tbuckley/cabot-search huggingface dataset:
Curbing tobacco's toll starts with the professionals: World No Tobacco Day
Authors: Peter Boyle, MAY Ariyaratne, Harry Bartelink, José Baselga, Anton Berns, Otis W Brawley, Harry Burns, Michail Davidov, KA Dinshaw, Carolyn Dresler, Alexander MM Eggermont, Damodar Gajurel, Galina Gordina, Nigel Gray, Tadao Kakizoe, Balman Singh Karki, Miklós Kásler, David J Kerr, David Khayat, Alexander Kiselev, Thiravud Khuhaprema, Helmut Klocker, Valdimir Levshin, Jose M Martin-Moreno, J Gordon McVie, John Mendelsohn, Nikolai P Napalkov, Twalib A Ngoma, Jae-Gahb Park, Thierry Philip, Martina Pötschke-Langer, Hom Nath Poudal, B Rajan, Ulrik Ringborg, Alan Rodger, John R Seffrin, V Shanta, Murari Man Shrestha, Robert Thomas, Thomas Tursz, Dominique de Valeriola, Umberto Veronesi, Otmar D Wiestler, David Zaridze, Witold Zatonski, Yi-Xin Zeng
Journal: The Lancet (2005)
Research ethics paperwork: what is the plot we seem to have lost?
Authors: Konrad Jamrozik
Journal: BMJ (2004)

The standardisation of applications to local research ethics committees seems likely to make ethical approval less efficient and more time consuming for everyone Researchers in the United Kingdom now have to submit their study proposals to local research ethics committees using a nationally standardised form. The form overcomes the problem of inconsistencies in the paperwork required by different committees.1 2 It is incredibly long, however, and threatens to overwhelm both committees and investigators with paperwork.2–4 The administrative burden is likely to be increased by the advent of a research management and governance framework for health and social care5 and the requirement for ethical clearance for all research by students on humans, including their tissues or data.6 Current trends are not sustainable in terms of time, money, or their impact on the environment, and it seems we have lost the plot. In this article, I examine how we can streamline the process. The first step is to determine the essential information required for ethical approval. Based on my experience as a member of three ethics committees in two countries, I think that members ask themselves four basic questions:
Toll-like receptor (TLR2) Regulates Organic Dust-Induced Airway Inflammation
Authors: J.A. Poole, T.A. Wyatt, T. Kielian, P. Oldenburg, A. Gleason, A. Bauer, W. West, J. Sisson, D.J. Romberger
Journal: Journal of Allergy and Clinical Immunology (2011)
Predominant Th1 cell infiltration in acute rejection episodes of human kidney grafts
Authors: Mario M. D'elios, Régis Josien, Marta Manghetti, Amedeo Amedei, Marco de Carli, Maria Cristina Cuturi, Gilles Blancho, Françoise Buzelin, Gianfranco Del Prete, Jean-Paul Soulillou
Journal: Kidney International (1997)
Adventitial Remodeling After Coronary Arterial Injury
Authors: Yi Shi, Marc Pieniek, Ali Fard, James O’Brien, John D. Mannion, Andrew Zalewski
Journal: Circulation (1996)

Background Intraluminal thrombus formation and medial smooth muscle (SM) cell proliferation are recognized responses of the arterial system to injury. In contrast to these well-characterized processes during vascular repair, changes involving the adventitia have been largely neglected in previous studies. Hence, the goal of this investigation was to assess the response of the adventitia to coronary arterial injury. Methods and Results Adventitial changes in porcine coronary arteries subjected to medial injury were characterized by immunohistochemistry, histochemistry, and microscopic morphometry. The rapid development of a hypercellular response in the adventitia was evident 3 days after balloon-induced medial injury. Cell proliferation, as assessed by proliferating cell nuclear antigen immunostaining, reached the maximum level in the adventitia at 3 days, whereas at 14 and 28 days, the number of replicating cells reverted toward the baseline. The proliferating activity in the adventitia exceeded that seen in the media at all times after injury. To further define the changes in the phenotype of adventitial cells, the expression of three cytoskeletal proteins (vimentin, α-SM actin, and desmin) was characterized. Fibroblasts in normal adventitia expressed vimentin but no α-SM actin or desmin. After injury, these cells acquired characteristics of myofibroblasts expressing α-SM actin, which peaked at 7 and 14 days. Desmin expression was patchy in the adventitia, as opposed to its homogeneous distribution in medial SM cells. The modulation of fibroblast phenotype was transient, inasmuch as α-SM actin immunostaining declined at 28 days after injury, when dense, collagen-rich scar was evident within the adventitia. The above-described changes involving hypercellularity of the adventitia, myofibroblast formation, and fibrosis were associated with a significant focal adventitial thickening at 3, 7, 14, and 28 days after injury ( P &lt;.01 versus uninjured coronary arteries). Conclusions This study demonstrates the involvement of the adventitia in the vascular repair process after medial injury. The hypercellularity of the adventitial layer, proliferation of fibroblasts, and modulation of their phenotype to myofibroblasts are associated with the development of the thickened adventitia. It is postulated that these phenomena affect vascular remodeling and may provide an important insight into the mechanisms of vascular disorders.
Pathologist's Opportunity To Assist in Follow-Up
Authors: M. Harold Book
Journal: JAMA (1967)

To the Editor:—  The increasing mobility of Americans in the last few decades and the advance of scientific medicine with its interest in accuracy of diagnosis and longterm follow-up of patients have presented pathologists with an opportunity to be of service which should be brought to the attention of members of the entire profession. Not infrequently a patient receives a thorough work-up in one part of the country and then, because of transfer in employment, migration to a different climate, etc, he may die in a hospital far removed from the site where he was first examined. Pathologists performing autopsies in these cases have an opportunity to assist the physician in the first place of hospitalization by informing him of their findings. As is well known, in spite of the great progress in diagnosis, mistakes are still made and are discovered only at autopsy. By communicating with the first physician
Diphenylhydantoin in the Prevention of Recurring Ventricular Tachycardia
Authors: NEIL STONE, MICHAEL D. KLEIN, BERNARD LOWN
Journal: Circulation (1971)

The efficacy of diphenylhydantoin in preventing recurrent ventricular tachycardia was studied in ten patients, nine of whom had documented coronary heart disease. Prolonged continuous ECG monitoring of up to 72 hr was performed in each case. Oral and intravenous loading doses of 1000 to 1500 mg were given on the first day of therapy to insure rapid attainment of therapeutic blood levels. Diphenylhydantoin was uniformly ineffective in preventing recurrence of ventricular tachycardia despite the presence of what is regarded as adequate therapeutic plasma concentrations (greater than 19.0 µg/ml in five patients, 10.8-18.0 µg/ml in the remaining five) shortly after onset of ventricular tachycardia. Nystagmus was noted in eight patients, but plasma diphenylhydantoin levels varied widely (8.6-35.0 µg/ml) when this sign of neurotoxicity was first detected.
Fulminant Ulcerative Colitis
Authors: Arun Swaminath, Daniel Feingold
Journal: New England Journal of Medicine (2010)

A 20-year-old man with a recent diagnosis of ulcerative colitis had increasingly frequent bloody diarrhea and weight loss. He was admitted to our hospital after showing no response to treatment with intravenous corticosteroids, total parenteral nutrition, and a transfusion of packed red cells at another institution. A computed tomographic scan of the abdomen (Panel A) showed a severely dilated transverse colon (arrow) and free air (arrowhead). The patient underwent an emergency laparoscopic total abdominal colectomy with end ileostomy. The surgical specimen showed parallel lines of ulceration surrounded by inflamed mucosa (Panel B). Microscopically, the presence of crypt abscesses, lymphoplasmacytic infiltrates, . . .
Visual word recognition and oculomotor control in reading
Authors: Lynn Huestegge, Jonathan Grainger, Ralph Radach
Journal: Behavioral and Brain Sciences (2003)

A central component in the E-Z Reader model is a two-stage word processing mechanism made responsible for both the triggering of eye movements and sequential shifts of attention. We point to problems with both the verbal description of this mechanism and its computational implementation in the simulation. As an alternative, we consider the use of a connectionist processing module in combination with a more indirect form of cognitive eye-movement control.
PM02734 (Elisidepsin) Induces Caspase-Independent Cell Death Associated with Features of Autophagy, Inhibition of the Akt/mTOR Signaling Pathway, and Activation of Death-Associated Protein Kinase
Authors: Yi-He Ling, Miguel Aracil, Yiyu Zou, Ziqiang Yuan, Bo Lu, José Jimeno, Ana Maria Cuervo, Roman Perez-Soler
Journal: Clinical Cancer Research (2011)

PM02734 (elisidepsin) is a synthetic marine-derived cyclic peptide of the kahalalide family currently in phase II clinical development. The mechanisms of cell death induced by PM02734 remain unknown.Human non-small-cell lung cancer (NSCLC) cell lines H322 and A549 were used to evaluate PM02734-induced cytotoxicity, apoptosis, and autophagy, as well as effects on cell death-related signaling pathways.PM02734 at clinically achievable concentrations (0.5-1 μmol/L) was cytotoxic to H322 and A549 cells but did not cause nuclear fragmentation, PARP cleavage, or caspase activation, suggesting that classical apoptosis is not its main mechanism of cell death. In contrast, PM02734-induced cell death was associated with several characteristics of autophagy, including an increase in acidic vesicular organelle content, levels of GFP-LC3-positive puncta, elevation of the levels of Atg-5/12 and LC3-II, and an associated compromise of the autophagic flux resulting in increased number of autophagosomes and/or autolysosomes. Cotreatment with 3-methyladenine (3-MA) and downregulation of Atg-5 gene expression by siRNA partially inhibited PM02734-induced cell death. PM02734 caused inhibition of Akt/mTOR signaling pathways and cotreatment with the Akt inhibitor wortmannin or with the mTOR inhibitor rapamycin led to a significant increase in PM02734-induced cell death. Furthermore, PM02734 caused the activation of death-associated protein kinase (DAPK) by dephosphorylation at Ser308, and downregulation of DAPK expression with siRNA caused also a partial but significant reduction of PM02734-induced cell death. In vivo, PM02734 significantly inhibited subcutaneous A549 tumor growth in nude mice (P < 0.05) in association with induction of autophagy.Our data indicate that PM02734 causes cell death by a complex mechanism that involves increased autophagosome content, due for the most part to impairment of autophagic flux, inhibition of the Akt/mTOR pathway, and activation of DAPK. This unique mechanism of action justifies the continued development of this agent for the treatment of NSCLC.
SIRT7 expression and epigenetic status determine variability in telomere length in breast cancer.
Authors: S Zino, CP Moran, LM McGlynn, W George, AP Payne, PG Shiels
Journal: Cancer Research (2009)

Abstract Abstract #4052 Background: As cancer is a disease of ageing, factors involved in biological ageing may be informative in investigating the underlying mechanisms of cancer pathogenesis. How biological age is affected by epigenetic changes remains to be fully determined. This is pertinent to cancer pathogenesis, as epigenetic changes can increase the risk of neoplasia. We have investigated the biological age of breast tumours, using telomere length and the expression of sirtuin 7, a gene involved in the regulation of ribosome biosynthesis and previously demonstrated as potentially prognostic in breast cancer. We have evaluated these for association with epigenetic status.&amp;#x2028; Materials and Methods: Telomere lengths and Sirtuin 7 (SIRT7) expression were determined using Q-PCR. Epigenetic status was determined using a Methylamp Global DNA methylation kit. Statistical analysis was performed using SPSS v15.&amp;#x2028; Results: Chronological age was negatively associated with telomere length (p=0.013) and positively associated with methylation levels (p=0.007). Furthermore, telomere length showed a negative association with global methylation levels (p=0.002). Individuals with shorter telomeres were older and demonstrated higher levels of global DNA methylation. SIRT7 expression was positively associated with telomere length (p=0.01), but showed no association with methylation levels. Linear regression analysis indicated that SIRT7 expression accounted for 52.2% of the observed variability in telomere length (p=0.001) and methlyation for 33.4% (p&amp;lt;0.001). Multiple linear regression analysis indicated that methylation status and SIRT7 expression combined accounted for 69.4% of the observed variability in telomere length. Chronological age was not a significant contributor in either analysis.&amp;#x2028; Discussion: Cells with critically short telomeres present a high risk of becoming neoplastic, as they are biologically aged. This study has demonstrated that both SIRT7 expression and global methylation levels significantly influence telomere attrition in breast cancer. This is consistent with a scenario whereby the rate of biological ageing in breast tumours is influenced by telomere mediated epigenetic changes and mechanistically by cellular proliferation requirements. The latter is manifest through SIRT7 regulated ribosome biogenesis. These findings support the use of SIRT7 as a potential prognostic tool and therapeutic target in breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4052.
Hospital admissions before and after shipyard closure: Authors' reply
Authors: L. Iversen, M. T. Damsgaard, S. Sabroe
Journal: BMJ (1989)

emergency caesarean section because of factors such as prolonged rupture of membranes and repeated vaginal examinations are more at risk of infections.2Fifteen patients (50%) in the group receiving prophylactic antibiotics and 23 (56%) of those not receiving prophylaxis had caesarean sections as emergency procedures.Although infection was more common in the patients having emergency operations compared with those having elective surgery, the difference was not significant
THE ELECTRON MICROSCOPE IN SPERMATOZOAL VISUALIZATION
Authors: Abner I. Weisman
Journal: JAMA (1941)

<h3>To the Editor:—</h3> Seymour and Benmosche reported inThe Journal(May 31, p. 2489) the use of the electron microscope in studying and photographing the spermatozoon. While I do not wish to detract from this contribution in photographing a spermatozoon at a magnification of 27,000 diameters, some comment is evoked by the conclusions which these authors have drawn. Seymour and Benmosche photographed one or two sperms from a single specimen and on this basis describe the shape of the heads of spermatozoa to be "pear shaped." Although it is accepted by spermatologists that pear-shaped (pyriform) sperm heads are present among the normal sperms to the extent of only 4 to 9 per cent, it seems that Seymour and Benmosche were unaware of this and instead have utilized a pearshaped head and set it up as a normal standard. These authors also claim to have found, among other things, a "crater-like
Measles virus and Crohn’s disease: view of a medical virologist
Authors: V TER MEULEN
Journal: Gut (1998)

Some recent reports have claimed that persistent measles virus infection is involved in the aetiology or pathogenesis, or both, of Crohn’s disease. Using a variety of techniques, such as direct electron microscopy, immunohistochemistry and in situ hybridisation, these authors report that measles virus particles, protein or RNA were detected in tissues from patients with Crohn’s disease.1-5 These observations led to the hypothesis that exposure to measles virus early in life, either during pregnancy, or as a consequence of postnatal infection by wild type measles virus or measles vaccination, predisposes to inflammatory bowel disease (IBD).6 7 These claims prompted publication of several critical commentaries and responses and led to a case control study which did not support an association between measles virus vaccination and IBD.8-19 The comments focused on the possible short-comings of the methods used by the researchers as well as the choice of control cohorts with respect to their exposure to the infectious agent and their incidence of IBD. Thus, for example, in many virus–host systems, it has been shown that diagnosis based on morphology can be misleading as viral structures may resemble normal cellular elements. …
THE CURE OF HYSTERICAL PARALYSIS BY RE-EDUCATION OF KINESTHETIC CENTERS.
Authors: HOWELL T. PERSHING
Journal: JAMA (1907)

The sudden disappearance of hysterical paralysis, through religious excitement, hypnotic suggestion or great faith in the assertion of a particular physician, has been made so familiar to the profession that many, no doubt, think of it as the normal and eminently desirable mode of recovery. I have had a moderate share of such cases, sometimes being able, within the clinic hour, to make a patient with hysterical hemiplegia or paraplegia throw away his crutches and run about the room These spectacular cures are intensely interesting and valuable from the purely scientific as well as from the practical standpoint, and they are within the reach of any physician who is sure of his diagnosis and able to pick out the favorable case. Nevertheless, the method that aims at such sudden cures is not the one to be generally chosen. It will succeed in only a few of the cases and it
Cytomegalovirus Mononucleosis in Previously Healthy Individuals
Authors: E. KLEMOLA
Journal: Annals of Internal Medicine (1969)

Five further cases of cytomegalovims (CMV) mononucleosis in previously healthy individuals are reported. This raises the total number of such patients seen by the authors to 18, all but one of whom were adults. A significant rise of complement-fixing antibodies to CMV was found during the disease. Cytomegalovirus was isolated from the urine of four patients. The disease was characterized by protracted fever, liver involvement, absence of pharyngitis and lymph node enlargement, hematologic changes similar to those seen in infectious mononucleosis, and a negative finding on the heterophil-agglutination test. A mixed cryoimmunoglobulinemia and other immunologic aberrations were found in three cases and intranuclear inclusion-bearing cells in the urine in three cases. Virologic and clinical follow-up studies have been performed in patients of the present as well as of previous series. Cytomegalovirus is often excreted in the urine for 1 to 2 years after the illness. Hepatosplenomegaly was found in one patient, a young child, 4 months after the illness. In the other cases nothing suggestive of liver disease has been observed after the results of liver function tests became normal within some weeks or months. In several cases lymphocytosis without the appearance of atypical lymphocytes continued for many months and even years after the illness.
Functional Evolution of the Yeast Protein Interaction Network
Authors: V. Kunin
Journal: Molecular Biology and Evolution (2004)

Protein interactions are central to most biological processes. We investigated the dynamics of emergence of the protein interaction network of Saccharomyces cerevisiae by mapping origins of proteins on an evolutionary tree. We demonstrate that evolutionary periods are characterized by distinct connectivity levels of the emerging proteins. We found that the most-connected group of proteins dates to the eukaryotic radiation, and the more ancient group of pre-eukaryotic proteins is less connected. We show that functional classes have different average connectivity levels and that the time of emergence of these functional classes parallels the observed connectivity variation in evolution. We take these findings as evidence that the evolution of function might be the reason for the differences in connectivity throughout evolutionary time. We propose that the understanding of the mechanisms that generate the scale-free protein interaction network, and possibly other biological networks, requires consideration of protein function.
Toxigenic<i>Escherichia coli</i>
Authors: Sherwood L. Gorbach, Chandra Mohini Khurana
Journal: New England Journal of Medicine (1972)

Approximately 1000 children per year are admitted to Cook County Hospital with acute diarrhea. The etiologic agent cannot be found in the majority of cases. Six hundred strains of Escherichia coli were isolated from the stools of 29 children with diarrhea not yielding salmonella and shigella. Classic serotypes of enteropathogenic Esch. coli (EPEC) were found in nine of 29 cases. Esch. coli enterotoxin was assayed in an infant rabbit model; strains causing fluid accumulation and distention of the small bowel were found in 24 of 29 cases. This reaction could be induced by sterile filtrates as well as viable cultures. Two or three enterotoxin-positive strains were often present in the same stool specimen. Simple serotyping for EPEC identified pathogens in 31 per cent of cases of diarrhea whereas the animal model incriminated pathogenic strains in 83 per cent of cases.
P4-09-18: Australian Decision Impact Study: The Impact of Oncotype DX Recurrence Score (RS) on Adjuvant Treatment Decisions in Hormone Receptor Positive (HR+), Node Negative (N0) and Node Positive (N+) Early Stage Breast Cancer (ESBC) in the Multidisciplinary Clinic (MDC).
Authors: Boer RH de, C Baker, D Speakman, B Mann
Journal: Cancer Research (2011)

Abstract Introduction: There has been increasing interest in more accurately defining the need for chemotherapy in patients with HR+ ESBC. Oncotype DX® has been shown to provide prognostic and predictive information beyond traditional histopathological factors. Prior clinical impact studies have focused on decisions made by individual practitioners. In Australia, the MDC has become the standard forum for determining treatment decisions. In this study, we have assessed how the RS influences adjuvant systemic treatment decisions in the MDC at 4 separate hospitals. Methods: Patients with unifocal HR+, HER2−ve ESBC, N0 and N+ (1-3 positive nodes, including micrometastases and isolated tumour cells) and no contraindication to adjuvant chemotherapy (CTx) or endocrine therapy (H) were eligible. A total of 150 patients will be entered. Systemic adjuvant treatment recommendations were made and recorded in the MDC, both before and after testing with Oncotype DX. The primary endpoint was the overall change in the treatment recommendation. Other endpoints included confidence in recommendations, assessment of impact of the RS, and treatment the patient actually received. Results: Currently, RS results on 84 patients are available. Patient age range is 33–82 years. There are 56 (67%) N0 pts and 28 (33%) N+. Overall, 37 (44%) women had low, 36 (43%) intermediate and 11 (13%) high RS. The RS changed the initial treatment recommendations in 20 (24%) patients. Of the 34 patients initially recommended CTx+H, there was a shift to H alone for 12 (35%), whilst of the 50 patients initially recommended H alone, 8 (16%) shifted to CTx+H. A shift in treatment recommendations was reported for 8/37 (22%) pts with low, 8/36 (22%) with intermediate and 4/11 (36%) with high RS. 13/56 (23%) of N0 pts had a change in recommendation, whilst 7/28 (25%) N+ pts changed (table 1). 5 patients have decided against the final MDC recommendations: 3 chose CTx+H after recommendation of H (RS of 13,19 and 21 respectively), and 2 declined a CTx+H recommendation (RS of 19 and 25). Conclusion: Early results of our Australian study suggest an impact of Oncotype DX RS on adjuvant treatment decision making in the MDC setting. Updated results on the full 150 patients will be presented at the meeting. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-18.