bluuebunny/crossref_metadata_2025 huggingface dataset:
Recursive Bayesian Estimation of Conceptual Rainfall‐Runoff Model Errors in Real‐Time Prediction of Streamflow
Authors: Tajiki M. , Schoups G. , Hendricks Franssen H. J. , Najafinejad A. , Bahremand A.
Published: January 2020

Conceptual rainfall‐runoff models account for the spatial dynamics of hydrological processes in a basin using simple spatially lumped storage‐flow relations. Such rough approximations introduce model errors that are often difficult to characterize. Here, we develop and apply a methodology that recursively estimates and accounts for model errors in real‐time streamflow prediction settings by adding time‐dependent random noise to the internal states (storages) of the hydrological model. Magnitude of the added noise depends on a precision (inverse variance) parameter that is estimated from rainfall‐runoff data. A recursive Bayesian technique is used for estimation: posteriors of hydrological parameters and states are updated through time with an ensemble Kalman filter, whereas the posterior of the precision parameter is updated recursively using a novel gamma density approximation technique. Applying this algorithm to different model error scenarios allows identification of the main source of model errors. The methodology is applied to short‐term streamflow prediction with the Hymod rainfall‐runoff model in a semi‐cold, semi‐humid basin in Iran. Results show that (i) streamflow prediction in this snow‐dominated basin is more affected by model errors in the slow flow than the quick flow component of the model, (ii) accounting for model errors in the slow flow component improves both low and high flow predictions, and (iii) predictive performance further improves by accounting for Hymod parameter uncertainty in addition to model errors. Overall, accounting for model errors increased Nash‐Sutcliffe efficiency (by 1–5%), reduced mean absolute error (by 2–43%), and improved probabilistic predictive performance (by 50–80%).
Many Commonly Used Rainfall‐Runoff Models Lack Long, Slow Dynamics: Implications for Runoff Projections
Authors: Fowler Keirnan , Knoben Wouter , Peel Murray , Peterson Tim , Ryu Dongryeol , Saft Margarita , Seo Ki‐Weon , Western Andrew
Published: January 2020

Evidence suggests that catchment state variables such as groundwater can exhibit multiyear trends. This means that their state may reflect not only recent climatic conditions but also climatic conditions in past years or even decades. Here we demonstrate that five commonly used conceptual “bucket” rainfall‐runoff models are unable to replicate multiyear trends exhibited by natural systems during the “Millennium Drought” in south‐east Australia. This causes an inability to extrapolate to different climatic conditions, leading to poor performance in split sample tests. Simulations are examined from five models applied in 38 catchments, then compared with groundwater data from 19 bores and Gravity Recovery and Climate Experiment data for two geographic regions. Whereas the groundwater and Gravity Recovery and Climate Experiment data decrease from high to low values gradually over the duration of the 13‐year drought, the model storages go from high to low values in a typical seasonal cycle. This is particularly the case in the drier, flatter catchments. Once the drought begins, there is little room for decline in the simulated storage, because the model “buckets” are already “emptying” on a seasonal basis. Since the effects of sustained dry conditions cannot accumulate within these models, we argue that they should not be used for runoff projections in a drying climate. Further research is required to (a) improve conceptual rainfall‐runoff models, (b) better understand circumstances in which multiyear trends in state variables occur, and (c) investigate links between these multiyear trends and changes in rainfall‐runoff relationships in the context of a changing climate.
The Subterranean Estuary: Technical Term, Simple Analogy, or Source of Confusion?
Authors: Duque Carlos , Michael Holly A. , Wilson Alicia M.
Published: January 2020

Twenty years ago, the term subterranean estuary was proposed by Moore (1999, https://doi.org/10.1016/S0304-4203(99)00014-6) as a call of attention to the ocean sciences community about the importance of coastal groundwater systems, which can compete in relevance and impact to oceans with fresh runoff coming from the continent. Coastal aquifers were presented as an analogy to surface estuaries in that water of different density comes together and establishes a saline wedge underlying fresher water. In the past two decades, the use of this term has expanded. Initially limited to studies with an oceanographic viewpoint considering the impact of groundwater on the ocean, it is now common in the literature, competing with classical hydrogeological terminology such as coastal aquifer or seawater intrusion and reaching publications with a traditional hydrogeological focus. The popularity of this terminology suggests that it fills a need not met by existing coastal hydrogeological terms, although these classical terms have their roots in a long history of study of coastal groundwater. This term may serve to enhance communications between the traditionally disparate communities of hydrogeology and ocean sciences—imbricating saltwater intrusion studies with marine sciences and bringing an opportunity to enhance interactions. But does the term also carry an element of confusion? This essay is intended to open a discussion within the coastal research community about the use and meaning of terminology in future studies of coastal and offshore groundwater systems.
VDR activation attenuate cisplatin induced AKI by inhibiting ferroptosis
Authors: Hu Zhaoxin , Zhang Hao , Yi Bin , Yang Shikun , Liu Jun , Hu Jing , Wang Jianwen , Cao Ke , Zhang Wei
Published: January 2020

Our preliminary work has revealed that vitamin D receptor (VDR) activation is protective against cisplatin induced acute kidney injury (AKI). Ferroptosis was recently reported to be involved in AKI. Here in this study, we investigated the internal relation between ferroptosis and the protective effect of VDR in cisplatin induced AKI. By using ferroptosis inhibitor ferrostatin-1 and measurement of ferroptotic cell death phenotype in both in vivo and in vitro cisplatin induced AKI model, we observed the decreased blood urea nitrogen, creatinine, and tissue injury by ferrostatin-1, hence validated the essential involvement of ferroptosis in cisplatin induced AKI. VDR agonist paricalcitol could both functionally and histologically attenuate cisplatin induced AKI by decreasing lipid peroxidation (featured phenotype of ferroptosis), biomarker 4-hydroxynonenal (4HNE), and malondialdehyde (MDA), while reversing glutathione peroxidase 4 (GPX4, key regulator of ferroptosis) downregulation. VDR knockout mouse exhibited much more ferroptotic cell death and worsen kidney injury than wild type mice. And VDR deficiency remarkably decreased the expression of GPX4 under cisplatin stress in both in vivo and in vitro, further luciferase reporter gene assay showed that GPX4 were target gene of transcription factor VDR. In addition, in vitro study showed that GPX4 inhibition by siRNA largely abolished the protective effect of paricalcitol against cisplatin induced tubular cell injury. Besides, pretreatment of paricalcitol could also alleviated Erastin (an inducer of ferroptosis) induced cell death in HK-2 cell. These data suggested that ferroptosis plays an important role in cisplatin induced AKI. VDR activation can protect against cisplatin induced renal injury by inhibiting ferroptosis partly via trans-regulation of GPX4.
RETRACTED ARTICLE: Schnurri-3 regulates BMP9-induced osteogenic differentiation and angiogenesis of human amniotic mesenchymal stem cells through Runx2 and VEGF
Authors: Li Yuwan , Liu Ziming , Tang Yaping , Feng Wei , Zhao Chen , Liao Junyi , Zhang Chengmin , Chen Hong , Ren Youliang , Dong Shiwu , Liu Yi , Hu Ning , Huang Wei
Published: January 2020

Human amniotic mesenchymal stem cells (hAMSCs) are multiple potent progenitor cells (MPCs) that can differentiate into different lineages (osteogenic, chondrogenic, and adipogenic cells) and have a favorable capacity for angiogenesis. Schnurri-3 (Shn3) is a large zinc finger protein related to Drosophila Shn, which is a critical mediator of postnatal bone formation. Bone morphogenetic protein 9 (BMP9), one of the most potent osteogenic BMPs, can strongly upregulate various osteogenesis- and angiogenesis-related factors in MSCs. It remains unclear how Shn3 is involved in BMP9-induced osteogenic differentiation coupled with angiogenesis in hAMSCs. In this investigation, we conducted a comprehensive study to identify the effect of Shn3 on BMP9-induced osteogenic differentiation and angiogenesis in hAMSCs and analyze the responsible signaling pathway. The results from in vitro and in vivo experimentation show that Shn3 notably inhibits BMP9-induced early and late osteogenic differentiation of hAMSCs, expression of osteogenesis-related factors, and subcutaneous ectopic bone formation from hAMSCs in nude mice. Shn3 also inhibited BMP9-induced angiogenic differentiation, expression of angiogenesis-related factors, and subcutaneous vascular invasion in mice. Mechanistically, we found that Shn3 prominently inhibited the expression of BMP9 and activation of the BMP/Smad and BMP/MAPK signaling pathways. In addition, we further found activity on runt-related transcription factor 2 (Runx2), vascular endothelial growth factor (VEGF), and the target genes shared by BMP and Shn3 signaling pathways. Silencing Shn3 could dramatically enhance the expression of Runx2, which directly regulates the downstream target VEGF to couple osteogenic differentiation with angiogenesis. To summarize, our findings suggested that Shn3 significantly inhibited the BMP9-induced osteogenic differentiation and angiogenesis in hAMSCs. The effect of Shn3 was primarily seen through inhibition of the BMP/Smad signaling pathway and depressed expression of Runx2, which directly regulates VEGF, which couples BMP9-induced osteogenic differentiation with angiogenesis.
Selection of diverse strains to assess broad coverage of the bivalent FHbp meningococcal B vaccine
Authors: Harris Shannon L. , Tan Cuiwen , Perez John , Radley David , Jansen Kathrin U. , Anderson Annaliesa S. , Jones Thomas R.
Published: January 2020

MenB-FHbp is a recombinant meningococcal serogroup B (MenB) vaccine composed of 2 factor H binding proteins (FHbps). Meningococcal vaccines targeting polysaccharide serogroup A, C, Y, and W capsules were licensed upon confirmation of bactericidal antibody induction after initial efficacy studies with serogroup A and C vaccines. Unlike meningococcal polysaccharide vaccines, wherein single strains demonstrated bactericidal antibodies per serogroup for each vaccine, MenB-FHbp required a more robust approach to demonstrate that bactericidal antibody induction could kill strains with diverse FHbp sequences. Serum bactericidal assays using human complement were developed for 14 MenB strains, representing breadth of meningococcal FHbp diversity of ~80% of circulating MenB strains. This work represents an innovative approach to license a non-toxin protein vaccine with 2 antigens representing a single virulence factor by an immune correlate, and uniquely demonstrates that such a vaccine provides coverage across bacterial strains by inducing broadly protective antibodies.
Scale and translation-invariance for novel objects in human vision
Authors: Han Yena , Roig Gemma , Geiger Gad , Poggio Tomaso
Published: January 2020

Though the range of invariance in recognition of novel objects is a basic aspect of human vision, its characterization has remained surprisingly elusive. Here we report tolerance to scale and position changes in one-shot learning by measuring recognition accuracy of Korean letters presented in a flash to non-Korean subjects who had no previous experience with Korean letters. We found that humans have significant scale-invariance after only a single exposure to a novel object. The range of translation-invariance is limited, depending on the size and position of presented objects. To understand the underlying brain computation associated with the invariance properties, we compared experimental data with computational modeling results. Our results suggest that to explain invariant recognition of objects by humans, neural network models should explicitly incorporate built-in scale-invariance, by encoding different scale channels as well as eccentricity-dependent representations captured by neurons’ receptive field sizes and sampling density that change with eccentricity. Our psychophysical experiments and related simulations strongly suggest that the human visual system uses a computational strategy that differs in some key aspects from current deep learning architectures, being more data efficient and relying more critically on eye-movements.
Facile One Pot Greener Synthesis of Sophorolipid Capped Gold Nanoparticles and its Antimicrobial Activity having Special Efficacy Against Gram Negative Vibrio cholerae
Authors: Shikha Sristy , Chaudhuri Saumya Ray , Bhattacharyya Mani Shankar
Published: January 2020

Microbes develop several strategies to survive in the adverse condition such as biofilm formation, attaining non-dividing state, altering drug target or drug, thereby increases the burden of drug dosage. To combat these issues, nanoparticles have shown an alternative approach for new treatment strategy but synthesis via chemical synthetic route limits their application in biomedical field. Here, green method for the synthesis of gold nanoparticles using sophorolipid (SL) is discussed that is characterized by various techniques. Initially, the antimicrobial activity was checked against metabolically active state of microbes; Gram-positive Staphylococcus aureus and Gram-negative Vibrio cholerae using XTT assay and growth kinetics assay. Results suggested higher efficacy of nanoparticles for Gram-negative, therefore further analyzed against Escherichia coli that confirmed its potency for the same. AuNPs-SL also signifies its efficiency at least metabolically active state; non dividing cells and biofilm of these microbes. Induced morphological changes were studied by SEM that revealed AuNPs-SL led to disruption of cell membrane and leakage of intracellular fluid to the surroundings. Inhibition of respiratory enzymes activity also plays a crucial role in bactericidal action as indicated by LDH assay. Synergy of AuNPs-SL with different antibiotics was also analyzed using checkerboard assay. These results suggested the possible use of AuNPs-SL as an antimicrobial therapy in the field of nanomedicine.
Local habitat conditions shaping the assemblages of vespid wasps (Hymenoptera: Vespidae) in a post-agricultural landscape of the Kampinos National Park in Poland
Authors: Szczepko Katarzyna , Kruk Andrzej , Wiśniowski Bogdan
Published: January 2020

The landscape of the Kampinos National Park (KPN), a UNESCO Biosphere Reserve in Poland, is a mosaic of habitats created by natural processes and human activities. However, ongoing abandonment of traditional management has led to the development of forest communities in formerly open areas. The aim of the study was to identify the local habitat conditions promoting the abundance and diversity of wasp species (Vespidae) in the post-agricultural landscape of KPN. A total of 52 samples of Vespidae caught per unit effort (CPUE) were collected across various habitats with different levels of soil humidity, bare ground and mosaicity. The highest numbers and greatest species richness of vespids were recorded in open habitats on semihydrogenic and dry soil, which provided nesting sites for hypergeic (nesting above the ground) and endogeic (ground nesting) wasps. Many solitary species that are hypergeic were significantly associated with old, abandoned wooden buildings. As vespids need resources to build and provision the nest, their communities were shaped not only by the nature of the habitat sampled but also by the mosaicity of the surrounding area. The highest abundance and species richness were recorded in samples from a heterogenous landscape, which provided a wider range of available resources in the vicinity of the nest. Our findings have significant implications for the management of park landscapes: afforestation of open habitats, both human-induced and resulting from natural succession, and the removal of old abandoned wooden buildings may limit landscape mosaicity and thus decrease hymenopteran diversity.
Dynamic Stiffness Analysis and Measurement of Radial Active Magnetic Bearing in Magnetically Suspended Molecular Pump
Authors: Sun Jinji , Zhou Han , Ju Ziyan
Published: January 2020

Current stiffness and displacement stiffness are two important parameters of radial active magnetic bearing (RAMB) that are generally considered as constants in a control system. However, such presumption may lead to the probable degradation of the control performance of the RAMB system when the perspective that the current and displacement stiffness should be variable due to variations in the speed. On this regard, a structure analysis and stiffness measurement method based on non-variable stiffness would not be feasible for RAMB under high-speed conditions. This paper presented an analysis of the dynamic stiffness characteristics of RAMB by means of a dynamic equivalent magnetic circuit method and laid out a comparison between the results of the theoretical analysis and the simulation results of finite element method. In particular, a novel dynamic stiffness measurement method of RAMB under high-rotation frequency was introduced. Results of experiments on the dynamic stiffness of RAMB demonstrated an excellent agreement with the theoretical research and the finite element analysis results, thereby verifying the rationality of the discussed dynamic stiffness characteristics. Practically, the proposed measurement method of RAMB dynamic stiffness provides an accurate analysis for the dynamic stiffness and contributes inspiring research significance for the dynamic properties of RAMB.
Author Correction: Metabolomic Changes of Human Proximal Tubular Cell Line in High Glucose Environment
Authors: Wei Pascal Zhongping , Fung Winston Wing-Shing , Ng Jack Kit-Chung , Lai Ka-Bik , Luk Cathy Choi-Wan , Chow Kai Ming , Li Philip Kam-Tao , Szeto Cheuk Chun
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Markerless Measurement and Evaluation of General Movements in Infants
Authors: Tsuji Toshio , Nakashima Shota , Hayashi Hideaki , Soh Zu , Furui Akira , Shibanoki Taro , Shima Keisuke , Shimatani Koji
Published: January 2020

General movements (GMs), a type of spontaneous movement, have been used for the early diagnosis of infant disorders. In clinical practice, GMs are visually assessed by qualified licensees; however, this presents a difficulty in terms of quantitative evaluation. Various measurement systems for the quantitative evaluation of GMs track target markers attached to infants; however, these markers may disturb infants’ spontaneous movements. This paper proposes a markerless movement measurement and evaluation system for GMs in infants. The proposed system calculates 25 indices related to GMs, including the magnitude and rhythm of movements, by video analysis, that is, by calculating background subtractions and frame differences. Movement classification is performed based on the clinical definition of GMs by using an artificial neural network with a stochastic structure. This supports the assessment of GMs and early diagnoses of disabilities in infants. In a series of experiments, the proposed system is applied to movement evaluation and classification in full-term infants and low-birth-weight infants. The experimental results confirm that the average agreement between four GMs classified by the proposed system and those identified by a licensee reaches up to 83.1 ± 1.84%. In addition, the classification accuracy of normal and abnormal movements reaches 90.2 ± 0.94%.
Field generated nematic microflows via backflow mechanism
Authors: Kos Žiga , Ravnik Miha
Published: January 2020

Generation of flow is an important aspect in microfluidic applications and generally relies on external pumps or embedded moving mechanical parts which pose distinct limitations and protocols on the use of microfluidic systems. A possible approach to avoid moving mechanical parts is to generate flow by changing some selected property or structure of the fluid. In fluids with internal orientational order such as nematic liquid crystals, this process of flow generation is known as the backflow effect. In this article, we demonstrate the contact-free generation of microfluidic material flows in nematic fluids -including directed contact-free pumping- by external electric and optical fields based on the dynamic backflow coupling between nematic order and material flow. Using numerical modelling, we design efficient shaping and driving of the backflow-generated material flow using spatial profiles and time modulations of electric fields with oscillating amplitude, rotating electric fields and optical fields. Particularly, we demonstrate how such periodic external fields generate efficient net average nematic flows through a microfluidic channel, that avoid usual invariance under time-reversal limitations. We show that a laser beam with rotating linear polarization can create a vortex-like flow structure and can act as a local flow pump without moving mechanical parts. The work could be used for advanced microfluidic applications, possibly by creating custom microfluidic pathways without predefined channels based on the adaptivity of an optical set-up, with a far reaching unconventional idea to realize channel-less microfluidics.
Clinical Genome Data Model (cGDM) provides Interactive Clinical Decision Support for Precision Medicine
Authors: Kim Hyo Jung , Kim Hyeong Joon , Park Yoomi , Lee Woo Seung , Lim Younggyun , Kim Ju Han
Published: January 2020

In light of recent developments in genomic technology and the rapid accumulation of genomic information, a major transition toward precision medicine is anticipated. However, the clinical applications of genomic information remain limited. This lag can be attributed to several complex factors, including the knowledge gap between medical experts and bioinformaticians, the distance between bioinformatics workflows and clinical practice, and the unique characteristics of genomic data, which can make interpretation difficult. Here we present a novel genomic data model that allows for more interactive support in clinical decision-making. Informational modelling was used as a basis to design a communication scheme between sophisticated bioinformatics predictions and the representative data relevant to a clinical decision. This study was conducted by a multidisciplinary working group who carried out clinico-genomic workflow analysis and attribute extraction, through Failure Mode and Effects Analysis (FMEA). Based on those results, a clinical genome data model (cGDM) was developed with 8 entities and 46 attributes. The cGDM integrates reliability-related factors that enable clinicians to access the reliability problem of each individual genetic test result as clinical evidence. The proposed cGDM provides a data-layer infrastructure supporting the intellectual interplay between medical experts and informed decision-making.
Increased circulating galectin-1 levels are associated with the progression of kidney function decline in patients undergoing coronary angiography
Authors: Kuo Chin-Sung , Chou Ruey-Hsing , Lu Ya-Wen , Tsai Yi-Lin , Huang Po-Hsun , Lin Shing-Jong
Published: January 2020

Galectin-1 modulates acute and chronic inflammation, and is associated with glucose homeostasis and chronic renal disease. Whether the serum galectin-1 level can predict short-term and long-term renal outcomes after contrast exposure in patients undergoing coronary angiography (CAG) remains uncertain. This study aimed to evaluate the relationship between the serum galectin-1 level and the incidence of contrast-induced nephropathy (CIN), and to investigate the predictive role of the circulating galectin-1 level for renal function decline in patients undergoing CAG. In total, 798 patients who had undergone CAG were enrolled. Baseline creatinine and serum galectin-1 levels were determined before CAG. CIN was defined as an increase in the serum creatinine level of 0.5 mg/dl or a 25% increase from baseline within 48 h after the procedure, and renal function decline was defined as > 30% reduction of the estimated glomerular filtration rate from baseline. All patients were followed for at least 1 year or until the occurrence of death after CAG. Overall, CIN occurred in 41 (5.1%) patients. During a median follow-up period of 1.4 ± 1.1 years, 80 (10.0%) cases showed subsequent renal function decline. After adjustment for demographic characteristics, kidney function, traditional risk factors, and medications, higher galectin-1 levels were found to be associated independently with a greater risk of renal function decline [tertile 2: hazard ratio (HR) 5.56, 95% confidence interval (CI) 1.79–17.22; tertile 3: HR 5.56, 95% CI 1.97–16.32], but not with CIN, regardless of the presence of diabetes. In conclusion, higher baseline serum galectin-1 levels were associated with a greater risk of renal function decline in patients undergoing CAG, but were not associated independently with CIN.
Combining deep learning with token selection for patient phenotyping from electronic health records
Authors: Yang Zhen , Dehmer Matthias , Yli-Harja Olli , Emmert-Streib Frank
Published: January 2020

Artificial intelligence provides the opportunity to reveal important information buried in large amounts of complex data. Electronic health records (eHRs) are a source of such big data that provide a multitude of health related clinical information about patients. However, text data from eHRs, e.g., discharge summary notes, are challenging in their analysis because these notes are free-form texts and the writing formats and styles vary considerably between different records. For this reason, in this paper we study deep learning neural networks in combination with natural language processing to analyze text data from clinical discharge summaries. We provide a detail analysis of patient phenotyping, i.e., the automatic prediction of ten patient disorders, by investigating the influence of network architectures, sample sizes and information content of tokens. Importantly, for patients suffering from Chronic Pain, the disorder that is the most difficult one to classify, we find the largest performance gain for a combined word- and sentence-level input convolutional neural network (ws-CNN). As a general result, we find that the combination of data quality and data quantity of the text data is playing a crucial role for using more complex network architectures that improve significantly beyond a word-level input CNN model. From our investigations of learning curves and token selection mechanisms, we conclude that for such a transition one requires larger sample sizes because the amount of information per sample is quite small and only carried by few tokens and token categories. Interestingly, we found that the token frequency in the eHRs follow a Zipf law and we utilized this behavior to investigate the information content of tokens by defining a token selection mechanism. The latter addresses also issues of explainable AI.
Cell type, sub-region, and layer-specific speed representation in the hippocampal–entorhinal circuit
Authors: Iwase Motosada , Kitanishi Takuma , Mizuseki Kenji
Published: January 2020

It has been hypothesised that speed information, encoded by ‘speed cells’, is important for updating spatial representation in the hippocampus and entorhinal cortex to reflect ongoing self-movement during locomotion. However, systematic characterisation of speed representation is still lacking. In this study, we compared the speed representation of distinct cell types across sub-regions/layers in the dorsal hippocampus and medial entorhinal cortex of rats during exploration. Our results indicate that the preferred theta phases of individual neurons are correlated with positive/negative speed modulation and a temporal shift of speed representation in a sub-region/layer and cell type-dependent manner. Most speed cells located in entorhinal cortex layer 2 represented speed prospectively, whereas those in the CA1 and entorhinal cortex layers 3 and 5 represented speed retrospectively. In entorhinal cortex layer 2, putative CA1-projecting pyramidal cells, but not putative dentate gyrus/CA3-projecting stellate cells, represented speed prospectively. Among the hippocampal interneurons, approximately one-third of putative dendrite-targeting (somatostatin-expressing) interneurons, but only a negligible fraction of putative soma-targeting (parvalbumin-expressing) interneurons, showed negative speed modulation. Putative parvalbumin-expressing CA1 interneurons and somatostatin-expressing CA3 interneurons represented speed more retrospectively than parvalbumin-expressing CA3 interneurons. These findings indicate that speed representation in the hippocampal-entorhinal circuit is cell-type, pathway, and theta-phase dependent.
Insulin-independent stimulation of skeletal muscle glucose uptake by low-dose abscisic acid via AMPK activation
Authors: Magnone Mirko , Emionite Laura , Guida Lucrezia , Vigliarolo Tiziana , Sturla Laura , Spinelli Sonia , Buschiazzo Ambra , Marini Cecilia , Sambuceti Gianmario , De Flora Antonio , Orengo Anna Maria , Cossu Vanessa , Ferrando Sara , Barbieri Ottavia , Zocchi Elena
Published: January 2020

Abscisic acid (ABA) is a plant hormone active also in mammals where it regulates, at nanomolar concentrations, blood glucose homeostasis. Here we investigated the mechanism through which low-dose ABA controls glycemia and glucose fate. ABA stimulated uptake of the fluorescent glucose analog 2-NBDG by L6, and of [18F]-deoxy-glucose (FDG) by mouse skeletal muscle, in the absence of insulin, and both effects were abrogated by the specific AMPK inhibitor dorsomorphin. In L6, incubation with ABA increased phosphorylation of AMPK and upregulated PGC-1α expression. LANCL2 silencing reduced all these ABA-induced effects.In vivo, low-dose oral ABA stimulated glucose uptake and storage in the skeletal muscle of rats undergoing an oral glucose load, as detected by micro-PET. Chronic treatment with ABA significantly improved the AUC of glycemia and muscle glycogen content in CD1 mice exposed to a high-glucose diet. Finally, both acute and chronic ABA treatment of hypoinsulinemic TRPM2-/-mice ameliorated the glycemia profile and increased muscle glycogen storage. Altogether, these results suggest that low-dose oral ABA might be beneficial for pre-diabetic and diabetic subjects by increasing insulin-independent skeletal muscle glucose disposal through an AMPK-mediated mechanism.
Associations between untraditional risk factors, pneumonia/lung cancer, and hospital fatality among hypertensive men in Guangzhou downtown
Authors: Shen Yuechun , Chen Yuelin , Huang Zheng , Huang Junyao , Li Xinchun , Tian Zuojun , Li Jun
Published: January 2020

Mortality of primary hypertension is high worldwide. Whether untraditional factors exist in modern life and affect the mortality is not well studied. The aim of the study was to evaluate the risk factors for fatality rate of hypertensive men in downtown area. A cross-sectional study was performed on hypertensive men, who were hospitalized into our hospital and lived in eligible urban areas. The characteristics of the patients and factors for the fatality were analyzed and of the risks or the contributors on the status were investigated. 14354 patients were identified. Mean age was 68.9 ± 12.4 year old (y) and dead ones was 75.9 ± 9.5 y. The overall hospitalized fatality was 5.9%, which was increased with age: fatality with 0.7%, 2.2%, 2.9%, 7.1%, 11.1% and 16.6% was for age group ≦ 49 y, 50–59 y, 60–69 y, 70–79 y, 80–89 y and ≧ 90 y respectively. The increased fatality was significantly positively correlated with the incidence of pneumonia, P < 0.05, r = 0.99. Pneumonia was prone to involve in men with older age and severer organ damage by hypertension. Similar to traditional risks such as coronary heart disease and stroke, pneumonia and lung cancer were also significantly associated with the fatality. Odds ratio (95% CI) for pneumonia and lung cancer were 6.18 (4.35–8.78) and 1.55 (1.14–2.11). The study provides evidence that pneumonia and lung cancer are highly associated with fatality of hypertensive men in downtown area, indicating that in order to reduce the fatality of hypertension, these lung diseases should be prevented and treated intensively in modern life.
Optimisation of monolithic nanocomposite and transparent ceramic scintillation detectors for positron emission tomography
Authors: Wilson Keenan J. , Alabd Roumani , Abolhasan Mehran , Safavi-Naeini Mitra , Franklin Daniel R.
Published: January 2020

High-resolution arrays of discrete monocrystalline scintillators used for gamma photon coincidence detection in PET are costly and complex to fabricate, and exhibit intrinsically non-uniform sensitivity with respect to emission angle. Nanocomposites and transparent ceramics are two alternative classes of scintillator materials which can be formed into large monolithic structures, and which, when coupled to optical photodetector arrays, may offer a pathway to low cost, high-sensitivity, high-resolution PET. However, due to their high optical attenuation and scattering relative to monocrystalline scintillators, these materials exhibit an inherent trade-off between detection sensitivity and the number of scintillation photons which reach the optical photodetectors. In this work, a method for optimising scintillator thickness to maximise the probability of locating the point of interaction of 511 keV photons in a monolithic scintillator within a specified error bound is proposed and evaluated for five nanocomposite materials (LaBr3:Ce-polystyrene, Gd2O3-polyvinyl toluene, LaF3:Ce-polystyrene, LaF3:Ce-oleic acid and YAG:Ce-polystyrene) and four ceramics (GAGG:Ce, GLuGAG:Ce, GYGAG:Ce and LuAG:Pr). LaF3:Ce-polystyrene and GLuGAG:Ce were the best-performing nanocomposite and ceramic materials, respectively, with maximum sensitivities of 48.8% and 67.8% for 5 mm localisation accuracy with scintillator thicknesses of 42.6 mm and 27.5 mm, respectively.
Cost-effectiveness of transplanting lungs and kidneys from donors with potential hepatitis C exposure or infection
Authors: Scott Nick , Snell Greg , Westall Glen , Pilcher David , Raggatt Michelle , Walker Rowan G. , Hellard Margaret , Peleg Anton Y. , Doyle Joseph
Published: January 2020

Organ transplant guidelines in many settings recommend that people with potential hepatitis C virus (HCV) exposure or infection are deemed ineligible to donate. The recent availability of highly-effective treatments for HCV means that this may no longer be necessary. We used a mathematical model to estimate the expected difference in healthcare costs, difference in disability-adjusted life years (DALYs) and cost-effectiveness of removing HCV restrictions for lung and kidney donations in Australia. Our model suggests that allowing organ donations from people who inject drugs, people with a history of incarceration and people who are HCV antibody-positive could lead to an estimated 10% increase in organ supply, population-level improvements in health (reduction in DALYs), and on average save AU$2,399 (95%CI AU$1,155-3,352) and AU$2,611 (95%CI AU$1,835-3,869) per person requiring a lung and kidney transplant respectively. These findings are likely to hold for international settings, since this policy change remained cost saving with positive health gains regardless of HCV prevalence, HCV treatment cost and waiting list survival probabilities. This study suggests that guidelines on organ donation should be revisited in light of recent changes to clinical outcomes for people with HCV.
Isolation and identification of two pairs of cytotoxic diterpene tautomers and their tautomerization mechanisms
Authors: Dai Li-Ping , Li Xiao-Fei , Feng Qing-Mei , Zhang Ling-Xia , Liu Qiu-Yan , Xu Er-Ping , Wu Hong , Wang Zhi-Min
Published: January 2020

Discovering anticancer drugs that do not have adverse side effects has been a developing research field worldwide in recent decades. In this work, four previously undescribed cytotoxic diterpenoids were isolated from the aerial parts of Isodon excisoides. Interestingly, these four diterpenoids were two pairs of tautomers that were first reported in plants. Their structures were further elucidated using various spectroscopic methods. The tautomerization phenomenon and mechanism for these two pairs of tautomers were emphatically described. The theoretical simulation results indicated that the diterpene tautomerization is greatly related to certain factors, including the existence of a transition state, the change of bond length and the level of conversion energy; the tautomerization for the two pairs of tautomers is mainly caused by proton transfer. For bioassays, the cytotoxicities of the tautomers against five human cancer cell lines were also investigated. The results indicated that each of the four diterpenoids showed significant cytotoxicity in at least three cell lines and could serve as potential anticancer agents for further investigation.
Depressive symptoms are associated with social isolation in face-to-face interaction networks
Authors: Elmer Timon , Stadtfeld Christoph
Published: January 2020

Individuals with depressive symptoms are more likely to be isolated in their social networks, which can further increase their symptoms. Although social interactions are an important aspect of individuals’ social lives, little is known about how depressive symptoms affect behavioral patterns in social interaction networks. This article analyzes the effect of depressive symptoms on social interactions in two empirical settings (Ntotal = 123, Ndyadic relations = 2,454) of students spending a weekend together in a remote camp house. We measured social interactions between participants with Radio Frequency Identification (RFID) nametags. Prior to the weekend, participants were surveyed on their depressive symptoms and friendship ties. Using state-of-the-art social network analysis methods, we test four preregistered hypotheses. Our results indicate that depressive symptoms are associated with (1) spending less time in social interaction, (2) spending time with similarly depressed others, (3) spending time in pair-wise interactions rather than group interactions but not with (4) spending relatively less time with friends. By “zooming in” on face-to-face social interaction networks, these findings offer new insights into the social consequences of depressive symptoms.
The Prevalence of Dystonic Tremor and Tremor Associated with Dystonia in Patients with Cervical Dystonia
Authors: Hvizdošová Lenka , Nevrlý Martin , Otruba Pavel , Hluštík Petr , Kaňovský Petr , Zapletalová Jana
Published: January 2020

The link between dystonia and tremor has been known for decades, but the question of whether they are two separate illnesses or just different manifestations of one disease with the same pathophysiological background remains unanswered. We distinguish two types of tremor in dystonia: dystonic tremor (DT), which appears on the body part affected by dystonia, and tremor associated with dystonia (TAWD), which appears in locations where the dystonia does not occur. In this study, the frequency of occurrence of different forms of tremor was determined by clinical examination in a group of adult-onset isolated cervical dystonia (CD) patients treated with regular local injections of botulinum toxin A in our department. In total, 120 patients were included in the study, of which 70 (58.3%) had DT of the head. TAWD was, in all 14 cases (11.7%), observed on the upper limbs, in the form of static or intentional tremor. The aim of this study was to point out the presence of TAWD as one of the clinical signs of CD. DT occurred in more than half of the patients and appears to be a relatively common part of the clinical picture in patients with CD.
Blood pressure estimation based on pulse rate variation in a certain period
Authors: Hayase Toshiyuki
Published: January 2020

Availability of daily continuous blood pressure (DCBP) has a strong impact to realization of healthy society. However, existing methods to obtain blood pressure of cuff type and cuff-less types utilizing correlation with pulse waveform, pulse transit time or pulse rate; or computation of circulation model are not suitable to obtain DCBP. Here we implemented a method based on a simple circulatory system model using pulse rate measurement to overcome the limitations, and showed that it provides appropriate estimation of DCBP. The present model consists of a circulatory dynamic system model and an inverse model of a circulatory control system with input of pulse rate and six model parameters representing standard pulse rate, elasticity of systemic arteries, peripheral vascular resistance, and characteristics of resistance and stroke volume control. Validity of the DCBP estimation method was examined by preliminary experiment for one subject in four days and that for four subjects in one day. DCBP estimation was performed with 24-hour pulse rate measurement by a wearable device and sphygmomanometer measurement for parameter determination and verification. Mean absolute errors in systolic/diastolic pressures were appropriate ones for preliminary experiments with 9.4/6.4 mmHg in four days and 7.3/5.9 mmHg in five subjects.
A compression transmission device for the evaluation of bonding strength of biocompatible microfluidic and biochip materials and systems
Authors: Kratz S. R. A. , Bachmann B. , Spitz S. , Höll G. , Eilenberger C. , Goeritz H. , Ertl P. , Rothbauer M.
Published: January 2020

Bonding of a variety of inorganic and organic polymers as multi-layered structures is one of the main challenges for biochip production even to date, since the chemical nature of these materials often does not allow easy and straight forward bonding and proper sealing. After selection of an appropriate method to bond the chosen materials to form a complex biochip, function and stability of bonding either requires qualitative burst tests or expensive mechanical multi-test stations, that often do not have the right adaptors to clamp biochip slides without destruction. Therefore, we have developed a simple and inexpensive bonding test based on 3D printed transmission elements that translate compressive forces via manual compression, hand press or hydraulic press compression into shear and tensile force. Mechanical stress simulations showed that design of the bonding geometry and size must be considered for bonding tests since the stress distribution thus bonding strength heavily varies with size but also with geometry. We demonstrate the broad applicability of our 3D printed bonding test system by testing the most frequent bonding strategies in combination with the respective most frequently used biochip material in a force-to-failure study. All evaluated materials are biocompatible and used in cell-based biochip devices. This study is evaluating state-of-the-art bonding approaches used for sealing of microfluidic biochips including adhesive bonding, plasma bonding, solvent bonding as well as bonding mediated by amino-silane monolayers or even functional thiol-ene epoxy biochip materials that obviate intermediate adhesive layers.
Influence of MUC5B gene on antisynthetase syndrome
Authors: López-Mejías Raquel , Remuzgo-Martínez Sara , Genre Fernanda , Pulito-Cueto Verónica , Rozas Sonia M. Fernández , Llorca Javier , Fernández David Iturbe , Cuesta Víctor M. Mora , Ortego-Centeno Norberto , Gómez Nair Pérez , Mera-Varela Antonio , Martínez-Barrio Julia , López-Longo Francisco Javier , Mijares Verónica , Lera-Gómez Leticia , Usetti María Piedad , Laporta Rosalía , Pérez Virginia , Gafas Alicia De Pablo , González María Aránzazu Alfranca , Calvo-Alén Jaime , Romero-Bueno Fredeswinda , Sanchez-Pernaute Olga , Nuno Laura , Bonilla Gema , Balsa Alejandro , Hernández-González Fernanda , Grafia Ignacio , Prieto-González Sergio , Narvaez Javier , Trallero-Araguas Ernesto , Selva-O’Callaghan Albert , Gualillo Oreste , Castañeda Santos , Cavagna Lorenzo , Cifrian José M. , González-Gay Miguel A.
Published: January 2020

MUC5B rs35705950 (G/T) is strongly associated with idiopathic pulmonary fibrosis (IPF) and also contributes to the risk of interstitial lung disease (ILD) in rheumatoid arthritis (RA-ILD) and chronic hypersensitivity pneumonitis (CHP). Due to this, we evaluated the implication of MUC5B rs35705950 in antisynthetase syndrome (ASSD), a pathology characterised by a high ILD incidence. 160 patients with ASSD (142 with ILD associated with ASSD [ASSD-ILD+]), 232 with ILD unrelated to ASSD (comprising 161 IPF, 27 RA-ILD and 44 CHP) and 534 healthy controls were genotyped. MUC5B rs35705950 frequency did not significantly differ between ASSD-ILD+ patients and healthy controls nor when ASSD patients were stratified according to the presence/absence of anti Jo-1 antibodies or ILD. No significant differences in MUC5B rs35705950 were also observed in ASSD-ILD+ patients with a usual interstitial pneumonia (UIP) pattern when compared to those with a non-UIP pattern. However, a statistically significant decrease of MUC5B rs35705950 GT, TT and T frequencies in ASSD-ILD+ patients compared to patients with ILD unrelated to ASSD was observed. In summary, our study does not support a role of MUC5B rs35705950 in ASSD. It also indicates that there are genetic differences between ILD associated with and that unrelated to ASSD.
Wheat dwarfing influences selection of the rhizosphere microbiome
Authors: Kavamura Vanessa N. , Robinson Rebekah J. , Hughes David , Clark Ian , Rossmann Maike , Melo Itamar Soares de , Hirsch Penny R. , Mendes Rodrigo , Mauchline Tim H.
Published: January 2020

The development of dwarf wheat cultivars combined with high levels of agrochemical inputs during the green revolution resulted in high yielding cropping systems. However, changes in wheat cultivars were made without considering impacts on plant and soil microbe interactions. We studied the effect of these changes on root traits and on the assembly of rhizosphere bacterial communities by comparing eight wheat cultivars ranging from tall to semi-dwarf plants grown under field conditions. Wheat breeding influenced root diameter and specific root length (SRL). Rhizosphere bacterial communities from tall cultivars were distinct from those associated with semi-dwarf cultivars, with higher differential abundance of Actinobacteria, Bacteroidetes and Proteobacteria in tall cultivars, compared with a higher differential abundance of Verrucomicrobia, Planctomycetes and Acidobacteria in semi-dwarf cultivars. Predicted microbial functions were also impacted and network analysis revealed a greater level of connectedness between microbial communities in the tall cultivars relative to semi-dwarf cultivars. Taken together, results suggest that the development of semi-dwarf plants might have affected the ability of plants to recruit and sustain a complex bacterial community network in the rhizosphere.