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Haug, James D. "Watson-Boone, Rebecca. Constancy and Change in the Worklife of Research University Librarians. Chicago: ALA (ACRL Publications in Librarianship, no. 51), 1998. 172p. $30, alk. paper (ISBN 0‐8389-7984-X). LC 98-26935." College & Research Libraries 60, no. 5 (September 1, 1999): 503–4. http://dx.doi.org/10.5860/crl.60.5.503.
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KITLV, Redactie. "Book Reviews." Bijdragen tot de taal-, land- en volkenkunde / Journal of the Humanities and Social Sciences of Southeast Asia 158, no. 1 (2002): 95–144. http://dx.doi.org/10.1163/22134379-90003788.
Повний текст джерелаАнотація:
-Stephen J. Appold, Heidi Dahles ,Tourism and small entrepreneurs; Development, national policy, and entrepreneurial culture: Indonesian cases. Elmsford, New York: Cognizant Communication Corporation, 1999, vi + 165 pp., Karin Bras (eds) -Jean-Pascal Bassino, Peter Boothroyd ,Socioeconomic renovation in Vietnam; The origin, evolution and impact of Doi Moi. Singapore: Institute of Southeast Asian Studies, 2001, xv + 175 pp., Pham Xuan Nam (eds) -Peter Boomgaard, Patrick Vinton Kirch, The wet and the dry; Irrigation and agricultural intensification in Polynesia. Chicago: The University of Chicago Press, 1994, xxii + 385 pp. -A.Th. Boone, Chr.G.F. de Jong, De Gereformeerde Zending in Midden-Java 1931-1975; Een bronnenpublicatie. Zoetermeer: Boekencentrum, 1997, xxiv + 890 pp. [Uitgaven van de Werkgroep voor de Geschiedenis van de Nederlandse Zending en Overzeese Kerken, Grote Reeks 6.] -Okke Braadbaart, Colin Barlow, Institutions and economic change in Southeast Asia; The context of development from the 1960s to the 1990s. Cheltenham: Edward Elgar, xi + 204 pp. -Freek Colombijn, Abidin Kusno, Behind the postcolonial; Architecture, urban space, and political cultures in Indonesia. London: Routledge, 2000, xiv + 250 pp. -Raymond Corbey, Michael O'Hanlon ,Hunting the gatherers; Ethnographic collectors, agents and agency in Melanesia, 1870s -1930s. Oxford: Bergahn Books, 2000, xviii + 286 pp. [Methodology and History in Anthropology 6.], Robert L. Welsch (eds) -Olga Deshpande, Hans Penth, A brief histroy of Lan Na; Civilizations of North Thailand. Chiang Mai: Silkworm Books, 2000, v + 74 pp. -Aone van Engelenhoven, I Ketut Artawa, Ergativity and Balinese syntax. Jakarta: Badan Penyelenggaran Seri NUSA, Universitas Katolik Indonesia Atma Jaya, 1998, v + 169 pp (in 3 volumes). [NUSA Linguistic Studies of Indonesian and Other Languages in Indonesia 42, 43, 44.] -Rens Heringa, Jill Forshee, Between the folds; Stories of cloth, lives, and travels from Sumba. Honolulu: University of Hawai'i Press, 2001, xiv + 266 pp. -Roy E. Jordaan, Marijke J. Klokke ,Fruits of inspiration; Studies in honour of Prof. J.G. de Casparis, retired Professor of the Early History and Archeology of South and Southeast Asia at the University of Leiden, the Netherlands on the occasion of his 85th birthday. Groningen: Egbert Forsten, 2001, xxiii + 566 pp. [Gonda Indological Studies 11.], Karel R. van Kooij (eds) -Gerrit Knaap, Germen Boelens ,Natuur en samenleving van de Molukken, (met medewerking van Nanneke Wigard). Utrecht: Landelijk Steunpunt Educatie Molukkers, 2001, 375 pp., Chris van Fraassen, Hans Straver (eds) -Henk Maier, Virginia Matheson Hooker, Writing a new society; Social change through the novel in Malay. Leiden: KITLV Press (in association with the Asian Studies Association of Australia), 2000, xix + 492 pp. -Niels Mulder, Penny van Esterik, Materializing Thailand. Oxford: Berg, 2000, xi + 274 pp. -Jean Robert Opgenort, Ger P. Reesink, Studies in Irian Languages; Part II. Jakarta: Badan Penyelenggara Seri NUSA, Universitas Katolik Indonesia Atma Jaya. [NUSA Linguistic Studies of Indonesian and Other Languages in Indonesia 47.] 2000, iv + 151 pp. -Gerard Termorshuizen, Kester Freriks, Geheim Indië; Het leven van Maria Dermoût, 1888-1962. Amsterdam: Querido, 2000 (herdurk 2001), 357 pp. -Donald Tuzin, Eric Kline Silverman, Masculinity, motherhood, and mockery; Psychoanalyzing culture and the naven rite in New Guinea. Ann Arbor: University of Michigan Press, 2001, vi + 243 pp. -Alexander Verpoorte, Jet Bakels, Het verbond met de tijger; Visies op mensenetende dieren in Kerinci, Sumatra. Leiden: Research School of Asian, African, and Amerindian Studies (CNWS), 2000, XV + 378 pp. [CNWS Publications 93.] -Sikko Visscher, Twang Peck Yang, The Chinese business elite in Indonesia and the transition to independence, 1940-1950. Kuala Lumpur: Oxford University Press, 1998, xix + 372 pp. -René Vos, Gerard Termorshuizen, Journalisten en heethoofden; Een geschiedenis van de Indisch-Nederlandse dagbladpers, 1744-1905. Amsterdam: Nijgh en Van Ditmar, Leiden: KITLV Uitgeverij, 2001, 862 pp. -Edwin Wieringa, Marijke J. Klokke, Narrative sculpture and literary traditions in South and Southeast Asia. Leiden: Brill, 2000, xiv + 127 pp. [Studies in Asian Art and Archaeology (continuation of: Studies in South Asian Culture) 23.] -Catharina Williams-van Klinken, Mark Donohue, A grammar of Tukang Besi. Berlin: Mouton de Gruyter, 1999, xxvi + 576 pp. [Mouton Grammar Library 20.] -Kees Zandvliet, Thomas Suárez, Early mapping of Southeast Asia. Singapore: Periplus Editions, 1999, 280 pp. -Claudia Zingerli, Bernhard Dahm ,Vietnamese villages in transition; Background and consequences of reform policies in rural Vietnam. Passau: Department of Southeast Asian Studies, University of Passau, 1999, xiv + 224 pp. [Passau Contributions to Southeast Asian Studies 7.], Vincent J.H. Houben (eds)
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McMahon, Seamus. "Refurbishing, Extending, Recreating, and Renewing the Boole Library at University College Cork, Ireland." LIBER Quarterly 18, no. 2 (September 1, 2008): 150. http://dx.doi.org/10.18352/lq.7918.
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Živković, Vesna. "Uništenje Univerzitetske biblioteke u Luvenu u Prvom svetskom ratu i njena obnova u posleratnom period = Destructon of the University of Leuven Library in First World War and its Renovation in the Post-War Period." Bosniaca 26, no. 26 (December 2021): 112–22. http://dx.doi.org/10.37083/bosn.2021.26.112.
Повний текст джерелаАнотація:
Uništavanje biblioteka i njenih kolekcija od davnina su sastavni deo ratova i osvajačkih pohoda: od uništenja Aleksandrijske biblioteke u starom veku, jezuitskih biblioteka u Kini tokom 17. i 18. veka, Narodne biblioteke u Beogradu u Drugom svetskom ratu, Nacionalne i univerzitetske biblioteke Bosne i Hercegovine u Sarajevu 1992. godine, pa sve do spaljivanja rukopisa u biblioteci u Timbuktuu 2013. godine. U fokusu ovog rada je uništenje Univerzitetske biblioteke u Luvenu, od strane nemačke okupacione vojske u Prvom svetskom ratu, kao i njena obnova u posleratnom periodu. = The destruction of libraries and its collections has long been an integral part of wars and conquests: from the destruction of the Library of Alexandria in the old century, Jesuit libraries in China during the 17th and 18th centuries, the National Library in Belgrade in World War II, the National and University Library of Bosnia and Herzegovina in Sarajevo in 1992, until the manuscript was burned in the library in Timbuktu in 2013. The focus of this paper is the destruction of the University Library in Leuven by the German occupation army in First World War, as well as its restoration in the post-war period.
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Waidmann, Simone. "Bibliotheken in Irland 2013." Bibliotheksdienst 47, no. 11 (November 27, 2013): 862–72. http://dx.doi.org/10.1515/bd-2013-0098.
Повний текст джерелаАнотація:
Zusammenfassung: Dieser Bericht ist das Ergebnis eines Fachaufenthalts an der Dublin Central Public Library und an der Boole Bibliothek des University College Cork. Er beschreibt die dortigen Angebote und Arbeitsweisen mit einem Fokus auf Angeboten zum Selbststudium, insbesondere zum Fremdsprachenerwerb, und auf Fachreferatsarbeit in den Geisteswissenschaften und im Bereich historischer Bestände.
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Ovčina, Ismet, Azra Smajić Gačević, Muamera Smajić, Anja Mastilović, and Teufik Osmanović. "Objedinjavanje građe u fondovima Nacionalne i univerzitetske biblioteke BiH i Nacionalne biblioteke Austrije o kulturnohistorijskoj zaostavštini Mehmed-bega Kapetanovića Ljubušaka = The Consolidation of Materials in the Collections of the National and University Library of Bosnia and Herzegovina and the National Library of Austria on the Cultural and Historical Heritage of Mehmed-Bey Kapetanović Ljubušak." Bosniaca 22, no. 22 (December 2017): 63–76. http://dx.doi.org/10.37083/bosn.2017.22.63.
Повний текст джерелаАнотація:
Objedinjavanje građe u fondovima Nacionalne i univerzitetske biblioteke Bosne i Hercegovine i Naci-onalne biblioteke Austrije o kulturnohistorijskoj zaostavštini Mehmed-bega Kapetanovića Ljubušakarezultat je realizacije projekta Nacionalne i univerzitetske biblioteke Bosne i Hercegovine (NUBBiH), koji je finansiralo Federalno ministarstvo obrazovanja i nauke. Predmet istraživanja bila je građa Specijalnih zbirki i Stare periodike NUBBiH i fondova Nacionalne biblioteke Austrije u Beču.U fondovima NUBBiH čuva se građa Mehmed-bega Kapetanovića Ljubušaka pogodna za kulturo-loška, historijska, lingvistička, književna i politička istraživanja. Kapetanović je radio i djelovao u vrijeme austrougarske uprave u BiH te je, stoga, istraživanje provedeno i u Austriji, u Beču, i na taj način je objedinjena i popisana građa iz ove dvije institucije.Ovaj popis sadrži 157 jedinica. = The consolidation of materials in the collections of the National and University Library of Bosnia and Herzegovina and the National Library of Austria is the result of the realization of the project of the National and University Library of Bosnia and Herzegovina (NULB&H) on the cultural and historical heritage of Mehmed-bey Kapetanović Ljubušak, funded by the Federal Ministry of Education and Science. The topic of the research were documents of the Special Collections and Old Periodicals of NULB&H and the collections of the National Library of Austria in Vienna.The documents about Mehmed-bey Kapetanovic Ljubušak in collections of NULB&H, are convenient for cultural, historical, linguistic, literary and political research. Kapetanović worked in the time of the Austro-Hungarian administration in B&H. That is why the research was also carried out in Austria, Vienna, and at the end, the materials from these two institutions were consolidated in a list that contains 157 units.
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Ashton, Susanna. "On document supply in Ireland and the USA: experiences at the Boole Library, Cork University." Interlending & Document Supply 35, no. 4 (November 20, 2007): 226–27. http://dx.doi.org/10.1108/02641610710837545.
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Ovčina, Ismet, Muamera Smajić, and Alma Mešić. "Ostavština Hamdije Kapidžića u fondovima specijalnih zbirki Nacionalne i univerzitetske biblioteke Bosne i Hercegovine." BOSNIACA 25, no. 25 (December 14, 2020): 148. http://dx.doi.org/10.37083/bosn.2020.25.148.
Повний текст джерелаАнотація:
Korisnici Nacionalne i univerzitetske biblioteke Bosne i Hercegovine u svrhu različitih istraživanja često traže građu koja sadrži podatke o nacionalnoj i lokalnoj historiji; politici; kulturi. Nacionalna i univerzitetska biblioteka Bosne i Hercegovine svoje fondove; pored obaveznog primjerka; popunjava razmjenom i poklonima. Jedan takav poklon jeste i zaostavština historičara Hamdije Kapidžića. Biblioteka je ovaj poklon zaprimila 2008. godine. Dio poklona; koji čine nekoliko predmeta; korespondencija; pisma; razglednice; stare knjige; karte; nalazi se na Odjeljenju Specijalnih zbirki. Građa već duže vrijeme stoji neobrađena pa smo odlučili kroz ovaj kratki pregled i popis javnosti predočiti arhivu ovog znamenitog bosanskohercegovačkog kulturnog i naučnog radnika. Nadamo se da će ovaj kratak osvrt na zaostavštinu historičara Hamdije Kapidžića donijeti nove poglede na njegov život i znanstveni rad i poslužiti kao izvor za nova istraživanja.---------------------------------------------Heritage of Hamdija Kapidžić in the funds of National and University Library of Bosnia and Herzegovina special collectionsUsers of the National and University Library of Bosnia and Herzegovina; for the purpose of various researches; often look for material that contains national; local heritage; history; material about politics and culture. In addition to the obligatory copy; NUBBIH replenishes its funds with exchanges and gifts. One such gift is the legacy of historian Prof. Dr. Hamdija Kapidžić. The Library got this gift in 2008. Part of this gift – correspondence; letters; postcards; old books; maps; etc.; are located in the Department of Special Collections. The material has been undocumented for a long time and we decided to present to the public the archives of this famous Bosnian cultural and scientific worker through this brief overview and list. We hope that this brief review of the legacy of the historian Hamdija Kapidžić will bring new views on his life and scientific work and serve as a source for new research.
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Vasantha, B., and M. Dhanamjaya. "Usage of Mobile Phones for Library Services by Students of REVA University, Bangalore: A Study." Asian Journal of Information Science and Technology 8, no. 2 (August 5, 2018): 29–31. http://dx.doi.org/10.51983/ajist-2018.8.2.185.
Повний текст джерелаАнотація:
There are evidences of existence of libraries as treasure houses of knowledge in ancient history, earliest reference being “The Great Alexandrian Library”. A continuous transition in the libraries has happened in phased manner over the years to get into the present “Digital Era”. Containers of information have changed stage by stage from parchment to papyrus to paper to digital media. Information & Communication Technology has revolutionized all walks of human life starting from shopping, banking or booking a cinema ticket etc. Technology has become a vital part of common life in different forms. Mobile phones are considered as basic necessity in digital era for many of the chores. The academic world is also an area to take advantages of mobile technology in connecting its stakeholders. For librarians, mobile technology is a boon to extend services quickly to users and connecting them. Library services and sources can be made available on finger tips of users for 24/7 without any geographical jurisdiction. In this regards REVA University central library surveyed 200 students in order to find out the level of smart phones usage among them and what are their expectation.
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Martinčević-Huseinčehajić, Viktorija. "CIP program u Bosni i Hercegovini: iskustvo Nacionalne i univerzitetske biblioteke Bosne i Hercegovine." BOSNIACA 25, no. 25 (December 14, 2020): 9. http://dx.doi.org/10.37083/bosn.2020.25.9.
Повний текст джерелаАнотація:
U članku je predstavljena realizacija CIP programa u Bosni i Hercegovini i njegov značaj za izdavače i biblioteke. Istaknuto je koliko je bitna suradnja između izdavača i biblioteka. Dat je prikaz CIP programa u Bosni i Hercegovini, ali i naznačene smjernice za daljnji rad.-----------------------------------------CIP programme in Bosnia and Herzegovina: the experience of the National and University Library of Bosnia and HerzegovinaThe article presents the implementation of the CIP programme in Bosnia and Herzegovina and its significance for publishers and libraries. The importance of cooperation between publishers and libraries was emphasized. An overview of the CIP programme in Bosnia and Herzegovina is given, as well as guidelines for further work.
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Moody, Laura L. "The Global Music Archive at Vanderbilt University: An Interview with Holling Smith‐Borne." Music Reference Services Quarterly 11, no. 1 (August 2008): 77–86. http://dx.doi.org/10.1080/10588160802157306.
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Tuzlak, Dženana. "Sedamdeset godina Muzičke zbirke Nacionalne i univerzitetske biblioteke Bosne i Hercegovine / Seventy Years of the Music Collection of the National and University Library of Bosnia and Herzegovina." Pregled: časopis za društvena pitanja / Periodical for social issues 63, no. 1 (June 6, 2022): 101–15. http://dx.doi.org/10.48052/19865244.2021.1.101.
Повний текст джерелаАнотація:
This paper presents the Music Collection of the National and University Library of Bosnia and Herzegovina, founded in 1951 within the Department of Rare Books and Manuscripts. During 70 years, the Collection's stock building was systematically with a legal deposit from the all over Yugoslavia until 1992, through purchases, gift and exchange. In that way the Bosnian-Herzegovinian national collection was founded, which contributed to the preservation of national and cultural identity. In 1980, it owned 9.500 bibliographic units. Unfortunately, the Collection was destroyed on 25 August, 1992, in a shelling of the Vijećnica (City Hall), where was the National and University Library of Bosnia and Herzegovina. Its restoration is still being. Today, the funds of this Collection contain approximately 5.000 bibliographic units and is organized into three separate parts: the Musicological Book Collection, the Music Collection and the Sound Collection. For the most part of the materials – 3.304 bibliographic units, was processed within the COBISS.BH system (Co-operative Online Bibliographic System and Services), according to international bibliographic standards and the COMARC/B format (Cooperative Machine-Readable Cataloging). All bibliographic records can be searched in the electronic catalog of the Library by several parameters. The Collection has invaluable documentary value, especially for our Bosnian-Herzegovinian national music culture. In the following period, it is necessary to enrich the Collection with new contents and present it with quality on high level by bibliographic processing. The best protection of these collected sound records, in Music Collection, as part of the cultural heritage of Bosnia and Herzegovina, is its digitization at the national level in compliance with the legislation about copyright and related rights.
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Bailly, Rodolphe, Christelle Pons, Anne-Charlotte Haes, Lisa Nguyen, Matthias Thepaut, Laëtitia Houx, Mathieu Lempereur, and Sylvain Brochard. "Bone Deformities through the Prism of the International Classification of Functioning, Disability and Health in Ambulant Children with Cerebral Palsy: A Systematic Review." Children 11, no. 2 (February 16, 2024): 257. http://dx.doi.org/10.3390/children11020257.
Повний текст джерелаАнотація:
(1) Aim: The aim of this study was to determine the relationship between lower limb bone deformities and body functions, activity, and participation in ambulant children with CP and whether changing bone morphology affects outcomes in these domains. (2) Methods: A systematic literature search (PROSPERO CRD42020208416) of studies reporting correlations between measures of lower limb bone deformities and measures of body function, activity or participation, or post-surgical outcomes in these domains was conducted from 1990 to 2023 in Medline, Scopus, and Cochrane Library. We assessed study quality with the Checklist for Case Series (CCS) and a quality assessment developed by Quebec University Hospital. Meta-analysis was not possible; therefore, descriptive synthesis was performed. (3) Results: A total of 12 of 3373 screened articles were included. No studies evaluated the relationships between bone deformities and activity or participation, or the effect of isolated bone surgery on these domains. Correlations between bone deformities and body functions were poor-to-moderate. Internal hip rotation during gait improved after femoral derotation osteotomy. (4) Conclusions: A shift in paradigm is urgently required for the research and management of bone deformities in children with CP to include the activity and participation domains of the ICF, as well as consider more psychological aspects such as self-image.
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Pollé, Ad. "Stories from where it all began / The Europeana 1914-1918 roadshow at the National & University Library of B&H = Priče iz mjesta gdje je sve počelo." Bosniaca 21, no. 21 (December 2016): 47–49. http://dx.doi.org/10.37083/bosn.2016.21.47.
Повний текст джерелаАнотація:
Project Europeana 1914-1918 was created in an effort to gather in one place untold and unpublished stories of individuals and their families. Items that are citizens of Bosnia and Herzegovina brought to the show have been digitized and published together with stories (with the permission from the owner) in the pan-European digital library “Europeana 1914-1918“with the location http://www.europeana1914-1918.eu/bs.This paper deals with the Days of collecting memories in Sarajevo in the National and University Library of Bos-nia and Herzegovina, which was the co-organizer of this event. = Projekat Europeana 1914-1918 je nastao u želji da se neispričane i neobjavljene priče pojedinaca i njihovih po-rodica skupe na jednom mjestu. Predmeti koje su građani BiH donijeli da predstave su digitalizovani i objavljeni zajedno sa pričama, uz dozvolu vlasnika, u paneuropskoj digitalnoj biblioteci “Europeana 1914-1918” sa lokaci-jom http://www.europeana1914-1918.eu/bs.U ovom radu se govori o Danima prikupljanja uspomena u Sarajevu u Nacionalnoj i univerzitetskoj biblioteci Bosne i Hercegovine, koja je bila i suorganizator ovog događaja.
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Ovčina, Ismet, Mehmed Kardaš, and Muamera Smajić. "Poljičke isprave – čuvanje, zaštita i prezentacija dokumenata iz arhiva Poljičke republike pisanih bosančicom = Poljica Documents – Protection and Presentation of Documents from the Archive of the Poljica Republic Written in Bosančica." Bosniaca 26, no. 26 (December 2021): 72–80. http://dx.doi.org/10.37083/bosn.2021.26.72.
Повний текст джерелаАнотація:
Zbog svojih jedinstvenih i rijetkih kolekcija, Specijalne zbirke Nacionalne i univerzitetske biblioteke Bosne i Hercegovine (NUBBiH) su nezamjenjiv izvor za mnogostruke istraživačke projekte i naučne radove. Već dugi niz godina NUBBiH ulaže napor da putem svojih projekata naučnoj zajednici pobliže predstavi vrijedne kolekcije Specijalnih zbirki. Da bi se korisnicima osigurao brži i lakši pristup građi, a ujedno i zaštitili originalni dokumenti od njihovog daljeg propadanja, građa koja je obuhvaćena projektima digitalizira se i prezentira kroz Digitalne kolekcije NUBBiH. U ovom radu predstavit ćemo jedan takav projekt, a to je projekt zaštite i prezentacije Arhiva poljičkih isprava iz Zbirke Aleksandra Poljanića te ćemo prikazati dosadašnje rezultate, kao i krajnje ciljeve ovoga projekta. = The Special Collections of the National and University Library of Bosnia and Herzegovina (NULBIH) are an irreplaceable source for multiple research projects and scientific papers. For many years, NULBIH has been strengthening efforts to present values of Special Collections to the scientific community through its projects. To provide users with faster and easier access to the material, and at the same time to protect the original documents from their further deterioration, the materials covered by the projects are digitized and presented through the Digital Collections portal of the National and University Library of BIH. In this article, we will present the ongoing project “Protection and presentation of the Poljica Documents Archive from the Collection of Aleksandar Poljanić” and so far, the results and ultimate goals of this project.
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Needham, Gill. "A Web-based Tutorial May Produce the Same Cognitive Outcomes as Face to Face Instruction." Evidence Based Library and Information Practice 1, no. 2 (June 5, 2006): 30. http://dx.doi.org/10.18438/b8sg60.
Повний текст джерелаАнотація:
A review of:
Beile, Penny M. and David N. Boote. “Does the Medium Matter?: A Comparison of a Web-Based Tutorial with Face-to-Face Library Instruction on Education Students’ Self-Efficacy Levels and Learning Outcomes.” Research Strategies 20 (2004): 57-68.
Objective – To determine whether library skills self-efficacy levels and learning outcomes of postgraduate education students varied with different instructional delivery methods, specifically Web-based or face to face.
Design – Pre- and post-intervention survey comparing three groups receiving different types of instruction.
Setting – Department of Educational Studies at a large U.S. urban university.
Subjects – Forty-nine masters, doctoral, and certificate-seeking education students enrolled in one of three sections of a research methods course. There were 40 female and 9 male students.
Methods – Immediately before receiving library instruction, the three student groups were asked to complete a library skills self-efficacy questionnaire, comprising 30 items designed to measure students’ perceptions of their ability to successfully perform library research. They also completed a library skills test, consisting of 20 multiple choice questions, designed to assess conceptual knowledge, knowledge of database searching, and institution-specific knowledge. The intervention groups were:
Group 1 (Sixteen students) – an on-campus class that received a face to face instruction session comprised of a 70-minute demonstration of key library databases followed by an activity that allowed students to practice their skills.
Group 2 (Nineteen students) – an on-campus class that received a Web-based tutorial comprised of four interactive modules, requiring an average 80 minutes to complete.
Group 3 (Nineteen students) - a Web-based class that received the same Web-based tutorial as Group 2.
The survey and test were repeated six weeks after the instruction.
Main results – Both self-efficacy scores and library skills test scores increased for all three groups post-intervention. Average self-efficacy levels increased from a mean of 68.88 (SD=19.92) to a mean of 91.90 (SD=16.24); library skills scores increased from an average score of 58.78 (SD=13.80) to an average of 73.16 (SD=12.65). There was no statistically significant difference between the post- intervention scores of the three groups on the library skills test. However, the Web-based students in Group 3 showed a statistically significant greater increase in self-efficacy score (78.86 to 102.36) when compared with Group 2 participants (64.74 to 83.68).
Conclusion – The study provides evidence that library instruction is effective in increasing both skill levels and self-efficacy levels. It does not give a clear indication of the relative value of different modes of delivery, but it does support the contention that Web-based tutorials are at least as effective as face to face sessions.
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Koyejo, T., O. Olusunmade, and O. Olufemi. "Epidemiology of primary bone tumours in Nigeria: a systematic review." SA Orthopaedic Journal 61, no. 3 (2022): 167–71. http://dx.doi.org/10.17159/2309-8309/2022/v21n3a5.
Повний текст джерелаАнотація:
BACKGROUND: Primary bone tumours, although rare, are an important rising cause of morbidity and mortality in Africa. Late presentation, delayed diagnosis and failure to obtain consent for surgical procedures are important causes of loss of limb and life especially in the West African subregion. Existing data on primary bone tumours in Nigeria have been based on studies performed at various regional levels. The aim of this study is to determine the epidemiological pattern of primary bone tumours in Nigeria in general, including demographics, predominant tumour types and predominant skeletal location by reviewing existing data METHODS: A search of the following databases: University of Edinburgh Library, PubMed, CINAHL and SCOPUS from 2000 till January 2021 following PRISMA guidelines was conducted to identify studies conducted in Nigeria with relevant epidemiological data on primary bone tumours in Nigeria RESULTS: The search yielded a total of 952 hits from which seven hospital-based retrospective studies met the inclusion criteria for review. The estimated incidence rate of primary bone tumours ranged from 0.08 to 0.31 per 100 000 population. All studies showed a male preponderance. The peak age group of individuals presenting with both benign and malignant primary bone tumours was 11-20 years. Overall, benign tumours were more common. Osteochondromas were the most common benign tumours, while the commonest malignant tumours identified were osteosarcomas. The most common location for both benign and malignant tumours were the tibia and fibula CONCLUSION: Nigeria shares some similar epidemiological characteristics of primary bone tumour with other countries; however, some peculiar differences have been identified in this study. Population-based studies are required to obtain more accurate epidemiological data about this disease Level of evidence: Level 2
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Alotaibi, Faiz, and Frances Johnson. "Why we like Google Scholar: postgraduate students' perceptions of factors influencing their intention to use." Aslib Journal of Information Management 72, no. 4 (July 3, 2020): 587–603. http://dx.doi.org/10.1108/ajim-10-2019-0304.
Повний текст джерелаАнотація:
PurposeThis study examines the use of the search engine, Google Scholar, from the perspective of a specific study group, that of international postgraduate students. Based on the theory of task perceived performance and effort expectancy influencing intention to use, further factors of system, individual, social and organisational, in the postgraduate student context are explored.Design/methodology/approachThe questionnaire for the measurement of 11 factors was developed from related studies of e-library use, and data were collected from 200 international postgraduate students studying in the UK. Analysis using confirmatory factor analysis established the contextual influencing factors, and structural equation modeling examined the predicted model.FindingsThe findings confirmed the influence of the task-based factors of performance and expectancy and revealed that these were based on the perception of the visibility, accessibility and relevance of the system, and on perceived self-efficacy. The perception postgraduates held of themselves as competent users of Google Scholar was further borne out in the participants' own words when asked for the reason for their preference.Originality/valueThe approach taken enables research into use of search tools to go beyond ease of use as a main driver and to explore the relationship held among the internal and external influences of use. Recommendations for further user research are suggested as well as possible impact on the university library provision and support of services for students.
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Khandoker, A., MA Islam, MM Rahman, AA Husna, S. Das, and MM Khatun. "Bacterial contamination of street-vended spicy puffed-rice sold at Bangladesh Agricultural University campus." Bangladesh Veterinarian 31, no. 1 (March 31, 2015): 20–26. http://dx.doi.org/10.3329/bvet.v31i1.22839.
Повний текст джерелаАнотація:
This study was undertaken to investigate the bacterial contamination of spicy puffed rice (Jhalmuri) sold by the street vendors at Bangladesh Agricultural University (BAU) campus. Fifteen spicy puffed rice samples were collected from street vendors at the Botanical Garden, Library premises, Riverside, Krishi Bishhobiddaloy (KB) High School and Veterinary Teaching Hospital compound at BAU campus. Microbial quality was assessed by total viable count (TVC), total coliform count (TCC) and total staphylococcal count (TSC). Samples were inoculated into selective media Eosin Methylene Blue (EMB) agar, Salmonella Shigella (SS) agar, Thiosulphate Citrate Bile Salts Sucrose (TCBS) agar and Mannitol Salt (MS) agar. E. coli and Staphylococcus spp. were identified from the samples. The TVC in spicy puffed rice sample ranged from log 4.5 cfu/g to log 5.4 cfu/g, TSC ranged from log 4.4 cfu/g to log 5.2 cfu/g and TCC ranged from log 1.4 cfu/g to log 4.3 cfu/g. Antibiotic sensitivity test showed that the isolates were sensitive to ciprofloxacin and gentamicin. E. coli were resistant to ampicillin, chloramphenicol and cephalexin and Staphylococcus spp. were resistant to ampicillin, cephalexin and vancomycin. Spicy puffed rice sold by the street vendors at BAU campus harboured multidrug resistant food borne bacteria which may cause public health hazard. DOI: http://dx.doi.org/10.3329/bvet.v31i1.22839 Bangl. vet. 2014. Vol. 31, No. 1, 20-26
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De Lange, Nicholas. "Byzantium in the Cairo Genizah." Byzantine and Modern Greek Studies 16 (1992): 34–47. http://dx.doi.org/10.1017/s0307013100007539.
Повний текст джерелаАнотація:
On the occasion of the Byzantine Symposium at Cambridge in March 1990, an exhibition of manuscripts of Byzantine interest recovered from the Cairo Genizah was mounted in the University Library. Although these manuscripts have been in Cambridge for nearly a century, they are still not as well known as they deserve to be, and the exhibition provoked a good deal of interest among participants. It therefore seemed useful to provide this more permanent record. I have taken the opportunity to add one or two items which, for various reasons, could not be exhibited. I have also introduced references to publications in English or other western languages; it should be remembered, however, that there is a growing quantity of Genizah publication now in Hebrew. It should also be borne in mind that, although most of the Genizah manuscripts are in Cambridge, other smaller collections are to be found in many other libraries, notably (so far as Byzantine material is concerned) in St Petersburg, New York and Oxford.
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Richards, Daniel. "Graves, R. & Hyland, T. (Eds.). (2017). Writing assignments across university disciplines. Bloomington, IN: Trafford." Canadian Journal for Studies in Discourse and Writing/Rédactologie 28 (December 4, 2018): 270–80. http://dx.doi.org/10.31468/cjsdwr.741.
Повний текст джерелаАнотація:
For the last three years, I have been part of a team of multi-disciplinary faculty that holds a weeklong workshop each semester for approximately twenty teachers. These teachers, migrating to our cozy space in the library from all corners of campus, have applied—they get paid a modest sum, which is not nothing—to attend our workshop in the hopes of improving their ability to integrate writing assignments into their courses. The workshops are part of a larger initiative, Improving Disciplinary Writing, which was borne out of a needs assessment from our regional assessment body. It is designed to bring together faculty, through workshops and grants, to think collectively about how writing gets taught and ought to be taught differently across and within disciplines. And what we see time and time again is that although each group of twenty teachers is new each semester, and although the ranks consistently vary from adjunct (sessional) to full professor, and although some work in musty chemistry buildings and some in obscure art buildings and some in sleek see-through engineering buildings, the disembodied echoes of frustrations and complaints and discovery and hope and solace from groups past get re-vocalized by groups present. As facilitators, we are not flustered by this fact; rather, we find our own solace in the connection and camaraderie through shared experience happening across disciplines and spaces on campus.
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Hakami, Zaki. "Is Orthodontic Treatment an Etiologic Factor for Altered Passive Eruption? A Clinical Study and Systematic Review." Applied Sciences 13, no. 14 (July 18, 2023): 8291. http://dx.doi.org/10.3390/app13148291.
Повний текст джерелаАнотація:
This research aims to investigate the relationship between orthodontic treatment (OT) and altered passive eruption (APE). Materials and Methods: A case–control study was carried out among the dentistry students at Jazan University. A total of 21 students were recruited for the case group and 20 others for the control group. Variables were measured on the maxillary incisor teeth. They included an image analysis of the teeth width-to-height (W/H) ratio, a cone beam computed tomography (CBCT) analysis of buccal bone thickness (BCT), and the distance from the cementoenamel junction (CEJ) to the bone crest (BC) (CEJ–BC). In addition, a systematic review was performed following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Prominent literature databases, including Medline/PubMed, the Cochrane Library, Embase, Scopus, Saudi Digital Library, and Google Scholar, were searched for articles published before November 2022 on two main concepts (APE and orthodontics). Quality of evidence was assessed using the Newcastle–Ottawa scale (NOS), and the certainty of evidence was assessed using the grading of recommendations assessment development and evaluation (GRADE) approach. Results: A total of 164 teeth were evaluated. No statistical differences were observed in the W/H ratio and BCT between the two groups. A significant increase in the CEJ–BC distance in the right and left maxillary lateral incisors was observed for people who had undergone OT (p ≤ 0.002 and 0.001, respectively). In the systematic review, two articles were included for qualitative synthesis. One of the included studies showed an increase in the post-orthodontics clinical crown length of the maxillary anterior teeth. Another study reported no difference in the prevalence of APE between orthodontically treated and untreated people. Conclusion: This research concludes that OT might not be an etiological factor for APE. However, more clinical and radiological studies must be conducted to arrive at decisive conclusions.
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Skrzypczak, Wojciech, Łukasz Słowik, Maciej Okła, Zuzanna Ślebioda, and Krzysztof Osmola. "Comparison of the effects of orbital decompression in Graves' ophthalmopathy." Postępy Higieny i Medycyny Doświadczalnej 77, no. 1 (January 1, 2023): 154–62. http://dx.doi.org/10.2478/ahem-2023-0021.
Повний текст джерелаАнотація:
Abstract Introduction Graves' disease is an autoimmune disorder. One of the symptoms is an overgrowth of the soft tissues of the orbit. Orbital involvement can cause exophthalmos, diplopia, or vision loss. Treatment strategies include a surgical approach that limits the ailments mentioned above. Decompression can be achieved by reducing the amount of enlarged tissues (fat removal) or increasing the space for enlarged tissues (bone removal). Numerous authors discuss the advantages and disadvantages of various techniques in terms of reducing the exophthalmos, the number and persistence of complications, and the long-term prognosis. Materials and Methods A literature search of PubMed and the Poznan University of Medical Sciences Main Medical Library resources from 1993–2022 was performed. Thirty articles were reviewed with attention to the surgical treatment of Graves' ophthalmopathy. Results The main surgical techniques include fat decompression and bone wall decompression. The results of exophthalmos fat removal are characterized by a significant decrease in proptosis (5.45mm) with a small percentage of newly formed diplopia (9%). Bone reduction in the lateral wall of the orbit shows similar effects: reducing exophthalmos (4.33mm) and the newly formed diplopia, as with fat removal (3.7%). Bone reduction in the medial- lateral wall, medial- inferior- lateral wall, and medial–inferior wall shows a decrease in proptosis ( 4.9 mm, 4.6 mm, 3.77 mm) and a higher percentage of new-onset diplopia (18%, 15%, 28%). Conclusion The smallest amount of newly formed diplopia at the highest proptosis reduction occurs with the self-removal of fat or resection of the lateral orbital wall.
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Tuzlak, Dženana. "Osvrt na historijski razvoj tekuće nacionalne bibliografije Bosne i Hercegovine = Review on the Historical Development of Current National Bibliography of Bosnia and Herzegovina." Bosniaca 22, no. 22 (December 2017): 29–33. http://dx.doi.org/10.37083/bosn.2017.22.29.
Повний текст джерелаАнотація:
Nacionalna i univerzitetska biblioteka Bosne i Hercegovine je centralna, državna biblioteka koja izrađuje i izdaje tekuću nacionalnu bibliografiju knjiga, periodičnih publikacija i priloga u periodičnim publikacijama, na osnovu obaveznog primjerka. Cilj ovoga rada jeste kraći historijski osvrt na izradu bh. tekuće nacionalne bi-bliografije, od prve “Bosanskohercegovačke bibliografije knjiga i brošura 1945–1951” autora Đorđa Pejano-vića iz 1953. pa sve do 2017. godine, kada su štampane “Bosanskohercegovačka bibliografija monografskih publikacija. NIZ A za 2013. godinu” i “Bosanskohercegovačka bibliografija priloga u serijskim publikacijama. NIZ C, God. 14, sv. 14”. Ujedno je i podsjećanje na bibliotekare i bibliografe koji su stvarali te bibliografije i ostavili ih nama u naslijeđe. Nacionalna bibliografija ima informativni, edukativni, naučni i kulturni značaj. = The National and University Library of Bosnia and Herzegovina is a central, state library that creates and publishes the current national bibliography of books, serial publications and supplements in serial publications, based on a legal deposit. The aim of this paper is a shorter historical review of the current national bibliography production in Bosnia and Herzegovina, from the first “Bosanskohercegovačka bibliografija knjiga i brošura 1945–1951” (Bosnian-Herzego-vinian bibliography of books and brochures 1945–1951), by Đorđe Pejanović in 1953, until the year 2017, when Bosanskohercegovačka bibliografija monografskih publikacija. NIZ A za 2013. godinu (Bosnian-Herzegovinian bibliog-raphy of monographic publications. Series A for 2013) and Bosanskohercegovačka bibliografija priloga u serijskim pub-likacijama. NIZ C, God. 14, sv. 14 (Bosnian-Herzegovinian bibliography of supplements in serial publications. Series C, year 14, vol. 14) were published.It is also a reminder of the librarians and bibliographers who created these bibliographies and left them to us in legacy. National bibliography has informative, educational, scientific and cultural significance.
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Ali Arslan, Syed Muhammad Yousaf Farooq, Syeda Khadija Tul Sugrah, Syed Amir Gilani, Amjad Iqbal, Hafiz Syed Arslan Gilani, Shumaila Sarwar, and Maleeha Manzoor. "Ultrasonographic assessment of rheumatoid arthritis: A systematic review." Professional Medical Journal 29, no. 08 (July 31, 2022): 1181–90. http://dx.doi.org/10.29309/tpmj/2022.29.08.6983.
Повний текст джерелаАнотація:
Objective: To evaluate the reliability of ultrasound for the detection of rheumatoid arthritis (RA). Study Design: Systematic Review. Setting: The University of Lahore. Period: 2001 to 2021. Material & Methods: A systematic exploration of the literature was achieved by collecting articles related to our topic. Articles reporting the reliability result for the assessment of rheumatoid arthritis by ultrasonography were included in this study. Exclusion criteria were articles reporting large joints including shoulder and knees as well as that articles which were not reporting sufficient information of sensitivity and specificity of US regarding RA. These articles were provided by an online source of PubMed, google scholar, research gate, Embase, Wiley online library, BMJ Journal, AJR, Springer, and Elesvier link. Results: Results shows that the specificity and sensitivity of gray-scale US for synovitis assessment ranged from 50% to 90.9% and 47.4% to 100% respectively, specificity and sensitivity of Power Doppler ultrasonography for the evaluation of synovitis hypervascularity ranged from 60% to 98% and 21% to 92% respectively, and specificity and sensitivity of ultrasonography to assess the bone erosion in rheumatoid arthritis patients ranged from 69% to 98.7% and 35.9% to 83% respectively. Conclusion: This systematic review concluded that ultrasound is a vital diagnostic tool as compared to X-ray, CT, MRI, clinical and laboratory examination for the evaluation of bone erosion, synovitis, and synovial hypervascularity.
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Szymczak-Pajor, Izabela, Józef Drzewoski, and Agnieszka Śliwińska. "The Molecular Mechanisms by Which Vitamin D Prevents Insulin Resistance and Associated Disorders." International Journal of Molecular Sciences 21, no. 18 (September 11, 2020): 6644. http://dx.doi.org/10.3390/ijms21186644.
Повний текст джерелаАнотація:
Numerous studies have shown that vitamin D deficiency is very common in modern societies and is perceived as an important risk factor in the development of insulin resistance and related diseases such as obesity and type 2 diabetes (T2DM). While it is generally accepted that vitamin D is a regulator of bone homeostasis, its ability to counteract insulin resistance is subject to debate. The goal of this communication is to review the molecular mechanism by which vitamin D reduces insulin resistance and related complications. The university library, PUBMED, and Google Scholar were searched to find relevant studies to be summarized in this review article. Insulin resistance is accompanied by chronic hyperglycaemia and inflammation. Recent studies have shown that vitamin D exhibits indirect antioxidative properties and participates in the maintenance of normal resting ROS level. Appealingly, vitamin D reduces inflammation and regulates Ca2+ level in many cell types. Therefore, the beneficial actions of vitamin D include diminished insulin resistance which is observed as an improvement of glucose and lipid metabolism in insulin-sensitive tissues.
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Hajdarpašić, Lejla, Senada Dizdar, and Džejla Khattab. "Informacijske usluge visokoškolskih biblioteka u Federaciji Bosne i Hercegovine za vrijeme pandemije covid-19 = Information Services of Academic Libraries in Federation of Bosnia and Herzegovina during The Covid-19 Pandemic." Bosniaca 26, no. 26 (December 2021): 123–36. http://dx.doi.org/10.37083/bosn.2021.26.123.
Повний текст джерелаАнотація:
Globalna pandemija prouzrokovana virusom COVID-19 bitno je utjecala na poslovanje u visokoškolskim bibliotekama u cijelom svijetu, a cilj ovoga istraživanja je utvrditi kako su javne visokoškolske biblioteke u Federaciji Bosne i Hercegovine prilagodile i/ili redefinirale svoje bibliotečko-informacijske usluge pandemijskim okolnostima rada. Za potrebe prikupljanja takvih podataka, anketirani su samo bibliotekari/ke onih javnih visokoškolskih biblioteka koje imaju kontakt (e-mail) na web stranici fakulteta / akademije / univerziteta, a samo istraživanje, koje je kvantitativne prirode, realizirano je korištenjem posebno kreiranog anketnog upitnika, upotrebom Google Forms, u junu 2021. godine. Od ukupno 47 mapiranih biblioteka, 26 biblioteka je sudjelovalo u ispunjavanju ankete (ukupno 55,3%). U ovom istraživačkom radu, koji je prvi ove vrste u Federaciji Bosne i Hercegovine, donose se pristupi visokoškolskih biblioteka koje, za razliku od visokoškolskih biblioteka iz razvijenih evropskih zemalja, djeluju u vrlo specifičnim uslovima koje, prije svega, karakteriziraju ograničeni i nedovoljni budžeti za nabavku građe, ali i nedostatak osnovne IT opreme. Rezultati pokazuju da su uprkos zatečenim, često neodgovarajućim elementarnim uslovima rada, visokoškolski bibliotekari ulagali izvjesne napore orijentirane ka zadovoljenju informacijskih potreba korisnika tokom svjetske zdravstvene krize, ali i da je pandemija naglasila hitnu potrebu digitalne transformacije istraživanjem obuhvaćenih visokoškolskih biblioteka. = The global pandemic caused by the COVID-19 virus has significantly affected library processes and procedures in academic libraries worldwide, and the aim of this study is to determine how public academic libraries in the Federation of Bosnia and Herzegovina (FB&H) have adapted and/or redefined their library and information services to pandemic circumstances. For the purposes of collecting such data, only librarians of those public academic libraries who have contact information (e-mail) displayed on the faculty / academy / university website were surveyed. The research itself, which is of a quantitative nature, was realized by using a survey questionnaire, which was created on Google Forms, in June 2021. Out of a total of 47 mapped libraries, 26 academic libraries participated in the survey (response rate of 55.3%). This research paper, which is first of its kind in Federation of Bosnia and Herzegovina, brings approaches of academic libraries which, unlike academic libraries from developed European countries, operate in very specific circumstances which are primarily characterized by limited and insufficient budgets for procurement of collections but also basic IT equipment. Results showed that despite the found inadequate elementary working conditions, academic librarians made certain efforts aimed towards meeting the information needs of library users during the world health crisis, but also that the pandemic emphasized the urgent need for digital transformation of surveyed academic libraries.
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Nascimento, Marvin do, Bruno Martins de Souza, and Aline Tany Posch. "peri-implant ligament." Brazilian Journal of Oral Sciences 22 (January 26, 2023): e231269. http://dx.doi.org/10.20396/bjos.v22i00.8671269.
Повний текст джерелаАнотація:
The peri-implant ligament is formed from the interface of bone tissue, through the anchoring of proteins and the surface of the dental implant. In this sense, it is relevant to understand the extent to which this ligament is structured and biomimics the periodontal ligament functions. Aim: The goal of this scoping review is to present and analyze the peri-implant ligament composition and compare the extent to which this ligament is structured and biomimics the periodontal ligament functions. Methods: This scoping review was performed according to the Joanna Briggs Institute methodology for scoping reviews and following the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping review. Two independent researchers searched Pubmed, Cochrane, Embase, Virtual Health Library, Scielo, Scopus, Web of Science, Brazilian Bibliography of Dentistry, Latin American and Caribbean Literature in Health Sciences, Digital Library of Theses and Dissertations from the University of São Paulo and Portal Capes. Studies published in English, Portuguese and Spanish, over the last 21 years (2000-2021). Results: A total of 330 titles were identified and after applying inclusion and exclusion factors, 27 studies were included in this review. All proteins were identified regarding their tissue function and classified into 6 major protein groups. After that this new protein ligament was compared with the periodontal ligament regarding its function and composition. The main proteins associated with osseointegration, and thus, with the peri-implant ligament are recognized as belonging to the periodontal ligament. Conclusion: This scoping review results suggest evidence of the composition and function of the periimplant ligament. However, variations may still exist due to the existence of several modulants of the osseointegration process.
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Kirkwood, Keith. "The SNAP Platform: social networking for academic purposes." Campus-Wide Information Systems 27, no. 3 (June 29, 2010): 118–26. http://dx.doi.org/10.1108/10650741011054429.
Повний текст джерелаАнотація:
PurposeThis paper aims to introduce an enterprise‐wide Web 2.0 learning support platform – SNAP, developed at Victoria University in Melbourne, Australia.Design/methodology/approachPointing to the evolution of the social web, the paper discusses the potential for the development of e‐learning platforms that employ constructivist, connectivist, and participatory pedagogies and actively engage the student population. Social networking behaviours and peer‐learning strategies, along with knowledge management through guided folksonomies, provide the back‐bone of a social systems approach to learning support.FindingsThe development of a cloud‐based read‐write enterprise platform can extend the responsiveness of the learning institution to its students and to future e‐learning innovations.Originality/valueThe full potential of e‐learning platforms for the development of learning communities of practice can now be increasingly realised. The SNAP Platform is a step in this direction.
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Lauretti, Laura, Maria Letizia Riccio, Annarita Mazzariol, Giuseppe Cornaglia, Gianfranco Amicosante, Roberta Fontana та Gian Maria Rossolini. "Cloning and Characterization of blaVIM, a New Integron-Borne Metallo-β-Lactamase Gene from a Pseudomonas aeruginosa Clinical Isolate". Antimicrobial Agents and Chemotherapy 43, № 7 (1 липня 1999): 1584–90. http://dx.doi.org/10.1128/aac.43.7.1584.
Повний текст джерелаАнотація:
ABSTRACT Production of a metallo-β-lactamase activity was detected in a carbapenem-resistant Pseudomonas aeruginosa clinical isolate (isolate VR-143/97) from an Italian inpatient at the Verona University Hospital (northern Italy). The metallo-β-lactamase determinant was isolated from a genomic library of VR-143/97, constructed in an Escherichia coli plasmid vector, by screening for clones with reduced susceptibility to imipenem. Sequencing of the cloned gene revealed that it encoded a new class B β-lactamase that was named VIM-1. At the sequence level VIM-1 was rather divergent from the other class B enzymes (16.4 to 38.7% identity), overall being more similar to members of subclass B1 including the β-lactamase II of Bacillus cereus (Bc-II), the Bacteroides fragilis CcrA, the Chryseobacterium meningosepticum BlaB, and the cassette-encoded IMP-1 enzymes. Among these, VIM-1 showed the highest degree of similarity to Bc-II. Similarly to bla IMP,bla VIM was also found to be carried on a gene cassette inserted into a class 1 integron. Thebla VIM-containing integron was located on the chromosome of P. aeruginosa VR-143/97, and the metallo-β-lactamase-encoding determinant was not transferable toE. coli by conjugation. Expression of the integron-bornebla VIM gene in E. coli resulted in a significant decrease in susceptibility to a broad array of β-lactams (ampicillin, carbenicillin, piperacillin, mezlocillin, cefotaxime, cefoxitin, ceftazidime, cefoperazone, cefepime, and carbapenems), revealing a very broad substrate specificity of the VIM-1 enzyme.
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Chen, Y., Y. Tian, H. Liu, Q. LI, Z. Luo, G. Yin, and Q. Xie. "POS0838 AGOMELATINE IDENTIFIED FROM THE FDA-APPROVED DRUG LIBRARY IS THERAPEUTIC AGAINST COLLAGEN INDUCED ARTHRITIS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 717.1–717. http://dx.doi.org/10.1136/annrheumdis-2023-eular.147.
Повний текст джерелаАнотація:
BackgroundTreatment effect of tumor necrosis factor α (TNFα) inhibitors is still low in patients with rheumatoid arthritis (RA), around 50%-70%. Thus more drugs by targeting proliferation of synovial fibroblasts (FLS) and TNFα induced inflammatory cytokine production are needed. Repurposed use of drugs that have been used in clinic is a quick and cost-effective way to find new drugs.ObjectivesThis study aims to screen drugs that could inhibit the proliferation and inflammation induced by TNFα in FLS from FDA approved on market drug library, then to assess the treatment effect of the identified drugs on collagen-induced arthritis (CIA) mouse model.MethodsCCK8 assay was performed to screen the drugs that could inhibit FLS proliferation, followed by qRT-PCR and ELISA to select the drugs that could suppress TNFα induced inflammatory cytokine production. Then, treatment effects of the identified drugs were assessed in CIA mouse model.ResultsThe first and second round drug librabry screening aimed to select out the drugs that could inhibit the proliferation of FLS. Results showed, from 1815 drugs, 372 drugs were indentified at the initial screening (Figure 1A) and 121 drugs were identified from the second screening (Figure 1B). The third round screening was performed to screen the drugs that could inhibit TNFα-induced inflammation, and results showed that a total of 77 drugs could inhibit mRNA expression levels of both IL-6 and IL-8 by over 50%, and 64 drugs could suppress secretion levels of both IL-6 and IL-8 for more than 20% (Figure 1C-F). Then a total of 14 drugs that were not anti-cancer drugs were used to further confirm the inhibitory effect on the TNFα induced inflammation, and results showed only Agomelatine (AOM), Cinacalcet (CCC), Amlodipine (ALM), Simvastatin (SV), and Pindolol (PDL) could suppress mRNA expression and secretion levels of IL-6, IL-8 (Figure 1G-J).As highly proliferated FLS and inflammatory cytokines play a critical role in the pathology of rheumatoid arthritis (RA), we tested the treatment effect of AOM, CCC, ALM, SV, and PDL in the CIA mose model. Results showed ALM (5mg/kg), CCC (10mg/kg), and PDL (10mg/kg) had a trend to reduce the clinical score but did not reach statistical meaning while SV (10mg/kg) did not show any treatment effect. Whereas, AOM (10mg/kg) could effectively alleviate the swelling of the the joint, which was as effective as the positive control drug methotrexate (MTX) (Figure 1K). ALM, AOM, as well as MTX could reduce the pathological score of inflammation and bone erosion at both the knee and the anke while PDL could only reduce the inflammation and relieve bone erosion at the knee(Figure 1L-N).ConclusionAgomelatine indentified from the FDA approved drug library could inhibit FLS proliferation and TNFα induced inflammation, and was therapeutic against CIA mouse model.Figure 1.Agomelatine identified from the FDA-approved drug library is therapeutic against collagen induced arthritis. (A) The first round screening by CCK8 assay. The drugs could inhibit more than 20% absorbance at 450nm, under the red lines, were the target ones, n=372. (B) The second round screening. The drugs could inhibit more than 10% absorbance at 450nm, under the red lines, were the target ones, n=121. (C-F) The third round screening. (C-D) mRNA expression levels of IL-6 and IL-8. (E-F) the secretion levels of IL-6 and IL-8. (G-J) The confirmation of drugs’ inhibitory effect on the inflammation cytokine production. Red asterisk indicated the conparison between TNFα group and DMSO group and blue pound signs suggested the conparison between drugs and TNFα group. (G-H) the mRNA expression levels of IL-6 and IL-8. (I-J) the secretion levels of IL-6 and IL-8. CIA mouse model was established to test the treatment effect of SV (10mg/kg), PDL (10mg/kg), ALM (5mg/kg), CCC (10mg/kg), and AOM (10mg/kg), and MTX (2mg/kg) was set as the positive control. (K) clinical score of joint swelling (L) H&E staining of knee joint (M) H&E staining of ankle joint (N) pathological scoring of H&E staining for joint inflammation and bone erosion.AcknowledgementsThis study is supported by Sichuan Science and Technology Program (2021JDRC0045 and 2021YFS0164), Post-doctoral Research and Development Fund of West China Hospital of Sichuan University (2019HXBH090), and National Natural Science Foundation of China (No. 82201985).Disclosure of InterestsNone Declared.
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Wang, Jiaqian, Liang Zhou, Yong Zhang, Lixin Huang, and Qin Shi. "Mesenchymal stem cells - a promising strategy for treating knee osteoarthritis." Bone & Joint Research 9, no. 10 (October 1, 2020): 719–28. http://dx.doi.org/10.1302/2046-3758.910.bjr-2020-0031.r3.
Повний текст джерелаАнотація:
Aims The purpose of our study was to determine whether mesenchymal stem cells (MSCs) are an effective and safe therapeutic agent for the treatment of knee osteoarthritis (OA), owing to their cartilage regeneration potential. Methods We searched PubMed, Embase, and the Cochrane Library, with keywords including “knee osteoarthritis” and “mesenchymal stem cells”, up to June 2019. We selected randomized controlled trials (RCTs) that explored the use of MSCs to treat knee OA. The visual analogue scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), adverse events, and the whole-organ MRI score (WORMS) were used as the primary evaluation tools in the studies. Our meta-analysis included a subgroup analysis of cell dose and cell source. Results Seven trials evaluating 256 patients were included in the meta-analysis. MSC treatment significantly improved the VAS (mean difference (MD), –13.24; 95% confidence intervals (CIs) –23.28 to –3.20, p = 0.010) and WOMAC (MD, –7.22; 95% CI –12.97 to –1.47, p = 0.010). The low-dose group with less than 30 million cells showed lower p-values for both the VAS and WOMAC. Adipose and umbilical cord–derived stem cells also had lower p-values for pain scores than those derived from bone marrow. Conclusion Overall, MSC-based cell therapy is a relatively safe treatment that holds great potential for OA, evidenced by a positive effect on pain and knee function. Using low-dose (25 million) and adipose-derived stem cells is likely to achieve better results, but further research is needed. Cite this article: Bone Joint Res 2020;9(10):719–728.
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Gursoy, M., Bauyrzhan A. Baitanayev, Emel Acar, and Bagdaulet S. Sizdikov. "Paleoanthropological Analysis of Osteological Material from the Myntobe Burial Ground." Povolzhskaya Arkheologiya (The Volga River Region Archaeology) 1, no. 47 (March 29, 2024): 173–90. http://dx.doi.org/10.24852/pa2024.1.47.173.190.
Повний текст джерелаАнотація:
The article deals with the paleoanthropological analysis of the skeletons unearthed from the Myntobe necropolis and dated to the II – IV centuries AD. Myntobe necropolis is located 2 km south of Gani Muratbayev village in the Keles district of Turkestan province. The burial ground consists of more than 600 randomly located mounds of various sizes. All mounds have a dirt embankment. Archaeological excavations were carried out at the burial ground in 2017 and 2022, as a result of which burials in the catacombs and naus were unearthed. An analysis of the burial tradition and recovered material allows researchers to speak about the belonging of these burials to the Kangli tribes. Since the burials date back to the Kangli period, the theoretical part reveals the issues of the location and political structure of the tribes and, most importantly, the determination of the paleopathology of the Myntobints by conducting a macroscopic analysis of the discovered skeletons. The results of the analysis allowed for drawing preliminary conclusions about lifestyle, social life, and nutritional status. When writing the theoretical part of the article, electronic textbooks and resources from the book fund of the National Library of Kazakhstan and the library of the International Kazakh-Turkish University named after Kozh Ahmet Yasawi were used. In total, 9 skeletons were selected for paleoanthropological and paleopathological analysis, from mounds No. 3, No. 6, and No. 7. Paleoanthropological reasoning in the main section is written on the basis of materials in Turkish and English from the collections of Turkish libraries. The skeletons found were analyzed macroscopically and many diseases were identified, such as osteoarthritis (joint deformity), osteopathy, ankylosing spondylitis, heel spurs, thickening of the cranial bone, and deformity of the mandibular joint. Preliminary conclusions about the paleopathology of the discovered skeletons are made.
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Emelyanov, Sergey A., Roman V. Chumakov, and Alexey N. Peregorodov. "Features of modern methods for osteoporosis diagnostics (review article)." Tambov Medical Journal 6, no. 2 (2024): 12–24. http://dx.doi.org/10.20310/2782-5019-2024-6-2-12-24.
Повний текст джерелаАнотація:
Abstract. Currently, osteoporosis is one of the most common diseases that significantly reduce the quality of life of patients, leading to their disability and death from related complications. The growing prevalence of osteoporosis in the population over the years, both among people over 60 years of age and among children under 18 years of age, as well as the high prevalence of osteoporotic fractures and their projected increase, requires improvement in the organization of care for patients, which primarily implies timely diagnosis with determination of the risk of low-energy fractures and timely treatment. Purpose: based on an analysis of the literature, to evaluate the current state of the problem and the effectiveness of modern methods for diagnosing osteoporosis. Materials and methods: a search was conducted in the open electronic scientific databases PubMed and the databases of the Russian scientific electronic library eLibrary using keywords and phrases: osteoporosis, osteodensitometry, bone mineral density, osteoporotic fracture. The results were obtained using the equipment of the Center for Collective Use of Scientific Equipment at Derzhavin Tambov State University. Results. The research presents data on risk factors for osteoporosis, possible clinical manifestations and existing methods for diagnosing this disease, indicating the advantages and disadvantages of each of the presented methods. The standard research method, if there is reason to assume a diagnosis, will be osteodensitometry. Ultrasound osteodensitometry serves as an indirect method for assessing bone tissue density. To determine bone mineral density it is recommended to use single energy X-ray absorptiometry (SXA), dual energy X-ray absorptiometry (DXA), radiographic absorptiometry (RA) and quantitative computed tomography. The standard radiographic method of radiation visualization of bone structures is the most accessible and widespread in the Russian Federation; however, for the purpose of diagnosing osteoporosis, this technique in most cases is not the method of choice, since radiographs can reveal reliable, but rather late signs of this disease. Conclusion. Each of the diagnostic methods has its own individual advantages, unique to it; to identify this disease in the early stages of its development, there is a need to use several methods for quantitative determination of bone density simultaneously.
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Alfred Maroyi. "Medicinal Uses, Biological and Chemical Properties of Wild Plum (Harpephyllum caffrum): An Indigenous Fruit Plant of Southern Africa." Journal of Pharmacy and Nutrition Sciences 9, no. 5 (January 5, 2019): 258–68. http://dx.doi.org/10.29169/1927-5951.2019.09.05.4.
Повний текст джерелаАнотація:
Harpephyllum caffrum is a fruit plant widely used as herbal medicine throughout its distributional range in southern Africa. This study was aimed at providing a critical review of the biological activities, phytochemistry and medicinal uses of H. caffrum. Documented information on the botany, biological activities, medicinal uses and phytochemistry of H. caffrum was collected from several online sources which included BMC, Scopus, SciFinder, Google Scholar, Science Direct, Elsevier, Pubmed and Web of Science. Additional information on H. caffrum was gathered from pre-electronic sources such as book chapters, books, journal articles and scientific publications sourced from the University library. This study showed that the bark, fruits and roots of H. caffrum are used as blood purifier and emetic, and as herbal medicine against asthma, wounds, bone fractures, sprains and skin problems. Phytochemical compounds identified from the fruits, leaves and stem bark of H. caffrum include cardanols, fatty acid esters, flavonoids, phenolics and triterpenoids. Ethnopharmacological research revealed that H. caffrum extracts and compounds have in vitro and in vivo pharmacological activities such as acetylcholinesterase, analgesic, antibacterial, anticonvulsant, antimycobacterial, antifungal, anti-HIV, anti-inflammatory, antioxidant, antipyretic, melanogenesis and antityrosinase, hypoglycaemic and hypotensive, hepatoprotective and cytotoxicity activities. Harpephyllum caffrum should be subjected to detailed phytochemical, pharmacological and toxicological evaluations aimed at correlating its medicinal uses with its phytochemistry and pharmacological activities of the species.
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Valkema Blouw, Paul. "Printers to the 'arch-heretic' David Joris Prolegomena to a bibliography of his works." Quaerendo 21, no. 3 (1991): 163–209. http://dx.doi.org/10.1163/157006991x00183.
Повний текст джерелаАнотація:
AbstractDespite the increased interest in all aspects of the Radical Reformation we are still in need of a bibliography of David Joris which might satisfy reasonable requirements. A. van der Linde's book, which presented itself as such over a century ago, is imprecise and not unnaturally entirely out of date. A new version would thus fulfil an obvious need. The reasons for which it has not yet been undertaken must be sought in the complication created by the fact that the hundreds of writings all appeared without an imprint. The dates, if indeed any are given, generally apply to the composition of the text and only coincide exceptionally with the often considerably later year of publication. All we can conclude from historical sources is that a number of his tracts were published in Deventer in about 1540 by Albert Pafraet and Dirk (II) van den Borne. In order to determine who dared to work for the arch-heretic (or, after his death, for later followers of his teaching) it is impossible to avoid a bibliographical analysis. In this manner we find the names of various of his printers and, from the years of their activity, we can deduce sufficient indications to date the publication of the writings within certain limits. This investigation shows that the first were indeed printed in Deventer, the very earliest being a treatise which has so far been ascribed to the Anabaptist Bernhard Rothmann. Thereafter David Joris gave orders for his works to be printed alternately in Antwerp, to Adriaen van Berghen, and in Deventer. After he had left for Basel he briefly applied to the services of two printers in the German-speaking area until he discovered a permanent supplier in the future university printer Ludwig Dietz in Rostock. The sectarian's death and his posthumous execution in 1559 were succeeded by a few decades of silence in the camp of his followers. In 1584, however, an edition of the Wonderboeck, entirely revised by the author, appeared and was soon followed by a series of other publications. Much previously unpublished work proved to have remained in the possession of David Joris's family. The printer, as he himself was later to admit, was Dirk Mullem in Rotterdam. When his activities came to an end in the last years of the century, other publishers took over the task.
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Li, Lei, Chao Pan, Xingyan Zhang, Wei Liu, Tingting Zhang, Yufan Liu, Jingyi Li, et al. "Efficacy of cementless porous tantalum tibial components versus cemented tibial components in primary total knee arthroplasty: A meta-analysis." Medicine 103, no. 14 (April 5, 2024): e37697. http://dx.doi.org/10.1097/md.0000000000037697.
Повний текст джерелаАнотація:
Background: Total knee arthroplasty involves the use of cemented tibial components for fixation. In recent years, cementless porous tantalum tibial components have been increasingly utilized. The aim of this meta-analysis was to compare the efficacy of cementless porous tantalum tibial components with traditional cemented tibial components in terms of postoperative outcomes following total knee arthroplasty. Methods: Relevant literature was retrieved from Cochrane Library, PubMed, Embase, and Web of Science using the search terms “(trabecular metal OR Porous tantalum)” AND “knee” up to July 2023. The weighted mean difference with a 95% confidence interval was used as the effect size measure to evaluate the functional recovery of the knee joint, radiological analysis, complications, and implant revisions between cementless porous tantalum tibial components and traditional cemented tibial components after total knee arthroplasty. Review Manager 5.3 was utilized to conduct a comparative analysis of all included studies. Results: Nine studies with a total of 1117 patients were included in this meta-analysis, consisting of 447 patients in the porous tantalum group and 670 patients in the cemented group. Radiological analysis demonstrated that the porous tantalum group had better outcomes than the cemented group (P < .05). The combined results for the 5-year and 10-year follow-ups, range of motion, Western Ontario and McMaster University Osteoarthritis Index, complications, and implant revisions showed no significant differences between the porous tantalum and cemented groups. Conclusion: The results of the 5-year and 10-year follow-ups indicate that the use of cementless porous tantalum tibial components is comparable to traditional cemented tibial components, with no significant advantages observed. However, at the 5-year follow-up, the porous tantalum group demonstrated a good bone density in the proximal tibia. Future studies with a larger sample size, long-term clinical follow-up, and radiological results are needed to verify the differences between the 2 implants.
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Girma, Abayeneh, and Aleka Aemiro. "Prevalence and Associated Risk Factors of Intestinal Parasites and Enteric Bacterial Infections among Selected Region Food Handlers of Ethiopia during 2014–2022: A Systematic Review and Meta-Analysis." Scientific World Journal 2022 (October 12, 2022): 1–14. http://dx.doi.org/10.1155/2022/7786036.
Повний текст джерелаАнотація:
Food-borne disease due to intestinal parasites (IPs) and enteric bacterial infections (EBIs) remain a major public health problem. Food handlers, individuals involved in preparing and serving food, working with poor personal hygiene could pose a potential threat of spreading IPs and EBIs to the public. The aim of this study was to examine the overall prevalence and risk factors of IPs and EBIs among food handlers in four selected regions of Ethiopia. Scientific articles written in English were recovered from PubMed, ScienceDirect, Web of Science, Google Scholar, Cochrane Library, and other sources from Google Engine and University Library Databases. “Prevalence,” “Intestinal Parasites,” “Enteric Bacterial Infections,” “Associated Factors,” “Food Handlers,” and “Ethiopia” were the search terms used for this study. For critical appraisal, PRISMA 2009 was applied. Stata software version 16 was used to perform the meta-analysis. Heterogeneity and publication bias were evaluated using Cochran’s Q, inverse variance (I2), and funnel plot asymmetry tests. A random-effects model was used to calculate the pooled burden of IPs and EBIs and its associated factors among food handlers, along with the parallel odds ratio (OR) and 95% confidence interval (CI). For this meta-analysis, a total of 5844 food handlers were included in the 20 eligible studies. The overall pooled prevalence of IPs and EBIs among food handlers in four selected regions of Ethiopia was 29.16% (95% CI: 22.61, 35.71), with covering (25.77%) and (3.39%) by IPs and EBIs, respectively. Ascaris lumbricoides, Entamoeba histolytica/dispar, Giardia lamblia, and hookworm were the most prevalent IPs among food handlers with a pooled prevalence of 7.58%, 6.78%, 3.67%, and 2.70%, respectively. Salmonella and Shigella spp. were the most prevalent EBIs among food handlers with a pooled prevalence of 2.78% and 0.61%, respectively. A high prevalence of IPs and EBIs among food handlers was observed in Oromia (38.56%; 95% CI: 29.98, 47.14), while a low prevalence was observed in the Tigray region (19.45%; 95% CI: 6.08, 32.82). Food handlers who had not taken food hygiene training (OR: 0.68, 95% CI: −0.34, 1.69), untrimmed finger nail (OR: 2.23, 95% CI: 1.47, 2.99), lack of periodic medical checkup (OR: 1.52, 95% CI: 0.41, 2.64), lack of handwashing habits (OR: 1.97, 95% CI: 0.53, 3.41), and eating raw vegetables and meat (OR: 2.63, 95% CI: 0.92, 4.34) were factors significantly associated with the prevalence of IPs and EBIs. The prevalence of IPs and EBIs was high in the selected Ethiopian region (Amhara, Oromia, SNNPR, and Tigray) food handlers along an increasing prevalence trend from 2014 to 2022. Therefore, this study recommends the provision of proper health education and training regarding personal hygiene, hand washing, food handling, medical checks, as well as raw vegetable and meat safety.
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Parkinson, Hayley, James Breen, Nhi Hin, Vasilios Panagopoulos, Andrew Zannettino, Kate Vandyke, and Duncan Hewett. "A Functional Genomic Screen to Identify Novel Genes Involved in Multiple Myeloma Tumour Development." Blood 142, Supplement 1 (November 28, 2023): 1947. http://dx.doi.org/10.1182/blood-2023-174601.
Повний текст джерелаАнотація:
Multiple myeloma (MM) is an incurable malignancy characterised by uncontrolled proliferation of plasma cells (PCs) in the bone marrow (BM). MM is a genetically heterogeneous disease with each patient's PCs harbouring unique genetic mutations, however the development of MM tumours is not only dependent on the underlying genetics but also on the selective pressures applied by the BM microenvironment. Hence, we hypothesise that identifying the dependencies which promote MM cell outgrowth in the BM microenvironment will allow for the identification of new drug targets. This project aims to use an in vivo functional screen, combining CRISPR-Cas9 gene editing, using a single guide RNA (sgRNA) library targeting thousands of genes, with a murine model of MM, to identify novel genes involved in MM tumour development. The Bassik human apoptosis and cancer CRISPR knockout library (Addgene #101926) was used to transduce MM cells with 31,324 unique sgRNAs targeting 3,015 genes and 1,500 control regions. The human MM cell line OPM2 was transduced with the Cas9 transgene (FuCas9GFP), followed by the sgRNA expression vector (pMCB320) generating OPM2-Cas9-sgRNA cells. These cells were then injected (5x10 5 cells/mouse, n=8 mice + 1 tumour-naive control) into the tibiae of immunodeficient NOD.Cg-Prkdc scid Il2rg tm1Wjl/SzJ (NSG) mice. Four weeks post-injection, the primary tumour within the injected tibia was isolated and sgRNA frequencies were assessed via next generation sequencing and compared with that of the initial library and the injected cells using the MAGeCK algorithm. To identify genes that play roles in MM tumour formation in patients, we assessed the expression of our identified genes in CD138-selected BM PCs from newly diagnosed MM patients (n=155) when compared with normal PCs from healthy donors (n=5) in microarray dataset E-MTAB-363 (ArrayExpress). Furthermore, to identify potential pathway involvement of our identified genes we performed gene set enrichment analysis (GSEA) using the University of California San Diego and Broad Institute developed GSEA software, comparing to Hallmark Gene Sets. Comparison of the in vitro cultured cells with the initial library identified 34 genes with undetectable (p<0.05) sgRNAs post in vitro culture, suggesting these genes play key roles in the survival of OPM2 cells. This list contained a number of genes known to control MM cell survival, such as IRF4 and CCND2. Additionally, sgRNAs targeting a further 115 genes were significantly depleted (p<0.05) in vitro and were completely undetectable in vivo, suggesting that these are implicated in cell proliferation and tumour formation in vivo. This gene list contained some already known MM drivers such as MYC, KRAS and DIS3. Furthermore, we identified 28 genes where CRISPR knockout had no significant effect in vitro but were critical dependencies for tumour development, with sgRNAs being undetectable (p<0.05) in vivo. This list contained genes known to be important for MM and BM stromal cell interaction such as ALCAM and SPP1. Notably, 25% of the genes identified as critical dependencies for OPM2 cells in vitro and/or in vivo are significantly upregulated >2-fold (p<0.05; limma) in MM patient PCs when compared with normal PCs (E-MTAB-363), suggesting these may play a role in tumour development in patients. Gene set enrichment analysis revealed that the genes that were essential in vitro were predominantly involved in cell survival related pathways such as cell cycle regulation (G2M checkpoint) and DNA replication/repair; however, the uniquely in vivo genes are predominantly involved in cell metabolism pathways such as MTORC1 signalling, oxidative phosphorylation and glycolysis. Overall, this study has successfully used a functional genetic screen to identify novel gene dependencies required for in vitro MM cell growth and in vivo MM tumour development. A secondary genetic screen will be performed in vivo to validate and refine this list of candidate genes. These validated genes will be further investigated using patient derived data sets to determine if they represent common vulnerabilities in patients and in multiple MM cell lines to investigate their specific mechanistic and pathway involvement. Identification and understanding the driving dependencies which promote MM cell outgrowth in the BM microenvironment will allow for the identification and development of new drug targets to improve patient outcomes.
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Robinson, Danielle E., M. Sanni Ali, Victoria Y. Strauss, Leena Elhussein, Bo Abrahamsen, Nigel K. Arden, Yoav Ben-Shlomo, et al. "Bisphosphonates to reduce bone fractures in stage 3B+ chronic kidney disease: a propensity score-matched cohort study." Health Technology Assessment 25, no. 17 (March 2021): 1–106. http://dx.doi.org/10.3310/hta25170.
Повний текст джерелаАнотація:
BackgroundBisphosphonates are contraindicated in patients with stage 4+ chronic kidney disease. However, they are widely used to prevent fragility fractures in stage 3 chronic kidney disease, despite a lack of good-quality data on their effects.ObjectivesThe aims of each work package were as follows. Work package 1: to study the relationship between bisphosphonate use and chronic kidney disease progression. Work package 2: to study the association between using bisphosphonates and fracture risk. Work package 3: to determine the risks of hypocalcaemia, hypophosphataemia, acute kidney injury and upper gastrointestinal events associated with using bisphosphonates. Work package 4: to investigate the association between using bisphosphonates and changes in bone mineral density over time.DesignThis was a new-user cohort study design with propensity score matching.Setting and data sourcesData were obtained from UK NHS primary care (Clinical Practice Research Datalink GOLD database) and linked hospital inpatient records (Hospital Episode Statistics) for work packages 1–3 and from the Danish Odense University Hospital Databases for work package 4.ParticipantsPatients registered in the data sources who had at least one measurement of estimated glomerular filtration rate of < 45 ml/minute/1.73 m2were eligible. A second estimated glomerular filtration rate value of < 45 ml/minute/1.73 m2within 1 year after the first was requested for work packages 1 and 3. Patients with no Hospital Episode Statistics linkage were excluded from work packages 1–3. Patients with < 1 year of run-in data before index estimated glomerular filtration rate and previous users of anti-osteoporosis medications were excluded from work packages 1–4.Interventions/exposureBisphosphonate use, identified from primary care prescriptions (for work packages 1–3) or pharmacy dispensations (for work package 4), was the main exposure.Main outcome measuresWork package 1: chronic kidney disease progression, defined as stage worsening or starting renal replacement. Work package 2: hip fracture. Work package 3: acute kidney injury, hypocalcaemia and hypophosphataemia identified from Hospital Episode Statistics, and gastrointestinal events identified from Clinical Practice Research Datalink or Hospital Episode Statistics. Work package 4: annualised femoral neck bone mineral density percentage change.ResultsBisphosphonate use was associated with an excess risk of chronic kidney disease progression (subdistribution hazard ratio 1.12, 95% confidence interval 1.02 to 1.24) in work package 1, but did not increase the probability of other safety outcomes in work package 3. The results from work package 2 suggested that bisphosphonate use increased fracture risk (hazard ratio 1.25, 95% confidence interval 1.13 to 1.39) for hip fractures, but sensitivity analyses suggested that this was related to unresolved confounding. Conversely, work package 4 suggested that bisphosphonates improved bone mineral density, with an average 2.65% (95% confidence interval 1.32% to 3.99%) greater gain in femoral neck bone mineral density per year in bisphosphonate users than in matched non-users.LimitationsConfounding by indication was a concern for the clinical effectiveness (i.e. work package 2) data. Bias analyses suggested that these findings were due to inappropriate adjustment for pre-treatment risk. work packages 3 and 4 were based on small numbers of events and participants, respectively.ConclusionsBisphosphonates were associated with a 12% excess risk of chronic kidney disease progression in participants with stage 3B+ chronic kidney disease. No other safety concerns were identified. Bisphosphonate therapy increased bone mineral density, but the research team failed to demonstrate antifracture effectiveness.Future workRandomised controlled trial data are needed to demonstrate antifracture efficacy in patients with stage 3B+ chronic kidney disease. More safety analyses are needed to characterise the renal toxicity of bisphosphonates in stage 3A chronic kidney disease, possibly using observational data.Study registrationThis study is registered as EUPAS10029.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 25, No. 17. See the NIHR Journals Library website for further project information. The project was also supported by the National Institute for Health Research Biomedical Research Centre, Oxford.
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Doudican, Nicole A., Ravi Vij, Mark A. Fiala, Justin King, Shireen Vali, Kabya Basu, Ansu Kumar, et al. "Therapy Personalization Using Predictive Simulation Approach with Ex-Vivo Clinical Validations." Blood 124, no. 21 (December 6, 2014): 2232. http://dx.doi.org/10.1182/blood.v124.21.2232.2232.
Повний текст джерелаАнотація:
Abstract Background The epitome of cancer treatment personalization is N=1 segmentation where a custom therapy is designed for every patient. Because most cancer aberrations are not actionable mutations and tumors can have more than one actionable mutation, this one biomarker/one drug approach to cancer personalization has inherent limitations due to its over simplification. Personalization 2.0 methodology creates a patient simulation avatar incorporating a patient’s genomic profile information holistically. Methods Bone marrow samples from two myeloma patients (P1 and P2) refractory to most recent treatment was collected, and P1’s sample was sorted into CD138+ and CD138- cells. The patient cells were analyzed for chromosomal alterations using Comparative Genomic Hybridization (aCGH) arrays by GenPath Diagnostics and cytogenetic chromosome analysis by Washington University School of Medicine and New York University (NYU), respectively. Using this information, a predictive simulation avatar model of each patient was created by Cellworks based on genomic profile of patients. A digital functional library of over 80 FDA-approved drugs and agents currently in clinical trials were simulated individually and in combination using the two patient avatars to create a personalized treatment for each patient. The findings were prospectively validated using patient cells ex vivo as assessed by MTT assay at New York University. Results P1 aberrations included trisomy of CCND1 and deletion of TP53 along with single copy losses in different arms of chromosomes 1, 6, 8, 12, 13, 14, 16, 17 and 22 and gains in different arms and regions of chromosomes X, 1, 4, 7, 9, 17, 3, 5, 11, 15 and 19, indicating the presence of hyperdiploid clones. Using this information, 897 gene perturbations were included to model this patient simulation avatar. Simulation predicted high beta-catenin (CTNNB1) activity with increased hedgehog and NOTCH pathways that were inherent causes of Bortezomib resistance. Significant activation of STAT3 and STAT5 due to amplification of IL6 pathway, JAK2 and JAK3 was noted. Amplifications of MET, IGFR and FGFR converged at ERK and AKT signaling loops. Along with deletion of TP53, this profile had amplification of many anti-apoptotic genes including survivin, MCL1 and XIAP. Modeling predicted sensitivity to the JAK inhibitor Tofacitinib, a drug approved for rheumatoid arthritis. This was prospectively validated ex vivo, and the experimental data correlated with the prediction showing a reduction in viability. P2 aberrations include losses in chromosomes X and 9 and a chromosome 11:14 translocation that is a common occurrence in MM. This translocation results in an amplification of CCND1 expression. The genomic aberrations reported include knockdown of tumor suppressors RXRA, TGFBR1, TJP2 and TSC1. TSC1 regulates the mTOR pathway, and its deletion causes an aberrant activation of mTOR and its downstream targets. Reduced expression of RXRA and TJP2 both in different manners leads to increase in AP1 activation. NFkB is also activated due to RXRA reduction. TGFBR1 reduction decreases the expression of cell cycle inhibitors via SMAD2/3 down-regulation. In this patient avatar, modeling predicted sensitivity to a combination of Sirolimus and Trametinib. Ex vivo validation confirmed this prediction of additive synergy of these two drug agents in the context of this patient. Conclusions This study demonstrates and validates the personalization of treatment through two patient cases based on creating predictive simulation avatar models using genomic profile information. This modeling holistically incorporates all genomic aberration information and is not limited to associating drugs to actionable mutations. Disclosures Doudican: Cellworks: Research Funding. Vali:Cellworks: Employment. Basu:Cellworks: Employment. Kumar:cellworks: Employment. Singh:Cellworks: Employment. Sultana:Cellworks: Employment. Abbasi:Cellworks: Employment, Equity Ownership.
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Cafiero, Rebecca M., Steven Holshouser, Craig Kutz, Julie Kanter, and Patrick Woster. "Novel Epigenetic Modulators That Promote Fetal Hemoglobin Production for the Prevention of Sickle Cell Disease Related Complications." Blood 126, no. 23 (December 3, 2015): 973. http://dx.doi.org/10.1182/blood.v126.23.973.973.
Повний текст джерелаАнотація:
Abstract Background: Sickle cell disease (SCD) is the most common inherited blood disorder in the United States. Affected patients are at risk of multi-organ complications, significant morbidity and early mortality with an average age at death of 42 and 48 years for men and women, respectively. Complications include acute and chronic pain due to vascular occlusion, end organ damage, acute chest syndrome and increased risk of sepsis. SCD is caused by a point mutation on chromosome 11, which codes for the beta chain of adult hemoglobin. Fetal hemoglobin is not affected by the mutation. Persons with SCD who maintain persistent fetal hemoglobin demonstrate a decreased number of pain crises and acute chest episodes along with a decreased risk of mortality compared to other patients with SCD. The only FDA approved fetal hemoglobin inducer, Hydroxyurea, remains highly underutilized due to the risk of complications and unwanted side effects. The discovery of a new agent that promotes re-expression of fetal hemoglobin could revolutionize the care of affected patients by reducing morbidity and mortality. Epigenetic modulation is one possible mechanistic approach to accomplish this goal. Recent studies with lysine specific demethylase-1 (LSD1) inhibitors, including tranylcypromine (TCP) have shown promising results. Unfortunately, TCP also affects monoamine oxidase and thus has significant side effects. Developing a molecule with high specificity, low cross reactivity and negligible toxicity would increase desired effects while reducing unwanted side effects. Objectives: To discover small-molecule inhibitors of LSD1 that exhibit high selectivity for LSD1 and low in-vivo toxicity that can be used to promote re-expression of fetal hemoglobin in SCD patients. Design/Methods: Our laboratory at the Medical University of South Carolina has recently described a library of potent, non-toxic LSD1 inhibitors. Our preliminary results suggest that these inhibitors show promise as fetal hemoglobin inducers. Using K562 cells, an erythroleukemic cell line known to model in-vivo hemoglobin production, we are screening this library to identify the most effective compounds using Western blotting for the gamma globin chain that is unique to fetal hemoglobin. Following identification of the most effective compounds in initial screens, we will confirm results with RT-qPCR. Subsequent studies will involve culturing and treating erythroid progenitor cells from healthy subject samples and from patients with SCD obtained through bone marrow sampling. HPLC will be used for identification and quantification of hemoglobin chains, including fetal hemoglobin, after ex-vivo treatment with selected compounds. Results: Initial results from Western blots for fetal hemoglobin (gamma globin protein) demonstrate that TCP, as well as the experimental compounds C1, 107-3 and 107-15, promote the re-expression of fetal hemoglobin in K562 cells. Experimental compounds were compared to DMSO as negative control, and hemin (10 mM) and hydroxyurea (200 mM) as positive controls. All experimental compounds evaluated are significantly less toxic than hydroxyurea, and do not impact cell viability in trypan blue exclusion studies. Conclusion: Initial studies show promising results for fetal hemoglobin production using these novel LSD-1 inhibitors. Viability data is also encouraging. Continued investigation is warranted to further investigate the efficacy of these compounds. Disclosures No relevant conflicts of interest to declare.
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Ley, Timothy James, J. DiPersio, L. Ding, R. Ries, V. Magrini, J. Payton, S. McGrath, et al. "Sequencing an Acute Myeloid Leukemia (AML) Genome with “Next Generation” Technologies." Blood 110, no. 11 (November 16, 2007): 205. http://dx.doi.org/10.1182/blood.v110.11.205.205.
Повний текст джерелаАнотація:
Abstract The genetic events responsible for the initiation and progression of AML are unknown for most patients. Although many important mutations for pathogenesis have been discovered, unbiased genomic approaches will be required to discover all relevant mutations. The development of “Next Generation” massively parallel sequencing approaches (454 and Solexa) have substantially reduced the cost of whole genome sequencing, and have allowed us to initiate a study designed to identify all potentially relevant mutations in a case of M1 AML. The first patient selected for study was a previously healthy 57-year-old Caucasian female who presented with a white blood count of 102,500 (91% blasts); the bone marrow biopsy revealed 100% blasts. Cytogenetics were normal. Tumor and skin (normal) samples were banked with informed consent, using our Washington University IRB-approved protocol that specifically permits whole genome sequencing. Resequencing of 14 genes frequently mutated in AML revealed somatic mutations in FLT3 (ITD) and NPM. Oligomer array-based comparative genomic hybridization using the 2.1 million-oligomer NimbleGen array revealed only one small (<10Kb) region of somatic amplification on chromosome 1p. 500K SNP array analysis of both tumor and skin DNA revealed no regions of “copy number neutral” LOH. Expression analysis of tumor RNA on the Affymetrix Hu133+2 platform revealed a signature that is typical for most patients with M1 AML. The patient’s bone marrow RNA was used to prepare a polyA-primed cDNA library that was enzymatically normalized (to bias towards less abundant mRNAs). Two runs of this material on the Solexa platform yielded approximately 1.5 billion bases of sequence (8x coverage). These reads were stringently aligned to micro-repeat masked versions of the human transcriptome and the human genome (Build 36) and then scored for single-nucleotide and small (1–3bp) indel variants. We further evaluated the coverage extent, depth, and gap size across the transcriptome, using custom scripts and the Synamatix Synamer™ algorithm. ∼4,500 sequence variants have been identified thusfar, which are currently being classified (e.g. known SNPs, non-synonymous variants, etc.) for further analysis. Non-amplified tumor and skin DNA samples were also prepared for sequencing. 25 Solexa runs have been completed on the tumor genome (∼19 billion bases; 6.3X coverage). ‘Actual’ coverage is being assessed by comparing the Solexa data to informative (i.e. heterozygous) SNPs detected in the patient’s tumor and/or skin samples on the 500K SNP array. At this time, 18% of the 135,167 informative SNPs have been detected in Solexa reads. Within a few months, we will complete ∼25x coverage of the patient’s tumor cDNA and genomic DNA. The patient’s skin DNA will then be sequenced to identify private SNPs. Potential somatic mutations will be verified with an established PCR-based resequencing pipeline, and the frequencies of validated somatic mutations will be further determined in 93 additional cases of AML. Using comprehensive array-based genomic platforms and Next Generation sequencing, we hope to define all of the inherited and acquired mutations that were relevant for AML pathogenesis in this patient.
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Chen, Xiao, Jing Chen, Yanji Duan, Chang Chen, and Yuan Cao. "Could BMMNCs therapy reduce the mid- and long-term rate of total hip arthroplasty of femoral head necrosis?: A systematic review and meta-analysis." Medicine 102, no. 30 (July 28, 2023): e34311. http://dx.doi.org/10.1097/md.0000000000034311.
Повний текст джерелаАнотація:
Background: Osteonecrosis of the femoral head (ONFH) is a cause of hip pain and early joint lesion in patient. The hip-preserving treatments are especially important for patients in early stage of ONFH. However, it is controversial of the effectiveness and safety of bone marrow mononuclear cells (BMMNCs) in the treatment of ONFH. The aim of the study was to explore the mid- and long-term efficacy (particularly the rate of total hip arthroplasty [THA]) with BMMNCs in treatment of ONFH. Methods: PubMed, Web of Science, Embase, OVID, Cochrane Libriary, CNKI, and Google Scholar databases were searched for relevant randomized controlled trials or non-randomized controlled trials from inception to October 15, 2022. Methodological quality of the trials was assessed, relevant data were extracted, and RevMan 5.3 and Stata 15.0 software were used to perform the meta-analysis of parameters related to the consequences. Results: A total of 22 articles were included, including 1923 patients. Meta-analysis results showed that the treatment of BMMNCs has a significantly lower incidence of THA (odds ratio [OR] = 0.33; 95% confidence interval [CI] = 0.27–0.41, P < .00001), radiographic progression rate (OR = 0.37; 95% CI = 0.21–0.63, P = .0003) and visual analog score at 24 months (mean difference [MD] = −11.84; 95% CI = −14.86 to −8.82, P < .00001), and has higher Harris hip score (MD = 6.90; 95% CI = 4.56–9.24, P < .00001), improvement of visual analog score at 24 months (MD = 6.87; 95% CI = 1.84–11.89, P = .007) and Merle D’Aubigne and Postel hip score (MD = 0.79; 95% CI = 0.14–1.44, P = .02). But there was no significant difference in the Western Ontario and McMaster University Osteoarthritis index (MD = −6.32; 95% CI = −16.76 to 4.12, P = .24) and incidence of complication (OR = 0.86; 95% CI = 0.52–1.42, P = .56). Conclusion: Current evidence supports that BMMNCs therapy could reduce the mid- and long-term rate of THA, improve hip function, alleviated the degree of hip pain, delay the progression of imaging staging and not increase the rate of complication, which maybe serve as a preferred option for treating ONFH.
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Leerling, A., O. Dekkers, N. Appelman-Dijkstra, and E. Winter. "POS1173 CLINICAL PRESENTATION AND TREATMENT OF STERNOCOSTOCLAVICULAR HYPEROSTOSIS (SCCH): A SYSTEMATIC REVIEW AND META-ANALYSIS OF SCATTERED EVIDENCE." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 915.1–915. http://dx.doi.org/10.1136/annrheumdis-2022-eular.4688.
Повний текст джерелаАнотація:
BackgroundSternocostoclavicular hyperostosis (SCCH) is an inflammatory bone disorder within the spectrum of chronic non-bacterial osteomyelitis. SCCH can be a manifestation of SAPHO syndrome, standing acronym for synovitis, acne, pustulosis, hyperostosis and osteitis, but also appears as an isolated clinical entity without joint and skin involvement1,2. Consensus on nomenclature, diagnostic classification, and therapy for SCCH is currently lacking3. Literature is diffuse, and spreads over a wide range of medical disciplines, calling for a first systematic overview.ObjectivesWe critically appraised literature with the aim to i) gain overview on the clinical presentation of SCCH and features leading to diagnosis and to ii) evaluate different treatment modalities and treatment response. We focused on the clinical entity of SCCH in adults, either isolated or as a part of SAPHO syndrome.MethodsWe conducted a systematic review and meta-analysis according to the PRISMA guidelines on the clinical presentation and therapeutic modalities applied in adult SCCH patients. Studies covering these respective domains were selected. Risk of bias was assessed using validated tools according to study type. Untransformed numerical data and double-arcsine transformed proportional data were analyzed in a random effects model in R-4.0.5; pooled proportions were reported with 95% confidence intervals (95%CI). Treatment response was categorized as good, partial, or none.Results28(i) and 12(ii) studies were included, containing heterogeneous data on 1818 patients. A female predisposition (67%, 95%CI 60-73) and major diagnostic delay (5 years 95%CI 3-7) were noted. Clinical presentation was marked by anterior chest pain (89%, 95%CI 79-96), and swelling (79%, 95%CI 62-91). Pustulosis palmoplantaris was present in 53%, 95%CI37-68, whereas acne (8%, 95%CI4-13) and peripheral arthritis (24%, 95%CI 11-39) were less prevalent. Inflammatory markers were inconsistently elevated and autoantibodies and HLA-B27 prevalence normal. Histopathology was unspecific, and cultures almost exclusively negative. Increased isotope uptake (99%, 95%CI96-100) was the most consistent imaging finding. Amongst manifold treatments (see Figure 1), NSAIDs were mainly partially effective. Pamidronate and biologicals (mainly TNF-α inhibitors) yielded good, though heterogeneous, response in 83%, 95%CI 60-98 and 56%, 95%CI 26-85 respectively.Figure 1.Treatment modalities applied in SCCH and their effects on bone pain (data from trials and several cohort studies combined)ConclusionLiterature on SCCH is extremely heterogeneous. Timely diagnosis proves challenging and mainly follows from the increased isotope uptake on nuclear examination. Biopsies, autoantibodies and HLA-status are non-contributory, and inflammatory biochemical profiles only variably detected. Pamidronate and TNF-α inhibitors emerged as promising therapies, but powered, placebo-controlled research with standardized measures of response is warranted. Inherently, international consensus on SCCH’s diagnostic classification and name appears critical to improve scientific collaboration on this rare disease, and to advance the development of clinical guidelines.References[1]Saghafi M, Henderson MJ and Buchanan WW. Sternocostoclavicular hyperostosis. YSARH 1993; 22: 215-223. 10.1016/0049-0172(93)80070-v. DOI: papers3://publication/doi/10.1016/0049-0172(93)80070-v.[2]Carroll MB. Sternocostoclavicular hyperostosis: a review. Therapeutic advances in musculoskeletal disease 2011; 3: 101-110. 10.1177/1759720X11398333. DOI: papers3://publication/doi/10.1177/1759720X11398333[3] Kalke S, Perera SD, Patel ND, et al. The sternoclavicular syndrome: experience from a district general hospital and results of a national postal survey. Rheumatology 2001; 40: 170-177. 10.1093/rheumatology/40.2.170. DOI: papers3://publication/doi/10.1093/rheumatology/40.2.170AcknowledgementsThe authors would like to thank Drs. J.W. Schoones, information specialist at the Walaeus Library, Leiden University Medical Center, for his contribution to the search strategy and selection of studies.Disclosure of InterestsNone declared
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Davis, Sarah, Emma Simpson, Jean Hamilton, Marrissa Martyn-St James, Andrew Rawdin, Ruth Wong, Edward Goka, Neil Gittoes, and Peter Selby. "Denosumab, raloxifene, romosozumab and teriparatide to prevent osteoporotic fragility fractures: a systematic review and economic evaluation." Health Technology Assessment 24, no. 29 (June 2020): 1–314. http://dx.doi.org/10.3310/hta24290.
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Background Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. Objectives The objectives were to evaluate the clinical effectiveness, safety and cost-effectiveness of non-bisphosphonates {denosumab [Prolia®; Amgen Inc., Thousand Oaks, CA, USA], raloxifene [Evista®; Daiichi Sankyo Company, Ltd, Tokyo, Japan], romosozumab [Evenity®; Union Chimique Belge (UCB) S.A. (Brussels, Belgium) and Amgen Inc.] and teriparatide [Forsteo®; Eli Lilly and Company, Indianapolis, IN, USA]}, compared with each other, bisphosphonates or no treatment, for the prevention of fragility fracture. Data sources For the clinical effectiveness review, nine electronic databases (including MEDLINE, EMBASE and the World Health Organization International Clinical Trials Registry Platform) were searched up to July 2018. Review methods A systematic review and network meta-analysis of fracture and femoral neck bone mineral density were conducted. A review of published economic analyses was undertaken and a model previously used to evaluate bisphosphonates was adapted. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years for a simulated cohort of patients with heterogeneous characteristics. This was done for each non-bisphosphonate treatment, a strategy of no treatment, and the five bisphosphonate treatments previously evaluated. The model was populated with effectiveness evidence from the systematic review and network meta-analysis. All other parameters were estimated from published sources. An NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture® (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX® (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net monetary benefit was estimated using non-parametric regression. A probabilistic sensitivity analysis and scenario analyses were used to assess uncertainty. Results Fifty-two randomised controlled trials of non-bisphosphonates were included in the clinical effectiveness systematic review and an additional 51 randomised controlled trials of bisphosphonates were included in the network meta-analysis. All treatments had beneficial effects compared with placebo for vertebral, non-vertebral and hip fractures, with hazard ratios varying from 0.23 to 0.94, depending on treatment and fracture type. The effects on vertebral fractures and the percentage change in bone mineral density were statistically significant for all treatments. The rate of serious adverse events varied across trials (0–33%), with most between-group differences not being statistically significant for comparisons with placebo/no active treatment, non-bisphosphonates or bisphosphonates. The incremental cost-effectiveness ratios were > £20,000 per quality-adjusted life-year for all non-bisphosphonate interventions compared with no treatment across the range of QFracture and FRAX scores expected in the population eligible for fracture risk assessment. The incremental cost-effectiveness ratio for denosumab may fall below £30,000 per quality-adjusted life-year at very high levels of risk or for high-risk patients with specific characteristics. Raloxifene was dominated by no treatment (resulted in fewer quality-adjusted life-years) in most risk categories. Limitations The incremental cost-effectiveness ratios are uncertain for very high-risk patients. Conclusions Non-bisphosphonates are effective in preventing fragility fractures, but the incremental cost-effectiveness ratios are generally greater than the commonly applied threshold of £20,000–30,000 per quality-adjusted life-year. Study registration This study is registered as PROSPERO CRD42018107651. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 29. See the NIHR Journals Library website for further project information.
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Mascarenhas, Cintia Do Couto, Anderson Ferreira Cunha, Ana Flavia Brugnerotto, Sheley Gambero, Joao Machado-Neto, Adriana S. S. Duarte, Katia B. Pagnano, Fernando Ferreira Costa, and Carmino Antonio De Souza. "The Alteration of SEPT5 Gene Expression in BCR-ABL Positive Cells and Its Possible Correlation with the Development and / or Progression of Chronic Myeloid Leukemia (CML)." Blood 118, no. 21 (November 18, 2011): 4415. http://dx.doi.org/10.1182/blood.v118.21.4415.4415.
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Abstract Abstract 4415 The CML is a clonal disease of stem cells and its main feature is the unregulated production of a tyrosine kinase protein called BCR-ABL, the progression of the disease to accelerated phase or blast crisis may be associated with genomic instability. Because of this, the use of tools for the study of gene expression could bring new insights in the understanding of these mechanisms in the CML. In a recent study using SSH libraries, we compared the gene expression pattern between granulocytes of health control and CML patients, and we identified the gene SEPT5 expressed only in CML patients. Although the studies in the literature, there is not a clear relationship between the expression of this gene and the development or progression of CML. SEPT5 is a member of nucleotide binding proteins called septins that were firstly described in yeast as cell division cycle regulatory proteins. This gene was reported in patients with AML translocated with MLL gene, in adult human brain and heart; it is also associated with alpha granules of human blood platelets. The aims of this study are to carry a functional analysis of SEPT5 in differents cells line and to study the relationship of this gene and the development and/or progression of CML. The gene expression evaluation was made in granulocytes, mononuclear cells and total leukocytes of CML patients and healthy blood donors in peripheral blood. It was also evaluated in bone marrow donors, in human cell lines (K562, HL60 and NB4) and in mice cell lines (BaF3/BCR-ABLp210 and BaF3T315I), performed by real-time PCR for the following genes: SEPT5, β-actin and GAPDH. Experiments were also performed to verify the difference between the chemotaxis of granulocytic cells from controls and patients by ELISA. Data were analysed statistically using the ANOVA followed by Dunnett’s test – P value of less than 0.05 was considered to be significant. The study was approved by the Research Ethic Committee of the Faculty of Medical Sciences of University of Campinas. The gene expression of SEPT5 was evaluated by real time PCR using the same samples used in the library construction to validate the results found in the SSH library. The data confirmed our previous results, showing that the SEPT5 expression is increased in all cells of patients compared to controls. The same results were observed when we studied the expression comparing individually patients and health blood donors, suggesting that this protein could be increased in all human cells that present the translocation BCR-ABL. The level of expression of this gene in HL60 and NB4 was significantly lower than in K562 cell line. The experiments with mice cell lines showed a higher expression of this gene in BaF3T315I when compared to BaF3BCR-ABLp210. We obtained a significant expression difference in all experiments (p <0.05). The spontaneous and stimulated with IL-8 chemotaxis assays used granulocytes and were assessed using chamber containing 96 wells. However, although the results suggest an increased chemotactic activity in patients, there were no significant differences (p<0.05) between controls and patients – regardless of whether the chemotaxis was spontaneous or stimulated with IL-8. In mammals the SEPT5 gene is associated with cellular processes such as exocytosis, apoptosis, leukemogenesis, carcinogenesis and neurodegeneration. Therefore, molecules capable of interacting with the septins, either at biochemical or molecular level, can bring information about their functions in cytokinesis. Studies indicate that the human septins can interact among themselves and with other components of the cytoskeleton – this may be a relevant observation regarding the function of this gene in cancer. The SEPT5 can be activated by different pathways – this may increase expression in translocated cells. Despite major advances in the treatment of CML, the treatments available are not capable of inactivating all the signaling pathways activated by BCR/ABL. Our results demonstrate that SEPT5 may be involved in the pathophysiology of CML. Also, it is clear the importance of the study of pathways that could culminate in its high expression or the triggering of other unknown pathways involved in the development of CML. The increased expression of this gene may be related to disease progression, and finally, the identification of several important genes may lead to a better understanding of CML and helping to identify new therapeutic targets. FAPESP/INCT. Disclosures: No relevant conflicts of interest to declare.
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Melchor, Lorenzo, John R. Jones, Oleg Lenive, Erich Allen Peterson, Annamaria Brioli, Alex Murison, Christopher P. Wardell, et al. "Spatiotemporal Analysis of Intraclonal Heterogeneity in Multiple Myeloma: Unravelling the Impact of Treatment and the Propagating Capacity of Subclones Using Whole Exome Sequencing." Blood 126, no. 23 (December 3, 2015): 371. http://dx.doi.org/10.1182/blood.v126.23.371.371.
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Abstract Introduction Multiple myeloma (MM) is characterised by the malignant expansion of clonal plasma cells in the bone marrow (BM). We and others have used massive parallel sequencing to describe the somatic aberrations acquired in different subclones in newly diagnosed MM (NDMM). These studies have showed that chemotherapy has an impact on intra-clonal heterogeneity, but more analyses are required in paired presentation/relapse samples and samples from multiple sites at the same and different time points. Materials and methods We have studied 49 paired presentation/relapse patients from a series of 463 NDMM patients entered into the Myeloma XI trial (NCT01554852). To understand the impact of spatial separation within the MM clone and the consideration that MM is a metastatic disease, we examined BM aspirates and compared them to targeted biopsies from extramedullary disease sites in 9 MM patients. These cases were 1 patient with samples bilaterally collected from the hip during the course of the disease, 4 MM cases with plasma cell leukemia (PCL), 3 MM cases with plasmacytomas, 1 MM patient with ascites, and 1 MM case with pleural effusion. DNA from both BM and peripheral blood samples were used for whole exome sequencing plus a pull down of the MYC, IGH, IGL and IGK loci following the SureSelect Target Enrichment System for Illumina Paired-End Sequencing Library v1.5. Exome reads were used to call single nucleotide variants, indels, translocations, and copy number aberrations. Mean sequencing depth was 59.3x. The proportion of mutant tumor cells carrying a mutation was inferred. The presence and proportion of subclones will be defined using bioinformatics tools. Results For the 463 NDMM samples, the following 15 significantly mutated genes are seen KRAS (n=103 mutations), NRAS (n=88), LTB (n=53), DIS3 (n=49), BRAF (n=37), EGR1 (n=22), FAM46C (n=20), IRF4 (n=19), TRAF3 (n=17), HIST1H1E (n=16), TP53 and FGFR3 (n=14), CYLD (n=13), MAX (n=12), and RB1 (n=5). These mutations were seen within all clonal cells and at subclonal levels, consistent with the mutations being acquired at different time points and being associated with different subclonal fitness. We show that NDMM have a mean number of exonic mutations of 61.1±13.0, in contrast to samples taken at the time of relapse, which show an average of 80.6±25.4, Figure 1A. We report diverse patterns of subclonal evolution: no change, subclonal tiding, and subclonal tiding with new subclones arising. We are currently examining samples taken during clinical remission to track subclones at the time of response. For patient with multiple samples taken at different timepoints, 77 mutations were shared across all samples but, of note, specific mutations were seen at the same timepoint in different sites (13/1662 R2R vs 13/1662 R2L), which illustrates the impact of sampling differences in reporting mutation calls and differential response to therapy, Figure 1B. This is also observed in a plasmacytoma case with both a BM aspirate sample containing 11 mutations (including NRAS c.183A>T and BRAF c.1783T>C), and a femur plasmacytoma with 18 mutations, of which only 2 are shared with the BM sample, Figure 3. One of these shared lesions is BRAF c.1783T>C, the cancer clonal fraction of which increases ten-fold, suggesting that the sub-clone with this mutation disseminated from the BM and founded the plasmacytoma. Conclusion Our preliminary data demonstrate that MM subclones not only respond differently to clinical treatment, but also have different biological properties leading to cause extramedullary disease. To our knowledge, this is the first comprehensive genetic analysis of the spatio-temporal heterogeneity in myeloma and reveals genetic differences due to sampling bias. Figure 1. (A) Number of mutations in MM patients at clinical presentation and relapse. Each patient sample is represented by a dot. Lines and error bars correspond to the average and the standard error of the mean values, respectively. Difference was not statistically significant (p >0.05, t-test). (B) MM patient analysed at presentation and following two relapses (top). The number of mutations increases through disease (bottom, left panel). Venn plot shows the number of shared and specific mutations for each time point (bottom, right panel). (C) Case with a MM sample (green) and a femur plasmacytoma (blue). Venn plot shows shared and specific mutations to the bone marrow or the plasmacytoma site. Figure 1. (A) Number of mutations in MM patients at clinical presentation and relapse. Each patient sample is represented by a dot. Lines and error bars correspond to the average and the standard error of the mean values, respectively. Difference was not statistically significant (p >0.05, t-test). (B) MM patient analysed at presentation and following two relapses (top). The number of mutations increases through disease (bottom, left panel). Venn plot shows the number of shared and specific mutations for each time point (bottom, right panel). (C) Case with a MM sample (green) and a femur plasmacytoma (blue). Venn plot shows shared and specific mutations to the bone marrow or the plasmacytoma site. Disclosures Jones: Celgene: Other: Travel support, Research Funding. Peterson:University of Arkansas for Medical Sciences: Employment. Brioli:Celgene: Honoraria; Janssen: Honoraria. Pawlyn:Celgene: Honoraria, Other: Travel support; The Institute of Cancer Research: Employment. Gregory:Janssen: Honoraria; Celgene: Honoraria. Davies:Onyx-Amgen: Membership on an entity's Board of Directors or advisory committees; Array-Biopharma: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda-Millennium: Membership on an entity's Board of Directors or advisory committees; University of Arkansas for Medical Sciences: Employment. Morgan:CancerNet: Honoraria; University of Arkansas for Medical Sciences: Employment; MMRF: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Weisman Institute: Honoraria; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda-Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees.
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Hu, Eileen, Hatice Gulcin Ozer, Arletta Lozanski, Tzyy-Jye Doong, Chi-Ling Chiang, Seema A. Bhat, Kerry A. Rogers, et al. "LC-Facseq: A Novel Method for Detecting Rare Resistant Clones in Leukemia." Blood 134, Supplement_1 (November 13, 2019): 3377. http://dx.doi.org/10.1182/blood-2019-126070.
Повний текст джерелаАнотація:
Introduction: Targeted irreversible Bruton's Tyrosine Kinase (BTK) inhibitors ibrutinib and acalabrutinib, have revolutionized treatment for chronic lymphocytic leukemia (CLL). While BTK inhibition (BTKi) achieves durable responses in 90% of patients, only 10% achieve minimal residual disease (MRD) negative status. MRD positive patients have persistent residual CD5+CD19+ tumor B cells at approximately 1-5 /mm3 in peripheral blood. These cells may represent a subpopulation of B-cell lymphocytosis pre-malignant cells or may carry a BTK C481, PLCG2, or other CLL mutation that is ultimately responsible for disease relapse. Alternatively, MRD could be derived from the original clones present at initial disease presentation that are not dependent on BTK signaling. Readily available clinical DNA sequencing and MRD monitoring techniques lack the ability to characterize these cells adequately due to their rarity in peripheral blood. To address this problem, we developed a novel method for limited-cells using fluorescence activated cell sorting in tandem with next generation sequencing (LC-FACSeq) to characterize rare tumor subpopulations in the blood and bone marrow. LC-FACSeq may be useful not only for CLL but also other leukemias. Methods: LC-FACSeq uses fluorescent activated cell sorting (FACS) to isolate pure populations of rare tumor cells after which targeted deep sequencing is performed to monitor CLL-related mutations in NOTCH1, SF3B1, and TP53, as well as genes associated with BTKi relapse and resistance: BTK and PLCG2. For validation of this method, we generated libraries from DNA isolated from FACS isolated bulk (n >15000) versus n= 50, 100, 300, or 500 CD5+/CD19+ cells from CLL patients (n=5). Results: All samples analyzed had an average read depth of 1212 (SEM=56) per gene and an average coverage uniformity of 88.24% (SEM=.01). We show that showed that 300-cell LC-FACSeq libraries demonstrated comparable variant calling and minimal noise to standard libraries generated from purified DNA from bulk cells. Using samples from patients with previously identified BTK C481S mutations, we found that both sensitivity and specificity of LC-FACSeq for BTK C481S was 100%. Furthermore, LC-FACSeq reliably amplified BTK C481S signals from subclones as small as 6 in 300 total cells (2%) when mutated tumor cells were serially diluted into BTK wild type tumor cells. In using LC-FACSeq to retrospectively analyze four independent patients who developed Ibrutinib resistance, we found that we could see the emergence of small BTKi resistant subclones as early as 10 months before clinical detection. We next extended LC-FACSeq to examine the clonal architecture of long-term (> 12 months) ibrutinib-treated MRD positive patients. Median treatment time was 5 years. BTK C481S mutations were observed in the latest available on-treatment samples of only one patient. Using LC-FACSeq we observed canonical CLL-associated clonal mutations similar to those observed in previous studies. Of the 14 MRD positive patients, 7 showed subclonal changes in TP53, NOTCH1, POT1, SF3B1, and MYD88 over the course of ibrutinib treatment although we found no correlation or consensus in these clonal shifts. Conclusion: LC-FACSeq is a highly sensitive method of characterizing clonal evolution in rare cells. Our data shows that LC-FACSeq is useful for monitoring sequential acquisition of mutations conferring therapy resistance and clonal evolution in long-term ibrutinib treated chronic lymphocytic leukemia (CLL) patients. We also observe that in most cases, MRD clones after long-term ibrutinib treatment are genetically similar to disease clones from pretreatment baseline. Compared to current MRD monitoring strategies, the main advantages of LC-FACSeq are that 1) variants can be confidently called from rare sorted tumor populations and subpopulations, 2) library generation can be completed in less than a day in a diagnostic laboratory compared to the labor-intensive protocols of traditional NGS approaches, and 3) amplicon panels can be easily customized for application to other types of leukemia and lymphoma. (EH is supported by the Graduate Pelotonia Fellowship and the NIH F30) Disclosures Bhat: Janssen: Consultancy; Pharmacyclics: Consultancy. Rogers:Janssen: Research Funding; AbbVie: Research Funding; Genentech: Research Funding; Acerta Pharma: Consultancy. Woyach:AbbVie: Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Karyopharm: Research Funding; Loxo: Research Funding; Morphosys: Research Funding; Verastem: Research Funding. Lozanski:Beckman Coulter: Research Funding; Stemline Therapeutics Inc.: Research Funding; Genentec: Research Funding; Boehringer Ingelheim: Research Funding. Muthusamy:Ohio State University: Patents & Royalties: OSU-2S. Byrd:Novartis: Other: Travel Expenses, Speakers Bureau; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; BeiGene: Research Funding; Ohio State University: Patents & Royalties: OSU-2S; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Ohio State University: Patents & Royalties: OSU-2S; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Acerta: Research Funding; BeiGene: Research Funding; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Genentech: Research Funding; Genentech: Research Funding; Acerta: Research Funding.
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Bell, Jill A., Farrah Anne Pompilus, Alissa Rams, Yanyan Zhu, Anna Ciesluk, Rafael Bejar, Robert J. Fram, Douglas V. Faller, and Patrick Marquis. "Patient-Centered Evaluation of Clinical Benefit in Acute Myeloid Leukemia: Importance of Early Engagement with Patients." Blood 134, Supplement_1 (November 13, 2019): 5898. http://dx.doi.org/10.1182/blood-2019-128517.
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INTRODUCTION Acute myeloid leukemia (AML), the most common form of acute leukemia among adults, is characterized by proliferation of immature myeloid cells in the peripheral blood, bone marrow, and/or other tissues, resulting in cytopenias. Clinical features such as anemia cause fatigue and dyspnea, which may negatively impact health-related quality of life, emphasizing the need for patient-centered outcomes to evaluate new therapies. Patients are uniquely positioned to inform the understanding of the therapeutic context for clinical development and provide additional information not captured by traditional clinical measures. Understanding the AML patient experience is essential for selecting relevant patient-reported outcome (PRO) measures. The purpose of this research was to incorporate the patient voice and generate an evidence base for selecting PRO endpoints for assessing clinical benefit. METHODS A cross-sectional, qualitative study was implemented among AML patients identified through clinical recruitment agencies and a patient advocacy organization. A targeted literature review (PubMed, Jan '00-Feb '19) and expert clinician consultation were conducted to explore the clinical perspective on treatment and observed patient experience. Following approval from an independent review board, qualitative concept-elicitation interviews were conducted with AML patients using a semi-structured interview guide. Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and items from the EORTC item library; items were selected based on previous research in patients with myelodysplastic syndromes. All interviews were audio-recorded, transcribed, and analyzed thematically using inductive coding targeting manifestations of symptoms and impacts. To ensure enough patients were interviewed, saturation was assessed based on the number of new codes emerging in the data. RESULTS Patients were 63 (±6.3) years old; 65% female; 80% white; 75% retired; 95% married. Half were diagnosed within the last 6 months and 25% within 7-12 months of the interviews. Approximately 60% of patients were receiving treatment. Eastern Cooperative Oncology Group status (range: 0, fully active without restriction to 4, completely disabled and confined to bed or chair) was reported by patients (0=5%; 1=25%; 2=35%; 3=30%; 4=5%). A wide range of symptoms was reported by patients; among the most frequent were tiredness, general fatigue, lack of energy, shortness of breath on exertion, weakness, dizziness or lightheadedness, bruising, bleeds (nose/gums), body aches/pain, fever, night sweats, constipation, and diarrhea (Figure). The following themes emerged from the analysis of symptom-related codes: fatigue, shortness of breath, dizziness, bleeding, general malaise/pain, and gastrointestinal issues. Patients reported a wide range of impacts on their daily lives, which included having to stay in bed/chair/couch, difficulty walking, difficulty lifting heavy objects, moving slowly, needing to take breaks, napping/sleeping during the day, not getting restful sleep, needing to lie down, difficulty doing various activities (e.g., driving, shopping, preparing food, doing yardwork, laundry), spending less time with family/friends or caring for yourself/others, depressed mood, worry, and having to be careful/mindful of risk of infection. The following main themes emerged from the analysis of impact-related codes: daily life functioning, leisure activities, physical mobility, sleep, social limitations, and psychological impact. Other themes that were reported by patients included appearance, cognition, and work (Figure). Debriefing results indicated that all patients comprehended the EORTC items tested and confirmed their relevance. CONCLUSIONS Direct patient engagement via qualitative research and thematic analysis provided a valuable evidence base to inform the selection of conceptually relevant PRO measures. The themes suitable for inclusion in clinical programs should be further discussed. Based on this research, the EORTC QLQ-C30 is a reasonable instrument for use in patients with AML. Early involvement of patients allows for potential inclusion of supplemental symptom and impact items from the EORTC Item Library in clinical programs to improve conceptual coverage of the patient experience. Disclosures Bell: Takeda Pharmaceuticals: Employment, Equity Ownership. Pompilus:Takeda Pharmaceuticals: Research Funding; Modus Outcomes: Employment. Rams:Modus Outcomes: Employment; Takeda Pharmaceuticals: Research Funding. Zhu:Takeda Pharmaceuticals: Employment. Ciesluk:Modus Outcomes: Employment; Takeda Pharmaceuticals: Research Funding. Bejar:Celgene: Consultancy; Takeda Pharmaceuticals: Research Funding; AbbVie/Genentech: Consultancy, Honoraria; Astex/Otsuka: Consultancy; Modus Outcomes: Consultancy; Daiichi-Sankyo: Consultancy. Fram:BeyondSpring Pharmaceuticals, Inc.: Consultancy; Takeda Pharmaceuticals: Employment. Faller:Boston University: Employment; Phoenicia Biosciences: Equity Ownership; Viracta Pharmaceuticals: Equity Ownership; Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment; Briacell Pharmaceuticals: Equity Ownership. Marquis:Takeda Pharmaceuticals: Research Funding; Modus Outcomes: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.