end points were progression-free survival (PFS) at 6 months and toxicity by National Cancer Institute criteria. Secondary end points were tumor response and duration of PFS and overall survival. Biomarker analyses included measurement of ERK and b-Raf expression in tumors and phosphorylation of ERK (pERK) in peripheral-blood lymphocytes (PBLs) before and after 1 month of treatment. Results Seventy-three patients were enrolled, of which 71 were eligible. Fifty-nine eligible patients (83%) had measurable disease, and 12 (17%) had detectable disease. Significant grade 3 or 4 toxicities included the following: rash (n = 7), hand-foot syndrome (n = 9), metabolic (n = 10), GI (n = 3), cardiovascular (n = 2), and pulmonary (n = 2). Only patients with measurable disease were used to assess efficacy. Fourteen survived progression free for at least 6 months (24%; 90% CI, 15% to 35%). Two patients had partial responses (3.4%; 90% CI, 1% to 10%); 20 had stable disease; 30 had progressive disease; and seven could not have their tumor assessed. ERK and b-Raf were expressed in all tumors. Exploratory analyses indicated that pERK in post-treatment PBL specimens was associated with PFS. CONCLUSION Sorafenib has modest antitumor activity in patients with recurrent OC, but the activity was at the expense of substantial toxicity.
Anti–IFN-γ autoantibodies are strongly associated with HLA-DR*15:02/16:02 and HLA-DQ*05:01/05:02 across Southeast Asia
Authors: Cheng-Lung Ku, Chia-Hao Lin, Su-Wei Chang, Chen-Chung Chu, Jasper F.W. Chan, Xiao-Fei Kong, Chen-Hsiang Lee, Emily A. Rosen, Jing-Ya Ding, Wen-I. Lee, Jacinta Bustamante, Torsten Witte, Han-Po Shih, Chen-Yen Kuo, Ploenchan Chetchotisakd, Sasisopin Kiertiburanakul, Yupin Suputtamongkol, Kwok-Yung Yuen, Jean-Laurent Casanova, Steven M. Holland, Rainer Doffinger, Sarah K. Browne, Chih-Yu Chi
Journal: Journal of Allergy and Clinical Immunology (2015)
Conservation Surgery for Breast Cancer As the Preferred Choice: A Prospective Analysis
Authors: Walley J. Temple, Margaret L. Russell, Louise L. Parsons, Sylvia M. Huber, Charlotte A. Jones., Jane Bankes, Michael Eliasziw
Journal: Journal of Clinical Oncology (2006)

To describe the proportion of women who anticipate having breast-conserving surgery (BCS) versus modified radical mastectomy (MRM), the factors they considered when making treatment choices, the degree to which they perceived they had participated in and had control of the treatment decision, and to explore factors associated with type of planned surgery.Prospective cohort study conducted among patients attending a tertiary care hospital in Alberta, Canada from 1992 to 1995. Participants had a first diagnosis of localized unilateral breast cancer, and were, in the opinions of their surgeons, candidates for either BCS or MRM.Of 157 participants, 71.3% anticipated having BCS and 28.7% anticipated MRM. Referents perceived to play an important role in decision making included self, doctor, and significant other. The two top-ranked items perceived to have influenced treatment choice were doctor's advice and possibility of complete cure. Most women (60%) participated in treatment choice to the degree that they preferred, but only 13.6% received their preferred amount of information. The type of planned surgery was predicted by surgeon, contribution of doctor to choice of treatment, importance of breasts to sexuality, self-efficacy, and concerns about cancer recurrence from a multivariable logistic regression model.Both patient and surgeon factors are important predictors of type of planned surgery. There is a gap between women's preferences and actual experiences with regard to information provided and patient participation in treatment choices, with women's desire for more information about their treatment being most prevalent.
Red and Processed Meat Consumption and Risk of Incident Coronary Heart Disease, Stroke, and Diabetes Mellitus
Authors: Renata Micha, Sarah K. Wallace, Dariush Mozaffarian
Journal: Circulation (2010)

Background— Meat consumption is inconsistently associated with development of coronary heart disease (CHD), stroke, and diabetes mellitus, limiting quantitative recommendations for consumption levels. Effects of meat intake on these different outcomes, as well as of red versus processed meat, may also vary. Methods and Results— We performed a systematic review and meta-analysis of evidence for relationships of red (unprocessed), processed, and total meat consumption with incident CHD, stroke, and diabetes mellitus. We searched for any cohort study, case-control study, or randomized trial that assessed these exposures and outcomes in generally healthy adults. Of 1598 identified abstracts, 20 studies met inclusion criteria, including 17 prospective cohorts and 3 case-control studies. All data were abstracted independently in duplicate. Random-effects generalized least squares models for trend estimation were used to derive pooled dose-response estimates. The 20 studies included 1 218 380 individuals and 23 889 CHD, 2280 stroke, and 10 797 diabetes mellitus cases. Red meat intake was not associated with CHD (n=4 studies; relative risk per 100-g serving per day=1.00; 95% confidence interval, 0.81 to 1.23; P for heterogeneity=0.36) or diabetes mellitus (n=5; relative risk=1.16; 95% confidence interval, 0.92 to 1.46; P =0.25). Conversely, processed meat intake was associated with 42% higher risk of CHD (n=5; relative risk per 50-g serving per day=1.42; 95% confidence interval, 1.07 to 1.89; P =0.04) and 19% higher risk of diabetes mellitus (n=7; relative risk=1.19; 95% confidence interval, 1.11 to 1.27; P &lt;0.001). Associations were intermediate for total meat intake. Consumption of red and processed meat were not associated with stroke, but only 3 studies evaluated these relationships. Conclusions— Consumption of processed meats, but not red meats, is associated with higher incidence of CHD and diabetes mellitus. These results highlight the need for better understanding of potential mechanisms of effects and for particular focus on processed meats for dietary and policy recommendations.
PATHOLOGIC CHANGES IN SENILE PSYCHOSES AND THEIR PSYCHOBIOLOGIC SIGNIFICANCE
Authors: D. Rothschild, M. A. Trainor
Journal: American Journal of Psychiatry (1937)

The results of a pathologic study of 24 cases of senile psychoses are reported. In all cases the cerebral cortex showed widespread nonspecific cell changes with less extensive but diffuse cell losses, an abundance of senile plaques and variable amounts of lipoid material. Neurofibril lesions of the Alzheimer type, usually in small or moderate numbers, occurred in all but two cases. The neuroglial reaction was as a rule weak. Involvement of the basal ganglia was common. Proliferative alterations of the small cerebral vessels were regularly observed but were regarded as secondary or complicating features. Atherosclerotic changes were frequent, though in the great majority of instances they were not severe enough to occupy a prominent place in the pathologic picture. A search for physical factors that might modify the normal aging process and be responsible for the development of a senile psychosis has proved unproductive. There was a lack of correlation between the histologic changes and the degree of intellectual impairment. Attention was also called to the fact that equally severe alterations may be found in the brains of old persons of normal mentality. These inconsistencies were attributed to differences in the capacity of different persons to compensate for the cerebral damage. The view is expressed that this capacity rather than the pathologic changes themselves is the determining factor in the origin of a senile psychosis. A scrutiny of the senile group showed that strong compensatory mental reactions were usually associated with compensatory somatic processes. The need of studying psychologic aspects of old age is emphasized, and the suggestion is advanced that the inability to meet personal problems may be the crucial factor that impairs the person's compensatory capacity, thereby leading to the development of a senile psychosis.
Reading Disorders in Children
Authors: Lloyd J. Thompson
Journal: JAMA (1969)

<h3>To the Editor:—</h3> The importance of your editorial on reading disorders in children may not be fully appreciated by physicians (<b>206</b>:638, 1968). Authorities agree that about 10% of children (mostly boys) have some degree of specific reading disability or developmental dyslexia while only 3% are mentally retarded and about 5% have some speech disorder. Although reading disability is largely a problem for our schools, physicians are frequently called upon to participate in the diagnosis and recommendations. Yet many physicians are quite vague in their knowledge about reading disability. Your editorial helped to clarify the "diametrically opposed" concepts concerning developmental dyslexia. Much of the confusion arises from the fact that the majority of physicians, educators, and others think that disabilities in children must be due to either brain damage or emotional and environmental factors. For them it must be one or the other and they overlook or reject the possibility
Diagnosis and Treatment of Depression in Late Life
Authors: Arnold J. Friedhoff
Journal: JAMA (1992)

DEPRESSION in the aging and the aged is a major public health problem. It causes suffering to many who go undiagnosed, and it burdens families and institutions providing care for the elderly by disabling those who might otherwise be able-bodied. What makes depression in the elderly so insidious is that neither the victim nor the health care provider may recognize its symptoms in the context of the multiple physical problems of many elderly people. Depressed mood, the typical signature of depression, may be less prominent than other depressive symptoms such as loss of appetite, sleeplessness, anergia, and loss of interest in, and enjoyment of, the normal pursuits of life. There is a wide spectrum of depressive symptoms as well as types of available therapies. Because of the many physical illnesses and social and economic problems of the elderly, individual health care providers often conclude that depression is a normal consequence
Variations in Adrenergic Innervation and Contractile Responses of the Rabbit Saphenous Artery
Authors: JOHN A. BEVAN, RALPH E. PURDY
Journal: Circulation Research (1973)

The Falck fluorescence histochemical method was used to compare the adrenergic innervation in segments from the proximal saphenous artery, the distal saphenous artery and the popliteal artery. Adrenergic neurons penetrated the media of the proximal saphenous artery but not that of the distal saphenous artery or the popliteal artery. Responses of these vessel segments to exogenous l -norepinephrine and to electrical stimulation of their intramural innervation were measured. The median effective dose (ED 50 ) of l -norepinephrine was ten times greater in the proximal saphenous artery than it was in the distal saphenous artery and the popliteal artery. The response of the proximal saphenous artery to neural stimulation was nearly double that of the distal vessel and required one-fifth of the time to achieve maximum tension; the response of the popliteal artery was negligible due to its low density of innervation. The three-dimensional medial distribution of the adrenergic neuronal plexus in the proximal saphenous artery should (1) increase the efficiency of neuronal uptake of l -norepinephrine and thereby account for the increased ED 50 of l -norepinephrine, and (2) decrease the mean distance between adrenergic nerves and medial smooth muscle cells. Therefore, transmitter would accumulate more rapidly and reach a higher level in the media during neural activity.
A Noncoding RNA Antisense to Moesin at 5p14.1 in Autism
Authors: Tara Kerin, Anita Ramanathan, Kasey Rivas, Nicole Grepo, Gerhard A. Coetzee, Daniel B. Campbell
Journal: Science Translational Medicine (2012)

An antisense RNA, transcribed from an autism-associated region on chromosome 5, is highly expressed in autism brains and could regulate the developmental brain protein moesin.
A Critical Role for Induced IgM in the Protection against West Nile Virus Infection
Authors: Michael S. Diamond, Elizabeth M. Sitati, Lindzy D. Friend, Stephen Higgs, Bimmi Shrestha, Michael Engle
Journal: The Journal of Experimental Medicine (2003)

In humans, the elderly and immunocompromised are at greatest risk for disseminated West Nile virus (WNV) infection, yet the immunologic basis for this remains unclear. We demonstrated previously that B cells and IgG contributed to the defense against disseminated WNV infection (Diamond, M.S., B. Shrestha, A. Marri, D. Mahan, and M. Engle. 2003. J. Virol. 77:2578-2586). In this paper, we addressed the function of IgM in controlling WNV infection. C57BL/6J mice (sIgM-/-) that were deficient in the production of secreted IgM but capable of expressing surface IgM and secreting other immunoglobulin isotypes were vulnerable to lethal infection, even after inoculation with low doses of WNV. Within 96 h, markedly higher levels of infectious virus were detected in the serum of sIgM-/- mice compared with wild-type mice. The enhanced viremia correlated with higher WNV burdens in the central nervous system, and was also associated with a blunted anti-WNV IgG response. Passive transfer of polyclonal anti-WNV IgM or IgG protected sIgM-/- mice against mortality, although administration of comparable amounts of a nonneutralizing monoclonal anti-WNV IgM provided no protection. In a prospective analysis, a low titer of anti-WNV IgM antibodies at day 4 uniformly predicted mortality in wild-type mice. Thus, the induction of a specific, neutralizing IgM response early in the course of WNV infection limits viremia and dissemination into the central nervous system, and protects against lethal infection.
Electrocardiographic Studies of Romidepsin Demonstrate Its Safety and Identify a Potential Role for KATP Channel
Authors: Anne M. Noonan, Robin A. Eisch, David J. Liewehr, Tristan M. Sissung, David J. Venzon, Thomas P. Flagg, Mark C. Haigney, Seth M. Steinberg, William D. Figg, Richard L. Piekarz, Susan E. Bates
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Romidepsin is a histone deacetylase inhibitor (HDI) approved for the treatment of both cutaneous and peripheral T-cell lymphoma (CTCL and PTCL). During development, a thorough assessment of cardiac toxicity was conducted. Experimental Design: A phase II single-agent nonrandomized study of romidepsin was conducted in patients with CTCL or PTCL who had progressed after at least 1 prior systemic therapy. Results: Results for the first 42 patients enrolled on the NCI 1312 phase II study of romidepsin in CTCL or PTCL showed no cardiac toxicity based on serial electrocardiograms (ECG), troponins, and MUGA scans/echocardiograms. The cardiac assessments reported herein confirm the safety of romidepsin among 131 enrolled patients, while supporting a role for electrolyte replacement. Heart rate increased an average 11 bpm following romidepsin infusion; there was no evidence of increased arrhythmia. Criteria for potassium/magnesium replacement were met before 55% of 1365 romidepsin doses; an association with hypoalbuminemia was confirmed. We propose a mechanism for ST segment flattening and depression, the most common ECG abnormalities observed: HDI-induced alteration of the activity or expression of KATP channels. In addition, examination of the variants of the active transporter of romidepsin, ABCB1, showed a trend toward smaller heart rate changes in the peri-infusion period among wild-type than variant diplotypes. Conclusions: We conclude that in the context of appropriate attention to electrolyte levels, the data support the cardiac safety of romidepsin. Clin Cancer Res; 19(11); 3095–104. ©2013 AACR.
Effect of Elevation of Intraluminal Pressure on Renal Vascular Resistance
Authors: FRANCIS J. HADDY, Jerry Scott, Edwin Armstrong
Journal: Circulation Research (1956)

Elevation of renal venous pressure in pentobarbitalized laparotomized dogs elicits renal vascular constriction. Part of the vasoconstriction appears to be dependent upon a venous-arteriolar reflex. The reflex pathway is not distributed locally. A portion of the vasoconstriction is dependent upon still unrecognized local factors.
Growth inhibition of follicular small-cleaved-cell lymphoma cells in short-term culture by interleukin-3
Authors: A. Younes, J. Drach, R. Katz, D. Jendiroba, M.H. Sabourian, A.H. Sarris, F. Swan, D. Hill, F. Cabanillas, R. Ford, M. Andreeff
Journal: Annals of Oncology (1994)
A nail psoriasis severity index
Authors: R.L. Baran
Journal: British Journal of Dermatology (2004)

The Psoriasis Area and Severity Index does not take the severity of nail involvement into account.To devise a system of scoring for nail psoriasis.A system of scoring for nail psoriasis was devised that takes into account the site of the pathology, i.e. (i) the matrix, (ii) the subungual tissues distal to the lunula, or (iii) the whole nail unit.The proposed scoring system evaluates several signs of nail psoriasis separately, each on a 1-3 scale: pitting, Beau's lines, subungual hyperkeratosis and onycholysis.Using this classification it will be possible to assess and grade nail pathology simply and accurately.
1100 DIRECT INHIBITION OF NS3/4A WITH BOCEPREVIR DOES NOT INCREASE INDUCTION OF ISG: AN ANALYSIS OF THE PIVOTAL BOCEPREVIR TRIALS (SPRINT-2/RESPOND-2)
Authors: C. Molony, R. Cristescu, P. Shaw, N. Shire, J. Wahl, C. Brass, M. Cooreman
Journal: Journal of Hepatology (2012)
Hypermethylation of the alternative AWT1 promoter in hematological malignancies is a highly specific marker for acute myeloid leukemias despite high expression levels
Authors: Amy Guillaumet-Adkins, Julia Richter, Maria D Odero, Juan Sandoval, Xabi Agirre, Albert Catala, Manel Esteller, Felipe Prósper, María José Calasanz, Ismael Buño, Mi Kwon, Franck Court, Reiner Siebert, David Monk
Journal: Journal of Hematology & Oncology (2014)

Wilms tumor 1 (WT1) is over-expressed in numerous cancers with respect to normal cells, and has either a tumor suppressor or oncogenic role depending on cellular context. This gene is associated with numerous alternatively spliced transcripts, which initiate from two different unique first exons within the WT1 and the alternative (A)WT1 promoter intervals. Within the hematological system, WT1 expression is restricted to CD34+/CD38- cells and is undetectable after differentiation. Detectable expression of this gene is an excellent marker for minimal residual disease in acute myeloid leukemia (AML), but the underlying epigenetic alterations are unknown. To determine the changes in the underlying epigenetic landscape responsible for this expression, we characterized expression, DNA methylation and histone modification profiles in 28 hematological cancer cell lines and confirmed the methylation signature in 356 cytogenetically well-characterized primary hematological malignancies. Despite high expression of WT1 and AWT1 transcripts in AML-derived cell lines, we observe robust hypermethylation of the AWT1 promoter and an epigenetic switch from a permissive to repressive chromatin structure between normal cells and AML cell lines. Subsequent methylation analysis in our primary leukemia and lymphoma cohort revealed that the epigenetic signature identified in cell lines is specific to myeloid-lineage malignancies, irrespective of underlying mutational status or translocation. In addition to being a highly specific marker for AML diagnosis (positive predictive value 100%; sensitivity 86.1%; negative predictive value 89.4%), we show that AWT1 hypermethylation also discriminates patients that relapse from those achieving complete remission after hematopoietic stem cell transplantation, with similar efficiency to WT1 expression profiling. We describe a methylation signature of the AWT1 promoter CpG island that is a promising marker for classifying myeloid-derived leukemias. In addition AWT1 hypermethylation is ideally suited to monitor the recurrence of disease during remission in patients undergoing allogeneic stem cell transfer.