bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glial cell derived neurotrophic factor prevents western diet and palmitate-induced hepatocyte oxidative damage and death through SIRT3
Authors: Mwangi Simon Musyoka , Li Ge , Balasubramaniam Arun , Merlin Didier , Dawson Paul A. , Jang Young C. , Hart C. Michael , Czaja Mark J. , Srinivasan Shanthi 
Published: September 2022

AbstractNonalcoholic fatty liver disease (NAFLD) is associated with increased oxidative stress that leads to hepatocyte and mitochondrial damage. In this study we investigated the mechanisms involved in the induction of oxidative stress and impairment of mitochondrial quality control and mitophagy in hepatocytes by the saturated fatty acid palmitate and Western diet feeding in mice and if their harmful effects could be reversed by the neurotrophic factor glial cell derived neurotrophic factor (GDNF). Western diet (WD)-feeding increased hepatic lipid peroxidation in control mice and, in vitro palmitate induced oxidative stress and impaired the mitophagic clearance of damaged mitochondria in hepatocytes. This was accompanied by reductions in hepatocyte sirtuin 3 (SIRT3) deacetylase activity, gene expression and protein levels as well as in superoxide dismutase enzyme activity. These reductions were reversed in the liver of Western diet fed GDNF transgenic mice and in hepatocytes exposed to palmitate in the presence of GDNF. We demonstrate an important role for Western diet and palmitate in inducing oxidative stress and impairing mitophagy in hepatocytes and an ability of GDNF to prevent this. These findings suggest that GDNF or its agonists may be a potential therapy for the prevention or treatment of NAFLD.
Metal chelating and anti-radical activity of Salvia officinalis in the ameliorative effects against uranium toxicity
Authors: Aydin Deniz , Yalçin Emine , Çavuşoğlu Kültiğin 
Published: September 2022

AbstractUranium is a highly radioactive heavy metal that is toxic to living things. In this study, physiological, cytogenetic, biochemical and anatomical toxicity caused by uranium and the protective role of sage (Salvia officinalis L.) leaf extract against this toxicity were investigated with the help of Allium test. Germination percentage, root length, weight gain, mitotic index (MI), micronucleus (MN) formation, chromosomal aberrations (CAs), superoxide dismutase (SOD) and catalase (CAT) enzyme activities, malondialdehyde (MDA) levels and changes in root meristem cells were used as indicators of toxicity. In the experimental stage, a total of six groups, one of which was the control, were formed. Group I was treated with tap water, while group II and III were treated only with sage (190 mg/L and 380 mg/L). Groups IV, V and VI were germinated with uranyl acetate dihydrate (0.1 mg/mL), uranyl acetate dihydrate + 190 mg/L sage and uranyl acetate dihydrate + 380 mg/L sage, respectively. Allium cepa L. bulbs of each group were germinated for 72 h, and at the end of the period, routine preparation techniques were applied and physiological, cytogenetic, biochemical and anatomical analyzes were performed. As a result, uranium application caused a significant decrease (p < 0.05) in all physiological parameters and MI values. MN, CAs numbers, SOD and CAT enzyme activities and MDA levels increased significantly (p < 0.05) with uranium application. Uranium promoted CAs in the root tip cells in the form of fragment, vagrant chromosome, sticky chromosome, bridge and unequal distribution of chromatin. In addition, it caused anatomical damages such as epidermis cell damage, cortex cell damage and flattened cell nucleus in root tip meristem cells. Sage application together with uranium caused significant (p < 0.05) increases in physiological parameters and MI values and significant decreases in MN, CAs, SOD and CAT activities and MDA levels. In addition, the application of sage resulted in improvement in the severity of anatomical damages induced by uranium. It was determined that the protective role of sage observed for all parameters investigated was even more pronounced at dose of 380 mg/L. The protective role of sage against uranium toxicity is related to its antioxidant activity, and sage has 82.8% metal chelating and 72.9% DPPH removal activity. As a result, uranyl acetate exhibited versatile toxicity in A. cepa, caused cytotoxicity by decreasing the MI rate, and genotoxicity by increasing the frequencies of MN and CAs. And also, Sage acted as a toxicity-reducing agent by displaying a dose-dependent protective role against the toxic effects induced by uranyl acetate.
A unified Gaussian copula methodology for spatial regression analysis
Authors: Hughes John 
Published: September 2022

AbstractSpatially referenced data arise in many fields, including imaging, ecology, public health, and marketing. Although principled smoothing or interpolation is paramount for many practitioners, regression, too, can be an important (or even the only or most important) goal of a spatial analysis. When doing spatial regression it is crucial to accommodate spatial variation in the response variable that cannot be explained by the spatially patterned explanatory variables included in the model. Failure to model both sources of spatial dependence—regression and extra-regression, if you will—can lead to erroneous inference for the regression coefficients. In this article I highlight an under-appreciated spatial regression model, namely, the spatial Gaussian copula regression model (SGCRM), and describe said model’s advantages. Then I develop an intuitive, unified, and computationally efficient approach to inference for the SGCRM. I demonstrate the efficacy of the proposed methodology by way of an extensive simulation study along with analyses of a well-known dataset from disease mapping.
Superconducting quantum circuit of NOR in quantum annealing
Authors: Saida Daisuke , Hidaka Mutsuo , Miyake Kouhei , Imafuku Kentaro , Yamanashi Yuki 
Published: September 2022

AbstractThe applicability of quantum annealing to various problems can be improved by expressing the Hamiltonian using a circuit satisfiability problem. We investigate the detailed characteristics of the NOR/NAND functions of a superconducting quantum circuit, which are the basic building blocks to implementing various types of problem Hamiltonians. The circuit is composed of superconducting flux qubits with all-to-all connectivity, where direct magnetic couplers are utilized instead of the variable couplers in the conventional superconducting quantum circuit. This configuration provides efficient scalability because the problem Hamiltonian is implemented using fewer qubits. We present an experiment with a complete logic operation of NOR/NAND, in which the circuit produces results with a high probability of success for arbitrary combinations of inputs. The features of the quantum circuit agree qualitatively with the theory, especially the mechanism for an operation under external flux modulation. Moreover, by calibrating the bias conditions to compensate for the offset flux from the surrounding circuit, the quantum circuit quantitatively agrees with the theory. To achieve true quantum annealing, we discuss the effects of the reduction in electric noise in quantum annealing.
Forecasting admissions in psychiatric hospitals before and during Covid-19: a retrospective study with routine data
Authors: Wolff J. , Klimke A. , Marschollek M. , Kacprowski T. 
Published: September 2022

AbstractThe COVID-19 pandemic has strong effects on most health care systems. Forecasting of admissions can help for the efficient organisation of hospital care. We aimed to forecast the number of admissions to psychiatric hospitals before and during the COVID-19 pandemic and we compared the performance of machine learning models and time series models. This would eventually allow to support timely resource allocation for optimal treatment of patients. We used admission data from 9 psychiatric hospitals in Germany between 2017 and 2020. We compared machine learning models with time series models in weekly, monthly and yearly forecasting before and during the COVID-19 pandemic. A total of 90,686 admissions were analysed. The models explained up to 90% of variance in hospital admissions in 2019 and 75% in 2020 with the effects of the COVID-19 pandemic. The best models substantially outperformed a one-step seasonal naïve forecast (seasonal mean absolute scaled error (sMASE) 2019: 0.59, 2020: 0.76). The best model in 2019 was a machine learning model (elastic net, mean absolute error (MAE): 7.25). The best model in 2020 was a time series model (exponential smoothing state space model with Box-Cox transformation, ARMA errors and trend and seasonal components, MAE: 10.44). Models forecasting admissions one week in advance did not perform better than monthly and yearly models in 2019 but they did in 2020. The most important features for the machine learning models were calendrical variables. Model performance did not vary much between different modelling approaches before the COVID-19 pandemic and established forecasts were substantially better than one-step seasonal naïve forecasts. However, weekly time series models adjusted quicker to the COVID-19 related shock effects. In practice, multiple individual forecast horizons could be used simultaneously, such as a yearly model to achieve early forecasts for a long planning period and weekly models to adjust quicker to sudden changes.
Construction and validation model of necroptosis-related gene signature associates with immunity for osteosarcoma patients
Authors: Hua Long , Lei Pengfei , Hu Yihe 
Published: September 2022

AbstractOsteosarcoma is the most common malignant tumor in children and adolescents and its diagnosis and treatment still need to be improved. Necroptosis has been associated with many malignancies, but its significance in diagnosing and treating osteosarcoma remains unclear. The objective is to establish a predictive model of necroptosis-related genes (NRGs) in osteosarcoma for evaluating the tumor microenvironment and new targets for immunotherapy. In this study, we download the osteosarcoma data from the TARGET and GEO websites and the average muscle tissue data from GTEx. NRGs were screened by Cox regression analysis. We constructed a prediction model through nonnegative matrix factorization (NMF) clustering and the least absolute shrinkage and selection operator (LASSO) algorithm and verified it with a validation cohort. Kaplan–Meier survival time, ROC curve, tumor invasion microenvironment and CIBERSORT were assessed. In addition, we establish nomograms for clinical indicators and verify them by calibration evaluation. The underlying mechanism was explored through the functional enrichment analysis. Eight NRGs were screened for predictive model modeling. NRGs prediction model through NMF clustering and LASSO algorithm was established. The survival, ROC and tumor microenvironment scores showed significant statistical differences among subgroups (P < 0.05). The validation model further verifies it. By nomogram and calibration, we found that metastasis and risk score were independent risk factors for the poor prognosis of osteosarcoma. GO and KEGG analyses demonstrate that the genes of osteosarcoma cluster in inflammatory, apoptotic and necroptosis signaling pathways. The significant role of the correlation between necroptosis and immunity in promoting osteosarcoma may provide a novel insight into detecting molecular mechanisms and targeted therapy.
Co-ingestion of glutamine and leucine synergistically promotes mTORC1 activation
Authors: Yoshimura Ryoji , Nomura Shuichi 
Published: September 2022

AbstractLeucine (Leu) regulates protein synthesis and degradation via activation of mammalian target of rapamycin complex 1 (mTORC1). Glutamine (Gln) synergistically promotes mTORC1 activation with Leu via glutaminolysis and Leu absorption via an antiporter. However, Gln has also been shown to inhibit mTORC1 activity. To resolve this paradox, we aimed to elucidate the effects of Gln on Leu-mediated mTORC1 activation. We administered Leu, Gln, tryptophan, Leu + Gln, or Leu + tryptophan to mice after 24-h fasting. The mice were then administered puromycin to evaluate protein synthesis and the gastrocnemius muscle was harvested 30 min later. Phosphorylated eukaryotic initiation factor 4E-binding protein 1, 70-kDa ribosomal protein S6 kinase 1, and Unc-51 like kinase 1 levels were the highest in the Leu + Gln group and significantly increased compared with those in the control group; however, Gln alone did not increase the levels of phosphorylated proteins. No difference in glutamate dehydrogenase activity was observed between the groups. Leu concentrations in the gastrocnemius muscle were similar in the Leu-intake groups. Our study highlights a novel mechanism underlying the promotive effect of Gln on Leu-mediated mTORC1 activation, providing insights into the pathway through which amino acids regulate muscle protein metabolism.
Positive geographic correlation between soldiers’ weapon size and defensive prowess in a eusocial aphid, Ceratovacuna japonica
Authors: Hattori Mitsuru , Ono Masato , Itino Takao 
Published: September 2022

AbstractSome aphid species produce a soldier caste with enlarged forelegs and horns (weapons). It has been hypothesised that the evolution of morphological specialization by soldiers in social aphids is accelerated by high predation pressure, but this possibility has not been tested. Here, we investigated the relationship between local predator abundance and soldiers’ weapon size and aggressiveness in a prey–predator system comprising a eusocial aphid, Ceratovacuna japonica, and its predators (larvae of the butterfly Taraka hamada and of the moth Atkinsonia ignipicta) in two populations with different predator abundances. We found that the soldiers in the predator-abundant population had larger weapons and were more aggressive than those in the population with lower predator abundance. Furthermore, the soldiers’ defensive prowess (evaluated as the survival of aphids in the presence of predators) was greater in the predator-abundant population. These results provide the first evidence that a population of eusocial aphids experiencing high predation pressure has soldiers with pronounced defensive traits and defensive prowess.
Experimental demonstration of multiple Fano resonances in a mirrored array of split-ring resonators on a thick substrate
Authors: Kamarauskas Andrius , Seliuta Dalius , Šlekas Gediminas , Sadauskas Modestas , Kvietkauskas Evaldas , Trusovas Romualdas , Ratautas Karolis , Kancleris Žilvinas 
Published: September 2022

AbstractThis work demonstrates the first experimental observation of multiple Fano resonances in the terahertz range in a system based on an array of mirror-symmetric split-ring resonators deposited on low-loss and low-refractive index polytetrafluoroethylene (PTFE) substrate. For the first time, selective surface activation induced by laser technology has been used to deposit a copper layer on a PTFE substrate with the further application of standard mask lithography for metasurface manufacturing.
Combatting antimicrobial resistance via the cysteine biosynthesis pathway in bacterial pathogens
Authors: Hicks Joanna L. , Oldham Keely E.A. , McGarvie Jack , Walker Emma J. 
Published: September 2022

Abstract
Antibiotics are the cornerstone of modern medicine and agriculture, and rising antibiotic resistance is one the biggest threats to global health and food security. Identifying new and different druggable targets for the development of new antibiotics is absolutely crucial to overcome resistance. Adjuvant strategies that either enhance the activity of existing antibiotics or improve clearance by the host immune system provide another mechanism to combat antibiotic resistance. Targeting a combination of essential and non-essential enzymes that play key roles in bacterial metabolism is a promising strategy to develop new antimicrobials and adjuvants, respectively. The enzymatic synthesis of L-cysteine is one such strategy. Cysteine plays a key role in proteins and is crucial for the synthesis of many biomolecules important for defense against the host immune system. Cysteine synthesis is a two-step process, catalyzed by two enzymes. Serine acetyltransferase (CysE) catalyzes the first step to synthesize the pathway intermediate O-acetylserine, and O-acetylserine sulfhydrylase (CysK/CysM) catalyzes the second step using sulfide or thiosulfate to produce cysteine. Disruption of the cysteine biosynthesis pathway results in dysregulated sulfur metabolism, altering the redox state of the cell leading to decreased fitness, enhanced susceptibility to oxidative stress and increased sensitivity to antibiotics. In this review, we summarize the structure and mechanism of characterized CysE and CysK/CysM enzymes from a variety of bacterial pathogens, and the evidence that support targeting these enzymes for the development of new antimicrobials or antibiotic adjuvants. In addition, we explore and compare compounds identified thus far that target these enzymes.
Astrocytes in memory formation and maintenance
Authors: Bohmbach Kirsten , Henneberger Christian , Hirrlinger Johannes 
Published: September 2022

Abstract
Learning and memory are fundamental but highly complex functions of the brain. They rely on multiple mechanisms including the processing of sensory information, memory formation, maintenance of short- and long-term memory, memory retrieval and memory extinction. Recent experiments provide strong evidence that, besides neurons, astrocytes crucially contribute to these higher brain functions. However, the complex interplay of astrocytes and neurons in local neuron–glia assemblies is far from being understood. Although important basic cellular principles that govern and link neuronal and astrocytic cellular functions have been established, additional mechanisms clearly continue to emerge. In this short essay, we first review current technologies allowing the experimenter to explore the role of astrocytes in behaving animals, with focus on spatial memory. We then discuss astrocytic signaling mechanisms and their role in learning and memory. We also reveal gaps in our knowledge that currently prevent a comprehensive understanding of how astrocytes contribute to acquisition, storage and retrieval of memory by modulating neuronal signaling in local circuits.
Volatile-rich comets ejected early on during Solar System formation
Authors: Anderson Sarah E. , Petit Jean-Marc , Noyelles Benoît , Mousis Olivier , Rousselot Philippe 
Published: September 2022

Context. Comet C/2016 R2 PanSTARRS (hereafter C/2016 R2) presents an unusually high N2/CO abundance ratio, as well as a heavy depletion in H2O, making it the only known comet of its kind. Understanding its dynamical history is therefore of essential importance as it would allow us to gain a clearer understanding of the evolution of planetesimal formation in our Solar System. Two studies have independently estimated the possible origin of this comet from building blocks formed in a peculiar region of the protoplanetary disk, near the ice line of CO and N2.
Aims. We intend to investigate the fates of objects formed from the building blocks in these regions. We hope to find a possible explanation for the lack of C/2016 R2-like comets in our Solar System.
Methods. Using a numerical simulation of the early stages of Solar System formation, we track the dynamics of these objects in the Jumping Neptune scenario based on five different initial conditions for the protosolar disk. We integrate the positions of 250 000 planetesimals over time in order to analyze the evolution of their orbits and create a statistical profile of their expected permanent orbit.
Results. We find that objects formed in the region of the CO- and N2- ice lines are highly likely to be sent towards the Oort Cloud or possibly ejected from the Solar System altogether on a relatively short timescale. In all our simulations, over 90% of clones formed in this region evolved into a hyperbolic trajectory, and between 1% and 10% were potentially captured by the Oort Cloud. The handful of comets that remained were either on long-period, highly eccentric orbits like C/2016 R2, or absorbed into the Edgeworth-Kuiper belt.
Conclusions. Comets formed <15 au were predominantly ejected early in the formation timeline. As this is the formation zone likely to produce comets of this composition, this process could explain the lack of similar comets observed in the Solar System.
CHEMOUT: CHEMical complexity in star-forming regions of the OUTer Galaxy
Authors: Colzi L. , Romano D. , Fontani F. , Rivilla V. M. , Bizzocchi L. , Beltran M. T. , Caselli P. , Elia D. , Magrini L. 
Published: September 2022

Context. Nitrogen isotopic ratios are a key tool for tracing Galactic stellar nucleosynthesis.
Aims. We present the first study of the 14N/15N abundance ratio in the outer regions of the Milky Way (namely, for galactocentric distances, RGC, from 12 up to 19 kpc), with the aim to study the stellar nucleosynthesis effects in the global Galactic trend.
Methods. We analysed IRAM 30 m observations towards a sample of 35 sources in the context of the CHEMical complexity in star-forming regions of the OUTer Galaxy (CHEMOUT) project. We derived the 14N/15N ratios from HCN and HNC for 14 and 3 sources, respectively, using the J = 1–0 rotational transition of HN13C, H15NC, H13CN, and HC15N.
Results. The results found in the outer Galaxy have been combined with previous measurements obtained in the inner Galaxy. We find an overall linear decreasing H13CN/HC15N ratio with increasing RGC. This translates to a parabolic 14N/15N ratio with a peak at 11 kpc. Updated Galactic chemical evolution models have been taken into account and compared with the observations. The parabolic trend of the 14N/15N ratio with RGC can be naturally explained (i) by a model that assumes novae as the main 15N producers on long timescales (≥1 Gyr) and (ii) by updated stellar yields for low- and intermediate-mass stars.
Risk of Recurrent Venous Thromboembolism in Selected Subgroups of Men: A Danish Nationwide Cohort Study
Authors: Albertsen Ida Ehlers , Konstantinides Stavros V. , Piazza Gregory , Goldhaber Samuel Z. , Larsen Torben Bjerregaard , Søgaard Mette , Nielsen Peter Brønnum 
Published: September 2022

Abstract
Background Although men are considered at high risk for recurrent venous thromboembolism (VTE), sex-specific data on prognostic factors are lacking. We estimated the cumulative recurrence risks associated with clinical characteristics and comorbidities known or suspected to be associated with the development of VTE recurrence: major surgery, trauma, history of cancer, rheumatic disorder, ischemic heart disease, congestive heart failure, chronic obstructive pulmonary disease, diabetes, chronic renal disease, varicose veins, alcohol-related diseases, and arterial hypertension.
Methods We linked nationwide Danish health registries to identify all incident VTE in- and outpatients in men from 2008 through 2018. Recurrent VTE risk 2 years after anticoagulant discontinuation was calculated using the Aalen-Johansen estimator, stratified by age above/below 50 years.
Results The study included 13,932 men with VTE, of whom 21% (n = 2,898) were aged <50 years. For men aged <50 years with at least one of the clinical characteristics, 2-year recurrence risk ranged from 6% (major surgery) to 16% (history of cancer). For men ≥50 years with at least one of the characteristics, recurrence risk ranged from 7% (major surgery) to 12% (ischemic heart disease, chronic obstructive pulmonary disease, and chronic renal disease). Men aged <50 and ≥50 years without the clinical characteristics all had a recurrence risk of 10%.
Discussion We demonstrated a 2-year recurrence risk of at least 6%, regardless of age category and disease status, in this nationwide cohort of men with VTE. The recurrence risk must be balanced against bleeding risk. However, the high recurrence risk across all subgroups might ultimately lead to greater emphasis on male sex in future guidelines focusing on optimized secondary VTE prevention.