bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of hydrolyzed fish protein and autolyzed yeast as substitutes of fishmeal in the gilthead sea bream (Sparus aurata) diet, on fish intestinal microbiome
Authors: Rimoldi S. , Gini E. , Koch J. F. A. , Iannini F. , Brambilla F. , Terova G. 
Published: April 2020

Abstract
Background
This study evaluated the effects of partial substitution of dietary fishmeal (FM) with either fish protein hydrolysate (FPH) or autolysed dried yeast (HiCell®, Biorigin, Brazil) on intestinal microbiota of gilthead sea bream (Sparus aurata). A total number of 720 fish of 122.18 ± 6.22 g were fed for 92 days with three different diets in triplicate (3 tanks/diet). A diet based on FM/vegetable meal was used as control. The other two diets were formulated by replacing FM with 5% of either FPH or HiCell®. To analyze the gut microbiota associated to autochthonous and allochthonous microbial communities, the Illumina MiSeq platform for sequencing of 16S rRNA gene and QIIME pipeline were used.

Results
A total number of 102 OTUs (operational taxonomic units) at 97% identity were identified in fish gut samples collected at the end of feeding trial. Fourteen OTUs constituted the core gut microbiota, i.e. those OTUs found in at least nine out of fifteen samples per group and shared regardless of the diet. Eight OTUs were assigned to Firmicutes represented by Lactobacillus, Staphylococcus, and Bacillus genera, and six to Proteobacteria phylum. Dietary dried yeast autolysate modulated the intestinal microbiota by promoting the growth of some beneficial bacteria. At order level, fish fed yeast showed an enrichment in Bacillales and Clostridiales as compared to the control group, whereas fish fed FPH showed a significantly lower amount of bacteria belonging to Alteromonadales and Enterobacteriales than the other two feeding groups. Although we did not observe any effect of 5% FM replacement with alternative nitrogen sources at phylum level, at lower taxonomical levels, the composition of gut microbiota, in terms of relative abundance of specific taxa, was significantly influenced by the dietary treatment.

Conclusions
The metabarcoding analysis revealed a clearly intestinal microbiota modulation in response to dietary autolyzed yeast. The abundance of some beneficial bacteria, i.e. indigestible carbohydrate degrading- and SCFA producing bacteria, was positively affected. Brewer’s yeast autolysate could be a valid alternative protein source to FM as well as a valid functional ingredient for aquafeed production.
Adherence to the dietary approaches to stop hypertension (DASH) diet in relation to all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis of prospective cohort studies
Authors: Soltani Sepideh , Arablou Tahereh , Jayedi Ahmad , Salehi-Abargouei Amin 
Published: April 2020

AbstractBackgroundAlthough previous investigations have proposed an association between Dietary Approaches to Stop Hypertension (DASH)-style diet and lower mortality from chronic diseases, the exposure-response relationship is not clear. The present systematic review andmeta-analysis aimed to explore the linear and non-linear dose-responseassociation between adherence to the DASH diet andall-cause and cause-specific mortality.MethodsDatabase search was performed in PubMed, Scopus, and EMBASE for prospective cohort studies investigating the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and risk of mortality. Summary hazard ratios (HRs) and 95% confidence intervals (CI) were estimated with the use of a random-effects model for the linear and nonlinear relationships. The two-stage hierarchical regression model was applied to test the potential non-linear dose-response associations.ResultsThe inclusion criteria were met by 17 studies (13 publications). The scores reported for adherence to the DASH diet in different studies were converted to a conventional scoring method in which the adherence score might range between 8 to 40. The linear analysis revealed that summary HRs were 0.95 (95% CI: 0.94–0.96, I2 = 91.6%,n = 14) for all-cause, 0.96 (95% CI: 0.95–0.98, I2 = 82.4%,n = 12) for CVD, 0.97 (95% CI: 0.96–0.98, I2 = 0.00%,n = 2) for stroke, and 0.97 (95% CI: 0.95–0.98, I2 = 63.7%,n = 12) for cancer mortality per each 5-point increment of adherence to the DASH diet. There was also evidence of non-linear associations between the DASH diet and all-cause and cause-specific mortality as the associations became even more evident when the adherence scores were more than 20 points (P < 0.005).ConclusionEven the modest adherence to the DASH diet is associated with a lower risk of all-cause and cause-specific mortality. The higher adherence to the diet also strengthens the risk-reducing association.RegistrationThis review was registered in the international prospective register of systematic reviews (PROSPERO) database (registration ID: CRD42018086500).
Reducing exposure to high levels of perfluorinated compounds in drinking water improves reproductive outcomes: evidence from an intervention in Minnesota
Authors: Waterfield Gina , Rogers Martha , Grandjean Philippe , Auffhammer Maximilian , Sunding David 
Published: April 2020

Abstract
Background
Per- and polyfluoroalkyl substances (PFASs) have been detected in drinking water supplies around the world and are the subject of intense regulatory debate. While they have been associated with several illnesses, their effects on reproductive outcomes remains uncertain.

Methods
We analyzed birth outcomes in the east Minneapolis-St. Paul metropolitan area from 2002 to 2011, where a portion of the population faced elevated exposure to PFASs due to long-term contamination of drinking water supplies from industrial waste disposal. Installation of a water filtration facility in the highly contaminated city of Oakdale, MN at the end of 2006 resulted in a sharp decrease in exposure to PFASs, creating a “natural experiment”. Using a difference-in-differences approach, we compare the changes in birth outcomes before and after water filtration in Oakdale to the changes over the same period in neighboring communities where the treatment of municipal water remained constant.

Results
Average birth weight and average gestational age were statistically significantly lower in the highly exposed population than in the control area prior to filtration of municipal water supply. The highly exposed population faced increased odds of low birth weight (adjusted odds ratio 1.36, 95% CI 1.25–1.48) and pre-term birth (adjusted odds ratio 1.14, 95% CI 1.09–1.19) relative to the control before filtration, and these differences moderated after filtration. The general fertility rate was also significantly lower in the exposed population (incidence rate ratio 0.73, 95% CI 0.69–0.77) prior to filtration and appeared to be rebounding post-2006.

Conclusions
Our findings provide evidence of a causal relationship between filtration of drinking water containing high levels of exposure to PFASs and improved reproductive outcomes.
Questions for future evidence-informed policy initiatives: insights from the evolution and aspirations of National Immunization Technical Advisory Groups
Authors: Buffardi Anne L. , Njambi-Szlapka Susan 
Published: April 2020

Abstract
Background
Attention to evidence-informed policy has grown; however, efforts to strengthen the quality and use of evidence are not starting from a blank slate. Changes in health architectures and financing pose different considerations for investments in evidence-informed policy than in the past. We identify major trends that have shifted the environment in which health policies are made, and use the evolution and future aspirations of National Immunization Technical Advisory Groups (NITAGs) in low- and middle-income countries to identify questions the sector must confront when determining how best to structure and strengthen evidence-informed health policy.

Discussion
Trends over the last two decades have resulted in a dense arena with many issue-specific groups, discrete initiatives to strengthen evidence-informed policy and increasing responsibility for subnational institutions. Many countries face a shifting resource base, which for some reduces the amount of resources for health. There is global momentum around universal health coverage, reflecting a broader systems approach, but few examples of how the vast array of stakeholders relate within it are available. NITAG aspirations reflect four interconnected themes related to their scope, their integration in national policy processes, health financing and relationships with ministries of finance, and NITAG positioning relative to other domestic and international entities, raising questions such as, What are the bounds of issue-specific groups and their relationship to allocation decision-making processes across health areas? How do technical advisory groups interface with what are inherently political processes? When are finances considered, by whom and how? What is the future of existing groups whose creation was intended to enhance national ownership but who need continued external support to function? When should new entities be created, in what form and with what mandate?

Conclusions
Countries must determine who makes decisions about resources, when, using what criteria, and how to do so in a robust yet efficient way given the existing and future landscape. While answers to these questions are necessarily country specific, they are collective matters that cannot be addressed by specialised groups alone and have implications for new investments in evidence-informed policy.
Effect of CIP2A and its mechanism of action in the malignant biological behavior of colorectal cancer
Authors: Chen Wei , Liang Jing-Lin , Zhou Kai , Zeng Qing-Li , Ye Jun-Wen , Huang Mei-Jin 
Published: April 2020

Abstract
Background
Increasing evidence has revealed a close correlation between cancerous inhibitor of protein phosphatase 2A (CIP2A) and cancer progression. CIP2A has been shown to participate in diverse biological processes, such as development, tumorigenic transformation and chemoresistance. However, the functions of CIP2A in colorectal cancer (CRC) and its underlying mechanisms of action are not yet completely understood. The purpose of this study was to explore its clinical significance, function and relevant pathways in CRC.

Methods
Quantitative RT-PCR (qRT-PCR), immunohistochemistry (IHC), western blotting and enzyme-linked immunosorbent assay (ELISA) were used to identify the expression of CIP2A in CRC tissues, sera and CRC cell lines. The association between the expressions of CIP2A and patient survival was analyzed using the Kaplan-Meier curves. Additionally, the functional role of CIP2A in the cell lines was identified through small interfering RNA (siRNA)-mediated depletion of the protein followed by analyses of proliferation and xenograft growth in vivo using short hairpin (sh) RNAs. Effects of the C-myc inhibitor 10,058-F4 on the expressions of C-myc, and CIP2A in CRC cell lines and its potential mechanisms of action were investigated. Finally, the potential molecular pathways associated with CIP2A were screened using the phosphokinase array and identified through western blotting.

Results
CIP2A mRNA and protein levels were upregulated in CRC tissues compared to those of the corresponding normal tissues. It can be used as an independent prognostic indicator to determine overall survival (OS) and disease-free survival (DFS). Depletion of CIP2A substantially suppressed the growth of CRC cells and colony formation in vitro, and inhibited the growth of xenograft tumors in vivo. Additionally, the levels of CIP2A in the sera of patients with CRC were higher than those of the control subjects. Multivariate analyses revealed that the levels of CIP2A in the sera were not independent prognostic indicators in patients with CRC. Moreover, 10,058-F4 could effectively inhibit the growth of CRC cells in vitro, which could be correlated with an inhibition in the expressions of C-myc, CIP2A and its downstream regulatory anti-apoptotic proteins. Furthermore, the Human Phosphokinase Antibody Array was used to gain insights into the CIP2A-dependent intermediary signaling pathways. The results revealed that several signaling pathways were affected and the protein levels of p-p53 (S392), p-STAT5a (Y694), Cyclin D1, p-ERK1/2 and p-AKT (T308) had decreased in CIP2A-shRNA group based on the results of the western blot analysis.

Conclusions
CIP2A could promote the development of CRC cells and predict poor prognosis in patients with CRC, suggesting that it may serve as a potential prognostic marker and therapeutic target against CRC.

Graphical abstract
Suppression of histone deacetylases by SAHA relieves bone cancer pain in rats via inhibiting activation of glial cells in spinal dorsal horn and dorsal root ganglia
Authors: He Xiao-Tao , Hu Xiao-Fan , Zhu Chao , Zhou Kai-Xiang , Zhao Wen-Jun , Zhang Chen , Han Xiao , Wu Chang-Le , Wei Yan-Yan , Wang Wei , Deng Jian-Ping , Chen Fa-Ming , Gu Ze-Xu , Dong Yu-Lin 
Published: April 2020

Abstract
Background
Robust activation of glial cells has been reported to occur particularly during the pathogenesis of bone cancer pain (BCP). Researchers from our group and others have shown that histone deacetylases (HDACs) play a significant role in modulating glia-mediated immune responses; however, it still remains unclear whether HDACs are involved in the activation of glial cells during the development of BCP.

Methods
BCP model was established by intra-tibia tumor cell inoculation (TCI). The expression levels and distribution sites of histone deacetylases (HDACs) in the spinal dorsal horn and dorsal root ganglia were evaluated by Western blot and immunofluorescent staining, respectively. Suberoylanilide hydroxamic acid (SAHA), a clinically used HDAC inhibitor, was then intraperitoneally and intrathecally injected to rescue the increased expression levels of HDAC1 and HDAC2. The analgesic effects of SAHA administration on BCP were then evaluated by measuring the paw withdrawal thresholds (PWTs). The effects of SAHA on activation of glial cells and expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) in the spinal dorsal horn and dorsal root ganglia of TCI rats were further evaluated by immunofluorescent staining and Western blot analysis. Subsequently, the effects of SAHA administration on tumor growth and cancer cell-induced bone destruction were analyzed by hematoxylin and eosin (HE) staining and micro-CT scanning.

Results
TCI caused rapid and long-lasting increased expression of HDAC1/HDAC2 in glial cells of the spinal dorsal horn and dorsal root ganglia. Inhibiting HDACs by SAHA not only reversed TCI-induced upregulation of HDACs but also inhibited the activation of glial cells in the spinal dorsal horn and dorsal root ganglia, and relieved TCI-induced mechanical allodynia. Further, we found that SAHA administration could not prevent cancer infiltration or bone destruction in the tibia, which indicated that the analgesic effects of SAHA were not due to its anti-tumor effects. Moreover, we found that SAHA administration could inhibit GSK3β activity in the spinal dorsal horn and dorsal root ganglia, which might contributed to the relief of BCP.

Conclusion
Our findings suggest that HDAC1 and HDAC2 are involved in the glia-mediated neuroinflammation in the spinal dorsal horn and dorsal root ganglia underlying the pathogenesis of BCP, which indicated that inhibiting HDACs by SAHA might be a potential strategy for pain relief of BCP.
Mouse connective tissue mast cell proteases tryptase and carboxypeptidase A3 play protective roles in itch induced by endothelin-1
Authors: Magnúsdóttir Elín I. , Grujic Mirjana , Bergman Jessica , Pejler Gunnar , Lagerström Malin C. 
Published: April 2020

Abstract
Background
Itch is an unpleasant sensation that can be debilitating, especially if it is chronic and of non-histaminergic origin, as treatment options are limited. Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor that also has the ability to induce a burning, non-histaminergic pruritus when exogenously administered, by activating the endothelin A receptor (ETAR) on primary afferents. ET-1 is released endogenously by several cell-types found in the skin, including macrophages and keratinocytes. Mast cells express ETARs and can thereby be degranulated by ET-1, and mast cell proteases chymase and carboxypeptidase A3 (CPA3) are known to either generate or degrade ET-1, respectively, suggesting a role for mast cell proteases in the regulation of ET-1-induced itch. The mouse mast cell proteases (mMCPs) mMCP4 (chymase), mMCP6 (tryptase), and CPA3 are found in connective tissue type mast cells and are the closest functional homologs to human mast cell proteases, but little is known about their role in endothelin-induced itch.

Methods
In this study, we evaluated the effects of mast cell protease deficiency on scratching behavior induced by ET-1. To investigate this, mMCP knock-out and transgenic mice were injected intradermally with ET-1 and their scratching behavior was recorded and analyzed.

Results
CPA3-deficient mice and mice lacking all three proteases demonstrated highly elevated levels of scratching behavior compared with wild-type controls. A modest increase in the number of scratching bouts was also seen in mMCP6-deficient mice, while mMCP4-deficiency did not have any effect.

Conclusion
Altogether, these findings identify a prominent role for the mast cell proteases, in particular CPA3, in the protection against itch induced by ET-1.
Sex-dependent effects of ambient PM2.5 pollution on insulin sensitivity and hepatic lipid metabolism in mice
Authors: Li Ran , Sun Qing , Lam Sin Man , Chen Rucheng , Zhu Junyao , Gu Weijia , Zhang Lu , Tian He , Zhang Kezhong , Chen Lung-Chi , Sun Qinghua , Shui Guanghou , Liu Cuiqing 
Published: April 2020

Abstract
Background & aims
Emerging evidence supports ambient fine particulate matter (PM2.5) exposure is associated with insulin resistance (IR) and hepatic lipid accumulation. In this study, we aimed to evaluate the sex-dependent vulnerability in response to PM2.5 exposure and investigate the underlying mechanism by which PM2.5 modulates hepatic lipid metabolism.

Methods
Both male and female C57BL/6 mice were randomly assigned to ambient PM2.5 or filtered air for 24 weeks via a whole body exposure system. High-coverage quantitative lipidomics approaches and liquid chromatography-mass spectrometry techniques were performed to measure hepatic metabolites and hormones in plasma. Metabolic studies, histological analyses, as well as gene expression levels and molecular signal transduction analysis were applied to examine the effects and mechanisms by which PM2.5 exposure-induced metabolic disorder.

Results
Female mice were more susceptible than their male counterparts to ambient PM2.5 exposure-induced IR and hepatic lipid accumulation. The hepatic lipid profile was changed in response to ambient PM2.5 exposure. Levels of hepatic triacylglycerols (TAGs), free fatty acids (FFAs) and cholesterol were only increased in female mice from PM group compared to control group. Plasmalogens were dysregulated in the liver from PM2.5-exposed mice as well. In addition, exposure to PM2.5 led to enhanced hepatic ApoB and microsomal triglyceride transport protein expression in female mice. Finally, PM2.5 exposure inhibited hypothalamus-pituitary-adrenal (HPA) axis and decreased glucocorticoids levels, which may contribute to the vulnerability in PM2.5-induced metabolic dysfunction.

Conclusions
Ambient PM2.5 exposure inhibited HPA axis and demonstrated sex-associated differences in its effects on IR and disorder of hepatic lipid metabolism. These findings provide new mechanistic evidence of hormone regulation in air pollution-mediated metabolic abnormalities of lipids and more personalized care should be considered in terms of sex-specific risk factors.
Inverted urothelial papilloma of the upper urinary tract: description of two cases with systematic literature review
Authors: Santi R. , Galli I. C. , Canzonieri V. , Lopez J. I. , Nesi G. 
Published: April 2020

Abstract
Background
Inverted urothelial papilloma (IUP) of the upper urinary tract is an uncommon benign tumour that occasionally presents as a polypoid mass causing urinary obstruction. Histologically, IUP is characterised by a proliferating urothelium arranged in cords and trabeculae, in continuity with overlying intact epithelium, and extending into the lamina propria in a non-invasive, endophytic manner. Cytological atypia is minimal or absent. Top differential diagnoses include urothelial carcinoma with inverted growth pattern and florid ureteritis cystica. Although urothelial carcinomas of the upper urinary tract with prominent inverted growth pattern commonly harbour microsatellite instability, the role of the mutator phenotype pathway in IUP development is still unclear. The aim of this study was to describe two additional cases of IUP of the upper urinary tract, along with an extensive literature review.

Case presentation
We observed two polypoid tumours originating in the renal pelvis and the distal ureter, respectively. Both patients, a 76-year-old woman and a 56-year-old man, underwent surgery because of the increased likelihood of malignancy. Histology was consistent with IUP and patients are alive and asymptomatic after long-term follow-up (6 years for the renal pelvis lesion and 5 years for the ureter lesion). The tumours retained the expression of the mismatch-repair protein MLH1, MSH2, and PMS2 whereas loss of MSH6 was found in both cases.

Conclusions
When completely resected, IUP does not require rigorous surveillance protocols, such as those for urothelial carcinoma and exophytic urothelial papilloma. It is therefore important for the surgical pathologist to be aware of this rare entity in order to ensure correct patient management.