bluuebunny/crossref_metadata_2025 huggingface dataset:
The Diagnostic Accuracy of Direct Agglutination Test for Serodiagnosis of Human Visceral Leishmaniasis: A Systematic Review with Meta-analysis
Authors: Mohebali Mehdi , Keshavarz Hossein , Shirmohammad Sedigheh , Akhoundi Behnaz , Borjian Alireza , Hassanpour Gholamreza , Mamishi Setareh , Mahmoudi Shima
Published: October 2020

Background: Direct agglutination test (DAT) as simple, accurate and non-expensive tool that has been used widely for serodiagnosis of visceral leishmaniasis (VL) during the last three decades. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of DAT for serodiagnosis of human VL. Methods: Electronic databases, including MEDLINE (via PubMed), SCOPUS, Web of Science, SID and Mag Iran (two Persian scientific search engines) were searched from December 2004 to April 2019. The study quality was evaluated using the QUADAS checklist. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic(ROC) curves parameters. Results: Of the 2928 records identified in the mentioned electronic databases and through articles’ reference lists, 25 articles met inclusion criteria and enrolled into the systematic review and among them 22 records were qualified for meta-analysis. The pooled sensitivity and specificity of DAT was 96% [(95% CI, 93–98])and 95% [(95% CI, 88–98]), respectively. The likelihood ratio of a positive test (LR+) was found to be 19.8 [CI95%, 7.6–51.8] and the likelihood ratio of a negative test (LR−) was found to be 0.04 [CI95%, 0.02–0.08]. The combined estimate of the diagnostic odds ratio for DAT was high [454)136-1561]) ].We found that the summary receiver operating characteristic curve (SROC) is positioned near the upper left corner of the curve and the area under curve (AUC) was 0.98 (95% CI, 0.97 to 0.99). Conclusion: Based on our analysis, we find DAT can be considered as valuable tool for the serodiagnosis and seroprevalence of human VL with high sensitivity and specificityrates. As DAT is simple, accurate, non-invasive and efficient serological test, it can be used for serodiagnosis of human VL particularly in endemic areas of the disease.
Going web or staying paper? The use of web-surveys among older people
Authors: Kelfve Susanne , Kivi Marie , Johansson Boo , Lindwall Magnus
Published: October 2020

Background: Web-surveys are increasingly used in population studies. Yet, web-surveys targeting older individuals are still uncommon for various reasons. However, with younger cohorts approaching older age, the potentials for web-surveys among older people might be improved. In this study, we investigated response patterns in a web-survey targeting older adults and the potential importance of offering a paper questionnaire as an alternative to the web questionnaire. Methods: We analyzed data from three waves of a retirement study, in which a web-push methodology was used and a paper questionnaire was offered as an alternative to the web questionnaire in the last reminder. We mapped the response patterns, compared web- and paper respondents and compared different key outcomes resulting from the sample with and without the paper respondents, both at baseline and after two follow-ups.Results: Paper-respondents, that is, those that did not answer until they got a paper questionnaire with the last reminder, were more likely to be female, retired, single, and to report a lower level of education, higher levels of depression and lower self-reported health, compared to web-respondents. The association between retirement status and depression was only present among web-respondents. The differences between web and paper respondents were stronger in the longitudinal sample (after two follow-ups) than at baseline.Conclusions: We conclude that a web-survey might be a feasible and good alternative in surveys targeting people in the retirement age range. However, without offering a paper questionnaire, a small but important group will likely be missing with potential biased estimates as the result.
Comparative transcriptome analysis of genes involved in the drought stress response of two peanut (Arachis hypogaea L.) varieties
Authors: Jiang Chunji , Li Xinlin , Zou Jixiang , Ren Jingyao , Jin Chunyi , Zhang He , Yu Haiqiu , Jin Hua
Published: October 2020

Background: The peanut is one of the most important oil crops worldwide. Qualities and yields of peanut can be dramatically diminished by abiotic stresses particularly by drought. Therefore, it would be beneficial to gain a comprehensive understanding on peanut drought-responsive transcriptional regulatory activities, and hopefully to extract critical drought-tolerance-related molecular mechanism from it. Results: In this study, two peanut Arachis hypogaea L. varieties, NH5 (tolerant) and FH18 (sensitive), which show significantly differential drought tolerance, were screened from 23 main commercial peanut cultivars and used for physiological characterization and transcriptomic analysis. NH5 leaves showed higher water and GSH contents, faster stomatal closure, and lower relative conductivity (REC) than FH18. Under the time-course of drought-treatments 0 h (CK), 4 h (DT1), 8 h (DT2) and 24 h (DT3), the number of down-regulated differential expressed genes (DEGs) increased with the progression of treatments indicating repressive impacts on transcriptomes by drought in both peanut varieties. Conclusions: Nevertheless, NH5 maintained more stable transcriptomic dynamics than FH18. Furthermore, annotations of identified DEGs implicate signal transduction, the elimination of reactive oxygen species, and the maintenance of cell osmotic potential which are key drought-tolerance-related pathways. Finally, evidences from the examination of ABA and SA components suggested that the fast stomatal closure in NH5 was likely mediated through SA rather than ABA signaling. In all, these results have provided us a comprehensive overview of peanut drought-responsive transcriptomic changes, which could serve as solid foundation for further identification of the molecular drought-tolerance mechanism in peanut and other oil crops.
Identifying competing interest disclosure in systematic reviews of surgical interventions and devices: a cross-sectional survey
Authors: Yu Jiajie , Su Guanyue , Hirst Allison , Yang Zengyue , Zhang You , Li Youping
Published: October 2020

Background: Competing interest is an important source of bias in research and disclosure is frequently employed as a strategy to manage it. Considering the importance of systematic reviews (SRs) and the varying prevalence of competing interest in different research fields, we conducted a survey to identify the range of competing interest in SRs assessing surgical intervention or devices and explored the association between competing interest disclosure and authors’ conclusion. Methods: We retrieved SRs of surgical interventions and devices published in 2017 via PubMed. Information regarding general characteristics, funding source, and competing interest disclosure were extracted. We conducted a descriptive analysis of the studies’ characteristics and compared them between Cochrane SRs (CSRs)and non-Cochrane SRs using the Chi-square test. Results were expressed as odds ratio and their 95% confidence interval. Results: 155 SRs published in 2017 were included in the study. More than half of the SRs (58.7%) reported their funding source and 94.2% reported authors’ competing interest disclosure. Among 146 SRs that stated competing interest disclosures, only 35 (22.6%) SRs declared at least one author had a competing interest. More than 40 terms were used to describe competing interests. Cochrane SRs (CSRs) were more likely to provide a detailed description of competing interest compared to those in non-CSRs (48.0% versus 25.4%, P=0,023). No association between a positive conclusion and competing interest disclosure was found (P=0.484, OR=0.43, 95%CI: 0.08, 2.16). In the subgroup analyses, SRs stating no competing interest disclosure were more likely to report positive conclusion than those stating at least one type of competing interest, but the difference is not significantly different (P=0.406, OR=1.38, 95%CI: 0.64, 2.98) Conclusion: In surgical SRs, there is a high percentage of competing interest disclosure but without detailed information. The identification and statement of competing interests with a detailed description, particularly the non-financial ones, needs improvement. Some efficient and effective methods/tools for identifying, quantifying, and minimizing potential competing interest in systematic reviews remains valuable.
WRN modulates translation by influencing nuclear mRNA export in HeLa cancer cells
Authors: Iglesias-Pedraz Juan Manuel , Jara Diego Matia Fossatti , Felice Valeria Del Carmen Valle-Riestra , Visalaya Sergio Rafael Cruz , Felix Jose Antonio Ayala , Comai Lucio
Published: October 2020

BackgroundThe Werner syndrome protein (WRN) belongs to the RecQ family of helicases and its loss of function results in the premature aging disease Werner syndrome (WS). We previously demonstrated that an early cellular change induced by WRN depletion is a posttranscriptional decrease in the levels of enzymes involved in metabolic pathways that control macromolecular synthesis and protect from oxidative stress. This metabolic shift is tolerated by normal cells but causes mitochondria dysfunction and acute oxidative stress in rapidly growing cancer cells, thereby suppressing their proliferation.ResultsTo identify the mechanism underlying this metabolic shift, we examined global protein synthesis and mRNA nucleocytoplasmic distribution after WRN knockdown. We determined that WRN depletion in HeLa cells attenuates global protein synthesis without affecting the level of key components of the mRNA export machinery. We further observed that WRN depletion affects the nuclear export of mRNAs and demonstrated that WRN interacts with mRNA and the Nuclear RNA Export Factor 1 (NXF1).ConclusionsOur findings suggest that WRN influences the export of mRNAs from the nucleus through its interaction with the NXF1 export receptor thereby affecting cellular proteostasis. In summary, we identified a new partner and a novel function of WRN, which is especially important for the proliferation of cancer cells.
Pharmacological intervention to restore connectivity deficits of neuronal networks derived from ASD patient iPSCs with a TSC2 mutation
Authors: Alsaqati Mouhamed , Heine Vivi M , Harwood Adrian J.
Published: October 2020

Background Tuberous sclerosis complex (TSC) is a rare genetic multisystemic disorder resulting from autosomal dominant mutations in the TSC1 or TSC2 genes. It is characterised by hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway and has severe neurodevelopmental and neurological components including autism, intellectual disability and epilepsy. In human and rodent models, loss of the TSC proteins causes neuronal hyperexcitability and synaptic dysfunction, although the consequences of these changes for the developing central nervous system is currently unclear.Methods Here we apply Multi-electrode array (MEA)-based assays to study the effects of TSC2 loss on neuronal network activity using Autism Spectrum Disorder (ASD) patient-derived iPSCs. We examine both temporal synchronisation of neuronal bursting, and spatial connectivity between electrodes across the network. Results We find that ASD patient-derived neurons with a functional loss of TSC2, in addition to possessing neuronal hyperactivity, develop a dysfunctional neuronal network with reduced synchronisation of neuronal bursting and lower spatial connectivity. These deficits of network function are associated with elevated expression of genes for inhibitory GABA signalling and glutamate signalling, indicating a potential abnormality of synaptic inhibitory-excitatory signalling. mTORC1 activity functions within a homeostatic triad of protein kinases, mTOR, AMP-dependent protein Kinase 1 (AMPK), and Unc-51 like Autophagy Activating Kinase 1 (ULK1) that orchestrate the interplay of anabolic cell growth and catabolic autophagy while balancing energy and nutrient homeostasis. The mTOR inhibitor rapamycin suppresses neuronal hyperactivity, but does not increase synchronised network activity, whereas activation of AMPK restores some aspects of network activity. In contrast, the ULK1 activator, LYN-1604 increases the network behaviour, shortens the network burst lengths, and reduces the number of uncorrelated spikes.Limitations Although a robust and consistent phenotype is observed across multiple independent iPSC cultures, the results are based on one patient. There may be more subtle differences between patients with different TSC2 mutations or differences of polygenic background within their genomes. This may affect the severity of the network deficit or the pharmacological response between TSC2 patients.Conclusions Our observations suggest that there is a reduction in the network connectivity of the in vitro neuronal network associated with ASD patients with TSC2 mutation, which may arise via an excitatory/inhibitory imbalance due to increased GABA-signalling at inhibitory synapses. This abnormality can be effectively suppressed via activation of ULK1.
Genomic Regions Associated with Important Seed Quality Traits in Food-grade Soybeans
Authors: Whiting Rachel M. , Torabi Sepideh , Lukens Lewis , Eskandari Mehrzad
Published: October 2020

Background: The production of soy-based food products requires specific physical and chemical characteristics of the soybean seed. Identification of quantitative trait loci (QTL) associated with value-added traits, such as seed weight, seed protein and sucrose concentration, could accelerate the development of competitive high-protein soybean cultivars for the food-grade market through marker-assisted selection (MAS). The objectives of this study were to identify and validate QTL associated with these value-added traits in two high-protein recombinant inbred line (RIL) populations.Results: The RIL populations were derived from the high-protein cultivar ‘AC X790P’ (49% protein, dry weight basis), and two high-yielding commercial cultivars, ‘S18-R6’ (41% protein) and ‘S23-T5’ (42% protein). Fourteen large-effect QTL (R2 >10%) were identified associated with seed protein concentration. Of these QTL, seven QTL were detected in both populations, and eight of them were co-localized with QTL associated with either seed sucrose concentration or seed weight. None of the protein-related QTL was found to be associated with seed yield in either population. Sixteen candidate genes with putative roles in protein metabolism were identified within seven of these protein-related regions: qPro_Gm02-3, qPro_Gm04-4, qPro_Gm06-1, qPro_Gm06-3, qPro_Gm06-6, qPro_Gm13-4 and qPro-Gm15-3.Conclusion: The use of RIL populations derived from high-protein parents created an opportunity to identify four novel QTL that may have been masked by large-effect QTL segregating in populations developed from diverse parental cultivars. In total, we have identified nine protein QTL that were detected either in both populations in the current study or reported in other studies. These QTL may be useful in the curated selection of new soybean cultivars for optimized soy-based food products.
Superparamagnetic iron oxide nanoparticles conjugated with Aβ oligomer-specific scFv antibody and class A scavenger receptor activator show therapeutic potentials for Alzheimer’s Disease
Authors: Liu Xiao-ge , Zhang Lun , Lu Shuai , Liu Dong-qun , Huang Ya-ru , Zhu Jie , Zhou Wei-wei , Yu Xiao-lin , Liu Rui-tian
Published: October 2020

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. No disease-modifying strategy to prevent or delay AD progression currently exists. Aβ oligomers (AβOs), rather than monomers or fibrils, are considered as the primary neurotoxic species. Therapeutic approaches that direct against AβOs and promote Aβ clearance may have great value for AD treatment. Results: We here reported a multifunctional superparamagnetic iron oxide nanoparticle conjugated with oligomer-specific scFv antibody W20 and class A scavenger receptor activator XD4 (W20/XD4-SPIONs). Besides the diagnostic value, W20/XD4-SPIONs retained the anti-Aβ properties of W20 and XD4 by inhibiting Aβ aggregation, attenuating AβO-induced cytotoxicity and increasing microglial phagocytosis of Aβ. When applied to APP/PS1 mice, W20/XD4-SPIONs significantly rescued cognitive deficits and alleviated neuropathology of AD mice. Conclusion: These results suggest that W20/XD4-SPIONs show therapeutic benefits for AD. In combination with the early diagnostic property, W20/XD4-SPIONs present as a promising agent for early-stage AD diagnosis and intervention.
Exosomes containing miRNAs targeting HER2 synthesis and engineered to adhere to HER2 on tumor cells surface exhibit enhanced antitumor activity
Authors: Wang Lei , Zhou Xusha , Zou Weixuan , Wu Yinglin , Zhao Jing , Chen Xiaoqing , Zhou Grace Guoying
Published: October 2020

Background: Exosomes are small, cellular membrane-derived vesicles with a diameter of 50-150 nm. Exosomes are considered ideal drug delivery systems with a wide range of applications in various diseases, including cancer. However, nonspecific delivery of therapeutic agents by exosomes in vivo remains challenging. Human epidermal growth factor receptor 2 (HER2) is an epidermal growth factor receptor tyrosine kinase, and its overexpression is usually associated with cell survival and tumor progression in various cancers. In this study, we aim to develop novel exosomes with dual HER2-targeting ability as a nanoparticle delivery vehicle to enhance antitumor efficacy in vivo.Results: Here, we report the generation of two kinds of exosomes carrying miRNAs designed to block HER2 synthesis, which consequently showed a distinct anti-tumor effect. The 293-miR-HER2 exosomes package and deliver miRNAs targeting HER2 to recipient cells to block HER2 synthesis. The anti-tumor effect of these exosomes on cancer cells dependent on HER2 for survival but do not affect cells that lack HER2 or that are engineered to express HER2 but are not dependent on it for survival. In contrast, 293-miR-XS-HER2 exosomes carry an additional peptide, which enables them to adhere to HER2 on the surface of cancer cells. Consequently, these exosomes preferentially enter these cells with surface expression of HER2 and further displayed a tumoricidal effect. The 293-miR-XS-HER2 exosomes are significantly more effective than the 293-miR-HER2 exosomes in shrinking HER2-positive tumors implanted in mice.Conclusions: Collectively, as novel antitumor drug delivery vehicles, HER2 dual-targeting exosomes exhibit increased target-specific delivery efficiency and can be further utilized to develop new nanoparticle-based targeted therapies.
Serum heme oxygenase-1 measurement is useful for evaluating disease activity and outcomes in patients with acute respiratory distress syndrome and acute exacerbation of interstitial lung disease
Authors: Nagasawa Ryo , Hara Yu , Murohashi Kota , Aoki Ayako , Kobayashi Nobuaki , Takagi Shigeto , Hashimoto Satoru , Kawana Akihito , Kaneko Takeshi
Published: October 2020

Background: Oxidative stress plays an important role in acute lung injury, which is associated with the development and progression of acute respiratory failure. Here, we investigated whether the degree of oxidative stress as indicated by serum heme oxygenase-1 (HO-1) is clinically useful for predicting prognosis among the patients with acute respiratory distress syndrome (ARDS) and acute exacerbation of interstitial lung disease (AE-ILDs).Methods: Serum HO-1 levels of newly diagnosed or untreated ARDS and AE-ILD patients were measured at diagnosis. Relationships between serum HO-1 and other clinical parameters and 1 and 3-month mortality were evaluated. Results: Fifty-five patients including 22 of ARDS and 33 of AE-ILD were assessed. Serum HO-1 level at diagnosis was significantly higher in ARDS patients than AE-ILD patients (87.8 ± 60.0 ng/mL vs. 52.5 ± 36.3 ng/mL, P < 0.001). Serum HO-1 correlated with serum total bilirubin (R = 0.454, P < 0.001) and serum LDH (R = 0.500, P < 0.001). In both patients with ARDS and AE-ILDs, serum HO-1 level tended to decrease from diagnosis to 2 weeks after diagnosis, however, did not normalized. Composite parameters including serum HO-1, age, sex, and partial pressure of oxygen in arterial blood/fraction of inspired oxygen (P/F) ratio for prediction of 3-month mortality showed a higher AUC (ARDS: 0.925, AE-ILDs: 0.892) than did AUCs of a single predictor or combination of two or three predictors. Conclusion: Oxidative stress assessed by serum HO-1 is persistently high among enrolled patients for 2 weeks after diagnosis. Also, serum HO-1 levels at the diagnosis combined with age, sex, and P/F ratio could be clinically useful for predicting 3-month mortality in both ARDS and AE-ILD patients.
Quantitative Sonographic Assessment of Quadriceps Muscle Thickness for Prospective Fall Injury in Patients Undergoing Maintenance Hemodialysis: an Observational Cohort Study
Authors: Sai Asuka , Tanaka Kentaro , Ohashi Yasushi , Kushiyama Akifumi , Tanaka Yoshihide , Motonishi Shuta , Sakai Ken , Hara Shigeko , Ozawa Takashi
Published: October 2020

Introduction: Accidental fall risk is high in patients undergoing maintenance hemodialysis. Falls are associated with fatal injury, comorbidities, and mortality. Risk assessment should be conducted as a primary intervention to prevent falls. This study investigated whether quadriceps muscle thickness measured using ultrasonography can prospectively predict fall injury among dialysis patients.Methods: Using an observational cohort study design, 180 ambulatory hemodialysis patients during the period 2015–2016 were recruited in the four dialysis clinics. The sum of the maximum quadriceps muscle thickness on both sides and the average of the maximum thigh circumference and handgrip strength after hemodialysis were calculated. Patients were stratified according to tertiles of quadriceps muscle thickness. Fall injury was surveyed according to the patient’s self-report for the one-year period.Results: Among the 180 hemodialysis patients, 42 (23.3%) had fall injury during the 12-month follow-up period. When the quadriceps muscle thickness levels were stratified into sex-specific tertile, patients in the lowest tertile (men <3.66 cm and women <3.50 cm) were more likely to have higher incidence of fall injury compared with those in the higher two tertiles (0.56 vs. 0.18 and 0.15 fall injuries/person-year). After adjusting for covariates, lower quadriceps muscle thickness was found to be an independent predictor for fall injury (hazard ratio [95% confidence interval], 2.99 [1.46–6.32], P < 0.001). Conversely, no significant differences were found in the thigh circumference and handgrip strength between women with fall injury and those women without fall injury.Conclusions: Quadriceps muscle thickness using ultrasonography can be measured easily at the bedside and is a precise predictor of fall injury in patients undergoing maintenance hemodialysis.
Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line
Authors: López-Carrasco Amparo , Martín-Vañó Susana , Burgos-Panadero Rebeca , Monferrer Ezequiel , Berbegall Ana P , Fernández-Blanco Beatriz , Navarro Samuel , Noguera Rosa
Published: October 2020

Background: Increased tissue stiffness is a common feature of malignant solid tumors, often associated with metastasis and poor patient outcomes. Vitronectin, as an extracellular matrix anchorage glycoprotein related to a stiff matrix, is present in a particularly increased quantity and specific distribution in high-risk neuroblastoma. Furthermore, as cells can sense and transform the proprieties of the extracellular matrix into chemical signals through mechanotransduction, genotypic changes related to stiffness are possible.Methods: We applied high density SNPa and NGS techniques to in vivo and in vitro models (orthotropic xenograft vitronectin knock-out mice and 3D bioprinted hydrogels with different stiffness) using two representative neuroblastoma cell lines (the MYCN-amplified SK-N-BE(2) and the ALK -mutated SH-SY5Y), to discern how tumor genomics patterns and clonal heterogeneity of the two cell lines are affected. Results: We describe a remarkable subclonal selection of genomic aberrations in SK-N-BE(2) cells grown in knock-out vitronectin xenograft mice that also emerged when cultured for long times in stiff hydrogels. In particular, we detected an enlarged subclonal cell population with chromosome 9 aberrations in both models. Similar abnormalities were found in human high-risk neuroblastoma with MYCN amplification. The genomics of the SH-SY5Y cell line remained stable when cultured in both models. Conclusions: Focus on heterogeneous intratumor segmental chromosome aberrations and mutations, as a mirror image of tumor microenvironment, is a vital area of future research.
Cytotype Distribution and Chloroplast Phylogeography of Actinidia Chinensis Complex
Authors: Wang Zhi , Zhong Caihong , Li Dawei , Yan Chunlin , Yao Xiaohong , Li Zuozhou
Published: October 2020

Background: Previous plant phylogeography in subtropical China mostly focused on rare and endangered species, whereas few studies conducted on the taxa with relatively wide distribution, especially for polyploid species. We used Actinidia chinensis complex, a widespread geographically woody liana of variable ploidy in subtropical China, to investigate its cytotype and haplotype distribution pattern based on three chloroplast fragments (ndhF-rpl132, ps16-trnQ and trnE-trnT). Macroevolutionary, microevolutionary and niche modeling tools were also combined to disentangle the origin and the demographic history of the species or cytotypes. Results: The ploidy levels of 3569 individuals from 128 populations sampled throughout the species distribution range were estimated using flow cytometry. The widespread cytotypes were diploids followed by tetraploids and hexaploids, while triploids and octaploids occasionally occurred in a few populations. Thirty-one chloroplast haplotypes were detected and the genetic diversity and genetic structure were great differences between the var. chinensis and var. deliciosa. Our results also revealed these two varieties (or ploidy races) inhabit significantly different climatic niche spaces. Ecological niche models (ENMs) indicate that all varieties’ ranges contracted during the Last Interglacial (LIG), and expanded eastward or northward during the Last Glacial Maximum (LGM). Conclusions: Pliocene and Plio-Pleistocene climatic fluctuations and vicariance may have played key roles in shaping the current population structure and historical demography in the A. chinensis complex. The polyploidization process also played an important role in the historical demography of the A. chinensis complex through improving their adaptability to environmental changes.
Combined effects of low-dose gambogic acid and NaI131 in drug-resistant non-small-cell lung cancer cells
Authors: Huang Jing , Ding Ming , Wu Ying , Han Shuhua , Xie Yan , Yang Sufang , Zhu Xiaoli , Chen Pingsheng
Published: October 2020

Background

Radioactive seed is a method for treating drug-resistant, late-stage non-small cell lung cancer (NSCLC), but has undesirable side effects. Gambogic acid (GA), an ingredient of traditional Chinese medicine, exerts broad-spectrum antitumour activities via several pathways. This study aimed to elucidate the mechanism involved in the combined effect of low-dose GA and NaI131 to sensitize the antitumour activity of NaI131 in drug-resistant NSCLC cells.
Methods

Human NSCLC cell line A549 and drug-resistant cell lines A549/DDP and A549/Taxol were treated with NaI131, low-dose GA or a combination of both; control group of each cell line was treated with phosphate-buffered saline. Following treatment, cell proliferation, apoptosis, cell cycle, and levels of expression of apoptosis-related proteins namely CDK1, Cyclin B, mtp53, HSP90, and Bax, Bcl-2 respectively, and P-glycoprotein 1 (P-gp) known to confer resistance to chemotherapy, were detected using western blotting and immunofluorescence. mRNA levels of mtp53 and HSP90 were measured using qRT-PCR.
Results

Compared to the control group, A549, A549/DDP, and A549/Taxol cells treated with NaI131, GA or combination of drugs exhibited G2/M arrest, increased percentage of total apoptotic cells, significantly reduced protein levels of CDK1, Cyclin B, mtp53, HSP90, Bcl-2 and P-gp, increased protein levels of Bax and decreased mRNA levels of mtp53 and HSP90. The changes in the combination group were significantly different from the other groups.
Conclusion

In NSCLC cell lines, low-dose GA could enhance the effect of NaI131 on G2/M arrest, promote cell apoptosis, reduce drug-resistance and hence could be explored as a potential radionuclide sensitizer.
Comparison of the efficacy of five front-of-pack nutrition labels in helping the Brazilian consumer make a healthier choice
Authors: Blom Wendy A.M. , Goenee Chantal , Juliano Lucia , de Groene Els M. , Martins Fernanda de Oliveira
Published: October 2020

Background:
We tested, in an online survey, how well five different front-of-pack (FOP) labels helped Brazilian consumers make a healthier choice between two food or beverage products as compared to a no FOP label control.
Methods:
All 1072 respondents were randomly assigned to one of six groups 1) no FOP label (control), 2) ABIA label, 3) GGALIii Nutrient Profile label, 4) IdeC label, 5) Hybrid label or 6) Nutri-Score label and were all shown 9 food stimuli consisting of two products. The nutrient profile of the ABIA and Hybrid labels take into account the serving size of the food, while the other three labels score per 100 g. Respondents were asked which of the two products they thought was the healthier choice.
Results:
Overall, the Hybrid and ABIA labels performed best, resulting in a statistically significantly higher percentage of correct answers compared to the control for 9/9 and 8/9 of the food stimuli, respectively. Nutri-Score performed reasonably well and outperformed the control in 6/9 cases. The IdeC and GGALIii NP warning labels were the least useful, performing only one and two times better, respectively, than the control group.
Conclusion:
The Hybrid and the ABIA FOP labels, two interpretative traffic light labels that use colours and provide nutritional information per serving, were best suited to help Brazilian consumers choose the healthier product. They especially outperformed the other FOP labels when serving sizes differed significantly or when deeper consideration of nutritional information was needed to make an informed decision.
Predictors of Caregiver Burden in Aged Caregivers of Demented Older Patients
Authors: Tsai Chia-Fen , Hwang Wei-Shen , Lee Jun-Jun , Wang Wen-Fu , Huang Ling-Chun , Huang Li-Kai , Lee Wei-Ju , Sung Pi-Shan , Liu Yi-Chien , Hsu Chih-Cheng , Fuh Jong-Ling
Published: October 2020

BackgroundDementia in the oldest-old is projected to increase exponentially as is the burden of their caregivers who may experience unique challenges and suffering. Thus, we aim to investigate which factors are associated with older caregivers’ burden in caring demented outpatients in a multicenter cohort.MethodsPatients and their caregivers, both aged ≧65 years, in the National Dementia Registry Study in Taiwan (T-NDRS) were included in this study. Caregiver burden was measured with the short version of the Zarit Burden Interview (ZBI). The correlations between the ZBI scores and characteristics of caregivers and patients, including severity of dementia, physical comorbidities, instrumental activities of daily living (IADL), neuropsychiatric symptoms assessed by the Neuropsychiatric Inventory (NPI), and family monthly income, were analyzed.ResultsWe recruited 328 aged informal caregiver-patient dyads. The mean age of caregivers was 73.7± 7.0 years, with female predominance (66.8%), and the mean age of patients was 78.8±6.9 years, with male predominance (61.0%). Multivariable linear regression showed that IADLs (β=0.83, p<0.001) and NPI subscores of apathy (β=3.83, p<0.001)and irritability (β=4.25, p<0.001) were positively associated with ZBI scores. The highest family monthly income (β= -10.92, p=0.001) and caregiver age (β= -0.41, p=0.001) were negatively correlated with ZBI scores.ConclusionsOlder caregivers of older demented patients experience a higher care burden when patients had greater impaired functional autonomy and the presence of NPI symptoms of apathy and irritability. Our findings provide the direction to identify risky older caregivers, and we should pay more attention to and provide support for these exhausted caregivers.
Tubularized Urethral Reconstruction Using Everted Saphenous Vein Graft in A Beagle Model
Authors: Li Dan , Shen Zhou , Xu Yujie
Published: October 2020

Background: The repair of anterior urethral stricture and hypospadias require urethral reconstruction. We conduct the study to investigate the efficacy of anterior urethral reconstruction using everted saphenous vein graft in tubular fashion. Methods: Twelve male beagles were randomly divided into three groups: experimental group( n=5), control group( n=5) and normal group( n=2). A 3 cm defect in anterior urethra was created. Autologous saphenous vein graft was harvested. In experimental group, urethral defect was replaced by everted saphenous vein graft in tubular fashion. In control group, urethral reconstruction was performed using uneverted saphenous vein graft. At 6 months postoperatively, beagles in all groups received retrograde urethrography to evaluate urethral patency and were killed for histological examination. Results: Retrograde urethrography showed the urethral caliber of beagles in experimental group were similar to those of normal. Ether urethral stricture or fistula were detected in all animals in control group. In experimental group, the everted saphenous vein graft completely integrated into the urethra. The reconstructed urethra had a wide lumen and was completely covered by urothelium. The subepithelial collagen and muscle fibers were well formed and highly organized. Everted saphenous vein graft had a high ability of neovascularization. In control group, the reconstructed segment had a fibrotic urethral lumen in which urothelium was not intact. And there were few newly formed capillaries. Conclusions: Everted saphenous vein graft can be used as tubular substitute material for anterior urethral strictures and hypospadias.
Development of A Nomogram to Predict Survival Outcome Among Epithelial Ovarian Cancer Patients With Site-Distant Metastases: A Population-Based Study
Authors: Wang Bo , Wang Shixuan , Ren Wu
Published: October 2020

Objective. The incidence of initial diagnosis with distant metastasis in patients with epithelial ovarian cancer is not rare, for which the available prognostic evaluation criteria is absent. This study aimed to develop a nomogram score to predict long-term prognosis.Methods. This study analyzed patients with epithelial ovarian cancer from the Surveillance, Epidemiology, and End Results (SEER) database between 1975 and 2016. Multivariable logistic and Cox regression were performed to identify survival trajectories. A nomogram score was used to predict long-term survival probability. Results. A total of 131050 patients were included, 18.2%, 7.8% and 66.1% had localized, regional and distant metastases, respectively. Metastases were inversely associated with high probability of 5-year overall survival outcome, localized (OR, 4.62; 95%CI, 4.45-4.80), regional (OR, 2.47; 95%CI, 2.36-2.59) compared with distant metastases. Survival was poorer among regional (HR, 1.72; 95%CI, 1.65-1.79) and distant (HR, 3.39; 95%CI, 3.29-3.49) metastases at diagnosis. For incidence, 0.9%, 6.7%, 5.8% and 0.2% had bone, liver, lung and brain metastases in the all-cause mortality cohort respectively, 1.6%, 9.9%, 8.8% and 0.3% had bone, liver, lung and brain metastases in the cancer-specific mortality cohort respectively. The median survival among the all-cause mortality cohort was 21.0 months, cancer-specific mortality cohort was 15.0 months. Organ-specific metastases were independently associated with survival prognosis.Conclusions. Nomogram score in estimating the long-term prognosis is feasible, for which contribute to directing clinical treatment and prognosis assessment in patient harboring site-distant metastases.
Extracting Knowledge Networks from Plant Scientific Literature: Potato Tuber Flesh Color as an Exemplary Trait
Authors: Singh Gurnoor , Papoutsoglou Evangelia , Keijts-Lalleman Frederique , Vencheva Bilyana , Rice Mark , Visser Richard G.F. , Bachem Christian , Finkers Richard
Published: October 2020

Background: Scientiﬁc literature carries a wealth of information crucial for research, but only a fraction of it is present as structured information in databases and therefore can be analyzed using traditional data analysis tools. Natural language processing (NLP) is often and successfully employed to support humans by distilling relevant information from large corpora of free text and structuring it in a way that lends itself to further computational analyses. For this pilot, we developed a pipeline that uses NLP on biological literature to produce knowledge networks. We focused on the ﬂesh color of potato, a well-studied trait with known associations, and we investigated whether these knowledge networks can assist us in formulating new hypotheses on the underlying biological processes. Results: We trained an NLP model based on a manually annotated corpus of 34 full-text potato articles, to recognize relevant biological entities and relationships between them in text (genes, proteins, metabolites and traits). This model detected the number of biological entities with a precision of 97.65% and a recall of 88.91% on the training set. We conducted a time series analysis on 4023 PubMed abstract of plant genetics-based articles which focus on 4 major Solanaceous crops (tomato, potato, eggplant and capsicum), to determine that the networks contained both previously known and contemporaneously unknown leads to subsequently discovered biological phenomena relating to ﬂesh color. Analysis of these networks indicates a connection between our trait and a candidate gene (zeaxanthin epoxidase) already two years prior to explicit statements of that connection in the literature. Conclusions: Our time-based analysis indicates that network-assisted hypothesis generation shows promise for knowledge discovery, data integration and hypothesis generation in scientiﬁc research.
High Body Mass Index Was Related to Favorable Therapeutic Efficacy of Epidermal Growth Factor Receptor Targeted Therapy in Advanced Non-Small Cell Lung Cancer
Authors: Chen Yue-Yun , Yin Xu-De , Xie Ke , Wang Pei-Pei , Fu Yang , Li Qing , Liu Bi-Sheng , Liu Ting , Ding Zhen-Yu
Published: October 2020

BackgroundIt’s widely accepted that Obesity is closely associated with the elevated risk of various cancers. However, there’s no consensus regarding the impact of body mass index (BMI) on the outcome of targeted therapy targeted-therapy efficacy in lung cancer. MethodsTreatment-naive advanced NSCLC patients harboring EGFR mutation prescribed TKI were screened and enrolled from 3 referral centers. Patients enrolled from West China Hospital were set as the training group, and the others as validation group. Both the demographic features including mutation status and BMI, and therapeutic effects including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were collected.ResultsIn the training group, patients were dichotomized according to their BMI. Those with higher BMI (>22.5) achieved a prolonged PFS compared with those with lower BMI (13.8 and 10.9 mon, HR: 0.68; 95% CI: 0.54-0.86; P = 0.001), and the priority persisted irrespective of different cut-off values. Besides, the favorable association of high BMI with long PFS was confirmed in the validation cohort (14.0 and 11.6 mon, P=0.089) and whole cohort (13.7 and 11.3 mon, P=0.004). In the multivariate analysis, BMI was an independent favorable factor of PFS, together with gender, albumin, and performance. By integration of these factors, a nomogram to predict to 1-,3-year PFS was established. Finally, higher BMI was associated with better objective response rate (ORR, 74% and 69%) and longer overall survival (OS, 41.4 and 33.5 mon, P=0.011). ConclusionHigh BMI was independently associated with efficacy of EGFR-TKI treatment in advanced NSCLC patients.
Family Health Climate: A Qualitative Exploration of Everyday Family Life and Health
Authors: Wäsche Hagen , Niermann Christina , Bezold Jelena , Woll Alexander
Published: October 2020

Background The family is an important social environment for children’s, adolescents’ and adults’ health. However, studies mostly focused on dyadic and unidirectional influences of parents on their children. Studies addressing influences arising from daily family life and including family level influences are rare and the existing studies solely focus on the relevance for children’s health or health-related behaviors. We use a qualitative approach to explore how daily family life and its inherent health-related cues affect family members’ physical activity and eating behavior. Methods Semi-structured interviews utilizing an interview guide were conducted. Since we aimed to examine family life, we analyzed both parents’ and their children’s views on health-related interaction patterns and family environmental influences on individuals’ health-related behavior. Twenty-two members of seven families were interviewed. Transcripts of the interviews were systematically analyzed following Grounded Theory principles.Results The interviews revealed that various individual as well as environmental factors shape health-related aspects of daily family life. A model was developed that organizes these influencing factors on family life with regard to health-related interactions and the emergence of the Family Health Climate (FHC) – reflecting shared perceptions and cognitions regarding a healthy lifestyle within families – and its consequences. Family interactions and family time, often realized through shared family meals, are key factors for families’ health with regard to nutrition and physical activity. The FHC showed to affect various aspects related to health behavior of individual family members.Conclusions The model allows to gain knowledge on underlying processes and mechanisms of family life that influences individuals’ health-related behavior. Based on a better understanding of the association between family life and individual health behavior the development of family-based interventions can be informed. Furthermore, the insights can help to guide further research focusing on families as a system.
BSR-Seq Analysis Provides Insights into Cold Stress in Actinidia Arguta F1 Populations
Authors: Lin Miao miao , Sun Shihang , Fang Jinbao , Qi Xiujuan , Sun Leiming , Zhong Yunpeng , Sun Yanxiang , Hong Gu , Wang Ran
Published: October 2020

BackgroundThe freezing injury, which is one of the important abiotic stresses in horticultural crops, can influences the growth and development and the production area of kiwifruit (Actinidia Lind1). Actinidia arguta has excellent cold resistance in Actinidia species, but knowledge relevant to molecular mechanisms is still limited so far. Understanding the mechanism of cold resistance in kiwifruit is important for cold-resistant breeding. ResultsIn our study, a cross of ‘Ruby-3’×‘Kuilv’ male was built for the A. arguta hardiness study, and 20 cold-tolerant and 20 cold-sensitive populations were selected from 492 populations according to LT50. Then, we performed Bulked segregant RNA-seq combined with single-molecule real-time sequencing to identify differentially expressed genes with cold hardiness. We found that the content of soluble sucrose and the activity of β-amylase were higher in the cold tolerant population pool than in the cold sensitive population pool. Upon -30°C low temperature treatment, 126 differentially expressed genes were found, and 59 genes were upregulated and 67 genes were downregulated when comparing the tolerant and sensitive pools, respectively. KEGG pathway analysis showed that the DEGs mainly belonged to starch and sucrose metabolism and amino sugar and nucleotide sugar metabolism. There were main 10 key enzyme encoding genes and two regulatory genes were up regulated in tolerant pool, regulated genes of CBF pathway were found to be different expressed, especially, 14-3-3 gene was down regulated and EBF gene was up regulated. To validate the BSR-Seq results, 24 DEGs were determined by qRT-PCR, and the results were consistent with BSR-Seq.ConclusionOur research provides valuable insights into the mechanism related to cold resistance in Actinidia and identified potential genes that are important for cold resistance in kiwifruit.
Integrative Bioinformatics Analysis Identified Hub Genes in Association with Development of Lung Adenocarcinoma
Authors: Hu Xilin , Xu Hanlin , Jiao Wenjie , Tian Kaihua
Published: October 2020

Background: Cancer-related death is mainly caused by lung adenocarcinoma (LUAD), an aggressive malignant tumor. Therefore, the identification of important LUAD-related genes and the further analysis of its prognostic significance are critical for the survival of LUAD patients.Methods: Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression analysis methods were adopted to screen out TCGA-LUAD database and the gene expression profiles of GSE32863 from GEO. Functional annotation analysis and protein-protein interaction (PPI) network were conducted on differential co-expression genes. Furthermore, survival analysis was carried out on twelve hub genes that were identified by applying the CytoHubba plugin of Cytoscape. Finally, we validated the protein level of survival-related gene in HPA database.Results: A total of 358 differential co-expression genes were extracted from the database of TCGA and GEO. These genes were mainly enriched in extracellular structure organization, cell−substrate adhesion and response to acid chemical (biological process), cell−cell junction and collagen−containing extracellular matrix (cellular component), DNA−binding transcription activator activity, glycosaminoglycan binding, and growth factor binding (molecular function). In the KEGG analysis, the main pathways were Drug metabolism−cytochrome P450. Moreover, in a PPI network, the 12 hub genes (GNG11, ADRB2, ADCY4, TGFBR2, IL6, GPC3, VIPR1, GRK5, CAV1, RAMP3, RAMP2, and CALCRL) were identified. The expression level of ADCY4, VIPR1, and TGFBR2 was corresponded with clinical stages and overall survival (OS) in LUAD patients. Finally, the protein level of ADCY4 and VIPR1 was down-regulated consistently with mRNA levels in LUAD samples.Conclusion: Perhaps, ADCY4, VIPR1 and TGFBR2 play important role in tumorigenesis, so they will serve as prognostic biomarkers and therapeutic targets of LUAD in the future.