bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential acute impact of therapeutically effective and overdose concentrations of lithium on human neuronal single cell and network function
Authors: Izsak Julia , Seth Henrik , Iljin Margarita , Theiss Stephan , Ågren Hans , Funa Keiko , Aigner Ludwig , Hanse Eric , Illes Sebastian 
Published: May 2021

AbstractLithium salts are used as mood-balancing medication prescribed to patients suffering from neuropsychiatric disorders, such as bipolar disorder and major depressive disorder. Lithium salts cross the blood-brain barrier and reach the brain parenchyma within few hours after oral application, however, how lithium influences directly human neuronal function is unknown. We applied patch–clamp and microelectrode array technology on human induced pluripotent stem cell (iPSC)-derived cortical neurons acutely exposed to therapeutic (<1 mM) and overdose concentrations (>1 mM) of lithium chloride (LiCl) to assess how therapeutically effective and overdose concentrations of LiCl directly influence human neuronal electrophysiological function at the synapse, single-cell, and neuronal network level. We describe that human iPSC-cortical neurons exposed to lithium showed an increased neuronal activity under all tested concentrations. Furthermore, we reveal a lithium-induced, concentration-dependent, transition of regular synchronous neuronal network activity using therapeutically effective concentration (<1 mM LiCl) to epileptiform-like neuronal discharges using overdose concentration (>1 mM LiCl). The overdose concentration lithium-induced epileptiform-like activity was similar to the epileptiform-like activity caused by the GABAA-receptor antagonist. Patch–clamp recordings reveal that lithium reduces action potential threshold at all concentrations, however, only overdose concentration causes increased frequency of spontaneous AMPA-receptor mediated transmission. By applying the AMPA-receptor antagonist and anti-epileptic drug Perampanel, we demonstrate that Perampanel suppresses lithium-induced epileptiform-like activity in human cortical neurons. We provide insights in how therapeutically effective and overdose concentration of lithium directly influences human neuronal function at synapse, a single neuron, and neuronal network levels. Furthermore, we provide evidence that Perampanel suppresses pathological neuronal discharges caused by overdose concentrations of lithium in human neurons.
Evidence of anthropogenic impacts on global drought frequency, duration, and intensity
Authors: Chiang Felicia , Mazdiyasni Omid , AghaKouchak Amir 
Published: May 2021

AbstractMost climate change detection and attribution studies have focused on mean or extreme temperature or precipitation, neglecting to explore long-term changes in drought characteristics. Here we provide evidence that anthropogenic forcing has impacted interrelated meteorological drought characteristics. Using SPI and SPEI indices generated from an ensemble of 9 CMIP6 models (using 3 realizations per model), we show that the presence of anthropogenic forcing has increased the drought frequency, maximum drought duration, and maximum drought intensity experienced in large parts of the Americas, Africa, and Asia. Using individual greenhouse gas and anthropogenic aerosol forcings, we also highlight that regional balances between the two major forcings have contributed to the drying patterns detected in our results. Overall, we provide a comprehensive characterization of the influence of anthropogenic forcing on drought characteristics, providing important perspectives on the role of forcings in driving changes in drought events.
PD-1 suppresses TCR-CD8 cooperativity during T-cell antigen recognition
Authors: Li Kaitao , Yuan Zhou , Lyu Jintian , Ahn Eunseon , Davis Simon J. , Ahmed Rafi , Zhu Cheng 
Published: May 2021

AbstractDespite the clinical success of blocking its interactions, how PD-1 inhibits T-cell activation is incompletely understood, as exemplified by its potency far exceeding what might be predicted from its affinity for PD-1 ligand-1 (PD-L1). This may be partially attributed to PD-1’s targeting the proximal signaling of the T-cell receptor (TCR) and co-stimulatory receptor CD28 via activating Src homology region 2 domain-containing phosphatases (SHPs). Here, we report PD-1 signaling regulates the initial TCR antigen recognition manifested in a smaller spreading area, fewer molecular bonds formed, and shorter bond lifetime of T cell interaction with peptide-major histocompatibility complex (pMHC) in the presence than absence of PD-L1 in a manner dependent on SHPs and Leukocyte C-terminal Src kinase. Our results identify a PD-1 inhibitory mechanism that disrupts the cooperative TCR–pMHC–CD8 trimolecular interaction, which prevents CD8 from augmenting antigen recognition, explaining PD-1’s potent inhibitory function and its value as a target for clinical intervention.
RIPK1 is a negative mediator in Aquaporin 1-driven triple-negative breast carcinoma progression and metastasis
Authors: Yin Zhuming , Chen Wenlin , Yin Jian , Sun Jingyan , Xie Qianrong , Wu Min , Zeng Fanxin , Ren Huiwen 
Published: May 2021

AbstractThe triple-negative breast carcinoma (TNBC) is the most aggressive subtype of breast cancer. In TNBC, Aquaporin 1 (AQP1), a water-transporting transmembrane protein, is aberrantly enriched in cytoplasm and causes tumor cell death evasion. However, the carcinogenetic bioactivities of cytoplasmic AQP1 cannot be attributed to the canonical “osmotic engine model”. In the present study, the receptor-interacting protein kinase 1 (RIPK1), a cell death regulator, was identified to negatively mediate AQP1-driven TNBC progression and metastasis. AQP1 overabundance and RIPK1 depletion occurred in TNBC, which were correlated with aggressive oncological features and poor prognosis. AQP1 bound with RIPK1, resulting in the inhibition of RIPK1/RIPK3/MLKL-mediated necroptosis and RIPK1/caspase-8/caspase-3-mediated apoptosis. Genetic inhibition of RIPK1 significantly exacerbated the pro-tumor effect of AQP1, while ectopic expression of RIPK1 notably blunted AQP1 signaling. Mechanistically, AQP1 binds to the D324 site of RIPK1, and facilitates RIPK1 cleavage and inactivation by excessively activating the caspase-8/RIPK1 negative feedback loop. RIPK1D324K overexpression significantly prevented RIPK1 cleavage and weakened the aggressiveness of AQP1-enriched TNBC cells. Overall, our findings clarify the underlying mechanism of cytoplasmic AQP1-driven TNBC progression and metastasis, in which RIPK1 exerts an essential role as a negative mediator and exhibits the potential as a therapeutic target for TNBC.
Revealing the activation mechanism of autoinhibited RalF by integrated simulation and experimental approaches
Authors: Dudas Balint , Perahia David , Balog Erika 
Published: May 2021

AbstractRalF is an Arf GEF from Legionella pneumophilia, the bacterium that causes severe pneumonia. In its crystal structure, RalF is in the autoinhibited form. A large-scale domain motion is expected to lift the autoinhibition, the mechanism of which is still unknown. Since RalF is activated in the presence of the membrane, its active structure and the structure of the RalF-Arf1 complex could not have been determined experimentally. On the simulation side, it has been proven that classical Molecular Dynamics (MD) alone is not efficient enough to map motions of such amplitude and determine the active conformation of RalF. In this article, using Molecular Dynamics with excited Normal Modes (MDeNM) combined with previous experimental findings we were able to determine the active RalF structure and the structure of the RalF-Arf1 complex in the presence of the membrane, bridging the gap between experiments and simulation.
Vincristine attenuates cardiac fibrosis through the inhibition of NLRP3 inflammasome activation
Authors: Ge Chenliang , Cheng Yang , Fan Yihao , He Yan 
Published: May 2021

Abstract
Vincristine (VCR) is widely used in cancer therapies, although its benefits on cardiac fibrosis remain unknown. Here, we investigated VCR’s efficacy on cardiac fibrosis and elucidated the underlying mechanism of action. Network pharmacology was employed to predict the mechanism of VCR action on cardiac fibrosis. We induced cardiac fibrosis in adult male Sprague–Dawley (SD) rats via isoproterenol (ISO) injection, followed by treatment with VCR or vehicle. After 10 days of treatment, VCR-treated rats exhibited a significantly lower heart/body weight ratio relative to those treated with the vehicle. Moreover, cardiac fibrosis was alleviated in VCR-treated rats relative to vehicle-treated rats. The results revealed the down-regulation of mature caspase-1, interleukin (IL)-1β, and IL-18 in VCR-treated rats relative to vehicle-treated rats. We also observed less colocalization between the nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) and apoptosis-associated speck-like protein containing a CARD (ASC) in VCR-treated rats compared with vehicle-treated rats. We then cultured neonatal rat cardiac fibroblasts (NRCFs) and exposed them to lipopolysaccharide (LPS) and adenosine triphosphate (ATP) in the presence or absence of VCR. The results indicated that VCR mediated the down-regulation of caspase-1, IL-1β, and IL-18 and the colocalization of NLRP3 and ASC in LPS+ATP-stimulated cardiac fibroblasts (CFs). We found evidence that VCR attenuates cardiac fibrosis by directly suppressing the activation of the NLRP3 inflammasome. These findings provide novel insights into VCR’s mechanism of action in alleviating cardiac fibrosis.
Combined hydrodynamic and gas-grain chemical modeling of hot cores
Authors: Barger C. J. , Lam K. H. , Li Z.-Y. , Davis S. W. , Herbst E. , Garrod R. T. 
Published: May 2021

Context. Gas-grain models have long been employed to simulate hot-core chemistry; however, these simulations have traditionally neglected to couple chemical evolution in tandem with a rigorous physical evolution of a source. This over-simplification particularly lacks an accurate treatment of temperature and spatial distribution, which are needed for realistic simulations of hot cores.
Aims. We aim to combine radiation hydrodynamics (RHD) with hot-core chemical kinetics in one dimension to produce a set of astrochemical models that evolve according to explicitly calculated temperature, density, and spatial profiles.
Methods. We solve radiation hydrodynamics for three mass-accretion-rate models using Athena++. We then simulate the chemistry using the hot-core chemical kinetic code MAGICKAL according to the physics derived from the RHD treatment.
Results. We find that as the mass-accretion rate decreases, the overall gas density of the source decreases. In particular, the gas density for the lowest mass-accretion rate is low enough to restrict the proper formation of many complex organic molecules. We also compare our chemical results in the form of calculated column densities to those of observations toward Sgr B2(N2). We find a generally good agreement for oxygen-bearing species, particularly for the two highest mass-accretion rates.
Conclusions. Although we introduce hot-core chemical modeling using a self-consistent physical treatment, the adoption of a two-dimensional model may better reproduce chemistry and physics toward real sources and thus achieve better chemical comparisons with observations.
Statistical strong lensing
Authors: Sonnenfeld Alessandro , Cautun Marius 
Published: May 2021

Context.The number of known strong gravitational lenses is expected to grow substantially in the next few years. The combination of large samples of lenses has the potential to provide strong constraints on the inner structure of galaxies.Aims.We investigate the extent to which we can calibrate stellar mass measurements and constrain the average dark matter density profile of galaxies by combining strong lensing data from thousands of lenses.Methods.We generated mock samples of axisymmetric lenses. We assume that, for each lens, we have measurements of two image positions of a strongly lensed background source, as well as magnification information from full surface brightness modelling, and a stellar-population-synthesis-based estimate of the lens stellar mass. We then fitted models describing the distribution of the stellar population synthesis mismatch parameterαsps(the ratio between the true stellar mass and the stellar-population-synthesis-based estimate) and the dark matter density profile of the population of lenses to an ensemble of 1000 mock lenses.Results.We obtain the averageαsps, projected dark matter mass, and dark matter density slope with greater precision and accuracy compared with current constraints. A flexible model and knowledge of the lens detection efficiency as a function of image configuration are required in order to avoid a biased inference.Conclusions.Statistical strong lensing inferences from upcoming surveys provide a way to calibrate stellar mass measurements and to constrain the inner dark matter density profile of massive galaxies.
Tinktur und Urtinktur – Gemeinsamkeiten und Unterschiede
Authors: Brendieck-Worm Cäcilia 
Published: May 2021

ZusammenfassungErfahrungsgemäß bieten Urtinkturen und Tiefpotenzen den Phytotherapeuten in der Tiermedizin wichtige Therapie-Optionen. Es hat sich als sinnvoll erwiesen, insbesondere solche Arzneipflanzen als Tiefpotenzen einzusetzen, deren therapeutische Breite gering ist. Dies gilt vor allem bei Patienten, deren Metabolisierungsfähigkeiten bekanntermaßen eingeschränkt sind (Neugeborene, Alte, Patienten mit Leber- und/oder Niereninsuffizienz, Karnivore, insbesondere Feliden), aber auch bei Patienten, deren Metabolisierungsfähigkeiten nicht bekannt sind (Exoten, Reptilien, Amphibien) 8.
Continuation Rates of the 52-mg Levonorgestrel-releasing Intrauterine System according to the Primary Reason for its Use
Authors: Miranda Laura , Sousa Maria Helena de , Faundes Anibal , Juliato Cássia 
Published: May 2021

Abstract
Objective To evaluate whether continuation rates with the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) up to 5 years after placement differed between women using the method exclusively for contraception and those using the device for medical reasons alone.
Methods A retrospective cohort study was conducted in a family planning clinic with 5,034 LNG-IUS users: 4,287 using the method exclusively for contraception and 747 for medical reasons alone. The continuation rate at 1 to 5 years of use was calculated by life table analysis.
Results Initially, the continuation rate was significantly higher in the contraception group: 85.8 versus 83.4 and 77.4 versus 76.0 per 100 women-years in the 1st and 2nd years of use, respectively. There were more discontinuations due to bleeding/spotting in the medical reasons group in the first two years. The discontinuation rate according to reason for use was not significantly different from the third to the fifth year of use. No women discontinued due to amenorrhea in either group.
Conclusion The continuation rate was significantly higher in the contraception group in the first two years of use. Amenorrhea was not a reason for discontinuation in either group, suggesting that counselling in this respect was adequate. Nevertheless, counselling could perhaps have been better with regards to the expected long period of bleeding and spotting in the first two years after placement.
Functional Anatomy of the Craniolateral and Caudomedial Bundles of the Caudal Cruciate Ligament in Beagle Dogs
Authors: Tanegashima Koji , Edamura Kazuya , Ogawa Takahiro , Tomo Yuma , Yamazaki Atsushi , Seki Mamiko , Asano Kazushi , Nakayama Tomohiro , Katsura Taro , Hayashi Kei 
Published: May 2021

AbstractObjective The aim of this study was to investigate functional anatomy of the craniolateral bundle (CrLB) and caudomedial bundle (CdMB) of caudal cruciate ligament in normal Beagles.Materials and Methods Twelve stifle joints of 12 Beagle cadavers that were euthanatized for reasons other than musculoskeletal disease were used. Anatomical characteristics of femoral and tibial attachment regions of the caudal cruciate ligament were described, and location and area of the footprints of the CrLB and CdMB were objectively determined. The CrLB was artificially divided into two equal fibre bundle units and the CdMB was artificially divided into four equal bundle units. Changes in the fibre arrangement were recorded during stifle range of motion, and the tension of each fibre bundle unit at various stifle joint angles was objectively measured.Results The CrLB was attached to the intercondylar fossa of the femur, and the CdMB was attached to the medial surface of the medial condyle of the femur. The centre of the CrLB attachment site was located craniomedial to that of the CdMB on the tibia. During stifle range of motion, each divided fibre bundle unit in the CrLB and CdMB was twisted externally. The tension of entire CdMB tended to be higher than that of entire CrLB at 180 to 135 degrees of the stifle angles. In full extension angle, the tension of entire CdMB was 1.55 times higher than that of entire CrLB.Clinical Significance This study contributes to understanding of the biomechanics and the function of the caudal cruciate ligament, which help to elucidate the pathophysiology of caudal cruciate ligament tear and to develop stifle joint stabilization surgery.
Efficient Clinical Data Sharing Framework Based on Blockchain Technology
Authors: Kanagi Karamo , Ku Cooper Cheng-Yuan , Lin Li-Kai , Hsieh Wen-Huai 
Published: May 2021

Abstract
Background While electronic health records have been collected for many years in Taiwan, their interoperability across different health care providers has not been entirely achieved yet. The exchange of clinical data is still inefficient and time consuming.
Objectives This study proposes an efficient patient-centric framework based on the blockchain technology that makes clinical data accessible to patients and enable transparent, traceable, secure, and effective data sharing between physicians and other health care providers.
Methods Health care experts were interviewed for the study, and medical data were collected in collaboration with Ministry of Health and Welfare (MOHW) Chang-Hua hospital. The proposed framework was designed based on the detailed analysis of this information. The framework includes smart contracts in an Ethereum-based permissioned blockchain to secure and facilitate clinical data exchange among different parties such as hospitals, clinics, patients, and other stakeholders. In addition, the framework employs the Logical Observation Identifiers Names and Codes (LOINC) standard to ensure the interoperability and reuse of clinical data.
Results The prototype of the proposed framework was deployed in Chang-Hua hospital to demonstrate the sharing of health examination reports with many other clinics in suburban areas. The framework was found to reduce the average access time to patient health reports from the existing next-day service to a few seconds.
Conclusion The proposed framework can be adopted to achieve health record sharing among health care providers with higher efficiency and protected privacy compared to the system currently used in Taiwan based on the client–server architecture.
Mechanism of Action of Diallyl Sulphide in Ameliorating the Hematopoietic Radiation Injury
Authors: Katoch Omika , Tiwari Mrinalini , Kalra Namita , Agrawala Paban K. 
Published: May 2021

AbstractDiallyl sulphide (DAS), the pungent component of garlic, is known to have several medicinal properties and has recently been shown to have radiomitigative properties. The present study was performed to better understand its mode of action in rendering radiomitigation. Evaluation of the colonogenic ability of hematopoietic progenitor cells (HPCs) on methocult media, proliferation and differentiation of hematopoietic stem cells (HSCs), and transplantation of stem cells were performed. The supporting tissue of HSCs was also evaluated by examining the histology of bone marrow and in vitro colony-forming unit–fibroblast (CFU-F) count. Alterations in the levels of IL-5, IL-6 and COX-2 were studied as a function of radiation or DAS treatment. It was observed that an increase in proliferation and differentiation of hematopoietic stem and progenitor cells occurred by postirradiation DAS administration. It also resulted in increased circulating and bone marrow homing of transplanted stem cells. Enhancement in bone marrow cellularity, CFU-F count, and cytokine IL-5 level were also evident. All those actions of DAS that could possibly add to its radiomitigative potential and can be attributed to its HDAC inhibitory properties, as was observed by the reversal radiation induced increase in histone acetylation.
Epitaxial stannate pyrochlore thin films: Limitations of cation stoichiometry and electron doping
Authors: Hensling Felix V. E. , Dahliah Diana , Dulal Prabin , Singleton Patrick , Sun Jiaxin , Schubert Jürgen , Paik Hanjong , Subedi Indra , Subedi Biwas , Rignanese Gian-Marco , Podraza Nikolas J. , Hautier Geoffroy , Schlom Darrell G. 
Published: May 2021

We have studied the growth of epitaxial films of stannate pyrochlores with a general formula A2Sn2O7 (A = La and Y) and find that it is possible to incorporate ∼25% excess of the A-site constituent; in contrast, any tin excess is expelled. We unravel the defect chemistry, allowing for the incorporation of excess A-site species and the mechanism behind the tin expulsion. An A-site surplus is manifested by a shift in the film diffraction peaks, and the expulsion of tin is apparent from the surface morphology of the film. In an attempt to increase La2Sn2O7 conductivity through n-type doping, substantial quantities of tin have been substituted by antimony while maintaining good film quality. The sample remained insulating as explained by first-principles computations, showing that both the oxygen vacancy and antimony-on-tin substitutional defects are deep. Similar conclusions are drawn on Y2Sn2O7. An alternative n-type dopant, fluorine on oxygen, is shallow according to computations and more likely to lead to electrical conductivity. The bandgaps of stoichiometric La2Sn2O7 and Y2Sn2O7 films were determined by spectroscopic ellipsometry to be 4.2 eV and 4.48 eV, respectively.
On defining functions and cores for unbounded domains. III
Authors: Harz T. , Shcherbina N. , Tomassini G. 
Published: May 2021

Abstract
We extend the authors’ results on existence of global defining functions to a number of different settings. In particular, we relax the assumption on strict pseudoconvexity of the domain to strict

-pseudoconvexity and we consider more general situations, where the ambient space is an almost complex manifold or a complex space. We also investigate to what extent the assumption on smoothness of the boundary of the domains under consideration is necessary in our results.
Bibliography: 27 titles.
Subsystem macroarchitecture of the intrinsic midbrain neural network and its tectal and tegmental subnetworks
Authors: Swanson Larry W. , Hahn Joel D. , Sporns Olaf 
Published: May 2021

Significance
The midbrain is one of the vertebrate brain’s three basic divisions, and it plays an especially important role in sensory–motor mechanisms, motivation and reward, reproductive and agonistic behaviors, and behavioral state. Network science methods were applied here to reveal organizing principles of intramidbrain circuitry, which include a hierarchy of subsystems that was used to construct a structure–function model of the circuitry. The results show fundamental differences between intramidbrain and previously determined intraforebrain network organization and provide a theoretical framework for experimental analysis of intramidbrain circuit involvement in specific behaviors.