bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of COPD and anemia on motor and cognitive performance in the general older population: results from the English longitudinal study of ageing
Authors: Padberg Inken , Schneider Alice , Rohmann Jessica Lee , Kelley Sean Walter , Grittner Ulrike , Siegerink Bob 
Published: February 2020

Abstract
Background
Cognitive and motor-performance decline with age and the process is accelerated by decline in general health. In this study, we aimed to estimate the effects of COPD and HB levels on cognitive and motor performance in the general older population and assess potential interaction.

Methods
The English Longitudinal Study of Aging is a population-based cohort study including measurements of lung-function and HB levels together with cognitive and motor performance testing. Data were collected from 5709 participants including three measurement time over eight years. COPD was defined using lung-function-parameters and clinical symptoms. HB was assessed continuously and low HB was defined using clinical anemia cutoffs. Linear mixed-effects regression models were used to quantify the associations of COPD and HB with outcome measures, both individually and in combination.

Results
Participants with both low HB and COPD demonstrated worse motor performance compared to individuals with only one exposure, resulting in up to 1 s (95%CI, 0.04–1.8) longer time needed to complete the five times sit to stand task than what would be expected based on purely additive effects. Additionally in individuals with COPD, the time to complete the motor-performance task per unit decrease in continuous HB levels was longer than in participants without COPD after full adjustment for confounding (up to 1.38 s/unit HB level, 95% CI: 0.65–2.11).

Conclusion
In persons with COPD low HB levels may contribute to low motor-performance in a supra additive fashion. Further studies should re-evaluate whether earlier treatment of lower HB in these individuals might be beneficial.
Positive effect of dapagliflozin on left ventricular longitudinal function for type 2 diabetic mellitus patients with chronic heart failure
Authors: Tanaka Hidekazu , Soga Fumitaka , Tatsumi Kazuhiro , Mochizuki Yasuhide , Sano Hiroyuki , Toki Hiromi , Matsumoto Kensuke , Shite Junya , Takaoka Hideyuki , Doi Tomofumi , Hirata Ken-ichi 
Published: February 2020

Abstract
Background
The effect of sodium glucose cotransporter type 2 (SGLT2) inhibitor on left ventricular (LV) longitudinal myocardial function in type 2 diabetes mellitus (T2DM) patients with heart failure (HF) has remained unclear.

Methods
We analyzed data from our previous prospective multicenter study, in which we investigated the effect of the SGLT2 inhibitor dapagliflozin on LV diastolic functional parameters of T2DM patients with stable HF at five institutions in Japan. Echocardiography was performed at baseline and 6 months after administration of dapagliflozin. LV diastolic function was defined as the ratio of mitral inflow E to mitral e′ annular velocities (E/e′). LV longitudinal myocardial function was assessed as global longitudinal strain (GLS), which in turn was determined as the averaged peak longitudinal strain from standard LV apical views.

Results
E/e′ significantly decreased from 9.3 to 8.5 cm/s 6 months after administration of dapagliflozin (p = 0.020) as previously described, while GLS showed significant improvement from 15.5 ± 3.5% to 16.9 ± 4.1% (p < 0.01) 6 months after administration of dapagliflozin. Furthermore, improvement of GLS in HF with preserved ejection fraction patients was more significant from 17.0 ± 1.9% to 18.7 ± 2.0% (p < 0.001), compared to that in HF with mid-range ejection fraction and HF with reduced ejection fraction patients from 14.4 ± 2.4% to 15.5 ± 1.8% (p = 0.06) and from 8.1 ± 1.5% to 7.8 ± 2.1% (p = 0.44), respectively. It was noteworthy that multiple regression analysis showed that the change in GLS after administration of dapagliflozin was the only independent determinant parameters for the change in E/e′ after administration of dapagliflozin.

Conclusion
Dapagliflozin was found to be associated with improvement of LV longitudinal myocardial function, which led to further improvement of LV diastolic function of T2DM patients with stable HF. GLS-guided management may thus lead to improved management of T2DM patients with stable HF.
Redesign and reconstruction of a steviol-biosynthetic pathway for enhanced production of steviol in Escherichia coli
Authors: Moon Jun Ho , Lee Kunjoong , Lee Jun Ho , Lee Pyung Cheon 
Published: February 2020

Abstract
Background
Steviol glycosides such as stevioside have attracted the attention of the food and beverage industry. Recently, efforts were made to produce these natural sweeteners in microorganisms using metabolic engineering. Nonetheless, the steviol titer is relatively low in metabolically engineered microorganisms, and therefore a steviol-biosynthetic pathway in heterologous microorganisms needs to be metabolically optimized. The purpose of this study was to redesign and reconstruct a steviol-biosynthetic pathway via synthetic-biology approaches in order to overproduce steviol in Escherichia coli.

Results
A genome-engineered E. coli strain, which coexpressed 5′ untranslated region (UTR)-engineered geranylgeranyl diphosphate synthase, copalyl diphosphate synthase, and kaurene synthase, produced 623.6 ± 3.0 mg/L ent-kaurene in batch fermentation. Overexpression of 5′-UTR–engineered, N-terminally modified kaurene oxidase of Arabidopsis thaliana yielded 41.4 ± 5 mg/L ent-kaurenoic acid. Enhanced ent-kaurenoic acid production (50.7 ± 9.8 mg/L) was achieved by increasing the cellular NADPH/NADP+ ratio. The expression of a fusion protein, UtrCYP714A2-AtCPR2 derived from A. thaliana, where trCYP714A2 was 5′-UTR–engineered and N-terminally modified, gave 38.4 ± 1.7 mg/L steviol in batch fermentation.

Conclusions
5′-UTR engineering, the fusion protein approach, and redox balancing improved the steviol titer in flask fermentation and bioreactor fermentation. The expression engineering of steviol-biosynthetic enzymes and the genome engineering described here can serve as the basis for producing terpenoids—including steviol glycosides and carotenoids—in microorganisms.
CircZDHHC20 represses the proliferation, migration and invasion in trophoblast cells by miR-144/GRHL2 axis
Authors: Zhou Bing , Zhang Xia , Li Ting , Xie Rongping , Zhou Jianbin , Luo Yu , Yang Chunfen 
Published: February 2020

Abstract
Background
Preeclampsia (PE) is a prevalent pregnancy disorder that has been one of the leading causes of maternal and perinatal mortality worldwide. Circular RNAs (circRNAs) have recently considered as important regulators in PE pathogenesis. In the current study, we aimed to explore the impact and mechanisms of circRNA zinc finger DHHC-type palmitoyltransferase 20 (circZDHHC20) in PE pathogenesis.

Methods
RNase R assay and reverse transcription with Oligo(dT)18 primers were performed to confirm that circZDHHC20 was indeed circular transcript. The expression of circZDHHC20, grainyhead-like 2 (GRHL2) and miR-144 were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Subcellular localization assay was used to determine whether circZDHHC20 was predominantly present in the cytoplasm. The target correlations between miR-144 and circZDHHC20 or GRHL2 were confirmed using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell proliferation, migration, and invasion were detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetr-azolium (MTS), wound healing and transwell assays, respectively. Western blot was used for the quantification of GRHL2 protein level.

Results
Our data indicated that circZDHHC20 was up-regulated and miR-144 was down-regulated in PE placenta. CircZDHHC20 sequestered miR-144 by acting as a miR-144 sponge. CircZDHHC20 overexpression repressed trophoblast cell proliferation, migration, and invasion, while its knockdown exerted opposite effects. Moreover, miR-144 mediated the regulation of circZDHHC20 on trophoblast cell behaviors. GRHL2 was directly targeted and inhibited by miR-144. MiR-144 exerted regulatory effects on trophoblast cell proliferation, migration and invasion by GRHL2. Furthermore, circZDHHC20 modulated GRHL2 expression through sponging miR-144.

Conclusion
Our study suggested that a high level of circZDHHC20 inhibited the proliferation, migration, and invasion in trophoblast cells at least partially through sponging miR-144 and up-regulating GRHL2, providing a novel mechanism of PE pathogenesis.
Knockdown of lncRNA SNHG16 suppresses multiple myeloma cell proliferation by sponging miR-342-3p
Authors: Yang Xi , Huang Hongming , Wang Xinfeng , Liu Haiyan , Liu Hong , Lin Zenghua 
Published: February 2020

Abstract
Background
Aberrant expression of long non-coding RNAs (lncRNAs) is closely associated with development and prognosis of human cancers. LncRNA SNHG16 is reportedly involved in human cancer; however, its roles in multiple myeloma (MM) remain unclear.

Methods
In this study, we investigated the function and molecular mechanisms of SNHG16 in MM. MM cells were transfected with si-SNHG16 or si-NC. SNHG16 expression levels was measured by qRT-PCR. Cell proliferation was monitored using the MTS. Flow cytometry assay was performed to measure the cell cycle and apoptosis. Luciferase reporter assay were performed to confirm the sponged miRNAs of SNHG16.

Results
SNHG16 expression was up-regulated in MM tissues. SNHG16 knockdown suppressed cell proliferation, arrested cell cycle transition from G1 to S phase, and promoted the apoptosis of MM cells. Moreover, SNHG16 knockdown promoted cleaved-Caspase-3, cleaved-Caspase-9, Foxa3a, and Bax expression, while markedly inhibiting CCND1, Bcl-2, Cyclin D1, PI3K, and p-AKT expression in MM cells. miR-342-3p was a direct target of SNHG16. SNHG16 knockdown significantly increased miR-342-3p expression in MM cells. Overexpression miR-342-3p markedly suppressed cell proliferation, arrested cell cycle transition from G1 to S phase, and promoted apoptosis of MM cells. Overexpression of miR-342-3p markedly promoted cleaved-Caspase-3/-9, Foxa3a, and Bax expression, and inhibited CCND1, Bcl-2, Cyclin D1, PI3K, and p-AKT expression in MM cells. Additionally, repression of miR-342-3p could rescue the effect of SNHG16 knockdown on MM cell proliferation, cycle arrest, apoptosis, and related protein expression.

Conclusion
Knockdown of lncRNA SNHG16 suppresses MM cell proliferation by sponging miR-342-3p, implicating SNHG16 as a novel therapeutic target for MM.
Plasmodium falciparum pre-erythrocytic stage vaccine development
Authors: Molina-Franky Jessica , Cuy-Chaparro Laura , Camargo Anny , Reyes César , Gómez Marcela , Salamanca David Ricardo , Patarroyo Manuel Alfonso , Patarroyo Manuel Elkin 
Published: February 2020

AbstractWorldwide strategies between 2010 and 2017 aimed at controlling malarial parasites (mainly Plasmodium falciparum) led to a reduction of just 18% regarding disease incidence rates. Many biologically-derived anti-malarial vaccine candidates have been developed to date; this has involved using many experimental animals, an immense amount of work and the investment of millions of dollars. This review provides an overview of the current state and the main results of clinical trials for sporozoite-targeting vaccines (i.e. the parasite stage infecting the liver) carried out by research groups in areas having variable malaria transmission rates. However, none has led to promising results regarding the effective control of the disease, thereby making it necessary to complement such efforts at finding/introducing new vaccine candidates by adopting a multi-epitope, multi-stage approach, based on minimal subunits of the main sporozoite proteins involved in the invasion of the liver.
The sensitivity of different methods for detecting abnormalities in auditory nerve function
Authors: Lu Tianhao , Li Qiang , Zhang Chen , Chen Min , Wang Zhengming , Li Shufeng 
Published: February 2020

Abstract
Background
Cochlear implants (CIs) have become important for the treatment of severe-to-profound sensorineural hearing loss (SNHL). Meanwhile, electrically evoked compound action potentials (ECAPs) and electrically evoked auditory brainstem responses (EABRs), which can be examined and evaluated with minimal patient cooperation, have become more reliable for tone measurement and speech recognition postoperatively. However, few studies have compared the electrophysiological characteristics of the auditory nerve using ECAPs and EABRs under different functional states of the auditory nerve (FSANs). We used guinea pig models in which six electrodes were implanted unilaterally with continuous electrical stimulation (ES) for 4 h. The amplitude growth functions (AGFs) of the alternating polarity ECAP (AP-ECAP) and forward-masking subtraction ECAP (FM-ECAP), as well as the EABR waves under “normal” and “abnormal” FSANs, were obtained.

Results
Both the AP-ECAP and FM-ECAP thresholds were significantly higher than those measured by EABR under both “normal” FSAN and “abnormal” FSANs (p < 0.05). There was a significant difference in the slope values between electrodes 1 and 2 and electrodes 3 and 4 in terms of the AP-ECAP under the “abnormal” FSAN (p < 0.05). The threshold gaps between the AP-ECAP and FM-ECAP were significantly larger under the “abnormal” FSAN than under the “normal” FSAN (p < 0.05).

Conclusions
Both of the ECAP thresholds were higher than the EABR thresholds. The AP-ECAP was more sensitive than the FM-ECAP under the “abnormal” FSAN.
Evaluating prevalence of depression, anxiety and hopelessness in patients with Vitiligo on an Iranian population
Authors: Hamidizadeh Nasrin , Ranjbar Sara , Ghanizadeh Ahmad , Parvizi Mohammad Mahdi , Jafari Peyman , Handjani Farhad 
Published: February 2020

Abstract
Introduction
Vitiligo is caused by partial or complete destruction of melanocytes in the affected skin area and influences the patient’s quality of life. Besides physical involvement, vitiligo patients experience a high level of stress. Depression and Anxiety are common psychiatric disorders in vitiligo patients.

Aim
This study, as the first study, evaluates hopelessness, anxiety, depression and general health of vitiligo patients in comparison with normal controls in an Iranian population.

Method
Hundred patients with vitiligo and hundred healthy controls were examined. General health, depression, hopelessness and anxiety were evaluated based on general health questionnaire. Anxiety, depression and hopelessness levels were analyzed using Chi–Square, and the mean value of general health was evaluated through t-test.

Results
The results showed that anxiety and hopelessness levels were significantly higher in vitiligo patients than those who are in healthy controls. This significant difference refers to high levels of anxiety and hopelessness among women with vitiligo.
It was also found that the single patients were more anxious, hopeless and depressive, while the married patients were only more anxious and hopeless than those who are in the control group, respectively.
General health of patients was significantly worse than in healthy controls. The low level of general health in patients was related to poorer level of general health among women with vitiligo.

Conclusion
It seems that women with vitiligo are more mentally stressed than men with vitiligo. Both singles and married vitiligo patients suffer from anxiety and hopelessness.
Regeneration of skin appendages and nerves: current status and further challenges
Authors: Weng Tingting , Wu Pan , Zhang Wei , Zheng Yurong , Li Qiong , Jin Ronghua , Chen Haojiao , You Chuangang , Guo Songxue , Han Chunmao , Wang Xingang 
Published: February 2020

AbstractTissue-engineered skin (TES), as an analogue of native skin, is promising for wound repair and regeneration. However, a major drawback of TES products is a lack of skin appendages and nerves to enhance skin healing, structural integrity and skin vitality. Skin appendages and nerves are important constituents for fully functional skin. To date, many studies have yielded remarkable results in the field of skin appendages reconstruction and nerve regeneration. However, patients often complain about a loss of skin sensation and even cutaneous chronic pain. Restoration of pain, temperature, and touch perceptions should now be a major challenge to solve in order to improve patients’ quality of life. Current strategies to create skin appendages and sensory nerve regeneration are mainly based on different types of seeding cells, scaffold materials, bioactive factors and involved signaling pathways. This article provides a comprehensive overview of different strategies for, and advances in, skin appendages and sensory nerve regeneration, which is an important issue in the field of tissue engineering and regenerative medicine.
Predictors of mental distress among undergraduate health science students of Hawassa University, College of Medicine and Health Sciences, Hawassa, SNNPR, Ethiopia: a cross-sectional study
Authors: Bedaso Asres , Duko Bereket , Yeneabat Tebikew 
Published: February 2020

Abstract
Introduction
Mental distress is a mental health problem which includes anxiety, depression and somatic symptoms. Mental health problems affect society as a whole and no group is immune to mental disorders; however, students have significantly high level of mental distress than their community peers.

Objective
The aim of the study is to assess magnitude of mental distress and its predictors among undergraduate health science students of Hawassa University, College of Medicine and Health Sciences, SNNPR, Ethiopia.

Methods
Institution-based cross-sectional study was conducted among 311 students. Simple random sampling technique was used to select the study participants. Data were collected using pre-tested and structured self-administered questionnaire. Mental distress among students was assessed using SRQ-20, which is validated in Ethiopia. Bivariate and multivariate logistic regression model was fitted to identify predictors of mental distress among students. An adjusted odds ratio with 95% confidence interval was computed to determine the level of significance with P-value less than 0.05.

Result
A total of 309 study participants were interviewed with a response rate of 99.34%. Among the total respondents 105 (34%) of them were found to have mental distress. In multiple logistic regression analysis, poor social support (AOR = 5.28; 95% CI (2.176–12.84) and current substances use (AOR = 12.83, 95% CI (7.13–23.13), were significant predictors of mental distress among respondents.

Conclusion and recommendations
The overall magnitude of mental distress among students was found to be high. Therefore, it is recommended that mental distress needs due attention and remedial action from policy-makers, college officials, non-governmental organizations, parents, students and other concerned bodies.
Applications of patient-derived tumor xenograft models and tumor organoids
Authors: Yoshida Go J. 
Published: February 2020

AbstractPatient-derived tumor xenografts (PDXs), in which tumor fragments surgically dissected from cancer patients are directly transplanted into immunodeficient mice, have emerged as a useful model for translational research aimed at facilitating precision medicine. PDX susceptibility to anti-cancer drugs is closely correlated with clinical data in patients, from whom PDX models have been derived. Accumulating evidence suggests that PDX models are highly effective in predicting the efficacy of both conventional and novel anti-cancer therapeutics. This also allows “co-clinical trials,” in which pre-clinical investigations in vivo and clinical trials could be performed in parallel or sequentially to assess drug efficacy in patients and PDXs. However, tumor heterogeneity present in PDX models and in the original tumor samples constitutes an obstacle for application of PDX models. Moreover, human stromal cells originally present in tumors dissected from patients are gradually replaced by host stromal cells as the xenograft grows. This replacement by murine stroma could preclude analysis of human tumor-stroma interactions, as some mouse stromal cytokines might not affect human carcinoma cells in PDX models. The present review highlights the biological and clinical significance of PDX models and three-dimensional patient-derived tumor organoid cultures of several kinds of solid tumors, such as those of the colon, pancreas, brain, breast, lung, skin, and ovary.
The interplay between HIF-1α and noncoding RNAs in cancer
Authors: Peng Xiafeng , Gao Han , Xu Rui , Wang Huiyu , Mei Jie , Liu Chaoying 
Published: February 2020

AbstractHypoxia is a classic characteristic of the tumor microenvironment with a significant impact on cancer progression and therapeutic response. Hypoxia-inducible factor-1 alpha (HIF-1α), the most important transcriptional regulator in the response to hypoxia, has been demonstrated to significantly modulate hypoxic gene expression and signaling transduction networks. In past few decades, growing numbers of studies have revealed the importance of noncoding RNAs (ncRNAs) in hypoxic tumor regions. These hypoxia-responsive ncRNAs (HRNs) play pivotal roles in regulating hypoxic gene expression at the transcriptional, posttranscriptional, translational and posttranslational levels. In addition, as a significant gene expression regulator, ncRNAs exhibit promising roles in regulating HIF-1α expression at multiple levels. In this review, we briefly elucidate the reciprocal regulation between HIF-1α and ncRNAs, as well as their effect on cancer cell behaviors. We also try to summarize the complex feedback loop existing between these two components. Moreover, we evaluated the biomarker potential of HRNs for the diagnosis and prognosis of cancer, as well as the potential clinical utility of shared regulatory mechanisms between HIF-1α and ncRNAs in cancer treatment, providing novel insights into tumorigenicity, which may lead to innovative clinical applications.
Decreased ovarian function and autophagy gene methylation in aging rats
Authors: Li Qiuyuan , Cai Minghui , Wang Jiao , Gao Qiang , Guo Xiaocheng , Jia Xiaotong , Xu Shanshan , Zhu Hui 
Published: February 2020

Abstract
Background
Degeneration of ovarian function is an obvious feature of female aging. In addition, studies have shown that autophagy decreases with age, and DNA methylation is a hallmark epigenetic pattern during aging. However, it is not clear whether the expression and DNA methylation of autophagy genes are involved in the declines in ovarian function that occur during aging.

Results
Three groups of rats were used: 6-month-old (6 M) rats, 12-month-old (12 M) rats and 24-month-old (24 M) rats. Serum E2 levels and the mRNA and protein expression levels of Atg5, Atg12, Atg16L, Beclin1 and Lc3B were significantly decreased in aged rats. In addition, the methylation levels of the Atg5 gene were significantly increased in aged rats. The expression of the Dnmt1 and Dnmt2 genes decreased with aging; however, the expression of the Dnmt3A and Dnmt3B genes gradually increased with aging.

Conclusions
Decreased autophagic activity was involved in the declines in ovarian function in aging rats. Upregulation of the DNA methyltransferases Dnmt3A and Dnmt3B may have led to methylation of the autophagy genes Atg5 and Lc3B to ultimately cause the observed decreases in autophagic activity.