bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Epidemiology of Staphylococcus aureus in African Children from Rural and Urban Communities with Atopic Dermatitis
Authors: NDHLOVU Gillian , Abotsi Regina , Shittu Adebayo , Abdulgader Shima M , Jamrozy Dorota , Dupont Christopher , Mankahla Avumile , Nicol Mark , Hlela Carol , Levin Micheal , Lunjani Nonhlanhla , Dube Felix Sizwe
Published: December 2020

Background: Staphylococcus aureus has been associated with the exacerbation and severity of atopic dermatitis (AD). Studies have not investigated the colonisation dynamics of S. aureus lineages in African children with AD. We determined the prevalence and population structure of S. aureus in children with and without AD from rural and urban South African settings. Methods: We conducted a study of AD-affected and non-atopic AmaXhosa children from rural Umtata and urban Cape Town, South Africa. S. aureus was screened from skin and nasal specimens using microbiological culture, and S. aureus clonal lineages were determined by spa typing. Logistic regression analyses were employed to assess risk factors associated with S. aureus colonisation. Results: S. aureus colonisation was higher in cases compared to controls (60% vs. 21%, p=0.000) and when stratified for location (54% vs. 13%, p=0.000 and 70% vs. 35%, p=0.005 in Umtata and Cape Town, respectively). Severe AD was associated with higher colonisation compared with moderate AD (86% vs. 52%, p=0.022) among urban cases. Having AD was associated with colonisation in both rural (odds ratio [OR] 7.54, 95% CI 2.92–19.47) and urban (OR 4.2, 95% CI 1.57–11.2) children. In rural children, living in an electrified house that also uses gas (OR 4.08, 95% CI 1.59–10.44) or in a house that uses kerosene and paraffin (OR 2.88, 95% CI 1.22–6.77) for heating and cooking were associated with increased S. aureus colonisation, while exposure to animals (OR 0.3, 95% CI 0.11–0.83) as well living in a house that uses wood and coal (OR 0.14, 95% CI 0.04–0.49) and an outdoor fire (OR 0.31, 95% CI 0.13–0.73) were protective. Among urban children, t272 and t1476 dominant among cases but no single spa type dominated among controls. In urban cases, spa types t002 and t442 isolates were only identified in severe AD and t174 was more frequent in moderate AD while t1476 in severe AD. Conclusion: The strain genotype of S. aureus differed by AD phenotypes and rural-urban living. Continued surveillance of colonising S. aureus lineages is key in understanding alterations in skin microbial composition associated with AD pathogenesis and exacerbation.
Pancytopenia with severe thrombocytopenia in asymptomatic malaria in advanced pregnancy: a case report
Authors: Murewanhema Grant , Musiniwa Tapuwa Carol , Chimhina Maxwell Takura , Madombi Simbarashe , Nyakanda Munyaradzi Innocent , Madziyire Mugove Gerald
Published: December 2020

Background
Malaria in pregnancy is associated with significant morbidity and mortality, and requires early diagnosis and intervention. Plasmodium falciparum is responsible for 98% of malaria cases in Zimbabwe and causes the most severe disease. Abnormal haematological parameters are a frequent finding in patients with malaria; however, they are rarely the sole presenting feature.
Case presentation
We present the case of a 32-year-old woman in her fifth pregnancy, with a history of one previous caesarean section, who presented for caesarean section and was incidentally noted to have severe thrombocytopenia. Subsequent investigations at a tertiary institution revealed a pancytopenia with thrombocytopenia as the most prominent feature in an asymptomatic patient. The unavoidable caesarean section done under platelet cover was eventful, with severe intractable haemorrhage necessitating an emergency hysterectomy. However, the patient made a full recovery with antimalarial treatment and blood product transfusions.
Conclusion
This case is presented to illustrate the need to consider malaria as a differential diagnosis in pregnant patients from malaria-transmitting areas who have thrombocytopenia. Previous studies have shown that thrombocytopenia can be a predictor of malaria in patients who present with fever, and a marker of disease severity, but has no utility in prognostication and follow-up.
Non-verbal IQ and change in restricted and repetitive behaviors throughout childhood in autism: A longitudinal study using the Autism Diagnostic Interview-Revised.
Authors: Courchesne Valérie , Bedford Rachael , Pickles Andrew , Duku Eric , Kerns Connor , Mirenda Pat , Bennett Terry , Georgiades Stelios , Smith Isabel , Ungar Wendy , Vaillancourt Tracy , Zaidman-Zait Anat , Zwaigenbaum Lonnie , Szatmari Peter , Elsabbagh Mayada , Team Pathways
Published: December 2020

Background: Restricted and repetitive behaviors are one of the characteristic features of Autism Spectrum Disorder. This domain of symptoms includes a broad range of behaviors. There is a need to study each behavior individually to better understand the role they each have in the development of autistic children. Moreover, there are currently no longitudinal studies investigating change in these behaviors over development. Methods: The goal of the present study was to explore the association between age and non-verbal IQ (NVIQ) on 15 RRB symptoms included in the Autism Diagnostic Interview-Revised (ADI-R) over time. A total of 205 children with ASD were assessed using the ADI-R at time of diagnosis, at age 6 years, and at age 11 years, and with the addition of the Wechsler Intelligence Scales for Children – Fourth Edition (WISC-IV) at age 8 years.Results: The proportion of children showing each RRB tended to diminish with increasing age (p < 0.001), except for sensitivity to noise and circumscribed interests, where the proportion increased over time. Although there was no significant main effect of NVIQ (p = 0.101), there was a significant interaction between age and NVIQ (p < 0.01). This was mainly driven by Difficulties with change in routine, for which higher NVIQ was associated with the prevalence of the behavior remaining relatively stable with age, while lower NVIQ was associated with the behavior becoming more prevalent with age.Limitations: The study focused on the presence/absence of each RRB but did not account for potential changes in frequency or severity of the behaviors over development. Furthermore, some limitations are inherent to the measures used. The ADI-R relies on parent-report and hence has some level of subjectivity, while the Wechsler intelligence scales can underestimate the intellectual abilities of some autistic children.Conclusions: These results confirm that specific RRBs are differentially linked to age and NVIQ. Studying RRBs individually is a promising approach to better understand how RRBs change over the development of autistic children and are linked to other developmental domains.
Comprehensive Analysis of Aberrantly Expressed Profiles of ncRNAs Revealed lncRNA AGPAT4-IT1 is a Potential Prognostic Marker for Breast Cancer Metastasis
Authors: Zhang Feng chun , yan ning ning , Li Ming jun , Xu Ying chun , Li Xing ya
Published: December 2020

Aims: we investigated the relationship between long non-coding RNAs (lncRNAs) and breast cancer lung metastasis (BCLM). Methods: We performed lncRNA microarray analyses to establish the lncRNA profile of BCLM. Bioinformatics analyses were carried out to analyzed functional roles of identified lncRNAs. Kaplan-meier analysis was conducted to determine the relation between lncRNA AGPAT4-IT1 and prognosis of breast cancer. Results: We found 317 upregulated and 166 downregulated lncRNAs in BCLM group. We showed AGPAT4-IT1 was positively correlated with its parental gene APGAT4. Furthermore, we suggested AGPAT4-IT1 were highly expressed in higher tumour grade and predicted poorer prognosis. Conclusions: These findings provide evidence for exploring the mechanisms of BCLM and indicate AGPAT4-IT1 is a prospective prognostic marker for breast cancer metastasis.
Inhibition of Histamine H3 receptor Attenuates Neuroinflammation and Cognitive Impairments in Alzheimer’s Disease via activating CREB Pathway
Authors: Wang Jiangong , Liu Bin , Xu Yong , Wang Chaoyun , Yang Meizi , Song Mengmeng , Liu Jing , You Jingjing , Sun Fengjiao , Wang Wentao , Yan Haijing
Published: December 2020

BackgroundAlzheimer's disease (AD) is an age-related neurodegenerative disease, which characterized by deposition of amyloid-β (Aβ) plaques, neurofibrillary tangles, neuronal loss, and accompanied by neuroinflammation. Neuroinflammatory processes are well acknowledged to contribute to the progression of AD pathology. Histamine H3 receptor (H3R) is a presynaptic autoreceptor regulating histamine release via negative feedback way. H3R antagonist has been reported to have anti-inflammatory efficacy. However, whether inhibition of H3R is responsible for the anti-neuroinflammation and neuroprotection on APP/PS1 Tg mice remains unclear. MethodsIn this study, microgliosis, astrogliosis, A1 type astrocytes and A2 type astrocytes in APP/PS1 Tg mice were measured by immunostaining by Iba1, GFAP, C3 and S100A10 with and without treatment of thioperamide, an H3R antagonist. Inflammatory response of APP/PS1 Tg mice and effects of thioperamide were studied by measuring levels of pro-inflammatory cytokines (tumor necrosis factor α [TNFα] and interleukin-1β [IL-1β]) and anti-inflammatory cytokines (interleukin-4 [IL-4]). Protein levels of p-CREB and p-P65 NF-kB was tested by western blot to study the mechanism of thioperamide on AD. H89 was applied to study whether the mechanism offered by thioperamide was dependent on CREB activating. The effect of thioperamide and H89 on Aβ deposition was measured by immunostaining and ELISA. The cognitive function was tested by novel object recognition, Y maze and morris water maze. ResultsInhibition of H3R by thioperamide reduced the gliosis and induced a phenotypical switch from A1 to A2 in astrocytes, and ultimately attenuated neuroinflammation in APP/PS1 Tg mice. Additionally, thioperamide rescued the decrease of cyclic AMP response element-binding protein (CREB) phosphorylation and suppressed the phosphorylated nuclear factor kappa B (NF-κB) in APP/PS1 Tg mice. H89, an inhibitor of CREB signaling, abolished these effects of thioperamide to suppress gliosis and proinflammatory cytokine release. Lastly, thioperamide alleviated the deposition of Aβ and cognitive dysfunction in APP/PS1 mice, which were both reversed by administration of H89. ConclusionsTaken together, these results suggested the H3R antagonist thioperamide improved cognitive impairment in APP/PS1 Tg mice via modulation of the CREB-mediated gliosis and inflammation inhibiting, which contributed to Aβ clearance. This study uncovered a novel mechanism involving inflammatory regulating behind the therapeutic effect of thioperamide in AD.
Analysis of Radiotherapy Impact on Survival in Resected Stage I/ii Pancreatic Cancer Patients: A Population-based Study
Authors: Han Dong , Gao Fei , Liu JinLong , Wang Hao , Fu Qi
Published: December 2020

Background: The application of radiotherapy (RT) in pancreatic cancer remains controversial. The aim of the study was to evaluate the efficacy of radiotherapy (neoadjuvant and adjuvant radiotherapy) for resectable I/II pancreatic cancer. Methods: 14977 patients with pancreatic cancer were identified from SEER database from 2004 to 2015. Multivariate analyses were performed to determine factors including RT on overall survival. Overall survival and overall mortality among the different groups were evaluated using the Kaplan-Meier method and Gray’s test. Results: Patients were divided into groups according to whether they received radiotherapy or not. The median survival time of all 14977 patients without RT was 20 months, neoadjuvant RT was 24 months and adjuvant RT was 23 months (p < 0.0001) . Median survival time of 2089 stage I patients without RT was 56 months, significantly longer than those with RT regardless of neoadjuvant or adjuvant RT (no RT: 56 months vs adjuvant RT: 37 months vs neoadjuvant RT: 27 months, P=0.0039). Median survival time of 12888 stage II patients with neoadjuvant RT was 24 months, adjuvant RT 22 months, significantly prolonged than those without radiotherapy(neoadjuvant RT: 24 months vs adjuvant RT: 22 months vs no RT: 17 months, P＜0.0001). Neoadjuvant RT (HR=1.434, P=0.023, 95% CI: 1.051-1.957) was independent risk factors for prognosis of stage I patients, and adjuvant RT (HR=0.904, P < 0.001, 95% CI: 0.861-0.950) predicted better outcomes for prognosis of stage II patients by multivariate analysis. The risk of cancer-related death caused by neoadjuvant RT in stage I and no-RT in stage II patients were significantly higher. Conclusions: The study identified a significant survival advantage for the use of adjuvant RT over surgery alone or neoadjuvant RT in treating stage II pancreatic cancer. RT was not associated with survival benifit in stage I patients.
The Correlation between Maternal Age and Fetal Sex Chromosome Aneuploidies: A 8-year Single Institution Experience in China
Authors: Hongge Li , Jin Jinglei
Published: December 2020

Background: Although a few studies have investigated the association between maternal age and fetal sex chromosome aneuploidies (SCAs), most of these studies were limited to advanced age women and the results were conflicting. This study aimed to investigate maternal age-specific rates for common fetal SCAs (including 45,X, 47,XXY, 47,XXX and 47,XYY) in pregnant women of different ages that not only limited to advanced age women. We retrospectively investigated a 8-year experience of prenatal diagnosis for fetal chromosome aberrations by second-trimester amniocentesis at a university teaching hospital in China. 20,409 amniotic fluid specimens collected at 19–22+6 gestational weeks were included in this study. The women were categorized into five age groups (≤23, 24-28, 29-33, 34-38, 39+ years) based on maternal age at the time of amniocentesis and entered as a categorical variable in all samples. The correlation between fetal SCAs and maternal age was determined using the logistic regression analysis. A chi-square test was performed to compare the incidence of fetal SCAs among age groups. Results: A total of 179 cases of fetal SCAs were detected, and the incidence was 8.77‰ (about 1/114). The incidence of all SCAs increased significantly with advancing maternal age (SE, 0.014; odds ratio, 1.044; P=0.002), from 5.81 per 1,000 fetuses at the 24-28 years to 10.92 per 1,000 at the 39+ years. The incidence of all SCAs was also significantly different among age groups (χ2=10.197, P=0.037<0.05). Specifically, the incidence of 45,X (SE, 0.037; odds ratio, 0.916; P=0.017) and 47,XXY (SE, 0.024; odds ratio, 1.127; P=0.000) had significant correlation with maternal age, while the incidence of 47,XXX and 47,XYY had no correlation with maternal age (P=0.473; P=0.272, respectively). Conclusions: Maternal age was ascertained to be a strong risk factor for fetal SCAs.
A Novel Missense Mutation in NALCN cause CLIFAHDD Syndrome and Prenatal Diagnosis in China
Authors: Li Yuping , Zhou Chenglong , Chen Yangran , Shi Haihong , Chen Qiang , Li Ning , Zeng Qinlong , Hong Yan , Li Qing , Deng Choufen , Zhou Feng , Tan Jieliang , Yang Mei , Li Qiuli , Yang Yingsong , Feng Jianjiang , Sun Shuxiang , Tang Ziqian , Luo Liangping , Tang Jia
Published: December 2020

Background : CLIFAHDD is caused by mutation in NALCN and characterized by facial malformation, hypotonia, and developmental delay. Recently rare mutations in NALCN associated with of CLIFAHDD syndrome have been reported. Methods : Whole exome sequencing (WES) was applied to a diagnosis suspected CLIFAHDD syndrome proband based on clinical symptoms. Blood samples were taken from the parents of the proband for co-segregation analysis using Sanger sequencing. In addition, prenatal gene diagnosis was performed to the family. Finally bioinformatics analysis was utilized to predict the pathogenesis of novel variant. Result : We reported a 24-hour-old proband with a novel missense variant c.3016G>T (p.Val1006Phe) in NALCN by WES. The proband showed clinical symptoms of head abnormalities, neck shortage, thumbs adduction, positional foot deformities and elbows contracture. Prenatal diagnosis revealed that the proband’s sibling did not carry c.3016G>T. Conclusion : Our findings indicate c.3016G>T is a novel pathogenic mutation, while extending new phenotype CLIFAHDD syndrome and enriching the mutation spectrum of the NALCN gene.
Identification of an Anti-Plant-Virus Molecule in Alpinia Zerumbet
Authors: Hatanaka Tadashi , Narusaka Mari , Uraji Misugi , Yamaji Yasuyuki , Narusaka Yoshihiro
Published: December 2020

In plants, viral diseases are second only to fungal diseases in terms of occurrence, causing substantial damage to agricultural crops. The aqueous extract of Alpinia zerumbet exhibits inhibitory effect against virus infection in Solanaceae members. In this study, we isolated an anti-plant-virus molecule from the extract using a conventional method of a combination of reversed phase column chromatography, dialysis, and lyophilization. The anti-plant-virus molecule was identified as proanthocyanidin, which mostly consisted of epicatechin and showed more than 40 degrees of polymerization.
Nonadditivity in Public and Inhouse Data – Implications for Drug Design
Authors: Gogishvili Dea , Nittinger Eva , Margreitter Christian , Tyrchan Christian
Published: December 2020

Numerous ligand-based drug discovery projects are based on structure-activity relationship (SAR) analysis, such as Free-Wilson (FW) or matched molecular pair (MMP) analysis. Intrinsically they assume linearity and additivity of substituent contributions. These techniques are challenged by nonadditivity (NA) in protein-ligand binding where the change of two functional groups in one molecule results in much higher or lower activity than expected from the respective single changes. Identifying nonlinear cases and possible underlying explanations is crucial for a drug design project since it might influence which lead to follow. By systematically analyzing all AstraZeneca (AZ) inhouse compound data and publicly available ChEMBL25 bioactivity data, we show significant NA events in almost every second assay among the inhouse and once in every third assay in public data sets. Furthermore, 9.4% of all compounds of the AZ database and 5.1% from public sources display significant additivity shifts indicating important SAR features or fundamental measurement errors. Using NA data in combination with machine learning showed that nonadditive data is challenging to predict and even the addition of nonadditive data into training did not result in an increase in predictivity. Overall, NA analysis should be applied on a regular basis in many areas of computational chemistry and can further improve rational drug design.
ChemTables: A Dataset for Semantic Classification of Tables in Chemical Patents
Authors: Zhai Zenan , Druckenbrodt Christian , Thorne Camilo , Akhondi Saber A , Nguyen Dat Quoc , Cohn Trevor , Verspoor Karin
Published: December 2020

Chemical patents are a commonly used channel for disclosing novel compounds and reactions, and hence represent important resources for chemical and pharmaceutical research. Key chemical data in patents is often presented in tables. Both the number and the size of tables can be very large in patent documents. In addition, various types of information can be presented in tables in patents, including spectroscopic and physical data, or pharmacological use and effects of chemicals. Since images of Markush structures and merged cells are commonly used in these tables, their structure also shows substantial variation. This heterogeneity in content and structure of tables in chemical patents makes relevant information difficult to find. We therefore propose a new text mining task of automatically categorising tables in chemical patents based on their contents. Categorisation of tables based on the nature of their content can help to identify tables containing key information, improving the accessibility of information in patents that is highly relevant for new inventions. For developing and evaluating methods for the table classification task, we developed a new dataset, called ChemTables, which consists of 7,886 chemical patent tables with labels of their content type. We introduce this data set in detail. We further establish strong baselines for the table classification task in chemical patents by applying state-of-the-art neural network models developed for natural language processing, including TabNet, ResNet and Table-BERT on ChemTables. The best performing model, Table-BERT, achieves a performance of 88.66 micro F1 score on the table classification task. Availability: A 10% sample of the ChemTables dataset has been made publicly available, subject to a data usage agreement.
AR Deficiency Inhibits LPS-induced M1 Response in Macrophages by Activating Autophagy
Authors: Cheng Peng , Xie Jianwei , Liu Zhiyong , Wang Jian
Published: December 2020

Macrophage M1 polarization mediates inflammatory responses and tissue damage. Recently, aldose reductase (AR) has been shown to play a critical role in of M1 polarization in macrophages. However, the underlying mechanisms are unknown. Here, we demonstrated, for the first time, that AR deficiency repressed the induction of inducible nitric oxide synthase in lipopolysaccharide (LPS)-stimulated macrophages via activation of autophagy. This suppression was related to a defect in the inhibitor of nuclear factor κB (NF-κB) kinase (IKK) complex in the classical NF-κB pathway. However, the mRNA levels of the IKKβ and IKKγ were not reduced in LPS-treated AR knockout (KO) macrophages, indicating that their proteins were downregulated at the post-transcriptional level. We discovered that LPS stimuli induced the recruitment of more beclin1 and increased autophagosome formation in AR-deficient macrophages. Blocking autophagy by 3-methyladenine and ammonium chloride treatment restored IKKβ and IKKγ protein levels and increased nitric oxide synthase production in LPS-stimulated AR-deficient macrophages. More assembled IKKβ and IKKγ undergo ubiquitination and recruit the autophagic adaptor p62 in LPS-induced AR KO macrophages, promoting their delivery to autophagosomes and lysosomes. Collectively, these findings suggest that AR deficiency involves in the regulation of NF-κB signaling, and extends the role of selective autophagy in ﬁne-tuned M1 macrophage polarization.
Acteoside Repressed Microglia M1 Polarization Through Inhibited NF-κB Signalling Pathway and AMPK-Mediated Mitochondria Function Recovery
Authors: Li Ying-Qi , Chen Yi , Jiang Si-Qi , Shi Yuan-Yuan , Jiang Xiao-Li , Wu Shan-Shan , Zhou Ping , Wang Hui-Ying , Li Ping , Li Fei
Published: December 2020

Background: Alzheimer's disease (AD) is the most frequent type of dementia. While acteoside (ACT), a compound isolated from Cistanche tubulosa, possesses neuroprotective properties. However, the underlying mechanism in regulating microglia polarization remains ill-defined. Methods: Herein, AlCl3-induced AD model in zebrafish larvae was applied to uncover the therapeutic efficacy of ACT. BV-2 cells were used to demonstrate the role of ACT on microglia polarization. RNA-Sequence, HPLC-Q-TOF-MS, western blot and molecular docking were combined to confirm its mechanism. Results: ACT significantly ameliorated the experimental dyskinesia and nervous system disorders in zebrafish. Subsequently, it suppressed M1 polarization and promoted to the M2 phenotype in LPS-induced BV-2 cells. We first demonstrated that ACT exerted profound transcriptomic impact, which involved regulation of key signaling pathways in inflammation, arginine biosynthesis, as well as pantothenate and CoA biosynthesis, correlating with mitochondria function. ACT treatment reduced microglia M1 polarization by inhibiting the NF-κB signalling pathway. And the metabolic pathways were further confirmed by HPLC-Q-TOF-MS. In addition, ACT rectified excessive ROS to restore mitochondria function through AMPK-mediated PGC-1α and UCP-2 upregulation, consistent with metabolic changes. Intriguingly, ACT may directly bind to both NF-κB and AMPKα, as evidenced by molecular docking. Conclusions: The research provided an infusive mechanism of ACT and illustrated a new perspective based on mitochondrial dysfunction to reveal the connection between metabolism and microglia polarization.
Carbon Status and Regression Model for Tree Carbon by Crown Cover for Sal Forest of Nepal
Authors: Paudel Prashant , Kalakheti Rupesh , Maraseni Tek
Published: December 2020

Background: Volume, biomass and carbon of forest ecosystem are generally estimated using lookup tables or allometric equations known as models. These general equation-based models are usually exclusively based on dimensional measurement such as diameter at breast height (DBH) and/or height, which sometimes makes it difficult to judge applicability of equation to given forest condition or types. It is therefore important to estimate carbon stock and develop models to predict biomass or carbon stock with stratification by categorical variables like crown cover, slope, forest types, etc. Stratification of forest by remote sensing approach while designing forest inventory not only improves the reliability of the estimation but also reduces the cost of measurement and uncertainty in estimation. Taking crown coverage (<25%, 25-50%, 50-75% and >75%) and slope (0-8.5%, 8.5-19%, 19-31% and >31%) as a categorical variable, this study assessed the status of carbon stock and develop a regression model to predict carbon stock for each canopy class of Sal (Shorea robusta) forest in Nepal. DBH and height were measured for trees with more than 7 cm DBH in 82 sample plots (18, 22, 22 and 20 for <25%, 25-50%, 50-75% and >75 % respectively).Results: On average 297 stands per hectare were recorded with 94.80 m3/ha growing stock. Carbon stock was highest for >75% crown cover class (89.83 ton C/ha) and lowest for <25% crown cover class (27.47 ton C/ha) with average 60.41 ton C/ha, where per tree carbon stock was lowest in crown cover class 25-50% (0.16 ton C/tree). TukeyHSD shows that four pairs of crown cover classes have significant difference in carbon stock at 95% confidence interval. However, with increase in slope carbon stock per hectare was decreasing. Regression model with natural logarithm of DBH2 and total tree height (i.e. log transformed polynomial equation) was best fitted for estimation of carbon stock per tree in different crown cover class with adjusted R2 >0.99 and residuals were normally distributed. Conclusions: Adjustment of model (natural logarithm of DBH2 and height) with high accuracy (R2 >0.99) shows the importance of stratification especially by crown cover for accurate estimation of carbon stock for optimization of carbon benefits.
Exploration of Binary Protein-Protein Interactions Between Tick-Borne Flaviviruses and Ixodes Ricinus
Authors: LEMASSON Manon , CAIGNARD Grégory , UNTERFINGER Yves , ATTOUI Houssam , BELL-SAKYI Lesley , HIRCHAUD Edouard , MOUTAILLER Sara , JOHNSON Nicholas , VITOUR Damien , RICHARDSON Jennifer , LACOUR Sandrine A.
Published: December 2020

BackgroundLouping ill virus (LIV) and tick-borne encephalitis virus (TBEV) are tick-borne flaviviruses that are both transmitted by the major European tick, Ixodes ricinus. Despite the importance of I. ricinus as an arthropod vector, its capacity to acquire and subsequently transmit viruses, known as vector competence, is poorly understood. At the molecular scale, vector competence is governed in part by binary interactions established between viral and cellular proteins within infected tick cells.MethodsTo investigate virus-vector protein-protein interactions (PPIs), the entire set of open reading frames for LIV and TBEV was screened against an I. ricinus cDNA library established from three embryonic tick cell lines using yeast two-hybrid methodology (Y2H). PPIs revealed for each viral bait were retested in yeast by applying a gap repair (GR) strategy and notably against the cognate protein of both viruses, to determine whether the PPIs were specific for a single virus or common to both. The interacting tick proteins were identified by automatic BLASTX and in silico analyses were performed to expose the biological processes targeted by LIV and TBEV.ResultsFor each virus, we identified 24 different PPIs involving six viral proteins and 22 unique tick proteins, with all PPIs being common to both viruses. According to our data, several viral proteins (pM, M, NS2A, NS4A, 2K and NS5) target multiple tick protein modules implicated in critical biological pathways. Of note, the NS5 and pM viral proteins establish PPI with several tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins, which are essential adaptor proteins at the nexus of multiple signal transduction pathways.ConclusionWe provide the first description of the TBEV/LIV-I. ricinus PPI network, and indeed of any PPI network involving a tick-borne virus and its tick vector. While further investigation will be needed to elucidate the role of each tick protein in the replication cycle of tick-borne flaviviruses, our study provides a foundation for understanding the vector competence of I. ricinus at the molecular level. Indeed, certain PPIs may represent molecular determinants of vector competence of I. ricinus for TBEV and LIV, and potentially for other tick-borne flaviviruses.
Hypoxic ADSCs-derived EVs Promote the Proliferation and Chondrogenic Differentiation of Cartilage Stem/progenitor Cells
Authors: xue ke , Jiang Yongkang , Zhang Xiaodie , Wu Jun , Qi Lin , Liu Kai
Published: December 2020

Background： Cartilage tissue engineering is a promising option for repairing cartilage defects caused by trauma, inflammation and osteoarthritis, although harvesting a large number of seeding cells with stable phenotypes remains a major challenge. Cartilage stem/progenitor cells (CSPCs) seem to be a promising cell source. Hypoxic extracellular vesicles secreted by mesenchymal stem cells may play a major role in cell-cell and tissue-tissue communication by transporting various RNAs and proteins in mesenchymal stem cell-based therapy. In the current study, we aimed to evaluate the effect of hypoxic adipose-derived stem cells (ADSCs)-derived extracellular vesicles (EVs) on CSPCs proliferation and differentiation. Methods: The characteristics of ADSCs-derived EVs were identified by and flow cytometric analysis. Proliferation, migration, and cartilage-related gene expression of CSPCs were measured with or without the presence of hypoxic ADSCs-derived EVs. The effect of ADSC-derived EVs on CSPCs were evaluated in alginate hydrogel culture, and SEM, histological staining, biochemical and biomechanical analysis were performed to evaluate the effect of hypoxic ADSCs-derived EVs on CSPCs in alginate hydrogel culture. Results: The results indicated that the majority of ADSC-derived EVs exhibited a round-shaped or cup-shaped morphology with a diameter of 40–1000 nm and expressed CD9, CD63, and CD81. CSPCs migration and proliferation were enhanced by hypoxic ADSCs-derived EVs, which also increased the expression of cartilage-related genes. The hypoxic ADSCs-derived EVs induced CSPCs to produce significantly more cartilage matrix and proteoglycan. Conclusions: The present study indicated that hypoxic ADSCs-derived EVs improved the proliferation and chondrogenic differentiation of CSPCs for cartilage tissue engineering.
Geomineralogical, Physiochemical, Thermal and Kinetic Characterisation of Selected Coals From the Benue Trough and Anambra Basins in Nigeria
Authors: Nyakuma Bemgba B. , Jauro Aliyu , Akinyemi Segun A. , Wong Syie L. , Oladokun Olagoke , Abdullah Tuan Amran T.
Published: December 2020

This study examined the geomineralogical, physiochemical, thermal, and kinetic characteristics of selected coals from Chikila (CHK), Lafia Obi (LFB) and Okaba (OKB) in the Benue Trough and Anambra Basins of Nigeria. Physicochemical characterisation revealed significant quantities of carbon, volatiles, fixed carbon, and heating values (25–30 MJ/kg) but low moisture, and ash contents. The fuel properties indicate subbituminous to bituminous rank coals. The morphological, microstructure and elemental analyses revealed heterogeneous sized coal particles with a glassy sheen due to clay and aluminosilicate minerals such as quartz, alumina, kaolinite, and hematite. Based on thermal analysis, the coal samples are highly reactive and experienced significant thermal degradation as evident in the high mass losses (ML = 91.59 – 94.04%) and low residual masses (RM = 5.96% - 8.41%), which are observed in the orders LFB > OKB > CHK for ML and CHK > OKB > LFB for RM. LFB experienced the highest ML and lowest RM indicating it is more thermally reactive compared to OKB and CHK. Kinetic analysis by Coats-Redfern model revealed low values of activation energy, Ea (30.07 – 43.91) kJ/mol and frequency factor A (1.16×10-02 – 6.73×10-02) min-1 deduced at high R2 (0.98-0.99). The kinetic parameters demonstrated that the selected coal samples are highly reactive under oxidative conditions which are suited for energy recovery through pulverised coal combustion.
An Analysis of Economic Burden of Hypertensive Patients Based on “System of Health Accounts 2011” and Multiple Layer Perceptron Neural Network
Authors: Liu Guojie , Ji Xinyu , Yang Jingou , Zhu Yalan , Wang Leying , Wang Xin
Published: December 2020

Background: Hypertension requires long-term treatment and medication, which not only affects people’s health, but also brings heavy economic burden for families and society. Therefore, it is meaningful to reveal the actual personal and socio-economic burdens of hypertension based on a tool recognized internationally to improve management of hypertensive patients and provide more information for policy makers, analysts, and international comparisons. Methods: We collected expense records of 180441 hypertensive outpatients and 14763 inpatients in Shanxi Province of China in 2017. Curative care expenditure for hypertension(CCEht) were analyzed based on System of Health Accounts 2011, and influencing factors were analyzed by multiple layer perceptron (MLP) neural network.Results: In 2017, CCEht was US$ 307.71 million, accounted for 3.63% of the total CCE and 0.14% of GDP in Shanxi Province of China. CCE of hypertensive outpatients (CCEht-out) and inpatients (CCEht-in) accounted for 44.49% and 55.51% of the CCEht, drug fee accounted for 81.55% of CCEht-out and 22.50% of CCEht-in, respectively. CCEht increased from the age of 30, and the highest occured in age 60-69. The patients with the age of 40-79 accounted for 86.49% of total CCEht. CCEht of male patients were generally higher than that of female, and there is a significant difference between CCEht for male and female in terms of age. The diagnosis and treatment capacity of primary health care system had been enhanced. New rural cooperation medical insurance and urban employee basic medical insurance had the trend of overusing, and burden of family healthcare expenditure was still very heavy. In the MLP neural network, the top three influencing factors were drug fee, surgical fee and hospitalization days for inpatients, drug fee, examination fee and test fee for outpatients. Conclusions: To ease the economic burden of hypertensive patients and improve the utilization efficiency of social resources , the policy makers should pay more attention to the hypertensive patients aging 40-79, strengthen prevention and outpatient treatment for young men and the inpatient treatment for women at older ages, further increase support for primary health care system, standardize the treatment and reimbursement of hypertension, and incline the reimbursement policy to outpatient service.
The Status of Emergency Obstetric and Newborn Care in Post-Conflict Eastern DRC: A Facility-Level Cross-Sectional Study.
Authors: MIZERERO Serge-André Uwunva , Wilunda Calistus , Musumari Patou Masika , Ono-Kihara Masako , Mubungu Gerrye , Masahiro Kihara , Nakayama Takeo
Published: December 2020

Background Pregnancy-related mortality remains persistently higher in post-conflict areas. Part of the blame lies with continued disruption to vital care provision, especially emergency obstetric and newborn care (EmONC). In such settings, assessment of EmONC is essential for informed interventions needed to improve maternal and neonatal survival. In the North Kivu Province (NKP), the epicentre of armed conflict in eastern Democratic Republic of the Congo (DRC) between 2006-2013, the post-conflict status of EmONC is unknown. We assessed the availability, use, and quality of EmONC in 3 health zones (HZs) of the NKP.Method A cross-sectional survey of all 42 public facilities designated to provide EmONC in 3 HZs (Goma, Karisimbi, and Rutshuru), purposively selected based on their relative proximity to previous conflicts and their respective locations encompassing the entire economic landscape of the province, was conducted in 2017. Interviews, reviews of maternity ward records, and observations were used to assess the accessibility, use, and quality of EmONC against WHO standards.Results The 3 HZs fell short of WHO standards. Only three referral facilities (two faith-based facilities in Goma and the MSF-run referral hospital of Rutshuru) met the criteria for comprehensive EmONC, i.e., 1.5 EmONC facilities per 500,000 population. None of the health centres qualified as basic EmONC, nor could offer obstetric and neonatal care services 24 hours, 7 days a week (24/7). Assisted vaginal delivery was the least performed signal function, followed by parenteral administration of anticonvulsants, mostly due to policy restrictions and lack of demand. Moreover, none of the HZs could achieve a direct-obstetric case facility rate of at most 1% and, the met need for EmONC was as low as 6.5% and 5.4% in Goma and Rutshuru, respectively. However, the proportion of births by caesarean section in EmONC facilities met the minimum standard in both HZs. Overall, the intrapartum and very early neonatal death rate was 1.5%.Conclusion This study provides grounds for the development of coordinated and evidence-based programming, involving local and external stakeholders, as part of the post-conflict effort to improve maternal and neonatal health in the NKP. Particular attention to basic EmONC is required, focusing on strengthening human resources, equipment, supply chains, and referral capacity, on the one hand, and on tackling residual insecurity that might hinder 24/7 staff availability, on the other.
The Potential Diagnostic and Predictive Role of HbA1c in Diabetic, Septic Patients - a Retrospective Single Center Study
Authors: Juhász Imre , Juhász Janka , Lőrincz Hajnalka , Seres Ildikó , Végh Lilla , Ujfalusi Szilvia , Harangi Mariann , Szabó Zoltán , Paragh György
Published: December 2020

Background: Diabetes mellitus is a major risk factor of sepsis. The potential role of hemoglobin A1c (HbA1c) in diabetic, septic patients has not yet been studied. Results: In our retrospective study we included diabetic, septic patients - in whom the diagnosis of sepsis was based on the Systemic Inflammatory Response Syndrome (SIRS) criteria (112 patients, SIRS group) - who had HbA1c levels measured either in the previous 30 days (SIRS 30d subgroup – 39 patients) or within 24 hours after their Emergency Department admission (SIRS 24h subgroup – 73 patients). We later selected those patients from the SIRS group, whose Sequential Organ Failure Assessment (SOFA) score was ≥ 2 (55 patients, SOFA group) and these patients were also divided based on the time of HbA1c measurement (SOFA 30d subgroup – 21 patients and SOFA 24h subgroup – 34 patients). We analyzed the relationship between laboratory parameters, length of hospital stay and HbA1c. We found a significant positive correlation between glucose and HbA1c, significant negative correlations between white blood cell count (WBC) and glucose, WBC and HbA1c levels in the SIRS 24h and SOFA 24h subgroups. Furthermore there was a significant positive correlation between length of hospital stay and HbA1c in the SOFA 24h subgroup. No significant correlations were found in the SIRS 30d and SOFA 30d subgroups. Conclusions: Based on our results normal WBC with elevated HbA1c might be considered a positive SIRS criterium in diabetic, SIRS 24h patients. Besides this potential diagnostic role, HbA1c might also be an additional prognostic biomarker in diabetic, SOFA 24h patients.
White Matter Changes, Duration of Hypertension, and Age Are Associated With Cerebral Microbleeds in Hypertensive Patients of Different Stages
Authors: Liang Changhu , Wang Jing , Liu Cheng , Guo Lingfei
Published: December 2020

Purpose We aimed to investigate risk factors for the presence and number of cerebral microbleeds (CMBs) in patients with different hypertension stages, with an emphasis on the relationship between white matter changes (WMCs) and CMBs.Materials and methods Since 2016, participants aged 40 years or more have been evaluated for the presence of CMBs using enhanced 3D multi-echo GE T2*-weighted angiography (ESWAN) sequences. The Mann-Whitney U test and Pearson χ2 test were used to compare the clinical characteristics between the CMB and no-CMB groups of patients. Furthermore, we used Spearman’s rank correlation analyses to examine the association between the degree of CMB severity and other important factors.Results CMBs were detected in 110 (36.7%) of 300 participants. Among patients with stage 2 hypertension, the majority also had CMBs. CMBs were positively correlated with age, hypertension stage, duration of hypertension, WMCs, and silent cerebral infarction. Patients with grade 3 WMCs were significantly more likely to have CMBs than those without WMCs; this association was true for patients with both stage 1 and stage 2 hypertension. In patients with stage 1 or stage 2 hypertension lasting longer than 20 years, the majority had CMBs.Conclusions CMBs detected in hypertensive patients are more likely to occur in deep structures, and the grade of WMCs and duration of hypertension are more closely associated with the CMB degree than with age.Synopsis: The grade of WMCs and duration of hypertension are more closely associated with the CMB degree than with age.
Factors Influencing Prognosis of Patients with Intra-Abdominal Infection and Its Value in Assessing Prognosis
Authors: Pan Jianfei , Zhu Quanwei , Wu Xiao , Zhang Xiaoqian , Xu Jun , Pan Linlin , Mao Xiang
Published: December 2020

Background: To explore the distribution of pathogenic bacteria in patients with intra-abdominal infection, to clarify the independent factors that affect the prognosis of patients with intra-abdominal infection and its evaluation value for prognosis. Methods The pathogens, underlying diseases and related clinical data of patients with intra-abdominal infection from January 2012 to December 2019 in our hospital were retrospectively collected and the APACHE II score was calculated. The patients were divided into survival group and death group according to the prognosis, and the index between the two groups were compared. Spearman correlation analysis was used to evaluate the correlation between each index and prognosis, multivariate Logistic regression analysis was used to screen the independent prognostic factors. Results 282 patients were included in the study, including 183 males and 99 females, aged 56.99 ± 15.34 years. The survival group was 218cases, the death group was 64 cases, the total intra-abdominal infection mortality was 22.70%. There were significant differences between the two groups in age, serum albumin level, APACHE II score, basic cardiovascular disease and diabetes mellitus (P <0.05). Spearman correlation analysis showed that ALB level was negatively correlated with prognosis, age and APACHE II score were positively correlated with prognosis. Logistic regression analysis showed that age, ALB level and APACHE II score were independent prognostic factors. The area under the curve of the age, ALB level, APACHE II score and these three combined to assess the prognosis were 0.624, 0.698, 0.807 and 0.842 respectively. the sensitivity was 56.30%, 57.80%, 79.70% and 89.10% respectively, and the specificity was 69.30%, 75.20%, 68.80% and 65.10%, respectively. The formula of age combined ALB level and APACHE II score was Y= X1-3.6X2+6.5X3 (X1 was the age, X2 was the ALB level and X3 was the APACHE II score), Y was positively correlated with poor prognosis, and the optimal cutoff value was Y = 40.96. Conclusions Age, ALB level and APACHE II score are independent factors which influencing the prognosis of patients with intra-abdominal infection, and the combination of age, ALB level and APACHE II score can better assess the prognosis of patients with intra-abdominal infection.
Dysphagia Rehabilitation Following Acquired Brain Injury, Including Cerebral Palsy, Across The Lifespan: A Scoping Review Protocol
Authors: Halfpenny Rhiannon , Stewart Alexandra , Kelly Paula , Conway Eleanor , Smith Christina
Published: December 2020

Background: Swallowing impairment (dysphagia) following brain injury can lead to life-threatening complications such as dehydration, aspiration pneumonia and acute choking episodes. In adult therapeutic practice, there is research and clinical evidence to support the use of swallowing exercises to improve swallowing physiology in dysphagia, however, use of these exercises in treating children with dysphagia is largely unexplored. Fundamental questions remain regarding the feasibility and effectiveness of using swallowing exercises with children. This review aims to outline the published literature on exercise-based treatment methods used in the rehabilitation of dysphagia secondary to an acquired brain injury across the lifespan. This will allow the range and effects of interventions utilised to be mapped alongside differential practices between adult and child populations to be formally documented, providing the potential for discussions with clinicians about which interventions might be appropriate for further trial in paediatrics.Methods: This study will use a scoping review framework to identify and systematically review the existing literature using the Joanna Briggs Institute (JBI) and Preferred Reporting Items for Systematic Reviews (PRISMA) scoping review guidelines. Electronic databases (Medline, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED) and Cochrane Database of Systematic Reviews), grey literature and the reference lists of key texts will be searched. Information about the rehabilitation design, dosage and intensity of exercise programmes used as well as demographic information such as the age of participants and aetiology of dysphagia will be extracted. The number of articles in each area and the type of data source will be presented in written and visual format. Comparison between literature in adult and child populations will be discussed. Discussion: If therapy protocols from the adult literature are to be developed for use in paediatrics, it is important to have a clear understanding of the scope and effectiveness of interventions described in both adults and children. This review is unique as it directly compares dysphagia rehabilitation in adults with that of a paediatric population in order to formally identify and discuss the therapeutic gaps in child dysphagia rehabilitation. The results will inform the next stage of research, looking into current UK based Speech and Language Therapy practices when working with children with an acquired dysphagia. Systematic review registration: Not registered.