bluuebunny/crossref_metadata_2025_split huggingface dataset:
SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease
Authors: Kim So Ra , Lee Sang-Guk , Kim Soo Hyun , Kim Jin Hee , Choi Eunhye , Cho Wonhee , Rim John Hoon , Hwang Inhwa , Lee Chan Joo , Lee Minyoung , Oh Chang-Myung , Jeon Justin Y. , Gee Heon Yung , Kim Jeong-Ho , Lee Byung-Wan , Kang Eun Seok , Cha Bong-Soo , Lee Myung-Shik , Yu Je-Wook , Cho Jin Won , Kim Jung-Sun , Lee Yong-ho 
Published: May 2020

AbstractSodium–glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor’s glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.
Ultrastructural visualization of 3D chromatin folding using volume electron microscopy and DNA in situ hybridization
Authors: Trzaskoma Paweł , Ruszczycki Błażej , Lee Byoungkoo , Pels Katarzyna K. , Krawczyk Katarzyna , Bokota Grzegorz , Szczepankiewicz Andrzej A. , Aaron Jesse , Walczak Agnieszka , Śliwińska Małgorzata A. , Magalska Adriana , Kadlof Michal , Wolny Artur , Parteka Zofia , Arabasz Sebastian , Kiss-Arabasz Magdalena , Plewczyński Dariusz , Ruan Yijun , Wilczyński Grzegorz M. 
Published: May 2020

AbstractThe human genome is extensively folded into 3-dimensional organization. However, the detailed 3D chromatin folding structures have not been fully visualized due to the lack of robust and ultra-resolution imaging capability. Here, we report the development of an electron microscopy method that combines serial block-face scanning electron microscopy with in situ hybridization (3D-EMISH) to visualize 3D chromatin folding at targeted genomic regions with ultra-resolution (5 × 5 × 30 nm in xyz dimensions) that is superior to the current super-resolution by fluorescence light microscopy. We apply 3D-EMISH to human lymphoblastoid cells at a 1.7 Mb segment of the genome and visualize a large number of distinctive 3D chromatin folding structures in ultra-resolution. We further quantitatively characterize the reconstituted chromatin folding structures by identifying sub-domains, and uncover a high level heterogeneity of chromatin folding ultrastructures in individual nuclei, suggestive of extensive dynamic fluidity in 3D chromatin states.
Attention amplifies neural representations of changes in sensory input at the expense of perceptual accuracy
Authors: Mehrpour Vahid , Martinez-Trujillo Julio C. , Treue Stefan 
Published: May 2020

AbstractAttention enhances the neural representations of behaviorally relevant stimuli, typically by a push–pull increase of the neuronal response gain to attended vs. unattended stimuli. This selectively improves perception and consequently behavioral performance. However, to enhance the detectability of stimulus changes, attention might also distort neural representations, compromising accurate stimulus representation. We test this hypothesis by recording neural responses in the visual cortex of rhesus monkeys during a motion direction change detection task. We find that attention indeed amplifies the neural representation of direction changes, beyond a similar effect of adaptation. We further show that humans overestimate such direction changes, providing a perceptual correlate of our neurophysiological observations. Our results demonstrate that attention distorts the neural representations of abrupt sensory changes and consequently perceptual accuracy. This likely represents an evolutionary adaptive mechanism that allows sensory systems to flexibly forgo accurate representation of stimulus features to improve the encoding of stimulus change.
Taking a snapshot of the triplet excited state of an OLED organometallic luminophore using X-rays
Authors: Smolentsev Grigory , Milne Christopher J. , Guda Alexander , Haldrup Kristoffer , Szlachetko Jakub , Azzaroli Nicolo , Cirelli Claudio , Knopp Gregor , Bohinc Rok , Menzi Samuel , Pamfilidis Georgios , Gashi Dardan , Beck Martin , Mozzanica Aldo , James Daniel , Bacellar Camila , Mancini Giulia F. , Tereshchenko Andrei , Shapovalov Victor , Kwiatek Wojciech M. , Czapla-Masztafiak Joanna , Cannizzo Andrea , Gazzetto Michela , Sander Mathias , Levantino Matteo , Kabanova Victoria , Rychagova Elena , Ketkov Sergey , Olaru Marian , Beckmann Jens , Vogt Matthias 
Published: May 2020

AbstractOLED technology beyond small or expensive devices requires light-emitters, luminophores, based on earth-abundant elements. Understanding and experimental verification of charge transfer in luminophores are needed for this development. An organometallic multicore Cu complex comprising Cu–C and Cu–P bonds represents an underexplored type of luminophore. To investigate the charge transfer and structural rearrangements in this material, we apply complementary pump-probe X-ray techniques: absorption, emission, and scattering including pump-probe measurements at the X-ray free-electron laser SwissFEL. We find that the excitation leads to charge movement from C- and P- coordinated Cu sites and from the phosphorus atoms to phenyl rings; the Cu core slightly rearranges with 0.05 Å increase of the shortest Cu–Cu distance. The use of a Cu cluster bonded to the ligands through C and P atoms is an efficient way to keep structural rigidity of luminophores. Obtained data can be used to verify computational methods for the development of luminophores.
Accelerating invasion potential of disease vector Aedes aegypti under climate change
Authors: Iwamura Takuya , Guzman-Holst Adriana , Murray Kris A. 
Published: May 2020

AbstractVector-borne diseases remain a major contributor to the global burden of disease, while climate change is expected to exacerbate their risk. Characterising vector development rate and its spatio-temporal variation under climate change is central to assessing the changing basis of human disease risk. We develop a mechanistic phenology model and apply it to Aedes aegypti, an invasive mosquito vector for arboviruses (e.g. dengue, zika and yellow fever). The model predicts the number of life-cycle completions (LCC) for a given location per unit time based on empirically derived biophysical responses to environmental conditions. Results suggest that the world became ~1.5% more suitable per decade for the development of Ae. aegypti during 1950–2000, while this trend is predicted to accelerate to 3.2–4.4% per decade by 2050. Invasion fronts in North America and China are projected to accelerate from ~2 to 6 km/yr by 2050. An increase in peak LCC combined with extended periods suitable for mosquito development is simulated to accelerate the vector’s global invasion potential.
Molecular mechanism of light-driven sodium pumping
Authors: Kovalev Kirill , Astashkin Roman , Gushchin Ivan , Orekhov Philipp , Volkov Dmytro , Zinovev Egor , Marin Egor , Rulev Maksim , Alekseev Alexey , Royant Antoine , Carpentier Philippe , Vaganova Svetlana , Zabelskii Dmitrii , Baeken Christian , Sergeev Ilya , Balandin Taras , Bourenkov Gleb , Carpena Xavier , Boer Roeland , Maliar Nina , Borshchevskiy Valentin , Büldt Georg , Bamberg Ernst , Gordeliy Valentin 
Published: May 2020

AbstractThe light-driven sodium-pumping rhodopsin KR2 from Krokinobacter eikastus is the only non-proton cation active transporter with demonstrated potential for optogenetics. However, the existing structural data on KR2 correspond exclusively to its ground state, and show no sodium inside the protein, which hampers the understanding of sodium-pumping mechanism. Here we present crystal structure of the O-intermediate of the physiologically relevant pentameric form of KR2 at the resolution of 2.1 Å, revealing a sodium ion near the retinal Schiff base, coordinated by N112 and D116 of the characteristic NDQ triad. We also obtained crystal structures of D116N and H30A variants, conducted metadynamics simulations and measured pumping activities of putative pathway mutants to demonstrate that sodium release likely proceeds alongside Q78 towards the structural sodium ion bound between KR2 protomers. Our findings highlight the importance of pentameric assembly for sodium pump function, and may be used for rational engineering of enhanced optogenetic tools.
A deep-learned skin sensor decoding the epicentral human motions
Authors: Kim Kyun Kyu , Ha InHo , Kim Min , Choi Joonhwa , Won Phillip , Jo Sungho , Ko Seung Hwan 
Published: May 2020

AbstractState monitoring of the complex system needs a large number of sensors. Especially, studies in soft electronics aim to attain complete measurement of the body, mapping various stimulations like temperature, electrophysiological signals, and mechanical strains. However, conventional approach requires many sensor networks that cover the entire curvilinear surfaces of the target area. We introduce a new measuring system, a novel electronic skin integrated with a deep neural network that captures dynamic motions from a distance without creating a sensor network. The device detects minute deformations from the unique laser-induced crack structures. A single skin sensor decodes the complex motion of five finger motions in real-time, and the rapid situation learning (RSL) ensures stable operation regardless of its position on the wrist. The sensor is also capable of extracting gait motions from pelvis. This technology is expected to provide a turning point in health-monitoring, motion tracking, and soft robotics.
Twist-tailoring Coulomb correlations in van der Waals homobilayers
Authors: Merkl Philipp , Mooshammer Fabian , Brem Samuel , Girnghuber Anna , Lin Kai-Qiang , Weigl Leonard , Liebich Marlene , Yong Chaw-Keong , Gillen Roland , Maultzsch Janina , Lupton John M. , Malic Ermin , Huber Rupert 
Published: May 2020

AbstractThe recent discovery of artificial phase transitions induced by stacking monolayer materials at magic twist angles represents a paradigm shift for solid state physics. Twist-induced changes of the single-particle band structure have been studied extensively, yet a precise understanding of the underlying Coulomb correlations has remained challenging. Here we reveal in experiment and theory, how the twist angle alone affects the Coulomb-induced internal structure and mutual interactions of excitons. In homobilayers of WSe2, we trace the internal 1s–2p resonance of excitons with phase-locked mid-infrared pulses as a function of the twist angle. Remarkably, the exciton binding energy is renormalized by up to a factor of two, their lifetime exhibits an enhancement by more than an order of magnitude, and the exciton-exciton interaction is widely tunable. Our work opens the possibility of tailoring quasiparticles in search of unexplored phases of matter in a broad range of van der Waals heterostructures.
A modular biomimetic strategy for the synthesis of macrolide P-glycoprotein inhibitors via Rh-catalyzed C-H activation
Authors: Chen Lu , Quan Haitian , Xu Zhongliang , Wang Hao , Xia Yuanzhi , Lou Liguang , Yang Weibo 
Published: May 2020

AbstractOne of the key challenges to overcome multidrug resistance (MDR) in cancer is the development of more effective and general strategies to discover bioactive scaffolds. Inspired by natural products, we describe a strategy to achieve this goal by modular biomimetic synthesis of scaffolds of (Z)-allylic-supported macrolides. Herein, an Rh(III)-catalyzed native carboxylic acid-directed and solvent-free C−H activation allylation with high stereoselectivity and chemoselectivity is achieved. The generated poly-substituted allylic alcohol as a multifunctional and biomimetic building block is crucial for the synthesis of (Z)-allylic-supported macrolides. Moreover, the unique allylic-supported macrolides significantly potentiate the sensitivity of tumor cells to cytotoxic agents such as vinorelbine and doxetaxel by reversing p170-glycoprotein-mediated MDR. Our findings will inspire the evolution of synthetic chemistry and open avenues for expedient and diversified synthesis of bioactive macrocyclic molecules.
The clinical course of schizophrenia in women and men—a nation-wide cohort study
Authors: Sommer Iris E. , Tiihonen Jari , van Mourik Anouk , Tanskanen Antti , Taipale Heidi 
Published: May 2020

AbstractGender differences in schizophrenia have been reported in different aspect of the course of disease and may urge special clinical interventions for female patients. Current literature provides insufficient information to design guidelines for treating women with schizophrenia. We aim to quantify the clinical course of schizophrenia in men and women on premorbid hospitalizations and prescription drugs, age at diagnosis, pharmacological treatment, comorbidity, number of re-hospitalizations, and mortality. Our nationwide cohort study included all patients admitted for the first time to hospital during 2000–2014 for schizophrenia or schizo-affective disorder in Finland. Gender differences were compared with logistic regression, by calculating incidence rates, and mortality was assessed with Cox proportional hazard model. We included 7142 women and 9006 men with schizophrenia/schizo-affective disorder and found that both women (71%) and men (70%) had often been hospitalized for another psychiatric disorder in the 5 years before diagnosis. In women, the last psychiatric hospitalization before schizophrenia/schizo-affective diagnosis was often for mood disorders (62%, OR 2.56, 95% CI 2.28–2.87). Men were diagnosed earlier (mean 34.4 [SD12.6] vs. 38.2 [SD 13.8]) with peak incidence around 22, while incidence in women declining only slowly between age 18 and 65. During ten years follow-up, 69.5% of both genders needed at least one re-hospitalization, with slightly more hospitalizations in women. Women were less often prescribed clozapine or long-acting antipsychotics. Mortality was lower in women (HR = 0.54, 95% CI 0.50–0.60), with fewer suicide and cardiovascular deaths, but more cancer deaths. These results suggest a diagnostic delay for women, which might be shortened by screening women aged 20–65 participating in affective disorder programs. As number of hospitalizations is not lower for women, clinicians should take care not to undertreat women with schizophrenia.
Brain-transportable soy dipeptide, Tyr-Pro, attenuates amyloid β peptide25-35-induced memory impairment in mice
Authors: Tanaka Mitsuru , Kiyohara Hayato , Yoshino Atsuko , Nakano Akihiro , Takata Fuyuko , Dohgu Shinya , Kataoka Yasufumi , Matsui Toshiro 
Published: May 2020

AbstractIn this study, experiments on amyloid β peptide25-35-induced mice were performed to provide in vivo evidence on the potential of the blood–brain barrier transportable soy dipeptide, Tyr-Pro, in combating memory impairment. We demonstrated for the first time that oral administration of Tyr-Pro (100 mg/kg, twice a day) in mice for 16 days significantly improved impaired memory by spontaneous alternation and shortened step-through latency in amyloid β-induced mice.
Accurate diagnosis of lymphoma on whole-slide histopathology images using deep learning
Authors: Syrykh Charlotte , Abreu Arnaud , Amara Nadia , Siegfried Aurore , Maisongrosse Véronique , Frenois François X. , Martin Laurent , Rossi Cédric , Laurent Camille , Brousset Pierre 
Published: May 2020

AbstractHistopathological diagnosis of lymphomas represents a challenge requiring either expertise or centralised review, and greatly depends on the technical process of tissue sections. Hence, we developed an innovative deep-learning framework, empowered with a certainty estimation level, designed for haematoxylin and eosin-stained slides analysis, with special focus on follicular lymphoma (FL) diagnosis. Whole-slide images of lymph nodes affected by FL or follicular hyperplasia were used for training, validating, and finally testing Bayesian neural networks (BNN). These BNN provide a diagnostic prediction coupled with an effective certainty estimation, and generate accurate diagnosis with an area under the curve reaching 0.99. Through its uncertainty estimation, our network is also able to detect unfamiliar data such as other small B cell lymphomas or technically heterogeneous cases from external centres. We demonstrate that machine-learning techniques are sensitive to the pre-processing of histopathology slides and require appropriate training to build universal tools to aid diagnosis.
Physical activity and markers of glycation in older individuals: data from a combined cross-sectional and randomized controlled trial (EXAMIN AGE)
Authors: D.G. Van den Eynde Mathias , Streese Lukas , J.H.M. Houben Alfons , D.A. Stehouwer Coen , L.J.M. Scheijen Jean , G. Schalkwijk Casper , M.J. Hanssen Nordin , Hanssen Henner 
Published: May 2020

Abstract
Background: Advanced glycation end products (AGEs) are protein modifications that are predominantly formed from dicarbonyl compounds that arise from glucose and lipid metabolism. AGEs and sedentary behavior have been identified as a driver of accelerated (vascular) aging. The effect of physical activity on AGE accumulation is unknown. Therefore, we investigated whether plasma AGEs and dicarbonyl levels are different across older individuals that were active or sedentary and whether plasma AGEs are affected by high-intensity interval training (HIIT).
Methods: We included healthy older active (HA, n=38, 44.7% female, 60.1 ± 7.7 years old) and healthy older sedentary (HS, n=36, 72.2% female, 60.0 ± 7.3 years old) individuals as well as older sedentary individuals with increased cardiovascular risk (SR, n=84, 50% female, 58.7 ± 6.6 years old). The SR group was randomized into a 12-week walking-based HIIT program or control group. We measured protein-bound and free plasma AGEs and dicarbonyls by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) at baseline and after the HIIT intervention.
Results: Protein-bound AGE Nε-(carboxymethyl)lysine (CML) was lower in SR (2.6 ± 0.5 μmol/l) and HS (3.1 ± 0.5 μmol/l) than in HA (3.6 ± 0.6 μmol/l; P&lt;0.05) and remained significantly lower after adjustment for several potential confounders. None of the other glycation markers were different between HS and HA. HIIT did not change plasma AGEs and dicarbonyls in SR.
Discussion: Although lifestyle interventions may act as important modulators of cardiovascular risk, HIIT is not a potent short-term intervention to reduce glycation in older individuals, underlining the need for other approaches, such as pharmacological agents, to reduce AGEs and lower cardiovascular risk in this population.
Masern-Impfung bei Asylsuchenden in der Erstaufnahmeeinrichtung (EAE)
Bielefeld: Impfquote 73%, Impfablehnung 21%
Authors: van den Heuvel Rick , Stammnitz Anke 
Published: May 2020

Zusammenfassung
Ziel der Studie Ziel der Studie ist es, eine Masern-Impfquote und
-Ablehnungsquote (bezüglich zumindest einer Masern-Impfdosis) der
Asylsuchenden der Erstaufnahmeeinrichtung (EAE) Bielefeld zu identifizieren.
Diese Quoten repräsentieren den Ist-Zustand in Bielefeld vor
Implementierung der Impfpflicht.
Methodik Diese Studie ist eine Querschnittstudie. Anhand von
Erstuntersuchungslisten sind demografische Daten (Alter, Geschlecht,
Nationalität) und routinemäßig gesammelte Impfdaten
analysiert worden.
Ergebnisse In dieser Studie wurden die Daten von insgesamt 4606
Asylsuchenden der EAE Bielefeld (01. Januar 2018–31. Dezember 2018)
analysiert. Die Geschlechterverteilung ergab 59% männliche und
41% weibliche Asylsuchende, das Alter lag bei 62% unter 30
Jahre. Die Flüchtlinge in Bielefeld kamen v. a. aus den
folgenden Ländern: Türkei 15%, Syrien 13%, Irak
9%, Iran 9%, Nigeria 5%, Afghanistan 4%, Guinea
3%, Albanien 3%, Somalia 3% und Pakistan 3%.
4326 der erwähnten 4606 Asylsuchenden hatten ein Lebensalter von 1 bis
einschließlich 49 Jahren; bei 3150 davon gab es zumindest eine
dokumentierte Masern-Impfdosis. Die Masern-Impfquote lag somit bei 73%.
Die Masern-Impfquote variierte zwischen 67% (bei 1 bis
einschließlich 4 Jährigen) und 78% (bei 10 bis
einschließlich 14 Jährigen). Die wichtigsten Gründe
warum ein Teil der Flüchtlinge in Bielefeld nicht gegen Masern geimpft
worden sind, waren: Ablehnung (21%), Erkrankungen(2%),
Schwangerschaft (2%) oder „Sonstige“ (1%).
Schlussfolgerung Die Masern-Impfquote in der EAE Bielefeld war
73%. Der wichtigste Grund für die genannte Quote war, dass
21% der zu impfenden Asylsuchenden die Masern-Impfung ablehnte. Es ist
dringend notwendig diese Masern-Impfquote zu erhöhen. Die geplante
Impfpflicht und interne Maßnahmen in der EAE Bielefeld werden helfen die
Impflücken zu schließen. Weitere Studien mit Beteiligung von
mehreren Asylzentren in Deutschland sind zur Feststellung von validen Impfdaten
der Asylsuchenden in diesem Land notwendig.
Komplizierte Trauer erfassen: Ein systematischer Review
Authors: Müller Heidi , Berthold Daniel , Bongard Stephan , Gramm Jan , Hauch Holger , Sibelius Ulf 
Published: May 2020

ZusammenfassungZiel Überblick englisch- und deutschsprachiger Messinstrumente zur Diagnostik von klinisch relevanten Trauerverläufen und Trauer in ihrer Multidimensionalität.Methodik Systematischer Literaturreview.Ergebnisse Insgesamt konnten 22 Inventare extrahiert werden, die sich unterteilen lassen in allgemeine und spezielle Verfahren zur Akutdiagnostik sowie Verfahren zur Früherkennung. Alle Inventare weisen überwiegend gute psychometrische Kennwerte auf.Diskussion International existiert eine Vielzahl an Messverfahren. Für den deutschen Sprachraum liegen 3 allgemeine und 3 spezielle Inventare vor.Schlussfolgerung Bislang fehlen deutschsprachige Verfahren zur Früherkennung schwieriger Trauerverläufe.
Co-administration of Erythromycin and Leech Salivary Extract Alleviates Osteomyelitis in Rats Induced by Methicillin-Resistant Staphylococcus aureus
Authors: Gerivani Bahar , Staji Hamid , Rassouli Maryam , Ghazaleh Nooshin , Vayeghan Abbas Javaheri 
Published: May 2020

Abstract
Objective Erythromycin (Ery) and leech saliva (LS) can inhibit Staphylococcus aureus growth in in vitro conditions. This study aimed to evaluate the activities and synergy between Ery and LS on chronic osteomyelitis in male Wistar rat's tibia induced by methicillin-resistant S. aureus (MRSA).
Materials and Methods Four weeks after osteomyelitis induction, rats were divided into four groups including no treatment (control), Ery monotherapy (orally), LS monotherapy, or Ery + LS twice daily for 2 weeks. Staphylococcus aureus growth, pathological signs and inflammatory cytokine tumour necrosis factor-alpha (TNF-α) levels were assessed.
Results Rats tolerated all therapeutic strategies well during the experiment. The Ery treatment alone significantly decreased bacterial growth, pathological signs and TNF-α levels. Leech saliva alone reduced TNF-α level significantly, but did not produce a significant reduction in bacterial growth and pathological signs. Ery + LS treatment significantly decreased bacterial growth, considerably alleviated bone pathological signs and decreased TNF-α levels compared with other groups. Statistical analysis suggested that there was a stronger efficiency and synergistic action of Ery and LS when combined against MRSA-induced osteomyelitis in rats.
Clinical Significance The present study suggests that LS may have clinical utility to treat MRSA-induced osteomyelitis when combined with Ery or other therapeutics.