bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progestins counteract estrogens to shift breast cancer cells into a quiescent metabolic profile
Authors: Matthews Shawna , Fettig Lynsey M. , Ward Ashley V. , Finlay-Schultz Jessica , Kabos Peter , Jackman Matthew , MacLean Paul S. , Sartorius Carol A. 
Published: February 2020

Abstract

Background

Progestins generally suppress the growth of estrogen receptor (ER) and progesterone receptor (PR) positive breast cancers and are occasionally used as treatments. However, progestins also increase populations of therapy-resistant cancer stem cells. We speculated that the downstream effects of progestins on cell metabolism might help explain its unusual impact on cell phenotype. Thus, in this study we investigated how progestins, in the absence or presence of estrogens, affect cell metabolism in ER+PR+ breast cancer.

Methods

Metabolites were quantified and compared from ER+PR+ breast cancer cell lines T47D and UCD65 treated with vehicle, estrogen only, progestin only, or the combination using ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS). Metabolic flux analysis was performed on cells given the same hormone treatments. Likewise, the influence of treatments on mitochondrial morphology was measured using transmission electron microscopy in cell lines and patient-derived xenograft tumors and mitochondrial-targeted GFP in cell lines. Mitochondrial biogenesis was measured via fluorescence shift in the photoconvertible MitoTimer reporter coupled with confocal microscopy, and biogenesis regulators were measured by qPCR. Select metabolites and ATP were measured using fluorometric assays.

Results

Estrogen plus progestin treatment largely reverses estrogen-stimulated metabolic activities in breast cancer cells including increased TCA cycle metabolites, amino acid metabolism, and glutathione metabolism. Addition of progestins to estrogen impaired mitochondrial oxygen consumption and ATP production of cancer cells. Moreover, while estrogen-treated cells had elongated mitochondrial morphology, progestin co-treatment resulted in a more aged and less elongated mitochondrial population. Notably, progestins blocked the estrogen-induced expression of mitochondrial biogenesis regulators PGC1α and PGC1β and their downstream targets. While progestin treatment reduced total intracellular amino acid and glutathione pools, a subpopulation of progestin-inducible cancer stem cells revealed a dependence on glutathione.

Conclusions

These findings indicate that progestins antagonize estrogen’s effects on cellular metabolism and shift cells to a more quiescent phenotype, with reduced mitochondrial functional capacity, more reliance on glycolysis, and increased cell survival traits. Our results have implications for current clinical studies testing selective PR modulators in ER+ breast cancers.
Assessment of dynamic balancing responses following perturbations during slow walking in relation to clinical outcome measures for high-functioning post-stroke subjects
Authors: Zadravec Matjaž , Olenšek Andrej , Rudolf Marko , Bizovičar Nataša , Goljar Nika , Matjacic Zlatko 
Published: February 2020

Abstract
Background: Generating appropriate balancing reactions in response to unexpected loss of balance during walking is important to prevent falls. The purpose of this study was to assess dynamic balancing responses following pushes to the pelvis in groups of post-stroke and healthy subjects. Methods: Forty-one post-stroke subjects and forty-three healthy subjects participated in the study. Dynamic balancing responses to perturbations triggered at heel strike of the left or right leg, directed in the forward, backward, inward and outward directions during slow treadmill walking were assessed. Responses of the healthy group provided reference values used to classify responses of the post-stroke group into two subgroups; one within the reference responses (“inside” subgroup) and the other that falls out (“outside” subgroup). A battery of selected clinical outcome measures (6-Minute Walk Test, 10-Meter Walk Test, Timed-Up-and-Go test, Four Square Step Test, Functional Gait Assessment, Functional Independence Measure and One-legged stance test) was assessed for the post-stroke group to examine whether any of these outcome measures could discriminate between both subgroups. Results: Both subgroups of stroke subjects were comparable in terms of clinical outcome measures but their capacity to react to unexpected loss of balance during walking differed considerably. The “inside” subgroup was able to appropriately modulate centre-of-pressure and ground-reaction-force both under the impaired and non-impaired leg. The “outside” subgroup showed limited modulation capacity under the impaired leg; their responses utilised a stepping strategy in which the non-impaired leg was placed such as to make a longer step (forward perturbation), to make a shorter step (backward perturbation) or to make a cross-step (outward perturbation). Consequently, peak centre-of-mass displacements following perturbations were significantly higher in the “outside” subgroup compared to the “inside” subgroup. Responses in both subgroups following inward perturbations did not differ considerably. One-legged stance test showed the largest potential to discriminate between both subgroups of stroke subjects. Conclusions: The One-legged stance test could be used to obtain an indication of the abilities of each particular post-stroke subject to counteract an unexpected loss of balance. This may be relevant in clinical practice for the identification of post-stroke subjects who could benefit from perturbation-based training.
Distribution of 31 endocrine disrupting compounds in the Taihu Lake and application of the fish plasma model
Authors: Bao Yifan , Huang Wenping , Xialin Hu , Yin Daqiang 
Published: February 2020

Abstract
Background: The successful application of Fish plasma model (FPM) will greatly simplify the risk assessment of drugs. At present, the FPM has been applied to the risk assessment of several human drugs with high hydrophobicity. However, its applicability to a wide variety of compounds needs to be tested. Filed work about distribution characteristics of endocrine disrupting compounds (EDCs) in water and in fish plasma plays a key role in promoting the successful application of FPM. However, there are few reports on the distribution of EDCs in fish, especially in wild fish plasma. Results: The distribution of 31 EDCs, including seven estrogens, eight androgens, six progesterones, five glucocorticoids and five industrial compounds, in water and in plasma of five categories of wild fishes in Taihu Lake was studied and the typical FPM was tested by the field data. The detected concentration of most compounds is relatively low (< 10 ng/L), and the industrial compounds are the predominant pollutants with the highest concentration up to 291.7 ng/L (Bisphenol A) in water. In general, glucocorticoids were detected at highest concentrations in plasma of all kinds of fishes, followed by industrial compounds and estrogens. Except for glucocorticoids (up to 43.61 for Cortisone), the average concentrations of other four categories of EDCs in fish plasma were generally low (< 10 μ g / L). The available measured bioaccumulation factors (BAFs) of 20 kinds of EDCs were in the range of 0 to 5626. The bioaccumulation of EDCs in fish plasma is not only hydrophobicity dependent, and it is both fish species-specific and compound-dependent. The classical FPM was tested and the results indicated that the good coincide of measured logBAFs and the theoretical logBCFs was only observed for limited EDCs (7 out of 20). The present available FPM generally underestimated the LogBAFs of most hydrophilic EDCs (logKow <3.87, 11 out of 20) whereas overestimated the LogBAFs of several high hydrophobic EDCs (LogKow >3.87) in fish plasma. Conclusion：Although the present FPM is barely satisfactory, it is still promising for predicating the accumulation of EDCs in fish plasma and for further environmental risk assessment.
Cost-effectiveness of a proportionate universal offer of free exercise: Leeds Let’s Get Active
Authors: Candio Paolo , Meads David , Hill Andrew J. , Bojke Laura 
Published: February 2020

Abstract
Objectives To assess the cost-effectiveness of a proportionate universal programme to reduce physical inactivity (Leeds Let’s Get Active) in adults. Methods A continuous-time Markov chain model was developed to assess the cost implications and QALY gains associated with increases in physical activity levels across the adult population. An ordered logistic model was specified to estimate the effectiveness of the Leeds Let’s Get Active programme and derive transition probabilities between physical activity categories. A parametric survival analysis approach was applied to estimate the decay of intervention effect over time. Baseline model data were obtained from previous economic models, population-based surveys and other published literature. A cost-utility analysis was conducted from a health care sector perspective over the programme duration (39 months). Scenario and probabilistic sensitivity analyses were performed to test the robustness of cost-effectiveness results. Results 51,874 adult residents registered to the programme and provided baseline data, 19.5% of which were living in deprived areas. Under base case assumptions, Leeds Let’s Get Active was found to be likely to be cost-effective. However, variations in key structural assumptions showed sensitivity of the results. Conclusions Evidence from this study suggests that a universal offer of access to free off-peak leisure centre-based exercise that targets hard to reach groups can provide good value for money. Further data collection is needed to reduce the uncertainty surrounding the decision.
Plasmonic random laser biosensor on fiber facet for label-free detecting biomolecules
Authors: Shi Xiaoyu , Ge Kun , Tong Junhua , Zhai Tianrui 
Published: February 2020

Abstract
Low-cost and miniaturized biosensors are key factors leading to the possibility of portable and integrated biomedical system, which play an important role in clinical medicine and life sciences. Random lasers with simple structures provide opportunities for detecting biomolecules. Here, a low-cost biosensors on fiber facet for label-free detecting biomolecules is demonstrated resorting to plasmonic random laser. The random laser is achieved resorting to a random plasmonic scattering structure of Ag nanoparticles and polymer film on fiber facet. Refractive index sensitivity and near-surface sensitivity of the biosensor are systematically studied. Furthermore, the biosensor is used to detect lgG through specific binding to protein A , exhibiting the detecting limit of 0.68 nM. It is believed that this work may promote the applications of plasmonic random laser bio-probe in portable or integrated medical diagnostic platforms, and provide fundamental understanding for the life science.
Coagulopathy on the first postoperative day predicting the long-term survival of traumatic brain injury patients
Authors: Cui Wenxing , Ge Shunnan , Shi Yingwu , Wu Xun , Luo Jianing , Feng Dayun , Zhu Gang , Wang Bao , Guo Hao , Liu Haixiao , Qu Yan 
Published: February 2020

Abstract
Objective: The purpose of this study was to identify the relationship between coagulopathy during the perioperative period (before the operation and on the first day after the operation) and the long-term survival of TBI patients undergoing surgery, as well as to explore the predisposing risk factors that may cause perioperative coagulopathy.Methods: This retrospective study included 447 TBI patients who underwent surgery from January 1, 2015 to April 25, 2019. Clinical parameters, including patient demographic characteristics, biochemical tests, perioperative coagulation function tests (before the operation and on the first day after the operation) and intraoperative factors were collected. Log-rank univariate analysis and Cox regression models were conducted to assess the relationship between perioperative coagulopathy and the long-term survival of TBI patients. Furthermore, univariate and multivariate analyses were performed to identify the underlying risk factors for perioperative coagulopathy.Results: Multivariate Cox regression analysis identified age, AIS(head) = 5, GCS ≤ 8, systolic pressure at admission < 90 mmHg and postoperative coagulopathy (all P < 0.05) as independent risk factors for survival following TBI; we were the first to identify postoperative coagulopathy as an independent risk factor. According to multivariate logistic regression analysis, for the first time, abnormal ALT and RBC at admission, preoperative coagulopathy, infusion of colloidal solution > 1100 mL and intraoperative bleeding > 950 mL (all P < 0.005) were identified as independent risk factors for postoperative coagulation following surgery after TBI.Conclusions: Those who suffered from postoperative coagulopathy due to TBI had a higher hazard for poor prognosis than those who did not. Closer attention should be paid to postoperative coagulopathy and more emphasis should be placed on managing the underlying risk factors.
The Impact of Intervention on Survival of Elderly Patients with Gastric Cancer at IV Stage: A SEER Population-Based Study.
Authors: Cao Bo , Liang Wenquan , Zhang Wang , Wang Chuang , Shi Yajiao , Zhou Xin , Wei Bo 
Published: February 2020

Abstract
Background The selection of therapeutic regimens for elderly patients with gastric cancer (GC) has attracted much attention. However, few clinical trials have been conducted concerning the subpopulation of patients diagnosed with stage IV disease. In this study, cases from the Surveillance, Epidemiologic and End Results (SEER) database were collected to investigate the effects of surgery and chemotherapy (CT) on the survival benefit in elderly GC patients with stage IV disease. Methods GC patients aged >65 years diagnosed with stage IV disease between 1973 and 2014 in the SEER database were included in the study pool based on strict inclusion and exclusion criteria. Univariate and multivariate analyses were employed to determine prognostic factors for overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier survival analysis was conducted to investigate the effects of different intervention methods on OS and CSS. Results A total of 9,306 patients were selected from the SEER database. The results showed that patients who received both surgery and chemotherapy significantly obtained OS and CSS benefits (P < 0.0001). Compared with the no surgery and CT group, the CT alone group (P < 0.0001) and the surgery alone group (P < 0.0001) had prolonged survival time. Furthermore, age and grade stratifications served as important indicators for the selection of therapeutic regimens Conclusions Surgery combined with CT outperformed monotherapy or no therapy strategies for elderly patients with stage IV disease.
FluA-p score: a novel prediction rule for mortality in influenza A-related pneumonia patients
Authors: Chen Liang , Han Xiudi , Li YanLi , Zhang Chunxiao , Xing Xiqian 
Published: February 2020

Abstract
Background The pneumonia severity index (PSI) and the CURB-65 (confusion, urea, respiratory rate, blood pressure, age ≥ 65 years) score have been shown to predict mortality in community-acquired pneumonia. Their ability to predict influenza-related pneumonia, however, is less well-established. Methods A total of 693 laboratory-confirmed FluA-p patients diagnosed between Jan 2013 and Dec 2018 and recruited from five teaching hospitals in China were included in the study. The sample included 494 patients in the derivation cohort and 199 patients in the validation cohort. The prediction rule was established based on independent risk factors for 30-day mortality in FluA-p patients from the derivation cohort. Results The 30-day mortality of FluA-p patients was 19.6% (136/693). The FluA-p score was based on a multivariate logistic regression model designed to predict mortality. Results indicated the following significant predictors (regression statistics and point contributions toward total score in parentheses): blood urea nitrogen > 7 mmol/L ( OR 1.604, 95% CI 1.150-4.492, p = 0.040; 1 points), pO 2 /F i O 2 ≤ 250 mmHg ( OR 2.649, 95% CI 1.103-5.142, p = 0.022; 2 points), cardiovascular disease ( OR 3.967, 95% CI 1.269-7.322, p <0.001; 3 points), arterial PH < 7.35 ( OR 3.959, 95% CI 1.393-7.332, p < 0.001; 3 points), smoking history ( OR 5.176, 95% CI 2.604-11.838, p = 0.001; 4 points), lymphocytes < 0.8×10 9 /L ( OR 8.391, 95% CI 3.271-16.212, p <0.001; 5 points), and early neurominidase inhibitor therapy ( OR 0.567, 95% CI 0.202-0.833, p = 0.005; -2 points). Seven points was used as the cut-off value for mortality risk stratification. The model showed a sensitivity of 0.941, a specificity of 0.762, and overall better predictive performance than the PSI risk class (AUROC = 0.908 vs 0.560, p < 0.001) and the CURB-65 score (AUROC = 0.908 vs 0.777, p < 0.001). Conclusions Our results showed that a FluA-p score was easy to derive and that it served as a reliable prediction rule for 30-day mortality in FluA-p patients. The score could also effectively stratify FluA-p patients into relevant risk categories and thereby help treatment providers to make more rational clinical decisions.
LOXL1 modulates the malignant progression of colorectal cancer by inhibiting the transcriptional activity of YAP
Authors: Hu Lin , Wang Jing , Wang Yunliang , Wu Linpeng , Wu Chao , Mao Bo , E. Maruthi Prasad , Wang Yuhong , Chin Y. Eugene 
Published: February 2020

Abstract
Background LOX-like 1 (LOXL1), as a lysyl oxidase, emerging evidences revealed the effect in cancer malignant progression. However, its role in colorectal cancer (CRC) and the underlying molecular mechanisms have not yet been elucidated. Methods LOXL1 expression in colorectal cancer was detected by immunohistochemistry, western blot and real-time PCR. In vitro , colony formation assay, wound healing assay, migration and invasion experiment were performed to investigate the effects of LOXL1 in cell proliferation, migration and invasion, respectively. In vivo , metastasis models and mouse xenograft were used to determine tumorigenicity and metastasis ability. Molecular biology experiments were utilized to reveal the underlying mechanisms of LOXL1 modulating Hippo pathway. Results LOXL1 is highly expressed in normal colon tissues compared with cancer tissues. In vitro, Silencing LOXL1 in CRC cell lines dramatically enhanced migration, invasion, and colony formation, while overexpression of LOXL1 manifested the opposite effects. Results of the in vivo experiments demonstrated that the enforced expression of LOXL1 in CRC cell lines had drastically inhibited the progression of metastasis and tumour growth. Mechanistically, LOXL1 inhibited the transcriptional activity of Yes-associated protein (YAP) was through interaction with MST1/2 and increasing the phosphorylation of MST1/2. Conclusions LOXL1 may function as an important tumour suppressor in regulating tumour growth, invasion and metastasis via negative regulating of YAP activity.
The association between dietary total antioxidant capacity and glioma among Iranian adults
Authors: Heydari Marzieh , Shayanfar Mehdi , Sharifi Giuve , Saneei Parvane , Sadeghi Omid , Esmaillzadeh Ahmad 
Published: February 2020

Abstract
Background: Dietary total antioxidant capacity (TAC) has been investigated in relation to different types of cancer. However, data on the link between dietary TAC and glioma are scarce and conflicting. We assessed the relation between dietary TAC and risk of glioma among Iranian adults.
Methods: This investigation was a hospital-based case-control study that was done in Tehran between November 2009 and September 2011. Cases were individuals with pathologically confirmed glioma that were diagnosed during the last month (n=128). Controls were individuals, aged between 20 and 75 years, who were hospitalized or were outpatients referred to other wards of the same hospitals (n=256). Usual dietary intakes of participants during the preceding year were examined using a food frequency questionnaire. Data on dietary TAC from foods was gathered from published databases that provided the antioxidant capacity for each food item, measured by ferric reducing antioxidant power (FRAP).
Results: Mean age of study participants in case and control groups was 43.4 and 42.7 y, respectively. Compared with participants in the lowest quartile, those in the highest quartile of dietary TAC had a lower odds of glioma (OR: 0.28, 95% CI: 0.15-0.45). This association was strengthened when potential confounders were taken into account (OR: 0.13; 95% CI: 0.05-0.35). Such inverse association was also seen for men (OR: 0.05, 95% CI: 0.01-0.19), but not for women. Furthermore, significant inverse associations were seen between dietary intakes of vitamin C (OR for Q4 vs. Q1: 0.14, 95% CI: 0.05-0.36; P-trend<0.01), vitamin B6 (OR for Q4 vs. Q1: 0.35, 95% CI: 0.13-0.97; P-trend=0.02) and β-carotene (OR for Q3 vs. Q1: 0.43, 95% CI: 0.19-0.98; P-trend=0.57) and glioma, after controlling for potential covariates. Conclusion: We found that dietary TAC as well as dietary intake of vitamin C, vitamin B6 and β-carotene was inversely associated with odds of glioma in Iranian adults.
Indicators of a healthy dietary pattern among adolescents -A cross-sectional study from 2009 until 2015
Authors: Tell Maria Norburg , Hedin Katarina , Nilsson Mats , Golsäter Marie , Lingfors Hans 
Published: February 2020

Abstract
BackgroundDietary pattern early in life is to some degree preserved into adulthood and may have implications for future health. There is scarce knowledge on associations between choices of certain foods among adolescents. The aim of this study was to explore how intakes of different food groups, correspond to each other from a health perspective among adolescents. MethodsThis cross-sectional study used data from 16-year-olds (n=13 451), who completed a health questionnaire within School Health Services from 2009 until 2015, in a county from Southern Sweden. Dietary pattern based on the response-alternatives from the ten items regarding intake of food and food frequency intake were grouped as healthy, moderately healthy, and unhealthy intakes, based on Nordic Nutrition Recommendations. ResultsIn the student cohort healthy reported intakes of different healthy food groups were closely connected to each other. Association between intakes of certain food groups were seen. High intake of fish, vegetables and fruit were associated to each other, as well as low intake of sweet drinks, sweets and snacks. The highest association was seen between high intake of fruit and high intake of vegetables, with OR=23 (95% CI 12 to 44).ConclusionHealthy food intakes were associated with each other among 16-year-old adolescents; High intake of fruit and vegetables could serve as a key indicator for a healthy dietary pattern in this age group. This knowledge increases the understanding of food patterns among adolescents and can be used for designing interventions. It also raises a hypothesis that focusing on offering healthy foods, more than restricting unhealthy foods could have a positive impact on the dietary pattern.