tbuckley/cabot-search huggingface dataset:
An epigenetically distinct breast cancer cell subpopulation promotes collective invasion
Authors: Jill M. Westcott, Amanda M. Prechtl, Erin A. Maine, Tuyen T. Dang, Matthew A. Esparza, Han Sun, Yunyun Zhou, Yang Xie, Gray W. Pearson
Journal: Journal of Clinical Investigation (2015)

Tumor cells can engage in a process called collective invasion, in which cohesive groups of cells invade through interstitial tissue. Here, we identified an epigenetically distinct subpopulation of breast tumor cells that have an enhanced capacity to collectively invade. Analysis of spheroid invasion in an organotypic culture system revealed that these "trailblazer" cells are capable of initiating collective invasion and promote non-trailblazer cell invasion, indicating a commensal relationship among subpopulations within heterogenous tumors. Canonical mesenchymal markers were not sufficient to distinguish trailblazer cells from non-trailblazer cells, suggesting that defining the molecular underpinnings of the trailblazer phenotype could reveal collective invasion-specific mechanisms. Functional analysis determined that DOCK10, ITGA11, DAB2, PDFGRA, VASN, PPAP2B, and LPAR1 are highly expressed in trailblazer cells and required to initiate collective invasion, with DOCK10 essential for metastasis. In patients with triple-negative breast cancer, expression of these 7 genes correlated with poor outcome. Together, our results indicate that spontaneous conversion of the epigenetic state in a subpopulation of cells can promote a transition from in situ to invasive growth through induction of a cooperative form of collective invasion and suggest that therapeutic inhibition of trailblazer cell invasion may help prevent metastasis.
ABDOMINAL PAIN IN PREGNANCY
Authors: STUART B. BLAKELY
Journal: JAMA (1933)

Abdominal pain in pregnancy is frequent and has not been thoroughly studied. Few pregnant women escape some abdominal discomfort or distress. Eighty-five per cent definitely complain of such pain at some time during the nine months. The literature on the subject is meager. Brief references are scattered through obstetric textbooks.<sup>1</sup>Only two journal articles in English could be found;<sup>2</sup>hence this clinical study of abdominal pain in 300 consecutive private obstetric cases. Since it is entirely unpractical to attempt to name all the causes of abdominal pain, with or without pregnancy, this paper will deal only with abdominal pain that is directly caused by or closely associated with the enlarging uterus or the pregnant state. Pregnancy is, of course, not immune to any of the numerous intra-abdominal and extra-abdominal conditions that cause pain in the abdomen, a fact to be most strongly emphasized and ever borne in mind.
Reporting Randomized Controlled Trials
Authors: Carl D. Atkins
Journal: JAMA (1995)

<h3>To the Editor.</h3> —I am enthusiastic about your experiment in the structured reporting of randomized controlled trials.<sup>1</sup>I agree that current methods provide too little detail about methods to determine a study's statistical validity. However, the structured system you suggest is cumbersome. I suggest the following solution. Rather than delineating randomization issues one by one, why not have an authoritative statistician publish an article in<i>JAMA</i>with appropriate methods outlined and named so that they can be referenced by authors? This would be similar to current style in reporting postrandomization statistical methods, eg, the Cox proportional hazards test. Where specifics are required or variances need to be reported, this could easily be explained without undue verbiage in the text. In this way, full details of the methods could be reported without throwing an undue burden on either author or reader.
Early Parathyroid MIBI SPECT Imaging in the Diagnosis of Persistent Hyperparathyroidism
Authors: V Gilberto González, B Pilar Orellana, M José Manuel López, M Marcela Jiménez, Y Juan Carlos Quintana
Journal: Clinical Nuclear Medicine (2008)

We present a case that demonstrates the utility of early SPECT images associated with fusion images with MRI for presurgical localization in a case of persistent hyperparathyroidism after a first surgery. Three years after that surgery, severe hypercalcemia (14.7 mg/dL) and elevated parathormone (PTH) (944 pg/mL) were detected. MRI and SPECT parathyroid scintigraphy showed an abnormal parathyroid lesion localized behind the inferior pole of the thyroid right lobe. At surgical reexploration a right inferior parathyroid adenoma was removed (258 mg). However, intraoperative PTH remained high and a total thyroidectomy was performed looking for an intrathyroid lesion. After that, the elevated PTH persisted and an ectopic parathyroid gland was identified in the tracheoesophageal groove (958 mg), corresponding with the lesion seen on the fusion image of MRI and SPECT. After removal of this lesion, the PTH dropped to 85%.
SPIROCHAETA PALLIDA: METHODS OF EXAMINATION AND DETECTION, ESPECIALLY BY MEANS OF THE DARK GROUND ILLUMINATION
Authors: A. C. Coles
Journal: BMJ (1909)

Now that it is very generally conceded that the Spiro- chaeta pallidd is the cause of syphilis, its recognition, especially in the early stages of the disease, is a matter of considerable diagnostic importance.I have endeavoured to describe briefly the method of taking the material for examination, the most approved methods of staining, and the method of examining the living organism by means of the dark-ground illumination.I. TAKING THE MATERIAL.Although the Spirochaeta pallida has been found in almost all forms and stages of syphilis, including even the gumma, the most usually selected lesions for examination purposes are:(a) The primary sore, either in its unbroken or papular stage or in the usual form, the ulcerative chancre.(b) Condylomata and mucous patches,, which are so highly infectious, and in which the spirochaetes occur probably in the largest number.(c) The indurated glands.(d) The various forms of eruptive lesions, especially the papular and vesicular forms, more rarely in the roseola.From the Primary Papule.
Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular function
Authors: Y. Cheng
Journal: Journal of Clinical Investigation (2006)

We investigated the mechanisms by which inhibitors of prostaglandin G/H synthase-2 (PGHS-2; known colloquially as COX-2) increase the incidence of myocardial infarction and stroke. These inhibitors are believed to exert both their beneficial and their adverse effects by suppression of PGHS-2-derived prostacyclin (PGI(2)) and PGE(2). Therefore, the challenge remains to identify a mechanism whereby PGI(2) and PGE(2) expression can be suppressed while avoiding adverse cardiovascular events. Here, selective inhibition, knockout, or mutation of PGHS-2, or deletion of the receptor for PGHS-2-derived PGI(2), was shown to accelerate thrombogenesis and elevate blood pressure in mice. These responses were attenuated by COX-1 knock down, which mimics the beneficial effects of low-dose aspirin. PGE(2) biosynthesis is catalyzed by the coordinate actions of COX enzymes and microsomal PGE synthase-1 (mPGES-1). We show that deletion of mPGES-1 depressed PGE(2) expression, augmented PGI(2) expression, and had no effect on thromboxane biosynthesis in vivo. Most importantly, mPGES-1 deletion affected neither thrombogenesis nor blood pressure. These results suggest that inhibitors of mPGES-1 may retain their antiinflammatory efficacy by depressing PGE(2), while avoiding the adverse cardiovascular consequences associated with PGHS-2-mediated PGI(2) suppression.
MB-21 * INTEGRATED GENOMICS ELUCIDATES RELATIVE SPATIAL HOMOGENEITY OF EMBRYONAL BRAIN TUMORS
Authors: M. Remke, F. Cavalli, A. S. Morrissy, V. Ramaswamy, D. Jones, R. Packer, E. Bouffet, G. Bader, S. Pfister, N. Jabado, M. Marra, M. Taylor
Journal: Neuro-Oncology (2015)

INTRODUCTION: Comprehensive, genome-wide profiling and next-generation based sequencing studies have dramatically improved our understanding of pediatric brain tumor biology in the recent years. However, the vast majority of theses studies are based on the assumption that single biopsies are representative for the entire primary tumor. Intratumor heterogeneity constitutes a common phenomenon previously described in renal cell carcinoma (RCC), breast cancer, and high-grade glioma (HGG). Highly disparate molecular profiles of spatially separated tumor areas within the same tumor may preclude development of personalized, molecularly targeted therapies based on single tumor biopsies. MATERIAL AND METHODS: To address this issue, we conducted multiregion whole exome sequencing, high-resolution DNA copy number analysis (Cytoscan HD), and transcriptional profiling on 39 distinct pediatric and adult tumors with a median of six spatially distant biopsies per tumor (range 4-11). Histological entities included AT/RT (n = 2), HGG (n = 17), medulloblastoma (n = 9), medulloepithelioma (n = 1), and RCC (n = 10). We assessed the degree of intratumor heterogeneity and subgroup affiliation using integrated genomics and unsupervised hierarchical clustering algorithms. RESULTS: Embryonal brain tumors demonstrated highly spatially homogenous transcriptomes. In contrast to adult glioblastoma, we showed that subgroup affiliation was stable in multiregion biopsies from the same medulloblastoma patient. Furthermore, embryonal brain tumors displayed highly similar focal and broad DNA copy number alterations compared to HGG and RCC. Multiregion sequencing further reinforced the relatively higher degree of intratumor homogeneity in embryonal brain tumors. Compared to HGG or RCC, somatic mutations in embryonal tumors were much more likely to be ubiquitous throughout the tumor. CONCLUSIONS: The relative spatial homogeneity of embryonal brain tumors suggests that limited biopsies are representative of the tumor genomics landscape, which has important implications for biological classification and development of targeted therapies for these tumors.
Coexistent chronic idiopathic intestinal pseudo obstruction and inflammatory bowel disease
Authors: Ohlsson B, Fork Ft, Veress B, Toth E
Journal: Gut (2005)

Chronic idiopathic intestinal pseudo obstruction (CIIP) is a severe condition presenting with abdominal pain and dysmotility. Inflammatory or degenerative changes of the autonomic nervous system or of the muscles of the bowel have been observed in CIIP.1,2 As patients with inflammatory bowel disease (IBD) may show clinical3,4 and histological5 signs of autonomic neuropathy and dysmotility,6,7 the aim of this study was to examine whether there is an association between CIIP and IBD.

Six patients at our hospital presenting with signs and symptoms of intestinal dysmotility were diagnosed with CIIP based on clinical features, antroduodenojejunal manometry, and full thickness biopsies (table 1).8,9 Patient No 1 had an acute erosive colitis some years previously with bloody diarrhoea and an enhanced sedimentation rate, which was treated with steroids, …
Sanguineous Discharge from the Vagina of an Infant
Authors: J. Birchenall
Journal: BMJ (1865)

work; but the bowels did not act copiously until the 12th, after an active pill of calomel, gamboge, aloes, and soap.Nov. 14th.He had no choleraic symptoms, but was weak, depressed, and without appetite.His bodily discomforts seemed now to arise from his still breathing an air that was fall of a foul smell.
Audit of basal cell carcinoma: registration practice
Authors: N.M. McLoone, R.J. Middleton, A.T. Gavin, M. Walsh, O.M. Dolan
Journal: British Journal of Dermatology (2003)

Journal Article Audit of basal cell carcinoma: registration practice Get access N.M. McLoone, N.M. McLoone Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar R.J. Middleton, R.J. Middleton Pathology, The Royal Hospitals, Grosvenor Road, Belfast BT12 6BA, U.K Search for other works by this author on: Oxford Academic Google Scholar A.T. Gavin, A.T. Gavin Pathology, The Royal Hospitals, Grosvenor Road, Belfast BT12 6BA, U.K Search for other works by this author on: Oxford Academic Google Scholar M. Walsh, M. Walsh The Northern Ireland Cancer Registry, Belfast BT12 6BJ, U.K. E‐mail: nablamcloone@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar O.M. Dolan O.M. Dolan Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 148, Issue 2, 1 February 2003, Page 371, https://doi.org/10.1046/j.1365-2133.2003.05097_7.x Published: 01 February 2003
Biological Clock May Be as Crucial as Stopwatch in Deciding Athletic Contests
Authors: Lynne Lamberg
Journal: JAMA (1996)

FROM THE OLYMPICS to football games, athletes who train and compete at optimal times on their biological clocks may gain a competitive edge, suggest 2 reports presented at the joint meeting of the American Sleep Disorders Association and Sleep Research Society in Washington, DC. But such synchrony, the reports imply, is not widely practiced. Roger Smith, DO, a clinical and research fellow in the Sleep Disorders Clinic and Research Center at Stanford (Calif) University School of Medicine, and his colleagues queried 16 US Olympic athletes and 12 Division I NCAA athletes to learn when they believed they performed best and when they trained and competed. The 10 men and 18 women included runners, swimmers, basketball players, and participants in other sports. More than 60% said they were at their peak in the afternoon, most often between 3 PM and 6 PM. Slightly more than 20% said they were in top
Strain-Rate Imaging During Dobutamine Stress Echocardiography Provides Objective Evidence of Inducible Ischemia
Authors: Jens-Uwe Voigt, Bert Exner, Kristin Schmiedehausen, Cord Huchzermeyer, Udo Reulbach, Uwe Nixdorff, Günther Platsch, Torsten Kuwert, Werner G. Daniel, Frank A. Flachskampf
Journal: Circulation (2003)

Interpretation of dobutamine stress echocardiography (DSE) is subjective and strongly dependent on the skills of the reader. Strain-rate imaging (SRI) by tissue Doppler may objectively analyze regional myocardial function. This study investigated SRI markers of stress-induced ischemia and analyzed their applicability in a clinical setting.DSE was performed in 44 patients with known or suspected coronary artery disease. Simultaneous perfusion scintigraphy served as a "gold standard" to define regional ischemia. All patients underwent coronary angiography. Segmental strain and strain rate were analyzed at all stress levels by measuring amplitude and timing of deformation and visual curved M-mode analysis. Results were compared with conventional stress echo reading. In nonischemic segments, peak systolic strain rate increased significantly with dobutamine stress (-1.6+/-0.6 s-1 versus -3.4+/-1.4 s-1, P<0.01), whereas strain during ejection time changed only minimally (-17+/-6% versus -16+/-9%, P<0.05). During DSE, 47 myocardial segments in 19 patients developed scintigraphy-proven ischemia. Strain-rate increase (-1.6+/-0.8 s-1 versus -2.0+/-1.1 s-1, P<0.05) and strain (-16+/-7% versus -10+/-8%, P<0.05) were significantly reduced (both P<0.01 compared with nonischemic). Postsystolic shortening (PSS) was found in all ischemic segments. The ratio of PSS to maximal segmental deformation was the best quantitative parameter to identify stress-induced ischemia. Compared with conventional readings, SRI curved M-mode assessment improved sensitivity/specificity from 81%/82% to 86%/90%.During DSE, SRI quantitatively and qualitatively differentiates ischemic and nonischemic regional myocardial response to dobutamine stress. The ratio of PSS to maximal strain may be used as an objective marker of ischemia during DSE.
Cardiorespiratory Arrest in Diabetic Autonomic Neuropathy
Authors: Samuel Vaisrub
Journal: JAMA (1978)

When resuscitating a patient who suddenly became breathless and pulseless, the physician generally assumes that the cardiorespiratory arrest was precipitated by serious heart disease. In the vast majority of cases, the assumption will prove to be correct. The ECG or, if resuscitation fails, the autopsy will disclose evidences of underlying pathology in the myocardium, the coronary vasculature, or the conducting system. Occasionally, however, no such pathology will be found. Classic examples are crib deaths and "near deaths," which still defy explanation. Whatever their cause, no cardiac lesions serious enough to account for the sudden death have been found in the stricken infants. Recently, a variant of cardiorespiratory arrest that could not be accounted for by a cardiac lesion has been described by several observers. Lloyd-Mostyn and Watkins<sup>1</sup>reported unexplained cardiorespiratory arrests in two diabetic patients with autonomic neuropathy. In a later and more extensive study, Page and Watkins<sup>2</sup>
Human parvovirus B19 causes cell cycle arrest of human erythroid progenitors via deregulation of the E2F family of transcription factors
Authors: Zhihong Wan, Ning Zhi, Susan Wong, Keyvan Keyvanfar, Delong Liu, Nalini Raghavachari, Peter J. Munson, Su Su, Daniela Malide, Sachiko Kajigaya, Neal S. Young
Journal: Journal of Clinical Investigation (2010)

Human parvovirus B19 (B19V) is the only human pathogenic parvovirus. It causes a wide spectrum of human diseases, including fifth disease (erythema infectiosum) in children and pure red cell aplasia in immunocompromised patients. B19V is highly erythrotropic and preferentially replicates in erythroid progenitor cells (EPCs). Current understanding of how B19V interacts with cellular factors to regulate disease progression is limited, due to a lack of permissive cell lines and animal models. Here, we employed a recently developed primary human CD36(+) EPC culture system that is highly permissive for B19V infection to identify cellular factors that lead to cell cycle arrest after B19V infection. We found that B19V exploited the E2F family of transcription factors by downregulating activating E2Fs (E2F1 to E2F3a) and upregulating repressive E2Fs (E2F4 to E2F8) in the primary CD36(+) EPCs. B19V nonstructural protein 1 (NS1) was a key viral factor responsible for altering E2F1-E2F5 expression, but not E2F6-E2F8 expression. Interaction between NS1 and E2F4 or E2F5 enhanced the nuclear import of these repressive E2Fs and induced stable G₂ arrest. NS1-induced G₂ arrest was independent of p53 activation and increased viral replication. Downstream E2F4/E2F5 targets, which are potentially involved in the progression from G₂ into M phase and erythroid differentiation, were identified by microarray analysis. These findings provide new insight into the molecular pathogenesis of B19V in highly permissive erythroid progenitors.
End-of-life decisions in an Indian intensive care unit
Authors: Raj Kumar Mani, Amit Kumar Mandal, Sabyasachi Bal, Yash Javeri, Rakesh Kumar, Deepak Kumar Nama, Praveen Pandey, Tara Rawat, Navneet Singh, Hemant Tewari, Rajiv Uttam
Journal: Intensive Care Medicine (2009)
Do imaging methods that guide needle placement improve outcome?
Authors: S Hall, R Buchbinder
Journal: Annals of the Rheumatic Diseases (2004)

For most joints injections following an anatomical landmark are sufficient

The year 1949 was a watershed for rheumatology. In that year Hench and his colleagues first described the use of corticosteroids for therapy in rheumatoid arthritis. Within a year Hollander and his colleagues, having seen the striking topical anti-inflammatory effects of cortisone, injected cortisone suspension into 25 knee joints inflamed by rheumatoid arthritis, but found only a minimal and transitory benefit.1 However, by 1954, depot steroid preparations for intra-articular injection were part of the standard therapeutic armamentarium.1

Despite the enthusiasm with which injected corticosteroids have been greeted and their widespread continued use, until recently, there has been limited evidence from controlled trials of their effectiveness in conditions such as shoulder disorders.2 Furthermore, for the first 40 years of their use, the accuracy of needle placement was not methodically studied. In 1993, Jones et al studied the accuracy of 109 injections into various joints, by mixing the depot steroid with a radiographic contrast medium.3 They found that approximately one third of knee and ankle injections were extra-articular, only half of the wrist injections were definitely intra-articular, with even less accuracy reported for shoulder injections. Remarkably, even the ability to aspirate synovial fluid was not a perfect predictor of intra-articular placement of steroid injections with almost half of extra-articular injections having been associated with successful aspiration of synovial fluid. Experience beyond advanced trainee/registrar level did not appear to influence the accuracy of injection placement. Despite these findings, almost half of those …
Psychosomatic Interrelations in General Medicine
Authors: Gertrude F. Frisbie
Journal: New England Journal of Medicine (1945)

THE efficiency of the general medical practitioner is conditioned by the following factors: first, his knowledge and appreciation of the normal human organism as a complex and integrated whole of physical, mental and emotional elements and his understanding and appreciation of the types of pathologic variations from normality that may arise, with their respective symptomatology and etiology; second, his knowledge of how to determine the nature and extent of these variations; and third, his selection of treatment.Knowledge and appreciation of the normal human organism of integrated physical, mental and emotional elements include the following concepts: the body as a . . .
Ipratropium bromide aqueous nasal spray for patients with perennial allergic rhinitis: A study of its effect on their symptoms, quality of life, and nasal cytology
Authors: Eli O. Meltzer, H.Alice Orgel, Edwin A. Bronsky, Steven R. Findlay, John W. Georgitis, Jay Grossman, Paul Ratner, Chester C. Wood
Journal: Journal of Allergy and Clinical Immunology (1992)
CCAAT/enhancer binding protein ? (C/EBP?) is an important mediator of mouse C/EBP? protein isoform production
Authors: Bonnie L. Burgess-Beusse, Nikolai A. Timchenko, Gretchen J. Darlington
Journal: Hepatology (1999)

Both CCAAT/enhancer binding protein α (C/EBPα) and C/EBPβ are intronless, yet can create various N–terminally truncated protein products with distinct DNA binding and transactivation potentials. These proteins can be generated via two distinct mechanisms, one translational and the other post–translational. In the translational mechanism, there is alternative translational start site selection of the different AUG codons present in the single messenger RNA (mRNA) species via a process of leaky ribosome scanning. Additionally, a post–translational method of isoform formation, through specific proteolytic cleavage of the full length protein has also been described. In this manuscript, we present evidence that the production of C/EBPβ protein isoforms in the neonatal mouse liver is regulated by C/EBPα. In C/EBPα knockout mice, the predominant C/EBPβ proteins are the larger 38– and 35–kd isoforms, whereas wild–type animals primarily possess the smaller 21– and 14–kd isoforms. These C/EBPα–dependent differences are liver specific, not present in lung or adipose tissues, and present at day 18 of development. Additionally, we show that induction of C/EBPα expression leads to an increase in the production of the 21–kd C/EBPβ isoform in cell culture studies. As the various C/EBPβ protein isoforms have different transcriptional capabilities, it is important to understand the regulation of the production of these isoforms. Our observations suggest a novel role for the C/EBPα transcription factor in this process.