bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility study of using high‐throughput drug sensitivity testing to target recurrent glioblastoma stem cells for individualized treatment
Authors: Skaga Erlend , Kulesskiy Evgeny , Brynjulvsen Marit , Sandberg Cecilie J. , Potdar Swapnil , Langmoen Iver A. , Laakso Aki , Gaál‐Paavola Emília , Perola Markus , Wennerberg Krister , Vik‐Mo Einar O. 
Published: December 2019

AbstractBackgroundDespite the well described heterogeneity in glioblastoma (GBM), treatment is standardized, and clinical trials investigate treatment effects at population level. Genomics‐driven oncology for stratified treatments allow clinical decision making in only a small minority of screened patients. Addressing tumor heterogeneity, we aimed to establish a clinical translational protocol in recurrent GBM (recGBM) utilizing autologous glioblastoma stem cell (GSC) cultures and automated high‐throughput drug sensitivity and resistance testing (DSRT) for individualized treatment within the time available for clinical application.ResultsFrom ten patients undergoing surgery for recGBM, we established individual cell cultures and characterized the GSCs by functional assays. 7/10 GSC cultures could be serially expanded. The individual GSCs displayed intertumoral differences in their proliferative capacity, expression of stem cell markers and variation in their in vitro and in vivo morphology. We defined a time frame of 10 weeks from surgery to complete the entire pre‐clinical work‐up; establish individualized GSC cultures, evaluate drug sensitivity patterns of 525 anticancer drugs, and identify options for individualized treatment. Within the time frame for clinical translation 5/7 cultures reached sufficient cell yield for complete drug screening. The DSRT revealed significant intertumoral heterogeneity to anticancer drugs (p < 0.0001). Using curated reference databases of drug sensitivity in GBM and healthy bone marrow cells, we identified individualized treatment options in all patients. Individualized treatment options could be selected from FDA‐approved drugs from a variety of different drug classes in all cases.ConclusionsIn recGBM, GSC cultures could successfully be established in the majority of patients. The individual cultures displayed intertumoral heterogeneity in their in vitro and in vivo behavior. Within a time frame for clinical application, we could perform DSRT in 50% of recGBM patients. The DSRT revealed a remarkable intertumoral heterogeneity in sensitivity to anticancer drugs in recGBM that could allow tailored therapeutic options for functional precision medicine.
Cysteine catabolism and the serine biosynthesis pathway support pyruvate production during pyruvate kinase knockdown in pancreatic cancer cells
Authors: Yu Lei , Teoh Shao Thing , Ensink Elliot , Ogrodzinski Martin P. , Yang Che , Vazquez Ana I. , Lunt Sophia Y. 
Published: December 2019

AbstractBackgroundPancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with limited treatment options. Pyruvate kinase, especially the M2 isoform (PKM2), is highly expressed in PDAC cells, but its role in pancreatic cancer remains controversial. To investigate the role of pyruvate kinase in pancreatic cancer, we knocked down PKM2 individually as well as both PKM1 and PKM2 concurrently (PKM1/2) in cell lines derived from aKrasG12D/-; p53-/-pancreatic mouse model.MethodsWe used liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine metabolic profiles of wildtype and PKM1/2 knockdown PDAC cells. We further used stable isotope-labeled metabolic precursors and LC-MS/MS to determine metabolic pathways upregulated in PKM1/2 knockdown cells. We then targeted metabolic pathways upregulated in PKM1/2 knockdown cells using CRISPR/Cas9 gene editing technology.ResultsPDAC cells are able to proliferate and continue to produce pyruvate despite PKM1/2 knockdown. The serine biosynthesis pathway partially contributed to pyruvate production during PKM1/2 knockdown: knockout of phosphoglycerate dehydrogenase in this pathway decreased pyruvate production from glucose. In addition, cysteine catabolism generated ~ 20% of intracellular pyruvate in PDAC cells. Other potential sources of pyruvate include the sialic acid pathway and catabolism of glutamine, serine, tryptophan, and threonine. However, these sources did not provide significant levels of pyruvate in PKM1/2 knockdown cells.ConclusionPKM1/2 knockdown does not impact the proliferation of pancreatic cancer cells. The serine biosynthesis pathway supports conversion of glucose to pyruvate during pyruvate kinase knockdown. However, direct conversion of serine to pyruvate was not observed during PKM1/2 knockdown. Investigating several alternative sources of pyruvate identified cysteine catabolism for pyruvate production during PKM1/2 knockdown. Surprisingly, we find that a large percentage of intracellular pyruvate comes from cysteine. Our results highlight the ability of PDAC cells to adaptively rewire their metabolic pathways during knockdown of a key metabolic enzyme.
Cost-effectiveness analysis of malaria rapid diagnostic tests: a systematic review
Authors: Ling Xiao-Xiao , Jin Jia-Jie , Zhu Guo-Ding , Wang Wei-Ming , Cao Yuan-Yuan , Yang Meng-Meng , Zhou Hua-Yun , Cao Jun , Huang Jia-Yan 
Published: December 2019

Abstract
Background
Rapid diagnostic tests (RDT) can effectively manage malaria cases and reduce excess costs brought by misdiagnosis. However, few studies have evaluated the economic value of this technology. The purpose of this study is to systematically review the economic value of RDT in malaria diagnosis.

Main text
A detailed search strategy was developed to identify published economic evaluations that provide evidence regarding the cost-effectiveness of malaria RDT. Electronic databases including MEDLINE, EMBASE, Biosis Previews, Web of Science and Cochrane Library were searched from Jan 2007 to July 2018. Two researchers screened studies independently based on pre-specified inclusion and exclusion criteria. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was applied to evaluate the quality of the studies. Then cost and effectiveness data were extracted and summarized in a narrative way.
Fifteen economic evaluations of RDT compared to other diagnostic methods were identified. The overall quality of studies varied greatly but most of them were scored to be of high or moderate quality. Ten of the fifteen studies reported that RDT was likely to be a cost-effective approach compared to its comparisons, but the results could be influenced by the alternatives, study perspectives, malaria prevalence, and the types of RDT.

Conclusions
Based on available evidence, RDT had the potential to be more cost-effective than either microscopy or presumptive diagnosis. Further research is also required to draw a more robust conclusion.
Trust and respect in the patient-clinician relationship: preliminary development of a new scale
Authors: Crits-Christoph Paul , Rieger Agnes , Gaines Averi , Gibbons Mary Beth Connolly 
Published: December 2019

Abstract
Background
Trust and respect may be an important component of client-provider relationships. This study aimed to develop and report preliminary psychometric analyses of a new brief measure to evaluate a patient’s level of trust and respect for their clinician. The scale was designed to be applicable in multiple healthcare contexts, with a particular focus on mental healthcare.

Methods
Adult patients completed the study survey in an academic outpatient psychiatric clinic waiting room. Classical and Item Response Theory (IRT) analyses were utilized to examine the adequacy of scale items. Validity was examined in relation to the patient-therapist alliance and to willingness to share private information (social media content) with one’s clinician.

Results
Beginning with 10 items, a final 8-item version of the measure was created with an internal consistency reliability of .91. Principal components analysis indicated that the scale was best viewed as capturing one overall dimension. A Graded Response Model IRT model indicated that all items contributed information on the latent dimension, and all item curves were not flat at any region. The correlation of the trust/respect total score with the alliance was .53 when respect-related items were deleted from the alliance score. The trust/respect scale was significantly associated with patient willingness to share social media posts with their clinician but the alliance was not.

Conclusions
The brief measure of patient trust and respect towards their clinician was unidimensional, showed good internal consistency, and was not redundant with existing measures of the alliance. The scale has the potential to be used in a wide variety of healthcare settings.
Synapse alterations precede neuronal damage and storage pathology in a human cerebral organoid model of CLN3-juvenile neuronal ceroid lipofuscinosis
Authors: Gomez-Giro Gemma , Arias-Fuenzalida Jonathan , Jarazo Javier , Zeuschner Dagmar , Ali Muhammad , Possemis Nina , Bolognin Silvia , Halder Rashi , Jäger Christian , Kuper Willemijn F. E. , van Hasselt Peter M. , Zaehres Holm , del Sol Antonio , van der Putten Herman , Schöler Hans R. , Schwamborn Jens C. 
Published: December 2019

AbstractThe juvenile form of neuronal ceroid Lipofuscinosis (JNCL) is the most common form within this group of rare lysosomal storage disorders, causing pediatric neurodegeneration. The genetic disorder, which is caused by recessive mutations affecting the CLN3 gene, features progressive vision loss, cognitive and motor decline and other psychiatric conditions, seizure episodes, leading to premature death. Animal models have traditionally aid the understanding of the disease mechanisms and pathology and are very relevant for biomarker research and therapeutic testing. Nevertheless, there is a need for establishing reliable and predictive human cellular models to study the disease. Since patient material, particularly from children, is scarce and difficult to obtain, we generated an engineered a CLN3-mutant isogenic human induced pluripotent stem cell (hiPSC) line carrying the c.1054C → T pathologic variant, using state of the art CRISPR/Cas9 technology. To prove the suitability of the isogenic pair to model JNCL, we screened for disease-specific phenotypes in non-neuronal two-dimensional cell culture models as well as in cerebral brain organoids. Our data demonstrates that the sole introduction of the pathogenic variant gives rise to classical hallmarks of JNCL in vitro. Additionally, we discovered an alteration of the splicing caused by this particular mutation. Next, we derived cerebral organoids and used them as a neurodevelopmental model to study the particular effects of the CLN3Q352X mutation during brain formation in the disease context. About half of the mutation -carrying cerebral organoids completely failed to develop normally. The other half, which escaped this severe defect were used for the analysis of more subtle alterations. In these escapers, whole-transcriptome analysis demonstrated early disease signatures, affecting pathways related to development, corticogenesis and synapses. Complementary metabolomics analysis confirmed decreased levels of cerebral tissue metabolites, some particularly relevant for synapse formation and neurotransmission, such as gamma-amino butyric acid (GABA). Our data suggests that a mutation in CLN3 severely affects brain development. Furthermore, before disease onset, disease -associated neurodevelopmental changes, particular concerning synapse formation and function, occur.
IDC theory: creation and the creation loop
Authors: Chan Tak-Wai , Looi Chee-Kit , Chang Ben , Chen Wenli , Wong Lung-Hsiang , Wong Su Luan , Yu Fu-Yun , Mason Jon , Liu Chen-Chung , Shih Ju-Ling , Wu Ying-Tien , Kong Siu-Cheung , Wu Longkai , Chien Tzu-Chao , Liao Calvin C. Y. , Cheng Hercy , Chen Zhi-Hong , Chou Chih-Yueh 
Published: December 2019

AbstractThe interest-driven creator (IDC) theory is being developed as a group endeavor by Asian researchers to articulate a holistic learning design theory for future education in Asia. The theory hypothesizes that students, driven by interest, can be engaged in the creation of knowledge (generating ideas and artifacts). By repeating this creation process in their daily learning routines, they will excel in learning performance, develop twenty-first-century competencies, and form creation habits. We hope that with such practices in education, our future generations will ultimately become lifelong interest-driven creators. In IDC Theory, there are three anchored concepts, namely, interest, creation, and habit. Each anchored concept comprises three component concepts which form a concept loop. For example, the creation loop consists of three component concepts—imitating, combining, and staging. Imitating is concerned with taking in (or inputting) an abundant amount of existing knowledge from the outside world to form one’s background knowledge. Combining refers to delivering (or outputting) new ideas or artifacts prolifically by synthesizing existing information encountered in the world and thoughts arising from the students’ background knowledge. Staging relates to frequently demonstrating the generated ideas or artifacts to the relevant communities and receiving feedback from these communities to improve the novelty and value of the demonstrated outcomes while gaining social recognition and nurturing positive social emotions. This paper focuses on describing the three components of the creation loop. We provide three case studies to illustrate the creation loop at work, as well as how it intertwines with both the interest and habit loops in supporting students to develop their creation capabilities. In presenting this iteration of the creation concept, an anchored concept in IDC theory, we acknowledge the roles played of imitation, combination, and staging in different learning and education contexts—indeed, there are multiple theories that inform and intersect with it.
Population genetic structure based on mitochondrial DNA analysis of Ikonnikov’s whiskered bat (Myotis ikonnikovi—Chiroptera: Vespertilionidae) from Korea
Authors: Park Soyeon , Noh Pureum , Choi Yu-Seong , Joo Sungbae , Jeong Gilsang , Kim Sun-Sook 
Published: December 2019

Abstract
Background
Ikonnikov’s whiskered bat (Myotis ikonnikovi) is found throughout the Korean Peninsula, as well as in Kazakhstan, Russia, Mongolia, China, and Japan. It is small-sized and primarily inhabits old-growth forests. The decrease and fragmentation of habitats due to increased human activity may influence the genetic structure of bat populations. This study was designed to elucidate the population genetic structure of M. ikonnikovi using mitochondrial genes (cytochrome oxidase I and cytochrome b).

Results
The results showed that M. ikonnikovi populations from Korea have high genetic diversity. Although genetic differentiation was not detected for the COI gene, strong genetic differentiation of the Cytb gene between Mt. Jeombong and Mt. Jiri populations was observed. Moreover, the results indicated that the gene flow of the maternal lineage may be limited.

Conclusions
This study is the first to identify the genetic population structure of M. ikonnikovi. We suggest that conservation of local populations is important for sustaining the genetic diversity of the bat, and comprehensive studies on factors causing habitat fragmentation are required.
Traffic Shaping Menggunakan Metode HTB (Hierarchical Token Bucket) pada Jaringan Nirkabel
Authors: Budin Shiha , Riadi Imam 
Published: December 2019

Perkembangan zaman yang semakin pesat menuntut adanya layanan informasi yang lebih cepat, tepat, dan akurat menjadikan jaringan komputer sebagai kebutuhan utama. Traffic Shaping dengan Quality of Service (QoS) dapat digunakan dalam mengoptimalkan bandwidth suatu jaringan untuk menentukan jenis-jenis lalu lintas jaringan. Metode Hierarchical Token Bucket (HTB) dapat mengimplementasi pembagian trafik yang lebih akurat, dengan bandwidth yang tidak digunakan dapat dioptimalkan oleh pengguna lain. Hasil traffic shaping menggunakan metode HTB menghasilkan rata-rata indeks QoS yaitu 3,75 dan dapat dikategorikan Baik, dibandingkan sebelum menerapkan traffic shaping yaitu rata-rata 2,25 yang dikategorikan Kurang Baik. Berdasarkan hasil pengujian dapat disimpulkan bahwa kinerja jaringan hotspot dengan Traffic Shaping dan Quality of Service (QoS) dapat meningkatkan kualitas jaringan daripada sebelumnya.The development of an increasingly rapid era requires the existence of information services that are faster, more precise, and accurate, making computer networks a primary need. Traffic Shaping with Quality of Service (QoS) can be used in optimizing the bandwidth of a network to determine the types of network traffic. The Hierarchical Token Bucket (HTB) method can implement more accurate traffic sharing, with unused bandwidth being optimized by other users. The results of traffic shaping using the HTB method produces an average QoS index of 3.75 and can be categorized Good, compared to before applying traffic shaping which is an average of 2.25 which is categorized as Poor. Based on the test results it can be concluded that the performance of hotspot networks with Traffic Shaping and Quality of Service (QoS) can improve network quality than before.
Genetic Characterization of Melipona subnitida Stingless Bee in Brazilian Northeast
Authors: Barbosa Marcela De Matos , Bonatti Vanessa , Galaschi Teixeira Juliana S. , Correia Rêgo Márcia Maria , Francoy Tiago Maurício 
Published: December 2019

The study of M. subnitida, stingless bee well adapted to extreme environmental conditions, is noteworthy once the Northeastern Brazil faces climate changing predictions in which the precipitation rates are expected to decrease, and the average of temperatures to increase. The well-studied populations are limited to the Caatinga biome, where the species was considered endemic. However, the occurrence of this species has been reported in contrasting environments from arid region, such as mangrove and sandbanks in Maranhão state. Our primary goal was to characterize samples from these different environments and compare them with previously studied populations. We identified a unique mitochondrial haplotype per region. The haplotype found in Lençóis Maranhenses National Park was exclusive from this location and differed regarding the amino acid sequence when compared to the literature presented haplotypes from Caatinga, which might be related with different evolutionary processes in the distinct environments, though further studies are needed to confirm. Melipona subnitida is highly adapted to extreme environmental conditions and can survive under long drought periods, since during water and resource scarcity, the bees reduce the colony size to a minimum number of brood and workers. Thus, the species maintains only essential tasks for the nest, being an important mechanism to save the resources stored during the bloom of rainy periods (Maia-Silva et al., 2014; 2015). Assuming the climate change predictions for Northeastern Brazil (Marengo et al., 2011) in the semi-arid region, where average reductions in precipitation rates of up to 40–50% are expected (PBMC, 2013), the study bees resistant to these conditions, such as M. subnitida, is noteworthy. Considering the importance of this species regarding resistance to extreme climatic conditions, distributional modeling
Myrmecophily and Myrmecophagy of Attacobius lavape (Araneae: Corinnidae) on Solenopsis saevissima (Hymenoptera: Myrmicinae)
Authors: Mendonça Cindy Anne Ferreira , Pesquero Marcos Antônio , Carvalho Rosalinda Dos Santos Damasceno , Arruda Filipe Viegas de 
Published: December 2019

Attacobius lavape, a small spider from the Corinnidae family, has been recently described living inside a fire ant colony of Solenopsis saevissima species in the municipality of Morrinhos, south region of the Goiás State, Brazil. Yet several aspects of this spider relationship with the host ant remain unknown. In this way, we performed an extension study to determine its local (Morrinhos) and regional (latitudinal transect) occurrence. We also investigated if the spider uses the host ant as a feeding source. For this, we established arenas with a known number of young and adult ant individuals plus one spider and observed the feeding rate for some determined time. Regarding local distribution, differently from most socially parasitic myrmecophiles, A. lavape showed high local infestation, being found in 47% of the colonies in the sites where the spider occurred, and high transmission, being found in 42% of the 12 collection sites. Regionally, among the 11 study sites, this species only occurred in the municipality of Morrinhos, but its distribution still needs to be verified in the north region. Attacobius lavape consumed eggs, larvae and pupae, confirming that the myrmecophily was explained by myrmecophagy. The spiders consumed eggs (not estimated), 4.45 ± 2.14 larvae and/or 3 ± 0.87 pupae per day. Considering that the mean abundance was approximately seven spiders per colony (extent 1-23), we foresee an impact of 35 larvae and/or 21 pupae consumed per day in each hosting colony. The possibility of consuming sexual eggs, larvae and pupae classifies A. lavape as a potential agent of biological control of S. saevissima.
Análise sobre Accountability, Participação social e Transparência Pública no Estado de Alagoas: Um estudo de Caso / Analysis on Accountability, Social Participation and Public Transparency in the State of Alagoas: A Case Study
Authors: Mota Paulo Rocha , Valente Maria José Andrade Pais 
Published: December 2019

Uma abordagem extremamente emergente na Gestão Pública é a ação e atuação da Accountability, que como descrito trata-se de um conceito novo e que tem desempenhado função de levar até a sociedade informações sobre o orçamento (arrecadação, utilização e alocação dos recursos públicos), abrindo canais de contato com a mesma para que eventuais discordâncias e inquietações sejam protocoladas e, neste sentido, atendidas pelos órgãos de comunicação e competência. O presente estudo objetivou uma Análise sobre Accountability, Participação social e Transparência Pública no Estado de Alagoas. Trata-se de um estudo de caso, descritivo, em instituição, selecionada pela sua especificidade, quanto a transparência das informações sobre as contas públicas, e baseado em algumas fontes de informação eletrônica. Os resultados demonstraram que, embora os sites pesquisados estejam em conformidade com a Lei de Acesso à Informação e Lei da Transparência, ainda há bastante espaço para a participação social no processo de elaboração e discussão do planejamento do Orçamento Público. Palavras-chave: Accountability, Contas públicas, Portal da Transparência.
Diversidade de Gênero no Mercado de Trabalho / Gender Diversity in the Labor Market
Authors: Dantas João Victor Diógenes , Gomes Filho Antoniel Dos Santos 
Published: December 2019

A temática da diversidade tornou-se constantemente debatida, principalmente em um país como o Brasil, que é conhecido por sua riqueza cultural. Assim, os processos de gestão da diversidade por meio da organização das pessoas no âmbito organizacional busca meios para integração e inclusão social, inclusive no que tange as questões do gênero. A busca pela igualdade e o combate das desigualdades de gênero e orientação sexual é parte da história do Brasil. O presente estudo objetiva apresentar a partir de uma pesquisa bibliográfica os principais desafios enfrentados pelas pessoas LGBTs no mercado de trabalho. Metodologicamente a pesquisa possui uma abordagem qualitativa, sendo classificada como exploratória e de tipo bibliográfica, onde foram utilizados livros e artigos que tratassem do tema diversidade nas organizações. Pode-se considerar que as recentes tendências empresariais da globalização e o aumento da diversidade étnica e de gênero estão voltando a atenção dos gerentes para a gestão das diferenças culturais. A literatura de gestão sugeriu que as organizações deveriam valorizar a diversidade para aumentar a eficácia organizacional.