tbuckley/cabot-search huggingface dataset:
The UCLA-University of Utah epidemiologic survey of autism: the etiologic role of rare diseases
Authors: E R Ritvo, A Mason-Brothers, B J Freeman, C Pingree, W R Jenson, W M McMahon, P B Petersen, L B Jorde, A Mo, A Ritvo
Journal: American Journal of Psychiatry (1990)

Twelve rare diseases known to cause CNS pathology were found in 26 (11%) of 233 autistic probands identified during a recent epidemiologic survey of Utah. These 26 probands had significantly lower mean IQs than the remaining patients (43 versus 60) but similar sex distribution and prevalence of abnormal EEGs and seizures. The rarity and diversity of these 12 diseases make it highly unlikely that they randomly occurred with autism. Their presence in this epidemiologic survey is the most compelling evidence to date to support the hypothesis that different diseases producing different types of CNS pathology can play an etiologic role in autism.
The Management of Burns
Authors: Jane F. Desforges, Edwin A. Deitch
Journal: New England Journal of Medicine (1990)

IN the United States, it is conservatively estimated that each year 2.5 million people seek medical care for burns. More than 100,000 patients are hospitalized with burns each year, and 12,000 burn victims die of their injuries.1 The care of burn victims has progressed rapidly over the past 50 years. Before World War II, the average burn size associated with a 50 percent mortality rate in healthy young adults was less than 30 percent of the total body-surface area. Today, the mean burn size associated with a 50 percent mortality rate in most burn centers ranges from 65 to 75 . . .
Abstract P2-08-07: Prognostic significance of immune checkpoint receptors in node-negative breast cancer
Authors: M Schmidt, L van de Sandt, A-S Heimes, M Battista, A Lebrecht, K Almstedt, G Hoffmann, J Rahnenführer, JG Hengstler
Journal: Cancer Research (2016)

Abstract Background: Immune checkpoint blockade is increasingly discussed in breast cancer. We examined the prognostic significance of the immune checkpoint receptors cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) in node-negative breast cancer. Methods: Microarray based gene-expression data for CTLA-4 (221331_x_at) and PD-1 (207634_at) were analysed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n=824). A meta-analysis of previously published cohorts was performed using a random effects model. Prognostic significance of CTLA-4 as well as PD-1 for metastasis-free survival (MFS) was examined in the whole cohort and in different molecular subtypes: luminal (ER+/HER2-), basal-like (ER-/HER2-) and HER2+. Independent prognostic relevance was analysed using multivariate Cox regression. Results: Higher RNA expression of CTLA-4 was related to better MFS in a meta-analysis of the whole cohort (HR 0.58, 95% CI 0.38-0.88, P=0.0102). Prognostic significance was most pronounced in the HER2+ positive molecular subtype (HR 0.23, 95% CI 0.08-0.65, P=0.0062) as compared to luminal (HR 0.68, 95% CI 0.39-1.18, P=0.1744) and basal-like (HR 0.53, 95% CI 0.25-1.15), P=0.1087) carcinomas of the breast. PD-1 RNA expression, however, was not associated with outcome in the whole cohort of patients (HR 0.88, 95% CI 0.32-2.43, P=0.1853). A trend for improved survival was noticed in basal-like breast cancer (HR 0.40, 95% CI 0.15-1.08, P=0.0701). Neither luminal (HR 0.81, 95% CI 0.28-2.36, P=0.2122) nor HER2+ (HR 0.85, 95% CI 0.27-2.68, P=0.7759) patients showed an association of PD-1 with MFS. CTLA-4 showed independent prognostic significance (HR 0.393, 95% CI 0.224-0.688, P=0.001) in multivariate analysis. In addition to CTLA-4, only histological grade of differentiation (HR 2.335, 95% CI 1.490-3.660, P&amp;lt;0.0001) and tumor size (HR 1.924, 95% CI 1.260-2.937, P=0.002), but neither PD-1 nor age nor HER2 status nor hormone receptor status retained an independent prognostic association with MFS. Conclusions: The immune checkpoint receptor CTLA-4 has independent prognostic significance in node-negative breast cancer. Higher expression of CTLA-4 is associated with improved outcome. The prognostic impact of CTLA-4 differs between molecular subtypes and is most pronounced in HER2+ breast cancer. Citation Format: Schmidt M, van de Sandt L, Heimes A-S, Battista M, Lebrecht A, Almstedt K, Hoffmann G, Rahnenführer J, Hengstler JG. Prognostic significance of immune checkpoint receptors in node-negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-07.
Molecular Biology and the Early Detection of Carcinoma of the Bladder -- The Case of Hubert H. Humphrey
Authors: Ralph H. Hruban, Peter van der Riet, Yener S. Erozan, David Sidransky
Journal: New England Journal of Medicine (1994)

Approximately 52,300 new cases of carcinoma of the bladder were diagnosed in the United States in 19931. These carcinomas struck primarily older men, who often presented with hematuria or increased frequency of urination. Patients whose cancers are detected in an early, localized stage have a 90 percent chance of surviving at least five years. If the cancer is detected after distant spread of the disease, however, the five-year survival rate drops to 9 percent1. Clearly, techniques for the early detection of carcinoma of the bladder can have a major impact on the outcome of the disease2. Cytologic . . .
Selective Revascularization of the Myocardium by Internal-Mammary-Artery Implant
Authors: Richard Gorlin, Warren J. Taylor
Journal: New England Journal of Medicine (1966)

IN 1946 Vineberg1 reported that implantation of the internal mammary artery into the anterior wall of the left ventricular myocardium of dogs effected an anastomosis with the intramyocardial branches of the left coronary arterial system. The likelihood of such a connection could be enhanced through induction of local myocardial ischemia by simultaneous stenosis of the anterior descending coronary artery. This work was extended to a small group of human subjects2 but remained incompletely tested because selection of cases based on identification of site and degree of arterial disease was not possible, and subsequent evaluation of results was not feasible. The . . .
Ventricular Premature Beats and Mortality after Myocardial Infarction
Authors: William Ruberman, Eve Weinblatt, Judith D. Goldberg, Charles W. Frank, Sam Shapiro
Journal: New England Journal of Medicine (1977)

To assess the role of ventricular premature beats in influencing mortality of coronary patients, 1739 men with prior myocardial infarction were monitored for ectopic activity for one hour at a standard base-line examination, and followed for mortality for periods up to four years (average, 24.4 months). Analyses of survival taking into account other important prognostic variables establish that the presence of complex premature beats (R on T, runs of 2 or more, multiform or bigeminal premature beats) in the monitoring hour is associated with a risk of sudden coronary death three times that of the men free of complex ventricular premature beats. The corresponding risk of death from any cause is twice that of men without such complex beats in the hour. These arrhythmias make an independent contribution to increased risk of death that persists over the length of this observation period. (N Engl J Med 297:750–757, 1977)
Bizarre Deformities in Offspring of User of Lysergic Acid Diethylamide
Authors: J. L. Eller, J. M. Morton
Journal: New England Journal of Medicine (1970)

An infant with a rare combination of severe congenital deformities was born to a woman with a history of using lysergic acid diethylamide. Previously described patients bearing a similarity to this infant were of Puerto Rican parents, most of consanguineous marriage, and in none of these cases was use of this drug indicated. The current state of knowledge of the effects of the compound is such that no definite inference can be made about the current case. All reported cases similar to this one appear to have been due to an unusual recessive mode of inheritance or chromosomal aberration.
Bilateral Anorchia with Persistent Testosterone Production
Authors: Marvin A. Kirschner, J. Bruce Jacobs, Elwin E. Fraley
Journal: New England Journal of Medicine (1970)

Two 19-year-old patients had bilateral anorchia, normal male phenotype and 46, XY karyotype, spontaneous but incomplete pubescence and eunuchoidal appearance, with high urinary excretion of gonadotrophins. In both, the concentrations of testosterone in spermatic-vein blood was 10 to 50 times greater than that found in peripheral blood, although laparotomy revealed no testicular tissue. In spite of absent testes, both patients had a source of testosterone-secreting tissue, presumably Leydig cells. This tissue apparently had sufficient function to result in normal male differentiation in utero, and to produce some signs of pubertal development.
Patients with Neuroendocrine Neoplasms: prevalence of Ectopic Cushing's Syndrome (ECS) in our experience
Authors: F. Bruder, D. Massa, E. Capasso, B. Stochino, P. Sulas, G.S. Porcu, S. Armeni, R. Cherchi, B. Demontis, R. Pinna, M. Barca, N. Giannoni, G. Almerighi, E. Mascia, C. Canu, C. Pusceddu, G. Sollai, M. Dessena, G. Murenu, E. Defraia, C. Loi
Journal: Annals of Oncology (2015)
P152 Fluticasone furoate (FF)/Vilanterol (VI) once daily reduces asthma symptoms both day and night
Authors: DA Leather, R Forth, L Yates, LA Jacques
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> FF/VI is the first once daily inhaled corticosteroid/long-acting b<sub>2</sub>-agonist combination available for the treatment of asthma. Results from five phase III studies that have previously been presented demonstrated a sustained 24 h improvement in lung function and improvement in symptom-free 24 h periods. <h3>Methods</h3> Post-hoc analyses of diary card data from these studies were performed to examine whether there was any difference in the contribution of the day and night time symptom-free period to the 24 h symptom-free period. The diary card scale used is described below. Day-time Symptom Score: 0 = No symptoms during the day 1 = Symptoms for one short period during the day 2 = Symptoms for two or more short periods during the day 3 = Symptoms for most of the day which did not affect my normal daily activities 4 = Symptoms for most of the day which did affect my normal daily activities 5 = Symptoms so severe that I could not go to work or perform normal daily activities Night-time Symptom Score: 0 = No symptoms during the night 1 = Symptoms causing me to wake once (or wake early) 2 = Symptoms causing me to wake twice or more (including waking early) 3 = Symptoms causing me to be awake for most of the night 4 = Symptoms so severe that I did not sleep at all To be counted as symptom-free during the day or night the patient needed to record a score of 0. <h3>Results</h3> The post-hoc analyses demonstrated that the improvements in day and night time symptom –free periods were similar to the 24 h symptom free periods. See Figure 1 below. <h3>Conclusions</h3> In general benefits in symptom free days and symptom free nights contributed to the benefit of FF/VI over comparator groups in terms of 24 h symptom free periods.
Urokinase plasminogen activator receptor polymorphisms and airway remodelling in asthma
Authors: Despo Ierodiakonou, Michael A. Portelli, Dirkje S. Postma, Gerard H. Koppelman, Jorrit Gerritsen, Nick H.T. ten Hacken, Wim Timens, H. Marike Boezen, Judith M. Vonk, Ian Sayers
Journal: European Respiratory Journal (2016)

In the past decade, several asthma genes have been identified [1]; however, the key challenge is to determine how these genetic changes contribute to the underlying lung biology. We identified the urokinase plasminogen activator receptor ( PLAUR ) as an asthma susceptibility gene by positional cloning [2]. We showed that the same single nucleotide polymorphisms (SNPs) were associated with soluble PLAUR levels in blood, airway hyperresponsiveness (AHR) and accelerated lung function decline in asthma; a clinical feature linked to airway wall remodelling [2]. Therefore, we hypothesised that PLAUR may contribute to structural changes in asthma via increased levels of the membrane bound or soluble receptor. We subsequently showed that PLAUR levels were elevated in the airway epithelium of asthma patients and that PLAUR has a role in epithelial repair responses [3]. The aim of the current study was to 1) test for association between PLAUR SNPs and markers of airway remodelling using bronchial biopsies from asthma patients; and 2) test for association between SNPs and staining for PLAUR in airway tissue. PLAUR polymorphisms and levels are associated with markers of airway remodelling in lung biopsies of asthma patients <http://ow.ly/X5Srl>
Fine Structure of Pancreatic Adenocarcinoma Induced In Rats by 7,12-Dimethylbenz[ a ]anthracene 2
Authors: Dale E. Bockman, Owen Black, Luther R. Mills, David L. Mainz, Paul D. Webster
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Fine Structure of Pancreatic Adenocarcinoma Induced In Rats by 7,12-Dimethylbenz[a]anthracene Get access Dale E. Bockman, Ph.D., Dale E. Bockman, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Owen Black, Jr., Ph.D., Owen Black, Jr., Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Luther R. Mills, M.D., Luther R. Mills, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar David L. Mainz, M.D., David L. Mainz, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul D. Webster, III, M.D. Paul D. Webster, III, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 57, Issue 4, October 1976, Pages 931–936, https://doi.org/10.1093/jnci/57.4.931 Published: 01 October 1976 Article history Received: 04 February 1976 Accepted: 05 April 1976 Published: 01 October 1976
Early Diagnosis of Medullary Carcinoma of the Thyroid Gland by Means of Calcitonin Assay
Authors: Kenneth E. W. Melvin, Harry H. Miller, Armen H. Tashjian
Journal: New England Journal of Medicine (1971)

Abstract Medullary thyroid carcinoma was predicted correctly by means of radioimmunoassay of serum and urine calcitonin in 11 members of one family. An increased concentration of calcitonin in serum and urine either basally or in response to calcium infusion was the only indication of disease. After total thyroidectomy, serum and urinary calcitonin fell to low or undetectable levels in 10 of the 11 patients. Carcinoma was present bilaterally in all cases, none exceeding 1.4 cm in diameter, and was without evidence of metastases in five. Tumor tissue contained calcitonin concentrations ranging from 650 to 16,000 times those in normal human thyroid tissue. Parathyroid hyperplasia was present in nine cases; increased levels of parathyroid hormone were present in the serum of six, but all were normocalcemic. Previously unsuspected pheochromocytomas were found in five patients. These results suggest an important role for measurements of calcitonin as a means for screening high-risk persons for medullary carcinoma.
Comparison of Age- and Sex-Specific Incidence Rate Patterns of the Leukemia Complex in the Cat and the Dog&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R Schneider
Journal: JNCI Journal of the National Cancer Institute (1983)

Data on cancer cases in cats and dogs were collected systematically by the Animal Neoplasm Registry of Alameda and Contra Costa Counties, Calif., a population-based animal tumor registry. Etiologic relationships were evaluated on the basis of comparisons of age-specific, sex-specific, and age-neutered-specific incidence rate patterns of the leukemias. Age-adjusted annual incidence rates for all leukemias per 100,000 cats or dogs were 224.3 and 30.5, respectively. The cat had 6.1 times more malignant lymphomas and 15.7 times more myeloproliferative disease than the dog. Feline age-specific rates indicated a bimodal age pattern for all leukemias and for malignant lymphoma alone and a single early peak for myeloproliferative disease. In the dog, all age-specific patterns increased with age and peaked later in life. Feline sex-specific, age-adjusted rates showed that the neutered female was at lowest risk, followed by the neutered male, entire female, and entire male. In the dog, the neutered male was at lowest risk while the other three sex categories were clustered. However, the magnitude of expression within each species separately was the same for the neutered male, entire male, and entire female, but not for the neutered female. Neutering decreased the risk of leukemias in the female cat by approximately one-half but did not affect the risk of leukemias in the female dog.
Extramural Preceptorships — A Return to the Pre-Flexner Era of Medical Education?
Authors: Mason Trowbridge
Journal: New England Journal of Medicine (1958)

FORMAL association of medical student and practitioner was common in the last century, but extramural preceptorships have been revived on a large scale only during the last decade.1 Under this system fourth-year students are sent to observe the work of a physician for a period of weeks or, less commonly, of months. The student usually becomes a member of the practitioner's family during this period and is virtually his shadow during his working and leisure hours. Nearly a third of the medical schools of the country have such programs for all or part of the fourth-year class.Thus, an increasing . . .
Nature of 3,6-Bis{5-chloro-2-piperidinyl)-2,5-piperazinedione-Induced Cytotoxicity in Chinese Hamster Ovary Cells 23
Authors: Suneeta Mahagaokar, Potu N. Rao, Barthel Barlogie
Journal: JNCI Journal of the National Cancer Institute (1976)

We studied the effect of 3,6-bis(5-chloro-2-piperidinyl)-2,5-piperazinedione (BCP) on various parameters of the replication cycle and cell growth on monolayer cultures of Chinese hamster ovary cells. The results indicated that BCP had no effect on the G1-S transition or the passage of cells from metaphase to G1. However, BCP prolonged S- and G2-phases because of its retarding effect on DNA synthesis. BCP was more toxic to Sphase cells than to G1 or mitotic cells. As with other alkylating agents, chromosome damage due to BCP could be seen only in cells that had undergone DNA replication after exposure to the drug.
Efficacy and Safety of Multiple Doses of Imab362 in Patients with Advanced Gastro-Esophageal Cancer: Results of a Phase Ii Study
Authors: T. Trarbach, M. Schuler, Z. Zvirbule, F. Lordick, A. Krilova, U. Helbig, H. Schulze-Bergkamen, P.C. Thuss-Patience, G. Wichert, W. Schmiegel, S. Bauer, C. Müller, S. Al-Batran, C. Huber, D. Maurus, M. Kühnle, U. Sahin, Ö. Türeci
Journal: Annals of Oncology (2014)
To B(MP-2) or Not To B(MP-2): Cytokines and Tumor Surgery—Letter
Authors: David S. Geller, Jonathan Gill, Michael Roth, Richard Gorlick
Journal: Clinical Cancer Research (2015)

In his editorial (1), Dr. Weiss divides his comments along two controversial themes within musculoskeletal oncology, the effects of surgical margins and of BMP-2 in the context of osteosarcoma. His comments regarding BMP-2 distill down to a belief that patient survival should never be compromised in exchange for improved orthopedic outcomes. Although we agree with this point in principle, additional discussion is warranted.Many who care for osteosarcoma patients hold common the belief that until a new therapeutic approach becomes available survival is unlikely to improve. This belief is rooted in numerous phase III trials, all of which have failed to demonstrate improved outcomes with the addition of cytotoxic chemotherapy and immunotherapy agents. This notion is further underscored by a paucity of current phase III clinical trials. Although improving survival remains paramount, at this juncture, it may be a reasonable and timely to consider the improvement of orthopedic outcomes.While we agree that survival remains more important than orthopedic outcomes, current standard of care appears discrepant in at least one manner. Given that the most recent international phase III clinical trial has definitively demonstrated the inability to salvage poor responders, tailoring chemotherapy with existing agents can no longer be considered advantageous. Furthermore, one could easily hypothesize that chemotherapy, in the context of a genetically unstable tumor, may lead to impaired survival through drug resistance. In addition, the impact of immediate versus delayed surgery has been previously explored (2). This markedly underpowered study has served as the basis for deeming delayed surgery as being safe, with immediate surgery having a survival advantage, but the result was not statistically significantly different. At a minimum, these results remind us that delayed surgery does not clearly improve overall survival. Beyond the smoothed logistical issues of delayed surgery, the only true benefit it provides is improving orthopedic outcomes.Local BMP-2 administration may theoretically increase the risk of osteosarcoma metastases, but the data remain controversial (3–5). The warnings in the BMP-2 prescribing information are for all cancer risk, not specifically osteosarcoma. Conversely, BMP-2 is known to stimulate bone production and fracture healing, and it is plausible that it may decrease non-union. Indeed, well-conducted clinical trials will be the only manner with which to answer these questions. We would argue that it is hypocritical to dismiss a carefully monitored clinical trial investigating the use of BMP-2 to improve orthopedic outcomes, while administering neoadjuvant chemotherapy for the very same purpose.See the Response, p. 4023No potential conflicts of interest were disclosed.
Technic of Controlled Drug Assay
Authors: Stanley E. Rosenbloom, Richard P. Shapera, Robert S. Goldbloom, Mindel C. Sheps, Alvin P. Shapiro, Martin Goldstein
Journal: New England Journal of Medicine (1963)

THE comparative value of the various hypotensive drugs must be judged in terms not only of their potential benefit but also of their undesirable side effects. This is particularly true when the potent sympatholytic and ganglionic drugs are compared in patients with nonaccelerated forms of hypertensive disease, who are often asymptomatic despite considerable elevation of blood pressure. When the task of evaluation is then compounded by a comparison of two pharmacologically different drugs, for each of which the individual dose must be determined empirically, a quite difficult problem of bioassay arises. To add further complication, even with quite potent drugs . . .
Growth and Pituitary-Adrenal Function in Children with Severe Asthma Treated with Inhaled Budesonide
Authors: Benjamin Volovitz, Jacob Amir, Hagit Malik, Arieh Kauschansky, Itzhak Varsano
Journal: New England Journal of Medicine (1993)

The increased use of inhaled corticosteroids in the management of asthma raises concern about the safety of these drugs in children. We sought to determine the safety of long-term administration of inhaled budesonide in young children with asthma.