bluuebunny/crossref_metadata_2025_split huggingface dataset:
Continuous Endometrial Volumetric Analysis for Endometrial Receptivity Assessment on Assisted Reproductive Technology Cycles
Authors: Martins Renato , Oliani Antonio Helio , Oliani Denise Vaz , de Oliveira Jose Martinez 
Published: August 2020

Abstract
Background: Human implantation is a complex process requiring synchrony between a healthy embryo and a functionally competent or receptive endometrium. In order to assess endometrial receptivity in Assisted Reproductive Technology (ART) cycles serial evaluation of endometrial volumetric analysis may have a predictive value on a positive outcome.Methods: Serial 3D transvaginal ultrasound performed in women on ART cycle to evaluate a pattern that better predicts implantation rates. Prospective case control study of 169 subjects were assessed. Endometrial pattern, thickness, volume and adjusted endometrial volume (ratio between endometrial volume and uterine volume) was performed to all subjects on a continuous process from baseline (prior to ovarian controlled stimulation), day 6, 8 and 10 of controlled ovarian stimulation, trigger day with human chorionic gonadotropin hormone (hCG) and at embryo transfer day.Results: No statistical difference was noted between the two groups in terms of demographics and ART procedures and scores. Endometrial morphology also didn’t show any difference between the two groups. Endometrial volume and adjusted endometrial volume was significantly higher in the positive group as soon as day 6 of ovarian controlled stimulation.Conclusions: Serial 3D endometrial volume and adjusted endometrial volumes may be a useful tool for clinicians in predicting endometrial receptivity enhancing elective embryo transfers in fresh ART cycle, and thus providing a non-invasive continuous technique for endometrial receptivity assessment that reflects endometrial changes during ART procedures.
Analyzing the Impact of a State Concussion Law using an Autoregressive Integrated Moving Average Intervention Analysis
Authors: Huang Lihong , Sullivan Lindsay , Yang Jingzhen (Ginger) 
Published: August 2020

Abstract
Background: Existing studies analyzing the impact of state concussion laws have found an increase in concussion-related medical encounters post-law, in some instances, such increases were observed during the pre-law period due to a potential “spillover” effect. This study assessed the effects of Ohio’s concussion law, while accounting for such a “spillover” effect, on the trends in monthly rates of concussion-related medical encounters in Medicaid insured children using autoregressive integrated moving average (ARIMA) analysis.Methods: We analyzed claim data obtained from the Partners For Kids database, a pediatric accountable care organization in Ohio. Concussion-related medical encounters for Medicaid-insured children (ages 0-18 years) treated between April 1, 2008 to December 31, 2016 were selected and analyzed. We assessed pre- and post-law trends in concussion-related medical encounters using an ARIMA intervention model. We also used traditional regression methods to validate the study results.Results: A total of 16,943 concussion-related medical encounters sustained by 15,545 unique patients were included. Monthly rates of concussion-related medical encounters significantly increased from 4.64 per 10,000 member months during the pre-law period to 6.69 per 10,000 member months in the post-law period (P < 0.0001). Three upward breaks in the monthly rates of concussion-related medical encounters were observed between 2009 and 2016, with two breaks observed during the pre-law period. Specifically, the increased breakpoint observed in July 2011 (P = 0.0186) was significantly associated with an estimated 7.3% increase (95% CI: 1.1-13.7) in the rate of concussion-related medical encounters. This finding was confirmed in the Poisson regression and curve fitting models. Furthermore, a seasonal trend in concussion-related medical encounters was observed with the highest rates in September and October of each year. Conclusions: Two of the three upward breaks identified in the monthly rate of concussion-related medical encounters occurred before the enactment of Ohio’s concussion law, suggesting a potential “spillover” effect. Further research is needed to confirm such an effect in children with other types of medical insurance.
YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells
Authors: Li Jie , Wu Lei , Pei Meili , Zhang Yun 
Published: August 2020

Abstract
RNA methylation can reverse the methylation modification at the RNA level, which is an extremely important epigenetic modification. The function and mechanism of YTHDF2, as a reader of m6A modification, in epithelial ovarian cancer (EOC) have not been elucidated so far. This study aimed to investigate how YTHDF2 and miR-145 modulated EOC progression through m6A modification. It demonstrated that YTHDF2 was significantly upregulated in EOC tissues compared with normal ovarian tissues. Further functional studies confirmed that YTHDF2 significantly promoted the proliferation and migration of EOC cell lines and reduced the global 6-methyladenine (m6A) mRNA levels. Next, the expression levels of miR-145 and YTHDF2 were found to be inversely correlated in ovarian cancer tissues and cells, and YTHDF2 was the direct target gene of miR-145. A crucial crosstalk occurred between miR-145 and YTHDF2 via a double-negative feedback loop. The overexpression of YTHDF2 rescued miR-145-induced reduction of the proliferation and migration of EOC cells. Hence, YTHDF2 and miR-145, as two crucial m6A regulators, were involved in the progression of EOC by indirectly modulating m6A levels. The findings of this study on YTHDF2 and miR-145 might provide new insights into carcinogenesis and new potential therapeutic targets for EOC.
Gamma-aminobutyric acid (GABA) alleviates salt damage in tomato by modulating Na+ uptake, the GAD gene, amino acid synthesis and reactive oxygen species metabolism
Authors: Wu Xiaolei , Jia Qiuying , Ji Shengxin , Gong Binbin , Li Jingrui , Lv Guiyun , Gao Hongbo 
Published: August 2020

Abstract
Background: Salt stress is a serious abiotic stress that caused crop growth inhibition and yield decline. Previous studies have reported on the the synthesis of gamma-aminobutyric acid (GABA) and its relationship with plant resistance under various abiotic stress. However, the relationship between exogenous GABA alleviating plant salt stress damage and ion flux, amino acid synthesis, and key enzyme expression remains largely unclear. We investigated plant growth, Na+ transportation and accumulation, reactive oxygen species (ROS) metabolism and evaluated the effect of GABA on amino acids especially SlGADs gene expression and the endogenous GABA content of tomato (Solanum lycopersicum L.) seedlings treated with or without 5 mmol·L-1 GABA under 175 mmol·L-1 NaCl stress. Results: Exogenous application of GABA significantly reduced the salt damage index and increased plant height, chlorophyll content and the dry and fresh weights of tomato plants exposed to NaCl stress. GABA significantly reduced Na+ accumulation in leaves and roots by preventing Na+ influx in roots and transportation to leaves. The transcriptional expression of SlGAD1-3 genes were induced by NaCl stress especially with GABA application. Among them, SlGAD1 expression was the most sensitive and contributed the most to the increase in glutamic acid decarboxylase (GAD) activity induced by NaCl and GABA application; Exogenous GABA increased GAD activity and amino acid contents in tomato leaves compared with the levels under NaCl stress alone, especially the levels of endogenous GABA, proline, glutamate and eight other amino acids. These results indicated that SlGADs transcriptional expression played an important role in tomato plant resistance to NaCl stress with GABA application by enhancing GAD activity and amino acid content. GABA significantly alleviated the active oxygen-related injury of leaves under NaCl stress by increasing the activities of antioxidant enzymes and decreasing the contents of active oxygen species and malondialdehyde.Conclusion: Exogenous GABA had a positive effect on the resistance of tomato seedlings to salt stress, which was closely associated with reducing Na+ flux from root to leaves, increasing amino acid content and strengthening antioxidant metabolism. Endogenous GABA content was induced by salt and exogenous GABA at both the transcriptional and metabolic levels.
Expression of in vivo biotinylated recombinant antigens SAG1 and SAG2A from Toxoplasma gondii for improved seroepidemiological bead-based multiplex assays
Authors: Klein Sandra , Stern Daniel , Seeber Frank 
Published: August 2020

Abstract
BACKGROUND Few bead-based multiplex assays have been described that detect antibodies against the protozoan parasite Toxoplasma gondii in large-scale seroepidemiological surveys. Moreover, each multiplex assay has specific variations or limitations, such as the use of truncated or fusion proteins as antigens, potentially masking important epitopes. Consequently, such an assay must be developed by interested groups as none are commercially available.RESULTS We report the bacterial expression and use of N-terminal fusion-free, soluble, in vivo biotinylated recombinant surface antigens SAG1 and SAG2A for the detection of anti-T. gondii IgG antibodies. The expression system relies on three compatible plasmids. An expression construct produces a fusion of maltose-binding protein with SAG1 (or SAG2A), separated by a TEV protease cleavage site, followed by a peptide sequence recognized by E. coli biotin ligase BirA (AviTag), and a terminal six histidine tag for affinity purification. TEV protease and BirA are encoded on a second plasmid, and their expression leads to proteolytic cleavage of the fusion protein and a single biotinylated lysine within the AviTag by BirA. Correct folding of the parasite proteins is dependent on proper disulfide bonding, which is facilitated by a sulfhydryl oxidase and a protein disulfide isomerase, encoded on the third plasmid. The C-terminal biotinylation allowed the oriented, reproducible coupling of the purified surface antigens to magnetic Luminex beads, requiring only minute amounts of protein per determination. We showed that an N-terminal fusion partner such as maltose-binding protein negatively influenced antibody binding, confirming that access to SAG1’s N-terminal epitopes is important for antibody recognition. We validated our bead-based multiplex assay with human sera previously tested with commercial diagnostic assays and found concordance of 98-100% regarding both, sensitivity and specificity, even when only biotinylated SAG1 was used as antigen. CONCLUSIONS Our recombinant in vivo-biotinylated T. gondii antigens offer distinct advantages compared to previously described proteins used in multiplex serological assays for T. gondii. They offer a cheap, specific and sensitive alternative to either parasite lysates or eukaryotic-cell expressed SAG1/SAG2A for BBMA and other formats. The described general expression strategy can also be used for other antigens where oriented immobilization is key for sensitive recognition by antibodies.
Genetic risk-factors for anxiety in healthy individuals: polymorphisms in genes important for the HPA axis
Authors: Lindholm Heléne , Morrison India , Krettek Alexandra , Malm Dan , Novembre Giovanni , Handlin Linda 
Published: August 2020

Abstract
Background: Two important aspects for the development of anxiety disorders are genetic predisposition and alterations in the hypothalamic-pituitary-adrenal (HPA) axis. In order to identify genetic risk-factors for anxiety, the aim of this exploratory study was to investigate possible relationships between genetic polymorphisms in genes important for the regulation and activity of the HPA axis and self-assessed anxiety in healthy individuals.Methods: DNA from 72 healthy participants, 37 women and 35 men, were included in the analyses. Their DNA was extracted and analysed for the following Single Nucleotide Polymorphisms (SNP)s: rs41423247 in the NR3C1 gene, rs1360780 in the FKBP5 gene, rs53576 in the OXTR gene, 5-HTTLPR in SLC6A4 gene and rs6295 in the HTR1A gene. Self-assessed anxiety was measured by the State and Trait Anxiety Inventory (STAI) questionnaire.Results: Self-assessed measure of both STAI-S and STAI-T were significantly higher in female than in male participants (p=0.030 and p=0.036, respectively). For SNP rs41423247 in the gene NR3C1, there was a significant difference in females in the score for STAI-S, where carriers of the G allele had higher scores compared to the females that were homozygous for the C allele (p<0.01). For the SNP rs53576 in the gene OXTR, there was a significant difference in males, where carriers of the A allele had higher scores in STAI-T compared to the males that were homozygous for the G allele (p<0.01). Conclusion: This study shows that SNP rs41423247 in the NR3C1gene and SNP rs53576 in the OXTR gene are associated with self-assessed anxiety in healthy individuals in a gender-specific manner. This suggests that these SNP candidates are possible genetic risk-factors for anxiety.
Urban heat resilience at the time of global warming: evaluating the impact of the urban parks on outdoor thermal comfort
Authors: Aram Farshid , Solgi Ebrahim , García Ester Higueras , Mosavi Amir 
Published: August 2020

Abstract
Background: In densely populated urban centers, increased air temperature due to urban heat island (UHI) effect can undermine the thermal comfort and health of citizens. Research has shown that large urban parks can mitigate the effect of UHIs and improve thermal comfort, especially in the warmer months of the year when temperature changes are more noticeable. This study investigated the cooling effect intensity (CEI) of the Retiro Park in the center of Madrid at three different distances from its southern edge and the impact of this cooling effect on thermal comfort from physiological and psychological perspectives. This investigation was performed by measuring microclimate data and conducting a survey simultaneously during the summer days. Results: The results showed that the CEI of the park varies with distance from its edge. Because of this effect, air temperature within the 130m and 280m distance of the park was respectively 1.6°C and 0.9°C lower than the temperature at the 520m distance (the nearest heat island). After examining the effect of the park in terms of Physiological Equivalent Temperature (PET), it was found that the PET at the 130m and 280m distance of the park was 9.3% and 5.4% less than the PET in the heat island domain. More than 81% of the respondents (in all three areas) had a mental image of the park as the place where they would experience the highest level of outdoor thermal comfort, and this rate was higher in the areas closer to the park. The analysis of citizens’ responses about perceived thermal comfort (PTC) showed that citizens in areas with higher CEI had perceived a higher degree of thermal comfort from the psychological perspective.Conclusion: This study demonstrates the significant role of large urban parks located in the core of the populated cities in providing thermal comfort for citizens from both physiological and psychological perspectives. Additionally, the results of this study demonstrated that among the environmental (natural and artificial) factors around the park (topography, urban structure, etc.), the aspect ratio has the greatest impact on thermal comfort.
T-cell lymphoma with a granulomatous lesion of the lungs after autologous hematopoietic stem cell transplantation for Epstein–Barr virus-positive diffuse large B-cell lymphoma: a unique rare case of metachronous B-cell and T-cell lymphoma
Authors: Kajimoto Yusuke , Terasaki Yasuhiro , Terasaki Mika , Kunugi Shinobu , Okabe Yugo , Wakita Satoshi , Inokuchi Koiti , Shimizu Akira 
Published: August 2020

Abstract
Background: Epstein–Barr virus (EBV) is associated with the pathogenesis of a variety of malignancies, most notably lymphomas. Especially in the background of immunodeficiency, such as primary immunodeficiency disorder (PID) and post-transplant lymphoproliferative disorder (PTLD), the role of EBV might be crucial. PIDs are rare heterogeneous diseases affecting the development and/or the function of the innate and adaptive immune system. Malignancy is the second-highest cause of death after infection, and lymphoma accounts for about half of malignancies. The most frequently reported lymphoma type is diffuse large B-cell lymphoma (DLBCL) and the incidence of T-cell lymphoma is rare. PTLDs are also rare serious lymphoid and/or plasmacytic proliferation disorders that occur after undergoing solid organ or hematopoietic stem cell transplantation (HSCT). In the context of HSCT, most reported PTLDs have occurred in patients who received allogenic HSCT, but only a few cases have been reported in autologous HSCT (AutoHSCT) recipients.Case presentation: A 53-year-old female patient initially presented with enlargement of the left cervical lymph nodes and was diagnosed with EBV-positive DLBCL. She was treated with R-CHOP, R-ACES, and AutoHSCT and went into remission. Four years later, computed tomography results revealed multiple lung nodules and abnormal infiltration, and sustained and progressing hypogammaglobulinemia was observed. The pathological specimen of video-assisted thoracoscopic surgical lung biopsy demonstrated extensive invasion of lymphocytes with notable granuloma findings. Flow cytometric immunophenotyping analysis showed that lymphocytes were positive for CD3 and CD5; especially, CD3 was expressed in the cytoplasm. Southern blot analysis revealed rearrangements of the T-cell receptor Cb1 gene. She was diagnosed with peripheral T-cell lymphoma, not otherwise specified, accompanied by notable granulomatous lesions.Conclusion: Here, as a unique case of metachronous B-cell and T-cell lymphoma, we report a rare case of T-cell lymphoma that mainly affected the lungs with the presentation of notable granulomatous findings following AutoHSCT for EBV-positive DLBCL at the age of 53 years. These lung lesions of granulomatous T-cell lymphoma could be related to the underlying primary immunodeficiency background associated with sustained hypogammaglobulinemia.
Epigenetic Immunomodulatory effect of Eugenol and Astaxanthin on Doxorubicin Cytotoxicity in Hormonal Positive Breast Cancer Cells
Authors: Fouad Mariam A. , Sayed-Ahmed Mohamed M. , Huwait Etimad A. , Hafez Hafez F. , Osman Abdel-Moneim 
Published: August 2020

Abstract
Background: Hormonal receptor positive (HR+) breast cancer is the most commonly diagnosed molecular subtype of breast cancer; which showed good response to doxorubicin (DOX)-based chemotherapy. Eugenol (EUG) and astaxanthin (AST) are natural compounds with proved epigenetic and immunomodulatory effects in several cancer cell lines. This study has been initiated to improve the cytotoxic activity and reduce resistance of DOX through combination with EUG and AST in MCF7 cells.Methods: Cytotoxic activity of DOX alone and combined with either 1mM EUG or 40µM AST was performed using sulphorhodamine-B assay in MCF7 cells. Global histones acetylation and some immunological markers were investigated using ELISA, western blotting and quantitative RT-PCR techniques. Functional assay of multidrug resistance was performed using rhodamine 123 and Hoechst 3342 dyes. Flow cytometry with annexin V and propidium iodide were used to assess the change in cell cycle and apoptosis along with the expression of some differentiation, apoptosis and autophagy proteins. Results: DOX alone resulted in concentration-dependent cytotoxicity with IC50 of 0.5 μM. Both EUG and AST significantly increased DOX cytotoxicity which is manifested as a significant decrease in DOX IC50 from 0.5 μM to 0.088 μM with EUG and to 0.06 μM with AST. Combinations of DOX with 1mM EUG or 40 µM AST significantly increased the level of histones acetylation and histone acetyl transferase expression, while reduced the expression of aromatase and epidermal growth factor receptor (EGFR) when compared with 0.25 µM DOX alone. Also both combinations showed higher uptake of rhodamine but lower of Hoechst stains, along with increased the percentage of caspase 3, and decreased the expression of CK7 and LC3BI/II ratio. EUG combination induced IFγ but reduced TNFα causing shifting of cells from G2/M to S and G0/ G1 phases. Combination of DOX with EUG induced apoptosis through the higher BAX/ BCl2 ratio, while with AST was through the increase in caspase 8 expressions. Conclusion: EUG and AST potentiated the anticancer activity of DOX through epigenetic histones acetylation along with the immunonomodulation of different apoptotic approaches in MCF7 cells.
Effectiveness of a mobile phone application to increase access to sexual and reproductive health information, goods, and services among university students in Uganda: A randomized controlled trial
Authors: Nuwamanya Elly , Nalwanga Robinah , Nuwasiima Afra , Babigumira Janet U. , Asiimwe Francis T. , Babigumira Joseph B. , Ngambouk Vitalis P. 
Published: August 2020

Abstract
Background: University students are one of the most vulnerable groups to sexual reproductive health [SRH] threats like sexually transmitted infections [STIs], unwanted pregnancies, and unsafe abortions and often have limited access to SRH information, goods, and services. This study assessed the effectiveness of using a mobile phone application (APP) to increase access to SRH information, goods, and services among university students in Uganda.Methods: Using data from a double-blinded randomized controlled trial, participants were randomly assigned to both the intervention (APP) and control (standard of care) arms. We executed descriptive analyses for baseline demographic characteristics by intervention, difference in difference (DID), and quantile regression analyses for both primary and secondary outcomes.Results: The median age of participants was 21 years of age, and the majority were female (over 60%), unemployed (over 85%) and Christian (90%). Over 50% were resident in off-campus hostels and in a relationship. Between baseline and end-line, there was a significant increase in SRH knowledge score (DID=2, P<0.001), contraceptive use (DID=6.6%, P<0.001), HIV Voluntary testing and counselling (DID=17.2%, P<0.001), STI diagnosis and treatment (DID=12.9%, P<0.001), and condom use at last sex (DID=4%,P=0.02) among students who used the APP. There was a significant 0.98 unit increase in knowledge score (adjusted coefficient= 0.98, P<0.001), a significant 1.6-fold increase in odds of contraceptive use (adjusted coefficient= 1.6, P=0.04), a significant 3.5-fold increase in HIV VCT (adjusted coefficient=3.5, P<0.001), and a significant 2-fold increase in odds of STI testing and treatment (adjusted coefficient =1.9, P<0.001) after adjusting for demographic characteristics among APP users.Conclusion: A mobile phone application increased sexual and reproductive health information (knowledge score), access to goods (contraceptives), and services (HIV voluntary testing and counseling and sexually transmitted infection diagnosis and management) among sexually active university students in Uganda. Further technical development, including the refinement of youth-friendly attributes, as well as further research into potential economic impact and paths to sustainability, is needed before the app is deployed to the general youth population in Uganda and other low-income settings.Trial registration: MUREC1/7 No. 07/05–18. Registered on June 29, 2018.