bluuebunny/crossref_metadata_2025 huggingface dataset:
New insights into malaria vector bionomics in Lao PDR: a nationwide entomology survey
Authors: Marcombe Sebastien , Maithaviphet Santi , Bobichon Julie , Phommavan Nothasin , Nambanya Simone , Corbel Vincent , Brey Paul Trevor
Published: June 2020

Background
. In Laos, the malaria burden remains high despite a significant reduction of cases during the last decade. In the context of the disease elimination by 2030, a nationwide entomological survey was conducted to better understand the distribution, abundance and behavior of major malaria vectors (Anopheles spp.) in the country.
Methods
. Mosquito collections were implemented in ten villages from ten provinces during the rainy and dry seasons of 2014 and 2015 by using human landing catch (HLC) and cow bait collection (CBC) methods. After morphological identification in the field, molecular identification of the sibling species of Anopheles mosquitoes from the Funestus, Leucosphyrus, and Maculatus groups were determined using PCR specific alleles. A screening of Plasmodium falciparum and P. vivax infections in in the vectors was carried out by quantitative PCR assays.
Results.
A total of 14,146 adult mosquitoes representing 25 different Anopheles species were collected and morphologically identified. Molecular identification revealed the presence of 13 sibling species within the main primary vector groups including An. maculatus s.s., An. rampae, An. sawadwongporni, An. pseudowillmori, An. dravidicus, An. willmori, An. minimus s.s., An. aconitus, An. pampanai, An. harrisoni, An. dirus s.s., An. baimaii, An. nemophilous. An. maculatus and An. minimus were predominant during both the dry and rainy seasons, but showed highly zoophilic preferences (Zoophilic index of 98% and 95%, respectively). Overall, solely 22% of the total malaria vectors were collected between 10:00 PM and 5:00 AM indoors when people are sleeping. Twenty-seven percent of primary and secondary vectors were collected outdoors before 10:00 PM or after 5:00 AM, times when people are usually awake and outdoors. Only two specimens were positive for P. falciparum, one Anopheles aconitus from Phongsaly and one An. minimus from Vientiane Province
Conclusions.
The results indicate that people living in rural areas in Laos are constantly exposed to malaria vectors throughout the year and specifically outdoors. The use of LLINs/IRS remains important but innovative tools and new strategies are needed to address locally, the early and outdoor malaria transmission. Lack of expertise in general entomological methods may further exacerbate the situation.
Bias Evaluation and Reduction in 3D OP-OSEM Reconstruction in Dynamic Equilibrium PET Studies
Authors: Brambilla Cláudia Régio , Scheins Jürgen , Issa Ahlam , Tellmann Lutz , Herzog Hans , Kops Elena Rota , Shah N. Jon , Neuner Irene , Lerche Christoph W.
Published: June 2020

Background: Iterative image reconstruction algorithms are widely used in positron emission tomography (PET). However, they are known to contribute to quantitation bias, which is particularly pronounced during dynamic PET studies such as neuroreceptor binding studies with 11C-labelled radiotracers where count rates become low towards the end of the examination. This problem is relevant in case simultaneous PET/MR studies which apply a bolus-infusion protocol to allow the multimodal comparison between control or resting state and stimulation effects in a single session of e.g. 60 min, i.e. 3 half-lives of 11C. A quantitation bias may interfere with stimulation related changes. In this study, we evaluated the impact of the 3D ordinary Poisson OSEM (3D OP-OSEM) on quantitation accuracy reconstructions and the subsequent propagation into binding potential values using a decay study of a 11C filled phantom and a human brain data set. To evaluate the reconstruction bias, we tested different reconstruction framing schemes and propose a framing scheme that keeps the counts per time frame constant over the full acquisition time. We also compared the vendor’s 3D OP-OSEM image reconstruction method to an in-house developed reconstruction (PRESTO toolkit). Results: In general, a bias for low and high activity concentration regions was observed in the range of ± 3% and - 3% to 5%, respectively. Using the alternative proposed framing scheme, a lower bias was achieved for regions with low activity concentration using PRESTO, and a stabilization of the mean bias for the binding potential was achieved at around 5% with the vendor’s reconstruction throughout the relevant activity curve time interval. Conclusions: The bias in activity concentration propagated into the binding potential values leading to a mean bias of around 5%, thus allowing the detection of changes in binding values during equilibrium of > 5%.
Potential Common Key Genes Associated with Chronic Periodontitis and Low Birth Weight: A Case Control Study Using Bioinformatics Analysis of Pooled mRNA Expression Datasets
Authors: Suzuki Asami , Horie Tetsuro , Nakai Akihito , Kikuchi Eriko , Numabe Yukihiro
Published: June 2020

Background: Chronic periodontitis (CP) is a multifactorial disease associated with many systemic diseases. However, the precise association between CP and low birth weight (LBW) remains unclear. Therefore, this study aimed to elucidate common differentially expressed genes (DEGs), biomarker candidates, and upstream regulators related to key genes between CP and LBW.Methods: We investigated molecular relations and biomarker candidates using pooled microarray datasets of CP (GSE12484) and LBW (GSE29807) in the Gene Expression Omnibus (GEO). Datasets were analyzed for common DEGs using GEO2R, an R-based web application for GEO data analysis. Common DEGs, biomarker candidates, and upstream regulators in DEGs between CP and LBW were analyzed using the Database for Annotation Visualization and Integrated Discovery (DAVID), Search Tool for the Retrieval of Interacting Genes (STRING), and QIAGEN’s Ingenuity Pathway Analysis (IPA).Results: Three significantly upregulated and 20 significantly downregulated common DEGs between CP and LBW were identified. Some biological processes and pathways of these downregulated genes were associated with the cell cycle. Biomarker candidates among common DEGs were proline-rich coiled-coil 2A (PPRC2A), topoisomerase (DNA) II alpha (TOP2A), neural cell adhesion molecule 1 (NCAM1), and calcium channel, voltage-dependent, alpha 2/delta subunit 3 (CACNA2D3). Many upstream regulators of these biomarker candidates were factors associated with inflammation, immunity, the cell cycle, and growth development, and were hormones related to pregnancy.Conclusions: The results of this study suggest that PPRC2A, TOP2A, NCAM1, and CACNA2D3 are common biomedical key genes between CP and LBW. The expression states of these genes, which are related to inflammation, hormones, the cell cycle, and growth development, were common in both CP and LBW in blood. To the best of our knowledge, the relations of PPRC2A, TOP2A, and CACNA2D3 to CP and LBW are reported for the first time. Thus, in the bloodstream, inflammatory-related upstream regulators of these key genes may control gene expression associated with fetal growth, and conversely, changes in female hormones due to pregnancy may affect the progress of CP.
Key Factors Associated with Oral Health-Related Quality of Life in Sri Lankan Adolescents: A Cross Sectional Study
Authors: Amilani Uttara , Jayasekara Prasanna , Carter Hannah E , Senanayake Sameera , Kularatna Sanjeewa
Published: June 2020

Background Oral Health Related Quality of Life (OHRQoL) measures have emerged as an important oral health outcome that is able to reveal the subjective burden of illness due to oral diseases.The association between socio-demographic and socio-economic factors, clinical dental conditions and OHRQoL indicators has been investigated in adolescents’ cohorts across the world. The purpose of this study was to investigate key factors associated with oral health-related quality of life of Sri Lankan adolescents. Methods A cross sectional study was conducted amongst a sample of 15-19 year-old secondary school students, Gampaha district, Sri Lanka. The data was collected using two self-administered questionnaires. A modified Sinhalese version of the Oral Impact on Daily Performance (OIDP) questionnaire that has been validated for Sri Lankan adolescents was administered. A second questionnaire collected information on socioeconomic characteristics, oral health care seeking and oral health behaviours. A clinical oral examination was performed on each participant. Oral health related quality of life was measured using OIDP domains and total OIDP scores. Multiple linear regression with stepwise selection was used to investigate the key factors associated with the OIDP additive score. Results A total of 1,332 adolescents participated in the study. Negative quality of life impacts were more prevalent in the social and psychological domain of OIDP as compared with the functional domain. Total OIDP scores ranged from 0 to 36 with a mean of 3.16 (SD=4.71). The multivariate analysis revealed that decayed teeth, presence of anomaly, age, family income, health care seeking pattern and consumption pattern of soft drinks were all significantly associated with higher total OIDP scores, reflecting poorer oral health related quality of life. Frequency of daily tooth brushing was negatively associated with total OIDP scores. ConclusionVarious factors were associated with OHRQoL and could have implications for the improvement of OHRQoL among Sri Lankan adolescents.
liver X receptors inhibit pulmonary inflammation and airway remodeling induced by ozone exposure in mice
Authors: Yu Fenfang , Zheng Lin , Wang Li , Yang Xiaobing , Ma Zhifei , Tang Yu , Li Nan , Wang Youran , Gu Wei , Shi Ying
Published: June 2020

Ozone (O3) exposure can lead to airway inflammation, hyperreactivity and airway remodeling. Liver X receptors (LXRs) play an important role in attenuating inflammation. The therapeutic effects of LXRs on ozone-induced pulmonary inflammation and airway remodeling were examined. C57/BL6 mice were exposed to ozone for 1 or 6 weeks. LXR agonist T0901317 was administered to mice at one hour before ozone exposure. As expected, ozone-exposed mice developed lung inflammation with augmented neutrophil, macrophage, TNF-α, IL-6, IL-8 and G-CSF in the bronchoalveolar lavage fluid and serum. The increase in MMP-9 and α-SMA expression, and collagen deposition around airway reflected the airway remodeling in ozone-exposed mice. Compared with ozone-exposed mice, LXR agonist T0901317 inhibited the ozone-induced inflammation after 1 and 6 weeks in the ozone exposure model. In addition, the treatment with the LXR agonist prevented alveolar enlargement and reduced airway remodeling in 6-week ozone-induced mice. Therefore, LXRs may repress pulmonary inflammation and attenuate the progression of airway remodeling.
Systematic evaluation of CdSe/ZnS Quantum Dots toxicity on the reproduction and offspring health in male BALB/c mice
Authors: Li Li , Lin Xiaotan , Chen Tingting , Liu Kan , Yang Zhiwen , Chen Yajing , Liu Dongmeng , Xu Gaixia , Wang Xiaomei , Lin Guimiao
Published: June 2020

Background: Increased applications of quantum dots (QDs) in biomedical field have aroused attention for their potential toxicological effects. Although many studies have been carried out on the toxicity of QDs, their effects on reproductive and development are still unclear. In this study, we systematically evaluated the male reproductive toxicity and developmental toxicity of CdSe/ZnS QDs in BALB/c mice.Results: The male mice were injected intravenously with CdSe/ZnS QDs at the dosage of 2.5 mg/kg BW or 25 mg/kg BW, respectively, and the survival status, biodistribution of QDs in testes, serum sex hormone levels, histopathology, sperm motility and acrosome integrity was measured on Day 1, 7, 14, 28 and 42 after injection. On Day 35 after treatment, male mice were housed with non-exposed female mice, and then offspring number, body weight, organ index and histopathology of major organs, blood routine and biochemical tests of offspring were measured to evaluate the fertility and offspring health. The results showed that CdSe/ZnS QDs could rapidly distribute in the testis, and the fluorescence of QDs could still be detected on Day 42 post-injection. QDs had no adverse effect on the structure of testis and epididymis, but high-dose QDs could induce apoptosis of Leydig cells in testis at an early stage. No significant differences in survival of state, body weight organ index of testis and epididymis, sex hormones levels, sperm quality, sperm acrosome integrity and fertility of male mice were observed in QDs exposed groups. However, the development of offspring was obviously influenced, which was mainly manifested in the slow growth of offspring, changes of organ index of main organs, and the abnormality of liver and kidney function parameters.Conclusion: Our findings revealed that CdSe/ZnS QDs were able to cross the blood-testis barrier (BTB), produce no discernible toxic effects on the male reproductive system, but could affect the healthy growth of future generations to some extent. In view of the broad application prospect of QDs in biomedical fields, our findings might provide insight into the biological safety evaluation of the reproductive health of QDs.
Everything Counts -- A Method To Determine Viral Suppression Among People Living With Hiv Using Longitudinal Data For The Hiv Care Continuum. - Results Of Two Large, German, Multi-Center Real-Life Cohort Studies Over 20 Years (1999-2018)
Authors: Schmidt Daniel , Kollan Christian , Stoll Matthias , Hamouda Osamah , Bremer Viviane , Kurth Tobias , Bartmeyer Barbara
Published: June 2020

Background
The aim of this study was to develop a standardized method to reconstruct persons' individual VL courses to determine viral suppression and duration of viremia for the HIV care continuum in Germany using data longitudinal cohort data.
Methods
We analyzed data from two large, multi-center German cohort studies under the direction of the Robert Koch Institute. We included data from 1998 to 2018 of all diagnosed people and of people who initiated antiretroviral treatment (ART). We developed a model generating virtual VL points and an individual VL course corresponding to real VL measurements with a maximum distance of 180 days, considering ART status and VL dynamics. If the distance between VL measurements was > 180 days, the time between was defined as gap-time. Additionally, we considered blips, which we defined as a single detectable VL < 1,000 copies/ml within 180 days.
Results
A total of 22,120 people (164,691 person-years, PY) after ART initiation were included in the analyses. The proportion of people with viral suppression (VL < 50 copies/ml) increased from 34% in 1999 to 93% in 2018. The proportion of people with VL < 200 copies/ml increased from 47% in 1999 to 96% in 2018. The proportion of people with viremia > 1,000 copies/ml decreased from 37% in 1999 to 3% in 2018. The proportion of people with gap-time fluctuated and ranged between 18% and 28%. An analysis of the first VL after gap-time showed that 90% showed viral suppression, 5% VL between 50-<1,000 copies/ml and 5% VL > 1,000 copies/ml.
Conclusion
We provide a method for estimating viral suppression and duration of viremia using longitudinal VL data. We observed a continuous and remarkable increase of viral suppression. Furthermore, a notable proportion of those with viremia showed low-level viremia and were therefore unlikely to transmit HIV. Individual health risks and HIV drug resistance among those with low-level viremia are problematic, and viral suppression remains the goal. In 2018, 93% and 96% of people after ART initiation showed VL < 50 copies/ml and VL < 200 copies/ml, respectively. Therefore, using the threshold of VL < 200 copies/ml, Germany reached the UNAIDS 95 target of viral suppression since 2017.
Spatial Distribution and Determinant Factors of Intimate Partner Violence Among Reproductive age Group Women in Ethiopia; Generalized Structural Equation Modeling
Authors: Tusa Biruk Shalmeno , Kebede Sewnet Adem , Weldesenbet Adisu Birhanu
Published: June 2020

Background: Intimate Partner Violence (IPV) is the most serious and pervasive yet under recognized human rights violation in the world as well as in Ethiopia. The objective of this study was to find the spatial distribution of IPV and its determinant factors in Ethiopia. Methods: Secondary data analysis was conducted among 2,687 reproductive age group women (15–49 years). The distribution of IPV across the country was observed by ArcGIS software. In SaTScan software, the Bernoulli model was fitted by Kulldorff methods to identify the purely spatial clusters of IPV. Generalized Structural Equation Model (GSEM) was used to determine factors associated with each domain of IPV (physical, emotional & sexual violence).Result: The spatial distribution of IPV was found to be clustered in Ethiopia with Global Moran’s I 0.09 (p < 0.001) and the highest IPV cluster was observed in Oromia (p < 0.001), Somali (p < 0.001) and Southern Nation and Nationality and Peoples (SNNP) (p < 0.001) regions . Watching television and not having attitudes toward wife beating were negatively associated with physical violence. Being richest and nonsmoker were inversely associated with emotional violence. The odds of experiencing sexual violence were increased among pregnant and wife of uneducated husband/partner. Women’s decision-making autonomy and husband/partner drinking alcohol have positive and negative association with all domains of IPV respectively. Conclusions: There was a significant clustering of IPV in Ethiopia and the highest IPV cluster was observed in Oromia, Somali and SNNP regions. Being richest, watching television, not having attitudes toward wife beating, women’s decision autonomy and husband’s/partner’s high education and non-alcohol drinker status were negatively associated with IPV. The likelihood of experiencing IPV was also increased among smoker and pregnant women. We recommend that improving the economic status of the household and power of women's decision autonomy, increasing community awareness about the consequences of IPV with particular emphasis in Oromia, Somali and SNNP regions.
Clinical Outcome of Meningitis and Its Risk Factors Among Children Admitted in Debre Markos Referral Hospital Pediatric Ward, Northwest Ethiopia,2019
Authors: Abiy Hailemariam , Shiferaw Zelalem , Tafere Yilkal
Published: June 2020

Background:Meningitis remains a major cause of mortality and morbidity in patients in many countries of the world including Ethiopia. This study aimed to assess clinical outcomes and associated risk factors of meningitis among children who were admitted to Debre Markos Referral Hospital from January 2017 to December 2018.A backward stepwise multivariable logistic regression was applied with 95% confidence interval of odds ratio (OR) andstatistical significance less than 0.05 p-value were taken as cut off value.Methods:A retrospective cross-sectional study was conducted. The study includesAll pediatric meningitis 211 cases from the age of one month to fourteen who were admitted due to meningitis in Debre Markos Referral Hospitalfrom January 2017 to December 2018.Data were entered, cleaned, and analyzed using SPSS for Windows, version 20.Results:The study showed that 18.9% of children with meningitis developed bad outcomes. In this study, children who were a worse clinical condition at admission 6 times more likely to develop bad outcomes [AOR= 6.321(2.121, 18.837)] and having a seizure at admission almost 19 times more likely to develop bad outcomes [AOR=18.953(6.677, 53.799)]. Conclusions:About one in five children with meningitis developed bad outcomes. The health care team should due attention to improving care for patients with severe conditions at admission and seizures were the alarming signs for poor outcomes in children.
Somatic Development in Children With Shwachman-diamond Syndrome
Authors: Bogusz-Wójcik Agnieszka , Kołodziejczyk Honorata , Klaudel-Dreszler Maja , Oracz Grzegorz , Pawłowska Joanna , Szalecki Mieczysław
Published: June 2020

Background: Shwachman-Diamond syndrome (SDS) is a rare genetic, multi-systemic diseasecharacterised by exocrine pancreatic insufficiency, immune deficiency, bone marrow failure and skeletal abnormalities.Most patients present with failure in somatic development and short stature, but systematic data concerning those features are limited. The aim of the study was to assess the prevalence of failure in somatic development in the children with SDS.Methods: An analysis of anthropometric measurements of 21 patients (14 girls and 7 boys),eaged 2 to 17 years (mean age 6.3 years) with SDS diagnosed in The Children’s Memorial Health Institute in Warsaw, Polandwas performed.The patients were measured using a Holtain Limited stadiometer, an electronic scale, a Harpenden anthropometer, a metric tape and a spreading caliper. The assessed anthropometric parameters were expressed as standard deviation scores in relation to the reference values in Poland, suitable for sex as well as calendar and growth age.Results: A total of66measurements was collected and analysed with a median number of 3 observations per patient.The group of boyspresented with a significantly lower height (-3.0 SD, p<0.0001) and BMI (-1.4 SD, p<0.00001), and in the relation to the growth age a lower weight ( -1.0 SD, p<0.001) as well as a smaller chest width (-0.9 SD, p<0.05), hip width (-0,5 SD, p<0,05) and lower limb length (-0,5 SD, p<0,05). The group of girls also showed significantly lower height (-2.6 SD, p<0.00001) and BMI (-0.8 SD, p<0.00001), and in relation to the growth age, lower weight (-0.5 SD, p<0.001) as well as decreased width of the chest (-1.7 SD, p<0.0001) and shoulder (‑1.0 SD, p<0.001) were observed. Boys and girls were alsocharacterised by significantly decreased circumference and width of head, additionally, girls had also smaller head length.Conclusions: Patients with SDS have abnormal somatic development. Both boys and girls are characterised by short stature, decreased weight, BMI, leg length, chest width as well as circumference and width of head. Anthropometric measurements provide important data on the process of growth and body proportions in children with SDS.
Formulation of traditional Chinese medicine and its application on intestinal flora of constipated rats
Authors: Huang Minghan , Li Sihan , He Youcheng , Zhang Haiou , Xu Ruoying , Liu Qihong , Tang Shuihua , Ke Xiao
Published: June 2020

In this study, the self-extracted constipation treatment of traditional Chinese medicine extracts was applied to constipated rats. To explore the mechanism and role of the Chinese medicine for the treatment of constipation, the 16S rRNA sequencing and qRT-PCR technology were used to analyze the abundance and diversity of intestinal flora in rats. We found that the relative abundance of Firmicutes in the intestinal flora of rats with constipation was significantly higher than that in the control group, and the Bacteroides was significantly lower than that in the control group, while the relative abundance of Firmicutes was significantly changed after taking a certain dose of Chinese medicine, and reduced the relative abundance of Lachnospiraceae, and greatly increased the relative abundance of Lactobacillus, enhanced the symbiotic relationships of Lactobacillus with other intestinal flora. There was no significant difference in the total copies of intestinal bacteria between the constipated rats and the control group. The total copies of intestinal bacteria in the constipated rats decreased after taking the traditional Chinese medicine. Finally, this study results provides a theoretical basis for the treatment and understand the mechanism and effect of traditional Chinese medicine on rate constipation.
A Genetic Predictive Model for Precision Treatment of Diffuse Large B-cell Lymphoma with Early Progression
Authors: Ma Jialin , Yan Zheng , Zhang Jiuyang , Zhou Wenping , Yao Zhihua , Wang Haiying , Chu Junfeng , Yao Shuna , Zhao Shuang , Zhang Peipei , Xu Yuanlin , Xia Qingxin , Ma Jie , Wei Bing , Yang Shujun , Liu Kangdong , Guo Yongjun , liu yanyan
Published: June 2020

Background: Early progression after standard immunochemotherapyleads to a very dismal outcome and necessitates alternative treatmentforpatients with diffuse large B-cell lymphoma (DLBCL). This study aimed todevelop a genetic predictive model for early progression and evaluate its potentialin advancing alternative treatment.Methods:Thirty-two hotspot driver genes were examined in 145 DLBCL patients and 5DLBCL cell linesusing next-generation sequencing. The association of clinical features, cell-of-origin, double expression, positive p53 protein, and gene alterations with early progression was analyzed, and the genetic predictive model was developed based on the related independent variables and assessed by the area under receiver operating characteristic.The potential of novel treatment based on the modeling was investigated ininvitro DLBCL cell lines and invivo xenograft mouse models.Results:The frequency of CD79B(42.86% vs 9.38%, p = 0.000)and PIM1 mutations (38.78% vs 17.71%, p = 0.005) showed asignificant increase in patients with early progression. CD79B and PIM1 mutations were associated with complex genetic events,double expression, non-GCB subtype, advance stageand unfavorable prognosis. Apowerful genetic predictive model (AUROC=0.771, 95% CI: 0.689-0.853)incorporatinglactate dehydrogenase levels(OR = 2.990, p = 0.018), CD79B mutations (OR = 5.970, p = 0.001), and PIM1 mutations (OR = 3.021, p=0.026)was created andverified in the other cohort. This modeling outperformed the prediction accuracy of conventional International Prognostic Index, and new molecular subtypes of MCD and Cluster 5. CD79B and PIM1 mutations indicateda better response to inhibitorsof BTK (ibrutinib) and pan-PIM kinase(AZD 1208) through repressingactivated oncogenic signaling. Since the two inhibitorsfailed to decrease BCL2level,BCL2 inhibitor (venetoclax) was added and demonstrated to enhancetheirapoptosis-inducing activityin mutant cells with double expression.Conclusions: Thegenetic predictive model provides a robust tool to identify early progression and determine precision treatment.These findings warrant the development of optimal alternative treatment in clinical trials.
The Social versus Food Preference Test: A behavioral paradigm for studying competing motivated behaviors in rodents
Authors: Reppucci Christina , Veenema Alexa H
Published: June 2020

Behavior is influenced by a combination of factors, with the expression of the appropriate behavior dependent on an individual’s current motivational state and the presence of stimuli in their surrounding environment. Thus far, most laboratory studies have focused on uncovering the peripheral and central systems that regulate the expression of a single behavior or the expression of a suite of behaviors associated with a single motivational state. In natural settings, however, an individual can be simultaneously experiencing multiple motivational states with multiple choices of how to act. Yet, the direct assessment of the roles of peripheral and central systems in coordinating motivated behavioral choice is largely understudied. This may be due to a lack of behavioral tests that are suitable for such investigations. Here, we describe a recently developed behavioral paradigm, hereafter called the Social versus Food Preference Test. This behavioral paradigm was validated in both rats and mice and is highly flexible, which will allow addressing of a wide range of research questions concerning the peripheral and central systems that coordinate the choice to seek social interaction versus the choice to seek food.
Galuteolin suppresses proliferation and inflammation in TNF-α-induced RA-FLS cells by activating HMOX1 to regulate IKKβ/NF-κB pathway
Authors: GUAN Yin , ZHAO Xiaoqian , LIU Weiwei , Wang Yue
Published: June 2020

Objective: Galuteolin (Galu) is a substance extracted and purified from honeysuckle. The purpose of this study was to explore the effects of Galu on the TNF-α-induced RA-FLS cells (synoviocytes) and reveal its potential molecular mechanism from the perspectives of anti-apoptosis and anti-inflammation.Methods: After TNF-α stimulation, cell proliferation of RA-FLS was assessed by CCK-8 assay. TUNEL staining was used to detect the apoptosis. Western Blot was used to detect the expressions of Iκκβ, p-p65, p65, p-IκB, IκB, Cleaved-caspase3, Caspase-3, Bcl-2, and Bax. HO-1 were determined by RT-PCR. The contents of pro-inflammatory cytokines IL-1β, IL-6, IL-8 and MMP-1 were determined by ELISA.Results: Galu significantly suppressed cell proliferation in a dose-dependent manner. Additionally, Galu obviously promote cell apoptosis rate of RA-FLS cells and elevated the expression levels of HO-1, caspase-3 and Bax, while reduced the expression level of Bcl-2. Furthermore, Galu apparently inhibited the levels of Iκκβ, p-p65 and p-IκB. Moreover, Galu also significantly reduced the levels of pro-inflammatory factors IL-1β, IL-6, IL-8 and MMP-1 in RA-FLS cells. Conclusion: Galuteolin exerts protective effects against TNF-α-induced RA-FLS cells by inhibiting apoptosis and inflammation, which can guide the clinical use of rheumatoid arthritis.
A new method for functional analysis of plastid EMBRYO-DEFECTIVEPPR genes by efficiently constructing cosuppression lines in Arabidopsis
Authors: Chen Jingli , Huang Jirong , Huang Weihua
Published: June 2020

Background: Pentatricopeptide-repeat proteins (PPRs) characterized by tandem arrays of a degenerate 35-amino-acid repeat (PPR motif) can bind a single strand RNA and regulate organell gene expression at the post-transcriptional level, including RNA cleavage, splicing, editing and stability etc. PPRs are conserved in all eukaryotes and extremely expanded in higher plants. Many knockout mutants of PPR genes are embryonic lethal. These genes are named EMB PPRs and their functional analysis is particularly difficult.Results: Here, we report a new method for functional analysis of plastid EMB PPRs by efficiently constructing their cosuppression lines in Arabidopsis. When we overexpressed a mutated full length or fragments lacking one or several PPR repeats of EMB PPRs, such as EMB2279, EMB2654 and EMB976 in the wild-type (WT) background, a large portion of T1 plants displayed chlorosis phenotypes, which is similar to those of their knockdown mutants. RT-PCR analysis showed that the exogenous transgene was overexpressed, while the corresponding endogenous mRNA was significantly downregulated in the transgenic lines. However, when these constructs were overexpressed in the PTGS (Post transcriptional Gene Silencing) deficient mutant, rdr6 (rna dependent rna polymerase 6), none of the T1 plants displayed chlorosis phenotypes. These results indicate that the chlorosis phenotype results from post transcriptional silencing of the corresponding endogenous gene (also known as sense cosuppression). Conclusions: Overexpression of an appropriately truncated PPR CDS in WT leads to a high frequency of cosuppression lines with apparent mutant phenotype, and this method can be employed to study the unknown function of EMB PPR genes. By this method, our preliminary data showed that EMB976 is required for splicing of plastid clpP1 intron 2 and ycf3 intron 1.
Aberrant activation within auditory network is associated with psychiatric comorbidities in interictal migraineurs without aura
Authors: Wei Heng-Le , Chen Yu-Chen , Yu Yu-Sheng , Guo Xi , Zhou Gang-Ping , Zhou Qing-Qing , Qu Li-Jie , Yin Xindao , Li Junrong , Zhang Hong
Published: June 2020

Background: Resting-state functional magnetic resonance imaging has confirmed auditory network dysfunction in migraine without aura (MwoA). Epidemiological investigations have disclosed that migraine is comorbid with many psychiatric symptoms. However, the underlying mechanisms of auditory cortex dysfunction linked to psychiatric disorders in MwoA remain unclear. The present study aimed to explore associations between brain activation in the auditory cortex and clinical and psychiatric characteristics in patients with MwoA during interictal periods.Methods: Resting-state data were acquired from patients with episodic MwoA (n=34) and healthy controls (n=30). Independent component analysis was used to extract and calculate the resting-state auditory network. Subsequently, we analyzed the correlations between spontaneous activation in the auditory cortex and clinical and psychiatric features in MwoA.Results: Compared with healthy controls, patients with MwoA showed increased activation in the left auditory cortex (i.e., superior temporal gyrus (STG), postcentral gyrus (PoCG) and insula). Brain activation in the left STG was positively correlated with anxiety scores, and activation in the left PoCG was negatively correlated with anxiety and depression scores. No significant differences were found in intracranial volume between the two groups.Conclusions: This study indicated that functional impairment and altered integration within the auditory cortex existed in patients with MwoA in the interictal period, suggesting that auditory cortex disruption as a biomarker may be implemented for the early diagnosis and prediction of neuropsychiatric impairment in MwoA.
Aspirin Does Not Increase the Need for Hemostatic Interventions in Blunt Liver and Spleen Injuries.
Authors: Huang Jen-Fu , Cheng Chi-Tung , Fu Chih-Yuan , Huang Yu-Tung Anton , Hsu Chih-Po , Yang Chun-Hsiang Ou , Liao Chien-Hung , Hsieh Chi-Hsun , Chang Shang-Hung
Published: June 2020

Background: The prohemorrhagic effect of aspirin may cause concern about worse prognoses when treating blunt hepatic or splenic injuries. This study investigated whether preinjury aspirin yields an increasing need for hemostatic interventions.Methods: Admission and outpatient records were extracted from the Taiwan National Health Insurance Research Database (NHIRD) from 2003 to 2015. Patients with splenic or hepatic injuries were identified. Patients with preinjury nonaspirin APAC or with penetrating injuries were excluded. The primary outcome measurement was the necessity of invasive procedures to stop bleeding, including transarterial embolization (TAE) and surgeries. One-to-two propensity score matching (PSM) was used to minimize selection bias. Multilogistic regression (MLR) analysis was used to identify factors associated with hemostatic interventions.Results: 20,470 (60.6%) had blunt hepatic injuries, and 15,235 (45.1%) had blunt splenic injuries, of whom 691 (3.4%) and 667 (4.4%) used preinjury aspirin, respectively. In the blunt hepatic injury cohort, there was no significant difference in the need for hemostatic procedures (TAE (6.1% vs 6.1%, p=1.000), exploratory laparotomy (6.1% vs 6.1%, p=1.000), hepatectomy (3.0% vs 2.7%, p=0.694) or hepatorrhaphy (14.3% vs 15.0%, p=0.681)). MLR analysis showed that preinjury aspirin did not increase the need for hemostatic interventions (OR 0.92, 95% CI 0.73-1.16, p=0.473). Regarding the blunt splenic injury cohort, there was no significant difference in the need for hemostatic procedures (TAE (11.5% vs 10.6%, p=0.547), splenectomy (43.5% vs 41.4%, p=0.407) or splenorrhaphy (3.0% vs 3.3%, p=0.698)). An MLR analysis showed that preinjury aspirin did not increase the need for hemostatic interventions (OR 1.12, 95% CI 0.91-1.38, p=0.290).Conclusions: Preinjury aspirin use is not associated with increased hemostatic procedures in blunt hepatic or splenic injuries.
Inclusive Education in the European Union: A Fuzzy-Set Qualitative Comparative Analysis of Education Policy for Autism
Authors: Kessel Robin van , Hrzic Rok , Cassidy Sarah , Brayne Carol , Baron-Cohen Simon , Roman-Urrestarazu Andres , Czabanowska Katarzyna
Published: June 2020

Background: Children with special education needs (SEN), such as autistic children, benefit from being included in education along with typical peers. However, development and implementation of inclusive education (IE) is considered difficult. This paper identifies conditions that facilitate IE development for autistic children in the European Union and benchmarks to track IE policy development. Methods: Education policy data from thirty legislative regions in the European Union were analyzed through a qualitative comparative analysis using eight conditions: a definition of SEN, the right to education for children with SEN, support for teaching staff, support services for children with SEN, individualized learning outcomes, parental involvement, and mixed mainstream classes.Results: The right to education for children with SEN is implemented in all regions under study. Seven of the examined conditions were associated with an environment of IE in the European Union from an autism perspective: an established definition of SEN, support for teaching staff, general availability of support services for children with SEN, individualized learning outcomes, parental involvement, IE policies, and mixed mainstream classrooms. Mixed classrooms and support services for children with SEN were identified as necessary for IE. IE policies and support for teaching staff were present in all scenarios that facilitated IE. Even though the analysis was initially focused on autism, the policies consisted predominantly of general SEN policies. As such, the results can be interpreted in a wider context, beyond autism.Conclusion: Mixed mainstream classrooms and support services for children with special needs were found essential for consistent IE development. Support for teaching staff and IE policies facilitate IE and should be further explored and implemented.
p63+Krt5+ Basal Cells are Increased in the Squamous Metaplastic Epithelium of Patients with Radiation-induced Chronic Rhinosinusitis
Authors: Huang Hongming , Tan Kai Sen , Zhou Suizi , Yuan Tian , Liu Jing , Ong Hsiao Hui , Chen Qianmin , Gao Junxiao , Xu Minghong , Zhu Zhenchao , Qiu Qianhui , Wang De Yun
Published: June 2020

Background: Squamous metaplasia (SM) is an irreversible form of airway epithelial remodeling. Hyperproliferation of basal cells was observed in squamous metaplastic epithelium of chronically inflamed airway. However, the association of such aberrant proliferation of basal cells with SM in the nasal epithelium after radiation damage remains unclear. The aim of this study was to investigate SM and accompanying levels of p63+Krt5+ (basal cell markers) cells in the nasal epithelium of patients with radiation-induced chronic rhinosinusitis (CRSr) and patients with chronic rhinosinusitis without nasal polyps (CRSsNP) compared to healthy controls.Methods: We assessed the prevalence of SM and the expression of p63+, Krt5+, p63+Krt5+, and Ki67+ cells through immunofluorescence(IF) staining of the inferior turbinate (IT) tissues from patients with CRSr (n = 36) , CRSsNP (n = 33) and controls (n = 28).Results: The prevalence of SM and the number of p63+Krt5+ cells were both significantly increased in patients with CRSr compared to patients with CRSsNP and controls. The number of Ki67+ cells were both significantly increased in patients with CRSr and CRSsNP compared to controls, but the ratio of Ki67+ cells to p63+Krt5+ cells was significantly lower in patients with CRSr compared to patients with CRSsNP. In patients with CRSr, an increased number of p63+Krt5+ basal cells was observed in SM epithelium compared to non-SM epithelium.Conclusion: SM is increased in the nasal epithelium of patients with CRSr, in which aberrant levels of p63+Krt5+ basal cells serves as an important pathologic feature in the squamous metaplastic epithelium.
NNT-AS1 Impairs CD4+ T Cells Infiltration by Up-Regulating TGF-β Signaling in Hepatocellular Carcinoma
Authors: Wang Yakun , Yang Lei , Dong Xichen , Yang Xin , Zhang Xinxue , Liu Zhe , Zhao Xin , Wen Tao
Published: June 2020

Background Nicotinamide Nucleotide Transhydrogenase-antisense RNA1 (NNT-AS1) is one of long non coding RNA, has been shown with high levels in several types of cancers. However, the molecular mechanism remains to be revealed for NNT-AS1 in the progession of hepatocellular carcinoma (HCC). TGF-β signaling pathway has been identified as one of negative factor for excessive immunological response. We sought to investigate the effects of NNT-AS1 mediating T cells infiltration by regulating TGF-β signaling pathway in patients with HCC.Methods RNAscope In Situ Hybridization and Real Time Quantitative PCR assays were applied to detect NNT-AS1 levels in HCC tissues. Immunohistochemistry (IHC) assays were used to observe the co-expressions of TGF-β, TGFBR1, SMAD1/5/9, and CD4+ T cells. The mechanisms as to how NNT-AS1 orchestrates TGF-β signaling were further explored in HepG2 and Huh7 cells. Results RNA-scope analyses revealed that the levels of NNT-AS1 were significant higher in cancerous tissues than in paired non-cancerous tissues (P=0.0001). Quantitative PCR assays validated the high expression of NNT-AS1 in HCC cancer tissues (n=64) when compared with normal tissues (n=26) (P=0.0003). The prognostic analysis indicated that the OS rates for HCC patients with high levels of NNT-AS1 were significantly lower than patients with low levels of NNT-AS1 (P=0.0402). Mechanistic analysis demonstrated that the downregulation of NNT-AS1 significantly reduced the expression of TGF-β, TGFBR1, and SMAD5. Moreover, the inhibition of NNT-AS1 decrease the expression of TGF-β，TGFBR1, and SMAD5. Importantly, IHC analyses indicated that the levels of NNT-AS1 were negatively correlated with CD4+ T lymphocyte cells infiltration in tissues from 16 HCC patients.Conclusions Our study depicts a novel mechanism regarding NNT-AS1 activates TGF-β signaling pathway and thus impairs the CD4+ T lymphocyte cells infiltration in HCC.
A Novel Analysis of the Differentiated Expression of Long Noncoding RNAs Profiles in Human Prostate Cancer
Authors: Sun Chuanyu , Ge Shengyang , Mi Yuanyuan , Hu Qingfeng , Guo Yijun , Zhong Fan , Zhang Yang , Xia Guowei
Published: June 2020

Background: Long noncoding RNAs (lncRNAs) have crucial roles in cancer biology. Increasing numbers of evidences have indicated that lncRNAs play an important role in the pathogenesis, invasion, and metastasis in almost all kinds of cancers. But, compared with the large amounts of patients, there is rare reports that showed the differential expression of lncRNAs in prostate cancer. Methods: In this study, lncRNA expression profiles were screened in PCa, by using 5 pairs of clinical specimens in PCa and matched non-PCa tissues with lncRNA chip. To affirm further clinical value, we extended the samples consisting of another 5 tumor specimens and 7 para-cancerous/benign contrasts by qRT-PCR in top 10 up-regulated and down-regulated lncRNAs. Results: A total of 817 lncRNAs were differentially expressed between PCa tumor and para-cancerous tissues (Fold Change ≥2.0, p < 0.05): 422 were upregulated, whereas 395 were downregulated in PCa tissues. Gene ontology and KEGG pathway analyses showed that many lncRNAs were implicated in carcinogenesis. Among differentially expressed lncRNAs, lnc-MYL2-4:1 (FC = 0.00141, p = 0.01909) and NR_125857 (FC = 59.27658, p = 0.00128) had the highest magnitude of change. The subsequent qPCR confirmed the expression of NR_125857 accorded with the clinical samples.Conclusions: Our study detected a relatively novel complicated map of lncRNAs in PCa, which may have the potential to investigate for diagnosis, treatment and follow-up in PCa. Our study revealed the expression of NR_125857 in human PCa tissues was most up-regulated. Further study of these meaningful candidates are need to research deep mechanisms.
Metabolic engineering of Saccharomyces cerevisiae for enhanced production of caffeic acid
Authors: Zhou Pingping , Yue Chunlei , Shen Bin , Du Yi , Xu Nannan , Ye Lidan
Published: June 2020

Background

As a natural phenolic acid product of plant source, caffeic acid displays diverse biological activities and acts as an important precursor for the synthesis of other valuable compounds. Limitations in chemical synthesis or plant extraction of caffeic acid trigger interest in its microbial biosynthesis. Recently, Saccharomyces cerevisiae has been reported sporadically for biosynthesis of caffeic acid via free plasmid‑mediated pathway assembly. However, the production was far from satisfactory and even relied on the addition of precursor.
Results

In this study, we first established a controllable caffeic acid pathway by employing a modified GAL regulatory system in S. cerevisiae and realized de novo biosynthesis of 313.8 mg/L caffeic acid from glucose. Combinatorial engineering strategies including eliminating the tyrosine-induced feedback inhibition, deleting genes involved in competing pathways and overexpressing rate-limiting enzymes led to about 2.5-fold improvement in the caffeic acid production, reaching up to 769.3 mg/L in shake-flask cultures. To our knowledge, this is the highest ever reported titer of caffeic acid de novo synthesized by engineered yeast.
Conclusions

Caffeic acid production in S. cerevisiae strain was successfully improved by adopting a glucose-regulated GAL system and comprehensive metabolic engineering strategies. This work showed the prospect for microbial biosynthesis of caffeic acid and laid the foundation for constructing biosynthetic pathways of its derived metabolites.
Pharmacovigilance of suspected or confirmed therapeutic ineffectiveness of artemisinin-based combination therapies: extent, associated factors, challenges and solutions to reporting
Authors: Kiguba Ronald , Ndagije Helen Byomire , Nambasa Victoria , Manirakiza Leonard , Kirabira Elijah , Serwanga Allan , Olsson Sten , Speybroeck Niko , Mukonzo Jackson
Published: June 2020

Background: This study aimed to determine the extent and associated factors of past 6-month reporting of artemisinin-based combination therapy (ACT)-failure by healthcare professionals (HCPs); and difficulties and solutions to the pharmacovigilance (PV) of ACT therapeutic ineffectiveness.Methods: Survey of 685 HCPs from June to July 2018 in purposively selected public and private health facilities in Uganda.Results: One in five [20%, 137/685; 95% confidence intervals (CI) 17% to 23%] HCPs reported ACT-failure to any authority in the previous 6-months. HCPs commonly reported ACT-failure to immediate supervisors (72%, 106/147), mostly verbally only (80%, 109/137); none had ever reported a written ACT-failure to Uganda’s National Pharmacovigilance Centre. Common difficulties to reporting ACT-failure were; unavailability of reporting procedures (31%, 129/421), poor follow-up of treated patients (22%, 93/421) and absence of reporting tools (16%, 68/421). Factors associated with reporting ACT-failure in past 6-months were: hospital-status (vs other; OR = 2.4, 95% CI, 1.41 to 4.21), HCPs aged under 25 years (OR = 2.2, 95% CI, 1.29 to 3.76), suspicion of ACT-failure in past 4-weeks (OR = 2.3, 95% CI, 1.29 to 3.92), receipt of patient-complaint(s) of ACT-failure in past 4-weeks (OR = 2.9, 95% CI, 1.62 to 5.12) and HCPs from northern (vs central; OR = 0.5, 95% CI, 0.28 to 0.93) and western (vs central; OR = 0.4, 95% CI, 0.17 to 0.77) parts of Uganda.Conclusion: One in five HCPs reported ACT-failure, mostly verbally to supervisors. The existing ADR-reporting infrastructure should be leveraged to promote the PV of ACT therapeutic ineffectiveness.