bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epimedokoreanin C, A Prenylated Flavonoid Isolated from Epimedium Koreanum, Induces Non-Apoptotic Cell Death with the Characteristics of Methuosis in Lung Cancer Cells
Authors: Liu Xiaoqing , Wang Shuqi , Zheng Hao , Liu Qingying , Shen Tao , Wang Xiaoning , Ren Dongmei 
Published: September 2020

Abstract
Background: Methuosis is a novel type of non-apoptotic cell death characterized by accumulation of cytoplasmic vacuoles. Identification of molecules that induce methuosis may provide alternative therapeutics for cancers that are refractory to apoptosis. Epimedokoreanin C (EKC) is a prenylated flavonoid isolated from a Chinese herb Epimedium koreanum. Methods: In this study, MTT assay, real-time cell analysis monitoring of cell growth and wound-healing assay were used for cell viability and migration evaluation. Flow cytometry was performed to assess apoptosis. Immunoblot analysis, immunofluorescence, pull-down assays and live cell imaging with fluorescent tracers were utilized to evaluate the regulation of signaling pathways.Results: EKC reduced cell viability accompanied by extreme vacuolation in lung cancer NCI-H292 cells. The EKC-induced cell death was clarified as non-apoptosis based on the absence of apoptotic changes. The vacuoles stimulated by EKC were supposed to be derived from macropinocytosis based on the engulfment of extracellular fluid tracer, Lucifer Yellow. The vacuoles acquired some characteristics of late endosomes supported that EKC-induced cell death could be described as methuosis. Rac1 and Arf6 were found to be regulated inversely after EKC treatment. Blocking Rac1 activation with the specific Rac1 inhibitor EHT 1864 prevented the accumulation of vacuoles induced by EKC markedly, suggested that the regulation of Rac1 and Arf6 was at least partial mechanism involved in EKC induced methuosis. EKC synergized the effects of doxorubicin and etoposide, demonstrating the effectiveness of using EKC to synergize conventional chemotherapy. Conclusions: Collectively, EKC was demonstrated as a methuosis-like cell death inducer in NCI-H292 cells. It has the potential to be used as an attractive prototype for developing drugs that could kill apoptosis-resistant cancer cells.
Serial Assessment of Circulating T lymphocyte Phenotype and Receptor Repertoire During Treatment of Non-Muscle Invasive Bladder Cancer with Adoptive T Cell Immunotherapy
Authors: Wang Xiaoli , Qiao Guoliang , Jiang Ni , Morse Michael A , Zhou Xinna , Wang Shuo , Wu Jiangping , Song Yuguang , Zhao Yanjie , Zhou Lei , Yuan Yanhua , Hobeika Amy , Ren Jun , Lyerly Herbert Kim 
Published: September 2020

Abstract
Background: Recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) are frequent despite intravesical therapy. We hypothesized that administration of an activated T cell immunotherapy (ACT) at times when immunosuppressive populations were noted to have increased in peripheral blood would prevent recurrence of disease.Method: This was an N-of-1 study. A subject with multiple primary bladder high grade urothelial carcinomas who had initially completed standard resection and chemotherapy was enrolled. ACT consisted of dendritic cells mixed with cytokine induced killer cells (DC/CIK)) which were infused intravenously 18 times over a 6 year period in response to observed increases in peripheral blood immunosuppressive CD8+/CD28- cells. Peripheral blood was analyzed for T cell phenotype by flow cytometry, T cell receptor (TCR) repertoire, and circulating tumor DNA (ctDNA) by next generation sequencing (NGS) at the time of each infusion. Standard of care cystoscopy and pelvic CT scans have been performed at routine intervals. Results: The patient’s resected bladder tumors did not express PD-1 or PD-L1. There has been no recurrence of urothelial carcinoma. Peripheral blood cytotoxic T cells and unique TCR clones increased and suppressive T cell populations decreased after DC/CIK infusions. ctDNA detected mutations in six tumor relevant genes (ARID1B, MYCN, CDH23, SETD2, NOTCH4 and FAT1) at baseline but all of them disappeared after the DC-CIK infusions.Conclusion: DC/CIK infusions were associated with beneficial changes in T cell phenotype, TCR repertoire, decreases in circulating tumor DNA and sustained recurrence-free survival.
Protective Effects of Berberine on Rat Model of Polycystic Ovary Syndrome Through the PI3K/AKT Pathway
Authors: Yu Jia , Ding Caifei , Hua Zhoujia , Jiang Xuejuan , Wang Chenye 
Published: September 2020

Abstract
Background: Berberine (Ber), a Chinese herbal monomer has been reported to exhibit an array of pharmacological activities relating to the lowering of blood glucose and the treatment of polycystic ovarian syndrome (PCOS). However, the related mechanism underlying these activites is not clear. In the current study, we aimed to elucidate the effect of Ber on rat model of PCOS by PI3K/AKT signaling pathway.Methods: A letrozole-induced rat PCOS model and primary ovarian granulosa cells model to explore the protective effect and the mechanism of action of Ber. In PCOS rats, the values of fasting blood glucose (FBG) insulin resistance (HOMA-IR), fasting insulin (FINS) values and the serum hormone levels were measured. The ovarian tissues were stained with HE and TUNEL to undergo pathological and apoptosis examination. Moreover, the effect of Ber on proliferation and apoptosis of granulosa cells was detected by CCK-8 and flow cytometry. And then the influence of Ber on granulosa cells was confirmed by blockade of the PI3K/AKT pathway. In addition, the modulatory effect on the expression of related proteins by blockade of PI3K/AKT was demonstrated via western blot.Results: We found that Ber was able to recover the serum hormone levels and improve insulin resistance (IR) in PCOS rat model. The morphological lesion and apoptosis of the ovary was also restored with the Ber treatment. Blockade of the PI3K/AKT pathway attenuated the influences of Ber on proliferation and apoptosis of granulosa cells. Due to this, we discovered a correlation between the PI3K/AKT signaling pathway and the beneficial effects of Ber, demonstrating that its application could alter the expression levels of key proteins in the PI3K/APT pathway.Conclusion: The beneficial effects of Ber on PCOS, including alter serum hormone levels, recover ovary morphological lesions, improve IR, improve cell viability and inhibition of apoptosis, which is mediated through the PI3K/AKT pathway.
Optimal Time Period of Wearing Protective Collar After Anterior Cervical Discectomy and Fusion
Authors: Qian Yu , Yu Zhiwei , Liu Zhenlei , Duan Wanru , Zhao Zhongjing , Zheng Hongyu , Jian Fengzeng 
Published: September 2020

Abstract
Background: There is still no consensus on the time period of wearing collar after anterior cervical discectomy and fusion (ACDF). We aim to investigate the optimal time period of wearing protective collar.Methods: We retrospectively reviewed patients with cervical spondylosis who underwent one to two segment ACDF during January 2016 and December 2017, and included 97 patients who meet inclusion and exclusion criterion. Patients were divided into three groups according to the actual time period of wearing collar after ACDF including 1-4 week group, 5-8 week group, and 9-12 week group. We analyzed Japanese Orthopedic Association (JOA) score, Axial Symptom (AS) score and Neck Disability Index (NDI) before surgery and at post-operative 3 months to investigate the optimal time period of wearing collar.Results: JOA score: All three groups have a better post-operative JOA score compared with that before surgery (paired t test, p<0.05). There is no significant difference among the three groups with respect to post-operative JOA (ANOVA, p>0.05).AS score: The post-operative AS scores of 1-4 week group and 5-8 week group were significantly better than that before surgery (paired t test, p>0.05). While the post-operative AS score of 9-12 week group was significantly worse than preoperative AS score (paired t test, p<0.05).NDI: All three groups have a better post-operative NDI compared with that before surgery (McNemar test, p<0.05). Of note, in 5-8 week group, the percentage of no deficit increased by 45%, and the percentage of mild deficit decreased by 45% accordingly. That percentage is 26% and 31% in 1-4 week group and 9-12 week group, respectively. There was significant difference among these three groups (Fisher's exact probability test, p<0.05)Conclusions: For cervical spondylosis patients who underwent 1-2 segment ACDF, the optimal time period of wearing protective is 5-8 weeks. This time period results in comparable neurological outcome, least axial symptom risk, and highest chance of no deficit on neck function.
Risk of QT Prolongation through Drug-drug Interactions between Hydroxychloroquine and Concomitant Drugs Prescribed in Real-world Practice
Authors: Choi Byung Jin , Koo Yeryung , Kim Tae Young , Chung Wou Young , Jung Yun Jung , Park Ji Eun , Lim Hong-Seok , Park Bumhee , Yoon Dukyong 
Published: September 2020

Abstract
Background: Hydroxychloroquine has recently received attention as a treatment for COVID-19. However, hydroxychloroquine may prolong the QTc interval, thus increasing the risk of life-threatening arrhythmia. Many patients with COVID-19 have comorbidities, necessitating the use of several drugs simultaneously with hydroxychloroquine. However, the risk of QT prolongation due to drug-drug interactions (DDIs) between hydroxychloroquine and these co-medications has not been identified. Therefore, it is necessary to investigate the risk of QT interval prolongation due to DDIs between hydroxychloroquine and frequently used concurrent drugs.Methods and Results: Using 447,632 patients and 1,040,752 electrocardiograms, we investigated the risk of QT prolongation due to DDIs between hydroxychloroquine and 118 concurrent drugs frequently used in real-world practice. In the analysis, we observed that 11 drugs (trimebutine, tacrolimus, tramadol, rosuvastatin, ciclosporin, sulfasalazine, rofecoxib, diltiazem, piperacillin/tazobactam, and isoniazid) show DDIs with hydroxychloroquine in the direction of QT prolongation.Conclusions: We found 11 drugs that show significant (p <0.05) DDIs with hydroxychloroquine, thereby increasing the risk of QT prolongation in patients. It is necessary to consider prescribing alternative drugs that have less DDI when these drugs are concurrently administered with hydroxychloroquine. Further investigation is needed to assess more profoundly the risk of QT prolongation due to DDI with hydroxychloroquine of each drug that we found in this analysis.
Tropospheric carbonyl sulfide mass-balance based on direct measurements of sulfur isotopes
Authors: Davidson Chen , Amrani Alon , Angert Alon 
Published: September 2020

Abstract
Carbonyl sulfide (COS) is the major long-lived sulfur bearing gas in the atmosphere and a promising proxy for terrestrial gross primary production (GPP; CO2 uptake). However, large uncertainties in estimating the relative magnitude of the COS sources and sinks limit this approach. Isotopic measurements have been suggested as a novel tool to constrain COS sources, yet such measurements are currently scarce. Here we present, for the first time, a complete data-based tropospheric COS isotopic mass balance, which allows improved partition of the sources. We found an isotopic (δ34S±SE) value of 13.9±0.1‰ (versus V-CDT standard) for the troposphere, with an isotopic seasonal cycle driven by plant uptake. This seasonality agrees with a fractionation of -1.9±0.3‰ which we measured in plant-chamber experiments. Anthropogenic-influenced air samples indicated an anthropogenic COS isotopic signal of 8±1‰. Samples of seawater-equilibrated-air indicate that marine COS emissions have an isotopic signal of 13±0.4‰. Using our new data-based mass balance, we constrained the relative contribution of the two main tropospheric COS sources resulting in 26±11% for the anthropogenic source and 74±23% for the oceanic source. This constraint is important for a better understanding of the global COS budget and its improved use for GPP determination.
Net Economic Benefits from Shifting Consumption, Labor Elasticity, and Productivity Gains During an Accelerated Renewable Energy Transition in China
Authors: Chen Yidan , Lin Jiang , Roland-Holst David , Wang Can 
Published: September 2020

Abstract
China is the world’s largest greenhouse gas (GHG) emitter, but declining wind and solar energy costs present opportunities to transform its electric power sector. In 2017, China launched a national emission trading scheme (ETS). Evidence to date suggests that the ETS mitigates CO2 emissions and promotes renewable energy deployment but constrains economic growth. These studies, however, do not account comprehensively for economic impacts. Ours is the first to account for three multiplier effects—shifting consumption patterns, job growth with elastic labor supply, and higher total factor productivity (TFP)—when modeling accelerated renewable electricity growth with the ETS in China. Results from a detailed economic forecasting model show low renewable energy costs interacting with the ETS to slash GHG emissions while directly stimulating incremental net positive economic growth by 2030, compared with a business-as-usual scenario that assumes slower renewable cost reductions and no ETS. Accounting for the multiplier effects reveals larger potential benefits, including up to 15.6% of additional GDP growth (over business as usual) by 2030 when shifting consumption patterns, job growth with elastic labor supply, and higher TFP are all considered. These results suggest that China should accelerate its clean energy transition, not only for the air-quality and climate benefits, but also for the broad and positive impact on innovation, employment, and economic growth.
Guided Imagery for Treatment (GIFT): Protocol of a Pilot Trial of Guided Imagery Versus Treatment as Usual to Address Radiotherapy-related Distress in Head and Neck Cancer
Authors: Kolva Elissa , Karam Sana D , Carr Alaina , Roberts Sydneyjane , Torkko Kathleen , Lanning Ryan , Cox-Martin Emily 
Published: September 2020

Abstract
Background: Cancers of the head and neck region are associated with high symptom burden and elevated levels of psychological distress. Radiotherapy (RT) is a common treatment for patients with head and neck cancer (HNC) that is associated with psychological distress related to the immobilizing nature of the treatment, frequency of treatment delivery, and side effects. Guided imagery is a relaxation technique that is beneficial in reducing psychological distress in patients with other cancer diagnoses but has not been studied in this patient population. The purpose of this study is to evaluate the feasibility and acceptability of a brief guided imagery intervention (Guided Imagery for Treatment; GIFT) to reduce RT-related anxiety and depression in patients with HNC relative to treatment as usual (TAU).Methods: Patients with HNC planning to receive RT will be recruited to participate in a randomized controlled trial evaluating a brief, two-session guided imagery intervention (GIFT) relative to TAU alone. Primary aims include acceptability and feasibility evaluated through quantitative and qualitative methods. Measures of anxiety and depression, symptom burden, health-related quality of life, and anxiolytic medication use will be collected at baseline, during treatment, and at one-month follow-up. Discussion: There are no published interventions of guided imagery for anxiety and depression in patients with HNC despite its efficacy in other populations of patients with cancer. This proposed project evaluates the feasibility and acceptability of an intervention that has the potential to reduce psychological distress in a vulnerable population. Additionally, we will preliminarily examine the impact of behavioral intervention on psychological distress and the use of anxiolytic medication, a novel area of study. Trial registration: Clinicaltrials.gov NCT03662698;registered on 9/6/2018. https://clinicaltrials.gov/ct2/show/NCT03662698?term=guided+imagery&cond=Head+and+Neck+Cancer&rank=1
Effects of the Oocyte Maturation Rate on Clinical Outcomes of Conventional IVF&nbsp;and ICSI&nbsp;in Female Patients Aged ≥38 Years
Authors: liu shuang , Yu Hongjun , Li Baoshan , Li Chunyi , Cheng Dongkai 
Published: September 2020

Abstract
Research Question: The average female reproductive potential peaks at age 25 and then begins to decline. As women are delaying childbearing, the prevalence of infertility has risen, leading to increasing demand for assisted reproductive technology (ART). Oocyte quality remains the most important issue during in vitro fertilization (IVF) cycles. This study investigated the effects of the oocyte maturation rate (OMR) on clinical outcomes of conventional IVF and intracytoplasmic sperm injection (ICSI) in female patients aged ≥38 years. Design: A retrospective analysis of 6562 infertile patients who were treated with IVF/ICSI at the reproductive medicine center of our hospital from January 2011 to December 2017 was performed. According to the oocyte maturity (the ratio of the number of mature oocytes to the number of oocytes) on the day of egg collection, the patients were divided into three groups: group A (oocyte maturity ≤30%, n=422), and group B (oocyte maturity from 30-75%, n=1290), and group C (oocyte maturity ≥75%, n=4850). The patient age, years of infertility years, days of gonadotropin (Gn), Gn dosage, serum luteinizing hormone (LH), estradiol (E2), and progesterone (P) levels on the day of human chorionic Gn (HCG) injection, E2 levels per mature oocyte, E2 levels per oocyte, number of mature oocytes, oocyte recovery rate, fertilization rate, cleavage rate, excellent embryo rate, blastocyst formation rate, pregnancy rate, and live birth rate were compared among the three groups. Results: Factors including age, years of infertility, number of eggs obtained, number of mature eggs, normal fertilization rate, cleavage rate, excellent embryo rate, blastocyst formation rate, pregnancy rate, and live birth rate were all found to be related to oocyte maturity on the day of HCG administration (P<0.05). Conclusions: There is a close relationship between oocyte maturity and embryo quality, and a low OMR may be related to a poor ovarian response or decreased sensitivity to Gn. Therefore, a low OMR may affect the fertilization and embryonic development potential in elderly patients undergoing IVF/ICSI, thus affecting the pregnancy rate.
Hsa-miRNA-143-3p Regulates&nbsp;Differentiation of Human Stem Cells From The Apical Papilla Through Targeting Nuclear Factor I-C
Authors: Gao Shuo , Li Pei , Zhao Yuming , Li Yao-yin , Ge Li-Hong , Zhao Wei 
Published: September 2020

Abstract
Background : Dental root development is independent and time-space-specific. Nuclear factor I-C (NFIC) plays a key role in human root development through regulating the differentiation of stem cells from the apical papillary (SCAPs). The function of microRNAs during the differentiation of SCAP and post-transcriptional regulation of NFIC remain unclear. Methods : We examined the microRNA expression profiles in human immature permanent teeth and SCAPs differentiation. hSCAPs were treated with miR-143-3p over/low-expression viruses, and the odonto/osteogenic differentiation of these stem cells and the involvement of NFIC pathway were investigated. Next, luciferase reporter and its mutant plasmids were used to confirm direct target gene of miR-143-3p. Mineralization induction assays ex vivo and in vitro were used to investigate the functional significance of miR-143-3p. Results : MiR-143-3p was screened by microarray expression profiling and bioinformatics technology, which decreased during hSCAPs differentiation. Overexpression of miR-143-3p inhibited the odontogenic differentiation of hSCAPs and downregulated the related genes, whereas the functional inhibition of miR-143-3p yielded the opposite effect. The luciferase reporter gene detection and bioinformatics approach identified NFIC as a potential target of miR-143-3p. Furthermore, NFIC Overexpression reversed the inhibitory effect of miR-143-3p on the odontogenic differentiation of hSCAP. Conclusions : MiR-143-3p maintains the stemness of hSCAPs and negatively modulates their differentiation and mineralization by directly targeting transcription factor NFIC, which serves as an contribution towards a better understanding of the developmental mechanisms of root formation.
The Bacterial Communities of Alaskan Mosses and Their Contributions to N2-Fixation
Authors: Holland-Moritz Hannah , Stuart Julia E. M. , Lewis Lily R. , Miller Samantha N. , Mack Michelle C. , Ponciano Jose Miguel , McDaniel Stuart F. , Fierer Noah 
Published: September 2020

Abstract
Background: Mosses in high latitude ecosystems harbor diverse bacterial taxa, including N2-fixers which are key contributors to nitrogen dynamics in these systems. Yet, the relative importance of moss host species, and environmental factors, in structuring these microbial communities and their N2-fixing potential remains unclear. We studied 26 boreal and tundra moss species across 24 sites in Alaska, USA from 61º to 69º N. We used cultivation-independent approaches to characterize the variation in moss-associated bacterial communities as a function of host species identity and site characteristics. We also measured N2-fixation rates via 15N2 isotopic enrichment and identified potential N2-fixing bacteria using available literature and genomic information. Results: Host species identity and host evolutionary history were both highly predictive of moss microbiome composition, highlighting strong phylogenetic coherence in these microbial communities. Although less important, light availability and temperature also influenced composition of the moss microbiome. Finally, we identified putative N2-fixing bacteria specific to some moss hosts, including potential N2-fixing bacteria outside well-studied cyanobacterial clades. Conclusions: The strong effect of host identity on moss-associated bacterial communities demonstrates mosses’ utility for understanding plant-microbe interactions in non-leguminous systems. Our work also highlights the likely importance of novel bacterial taxa to N2-fixation in high-latitude ecosystems.