bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular outcomes and mortality after initiation of canagliflozin: Analyses from the EASEL Study
Authors: Udell Jacob A. , Yuan Zhong , Ryan Patrick , Rush Toni , Sicignano Nicholas M. , Galitz Michael , Rosenthal Norman 
Published: October 2019

AbstractIntroductionIn the EASEL study of patients with type 2 diabetes and high cardiovascular risk, initiation of sodium glucose co‐transporter 2 inhibitors (SGLT2i) was associated with lower risk of cardiovascular events and mortality and higher risk of below‐knee lower extremity (BKLE) amputation versus non‐SGLT2i therapies. This analysis further examined risk of cardiovascular events, cardiovascular and noncardiovascular death and BKLE amputation with the SGLT2i canagliflozin versus non‐SGLT2i.MethodsNew user cohorts were constructed from Department of Defense Military Health System patients initiating canagliflozin or non‐SGLT2i (4/1/2013‐12/31/2016). Propensity score matching (1:1) controlled for imbalances in baseline covariates. Incidence rates, hazard ratios and 95% confidence intervals for time to first composite outcome of all‐cause mortality (ACM) and hospitalization for heart failure (HHF), composite major adverse cardiovascular events (MACE) and individual components were evaluated using conditional Cox models. The National Death Index was used to differentiate cardiovascular from noncardiovascular death. The exploratory safety end‐point was BKLE amputation.ResultsAfter propensity matching, 15 394 patients with well‐balanced baseline covariates were followed for a median of 2.03 years (intent‐to‐treat). Canagliflozin showed significant benefit for ACM and HHF (P < .0001), MACE (P = .0001), cardiovascular death (P < .0001) and noncardiovascular death (P = .0018). No significant difference in risk of BKLE amputation was observed (P = .20), though few events were observed. Results were generally consistent in on‐treatment analyses.ConclusionsIn this high cardiovascular risk cohort studied in routine clinical practice, canagliflozin was associated with lower risk of cardiovascular events, cardiovascular death and all‐cause mortality with no significant increase in BKLE amputation risk versus non‐SGLT2i.
Lithium and Boron in Calcified Tissues of Vicuna and Their Relation to Chronic Exposure by Water Ingestion in The Andean Lithium Triangle
Authors: López Steinmetz Romina Lucrecia , Fong Shao Bing , Boyer Emile , López Steinmetz Lorena Cecilia , Tejerina Norberto Elio , Meuric Vincent 
Published: October 2019

Abstract
Vicuna is a wild, endangered species of Andean camelid living in the hyperarid Andean plateau. In the central part of the plateau, the Lithium Triangle defines a zone with lithium-rich salt pans. Brine pools naturally form within the salt pans, and the adaptation strategy of vicuna consists of drinking from brine pools. Together with reporting the first chemical data on vicuna bones and teeth, we analyzed lithium, boron, and arsenic in water and brines, with the aim of assessing their relation to chronic exposure by water ingestion. We collected and analyzed bones of vicuna specimens lying in an Andean salt pan, together with brine and water samples. Brine and water samples are highly saline and contain large amounts of lithium, boron, and arsenic. Lithium (13.50–40 mg kg–1) and boron (40–46.80 mg kg–1), but not arsenic, were found in the vicuna bones and teeth. Based on our results and on previously reported data on human tissues in the Andes, we conducted statistical assessments of the relationships between lithium and boron in body tissues and water samples, and discuss their environmental significance in the context of the Lithium Triangle. Environ Toxicol Chem 2019;39:200–209. © 2019 SETAC
The compensating effect of glaciers: Characterizing the relation between interannual streamflow variability and glacier cover
Authors: van Tiel Marit , Kohn Irene , Van Loon Anne F. , Stahl Kerstin 
Published: October 2019

AbstractMeltwater from glaciers is not only a stable source of water but also affects downstream streamflow dynamics. One of these dynamics is the interannual variability of streamflow. Glaciers can moderate streamflow variability because the runoff in the glacierized part, driven by temperature, correlates negatively with the runoff in the non‐glacierized part of a catchment, driven by precipitation, thereby counterbalancing each other. This is also called the glacier compensation effect (GCE), and the effect is assumed to depend on relative glacier cover. Previous studies found a convex relationship between streamflow variability and glacier cover of different glacierized catchments, with lowest streamflow variability at a certain optimum glacier cover. In this study, we aim to revisit these previously found curves to find out if a universal relationship between interannual streamflow variability and glacier cover exists, which could potentially be used in a space‐for‐time substitution analysis. Moreover, we test the hypothesis that the dominant climate drivers (here precipitation and temperature) switch around the suggested optimum of the curve. First, a set of virtual nested catchments, with the same absolute glacier area but varying non‐glacierized area, were modelled to isolate the effect of glacier cover on streamflow variability. The modelled relationship was then compared with a multicatchment data set of gauged glacierized catchments in the European Alps. In the third step, changes of the GCE curve over time were analysed. Model results showed a convex relationship and the optimum in the simulated curve aligned with a switch in the dominant climate driver. However, the multicatchment data and the time change analyses did not suggest the existence of a universal convex relationship. Overall, we conclude that GCE is complex due to entangled controls and changes over time in glacierized catchments. Therefore, care should be taken to use a GCE curve for estimating and/or predicting interannual streamflow variability in glacierized catchments.
A new insight into thymosin β4, a promising therapeutic approach for neurodegenerative disorders
Authors: Shomali Navid , Baradaran Behzad , Deljavanghodrati Mina , Akbari Morteza , Hemmatzadeh Maryam , Mohammadi Hamed , Jang Yue , Xu Huaxi , Sandoghchian Shotorbani Siamak 
Published: October 2019

AbstractThymosin β4 (Tβ4), a G‐actin‐sequestering secreted peptide, improves neurovascular remodeling and central nervous system plasticity, which leads to neurological recovery in many neurological diseases. Inflammatory response adjustment and tissue inflammation consequences from neurological injury are vital for neurological recovery. The innate or nonspecific immune system is made of different components. The Toll‐like receptor pro‐inflammatory signaling pathway, which is one of these components, regulates tissue injury. The main component of the Toll‐like/IL‐1 receptor signaling pathway, which is known as IRAK1, can be regulated by miR‐146a and regulates NF‐κB expression. Due to the significant role of Tβ4 in oligodendrocytes, neurons, and microglial cells in neurological recovery, it is suggested that Tβ4 regulates the Toll‐like receptor (TLR) pro‐inflammatory signaling pathway by upregulating miR‐146a in neurological disorders. However, further investigations on the role of Tβ4 in regulating the expression of miR146a and TLR signaling pathway in the immune response adjustment in neurological disorders provides an insight into mechanisms of action and the possibility of Tβ4 therapeutic effect enhancement.
Compensatory endocytosis occurs after cortical granule exocytosis in mouse eggs
Authors: Gómez‐Elías Matías D. , Fissore Rafael A. , Cuasnicú Patricia S. , Cohen Débora J. 
Published: October 2019

AbstractCompensatory endocytosis (CE) is one of the primary mechanisms through which cells maintain their surface area after exocytosis. Considering that in eggs massive exocytosis of cortical granules (CG) takes place after fertilization, the aim of this study was to evaluate the occurrence of CE following cortical exocytosis in mouse eggs. For this purpose, we developed a pulse‐chase assay to detect CG membrane internalization. Results showed internalized labeling in SrCl2‐activated and fertilized eggs when chasing at 37°C, but not at a nonpermissive temperature (4°C). The use of kinase and calcineurin inhibitors led us to conclude that this internal labeling corresponded to CE. Further experiments showed that CE in mouse eggs is dependent on actin dynamics and dynamin activity, and could be associated with a transient exposure of phosphatidylserine. Finally, CE was impaired in A23187 ionophore‐activated eggs, highlighting once again the mechanistic differences between the activation methods. Altogether, these results demonstrate for the first time that egg activation triggers CE in mouse eggs after exocytosis of CG, probably as a plasma membrane homeostasis mechanism.
Production of acetone–butanol–ethanol (ABE) from concentrated yellow top presscake using Clostridium beijerinckii P260
Authors: Qureshi Nasib , Saha Badal , Liu Siqing , Harry‐O'kuru Rogers 
Published: October 2019

AbstractBACKGROUNDButanol, a superior biofuel to ethanol, can be produced by fermentation of renewable feedstocks such as corn or molasses. Since costs of these feedstocks are high, this biofuel should be produced from economic substrates. Recent studies have identified yellow top (YT) (Physaria fendleri) as an economical feedstock which is currently used for landfill, thus causing environmental pollution. In addition, cutting edge science and technology should be used, such as application of concentrated substrates. This study used concentrated YT ranging from 80 to 150 g L−1.RESULTSAt a YT concentration of 125 g L−1, the culture produced 28.8 g L−1 acetone–butanol–ethanol (ABE) as compared with 18.68 g L−1 using glucose (control) as substrate, which is 154% of the control fermentation. The control fermentation resulted in a productivity of 0.42 g L−1 h−1, while YT resulted in a productivity of 0.70 g L−1 h−1. In YT fermentation, specific ABE productivity was 543% of that obtained in the control run.CONCLUSIONA YT concentration of 125 g L−1 is beneficial for ABE fermentation. At this concentration, ABE production level, productivity and specific productivity were greatly enhanced. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.
Purification of a potent mitogenic homodimeric Penicillium griseoroseum lectin and its characterisation
Authors: Singh Ram S. , Walia Amandeep K. 
Published: October 2019

AbstractPenicillium griseoroseum lectin was 80‐fold purified by successive DEAE Sepharose anion exchange and Sephadex G‐100 gel permeation chromatography. P. griseoroseum lectin exhibited haemagglutination activity towards protease‐treated rabbit erythrocytes. It showed specificity towards various carbohydrates such as d‐mannose, N‐acetyl‐d‐glucosamine, mucins, and so forth. P. griseoroseum lectin was found as a glycoprotein with glycan content of 4.33%. Purified P. griseoroseum lectin is homodimeric having a molecular mass of 57 kDa with subunit molecular mass of 28.6 kDa. Haemagglutination activity of purified P. griseoroseum lectin was completely stable from 25°C to 35°C at a pH range of 6–7.5. Lectin activity was not influenced by divalent metal ions and denaturants. P. griseoroseum lectin manifested mitogenicity towards mice splenocytes and activity reached a peak at 75 μg/ml of lectin concentration. P. griseoroseum lectin in microgram concentrations stimulated proliferation of mice splenocytes. Thus, P. griseoroseum lectin exhibits potential mitogenicity, which can be exploited for further biomedical applications.
Generation of Human‐Induced Pluripotent Stem Cells From Anterior Cruciate Ligament
Authors: Woods Steven , Bates Nicola , Dunn Sara L. , Serracino‐Inglott Ferdinand , Hardingham Tim E. , Kimber Susan J. 
Published: October 2019

ABSTRACTHuman‐induced pluripotent stem cells (hiPSCs) are reprogrammed somatic cells and are an excellent cell source for tissue engineering applications, disease modeling, and for understanding human development. HiPSC lines have now been generated from a diverse range of somatic cell types and have been reported to retain an epigenetic memory of their somatic origin. To date, the reprogramming of a true ligament has not been reported. The aim of this study is to generate iPSCs from human anterior cruciate ligament (ACL) cells. ACL cells from three above‐knee amputation donors, with donor matched dermal fibroblasts (DFs) were tested for reprogramming using an existing DF reprogramming protocol. ACL cells were, however, more sensitive than donor matched DF to transforming growth factor‐β (TGF‐β); displaying marked contraction, increased proliferation and increased TNC and COMP expression in vitro, which hindered reprogramming to iPSCs. Modification of the protocol by scoring the cell monolayer or by removal of TGF‐β during ACL reprogramming resulted in emerging colonies being easier to identify and extract, increasing reprogramming efficiency. Following 30 passages in culture, the generated ACL derived iPSCs displayed pluripotency markers, normal karyotype and can successfully differentiate to cells of the three embryonic germ layers. This study illustrates it is possible to generate hiPSCs from ligament and identifies optimized ligament reprogramming conditions. ACL derived iPSCs may provide a promising cell source for ligament and related tissue engineering applications. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society J Orthop Res 38:92–104, 2020
R you ready? Using the R programme for statistical analysis and graphics
Authors: Stiglic Gregor , Watson Roger , Cilar Leona 
Published: October 2019

AbstractFor conducting research, nurses typically use commercial statistical packages. R software is a free, powerful, and flexible alternative, but is less familiar and used less frequently in nursing research. In this paper, we use data from a previous study to demonstrate a few typical steps in exploratory data analysis using R. A step‐by‐step description of some basic analyses in R is provided here, including examples of specific functions to read and manipulate the data, calculate scores from individual questionnaire items, and prepare a correlation plot and summary table.
Targeting the TMPRSS2/ERG fusion mRNA using liposomal nanovectors enhances docetaxel treatment in prostate cancer
Authors: Shao Longjiang , Kahraman Nermin , Yan Ge , Wang Jianghua , Ozpolat Bulent , Ittmann Michael 
Published: October 2019

AbstractBackgroundThe TMPRSS2/ERG (TE) fusion gene is present in half of the prostate cancers (PCas). The TMPRSS2 and ERG junction of the fusion messenger RNA (mRNA) constitutes a cancer‐specific target. Although docetaxel‐based chemotherapy is the second line of therapy following development resistance to androgen ablation therapies, it is not curative. Therefore, the development of nontoxic novel monotherapies for targeting TE mRNA in PCa patients and for increasing the clinical efficacy of docetaxel treatment are needed.MethodsWe evaluated multiple approaches to enhance the delivery of TE small interfering RNA (siRNA) containing liposomes including PEGylation, topical treatment with nitroglycerin (NG) to increase permeability and retention, and three different PEG modifications: folate, RGD cyclic peptide, and a bFGF fibroblast growth factor receptor‐targeting peptide. The efficacy of the optimized TE siRNA liposome in combination with docetaxel was then evaluated in vivo with or without topical NG in vivo using a VCaP xenograft model. TE fusion protein knockdown in residual tumors was assessed using Western blotting and immunohistochemistry.ResultsIn vivo therapeutic targeting of TE fusion gene by systemic delivery of RGD‐peptide‐coated liposomal siRNA nanovectors led to sustained target silencing, suppressed tumor growth in xenograft models and enhanced the efficacy of docetaxel chemotherapy. Simultaneous application of the vasodilator NG to the skin further increased tissue the delivery of siRNA and enhanced target knockdown.ConclusionTE‐targeted gene silencing therapy using liposomal nanovectors is a potential therapeutic strategy as a monotherapy and to enhance the efficacy of chemotherapy in patients with advanced PCa.
Sedimentation analysis of columnar ice crystals in viscous flow regimes
Authors: Bürgesser Rodrigo Exequiel , Giovacchini Juan Pablo , Castellano Nesvit Edit 
Published: October 2019

AbstractThe sedimentation process of columnar ice crystals was evaluated using data obtained by the lattice Boltzmann method. The data used correspond to columnar ice crystals with maximum dimension less than 100 μm and aspect ratios between 1 and 3. The terminal velocity was computed for different ice‐crystal bulk densities and for three falling orientations. The analysis corresponds to ice crystals falling in viscous flow regimes, where theoretical formulations overestimate the terminal velocity. Different characteristic lengths of columnar ice crystals and different theoretical proposals for the sedimentation process were tested in order to find the best representation of the data. Characteristic lengths reported in the literature do not represent the sedimentation process for all the falling orientations used in this study. Thus, it was not possible to obtain a unique relation between the Best and Reynolds numbers. In particular, columnar ice crystals falling with their longer dimension parallel to the vertical direction show a large dispersion that it does not seem possible to reduce. The theoretical and semi‐empirical formulations of the terminal velocity evaluated show large deviations in the computed velocity, with a strong dependence on ice‐crystal aspect ratio. The dispersion observed seems to be intrinsically related to the dimensionless variables used to parametrize the terminal velocity. To derive a unique scale law that could represent the sedimentation process of ice crystals, geometric, kinematic, and dynamic similarities are required. However, these conditions are not fulfilled in the sedimentation process.
Myelomeningocele sac associated with worse lower‐extremity neurological sequelae: evidence for prenatal neural stretch injury?
Authors: Oliver E. R. , Heuer G. G. , Thom E. A. , Burrows P. K. , Didier R. A. , DeBari S. E. , Martin‐Saavedra J. S. , Moldenhauer J. S. , Jatres J. , Howell L. J. , Adzick N. S. , Coleman B. G. 
Published: October 2019

ABSTRACTObjectiveTo determine whether the presence of a myelomeningocele (MMC) sac and sac size correlate with compromised lower‐extremity function in fetuses with open spinal dysraphism.MethodsA radiology database search was performed to identify cases of MMC and myeloschisis (MS) diagnosed prenatally in a single center from 2013 to 2017. All cases were evaluated between 18 and 25 weeks. Ultrasound reports were reviewed for talipes and impaired lower‐extremity motion. In MMC cases, sac volume was calculated from ultrasound measurements. Magnetic resonance imaging reports were reviewed for hindbrain herniation. The association of presence of a MMC sac and sac size with talipes and impaired lower‐extremity motion was assessed. Post‐hoc analysis of data from the multicenter Management of Myelomeningocele Study (MOMS) randomized controlled trial was performed to confirm the study findings.ResultsIn total, 283 MMC and 121 MS cases were identified. MMC was associated with a lower incidence of hindbrain herniation than was MS (80.9% vs 100%; P < 0.001). Compared with MS cases, MMC cases with hindbrain herniation had a higher rate of talipes (28.4% vs 16.5%, P = 0.02) and of talipes or lower‐extremity impairment (34.9% vs 19.0%, P = 0.002). Although there was a higher rate of impaired lower‐extremity motion alone in MMC cases with hindbrain herniation than in MS cases, the difference was not statistically significant (6.6% vs 2.5%; P = 0.13). Among MMC cases with hindbrain herniation, mean sac volume was higher in those associated with talipes compared with those without talipes (4.7 ± 4.2 vs 3.0 ± 2.6 mL; P = 0.002). Review of the MOMS data demonstrated similar findings; cases with a sac on baseline imaging had a higher incidence of talipes than did those without a sac (28.2% vs 7.5%; P = 0.007).ConclusionsIn fetuses with open spinal dysraphism, the presence of a MMC sac was associated with fetal talipes, and this effect was correlated with sac size. The presence of a larger sac in fetuses with open spinal dysraphism may result in additional injury through mechanical stretching of the nerves, suggesting another acquired mechanism of injury to the exposed spinal tissue. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Serial endometrial thickness and risk of non‐endometrial hormone‐dependent cancers in postmenopausal women in UK Collaborative Trial of Ovarian Cancer Screening
Authors: Burnell M. , Gentry‐Maharaj A. , Glazer C. , Karpinskyj C. , Ryan A. , Apostolidou S. , Kalsi J. , Parmar M. , Campbell S. , Jacobs I. , Menon U. 
Published: October 2019

ABSTRACTObjectiveEstrogen is a well‐established risk factor for various cancers. It causes endometrial proliferation, which is assessed routinely as endometrial thickness (ET) using transvaginal ultrasound (TVS). Only one previous study, restricted to endometrial and breast cancer, has considered ET and the risk of non‐endometrial cancer. The aim of this study was to explore the association between baseline and serial ET measurements and nine non‐endometrial hormone‐sensitive cancers, in postmenopausal women, using contemporary statistical methodology that attempts to minimize the biases typical of endogenous serial data.MethodsThis was a cohort study nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). In the ultrasound arm of UKCTOCS, 50639 postmenopausal women, aged 50–74, underwent annual TVS examination, of whom 38 105 had a valid ET measurement, no prior hysterectomy and complete covariate data, and were included in this study. All women were followed up through linkage to national cancer registries. The effect of ET on the risk of six estrogen‐dependent cancers (breast, ovarian, colorectal, bladder, lung and pancreatic) was assessed using joint models for longitudinal biomarker and time‐to‐event data, and Cox models were used to assess the association between baseline ET measurement and these six cancers in addition to liver cancer, gastric cancer and non‐Hodgkin's lymphoma (NHL). All models were adjusted for current hormone‐replacement therapy (HRT) use, body mass index, age at last menstrual period, parity and oral contraceptive pill use.ResultsThe 38 105 included women had a combined total of 267 567 (median, 8; interquartile range, 5–9) valid ET measurements. During a combined total of 407 838 (median, 10.9) years of follow‐up, 1398 breast, 351 endometrial, 381 lung, 495 colorectal, 222 ovarian, 94 pancreatic, 79 bladder, 62 gastric, 38 liver cancers and 52 NHLs were registered. Using joint models, a doubling of ET increased significantly the risk of breast (hazard ratio (HR), 1.21; 95% CI, 1.09–1.36; P = 0.001), ovarian (HR, 1.39; 95% CI, 1.06–1.82; P = 0.018) and lung (HR, 1.25; 95% CI, 1.02–1.54; P = 0.036) cancers. There were no statistically significant associations between ET and the remaining six cancers.ConclusionPostmenopausal women with high/increasing ET on TVS are at increased risk of breast, ovarian and lung cancer. It is important that clinicians are aware of these risks, as TVS is a common investigation. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.