bluuebunny/crossref_metadata_2025 huggingface dataset:
Consistency between Optical Coherence Tomography and Humphrey Visual Field for Evaluating Glaucomatous Defects in High Myopic Eyes
Authors: Wen Wen , Zhang Yuqiu , Zhang Ting , Sun Xinghuai
Published: October 2020

Background. The study is to investigate the influence of high myopia on the consistency between optical coherence tomography (OCT) and visual field in primary open-angle glaucoma (POAG). Methods. We enrolled 37 patients with POAG with high myopia (POAG-HM group), 27 patients with POAG without high myopia (POAG group), and 29 controls with high myopia (HM group). All subjects underwent Humphrey perimetry (30-2 and 10-2 algorithms). The peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thicknesses were measured using Cirrus HD-OCT. Spearman’s rank correlation analysis was used to determine correlations between OCT and perimetric parameters. Agreement was analyzed by cross-classification and weighted κ statistics. Results. In POAG group, the cross-classification analysis showed strong agreement between the inferior temporal GCIPL thickness and 10-2 MS (κ = 0.5447, P = 0.0048), and good agreement between the superior and inferior RNFL thicknesses and 30-2 MS (κ = 0.4407 and 0.4815; P < 0.05). In the POAG-HM group, only the inferior temporal GCIPL thickness showed good agreement with 10-2 MS (κ = 0.3155, P = 0.0289). Conclusions. In POAG patients with high myopia, changes in macular measurements were in accordance with visual field defects, and RNFL thickness did not consistently decline with visual field defects due to the effects of high myopia. This study suggests that during diagnosis and follow-up of glaucoma with high myopia, more attention need to be focused on structure and functional defects in macular areas.
Assessments of different inactivating reagents in formulating transmissible gastroenteritis virus vaccine
Authors: Zhao Fujie , Liu Lintao , Xu Menglong , Shu Xiangli , zheng Lanlan , Wei Zhanyong
Published: October 2020

Background: Background:Transmissible gastroenteritis virus (TGEV) causes enteric infection in piglets, characterized by vomiting, severe diarrhea and dehydration, and the mortality in suckling piglets is often high up to 100%. Vaccination is an effective measure to control the disease caused by TGEV. Methods: In this study, cell-cultured TGEV HN-2012 strain was inactivated by formaldehyde (FA), β-propiolactone (BPL) or binaryethylenimine (BEI), respectively. Then the inactivated TGEV vaccine was prepared with freund's adjuvant, and the immunization effects were evaluated in mice. The TGEV-specific IgG level was detected by ELISA. The positive rates of CD4+, CD8+, CD4+IFN-γ+, CD4+IL-4+ T lymphocytes were detected by flow cytometry assay. Lymphocyte proliferation assay and gross pathology and histopathology examination were also performed to assess the three different inactivating reagents in formulating TGEV vaccine.Results: The results showed that the TGEV-specific IgG level in FA group (n=17) was earlier and stronger, while the BEI group produced much longer-term IgG level. The lymphocyte proliferation test demonstrated that the BEI group had a stronger ability to induce spleen lymphocyte proliferation. The positive rates of CD4+ and CD8+ T lymphocyte subsets of peripheral blood lymphocyte in BEI group was higher than that in FA group and BPL groups by flow cytometry assay. The positive rate of CD4+IFN-γ+ T lymphocyte subset was the highest in the BPL group, and the positive rate of CD4+IL-4+ T lymphocyte subset was the highest in the FA group. There were no obvious pathological changes in the vaccinated mice and the control group after the macroscopic and histopathological examination. Conclusions: These results indicated that all the three experimental groups could induce cellular and humoral immunity, and the FA group had the best humoral immunity effect, while the BEI group showed its excellent cellular immunity effect.
Diminished adherence of Biomphalaria glabrata embryonic cell line to sporocysts of Schistosoma mansoni following programmed knockout of the allograft inflammatory factor
Authors: Coelho Fernanda Sales , Rodpai Rutchanee , Miller Andre , Karinshak Shannon E , Mann Victoria H , Carvalho Omar dos Santos , Cladeira Roberta Lima , Mourao Marina de Moraes , Brindley Paul J , Ittiprasert Wannaporn
Published: October 2020

Background: Larval development in an intermediate host gastropod snail of the genus Biomphalaria is an obligatory component of the life-cycle of Schistosoma mansoni. Understanding of the mechanism(s) of host defense may hasten the development of tools that block transmission of schistosomiasis. The allograft inflammatory factor 1, AIF, which is evolutionarily conserved and expressed in phagocytes, is a marker of macrophage activation in both mammals and invertebrates. AIF enhances cell proliferation and migration. The embryonic cell line, termed Bge, from Biomphalaria glabrata is a versatile resource for investigation of the snail-schistosome relationship since Bge exhibits a hemocyte-like phenotype. Hemocytes perform central roles in innate and cellular immunity in gastropods and in some cases can kill the parasite. However, the Bge cells do not kill the parasite in vitro.Methods: Bge cells were transfected by electroporation with plasmid pCas-BgAIFx4, encoding the Cas9 nuclease and a guide RNA specific for exon 4 of the B. glabrata AIF (BgAIF) gene. Transcript levels for Cas9 and for BgAIF were monitored by reverse-transcription-PCR and, in parallel, adhesion of gene-edited Bge cells during co-culture with of schistosome sporocysts was assessed.Results: Gene knockout manipulation induced gene-disrupting indels, frequently 1–2 bp insertions and/or 8–30 bp deletions, at the programmed target site; a range from 9 to 17% of the copies of the BgAIF gene in the Bge population of cells were mutated. Transcript levels for BgAIF were reduced by up to 73% (49.5 ± 20.2% SD, P ≤ 0.05, n =12). Adherence by BgAIF gene-edited (ΔBgAIF) Bge to sporocysts diminished in comparison to wild type cells, although cell morphology did not change. Specifically, as scored by a semi-quantitative cell adherence index (CAI), fewer ΔBgAIF than control wild type cells adhered to sporocysts; control CAI, 2.66 ± 0.10, ΔBgAIF, 2.30 ± 0.22 (P ≤ 0.01).Conclusions: The findings supported the hypothesis that BgAIF plays a role in the adherence of B. glabrata hemocytes to sporocysts during schistosome infection in vitro. This demonstration of the activity of programmed gene editing will enable functional genomics approaches using CRISPR/Cas9 to investigate additional components of the snail-schistosome host-parasite relationship.
Correlation between sestrin2 expression and airway remodeling in COPD
Authors: Zhang Da-Wei , Wei Yuan-Yuan , Ji Shuang , Fei Guang-He
Published: October 2020

Background. Airway remodeling is a major pathological characteristic of chronic obstructive pulmonary disease (COPD), and has been shown to be associated with oxidative stress. Sestrin2 has recently drawn attention as an important antioxidant protein. However, the underlying correlation between sestrin2 and airway remodeling in COPD has yet to be clarified.Methods. A total of 124 subjects were enrolled in this study, including 62 control subjects and 62 COPD patients. The pathological changes in airway tissues were assessed by different staining methods. The expression of sestrin2 and matrix metalloproteinase 9 (MMP9) in airway tissues was monitored by immunohistochemistry. Enzyme-linked immunosorbent assays (ELISAs) were used to detect the serum concentrations of sestrin2 and MMP9. The airway parameters on computed tomography (CT) from all participants were measured for evaluating airway remodeling. The relationship between serum sestrin2 and MMP9 concentration and airway parameters in chest CT was also analyzed. Results. In patients with COPD, staining of airway structures showed distinct pathological changes of remodeling, including cilia cluttered, subepithelial fibrosis, and reticular basement membrane (Rbm) fragmentation. Compared with control subjects, the expression of sestrin2 and MMP9 was significantly increased in both human airway tissues and serum. Typical imaging characteristics of airway remodeling and increased airway parameters were also found by chest CT. Additionally, serum sestrin2 concentration was positively correlated with serum MMP9 concentration and airway parameters in chest CT.Conclusion. Increased expression of sestrin2 is related to airway remodeling in COPD. We demonstrated for the first time that sestrin2 may be a novel biomarker for airway remodeling in patients with COPD.
Human Reproduction is Regulated by Retrotransposons derived from Ancient Hominin-Specific Viral Infections
Authors: Tao Yu , Xiang Xiinyu , Hsu Fei-Man , Pontis Julien , Trono Didier , Liu Wanlu , Clark Amander
Published: October 2020

Germ cells are essential to pass DNA from one generation to the next. In human reproduction, germ cell development begins with the specification of primordial germ cells (PGCs) and a failure to specify PGCs leads to human infertility. Recent studies have revealed that the transcription factor network required for PGC specification has diverged in mammals, and this has a significant impact on our understanding of human reproduction. Here, we evaluated the emerging epigenetic landscape during hPGC specification using a combination of in vivo and in vitro analysis of hPGCs/hPGC-like cells (hPGCLCs) and human embryonic stem cells (hESCs). Our data reveals that hominid restricted Transposable Elements (TEs) partly derived from ancient viruses are pre-bound by the transcription factors TFAP2C and NANOG in undifferentiated hESCs, become transcriptionally induced during PGC specification and undergo dynamic epigenetic reprogramming leading to increased chromatin accessibility, localized DNA demethylation and establishment of broad peaks of H3K27ac. Using KRAB mediated CRISPRi we show that blocking this remodeling has a significant impact on hPGC specification. In summary, our data reveals that human reproduction requires the establishment of an epigenetic landscape during hPGC specification driven by the acquisition of hominid-specific TEs that were derived from ancient viral infections that entered the hominid germline less than 5 million years ago.
Reversible formation of coordination bonds in Sn-based metal-organic frameworks for high-performance lithium storage
Authors: Liu Jingwei , Xie Daixi , Xu Xiufang , Jiang Luozhen , Si Rui , Shi Wei , Cheng Peng
Published: October 2020

Sn-based compounds with buffer matrixes possessing high theoretical capacity, low working voltage, and alleviation of the volume expansion of Sn are ideal materials for lithium storage. However, it is highly challenging to confine well-dispersed Sn within a lithium active matrix because low-melting-point Sn tends to agglomerate. Here, for the first time, we apply a metal-organic framework (MOF) chemistry between Sn-nodes and lithium active ligands to create two Sn-based MOFs comprising Sn2(dobdc) and Sn2(dobpdc) with extended ligands from H4dobdc (2,5-dioxido-1,4-benzenedicarboxylate acid) to H4dobpdc (4,4’-dioxidobiphenyl-3,3’-dicarboxylate acid) with molecule-level homodispersion of Sn in organic matrixes for lithium storage. The enhanced utilization of active sites and reaction kinetics are achieved by the isoreticular expansion of the organic linkers. The reversible formation of coordination bonds during lithium storage processes is first revealed by X-ray absorption fine structure characterization, providing an in-depth understanding of the lithium storage mechanism in coordination compounds.
Therapeutic Effects of Genetically Modified Wharton’s Jelly Mesenchymal Stem Cells Expressing Erythropoietin on Cancer-related Anemia in Mice Model
Authors: Estiri Mohammad , Estiri Bahareh , Fallah Asghar , Aghazadeh Marzyeh , Sedaqati Amir , Abdollahi Abbas , Rabienia Mahsa , Mortazavidehkordi Nahid , Farjadfar Akbar
Published: October 2020

BackgroundCancer-related anemia (CRA) negatively influences cancer patients’ survival, disease progression, treatment efficacy, and quality of life (QOL). Current treatments such as iron therapy, red cell transfusion, and erythropoietin-stimulating agents (ESAs) may cause severe adverse effects. Therefore, development of long-lasting and curative therapies is highly required. Combined cell and gene therapy platform can introduce a new route for permanent production of erythropoietin (EPO) in the body with various degrees of clinical benefits and avoiding the need for repeat treatments.MethodsIn this study, we developed cell and gene therapy strategy for in-vivo delivery of EPO cDNA via genetic engineering human Wharton’s jelly mesenchymal stem cells (hWJMSCs) to long-term produce and secret human EPO protein after transplantation into the mice model of CRA. To evaluate CRA's treatment in cancer-free and cancerous conditions, at first, we designed recombinant breast cancer cell line 4T1 expressing herpes simplex virus type 1 thymidine kinase (HSV1-TK) by a lentiviral vector encoding HSV1-TK and injected into mice. After 3 weeks, all mice develop the metastatic breast cancer associated to the acute anemia. Then, we administrated ganciclovir (GCV) for 10 days in half of the mice to clear cancer cells. Meanwhile, we designed another lentiviral vector encoding EPO to transduce hWJMSCs. Following implantation of rhWJMSCs-EPO, the whole peripheral blood samples were collected from the tail vein once per week which were immediately analyzed for the measurements of EPO, hemoglobin (Hb), and hematocrit (Hct) plasma levels. Results We found that after implantation of rhWJMSCs-EPO, plasma EPO, Hb, and Hct concentration significantly increased which rose to a peak in the fourth week and remained at a therapeutic level for >17 weeks in the cancer-free group and >10 weeks in the cancerous group.ConclusionOur data indicate that the EPO-transduced hWJMSCs could improve the anemia of cancer in both cancer-free and cancerous mice model. This significant difference in length of time that Hb and Hct are in therapeutic levels in both treatment groups indicates that developing a precise targeted-therapy to eliminate cancer cells along with an effective treatment for CRA, as we presented here, could bring important clinical benefits.
Quantifying the Effects of Post-surgery Recovery Time on the Migration Dynamics and Survival Rates in the Wild of Acoustically Tagged Atlantic Salmon Salmo Salar Smolts
Authors: Daniels Jason , Brunsdon Eric B. , Chaput Gerald , Dixon Heather , Labadie Holly , Carr Jonathan W.
Published: October 2020

Background: The experimental effects of surgically implanting fish with acoustic transmitters is likely to have negative effects on survival and behavior. Measuring the extent of these negative effects is important if we wish to extrapolate inferences from tagged animals to unmanipulated animals. In this study, we examine the effect of surgery and post-tagging recovery time on the survival and migration rate of acoustically tagged wild Atlantic Salmon (Salmo salar) smolts through freshwater, estuarine and ocean phases of migration. Four treatment groups were used: pre-smolt captured in the fall that overwintered in a hatchery and were tagged either 75 days prior to release (winter hatchery) or within 24 hours prior to release (spring hatchery) and smolt captured during the spring smolt run, tagged 24 hours prior to release and released during the day (day-released) or night (night-released).Results: The spring hatchery treatment group served as a reference treatment group such that surgical (comparison to winter hatchery treatment) and hatchery effects (comparison to day-released and night-released treatments) could both be discerned. The hatchery effect increased migration rate whereas short recovery times and captivity in a hatchery negatively affected survival. These effects were most pronounced within the first 5 days and/or 48 km downstream post-release, however, the residual surgical effects appeared to persist during the transition from the estuary into salt water.Conclusions: Even with smolts originating from the wild and spending relatively little time within the hatchery environment, post-release survival was still negatively affected. Migration speed was faster for hatchery smolts but is likely only due to their larger size. Surgical effects were most prominent during the initial migration period in freshwater and again in the transition from the estuary to saltwater which may be due to added stress during these transitional zones. As surgery related bias will likely never be completely removed from telemetry studies it is important to quantify and account for these effects in situ when making inferences on the unmanipulated component of the population.
The effects of Fe and NH4Cl on silicon nitridation
Authors: Yi X.M. , Zhang Senjing , Zhu Weijun , Li Qingda , Zhang Wenjie , Li Songze
Published: October 2020

Silicon nitride (Si3N4) with a high α-phase content is in demand due to its higher thermal conductivity for use in heat dissipation bases for electronic devices. However, more needs to be understood about its fibrous growth, therefore, rich fibrous morphologies were synthesized with the assistance of Fe powder and NH4Cl. The effects of these additives on the phase content and fiber morphologies of the products were investigated The results illustrate that the Si3N4 products possess upper and lower layers and that when the Fe powder content is 4 wt% and NH4Cl content is 5 wt%, the Si3N4 fibers have smooth surfaces, uniform diameters, and no floating particles. Moreover, the maximum α-Si3N4 content reached 94.8 wt%, demonstrating an increase in this phase. The double mechanisms of vapor-liquid-solid and vapor-solid are presented as the growth mechanism at the fiber.
Association of β-arrestin1 and p53-MDM2 signaling in the development of missed abortion
Authors: Liu Ting , Ma Yuyan , Yin Qihui , Zhou Huanyu , Fang Yan
Published: October 2020

BackgroundMissed abortion is a nonviable pregnancy before the 20th week of gestation with retained products of conception. The definite etiology and pathogenesis are not fully understood. β-arrestin1, the important dynamic multitask scaffold protein, it play an important regulatory role in interacting with G protein-coupled receptor (GPCR) to mediate its homologous desensitization and internalization. Recent studies have demonstrated that p53/Mdm2-mediated ubiquitination of the IGF-1R maybe closely related to G protein-coupled receptor kinases (GRK)/β-arrestin1 system. Our previous studies have confirmed that the elevated expression of p53 and Mdm2 may be responsible for apoptosis during missed abortion. However, there was no information surrounding β-arrestin1 in missed abortion.MethodsThe mRNA levels of β-arrestin1 in villous samples of 31 missed abortion patients and 31 healthy controls were determined by real-time quantitative PCR. Immunohistochemistry was used to explore the expression and location of β-arrestin1, p53, Mdm2, VEGF, HIF-lα in trophoblasts. We up-regulated and silenced the expression of β-arrestin1 by lentiviral transfection, transwell assays were performed to examine the influences of β-arrestin1 expression on cell invasion. Furthermore, we explored the expression of several important proteins which may be related to β-arrestin1.Resultsβ-arrestin1 mRNA levels in the villous samples from women with missed abortion were found to be dramatically lower than in women who had normal pregnancies. The immunohistochemistry results showed that β-arrestin1 positive staining was significantly lower in missed abortion group than that in normal pregnancies group. Furthermore, the patients with missed abortion showed significantly higher levels of p53, Mdm2 and HIF-lα, lower level of VEGF than healthy controls by immunohistochemistry. The protein expressions of p-ERK、p-AKT、p-p53 in HRT-8 cells were significantly downregulated by reducing β-arrestin1 expression, while the expression of p-NF-ΚB、p-Mdm2 were enhanced. Overexpression of β-arrestin1 exhibited the adverse effect. The loss expression of β-arrestin1 expression was significantly related with decreased cell invasion ability.ConclusionOur data indicated that β-arrestin1 could play an important role in maintaining the maternal-fetal tolerance, the decreased β-arrestin1 expression in the villous samples may be related to the development of missed abortion.
Widespread Mitochondrial DNA Methylation Drift Contributes to Postoperative Delirium in Young and Old Mice
Authors: Liu Yue , Yang Shuai , Zhang Wei , Yang Yan , Jiang Ming , Ma Zhengliang , Gu Xiaoping
Published: October 2020

Background: Mitochondrial dysfunction is linked to the etiopathogenesis of postoperative delirium (POD), which severely affects the prognosis of elderly patients undergoing surgery. The methylation of mitochondrial DNA (mtDNA), a new and incompletely described phenomenon that regulates the structure and function of mitochondria, is associated with aging. However, the relationship between mtDNA methylation and POD has not been established. Methods: 5-methylcytosine (5-mC) at 5 CpG sites of the displacement loop (D-loop) and at 60 CpG sites of coding gene loci in the mitochondrial genome after surgery of the hippocampus, prefrontal cortex, amygdala, and anterior cingulate cortex in 6- and 18-month-old mice were detected using bisulfite pyrosequencing. Mitochondrial structure, mitochondrial gene expression and mtDNA copy number were also examined using Electron microscopy and real time PCR to find the association with mtDNA methylationResults: The mtDNA methylation drift manifested as a decrease in the methylation levels at the D-loop and an increase or decrease in the methylation levels at several coding gene loci, ultimately resulting in reduced mtDNA copy numbers, altered mitochondrial gene expression, and damaged mitochondrial structures in the hippocampus and prefrontal cortex after surgery. The activation of Silent information regulator-1 (SIRT1) ameliorated anesthesia- and surgery-induced mitochondrial dysfunction and delirium-like behaviors by regulating mtDNA methyltransferase-mediated mtDNA methylation. Conclusions: These data support the existence of epigenetic mtDNA regulation in POD; however, further studies are required to explore the specific mechanisms.
The Aberrant Expression Levels of miR-423-5p and miR-664b-5p in Peripheral Blood of Patients With Familial and Sporadic Ovarian Carcinoma
Authors: KURT BUSRA , TUNCER Seref Bugra , ODEMIS Demet AKDENIZ , GHAFOUR Arash ADAMNEJAD , Sarali Mukaddes Avsar , KILIC Seda , Erdogan Ozge Sukruoglu , Celik Betul , Saip Pınar , Yazici Hulya
Published: October 2020

MicroRNAs (miRNAs), are endogenous noncoding single strand RNA molecules with approximate length of 22 nucleotides. Ovarian cancer is a heterogenous disease which includes different biologic behaviors in the clinical, and molecular level. miRNAs have roles in the early diagnosis, prognosis, and chemotherapy sensitivity for ovarian cancer, and in the regulation of reproduction by being expressed in the ovaries. The expression level of two miRNAs of miR-423-5p, and miR-664b-5p selected from the miRNAs which were detected to be important for the ovarian cancer etiology in our previous studies were investigated in the peripheral blood of familial and sporadic ovarian cancer patients, and in healthy individuals. The expression analyses were statistically evaluated with SPSS v21.0 program using the Quantitative Real-Time PCR technique. A statistically significant difference was detected for both miRNAs between the healthy controls and ovarian cancer patient groups (p:0.000). The miR-423-5p expression was detected to increase 2.35 fold, and miR-664b-5p was detected to increase 2.47 fold in ovarian cancer patients compared with the levels in the control group. miR-423-5p was reported to be overexpressed in various cancer types, and in different disease stages in previous study, and miR-423-5p was demonstrated to have increased in the lymphocytes in the peripheral circulation of ovarian cancer patients first in our literature. The miR-664b-5p expression level was detected in high levels in ovarian cancer patient group, however was detected to have decreased in 64% of ovarian cancer patients with BRCA mutation carrier. The expressions of both miRNA molecules were detected to have decreased in the ovarian cancer subgroups in patients with ovarian cancer with addition of a second primary cancer of endometrium cancer, however, were detected in the highest level in ovarian cancer patients in addition to another secondary cancer except breast and endometrium cancer. The results obtained from the study showed that the increased expression of both miRNA molecules were suggested to be associated with ovarian cancer, and decrease was suggested to be associated with endometrium cancer. In summary, the miRNA molecules in the present study might be the non-invasive biological indicator in ovarian cancer, and the demonstration of these molecules on the tumor tissue, and their change during treatment in future studies will be beneficial.
Exercise capacity, Cardiovascular- and Metabolic Risk of German Police officers in an international comparison
Authors: Strauß Markus , Foshag Peter , Jehn Ulrich , Vollenberg Richard , Littwitz Henning , Leischik Roman
Published: October 2020

Background: The police force has a mandate to protect citizens and enforce law for public safety. Employment in the police force is recognized as a dangerous occupation and characterized by job-related physical hazards. Therefore, good health and adequate physical condition are necessary. The aim of this study was to determine cardiovascular, cardiorespiratory and metabolic risk parameters of German police officer (POs) in comparison to POs from other nations. Methods: 55 male police officers from Germany participated in the survey. Anthropometric measurements, cardiovascular and metabolic risk factors and blood parameters were taken. 10-year cardiovascular risk was calculated by using the Framingham Risk Score. The diagnosis of metabolic syndrome was based on the criteria of the International Diabetes Federation. Cardiorespiratory status was assessed by exercise spirometry. Results: The analyzed group of POs demonstrated a high prevalence of preobesity (BMI: 28.0±3.2, waist circumference: 97.8±12.4 cm). 61.8 % of POs showed an increased waist circumference. POs shows elevated cholesterol and triglyceride values and high prevalence of abnormal systolic and diastolic blood pressure. 10-year cardiovascular system risk of examined POs were 9.6 ± 7.4 %. The cardiovascular risk profile of our examined German cohort seems to be in the higher range in comparison to international data. 32 % of POs in our study group were diagnosed with metabolic syndrome. Maximal relative oxygen uptake of POs was 34.1 ± 8.0 ml/kg-1 ·min-1. Conclusions: To our knowledge this study was one of the first to assess data on cardiovascular health, metabolic syndrome and cardiorespiratory status of police officers in Germany. The results of our study population demonstrated the high cardiovascular and metabolic risk of German police officers and displaying a decreased cardiorespiratory fitness. The present study results demonstrated the need for implementation of interventions and creating health-promoting concepts like corporate sports activities and nutrition courses to counteract cardiovascular and metabolic risk factors and the subsequent development of cardiovascular and metabolic disease in this occupational group.
The appearance and increase in the quantity and proportion of the clinical research coordinator's service fee in drug clinical trial research fund and its impact on trial quality
Authors: Chen Liran , Chen Zhimin , Chen Huafang
Published: October 2020

Objective: The changes of absolute value and relative value of clinical research coordinator service fee and its influence on the quality of drug clinical trial were analyzed.Methods: This study compared the amount and structural changes of drug clinical trial costs in before 3 years and after 3 years of self-examination and inspection initiated by the China Food and Drug Administration, identified the increase number and composition of each individual cost of a clinical trial research funds which including clinical research coordinator service fee, investigator labor fee, subjects examination fee, subjects traffic subsidy, documents management fee, drug management fee, etc.Result: The most significant appearance and increase in volume and proportion were the clinical research coordinator service fee. From the initial few to the global multicenter tumor drug clinical trials RMB31,624 or 34.92% of the proportion and domestic multicenter tumor drug clinical trials RMB16,500,accounted for 33.74%.Discussion: It has become common for more money to be spent on clinical trials to be accompanied by improved quality, but the occurrence and continuous increase of clinical research coordinator service fee were divided into two aspects, On the one hand, the quality of clinical trials was promoted by the large amount of low-skill trivial work undertaken by clinical research coordinator; on the other hand, the quality of clinical trials was undermined by the fact that clinical research coordinator did too much treatment evaluation work that should have been done by the investigator.
Dietary Dihydroartemisinin Supplementation Alleviates Intestinal Inflammatory Injury Through TLR4/NODs/NF-κB Signaling Pathway in Weaned Piglets with Intrauterine Growth Retardation
Authors: Niu Yu , Zhao Yongwei , He Jintian , Yun Yang , Shen Mingming , Gan Zhending , Zhang Lili , Wang Tian
Published: October 2020

Background: Intrauterine growth retardation (IUGR) leads to impaired intestinal morphology and function. IUGR infants are at a risk for intestinal inflammatory diseases. Dihydroartemisinin (DHA) is a derivative of artemisinin, which possesses anti-inflammatory activity and immunomodulatory effect. However, little is known about the effects of DHA on IUGR piglets. Therefore, the present study was conducted to investigate whether dietary DHA supplementation could attenuate intestinal injury in IUGR weaned piglets. Methods: Piglets with normal birth weight or IUGR were fed the basal diet or basal diet supplemented with 80 mg/kg DHA from 21 d to 49 days of age. At 49 days of age, eight piglets from each group with nearly similar body weight were sacrificed. The jejunal and ileal samples were collected for further analysis.Results: IUGR impaired intestinal morphology, increased intestinal inflammatory response, raised enterocyte apoptosis and reduced enterocyte proliferation and activated TLR4/NODs/NF-κB signaling pathway. DHA supplementation improved intestinal morphology, indicated by higher villus height, villus height to crypt depth ratio, villus surface area and lower villus width of IUGR piglets (P < 0.05). DHA inclusion exhibited higher apoptosis index and the expression of caspase-3, and lower proliferation index and the expression of proliferating cell nuclear antigen in the intestine of IUGR piglets (P < 0.05). Diet supplemented with DHA could attenuate intesitnal inflammation, indicated by higher concentrations of intestinal inflammatory cytokines and lipopolysaccharides in IUGR piglets (P < 0.05). In addition, DHA down-regulated the related mRNA expressions of TLR4/NODs/NF-κB signaling pathway and up-regulated mRNA expressions of TLR4 and NODs signaling negative regulators in the intestine of IUGR piglets (P < 0.05). Dietary DHA supplementation decreased the protein expressions of toll-like receptors 4, phosphorylated NF-κB (pNF-κB) inhibitor α, nuclear pNF-κB, and increased the protein expression of cytoplasmic pNF-κB in the intestine of IUGR piglets (P < 0.05). Conclusions: Dietary DHA supplementation may have beneficial effects in improving intestinal morphology, regulating enterocyte proliferation and apoptosis, and alleviating intestinal inflammation through TLR4/NODs/NF-κB signaling pathway in IUGR weaned piglets.
Deletion of an Enhancer in FGF5 is Associated With Ectopic Expression in Goat Hair Follicles and the Cashmere Growth Phenotype
Authors: Li Yefang , Song Shen , Liu Xuexue , Zhang Yanli , Wang Dandan , He Xiaohong , Zhao Qianjun , Pu Yabin , Guan Weijun , Ma Yuehui , Jiang Lin
Published: October 2020

BackgroundResearch on cashmere growth has a significant effect on the production of cashmere and a profound influence on cashmere goat breeding. Whole-genome sequencing is a powerful platform to rapidly gain novel insights into the identification of genetic mechanisms underlying cashmere fiber growth. ResultsIn this study, we generated whole-genome sequences of 115 domestic goats from China, Nepal and Pakistan, including 51 cashmere goats and 64 non-cashmere goats. We found genetically distinct clusters according to their geographic locations but genetic admixture or introgression may have occurred between the Chinese and Nepalese goats. We identified that the fibroblast growth factor 5 gene (FGF5) shows a strong signature for positive selection in the cashmere goat. The 505-bp indel variant at the FGF5 gene locus appeared to be strongly associated with cashmere growth. Functional validation showed that the insertion variant may serve as an enhancer for transcription factor binding, resulting in increased transcription of the upstream FGF5 gene in non-cashmere goats. ConclusionsOur study provides useful information for the sustainable utilization and improved conservation of goat genetic resources and demonstrates that the indel mutation in the FGF5 gene could potentially serve as a molecular marker of cashmere growth in cashmere goat breeding.
Association of Pericardial Adipose Tissue With Left Ventricular Structure and Function: A Region-specific Effect?
Authors: Kim Jin-Seok , Kim Seon Won , Lee Jong Seok , Lee Seung Ku , Abbott Robert , Lee Ki Yeol , Lim Hong Euy , Sung Ki-Chul , Cho Goo-Yeong , Koh Kwang Kon , Kim Sun H. , Shin Chol , Kim Seong Hwan
Published: October 2020

Background: The independent role of pericardial adipose tissue (PAT) as an ectopic fat associated with cardiovascular disease (CVD) remains controversial. This study aimed to determine whether PAT is associated with left ventricular (LV) structure and function independent of other markers of general obesity.Methods: We studied 2,471 participants (50.9% women) without known CVD from the Korean Genome Epidemiology Study, who underwent 2D-echocardiography with tissue Doppler imaging (TDI) and computed tomography measurement for PAT.Results: Study participants with more PAT were more likely to be men and had higher cardiometabolic indices, including blood pressure, glucose, and cholesterol levels (all P <0.001). Greater pericardial fat levels across quartiles of PAT were associated with increased LV mass index and left atrial volume index (all P <0.001) and decreased systolic (P = 0.015) and early diastolic (P <0.001) TDI velocities, except for LV ejection fraction. These associations remained after a multivariable-adjusted model for traditional CV risk factors and persisted after additional adjustment for general adiposity measures, such as waist circumference and body mass index. PAT was the only obesity index independently associated with systolic TDI velocity (P <0.001).Conclusions: PAT was associated with subclinical LV structural and functional changes, and these associations were independent of and stronger than with general and abdominal obesity measures.
Best Practices for Human Milk Collection for COVID-19 Research
Authors: McGuire Michelle K , Seppo Antti , Goga Ameena , Buonsenso Danilo , Collado Maria Carmen , Donovan Sharon M. , Muller Janis A. , Ofman Gaston , Monroy-Valle Michele , O'Connor Deborah L. , Pace Ryan M. , Perre Philippe Van de
Published: October 2020

In addition to providing life-giving nutrients and other substances to the breastfed infant, human milk can also represent a vehicle of pathogen transfer. As such, when an infectious disease outbreak, epidemic, or pandemic occurs – particularly when it is associated with a novel pathogen – the question will naturally arise as to whether the pathogen can be transmitted via breastfeeding. Until high-quality data are generated to answer this question, abandonment of breastfeeding due to uncertainty can result. The COVID-19 pandemic, which was in full swing at the time this document was written, is an excellent example of this scenario. During these times of uncertainty, it is critical for investigators conducting research to assess the possible transmission of pathogens via milk, whether by transfer through the mammary gland or contamination from respiratory droplets, skin, breast pumps, and milk containers, and/or close contact between mother and infant. To promote the most rigorous science, it is critical to outline optimal methods for milk collection, handling, storage, and analysis in these situations, and investigators should openly share their methods in published materials. Otherwise, the risks of inconsistent test results from pre-analytical and analytical variation, false positives, and false negatives are unacceptably high and the ability to provide public health guidance poor. Here we provide “best practices” for collecting human milk samples for COVID-19 research with the intention that this will also be a useful guide for future pandemics.
Association Between Pyrethrum Knockdown Time and Sodium Channel Genotypes in California Aedes Aegypti
Authors: Mack Lindsey K , Kelly Erin Taylor , Lee Yoosook , Brisco Katherine K , Shen Kaiyuan Victoria , Zahid Aamina , Schoor Tess van , Cornel Anthony J. , Attardo Geoffrey M
Published: October 2020

Background: Since their detection in 2013, Aedes aegypti has become a widespread urban pest in California. The availability of cryptic larval breeding sites in residential areas and resistance to insecticides pose significant challenges to control efforts. Resistance to pyrethroids is largely attributed to mutations in the voltage gated sodium channels (VGSC), the pyrethroid site of action. However, past studies have indicated that VGSC mutations may not be entirely predictive of the observed resistance phenotype. Methods: To investigate the frequencies of VGSC mutations and the relationship with pyrethroid insecticide resistance in California, we sampled Ae. aegypti from four locations in the Central Valley, and the Greater Los Angeles area. Mosquitoes from each location were subjected to an individual pyrethrum bottle bioassay to determine knockdown times. A subset of assayed mosquitoes from each location was then analyzed to determine the composition of 8 single nucleotide polymorphism (SNP) loci within the VGSC gene. Results: The distribution of knockdown times for each of the five Californian populations sampled was non-parametric with bimodal distributions. One group succumbs to insecticidal effects around 35-45 minutes and the second group lasts up to and beyond the termination of the assay (120+ minutes). We detected 5 SNPs polymorphic within California populations. One is potentially new and alternatively spliced (I915K), and four are known and associated with resistance: F1534C, V1016I, V410L and S723T. The Central Valley populations (Clovis, Dinuba, Sanger and Kingsburg) are fairly homogenous with only 5% of the mosquitoes showing heterozygosity at any given position. In the Greater LA mosquitoes 55% had at least one susceptible allele at any of the five SNPs. The known resistance allele F1534C was detected in almost all sampled mosquitoes (99.4%). We observe significant heterogeneity in individuals with the same genotypes, confirming that the resistance SNPs alone cannot. Conclusions: Resistance associated VGSC SNPs are prevalent, particularly in the Central Valley. Interestingly, among mosquitoes with all 4 resistance associated SNPs, we observe heterogeneity in bottle bioassay profiles suggesting that other mechanisms are important to the individual resistance of Ae. aegypti in California.
The Effectiveness of Synchronous Online Flipped Learning in College EFL Reading Course During the COVID-19 Epidemic
Authors: Ma Guihua
Published: October 2020

The purpose of this study was to examine the effectiveness of synchronous online flipped learning (SOFL) when no one can go to school and merely rely on online learning during the COVID-19 epidemic. According to community of inquiry (CoI), put forward by Garrison et al (2001), only when the three key elements of blended teaching, social presence, teaching presence and cognitive presence reach a high level, can effective learning occur, which were used as the framework of this study. Mixed methods were used to evaluate the effectiveness of SOFL teaching. A total of 60 undergraduates from pre-service English teacher training program participated in an online questionnaire survey and 25 of them voluntarily joined online in-depth interviews. Results showed that the learning effect was improved in SOFL context. Anonymity was found to improve learning in asynchronous online learning while distraction and lack of sustainable attention were found in synchronous online learning session. The findings suggest that instructors may need to have a careful design, strict organization and scientific implementation of synchronous online teaching and learning in order to achieve distinctive teaching effects, and that they may also consider the complex influence factors of synchronous and asynchronous online learning to arouse students’ interest and attention, and meet their learning needs (Wong 2020).
How informative are web searches for risk communication during COVID-19 in Germany?
Authors: Kristensen Kaja , Lorenz Eva , May Jürgen , Strauss Ricardo
Published: October 2020

Background: Risk communication during pandemics is an element of paramount importance. Understanding the level of public concern implicates expensive and time-consuming surveys. We hypothesize that the relative search volume from Google Trends could be used as an indicator of public concern towards prevention measures as well as of the adequacy of the official messages spread. Methods: The search terms ‘RKI’, ‘corona’ and ‘protective mask’ in German language were shortlisted. Cross-correlations between these terms and the reported cases from February 15th to April 27th were conducted for each German federal state. The findings were contrasted against a timeline of official communications concerning COVID-19.Results: The highest correlations of the term ‘RKI’ (Robert Koch Institute, national public health authority in Germany) with reported COVID-19 cases were found between lags of -2 and -12 days, meaning web searches were already performed two to twelve days before case numbers increased. A similar pattern was seen for the term ‘corona’. Cross-correlations indicated that most searches on ‘protective mask’ were performed six to twelve days after the increase of cases. Conclusions: The results for the term ‘protective mask’ indicate some degree of confusion in the population, which is supported by the contradictory recommendations on the wearing of face masks over time. In addition, the relative search volumes could be a useful tool to provide timely information on location-based risk communication strategies.
Clinical characteristics and outcomes of adult patients hospitalized with influenza, respiratory syncytial virus and human metapneumovirus infections: a prospective, cohort study
Authors: Chen Liang , Han Xiudi , Bai Lu , Zhang Jian
Published: October 2020

Background Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza virus infections cause countless adult hospitalizations each year, yet the clinical characteristics and outcomes of RSV and hMPV infections in adults remain poorly understood. This study was thus designed to compare the clinical findings and severity between adult patients hospitalized with RSV/hMPV infections relative to those hospitalized with influenza.Methods This study prospectively enrolled 594 patients that had been hospitalized with influenza-like illness and laboratory confirmed RSV, hMPV, or influenza viral infections over the course of three consecutive influenza seasons at a tertiary hospital in China. In order to identify clinical features associated with these three viral infections and with disease severity, univariate and multivariate logistic regression analyses were conducted. Results Myalgia and lymphocyte counts < 0.8×109/L were positively correlated with the incidence of influenza infection, whereas age ≥ 65 years, nasal congestion, dyspnea, and the presence of solid malignant tumors were positively associated with RSV or hMPV infections. However, none of these variables exhibited good predictive performance as a means of discriminating among patients infected with these three different viruses (AUC < 0.70). After controlling for potential confounding variables, RSV infections in pneumonia patients were associated with a comparable 30-day mortality risk [odds ratio (OR) 1.016, 95% confidence interval (CI) 0.267-3.856, p = 0.982], whereas hMPV infection was associated with a reduced risk of mortality (OR 0.144, 95% CI 0.027-0.780, p = 0.025). In patients without pneumonia, however, 30-day mortality risk in patients infected with influenza virus was comparable to that in patients infected with RSV (OR 1.268, 95% CI 0.172-9.355, p = 0.816) or hMPV (OR 1.128, 95% CI 0.122-10.419, p = 0.916). Conclusions Clinical features of influenza, RSV, and hMPV infections are helpful , but not sufficiently distinct to permit discrimination among these three different infection types, and specific pathogenic testing is thus necessary to understand the etiological basis for disease in patients with influenza-like illness. In addition, disease severity associated with these three types of viral infection was inconsistent when comparing patients with and without pneumonia.
Neuropsychiatric Adverse Events During 12 Months of Treatment with Efavirenz in a Treatment-Naïve HIV-Infected Population in China: A Prospective Cohort Study
Authors: Dai Lili , Wang Sen , Shao Ying , Wang Yali , Ye Jiangzhu , Su Bin , Jiang Taiyi , Zhang Tong , Wu Hao , Liu An , Hua Wei , Mahajan Supriya Dinkar , Li Zaicun , Sun Lijun
Published: October 2020

Background: Efavirenz (EFV) is a widely used antiretroviral therapy (ART), but side effect risks of neuropsychiatric adverse events (NPAEs) have not been investigated in Chinese populations receiving rapid ART. Methods: This prospective cohort study assessed HIV-infected patients initiating antiretroviral treatment with EFV to determine prevalence of and factors associated with NPAEs over a 12-month follow-up period using the Hospital Anxiety and Depression Scale (HADS) and the Pittsburgh Sleep Quality Index (PSQI). Results: A total of 546 patients were enrolled. Prevalence of anxiety, depression, and sleep disturbances at baseline were 30.4%, 22.7%, and 68.1%, respectively. Six patients discontinued treatment due to drug related NPAEs. Treatment was associated with improvements in HADS-A, HADS-D, and PSQI scores over the 12-month follow-up, and the frequencies of patients with anxiety, depression, and sleep disturbances significantly decreased after 12 months. Abnormal baseline HADS-A, HADS-D, and PSQI scores and other factors, including high school education or lower, unemployment, divorce, and WHO III/IV stages, were associated with severe neuropsychiatric disorders over the 12 months. Conclusions: These findings suggested EFV-based first-line antiretroviral therapy was well-tolerated and associated with improvements in HADS-A, HADS-D, and PSQI scores. Certain risk factors associated with neuropsychiatric disorders may be useful in identifying HIV-infected patients at higher NPAE risk.