bluuebunny/crossref_metadata_2025 huggingface dataset:
Dental caries in association with viral load in children living with HIV in Phnom Penh, Cambodia: a cross-sectional study
Authors: Kikuchi Kimiyo , Yasuoka Junko , Tuot Sovannary , Okawa Sumiyo , Yem Sokunthea , Chhuon Pheak , Murayama Makoto , Huot Chantheany , Yi Siyan
Published: September 2020

Background: Oral health status is known to be associated with overall health among people living with HIV. However, it is unclear whether dental caries is associated with viral load among this population. In particular, dental caries among children living with HIV needs to be better understood, as this can affect their overall health and future well-being. This study assessed the association between dental caries and viral load among children living with HIV in Phnom Penh, Cambodia.Methods: This cross-sectional study was conducted at the National Paediatric Hospital as a baseline survey of a randomized controlled trial. The study population included children living with HIV aged 3–15 years and their primary caregivers. We collected data on the children’s oral health status by oral examination and the latest HIV viral load data stored in the patients’ information system at the hospital. We also conducted a questionnaire-based interview of the children and their primary caregivers. Multiple logistic regression analysis was conducted to assess the association between dental caries and viral load. The cut-off point for undetectable viral load was set at <40 copies/mL.Results: Data from 328 children were included in the analysis; 68.3% had an undetectable viral load. The mean number of permanent or deciduous teeth with caries was 7.7 (standard deviation, 5.0). In the regression analysis, dental caries in permanent or deciduous teeth was positively associated with detectable viral load (adjusted odds ratio: 1.07, 95% confidence interval: 1.01–1.14). Conversely, antiretroviral therapy of ≥1 year and self-reported better adherence to antiretroviral drugs were negatively associated with detectable viral load. Among children with detectable viral load, dental caries in permanent or deciduous teeth was also positively associated with non-suppression of viral load (>1000 copies/mL) (adjusted odds ratio: 1.12, 95% confidence interval: 1.03–1.23).Conclusions: Dental caries was associated with viral load status detection among children living with HIV. This finding suggests that oral health status may affect the immune status of children. The oral health of children living with HIV should be strengthened, and further research is needed to clarify the causal relationship between viral load and oral health status.
Impact of relative dose intensity of oxaliplatin in adjuvant therapy among stage III colon cancer patients on early recurrence: a retrospective cohort study
Authors: Żok Jolanta , Bieńkowski Michał , Radecka Barbara , Korniluk Jan , Adamowicz Krzysztof , Duchnowska Renata
Published: September 2020

Background: Oxaliplatin-based therapy with FOLFOX-4 or CAPOX administered over 6 months remains the standard adjuvant treatment for stage III colon cancer (CC) patients. However, many patients experience dose reduction or early termination of chemotherapy due to oxaliplatin toxicity, which may increase the risk of early recurrence. The objective of this study was to analyze the relationship between the relative dose intensity of oxaliplatin (RDI-O) and early recurrence among stage III CC patients. Methods: The study included 365 patients treated at five oncology centers in Poland between 2000 and 2014.Survival analysis was performed using the Kaplan-Meier method. Univariate analysis was performed using the Cox proportional hazard model; multivariate analysis was performed with the stepwise forward approach. For all analyses the αlevel of 0.05 was employed. Results: The median follow-up was 51.8 months (range 8.2-115.1). Early recurrence <36 months after surgery occurred in 130 patients (37.8%). In this group 51 (39.2%) and 87 (66.9%) of patients were low and high-risk, respectively. Receipt <60% of RDI-O was associated with early recurrence within 18 months after surgery (OR=2.05; 95%CI: 1.18-3.51; p=0.010),especially in low-risk group (HR=1.56 (95%CI: 0.96-2.53), p=0.07). In the multivariate analysis early recurrence was correlated with grade (OR=2.47; 95% CI: 1.25-4.8; p=0.008), pN (OR=2.63; 95% CI: 1.55-4.54; p<0.001), the number of lymph nodes harvested (OR=0.51; 95% CI: 0.29-0.86; p=0.013) and RDI-O (OR=1.91; 95%CI: 1.06-3.39; p=0.028). The early vs. late recurrence negatively correlated with OS regardless of the RDI-O (HR=22.9 (95%CI: 13.9-37.6; p<0.001). Conclusions: RDI-O <60% in adjuvant therapy among stage III CC (especially in low-risk group) increases the risk of early recurrence within 18 months of surgery. Patients with early recurrence showed worse overall survival regardless of the RDI-O.
A full-length transcriptome and gene expression analysis reveal genes and molecular elements expressed during seed development in Gnetum luofuense
Authors: deng Nan , Hou Chen , He Boxiang , Ma Fengfeng , Song Qingan , Shi Shengqing , Liu Caixia , Tian Yuxin
Published: September 2020

Background: Gnetum is an economically important tropical and subtropical gymnosperm genus with various dietary, industrial and medicinal uses. Many carbohydrates, proteins and fibers accumulate during the ripening of Gnetum seeds. However, the molecular mechanisms related to this process remain unknown.Results: We therefore assembled a full-length transcriptome from immature and mature G. luofuense seeds using PacBio sequencing reads. We identified a total of 5,726 novel genes, 9,061 alternative splicing events, 3,551 lncRNAs, 2,160 transcription factors, and we found that 8,512 genes possessed at least one poly(A) site. In addition, gene expression comparisons of six transcriptomes generated by Illumina sequencing showed that 14,323 genes were differentially expressed from an immature stage to a mature stage with 7,891 genes upregulated and 6,432 genes downregulated. The expression of 14 differentially expressed transcription factors from the MADS-box, Aux/IAA and bHLH families was validated by qRT-PCR, suggesting that they may have important roles in seed ripening of G. luofuense.Conclusions: These findings provide a valuable molecular resource for understanding seed development of gymnosperms.
Water Loss During the Handwashing During COVID-19 Pandemic in Bangladesh
Authors: Sayeed Abu , Rahman Md Hafizur , Bundschuh Jochen , Herath Indika , Hasan M. Tasdik , Ahmed Fahad , Tariq Mohammad Raihan , Rahman Faujhia , Joy Md. Tarikul Islam , Abid Mohammad Tazrian , Saha Nondo
Published: September 2020

Handwashing is one of the vital public health measures to prevent COVID-19 pandemic from spread. However, water loss from excessive handwashing may put enormous pressure on the already overstretched groundwater resources and households’ economic well-being. Therefore, this study aimed to determine the water loss during handwashing amid the COVID-19 pandemic with an emphasis on the waste of groundwater from essential hygiene activities at domestic scale. Sociodemographic data were collected using a web-based survey tool among 1980 participants and an experiment was conducted among 126 voluntarily interested participants to estimate the amount of water wasted during handwashing. A total of 80% of the participants washed their hands regularly after returning home from outside. About 57.27% participants generally did not turn off their tap when washing their hands. A single participant, who keeps his tap on throughout the handwashing process, wasted approximately 1.7 L of water per handwash and 14.9 L of water per day. Handwashing when a tap is on, raised the water loss at 13-fold during this pandemic compared to the non-pandemic situation which cost extra 224.95 BDT (2.65$) per day for 1980 participants. A large number (57.27%) of people keep their faucet on during lathering hands with soap and scrubbing, thus wasting a considerable amount of water (1179% more compared to pre COVID-19 situation). The loss of water during handwashing is an alarming but less attentional issue. Behavioral change interventions are needed to aware people to shut off the faucet at periods when water is not being used.
Genome-wide characterization and expression analysis of the heat shock transcription factor family in pumpkin (Cucurbita moschata)
Authors: Shen Changwei , Yuan Jingping
Published: September 2020

Background: Crop quality and yield are affected by abiotic and biotic stresses, and heat shock transcription factors (Hsfs) are considered to play important roles in regulating plant tolerance under various stresses. To investigate the response of Cucurbita moschata to abiotic stress, we analyzed the genome of C. moschata. Results: In this research, a total of 36 C. moschata Hsf (CmHsf) members were identified and classified into three subfamilies (I, II, and III) according to their amino acid sequence identity. The Hsfs of the same subfamily usually exhibit a similar gene structure (intron-exon distribution) and conserved domains (DNA-binding and other functional domains). Chromosome localization analysis showed that the 36 CmHsfs were unevenly distributed on 18 of the 21 chromosomes (except for Cm_Chr00, Cm_Chr08 and Cm_Chr20), among which 18 genes formed 9 duplicated gene pairs that have undergone segmental duplication events. The Ka/Ks ratio showed that the duplicated CmHsfs have mainly experienced strong purifying selection. High-level synteny was observed between C. moschata and other Cucurbitaceae species. Conclusions: The expression profile of CmHsfs in the roots, stems, cotyledons and true leaves revealed that the CmHsfs exhibit tissue specificity. The analysis of cis-acting elements and quantitative real-time polymerase chain reaction (qRT-PCR) revealed that some key CmHsfs were activated by cold stress, heat stress, hormones and salicylic acid. This study lays the foundation for revealing the role of CmHsfs in resistance to various stresses, which is of great significance for the selection of stress-tolerant C. moschata.
Generation and molecular characteristics of a highly attenuated GPV strain through adaptation in GEF cells
Authors: Shao Hongxia , Jiang Yuchen , Yuan Huisha , Ji Lifei , Jin Wenjie , Qian Kun , Ye Jianqiang , Qin Aijian
Published: September 2020

Background: Goose parvoviruses (GPVs) spread globally and cause a huge economic loss to poultry industry. Although the attenuated GPV vaccines play a key role in preventing the disease caused by GPV, the molecular basis for the attenuation of GPV is barely known. Results: A highly attenuated GPV strain, GPV-CZM-142, was generated through blindly passaging of the highly pathogenic strain, GPV-CZM, in goose embryonic fibroblasts (GEF) for 142 generations. The virulence of the GEF-adapted GPV strain was 10000 times weaker than that of its wild type counterpart, GPV-CZM, based on the ELD50. By comparing with the wild type strain, genome sequencing analysis identified a novel insertion in ITR and several other mutations in both NS and VP1 of GPV-CZM-142.Conclusions: The highly attenuated GPV strain, GPV-CZM-142, provides a GPV vaccine candidate, and the identified virulence-related insertion/mutations give a novel insight into the molecular determinants of GPV virulence.
Ketamine-propofol (Ketofol) for Procedural Sedation and Analgesia in Children: A Systematic Review and Meta-Analysis
Authors: Foo Tze Yong , Noor Norhayati Mohd , Yazid Mohd Boniami , Fauzi Mohd Hashairi , Wahab Shaik Farid Abdull , Ahmad Mohammad Zikri
Published: September 2020

Objectives The aim of this review is to elucidate the efficacy and side effects of ketofol in comparison to other anaesthetic agents during procedural sedation and analgesia. Method The Cochrane Central Register of Controlled Trials (1996 to Feb 2019) and MEDLINE (1966 to Feb 2019) were searched, including the related randomised control trials and reviewed articles to find unpublished trials or trials not obtained via electronic searches. Inclusion criteria for the studies included comparing recovery time, recording clinician satisfaction, and assessing the adverse effects of ketofol. Results Eleven trials consisting of a total of 1274 patients met our criteria and were included in this meta-analysis. Five trials compared ketofol with a single agent, while six trials compared ketofol with combined agents. While comparing between ketofol and a single agent (either ketamine or propofol), ketofol showed significant effect on recovery time (MD: -9.88, 95% CI: -14.30 to -5.46; P=0.0003; I2=92%). However, no significant difference was observed while comparing ketofol with combined agents (RR: 0.75, 95% CI: -6.24 to 7.74; P<0.001; I2=98%). During single-agent comparison, ketofol showed no significant differences in terms of clinician satisfaction (RR: 2.86, 95% CI: 0.64 to 12.69; P=0.001; I2=90%), airway obstruction (RR: 0.72, 95% CI: 0.35 to 11.48; P=0.81; I2=0%), apnoea (RR: 0.9, 95% CI: 0.33 to 2.44; P=0.88; I2=0%), desaturation (RR: 1.11, 95% CI: 0.64 to 1.94; P=0.28; I2=21%), nausea (RR: 0.52, 95% CI: 0.91 to 1.41; P=0.2; I2=38%), and vomiting (RR: 0.63, 95% CI: 0.25 to 1.61; P=0.18; I2=42%). During comparison with combined agents, ketofol was more effective in reducing hypotension (RR: 4.2, 95% CI: 0.2 to 0.85; P=0.76; I2=0%), but no differences were observed in terms of bradycardia (RR: 0.70, 95% CI: 0.14 to 03.63; P=0.09; I2=53%), desaturation (RR: 1.9, 95% CI: 0.15 to 23.6; P=0.11; I2=61%), and respiratory depression (RR: 1.98, 95% CI: 0.18 to 21.94; P=0.12; I2=59%). Conclusion There is low certainty of evidence that ketofol improves recovery time and moderate certainty of evidence that it reduces the frequency of hypotension. There was no significant difference in terms of other adverse effects when compared to other either single or combined agents.Trial Registration PROSPERO CRD42019127278
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

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

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

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

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

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

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

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 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

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

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

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.
SARS-CoV-2 analysis on environmental surfaces collected in an intensive care unit. Keeping Ernest Shackleton´s spirit.
Authors: Escudero Dolores , Boga Jose Antonio , Fernández Javier , Forcelledo Lorena , Balboa Salvador , Albillos Rodrigo , Astola Iván , García-Prieto Emilio , Álvarez-Argüelles Marta Elena , Martín Gabriel , Jiménez Josu , Vázquez Fernando
Published: September 2020

Background: Intensive care unit workers are at high risk of acquiring COVID-19 infection, especially when performing invasive techniques and certain procedures that generate aerosols (<5 µm). Therefore, one of the objectives of the health systems should implement safety practices to minimize the risk of contagion among these health professionals. Monitoring environmental contamination of SARS-CoV-2 may help to determine the potential of the environment as a transmission medium in an area highly exposed to SARS-CoV-2, such as an intensive care unit. The objective of the study was to analyze the environmental contamination by SARS-CoV-2 on surfaces collected in an intensive care unit, which is dedicated exclusively to the care of patients with COVID-19 and equipped with negative pressure of -10 pascals and an air change rate of 20 cycles per hour. Furthermore, all ICU workers were tested for COVID-19 by quantitative RT-PCR and ELISA methods.Results: A total of 102 samples (72 collected with pre-moistened swabs used for collection of nasopharyngeal exudates and 30 with moistened wipes used in the environmental microbiological control of the food industry) were obtained from ventilators, monitors, perfusion pumps, bed rails, lab benches, containers of personal protective equipment, computer keyboards and mice, telephones, workers' shoes, floor and other areas of close contact with COVID-19 patients and healthcare professionals who cared for them. The analysis by quantitative RT-PCR showed no detection of SARS-CoV-2 genome in environmental samples collected by any of the two methods described. Furthermore, none of the ICU workers was infected by the virus.Conclusions: Presence of SARS-CoV-2 on the ICU surfaces could not be determined supporting that a strict cleaning protocol with sodium hypochlorite, a high air change rate and a negative pressure in the ICU are effective in preventing environmental contamination. These facts together with the protection measures used could also explain the absence of contagion among staff inside ICUs.
Bomb Atoms in Modern Honey Reveal a Regional Soil Control on Pollutant Cycling by Plants
Authors: Kaste James , Volante Paul , Elmore Andrew
Published: September 2020

One of the longer-lived and more dangerous fission products dispersed globally by mid-20th century atmospheric nuclear weapons testing was 137Cs, which has a 30-year radioactive half-life. It has generally been assumed that outside of the vicinity of the test sites, 137Cs fallout washed off vegetation and was immobilized by soil, and thus of no ecological concern. Here we show that native plants thousands of kilometers from testing sites continue to cycle 137Cs because it mimics the essential nutrient potassium, and consequently, bees magnify this potentially lethal radionuclide in honey. There were no atmospheric weapons tests in the eastern United States, but, most honey here has detectable 137Cs at >0.03 Bq kg-1 (~1 million atoms per tablespoon), and in the southeastern U.S. it can be over 500 times higher. By measuring honey, we show regional patterns in the biogeochemical cycling of 137Cs for the first time and conclude that plants and animals receive disproportionally high exposure to ionizing radiation from 137Cs in soils with low potassium. In several cases, the presence of 137Cs more than doubled the ionizing radiation from gamma rays and x-rays in the honey, indicating that despite its radioactive half-life, the environmental danger to honeybees from this fission product can persist for more than six decades.
Transcriptome Profiling Reveals Potential Genes Involved in Browning of Fresh-cut Eggplant (Solanum Melongena L.)
Authors: Liu Xiaohui , Shang Jing , Zhang Aidong , Zhu Zongwen , Zha Dingshi , Wu Xuexia
Published: September 2020

Background: Fresh-cut processing promotes enzymatic browning of fresh fruits and vegetables, which negatively affects the appearance of products and impacts their nutrition. We used the RNA-Seq technique to analyze the transcriptomic changes occurring during the browning of fresh-cut eggplant (Solanum melongena L.) fruit samples from a browning-sensitive cultivar and a browning-resistant cultivar to investigate the genes and molecular mechanisms involved in browning. Results: A total of 111.55 GB of high-quality reads were generated, the genomes of each sample were compared, and 83.50%–95.14% of the data was mapped to the eggplant reference genome. Furthermore, a total of 19631 differentially expressed genes were identified, among which 12 genes and two WRKY transcription factors were identified as potentially involved in enzymatic browning in fresh-cut eggplant fruit. Moreover, the 14 differentially expressed genes associated with browning were verified using qRT-PCR. Conclusions: Several genes associated with phenolic oxidation, phenylpropanoid biosynthesis, and flavonoid biosynthesis were found to be differentially regulated between the eggplant cultivars with different browning sensitivities. This work is of great theoretical significance, as it provides a basis for future molecular studies and improvement of eggplants, and lays a theoretical foundation for the development of browning-resistant fresh-cut fruits and vegetables.
Whole-transcriptome Analysis Reveals the Promising Bioresource of Total Flavonoid from Bitter-Pit Apples, Especially the Pitted Parts
Authors: YU Xian-Mei , XUE Xiao-Min , WANG Jin-Zheng , NIE Pei-Xian , CHEN Ru , HAN Xue-Ping
Published: September 2020

Background: Apple fruits are rich in flavonoids, and play important roles in human-health protection against chronic diseases. However, pitter pit in apple has affected apple fruit production worldwide. There must be some application values could be exploited from the bitter-pit apples so as to reduce the loss caused by bitter pit.Results: In the present study, the influence of bitter pit on the total flavonoid content and flavonoid biosynthesis in apples was investigated using the aluminum chloride colorimetric method, whole-transcriptome sequencing and qRT-PCR analysis. The results showed that the total flavonoid content in bitter-pit apples (BG), pitted parts (BGBB) and non-pitted parts (JKBF) was 4.28-fold, 4.68-fold and 0.57-fold respectively as that in healthy apples (JKG). By RNA-Seq analysis, 26, 23 and 3 DEGs involved in flavonoid biosynthesis were enriched in JKG vs. BG, JKG vs. BGBB and JKG vs. JKBF comparisons, respectively. Eight DEGs [CYP98A3(1), CYP98A3(2), BADH, DAT, HCT(1), HCT(2), CHI(1) and CHI(2)], were selected to be validated by qRT-PCR analysis, and the consistent expression patterns with RNA-Seq analysis were obtained, the results showed that the 8 DEGs were upregulated in BG and BGBB but downregulated in JKBF when compared with JKG.Conclusions: The flavonoid accumulation and biosynthesis in apples, especially the pitted parts, were stimulated greatly by bitter pit, while depressed slightly in non-pitted parts. The results indicated that the bitter-pit apples, especially the pitted parts, could be used as the promising bioresource of total flavonoid for the therapeutic utilization in human chronic diseases.
Penehyclidine mitigates intraoperative oculocardiac reflex and postoperative nausea and vomiting in the patients with strabismus surgery: a prospective, randomized, double-blinded comparison
Authors: Sun Jiacheng , Cao Xiaofei , Lu Ting , Li Nan , Min Xinxu , Ding Zhengnian
Published: September 2020

BackgroundPONV is one of the most frequent complications following anesthesia and strabismus surgery. Penehyclidine, an anticholinergic, is widely and preoperatively used for reducing glandular secretion in patients. This study investigated the effect of penehyclidine on PONV in strabismus surgery.MethodsIn this prospective, randomized, and double-blinded study, patients of strabismus surgery under general anesthesia were randomly assigned to either penehyclidine (n = 114) or normal saline (NS, n = 104) groups. Penehyclidine was administrated immediately after anesthesia induction, and patients treated with NS served as controls. PONV was investigated within 48 h after surgery. Intraoperative OCR was also recorded.ResultsCompared with NS controls, penehyclidine significantly reduced PONV incidence [30.7% vs. 54.8%, P < 0.001] and mitigated PONV severity as indicated by severity scoring (P < 0.001). When stratified by gender and age, the reduction of PONV incidence following penehyclidine treatment was found significant in all adult patients and male underaged patients. Unexpectedly, penehyclidine also significantly reduced OCR incidence [57.9% vs. 77.9%, P < 0.01] and mitigated OCR severity which indicated by requirement of atropine to rescue [77.3% vs. 90.1%, P < 0.05]. Moreover, penehyclidine did not significantly change anesthesia recovery time, facial flushing and drowsiness occurrence compared to NS controls.ConclusionsPenehyclidine administration after anesthesia induction significantly attenuated intraoperative OCR and PONV in strabismus surgery patients.Trial registrationClinicalTrials.gov (NCT04054479). Registered July 19, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04054479?id=NCT04054479&draw=2&rank=1
Characterizing the structural covariance network in AD-susceptible single nucleotide polymorphisms and the correlations with cognitive outcomes
Authors: Chang Hsin-I , Chang Yu-Tzu , Huang Chi-Wei , Huang Kuo-Lun , Hsu Jung-Lung , Hsu Shih-Wei , Tsai Shih-Jen , Chang Wen-Neng , Lee Chen-Chang , Huang Shu-Hua , Chang Chiung-Chih
Published: September 2020

BackgroundThe clinical manifestations of Alzheimer disease (AD) are related to brain network degeneration, while genetic differences may mediate network change patterns. A number of AD-susceptible loci have been reported using genome-wide association studies, however, how they modulate intracerebral volume and relationships to cognitive outcomes remains to be established. We hypothesized that different genotype groups may modulate large-scale brain networks independently or interact with apolipoprotein E4 (ApoE4) status to determine neurobehavior test scores.MethodsGray matter structural covariance networks were constructed in 324 patients with AD using T1 magnetic resonance imaging with independent component analysis (ICA). We assessed 15 genetic loci (rs9349407, rs3865444, rs670139, rs744373, rs3851179, rs11136000, rs3764650, rs610932, rs6887649, rs7849530, rs4866650, rs3765728, rs34011, rs6656401, rs597668) using the additive, recessive and dominant model on clinical outcomes. Statistical analysis was performed to explore the independent role of each locus, interactions with ApoE4 status, and relationships to brain ICA network integrity score. We used Cognitive Abilities Screening Instrument (CASI) total score or short-term memory (STM) subscore as the major outcome factors, adjusted for covariates of education, disease duration and age.ResultsClinically, the CD2AP G allele showed a protective role in CASI-total and CASI-STM scores independently or via interactions with non-ApoE4 status, while the CR1 A genotype group was associated with lower STM independently of ApoE4 status. Three loci showed synergic interactions with ApoE4: BIN 1 T allele and MS4A6A G allele with non-ApoE4 status, and FTMT G allele with ApoE4 status. The network integrity scores revealed 9 significant ICA networks (anterior and posterior hippocampus, right temporal, right or left thalamus, inferior cerebellum, medial cerebellum, default mode network, frontal attention network) that correlated with cognitive scores, in which only the ApoE4 and MS4A6A genotype group was independently related to the hippocampus network. Genetic loci of MS4A6A, BIN1, CD2AP, CD33, CLU, BIN1, P73, EXOC3L2, CR1 and MS4AE4 exerted network influence independently or via interactions with ApoE4 status.ConclusionsThis study suggests that AD-susceptible loci may exert clinical significance independently, through interactions with ApoE4 status or by modulating ICA networks to determine cognitive outcomes.