bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transient Responses of the Hepatic Lipidome to Acute Exercise Bouts in Mice
Authors: Henderson Gregory C , Tenorio Valeria P Martinez , Tuazon Marc A 
Published: August 2020

Abstract
BACKGROUND: The content of triacylglycerol (TAG) in the liver is known to rapidly increase after a single bout of exercise followed by recovery to sedentary levels. The response of other hepatic lipids, and acyl chain composition of lipid classes, would provide a deeper understanding of the response of hepatic lipid metabolism to acute exercise. METHODS: Female mice performed a single bout of continuous exercise (CE), high-intensity interval exercise (HIIE), or no exercise (CON). The total content of various lipids in the liver, and fatty acids within lipid classes, were measured in tissues collected 3 hours after exercise (Day 1) and the day following exercise (Day 2). RESULTS: The total concentration of TAG rose on Day 1 after exercise (P < 0.05), with a greater elevation in HIIE than CE (P < 0.05), followed by a decline toward CON levels on Day 2. The total concentration of other measured lipid classes was not significantly altered by exercise. However, n-6 polyunsaturated fatty acid relative abundance in diacylglycerol (DAG) was increased by HIIE (P < 0.05). In CON liver, TAG content was positively correlated with DAG and phosphatidylethanolamine (P < 0.05), while these statistical associations were disrupted in exercised mice on Day 1. CONCLUSIONS: Overall, the results characterize flexibility of the hepatic TAG pool size in the liver, and the relationship between TAG and other lipid abundances is altered during the transient TAG pool expansion after exercise. The transient expansion of the hepatic TAG pool and remodeling of the DAG pool may be fundamental components of the physiological response to intense exercise.
LncRNA CASC2 Plays an Indicative Role in Diagnosing Bladder Cancer
Authors: Zi Hao , Tao Wen-Lin , Gao Lei , Yu Zhao-Hua , Bai Xiao-Dong , Li Xiao-Dong 
Published: August 2020

Abstract
Background: Bladder cancer is a common cancer of urinary system, with high incidence and mortality. LncRNA CASC2 as a tumor suppressor has been reported to be involved in many human tumors. In this study, we aimed to explore the diagnostic value of CASC2 for bladder cancer patients.Methods: qRT-PCR was used to detect the expression level of CASC2 in 140 bladder cancer patients and 90 healthy volunteers. The differences of CASC2 expression between the cancer group and healthy group were analyzed using student’s t test. The correlation of CASC2 expression with clinical characteristics of the bladder cancer patients was estimated with Chi-square test. In addition, ROC curve was plotted to evaluate the diagnostic value of CASC2 for bladder cancer patients.Results: Serum CASC2 level was lower in bladder cancer patients than that in healthy group (P<0.05). The expression level of CASC2 was significantly associated with histological grade (P=0.000), TNM stage (P=0.000), and lymph node metastasis (P=0.001). The area under the ROC curve (AUC) was 0.864 and the optimal cutoff value was 0.955, suggesting the diagnostic value of CASC2 for bladder cancer. The diagnostic sensitivity was 77.8% and specificity was 85.7%.Conclusion: CASC2 may be a novel biomarker for early diagnosis of bladder cancer.
Chemotherapy Sensitizing Effects of Methadone in Glioblastoma Cells Are Drug- and Cell Line-dependent
Authors: Haas Bodo , Ciftcioglu Janine , Jermar Sanja , Weickhardt Sandra , Eckstein Niels , Kaina Bernd 
Published: August 2020

Abstract
Background

D,L-methadone (MET), an analgesic drug used for pain treatment and opiate addiction has achieved attention from oncologist and social media as possible chemosensitizing agent in glioblastoma multiforme (GBM) treatment. MET has been reported to enhance doxorubicin-induced cytotoxicity in GBM cells via activation of the µ-opioid receptor (MOR) and subsequent apoptosis induction. Here, we further aimed at quantifying MET effects in comparison to other opioids alone and in combination with doxorubicin and clinically more relevant temozolomide (TMZ) in a set of GBM cell lines and primary GBM cells.
Methods

MOR expression in GBM cells was investigated by immunofluorescence and immunoblotting. Resistance to drugs alone or in combination was assessed by MTT assays. Concentration effect curves were fitted to data points by nonlinear regression analysis and IC50 values were calculated. Apoptotic rates were determined by Annexin V staining.
Results

We found that MET alone was cytotoxic to GBM cells at high micromolar concentrations in MTT assays by induction of apoptosis and necrosis while morphine and oxycodone were hardly cytotoxic. Naloxone was not able to block MET-induced cytotoxicity, indicating that cell death inducing effects of MET are not MOR dependent. We recorded doxorubicin and TMZ concentration response curves by MTT assays in combination with fixed MET concentrations. MET only enhanced doxorubicin cytotoxicity in one cell line and in part in primary cells at certain MET concentrations. MET was not effective in sensitizing cells towards TMZ. Contrarily, in two cell lines MET even decreased sensitivity towards TMZ.
Conclusions

MET can be considered cytotoxic to GBM cells only at clinically not relevant concentrations by induction of apoptosis and necrosis. Sensitizing effects are only observed in combination with doxorubicin but not with TMZ and are highly dependent on cell line and applied drug concentrations.
Adherence to Veterinary Recommendations for Ectoparasiticides Purchased by Cat Owners in the United States.
Authors: Lavan Robert Philip , Armstrong Rob , Normile Dorothy , Vaala Wendy 
Published: August 2020

Abstract
Background: Safe and effective flea and tick treatment options for cats are important in companion animal practice because of feline ectoparasite infestation prevalence and the potential for parasitic disease transmission. Retrospective cat owner purchasing transactions at U.S. veterinary clinics were obtained for three topical feline flea and tick ectoparasiticides. One medication, fluralaner, had a 12-week redosing interval, while two other medications were approved for monthly redosing. The annual number of doses purchased by cat owners was determined for each of the three medications and then compared between medications. The objective was to evaluate whether 12-week retreatment intervals resulted in a different duration of coverage compared to monthly treatments for ectoparasiticide products. Methods: Study results were obtained by analyzing the transactional records from a commercial database derived from veterinary practice management software. The study database consisted of cat owner purchasing records from January 2017 through June 2019 from 671 veterinary practices representing approximately 46,700 cats.Results: Cat owners purchased an average of 1.5 doses of fluralaner per year which, based on a 12-week redosing interval, provides 4.2 months of treatment coverage. Cat owners who used monthly flea and tick medications purchased 3.6 months (fipronil combination) and 2.8 months (imidacloprid combination) annually of each of the two medications. Average yearly cat owner purchases of fluralaner provide a longer duration of coverage than for cat owners purchasing fipronil combination (17% more) or imidacloprid combination (50% more). Conclusion: Cat owners who obtained a flea and tick treatment with a 12-week redosing interval (fluralaner) protected their cats for up to 50% longer duration each year compared to the duration of protection obtained by cat owners who used a medication re-dosed monthly. Cat owners should increase their duration of flea and tick coverage to come closer to achieving veterinary recommendations.
Comparing Surgical and Conservative Treatment on Achilles Tendon Rupture: A Comprehensive Meta-Analysis of RCTs
Authors: She Guorong , Teng Qiang , Li Jieruo , Zheng Xiaofei , Chen Lin , Hou Huige 
Published: August 2020

Abstract
Background Achilles tendon is the strongest tendon in human and frequently injured mainly in young to middle age active population. Increasing incidence of Achilles tendon rupture (ATR) is still reported in several studies. Surgical repair and conservative treatment are two major management strategy widely adopted in ATR patients but the consensus of optimal treatment strategy is still debated. We aimed at fully reviewing the ATR topic with additional assessments and performed a most comprehensive meta-analysis of randomized controlled trials (RCTs).Method We comprehensively searched database of PubMed, Embase, Cochrane and ClinicalTrial.gov and retrieved all randomized controlled trials comparing surgical and conservative treatment on achilles tendon rupture for further analysis. Data extraction was performed by two independent reviewer and random effect model was adopted when I2 > 50%, with data presentation of risk ratio, risk difference or mean difference and 95% confidence interval. Results A total of 13 randomized control trials were included in this meta-analysis. Significant difference was observed in events of re-rupture, complication rate, adhesion to underlying tendon, sural nerve injury and superficial infection. For surgical treatment, significant reduction in re-rupture rate could be observed while complication rate was higher compared with conservative treatment. Conclusion Surgical treatment was revealed significance in reduction of re-rupture rate but associated with higher complication rate while conservative treatment showed similar outcomes with lower complication rate. Collectively, we recommend conservative treatment if patients’ status and expectation are suitable, but surgeon as well as physician’s discretion is also important in decision making.
The Whole Cell Proteome-based Study on The Mechanism of Apoptosis Induced by Soybean Agglutinin on IPEC-J2
Authors: Pan Li , Liu Yan , Farouk Mohammed Hamdy , Bao Nan , Zhao Yuan , Sun Hui , Qin Guixin 
Published: August 2020

Abstract
Background: Soybean agglutinin (SBA), a major anti-nutritional factor in soybean, may induce abnormal health and metabolism of intestinal cells, resulting in the reduction of the production performance of animals. The anti-nutritional mechanisms of SBA are not fully understood, in terms of the cell life activities and metabolism of intestinal cells. This research aims to find the effects of SBA on the cell cycle, apoptosis and proteomic, and furtherly to get more findings for verifying the mechanism of SBA anti-nutritional characters.Methods: The IPEC-J2 cell line was cultured with the medium containing 0.0, 0.5 or 2.0 mg/mL SBA, respectively, for 24 h. The percentage of the cells at different cell cycle phases (G0/G1 phase, S phase and G2 phase) and cell apoptosis rates were measured with flow cytometry. The expressions of Cyclin D1, active p21, Bcl-2, and Bax were determined by western blotting. The activity of caspase-3 (Casp-3) and caspase-9 (Casp-9) were tested with ELISA. The whole-cell quantitative proteome were detected by TMT/iTRAQ Labeling, HPLC fractionation and LC-MS/MS Analysis. The functions and characteristics of the differential expressed proteins in the proteome results were analyzed from the aspects of GO annotation and KEGG pathway. The relationship between the results of proteomics and apoptosis or cell cycle were analyzed and discussed.Results: The percentage of the cells at G0/G1 phase, cell apoptosis rates, expressions of Bax and p21, and the activities of Casp-3 and Casp-9 were increased, cyclin D1 and Bcl-2 expression were declined with the increased of the SBA treatment levels (p<0.05). The proteomic measurements showed that a numbers of differentially expressed proteins, caused by SBA treatment, were mainly enriched in the DNA replication, base excision repair, nucleus excision repair, mismatch repair, ubiquitin-mediated proteolysis pathway, cell structural-proteins, and structures and functions of mitochondria. Moreover, the differential expressed proteins enriched in AMP-activated protein kinase (AMPK) pathway and the process of synthesis and metabolism of proteins were only found in 2.0 mg/mL SBA treatment.Conclusion: The results of this experiment demonstrated that cell cycle arrest and apoptosis induced by SBA may be resulted from the downregulating the expression of the proteins related to DNA replication and repair, protein translation, signal-conducting relation, cell structure, and subcellular structure and function.
Lack of Cross-resistance Between Non-steroidal and Steroidal Aromatase Inhibitors in Breast Cancer Patients: The Potential Role of the Adipokine Leptin.
Authors: Bahrami Nazli , Jabeen Shakila , Sauer Torill , Ødegård Hilde Presterud , Geisler Stephanie Beate , Gravdehaug Berit , Reitsma Laurens Cornelus , Selsås Knut , Kristensen Vessela , Geisler Jürgen 
Published: August 2020

Abstract
Background: The aromatase inactivator exemestane may cause clinical disease stabilization following progression on non-steroidal aromatase inhibitors like letrozole in patients with metastatic breast cancer, indicating that additional therapeutic effects, not necessarily related to estrogen-suppression, may be involved in this well-known “lack of cross-resistance”. Experimental design: Postmenopausal women with ER positive, HER-2 negative, locally advanced breast cancer were enrolled in the NEOLETEXE-trial and randomized to sequential treatment starting with either letrozole (2.5 mg o.d.) or exemestane (25 mg o.d.) followed by the alternative aromatase inhibitor. Serum levels of 54 cytokines, including 12 adipokines were assessed using the Luminex xMAP technology (multiple ELISA). Results: Serum levels of leptin were significantly decreased during treatment with exemestane (p < 0.001), regardless whether exemestane was given as first or second neoadjuvant therapy. In contrast, letrozole caused a non-significant increase in serum leptin levels in vivo. Conclusions: Our findings suggest an additional and direct effect of exemestane on CYP-19 (aromatase) synthesis presumably due to effects on the CYP19 promoter use that is not present during therapy with non-steroidal aromatase inhibitors. Our findings provide a reasonable explanation for the clinically observed lack of cross-resistance between nonsteroidal and steroidal aromatase inhibitors in breast cancer patients.Trial registration: registered on March 23rd. 2015 in the National trial database of Norway (Registration number: REK-SØ-84-2015).
A rapid review of the impact of COVID-19 on the mental health of health and social care workers: implications for psychological interventions
Authors: De Kock Johannes H. , Latham Helen Ann , Leslie Stephen J , Grindle Mark , Munoz Sarah-Anne , Ellis Liz , Polson Rob , O’Malley Christopher M 
Published: August 2020

Abstract
BackgroundHealth and social care workers (HSCWs) have carried a heavy burden during the COVID-19 crisis and in the challenge to control the virus have directly faced its consequences. Supporting their psychological wellbeing continues therefore to be a priority. This rapid review was carried out to identify whether there are any identifiable risk factors for adverse mental health outcomes amongst HSCWs during the COVID-19 crisis. The review also sought to identify a participant population for the trial of a digital intervention to support HSCW’s psychological wellbeing during the pandemic. MethodsWe undertook a rapid review of the literature following guidelines by the WHO and the COVID-19 Cochrane Collaboration’s recommendations. We searched across 14 databases, executing the search at two different time points. We included published observational and experimental studies that reported the psychological effects on health and care workers during the COVID-19 pandemic. ResultsThe 24 studies included in this review reported data predominantly from China (18 out of 24 included studies) and most sampled urban hospital staff. Our study indicates that COVID-19 has a considerable impact on the psychological wellbeing of front line hospital staff. Results suggest that nurses may be at higher risk of adverse mental health outcomes during this pandemic, but no studies compare this group with the social care or primary care workforce. Other risk factors identified were underlying organic illness, gender (female), concern about family, fear of infection, lack of personal protective equipment (PPE) and close contact with COVID-19. Resilience was identified as a factor protecting against adverse mental health outcomes. ConclusionsThe evidence to date suggests that female nurses with close contact with COVID-19 patients may have the most to gain from psychological interventions. However, inconsistencies in findings and a lack of data outside of hospital settings, suggest that we should not exclude any groups when addressing psychological wellbeing in health and social care workers. Psychological interventions aimed at enhancing psychological resilience and utilising innovative methods to personalise treatments without excluding groups may be of benefit.
Emerging of a SARS-CoV-2 viral strain with a deletion in nsp1
Authors: Benedetti Francesca , Snyder Greg , Giovanetti Marta , Angeletti Silvia , Gallo Robert C. , Ciccozzi Massimo , Zella Davide 
Published: August 2020

Abstract
Background:The new Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was ﬁrst detected in Wuhan (China) in December of 2019 is responsible for the current global pandemic.Phylogenetic analysis revealed that it is similar to other betacoronaviruses, such as SARS-CoV and Middle-Eastern Respiratory Syndrome, MERS-CoV. Its genome is ∼30 kb in length and contains two large overlapping polyproteins, ORF1a and ORF1ab that encode for several structural and non-structural proteins. The non-structural protein 1 (nsp1) is arguably the most important pathogenic determinant, and previous studies on SARS-CoV indicate that it is both involved in viral replication and hampering the innate immune system response. Detailed experiments of site-specific mutagenesis and in vitro reconstitution studies determined that the mechanisms of action are mediated by i) the presence of specific amino acid residues of nsp1 and b) the interaction between the protein and the host’s small ribosomal unit. In fact, substitution of certain amino acids resulted in reduction of its negative effects.Methods: A total of 17928 genome sequences were obtained from the GISAID database (December 2019 to July 2020) from patients infected by SARS-CoV-2 from different areas around the world. Genomes alignment was performed using MAFFT (REFF) and the nsp1 genomic regions were identified using BioEdit and verified using BLAST. Nsp1 protein of SARS-CoV-2 with and without deletion have been subsequently modelled using I-TASSER.Results: We identified SARS-CoV-2 genome sequences, from several Countries, carrying a previously unknown deletion of 9 nucleotides in position 686-694, corresponding to the AA position 241-243 (KSF). This deletion was found in different geographical areas. Structural prediction modelling suggests an effect on the C-terminal tail structure.Conclusions: Modelling analysis of a newly identified deletion of 3 amino acids (KSF) of SARS-CoV-2 nsp1 suggests that this deletion could affect the structure of the C-terminal region of the protein, important for regulation of viral replication and negative effect on host’s gene expression. In addition, substitution of the two amino acids (KS) from nsp1 of SARS-CoV was previously reported to revert loss of interferon-alpha expression. The deletion that we describe indicates that SARS-CoV-2 is undergoing profound genomic changes. It is important to: i) confirm the spreading of this particular viral strain, and potentially of strains with other deletions in the nsp1 protein, both in the population of asymptomatic and pauci-symptomatic subjects, and ii) correlate these changes in nsp1 with potential decreased viral pathogenicity.
&nbsp;On Classification of the Earth's Crust Areas by the Level of Geodynamic Threat
Authors: Batugin Andrian 
Published: August 2020

Abstract
It is accepted as a well-known fact that a similar anthropogenic impact on the Earth's crust in different places causes dissimilar response. Seismic zoning maps are not designed to predict such geodynamic hazards as rock bursts, induced earthquakes, reactivation of tectonic faults, etc., and require careful adjustment in places of intense impact on the subsurface strata. In this regard, we consider the classification of the Earth's crust areas according to the degree of geodynamic hazard, i.e. its potential geodynamic response to anthropogenic intervention. This classification is based on the concept that there exists a critically stressed layer within the Earth’s crust. It is believed that such critically stressed layer within the Earth’s crust extends from the Earth's surface to a certain depth, which at each point depends on the nature of the interaction between crustal blocks of different hierarchical levels.From this perspective, anthropogenic impact, such as mining operations, represents a direct impact upon the critically stressed zone. The hypothesis is accepted that the thicker is the critical stressed rock layer, the stronger might be the response to anthropogenic intervention, as it has more accumulated energy. Four categorized of the geodynamic threat were found and mapped. To verify this classification, the manifestations of the geodynamic hazards were studied. The intensity of geodynamic hazard increases from the 1st area to the 4th area. The phenomenon of large induced seismic events with hypocenters at great depths is explained by the base of this idea and could be associated with anthropogenic impacts from the surface directly on the regional zone of the critical stressed rock massif. The approach can be used to assess the geodynamic consequences of human exposure to the Earth's crust.
Maternal Folic Acid Impacts DNA Methylation Profile in Male Rat Offspring Associated With Neurodevelopment and Learning/Memory Abilities
Authors: Wang Xinyan , Li Zhenshu , Zhu Yun , Yan Jing , Liu Huan , Huang Guowei , Li Wen 
Published: August 2020

Abstract
Background: Periconceptional folic acid (FA) supplementation not only reduces the incidence of neural tube defects, but also improves cognitive performances in offspring. However, the genes or pathways that are epigenetically regulated by FA in neurodevelopment were rarely reported. Methods: To elucidate the underlying mechanism, the effect of FA on the methylation profiles in brain tissue of male rat offspring was assessed by methylated DNA immunoprecipitation chip. Differentially methylated genes (DMGs) and gene network analysis were identified using DAVID and KEGG pathway analysis. Results: Compared with the FA-N group, 1939 DMGs were identified in the FA-D group, and 1498 DMGs were identified in the FA-S group, among which 298 DMGs were overlapped. The pathways associated with neurodevelopment and learning/memory abilities were differentially methylated in response to maternal FA intake during pregnancy, and there were some identical and distinctive potential mechanisms under FA deficiency or supplemented conditions. Conclusions: In conclusion, genes and pathways associated with neurodevelopment and learning/memory abilities were differentially methylated in male rat offspring in response to maternal FA deficiency or supplementation during pregnancy.