bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular and molecular effects of hyperglycemia on ion channels in vascular smooth muscle
Authors: Nieves-Cintrón Madeline , Flores-Tamez Víctor A. , Le Thanhmai , Baudel Miguel Martín-Aragón , Navedo Manuel F. 
Published: June 2020

AbstractDiabetes affects millions of people worldwide. This devastating disease dramatically increases the risk of developing cardiovascular disorders. A hallmark metabolic abnormality in diabetes is hyperglycemia, which contributes to the pathogenesis of cardiovascular complications. These cardiovascular complications are, at least in part, related to hyperglycemia-induced molecular and cellular changes in the cells making up blood vessels. Whereas the mechanisms mediating endothelial dysfunction during hyperglycemia have been extensively examined, much less is known about how hyperglycemia impacts vascular smooth muscle function. Vascular smooth muscle function is exquisitely regulated by many ion channels, including several members of the potassium (K+) channel superfamily and voltage-gated L-type Ca2+channels. Modulation of vascular smooth muscle ion channels function by hyperglycemia is emerging as a key contributor to vascular dysfunction in diabetes. In this review, we summarize the current understanding of how diabetic hyperglycemia modulates the activity of these ion channels in vascular smooth muscle. We examine underlying mechanisms, general properties, and physiological relevance in the context of myogenic tone and vascular reactivity.
Chemical carcinogen safety testing: OECD expert group international consensus on the development of an integrated approach for the testing and assessment of chemical non-genotoxic carcinogens
Authors: Jacobs Miriam N. , Colacci Annamaria , Corvi Raffaella , Vaccari Monica , Aguila M. Cecilia , Corvaro Marco , Delrue Nathalie , Desaulniers Daniel , Ertych Norman , Jacobs Abigail , Luijten Mirjam , Madia Federica , Nishikawa Akiyoshi , Ogawa Kumiko , Ohmori Kiyomi , Paparella Martin , Sharma Anoop Kumar , Vasseur Paule 
Published: June 2020

AbstractWhile regulatory requirements for carcinogenicity testing of chemicals vary according to product sector and regulatory jurisdiction, the standard approach starts with a battery of genotoxicity tests (which include mutagenicity assays). If any of the in vivo genotoxicity tests are positive, a lifetime rodent cancer bioassay may be requested, but under most chemical regulations (except plant protection, biocides, pharmaceuticals), this is rare. The decision to conduct further testing based on genotoxicity test outcomes creates a regulatory gap for the identification of non-genotoxic carcinogens (NGTxC). With the objective of addressing this gap, in 2016, the Organization of Economic Cooperation and Development (OECD) established an expert group to develop an integrated approach to the testing and assessment (IATA) of NGTxC. Through that work, a definition of NGTxC in a regulatory context was agreed. Using the adverse outcome pathway (AOP) concept, various cancer models were developed, and overarching mechanisms and modes of action were identified. After further refining and structuring with respect to the common hallmarks of cancer and knowing that NGTxC act through a large variety of specific mechanisms, with cell proliferation commonly being a unifying element, it became evident that a panel of tests covering multiple biological traits will be needed to populate the IATA. Consequently, in addition to literature and database investigation, the OECD opened a call for relevant assays in 2018 to receive suggestions. Here, we report on the definition of NGTxC, on the development of the overarching NGTxC IATA, and on the development of ranking parameters to evaluate the assays. Ultimately the intent is to select the best scoring assays for integration in an NGTxC IATA to better identify carcinogens and reduce public health hazards.
Dopamine boosts intention and action awareness in Parkinson’s disease
Authors: Di Costa Steven , Barow Ewgenia , Hidding Ute , Mainka Tina , Pötter-Nerger Monika , Buhmann Carsten , Moll Christian K. E. , Haggard Patrick , Ganos Christos 
Published: June 2020

AbstractDopaminergic deficiency in Parkinson’s disease (PD) has been associated with underactivation of the supplementary motor area and a reduction of voluntary actions. In these patients, awareness of intention to act has been shown to be delayed. However, delayed awareness of intention to act has also been shown in patients with hyperdopaminergic states and an excess of unwilled movements, as in Tourette’s, and in patients with functional movement disorders. Hence, the role of dopamine in the awareness of intention and action remains unclear. 36 PD patients were tested ON and OFF dopaminergic medication and compared with 35 healthy age-matched controls. In addition, 17 PD patients with subthalamic deep brain stimulation (DBS) were tested ON medication and ON and OFF stimulation. Participants judged either the moment a self-generated action was performed, or the moment the urge to perform the action was felt, using the “Libet method”. Temporal judgments of intention and action awareness were comparable between unmedicated PD patients and controls. Dopaminergic medication boosted anticipatory awareness of both intentions and actions in PD patients, relative to an unmedicated condition. The difference between ON/OFF DBS was not statistically reliable. Functional improvement of motor ability in PD through dopaminergic supplementation leads to earlier awareness of both intention, and of voluntary action.
The value of 18F-FDG PET/CT for the diagnosis of device-related infections in patients with a left ventricular assist device: a systematic review and meta-analysis
Authors: ten Hove D. , Treglia G. , Slart R. H. J. A. , Damman K. , Wouthuyzen-Bakker M. , Postma D. F. , Gheysens O. , Borra R. J. H. , Mecozzi G. , van Geel P. P. , Sinha B. , Glaudemans A. W. J. M. 
Published: June 2020

Abstract
Background
Left ventricular assist devices (LVADs) are increasingly used for the treatment of advanced heart failure. LVADs improve quality of life and decrease mortality, but the driveline carries substantial risk for major infections. These device-related LVAD and driveline infections are difficult to diagnose with conventional imaging. We reviewed and analysed the current literature on the additive value of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) imaging for the diagnosis of LVAD-related infections.”

Materials/methods
We performed a systematic literature review using several databases from their inception until the 31st of December, 2019. Studies investigating the diagnostic performance of FDG-PET/CT in patients with suspected LVAD infection were retrieved. After a bias risk assessment using QUADAS-2, a study-aggregate meta-analysis was performed on a per examination-based analysis.

Results
A total of 10 studies were included in the systematic review, eight of which were also eligible for study-aggregate meta-analysis. For the meta-analysis, a total of 256 FDG-PET/CT scans, examining pump/pocket and/or driveline infection, were acquired in 230 patients. Pooled sensitivity of FDG-PET/CT was 0.95 (95% confidence interval (CI) 0.89–0.97) and pooled specificity was 0.91 (95% CI 0.54–0.99) for the diagnosis of device-related infection. For pump/pocket infection, sensitivity and specificity of FDG-PET/CT were 0.97 (95%CI 0.69–1.00) and 0.93 (95%CI 0.64–0.99), respectively. For driveline infection, sensitivity and specificity were 0.96 (95%CI 0.88–0.99) and 0.99 (95%CI 0.13–1.00) respectively. Significant heterogeneity existed across studies for specificity, mostly caused by differences in scan procedures. Predefined criteria for suspicion of LVAD and/or driveline infection were lacking in all included studies.

Conclusions
FDG-PET/CT is a valuable tool for assessment of device-related infection in LVAD patients, with high sensitivity and high, albeit variable, specificity. Standardization of FDG-PET/CT procedures and criteria for suspected device-related LVAD infections are needed for consistent reporting of FDG-PET/CT scans.
Exploration of Concerns about the Evidence-Based Guideline Approach in Conservation Management: Hints from Medical Practice
Authors: Gutzat Fabian , Dormann Carsten F. 
Published: June 2020

AbstractThe importance of using evidence in decision-making is frequently highlighted in policy reports and scientific papers. However, subjective judgments of the reliability of environmental evidence vary widely, and large-scale systematic searches for evidence are only common for climate-related topics. In the medical field, evidence-based guidelines are routinely used to guide treatments. In the management of multiple-use landscapes similar guidelines could substantially narrow the science-practice gap but are largely absent. The challenges potential guidelines face are therefore unknown. For the case of forest conservation, we conducted 14 semistructured interviews with mainly forest practitioners and presented them an example medical guideline together with evidence-based statements on forest conservation (hereinafter: statement paper). We identified 28 concerns related to potential evidence-based guidelines in forest conservation. The interviews yielded approximately three major findings. First, recommendations on forest conservation are better accepted if they include clear instructions and are formulated for a specific context. Fragmentary conservation evidence complicates the formulation of specific recommendations. Second, the level of evidence framework, which indicates the strength of the available evidence, is perceived as too complex. Third, neglecting forest multifunctionality in a potential guideline hampers its application but, if addressed, potentially weakens its ecological relevance. We show that major concerns about potential evidence-based conservation guidelines are similar to the challenges experienced by medical guidelines. We also identify concerns unique to forestry.
Wide variation in tissue, systemic, and drain fluid exposure after oxaliplatin-based HIPEC: results of the GUTOX study
Authors: de Jong Loek A. W. , Elekonawo Fortuné M. K. , Lambert Marie , de Gooyer Jan Marie , Verheul Henk M. W. , Burger David M. , de Wilt Johannes H. W. , Chatelut Etienne , ter Heine Rob , de Reuver Philip R. , Bremers Andre J. A. , van Erp Nielka P. 
Published: June 2020

Abstract
Purpose
In this exploratory study, the effect of postprocedural flushing with crystalloids after oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) on platinum concentrations in peritoneal tissue, blood, and drain fluid was studied. Interpatient variability in oxaliplatin pharmacokinetics and the relation between platinum concentration in peritoneal fluid and platinum exposure in tissue and blood was explored.

Methods
Ten patients with peritoneal carcinomatosis of colorectal origin were treated with HIPEC including postprocedural flushing, followed by ten patients without flushing afterwards. Tissue, peritoneal fluid, blood, and drain fluid samples were collected for measurement of total and ultrafiltered platinum concentrations.

Results
Peritoneal tissue concentration and systemic ultrafiltered platinum exposure showed large inter individual variability, ranging from 65 to 1640 µg/g dry weight and 10.5 to 28.0 µg*h/ml, respectively. No effect of flushing was found on geometric mean platinum concentration in peritoneal tissue (348 vs. 356 µg/g dry weight), blood (14.8 vs. 18.1 µg*h/ml), or drain fluid (day 1: 7.6 vs. 7.7 µg/ml; day 2: 1.7 vs. 1.9 µg/ml). The platinum concentration in peritoneal fluid at the start of HIPEC differed twofold between patients and was positively correlated with systemic exposure (p = .04) and peak plasma concentration (p = .04).

Conclusion
In this exploratory study, no effect was found for postprocedural flushing on platinum concentrations in peritoneal tissue, blood, or drain fluid. BSA-based HIPEC procedure leads to large interpatient variability in platinum exposure in all compartments.
The study was registered at ClinicalTrials.gov on 7 December 2017 under registration number NCT03364907.
Clinically significant prostate cancer detection and segmentation in low-risk patients using a convolutional neural network on multi-parametric MRI
Authors: Arif Muhammad , Schoots Ivo G. , Castillo Tovar Jose , Bangma Chris H. , Krestin Gabriel P. , Roobol Monique J. , Niessen Wiro , Veenland Jifke F. 
Published: June 2020

Abstract
Objectives
To develop an automatic method for identification and segmentation of clinically significant prostate cancer in low-risk patients and to evaluate the performance in a routine clinical setting.

Methods
A consecutive cohort (n = 292) from a prospective database of low-risk patients eligible for the active surveillance was selected. A 3-T multi-parametric MRI at 3 months after inclusion was performed. Histopathology from biopsies was used as reference standard. MRI positivity was defined as PI-RADS score ≥ 3, histopathology positivity was defined as ISUP grade ≥ 2. The selected cohort contained four patient groups: (1) MRI-positive targeted biopsy-positive (n = 116), (2) MRI-negative systematic biopsy-negative (n = 55), (3) MRI-positive targeted biopsy-negative (n = 113), (4) MRI-negative systematic biopsy-positive (n = 8). Group 1 was further divided into three sets and a 3D convolutional neural network was trained using different combinations of these sets. Two MRI sequences (T2w, b = 800 DWI) and the ADC map were used as separate input channels for the model. After training, the model was evaluated on the remaining group 1 patients together with the patients of groups 2 and 3 to identify and segment clinically significant prostate cancer.

Results
The average sensitivity achieved was 82–92% at an average specificity of 43–76% with an area under the curve (AUC) of 0.65 to 0.89 for different lesion volumes ranging from > 0.03 to > 0.5 cc.

Conclusions
The proposed deep learning computer-aided method yields promising results in identification and segmentation of clinically significant prostate cancer and in confirming low-risk cancer (ISUP grade ≤ 1) in patients on active surveillance.

Key Points
• Clinically significant prostate cancer identification and segmentation on multi-parametric MRI is feasible in low-risk patients using a deep neural network.
• The deep neural network for significant prostate cancer localization performs better for lesions with larger volumes sizes (> 0.5 cc) as compared to small lesions (> 0.03 cc).
• For the evaluation of automatic prostate cancer segmentation methods in the active surveillance cohort, the large discordance group (MRI positive, targeted biopsy negative) should be included.
Experimental investigation of the effect of transpiration cooling on second mode instabilities in a hypersonic boundary layer
Authors: Camillo Giannino Ponchio , Wagner Alexander , Dittert Christian , Benjamin Leroy , Wartemann Viola , Neumann Jens , Hink Rüdiger 
Published: June 2020

Abstract
The influence of localized nitrogen transpiration on second mode instabilities in a hypersonic boundary layer is experimentally investigated. The study is conducted using a $$7^\circ$$

7
∘

half-angle cone with a length of 1100 mm and small nose bluntness at $$0^\circ$$

0
∘

angle-of-attack. Transpiration is realized through a porous Carbon/Carbon patch of $$44 \times 82$$

44
×
82

mm located near the expected boundary layer transition onset location. Transpiration mass flow rates in the range of 0.05–1% of the equivalent boundary layer edge mass flow rate were used. Experiments were conducted in the High Enthalpy Shock Tunnel Göttingen (HEG) at total enthalpies around 3 MJ/kg and unit Reynolds numbers in the range of $$1.4 \cdot 10^6 \,$$

1.4
·

10
6

to $$6.4 \cdot 10^6 \, {\text {m}}^{-1}$$

6.4
·

10
6

m

-
1

. Measurements were conducted by means of coaxial thermocouples, Atomic Layer Thermopiles (ALTP), pressure transducers and high-speed schlieren. The present study shows that the most amplified second mode frequencies were shifted to lower values as nitrogen is transpired into the boundary layer. In some cases the instability amplitudes were found to be significantly reduced. The observed frequency reduction was verified to correlate with the change of the relative sonic line height in the boundary layer. The amplitude damping was observed to occur only until the most amplified frequencies were reduced to around 50% of their undisturbed values. When transpiration within this limit was performed shortly upstream of the natural boundary layer transition onset, a transition delay of approximately 17% could be observed.

Graphic abstract
Nuclear ErbB2 expression in hepatocytes in liver disease
Authors: Döring Paula , Calvisi Diego F. , Dombrowski Frank 
Published: June 2020

AbstractErbB2 is a prominent representative of the epidermal growth factor receptors that mainly attract attention as oncogenic drivers and therapeutic targets in cancer. Besides transmembrane signaling, ErbB2 may also translocate into the nucleus and mediate distinct nuclear signaling effects including DNA repair and cell cycle arrest. Unexpectedly, we found nuclear ErbB2 expression in human hepatocytes in various liver diseases so we aimed to investigate the characteristics of liver disease leading to nuclear ErbB2 translocation. The immunohistochemical pattern of ErbB2 staining was analyzed in 1125 liver biopsy samples from patients with hepatic dysfunction. Further signaling and metabolic markers were analyzed by immunohistochemistry in selected liver biopsy samples. We found a cytoplasmic and nuclear ErbB2 expression in hepatocytes from different disease conditions with the strongest expression detected in alcoholic steatohepatitis. Nuclear ErbB2 positivity significantly correlated with histologic parameters of hepatocellular damage including inflammatory activity in steatohepatitis, hepatocellular ballooning, and cholestasis. ErbB2 overexpressing hepatocytes revealed an increase of phospho-STAT3, a downstream effector of nuclear ErbB2 signaling. Notably, we observed in nuclear ErbB2-positive hepatocytes a downregulation of estrogen receptor expression. In alcoholic steatohepatitis and other toxic liver diseases, hepatocytes revealed a nuclear ErbB2 expression implying a so far unknown mechanism in hepatocytes upon cellular stress that might lead to resistance to cell death. Nuclear ErbB2-positive hepatocytes showed downregulation of estrogen receptor expression and increased levels of pSTAT3, which are signs of functionality of nuclear ErbB2 signaling. Furthermore, analysis of hepatocellular ErbB2 expression could serve as helpful tool for diagnosis of liver disease.
Creatine, guanidinoacetate and homoarginine in statin-induced myopathy
Authors: Neu Axel , Hornig Sönke , Sasani Ali , Isbrandt Dirk , Gerloff Christian , Tsikas Dimitris , Schwedhelm Edzard , Choe Chi-un 
Published: June 2020

AbstractOur study evaluated the effect of creatine and homoarginine in AGAT- and GAMT-deficient mice after simvastatin exposure. Balestrino and Adriano suggest that guanidinoacetate might explain the difference between AGAT- and GAMT-deficient mice in simvastatin-induced myopathy. We agree with Balestrino and Adriano that our data shows that (1) creatine possesses a protective potential to ameliorate statin-induced myopathy in humans and mice and (2) homoarginine did not reveal a beneficial effect in statin-induced myopathy. Third, we agree that guanidinoacetate can be phosphorylated and partially compensate for phosphocreatine. In our study, simvastatin-induced damage showed a trend to be less pronounced in GAMT-deficient mice compared with wildtype mice. Therefore, (phospo) guanidinoacetate cannot completely explain the milder phenotype of GAMT-deficient mice, but we agree that it might contribute to ameliorate statin-induced myopathy in GAMT-deficient mice compared with AGAT-deficient mice. Finally, we agree with Balestino and Adriano that AGAT metabolites should further be evaluated as potential treatments in statin-induced myopathy.
A Mathematical Model of HIF-1 Regulated Cellular Energy Metabolism
Authors: Bocharov Gennady , Jäger Willi , Knoch Jonas , Neuss-Radu Maria , Thiel Manfred 
Published: June 2020

AbstractIn this study, we formulated a mathematical model of hypoxia-inducible factor 1 (HIF-1) mediated regulation of cellular energy metabolism describing the reprogramming of cell metabolic processes from oxidative phosphorylation to glycolysis under reduced oxygen levels. The model considers the dynamics of fifteen biochemical species and the proton concentration with the underlying reaction processes localized in three intracellular compartments, i.e. the cytoplasm, mitochondrion and nucleus. More than sixty parameters of the model were calibrated using both the published data and the system steady-state based identification procedure. The model was validated by generating predictions which could be compared to empirical observations. The model behaviors representing the cell metabolism switching over in response to transitioning from a normoxic to hypoxic environment are consistent with the current views of the role of HIF-1 in hypoxia.
Response to commentary ‘towards more meaningful scenarios of biodiversity responses to land-use change in Central Asia
Authors: Nunez Sarahi , Alkemade Rob , Kok Kasper , Leemans Rik 
Published: June 2020

AbstractWith this letter, we respond to the commentary by Kamp et al. on our paper (Nunez et al. in Reg Environ Chang 20:39, 2020) that reports on potential biodiversity change in Central Asian grasslands using climate and land-use change scenarios. In their commentary, Kamp et al. criticize data and methods employed and discuss several shortfalls of our approach. In this response, we argue that in our paper projections of future biodiversity already acknowledge the issues indicated by Kamp et al. We elaborate on the reasons why. We maintain our main finding that, based on a number of contrasting scenarios (shared socioeconomic pathways and representative concentration pathways combinations), biodiversity in grasslands in Central Asia will potentially decline under each scenario. We conclude that while our data and methods conservatively estimate potential biodiversity changes in the Central Asian grasslands, they could be enriched with more elements. The results, however, are likely to confirm the vulnerability of these grasslands and the possible decline in their biodiversity.