bluuebunny/crossref_metadata_2025 huggingface dataset:
Down-regulation of BRCA1-BARD1 Ubiquitin Ligase by CDK2
Authors: Hayami Ryosuke , Sato Ko , Wu Wenwen , Nishikawa Toru , Hiroi Junya , Ohtani-Kaneko Ritsuko , Fukuda Mamoru , Ohta Tomohiko
Published: June 2022

BRCA1, a breast and ovarian tumor suppressor, is a phosphoprotein whose cellular expression level is regulated in a cell cycle–dependent manner. BRCA1 interacts with BARD1 to generate significant ubiquitin ligase activity which catalyzes nontraditional Lys-6-linked polyubiquitin chains. However, it is not clear how the activity is regulated and how this affects BRCA1's multiple cellular functions. Here we show that the ubiquitin ligase activity of BRCA1-BARD1 is down-regulated by CDK2. During the cell cycle, BARD1 expression can largely be categorized into three patterns: moderately expressed in a predominantly unphosphorylated form in early G1 phase, expressed at low levels in both phosphorylated and unphosphorylated forms during late G1 and S phases, and highly expressed in its phosphorylated form during mitosis coinciding with BRCA1 expression. CDK2-cyclin A1/E1 and CDK1-cyclin B1 phosphorylate BARD1 on its NH2 terminus in vivo and in vitro. Intriguingly, the BRCA1-BARD1–mediated in vivo ubiquitination of nucleophosmin/B23 (NPM) and autoubiquitination of BRCA1 are dramatically disrupted by coexpression of CDK2-cyclin A1/E1, but not by CDK1-cyclin B1. The inhibition of ubiquitin ligase activity is not due to the direct effect of the kinases on BARD1 because an unphosphorylatable mutant of BARD1, S148A/S251A/S288A/T299A, is still inhibited by CDK2-cyclin E1. Alternatively, BRCA1 and BARD1 are likely exported to the cytoplasm and their expressions are remarkably reduced by CDK2-cyclin E1 coexpression. Recognizing the importance of cyclin E1 overexpression in breast cancer development, these results suggest a CDK2-BRCA1-NPM pathway that coordinately functions in cell growth and tumor progression pathways.
Deregulated Estrogen Receptor α Expression in Mammary Epithelial Cells of Transgenic Mice Results in the Development of Ductal Carcinoma In situ
Authors: Frech M. Silvina , Halama Ewa D. , Tilli Maddalena T. , Singh Baljit , Gunther Edward J. , Chodosh Lewis A. , Flaws Jodi A. , Furth Priscilla A.
Published: June 2022

A conditional tetracycline-responsive transgenic mouse model with deregulated estrogen receptor α expression in mammary epithelial cells developed ductal hyperplasia (DH), lobular hyperplasia, and ductal carcinoma in situ (DCIS) by 4 months of age. Higher proliferative rates were found in both normal and abnormal ductal and lobular structures. DH and DCIS but not normal ductal structures showed an increased percentage of cells with nuclear-localized cyclin D1. No differences in either the prevalence or extent of these phenotypes following exogenous 17β-estradiol treatment were found suggesting that alteration of ERα expression was the rate-limiting factor in initiation of DH, lobular hyperplasia, and DCIS.
Hyaluronic Acid Induces Osteopontin via the Phosphatidylinositol 3-Kinase/Akt Pathway to Enhance the Motility of Human Glioma Cells
Authors: Kim Mi-Suk , Park Myung-Jin , Moon Eui-Jung , Kim So-Jeong , Lee Chang-Hun , Yoo Heon , Shin Sang-Hoon , Song Eun-Sook , Lee Seung-Hoon
Published: June 2022

Hyaluronic acid (HA) binds to cell-surface receptors such as CD44, and seems to be involved in cell adhesion, motility, and tumor progression in brain. To identify gene expression changes that are initiated by HA, we explored human cytokine arrays in U87MG glioma cells and identified osteopontin, a secreted matrix protein, as a transcriptional target of HA. Interestingly, expression of osteopontin was induced by HA in glioma cells lacking functional PTEN, a tumor suppressor gene (U87MG, U251MG, and U373MG), but not in wild-type (wt)-PTEN-harboring cells (LN18 and LN428). To confirm the role of PTEN, adenoviral (Ad)-wt-PTEN was used to induce ectopic expression of wt-PTEN in U87MG cells, leading to reduced HA-mediated osteopontin induction. Reciprocally, transfection with dominant-negative Akt repressed HA-induced osteopontin expression. Furthermore, HA promoted the motility of glioma cells, and down-regulation of induced osteopontin activity via a neutralizing anti-osteopontin antibody repressed HA-induced motility in vitro. Together, these results strongly suggest that induction of osteopontin expression by HA is dependent on activation of the phosphatidylinositol 3-kinase/Akt pathway. Furthermore, our data indicate that PTEN can effectively modulate the expression of osteopontin, and HA-induced osteopontin plays an important role in the motility response induced by HA in human glioma cells.
Low-Dose Dietary Phytoestrogen Abrogates Tamoxifen-Associated Mammary Tumor Prevention
Authors: Liu Bolin , Edgerton Susan , Yang Xiaohe , Kim Aeree , Ordonez-Ercan Dalia , Mason Terza , Alvarez Kathy , McKimmey Christine , Liu Naxin , Thor Ann
Published: June 2022

Wild-type erbB-2/neu transgenic mice were used to study the interactions between tamoxifen and dietary phytoestrogens (or isoflavones) by dose and form in vivo. Mice were randomized to one of four dietary formulas and implanted with an 8-week continuous-release tamoxifen or placebo pellet at 8 weeks of age. In placebo-treated mice, soy meal diet (but not diets supplemented with low-dose or high-dose isoflavones or a casein diet) resulted in prolongation of tumor latency. In tamoxifen-treated mice fed the soy meal, casein, or high-dose isoflavone enriched diets, the majority (>80%) showed no tumor formation by 60 weeks of age. Of the mice that developed tumors, latency was significantly prolonged. In tamoxifen-treated mice fed the low-dose isoflavone enriched diet, a much higher rate of mammary tumor development (>50%; P < 0.002) and a shorter tumor latency were observed. In vitro studies of human and mouse mammary tumor cell lines confirm that low doses of genistein, co-administered with tamoxifen, promote cell proliferation. This is in contrast to tamoxifen alone or tamoxifen with higher doses of genistein that are growth inhibitory. In summary, low-dose dietary isoflavones abrogated tamoxifen-associated mammary tumor prevention in vivo. These interactions are supported by in vitro data from human and mouse mammary tumor cell lines. These dose-associated interactions likely have relevance to the human use of tamoxifen for prevention or treatment of breast cancer.
Tumor Susceptibility of Rassf1a Knockout Mice
Authors: Tommasi Stella , Dammann Reinhard , Zhang Zhongqiu , Wang Yian , Liu Limin , Tsark Walter M. , Wilczynski Sharon P. , Li Jie , You Ming , Pfeifer Gerd P.
Published: June 2022

The human Ras association domain family 1 (RASSF1) gene is located at 3p21.3 in an area that is believed to harbor at least one important tumor suppressor gene. The two major isoforms of RASSF1, RASSF1A and RASSF1C, are distinguished by alternative NH2-terminal exons and the two transcripts initiate in two separate CpG islands. RASSF1A is one of the most frequently inactivated genes described thus far in human solid tumors. Inactivation of RASSF1A most commonly involves methylation of the promoter and CpG island associated with the RASSF1A isoform. In contrast, RASSF1C is almost never inactivated in tumors. Here, we have derived Rassf1a knockout mice in which exon 1-α of the Rassf1 gene was deleted, leading to specific loss of Rassf1a but not Rassf1c transcripts. Rassf1a-targeted mice were viable and fertile. Rassf1a−/− mice were prone to spontaneous tumorigenesis in advanced age (18–20 months). Whereas only two tumors developed in 48 wild-type mice, six tumors were found in 35 Rassf1a+/− mice (P < 0.05) and thirteen tumors were found in 41 Rassf1a−/− mice (P < 0.001). The tumors in Rassf1a-targeted mice included lung adenomas, lymphomas, and one breast adenocarcinoma. Rassf1a−/− and wild-type mice were treated with two chemical carcinogens, benzo(a)pyrene and urethane, to induce skin tumors and lung tumors, respectively. Rassf1a−/− and Rassf1a+/− mice showed increased tumor multiplicity and tumor size relative to control animals. The data are consistent with the tumor-suppressive role of Rassf1a, which may explain its frequent epigenetic inactivation in human tumors.
Abstract 6296: Preclinical evaluation of a panel of FGFR inhibitors for their normal brain and brain tumor distribution
Authors: Knight William , Shaik Kamal , Margaryan Tigran , Mehta Shwetal , Sanai Nader , Tovmasyan Artak
Published: June 2022

Glioblastoma (GBM) is the most prevalent and lethal primary intrinsic brain tumor in adults with approximately 5-8% of GBM patients displaying fibroblast growth factor receptor (FGFR) gene mutations. This subset of GBM patients could potentially benefit from targeted FGFR inhibitor treatment, thus making it imperative to explore FGFR inhibitors as a therapeutic option. In this study, seven pan-FGFR inhibitors (infigratinib, AZD4547, debio1347, erdafitinib, LY2874455, pemigatinib, and TAS-120) were evaluated for their brain penetration ability employing cassette dosing strategy with an aim to identify the optimal candidates for brain tumor targeting. Cassette-dosing strategy was confirmed to be an acceptable approach for screening the panel of FGFR inhibitors by comparing pharmacokinetic parameters obtained from discrete- vs cassette-dosing studies. Subsequently, cassette-dosing strategy was utilized to investigate distributional kinetics of FGFR inhibitors in normal brain and brain tumor in wild-type and triple-knockout (Mdr1a/b-/-Bcrp1-/-) mice. The comparison of brain-to-plasma partition coefficients for total (Kp,brain) and unbound (Kp,brain) drug levels in wild-type and triple-knockout mice revealed the importance of major blood-brain barrier (BBB) efflux transporters in four out of seven FGFR inhibitors. The impact of BBB and efflux transporters were further evaluated in flank and orthotopic patient-derived xenograft mouse models of brain tumors. All FGFR inhibitors were shown to accumulate significantly in both flank and orthotopic brain tumors relative to normal brain. Furthermore, the levels in flank brain tumors were at least 10-fold higher as compared to the levels in orthotopic brain tumors with five FGFR inhibitors, indicating the critical role of efflux transporters and the impact of BBB disruption in the brain and brain tumor distribution. The predictive parameters of brain penetration calculated based on physico-chemical properties have been estimated and shown not to correlate with the experimentally obtained neuro-pharmacokinetic values. In summary, our study provides comprehensive evaluation of neuro-pharmacokinetic behavior of seven FGFR inhibitors and delivers rationale for selection of most optimal candidates for future investigation in brain tumor clinical trials.

Citation Format: William Knight, Kamal Shaik, Tigran Margaryan, Shwetal Mehta, Nader Sanai, Artak Tovmasyan. Preclinical evaluation of a panel of FGFR inhibitors for their normal brain and brain tumor distribution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6296.
Abstract SY23-01: Targeting the reciprocal interplay between inflammation, fibrosis, and pro-tumor immunity
Authors: Weaver Valerie M.
Published: June 2022

Tumors are characterized by increased levels of remodeled and crosslinked extracellular matrix (ECM) proteins that progressively stiffen the tissue stroma. Transformed cells exhibit a perturbed oncogene-stimulated and ECM-tuned mechanophenotype that further stimulates ECM remodeling and stiffening. We have been exploring how these aberrant cell and tissue level forces arise and by what means these forces contribute to malignancy and metastasis, and how they promote tumor recurrence and treatment resistance. We use two and three dimensional culture models with tuned ECM stiffness, as well as transgenic and syngeneic mouse models, human PDX models and human biospecimens, in which ECM crosslinking and stiffness and integrin mechanosignaling are manipulated and quantified. Our work has thus far revealed that the tumor ECM is progressively remodeled, and stiffened, primarily by stromal fibroblasts. We determined that infiltrating pro-tumorigenic myeloid cells secrete factors that stimulate stromal fibroblasts to remodel and crosslink the ECM and that this occurs quite early during tumor evolution. The stromal-fibroblast stiffened ECM thereafter disrupts tissue organization, promotes cell growth and survival and drives cell invasion. The stiffened tumor stroma additionally drives angiogenesis, and activates STAT3 to increase expression of cytokines and chemokines that further stimulate immune cell infiltration. The stiffened ECM thereafter reprograms the infiltrating myeloid cells by altering integrin adhesions and TGFβ SMAD signaling to induce an ECM synthetic metabolic phenotype in the myeloid cells. The metabolically reprogrammed myeloid cells ultimately compromise arginine tissue availability and increase tissue levels of ornithine that severely disrupt CD8 T cell tissue infiltration and perturb their anti-tumor function to accelerate tumor aggression and metastatic dissemination. I will discuss the dynamic and reciprocal interplay between tissue tension and innate and acquired immunity. I will then present data to show how ECM stiffness is able to promote tumor aggression and metastasis by dysregulating anti-tumor immunity. I will end with a short discussion regarding approaches to design therapies informed by these results to improve cancer treatment.

Citation Format: Valerie M. Weaver. Targeting the reciprocal interplay between inflammation, fibrosis, and pro-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr SY23-01.
An in vitro Comparative Assessment of Single-Use Flexible Ureteroscopes Using a Standardized Ureteroscopy Training Model
Authors: So Wei Zheng , Gauhar Vineet , Chen Kelven , Lu Jirong , Chua Wei Jin , Tiong Ho Yee
Published: June 2022

Introduction: Perceived benefits like decreased contamination rates and reduced postoperative incidence of complications after urolithiasis surgery have led to increased adoption of single-use flexible ureteroscopes (su-fURS). Using a validated, standardized simulator model with enhanced “fluoroscopic” capabilities, we performed an in vitro comparative assessment of four commercially available models of su-fURS. Both objective and subjective parameters were assessed in this study. Methods: Two standardized tasks, (1) exploration of the model’s kidney collecting system and (2) repositioning of a stone fragment from the upper renal to lower renal pole were assigned to participants, who performed these tasks on all four scopes. Four models of su-fURS (Boston LithoVue, PUSEN PU3033A, REDPINE, INNOVEX EU-ScopeTM) were assessed, with task timings as end-points for objective analysis. Cumulative “fluoroscopic” time was also recorded as a novel feature of our enhanced model. Post-task questionnaires evaluating specific components of the scopes were distributed to document subjective ratings. Results: Both subjective and objective performances (except stone repositioning time) across all four su-fURS demonstrated significant differences. However, objective performance (task timings) did not reflect subjective scope ratings by the participants (Rs < 0.6). Upon Kruskal-Wallis H test with post hoc analyses, REDPINE and INNOVEX EU-ScopeTM were the preferred su-fURS as rated by the participants, with overall scope scores of 9.00/10 and 9.57/10. Conclusions: Using a standardized in vitro simulation model with enhanced fluoroscopic capabilities, we demonstrated both objective and subjective differences between models of su-fURS. However, variations in perception of scope features (visibility, image quality, deflection, maneuverability, ease of stone retrieval) did not translate into actual technical performance. Eventually, the optimal choice of su-fURS fundamentally lies in individual surgeon preference, as well as cost-related factors.
Homofobia: um empreendimento político
Authors: Nunes Lauro Victor
Published: June 2022

De acordo com o portal web da Autêntica Editora2, Daniel Borrillo é um ítalo-argentino radicado na França. Diplomado em Jurisprudência pela Universidade de Buenos Aires e professor de Direito na Universidade de Paris X – Nanterre, é pesquisador associado do Centre National de la Recherche Scientifique (CNRS). Borrillo é especialista nas questões jurídicas internacionais referente às minorias étnicas e sociais. Foi responsável pelo “Manifesto pela igualdade de direitos”, documento responsável pela publicização da celebração do primeiro casamento gay da França, em 2004.  Em “Homofobia: história e crítica de um preconceito”, o autor traça uma periodização da história da homossexualidade, da Grécia Antiga à atualidade. Considerando a pluralidade dos contextos históricos e sociais em que esteve emergida a questão da orientação sexual de indivíduos que se relacionam com pessoas do mesmo sexo, o autor enfatiza o papel da cultura na produção de um estigma secular de marginalização, “pecado” e “doença” associado aos homossexuais e, posteriormente, à população LGBT como um todo. Neste sentido, define a homofobia como um conceito fluído e polissêmico, que descreve estratégias políticas diferenciadas de produção e reprodução da exclusão social deste coletivo tido como minoritário.
Transporte Público Escolar: de uma iniciativa local a uma política nacional
Authors: Caldas Eduardo de Lima , Mouette Dominique
Published: June 2022

Este trabalho é sobre o transporte público escolar e procura apresentar as várias modalidades de transporte escolar adequadas para cada região do país. O trabalho mostra a peculiaridade de cada região e o aspecto inovador dos gestores públicos locais ao implementares políticas públicas de transporte público escolar.Este trabalho é resultado de um conjunto de pesquisas realizadas em quatro municípios brasileiros: São Carlos e Piracicaba (2009), ambos em São Paulo (SP); Presidente Juscelino (2010) e Itacoatiara (2011), localizados respectivamente no Maranhão (MA) e Amazonas (AM).Este trabalho se beneficiou de estratégias diferentes no período em que foram realizadas as visitas de campo. No caso dos municípios paulistas foram feitas várias visitas que permitiram entrevistas, conversas e observações. Nos outros municípios, os pesquisadores realizaram apenas uma visita de campo de 15 dias em cada um deles.Nos quatro municípios, foram feitas observações livres. A coleta de informações foi feita por meio de entrevistas semi-estruturadas, e fundamentalmente por meio de “conversas” (SPINK, 2008), realizadas com gestores de políticas públicas, secretários municipais, alunos, pais de alunos, professores e diretores de escola, bem como com servidores e funcionários que trabalham diretamente com os respectivos programas de transporte escolar.Do trabalho foi possível observar essencialmente que por mais que se acredite nos processos de difusão de iniciativas a partir de um centro altamente capacitado, a experiência brasileira tem demonstrado que há, espalhada pelo país, em regiões muitas vezes distantes dos grandes centros decisórios, alta capacidade inovadora dos gestores e dirigentes públicos. Também foi possível observar que não há uma sequência de ações para garantir a implementação do projeto.
Didática no ensino superior: Um modelo integrativo articulado ao ensino de Psicologia
Authors: Librelotto Rubin Aline , Redressa Aline , Medeiros Gabriela , Bechara Laura , Carvalho Pedro , Cheng Rafael
Published: June 2022

As políticas públicas e legislações relacionadas à educação no Brasil vem sofrendo um processo de transformação desde a Constituição de 1988. O desenvolvimento do ensino superior privado no país foi influenciado pelo crescimento econômico e pelo mercado financeiro, ampliando o acesso ao ensino superior e a quantidade de Instituições de Ensino Superior (IES) no país. Este cenário provocou um grande interesse em pesquisas que visam explorar aspectos culturais, sociais e econômicos envolvidos no ensino superior e, dessa forma, o presente artigo visa compreender como se dá a formação docente em Psicologia e quais desafios são enfrentados nesta formação. Através de uma pesquisa documental e da hipótese de um projeto pedagógico integrativo, o artigo buscou articular discussões sobre o modelo integrativo na graduação, o ensino superior no Brasil, as diretrizes curriculares nacionais no ensino da Psicologia, a relação entre Psicologia e Transdisciplinaridade, bem como a aplicação deste conceito ao ensino na área, com a formação mais integrativa de um docente em Psicologia, e como ela se relaciona com a construção do conhecimento por parte de estudantes.
Rede de Accountability: um exemplo norte-americano para também pensar o Brasil
Authors: Kerche Fábio
Published: June 2022

Resenha da seguinte obra: The Accountability State: US Federal Inspectors General and the pursuit of democratic integrity. Autor: Nadia HilliardCidade: LawrenceEditora: University Press of Kansas Ano: 2017Páginas: 275
O Controle Interno como Instrumento de Gestão
Authors: Rodrigues Pinheiro Fátima Teresinha , Gomes Angela Quintanilha , Sampaio Thiago da Silva
Published: June 2022

O objetivo desse estudo é fazer uma análise dos dados disponíveis na literatura a respeito da importância do controle interno na organização, principalmente na pública. Inicia-se com a introdução ao assunto, após a conceituação e uma pequena abordagem do que de administração burocrática e gerencial e a relação com o controle interno. Ao final propõem-se medidas para que se estabeleça, de fato, uma integração entre o órgão central do sistema de controle interno e as unidades ou funções de controle da Administração Pública para ajudar no planejamento e gerenciamento do setor público.
Administração Comunitária de Prisões, Segregação Territorial e Identidades Prisionais
Authors: Massola Gustavo Martineli
Published: June 2022

Os vínculos entre segregação territorial e prisional estão bem estabelecidos no Brasil, onde muitas cidades constituem territórios de mútua exclusão entre centro e periferia. Surge uma percepção de sequestro da experiência do território, com subsequentes tentativas de reassumir acesso aos lugares segregados por meio de ações comunitárias, algumas das quais se dirigem à segregação prisional. Em São Paulo, desenvolveram-se, nas décadas de 1980-90, ações comunitárias cujo objetivo era reassumir controle sobre o processo de cumprimento da pena. Obtiveram resultados positivos na melhoria dos indicadores prisionais, tornando-se modelos de administração prisional e inspirando a criação de um programa oficial. Seus sucessos resultaram da tônica na relação entre presos e voluntários. Algumas das contradições desta relação vinculam-se ao dipolo centro-periferia, implicando uma violenta oposição entre presos que aderiram ao ideal voluntário e o restante da população prisional e reintroduzindo a violência que esta ação buscava superar
A educação vocal do ator - Terezinha Nackéd Zaratin
Authors: Cerasoli Jr Umberto
Published: June 2022

Entrevista concedida à revista PesquisAtor pela profa. dra. Terezinha Nackéd Zaratin. Nesta entrevista a professora trata da importância do desenvolvimento da voz para o ator e defende que o ensino da técnica vocal se dê “em separado” da expressão corporal e dramática, por meio de exercícios específicos realizados na disciplina poéticas da voz.
Relato de experiência: Myrian Muniz e Eu
Authors: Carvalho Marcelo Braga de
Published: June 2022

A pedagogia teatral desenvolvida por Myrian Muniz consiste em uma prática que lança um olhar muito particular sobre o trabalho do ator e que visa resgatar a experiência humana como base para este trabalho. Busco descrever, através desse relato, a minha experiência com a atriz, diretora e professora, sob a ótica do aprendiz-ator. Os objetivos são traçar um percurso de formação, através das diversas situações pedagógicas vivenciadas em um período de seis anos e, através dessas situações, propor uma análise dos principais pontos da pedagogia da Myrian Muniz. Esse relato permite que a linha de trabalho de Myrian, dentro da pedagogia teatral, seja associada ao processo de autoconhecimento do artista de teatro, à associação entre experiência e reflexão como fermento para o trabalho de criação teatral e a relação entre os indivíduos de um grupo como base para o trabalho do ator.
Um ator e dois encontros: Teatro e Cinema
Authors: Conde Rafael
Published: June 2022

O artigo investiga as aproximações e especificidades do trabalho do ator no teatro e no cinema. A partir da ideia do encontro no plateau do filme e da peça, conceitos como presença, rastro e espaço são testados para problematizar o ator como elo principal entre os dois campos.
Corpos em ação, artes vivas e interculturalidade
Authors: Mangieri Rocco
Published: June 2022

Este texto é ao mesmo tempo um breve compendio do curso sócio-antropologia teatral (Sociologia) y uma proposta complementar para o ensino das artes cênicas. Os aspectos teóricos de base são: a eliminação dos limites e fronteiras epistemológicas e ideológicas entre as áreas disciplinares e artísticas, o manejo da interculturalidade, os princípios da Sócio-antropologia teatral e em especial o conceito de restauração da conduta ordinária e a necessária vinculação de uma teoria do corpo, da ação e da personagem.
HULLETTIA King ex Hook. f. (Moraceae), A newly recorded genus to the Flora of Vietnam, with its lectotypification and a revised key to Vietnamese Moraceae
Authors: BUI VAN HUONG , VU DINH DUY , PHAM MAI HUONG , DO VAN HAI , DOAN HOANG SON , BUI VAN THANH , DAM NGOC ANH LUU , TRUONG BA VUONG , GARDNER ELLIOT M.
Published: June 2022

Hullettia King ex Hook. f. (Moraceae) is newly recorded to the flora of Vietnam. A specimen discovered in the lowland secondary evergreen forest of Song Hinh protection forest, Phu Yen province, central Vietnam was identified as Hullettia dumosa King ex Hook. f. It was earlier known from peninsular Myanmar, peninsular Thailand, peninsular Malaysia, Singapore, and Sumatra. Type material of this species is analyzed, and lectotype is designated (Scortechini s.n., K: K000898664). Photographic illustrations of studied specimens are provided. A key to the Vietnamese genera of Moraceae is presented.
Bredia bullata (Melastomataceae), a new species from limestone areas in Yunnan, China
Authors: ZENG SI-JIN , TONG YI-HUA , XIA NIAN-HE
Published: June 2022

A new species, Bredia bullata, from China, is described and illustrated based on morphological and molecular evidence. This new species is morphologically similar to B. malipoensis in having tomentose stems and leaves, cordate leaf blades in unequal pairs, an umbellate inflorescence, and undulate petals with an unguiculate base and retuse apex, but differs by having bullate leaf blades, white hypanthia and elliptic calyx lobes. Our phylogenetic analysis using the plastid genome strongly supports the generic placement of B. bullata and B. malipoensis within Bredia.
Taxonomic changes in Bostrichidae (Insecta, Coleoptera)
Authors: JERZY BOROWSKI
Published: June 2022

The taxonomic changes concern 6 species belonging to the family Bostrichidae. After a taxonomic analysis the following synonyms were established: Melalgus japonicus Chûjô, 1973 n. syn. of M. batillus (Lesne, 1902), Amphicerus (C.) malayanus (Lesne, 1898) n. syn. of A. (C.) caenophradoides (Lesne, 1895), Bostrychoplites megaceros Lesne, 1899 n. syn. of Bostrychoplites cornutus (Olivier, 1790), Bostrychoplites suturalis Lesne, 1931 n. syn. of Bostrychoplites peltatus Lesne, 1899, Lichenophanes fasciculatus (Fall, 1909) n. syn. of Lichenophanes penicillatus (Lesne, 1895), and Megabostrichus imatadei Chûjô, 1964 n. syn. of Phonapate stridula Lesne, 1909. The new synonymy results from a study of typical specimens as well as from latest publications concerning the taxonomy of this insect group.
Acceptability of a Preventative Coping and Connectedness Curriculum for High School Students Entering Accelerated Curricula
Authors: Shaunessy-Dedrick Elizabeth , Suldo Shannon M. , O’Brennan Lindsey , Dedrick Robert , Parker Janise , Ferron John , DiLeo Letty
Published: June 2022

Students report experiencing elevated levels of academic stress while in Advanced Placement (AP) and International Baccalaureate Diploma (IBD) classes. In response, we developed a classwide, preventative coping and connectedness curriculum, which consists of 12 50-minute modules for 9th-grade students enrolled in accelerated coursework. In this pilot study, we implemented the curriculum in 2 schools and sought user feedback. After describing the curriculum, we examine the acceptability of this social-emotional curriculum at three stages: prior to, during, and following implementation. Overall, all stakeholders—including students, parents, and educators—deemed the curriculum highly acceptable. Teachers, administrators, and parents rated the content and lessons as highly acceptable for addressing students’ academic stressors and development of necessary coping and strategies. Included is a discussion of these findings relative to prior acceptability research, including research with gifted learners, limitations, and the role of acceptability in the line of inquiry for this curriculum intervention development.
1-year outcomes of patients admitted to critical care with treatment limitations: A dual-centre observational study
Authors: Yakubi Masseh , Devlin Annie , Venn Richard , Hodgson Luke
Published: June 2022

Intensivists are increasingly involved in the care of frail patients as our population ages. Careful person-orientated, individualised decision-making, weighing benefits and harms of critical care are required in such situations. Few studies have reported outcomes of patients with treatment limitations. This dual-centre observational study reports outcomes of 3781 patients (2018-20). At least one treatment limitation was set at admission in 13% ( n = 486). Of this group 55% survived to hospital discharge, of whom 69% were discharged home; 39% remained alive at 1 year. These findings provide objective data to support clinicians, patients and relatives in shared decision-making. Future multi-centre work could explore how best to identify those most likely to benefit from critical care
Outcomes and molecular profile of oligomonocytic CMML support its consideration as the first stage in the CMML continuum
Authors: Calvo Xavier , Roman-Bravo David , Garcia-Gisbert Nieves , Rodriguez-Sevilla Juan Jose , Garcia-Avila Sara , Florensa Lourdes , Gibert Joan , Fernández-Rodríguez Concepción , Salido Marta , Puiggros Anna , Espinet Blanca , Colomo Luis , Bellosillo Beatriz , Ferrer Ana , Arenillas Leonor
Published: June 2022

Patients with oligomonocytic chronic myelomonocytic leukemia (OM-CMML) are currently classified according to the 2017 World Health Organization myelodysplastic syndromes classification. However, recent data support considering OM-CMML as a specific subtype of chronic myelomonocytic leukemia (CMML), given their similar clinical, genomic, and immunophenotypic profiles. The main purpose of our study was to provide survival outcome data of a well-annotated series of 42 patients with OM-CMML and to compare them to 162 patients with CMML, 120 with dysplastic type (D-CMML), and 42 with proliferative type (P-CMML). OM-CMML had significantly longer overall survival (OS) and acute myeloid leukemia–free survival than did patients with CMML, considered as a whole group, and when compared with D-CMML and P-CMML. Moreover, gene mutations associated with increased proliferation (ie, ASXL1 and RAS-pathway mutations) were identified as independent adverse prognostic factors for OS in our series. We found that at a median follow-up of 53.47 months, 29.3% of our patients with OM-CMML progressed to D-CMML, and at a median follow-up of 46.03 months, 28.6% of our D-CMML group progressed to P-CMML. These data support the existence of an evolutionary continuum of OM-CMML, D-CMML, and P-CMML. In this context, we observed that harboring more than 3 mutated genes, carrying ASXL1 mutations, and a peripheral blood monocyte percentage >20% significantly predicted a shorter time of progression of OM-CMML into overt CMML. These variables were also detected as independent adverse prognostic factors for OS in OM-CMML. These data support the consideration of OM-CMML as the first evolutionary stage within the proliferative continuum of CMML.
Multi-view heterogeneous molecular network representation learning for protein–protein interaction prediction
Authors: Su Xiao-Rui , Hu Lun , You Zhu-Hong , Hu Peng-Wei , Zhao Bo-Wei
Published: June 2022

Background

Protein–protein interaction (PPI) plays an important role in regulating cells and signals. Despite the ongoing efforts of the bioassay group, continued incomplete data limits our ability to understand the molecular roots of human disease. Therefore, it is urgent to develop a computational method to predict PPIs from the perspective of molecular system.

Methods

In this paper, a highly efficient computational model, MTV-PPI, is proposed for PPI prediction based on a heterogeneous molecular network by learning inter-view protein sequences and intra-view interactions between molecules simultaneously. On the one hand, the inter-view feature is extracted from the protein sequence by k-mer method. On the other hand, we use a popular embedding method LINE to encode the heterogeneous molecular network to obtain the intra-view feature. Thus, the protein representation used in MTV-PPI is constructed by the aggregation of its inter-view feature and intra-view feature. Finally, random forest is integrated to predict potential PPIs.

Results

To prove the effectiveness of MTV-PPI, we conduct extensive experiments on a collected heterogeneous molecular network with the accuracy of 86.55%, sensitivity of 82.49%, precision of 89.79%, AUC of 0.9301 and AUPR of 0.9308. Further comparison experiments are performed with various protein representations and classifiers to indicate the effectiveness of MTV-PPI in predicting PPIs based on a complex network.

Conclusion

The achieved experimental results illustrate that MTV-PPI is a promising tool for PPI prediction, which may provide a new perspective for the future interactions prediction researches based on heterogeneous molecular network.
Euclidean distance-optimized data transformation for cluster analysis in biomedical data (EDOtrans)
Authors: Ultsch Alfred , Lötsch Jörn
Published: June 2022

Background

Data transformations are commonly used in bioinformatics data processing in the context of data projection and clustering. The most used Euclidean metric is not scale invariant and therefore occasionally inappropriate for complex, e.g., multimodal distributed variables and may negatively affect the results of cluster analysis. Specifically, the squaring function in the definition of the Euclidean distance as the square root of the sum of squared differences between data points has the consequence that the value 1 implicitly defines a limit for distances within clusters versus distances between (inter-) clusters.

Methods

The Euclidean distances within a standard normal distribution (N(0,1)) follow a N(0,$$\sqrt{2}$$2) distribution. The EDO-transformation of a variable X is proposed as$$EDO= X/(\sqrt{2}\cdot s)$$EDO=X/(2·s)following modeling of the standard deviationsby a mixture of Gaussians and selecting the dominant modes via item categorization. The method was compared in artificial and biomedical datasets with clustering of untransformed data, z-transformed data, and the recently proposed pooled variable scaling.

Results

A simulation study and applications to known real data examples showed that the proposed EDO scaling method is generally useful. The clustering results in terms of cluster accuracy, adjusted Rand index and Dunn’s index outperformed the classical alternatives. Finally, the EDO transformation was applied to cluster a high-dimensional genomic dataset consisting of gene expression data for multiple samples of breast cancer tissues, and the proposed approach gave better results than classical methods and was compared with pooled variable scaling.

Conclusions

For multivariate procedures of data analysis, it is proposed to use the EDO transformation as a better alternative to the established z-standardization, especially for nontrivially distributed data. The “EDOtrans” R package is available athttps://cran.r-project.org/package=EDOtrans.
Automated versus conventional perioperative glycemic control in adult diabetic patients undergoing open heart surgery
Authors: Kaddoum Roland , Khalili Amro , Shebbo Fadia M. , Ghanem Nathalie , Daher Layal Abou , Ali Arwa Bou , Chehade Nour El Hage , Maroun Patrick , Aouad Marie T.
Published: June 2022

Background

Intraoperative glycemic variability is associated with increased risks of mortality and morbidity and an increased incidence of hyperglycemia after cardiac surgery. Accordingly, clinicians tend to use a tight glucose control to maintain perioperative blood glucose levels and therefore the need to develop a less laborious automated glucose control system is important especially in diabetic patients at a higher risk of developing complications.

Methods

Patients, aged between 40 and 75 years old, undergoing open heart surgery were randomized to either an automated protocol (experimental) or to the conventional technique at our institution (control).

Results

We showed that the percentage of patients maintained between 7.8–10 mmol.l−1 was not statistically different between the two groups, however, through an additional analysis, we showed that the proportion of patients whose glucose levels maintained between a safety level of 6.7–10 mmol.l−1 was significantly higher in the experimental group compared to control group, 14 (26.7%) vs 5 (17.2%) P = 0.025. In addition, the percentage of patients who had at least one intraoperative hyperglycemic event was significantly higher in the control group compared to the experimental group, 17 (58.6%) vs 5 (16.7%), P < 0.001 with no hypoglycemic events in the experimental group compared to two events in the control group. We also showed that longer surgeries can benefit more from using the automated glucose control system, particularly surgeries lasting more than 210 min.

Conclusion

We concluded that the automated glucose control pump in diabetic patients undergoing open heart surgeries maintained most of the patients within a predefined glucose range with a very low incidence of hyperglycemic events and no incidence of hypoglycemic events.

Trial registration

Registered with clinicaltrials.gov (NCT #NCT03314272, Principal investigator Roland Kaddoum, date of registration: 19/10/2017).
Breastfeeding and overweight/obesity among children and adolescents: a cross-sectional study
Authors: Liu Fange , Lv Di , Wang Lumin , Feng Xiaoyu , Zhang Rongjun , Liu Wendong , Han Wenchao
Published: June 2022

Background

Overweight and obesity are major public health crises among children and adolescents and contribute to a significant economic burden. We aimed to investigate the relationship between breastfeeding duration and overweight and obesity in children and adolescents in Qingdao, China in 2017.

Methods

This study conducted a survey with 10,753 students (5370 boys and 5383 girls) aged 6 to 16 years from the Shibei District of Qingdao, China in 2017. Anthropometric measurements were taken by well-trained personnel and self-completed questionnaires were used to collect data from students. A variety of statistical methods were used in this study, including univariate and multivariate analyses, as well as linear and nonlinear regression models.

Results

The prevalence of overweight and obesity was 15.45% and 19.76%, respectively. There was a significant negative correlation between breastfeeding duration and BMI in children and adolescents (β = -0.025, 95% CI: -0.033, -0.005, P < 0.01). Among boys, the BMI in children and adolescences of those who have been breastfed for more than 12 months was significantly lower than that of others whose breastfeeding duration was less than 12 months (β = -0.440, 95%CI -0.655, -0.224, P < 0.01). Breastfeeding has a particularly positive effect on the prevalence of obesity in boys aged 9 to 11 years (OR = 0.978, 95% CI: 0.958,0.999, P < 0.05).

Conclusion

Breastfeeding can significantly reduce the prevalence of overweight and obesity among children and adolescents aged 6 to 16 years. Those who were breastfed for more than 12 months had a lower risk of developing overweight and obesity, especially boys between the ages of 9 and 11.
Viral load monitoring for people living with HIV in the era of test and treat: progress made and challenges ahead – a systematic review
Authors: Pham Minh D. , Nguyen Huy V. , Anderson David , Crowe Suzanne , Luchters Stanley
Published: June 2022

Background

In 2016, we conducted a systematic review to assess the feasibility of treatment monitoring for people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in low and middle-income countries (LMICs), in line with the 90-90-90 treatment target. By 2020, global estimates suggest the 90-90-90 target, particularly the last 90, remains unattainable in many LMICs. This study aims to review the progress and identify needs for public health interventions to improve viral load monitoring and viral suppression for PLHIV in LMICs.

Methods

A literature search was conducted using an update of the initial search strategy developed for the 2016 review. Electronic databases (Medline and PubMed) were searched to identify relevant literature published in English between Dec 2015 and August 2021. The primary outcome was initial viral load (VL) monitoring (the proportion of PLHIV on ART and eligible for VL monitoring who received a VL test). Secondary outcomes included follow-up VL monitoring (the proportion of PLHIV who received a follow-up VL after an initial elevated VL test), confirmation of treatment failure (the proportion of PLHIV who had two consecutive elevated VL results) and switching treatment regimen rates (the proportion of PLHIV who switched treatment regimen after confirmation of treatment failure).

Results

The search strategy identified 1984 non-duplicate records, of which 34 studies were included in the review. Marked variations in initial VL monitoring coverage were reported across study settings/countries (range: 12–93% median: 74% IQR: 46–82%) and study populations (adults (range: 25–96%, median: 67% IQR: 50–84%), children, adolescents/young people (range: 2–94%, median: 72% IQR: 47–85%), and pregnant women (range: 32–82%, median: 57% IQR: 43–71%)). Community-based models reported higher VL monitoring (median: 85%, IQR: 82-88%) compared to decentralised care at primary health facility (median: 64%, IRQ: 48-82%). Suboptimal uptake of follow-up VL monitoring and low regimen switching rates were observed.

Conclusions

Substantial gaps in VL coverage across study settings and study populations were evident, with limited data availability outside of sub-Saharan Africa. Further research is needed to fill the data gaps. Development and implementation of innovative, community-based interventions are required to improve VL monitoring and address the “failure cascade” in PLHIV on ART who fail to achieve viral suppression.
Percutaneous posterior transiliac plate versus iliosacral screw fixation for posterior fixation of Tile C-type pelvic fractures: a retrospective comparative study
Authors: Kim Chul-Ho , Kim Jung Jae , Kim Ji Wan
Published: June 2022

Background

This study aimed to compare the clinical outcomes and complications between two minimally invasive surgical techniques: percutaneous transiliac plate fixation and iliosacral (IS) screw fixation for the treatment of Tile C-type pelvic bone fractures.

Methods

We retrospectively reviewed the data of 77 consecutive patients with Tile C pelvic ring injuries who underwent either percutaneous transiliac plate fixation or IS screw fixation in a single academic center between November 2007 and January 2018. We recorded patients’ demographics, surgery-related data, and postoperative surgical outcomes and compared the incidence of complications and revision surgery rates between the two groups.

Results

Overall, 14 patients were included in the plate group, while 63 were included in the IS screw fixation group. No significant differences were observed in the patients’ demographics between the two groups except for a longer interval from injury to surgery (13.5 days vs. 5.4 days, P = 0.001). Both groups acquired fracture union in all cases. There was one case of infection requiring surgical debridement in the plating group. Notably, nerve injury (n = 3) and implant loosening (n = 5) occurred in the IS screw group, but the difference was not significant.

Conclusions

Both percutaneous posterior transiliac plating and IS screw fixation in patients with Tile C-type pelvic bone fractures showed good results. We recommend IS screw fixation as the primary treatment and propose posterior plating as treatment for sacral dysmorphism and bilateral sacral alar fractures in patients with spinopelvic dissociation.

Level of evidence

III
Research based on existing clinical data and biospecimens: a systematic study of patients’ opinions
Authors: Eikemo Hilde , Roten Linda Tømmerdal , Vaaler Arne Einar
Published: June 2022

Background

The aim of the present survey was to investigate newly discharged hospital patients’ opinions on secondary use of their hospital data and biospecimens within the context of health research in general and, more specifically, on genetic research, data sharing across borders and cooperation with the health industry.

Methods

A paper questionnaire was sent to 1049 consecutive newly discharged hospital patients.

Results

The vast majority of the respondents preferred to be informed (passive consent) or to receive no notification at all for secondary research on their health data and biospecimens (88% and 91% for data and biospecimens respectively). The rest wanted to be asked for active consent. The same trend applied for the other aspects also. 81% of respondents were positive towards genetic research without active consent. 95% were positive towards cooperating with the health industry, and 90% were positive towards data sharing.

Conclusions

These results suggest that hospital patients generally are very positive to secondary research and support the concept of opting out rather than opting in.