tbuckley/cabot-search huggingface dataset:
Evolution of the Telomere-Associated Protein POT1a in Arabidopsis thaliana Is Characterized by Positive Selection to Reinforce Protein–Protein Interaction
Authors: Mark A. Beilstein, Kyle B. Renfrew, Xiangyu Song, Eugene V. Shakirov, Michael J. Zanis, Dorothy E. Shippen
Journal: Molecular Biology and Evolution (2015)

Gene duplication is a major driving force in genome evolution. Here, we explore the nature and origin of the POT1 gene duplication in Arabidopsis thaliana. Protection of Telomeres (POT1) is a conserved multifunctional protein that modulates telomerase activity and its engagement with telomeres. Arabidopsis thaliana encodes two divergent POT1 paralogs termed AtPOT1a and AtPOT1b. AtPOT1a positively regulates telomerase activity, whereas AtPOT1b is proposed to negatively regulate telomerase and promote chromosome end protection. Phylogenetic analysis uncovered two independent POT1 duplication events in the plant kingdom, including one at the base of Brassicaceae. Tests for positive selection implemented in PAML revealed that the Brassicaceae POT1a lineage experienced positive selection postduplication and identified three amino acid residues with signatures of positive selection. A sensitive and quantitative genetic complementation assay was developed to assess POT1a function in A. thaliana. The assay showed that AtPOT1a is functionally distinct from single-copy POT1 genes in other plants. Moreover, for two of the sites with a strong signature of positive selection, substitutions that swap the amino acids in AtPOT1a for residues found in AtPOT1b dramatically compromised AtPOT1a function in vivo. In vitro-binding studies demonstrated that all three sites under positive selection specifically enhance the AtPOT1a interaction with CTC1, a core component of the highly conserved CST (CTC1/STN1/TEN1) telomere protein complex. Our results reveal a molecular mechanism for the role of these positively selected sites in AtPOT1a. The data also provide an important empirical example to refine theories of duplicate gene retention, as the outcome of positive selection here appears to be reinforcement of an ancestral function, rather than neofunctionalization. We propose that this outcome may not be unusual when the duplicated protein is a component of a multisubunit complex whose function is in part specified by other members.
Abstract 1100: Macrophage infiltration is associated with release from dormancy in a novel model of dormant prostate cancer
Authors: Thomas Long, Cynthia C. Sprenger, Ilsa Coleman, Peter Nelson, Buddy Ratner, Stephen Plymate
Journal: Cancer Research (2014)

Abstract Background: Circulating tumor cells are found in approximately 70% of men with prostate cancer at the time of primary treatment. Less than a third of these men will develop recurrent cancer within 20 years of primary treatment, suggesting that only a subset of dormant tumor cells are able to escape dormancy and develop into clinical metastases. Escape from dormancy, though, is clinically significant since these men are at greatest risk of dying from prostate cancer. Mechanisms by which cancer cells escape dormancy are poorly understood and very few models exist to study dormancy, especially in prostate cancer. We previously found that when a dormant prostate cancer cell line was seeded into a bioscaffold and placed in vivo, tumor formation was detected after 6-8 weeks, whereas no growth was seen up to six months after the dormant cells were injected s.c. with Matrigel. Analysis of the tumors revealed significantly greater macrophage infiltration into the scaffold tumors. Gene expression and cytokine antibody arrays demonstrated increased expression of macrophage associated cytokines in scaffold tumors. While macrophages have been implicated in metastatic spread of various cancers, their role in escape from dormancy has not been elucidated. Objective: To determine if macrophages play a role in escape from tumor dormancy in prostate cancer. Methods: In vitro we cultured a dormant prostate cancer cell line, M12mac25, with macrophage conditioned media and then examined proliferation and gene expression. In vivo, mice were implanted with sphere-templated polyHEMA bioscaffolds pre-seeded with M12mac25 cells. To inhibit macrophage activity, mice received s.c. injections of clondronate liposomes or PBS liposomes as a control for 6 weeks. Results: In vitro culture of M12mac25 cells with macrophage-derived conditioned medium led to increased proliferation of the M12mac25 cells and similarly upregulated genes as those seen the in vivo bioscaffold-derived tumors. In vitro treatment of primary bone-marrow derived macrophages with clondronate liposomes resulted in apoptosis while exposure to PBS liposomes did not affect the macrophages. In contrast, M12mac25 cells were not affected by either PBS or clondronate liposomes. In vivo, clondronate liposomes effectively eliminated macrophages from the M12mac25 seeded scaffolds and prevented tumor growth in these scaffolds. Interpretation: Macrophages contribute to M12mac25 escape from dormancy. Citation Format: Thomas Long, Cynthia C. Sprenger, Ilsa Coleman, Peter Nelson, Buddy Ratner, Stephen Plymate. Macrophage infiltration is associated with release from dormancy in a novel model of dormant prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1100. doi:10.1158/1538-7445.AM2014-1100
Relation of anthropometric and dynamometric variables to serious postoperative complications.
Authors: A M Klidjian, K J Foster, R M Kammerling, A Cooper, S J Karran
Journal: BMJ (1980)

Prediction of serious postoperative complications by using standard anthropometric and biochemical nutritional variables was attempted in 225 patients admitted for major abdominal surgery. In 102 of the patients hand-grip dynamometry was also measured, and this proved the most sensitive test, predicting complications in 48 of the 55 patients (87%) who developed them (p < 0.001). Arm muscle circumference and forearm muscle circumference below 85% of the standard value were also of predictive value (p < 0.02 and p < 0.01 respectively); weight for height and serum albumin concentrations were less satisfactory, while weight loss of more than 10% was not significantly related to complications. Dynamometry is a useful, rapid, and inexpensive screening test for detecting malnutrition that is likely to predispose to serious postoperative morbidity.
Incidence of weapon injuries not related to interfactional combat in Afghanistan in 1996: prospective cohort study
Authors: M. Michael, D. R Meddings, S. Ramez, J. L. Gutierrez-Fisac
Journal: BMJ (1999)

To examine the descriptive epidemiology of weapon injuries not directly attributable to combat during armed conflict.Prospective cohort study.Nangarhar region of Afghanistan, which experienced effective peace, intense fighting, and then peace over six months in 1996.608 people admitted to Jalalabad hospital because of weapon injuries.Estimated incidence of injuries from combat or otherwise (non-combat injury) before, during, and after the fall of Kabul.Incidence of non-combat injury was initially 65 per 100 000. During the intense military campaign for Kabul the incidence declined dramatically, and then differentially increased dependent on injury subcategory-that is, whether injuries were accidental or intentional and whether they were inflicted by firearms or fragmenting munitions. Non-combat injuries accounted for 51% of weapon injuries observed over the study period. Civilians were more likely to have non-combat injuries than combat injuries.Weapon injuries that are not attributable to combat are common. Social changes accompanying conflict and widespread availability of weapons may be predictive of use of weapons that persists independently of conflict.
Radiographic Appearance of Mammary-Duct Ectasia with Calcification
Authors: Thane Asch, Charles Frey
Journal: New England Journal of Medicine (1962)

IN 1906 Bloodgood1 recognized as a separate entity the disease of the breast that was subsequently termed mammary-duct ectasia, secretory disease, plasma-cell mastitis and so forth. The disease, although benign, has a remarkable proclivity for clinically mimicking mammary carcinoma. This report is presented after our experience with a patient who was considered, on clinical grounds, to have an unequivocal carcinoma of the breast and in whom preoperative mammography established the true nature of the disease.Case ReportA 67-year-old woman (N.Y.H. 633910), para 1, gravida 1, was admitted to the hospital. One week before entry a discrete mass had been . . .
Public involvement in health care
Authors: D. Florin
Journal: BMJ (2004)

The NHS needs to be clear about the aims and how to achieve them 

The government is promoting public involvement in health care as part of new NHS policy.1 2 Proposals include allowing the public to elect members of the governing boards of foundation trusts3 and primary care trusts' obligations to engage with the public.4 However, clarity and consensus are lacking about what public involvement means in health care, why it is desirable, and whether current policies will meet the desired objectives. We examine the latest polices and their potential effects.

Public involvement and other allied terms are used to mean a variety of activities or objectives. In this article we use public involvement to refer to the involvement of members of the public in strategic decisions about health services and policy at local or national level—for instance, about the configuration of services or setting priorities. Public involvement is different from patient involvement, which refers to the involvement of individual patients, together with health professionals, in making decisions about their own health care. Clearly, a spectrum of possible involvement of patients and the public exists between these two extremes. For example, user involvement may refer to a group of patients helping to shape a particular service. Arnstein defined another spectrum of public involvement, ranging from professionals giving information to the public to a genuine hand over of power and decision making to the public.5

Advocates of increased public involvement argue that public services are paid for by the people and therefore should be shaped more extensively by them, preferably by a fully representative sample.6 One assumption made is that greater public involvement will lead to more democratic decision making and, in turn, better accountability, but, as we discuss below, neither is necessarily the case. A …
Cardiac Tamponade and Death in a Patient Receiving Total Parenteral Nutrition
Authors: Donald H. Kuiper
Journal: JAMA (1974)

ADMINISTRATION of hypertonic solutions for parenteral nutrition necessitates the use of a central venous catheter, a procedure fraught with complications.<sup>1</sup>We are reporting a case of cardiac perforation, tamponade, and death resulting from this procedure. <h3>Report of a Case</h3> A 63-year-old woman underwent partial gastrectomy and excision of the distal section of the esophagus in December 1970 for an adenocarcinoma of the gastroesophageal junction. Her immediate postoperative course was uneventful. Preoperatively, her weight was 45 kg (99 lb). Her late postoperative course was complicated by severe dumping symptoms, early satiety, and weight loss. During the subsequent 17 months, in spite of numerous attempts to increase the patient's caloric intake with various oral food supplements, her weight declined to 30 kg (66 lb). Repeated esophagoscopy, biopsy, cytologic studies, and barium contrast examinations of the upper gastrointestinal tract failed to disclose any evidence of recurrent neoplasm. We decided to begin total
Abstract LB-340: High pain prevalence is reported by patients with head and neck cancer: systematic review
Authors: Tatiana V. Macfarlane, Tanja Wirth, Sriyani Ranasinghe
Journal: Cancer Research (2012)

Abstract Background: Pain is a major symptom in patients with cancer; however information on head and neck cancer (HNC) related pain is limited. Aim: To investigate the prevalence of pain and associated factors among patients with HNC. Materials and Methods: The systematic review used a wide searching strategy to December 2011. Cancers of the oral mucosa, oropharynx, hypopharynx and larynx were included in this review with pain as main outcome. The review was restricted to full research reports of observational studies published in English. A checklist was used to assess the quality of selected studies. Results: There were 82 studies included in the review and most of them (84%) were conducted in the past ten years. Studies were relatively small, with a median of 80 patients (IQR 44, 154). The quality of reporting was variable, for example only 67% of the articles stated the study design and none of the papers justified sample size. The majority of the papers (84%) did not report efforts that were taken to address potential sources of bias and 35% did not specify the participation rate. Most studies (77%) used self-administered quality of life questionnaires, where pain was a component of the overall scale. Only 32 studies reported pain prevalence in HNC patients (combined estimate from meta-analysis 49%, 95% CI 41% - 57%), in contrast to levels of pain (scale 0-100: mean 55, 95% CI 51 - 59 based on 12 studies). Only 55 studies (67%) considered associated factors, mostly tumour- or treatment-related. Three out of ten studies reported higher levels of pain at older ages and three out of twelve found higher levels in women. There was no consistent evidence of an association with smoking and alcohol. Conclusion: The study has shown high levels of pain prevalence and some factors associated with higher levels of pain. There is a need for higher quality studies in a priority area for the care of patients with HNC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-340. doi:1538-7445.AM2012-LB-340
Prodromal myeloproliferative neoplasms: The 2008 WHO classification
Authors: Hans Michael Kvasnicka, Juergen Thiele
Journal: American Journal of Hematology (2009)

The concept of prodromal chronic myeloproliferative neoplasms has been endorsed by the WHO classification implicating a stepwise evolution of disease. Histology of the bone marrow (BM) and borderline to mildly expressed clinical features play a pivotal role for diagnosing prefibrotic-early primary myelofibrosis. By lowering the platelet count for essential thrombocythemia and regarding BM morphology, early manifestations are tackled. Pre-polycythemic stages of polycythemia vera with a low hemoglobin level at onset are diagnosed by positive JAK2V617F mutation status, a low erythropoietin value, and characteristic BM features. The revised WHO classification incorporates hematological, morphological, and molecular-genetic parameters to generate a consensus-based working diagnosis.
Twenty-year (1975–1995) community-wide trends in the incidence and in-hospital case-fatality rates (CFR's) associated with congestive heart failure (CHF) complicating acute myocardial infarction (AMI): the Worcester heart attack study
Authors: M. Hatton, J. Yarzebski, R. Goldberg, T. Meyer, J. Gore
Journal: Journal of the American College of Cardiology (1998)
Fears over radiotherapy fractionation regimens in breast cancer
Authors: A. Rodger
Journal: BMJ (1998)

In the early 1920s Regaud discovered the benefits of radiation treatment fractionation—that is, splitting the dose into several treatments over several days—when he was trying to sterilise the testes of rams with radiation without necrosing the scrotal skin.1 During the 1930s radiotherapy changed from a dangerous mystery that put patients and staff at risk2 to a therapeutic modality with a scientific basis. This was an era when radiotherapy fractionation and treatment guidelines were empirically developed from clinical observation tempered by pragmatic issues such as machine availability. Since then the science of radiotherapy has advanced considerably, but suspicions that pragmatic considerations still weigh too heavily are surrounding a proposed British trial of radiotherapy fractionation in breast cancer.

Early randomised clinical trials in cancer—and, therefore, in radiotherapy—reflected the management arguments of the time and addressed questions about what patients to treat with which modality. Trials of radiotherapy process—techniques, fractionation, overall treatment time—had to wait until the 1970s, when radiobiology was suggesting that these factors were crucial. In 1978 Withers showed for pig skin that acute radiotherapy reactions were worse after large numbers of small dose fractions than after a few high dose fractions, while the late reactions were worse after the latter.3 Therefore, side effects depended on total dose and fraction size. Other evidence suggested that tumour cells could repopulate a tumour rapidly during radiotherapy. Hence, prolonging treatment could be …
Nonhomologous End Joining Is Essential for Cellular Resistance to the Novel Antitumor Agent, β-Lapachone
Authors: Melissa S. Bentle, Kathryn E. Reinicke, Ying Dong, Erik A. Bey, David A. Boothman
Journal: Cancer Research (2007)

Abstract Commonly used antitumor agents, such as DNA topoisomerase I/II poisons, kill cancer cells by creating nonrepairable DNA double-strand breaks (DSBs). To repair DSBs, error-free homologous recombination (HR), and/or error-prone nonhomologous end joining (NHEJ) are activated. These processes involve the phosphatidylinositol 3′-kinase–related kinase family of serine/threonine enzymes: ataxia telangiectasia mutated (ATM), ATM- and Rad3-related for HR, and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) for NHEJ. Alterations in these repair processes can cause drug/radiation resistance and increased genomic instability. β-Lapachone (β-lap; also known as ARQ 501), currently in phase II clinical trials for the treatment of pancreatic cancer, causes a novel caspase- and p53-independent cell death in cancer cells overexpressing NAD(P)H:quinone oxidoreductase-1 (NQO1). NQO1 catalyzes a futile oxidoreduction of β-lap leading to reactive oxygen species generation, DNA breaks, γ-H2AX foci formation, and hyperactivation of poly(ADP-ribose) polymerase-1, which is required for cell death. Here, we report that β-lap exposure results in NQO1-dependent activation of the MRE11-Rad50-Nbs-1 complex. In addition, ATM serine 1981, DNA-PKcs threonine 2609, and Chk1 serine 345 phosphorylation were noted; indicative of simultaneous HR and NHEJ activation. However, inhibition of NHEJ, but not HR, by genetic or chemical means potentiated β-lap lethality. These studies give insight into the mechanism by which β-lap radiosensitizes cancer cells and suggest that NHEJ is a potent target for enhancing the therapeutic efficacy of β-lap alone or in combination with other agents in cancer cells that express elevated NQO1 levels. [Cancer Res 2007;67(14):6936–45]
Cuffed Tracheotomy Tube to Prevent Aspiration
Authors: James S. Benedict
Journal: JAMA (1965)

To the Editor:—  In response to the excellent letter by Stanley Stellar, MD, in the Feb 22, 1965, issue ofThe Journal( 191 :680), I would like to comment on the use of cuffed tracheotomy tubes. We have used these for the past three years with excellent results. The metal ones are preferred, as the nurses can easily clean the inner cannula, positive pressure can be given, and other advantages accrue, as pointed out by the letter writer. However, there are several points of caution which we have learned by bitter experience. First, the rubber cuff must be attached to the metal with a nonslip adhesive (Eastman 910) so that the cuff will not slip over the end of the tracheotomy tube and obstruct the airway, as occurred in one of our patients. Second, the use of acetylcystein (Mucomyst) helps break up tenacious sputum, but also damages the cuffs, so
Passive cigarette smoke, coal heating, and respiratory symptoms of nonsmoking women in China.
Authors: C A Pope, X Xu
Journal: Environmental Health Perspectives (1993)

In this study we evaluated data from a sample of 973 never-smoking women, ages 20-40, who worked in three similar textile mills in Anhui Province, China. We compared prevalence rates of respiratory symptoms across homes with and without coal heating and homes with different numbers of smokers. Multiple logistic regression models that controlled for age, job title, and mill of employment were also estimated. Respiratory symptoms were associated with combined exposure to passive cigarette smoke and coal heating. Effects of passive cigarette smoke and coal heating on respiratory symptoms appeared to be nearly additive, suggesting a dose-response relationship between respiratory symptoms and home indoor air pollution from these two sources. The prevalence of chest illness, cough, phlegm, and shortness of breath (but not wheeze) was significantly elevated for women living in homes with both smokers and coal heating.
Rhumatisme chronique. Methodes therapeutiques
Authors: D. Preiskel
Journal: Annals of the Rheumatic Diseases (1956)

In this monograph the author presents his investigations and theories into the aetiology, pathogenesis, and inter-relationship of rheumatoid arthritis and a group of erythemato-squamous dermatoses, including psoriasis vulgaris.He maintains that, by his special "cantharides blister" bacteriological technique, he can demonstrate a state of endoparasitism with the B. endoparasiticus (Benedek, 1927) in 90 per cent. of normal healthy individuals, and that this state is perpetuated by transmission from the maternal to the foetal circulation.The central pathogenetic principle of his theory is a bacterial-allergic inflammatory process occurring in connective tissue, the causative agent being the B. endo- parasiticus.He states that the intensity of the bacteraemia with this organism in psoriasis is only equalled or surpassed by that found in individuals with rheumatoid arthritis.During this phase of intense bacteraemia the organism escapes from the blood stream into the connective tissue and there provokes an immunobiological reaction.When the cutaneous con- nective tissue is the main target psoriasis may result, and when the articular tissue is primarily affected rheumatoid arthritis develops.He thus maintains that these cutaneous and articular manifestations are merely different aspects of the same process.
Allergic symptoms after pandemic influenza vaccination rarely mediated by vaccine-specific IgE
Authors: Isabelle Rouleau, Gaston De Serres, Jean Philippe Drolet, Devi Banerjee, Chantal Lemire, Andrew Moore, Louis Paradis, Reza Alizadhefar, Anne Des Roches, Edmond S. Chan, Donald Stark, Mélanie Benoit, Danuta M. Skowronski
Journal: Journal of Allergy and Clinical Immunology (2012)
SOME PRACTICAL EXPERIENCES WITH MUSCULAR ANOMALIES.Read in the Section on Ophthalmology at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: T. E. MURRELL
Journal: JAMA (1893)

I consider the Maddox rod the most valuable and reliable test for heterophoria that we possess. Until I became acquainted with it I often had much trouble in arriving at any satisfactory conclusion as to the muscular tendencies. Since its introduction diagnosis is in most instances made easy.  The Graefe test is perplexing and unreliable in determining small errors in the lateral, and espe cially, in the vertical plane, the latter being extremely important even to so small an amount as half of a degree, which amount, and even less, the rod test will quickly recognize. The phorometer of Prince is a most convenient and ready application of the rod test, and is extremely satisfactory in detecting any error less than four degrees. While far more accurate than any methods heretofore possessed for measuring the muscular balance, the rod test is not absolutely reliable owing to certain physiological laws resident