bluuebunny/crossref_metadata_2025_split huggingface dataset:
Partnership Among Hospitals To Reduce Healthcare Associated Infections: A Quasi-Experimental Study In Brazilian Icus
Authors: de Melo Ladjane Santos Wolmer , de Abreu Maria Verônica Monteiro , Santos Bernuarda Roberta de Oliveira , Carreteiro Maria das Graças Washington Casimiro , de Albuquerque Maria Carolina Andrade Lins , de Souza Maria Fernanda Aparecida Moura , Vidal Claudia Fernanda de Lacerda , Lacerda Heloisa Ramos 
Published: September 2020

Abstract
Background: Healthcare-associated infections (HAIs) are relevant in developing countries where frequencies can be at least 3 times higher than in developed countries. The purpose of this research was to describe the intervention implemented in intensive care units (ICUs) to reduce HAIs through collaborative project and analyze the variation over 18 months in the incidence density (ID) of the three main HAIs: ventilator associated pneumonia (VAP), central line-associated bloodstream infections (CLABSIs) and catheter-related urinary tract infections (CAUTIs) and also the length of stay and mortality in these ICUs. Methods: A quasi-experimental study in 5 public adult clinical-surgical ICUs, to reduce HAIs, through interventions using the BTS-IHI “Improvement Model”, during 18 months. In the project, promoted by the Ministry of Health, Brazilian philanthropic hospitals of excellence (HE), those certified as charities, excellence and exempt from security contributions, regularly trained and monitored public hospitals in diagnostics, data collection and in developing cycles to improve quality and to prevent HAIs (bundles). In the analysis regarding the length of stay, mortality, the IDs of VAP, CLABSIs and CAUTIs over time, a Generalized Estimating Equation (GEE) model was applied for continuous variables, using the constant correlation (exchangeable) between assessments over time. The model estimated the average difference (β coefficient of the model) of the measures analyzed during two periods: a period in the year 2017 (prior to implementing the project) and in the years 2018 and 2019 (during the project).Result: A mean monthly reduction of 0.427 in VAP ID (p = 0.002) with 33.8% decrease at the end of the period and 0.351 in CAUTI ID (p = 0.009) with 45% final decrease. The mean monthly reduction of 0.252 for CLABSIs was not significant (p = 0.068). Length of stay and mortality rates had no significant variation. Conclusions: Given the success in reducing VAP and CAUTIs in a few months of interventions, the achievement of the collaborative project is evident. This partnership among public hospitals/HE may be applied to other ICUs including countries with fewer resources.Trial registration: Promoted by Brazilian Ministry of Health. Approved by the Hospital das Clínicas – UFPE Ethics Committee (No. 3,307,293).
The quality of reporting general safety parameters and immune-related adverse events in clinical trials of FDA-approved immune checkpoint inhibitors
Authors: Karimian Zahra , Mavoungou Sandra , Salem Joe-Elie , Tubach Florence , Dechartres Agnes 
Published: September 2020

Abstract
Background – While immune-checkpoint inhibitors (ICIs) have transformed the field of oncology for advanced-stage cancers, they can lead to serious immune toxicities. Several systematic reviews have evaluated the risk of immune-related adverse events (irAEs); however, most have focused on published articles without evaluating trial registries. The objective of this methodological review was to compare the quality of reporting of safety information and in particular, serious irAEs (irSAEs), in both publications and ClinicalTrials.gov for all current FDA-approved ICIs.Methods – PubMed was searched to retrieve all published phase III randomized controlled trials (RCTs) evaluating ICIs. For each eligible trial, we searched for corresponding registration on ClinicalTrials.gov and extracted relevant safety data from both the publication and results posted on registry. We then compared the quality of reporting and the value of safety data between both sources.Results – Of 42 eligible published trials, 34 had results posted on ClinicalTrials.gov. Considerable variability was noted in the reporting of safety in both sources. SAEs were reported for all trial results in ClinicalTrials.gov compared to 23.5% of publications. An overall incidence for irAEs and irSAEs was reported in 58.8% and 8.8% of publications respectively, compared to 11.8% and 5.9% in registry results. Comparing the value of specific irSAEs was not possible between the two sources in 32/34 trials either due to different reporting formats (61.8%) or data not being reported in one or both sources (32.4%). From the 2 studies with compatible irSAE format, only 1 had matching data in both sources.Conclusions – The reporting of irAEs / irSAEs varies considerably in publications and registries, which outlines the importance of standardizing the terminologies and methodologies for reporting safety information relevant to ICIs.
Patient preferences on rheumatoid arthritis second-line treatment: A discrete choice experiment of Swedish patients
Authors: Bywall Karin Schölin , Kihlbom Ulrik , Hansson Mats , Falahee Marie , Raza Karim , Baecklund Eva , Veldwijk Jorien 
Published: September 2020

Abstract
Background: Preference assessments of patients with rheumatoid arthritis (RA) help inform clinical therapeutic decisions for including biologic and targeted synthetic drugs to use. This study assesses patient preferences for biologics or Janus kinases (JAK) inhibitors and heterogeneity within these preferences to estimate the relative importance of treatment characteristics and to calculate the minimum benefit levels patients require to accept higher levels of side effects.Methods: Between November 2018 to August 2019, patients were recruited to participate in a survey containing demographic and disease-related questions as well as a Discrete Choice Experiment to measure their preferences for second-line therapies using biologics or JAK inhibitors. Treatment characteristics (attributes) included in the DCE were mode of administration, frequency of use, probability of mild short-term side effects, probability of side effects affecting appearance, probability of psychological side effects, probability of severe side effects, and effectiveness of treatment.Results: A total of 358 patients were included in the analysis. Latent class analysis revealed three preference patterns. When choosing treatment, the respondents found either effectiveness of treatment (34%), mode of administration (28%), or probability of severe side effects as most important (38%). In addition, disease duration and mild side effects influenced the patients’ choices.Conclusion: Respondents found either effectiveness, severe side effects, or mode of administration as the most important attribute. Patients noting effectiveness as most important were more willing than other patients to accept higher risks of side effects.
Long-lasting insecticide-treated bed net ownership, utilization and associated factors among school-age children in Dara Mallo and Uba Debretsehay districts, Southern Ethiopia
Authors: Zerdo Zerihun , Bastiaens Hilde , Anthierens Sibyl , Massebo Fekadu , Masine Matios , Biresawu Gelila , Shewangizaw Misgun , Tunje Abayneh , Chisha Yilma , Yohannes Tsegaye , geertruyden Jean-Pierre Van 
Published: September 2020

Abstract
Background Malaria is one of the major causes of morbidity and mortality among school-age children (SAC) in sub-Saharan Africa. SAC account for more than 60% of the reservoir of malaria transmission, but they are given less emphasis in prioritizing malaria prevention interventions. This study was aimed at assessing the ownership of long-lasting insecticide treated bed nets (LLINs), its utilization and factors associated with ownership of LLINs by households and LLINs utilization among SAC in malaria-prone areas of Dara Mallo and Uba Debretsehay districts in Southern Ethiopia, October to December 2019. Methods This study is part of a baseline assessment in a cluster-randomized controlled trial. The data was collected through interview and observation, following a structured questionnaire, of 2,261 SAC households. Univariable and multivariable multilevel logistic regressions were used to assess the association between LLINs ownership and utilization and potential predictor variables. Odds ratio (OR) and corresponding 95% confidence interval (CI) were used to determine the strength and statistical significance of association.Results The ownership of at least one LLIN by households of SAC was about 19.3% (95% CI: 17.7-21.0%) but only 10.3% % (95% CI: 7.7-13.7%) of these households had adequate access of bed nets to the household members. Ownership of bed net was marginally affected by living in semi-urban area (adjusted OR= 2.6; 95% CI: 1.0-6.9) and occupational status of the household head being a civil servant (adjusted OR= 2.7; 95% CI: 0.9-7.9). About 7.8% (95% CI: 6.7-10.0%) of all SAC participated in the study and 40.4% (95% CI: 57.4-66.7%) of children in households owning at least one LLIN passed the previous night under LLIN. LLIN utilization by SAC conditional to presence of at least one net in the household was significantly correlated with education level of mother above grade 6 (adjusted OR= 3.4; 95% CI: 1.3-9.3) and the household size to bed net ratio less than or equal to 2 (adjusted OR= 20.7; 95% CI: 4.7-132.5). Conclusion Ownership of bed net was lower than universal coverage of at least one bed net for two individuals. It is important to monitor replacement needs and educate mothers with low education level with their SAC on the benefit of consistent utilization of bed nets.
Investigation of the role of AcTPR2 in kiwifruit and its response to Botrytis cinerea infection
Authors: Li Zhexin , Lan Jian-Bin , Liu Yi-Qing , Qi Li-Wang , Tang Jianmin 
Published: September 2020

Abstract
Background: Elucidation of the regulatory mechanism of kiwifruit response to gray mold disease caused by Botrytis cinerea can provide the basis for its molecular breeding to impart resistance against this disease. In this study, 'Hongyang' kiwifruit served as the experimental material; the TOPLESS/TOPLESS-RELATED (TPL/TPR) co-repressor gene AcTPR2 was cloned into a pTRV2 vector (AcTPR2-TRV) and the virus-induced gene silencing technique was used to establish the functions of the AcTPR2 gene in kiwifruit resistance to Botrytis cinerea.Results: Virus-induced silencing of AcTPR2 enhanced the susceptibility of kiwifruit to Botrytis cinerea. Defensive enzymes such as superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and phenylalanine ammonia-lyase (PAL) and endogenous phytohormones such as indole acetic acid (IAA), gibberellin (GA3), abscisic acid (ABA), and salicylic acid (SA) were detected. Kiwifruit activated these enzymes and endogenous phytohormones in response to pathogen-induced stress and injury. The expression levels of the IAA signaling genes—AcNIT, AcARF1, and AcARF2—were higher in the AcTPR2-TRV treatment group than in the control. The IAA levels were higher and the rot phenotype was more severe in AcTPR2-TRV kiwifruits than that in the control. These results suggested that AcTPR2 downregulation promotes expression of IAA and IAA signaling genes and accelerates postharvest kiwifruit senescence. Further, Botrytis cinerea dramatically upregulated AcTPR2, indicating that AcTPR2 augments kiwifruit defense against pathogens by downregulating the IAA and IAA signaling genes.Conclusions: The results of the present study could help clarify the regulatory mechanisms of disease resistance in kiwifruit and furnish genetic resources for molecular breeding of kiwifruit disease resistance.
Aß40 displays amyloidogenic properties in the non-transgenic mouse brain but does not exacerbate Aß42 toxicity in Drosophila.
Authors: de Mena Lorena , Smith Michael A , Martin Jason , Dunton Katie L , Ceballos-Diaz Carolina , Jansen-West Karen , Cruz Pedro E , Dillon Kristy D , Rincon-Limas Diego , Golde Todd E , Moore Brenda D , Levites Yona 
Published: September 2020

Abstract
Background Self-assembly of the amyloid-β (Aβ) peptide into aggregates, from small oligomers to amyloid fibrils, is fundamentally linked with Alzheimer’s disease (AD). However it is clear that not all forms of Aβ are equally harmful, and that linking a specific aggregate to toxicity also depends on the assays and model systems used [1, 2]. Though a central postulate of the amyloid cascade hypothesis, there remain many gaps in our understanding regarding the links between Aβ deposition and neurodegeneration. Methods In this study, we examined familial mutations of Aβ that increase aggregation and oligomerization, E22G and DE22, and induce cerebral amyloid angiopathy, E22Q and D23N. We also investigated synthetic mutations that stabilize dimerization, S26C, and a phospho-mimetic, S8E, and non-phospho-mimetic, S8A. To that end, we utilized BRI2-Aβ fusion technology and rAAV2/1 based somatic brain transgenesis in mice to selectively express individual mutant Aβ species in vivo. In parallel we generated PhiC31-based transgenic Drosophila melanogaster expressing wild type (WT) and Aβ40 and Aβ42 mutants, fused to the Argos signal peptide to assess the extent of Aβ42-induced toxicity as well as to interrogate the combined effect of different Aβ40 and Aβ42 species.Results When expressed in the mouse brain for 6 months, Aβ42 E22G, Aβ42 E22Q/D23N, and Aβ42WT formed amyloid aggregates consisting of some diffuse material as well as cored plaques, whereas other mutants formed predominantly diffuse amyloid deposits. Moreover, while Aβ40WT showed no distinctive phenotype, Aβ40 E22G and E22Q/D23N formed unique aggregates that accumulated in mouse brains. This is the first evidence that mutant Aβ40 overexpression leads to deposition under certain conditions. Interestingly, we found that mutant Aβ42 E22G, E22Q, and S26C, but not Aβ40, were toxic to the eye of Drosophila. In contrast, flies expressing a copy of Aβ40 (WT or mutants) in addition to Aβ42WT, showed improved phenotypes, suggesting possible protective qualities for Aβ40. Conclusions These studies suggest that while some Aβ40 mutants form unique amyloid aggregates in mouse brains, they do not exacerbate Aβ42 toxicity in Drosophila, which highlights the significance of using different systems for a better understanding of AD pathogenicity and more accurate screening for new potential therapies.
smORFunction: A Tool for Predicting Functions of Small Open Reading Frames and Microproteins
Authors: Ji Xiangwen , Cui Chunmei , Cui Qinghua 
Published: September 2020

Abstract
Background Small open reading frame (smORF) is open reading frame with a length of less than 100 codons. Microproteins, translated from smORFs, have been found to participate in a variety of biological processes such as muscle formation and contraction, cell proliferation, and immune activation. Although previous studies have collected and annotated a large abundance of smORFs, functions of the vast majority of smORFs are still unknown. It is thus increasingly important to develop computational methods to annotate the functions of these smORFs. Results In this study, we collected 617,462 unique smORFs from three studies. The expression of smORF RNAs was estimated by reannotated microarray probes. Using a speed-optimized correlation algorism, the functions of smORFs were predicted by their correlated genes with known functional annotations. After applying our method to 5 known microproteins from literatures, our method successfully predicted their functions. Further validation from the UniProt database showed that at least one function of 202 out of 270 microproteins was predicted. Conclusions We developed a method, smORFunction, to provide function predictions of smORFs/microproteins in at most 265 models generated from 173 datasets, including 48 tissues/cells, 82 diseases (and normal). The tool can be available at http://www.cuilab.cn/smorfunction.
Binding of human serum proteins to Plasmodium&nbsp;falciparum-infected erythrocytes and its association with malaria clinical presentation
Authors: Lopez-Perez Mary , Puije William van der , Castberg Filip C. , Ofori Michael F. , Hviid Lars 
Published: September 2020

Abstract
Background The pathogenesis of Plasmodium falciparum malaria is related to the ability of parasite‑infected erythrocytes (IEs) to adhere to the vascular endothelium (cytoadhesion/sequestration) or to surrounding uninfected erythrocytes (rosetting). Both processes are mediated by the expression of members of the clonally variant PfEMP1 parasite protein family on the surface of the IEs. Recent evidence obtained with laboratory-adapted clones indicates that P. falciparum can exploit human serum factors, such as IgM and α2‑macroglobulin (α2M), to increase the avidity of PfEMP1-mediated binding to erythrocyte receptors, as well as to evade host PfEMP1-specific immune responses. It has remained unclear whether PfEMP1 variants present in field isolates share these characteristics, and whether they are associated with clinical malaria severity. These issues were investigated here.Methods Children 1-12 years reporting with P. falciparum malaria to Hohoe Municipal Hospital, Ghana were enrolled in the study. Parasites from children with uncomplicated (UM) and severe malaria (SM) were collected. Binding of α2M and IgM from non-immune individuals to erythrocytes infected by P. falciparum isolates from 34 children (UM and SM) were analysed by flow cytometry. Rosetting in the presence of IgM or α2M was also evaluated. Experimental results were analysed according to the clinical presentation of the patients.Results Clinical data from 108 children classified as UM (n=54) and SM cases (n=54) were analysed. Prostration, severe malaria anaemia, and hyperparasitaemia were the most frequent complications. Three children were diagnosed with cerebral malaria, and one child died. Parasite isolates from UM (n=14) and SM (n=20) children were analysed. Most of the field isolates bound non‑immune IgM (33/34), whereas the α2M-binding was less common (23/34). Binding of both non-immune IgM and α2M was higher but not significant in IEs from children with SM than from children with UM. In combination, IgM and α2M supported rosette formation at levels similar to that observed in the presence of 10% human serum. Conclusions The results support the hypothesis that binding of non-immune IgM and/or α2M to IEs facilitates rosette formation and perhaps contributes to P. falciparum malaria severity.
Too sweet: cheminformatics for deglycosylation in natural products
Authors: Schaub Jonas , Zielesny Achim , Steinbeck Christoph , Sorokina Maria 
Published: September 2020

Abstract
Sugar units in natural products are pharmacokinetically important but often redundant and therefore obstructing the study of the structure and function of the aglycon. Therefore, it is recommended to remove the sugars before a theoretical or experimental study of a molecule. Deglycogenases, enzymes that specialized in sugar removal from small molecules, are often used in laboratories to perform this task. However, there is no standardized computational procedure to perform this task in silico. In this work, we present a systematic approach for in silico removal of ring and linear sugars from molecular structures. Particular attention is given to molecules of biological origin and to their structural specificities. This approach is made available in two forms, through a free and open web application and as standalone open-source software.
Comparative Transcriptome Analysis of a Fan-shaped Inflorescence in Pineapple Using RNA-seq
Authors: Xie Tao , Cai Zhiquan , Luan Aiping , Zhang Wei , Wu Jing , Yang Quannv , He Yehua 
Published: September 2020

Abstract
Background: Pineapple plant usually has a capitulum. However, a fan-shaped inflorescence was evolved in an exceptional material, having multiple crown buds. In order to reveal the molecular mechanisms of the formation of the fan-shaped inflorescence, fruit traits and the transcriptional differences between a fan-shaped inflorescence (FI) and a capitulum inflorescence (CI) pineapples were analyzed in the three tissues, i.e., the flower stem apex (FIs and CIs), the base of the inflorescence (FIb and CIb), and the inflorescence axis (FIa and CIa).Results: Except for a clear differentiation of inflorescence morphology, no significant differences in the structure of inflorescence organs and the main nutritional components (soluble solids, soluble sugar, titratable acid, and VC) in fruits were found between the two pineapples. Between the fan- and capitulum-shaped inflorescences, a total of 5370 differentially expressed genes (DEGs) were identified across the three tissues; and 3142, 2526 and 2255 DEGs were found in the flower stem apex, the base of the inflorescence, and the inflorescence axis, respectively. Of these genes, there were 489 overlapping DEGs in all three tissue comparisons. In addition, 5769 DEGs were identified between different tissues within each pineapple. Functional analysis indicated between the two pineapples that 444 transcription factors (TFs) and 206 inflorescence development related genes (IDGs) were differentially expressed in at least one tissue comparison, while 45 TFs and 21 IDGs were overlapped across the 3 tissues. Among the 489 overlapping DEGs in the 3 tissue comparisons between the two pineapples, excluding the IDGs and TFs, 80 of them revealed a higher percentage of involvement in the biological processes relating to response to auxin, and reproductive processes. RNA-seq value and real-time quantitative PCR analysis exhibited the same gene expression patterns in the three tissues. Conclusions: Our result provided novel cues for understanding the molecular mechanisms of the formation of fan-shaped inflorescence in pineapple, making a valuable resource for the study of plant breeding and the speciation of the pineapples.