bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagy stimulation and intracellular sodium reduction as mediators of the cardioprotective effect of sodium–glucose cotransporter 2 inhibitors
Authors: Packer Milton 
Published: February 2020

AbstractIn five large‐scale trials involving >40 000 patients, sodium–glucose cotransporter 2 (SGLT2) inhibitors decreased the risk of serious heart failure events by 25–40%. This effect cannot be explained by control of hyperglycaemia, since it is not observed with antidiabetic drugs with greater glucose‐lowering effects. It cannot be attributed to ketogenesis, since it is not causally linked to ketone body production, and the benefit is not enhanced in patients with diabetes. The effect cannot be ascribed to a natriuretic action, since SGLT2 inhibitors decrease natriuretic peptides only modestly, and they reduce cardiovascular death, a benefit that diuretics do not possess. Although SGLT2 inhibitors increase red blood cell mass, enhanced erythropoiesis does not favourably influence the course of heart failure. By contrast, experimental studies suggest that SGLT2 inhibitors may reduce intracellular sodium, thereby preventing oxidative stress and cardiomyocyte death. Additionally, SGLT2 inhibitors induce a transcriptional paradigm that mimics nutrient and oxygen deprivation, which includes activation of adenosine monophosphate‐activated protein kinase, sirtuin‐1, and/or hypoxia‐inducible factors‐1α/2α. The interplay of these mediators stimulates autophagy, a lysosomally‐mediated degradative pathway that maintains cellular homeostasis. Autophagy‐mediated clearance of damaged organelles reduces inflammasome activation, thus mitigating cardiomyocyte dysfunction and coronary microvascular injury. Interestingly, the action of hypoxia‐inducible factors‐1α/2α to both stimulate erythropoietin and induce autophagy may explain why erythrocytosis is strongly correlated with the reduction in heart failure events. Therefore, the benefits of SGLT2 inhibitors on heart failure may be mediated by a direct cardioprotective action related to modulation of pathways responsible for cardiomyocyte homeostasis.
Inexpensive, Underwater Filming of Rare Fishes in High Definition
Authors: Ulrich Taylor L , Bonar Scott A 
Published: February 2020

Abstract
Generating public interest in fish and their biology is often challenging. Many aquatic species are cryptic and largely invisible to the public. Therefore, increasing public awareness of cryptic fishes and elevating their visibility to broad audiences requires innovation. Inexpensive technological advancements now provide fisheries biologists, managers, and researchers with means never before possible for documenting fish in their natural habitat via underwater videography. We investigated cost efficient and simple methods for capturing and creating high quality, high definition, and informative underwater videos that could be used by people with little or no previous experience in videography. We tested 1) a variety of filming equipment including cameras and camera recording settings, lenses, batteries, and memory cards; 2) active and passive camera deployment techniques; and 3) a variety of free and paid postproduction software and compared them for ease of use, expense, and quality of output. Highest quality footage, i.e., highest resolution, clearest, and most stable, was obtained using a GoPro action camera deployed underwater in a stationary position mounted to a metal base plate using a combination of stock and macro lenses, and filming in 4K resolution at 30 frames per second. Final production videos were created using Adobe Premiere Pro.
Maternal and perinatal outcomes related to superimposed pre‐eclampsia in a Brazilian cohort of women with chronic hypertension
Authors: Casagrande Laura , Rezende Gabriela P. , Guida José P. , Costa Raquel S. , Parpinelli Mary A. , Surita Fernanda G. , Costa Maria L. 
Published: February 2020

AbstractObjectiveTo describe maternal and perinatal outcomes for women with chronic hypertension, comparing those with superimposed pre‐eclampsia (SPE) with those without pre‐eclampsia (NPE).MethodsIn a retrospective cohort study in a tertiary hospital in Brazil, the records of women with chronic hypertension were reviewed between January 1, 2012, and May 31, 2017, in order to compare maternal and perinatal outcomes among those with and without SPE. Poisson regression was performed to investigate factors independently associated with severe pre‐eclampsia.ResultsOf 385 women with chronic hypertension included in the study, 167 were in the SPE group and 218 in the NPE group. The majority were white, overweight (body mass index ≥30 kg/m2), with mean age around 31 years. Adverse neonatal outcomes were significantly more prevalent among women with SPE, including small for gestational age (SPE 17.46% vs NPE 9.63%, P=0.01), low birth weight (SPE 2577 g ± 938 vs NPE 3128 g ± 723, P=0.003), neonatal intensive care unit admission (SPE 44.91% vs NPE 18.34%, P=0.08), and incidence of cesarean delivery (SPE 79.64% vs NPE 62.38%, P=0.003). Fetal growth restriction (PR [prevalence ratio] 2.62, 95% confidence interval [CI] 1.39–4.94) and previous pre‐eclampsia (PR 1.96, 95% CI 1.17–3.28) were associated with severe pre‐eclampsia.ConclusionSPE is associated with prematurity and higher rates of admission to neonatal intensive care unit. Fetal growth restriction and previous pre‐eclampsia are factors associated with severe complications of pre‐eclampsia.
Di‐phase midway convolution and deconvolution network for brain tumor segmentation in MRI images
Authors: Chithra P. L. , Dheepa G. 
Published: February 2020

AbstractA novel automatic image segmentation technique in magnetic resonance imaging (MRI) based on di‐phase midway convolution and deconvolution network is proposed. It consists of three convolutional and deconvolutional blocks for downsampling and upsampling layers respectively. In first block, each input slice is separately convolved using two paths with 3 × 3 and 7 × 7 kernels to produce different feature maps. Then the mean value of these feature maps is processed into upcoming blocks in downsampling and upsampling layers. This processed outcome is classified and segmented using softmax classification. Further, the volume, probability density distribution of tumor, and normal tissue regions are calculated using tissue‐type mapping technique. This method is extensively tested with BRATS 2012, BRATS 2013, and BRATS 2018 data sets. Our experimental results achieved higher dice similarity coefficient values of 24.3%, 27.5%, and 3.4%, respectively, for these three data sets when compared to the state‐of‐art brain tumor segmentation methods.
Circulating miRNAs as diagnostic biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance
Authors: Li Jia , Zhang Man , Wang Chengbin 
Published: February 2020

AbstractBackgroundMultiple myeloma (MM) is still an incurable hematological malignancy evolved from asymptomatic monoclonal gammopathy of undetermined significance (MGUS). New evidence suggests that circulating microRNAs (miRNAs) can serve as stable diagnostic biomarkers for MM and MUGS.MethodsSerum miRNAs in MM patients, MUGS patients, and healthy controls (HC) were performed by Agilent Bioanalyzer 2100. MicroRNAs in MM detected as promising biomarkers were validated by using quantitative real‐time PCR (qRT‐PCR). Receiver operator characteristic (ROC) curve and multivariate logistic analysis were used to evaluate the diagnostic value of miRNAs for MM and MUGS.ResultsIn microarray analysis, the top ten differential expressed miRNAs in MM included miR‐134‐5p, miR‐107, miR‐15a‐5p, miR‐5159‐3p, miR‐1914‐3p, miR‐4723‐3p, miR‐5588‐3p, miR‐6893‐3p, miR‐7106‐3p, and miR‐6722‐5p. Three up‐regulated miRNAs (miR‐134‐5p, miR‐107, and miR‐15a‐5p) were further validated. The elevated expression levels of miR‐134‐5p, miR‐107, and miR‐15a‐5p in qRT‐PCR were increased consistent with microarray analysis. These miRNAs distinguished MM and MUGS from HC significantly. Multivariate logistic analysis showed combination miR‐107, miR‐15a‐5p with Hb, the AUC was 0.954 (95% CI: 0.890‐1.000), sensitivity of 91.3%, and specificity of 93.7% for distinguishing MM from MUGS.ConclusionsThese data demonstrate that miR‐134‐5p, miR‐107, and miR‐15a‐5p are potential diagnostic biomarkers in MM and MUGS. Moreover, the combination miR‐107 and miR‐15a‐5p with Hb can distinguish MM from MUGS.
lncRNA HOXB‐AS3 exacerbates proliferation, migration, and invasion of lung cancer via activating the PI3K‐AKT pathway
Authors: Jiang Wenyang , Kai Jindan , Li Donghang , Wei Zhongheng , Wang Ying , Wang Wei 
Published: February 2020

AbstractLung cancer remains the leading cause of cancer‐related death all over the world. In spite of the great advances made in surgery and chemotherapy, the prognosis of lung cancer patients is poor. A substantial fraction of long noncoding RNAs (lncRNAs) can regulate various cancers. A recent study has reported that lncRNA HOXB‐AS3 plays a critical role in cancers. However, its biological function remains unclear in lung cancer progression. In the current research, we found HOXB‐AS3 was obviously elevated in NSCLC tissues and cells. Functional assays showed that inhibition of HOXB‐AS3 was able to repress A549 and H1975 cell proliferation, cell colony formation ability and meanwhile, triggered cell apoptosis. Furthermore, the lung cancer cell cycle was mostly blocked in the G1 phase whereas the cell ratio in the S phase was reduced. Also, A549 and H1975 cell migration and invasion capacity were significantly repressed by the loss of HOXB‐AS3. The PI3K/AKT pathway has been implicated in the carcinogenesis of multiple cancers. Here, we displayed that inhibition of HOXB‐AS3 suppressed lung cancer cell progression via inactivating the PI3K/AKT pathway. Subsequently, in vivo experiments were utilized in our study and it was demonstrated that HOXB‐AS3 contributed to lung cancer tumor growth via modulating the PI3K/AKT pathway. Overall, we implied that HOXB‐AS3 might provide a new perspective for lung cancer treatment via targeting PI3K/AKT.
Early onset epileptic encephalopathy caused by novel compound heterozygous mutation of WWOX gene
Authors: Su Tangfeng , Yan Yu , Xu Shuang , Zhang Ke , Xu Sanqing 
Published: February 2020

AbstractThe human WW domain containing oxidoreductase (WWOX) gene has been identified as a tumor suppressor gene. However, recent reports have demonstrated its dominant role in autosomal recessive disorders of the central nervous system, especially in early onset epileptic encephalopathy. Here, we report a Chinese case with novel compound heterozygous mutation of WWOX gene (c.229_230+2del mutation originated from her mother and c.1065dup (p.Ala356Serfs*173) variation from her father), and compare them to previously reported 59 WWOX‐related epileptic encephalopathy (WOREE). Early onset and frequent epileptic seizures in the postnatal period, hypsarrhythmia patterns in EEG background and retarded development are the most important characteristics of WOREE in infants. Although the seizures in our case can be controlled by phenobarbital and topiramate, the prognosis of WOREE is poor.
Regulation of the hypothalamic GnRH–GnIH system by putrescine in adult female rats and GT1‐7 neuronal cell line
Authors: Fernandes Joseph R. D. , Moitra Abhishek , Tsutsui Kazuyoshi , Banerjee Arnab 
Published: February 2020

AbstractThe gonadotropin‐releasing hormone—gonadotropin inhibitor (GnRH–GnIH) system in the hypothalamus of mammals is the key factor that controls the entire reproductive system. The aim of this study was to immunolocalize GnIH (RFRP‐3) in the hypothalamus during the estrous cycle and to study the effect of putrescine on the expression of GnRH‐I and GnIH through both in vivo and in vitro (GT1‐7 cells) approach and the circulatory levels of GnRH‐I, GnIH, and gonadotropins were also investigated. The study also aims in analyzing all the immunofluorescence images by measuring the relative pixel count of an image. This study showed the effect of putrescine on the morphology of ovary, uterus, and the expression of the steroidogenic acute regulatory protein in the ovary. This study showed GnIH expression was intense during the diestrus and moderate during proestrus and estrus, whereas mild staining during the metestrus. The study further showed that putrescine supplementation to adult female rats increased both GnRH‐I expression in the hypothalamus as well as the GnRH‐I levels in circulation. The study, for the first time, also showed that putrescine supplementation decreased the expression and release of GnIH. These effects of upregulating GnRH‐I expression and downregulating GnIH expression were confirmed by in vitro experiments using GT1‐7 cells. Putrescine supplementation also increased the gonadotropin levels in the serum. To summarize, putrescine can regulate the hypothalamic–pituitary–gonadal axis by increasing the GnRH‐I, luteinizing hormone, and follicle‐stimulating hormone levels and suppressing GnIH levels. This is the first report showing the simultaneous effects of putrescine on the regulation of both GnRH‐I and GnIH in the hypothalamus.
The role of SLITRK6 in the pathogenesis of Tourette syndrome: From the conclusion of a family‐based study in the Chinese Han population
Authors: Liu Wenmiao , Zhang Xuzhan , Deng Ziwen , Li Guixia , Zhang Ru , Yang Zongjun , Che Fengyuan , Liu Shiguo , Li Hui 
Published: February 2020

AbstractBackgroundTourette syndrome (TS) is a complex neuropsychiatric disorder coupled with obvious genetic heterogeneity. Studies in recent years have confirmed the association of SLITRK genes with sensory and neuropsychiatric diseases. To detect whether SLITRK6 is involved in the progress of TS, a family‐based association study was performed to explore the possible genetic association between SLITRK6 and TS in the Chinese Han population.MethodsWe genotyped 399 TS nuclear families trios, and then analyzed three tag SLITRK6 single nucleotide polymorphisms using the transmission disequilibrium test (TDT) haplotype relative risk (HRR) and haplotype‐based haplotype relative risk (HHRR) methods.ResultsThe TDT showed no statistically significant allele transfer for the three polymorphisms. The HRR and HHRR also showed a negative association.ConclusionsDespite the results suggesting that these polymorphisms may not be associated with susceptibility to TS in the Chinese Han population, we are still unable to determine the potential role of SLITRK6 in the pathogenesis of TS. Furthermore, the results still need to be confirmed in a larger sample size and in different populations.
Fast Imaging for Hyperpolarized MR Metabolic Imaging
Authors: Gordon Jeremy W. , Chen Hsin‐Yu , Dwork Nicholas , Tang Shuyu , Larson Peder E. Z. 
Published: February 2020

MRI with hyperpolarized carbon‐13 agents has created a new type of noninvasive, in vivo metabolic imaging that can be applied in cell, animal, and human studies. The use of 13C‐labeled agents, primarily [1‐13C]pyruvate, enables monitoring of key metabolic pathways with the ability to image substrate and products based on their chemical shift. Over 10 sites worldwide are now performing human studies with this new approach for studies of cancer, heart disease, liver disease, and kidney disease. Hyperpolarized metabolic imaging studies must be performed within several minutes following creation of the hyperpolarized agent due to irreversible decay of the net magnetization back to equilibrium, so fast imaging methods are critical. The imaging methods must include multiple metabolites, separated based on their chemical shift, which are also undergoing rapid metabolic conversion (via label exchange), further exacerbating the challenges of fast imaging. This review describes the state‐of‐the‐art in fast imaging methods for hyperpolarized metabolic imaging. This includes the approach and tradeoffs between three major categories of fast imaging methods—fast spectroscopic imaging, model‐based strategies, and metabolite specific imaging—as well additional options of parallel imaging, compressed sensing, tailored RF flip angles, refocused imaging methods, and calibration methods that can improve the scan coverage, speed, signal‐to‐noise ratio (SNR), resolution, and/or robustness of these studies. To date, these approaches have produced extremely promising initial human imaging results. Improvements to fast hyperpolarized metabolic imaging methods will provide better coverage, SNR, resolution, and reproducibility for future human imaging studies.Level of Evidence5Technical Efficacy Stage1
A metabolomic study of the urine of rats with Alzheimer's disease and the efficacy of Ding‐Zhi‐Xiao‐Wan on the afflicted rats
Authors: He Yang , Wang Yimin , Liu Shu , Pi Zifeng , Liu Zhiqiang , Xing Junpeng , Zhou Hui 
Published: February 2020

AbstractAs a well‐known traditional Chinese medicine formula, Ding‐Zhi‐Xiao‐Wan has long been used for the routine treatment of Alzheimer's disease. However, the mechanism of Ding‐Zhi‐Xiao‐Wan in treating Alzheimer's disease is unclear. Therefore, a nontargeted metabolomics method based on ultrahigh performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry has been established to explore the metabolic variations in the urine of Alzheimer's disease rats and investigate the therapeutic mechanism of Ding‐Zhi‐Xiao‐Wan on Alzheimer's disease. To develop a better rat model of Alzheimer's disease, amyloid β25‐35 was injected into the bilateral hippocampus of Sprague–Dawley rats. Multivariate analysis approaches were applied to differentiate the urine components between the four groups. Thereafter, a targeted metabolomics method was used to verify the identified endogenous metabolites and determine the mechanism of action of Ding‐Zhi‐Xiao‐Wan. Altogether, 26 potential biomarkers were found, of which 15 biomarkers (10 of which are potential biomarkers found in nontargeted metabolomics) were identified. The results show that Ding‐Zhi‐Xiao‐Wan mainly affects the pathways of taurine and hypotaurine metabolism, tryptophan metabolism, and phenylalanine metabolism. Ding‐Zhi‐Xiao‐Wan might play a role in the treatment of Alzheimer's disease by mediating antioxidative stress, regulation of energy metabolism, improvement of intestinal microbes, and protection of nerve cells.
Anthropogenic Disturbance and Population Viability of Woodland Caribou in Ontario
Authors: Fryxell John M. , Avgar Tal , Liu Boyan , Baker James A. , Rodgers Arthur R. , Shuter Jennifer , Thompson Ian D. , Reid Douglas E. B. , Kittle Andrew M. , Mosser Anna , Newmaster Steven G. , Nudds Tom D. , Street Garrett M. , Brown Glen S. , Patterson Brent 
Published: February 2020

ABSTRACTOne of the most challenging tasks in wildlife conservation and management is to clarify how spatial variation in land cover due to anthropogenic disturbance influences wildlife demography and long‐term viability. To evaluate this, we compared rates of survival and population growth by woodland caribou (Rangifer tarandus caribou) from 2 study sites in northern Ontario, Canada that differed in the degree of anthropogenic disturbance because of commercial logging and road development, resulting in differences in predation risk due to gray wolves (Canis lupus). We used an individual‐based model for population viability analysis (PVA) that incorporated adaptive patterns of caribou movement in relation to predation risk and food availability to predict stochastic variation in rates of caribou survival. Field estimates of annual survival rates for adult female caribou in the unlogged ( 0.90) and logged ( 0.76) study sites recorded during 2010–2014 did not differ significantly (P > 0.05) from values predicted by the individual‐based PVA model (unlogged:  = 0.87; logged:  0.79). Outcomes from the individual‐based PVA model and a simpler stage‐structured matrix model suggest that substantial differences in adult survival largely due to wolf predation are likely to lead to long‐term decline of woodland caribou in the commercially logged landscape, whereas the unlogged landscape should be considerably more capable of sustaining caribou. Estimates of population growth rates (λ) for the 2010–2014 period differed little between the matrix model and the individual‐based PVA model for the unlogged (matrix model  = 1.01; individual‐based model  = 0.98) and logged landscape (matrix model  = 0.88; individual‐based model  = 0.89). We applied the spatially explicit PVA model to assess the viability of woodland caribou across 14 woodland caribou ranges in Ontario. Outcomes of these simulations suggest that woodland caribou ranges that have experienced significant levels of commercial forestry activities in the past had annual growth rates <0.89, whereas caribou ranges that had not experienced commercial forestry operations had population growth rates >0.96. These differences were strongly related to regional variation in wolf densities. Our results suggest that increased wolf predation risk due to anthropogenic disturbance is of sufficient magnitude to cause appreciable risk of population decline in woodland caribou in Ontario. © 2020 The Authors. The Journal of Wildlife Management published by Wiley Periodicals, Inc. on behalf of The Wildlife Society.
Smoking and Alcohol Consumption Are Associated With the Increased Risk of Peritonsillar Abscess
Authors: Kim So Young , Lim Hyoseob , Choi Hyo Geun 
Published: February 2020

Objectives/HypothesisThe purpose of this study was to evaluate the relationship among smoking, alcohol consumption, and peritonsillar abscess in a Korean population.Study DesignIndividuals ≥40 years old from the Korean National Health Insurance Service‐Health Screening Cohort were assessed from 2002 to 2013.MethodsIn total, 1,285 peritonsillar abscess participants were matched with 5,140 controls at a ratio of 1:4 with respect to age group, sex, income group, region of residence, hypertension, diabetes, and dyslipidemia. We analyzed the participants' previous histories of smoking (current smokers vs. nonsmokers or past smokers) and alcohol consumption (drinkers vs. nondrinkers) in the peritonsillar abscess and control groups. Peritonsillar abscess was defined using the International Classification of Disease‐10 code J36 combined with claim codes for incision and drainage or aspiration. Crude and adjusted odds ratios (ORs) were analyzed using unconditional logistic regression analyses, and 95% confidence intervals (CI) were calculated.ResultsThe rates of smoking and consuming alcohol were higher in the peritonsillar abscess group than in the control group. The adjusted OR of smoking for peritonsillar abscess was 1.23 (95% CI = 1.06–1.44, P = .009), and that of alcohol consumption was 1.18 (95% CI = 1.02–1.36, P = .024).ConclusionThe odds of smoking and alcohol consumption were increased in peritonsillar abscess patients compared to those in the control group.Level of EvidenceNA Laryngoscope, 2020