bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulídeos da Serra da Bocaina: observações bionômicas, revalidação de Simulium brevifurcatum Lutz e descrição de uma espécie nova, S. ana-mariae (Diptera, Simuliidae)
Authors: Vulcano M. A.
Published: April 2024

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Variações das conexões ósseas do ângulo orbital súpero-interno dos símios do gênero Alouatta (Primates, Cebidae)
Authors: Melhem Sérgio A. M.
Published: April 2024

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Lista preliminar dos mamíferos do Amapá
Authors: Carvalho Cory T. de
Published: April 2024

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Retoques à classificação das formigas neotropicais do gênero Heteroponera Mayr (Hym., Formicidae)
Authors: Kempf Walter W.
Published: April 2024

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Quatro novas espécies de microdontinae do Brasil (Diptera, Syrphidae)
Authors: Papavero Nelson
Published: April 2024

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Estrutura interna e presença de segmentos do êmbolo no epígino de Latrodectus geometricus (Araneida: Theridiidae)
Authors: De Biasi Persio
Published: April 2024

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Scolytoidea (Coleoptera). I. Notas sôbre algumas espécies neotropicais de Platypus, com descrição de uma nova espécie
Authors: Reichardt Hans
Published: April 2024

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Ibidionini (Coleoptera, Cerambycinae). XIX. Gênero Ibidion Serville: espécies próximas de Signatum Serv.
Authors: Martins Ubirajara R.
Published: April 2024

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Sôbre as raças geográficas brasileiras de Amazona brasiliensis (L., 1758) (Aves, Psittacidae)
Authors: Camargo Hélio F. de Almeida
Published: April 2024

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Nuevos Estafilinideos Parasitos de Roedo-Res y clave para las especies del gênero Amblyopinodes Seevers, 1955. (Col. Staphylinidae).
Authors: Machado-Allison C. E.
Published: April 2024

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Notes on the Myrmecomimicry of Syringogaster rufa Cresson, 1912 (Diptera, Acalyptratae, Megamerinidae)
Authors: Papavero Nelson
Published: April 2024

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Hoplomutilla triumphans Mickel, 1939 (Hymenoptera, Mutillidae) como parasito de abelhas do gênero Euplusia (Hymenoptera, Apoidea)
Authors: Lenko Karol
Published: April 2024

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Ocorrência de Iodopleura p. pipra no estado de São Paulo, Brasil, e algumas notas sôbre Iodopleura isabellae (Aves, Cotingidae)
Authors: Camargo Hélio F. de Almeida , Camargo Eurico A. de
Published: April 2024

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Sôbre o mimetismo do cerambicídeo Pertyia sericea (Perty, 1830) com Camponotus sericeiventris (Guérin, 1830)
Authors: Lenko Karol
Published: April 2024

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Nineteenth century south american araneology
Authors: Levi Herbert W.
Published: April 2024

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Insecta amapaensia: Hispinae (Col. Chrysomelidae). 218. Beitrag zur kenntnis der Hispinae
Authors: Uhmann Erich
Published: April 2024

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Ibidionini (Coleoptera, Cerambycinae). XXV. Ophtalmoplon, novo gênero com cinco novas espécies
Authors: Martins Ubirajara R.
Published: April 2024

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Considerações em tôrno de Thelastoma Leidy, 1850 e Cephalobellus Cobb, 1920 (Nematoda)
Authors: Kloss G. R.
Published: April 2024

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Notas sôbre o crescimento de Astyanax bimaculatus (Pisces, Characidae)
Authors: Vanzolini P. E. , Rebouças Regina
Published: April 2024

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Fauna helmintológica do Peru: alguns nematodeos parasitos de Bufo spinulosus limensis (Werner)
Authors: Freitas J. F. Teixeira de , Ibáñez Nicanor
Published: April 2024

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Novo gênero de Languriinae (Col., Languriidae)
Authors: Martins Ubirajara R.
Published: April 2024

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Notas sôbre Culicidae (Diptera). VI. Novos dados sôbre algumas espécies do subgênero Culex
Authors: Forattini Oswaldo P. , Rabello Ernesto X.
Published: April 2024

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Gênero Crotchia Fowler, 1886 (Col., Languriidae)
Authors: Martins Ubirajara R.
Published: April 2024

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Lista dos helmintos parasitos de peixes encontrados na Estação Experimental de Biologia e Piscicultura de Emas, Pirassununga, estado de São Paulo
Authors: Travassos Lauro , Kohn Anna
Published: April 2024

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Ibidionini (Coleoptera, Cerambycinae). XXIV. Divisão do gênero Compsa Perty, 1832
Authors: Martins Ubirajara R.
Published: April 2024

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Nova espécie de Coccoderus Buquet, 1840 (Col., Cerambycinae)
Authors: Lane Frederico , Martins Ubirajara R.
Published: April 2024

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Descrição da rainha de Plebeia (Plebeia) droryana (Friese, 1900) (Hymenoptera, Apoidea)
Authors: Oliveira Bernardete Lucas de
Published: April 2024

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Dois novos opiliões da Argentina (Opiliones: Cosmetidae, Gonyleptidae)
Authors: Soares Helia E. M.
Published: April 2024

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A contribution to the knowledge of the neotropical Rhinotoridae (Diptera, Acalyptratae)
Authors: Guimarães J. H. , Papavero Nelson
Published: April 2024

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Novas espécies do gênero Eulachnesia Bates, 1872 (Coleoptera, Lamiidae)
Authors: Lane Frederico
Published: April 2024

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Opiliões da "Coleção Gofferjé" (Opiliones: Gonyleptidae, Phalangodidae)
Authors: Soares Helia E. M.
Published: April 2024

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Three new brazilian species of Pseudogaurax with a synopsis of the genus in the western hemisphere (Diptera, Chloropidae)
Authors: Sabrosky Curtis W.
Published: April 2024

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Novos gêneros e espécies de Aerenicini. II. (Coleoptera, Lamiidae)
Authors: Lane Frederico
Published: April 2024

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Notes on the neotropical Agromysidae (Diptera). I
Authors: Spencer Kenneth A.
Published: April 2024

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Uma nova Olivancillaria (Gastropoda, Olividae) nas praias do Rio Grande do Sul, Brasil
Authors: Thomé José Willibaldo
Published: April 2024

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A new south american species of Nyssicostylus Melzer (Coleoptera, Carambycidae)
Authors: Chemsak Jonh A. , Martins Ubirajara R.
Published: April 2024

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Studies on south american anoles. Anolis transversalis A. Duméril
Authors: Williams Ernest E. , Vanzolini P. E.
Published: April 2024

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Contribuição ao estudo da bicefalia (Deródimos) em lagartos
Authors: Rosa Carlos Nobre
Published: April 2024

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Nueva especie de Modiolus (Mollusca, Pelecypoda) de la costa brasileña
Authors: Klappenbach Miguel A.
Published: April 2024

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Synonymic note on Coeloxenus guentheri Wasmann (Coleoptera, Carabidae)
Authors: Reichardt Hans
Published: April 2024

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On a new genus of Hypolithinae (Col., Elateridae)
Authors: Costa Cleide
Published: April 2024

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Notas sinonímicas. III. Sôbre a identidade de Acanthoibidion venezuelensis F. Lane, 1951, com Piezocera chevrolatii White, 1855 (Coleoptera, Cerambycidae)
Authors: Lane Frederico
Published: April 2024

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Observações sôbre o intestino posterior de alguns Passalidae (Col.) americanos
Authors: Pereira F. S. , Kloss G. R.
Published: April 2024

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A formiga Leptogenys bohlsi como predadora de isópodos (Hymenoptera: Formicidae)
Authors: Lenko Karol
Published: April 2024

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Influência da alimentação no desenvolvimento de algumas glândulas de Trigona (Scaptotrigona) postica Latreille (Hymenoptera – Apoidea)
Authors: Landim Carminda da Cruz , Akahira Yukio
Published: April 2024

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Novas espécies de Torneutini (Coleoptera, Cerambycidae)
Authors: Lane Frederico
Published: April 2024

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Considerações sôbre o grupo "Tripunctata" (Drosophila), com descrição de D. mirassolensis, nova espécie brasileira
Authors: Mourão Celso Abbade , Gallo Aluisio José
Published: April 2024

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Aplicação de princípios modernos à sistemática do gênero Melipona Illiger, com a divisão em dois subgêneros (Hymenoptera, Apoidea)
Authors: Kerr Warwick Estevam , Pisani José Furtado , Aily Dair
Published: April 2024

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Bionomia de Dinia aeagrus (Cramer, 1779) (Lepidoptera, Ctenuchidae)
Authors: Travassos Filho Lauro , Urban Helga
Published: April 2024

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Morfologia externa de Melipona (Melipona) marginata Lepeletier (Hymenoptera, Apoidea)
Authors: Camargo João M. F. de , Kerr Warwick E. , Lopes Catalina R.
Published: April 2024

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Rhynchosciara baschanti (Diptera, Nematocera, Sciaridae), a new brazilian species
Authors: Breuer Marta Erps
Published: April 2024

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Três novas espécies do gênero Characidium Reinhardt, 1866 (Actinopterygii, Characoidei)
Authors: Travassos Haroldo
Published: April 2024

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Gênero Crotchia Fowler (Col., Languriidae). III. Espécies com élitros de lados paralelos
Authors: Martins Ubirajara R. , Costa Cleide
Published: April 2024

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Ptyopteryx britskii, a new neotropical genus and species of the hitherto ethiopian Torridincolidae (Coleoptera, Myxophaga)
Authors: Reichardt Hans , Costa Cleide
Published: April 2024

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Sôbre o gênero Augastes, com a descrição de uma subespécie nova (Aves, Trochiliidae)
Authors: Grantsau Rolf
Published: April 2024

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Chelodesmid studies. III. Notes on the status of Gonioleptodesmus, the description of a new species from Minas Gerais, and a key to the presently known members of the genus (Diplopoda, Polydesmida)
Authors: Hoffman Richard L.
Published: April 2024

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Notas sôbre Cerambycinae (Col., Cerambycidae)
Authors: Martins Ubirajara R.
Published: April 2024

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A note on a new species of Strongyloides from the toad (Nematoda, Strongyloididae)
Authors: Rao P. Narayan , Singh S. N.
Published: April 2024

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Os ofiuróides existentes nas coleções do Museu de Buenos Aires coletados do La Plata até 42° latitude sul
Authors: Tommasi Luiz Roberto
Published: April 2024

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Neue hispinae aus brasilien (232. Beitrag zur kenntnis der Hispinae; Coleoptera, Chrysomelidae)
Authors: Uhmann Erich
Published: April 2024

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A new brazilian species of Phellopteron Hull (Diptera, Asilidae)
Authors: Hradský Milán
Published: April 2024

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Environmental temperature and number of body annuli in Amphisbaena alba: notes on a cline (Sauria, Amphisbaenidae)
Authors: Vanzolini P. E.
Published: April 2024

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On Stenocheila Castelnau (Coleoptera, Carabidae)
Authors: Reichardt Hans
Published: April 2024

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Deux agriides (Coleoptera, Carabidae) nouveaux
Authors: Straneo S. L.
Published: April 2024

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Records and descriptions of Tipulidae from South America (Diptera). II
Authors: Alexander Charles P.
Published: April 2024

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The genus Scleroderma in South America (Hymenoptera, Bethylidae)
Authors: Evans Howard E.
Published: April 2024

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A review of the genus Hyperalonia Rondani (Bombyliidae, Diptera) from South America
Authors: Painter Reginald H. , Painter Elizabeth M.
Published: April 2024

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Description of a new species of Bradysia (Diptera, Sciaridae)
Authors: Sauaia H. , Alves M. A. R.
Published: April 2024

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Notes on african Bolboceratini (Coleoptera, Geotrupidae)
Authors: Vulcano M. A. , Martinez A. , Pereira F. S.
Published: April 2024

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The food of Brycon and three closely related genera of the tribe Acestrorhynchini
Authors: Menezes Naércio A.
Published: April 2024

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Ocorrência de Mikadotrochus no Brasil, com descrição de uma nova espécie (Gastropoda, Pleurotomariidae)
Authors: Leme José Luiz Moreira , Penna Lícia
Published: April 2024

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Further notes on american Pentagonicini: on the venezuelan species (Coleoptera, Carabidae)
Authors: Reichardt Hans
Published: April 2024

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The subfamilies of the family Dolichopodidae in North and South America (Diptera)
Authors: Robinson Harold
Published: April 2024

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Notas sôbre Parandrinae (Col., Cerambycidae). I. Redescrição de Parandra expectata Lameere, 1902
Authors: Arigony Tania H. de Araujo
Published: April 2024

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Catalogue of new world Dermaptera (Insecta). Part III: Labioidea, Labiidae
Authors: Reichardt Hans
Published: April 2024

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A new mexican Saropogon (Diptera, Asilidae)
Authors: Papavero Nelson
Published: April 2024

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Contribuições das metodologias ativas de aprendizagem em contabilidade: uma revisão integrativa
Authors: Bazani Camila Lima , Santos Geovane Camilo
Published: April 2024

This research aims to conduct an integrative review to identify the contributions of active learning methodologies to the development of student's skills in accounting disciplines, as well as to present possibilities for future research. The articles were collected from the Scopus database, using the expressions "Accounting" and "Active Learning" and "Accounting" and "Active Methodology", linked by the connector "and". The final sample consists of 79 papers, and an integrative review is used to analyze the articles. The results revealed that: i) most studies were developed after 2011; ii) researchers are applying active methodologies in countries from 5 continents, predominantly in the United States of America; iii) the most used active methodologies were case studies, Problem-Based Learning (PBL), flipped classroom, and methodologies focused on technologies. It is concluded that active methodologies are valid and effective in developing a context that enhances students' professional and emotional competencies. This study contributes to researchers by presenting the results of previous research as well as indicating possibilities for future research and constant gaps in the literature, using the integrative review, which is a little methodology explored in the accounting area and can synthesize knowledge and present the applicability of results from existing studies.
Thorictus cirenaicus John, 1965 and Thorictus cirenaicus A. Fiori, 1914, a peculiar case of concomitant subjective synonymy and primary homonymy (Coleoptera, Dermestidae, Thorictinae)
Authors: POGGI ROBERTO
Published: April 2024

The description of Thorictus cirenaicus made by Andrea Fiori in a paper of 1914 escaped all subsequent entomologists who worked on the group, so much so that in 1965 Hans John described Thorictus cirenaicus as a new species from one of the syntypes recorded by Fiori, giving rise to a peculiar case of concomitant synonymy and homonymy.
Revision of the leafhopper genus Okubasca Dworakowska (Hemiptera: Cicadellidae: Typhlocybinae), with description of a new species from kiwifruit in China
Authors: ZHANG PENG-WEN , DIETRICH CHRISTOPHER H. , SU JIAN-XIONG , XU YE
Published: April 2024

The empoascine genus Okubasca Dworakowska is reviewed based on specimens from China. One new species, O. wuningensis Zhang & Xu, sp. nov. is described from Jiangxi in South China. An identification key to all species in the genus is provided. Empoascini associated with kiwi orchards in China are also discussed.
Description of twelve new species of Platypalpus Macquart from Europe and the Middle East (Diptera, Empidoidea, Hybotidae)
Authors: BARTÁK MIROSLAV , GROOTAERT PATRICK
Published: April 2024

Twelve new species of Platypalpus Macquart from Europe and the Middle East are described, classified in three out of the eleven West-Palaearctic species groups. The albiseta group is represented by only one species: P. flavisetoides sp. nov. (Turkey). Two species belong to the longicornis group: P. curvifemur sp. nov. (Turkey) and P. vercorsensis sp. nov. (France). The pallidiventris-cursitans group is the most abundant group with nine species: P. exsectus sp. nov. (Bulgaria), P. huzur sp. nov. (Turkey, Greece), P. kayakoyensis sp. nov. (Turkey), P. kubiki sp. nov. (Spain), P. lorcaensis sp. nov. (Spain), P. sanrossorensis sp. nov. (Italy), P. serviae sp. nov. (Spain, Portugal), P. slovacus sp. nov. (Slovakia) and P. turgidoides sp. nov. (Spain).
A new species of Sympodium (Octocorallia, Xeniidae) from Miyazaki, Japan
Authors: KOIDO TATSUKI , IMAHARA YUKIMITSU , FUKAMI HIRONOBU
Published: April 2024

In this study, a new soft coral species, Sympodium omasum sp. nov. (Malacalcyonacea, Xeniidae), is described from a warm-temperate region in Miyazaki, Japan. This new species has double-heads and platelet sclerites, and the platelets are covered with sinuous rodlets, which are fused and form many nodules at the sclerites surface. Sympodium omasum sp. nov. can be distinguished morphologically from a congeneric species by the double-head sclerites and unique platelet surface architecture.
Microedus LeConte, 1874 (Coleoptera: Staphylindae: Omaliinae: Anthophagini), a new genus for the Palaearctic Region
Authors: SHAVRIN ALEXEY V.
Published: April 2024

The genus Microedus LeConte, 1874 (Omaliinae: Anthophagini), previously known only from North America, is recorded for the Palaearctic fauna for the first time. Two palaearctic genera were synonymized with Microedus: Altaiodromicus Zerche, 1992 syn. n. and Liophilydrodes Nakane, 1983 syn. n. (replacement name for Lioplax Nakane & K. Sawada, 1956). The genus Microedus was redescribed, illustrated and its taxonomic relations with other genera of the Hygrogeus group are briefly discussed. Four species are (re-)described and illustrated: M. brevitarsis (Champion, 1925) comb. n. (from Geodromicus) (India: Uttarakhand), M. kastcheevi sp. n. (Altai and Dzhungar mts., eastern Kazakhstan), M. schilenkovi (Zerche, 1992) comb. n. (from Altaiodromicus) (Russia (Altai), Kazakhstan), and M. subtilis (Sharp, 1889) comb. n. (from Liophilydrodes) (Russia, Japan). An additional species from Kashmir remains unnamed due the absence of a male, and is compared with the Himalayan M. brevitarsis. A lectotype is designated for Anthophagus subtilis Sharp, 1889. Several new additional combinations are proposed (all these species were previously attributed to the genus Liophilydrodes): M. flavipennis (Watanabe, 1990) comb. n., M. pullus (Nakane & K. Sawada, 1956) comb. n., M. puncticollis (Nakane & K. Sawada, 1956) comb. n., M. suzukii (Watanabe, 1990) comb. n., and M. yamanakai (Watanabe, 1990) comb. n. The following new synonymies are established: M. subtilis = L. subtilis iturupensis Lafer, 2004 syn. n., = L. troglophilus Nakane & K. Sawada, 1956 syn. n. A key to Palaearctic species of Microedus is provided. Mouthparts and the aedeagus of the Nearctic M. austinianus LeConte, 1874 are illustrated for the first time. A distributional map of Microedus from Middle Asia is provided. Microedus schilenkovi is recorded from Kazakhstan for the first time. A checklist of the genus is presented. The genus Microdeus currently contains 16 species, seven in the Nearctic and nine in the Palaearctic Region.
Description of the female of Leptagrion itabaiana Vilela, Lencioni & Santos, 2021 (Odonata: Coenagrionidae) from Serra of Itabaiana National Park, Northeastern Brazil
Authors: FARIAS ANTONIO BRUNO SILVA , VENTURA IZA MAYRA CASTRO , VILELA DIOGO SILVA , SANTOS JEAN CARLOS
Published: April 2024

The unknown female, Leptagrion itabaiana Vilela, Lencioni & Santos, 2021 was described, illustrated, and diagnosed based on two specimens collected in the Serra of Itabaiana National Park (♀, Brazil, Sergipe, Areia Branca, Serra of Itabaiana National Park, -10.7484, -37.3390, 221 m, 24.v.2023, A. B. S. Farias leg., UFS). Leptagrion itabaiana female can be separated from their congeners by the following characteristic combinations: shape of the prothoracic hind lobe, body size, and ovipositor valves size.
BCR::ABL1 kinase N-lobe mutants confer moderate to high degrees of resistance to asciminib
Authors: Leyte-Vidal Ariel , Garrido Ruiz Diego , DeFilippis RosaAnna , Leske Inga B. , Rea Delphine , Phan Stacey , Miller Kaeli B. , Hu Feifei , Mase Anjeli , Shan Yibing , Hantschel Oliver , Jacobson Matthew P. , Shah Neil P.
Published: April 2024

Secondary kinase domain mutations in BCR::ABL1 represent the most common cause of resistance to tyrosine kinase inhibitor (TKI) therapy in patients with chronic myeloid leukemia. The first 5 approved BCR::ABL1 TKIs target the adenosine triphosphate (ATP)–binding pocket. Mutations confer resistance to these ATP-competitive TKIs and those approved for other malignancies by decreasing TKI affinity and/or increasing ATP affinity. Asciminib, the first highly active allosteric TKI approved for any malignancy, targets an allosteric regulatory pocket in the BCR::ABL1 kinase C-lobe. As a non–ATP-competitive inhibitor, the activity of asciminib is predicted to be impervious to increases in ATP affinity. Here, we report several known mutations that confer resistance to ATP-competitive TKIs in the BCR::ABL1 kinase N-lobe that are distant from the asciminib binding pocket yet unexpectedly confer in vitro resistance to asciminib. Among these is BCR::ABL1 M244V, which confers clinical resistance even to escalated asciminib doses. We demonstrate that BCR::ABL1 M244V does not impair asciminib binding, thereby invoking a novel mechanism of resistance. Molecular dynamic simulations of the M244V substitution implicate stabilization of an active kinase conformation through impact on the α-C helix as a mechanism of resistance. These N-lobe mutations may compromise the clinical activity of ongoing combination studies of asciminib with ATP-competitive TKIs.
Integrative single-cell chromatin and transcriptome analysis of human plasma cell differentiation
Authors: Alaterre Elina , Ovejero Sara , Bret Caroline , Dutrieux Laure , Sika Dassou , Fernandez Perez Raul , Espéli Marion , Fest Thierry , Cogné Michel , Martin-Subero José Ignacio , Milpied Pierre , Cavalli Giacomo , Moreaux Jérôme
Published: April 2024

Plasma cells (PCs) are highly specialized cells representing the end stage of B-cell differentiation. We have shown that PC differentiation can be reproduced in vitro using elaborate culture systems. The molecular changes occurring during PC differentiation are recapitulated in this in vitro differentiation model. However, a major challenge exists to decipher the spatiotemporal epigenetic and transcriptional programs that drive the early stages of PC differentiation. We combined single cell (sc) RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin with high throughput sequencing (scATAC-seq) to decipher the trajectories involved in PC differentiation. ScRNA-seq experiments revealed a strong heterogeneity of the preplasmablastic and plasmablastic stages. Among genes that were commonly identified using scATAC-seq and scRNA-seq, we identified several transcription factors with significant stage specific potential importance in PC differentiation. Interestingly, differentially accessible peaks characterizing the preplasmablastic stage were enriched in motifs of BATF3, FOS and BATF, belonging to activating protein 1 (AP-1) transcription factor family that may represent key transcriptional nodes involved in PC differentiation. Integration of transcriptomic and epigenetic data at the single cell level revealed that a population of preplasmablasts had already undergone epigenetic remodeling related to PC profile together with unfolded protein response activation and are committed to differentiate in PC. These results and the supporting data generated with our in vitro PC differentiation model provide a unique resource for the identification of molecular circuits that are crucial for early and mature PC maturation and biological functions. These data thus provide critical insights into epigenetic- and transcription–mediated reprogramming events that sustain PC differentiation.
Antibody-drug conjugate adverse effects can be understood and addressed based on immune complex clearance mechanisms
Authors: Taylor Ronald P. , Lindorfer Margaret A.
Published: April 2024

Numerous antibody-drug conjugates (ADCs) are being developed for cancer immunotherapy. Although several of these agents have demonstrated considerable clinical efficacy and have won Food and Drug Administration (FDA) approval, in many instances, they have been characterized by adverse side effects (ASEs), which can be quite severe in a fraction of treated patients. The key hypothesis in this perspective is that many of the most serious ASEs associated with the use of ADCs in the treatment of cancer can be most readily explained and understood due to the inappropriate processing of these ADCs via pathways normally followed for immune complex clearance, which include phagocytosis and trogocytosis. We review the key published basic science experiments and clinical observations that support this idea. We propose that it is the interaction of the ADC with Fcγ receptors expressed on off-target cells and tissues that can most readily explain ADC-mediated pathologies, which therefore provides a rationale for the design of protocols to minimize ASEs. We describe measurements that should help identify those patients most likely to experience ASE due to ADC, and we propose readily available treatments as well as therapies under development for other indications that should substantially reduce ASE associated with ADC. Our focus will be on the following FDA-approved ADC for which there are substantial literatures: gemtuzumab ozogamicin and inotuzumab ozogamicin; and trastuzumab emtansine and trastuzumab deruxtecan.
TEC-miTarget: enhancing microRNA target prediction based on deep learning of ribonucleic acid sequences
Authors: Yang Tingpeng , Wang Yu , He Yonghong
Published: April 2024

Background

MicroRNAs play a critical role in regulating gene expression by binding to specific target sites within gene transcripts, making the identification of microRNA targets a prominent focus of research. Conventional experimental methods for identifying microRNA targets are both time-consuming and expensive, prompting the development of computational tools for target prediction. However, the existing computational tools exhibit limited performance in meeting the demands of practical applications, highlighting the need to improve the performance of microRNA target prediction models.

Results

In this paper, we utilize the most popular natural language processing and computer vision technologies to propose a novel approach, called TEC-miTarget, for microRNA target prediction based on transformer encoder and convolutional neural networks. TEC-miTarget treats RNA sequences as a natural language and encodes them using a transformer encoder, a widely used encoder in natural language processing. It then combines the representations of a pair of microRNA and its candidate target site sequences into a contact map, which is a three-dimensional array similar to a multi-channel image. Therefore, the contact map's features are extracted using a four-layer convolutional neural network, enabling the prediction of interactions between microRNA and its candidate target sites. We applied a series of comparative experiments to demonstrate that TEC-miTarget significantly improves microRNA target prediction, compared with existing state-of-the-art models. Our approach is the first approach to perform comparisons with other approaches at both sequence and transcript levels. Furthermore, it is the first approach compared with both deep learning-based and seed-match-based methods. We first compared TEC-miTarget’s performance with approaches at the sequence level, and our approach delivers substantial improvements in performance using the same datasets and evaluation metrics. Moreover, we utilized TEC-miTarget to predict microRNA targets in long mRNA sequences, which involves two steps: selecting candidate target site sequences and applying sequence-level predictions. We finally showed that TEC-miTarget outperforms other approaches at the transcript level, including the popular seed match methods widely used in previous years.

Conclusions

We propose a novel approach for predicting microRNA targets at both sequence and transcript levels, and demonstrate that our approach outperforms other methods based on deep learning or seed match. We also provide our approach as an easy-to-use software, TEC-miTarget, at https://github.com/tingpeng17/TEC-miTarget. Our results provide new perspectives for microRNA target prediction.
Interpretable machine learning in predicting drug-induced liver injury among tuberculosis patients: model development and validation study
Authors: Xiao Yue , Chen Yanfei , Huang Ruijian , Jiang Feng , Zhou Jifang , Yang Tianchi
Published: April 2024

Background

The objective of this research was to create and validate an interpretable prediction model for drug-induced liver injury (DILI) during tuberculosis (TB) treatment.

Methods

A dataset of TB patients from Ningbo City was used to develop models employing the eXtreme Gradient Boosting (XGBoost), random forest (RF), and the least absolute shrinkage and selection operator (LASSO) logistic algorithms. The model's performance was evaluated through various metrics, including the area under the receiver operating characteristic curve (AUROC) and the area under the precision recall curve (AUPR) alongside the decision curve. The Shapley Additive exPlanations (SHAP) method was used to interpret the variable contributions of the superior model.

Results

A total of 7,071 TB patients were identified from the regional healthcare dataset. The study cohort consisted of individuals with a median age of 47 years, 68.0% of whom were male, and 16.3% developed DILI. We utilized part of the high dimensional propensity score (HDPS) method to identify relevant variables and obtained a total of 424 variables. From these, 37 variables were selected for inclusion in a logistic model using LASSO. The dataset was then split into training and validation sets according to a 7:3 ratio. In the validation dataset, the XGBoost model displayed improved overall performance, with an AUROC of 0.89, an AUPR of 0.75, an F1 score of 0.57, and a Brier score of 0.07. Both SHAP analysis and XGBoost model highlighted the contribution of baseline liver-related ailments such as DILI, drug-induced hepatitis (DIH), and fatty liver disease (FLD). Age, alanine transaminase (ALT), and total bilirubin (Tbil) were also linked to DILI status.

Conclusion

XGBoost demonstrates improved predictive performance compared to RF and LASSO logistic in this study. Moreover, the introduction of the SHAP method enhances the clinical understanding and potential application of the model. For further research, external validation and more detailed feature integration are necessary.
Role of NT-proBNP and lung ultrasound in diagnosing and classifying heart failure in a hospitalized oldest-old population: a cross-sectional study
Authors: Landolfo Matteo , Spannella Francesco , Giulietti Federico , Di Pentima Chiara , Giordano Piero , Borioni Elisabetta , Landi Laura , Di Rosa Mirko , Galeazzi Roberta , Sarzani Riccardo
Published: April 2024

Aim

Diagnosing and classifying heart failure (HF) in the oldest-old patients has technical and interpretation issues, especially in the acute setting. We assessed the usefulness of both N-terminal pro-brain natriuretic peptide (NT-proBNP) and lung ultrasound (LUS) for confirming HF diagnosis and predicting, among hospitalized HF patients, those with reduced ejection fraction (HFrEF).

Methods

We performed a cross-sectional study on 148 consecutive patients aged ≥ 80 years admitted to our Internal Medicine and Geriatrics ward with at least one symptom/sign compatible with HF and NT-proBNP ≥ 125 pg/mL. We measured serum NT-proBNP levels and performed LUS and transthoracic echocardiography (TTE) on admission before diuretic therapy. We divided our cohort into three subgroups according to the left ventricular ejection fraction (LVEF): reduced (LVEF ≤ 40%), mildly-reduced (LVEF = 41-49%) and preserved (LVEF ≥ 50%).

Results

The mean age was 88±5 years. Male prevalence was 42%. Patients with HFrEF were 19%. Clinical features and laboratory parameters did not differ between the three subgroups, except for higher NT-proBNP in HFrEF patients, which also had a higher number of total B-lines and intercostal spaces of pleural effusion at LUS. Overall, NT-proBNP showed an inverse correlation with LVEF (r = -0.22, p = 0.007) and a direct correlation with age, total pulmonary B-lines, and intercostal spaces of pleural effusion. According to the ROCs, NT-proBNP levels, pulmonary B-lines and pleural effusion extension were poorly predictive for HFrEF. The best-performing cut-offs were 9531 pg/mL for NT-proBNP (SP 0.70, SE 0.50), 13 for total B-lines (SP 0.69, SE 0.85) and one intercostal space for pleural effusion (SP 0.55, SE 0.89). Patients with admission NT-proBNP ≥ 9531 pg/mL had a 2-fold higher risk for HFrEF (OR 2.5, 95% CI 1.3-4.9), while we did not find any association for total B-lines ≥ 13 or pleural effusion ≥ 1 intercostal space with HFrEF. A significant association with HFrEF emerged for the combination of NT-proBNP ≥ 9531 pg/mL, total B-lines ≥ 13 and intercostal spaces of pleural effusion ≥ 1 (adjusted OR 4.3, 95% CI 1.5-12.9).

Conclusions

Although NT-proBNP and LUS help diagnose HF, their accuracy in discriminating HFrEF from non-HFrEF was poor in our real-life clinical study on oldest-old hospitalized patients, making the use of TTE still necessary to distinguish HF phenotypes in this peculiar setting. These data require confirmation in more extensive and longer prospective studies.
Correlation of sonographic with intraoperative findings in laparoscopic managed ectopic pregnancies, a 10-year synopsis: a restrospective observational study
Authors: Mutiso Steve Kyende
Published: April 2024

Background

Ectopic pregnancies (EP) are a common pregnancy complication that’s associated with significant morbidity and rarely mortality if not managed properly. Ultrasound examination forms the cornerstone of diagnosis of EP with some sonographic features occasionally not correlating with intraoperative findings. We set out to conduct an audit of EP managed surgically at our hospital for a 10-year period and discern the correlation and prediction of sonographic findings to intraoperative findings.

Methods

This study was designed as a Retrospective Observational Study based at the Aga Khan University Hospital (AKUH). Study population was all women admitted to AKUH with a diagnosis of ectopic pregnancy that was surgically managed between the period of January 1st 2011 to December 31st 2020. Analysis of data was done against a pre-set checklist. Descriptive statistics for continuous variables was calculated and tabulated in graphs and tables. SPSS version 22 was used for analysis of data.

Results

A total of 337 patients in this study had ultrasound findings. 99.7% (n = 336) of these patients had an intraoperatively confirmed EP. The commonest ultrasound finding was an adnexal mass in 97.1% (n = 309) of patients. These were confirmed surgically in 290 patients at the following locations: 76.6% (n = 222) were ampullary in location; 10.7% (n = 31) were fimbrial in location; 8.6%(n = 25) were isthmic in location; 2.4%(n = 7) were interstitial in location; 1%(n = 3) were abdominal in location; while 0.3% were located in the ovary(n = 1) or round ligament(n = 1) each. Interstitial EP on ultrasound were all (100%) confirmed in the same location intraoperatively, with ampullary EP also correlating fairly well with intraoperative location (75%). The distribution of location in the minor hemoperitoneum (HP) versus major HP groups were similar except for interstitial EP that increased from 1.4% in the minor HP group to 9.5% in the major HP group.

Conclusion

In conclusion, ultrasonography still represents the best imaging modality for EP. The most common finding is usually an adnexal mass with no specific location. Most (99.7%) of the patients with this sonographic finding usually have a confirmed EP. Interstitial EP are the most well localized with ultrasound followed by ampullary EP. Furthermore, the presence of major (> 500mls) hemoperitoneum may act as an adjunct for diagnosis of an interstitial EP.
Incidence and characteristics of aspiration pneumonia in the Nagasaki Prefecture from 2005 to 2019
Authors: Tomonaga Iku , Koseki Hironobu , Imai Chieko , Shida Takayuki , Nishiyama Yuta , Yoshida Daisuke , Yokoo Seiichi , Osaki Makoto
Published: April 2024

Background

Aspiration pneumoniae remains a major health concern, particularly in the older population and has poor prognosis; however, the concept itself remains vague worldwide. This study aimed to determine the actual situation and characteristics of aspiration pneumonia from 2005 to 2019 in Nagasaki Prefecture, Japan.

Methods

Cases of aspiration pneumonia that occurred in the Nagasaki Prefecture between 2005 and 2019 were analyzed using emergency transportation records. The number of occurrences and incidence were analyzed according to age, sex, month, day of the week, and recognition time to clarify the actual situation of aspiration pneumonia.

Results

The total number of new aspiration pneumonia cases was 8,321, and the mean age of the patients was 83.0 years. Annual incidence per 100,000 population increased from 12.4 in 2005 to 65.1 in 2019, with the most prominent increase in the ≥ 80-year-old stratum. Males (55.1%) were more commonly affected than females (44.9%), and 82.2% of the cases involved patients aged ≥ 70 years. No significant correlations were observed between the incidence of aspiration pneumonia and season, month, or day of the week. Aspiration pneumonia occurred frequently in houses (39.8%) and facilities for elderly individuals (40.8%). At 7 days after admission, 80.9% of patients were still hospitalized and 6.5% had died.

Conclusions

The incidence of aspiration pneumonia with risks of severity and mortality is increasing among elderly individuals. Valid preventive measures are urgently needed based on the findings that the disease occurs in both household and elderly care facility settings, regardless of the season.
How are new nurses satisfied with their jobs? From the work value perspective of Generations Y and Z nurses
Authors: Kim Eunkyung , Kim Heejung , Lee Taewha
Published: April 2024

Background

Job satisfaction has garnered significant interest across multiple disciplines as it plays a vital role in shaping human resource strategies. In the field of nursing, enhancing job satisfaction can help prevent workforce shortages. Work values and job-related characteristics are significant predictors of job satisfaction. However, the influence of factors may change as younger generations join the nursing workforce. Although research on generational commonalities and differences in work values is increasing, there is insufficient information on generational differences in the interplay between work values and job satisfaction. This study investigated the factors associated with job satisfaction of new nurses in each generational group based on a work value perspective.

Methods

A total of 280 new nurses (151 from Generation Y and 129 from Generation Z) were selected from the Graduates Occupational Mobility Survey. Multiple linear regression analyses were performed to determine the factors associated with job satisfaction in both groups.

Results

Most participants graduated with a diploma (61.1%), were paid less than the average salary of each group (60.4%), and conducted shift (72.9%) and overtime work (64.3%). Work values and job satisfaction levels were not significantly different between the two groups. Multiple linear regression analyses showed that career growth and task work values were associated with job satisfaction for Generation Z, while task, reputation, and environment work values were associated with job satisfaction for Generation Y. Among the job-related characteristics, nurses’ job tenure was associated with job satisfaction in both groups; salary and overtime had varying relationships with job satisfaction between the two generations.

Conclusions

Understanding generational differences is crucial for improving the effective management of new generational nurses. Our study findings support that different work value dimensions and job-related characteristics were associated with job satisfaction in each generation. Accordingly, it is essential to develop distinct initiatives, such as a well-structured program, to support the continued career growth of the new Generation Z nurses, thereby enhancing their job satisfaction. Furthermore, providing a conducive working environment that helps new-generation nurses overcome challenges and ensures personal lives should be considered.
A scoping review examining patient experience and what matters to people experiencing homelessness when seeking healthcare
Authors: Miller Jean-Philippe , Hutton Jennie , Doherty Claire , Vallesi Shannen , Currie Jane , Rushworth Katrina , Larkin Matthew , Scott Matthew , Morrow James , Wood Lisa
Published: April 2024

Background

Homelessness is associated with significant health disparities. Conventional health services often fail to address the unique needs and lived experience of homeless individuals and fail to include participatory design when planning health services. This scoping review aimed to examine areas of patient experience that are most frequently reported by people experiencing homelessness when seeking and receiving healthcare, and to identify existing surveys used to measure patient experience for this cohort.

Methods

A scoping review was undertaken reported according to the PRISMA-ScR 2020 Statement. Databases were searched on 1 December 2022: MEDLINE, EMBASE, APA PsychINFO and CINAHL. Included studies focused on people experiencing homelessness, healthcare services and patient experience, primary research, published in English from 2010. Qualitative papers and findings were extracted and synthesized against a modified framework based on the National Institute for Health and Care Excellence guidelines for care for people experiencing homelessness, the Institute of Medicine Framework and Lachman’s multidimensional quality model. People with lived experience of homelessness were employed as part of the research team.

Results

Thirty-two studies were included. Of these, 22 were qualitative, seven quantitative and three mixed methods, from the United States of America (n = 17), United Kingdom (n = 5), Australia (n = 5) and Canada (n = 4). Health services ranged from primary healthcare to outpatient management, acute care, emergency care and hospital based healthcare. In qualitative papers, the domains of ‘accessible and timely’, ‘person-centred’, and values of ‘dignity and respect’ and ‘kindness with compassion’ were most prevalent. Among the three patient experience surveys identified, ‘accessible and timely’ and ‘person-centred’ were the most frequent domains. The least frequently highlighted domains and values were ‘equitable’ and ‘holistic’. No questions addressed the ‘safety’ domain.

Conclusions

The Primary Care Quality-Homeless questionnaire best reflected the priorities for healthcare provision that were highlighted in the qualitative studies of people experiencing homelessness. The most frequently cited domains and values that people experiencing homelessness expressed as important when seeking healthcare were reflected in each of the three survey tools to varying degrees. Findings suggest that the principles of ‘Kindness and compassion’ require further emphasis when seeking feedback on healthcare experiences and the domains of ‘safety’, ‘equitable’, and ‘efficiency’ are not adequately represented in existing patient experience surveys.
Bacterial interactome disturbance in chronic obstructive pulmonary disease clinical stability and exacerbations
Authors: Xiao Wei , Chen Yi-long , Du Long-yi , Wu Jiqiu , Wang Zhang , Mao Bing , Wen Fu-qiang , Gibson Peter Gerard , McDonald Vanessa M. , Yu Haopeng , Fu Juan-juan
Published: April 2024

Rationale

Our understanding of airway dysbiosis in chronic obstructive pulmonary disease (COPD) remains incomplete, which may be improved by unraveling the complexity in microbial interactome.

Objectives

To characterize reproducible features of airway bacterial interactome in COPD at clinical stability and during exacerbation, and evaluate their associations with disease phenotypes.

Methods

We performed weighted ensemble-based co-occurrence network analysis of 1742 sputum microbiomes from published and new microbiome datasets, comprising two case-control studies of stable COPD versus healthy control, two studies of COPD stability versus exacerbation, and one study with exacerbation-recovery time series data.

Results

Patients with COPD had reproducibly lower degree of negative bacterial interactions, i.e. total number of negative interactions as a proportion of total interactions, in their airway microbiome compared with healthy controls. Evaluation of the Haemophilus interactome showed that the antagonistic interaction networks of this established pathogen rather than its abundance consistently changed in COPD. Interactome dynamic analysis revealed reproducibly reduced antagonistic interactions but not diversity loss during COPD exacerbation, which recovered after treatment. In phenotypic analysis, unsupervised network clustering showed that loss of antagonistic interactions was associated with worse clinical symptoms (dyspnea), poorer lung function, exaggerated neutrophilic inflammation, and higher exacerbation risk. Furthermore, the frequent exacerbators (≥ 2 exacerbations per year) had significantly reduced antagonistic bacterial interactions while exhibiting subtle compositional changes in their airway microbiota.

Conclusions

Bacterial interactome disturbance characterized by reduced antagonistic interactions, rather than change in pathogen abundance or diversity, is a reproducible feature of airway dysbiosis in COPD clinical stability and exacerbations, which suggests that we may target interactome rather than pathogen alone for disease treatment.
Trametinib sensitizes KRAS-mutant lung adenocarcinoma tumors to PD-1/PD-L1 axis blockade via Id1 downregulation
Authors: Puyalto Ander , Rodríguez-Remírez María , López Inés , Macaya Irati , Guruceaga Elizabeth , Olmedo María , Vilalta-Lacarra Anna , Welch Connor , Sandiego Sergio , Vicent Silvestre , Valencia Karmele , Calvo Alfonso , Pio Ruben , Raez Luis E. , Rolfo Christian , Ajona Daniel , Gil-Bazo Ignacio
Published: April 2024

Background

The identification of novel therapeutic strategies to overcome resistance to the MEK inhibitor trametinib in mutant KRAS lung adenocarcinoma (LUAD) is a challenge. This study analyzes the effects of trametinib on Id1 protein, a key factor involved in the KRAS oncogenic pathway, and investigates the role of Id1 in the acquired resistance to trametinib as well as the synergistic anticancer effect of trametinib combined with immunotherapy in KRAS-mutant LUAD.

Methods

We evaluated the effects of trametinib on KRAS-mutant LUAD by Western blot, RNA-seq and different syngeneic mouse models. Genetic modulation of Id1 expression was performed in KRAS-mutant LUAD cells by lentiviral or retroviral transductions of specific vectors. Cell viability was assessed by cell proliferation and colony formation assays. PD-L1 expression and apoptosis were measured by flow cytometry. The anti-tumor efficacy of the combined treatment with trametinib and PD-1 blockade was investigated in KRAS-mutant LUAD mouse models, and the effects on the tumor immune infiltrate were analyzed by flow cytometry and immunohistochemistry.

Results

We found that trametinib activates the proteasome-ubiquitin system to downregulate Id1 in KRAS-mutant LUAD tumors. Moreover, we found that Id1 plays a major role in the acquired resistance to trametinib treatment in KRAS-mutant LUAD cells. Using two preclinical syngeneic KRAS-mutant LUAD mouse models, we found that trametinib synergizes with PD-1/PD-L1 blockade to hamper lung cancer progression and increase survival. This anti-tumor activity depended on trametinib-mediated Id1 reduction and was associated with a less immunosuppressive tumor microenvironment and increased PD-L1 expression on tumor cells.

Conclusions

Our data demonstrate that Id1 expression is involved in the resistance to trametinib and in the synergistic effect of trametinib with anti-PD-1 therapy in KRAS-mutant LUAD tumors. These findings suggest a potential therapeutic approach for immunotherapy-refractory KRAS-mutant lung cancers.

Graphical Abstract