bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dapagliflozin effects on haematocrit, red blood cell count and reticulocytes in insulin-treated patients with type 2 diabetes
Authors: Aberle Jens , Menzen Markus , Schmid Sebastian M. , Terkamp Christoph , Jaeckel Elmar , Rohwedder Katja , Scheerer Markus F. , Xu John , Tang Weifeng , Birkenfeld Andreas L. 
Published: December 2020

AbstractRecent studies have shown that high-risk patients with type 2 diabetes mellitus (T2DM) treated with sodium glucose cotransporter 2 (SGLT2) inhibitors have improved cardiovascular (CV) outcomes. In an exploratory analysis of data from the EMPA-REG study, elevations in haematocrit were shown to be strongly associated with beneficial CV effects. As insulin treatment has been shown to be antinatriuretic, with an associated increase in extracellular fluid volume, it is important to confirm whether haematocrit increase is maintained with concomitant insulin therapy. Here, we investigate the effect of the SGLT2 inhibitor dapagliflozin on haematocrit, red blood cell (RBC) counts and reticulocyte levels in high-risk patients with T2DM receiving insulin. A 24-week, double-blinded, randomised, placebo-controlled trial (ClinicalTrials.gov: NCT00673231) was reported previously with extension periods of 24 and 56 weeks (total of 104 weeks). Patients receiving insulin were randomised 1:1:1:1 to placebo or dapagliflozin at 2.5, 5 or 10 mg. Haematocrit, RBC and reticulocyte measurements were conducted during this study, and a longitudinal repeated-measures analysis was performed here to examine change from baseline during treatment. Dapagliflozin treatment in combination with insulin resulted in a dose-dependent increase in haematocrit levels and RBCs over a 104 week period. There was a short-term increase in reticulocyte levels at the start of treatment, which dropped to below baseline after 8 weeks. SGLT2 inhibition with dapagliflozin leads to a sustained increase in haematocrit in patients receiving chronic insulin treatment.
Comprehensive phenotyping revealed transient startle response reduction and histopathological gadolinium localization to perineuronal nets after gadodiamide administration in rats
Authors: Habermeyer Johanna , Boyken Janina , Harrer Julia , Canneva Fabio , Ratz Veronika , Moceri Sandra , Admard Jakob , Casadei Nicolas , Jost Gregor , Bäuerle Tobias , Frenzel Thomas , Schmitz Christoph , Schütz Gunnar , Pietsch Hubertus , von Hörsten Stephan 
Published: December 2020

AbstractGadolinium based contrast agents (GBCAs) are widely used in clinical MRI since the mid-1980s. Recently, concerns have been raised that trace amounts of Gadolinium (Gd), detected in brains even long time after GBCA application, may cause yet unrecognized clinical consequences. We therefore assessed the behavioral phenotype, neuro-histopathology, and Gd localization after repeated administration of linear (gadodiamide) or macrocyclic (gadobutrol) GBCA in rats. While most behavioral tests revealed no difference between treatment groups, we observed a transient and reversible decrease of the startle reflex after gadodiamide application. Residual Gd in the lateral cerebellar nucleus was neither associated with a general gene expression pathway deregulation nor with neuronal cell loss, but in gadodiamide-treated rats Gd was associated with the perineuronal net protein aggrecan and segregated to high molecular weight fractions. Our behavioral finding together with Gd distribution and speciation support a substance class difference for Gd presence in the brain after GBCA application.
Vitamin D moderates the interaction between 5-HTTLPR and childhood abuse in depressive disorders
Authors: Bonk Sarah , Hertel Johannes , Zacharias Helena U. , Terock Jan , Janowitz Deborah , Homuth Georg , Nauck Matthias , Völzke Henry , Meyer zu Schwabedissen Henriette , Van der Auwera Sandra , Grabe Hans Jörgen 
Published: December 2020

AbstractA complex interplay between genetic and environmental factors determines the individual risk of depressive disorders. Vitamin D has been shown to stimulate the expression of the tryptophan hydroxylase 2 (TPH2) gene, which is the rate-limiting enzyme for serotonin production in the brain. Therefore, we investigate the hypothesis that serum vitamin D levels moderate the interaction between the serotonin transporter promotor gene polymorphism (5-HTTLPR) and childhood abuse in depressive disorders. Two independent samples from the Study of Health in Pomerania (SHIP-LEGEND: n = 1 997; SHIP-TREND-0: n = 2 939) were used. Depressive disorders were assessed using questionnaires (BDI-II, PHQ-9) and interview procedures (DSM-IV). Besides serum vitamin D levels (25(OH)D), a functional polymorphism (rs4588) of the vitamin D-binding protein is used as a proxy for 25(OH)D. S-allele carriers with childhood abuse and low 25(OH)D levels have a higher mean BDI-II score (13.25) than those with a higher 25(OH)D level (9.56), which was not observed in abused LL-carriers. This significant three-way interaction was replicated in individuals with lifetime major depressive disorders when using the rs4588 instead of 25(OH)D (p = 0.0076 in the combined sample). We conclude that vitamin D relevantly moderates the interaction between childhood abuse and the serotonergic system, thereby impacting vulnerability to depressive disorders.
A novel diagnostic map for computer‐aided diagnosis of skin cancer
Authors: Ashour Amira S. , Wahba Maram A. , Alaa Eman Elsaid , Guo Yanhui , Hawas Ahmed Refaat 
Published: December 2020

AbstractIn teledermoscopy, images are transmitted through a communication channel to the medical facility for medical consultation. This yields to bandwidth congestion and consumption of large storage size which impairs the transmission of the high‐resolution dermoscopy image. This study proposes a novel technique by generating a diagnostic feature map, named diagonal compressive sensing (CS) features map. This proposed map is generated using the significant diagnostic features by aligning the feature vector in a diagonal map, which is then compressed using CS technique. Eventually, the recovered feature map at the receiver side is applied to the classification system for decision‐making. In addition, physicians at the receiver side who were trained to read the feature maps can verify the classification decision, and then provide feedback to the patient. The results demonstrated that the proposed diagnostic map achieved less transmission time due to the small size of the feature map along with the compression process. Furthermore, the feature map has drastically improved the classification performance metrics, including the accuracy, which increased, for example, from 88.6% to 98% at 80% compression ratio compared to the traditional method on the compressed whole image.
Keypoint based comprehensive copy‐move forgery detection
Authors: Diwan Anjali , Sharma Rajat , Roy Anil K. , Mitra Suman K. 
Published: December 2020

AbstractVerifying the authenticity of a digital image has been challenging problem. The simplest of the image tampering tricks is the copy‐move forgery. In copy‐move forgery copied portion of the image is pasted on another part of the same image. Geometrical transformations are used on the copied portions of the image before pasting it for the tampered image to look realistic and visually convincing. To make it more complex, other processing approaches may also be applied in the forged region for hiding traces of forgery. These processings are the scale, rotation, JPEG compression, and AWGN. In this paper, an approach based on features of the CenSurE keypoint detector and FREAK descriptor is proposed. This combination has novelty in itself as it has never been used for this purpose before to the best of authors' literature studies. CenSurE detectors are fast and give stable and accurate output even in the case of rotated images, which we club with binary descriptor FREAK. Hierarchical clustering and Neighbourhood search is applied in such a way that it can locate and detect multiple copy‐move forgeries. The authors are hopeful that the proposed approach may be used in real‐time image authentication and copy‐move forgery detection.
Synthesis of Dihydroanthracenes via Palladium-Catalyzed Tandem Mizoroki–Heck/Reductive Heck Reactions Using Cyclic Diaryliodoniums and Alkenes
Authors: Peng Xiaopeng , Yang Jianfeng , Qiu Xinhua , Duan Yuansheng , Bao Zeqing , Chen Jingfeng 
Published: December 2020

AbstractAn efficient Pd-catalyzed domino Mizoroki–Heck and reductive Heck reaction of terminal alkenes with six-membered cyclic diaryliodoniums is reported for the facile access to a diverse set of novel dihydroanthracenes. The scope of alkenes is general, leading to concise generation of 30 dihydroanthracenes which are not easily accessed by conventional methods. Furthermore, one of the newly synthesized dihydroanthracene displayed excellent antiproliferative activity against PANC-1 cancer cells (IC50 = 11.74 μM).
Peripherally Donor-Installed 7,8-Diaza[5]helicenes as a Platform for Helical Luminophores
Authors: Esser Birgit , Data Przemyslaw , Takeda Youhei , Ikari Yuta , Kaihara Takahito , Goto Shimpei , Bovenkerk Marcel , Grenz David C. , Ferreira Marli , Stachelek Patrycja , Yoshida Takumu , Ikai Tomoyuki , Tohnai Norimitsu , Minakata Satoshi 
Published: December 2020

AbstractA new family of emissive donor–acceptor–donor (D-A-D) compounds has been developed by introducing two electron donors into the 7,8-diaza[5]helicene core as a novel helical electron acceptor. The X-ray crystallographic analyses revealed the uniquely twisted and helical structures of these compounds in the solid states. Notably, some D-A-D compounds developed herein display distinct mechanochromic luminescence (MCL) in the solid state, and a D-A-D helicene shows circularly polarized luminescence (CPL) with a relatively high luminescence dissymmetry factor g
lum of ca. 10–3. Time-resolved spectroscopic analysis revealed the aspects of thermally activated delayed fluorescence characters of the helicenes. Furthermore, the emissive helicenes were applied to organic light-emitting diodes as emitters.
On conservation laws in quantum mechanics
Authors: Aharonov Yakir , Popescu Sandu , Rohrlich Daniel 
Published: December 2020

Significance
Conservation laws are one of the most important aspects of nature. As such, they have been intensively studied and extensively applied, and are considered to be perfectly well established. We, however, raise fundamental question about the very meaning of conservation laws in quantum mechanics. We argue that, although the standard way in which conservation laws are defined in quantum mechanics is perfectly valid as far as it goes, it misses essential features of nature and has to be revisited and extended.
Massively parallel discovery of human-specific substitutions that alter enhancer activity
Authors: Uebbing Severin , Gockley Jake , Reilly Steven K. , Kocher Acadia A. , Geller Evan , Gandotra Neeru , Scharfe Curt , Cotney Justin , Noonan James P. 
Published: December 2020

Significance
Uniquely human biology is the result of genetic differences between humans and other primates, but identifying the critical changes still poses a major challenge. We screened >32,000 human-specific substitutions in two classes of putative transcriptional enhancers implicated in human evolution for their effects on enhancer activity in human neural stem cells, a cell type fundamental for cortical development and expansion. We identify hundreds of substitutions that modify enhancer activity either alone or in combination with other variants. We find different patterns of substitution effects in different enhancer types. Our data support substitutions often interacting by modifying the same transcription factor binding sites. The functional substitutions we identify provide a rich set of candidate loci for studies of human-specific regulatory evolution.
UFMylation inhibits the proinflammatory capacity of interferon-γ–activated macrophages
Authors: Balce Dale R. , Wang Ya-Ting , McAllaster Michael R. , Dunlap Bria F. , Orvedahl Anthony , Hykes Barry L. , Droit Lindsay , Handley Scott A. , Wilen Craig B. , Doench John G. , Orchard Robert C. , Stallings Christina L. , Virgin Herbert W. 
Published: December 2020

SignificanceInterferon-γ (IFN-γ)–dependent macrophage activation is an important component of the innate immune response. Although critical for cellular defenses against intracellular pathogens and activation of the adaptive immune system, overactive responses to IFN-γ could be harmful to the host. We conducted a genome-wide CRISPR knockout screen to identify pathways that, if perturbed, could lead to increased responses to IFN-γ and identify the UFMylation system as a negative regulator of IFN-γ activation. Increased responses to IFN-γ in UFMylation-deficient cells was dependent on the endoplasmic reticulum stress signal transducer Ern1 and myeloid-specific deletion of a UFMylation gene led to altered responses to infection in vivo. This work highlights the importance of maintaining endoplasmic reticulum homeostasis in macrophages during exposure to proinflammatory stimuli.
Statistical finite elements for misspecified models
Authors: Duffin Connor , Cripps Edward , Stemler Thomas , Girolami Mark 
Published: December 2020

Significance
Science and engineering have benefited greatly from the ability of finite element methods (FEMs) to simulate nonlinear, time-dependent complex systems. The recent advent of extensive data collection from such complex systems now raises the question of how to systematically incorporate these data into finite element models, consistently updating the solution in the face of mathematical model misspecification with physical reality. This article describes general and widely applicable methodology for the coherent synthesis of data with FEM models, providing a data-driven probability distribution that captures all sources of uncertainty in the pairing of FEM with measurements.
Gigantic vortical differential scattering as a monochromatic probe for multiscale chiral structures
Authors: Ni Jincheng , Liu Shunli , Wu Dong , Lao Zhaoxin , Wang Zhongyu , Huang Kun , Ji Shengyun , Li Jiawen , Huang Zhixiang , Xiong Qihua , Hu Yanlei , Chu Jiaru , Qiu Cheng-Wei 
Published: December 2020

Significance
Optical chirality by light–matter interaction is a powerful strategy for discriminating the chirality of materials in modern physics. Here we present a vortex-dependent approach to yield a direct chiroptical response with monochromatic light. The chiroptical signal of ∼120% is obtained on intrinsically chiral microstructures by optical vortices in the visible range. The chiroptical properties of microstructures can be flexibly controlled by tuning their geometric features. We further demonstrate the strong chiral light–matter interaction by optical vortices for sensitively detecting optical chirality of molecules.
The in-situ XAS study on the formation of Pd nanoparticles via thermal decomposition of palladium (II) acetate in hydroxyl functionalized ionic liquids
Authors: Yao Siyu , Sun Haolin , Ma Ding 
Published: December 2020

Abstract
The formation of palladium nanoparticles (NPs) via thermal decomposition of palladium (II) acetate in hydroxyl functionalized ionic liquid (IL) [C2OHmim]+[NTf2]− was studied using in-situ energy dispersive x-ray absorption fine structure spectroscopy (DXAFS) and complementary methods such as transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry. Detailed XAFS spectra analysis unraveled that the palladium acetate trimer precursor underwent dissociation after being dispersed in ILs, which accelerated the thermal decomposition compared with other organic solvents. Based on the reaction kinetics, extened x-ray absorption fine structure spectroscopy fitting and TEM characterization results, the thermal decomposition process can be divided three successive stages namely the explosive nucleation, autocatalytic surface growth and NP attachment growth.
Fabrication of CsPbBr3 films with high quality using a simple method
Authors: Yang Xingming , Li Mengmeng , Jiang Junjie , Ma Ligang , Tang Wenchao , Xu Cuiping , Cai H L , Zhang F M , Wu X S 
Published: December 2020

Abstract
Inorganic perovskite CsPbBr3 is a material used for fabricating highly efficient and stable perovskite solar cells. In this work, a two-step infiltration-spinning method is proposed to obtain CsPbBr3 films with pure phase. Phase transformations between CsPb2Br5, CsPbBr3 and Cs4PbBr6 are investigated by controlling the contact time between the CsBr solution and the PbBr2 substrate. CsPbBr3 films with large grain sizes are obtained after high temperature post-treatment. The CsPbBr3-based solar cells show a high efficiency (approximately 7%) with a short-circuit current density of 6.68 mA cm−2, an open-circuit voltage of 1.47 V and a fill factor of 70.9% under standard solar illumination.
Kant on Aesthetic Attention
Authors: Williams Jessica J 
Published: December 2020

AbstractIn this paper, I examine the role of attention in Kant’s aesthetic theory in the Critique of the Power of Judgment. While broadly Kantian aestheticians have defended the claim that there is a distinct way that we attend to objects in aesthetic experience, Kant himself is not usually acknowledged as offering an account of aesthetic attention. On the basis of Kant’s more general account of attention in other texts and his remarks on attention in the Critique of the Power of Judgment, I reconstruct Kant’s account of aesthetic attention. On his account, aesthetic attention is simultaneously directed at the form of an object and at the judging subject’s own mental states as she attends to the object. In the experience of beauty, we specifically attend to the harmonious relation between the faculties of imagination and understanding.
Machine learning application for patient stratification and phenotype/genotype investigation in a rare disease
Authors: Spiga Ottavia , Cicaloni Vittoria , Dimitri Giovanna Maria , Pettini Francesco , Braconi Daniela , Bernini Andrea , Santucci Annalisa 
Published: December 2020

Abstract
Alkaptonuria (AKU, OMIM: 203500) is an autosomal recessive disorder caused by mutations in the Homogentisate 1,2-dioxygenase (HGD) gene. A lack of standardized data, information and methodologies to assess disease severity and progression represents a common complication in ultra-rare disorders like AKU. This is the reason why we developed a comprehensive tool, called ApreciseKUre, able to collect AKU patients deriving data, to analyse the complex network among genotypic and phenotypic information and to get new insight in such multi-systemic disease. By taking advantage of the dataset, containing the highest number of AKU patient ever considered, it is possible to apply more sophisticated computational methods (such as machine learning) to achieve a first AKU patient stratification based on phenotypic and genotypic data in a typical precision medicine perspective. Thanks to our sufficiently populated and organized dataset, it is possible, for the first time, to extensively explore the phenotype–genotype relationships unknown so far. This proof of principle study for rare diseases confirms the importance of a dedicated database, allowing data management and analysis and can be used to tailor treatments for every patient in a more effective way.
SoluProt: prediction of soluble protein expression inEscherichia coli
Authors: Hon Jiri , Marusiak Martin , Martinek Tomas , Kunka Antonin , Zendulka Jaroslav , Bednar David , Damborsky Jiri 
Published: December 2020

AbstractMotivationPoor protein solubility hinders the production of many therapeutic and industrially useful proteins. Experimental efforts to increase solubility are plagued by low success rates and often reduce biological activity. Computational prediction of protein expressibility and solubility in Escherichia coli using only sequence information could reduce the cost of experimental studies by enabling prioritization of highly soluble proteins.ResultsA new tool for sequence-based prediction of soluble protein expression in E.coli, SoluProt, was created using the gradient boosting machine technique with the TargetTrack database as a training set. When evaluated against a balanced independent test set derived from the NESG database, SoluProt’s accuracy of 58.5% and AUC of 0.62 exceeded those of a suite of alternative solubility prediction tools. There is also evidence that it could significantly increase the success rate of experimental protein studies. SoluProt is freely available as a standalone program and a user-friendly webserver at https://loschmidt.chemi.muni.cz/soluprot/.Availability and implementationhttps://loschmidt.chemi.muni.cz/soluprot/.Supplementary informationSupplementary data are available at Bioinformatics online.
Damage to Broca’s area does not contribute to long-term speech production outcome after stroke
Authors: Gajardo-Vidal Andrea , Lorca-Puls Diego L , team PLORAS , Warner Holly , Pshdary Bawan , Crinion Jennifer T , Leff Alexander P , Hope Thomas M H , Geva Sharon , Seghier Mohamed L , Green David W , Bowman Howard , Price Cathy J 
Published: December 2020

Abstract
Broca’s area in the posterior half of the left inferior frontal gyrus has long been thought to be critical for speech production. The current view is that long-term speech production outcome in patients with Broca’s area damage is best explained by the combination of damage to Broca’s area and neighbouring regions including the underlying white matter, which was also damaged in Paul Broca’s two historic cases. Here, we dissociate the effect of damage to Broca’s area from the effect of damage to surrounding areas by studying long-term speech production outcome in 134 stroke survivors with relatively circumscribed left frontal lobe lesions that spared posterior speech production areas in lateral inferior parietal and superior temporal association cortices. Collectively, these patients had varying degrees of damage to one or more of nine atlas-based grey or white matter regions: Brodmann areas 44 and 45 (together known as Broca’s area), ventral premotor cortex, primary motor cortex, insula, putamen, the anterior segment of the arcuate fasciculus, uncinate fasciculus and frontal aslant tract. Spoken picture description scores from the Comprehensive Aphasia Test were used as the outcome measure. Multiple regression analyses allowed us to tease apart the contribution of other variables influencing speech production abilities such as total lesion volume and time post-stroke. We found that, in our sample of patients with left frontal damage, long-term speech production impairments (lasting beyond 3 months post-stroke) were solely predicted by the degree of damage to white matter, directly above the insula, in the vicinity of the anterior part of the arcuate fasciculus, with no contribution from the degree of damage to Broca’s area (as confirmed with Bayesian statistics). The effect of white matter damage cannot be explained by a disconnection of Broca’s area, because speech production scores were worse after damage to the anterior arcuate fasciculus with relative sparing of Broca’s area than after damage to Broca’s area with relative sparing of the anterior arcuate fasciculus. Our findings provide evidence for three novel conclusions: (i) Broca’s area damage does not contribute to long-term speech production outcome after left frontal lobe strokes; (ii) persistent speech production impairments after damage to the anterior arcuate fasciculus cannot be explained by a disconnection of Broca’s area; and (iii) the prior association between persistent speech production impairments and Broca’s area damage can be explained by co-occurring white matter damage, above the insula, in the vicinity of the anterior part of the arcuate fasciculus.