tbuckley/cabot-search huggingface dataset:
Notching up on the cellular origins of intrahepatic cholangiocarcinoma
Authors: Alphonse E. Sirica, Roberto J. Groszmann, Yasuko Iwakiri, Tamar H. Taddei
Journal: Hepatology (2013)

Abstract 1 Intrahepatic cholangiocarcinomas (ICCs) are primary liver tumors with a poor prognosis. The development of effective therapies has been hampered by a limited understanding of the biology of ICCs. Although ICCs exhibit heterogeneity in location, histology, and marker expression, they are currently thought to derive invariably from the cells lining the bile ducts, biliary epithelial cells (BECs), or liver progenitor cells (LPCs). Despite lack of experimental evidence establishing BECs or LPCs as the origin of ICCs, other liver cell types have not been considered. Here we show that ICCs can originate from fully differentiated hepatocytes. Using a mouse model of hepatocyte fate tracing, we found that activated NOTCH and AKT signaling cooperate to convert normal hepatocytes into biliary cells that act as precursors of rapidly progressing, lethal ICCs. Our findings suggest a previously overlooked mechanism of human ICC formation that may be targetable for anti-ICC therapy. Abstract 2 Intrahepatic cholangiocarcinoma (ICC) is the second most common primary malignancy in the liver. ICC has been classified as a malignant tumor arising from cholangiocytes; however, the co-occurrence of ICC and viral hepatitis suggests that ICC originates in hepatocytes. In order to determine the cellular origin of ICC, we used a mouse model of ICC in which hepatocytes and cholangiocytes were labeled with heritable, cell type–specific reporters. Our studies reveal that ICC is generated by biliary lineage cells derived from hepatocytes, rather than cholangiocytes. Additionally, we found that Notch activation is critical for hepatocyte conversion into biliary lineage cells during the onset of ICC and its subsequent malignancy and progression. These findings will help to elucidate the pathogenic mechanism of ICC and to develop therapeutic strategies for this refractory disease.
Community Case Management of Fever Due to Malaria and Pneumonia in Children Under Five in Zambia: A Cluster Randomized Controlled Trial
Authors: Kojo Yeboah-Antwi, Portipher Pilingana, William B. Macleod, Katherine Semrau, Kazungu Siazeele, Penelope Kalesha, Busiku Hamainza, Phil Seidenberg, Arthur Mazimba, Lora Sabin, Karen Kamholz, Donald M. Thea, Davidson H. Hamer
Journal: PLoS Medicine (2010)

In a cluster randomized trial, Kojo Yeboah-Antwi and colleagues find that integrated management of malaria and pneumonia in children under five by community health workers is both feasible and effective.
Management of refractive errors
Authors: G. M. Cochrane, R. du Toit, R. T. Le Mesurier
Journal: BMJ (2010)

Uncorrected refractive error accounts for half of the global burden of avoidable vision impairment and nearly a third of the global burden of avoidable blindness.1 2 Globally, 153 million people have visual impairment or are blind due to uncorrected refractive error and the majority live in low income countries.1 Additionally, 410 million people have difficulty with near tasks because they lack reading glasses.2 Interventions to treat refractive error, such as spectacles, are cost-effective and in high income settings are readily accessible, but refractive errors are often not diagnosed or referred and barriers to the use of services exist.1 Under-corrected refractive error can account for as much as 75% of all impairment of vision in high income countries 1 3 4 5 and it may markedly affect quality of life.5 Minor reduction in vision (<6/12 or just below the driving standard) has been associated with an increased risk of death and physical, social, and psychological problems in people older than 50 years (box 1).6 w1-7 The global economic impact of uncorrected refractive error is an estimated 268.8 billion international dollars, based on population and economic data combined with a meta-analysis of prevalence studies.7 We provide an overview of the public health significance of refractive error, its management, and referral strategies for primary care practitioners.

#### Box 1 Consequences of minor vision impairment (<6/12) in people older than 50 years

##### Increased social isolation

##### Increased morbidity

##### Increased mortality

#### Sources and selection criteria

In October 2008 and May 2009 we searched the Cochrane Collaboration database for reviews and clinicaltrials.gov for current trials, returning 420 studies. We also searched Medline and PubMed for articles published between 1 January 2000 and 1 May 2009, using MESH terms and combinations including …
EXTRACELLULAR MATRIX EXPANSION IN NON-INFARCTED MYOCARDIUM IS ASSOCIATED WITH SUBSEQUENT DEATH, HOSPITALIZATION FOR HEART FAILURE, OR BOTH ACROSS THE EJECTION FRACTION SPECTRUM
Authors: Erik B. Schelbert, Timothy Wong, Kayla Piehler, Karolina Zareba, James Moon, Martin Ugander, Daniel R. Messroghli, Uma Valeti, Chung-Chou H. Chang, Sanjeev Shroff, Chris Miller, Matthias Schmitt, Peter Kellman, Javed Butler, Mihai Gheorghiade
Journal: Journal of the American College of Cardiology (2014)
Management of Progressive Muscular Dystrophy of Childhood
Authors: Paul J. Vignos
Journal: JAMA (1963)

In a study of 27 patients with progressive muscular dystrophy of childhood, it was found that duration of ambulation from onset of symptoms could be increased from an average of 4.4 yr to 8.7 yr by a comprehensive rehabilitation program. The program included early diagnosis, close supervision of patients, a physical therapy program with emphasis on passive stretching of flexion contractures about joints, and bracing for ambulation when independent walking was no longer possible. The total increase in ambulation will be greater, since eight patients are still walking independently in braces. This positive program is directed toward assisting the patient to lead as normal a life as possible, both physically and emotionally. The better preservation of the child's physical status should increase the chance for benefit from any future specific pharmacologic therapy.
Blockade of CD47-mediated cathepsin S/protease-activated receptor 2 signaling provides a therapeutic target for hepatocellular carcinoma
Authors: Terence Kin-Wah Lee, Vincent Chi-Ho Cheung, Ping Lu, Eunice Yuen Ting Lau, Stephanie Ma, Kwan Ho Tang, Man Tong, Jessica Lo, Irene Oi Lin Ng
Journal: Hepatology (2014)

Identification of therapeutic targets against tumor-initiating cells (TICs) is a priority in the development of new therapeutic paradigms against cancer. We enriched a TIC population capable of tumor initiation and self-renewal by serial passages of hepatospheres with chemotherapeutic agents. In chemoresistant hepatospheres, CD47 was found to be up-regulated, when compared with differentiated progenies. CD47 is preferentially expressed in liver TICs, which contributed to tumor initiation, self-renewal, and metastasis and significantly affected patients' clinical outcome. Knockdown of CD47 suppressed stem/progenitor cell characteristics. CD47+ hepatocellular carcinoma (HCC) cells preferentially secreted cathepsin S (CTSS), which regulates liver TICs through the CTSS/protease-activated receptor 2 (PAR2) loop. Suppression of CD47 by morpholino approach suppressed growth of HCC in vivo and exerted a chemosensitization effect through blockade of CTSS/PAR2 signaling. Conclusion: These data suggest that CD47 may be an attractive therapeutic target for HCC therapy. (Hepatology 2014;60:179–191)
Probiotics in Crohn's disease
Authors: M Guslandi
Journal: Gut (2001)

Editor,—In their "therapy updates", Professor Shanahan ((2001) Gut 48:609–609; [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]) and Professor Colombel et al ((2001) Gut 48:647–647; [OpenUrl][5][CrossRef][6][PubMed][7][Web of Science][8]), respectively, addressed the issues of "probiotics in IBD" and of "antibiotics in Crohn's disease". I would like, shuffling the titles of their articles, to add a few comments on "probiotics in Crohn's disease". Colombel et al pointed out the importance of intestinal flora in the pathogenesis of Crohn's disease and the therapeutic role that antibiotics can play in this disorder. An alternative approach to … [1]: {openurl}?query=rft.jtitle%253DDigestive%2Bdiseases%2Band%2Bsciences%26rft.stitle%253DDig%2BDis%2BSci%26rft.aulast%253DGuslandi%26rft.auinit1%253DM.%26rft.volume%253D45%26rft.issue%253D7%26rft.spage%253D1462%26rft.epage%253D1464%26rft.atitle%253DSaccharomyces%2Bboulardii%2Bin%2Bmaintenance%2Btreatment%2Bof%2BCrohn%2527s%2Bdisease.%26rft_id%253Dinfo%253Adoi%252F10.1023%252FA%253A1005588911207%26rft_id%253Dinfo%253Apmid%252F10961730%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1023/A:1005588911207&link_type=DOI [3]: /lookup/external-ref?access_num=10961730&link_type=MED&atom=%2Fgutjnl%2F49%2F6%2F873.3.atom [4]: /lookup/external-ref?access_num=000088852500031&link_type=ISI [5]: {openurl}?query=rft.jtitle%253DInflammatory%2Bbowel%2Bdiseases%26rft.stitle%253DInflamm%2BBowel%2BDis%26rft.aulast%253DGasche%26rft.auinit1%253DC.%26rft.volume%253D6%26rft.issue%253D1%26rft.spage%253D8%26rft.epage%253D15%26rft.atitle%253DA%2Bsimple%2Bclassification%2Bof%2BCrohn%2527s%2Bdisease%253A%2Breport%2Bof%2Bthe%2BWorking%2BParty%2Bfor%2Bthe%2BWorld%2BCongresses%2Bof%2BGastroenterology%252C%2BVienna%2B1998.%26rft_id%253Dinfo%253Adoi%252F10.1097%252F00054725-200002000-00002%26rft_id%253Dinfo%253Apmid%252F10701144%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [6]: /lookup/external-ref?access_num=10.1097/00054725-200002000-00002&link_type=DOI [7]: /lookup/external-ref?access_num=10701144&link_type=MED&atom=%2Fgutjnl%2F49%2F6%2F873.3.atom [8]: /lookup/external-ref?access_num=000085301200002&link_type=ISI
Specific nasal provocation test with powder allergen
Authors: F. A. Salzano
Journal: Allergy (1997)

Reported here are the results of a large‐scale trial conducted under the guidance of Prof Giovanni Motta, which I coordinated. A total of 656 patients with nasal hyperreactivity were recruited in 51 Italian centres (18 in the north of Italy, 20 in central Italy and 13 in the south). The trial's results were as follows. 1) A clear clinical prevalence of sensitization to different allergens in the different areas of Italy, which could be roughly classified thus: a) in Northern Italy birch and grasses were the main species; b) in Central Italy mites prevailed but oleaceae were also sigmficant; c) in Southern Italy panetaria and oleaceae were the prevailing species. 2) Most cases were sensitive to several allergens, although a considerable proportion (22%) actually presented reactions only to one, the main allergen. 3) Taking account of the patients sensitive to only one allergen and those responding to a main allergen, the proportion of patients reacting clinically to only one allergen rises to 64%. 4) The specific nasal provocation test (sNFT) offers specificity comparable. to in vivo diagnostic methods such as the prick test, and in vitro methods such as RAST, but is much more sensitive. 5) The sNPT can be done in any season. 6) The sNPT is highly specific below a threshold value of nasal reactivity, which can be identified for each allergen studied and expressed in Allergenic Units. 7) In patients in whom the prick test shows multiple sensitivity, the specific NPT identifies the allergen presumably responsible for the nasal reactions (main allergen). In the light of these findings double‐blind specific immunotherapy was started, to last 1 year, in 107 patients (49 given placebo and 58 active treatment), with nasal allergy to grasses, parietaria and mites. The results of this treatment were as follows: 74.1% of patients presented a reduction in nasal resistance, measured by dynamic anterior rhinomanometry, indicating relief of nasal obstruction; mucociliary transport time became normal in 81% of patients, meaning that rhinorrhoea had become less marked; there was a significant rise in the nasal reactivity threshold in 74.1% of patients, illustrating the degree of desensitization achieved; nasal IgA increased in 62.5% of patients and IgG in 55.2% indicating improvement in the local immunological picture. No such improvements were detectable in the patients given placebo. In conclusion, therefore, the findings of this trial in allergic rhinitis underline that the specific NPT proved more sensitive than other in vivo and in vitro diagnostic methods and is unquestionably a fundamental investigational approach for assessing nasal allergies, identlfying the allergens causing the symptoms and setting up rational local immunotherapy. The sNPT also showed the efficacy of specific intranasal immunotherapy.
Identification of a calcium dependent atrial secretory binding protein as calmodulin
Authors: A. F Doubell, C. Lazure, J. Tremblay, G. Thibault
Journal: Cardiovascular Research (1994)

Objective: The role of calcium in the regulation of atrial natriuretic factor (ANF) secretion has focused attention on calcium binding proteins as regulatory components of the secretory machinery for ANF. Two members of the annexin family of calcium binding proteins have emerged as candidates for this role. The aim of this paper is to report the isolation, purification, and identification of another calcium dependent atrial secretory granule binding protein. Methods: A 20 kDa calcium binding protein was isolated from rat cardiac tissue by affinity chromatography and purified by ion exchange high pressure liquid chromatography followed by reverse phase high pressure liquid chromatography. Identification of the protein was based on its electrophoretic mobility, chromatographic properties, amino acid composition, and ability to stimulate the activity of calmodulin dependent phosphodiesterase. Results: Analysis of this protein and its interaction with atrial secretory granules revealed that it was identical to calmodulin and that the calcium dependent interaction with atrial secretory granules takes place at physiological calcium concentrations. Conclusions: The study identifies calmodulin as a calcium dependent atrial secretory binding protein. The interaction of calmodulin with atrial secretory granules at physiological calcium concentrations suggest a possible role for calmodulin in the regulation of ANF release from the secretory granules. Cardiovascular Research 1994;28:705-709
Induction of neointimal formation by local gene transfer of the antisense senescent cell-derived inhibitor 1 (SDI) delivered with the needle injection catheter
Authors: Sigrid Nikol, Tanya Y. Huehns, Serap Esin, Stefan Mrochen, Markus G. Engelmann, Matthias Schmidt, Berthold Höfling, Walter H. Günzburg
Journal: Journal of the American College of Cardiology (1996)
What makes perceptual symbols perceptual?
Authors: Murat Aydede
Journal: Behavioral and Brain Sciences (1999)

Three major attempts by Barsalou to specify what makes a perceptual symbol perceptual fail. One way to give such an account is to use symbols' causal/nomic relation to what they represent, roughly the way contemporary informational psychosemanticists develop their theories, but this fails to draw the distinction Barsalou seems to have in mind.
Emergency Department Utilization in an Urban Community
Authors: Arthur R. Jacobs
Journal: JAMA (1971)

Utilization of emergency departments in Rochester, NY, has increased dramatically in recent years. A sample of the community's emergency department cases were classified as to whether care could have been given in an emergency department, physician's office, or could have been delayed. Only 35% of the cases were classified as needing care in an emergency department. The rate of emergency department utilization for low socioeconomic areas was six times that of high socioeconomic areas. Analysis of a community's emergency department utilization provides data for planning ambulatory services. The emergency department is only one element in the community ambulatory health system. Part of the emergency department demand may be more appropriately met in another type of ambulatory care facility.
Histone Deacetylases Augment Cytokine Induction of the iNOS Gene
Authors: Zhiyuan Yu, Wenzheng Zhang, Bruce C. Kone
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. The inducible nitric oxide synthase (iNOS) gene plays an important role in renal diseases. Transcription is the principal mode of regulation. This study explores the role of acetylation in cytokine-mediated iNOS induction in cultured murine mesangial cells and RAW 264.7 cells. Nitric oxide production was measured by the Griess reaction. The activity of the iNOS promoter and a nuclear factor–κB (NF-κB) element promoter were assessed in transient transfection assays. Gel shift and supershift assays were used to identify NF-κB in nuclear extracts. Protein-protein interactions were assayed by co-immunoprecipitation and GST pull-down assays. Treatment with the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) and overexpression of HDAC isoforms were used to assess the impact of acetylation status on iNOS and NF-κB element promoter activity. TSA inhibited induction of endogenous NO production and iNOS as well as NF-κB element promoter activity in response to interleukin–1β (IL-1β) or lipopolysaccharide (LPS) + interferon-γ (IFN-γ) in both cell types without altering NF-κB DNA binding activity. Overexpression of specific HDAC isoforms enhanced cytokine induction of both the iNOS and the NF-κB element promoter. HDAC2 and NF-κB p65 co-immunoprecipitated from mesangial cell nuclear extracts, and in vitro translated HDAC2 specifically interacted with an NF-κB p65 GST fusion protein. Hyperacetylation diminishes cytokine induction of iNOS transcription activity, at least partially, by limiting the functional efficacy of NF-κB. The specific recruitment of HDAC2 to NF-κB at target promoters and the consequent effects on acetylation status may play an important role in regulating iNOS as well as other NF-κB–dependent genes involved in inflammation.
Screening for diabetes in general practice: cross sectional population study
Authors: J. M Lawrence, P. Bennett, A. Young, A. M Robinson
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To assess the policy proposed by the American Diabetes Association of universal screening in general practice of all patients aged over 45 years for diabetes. <b>Design:</b> Cross sectional population study. <b>Setting:</b> Local general practice in the United Kingdom. <b>Participants:</b> All patients aged over 45 not known to have diabetes. <b>Main outcome measures:</b> Prevalence of diabetes in the screened population, cardiovascular risk profile of patients diagnosed as having diabetes after screening. <b>Results:</b> Of 2481 patients aged over 45 and not known to have diabetes, 876 attended for screening. There were no significant demographic differences between the screened and unscreened patients. Prevalence of diabetes in patients with age as a sole risk factor was 0.2% (95% confidence interval 0% to 1.4%). Prevalence of diabetes in patients with age and one or more other risk factors (hypertension, obesity, or a family history of diabetes) was 2.8% (1.6% to 4.7%). Four hours a week for a year would be needed to screen all people over 45 in the practice9s population; about half this time would be needed to screen patients with risk factors other than age. More than 80% of patients newly diagnosed as having diabetes had a 10 year risk of coronary heart disease &gt;15%, 73% (45% to 92%) were hypertensive, and 73% (45% to 92%) had a cholesterol concentration &gt;5 mmol/l. <b>Conclusions:</b> Screening for diabetes in general practice by measuring fasting blood glucose is feasible but has a very low yield in patients whose sole risk factor for diabetes is age over 45. Screening in a low risk population would best be targeted at patients with multiple risk factors. <h3>What is already known on this topic</h3> Between a third and a half of cases of diabetes are undiagnosed at any one time New cases can be identified by screening groups of patients at risk The American Diabetes Association has proposed the screening of all patients aged over 45 every three years <h3>What this study adds</h3> Screening for diabetes in general practice by measuring fasting blood glucose is feasible but requires much staff time Screening solely on the basis of age has a very low yield and screening would best be targeted at patients with multiple risk factors for diabetes
Hyperoxia causes angiopoietin 2–mediated acute lung injury and necrotic cell death
Authors: Vineet Bhandari, Rayman Choo-Wing, Chun G Lee, Zhou Zhu, Jonathan H Nedrelow, Geoffrey L Chupp, Xucher Zhang, Michael A Matthay, Lorraine B Ware, Robert J Homer, Patty J Lee, Anke Geick, Antonin R de Fougerolles, Jack A Elias
Journal: Nature Medicine (2006)
Molecular phylogenetic analysis among bryophytes and tracheophytes based on combined data of plastid coded genes and the 18S rRNA gene
Authors: T. Nishiyama, M. Kato
Journal: Molecular Biology and Evolution (1999)

The basal relationship of bryophytes and tracheophytes is problematic in land plant phylogeny. In addition to cladistic analyses of morphological data, molecular phylogenetic analyses of the nuclear small-subunit ribosomal RNA gene and the plastic gene rbcL have been performed, but no confident conclusions have been reached. Using the maximum-likelihood (ML) method, we analyzed 4,563 bp of aligned sequences from plastid protein-coding genes and 1,680 bp from the nuclear 18S rRNA gene. In the ML tree of deduced amino acid sequences of the plastid genes, hornworts were basal among the land plants, while mosses and liverworts each formed a clade and were sister to each other. Total-evidence evaluation of rRNA data and plastid protein-coding genes by TOTALML had an almost identical result.
Remarks on whale cultures from a complex systems perspective
Authors: Gottfried Mayer-Kress, Mason A. Porter
Journal: Behavioral and Brain Sciences (2001)

The target article provides stimulating evidence for culture in cetaceans but does not provide a coherent theoretical framework. We argue that a complex, adaptive systems approach not only can provide such a framework but also can contribute advanced data analysis and simulation methods. For humpback whale songs, we suggest the framework of “small-world networks” to model the observed spatio-temporal dynamics.