bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spaceflight Induces Novel Regulatory Responses in Arabidopsis Seedling as Revealed by Combined Proteomic and Transcriptomic Analyses
Authors: Kruse Colin Peter Singer , Meyers Alexander D , Basu Proma , Hutchinson Sarahann , Luesse Darron R , Wyatt Sarah E. 
Published: April 2020

Abstract
Background: Understanding of gravity sensing and response is critical to long-term human habitation in space and can provide new advantages for terrestrial agriculture. To this end, the altered gene expression profile induced by microgravity has been repeatedly queried by microarray and RNA-seq experiments to understand gravitropism. However, the quantification of altered protein abundance in space has been minimally investigated. Results: Proteomic (iTRAQ-labelled LC-MS/MS) and transcriptomic (RNA-seq) analyses simultaneously quantified protein and transcript differential expression of three-day old, etiolated Arabidopsis thaliana seedlings grown aboard the International Space Station along with their ground control counterparts. Protein extracts were fractionated to isolate soluble and membrane proteins and analyzed to detect differentially phosphorylated peptides. In total, 968 RNAs, 107 soluble proteins, and 103 membrane proteins were identified as differentially expressed. In addition, the proteomic analyses identified 16 differential phosphorylation events. Proteomic data delivered novel insights and simultaneously provided new context to previously made observations of gene expression in microgravity. There is a sweeping shift in post-transcriptional mechanisms of gene regulation including RNA-decapping protein DCP5, the splicing factors GRP7 and GRP8, and AGO4,. These data also indicate AHA2 and FERONIA as well as CESA1 and SHOU4 as central to the cell wall adaptations seen in spaceflight. Patterns of tubulin-a 1, 3,4 and 6 phosphorylation further reveal an interaction of microtubule and redox homeostasis that mirrors osmotic response signaling elements. The absence of gravity also results in a seemingly wasteful dysregulation of plastid gene transcription. Conclusions: The datasets gathered from Arabidopsis seedlings exposed to microgravity revealed marked impacts on post-transcriptional regulation, cell wall synthesis, redox/microtubule dynamics, and plastid gene transcription. The impact of post-transcriptional regulatory alterations represents an unstudied element of the plant microgravity response with the potential to significantly impact plant growth efficiency and beyond. What’s more, addressing the effects of microgravity on AHA2, CESA1, and alpha tubulins has the potential to enhance cytoskeletal organization and cell wall composition, thereby enhancing biomass production and growth in microgravity. Finally, understanding and manipulating the dysregulation of plastid gene transcription has further potential to address the goal of enhancing plant growth in the stressful conditions of microgravity.
Dehydroxymethylepoxyquinomicin, a novel nuclear factor-κB inhibitor, prevents the development of cyclosporine A nephrotoxicity in a rat model
Authors: Morita Shinya , Shinoda Kazunobu , Yoshida Tadashi , Shimoda Masayuki , Kanno Yoshihiko , Mizuno Ryuichi , Kono Hidaka , Asanuma Hiroshi , Nakagawa Ken , Umezawa Kazuo , Oya Mototsugu 
Published: April 2020

Abstract
Background Cyclosporine A (CsA) is an essential immunosuppressant in organ transplantation. However, its chronic nephrotoxicity is an obstacle to long allograft survival that has not been overcome. Nuclear factor-kB (NF-kB) is activated in the renal tissue in CsA nephropathy. In this study, we aimed to investigate the effect of the specific NF-kB activation inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) in a rat model of CsA nephrotoxicity. Methods We administered CsA (15 mg/kg) daily for 28 days to Sprague-Dawley rats that underwent 5/6 nephrectomy under a low-salt diet. We administered DHMEQ (8 mg/kg) simultaneously with CsA to the treatment group, daily for 28 days and evaluated its effect on CsA nephrotoxicity. Results DHMEQ significantly inhibited NF-kB activation and nuclear translocation due to CsA treatment. Elevated serum urea nitrogen and creatinine levels due to repeated CsA administration were significantly decreased by DHMEQ treatment (serum urea nitrogen in CsA + DHMEQ vs CsA vs control, 69 ± 6.4 vs 113.5 ± 8.8 mg/dL vs 43.1 ± 1.1, respectively, p < 0.0001; serum creatinine in CsA + DHMEQ vs CsA vs control, 0.75 ± 0.02 vs 0.91 ± 0.02 vs 0.49 ± 0.02 mg/dL, respectively, p < 0.0001), and creatinine clearance was restored in the treatment group (CsA + DHMEQ vs CsA vs control, 2.57 ± 0.09 vs 1.94 ± 0.12 vs 4.61 ± 0.18 ml/min/kg, respectively, p < 0.0001). However, DHMEQ treatment did not alter the inhibitory effect of CsA on urinary protein secretion. The development of renal fibrosis due to chronic CsA nephrotoxicity was significantly inhibited by DHMEQ treatment (CsA + DHMEQ vs CsA vs control, 13.4 ± 7.1 vs 35.6 ±18.4 vs 9.4 ± 5.4%, respectively, p < 0.0001), and these results reflected the results of renal functional assessment. DHMEQ treatment also had an inhibitory effect on the increased expression of chemokines, monocyte chemoattractant protein-1, and chemokine (c-c motif) ligand 5 due to repeated CsA administration, which inhibited the infiltration of macrophages and neutrophils into the renal tissue. Conclusions These findings suggest that DHMEQ treatment in combination therapy with CsA-based immunosuppression is beneficial to prevent the development of CsA-induced nephrotoxicity.
Behavioral Profile, Lifestyle and Social Skills in Portuguese Adolescents
Authors: Magalhães Clarisse , Ribeiro Maria de Fátima , Esteves Maria Raquel , Aires Luísa , Lima Sara , Silva Gustavo , Nogueira Assunção , Herdeiro Maria Teresa , Pedras Susana 
Published: April 2020

Abstract
Background: Seventy percent of premature deaths in adults are due to behaviors initiated during adolescence. Therefore, it is essential to promote individual and social behaviors that educate adolescents in the ability to make healthy choices. Thus, the goals of this study were to characterize the lifestyle and social skills as well as to identify homogeneous subgroups in a sample of Portuguese adolescents. Methods : We conduct a cross-sectional study including 1008 adolescents attending 7 th to 9 th grade of five middle schools from Tâmega and Sousa region, of Portugal. My Lifestyle Questionnaire and the Social Skills Inventory were used. To establish a profile of the participants, a Cluster Analysis (K-means) was performed and the Jaccard coefficient was used to assess the stability of the solution found. Results: From the total sample, 556 adolescents with a mean age of 13.43 years (SD=1.1) were included in the analysis. The majority of the sample presented a good lifestyle (72.26% indicating good LS) and 50.7% of the adolescents had a highly elaborated repertoire of social skills. Moreover, three clusters were found. Cluster 1 (n=92) showed a less elaborate SS repertoire and was named the “Adjusted”. Cluster 2 (n=115) comprised adolescents with a good SS repertoire and was named the “Sociable”. Cluster 3 (n=258) was composed by adolescents with a highly elaborate SS repertoire and the best LS indicators, and was named the “Healthy”. Conclusions : The group of adolescents in cluster called “Sociable” needs to be included in health education and social skills programs. NUT and MS behaviors have low values and, therefore, present a greater need for awareness, sensitization and intervention in the school context. Promoting a healthy lifestyle should be part of the academic curriculum and be transversal to all academic disciplines.
Intermittent peripheral exposure to lipopolysaccharide induces exploratory behavior in mice and regulates brain glial activity in obese mice
Authors: Huang Hui-Ting , Chen Po-See , Kuo Yu-Min , Tzeng Shun-Fen 
Published: April 2020

Abstract
Background: Consecutive peripheral immune challenges can modulate the responses of brain resident microglia to stimuli. High-fat diet (HFD) intake has been reported to stimulate the activation of astrocytes and microglia in the arcuate nucleus (ARC) of the hypothalamus in obese rodents and humans. However, it is unknown whether intermittent exposure to additional peripheral immune challenge can modify HFD-induced hypothalamic glial activation in obese individuals. Methods: In this study, we administered 1 mg/kg LPS (or saline) by intraperitoneal (i.p.) injection to 8-week-old male mice after 1, 2, or 8 weeks of a regular diet (show) or HFD. The level of interleukin-1b (IL-1b) and tumor necrosis factor-a (TNF-a) expression in the plasma and hypothalamic tissue was analyzed 24 h after each LPS injection. The behaviors of the animals in the four groups (the chow-saline, chow-LPS, HFD-saline, and HFD-LPS groups) were examined 5 months after exposure to chow or a HFD. Morphological examination of microglia in related brain regions was also conducted. Results: The plasma levels and hypothalamic mRNA levels of IL-1b and TNF-a were significantly upregulated 24 h after the first injection of LPS but not after the second or third injection of LPS. Chow-LPS mice displayed increased exploratory behavior 5 months after feeding. However, this LPS-induced abnormal exploratory behavior was inhibited in HFD-fed mice. Chronic HFD feeding for 5 months induced apparent increases in the number and cell body size of microglia, mainly in the ARC, and also increased the size of microglia in the NAc and insula. Moreover, microglial activation in the nucleus accumbens (NAc), anterior cingulate cortex (ACC), insula, and basolateral amygdala (BLA) was observed in chow-LPS mice. However, microglial activation in the analyzed brain regions was suppressed in HFD-LPS mice.Conclusions: Altogether, the results indicate that intermittent peripheral challenge with LPS might prime microglia in the ARC and NAc to modify their response to chronic HFD feeding. Alternatively, chronic HFD feeding might mediate microglia in LPS-affected brain regions and subsequently suppress LPS-induced atypical exploratory behavior. Our findings suggest that the interaction of intermittent acute peripheral immune challenges with chronic HFD intake can drive microglia to amend the microenvironment and further modify animal behaviors in the later life.
Brain morphologic abnormalities in migraine patients: an observational study
Authors: Bonanno Lilla , Buono Viviana Lo , De Salvo Simona , Ruvolo Claudio , Torre Viviana , Bramanti Placido , Marino Silvia , Corallo Francesco 
Published: April 2020

Abstract
Background: Migraine is a common neurological disorder characterized by a complex physiopathology. We assessed brain morphologic differences in migraine and the possible pathogenetic mechanism underlying this disease.Methods: We analyzed brain morphologic images of migraine patients, 14 with aura (MwA) [the mean (SD) age was 42.36 (2.95) years (range, 37-47)] and 14 without aura (MwoA) [the mean (SD) age was 43.5 (3.25) years (range, 39-50)] during episodic attack compared with health subjects balanced (HS) [the mean (SD) age was 42.5 (5.17) years (range, 34-51)]. All subjects underwent a Magnetic Resonance Imaging (MRI) examination with a scanner operating at 3.0 T and voxel based morphometry (VBM) approach was used to examine the gray matter volume (GMV). The statistical analysis to compare clinicl characteristics was performed using unpaired t-test an one-way Anova. Results: Total cerebral GMV showed a significant difference between MwA and HS (p=0.02), and between MwoA and HS (p=0.003). In addition, not significative differences were found between MwA and MwoA groups (p=0.17). We found three clusters of regions which showed significant GMV reduction in MwA compared with MwoA. MwA subjects showed a less of GMV in 4 clusters if compared with HS, and MwoA subjects showed a less of GMV in 3 clusters if compared with HS. We observed that MwA and MwoA patients had a significant reduction of GMV in the frontal and temporal lobe and the cerebellum, if compared to HS. The bilateral fusiform gyrus and the cingulate gyrus were increase in MwoA patients compared with HS.Conclusion: Our findings could provide a approach to understand possible differences in the pathogenesis of two type of migraine.
Enrichment differentiation of human induced pluripotent stem cells into sinoatrial node-like cells by combined modulation of BMP, FGF and RA signaling pathways
Authors: Liu Feng , Fang YiBing , Hou XiaoJie , Yan Ying , Xiao HaiYing , Zuo DongChuan , Wen Jing , Wang LinLi , Zhou Zhichao , Dang XiTong , Zhou Rui , Liao Bin 
Published: April 2020

Abstract
Background: Biological pacemakers derived from pluripotent stem cell (PSC) have been considered as a potential therapeutic surrogate for sick sinus syndrome. So it’s essential to develop high efficient strategies for enrichment of sinoatrial node-like cells (SANLC) as seed cells for biological pacemakers. It has been reported that BMP, FGF and RA signaling pathways are involved in specification of different cardiomyocyte subtypes, pacemaker, ventricular, and atrial cells. Methods: During the differentiation process from human-induced pluripotent stem cell (hiPSC) to cardiomyocyte through small molecule based temporal modulation of the Wnt signaling pathway, signaling of BMP, FGF and RA was manipulated at cardiac mesoderm stage. qRT-PCR, immunofluorescence, flow cytometry and whole cell patch clamp were used to identify the SANLC. Results: qRT-PCR results showed that manipulating each one of bone morphogenetic protein (BMP), fibroblast growth factor (FGF) and retinoid acid (RA) signaling was effective for the upregulation of SANLC markers. Moreover, combined modulation of these three pathways displayed the best efficiency for the expression of SANLC markers, which was further confirmed at protein level using immunofluorescence and flow cytometry. Finally, the electrophysiological characteristics of upregulated SANLC were verified by patch clamp method. Conclusion: An efficient transgene-independent differentiation protocol for generating SANLC from hiPSC was developed, in which combined modulating BMP, FGF and RA signaling at cardiac mesoderm stage generates SANLC at high efficiency. This may serve as a potential approach for biological pacemaker construction.
Factors facilitating trained NIMART nurses’ adherence to treatment guidelines: A vital matter in the management of TB/HIV treatment in South Africa
Authors: MAKHADO LUFUNO , Davhana-Maselesele Mashudu , Lebese Rachel Tsakani , Maputle Sonto Maria 
Published: April 2020

Abstract
Background: Globally the burden of tuberculosis or human immunodeficiency virus (TB/HIV) is at 24% with 3% global health workforce and this an alarming rate that World Health Organization (WHO) declared African region as a critical workforce shortage area. To facilitate adherence to treatment guidelines, WHO recommended a strategy of task shifting for these countries with high health workforce shortages. The strategy aimed at the redistribution of health care tasks to available workers. The purpose of the study was to determine factors facilitating trained nurse-initiated management of antiretroviral therapy (NIMART) nurses’ adherence to TB/HIV treatment guidelines in KwaZulu-Natal (KZN) and North West (NW) Provinces of South Africa.Design: The study was qualitative, explorative and descriptive in nature. The population comprised of 24 participants who were purposively selected. The in-depth focus group discussion was conducted. Data analysis was through the used of ATLAS T.I. software program (version 7.0) and followed the basic steps of notice-collect-think (NCT) analysis. Trustworthiness and ethical consideration were ensured.Results: The following one theme namely; marked identified needs to be met to promote adherence to treatment guidelines and sub-themes emerged from raw data: Expected positive attitudinal needs outlined and an outline of a positive behavioural change. Conclusion: Factors such as continuous training, support supervision and improved relationships with colleagues need to be enhanced to enable NIMART nurses to adhere to treatment guideline.
Achieving objective response in treatment of non-resectable neuroendocrine tumors does not predict longer time to progression compared to achieving stable disease
Authors: Thiis-Evensen Espen , Poole Amalie Christine , Nguyen Hong-Thien Thi , Sponheim Jon 
Published: April 2020

Abstract
Background: There are several treatment modalities for unresectable neuroendocrine tumors. Traditionally, the aim of these treatments has been to reduce the tumor load; referred to as objective response (OR). Less emphasis has been put on inducing the tumors to stop growing without a reduction in total tumor load; termed as stable disease (SD). We wanted to investigate whether achieving OR compared to obtaining SD predicted a longer time to progression (TTP) in patients with neuroendocrine tumors (WHO Grade 1 and 2) treated with peptide receptor radionuclide therapy, chemotherapy or molecular targeted therapy. Methods : Patients treated with either peptide receptor radionuclide therapy (PRRT) with 177 Lutetium-DOTA-octreotate, the chemotherapy combination streptozotocin/5-fluorouracil or everolimus were retrospectively assessed to evaluate the effect of the treatments on disease progression. We analyzed the TTP for patients for each treatment modality and compared the TTP between those who achieved OR and those who achieved SD. Results: Altogether 56 patients treated with PRRT, 32 treated with streptozotocin/5-fluorouracil and 52 treated with everolimus were included in the analyses. The median TTP for those treated with PRRT and achieving OR was 31 months, the TTP for those achieving SD was 43 months (p=0,2). For patients treated with streptozotocin/5-fluorouracil the results were: OR: 18 months, SD: 23 months (p=0,9) and for those treated with everolimus; OR: 9 months, SD: 20 months (p=0,5), respectively. We found no differences between patients achieving OR compared to SD regarding age, sex, stage, primary tumor location, Ki-67% or ongoing treatment with somatostatinanalogues. Conclusions: We found no treatment benefit with regard to TTP for our patients that experienced OR compared to those who achieved SD, but a trend toward longer TTP among patients with SD.
Effect and Mechanism of Lycium Barbarum Polysaccharide on Hyperglycemia and Inflammation in Diabetic KKAy Mice
Authors: yin hong , Deng Shuying , Bai Lili , Li Lihua , Liu Tingting , Cai Huizhen 
Published: April 2020

Abstract
Scope The aim of this study is to examine whether lycium barbarum polysaccharide (LBP) supplementation improves hyperglycemia and inflammation in diabetic KKAy mice. Methods The successfully established diabetic KKAy mice are randomized into five groups: diabetic model, metformin, low‐dose LBP, middle‐dose LBP, and high‐dose LBP . C57BL/6J mice are fed a chow diet as normal control . The blood glucose and body weight of mice were measured at different time points. At the end of 90 days, serum inflammatory factors were determined with ELISA kits. The expression of TLR4, MyD88, TRAF6, IκKβ, IκB, P-IκB and nuclear NF-κB proteins in mouse peritoneal macrophages were detected by Western Blotting. Results Blood glucose decreased significantly after the intervention among low-, medium-dose LBP groups and Met group ( P <0.05). Met (40 mg/kg) inhibited the levels of IL-1β, TNF-α and IL-6 and elevated IL-10 level ( P <0.05). ELISA results showed that LBP promoted serum levels of IL-10 and decreased TNF-α level ( P <0.05). Compared with model group, KKAy mice in Met group expressed lower protein levels of MyD88, TRAF6, IκKβ, nuclear NF-κB and higher expression of IκB ( P <0.05); The expression of TLR4, MyD88, TRAF6, IκKβ and nuclear NF-κB protein in low- and medium-doses LBP groups were significantly declined ( P <0.05). Conclusion These findings indicate that dietary supplementation with LBP can improve hyperglycemia and inflammation in diabetic KKAy mice, which can be associated with potential benefits to human health.
Insights for the future of health system partnerships in low- and middle-income countries
Authors: Fanelli Simone , Salvatore Fiorella Pia , De Pascale Gianluigi , Faccilongo Nicola 
Published: April 2020

Abstract
Background: Despite growing support for the private sector involvement in the provision of public health services in Low- and Middle-Income Countries (LMICs), a lack of clear information on the future of the provision of such services restricts the ability of policy-makers to assess how feasible integration between public and private actors may be, especially in LMICs.Methods: This paper presents a structured literature review performed to comprehend the dynamics and boundaries of public-private partnerships for the healthcare sector in LMICs. A total of 723 articles indexed in Scopus were initially submitted to bibliometric analysis. Finally, 148 articles published in several academic journals were selected for independent full-text review by two researchers. Content analysis was made in order to minimise mistakes in interpreting the findings of studies in the sample.Results: Public-private partnerships identified through the content analysis were categorised into four research areas: 1) Transfer of resources; 2) Co-production of goods, services and health practices; 3) Governance networks; 4) Criteria for successful partnership development. The results provide a useful overview of the phenomenon and a useful baseline for policy implications of evolution of partnerships in LMIC healthcare sectors.Conclusions: The structured literature Review thus carries out a mapping of the areas and sectors where governments need support, and a careful analysis of all those factors which may or not facilitate a public-private partnership in LMICs.
Antioxidant Evaluation and Chemo-Profiling of Non-conventional Curcuma Species as Conservation of Drug Targeting Molecule
Authors: Jain Akanksha , Jain Parag 
Published: April 2020

Abstract
The objective of the present study was to determine and compare antioxidant activities of different species of Curcuma i.e. Curcuma longa, Curcuma caesia and Curcuma aromatic and their chemoprofiling for conservation of highest yield plants. The functional group analysis of the plants extract were determined by FTIR and structural features of phyto-constituents and Chemo-profiling of ethanol fractions of all targeted Curcuma species showing highest activity were analyzed by GC–MS/MS. Ethanolic extract of C. aromatica (ECA) was exhibited to determine high radical scavenging activity against DPPH (92.12%), lipid Peroxidation (85.13 ± 0.23%), nitric oxide scavenging, total reducing power (700.83 ± 8.14 μg/mg) and ferric reducing power assay. In ABTS·+ and phosphomolybdate assay Curcuma species showed a significant difference ranging from 67.53 – 98.57%. Furthermore, the amount of total phenolic and flavonoid content ranged from 3.63± 1.06 – 545.77 ± 2.76 μg/mg eq GAE and 21.18 –101.29 μg/mg eq QUE respectively. The results indicated that the ethanolic extracts showed highest in vitro antioxidant activity. It can be conclude from the study that Curcuma species may serve as an important bioresource as an antioxidant drug.